P01

PRIMARY CUTANEOUS MENINGIOMA OF THE SCALP: CASE REPORT

 E. Lovrić, S. Gašparov

 Department of Pathology and Cytology, Merkur University
Hospital, Zagreb, Croatia

 Meningiomas arise from the meninges of the brain or spinal
cord. They are the most common tumors of the central nervous system
(CNS). Cutaneous meningiomas are rare tumors. Most of them occur in the
head and neck. Several theories exist to explain their histogenesis.
Lopez et al. have postulated classification of cutaneous
meningiomas based on simple clinical and pathological features. Three
different types are described. Type I have benign behavior and are
localized in the skin of the scalp, forehead and paravertebral areas.
Type II are meningiomas of the soft tissue with extension to the skin,
have a less favorable prognosis and  usually are situated in
periorbital, perineural and periauricular soft tissue. Type III are
meningiomas of the CNS with extension to the skin, with dismal
prognosis. We present a case of primary cutaneous meningioma in a
39-year-old man with a history of myasthenia gravis. Physical
examination revealed a subcutaneous, firm, painless lump of the left
parietal scalp. Computed tomography showed a homogeneous
well-delineated soft tissue mass, without bone or intracranial invasion
and communication between the tumor and subdural space. The mass was
excised. Grossly, the tumor measured 5 cm in greatest dimension, with a
white, firm cut surface. Microscopically, it was composed of solid
sheets and strands of meningothelial cells embedded in dense
collagenous tissue, without atypia, mitoses or necrosis. Psammoma
bodies were present. In our patient, the tumor was classified as a type
II. Immunohistochemical staining showed positive expression for
epithelial membrane antigen, vimentin and negative for smooth muscle
actin, cytokeratins (CKAE1/AE3, CK20), chromogranin, desmin, sarcomeric
actin, NSE, S100, CD68, GFAP, CD34, CD31 and HMB45. The patient did not
show any sign of recurrence one year after the procedure. Cutaneous
meningiomas are microscopically and immunohistochemically identical to
their meningeal counterparts. Extracranial cutaneous meningiomas should
be considered on differential diagnosis of unusual scalp lesions. The
diagnosis is based on histologic and immunohistologic examination
confirming the meningothelial origin of the neoplastic cell population.

P02

MOSAIC MORPHOLOGY OF LEYDIG CELLS IN INFERTILE PATIENTS WITH
NON-OBSTRUCTIVE AZOOSPERMIA

N. Knežević, I. Krhen, Ž. Kaštelan, D. Ježek

University Department of Urology, Zagreb University Hospital Center;
Department of Histology and Embryology, School of Medicine, University
of Zagreb, Zagreb, Croatia

One of the most severe forms of male infertility is non-obstructive
azoospermia (NOA). NOA is frequently characterized by heavy damage to
seminiferous tubules that has already been described in the literature.
Much less is known about changes of Leydig cells. The hypothesis of
this study is based on the assumption that Leydig cells in patients
with NOA are significantly different (damaged) from the same type of
cells in the control group. Therefore, the aim of the current survey
was to investigate Leydig cells in two groups (control and the group of
infertile men with NOA) by use of qualitative and quantitative
histologic methods and immunohistochemistry (the expression of
testosterone in situ). In addition, blood levels of
gonadotropins and testosterone were determined. Results of qualitative
histologic analysis showed a kind of a ‘mosaic’ picture of regular and
irregular Leydig cells in NOA cases. Quantitative histologic analysis
indicated a significantly lower number of testosterone-producing cells.
NOA patients also had significantly lower testis volume and status of
spermatogenesis when compared to controls. The results of the study
pointed out that the patients with NOA could suffer from a deficit of
androgens as well as from premature andropause.

P03

PRIMARY LOCALIZED CUTANEOUS NODULAR AMYLOIDOSIS: CASE REPORT

V. Puzović, A. Jakovčević, I. Ilić, K. Žarković

Clinical Department of Pathology and Cytology, Zagreb University
Hospital Center, Zagreb, Croatia

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare
form of primary localized cutaneous amyloidosis that presents as
yellowish or reddish waxy nodules on the extremities, face, trunk or
genitalia. It is characterized by amyloid deposits in the dermis that
are produced by local plasma cells. Histologic findings are
indistinguishable from those of primary systemic amyloidosis. A
75-year-old man presented to our ENT department with solitary tumor
located on the right nostril. Complete excision was made and the
material was referred for pathologic examination. The tumor was 1 cm in
diameter, grey reddish on the cutting surface. Microscopic examination
revealed deposits of eosinophilic amorphous material in the dermis.
Mild infiltrate of plasma cells (CD138 positive) could be seen in the
amorphous material and next to small blood vessels in the dermis. The
amorphous material stained positively with Congo red and demonstrated
green birefringence with polarizing microscopy. The immunohistochemical
imaging revealed the cytoplasm of infiltrating plasma cells to stain
with both anti-kappa and anti-lambda chains. Additional extensive
clinical and laboratory workup revealed no systemic involvement. The
patient’s medical history revealed no diseases and previous or current
medical treatments. The patient was treated surgically. The diagnosis
of PLCNA was made in February 2011, and no further information on this
case can be presented. In conclusion, immunohistochemical analysis
revealed polyclonality of the infiltrating plasma cells, which is
generally a less common characteristic of primary localized cutaneous
amyloidosis. However, extensive clinical and laboratory workup showed
no systemic involment of amyloidosis nor revealed any other acute or
chronic disease that could result in secondary amyloidosis. This is an
even rarer case of PLCNA with plasma cell polyclonality.

P04

EX VIVO DEVELOPMENT OF SKIN IN THE
RAT LIMB BUD

V. Mužić^1,2, F. Bulić-Jakuš¹, G. Jurić-Lekić³,
M. Himelreich³, Ž. Majić¹, N. Sinčić¹,
A. Katušić-Bojanac¹, M. Vlahović¹, Lj. Šerman¹

¹Department of Medical Biology, School of Medicine,
University of Zagreb; ²Department of Rehabilitation and
Orthopedic Devices, Zagreb University Hospital Center; ³Department
of Histology and Embryology, School of Medicine, University
of Zagreb, Zagreb, Croatia

The aim of this investigation was to explore the ex vivo
developmental potential of rat limb buds to develop skin in a
serum-supplemented organ culture system. Fisher rat fore- and hind-limb
buds were microsurgically removed under a dissecting microscope from
13- and 14-day-old embryos and placed on a lens paper supported by a
stainless steel grid, where they spent three days or two weeks at the
air-liquid interface. Eagle’s Minimum Essential Medium was supplemented
with 50% rat serum and changed every other day. Samples were processed
by routine histology, embedded in paraffin, and uninterrupted serial
sections were stained by HE, Masson trichrome or Azan stain. In
isolated limb bud, immature epithelium covering its surface was
present. During the 3-day culture period, stratified epithelium
developed. In limb buds that spent two weeks in culture, keratinization
of the stratified epithelium and fully developed stratum granulosum
could be discerned in some explants. It is concluded that limb bud
organ-culture provides an appropriate model to follow skin development ex
vivo, which might be of interest for investigation of
pharmacological compounds in skin development.

