Main topic:
Dermatopathology
|
14th
Ljudevit Jurak International Symposium on
Comparative
Pathology
Zagreb,
Croatia
June
6-7, 2003
juraks@kbsm.hr
|
|
BIOMARKERS IN MELANOMA. WHAT’S NEW?
Ruiter J D, van Muijen N P G
Department of Pathology, University Medical Center St. Radboud, Nijmegen,
Netherlands
Biomarkers in tumors can be divided into differentiation (“lineage”) markers,
progression (“stage”) markers and other markers. They consist of DNA, RNA
or protein and their detection in tumor material or body fluids may contribute
to the assessment of diagnosis and/or prognosis. In melanoma several melanocytic
differentiation proteins that are currently used as immunohistochemical
markers in diagnostic histopathology and as a target for vaccination purposes
have been described. Furthermore, a large number of progression markers
that show a preference for one or a few stages of melanoma development
have been identified, but most of them lack prognostic information independent
of the current dominant prognostic parameters. However, the latter parameters
lose power as melanomas are diagnosed in an earlier stage now. Therefore,
further research is still needed so as to identify additional progression
markers, which may also reveal new molecules involved in the pathogenesis
of tumor invasion and metastasis.
Tumor progression, including metastasis, is only possible through close
interaction of the tumor cells with their microenvironment. The tumor microenvironment
implies the total functional and structural constellation of neoplastic
and non-neoplastic cells and extracellular components, with emphasis on
their functional interactions. Molecules derived from the tumor stroma
may exert paracrine effects on the adjacent neoplastic cells and they may
be shed into the circulation. Based on their tissue distribution molecules
derived (partially) from the tumor stroma can also be considered as a progression
marker and some of these molecules (e.g. proteinases and related components,
cytokines) were shown to have prognostic relevance. Therefore, they should
be included in the classification of melanoma progession markers.
Using high through-put (microarray) technology on the DNA (“genomics”),
RNA (“transcriptomics”), and/or protein (“proteomics”) level, a plethora
of tumors markers has been found. Pioneering microarray studies in melanoma
have identified gene products that may play a role in the pathogenesis
of metastasis. The potential value of RNA microarray technology and subsequent
sophisticated statistical analysis in the assessment of diagnosis and prognosis
has been shown recently in other types of solid tumors, e.g. non-Hodgkin
lymphoma, breast cancer and small, round blue-cell tumors in children,
but so far not in melanoma. Obstacles for such applications in melanoma
may be the requirement for fresh tissue, the amount of tissue needed and
the high costs. Therefore, robust techniques suitable for routinely fixed
and paraplast embedded tissue should be developed - and affordable
- commercially available testing systems should become available in order
to be able to integrate molecular pathology into diagnostic histopathology
of melanocytic lesions.
<PROGRAM>
DYSPLASTIC NEVI – MORPHOLOGY AND BIOLOGICAL SIGNIFICANCE
Rudolph P
Department of Pathology, University of Kiel, Germany
The “dysplastic nevus“ was conceived as a hypothetical intermediary between
benign nevus and malignant melanoma, based on the assumption that melanocytic
lesions progress through sequential stages from benignity to malignancy
as some epithelial tumors may do. However, the initial definition of the
clinical and histological features of “dysplastic nevi” is blurred, embracing
both typical nevi and early stages of melanoma. If rigorous criteria are
applied, the “dysplastic nevus” emerges as a characteristic benign melanocytic
tumor without signs of incipient malignant transformation. The distinction
between “dysplastic” nevi and “common” nevi of junctional or compound type
is unwarranted, as it probably reflects a continuum of evolutionary stages
in melanocytic nevi. Hence, flat pigmented nevi might be rallied under
the term “Clark’s nevus” expounding both clinical and histological attributes.
Although the histomorphology of Clark’s nevi is distinctive, irradiation,
trauma, special locations, and recurrence after incomplete excision may
cause diagnostic problems.
The low frequency of malignant melanomas arising in Clark‘s nevi argues
against a premalignant condition or a precursor lesion, the real precursor
of malignant melanoma being melanoma in situ. Although Clark‘s nevi may
be excised during a period of active growth the proliferative activity
is low compared with malignant melanoma, and the proliferative potential
appears to be limited by low or absent telomerase activity. Also, no genetic
background for a stepwise progression from nevi to melanoma, e.g. in analogy
to the adenoma-carcinoma sequence, could be established. The association
of high numbers of nevi with an increased risk for malignant melanoma reflects
systemic defects in growth regulation or insufficiencies in the immune
surveillance, both of which may entail a predisposition to other, non-melanocytic
tumors. Because Clark’s nevi account for the overwhelming majority of nevi
in adults they cannot be considered as specific markers for melanoma risk.
Instead, two recently described entities, the hybrid nevus and the white
dysplastic melanocytic nevus, might identify patients at increased risk
for malignant melanoma.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
DIFFERENTIAL DIAGNOSIS OF INFLAMMATORY
DERMATITIDES
Zelger Bernhard
Department of Dermatovenerology, University of Innsbruck, Austria
<PROGRAM>
GENODERMATOSES (INHERITED DISEASES WITH CUTANEOUS MANIFESTATIONS):
MOLECULAR BIOLOGY AND DIAGNOSTICS
Jukić D M
Departments of Dermatology and Pathology, University of Pittsburgh Medical
School, UPMC Health System, Shadyside, Pittsburgh, PA, USA
Genodermatoses are a variable group of inherited diseases that initially,
or at least very early in life, present with cutaneous findings. They include
divergent diseases, which could be divided into, for instance, disorders
of pigmentation (example– albinism); disorders of keratinization (example–congenital
ichthyosiform erythroderma), etc. The focus of this article is a subset
of genodermatoses that are associated with increased risk of various skin
neoplasms that develop either very early or later in life. Thus, this subset
has often been dubbed as “inherited or heritable cancer syndromes." However,
it is important to realize that not all of inherited cancer syndromes have
skin manifestations, and that indeed, not all of the genodermatoses have
neoplastic associations. The particular diseases this article deals with
are Muir-Torre syndrome, Cowden’s disease, and Carney’s complex.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
NEW ASPECTS IN JOINT AND BONE PROCESSES IN PSORIATRIC
ARTRITIS (PSA)
Fassbender H G
Zentrum Für Rheuma-Pathologie, Mainz, Germany
* Full article will be published in the next issue of Acta clinica Croatica
<PROGRAM>
DETECTION OF EBV, HTLV-1, HCV AND BORRELIA BURGDORFERI
GENOMES IN SKIN BIOPSIES OF PATIENTS WITH MYCOSIS FUNGOIDES
Miertusova S1, Bonin S1, 2, Stanta G 1, 2
1International Centre for Genetic Engineering and Biotechnology, Area Science
Park, Trieste, Italy, 2Department of Clinical, Morphological and Technical
Sciences, University of Trieste Italy
Several studies have investigated the possible involvement of viral agents
and other microorganisms in ethiopathogenesis of primary cutaneous lymphoma.
Our aim was to detect the presence of Epstein- Barr virus (EBV), human
T- cell lymphotrophic virus type I (HTLV-1) and hepatitis C virus (HCV)
genomes and Borrelia burgdorferi genome in the samples of mycosis
fungoides using polymerase chain reaction/ Southern blot assay. We examined
paraffin embedded tissues of skin lesions of 82 patients with mycosis fungoides
compared with 33 healthy controls, which were all excisions of homolocalized
naevi.
Fourteen of 82 mycosis fungoides samples (17%) showed positivity
for EBV whereas only 1 of 33 controls (3%); p= 0,0431. The incidence of
HTLV-1 tax proviral sequence in RNA extracts from 82 mycosis fungoides
samples was 42% (35/82), but only 18% in the group of controls (6/33);
p= 0,0131. We found HCV- specific RNA in 8 of 82 (10%) cases of mycosis
fungoides and in 3 of 33 controls (9%); p= 0,9129. We have detected flagellin
gene, the unique conserved region of B. burgdorferi in 17 of 82 (20%) mycosis
fungoides samples and in no healthy control; p< 0.0001.
These findings support the idea that EBV, HTLV-1 and Borrelia burgdorferi
may be involved in the ethiopathogenesis of myosis fungoides and
indicate that HCV seems not to play a role in it.
<PROGRAM>
CULTURE OF HUMAN KERATINOCYTES AND PRODUCTION OF
KERATINOCYTE GRAFTS IN VITRO
Boranić M, Zekušić Marija, Gabrilovac Jelka, Tomičić H, Vrtar Z, Kraus
O, Buljat G, Fattorini I, Jakić-Razumović Jasminka
Medical Faculty Osijek, Ruđer Bošković Institute Zagreb, Traumatology Clinics
Zagreb, Children’s Clinic Zagreb, Sestre milosrdnice University Hospital
Zagreb, Clinical Hospital Center Zagreb
Extensive skin defects after the burn injuries are covered by skin transplants,
lyophilized animal skin, artificial tissues made of biodegradable material
or the skin epithelial cells (keratinocytes) cultured in vitro. The biotechnological
method for the large-scale production of human keratinocytes has been discovered
about twenty years ago and today is used in several specialized centers.
Keratinocytes obtained from a skin biopsy of 1.5 cm2 may in three weeks
yield the progeny sufficient to cover as much as 1.5 m2 which is equivalent
to the whole body surface. The period required for the expansion of the
autologous keratinocytes of a burned patient is bridged by temporary transplants
of allogeneic skin or artificial material. The cultivation of human skin
has been started in our Institute and the first cultures have been obtained.
Clinical use of the cultured material is planned in collaboration with
the plastic surgeons. The biotechnological process for the production of
the material suitable for clinical use requires a highly skilled personnel
and strict sterility of the working environment.
<PROGRAM>
EXPRESSION OF p53, bcl-2 AND GROWTH HORMONE
RECEPTOR IN ACTINIC KERATOSIS AND SQUAMOUS CELL CARCINOMA OF THE SKIN
Stanimirović A, Čupić H, Bošnjak B, Tomas D, Krušlin B, Belicza M
Ljudevit Jurak University Department of Pathology, Sestre milosrdnice University
Hospital, Zagreb, Croatia
INTRODUCTION: Actinic keratosis (AK) and squamous cell carcinoma of the
skin (SCC) are becoming extremely common epithelial lesions. Besides skin
type and individual susceptibility, the most important causative factor
is a long-term UV exposure. Variables such as time of exposure, gender,
occupation, place of residence, and especially age significantly influence
on prevalence and incidence of AK and SCC. AK was initially considered
precancerous or premalignant skin lesion, because it presents no invasion
into the dermis, in contrast to SCC. However, AK shares many similarities
with SCC: causative factor (UV light), clinical and pathological properties
(i.e. localization, atypical keratinocytes, …) as well as molecular abnormalities
(i. e. DNA aneuploidy, loss of heterozygosity). Thus, novel investigations
consider AK as an early stage in biologic continuum that leads from carcinoma
in situ to invasive SCC. Although this opinion is favored by a finding
that SCC often develops from AK, there is still no generally accepted agreement
about this new postulation.
AIM OF THE STUDY: The relationship between activated protooncogenes
and inactivated tumor suppressor genes play a crucial role in the development
and progression of AK and SCC. The results of previous studies of genes
p53 and bcl-2 in these two entities by imunohistochemical (IHC) techniques
are controversial. Recent studies confirmed that growth hormone (GH) is
involved in the development of different types of human neoplasms. In order
to compare and try to elucidate relationship between AK and SCC we have
studied p53, bcl-2 and GH receptor (GHR) expression in AK and SCC.
PATIENTS AND METHODS: Thirty-three specimens of hypertrophic type of
actinic keratosis (HAK), 25 of atrophic actinic keratosis (AAK) and 27
specimens of SCC (grade G1), taken from sun-exposed areas in group of patients
of both sexes, older than 60 years of age, were investigated. Expression
of p53 and bcl-2 was determined by Microwave Streptavidin ImmunoPeroxidase
(MSIP) protocol on DAKO TechMateTM Horizon automated immunostainer. Immunohistochemical
technique Strept-HRP with the monoclonal antibody MAb263 was used to demonstrate
the expression of GHR. The relative proportion of immunoreactive cells
was studied.
RESULTS: Detected pattern of p53, bcl-2 and GHR expression in HAK, AAK
and SCC are presented in Tables 1-3.
DISCUSSION AND CONCLUSION: Nuclear staining for P53 protein was detected
in 91% of HAK and 100% AAK specimens, as well in 89% of SCC specimens.
This finding is among the highest percentages of P53-positive AK and SCC
determined in up-to-date investigations. Highly increased expression of
gene p53 in AK and SCC from sun-exposed areas indicates its major role
in photocarcinogenesis.