P05

INFLUENCE OF THE ANTIOXIDANT PBN AND TERATOGEN 5-AZACYTIDINE
ON RAT EMBRYO DEVELOPMENT EX VIVO

N. Sobočan^{1, 2}, N. Sinčić¹, Ž. Majić¹,
R. Beuc³, A. Katušić¹, M. Vlahović¹,
Lj. Šerman¹, G. Jurić-Lekić⁴, F. Bulić-Jakuš¹

¹Department of Medical Biology, School of Medicine,
University of Zagreb; ²University Department of Medicine,
Merkur University Hospital; ³Institute of Physics; ⁴Department
of Histology and Embryology, School of Medicine, University of Zagreb,
Zagreb, Croatia

The influence of the antioxidant PBN (N-tert-butyl-a-phenylnitrone)
and the DNA demethylating agent 5-azacytidine (5-azaC) on the most
critical stage of mammalian development (gastrulation) was investigated
ex vivo. Microsurgically isolated 9.5-day-old Fisher rat
embryos were cultivated for two weeks at the air-liquid surface in
Eagle’s MEM with 5-azacytidine (5 μM) and/or PBN (22.6 ֍) and controls
in MEM or in MEM with 50% rat serum. Explant diameters were measured by
an ocular micrometer at the beginning of culture and then every other
day. Growth areas were determined in arbitrary units and data
normalized to those obtained in MEM. 5-azaC impaired growth in
comparison to MEM by approximately 40%. PBN applied with 5-azaC
ameliorated growth of 5-azaC treated explants by approximately 25%, and
in comparison to control grown in MEM by 25%, although it was less than
in the medium with serum. Ex vivo in a chemically defined
proteinless medium, it was possible to discover an ameliorating
influence of PBN alone upon the embryo development, which was not
possible before in the complicated in vivo system during
gestation. These results are of importance for new therapeutic
strategies in human medicine using antioxidants and epigenetic drugs.

P06

MESENCHYMAL CHONDROSARCOMA OF THE SUBOCCIPITAL REGION: CASE
REPORT

I. Košuta, A. Jakovčević, Z. Hutinec, K. Potočki, M. Rožanković

Department of Pathology, School of Medicine, University of Zagreb,
Zagreb, Croatia

Mesenchymal chondrosarcoma is a rare malignancy, which differs from
conventional chondrosarcoma by both specific morphology and clinical
features. The rare mesenchymal variant is characterized by a biphasic
histologic pattern of small undifferentiated round cells intermixed
with islands of malignant cartilage differentiation. Areas resembling a
vascular tumor such as hemangiopericytoma may also be present. It
typically occurs in young adults, rarely after 40 years of age, with no
sex predilection. Mesenchymal chondrosarcoma is a particularly
aggressive neoplasm with a strong tendency toward late local and
metastatic recurrences, leading to 10-year survival rates below 50%. A
45-year-old female presented with a history of right-sided hearing
impairment and headache in the right suboccipital region. Apart from
the hearing loss, neurologic examination revealed no other deficits.
Multislice computed tomography identified the presence of a poorly
vascularized tumor of the suboccipital region. The tumor was surgically
resected in toto and referred for pathologic analysis.
Histology revealed tumorous tissue consisting of small uniform
mesenchymal cells with hyperchromatic nuclei and sparse cytoplasm. Some
tumor regions showed hemangiopericytoma-like features. Areas of
chondroid differentiation with focal ossification were noted between
the sheets of small round cells. The cells showed a low mitotic count,
without pathologic mitosis. Immunohistochemical staining revealed CD99,
BCL2 and vimentin positivity. The diagnosis of mesenchymal
chondrosarcoma was made. Because of its specific biological and
clinical behavior, it is important to differentiate mesenchymal
chondrosarcoma histologically from similar lesions such as
hemangiopericytoma, Ewing’s sarcoma, primitive neuroectodermal tumor,
and other subtypes of chondrosarcoma. 

P07

TRANSITION OF EPIGLOTTAL EPITHELIUM DURING HUMAN
DEVELOPMENT     

M. Himelreich¹, G. Jurić-Lekić¹, F. Bulić-Jakuš²,
A. Katušić²

¹Department of Histology and Embryology, ²Department
of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia

Our previous results have shown that human epiglottal epithelium
changes during development, from single-layered squamous epithelium in
the 6-week-old embryo to two-layered cuboidal epithelium in the early
8-week-old embryo; in the newborn, pseudostratified epithelium with
goblet cells predominates and after the air-flow is established,
stratified squamous epithelium predominates. Seven-week-old and
9-week-old embryo epiglottal epithelium was now analyzed in more detail
and compared. Embryos from the celloidin collection of human embryos
belonging to the Archive of the Department of Histology and Embryology
were stained by HE, Azan, Masson trichrome stain, Verhoeff iron
hematoxylin and PAF-Halmi. Epiglottal epithelia were investigated by
light microscopy. In the 6-week-old embryo, epiglottal swelling was
covered by a single layer of cuboidal cells. In the 7-week-old embryo,
two-layered cuboidal epithelium was discovered. In 9-week-old fetus,
epiglottal epithelium was multilayered columnar without cilia and
goblet cells. It has now been confirmed that single-layered
epiglottal epithelium has changed to the two-layered epithelium already
in the 7-week-old embryo. Developmental studies like this one might be
of importance for tissue engineering purposes.

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P08

DETECTION OF CLONAL T-CELL RECEPTOR GAMMA CHAIN GENE
REARRANGEMENTS IN SUSPECTED CUTANEOUS T CELL LYMPHOMAS

M. Katunarić, I. Hadžisejdić, G. Zamolo, N. Jonjić, B. Grahovac

Department of Pathology, School of Medicine, University of Rijeka,
Rijeka, Croatia

Molecular analysis of rearranged T cell receptor (TCR) represents an
important diagnostic tool in diagnosing cutaneous T cell lymphomas. We
report here three cases suspected of cutaneous T cell lymphomas, for
which dermatopathologists were unable to give final diagnosis without
the use of T cell clonality analysis. Working diagnoses in study
patients were mycosis fungoides, cutaneous lymphoma and pseudolymphoma.
DNA was extracted by NucleoSpin Tissue XS kit (Macherey-Nagel, Germany)
designed for extra small amount of material (less than 100 cells), and
suspected cells were selected by laser-microdissection from microscopic
slides of paraffin embedded biopsy materials. Using modified BIOMED
multiplex nested PCR and primers specific for gamma chain of the T cell
receptor (TCR-γ), we were able to amplify the specific gene region. The
PCR products of 65 to 95 bp in length, labeled with 6-FAM flourescent
dye, were separated by capillary electrophoresis on the ABI Prism 310
Genetic Analyzer; results were analyzed by use of GeneMapper software
(Appl. Biosystems). In all experiments, positive and negative controls
were included. Multiplex nested PCR analysis was performed in
triplicates. Specific amplification products of 65 to 95 bp were
obtained in all experiments, and separation and analysis of amplicons
revealed polyclonal rearrangement patterns in all three cases. The
results obtained showed absence of clonal rearrangement and indicated
reactive proliferation. In conclusion, capillary electrophoresis
sensitivity reached down to1 bp, so we were able to easily distinguish
different clones. The multiplex nested PCR method and capillary
electrophoresis proved to be a highly sensitive screening tool for
clonal TCR-γ chain gene rearrangements.