Expression of BCL-2 protein was detected in all investigated (100%)
AK specimens of both types. On the other hand, only 66% of investigated
SCC specimens showed bcl-2 expression. Relatively decreased expression
of bcl-2 in SCC - in comparison to AK - suggests that there are certain
molecular differences between these two lesions. This finding points out
to possible role of other pro- and anti-apoptotic genes of BCL-2 family
(i.e. bax, bad, bcl-x) in cell protection from apoptosis. There is a need
for further investigations to confirm this hypothesis.
We had detected GHR positivity in 36% of HAK specimens, while 80% of
AAK specimens were positive. This is the first report of GHR positivity
in AK. Detected finding of significantly increased GHR expression in atrophic
AK compared to hypertrophic AK, indicates that atrophic AK might have higher
proliferative potential. This opinion is favored by finding of an increased
GHR expression in SCC (93%).
In our investigation we have determined the great similarity in expression
of investigated immunohistochemical markers (tumor suppressor gene p53,
oncogene bcl-2 and GHR) between AK and SCC. Our results support novel
opinions that AK is not precancerosis but the initial stage of SCC. We
suggest that further investigations of other immunohistochemical markers
in different types of AK and different grades of SCC are necessary to confirm
these new attitudes completely.
TABLES
Table 1. Expression of p53, bcl-2
and GHR in hypertrophic actinic keratosis (n=33).
| IHC expression |
p53 |
bcl-2 |
GHR |
| - |
3 |
9% |
0 |
0% |
21 |
64% |
| + |
8 |
24% |
30 |
91% |
4 |
12% |
| ++ |
8 |
24% |
0 |
0% |
4 |
12% |
| +++ |
14 |
43% |
3 |
9% |
4 |
12% |
| Total positive |
30 |
91% |
33 |
100% |
12 |
36% |
(-) no positive cells
(+) less than 10% positive cells
(++) 10 to 25% positive cells
(+++) more than 25% positive cells
Table 2. Expression of p53, bcl-2
and GHR in atrophic actinic keratosis (n=25).
| IHC expression |
p53 |
bcl-2 |
GHR |
| - |
0 |
0% |
0 |
0% |
5 |
20,0% |
| + |
18 |
72,0% |
22 |
88,0% |
12 |
48,0% |
| ++ |
6 |
24,0% |
3 |
12,0% |
8 |
32,0% |
| +++ |
1 |
4,0% |
0 |
0% |
0 |
0% |
| Total positive |
25 |
100% |
25 |
100% |
20 |
80,0% |
(-) no positive cells
(+) less than 10% positive cells
(++) 10 to 25% positive cells
(+++) more than 25% positive cells
Table 3. Expression of p53, bcl-2
and GHR in squamous cell carcinoma of the skin (n=27).
| IHC expression |
p53 |
bcl-2 |
GHR |
| - |
3 |
11% |
9 |
33% |
2 |
7% |
| + |
8 |
30% |
17 |
63% |
2 |
7% |
| ++ |
11 |
41% |
1 |
4% |
5 |
19% |
| +++ |
5 |
18% |
0 |
0% |
18 |
67% |
| Total positive |
24 |
89% |
18 |
67% |
25 |
93% |
(-) no positive cells
(+) less than 10% positive cells
(++) 10 to 25% positive cells
(+++) more than 25% positive cells
REFERENCES:
Ginarte M, García-Cabarello T, Fernández-Redondo V, Beiras A, Toribio
J. Expression of growth hormone receptor in benign and malignant cutaneous
proliferative entities. J Cutan Pathol 2000; 27:276-82.
Lincoln DT, Sinowatz F, Temmim-Baker L, Baker HI, Kölle S, Waters MJ.
Growth hormone receptor expression in the nucleus and cytoplasm of normal
and neoplastic cells. Histochem Cell Biol 1998; 109:141-59.
Lober BA, Lober CW. Actinic keratosis is squamous cell carcinoma. South
Med J 2000; 93:650-5.
Nagano T, Ueda M, Ichihashi M. Expression of p53 protein is an early
event in ultraviolet light-induced cutaneous squamous cell carcinogenesis.
Arch Dermatol 1993; 129: 1157-61.
Nakagawa K, Yamamura K, Maeda S, Ichihashi M. bcl-2 expression in epidermal
keratinocytic diseases. Cancer 1994; 74: 1720-4.
Onodera H, Nakamura S, Sugai T. Cell proliferation and p53 protein
expression in cutaneous epithelial neoplasms. Am J Dermatopathol 1996;18:
580-8.
Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma.
J Am Acad Dermatol 2000;42:S4-S7
Shimizu T, Oga A, Murakami T, Muto M. Overexpression of P53 protein
associated with proliferative activity and histological degree of malignancy
in solar keratosis. Dermatology 1999;199: 113-8.
Tucci MG, Offidani A, Lucarini G, Simonelli L, Amati S, Cellini A,
et al. Advances in the understanding of malignant transformation of keratinocytes:
an immunohistochemical study. J Eur Acad Dermatol Venereol 1998;10: 118-24.
Wikonkal NM, Berg RJ, van Haselen CW, Horkay I, Remenyik E, Begany
A, Hunyadi J, van Vloten WA, de Gruijl FR. bcl-2 vs. p53 expression and
apoptotic rate in human nonmelanoma skin cancers. Arch Dermatol 1997;133:599-602.
<PROGRAM>
SMALL VESSEL VASCULITIS OF THE SKIN WITH IgA-POSITIVE
IMMUNE DEPOSITS
Pižem J, Perković Tatjana, Jurčić Vesna, Vizjak Alenka
Institute of Pathology, Faculty of Medicine University of Ljubljana, Slovenia
AIMS: To evaluate the significance of skin vascular IgA-positive immune
deposits in differentiating Henoch-Schönlein purpura (HSP) from other types
of immune-complex small-vessel vasculitides.
METHODS: Among 695 skin biopsies, analysed by light and immunoflorescence
microscopy techniques in the period from 2001-2002, 70 were found to have
IgA-positive vascular immune deposits and were included in the study. The
clinical diagnoses were vasculitis, HSP, or purpura.
RESULTS: The median age of patients was 59 years (range 8 - 80 years).
Only 3 patients were younger than 16 years. Histological findings were
leucocytoclastic vasculitis (43/70), perivascular mononuclear or mixed
cell inflammatory infiltrate (15/70) and no changes (12/70). Granular immune
deposits, demonstrated in superficial vessels in 70 cases and in deep dermal
vessels in 9, stained positive for IgA and C3 in all cases, for IgM in
29, for IgG in 5, for C1q in 6, and for fibrin/fibrinogen in 68. They were
IgA-dominant in 56 and IgM-dominant in 14 cases. Complement component C1q
was detected in 5 IgM-dominant and in one IgA-dominant case. The deep vessels
were significantly more often involved by inflammation (28/70) then by
immune deposits (9/70). Leucocytoclastic vasculitis was more frequently
found in the IgM-dominant group. There was a strong clinical suggestion
for drug induced vasculitis in one IgM-dominant C1q-positive case and a
diagnosis of mixed cryoglobulinemic vasculitis, based on serologic finding
of mixed IgA, IgG and IgM cryoglobulins was established in one IgA-dominant
C1q positive case.
DISCUSSION AND CONCLUSION: The majority of cases with IgA-positive
skin vasculitis show predominance of IgA in vascular immune deposits and
most probably, even in the older age group, represent HSP. Dominant IgM,
accompanying IgA in vascular deposits, may be rarely found in late lesions
of HSP and presumably represent secondary nonspecific deposition. Frequently,
despite inflammation, no immune deposits can be found in the deep vessels,
probably as a consequence of their clearance by inflammatory cells. The
positivity for C1q, indicating the classical pathway of complement activation,
can be demonstrated also in IgA-dominant vascular immune deposits and suggests
other types of immune-complex vasculitis, such as cryoglobulinemic and
drug induced. The clinical and serologic data as well as biopsy histologic
and immunofluorescence findings should be considered in the final diagnosis
of skin small vessel vasculitis.
REFERENCES:
Jennette JC, Falk RJ, Andrassy K, et al: Nomenclature of systemic vasculitides.
Proposal of an International Consensus Conference. Arthritis Rheum
1994, 37:187-192
Jennette JC, Falk R. Small-vessel vasculitis. New Engl J Med 1997;
20: 1512-1523
<PROGRAM>
GENE EXPRESION PROFILES OF HEPATOCELLULAR CARCINOMAS
Denk H
Department of Pathology, University of Graz, Austria
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
ZOONOTIC DERMATITIDES
Del Piero F
University of Pennsylvania, School of Veterinary Medicine, Department of
Pathobiology and Department of Clinical studies New Bolton Center, Philadelphia
Zoonoses are those diseases and infections which are naturally transmitted
between vertebrate animals and man. Viruses, bacteria, fungi protozoa,
helminthes and arthropods can be transmitted directly or indirectly from
animals to humans. A restricted number of agents are able to cause skin
disease. The etiologic agent can be passively transmitted to the human
host or can be actively inoculated in the skin with bites and scratches
or arthropod bite. Although all humans are at risk for these skin diseases,
some job categories are associated with greater exposure. Immunodeficient
human patients are at particular risk of infection by zoonotic agents and,
for them, the outcome can be easily fatal. Here we described the lesions
caused by zoonotic agents able to induce dermatitis in humans.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
NEW OUTBREAK OF ENDEMIC UROPATHY IN “CRNAC POLJE” FOCUS,
CROATIA: A PRELIMINARY REPORT
Božić Z1, Matijašević Maja2, Duančić V3
1Urologist, Private Practice, Zagreb, Croatia, 2General Practice Unit,
Davor, Croatia, 3Department of Epidemiology, Medical Centre for Prevention
and Rehabilitation of Heart Diseases, Zagreb, Croatia
The authors previously defined Panonian-Balkan endemic uropathy (PBEU)
as a single rural household environmental disease of the entire urinary
tract due to shared living conditions and nourishment, with imprecisely
determined but usually long latency. Clinical manifestations, including
chronic renal failure (CRF) due to the tubulointerstitial nephropathy,
renal cell carcinoma and urotheliomas observed with a significantly higher
frequency in the affected population, represent a complex, however one
unique nosological entity which can be found in a single patient.
The follow-up performing in an endangered part of Croatia recently
detected an unexpected outbreak of PBEU in the villages Davor and Orubica
(3255 inhabitants), belonging to almost forgotten “Crnac Polje” endemic
focus on the Sava river-bank. In 2002 the prevalence rate of endemic terminal
stage CRF cases and CRF cases with associated endemic urotheliomas has
risen to 12/3255 and 8/3255 respectively, or alternatively to crude prevalence
rates of 369/100 000 and 246/100 000. The prevalence of exclusively terminal
stage CRF endemic nephropaths in Davor and Orubica population (12/3255)
was significantly higher (?2=17.3 ; p=0.0000) in comparison with the total
prevalence of terminal stage CRF patients in the rural area of Sesvete,
north-west Croatia (12/11 481). The prevalence of exclusively endemic urothelioma
cases in Davor and Orubica population (8/3255) was also significantly higher
(?2=19.9 ; p=0.0000) in comparison with the total prevalence of patients
with urotheliomas in the rural area of Sesvete (4/11 481). Screening based
on the WHO diagnostic criteria for PBEU has never been conducted in the
observed villages making possible the recognition of more, still undetected
cases. The latest literature estimations suggesting that “PBEU is decreasing
in incidence and prevalence in Croatia” appear to be premature like all
other so far.
<PROGRAM>
NEONATICIDE AND INFANTICIDE IN THE EAST CROATIA
OSIJEK COUNTY
Marcikić M1, Dumenčić B1, Matuzalem Elizabeta1, Marjanović Ksenija2, Ugljarević
M2
1Department of Pathology and Forensic Medicine, Medical Faculty, Osijek,
Croatia and 2Department of Pathology General Hospital Vukovar, Croatia
For the lay person no crime is more difficult to comprehend than the killing
of child by their own parents. This is a retrospective study of neonaticide
and infanticide in the East Croatia, Osijek County from 1980 to 2002. A
judicial records of infanticide cases stored in County Court were analyzed
for the circumstances surrounding the offence, personal data, witness testimony,
mothers` motivation, autopsy findings, and the legal procedures. Twenty
four babies were discovered in various places during investigation. The
victims were almost equally divided between boys (12) and girls (11). For
one baby gender was unknown. The mean weight of babies were 2733 grams.
Neonaticide rate were approximately 8 per 100 000 live born. The
perpetrators preferred rubbish-heap (33.4%), burying in soil (16.7%), various
premises in or around house (16.7%) and garbage can (12.5%) as a place
for hiding the dead baby. The most dominant cause of death in sixteen cases
of live birth was mechanical asphyxia (37.5%) with equal distribution of
smothering, stuffing the mouth with rags and strangulation. The other frequent
causes of death were placing the child in plastic bag and abandonment (25%),
brain injury (25%), and wounding by a sharp weapon (12.5%). The cause of
death for six babies remained unknown due to advanced decomposition. Two
babies were stillborn. The age of accused mothers varied from 16 to 33
years. Most of them were unmarried (60%) and had limited formal education.
They usually kept pregnancy a secret (73%) and gave birth (93%) out
of public health service. The mother lived in terror of shame and guilt
that accompany conception without marriage. A fear (60%) seemed to be a
pronounced motivating factor for committing the crime.
Data on court procedure were available in fifteen cases. Mothers were
officially indicted in all cases for infanticide under Croation Penal Code.
The perpetrator remained unidentified in nine suspicious crimes.
Finally, the court convicted ten mothers for infanticide. Juries were
often unwilling to punish the woman. This trend was a consequence of the
belief that the woman who has killed her child has constructed enough guilt
by the act and it is already the punishment. Nine mothers were put on probation
from one to three years. Only one mother was sentenced to ten
months of imprisonment.
A continuous effort is needed for providing a better „sexual
education”, better communication within families and more outreach by pregnancy
service providers to prevent future neonaticide. A desparate young woman
should be advised that there is an alternative to neonaticide in her community.
Hence, more research and further attention to this problem is warranted.
<PROGRAM>
SIDE ARM HOMICIDE IN THE ITALIAN PROVINCE OF TRIESTE
BETWEEN 1953 AND 2002
Nardi U, Tomasella F, Gongolo F, Peretti A, Costantinides F
Department of Science of Public Health – Forensic Pathology Unit, University
of Trieste School of Medicine
The authors present a complete overview of the phenomenon of side arm homicide,
basing the study on the data collected at the Forensic Pathology Unit of
the University of Trieste School of Medicine. Side arms are the most frequently
used homicidal method in the town and province of Trieste in a considered
study period of 50 years from 1953 to 2002.
The analysis of the collected data shows that the town and province
of Trieste are communities still very well disjoined from a reality in
which crimes against life are yet very uncommon occurrences. This conclusion
is well supported by the fact that it has not been possible to define a
category of potential victims, which is on the contrary quite easy among
societies where organised crime is consistent and widespread.
The popularity of side arm as homicide method in our province supports
the hypothesis that these crimes are often not aforethought murders, perpetrated
by subjects often afflicted by recorded mental health problems, acting
during an insanity raptus. Knives are not only actually the easiest weapons
to obtain in a household, but are very easily used as well, even by the
subjects not accustomed to handle weapons.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
CELL PROLIFERATION AND p53 PROTEIN EXPRESSION IN
PROLIFERATIVE SKIN DISEASES
Batinac Tanja1, Zamolo Gordana2, Gruber F1, Lipozenčić Jasna3, Jonjić Nives2
1Department of Dermatovenerology, Clinical Hospital Center, Rijeka, Croatia
2Department of Pathology, Medical Faculty, University of Rijeka, Rijeka
Croatia
3Department of Dermatovenerology, Clinical Hospital Center, Zagreb, Croatia
AIM OF THE STUDY: The aim of this study is to elucidate the role of the
p53 tumor-suppressor protein in the pathogenesis of different hyperproliferative,
non-malignant and malignant skin diseases, and association between p53
overexpression and cell proliferation. We also investigated the influence
of aging on p53 and Ki-67 protein expression.
MATERIAL AND METHODS: Hundred and fifty skin specimens, consisting of
30 cases of each: normal skin (NS), psoriatic skin (PS), keratoacanthomas
(KA), basal cell carcinomas (BCC), squamous cell carcinomas (SCC) were
examined immunohistochemicaly to assess p53 and Ki-67 protein expression.
RESULTS: p53 immunostaining of NS, PS, KA, BCC and SCC was positive
in 39.0%, 46.7%, 66.7%, 80% and 86.7% cases, respectively. P53 and Ki-67
positive cells were present in basal (NS) and suprabasal layers (PS), and
not only in cancer nests of KA, BCC and SCC, but also in dysplastic and
even morphologically normal epidermis adjoining cancers. The positivity
of p53 and Ki-67 protein differed significantly among the groups, with
no differences in p53 expression between NS and PS, and in Ki-67 expression
between PS and KA. Within all groups, there was a significant correlation
between p53 and Ki-67 protein expression.
CONCLUSION: Our findings suggest that p53 overexpression occurs widely
in neoplastic and non-neoplastic skin lesions. It is associated with the
cell proliferation in the normal, as well as in the changed epithelium.
P53 accumulation is an age related process and significantly related to
sun exposure, especially in NS and PS, as well as in KA and SCC. We also
suggest that p53 overexpression begins in the early stage of carcinogenesis,
before the appearance of malignancies in skin, and may be a useful predictor
for the detection of nonmelanocytic skin cancer.
REFERENCES:
1. Heenen M., Ann Dermatol Venereol 1997;124:452.
2. Liang SB, et al., Virchows Arch 1999;434:193.
3. Hannuksela-Svahn A, et al., Acta Derm Venerol 1999;79:195.
<PROGRAM>
EXPRESSION OF CATHEPSIN D AND G IN CUTANEOUS MALIGNANT
MELANOMA
Lipozenčić Jasna, Jakić-Razumović Jasminka1, Batinac Tanja2, Pašić A, Šitum
Mirna3, Herman S
Department of Dermatology and Venerology and 1Department of Pathology Zagreb
University Hospital Center, Zagreb, Croatia; 2Department of Dermatovenerology,
Clinical Hospital Center, Rijeka, Croatia; 3Department of Dermatology and
Venerology , Sestre milosrdnice University Hospital , Zagreb, Croatia
AIM OF THE STUDY: To elucidate the prognostic significance of cathepsin
D and G expression in malignant melanoma. Tumor invasion and metastases
are associated with proteolytic action of various proteases. Increased
levels of cathepsin D and G have been observed in primary and metastatic
cancer types. The correlation between cathepsin D tissue concentration
and aggressiveness of tumors has been detected in melanoma patients.
MATERIAL AND METHODS: The study was performed on a group of 18 patients
with histopathological proven primary cutaneous malignant melanoma. There
were 18 patients aged between 22 and 66 years. All tumors were thinner
than 5 mm (Breslow Index from I to V) and Clark level from I to IV. No
previous treatment and no evidence of infection disease 2 month before.
Cathepsin D and G analysis in all 18 patients was performed by standard
immunohistochemically staining using monoclonal antibodies anti-cathepsin
D and anti-cathepsin G.
RESULTS: Cathepsin D was proved in all 18 tumors and macrophages and
in 17 patients in surrounding epidermis. Cathepsin G was proven in 11 tumors;
in macrophages in all 18 samples, but Cathepsin G in surrounding epidermis
was found only in 2 patients.
CONCLUSION: Our results indicate that cathepsin D and G are expressed
at high levels by melanoma cells. The extremely high expression of cathepsin
D was in the three of our patients in tumors with progression of the disease
over a 36-month follow-up period. It seems that there is a significant
correlation between cathepsin D and cathepsin G expression with disease
free interval.
<PROGRAM>
DIRECT IMMUNOFLUORESCENCE AS A DIAGNOSTIC TOOL
IN DERMATOLOGY
Marinović B, Lakoš-Jukić I
Department of Dermatology and Venerology, Zagreb Unviersity Hospital Center,
Zagreb, Croatia
Immunofluorescence has been used for about half a century, both to investigate
the pathophysiology of skin disorders and to help physicians in the diagnosis
of various cutaneous disorders, especially bullous diseases and connective
tissue diseases. Direct immunofluorescence (DIF) is a histologic stain
that helps detect immunoglobulins and complement components within biopsy
specimens. Interpretation of DIF specimen takes into account several parameters,
including site of immune deposition, class of immunoglobulin or other type
of deposit, intensity of immune deposits and morphology of deposition,
i.e. linear, granular, shaggy, etc.
The most common patterns of DIF findings are deposition of IgG, IgA
and/or C3 found in the intercellular spaces of the epithelium (pemphigus
diseases) or in the basement membrane zone (subepidermal blistering diseases,
lupus erythematosus). These immunofluorescent findings are valuable in
confirming a diagnosis that is suspected by clinical or histologic examination,
especially in the group of subepidermal blistering diseases where clinical
and histologic findings may quite frequently overlap.
<PROGRAM>
EXPRESSION OF AMINOPEPTIDASE N (APN; EC 3.4.11.2;
CD13) AND NEUTRAL ENDOPEPTIDASE (NEP; EC 3.4.24.11; CD10) ON CULTURED HUMAN
KERATINOCYTES
Gabrilovac Jelka1, Buza-Vidas Barbara1, Zekušić Marija1, Breljak Davorka1,
Kraus O2, Boranić M1
1Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia;
2Sestre milosrdnice University Hospital Zagreb, Clinical Hospital Center
Zagreb
By secreting cytokines and growth factors keratinocyte actively participate
in immune response and inflammation. Recently membrane-bound aminopeptidases
have been proposed as additional mechanism of cell-to-cell interaction,
as well as a negative loop in controlling concentration of peptide signalling
molecules. In this study we examined expression of two membrane-bound peptidases:
aminopeptidase N (APN; EC 3.4.11.2; CD13) and neutral endopeptidase (NEP;
EC 3.4.24.11; CD10) on nonstimualted cultured human keratinocytes
obtained from healthy skin. Membrane expression of CD13 and CD10
at the population level was analysed by FACS and at the single cell level
by means of fluorescent microscope. Functional properties of CD13 and CD10
were examined by testing their enzymatic activity in the presence of selective
substrates and inhibitors. The data were compared to those obtained on
cultured nonstimulated human skin fibroblasts expressing both CD13/APN
and CD10/NEP. The data obtained have shown that cultured, nonstimulated
keratinocytes from normal healthy skin express CD13. At the population
level 31.7 % ? 2.8% of keratinocytes (n = 3) are CD13+, as compared to
fibroblasts which are 100% CD13+ (n = 3). On the per cell basis, the density
of CD13 is several times lower on keratinocytes than on fibroblasts. Distribution
of CD13 on keratinocytes is homogenous throughout the membrane, appearing
in a typical ring-like fluorescence, whereas distribution of CD13 on fibroblasts
is predominantly patchy or polarized. Membrane CD13 expression on keratinocytes
was associated with significant enzyme activity, which on the basis
of substrate (Ala-pNA and Ala-?NA) and inhibitor (bestatin, actinonin)
selectivity could be ascribed to aminopeptidase N. APN activity on keratinocytes
was several times lower than on fibroblasts, and could be abrogated to
comparable level in both cell types by the APN inhibitor actinonin. In
contrast to membrane CD13 associated with APN enzyme activity, neither
membrane CD10, nor its enzyme (NEP) activity could be found on the same
keratinocyte samples. These data suggest that detection of CD13/APN
is not likely to be due to its activation during the cell cultivation,
but rather represents its constitutive expression. Presence of CD13 with
catalytic activity on keratinocytes may be relevant for their communication
with surrounding cells in the course of immune response and inflammation.
<PROGRAM>
IMMUNOFLUORESCENT DIAGNOSTIC OF AUTOIMMUNE
BULLOUS DISEASES
Kotrulja Lena
Sestre milosrdnice University Hospital, Department of Dermatovenereology,
Zagreb
Immunofluorescence (IF) was introduced in dermatology in 1960s and has
since then contributed greatly to the development of contemporary
concepts and knowledge of bullous and connective tissue disease, at the
same time becoming an important diagnostic tool in routine practice. Histological
finding in differential diagnosis of autoimmune bullous disease has only
orientational role and IF finding is indispensable for definitive diagnosis.
Direct immunofluorescence (DIF) is histological stain used to
detect antigens such as immunoglobulins, complement and fibrin deposited
in the skin utilizing fluoresceinated antibodies specific to the antigen.
Indirect immunofluorescence (IIF) is a serologic technique based on the
capacity of circulating antibodies to bind to the corresponding target
antigen.
Apart from the diagnostic importance, this reaction has a substantial
prognostic value, particularly for pemphigus cases, since it is well known
that the titers of circulating pemphigus antibodies correlate with the
disease activity. Thus, IIF is performed at regular intervals as an important
part of the follow-up of these patients.
In this paper we emphasize the clinical and specific DIF and IIF findings
of the most important autoimmune bullous diseases such as pemphigus
vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, drug induced
pemphigus, IgA pemphigus (intraepidermal IgA neutrophilic dermatosis and
subcorneal pustular dermatosis), bullous pemphigoid, cicatricial pemphigoid,
pemphigoid (herpes) gestationis, linear IgA bullous dermatosis, and epidermolysis
bullosa acquisita.