P09

ROE DEER (CAPREOLUS CAPREOLUS) WARTS – FIBROMAS,
PAPILLOMAS OR FIBROPAPILLOMAS

V. Farkaš, D. Konjević, Ž. Grabarević, Z. Janicki, A. Slavica, R.
Sabočanec

Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia

Roe deer fibropapillomatosis is mainly a benign neoplastic disease
caused by papillomaviruses. Previously, based on the gross appearance
of the lesions, such skin tumors were usually classified by
practitioners as fibromas and papillomas. On the other hand, a part of
the literature describes these lesions as fibropapillomas. The aim of
the study was to determine histologic characteristics of the lesions in
roe deer in order to improve the knowledge of the appearance of
papillomavirus induced neoplastic lesions in roe deer in Croatia. As
part of the surveillance of wildlife diseases, three roe deer with few
clearly visible skin lesions were presented to the Faculty of
Veterinary Medicine. Gross examination was taken on the field, while
samples of the lesions were alcohol fixed and submitted for
histopathologic analysis (routine HE staining). Grossly, lesions were
ranging in size from 1.5 to 19 cm. Some of these lesions were covered
with intact skin, while in others the surface was hyperkeratotic and
hyperpigmented with several ulcerations. Histopathologic analysis
revealed elements that are characteristic of both fibromas and
papillomas. Roe deer fibropapillomatosis is present in Croatia as an
endemic disease, similarly to other European countries. It is a benign,
in wild animals incurable disease, which depending on the location of
the lesions can, with duration of the disease, cause severe or minor
effects on the overall health and survival rate of the affected
individual. From the results obtained, it is concluded that the
majority of analyzed lesions contain both fibromatous and papillomatous
characteristics, and therefore we find the term fibropapillomatosis
suitable to describe this condition. Systematic survey and detailed
examination of papillomavirus induced neoplasms is necessary for better
understanding of its epidemiology.

P10

MORPHOLOGICAL FEATURES OF PLAQUE LESION OF MYCOSIS FUNGOIDES

R. Taradi¹, I. Ilić², R. Čeović³,
S. Dotlić²

¹Department of Cytology, Dr. Josip Benčević General
Hospital, Slavonski Brod; ²Department of Pathology, ³University
Department of Dermatology and Venereology, Zagreb University Hospital
Center, Zagreb, Croatia

The aim of the study was to show the frequency of lichenoid dermal
infiltrate, Pautrier’s microabscesses, sentinel lymphocytes, atypia and
antigen loss of T cells in mycosis fungoides (MF). The diagnosis of
early patch lesion of MF is difficult because of the lack of
characteristic morphological features. This study showed that even in
plaque lesions, not all MF features are always present. In this
retrospective study, we reviewed 54 skin biopsies from patients with
plaque stage MF diagnosed and treated at Department of Pathology and
Cytology and Department of Dermatology and Venereology, Zagreb
University Hospital Center from January 2006 to December 2010. There
were 25 females and 29 males, median age 48 (range 38-77) years. The
following criteria of MF were evaluated: presence of lichenoid
infiltrate, Pautrier’s microabscesses and sentinel lymphocytes, atypia
and surface antigen loss of T cells. Lichenoid infiltrate and atypia of
T cells with intermediate size lymphocytes and irregular or cerebriform
nuclei were found in all 54 study cases. Pautrier’s microabscesses were
found in 33 (61.1%), sentinel lymphocytes in 32 (59.3%) and antigen
loss in 38 (70.4%) cases. On antigen loss analysis, the most frequent
feature was loss of CD7 (36/54; 66.6%), followed in the order of
frequency by CD2 (6/54; 11.1 %), CD5 (8/54; 14.8%) and CD3 (2/54;
3.7%). There were 25 cases with the loss of only one surface antigen,
10 cases with the loss of two surface antigens and two cases with the
loss of three surface antigens. Two of our cases were found to be
double positive for both CD4 and CD8. In conclusion, since the
morphological criteria are not invariably present in all biopsies of MF
cases, it is crucial to know the clinical appearance of the lesion but
also the information about previous treatment.

P11

METASTATIC GRANULOSA CELL TUMOR OF THE SPLEEN: CASE REPORT

M. Ulamec¹, I. Ledinsky², D. Tomas¹,
B. Krušlin¹

¹Ljudevit Jurak University Department of Pathology, ²University
Department of Surgery, Sestre milosrdnice University Hospital Center,
Zagreb, Croatia

Granulosa cell tumor is a rare and uncommon stromal cell tumor of
the ovary, considered to be of low grade malignancy with an indolent
clinical course. The 10-year survival is higher than 90%. These tumors
are known to manifest metastatic disease years after treatment of the
primary tumor. A 64-year-old female with left upper quadrant abdominal
pain underwent magnetic resonance, which revealed a tumorous process of
the spleen. Splenectomy was performed and the material was referred for
histopathologic analysis. Pathologic examination revealed a tumor
measuring up to 8 cm, with relatively sharp demarcation. The tumor was
grey to brown in color, with necrotic areas and hemorrhage.
Microscopically, it was composed of solid sheets, nests and papillary
formations lined with atypical cells. Anastomotic vascular-like spaces
were also found, lined with relatively uniform atypical cells. Mitotic
rate was high (20 mitosis/10HPF). The tumor occupied almost the entire
spleen. Extensive histochemical (PAS, Giemsa, Gomori) and
immunohistochemical analyses (vimentin, CD31, CD34, FVIII, CD68, CK7,
CK20, CD3, CD20, CD30, bcl-6, Ki-67, HMB-45) were done. Tumor cells
showed positive reaction to vimentin and proliferative activity defined
with Ki-67 was up to 40%. Metastatic tumor was suspected. Retrospective
history data revealed a granulosa cell tumor of the ovary 15 years
before. Immunohistochemical analysis with inhibin and calretinin was
positive. It was diagnosed as a granulosa cell tumor metastatic to the
spleen. Metastases of granulosa cell tumor are extremely rare; they are
usually local recurrences or foci of peritoneal spread and occur in
25%-30% of cases. To our knowledge, this is the fourth case of a
metastatic granulosa cell tumor in the spleen described in the English
literature.