We present two case reports of the patients who, with their clinical,
histological and immunofluorescent (DIF and IIF) findings, present a
typical example of pemphigus foliaceus and bullous pemphigoid.
<PROGRAM>
PIGMENTED MAMMARY PAGET DISEASE IN A 65 YEAR OLD MAN
- CASE REPORT
Monsef Ali Reza, Eghbalian Fatemeh
Dermatopathology Dept., Sina hospital, Hamedan University of Medical Sciences
Hamedan, Iran
Mammary Paget disease results from intraductal mammary Paget carcinoma,
which extends to the epidermis of the nipple and areola through a
lactiferous duct or from invasive breast carcinoma that reaches the epidermis
via direct extension from the dermis. Pigmented mammary Paget disease is
a rare clinicopathologic variant of mammary Paget disease. It may mime
malignant melanoma both clinically and histopathologically. The involvement
of the dermo-epidermal junction by neoplastic cells of the mammary Paget
carcinoma seems to be a prerequisite for development of the clinical pigmentation.
We report a case of pigmented mammary Paget disease. He was a 65-year-old
male complaining of an erythematous, pigmented scaly plaque around his
right nipple measuring 8x6 cm with mild fissuring from two years
ago. The histopathology revealed pagetoid spread of large cells in the
epidermis with pigmentation of basal cells and melanocytes. The IHC confirmed
the mammary Paget disease and exclude malignant melanoma and squamous cell
carcinoma.
<PROGRAM>
AN INDOLENT SUBCUTANEOUS NODULE OF THE FACE? - CASE
REPORT
Puizina-Ivić N, Stipić T
Department of Dermatovenerology, Clinical Hospital Split, Split, Croatia
A 67-year-old woman was admitted at the Department of Dermatology in the
Clinical Hospital Split, because of one nontender and indolent nodule in
the right temporal region. The nodule was first noticed two months before,
it was not visible, but palpable 1,5 cm in diameter, firm, slightly movable
and painless. She had no other symptoms. She was treated with corticosteroid
ointments but without any improvement. Under the suspicion of atheroma,
cyst or benign tumor, an excisional biopsy was done. Histologic examination
revealed a transverse and longitudinal section of immature female worm
of Dirofilaria with numerous eosinophils in surrounding tissue. Now it
is sure that dirofilariasis exists in Croatia as well as infected dogs
and its vectors.
<PROGRAM>
DERMATITIS ARTEFACTA – CASE REPORT
Gregurek-Novak T1, Novak-Bilić G 1, Vučić Majda2
University Department of Dermatology1 and “Ljudevit Jurak” University Department
of Pathology2 Sestre milosrdnice University Hospital, Zagreb, Croatia
INTRODUCTION: Self-induced factitial dermatitis, or dermatitis artefacta,
is a rare and difficult condition to diagnose and treat. The patient is
friendly but bewildered and the relatives are angry and frustrated. Because
of a lack of diagnostic stringency, quoted female-to-male ratios range
from 3:1 to 20:1, with the highest incidence of onset in late adolescence
to early adult life. Most patients have a personality disorder; borderline
features are common. The patient's denial of psychic distress and negative
feelings aroused in healthcare personnel make the management difficult.
There is a variety of means that patients are using to cause the skin changes.
CASE REPORT: We report a case of 72 years old woman with characteristic
symmetric changes under breast and right inguinal region. The clinical
expression was a very symmetric, partly composed of hemorrhagic round lesions
and partly of scars, which were «cigarette paper»-like. Patient had myocardial
infarct 6 months earlier and diagnosed diabetes mellitus one year before.
Routine laboratory data were within normal ranges. Special consultations
with psychiatrist, internist and diabetologist excluded the possibility
of side effects due to the use of medication. We made skin biopsy (inguinal
lesion) and hystopathology revealed edema in the dermis and strong extravagation
of red blood cell suggesting mechanical irritation on the skin. The skin
lesions were covered for 24 hours in occlusion techniques. In few days
under medical control, the skin lesions improved by 50 %. The patient was
discharged from the hospital under psychiatric and family care.
DISCUSSION: Typical symmetric clinical findings, histology findings,
consultations with psychiatric and family were proof for the diagnosis
of dermatitis artefacta. The patient has many problems in family, lives
alone, far away from the family and she wants to have every day care and
someone to pay attention to her. Our patient was in older age group, in
which dermatitis artefacta is not common. In such cases team work and cooperation
of dermatologist, hystopathologist, psychiatrist and patient's family is
necessary. Research studies are necessary to document more accurately the
expectable cause, treatment outcome and prognosis for this group of patients.
REFERENCES:
Farrier JN, Mansel RE. Dermatitis artefacta of the breast: a series
of case reports.
Eur J Surg Oncol 2002;28:189-92.
Joe EK, Li VW, Magro CM, Arndt KA. Diagnostic clues to dermatitis artefacta.
Cutis 1999;63:209-14.
Koblenzer CS. Dermatitis artefacta. Clinical features and approaches
to treatment. Am J Dermatol 2000;1:47-55.
Antony SJ, Mannion SM. Dermatitis artefacta revisited. Cutis 1995;55:362-4.
<PROGRAM>
GRANULOMA ANNULARE AND NECROBIOSIS LIPOIDICA; CLINICAL
AND HISTOPATOLOGICAL RESEMBLANCES AND DIFFERENCES. CASE REPORT.
Meštrović-Štefekov Jelena1, Šitum Mirna1, Zarubica Jelena2, Kotrulja Lena1,
Vučić Majda2
1Department of Dermatology and Venerology and 2Ljudevit Jurak University
Department of Pathology, Sestre milosrdnice University Hospital, Zagreb
Two granulomatous diseases of unknown etiology - granuloma annulare and
necrobiosis lipoidica are very easy to diagnose in their typical clinical
forms, but in some rarer variants (or/and localization) may be difficult
to distinguish.
Both diseases have been related to diabetes mellitus (about 20% of
patients with disseminated form of granuloma annulare and 40% patients
with necrobiosis lipoidica).
Typically, granuloma annulare was characterized with confluent papules
arranged in a ring, mostly in the back of hand and foot, but also fingers,
toes and elbows (over a joint). In less typical forms, for instance plague
form, granuloma annulare may clinically resemble to necrobiosis lipoidica,
but also other granulomatous diseases of unknown etiology.
Necrobiosis lipoidica typically consist of yellow-brown, indurate plaques
with an atrophic and slightly depressed center and a well-defined raised
erythematous edge. The legs, particularly the shins, are the most common
sites of involvement with symmetric and bilateral distribution. Typical
form of necrobiosis lipoidica is a one-look diagnosis. About 15% of those
lesions are estimated to appear elsewhere on the body and usually causes
problem in differential diagnosis, especially if the patient has no diabetes
mellitus. In those cases, other granulomatous diseases, primary granuloma
annulare and sarcoidosis (scalp lesions) must be excluded.
These atypical, rare clinical variants of granuloma annulare and necrobiosis
lipoidica may be distinguished by histopathology, but also histological
overlaps may occur.
Histologically, differences between these two diagnoses are mostly
in a number of multinucleate giant cells, presence or absence of palisading
histyocites and changes on blood vessels in the middle and lower dermis.
We report a case of acral and truncal multilocular annular and serpiginous
lesion clinically indicative for disseminated form of granuloma annulare,
in a diabetic, 70-year old male patient, the histopathological study of
which showed focal collagen degeneration surrounding with large number
of multinucleate giant cells of foreign body types that is histopathological
characteristic of necrobiosis lipoidica.
<PROGRAM>
SCARRING ALOPECIA AS A MANIFESTATION OF DIFFERENT
SKIN CHANGES
Oremović L, Lugović Liborija, Nola Ivana, Sjerobabski-Masnec Ines, Ožanić-Bulić
S
Department for Dermatology and Venereology, Sestre milosrdnice University
Hospital, Zagreb
BACKGROUND: All scarring processes can damage the hair follicle, leading
to hair loss and by definition irreversible alopecia. Histologically, it
is characterized by dermal scarring, often relatively deep, along with
absent or reduced hair follicles and reduced numbers of erector pili muscles.
The most common causes of scarring alopecia are discoid lupus erythematosus
(DLE), lichen planus, pseudopelade, chronic folliculitis, sarcoidosis,
morphea, mucinosis follicularis, etc.
OBJECTIVE: The purpose of this study was to examine the causes of scarring
alopecia by anamnestic data and different tests, particularly by pathohistologic
examination of patients in our Clinic during 12-month period. We also analysed
the obtained data, different examinations and previous treatment in each
patient.
METHODS: A total of 10 patients with clinically scarring alopecia were
involved in this study. The examination included anamestic data, duration,
previous treatment, light pull test, trichogram, antinuclear antibodies,
allergic tests, etc.
RESULTS: Skin biopsies and pathohistologic examination of the patients
showed different skin disorders - pseudopelade, lichen planus, discoid
lupus erythematosus (DLE), chronic folliculitis etc. There were no important
medical or dermatological associations with other disorders or related
medical conditions.
CONCLUSION: The pathohistologic examination of most scarring alopecia
patients showed different skin disorders (pseudopelade, lichen planus,
DLE, chronic folliculitis) although some patients showed nonspecific histology.
This experience is going to take us to more complex investigation to extend
our knowledge and we hope that this type of alopecia may attract more attention
and investigation in the future.
<PROGRAM>
SUBCUTANEOUS PANNICULITIS-LIKE T-CELL LYMPHOMA -
CASE
REPORT
Troskot N1, Lugović Liborija1, Vučić Majda2, Ožanić-Bulić S1
1Department for Dermatology and Venereology and 2Ljudevit Jurak University
Department of Pathology, Sestre milosrdnice University Hospital, Zagreb
A 45-year-old male, with a 6-month history of tender erythematous subcutaneous
skin lesions and with no signs of systemic symptoms is presented. The patient
denied exposure to trauma or thick bite. The patient noticed erythematous
tender lesion on his left pectoral region, which was gradually enlarging
and spreading centrifugally. It appeared livid in colour, and significantly
hard on palpation. The cytopunction of the lesion indicate a mesenchymal
tumour. Borrelia burgdorferi serologic test was negative. The lesion showed
significant deterioration in respect of clinical signs as well as the worsening
in pain followed by restriction in motion of the left shoulder. The result
of the biopsy showed Morphea (Sclerodermia circumscripta). On patient`s
arrival at our Clinic, the area affected was livid-brown in colour, 5 cm
in size, hard and tender on palpation with central postoperative scar 1
cm in diameter. In the infraumbilical region, there were
two subcutaneous nodular lesions of 1,5 cm, covered with erythematous-livid
skin. In the left pectoral region, similar skin changes – 1 cm in
size - were also present. No axillary lymph nodes were detected.
During hospitalisation two biopsies were taken from the subcutaneous lesions
on the abdominal skin, and the pathohistological analysis indicated
primary to panniculitis in complex of Morphea. Results of the tumorous
tissue obtained from the patient's back, as well as the immunohistochemistry
showed Subcutaneous panniculitis-like T-cell lymphoma. Specific haematological
analysis and medical treatment was continued.
<PROGRAM>
PATHOHISTOLOGIC VERIFICATION OF CLINICALLY SUSPECTED
PSORIASIS VULGARIS SKIN CHANGES
Lugović Liborija1, Šitum Mirna1, Soldo-Belić A1, Vučić Majda2
1Department for Dermatology and Venereology and 2Ljudevit Jurak University
Department of Pathology, Sestre milosrdnice University Hospital,
Zagreb
Psoriasis vulgaris is a skin disease connected with keratinocyte hiperproliferation
and abnormal epidermal differentiation. The classic histological features
that are called psoriasiform, delineate the fully developed scaly silvery
plaque and include uniform elongation of the rete ridges, a thinned suprapapilary
plate, mounds of parakeratosis and several accumulations of neutrophils.
There is exocytosis of erythrocytes and lymphocytes from the dilated and
tortuous papillary vessels, producing the so-called squirting papillae.
This study was performed to compare the equality of clinical and pathohistologic
picture of psoriasis vulgaris, what may be of importance for the treatment
of patients skin changes. Fifty patients were examined in our Clinic and
were included in the study. The patients with skin picture suspected on
psoriasis vulgaris were included in this study. The biopsies of skin changes
on predilection sites typical for psoriasis were performed.
The obtained results showed that most of the patients with clinical
pictures suspected on psoriasis vulgaris had histological verified pictures
typical for psoriasis vulgaris. Among the examined patients, there
were many patients with skin changes suspected on psoriasis vulgaris in
whom histologic analysis showed another clinical picture (e.c. dermatitis
psoriasiformis, dermatitis subacuta, dermatitis eczematoides). Although
most of the patients with clinical suspected psoriasis vulgaris had pathohistologically
verified psoriasis vulgaris, there were also many patients in whom pathohistologic
picture showed other dermatoses, mostly dermatitis psoriasiform. This experience
is especially important to keep in mind when choosing a kind of therapy.
<PROGRAM>
HISTOLOGICAL TYPES OF POLYPOID CUTANEOUS MELANOMA
II
Knežević F, Petrovečki M, Duančić V, Horvat-Knežević Anica, Kostović K
University Hospital for Tumors - Department of Pathology, Dubrava University
Hospital, Institute for Cardiovascular Prevention and Rehabilitation, Faculty
of Science, Department of Animal Physiology; Sestre milosrdnice University
Hospital
In the study of 645 cases of primary cutaneous melanoma, we found 147 (22.8%)
polypoid melanomas. By analysing the growth phases, the type of the neoplastic
melanocytes and the epidermis appearance in this series we defined
2 (1.4%) acral lentigo maligna melanomas (ALMM), 4 (2.8%) lentigo maligna
melanomas (LMM), 42 (28.6%) superficially spreading melanomas (SSM) and
99 (67.2%) nodular melanomas (NM). Based on these results, the authors
classified the polypoid cutaneous melanoma as a morphological variant with
different histological types (ALMM, LMM, SSM, NM) all of which display
an exophytic vertical phase of growth. The majority of the polypoid cutaneous
melanoma are of nodular histological type.
REFERENCES:
McGovern VJ et al. Prognostic significance of a polypoid configuration
in malignant melanoma. Histopathology 1983;7:663-72.
Manci E et al. Polypoid melanoma, a virulent variant of the nodular
growth pattern. Am J Clin Pathol 1981;75(6):810-15.
Reed KM et al. Prognosis for polypoidal melanoma is determined by primary
tumor thickness. Cancer 1986;57(6):1201-3.
Knežević F. Polipoidni melanom kože (magistarski rad) Zagreb, Republika
Hrvatska: Sveučilište u Zagrebu; 1990.
Knežević F et al. Histological types of polypoid cutaneous melanoma.
Croat Med J 1992;33(4):220-4.
Knežević F. Multifaktorijalna analiza polipoidnog melanoma kože (doktorska
disertacija) Zagreb, Republika Hrvatska: Sveučilište u Zagrebu; 2002
<PROGRAM>
A MULTIFACTORIAL ANALYSIS OF POLYPOID CUTANEUS
MELANOMA I (Influence of Examined Parameters on Disease Free Survival)
Knežević F, Duančić V, Horvat-Knežević Anica, Petrovečki M
University Hospital for Tumors, Department of Pathology; Institute for
Cardiovascular Prevention and Rehabilitation, Faculty of Science, Department
of Animal Physiology, Dubrava University Hospital
The basic goal of our study is to determine the dominant, mutually independent
prognostic parameters in polypoid cutaneous melanoma and their influence
on the disease free survival.
645 primary melanoma cases have been investigated and 147 (22.8%) polypoid
cutaneous melanoma cases have been found.
23 morphological-clinical data among them have been statistically evaluated
with MedCalc and SPSS programs, t-test and ?2 test, Kaplan-Meier method
and Cox regression test. Statistical inference have been carried out with
95% reliability, i.e. p < 0.05.
A single-factor analysis of the parameters examined has shown: that
the disease free survival is relatively influenced by sex (p = 0.024),
clinical stages of the disease, clinical stage I, clinical stage II (p
< 0.001); and the thickness of the tumor in mm (p = 0.016).
A multifactorial analysis of the parameters examined has shown that
the disease free survival is independently influenced by the clinical stages
of the disease and clinical stage I (p < 0.001).
In clinical stage I 38% of polypoid melanoma patients have 24 months
of disease free survival and ca. 22% have 72 months of disease free survival.
REFERENCES:
Balch CM et al. An analysis of prognostic factors in 4000 patients
with cutaneous melanoma. ln: Balch CM et al. Cutaneous melanoma. Clinical
management and treatment results worldwide 1st ed.. Philadelphia: J.B.Lippincott
Company;1985, pp. 321–52.
Cox DR. Regression model and life tables. J Royal Stat Soc 1972;B34:187–220.
Balch CM et al. A multifactorial analysis of melanoma III. Prognostic
factors in melanoma patients with lymph node metastases (stage II). Ann
Surg 1981;193:377–88.
Balch CM et al. A multifactorial analysis of melanoma. IV. Prognostic
factors in 200 melanoma patients with distant metastases (stage III). J
Clin Oncol 1983;1:126–34.
Day CL et al. A multivariate analysis of prognostic factors for melanoma
patients with lesion ? 3.65 mm in thickness. The importance of revealing
alternative Cox models. Ann Surg 1982;195:44–9.
Drzewiecki KT et al. Malignant melanoma. Changing trends in factors
influencing metastasis-free survival from 1964 to 1982. Cancer 1990;65:362–6.
Knežević F. Multifaktorijalna analiza polipoidnog melanoma kože (doktorska
disertacija) Zagreb, Republika Hrvatska: Sveučilište u Zagrebu; 2002.
<PROGRAM>
A MULTIFACTORIAL ANALYSIS OF POLYPOID CUTANEOUS
MELANOMA II (Influence of Examined Parameters on Cumulative
Survival Rates)
Knežević F, Duančić V, Petrovečki M, Horvat-Knežević Anica
University Hospital for Tumors, Department of Pathology; Institute for
Cardiovascular Prevention and Rehabilitation, Dubrava University Hospital,
Faculty of Science, Department of Animal Physiology
The basic goal of our study is to determine the dominant, mutually independent
prognostic parameters in polypoid cutaneous melanoma and their influence
on the cumulative survival rates.
645 primary melanoma cases have been investigated and 147 (22.8%) polypoid
cutaneous melanoma cases have been found.
23 morphological-clinical data among them have been statistically evaluated
with MedCalc and SPSS programs, t-test and ?2 test, Kaplan-Meier method
and Cox regression test. Statistical inference have been carried out with
95% reliability, i.e. p < 0.05.
A single-factor analysis of the parameters examined has shown that
the cummulative survival rates is relatively influenced by clinical stages,
clinical stage I, clinical stage II, degree of malignancy to Clark (p<0.00l)
and M/V in mm2 of the tumor tissue ( p=0.016).
A multifactorial analysis od the parameters examined has shown that
the overall survival is independently influenced by the clinical stages
of the disease and clinical stage I ( p<0.001). In the clinical stage
I 64% of the patients live 5 years and 44% ten years. In the clinical
stage II 18% of the patients live one year while patients in the clinical
stage III die within one year.
As for the prognosis of polypoid cutaneous melanoma patients the most
important independent prognostic parameter is the clinical stage
of the disease in the moment when the diagnosis of melanoma is being
made.
REFERENCES:
Balch CM et al. An analysis of prognostic factors in 4000 patients
with cutaneous melanoma. ln: Balch CM et al. Cutaneous melanoma. Clinical
management and treatment results worldwide 1st ed. Philadelphia: J.B.Lippincott
Company;1985, pp. 321–52.
Cox DR. Regression model and life tables. J Royal Stat Soc 1972;B34:187–220.
Balch CM et al. A multifactorial analysis of melanoma III. Prognostic
factors in melanoma patients with lymph node metastases (stage II). Ann
Surg 1981;193(3):377–88.
Balch CM et al. A multifactorial analysis of melanoma. IV. Prognostic
factors in 200 melanoma patients with distant metastases (stage III). J
Clin Oncol 1983;1(2):126–34.
Day CL et al. A multivariate analysis of prognostic factors for melanoma
patients with lesion ? 3.65 mm in thickness. The importance of revealing
alternative Cox models. Ann Surg 1982;195(1):44–9.
Lipponen PK et al. Volume corrected mitotic index (M/V index) in human
bladder cancer; relation to histological grade (WHO), clinical stage (UICC)
and prognosis. Scand J Urol Nephrol 1990;24:39–45.
Haapasalo H et al. Prognosis of ovarian carcinomas: prediction by histoquantitative
methods. Histopathology 1989; 15:167–78.
Haapasalo H, Pesonen E. Volume corrected mitotic index (M/V - INDEX).
The standard of mitotic activity in neoplasms. Pathol Res Pract 1989;185:551–54.
Knežević F. Multifaktorijalna analiza polipoidnog melanoma kože (doktorska
disertacija) Zagreb, Republika Hrvatska: Sveučilište u Zagrebu; 2002.
<PROGRAM>
SKIN TUMORS OF THE PERIORBITAL REGION AND EYELIDS IN
THE 1998-2002 PERIOD
Vučić Majda, Talan-Hranilović Jasna, Vucelić Vesna, Rožanković Sanda, Iveković
Renata1
Ljudevit Jurak University Department of Pathology and 1Department of Ophthalmology,
Sestre milosrdnice University Hospital, Zagreb, Croatia
The aim of this study was to determine the prevalence, year distribution
and localisation of the skin tumours and precancerous skin lesions in the
periorbital region and eyelids during the 1998-2002 period among
biopsy specimens in the Ljudevit Jurak University Department of Pathology
. We also analysed their relationship with sex and age of the patients.
During the observed period there were total number of 286 tumors and precancerous
lesions. The most common was basal cell carcinoma with slightly female
prevalence. Other analysed lesions; nevus lesions, precancerous lesions
and squamous cell carcinoma were found with significantly higher female
prevalence. The most frequent localisation for all lesions was on the eyelids
probably as the consequence of UV irradiation. Average age for all
lesions in time of diagnoses was 65 years for males and 64 years for females.
All patients with skin lesions should be advised of the risk of recurrent
or new tumors. Prevention remains the most important in minimising the
morbidity and mortality due to lesions in this region. Exposure to ultra-violet
(UV), especially UV-B, radiation is the most common cause for genetic abnormalities
in cells and provoked factor in oncogenesis of skin tumors.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
PRIMARY SYNCHRONOUS UVEAL AND SKIN MALIGNANT MELANOMA
- CASE REPORT
Talan-Hranilović Jasna 1, Vučić Majda 1, Iveković R 2, †Kušić V 2
1Ljudevit Jurak University Department of Pathology, 2University Department
of Ophthalmology, Sestre milosrdnice University Hospital, Zagreb, Croatia
Simultaneous occurrence of primary uveal melanoma and skin melanoma is
rare. We presented a 66 year old female patient with primary synchronous
choroidal and skin malignant melanoma on right upper-arm. The patient has
a negative family history for cutaneous or uveal melanomas and did not
display the dysplastic nevus syndrome phenotype. Six years after enucleation
of left bulbous and skin excision of malignant melanoma, the patient presented
with lymphatic metastasis in right axillary lymph nodes and two years after
those metastases in mesenteric lymph nodes and solitary nodules in spleen.
After nine years, the patient developed metastatic inquinal lymph node.
Metastatic spread was due to lymphatic dissemination of more biologically
aggressive primary skin malignant melanoma. Ten years have passed after
the initial presentation of the tumors.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
CLINICAL CASE OF ACRAL HEMORRHAGIC DARIER'S DISEASE
IS NOT CAUSED BY MUTATIONS IN EXON 15 OF THE ATP2A2 GENE
Pećina-Šlaus Nives1, Milavec-Puretić Višnja2, Nikuševa-Martić Tamara1,
Kubat M3, Fischer-Žigmund Martina 1, Lipozenčić Jasna2
1Department of Biology, Zagreb University School of Medicine, Zagreb, Croatia,
2Department of Dermatovenereology, Clinical Hospital, Zagreb University
School of Medicine, 3Department of Forensic Medicine, Zagreb University
School of Medicine.
Dyskeratosis follicularis (Darier's Disease, DD, MIM#124200) is a genetic
skin disorder characterized by the loss of adhesion between epidermal cells
(acantholysis) and pathogenetic changes of keratinization with variant
forms of cutaneous phenotype. Recently it has been shown that DD cause
mutations in the ATP2A2 gene, at 12q24.1. This gene (GenBank accession
nos M23115 and M23114) encodes the sarco/endoplasmic reticulum calcium-pumping
ATPase (SERCA2), which is highly expressed in keratinocytes. We report
on a severe case of the acral hemorrhagic type of DD with an unusual manifestation
involving Staphylococcal sepsis. The patient was treated systemically with
infusions, oral antibiotics, and retinoids. Antiseptics, keratolytic ointments
and creams were given topically to promote epithelization. His condition
improved dramatically after 14 days of treatment. All erosions of the trunk,
extremities, neck, and head had epithelized. Mutations in exon 15 of the
ATP2A2 gene are reported to be the most consistent mutations associated
with the acral hemorrhagic type of DD (Ruiz-Perez, et al. Hum Molec Genet
1999; 8: 1621-1630; Sakuntabhai, et al. Nat Genet 1999; 21: 271-277). In
order to establish genetic background of our patient`s clinical phenotype
we investigated exon 15 of the ATP2A2 gene. By direct sequencing of the
PCR amplified
exon 15 of the ATP2A2 gene we did not detect any mutation in our patient`s
DNA (skin biopsy and blood), nor did we detect mutations in 4 members of
his family. Our results show that mutations in exon 15 of the ATP2A2 gene
are not a necessary prerequisite for acral hemorrhagic type of DD. Our
finding support the variability of clinical manifestations of DD and a
lack of genotype/phenotype consistency.