 

P12

BILATERAL SYNCHRONOUS BENIGN AND MALIGNANT KIDNEY TUMORS:
CASE REPORT

A. Mustafa-Guguli¹, B. Spajić², H. Kokić²,
B. Krušlin¹

¹Ljudevit Jurak University Department of Pathology, ²University
Department of Urology, Sestre milosrdnice University Hospital Center,
Zagreb, Croatia

Angiomyolipomas are renal mesenchymal neoplasms with a variable
mixture of fat, muscle and blood vessels, accounting for less than 1%
of all kidney tumors. They are very common in tuberous sclerosis, while
renal cell carcinomas are most common accounting for 85% of all kidney
tumors with several different macroscopic and microscopic appearances.
We present a case of bilateral renal cell carcinomas associated with
angiomyolipoma and renomedullary interstitial cell tumor. A 63-year-old
woman presented with bilateral kidney tumors detected incidentally on
routine CT scan with no prior symptoms. Bilateral partial nephrectomy
was done and biopsy specimens were referred for histopathology.
Histopathologic analysis revealed a chromophobe renal cell carcinoma in
the specimen marked as left kidney tumor. In the specimen marked as
right kidney tumor, clear-cell renal cell carcinoma and a small
angiomyolipoma were detected, while a small renomedullary interstitial
cell tumor was found in the third specimen marked as right-sided
resection surface. Synchronous occurrence of benign and malignant
kidney tumors is very rare. There are only few studies of the
association of angiomyolipoma and adult renal-cell neoplasia. In
patients with or without tuberous sclerosis, conventional clear-cell
carcinoma accounted for approximately two-thirds, while oncocytoma
accounted for 8%-25% of the tumors described. Papillary neoplasia,
chromophobe, and collecting-duct renal-cell carcinoma were only found
in sporadic cases, which also holds for angiomyolipoma, which was
almost always an incidental finding.

P13

ADENOID CYSTIC CARCINOMA METASTATIC TO THE KIDNEY  

M. Magazin¹, I. Tomašković², D. Trnski²,
B. Krušlin³

¹Department of Pathology and Cytology, Sveti Duh
University Hospital; ²University Department of Urology, ³Ljudevit
Jurak University Department of Pathology, Sestre milosrdnice University
Hospital Center, Zagreb, Croatia

Adenoid cystic carcinoma (ACC) is an uncommon form of malignant
neoplasm that arises within secretory glands, most commonly major and
minor salivary glands of the head and neck. It is a slow-growing but
aggressive tumor. Kidney metastases are very rare and here we report
such a case. A 76-year-old female patient presented with hematuria and
flank pain. CT scan revealed a tumor mass on the right kidney. The
patient was treated with right radical nephrectomy. Macroscopically, a
well-circumscribed, firm, gray mass measuring up to 7.8 cm was found on
one pole of the kidney. The tumor was composed of cribriform, tubular
and solid formations of atypical epithelial cells with dark compact
angular nuclei and frequent mitotic figures. Tumor cells showed
positive immunohistochemical reaction to CKHMW and EMA, and negative to
synaptophysin, CD10, CD15, CK8 and RCC. Retrospective history data
showed ACC of the lacrimal gland with metastasis to the lung, which had
been surgically treated 14 years before. Based on clinical data,
histologic appearance and immunohistochemical analysis, the suggested
diagnosis was metastatic ACC to the kidney. In conclusion, adenoid
cystic carcinoma, formerly known as cylindroma, is a relatively
uncommon but highly malignant neoplasm with a remarkable capacity for
recurrence. Besides salivary glands, the tumor can arise in the
trachea, lacrimal gland, breast, skin and vulva. The tumor is
slow-growing but aggressive; 50% metastasize, often silently to the
lung or bone; recurrences are frequent and often late. To our
knowledge, in the English speaking area (Pub Med), 7 cases of ACC
metastatic to the kidney have been described to date.

P14

SAMPUS OR MELANOMA IN SITU IN THE SCROTAL AREA

M. Perković¹, M. Ulamec², I. Grubišić³,
D. Tomas², M. Vučić²

¹Department of Pathology and Forensic Pathology, Pula
General Hospital, Pula; ²Ljudevit Jurak University
Department of Pathology, ³University Department
of Urology, Sestre milosrdnice University Hospital Center, Zagreb,
Croatia

Superficial atypical melanocytic proliferations of uncertain
significance (SAMPUS) is a descriptive term for a heterogeneous group
of melanocytic tumors that exhibit some features indicative of possible
malignancy, but in number or degree insufficient to justify a malignant
diagnosis. Tumors involving the scrotum are rare and primary malignant
melanoma is the rarest of these lesions. To our knowledge, only 17
cases have been described since 1949 in the English speaking area. We
present a case of a 59-year-old male patient diagnosed with SAMPUS in
2009, after excision of a scrotal skin lesion. Two years later, he
presented with a brown pigmented area near the postoperative scar,
measuring 0.6 cm in diameter. Histology showed partially thinned
epidermis on the surface. In the basal layers of the epidermis,
continuous lentiginous proliferation of single atypical melanocytes
with nest formation and pagetoid spread to the upper layers of the
epidermis was found. The basal membrane was preserved and continuous.
Among the epidermal melanocytic nests, two mitoses were found. In the
dermis, there were band-like dense lymphocytic infiltrates and
pigmentophages, but no melanocytes. The lesion was diagnosed as
melanoma in situ. Although most histologic diagnoses are made
with relative ease, there is a subset of cases in which diagnosis is
difficult or even impossible. The SAMPUS category includes certain
atypical junctional melanocytic proliferations and proliferations in
both the epidermis and papillary dermis that are not accompanied by
intradermal tumorigenic architecture or mitotic activity. The prognosis
for cure of these lesions as for melanoma in situ is
excellent, if they are completely excised.

P15

PRIMARY RENAL ANGIOSARCOMA

P. Sesar¹, M. Ulamec², S. Šoša³, D.
Trnski³, D. Tomas²

¹Department of Pathology and Forensic Pathology, Dr Ivo
Pedišić General Hospital, Sisak; ²Ljudevit Jurak University
Department of Pathology, ³University Department of Urology,
Sestre milosrdnice University Hospital Center, Zagreb, Croatia

Angiosarcomas are localized or multicentric tumors with various
grades of differentiation that originate in the endothelium of the
blood and lymphatic vessels. Angiosarcoma is an extremely aggressive
malignant neoplasm with a 6-month median survival. Primary occurrence
in the kidney is rare, with 24 cases described to date. We present a
case of primary renal angiosarcoma in a 65-year-old male patient. It
was an incidental CT scan finding that showed 3 tumors in the left
kidney. Nephrectomy with ureterectomy was performed. Macroscopic
examination revealed 3 nodular hemorrhagic yellowish tumors located
subcapsularly in the central area of the left kidney, measuring 0.5 to
4.5 cm in diameter. Microscopically, it was a malignant neoplasm
composed of large sheets, cords and small anastomosing vascular spaces,
covered by pleomorphic epithelioid and spindle-shaped cells with
voluminous and hyperchromatic irregular nuclei. Mitotic figures were
frequent. Immunohistochemically, neoplastic cells showed strong
positivity for C31, C34 and factor VIII. In conclusion, primary renal
angiosarcomas are extremely rare aggressive tumors of endothelial
cells. About 24 cases of this tumor have been documented. The mean
patient age is 58 years. The etiology is unknown. They usually occur
near renal capsule. Clinical symptoms are flank pain and hematuria.
Differential diagnosis includes retroperitoneal hematoma and
hemorrhagic renal tumors. The prognosis of renal angiosarcoma is poor,
with rapid development of hematogenous metastasis.