<PROGRAM>
NEVUS DYSPLASTICUS - PRECURSOR OF MELANOMA MALIGNUM?
Šitum Mirna, Papić Marijana, Bučan Željana, Nola Ivana
Department of Dermatology, Sestre milosrdnice University Hospital
BACKGROUND: Nevus dysplasticus is an acquired melanocytic nevus, typically
flat, and with allegedly specific histological features. There are some
disagreements among the authors. Some authors prefer to use the term atypical
nevus for lesions that attract clinical attention and reserve dysplastic
nevus for those lesions with proven histological changes. Histological
features of dysplastic nevi according to Clark are (1) persistent lentiginous
melanocytic hyperplasia; (2) atypical melanocytic hyperplasia (melanocytic
nuclear atypia); (3) lamellar fibroplasia; (4) concentric eosinophilic
fibroplasia; and (5) sparse patchy lymphocytic infiltrates, whereas according
to Ackerman criteria for dysplastic nevi are silhouette of a benign neoplasm
(e.g., symmetric, sharply circumscribed, relatively flat base), with only
a slight, if any, elevation, in its center, and nests of melanocytes with
small, oval, monomorpheus nuclei confined to the dermoepidermal junction
and the upper part of the dermis.
We classified dysplastic nevus as small, dark, flat, sharply bordered
lesion measuring a few millimeters in diametar. They are located most commonly
on the trunk and tend to increase in number during adolescence, pregnancy,
following intense exposure to sun and immunosuppression. Larger dysplastic
nevi, may be up to 10-15 mm in diametar, multicolored, contain central
elevated or dark nodule, white areas of regression or have an erythematous
border. Thus, they can be very difficult to distinguish from melanoma malignum.
It is still unclear whether these multiple nevi are precursors of melanoma
malignum or markers for melanoma malignum susceptibility.
AIM: Aim of the study was to find out the total number of melanoma
malignum in patients from Department of Dermatology of Sestre milosrdnice
University Hospital and whether melanoma malignum develop from pigmented
lesions or de novo.
MATERIAL AND METHODS: In this retrospective trial we used files and
pathohistological documentation of 661 patients in Department Dermatology
with following diagnoses: solitary, sporadic nevi, multiple nevi, dysplastic
nevus syndrome and melanoma malignum.
RESULTS: Total number of patients with sporadic dysplastic nevi is 208;
among them 103 has histologicaly verified diagnosis, and 105 has typical
clinical features of dyspalstic nevi and are in observation.
The overall number of patients with multiple dysplastic nevi is 149;
among them 90 have histological verification and 59 have typical clinical
features and are in observation.
Dysplastic nevi syndrome was established in 129 patients: among them
108 have histological verified diagnosis and 21 have clinical features
of syndrome and we are observing them.
The total number of patients with histological diagnosis of melanoma
malignum is 175.
Our study showed that melanoma malignum developed from solitary and
multiple dysplastic nevi in 24 %, from dysplastic nevus syndrome in 17
%, from pigmented nevi in 31%, from lentigo maligna in 3 % and de novo
in 25 % of cases.
CONCLUSION: Based on our study, we conclude that melanoma malignum develops
more frequently from dysplastic nevi (41%) rather then other lesions such
as pigmented nevi (31%), lentigo maligna (3%) or de novo (25%).
<PROGRAM>
CLINICAL AND HISTOPATHOLOGICAL PARAMETERS AS PREDICTORS
OF CLINICAL OUTCOME FOR PATIENTS WITH VULVAR CARCINOMA
Blažanović A1, Dotlić S2, Morović A3, Milošević M3, Munivrana H3
1Department of Pathology, General Hospital Vinkovci, Vinkovci, Croatia,
2Department of Pathology, Clinical Hospital Center Zagreb, 3Medical University,
Zagreb, Croatia
AIM OF THE STUDY: The aim of this study was to determine the most important
clinical and pathohistological parameters that influence the prognosis
and outcome of patients with invasive squamous carcinoma of the vulva
in order to offer them the most suitable form of therapy. Moreover, it
was designed to assess the clinical significance of DNA content analysis
by flow cytometry.
PATIENTS AND METHODS: Forty-three cases of squamous cell carcinoma of
the vulva, diagnosed between 1978 and 1996 were selected. In order to assess
the influence of the various prognostic factors on survival, the study
included clinical and
pathohistological parameters as well as the results of flow cytometric
DNA analysis of paraffin-embedded tumor samples from all cases. Clinicopathological
parameters focused on the age of patients, clinical stage of the disease,
menstrual status, diameter and localization of the tumor, histological
grade, nuclear grade, combined histological and nuclear grade, depth of
tumor invasion, tumor growth pattern, the presence of giant cells in the
tumor and the form of therapy, while flow cytometric DNA analysis comprised
DNA ploidy, proliferative activity and DNA index.
RESULTS: Five-year survival of our selected population of patients was
62,3 + 7,8%.
The results of univariate statistical analysis confirmed that statistically
significant prognostic parameters included the age of patients (p=0,033),
clinical
stage of the disease (p=0,014), histological grade (p=0,047), nuclear grade
(p<0,001) and the depth of invasion (p<0,001). On the other hand,
the results of multivariate statistical analysis showed that only combined
histological and nuclear grade (p=0,015) and the depth of tumor invasion
(p<0,001) can be considered independent, statistically significant prognostic
parameters.
CONCLUSION: The age of patients at the time of diagnosis, clinical stage
of the disease, histological grade and nuclear grade are considered to
be the parameters of crucial relevance for the prognosis of patients with
squamous cell carcinoma of the vulva. However, only combined histological
and nuclear grade, as well as the depth of tumor invasion were proven to
be independent statistically significant parameters relevant for the outcome
of patients with this disease.
<PROGRAM>
NON-MELANOMA SKIN CANCERS AND PRECANCEROUS SKIN LESIONS
IN THE 1996 – 2002 PERIOD
Vučić Majda, Rožanković Sanda, Vucelić Vesna, Belicza Mladen, Šitum Mirna1
Ljudevit Jurak University Department of Pathology and 1Department of Dermathology,
Sestre milosrdnice University Hospital, Zagreb, Croatia
Non-melanoma skin cancers and precancerous skin lesions have a significant
morbidity although with relatively low mortality rates in geriatric population.
These lesions developed especially on every day sun exposed skin regions.
The aim of this study was to determine the prevalence, age and sex distribution
of non-melanoma skin cancers and precancerous skin lesions among biopsy
specimens collected during seven years (1996-2002) in the Ljudevit Jurak
University Department of Pathology. Their relationship with sun exposure
on different body regions has also been analyzed. During the observed period
there were 2486 basal cell carcinoma, 419 squamous cell carcinoma and 468
precancerous skin lesions. Basal cell carcinoma was more common in males
then in females with ratio 1:0,9 as well as squamous cell carcinoma with
male to female ratio 1:0,8. Precancerous skin lesions were more frequent
in the female population with male to female ratio 1:1,3. Maximal incidence
for booth types of non-melanoma tumours was between 70 and 79 years in
both sexes while precancerous skin lesions appeared one-decade erlier.
It has also been found that all analyzed skin lesions appear in 60-70%
on skin of the head, which is the body region almost permanently exposed
to the sun.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
CUTANEOUS PSEUDOLYMPHOMAS
Pešut A, Gašparov S, Džebro S, Šitić S, Milković M, Dominis M
Department of Clinical Pathology and Cytology, Merkur University Hospital,
Zagreb, Croatia
Cutaneous pseudolymphomas (CPL) are heterogeneous group of benign reactive
T- or B- cell lymphoproliferative processes of diverse causes that simulate
cutaneous lymphomas clinically and/or histopathologically. Depending on
the predominant cell type in the infiltrate, according to histologic, immunophenotypic
and molecular analyses, they are divided into T- and B- cell pseudolymphomas.
The differentiation between CPL and primary cutaneous lymphomas (PCL) is
often very difficult, but it is important because it has therapeutic consequences.
Aims of this study are to show experiences in CPL in our practice in
the past 9 years (1995-2003). 33 cases of CPL were diagnosed and classified
according to EORTC and WHO classifications of primary cutaneous lymphomas.
Samples were sent to our department as suspected cases of PCL.
Specimens were surgical biopsies, paraffin- embedded tissue and sections
of skin. We used routinely fixed paraffin- embedded tissue sections stained
with HE, PAS, Giemsa, Gomori and panel of antibodies for immunohistochemical
analyses. According to the above mentioned classifications 21 of the cases
were classified as B- cell and 10 cases as T-cell pseudolymphomas, respectively.
In two patients skin lesions were skin manifestations in the course of
rheumatoid arthritis.
REFERENCES:
Jaffe E.S. et al. World Health Organization Classification of Tumours.
Pathology and Genetics of Tumours of Haemathopoietic and Lymphoid Tissues.
IARC Press: Lyon 2001
Cerroni L. et al. An Illustrated Guide to Skin Lymphoma. Press: Blackwell
Science Ltd. 1998
<PROGRAM>
ORAL MANIFESTATIONS OF AUTOIMMUNE DISEASES
Nola Ivana, Kostović K, Kotrulja Lena, Sjerobabski-Masnec Ines, Lugović
Liborija, Meštrović-Štefekov Jelena
Sestre milosrdnice University Hospital, Department of Dermatovenereology
Zagreb, Croatia
The oral mucous membrane has properties in common with the skin because
both originate from the ectoderm. Reactibility related both to skin and
mucosa is the reason for transition of pathological process from skin to
mucosa and vice versa. Collagen tissue diseases, bullous dermatoses and
diseases with possible immunopathogenesis are only some of the skin diseases,
which occur relatively frequently in the region of oral cavity. Pemphigus
is a group of bullous disorders characterized by the development of autoantibodies
against desmocollins and desmogleins in the epidermis, giving rise to superficial
erosions and blister on both epidermal and mucosal surfaces. The most common
variety of pemphigus is pemphigus vulgaris, that usually begins with shallow
erosions and easily ruptured blisters on mucosal surfaces (in over 50%
of cases). Oral lesions in patients with bullous pemphigoid are less frequent
than in pemphigus but should be sought. Mucous membranes are affected in
about 20% of patients with epidermolysis bullosa dystrophica. Also, in
patient with systemic scleroderma the soft tissue of the mouth and palate
are affected, as well as, the mouth gradually shrinks. The oral mucosa
is involved in 15-25% of the cases of discoid lupus erythematosus, and
in 30-45% of the patients with systemic lupus erythematosus. The diagnosis
should be confirmed by histopathology, direct and indirect immunofluorescence
and by confirmation of circulating autoantibodies.
<PROGRAM>
DISTRIBUTION AND AMOUNT OF CATHEPSIN B IN ACUTE KIDNEY
INJURY INDUCED BY GENTAMICIN
Svara T, Juntes P, Pogačnik M
University of Ljubljana, Veterinary Faculty, Ljubljana, Slovenia
Cathepsin B is a lysosomal enzyme important for degradation of proteins.
The largest amount of cathepsin B was found in kidney, in the epithelial
cells of proximal convoluted tubules. Only few references about the role
of cathepsin B in kidney diseases were found. The aim of our study was
to establish in what way the amount and distribution of cathepsin B changes
in tubules during acute kidney injury and if there is any connection between
the degree of kidney injury and the amount of cathepsin B in damaged tubules.
The hypothesis was explored on the model of acute kidney injury induced
by application of nephrotoxic antibiotic gentamicin. Gentamicin was injected
at a dose of 40 mg /kg body weight (first treated group) and 80 mg /kg
body weight (second treated group) for 14 days. Control groups received
injection of physiological saline only. Pathohistological examination was
done on tissue sections of kidneys stained with haematoxylin and eosin.
Monoclonal antibodies against humane cathepsin B (product of Krka, catalogue
number CATHBM1) were applied on formalin - fixed, paraffin - embedded tissue
sections of kidneys. Results of immunohistochemical examination were statistically
processed.
Application of gentamicin provoked vacuolisation of proximal convoluted
tubules in the first treated group. In the second treated group, necrosis
of proximal convoluted tubules was observed, as well as the signs of regeneration.
In both treated groups weaker positive reaction for cathepsin B was noticed
in comparison to the same tubules of control groups. Positive reaction
for cathepsin B was also statistically weaker in the proximal convoluted
tubules of the second treated group in comparison to the first treated
group (P < 0.05). Decrease in positive immunohistochemical reaction
was larger in outer renal cortex, where pathohistological lesions were
more expressed. At the same time, stronger positive immunohistochemical
reaction for cathepsin B was found in proximal straight tubules, but the
differences were not statistically significant (P > 0.05). A comparison
between the treated groups showed a significantly stronger reaction for
cathepsin B in the second treated group in comparison to the first treated
group (P < 0.05).
The results suggest that during acute kidney injury the amount of cathepsin
B decreases in damaged tubules, but at the same time, according to the
degree of injury, its amount in proximal straight tubules increases and
probably proximal straight tubules take over the function of damaged segments
of the proximal tubules.
REFERENCES:
Eisenberger U et al. Renal Physiol Biochem 1995;18:89
Olbricht CJ et al. Kidney Int 1991;39:639
Olbricht CJ, Euro J Chem Clin Biochem 1992;30:675
<PROGRAM>
ANALYSIS OF DEVELOPMENTAL POTENTIAL OF POSTIMPLANTATION
RAT EMBRYO IN METABOLICALLY POOR CONDITIONS BY USING COMBINED IN VITRO
AND IN VIVO TECHNIQUES
Belovari Tatjana1, Stević Nataša1, Gajović S2, Kostović-Knežević Ljiljana2
1Dpt. of Histology and Embriology, School of Medicine, University of Osijek,
Osijek, Croatia, 2Croatian Institute for Brain Research, Zagreb University
School of Medicine, Zagreb, Croatia
In vitro cultures are used in experimental embryology for investigation
of developmental processes, regulatory factors and embryotoxic substances.
However, differentiation is restricted in in vitro conditions, even
in the optimal cultivation medium with serum (1). Subsequent grafting under
the kidney capsule shows that differentiation can be improved in richer
environment (2). Since serum-free cultures are used for precise investigations,
the question is how metabolically poor conditions affect developmental
potential. In rat embryo cultivated 14 days in serum-free medium only epidermis
and cartilage differentiates well, while other differentiated tissues are
rare or absent. Epidermis retains its developmental potential during cultivation
in serum-free medium (3).
To analyze stability of in vitro restriction of developmental potential,
rat embryos were cultivated in serum-free medium and then transplanted
in vivo.
Fisher rat embryos (E 9.5) were cultivated for 14 days in Eagle's minimal
essential medium (MEM) alone and with 50% rat serum, as a control. The
resulting teratomas were transplanted under the kidney capsule. After 14
days grafts were processed for histology, serially sectioned and analysed
with light microscope.
Regardless of the presence of the serum epidermis with derivatives,
respiratory and gut epithelium developed well in grafts. Cartilage and
enchondral ossification were found. However, neural and adipose tissue,
glandular epithelia, skeletal and smooth muscles differentiation was statistically
lower in grafts precultivated in serum-free medium.
It can be concluded that although the differentiation of that embryo
cells in the serum-free conditions was restricted, cells retained to significant
extent their developmental potential, which could be revealed after in
vivo transplantation.
REFERENCES:
Cockroft DL. Int J Dev Biol 1997; 41: 127.
Škreb N. et al. J Embryol Exp Morph 1977; 42: 127.
Bulić-Jakuš F. et al. Cells Tissues Organs 2001; 169: 134.
<PROGRAM>
THE EFFECT OF LEVAMISOLE ON GUT MUCOSA OF WEANED PIGS
VACCINATED AGAINST COLIBACILLOSIS
Božić F1, Smolec O1, Lacković G2, Valpotić I1, Sabočanec R1
1Faculty of Veterinary Medicine & 2Faculty of Science, University of
Zagreb, Zagreb, Croatia
Apart from its anthelmintic activity in domestic food animals, levamisole
may be used as an adjuvant for preventive vaccines but information on its
potential adjuvant activity in hosts vaccinated against gastrointestinal
pathogens is generally lacking. In the present study we aimed to test whether
levamisole acts in weaned pigs vaccinated against colibacillosis by priming
the lymphocytes in the gut mucosa. Ten weaned piglets were used and allocated
into 2 equal groups. The experimental group was intramuscularly primed
with levamisole in immunostimulatory dose of 2.5 mg/kg given daily - in
3 consecutive days - and the control group received saline according to
the same schedule. Both groups were orally vaccinated with the vaccinal
Escherichia coli strain on day 0. Seven days later all pigs were infected
with the virulent E. coli strain and sacrificed on post-challenge day 6.
Histological examination of the gut mucosa did not reveal significant morphological
changes in the controls. However, in the vaccinated weaned pigs primed
by levamisole jejunal villi were shortened and their lamina propria was
infiltrated with mononuclear cells. In the latter pigs, jejunal submucosa
was oedematous but hyperplasia of the crypts was not generally observed.
The immunohistochemical in situ staining results showed that priming by
levamisole of the vaccinated weaned pigs selectively recruits and activates
T-cells in the villous epithelium as well as in the ileal Peyer’s patch,
a primary lymphoid organ generating B-lymphocytes. Our overall data
suggest that levamisole appeared to stimulate the effector sites of the
gut immune system in the vaccinated weaned pigs, serving as a critical
component in the establishment of protective immunity against enterotoxigenic
E. coli-induced clinical disease.
<PROGRAM>
DAILY MORTALITY AND DAILY AMBIENT POLLUTANT CONCENTRATIONS
IN ZAGREB AND LJUBLJANA 1995-1997.
Pavlović M1, Gale I2
1Institute for medical research and occupational health, Zagreb, 2Institute
of public health of the Republic of Slovenia, Ljubljana
The data on daily mortality and specific daily mortality - respiratory
and cardiovascular diseases (ICD 10) - were collected in Zagreb and Ljubljana
for the period of 1096 days – from 1995-1997. In the same period
(average daily) temperature, relative humidity and pressure were analyzed.
Additionally, we collected data on daily cases of flu in Zagreb. In the
same period daily average concentrations of nitrogen oxides (NO2), sulfur
dioxide (SO2) and black smoke (BS) were measured for both cities, due to
analysis according to APHEA II EC protocol.
The aim of this study was to analyze the relationship between daily
data on air-pollution and general and specific mortality in both cities.
In Zagreb, the correlation between daily NO2 and SO2 concentrations
and daily general mortality and cardiovascular mortality was statistically
significant. In the period from 1995-1997 standardized general mortality
(Ljubljana), cardiovascular mortality (Zagreb) and respiratory mortality
(Ljubljana) were statistically different, as well as daily concentrations
of NO2, SO2 and BS.
Results because of a vital data frequency for Zagreb and Ljubljana
indicate a longer follow-up.
<PROGRAM>
INFLUENCES ON HELICOBACTER SP. INFECTION OF DOGS IN
SLOVENIA
Gombač M, Černe M, Pogačnik M
University of Ljubljana, Veterinary Faculty, Ljubljana, Slovenia
Helicobacters have been identified and isolated from dogs, but their prevalence
and influence of different parameters on infection in different populations
of dogs are still unknown.
The aim of our study was to establish the prevalence of Helicobacter
infection in dogs in Slovenia and to evaluate the influence of epidemiological
parameters (gender, age, breed, nutrition, region and housing condition)
on infection.
In our research we included 213 randomly chosen dogs of 44 different
breeds from all parts of Slovenia, which died or had been euthanised. Both
genders were included in the age from 9 days to 15 years. They lived indoors
or outdoors and were still suckling or were fed either with commercially
prepared food or home made food.
Using Toluidin blue staining method on necropsy taken stomach tissue
samples we detected Helicobacter in 92,4% of dogs in all examined parts
of stomach i.e. fundus, corpus and antrum. Helicobacters were located in
mucus layer, covering the stomach epithelium, gastric pits and in gastric
gland’s lumen.
The determination of effects of gender, age, breed, nutrition, region
and housing condition on infection with Helicobacters was made calculating
the prevalence of infection and statistically evaluating the results.
We established that age and feeding regimen affect the infection, whereas
gender, breed, location and housing condition do not. The rate of infection
was 33,3% in dogs up to 2 months of age and 94,4% in dogs older than 2
months. The infection rate of dogs fed with home prepared food was 95,9%
and in dogs fed with commercially prepared food 91,5%. All suckling puppies
were uninfected.
REFERENCES:
Happonen I et al., J Vet Med A 1996;43:305
Hermanns W et al., J Comp Pathol 1995;112:307
Peyrol S et al., J Submicrosc Cytol Pathol 1998;30:425
<PROGRAM>
INCIDENCE OF SQUAMOUS METAPLASIA IN TRANSITIONAL
CELL CARCINOMA OF URINARY BLADDER
Baličević D1 , Novosel Irena2 , Pirkić A1
1Ljudevit Jurak University Department of Pathology, Sestre milosrdnice
University Hospital, Zagreb, Croatia
2Department of Pathology, «Dr Ivo Pedišić» County Hospital, Sisak, Croatia
Squamous metaplasia in transitional cell carcinoma of urinary bladder is
considered as an adverse prognostic factor. These patients
have weaker response on therapy and lower survival rate.
In our study we used pathohistological data of 1781 patients
operated for urinary bladder cancer in the Department of Urology
of Sestre milosrdnice University Hospital during the period from
1989 to 2000. The aim of our study was to determine the incidence
of squamous metaplasia in the bioptic material according to
histologic grade and growth pattern.
Squamous metaplasia was found in 5.7% of patients. According to growth
pattern, this phenomenon is more frequent in patients with solid growth
pattern. In papillary cancers, the higher incidence of squamous metaplasia
was determined in G1 and G2 histologic grade, while in the solid growth
pattern, the most of the cases with squamous metaplasia or over 80%
were of G3 histologic grade.
Muscle layer invasion was present in high percentage of both,
papillary and solid urothelial cancers with squamous metaplasia, which
imply the high malignant potential of cancers with foci of squamous metaplasia.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
MYOFIBROBLASTS IN INVASIVE AND IN SITU UROTHELIAL
CARCINOMA OF THE BLADDER
Zarubica Jelena, Gabelić Tereza, Bulimbašić Stela, Turčić Marijana, Trnski
D, Krušlin B
General Hospital Pula, Medical Faculty, University of Zagreb, Sveti duh
General Hospital, Ljudevit Jurak University Department of Pathology, Sestre
milosrdnice University Hospital, Zagreb, Croatia
INTRODUCTION
Invasive carcinomas are usually accompanied with stromal response in
which myofibroblasts may have an important role. Such a reaction
may not be present in in situ carcinomas that are in majority of cases
associated with lymphocytic reaction.
AIM
The aim of this study was to analyze the presence and quantity of myofibroblasts
in in situ and invasive urothelial carcinoma of the bladder.
PATIENTS AND METHODS
Urological pathology registry at the Ljudevit Jurak University Department
of Pathology was canvassed for patients with both, in situ and invasive
urothelial carcinoma. Relevant patient data including age, sex, tumor
grade and stage of the disease were analyzed. All cases were examined
by routine histology. In this study we analyzed the expression of alpha
smooth muscle actin and vimentin as imunohistochemical markers for myofibroblasts.
The intensity of reaction was graded semiquantitatively and expresssed
as (-) for negative, (+) for weak staining, (++) for moderate and (+++)
for strong staining.
RESULTS
In the period from 1998-2002 there were 1243 biopsies with the diagnosis
of urothelial carcinoma. Thirty-three biopsies with urothelial carcinoma
in situ were found. We identified 10 patients with both in situ and invasive
carcinoma. All of them were males ranging in age from 61-77 years (mean
age 70.2 years). Imunohistochemical analysis revealed that in cases
of invasive urothelial carcinoma reactive stromal cells are alpha smooth
muscle actins positive indicating the myofibroblast phenotype. In areas
with in situ carcinoma the intensity of SMA reaction was moderate in 3
cases, weak in 5 cases and negative in 2 cases and intensity of vimentin
reaction was strong in 2 cases, moderate in 7 cases and weak in 1 case.
In areas with invasive carcinoma the intensity of SMA reaction was strong
in 5 cases and mild in 5 cases and intensity of vimentin reaction was strong
in all of 10 cases.
CONCLUSION
We found that the expression of myofibroblastic markers was strong
in stroma of invasive carcinoma but absent or weak in in situ urothelial
carcinoma.
This finding may indicate a role of myofibroblasts in the stromal reaction
to invasion but may also be useful in diagnosis of in situ versus invasive
urothelial carcinoma. Further studies on larger groups of tumors are certainly
needed.