P16

CANINE ATOPIC DERMATITIS: THE COMPARATIVE APPROACH

I. Šimić, M. Tadić, N. Lemo

Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia

It is well known that dogs are affected with a natural homolog of
human atopic dermatitis. The aim is to describe canine atopic
dermatitis (CAD) and its points of clinical interests for veterinary
and human dermatologists. Relevant articles were identified from three
databases: MEDLINE (since 1966), ISI (Thomson) Science Citation Index
Expanded (since 1945) and CAB Abstracts (since 1975). CAD is a
genetically predisposed inflammatory and pruritic allergic skin disease
with characteristic clinical features associated with IgE antibodies
most commonly directed against environmental allergens. It is the most
common allergic skin disease of the dog. Pruritus is the essential
clinical feature, along with normal appearing skin or skin with
erythema, small erythematous papular dermatitis, or erythematous
macules. In dogs, pruritus is considered a hallmark of atopic
dermatitis and is emphasized by feet licking and nose or head rubbing.
Recently, new diagnostic criteria for CAD have been proposed by Favrot et
al., including a set of 8 clinical features. Methods such as
intradermal testing (ASIT) and allergen-specific IgE serology serve as
orientation for clinicians in the diagnostic and therapeutic approach.
Treatment of acute flares of CAD includes identification and removal of
the allergenic causes of flares, antimicrobial therapy, improvement of
skin and coat hygiene, and care and reduction of pruritus and skin
lesions with pharmacological agents. Human atopic dermatitis is a
common, multifactorial, chronic and often relapsing inflammatory skin
disease. In the etiopathogenesis of human atopic dermatitis, there are
well known interactions among genetic, environmental, skin barrier,
immune factors, and stress. Current treatment of severe atopic
dermatitis consists almost exclusively of topical and systemic
corticosteroids. Disease management involves skin hydration through
daily baths and intensive emollient therapy, avoidance of allergens,
and in some cases use of anti-histamines to alleviate pruritus.

[Back
to Awards]

P17

CUTANEOUS OSTEOMAS IN A SEVEN-MONTH-OLD CHILD

P. Radulović¹, I. Pavić¹, L. Kotrulja²,
S. Ožanić-Bulić², I. Dediol²

¹Ljudevit Jurak University Department of Pathology, ²University
Department of Dermatovenereology, Sestre milosrdnice University
Hospital Center, Zagreb, Croatia

Cutaneous osteoma (CO) is a rare entity with only scattered cases
reported in the literature. Cutaneous ossifications are divided into
primary and secondary CO. Secondary CO accounts for 85% of cutaneous
ossifications and develops within preexisting neoplastic or
inflammatory skin lesions. Primary CO accounts for about 15% of
cutaneous ossifications and develops on its own. A 7-month-old child,
born as second trigeminus by cesarean section after IVF pregnancy,
presented with incidental finding of multiple firm, nontender,
subcutaneous pale-brownish papules scattered on the skin of the lower
abdomen, arms and legs, measuring up to 7 mm. Changes were unremarkable
in neonatal period. Changes became visible by the end of the fourth
month of life. History specified no trauma, inflammatory changes, nevi,
dermatologic or other significant medical conditions. Family history
for CO or other associated diseases was negative. First punch biopsy (3
mm) obtained from the lower abdomen showed unremarkable epidermis but
the dermis underneath showed well circumscribed spicules of mature
lamellar bone entrapped mature adipose tissue without hematopoietic
elements. Pathologist indicated CO. One month later, second 2-mm punch
biopsy obtained from the left lower extremity confirmed CO indicated in
first biopsy. Laboratory revealed elevated thyrotropin (TSH) up to 8.79
mIU/L (reference range: 0.4-4.0 mIU/L) and parathyroid
hormone (PTH) up to 88 pg/mL (reference range: 15-65 pg/mL). Other
tests regarding thyroid hormone, calcium and phosphorous levels were
unremarkable. Final pathology report of CO found in biopsies suggested
three possibilities: Albright’s hereditary osteodystrophy (AHO),
Gardner syndrome and progressive osseous heteroplasia. CO as primary
form can occur de novo in the form of multiple miliary
osteomas, widespread osteoma or plaque-like presenting as a single
lesion, both found in neonatal period. All previously mentioned osteoma
changes have a good prognosis. Unlike previously mentioned states with
CO, AHO-psuedohypoparathyroidism type 1a has poor long term prognosis,
where besides CO it manifests with obesity, developmental disability,
short stature, round face and ganglia calcification. In our case,
laboratory findings supported by histology suggested the AHO syndrome,
although the phenotype-associated symptoms of disease were not present
yet in infancy. Further follow up is needed. The initially mild
cutaneous manifestations may herald a more progressive
ossification disorder, as it could be associated with
multiple endocrine hormone resistance enhanced with neurobehavioral
and developmental problems. Treatment of the present
underlying disease is the first step. If the patient is symptomatic,
surgical excision including punch excisions is currently the treatment
of choice for CO.

P18

COMBINED CARCINOID AND LOW-GRADE MUCINOUS NEOPLASM OF
APPENDIX: CASE REPORT

T. Džombeta¹, C. Lež², F. Szerda³,
B. Krušlin^1,4

¹Department of Pathology, School of Medicine, University
of Zagreb; ²Department of Pathology, ³Department
of Surgery, Zabok General Hospital, Zabok; ⁴Ljudevit Jurak
Department of Pathology, Sestre milosrdnice University Hospital Center,
Zagreb, Croatia

Mucinous tumors and carcinoids are the most common appendiceal
neoplasms, but overall, they account for approximately 1% of all
pathologic conditions in appendicectomy specimens. They usually appear
as an incidental finding in appendices removed due to suspected acute
inflammation. Synchronous occurrence of these neoplasms is extremely
rare and only a few cases have been reported in the literature to date.
We present a case of combined low-grade appendiceal mucinous neoplasm
and carcinoid in a 25-year-old female patient. The patient was admitted
to the hospital due to abdominal pain. Ultrasonography showed a tumor
mass near the right ovary. Diagnostic laparoscopy was performed and
enlarged appendix, but no adnexal abnormalities, was found. The
appendix was removed and referred for pathology. Grossly, the appendix
was enlarged and filled with mucinous material. Histologically, it
contained two distinct tumor areas. The mucinous component, confined to
mucosa and submucosa, was composed of mucinous-type tall columnar
epithelium, which showed positive immunohistochemical reaction to CK.
The carcinoid component, composed of nests of uniform, chromogranin
positive tumor cells, which showed up to 4 mitoses on 10 high power
fields, infiltrated the whole thickness of appendiceal wall and
extended to periappendiceal fat tissue. In conclusion, the incidence of
neoplasms in appendicectomy specimens varies from 1% to 10% according
to different studies. Hence, it is important to thoroughly examine the
potentially inflamed appendices, particularly when there is no sign of
acute pathologic condition.

P19

ATYPICAL SYMPLASTIC GLOMUS TUMOR OF THE LEFT HALLUX

D. Janković¹, T. Džombeta², J. Kovjanić³
, B. Krušlin^2,4

¹Department of Pathology, Dr Ivo Pedišić General
Hospital, Sisak; ²Department of Pathology, School of
Medicine, University of Zagreb; ³Department of Surgery, Dr
Ivo Pedišić General Hospital, Sisak; ⁴Ljudevit Jurak
Department of Pathology, Sestre milosrdnice University Hospital Center,
Zagreb, Croatia

Glomus tumors are benign perivascular tumors, which result from
hyperplasia of normal glomus body, a specialized form of arteriovenous
anastomosis that regulates heat. Occasionally, glomus tumors may
exhibit some atypical histologic features and rarely can even
metastasize. Here, we report a case of a symplastic glomus tumor, a
variant of histologically atypical, but still benign glomus tumor. An
81-year-old male patient was surgically treated due to a tumor
of his left great toe. Macroscopically, the tumor was
well-circumscribed, measured 4x3x2.5 cm and was located in the
subcutis. Histologically, it was encapsulated, composed of solid sheets
of cells separated by vessels of a varying size. The neoplastic cells
showed pronounced nuclear pleomorphism, hyperchromasia and occasional
intranuclear inclusions. Mitotic rate was sparse, up to 2 mitoses on 50
high power fields, but proliferative rate measured
immunohistochemically was extraordinarily high, about 25%. Tumor cells
were immunohistochemically diffusely positive for SMA and desmin.
According to classification of glomus tumors proposed by Folpe and
coworkers, we declared this tumor as symplastic, considering marked
cellular atypia, but the lack of other criteria that could point to its
possible malignant behavior. In conclusion, glomus tumors may rarely
present with atypical features, but in the absence of other
criteria such as large size, deep location, high mitotic index or
atypical mitotic activity, they should be considered merely as a
consequence of degenerative change and not a sign of malignancy.

P20

CLINICAL PRESENTATION OF A PATIENT WITH PALMOPLANTAR
PUSTULAR PSORIASIS: CASE REPORT

V. Bulat¹, I. Borovečki¹, M. Šitum¹,
I. Dediol¹, I. Pavić², I. Ljubičić¹

¹University Department of Dermatology and Venereology, ²
Ljudevit Jurak University Department of Pathology, Sestre
milosrdnice University Hospital Center, Zagreb, Croatia

Palmoplantar pustular psoriasis is a rare, chronic dermatosis
characterized by sterile pustules that develop within areas of erythema
and scaling on the palms, soles or both. The minority of patients have
chronic plaque psoriasis elsewhere. Focal infections and stress have
been reported as triggering factors. Smoking aggravates the disease and
negatively reflects on treatment success. The disorder occurs more
commonly during the fourth decade of life. There is a slight female
predilection. In most patients, lesions are asymptomatic; however,
intermittent pruritus, and burning have been described. The histologic
hallmark of palmoplantar pustular psoriasis is large accumulation of
neutrophils within the stratum spinosum, known as spongiform pustule of
Kogoj. Palmoplantar pustular psoriasis must be differentiated from
other dermatoses, which are characterized by intraepidermal
neutrophilic pustules including impetigo, superficial candidiasis,
dermatophyte infection, superficial folliculitis, dyshidrotic eczema,
and pustular drug eruption. Therefore, biopsy and histologic analysis
is recommended in order to confirm the diagnosis. The aim of this case
report is to present our patient suffering from palmoplantar pustular
psoriasis, and to evaluate clinical presentation, diagnostic and
therapeutic difficulties in this rare condition. A 38-year-old female
patient was admitted to our hospital due to numerous sterile pustules
on well-defined erythematous plaques with desquamation on the palms and
soles three months before. The pustules were large (about five mm in
diameter), and several stages of evolution of pustules were present
concurrently. The patient complained of occasional pruritus and
burning. Chronic plaque psoriasis on elbows was confirmed seven years
before, for which she received topical corticosteroids. Focal
infections were not found on clinical examination. It is important to
note that the patient’s smoking habit aggravated the condition.
Palmoplantar pustular psoriasis was diagnosed based on clinical picture
and histopathologic appearance. Histopathologic analysis of skin lesion
of the sole showed epidermal acanthosis with parakeratosis and large
accumulation of neutrophils within the stratum spinosum, known as
spongiform pustule of Kogoj. In the dermis, the capillaries were
elongated and tortuous. PUVA cream phototherapy was administered five
times weekly for four weeks of her hospital stay. Topical
corticosteroids were applied under hydrocolloid occlusion, which
significantly enhanced regression of the skin lesions. Most patients
with palmoplantar pustular psoriasis have an underlying disease that
can be identified, but in our case the onset, fluctuations and duration
of the disease were not associated with focal infections. It is
important to note that smoking aggravates the disease and has
unfavorable impact on treatment success. PUVA cream phototherapy and
topical corticosteroids result in dramatic improvement of the disease
with significant psychosocial benefit.

P21

DETERMINATION OF EGFR, bcl-2 AND Ki 67 IN PATIENTS WITH ORAL
LICHEN PLANUS

I. Pavić¹, I. Canjuga², A. Carek³,
V. Vučićević-Boras⁴, D. Biočin-Lukenda⁵, D.
Baličević¹

¹Ljudevit Jurak University Department of Pathology,
Sestre milosrdnice University Hospital Center; ²Zagreb
Universitiy Hospital Center; ³Department of Prosthodontics,
⁴Department of Oral Medicine, School of Dental Medicine,
Zagreb; ⁵Department of Oral Medicine and Periodontology,
School of Medicine, Split, Croatia