<PROGRAM>
MYOID CELL HYPERPLASIA IN AN INFERTILE PATIENT WITH
AZOOSPERMIA: A CASE REPORT
Ježek D1, Mužić V1, Krhen I2, Knežević N2, Podobnik P1, Mareković Z2
1Institute of Histology & Embryology, 2Urology Clinic, Medical School,
University of Zagreb, Zagreb, Croatia
AIM OF THE STUDY: In the testis, myoid (peritubular) cells are situated
within the lamina propria. These cells are thought to contract at intervals
of 12-15 min. in order to “push” sperms towards the epididymis. The aim
of the present study is to present a case of a male infertility with hyperplasia
of myoid cells.
MATERIALS AND METHODS: A 36-year old patient has suffered form azoospermia
due to the unilateral testicular tumour. One testicle (in which the tumour
was located) has been removed. An irradiation therapy was meant to
follow after the unilateral orchiectomy. A biopsy of the remaining
testicle was indicated in order to preserve sperms before the irradiation.
Small pieces of the testicular tissue obtained by the open testicular biopsy
were immediately fixed in 5.5% buffered glutaraldehyde followed by a postfixation
with 1% OsO4. After dehydration, tissue was embedded in Durcopan. Semithin
sections were performed by a Reichert ultramicrotome and stained with toluidine
blue.
RESULTS: Testicular biopsy revealed hyperplasia of myoid cells. Instead
of 5-7 layers of these cells, the lamina propria consisted of 7-14 layers
of peritubular cells. Seminiferous tubules displayed a “mixed atrophy”.
However, in some seminiferous tubules elongated spermatids and sperms were
found.
CONCLUSION: Hyperplasia of myoid cells could be the cause of the male
infertility and azoospermia.
<PROGRAM>
ADENOMATOID TUMOR OF FALLOPIAN TUBE
Labinac-Peteh Loredana1, Matković-Bilin M1, Pirkić A1, Končar M2
1Ljudevit Jurak University Department of Pathology, 2University Department
of Gynecology and Obstetrics, Sestre milosrdnice University Hospital, Zagreb,
Croatia
Although it is rare, adenomatoid tumor is the most frequent benign primary
tumor of Fallopian tube. In female genital tract, similar lesions appear
in the uterus and rarely in the ovary. Usually it has asymptomatic course
and represent incidental finding during a routine pathomorphological adnexal
examination. Previously it was confused with adenoma, leiomyoma or mesonephroid
tumor and cases of ovarian lymphangioma that were reported earlier probably
were adenomatoid tumor in fact. Today it is considered to be of mesothelial
origin based on microscopic, ultrastructural and immunohistochemical analysis.
On gross examination tumor has nodular pattern, its size is usually
one to 2 cm and it is yellow or whitish gray on the cut surface.
Greater tumors may displace the tubal lumen eccentrically and it may grow
in an infiltrating manner. On microscopic examination tumor is composed
of branching tubular or cystic spaces lined by epithelial-like cells that
are of mesothelial profile and surrounded by fibrovascular stroma.
51-years old nulipara was admitted to Department of Gynecology and
Obstetrics, Sestre milosrdnice University Hospital, because of the single
cyst of the left ovary, measuring 80 mm in diameter. Hysterectomy with
bilateral salpingoophorectomy was performed and cyst having smooth surface
and thin fibrous wall in the left ovary was found. Histologically it was
determinated as a simple cyst. There were no particular changes in the
right adnexa. One endometrial polyp of hyperplastic type, one mural leiomyoma
and adenomyosis were found in the uterus.
The left tube was 60 mm long and 5 mm wide containing well circumscribed
round yellowish nodule of medium firm consistency measuring 6:5 mm, which
was situated under serosa and partially in the muscular layer. Tubal lumen
was strongly displaced by the tumor.
Histologically tumor was composed of many irregular clefts or tubular
partially cystic dilated spaces covered mainly by flat to cubical epithelial-like
cells. There were no blood cells in described spaces. An anastomosing fibrovascular
partially hyalinized stromal network among tumor clefts and tubules was
shown.
Findings of performed immunohistochemical analysis revealed the mesothelial
immunophenotype of the tumor and were as follows: expressions of EMA (epithelial
membrane antigen) as well as of cytokeratin 8 (LMW) were negative and faint
mosaically positive reaction of cytokeratin MNF 116 (PAN) was observed.
Expressions of CD34 and of FVIII were negative in tumor cells, but positive
in the vascular stroma. Expression of vimentin was strongly positive and
intense equally in tumor cells as well as in the stroma.
Presented adenomatoid tumor of Fallopian tube represents incidental
finding and its practical importance is in differential diagnosis vs. tubal
adenocarcinoma. These tumors may also be the cause of extrauterine pregnancy.
<PROGRAM>
IS THERE A CORRELATION BETWEEN HER-2/NEU STATUS AND
GRADE OF THE PRIMARY BREAST CANCER?
Vučić Majda, Leniček Tanja, Čupić H, Tomas D, Krušlin B, Belicza M
Ljudevit Jurak University Department of Pathology, Sestre milosrdnice University
Hospital, Zagreb, Croatia
HER-2/neu amplification/overexpression is a marker of poor prognosis in
breast cancer. Patients whose tumors show overexpression of HER-2/neu have
shortened disease-free and overall survival. The aim of this study was
to determinate immunohistochemically HER-2/neu overexpression in 121 cases
of primary breast cancer. In addition HER-2/neu status is correlated with
hormone receptor status, grade and pTNM stage. The median age of both groups
of HER-2/neu negative and HER-2/neu positive patients was about 60 years.
In all the HER-2/neu groups (negative, 1+, 2+ and 3+) estrogen and progesterone
receptor were strongly positive in a high percentage of cases. Also in
both groups of HER-2/neu negative and HER-2/neu positive invasive ductal
carcinoma the most common grades were 2, but in HER-2/neu 3+ group, there
were also 30% of cases having grade 3. Our results support a correlation
between HER-2/neu overexpression and higher grade of breast cancer. The
two most common pTNM stages were T1N0MX and T2N1MX. HER-2/neu receptor
is an important therapeutic target and testing for HER-2/neu status is
now recommended as a part of the routine breast cancer diagnosis. The role
of new biomarkers, such as HER2/neu and clinical value of its determination
must be confirmed by prospective clinical studies.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
COLORECTAL CANCER TRENDS BY AGE AND SEX DISTRIBUTION,
ANATOMIC SUBSITE AND SURVIVAL (1989 - 2002)
Tomas D, Belicza M, Baličević D, Brezovečki-Biđin Dora, Ciglar D, Leniček
Tanja, Dokozić D, Dujmović A, Radotić Vladna, Gladić Vedrana, Krušlin B
Ljudevit Jurak University Department of Pathology, Sestre milosrdnice University
Hospital, Zagreb, Croatia
Recent epidemiological studies have suggested that the anatomic distribution
of colorectal carcinoma, especially in developed countries may have undergone
a distal to proximal shift over several decades, which has been attributed
variously to environmental and genetics factors as well as preventive measures.
The aim of the study was to compare some colorectal cancer features (age
and sex distribution, anatomic localization, and survival) during fourteen
years, in order to assess the possible changing trends of these disease
during the observed period and to compare observed data with our previous
study published in 1985 as well as with similar colorectal cancer features
reported worldwide. The mean age of patients with right-sided carcinomas
was slightly higher than in patients with left-sided colorectal carcinomas
(65.9 vs. 65.2). Sex distribution showed male predominance (57.3% vs. 42.7%).
Males and females had similar anatomic distribution. Recto-sigmoid was
the most common site (77.9%) followed by transverse colon cancers (6.8%),
ascending colon cancers (6.5%), cancers in cecum (6.2%) and descending
colon cancers (2.6%). In the last four years of the observed period
(1999 to 2002) the incidence of right-sided cancers was increased compared
to the previous period. Our study showed a continuing trend of the increased
incidence of right-sided carcinomas that is similar with reports from western
European countries and North America.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
TREND OF INCREASING AGE OF PATIENTS WITH INTRACRANIAL
TUMORS BY HISTOLOGICAL SUBTYPES DURING 14-YEAR PERIOD (1989-2002)
Rumboldt Tihana, Vučić Majda, Talan-Hranilović Jasna, Belicza M
Ljudevit Jurak University Department of Pathology, Sestre milosrdnice University
Hospital, Zagreb, Croatia
The aim of this study was to analyse distributions and proportions of intracranial
tumors from the data obtained in the Ljudevit Jurak University Department
of Pathology from 1989 to 2002. The data from our computer database were
analyzed according to the histological diagnosis, patient age (four groups),
and sex.
There were 2403 intracranial tumors, out of which 667 (27,8%) were
malignant gliomas, 593 (24.7%) meningiomas, 328 (13.6%) pituitary adenomas,
and 159 (6.6%) schwannomas. Metastatic intracranial tumors were diagnosed
in 326 (13.6%) patients. We found a statistically significant trends of
increasing incidence over time in the oldest age group (over 65 years of
age) for meningiomas in women, and for malignant gliomas for both sexes.
The observed distributions and proportions of intracranial tumors are
predominantly in accordance with the recent European, North American, and
Japanese reported studies.
* Full article will be published in the next issue of Acta clinica Croatica
http://www.acta-clinica.kbsm.hr
<PROGRAM>
MELANOCYTIC NAEVI (COMPOUND AND SPITZ) – CASE
REPORT
Bogoeva B, Kostadinova S, Ilievski B, Kocmanovska S
Institute of Pathology, Faculty of Medicine, Skopje, Macedonia
Benign melanocytic lesions comprise a wide spectrum of tumors including
melanocytic naevi. Some of them have the features important for the differential
diagnosis with malignant melanoma.
The aim of this study is to present specific variants of melanocytic
naevi: compound and Spitz naevus (benign juvenile melanoma).
MATERIAL AND METHODS: We analyzed 30 cases of benign melanocytic lesions.
In this series we found 3 compound and 1 Spitz naevus. Standard histopathological
stainings of paraffin sections were done. Immunohistochemical stainings
for S-100 protein and HMB-45 have been used.
CASE REPORT: Compound naevi were elevated, usually pigmented papules
and polyps with average diameter of 8 mm. Histologically, almost all dermal
elements were symmetrical and had homogenous growth patterns. There were
typically round or epithelioid melanocytes in the papillary or superficial
zones and fusiform melanocytes in the deeper portions. Cytoplasmic pigmentation
varied from lesion to lesion. Immunohistochemically, melanocytes showed
cytoplasmic and nuclear positivity for S-100 protein.
The Spitz naevus was discrete, well-demarcated, typically skin-colored
macule with a diameter of 8 mm from an 8-year-old girl. Histologically
it was a compound lesion. The epidermal portion had regular spaces composed
of spindle and epithelioid melanocytes. Solitary melanocytes were presented
in the higher portion of the epidermis (pagetoid spread). The dermal portion
was composed of nests of spindle and large epithelioid cells. There were
small groups and single melanocytes in the deeper spaces. The epithelioid
melanocytes had abundant eosinophilic cytoplasm without melanin, being
similar to myoblastoid cells. The nuclei were circular with small apparent
nucleoli. The spindle cells were usually more uniform and followed the
surface line of the adnexal epithelium. Mitotic figures were absent. Immunohistochemically
melanocytes were positive for S-100 protein and weakly positive for HMB-45.
CONCLUSION: Some melanocytic naevi may have features associated with
malignancy, which can make the histological distinction between them very
difficult. The use of valid differential diagnostic criteria greatly increases
the possibility of correct diagnosis.
REFERENCES: Barnhill RL. et al. Atypical Spitz Nevi/Tumors: Lack of
consensus for diagnosis, discrimination from melanoma and prediction of
outcome. Human Pathology 1999; 30:513-20.
Expert opinion. What criteria reliably distinguish melanoma from benign
melanocytic lesions? Histopathology 2000; 37:464-72.
Okun MR. Histological demarcation of lateral borders: an unsupportable
criterion for distinguishing malignant melanoma from Spitz naevus and compound
naevus. Histopathology 1998; 33:158-62.
Fletcher CDM. Diagnostic histopathology of tumors. Churchill Livingstone,
London. 1995. (Tumors of the Skin).
<PROGRAM>
SKIN METASTASIS OF HEAD AND NECK SQUAMOUS CELL CARCINOMA
Jakovina K, Đanić D, Jakovina Tratinčica, Fuštar-Preradović LJ
Department of Otorhinolaryngology and Cervicofacial Surgery, Department
of pathology and forensic medicine, General Hospital Slavonski Brod
Metastasis to skin sites from squamous cell carcinoma of the mucosa of
head and neck are very rare. Skin metastases may represent the first clinical
evidence of the malignant disease, loco-regional recurrence or distant
metastasis. Patients with skin metastases have very poor prognosis. Herein
we report three new cases and the first patient with multiple skin metastases
of the squamous cell carcinoma from the cervical part of the oesophagus
above and below the level of the diaphragm.
<PROGRAM>