Oral lichen planus (OLP) affects 1% to 2% of the population.
Typically, it affects middle-aged and elderly women, although it can
affect men, and rarely children. The cause of OLP is not known, but it
is known to be mediated through T-lymphocytes to as yet unknown
antigen. There is about a 1% risk of cancerous change over a 10-year
period. The main problem is to identify lesions that will transform
into cancer. Normally, tumor markers are used to identify cancer, but
in some instances they can suggest potentially malignant lesions.
Therefore, we evaluated OLP lesions using immunohistochemistry markers
(epidermal growth factor receptor (EGFR), bcl-2, Ki67) in comparison to
the density of subepithelial band inflammatory infiltrate. OLP patients
were divided into smokers and non-smokers. There were 15 OLP patients
in smoker group (age range 28-70 years) and 49 OLP patients in
non-smoker group (age range 21-72 years). The mean age at OLP diagnosis
was lower in OLP smokers (48.7ѱ0.6) than in OLP non-smokers
(55.8ѱ1.5). Conventional hematoxylin and eosin staining showed no
difference in the diagnosis of OLP between smoking and non-smoking
group. Spearman’s correlation test for EGFR expression showed no
between-group difference (p=0.4). Comparing EGFR, Ki67 and
bcl-2 expression in squamous epithelium according to density of
subepithelial band inflammatory infiltrate (using semi-quantitative
method; low-1, medium-2, high-3), we found significant difference (p<0.01)
between smokers and non-smokers with OLP. Immunohistochemical
expression of EGFR, bcl-2 and Ki67 in squamous epithelium in relation
to the density of subepithelial inflammatory infiltrate showed
significant difference between OLP smokers and OLP non-smokers (p=0.0005).
Study results suggested that smokers were younger than non-smokers at
the time of OLP diagnosis, which may imply the possibility of cancer
development at younger age than statistically reported for oral
carcinoma. Additional immunohistochemical analysis revealed smokers
with OLP to show a statistically significant expression of EFGR, Ki67
and bcl-2 markers in squamous epithelium in relation to the density of
subepithelial band inflammatory infiltrate as compared to OLP
non-smokers. These findings could contribute to understanding the
carcinogenesis and pathogenesis of OLP. Additional researches in a
larger sample are needed to confirm our presumption.

P22

PEDIATRIC LYMPHOMATOID PAPULOSIS WITH CYTOTOXIC
IMMUNOPHENOTYPE: CASE REPORT

S. Dotlić¹, I. Ilić¹, S. Murat-Sušić²,
J. R. Goodlad³

¹Department of Pathology and Cytology, ²University
Department of Dermatology and Venereology, Zagreb University Hospital
Center, Zagreb, Croatia; ³Department of Pathology, NHS
Lothian, Western General Hospital, Edinburgh, UK

According to the WHO/EORTC classification, lymphomatoid papulosis
(LyP) is a recurrent, self-healing papular eruption belonging to the
spectrum of cutaneous CD30+ lymphoproliferative disorders. The
neoplastic cell is typically a CD4+ T-lymphocyte, also manifesting CD30
expression. Three main histologic subtypes are recognized: type A
(histiocytic), type B (mycosis fungoides-like), and type C (anaplastic
large cell lymphoma-like). Although it is well documented in adults,
LyP is very uncommon in children. Clinical presentation and
histopathologic features of LyP in children are comparable to those in
adults. A 6-year-old boy presented with multiple erythematous papules,
measuring up to 1 cm in diameter, located predominantly on his legs.
Over time, some papules would necrotize, as new ones appeared. His past
medical history was unremarkable. According to this clinical
presentation, referring differential diagnosis included Langerhans cell
histiocytosis or lymphoproliferative disease. Punch biopsy of skin
lesions was performed. Microscopically, skin sections showed a dense,
nodular, perivascular infiltrate that extended throughout the full
thickness of the dermis. The infiltrate consisted predominantly of
large, blast-like lymphoid cells with moderate amounts of cytoplasm and
irregular vesicular nuclei with prominent nucleoli. Relatively frequent
mitotic figures and apoptotic bodies were seen. The blasts were admixed
with occasional small lymphocytes, neutrophils and eosinophils. The
overlying epidermis was ulcerated, focally infiltrated with lymphoid
cells. Immunostaining revealed blast cells of T-cell lineage, with
expression of pan-T-cell antigens CD2, CD3, CD5, and lack of CD7. They
were positive for CD8 and the cytotoxic molecules perforin, TIA-1 and
granzyme B, but negative for CD4. They also showed strong expression of
CD30 and weak, focal expression of CD56, but absence of CD57. Staining
for beta-F1 was positive, and there was no evidence of Epstein-Barr
virus, either by immunohistochemistry (LMP1) or in situ hybridisation
(EBERs). These features were consistent with a CD30-positive
lymphoproliferative disorder with a cytotoxic phenotype. Definitive
diagnosis required clinical correlation. The patient underwent thorough
hematologic work-up, and no evidence of underlying systemic lymphoma
was detected. Also, transformation of pre-existing mycosis fungoides
was excluded. Final diagnosis was consistent with CD8+ lymphomatoid
papulosis type C. The patient received only topical corticosteroid
therapy, followed by complete regression of skin lesions. After 7-month
follow-up, the patient was healthy, with no evidence of disease. The
rarity of childhood LyP, the multifocal skin lesions and the atypical
histologic features can produce erroneous diagnosis of malignancy,
leading to unnecessary aggressive treatment. Nevertheless, compared
with the general population, patients with childhood-onset LyP have a
significantly increased risk of developing non-Hodgkin lymphoma. That
is why they should be carefully monitored throughout their lives.

P23

POTENTIAL MARKERS OF MELANOMA PROGRESSION: PRELIMINARY STUDY
ON NODULAR MELANOMA

S. Ramić¹, M. Perić-Balja¹, F. Paić²,
F. Knežević¹

¹Department of Pathology, University Hospital for Tumors,
Sestre milosrdnice University Hospital Center; ²Department
of Biology, School of Medicine, Zagreb, Croatia

Melanoma is one of the most aggressive cancers with a constantly
increasing incidence, the migration, invasion and growth of which
depend on adhesive and proteolytic mechanisms of neoplastic cells.
Matrix metalloproteinases (MMPs) involved in degradation and remodeling
of surrounding tissue play a critical role in tumor progression.
Laminin and galectin-3, involved in cell adhesion, migration and growth
are also substrates for MMP-2 and MMP-9. Therefore, we presumed that
they might be used as potential markers of melanoma progression.
Protein expression patterns of MMP2, MMP9, laminin, and galectin-3 were
determined by immunohistochemical analysis of tumor tissue obtained
from 27 nodular melanoma cases (15 female and 12 male). The values
obtained were correlated using Spearman correlation rank. The median
patient age was 60 years, median of tumor thickness 2.3 mm and median
of Clark’s level of penetration 3. Positive lymph nodes were shown in
48% of cases. All markers were expressed at higher values in melanoma
cells than in surrounding tissue. MMP2 was more prominent in the zone
with strong lymphocyte infiltration (P=0.018) and deeper
layers of tumor penetration. MMP2 exhibited stronger correlation with
laminin (P=0.035), while MMP9 correlated with galectin-3
expression (P<0.001). Laminin and galectin-3 were
coexpressed in melanoma cells (P=0.044). Although not
significant, decreased expression of both markers was found in cases
with positive lymph nodes. The study pinpointed the possible markers of
melanoma progression. A higher MMP2 expression was found in deeper
layers of tumor penetration. However, additional studies in a larger
cohort and other histologic melanoma types are necessary to reach more
precise conclusions.

P24

TUBULOCYSTIC CARCINOMA OF THE KIDNEY

M. Bezjak¹, A. Mustafa-Guguli², J. Dimanovski³,
H. Čupić²

¹School of Medicine, University of Zagreb; ²Ljudevit
Jurak University Department of Pathology, ³University
Department of Urology, Sestre milosrdnice University Hospital Center,
Zagreb, Croatia

Tubulocystic carcinoma, in the past also known by the terms Bellini
epithelioma and low grade collecting duct carcinoma, is a subtype of
renal cell carcinoma, not classified in the 2004 WHO classification. It
has a distinctive histology, composed of variably sized tubules and
cysts surrounded by fibrotic stroma. Recent studies of tubulocystic
carcinoma showed it to have a strong male predominance and low but
definitive metastatic potential. A 71-year-old man with unspecific
abdominal pain underwent ultrasonography and computed tomography
studies, which revealed a tumorous mass of the kidney. Nephrectomy with
ureteretomy was performed and materials were referred for
histopathologic analysis. The tumor measured up to 4.5 cm and was
partly cystic with areas of hemorrhage and necrosis. Microscopically,
it was composed of irregular cysts and tubules lined with single layer
of cuboidal to flat epithelial cells with abundant eosinophilic
cytoplasm and large nuclei with prominent nucleoli.
Immunohistochemically, tumor cells were diffusely positive for CK7.
Histopathologic report corresponded to unclassified renal cell
carcinoma , nuclear grade 3 according to WHO classification, and to
tubulocystic carcinoma according to recent literature. Tubulocystic
carcinoma is an uncommon tumor with 55 cases reported in the
literature. In the Ljudevit Jurak University Department of Pathology
archive, two cases of this tumor were diagnosed in the last five years.
It is important to recognize this rare subtype of renal carcinoma,
although appearing relatively bland, tubulocystic carcinoma can behave
aggressively.

P25

ESTROGEN RECEPTOR POSITIVE CELLS IN GASTRIC AND DUODENAL
ULCER: A PILOT STUDY

P. Radulović¹, A. Fučić², A. Mijić²,
B. Krušlin¹

¹Ljudevit Jurak University Department of Pathology,
Sestre milosrdnice University Hospital Center; ²Institute
for Medical Research and Occupational Health, Zagreb, Croatia

It is known that gastric and duodenal peptic ulcer is more common in
males. Estrogen has an anti-inflammatory effect, acts on prostaglandin
E2 induced mastocyte degranulation and release of vascular endothelial
growth factor (VEGF), and also has a role in experimental model of
wound healing by converting fibroblasts into myofibroblasts. It also
has a sex-specific protective effect in gastroduodenal ulcer. The aim
of the present study was to investigate the expression of estrogen
receptors alpha (ERα) in gastric and duodenal ulcer tissue in order to
elucidate the observed sex difference in the incidence and impairment
process of this disease. Twelve surgical specimens of gastric and
duodenal ulcer biopsies were found in the database of the Ljudevit
Jurak University Department of Pathology, Sestre milosrdnice University
Hospital Center, during the 2000-2010 period. There were six male
 (aged 30-74 years) and six female (aged 50-81 years) patients.
Paraffin embedded gastric and duodenal ulcer tissue was cut on
microtome and analyzed on routine stained sections and
immunohistochemically with ERα monoclonal antibody. Estrogen receptor
positive cells were found in nine of twelve biopsies. ERα positive
cells were neutrophils and fibroblasts in the zone of detritus, while
ERα positive mastocytes were found in the zone of granulation tissue
and fibrosis. This is the first study describing the expression of ERα
in fibroblasts, neutrophils and mastocytes located in the area of
gastric and duodenal ulcer. Our findings suggest that the process of
ulcer healing may be modulated by estrogen. Future research should
include determination of ER type (α or β) in ulcer tissue;
investigation of the possible correlation of estrogen receptor
distribution in ulcer versus gastric cancer (as ERβ
positive); elucidation of the role of mastocytes in gastric cancer
etiology as estrogen receptor positive cells that promote angiogenesis;
and research of the possible application of hormone therapy in gastric
and duodenal ulcer disease.

P26

SKIN AND RENAL MANIFESTATIONS OF PAUCI-IMMUNE SMALL-VESSEL
VASCULITIS

J. Bacalja¹, S. Bulimbašić¹, V. Sredoja-Tišma²,
M. Tišljar³, K. Galešić³, D. Galešić³
Ljubanović¹, Š. Križanac¹

¹Department of Pathology, ²Department of
Dermatology, ³Department of Nephrology, Dubrava University
Hospital, Zagreb, Croatia

Pauci-immune small-vessel vasculitis is characterized by
leukocytoclastic necrotizing vasculitis with little or absent immune
deposits. This type of vasculitis may represent localized disease
(cutaneous vasculitis) or may involve, concomitantly or sequentially,
other organs such as the kidneys, lungs, nervous and musculoskeletal
system, eye and intestines. Up to 50% of patients with pauci-immune
glomerulonephritis (GN) have skin changes related to vasculitis. We
reviewed renal pathology archives over a 7-year period and identified
52 patients with pauci-immune GN, 18 of which had
pre-existing/concurrent skin manifestations of small-vessel vasculitis.
Clinical and laboratory data were reviewed as well as the results of
skin biopsies where available. In addition, due to assessing the extent
of the disease, Birmingham Vasculitis Activity Score (BVAS) was
calculated. Of 52 patients (29 male and 23 female, age range 17-83;
median 60.01) treated for pauci-immune GN at Dubrava University
Hospital, 10 had pre-existing skin changes related to small-vessel
vasculitis. Skin biopsy was performed in 8 patients and the most common
finding was leukocytoclastic vasculitis (7/8) with focal fibrinoid
necrosis (5/8). Circulating anti-neutrophil cytoplasmic antibodies
(ANCA) were detected in 24/52 (46%), anti-proteinase 3 (cANCA) in 4/52
(7.69%), anti-myeloperoxidase (pANCA) in 18/52 (34.6%), and both pANCA
and cANCA in 2/52 (3.8%) patients. All but one patient (BVAS index 3)
with skin involvement had high BVAS index ranging from 12 to 33.
Although most skin small-vessel vasculitides represent mild,
self-limiting conditions, they could be the first sign of a more
serious, potentially life-threatening systemic disease. The two organs
most typically involved and often defining prognosis of systemic
vasculitis are the kidneys and the lungs. Untreated patients with
severe pauci-immune vasculitis and multi-organ involvement (presenting
rapidly progressive crescentic GN and/or alveolar hemorrhage) have a
poor prognosis, which may be improved by prompt therapy with
immunosuppressive agents and plasmapheresis. Early diagnosis of
small-vessel vasculitis and recognition of visceral involvement,
followed by aggressive therapy is required in order to preserve or
restore the function of vital organs.