PP1.

SYSTEMIC AL AMYLOIDOSIS: CASE
REPORT

V. Gverić-Krečak1, I. Karaman2,
B. Vrbičić1, E. Čubrić1, I.
Krečak1

 1Division
of Internal Medicine, Šibenik General
Hospital, Šibenik, 2Department of Pathology,
Forensic Medicine and Cytology, Split University Hospital Center,
Split, Croatia

AL amyloidosis is characterized by
light chain depositions that have
amyloidogenic potential. The disease has no specific symptoms and is
diagnosed late. Commonly affected organs are the kidneys, heart, liver,
and soft tissues (usually macroglossia). It is confirmed by the
evidence of amyloid in the affected organ, bone marrow, adipose tissue,
or gastrointestinal tract. The presence of monoclonal immunoglobulin
free light chains in serum and their presence in amyloid distinguish AL
amyloidosis from other types of amyloidosis. The aim is to show how
purpura may be an early symptom of AL amyloidosis. A 79-year-old
patient was hospitalized with symptoms of congestive heart failure and
obvious facial purpura, ecchymoses around the eyes, and macroglossia.
Four years earlier, he had the same skin changes assessed by a
dermatologist and an ophthalmologist. Biochemical tests, coronary
angiography and echocardiography were normal at that time. On
admission, biochemical findings showed slightly decreased hemoglobin,
no proteinuria, mildly elevated troponin I and normal beta-2
microglobulin. ECG showed low voltage complexes in limb leads and right
bundle branch block. Echocardiography indicated restrictive
cardiomyopathy. Immunoglobulin free monoclonal lambda light chains were
revealed in serum, about 10% of monoclonal plasma cell infiltration was
demonstrated in bone biopsy, histochemical staining (Congo red) and
polarization microscopy confirmed amyloid in adipose tissue and skin
biopsies. In conclusion, AL amyloidosis is a rare disease with no
specific symptoms. Pathognomonic purpura, ecchymoses around the eyes
and macroglossia make the diagnosis likely. We confirmed the
histopathologic diagnosis of amyloid in tissue, monoclonal
immunoglobulin free light chains in serum, and bone marrow infiltration
of monoclonal plasma cells, with no criteria for multiple myeloma.

PP2.

HYPERCALCEMIC CRISIS DUE TO
PARATHYROID ADENOMA

 B. Pigac1, D. Mužinić1, S. Mašić2, Z.
Hutinec3

 1Pathology,
Cytology and Forensic Medicine Unit,
Varaždin General Hospital, Varaždin, 2Emergency
Medical Service, Zagreb, 3Department of Pathology
and Cytology, Zagreb University Hospital Center, Zagreb, Croatia

Although primary
hyperparathyroidism is a common endocrinopathy,
hypercalcemic crisis is one of its rare manifestations. Serum level of
calcium higher than 3.75 mmol/L is associated with rapid deterioration
of the central nervous system, cardiac, gastrointestinal and renal
function. If not treated, its outcome is fatal. We present a case of a
51-year-old female with hypercalcemic crisis associated with
parathyroid adenoma. The patient had experienced gastrointestinal
dysfunction (vomiting, constipation), joint pain, general weakness,
renal dysfunction, and sudden vision loss followed by coma and, despite
conservative therapy, death. On autopsy, a node was found below the
inferior thyroid lobe. Histologically, the tumor was well limited and
consisted of unimorphous small cells arranged in nests,
immunohistochemically positive for PTH, suggesting the diagnosis of
parathyroid adenoma. Serum calcium levels higher than 3.75 mmol/L
require immediate action in order to prevent death. The treatment of
choice for patients with hypercalcemic crisis due to parathyroid
adenoma is parathyroidectomy. This case demonstrated that if untreated,
hypercalcemic crisis has fatal outcome.

PP3.

RENAL CELL CARCINOMA WITH
INTRAVASCULAR LARGE B-CELL
NON-HODGKIN’S LYMPHOMA: CASE REPORT

M. Ćorić, I. Aurer, D. Kolenc, J.
Pasini, S. Dotlić

Zagreb University Hospital Center,
School of Medicine, University
of Zagreb, Zagreb, Croatia

Intravascular large B-cell lymphoma
(IVLBCL) is a rare non-Hodgkin’s
lymphoma entity according to the current WHO classification. This rare
form of B-cell lymphoma is characterized by selective growth of tumor
cells in the lumina of small vessels of various organs. The prognosis
of IVLBCL is extremely poor. IVLBCL typically presents as a primary
intravascular neoplasm without a solitary component; however, it rarely
can result from a disseminated lymphoma. IVLBCL has been associated
with involvement of multiple organs, including the spleen, kidney,
lung, endocrine organs, and heart. The central nervous system and skin,
however, are by far the most common sites of involvement, occurring in
32% and 47% of cases, respectively. Malignant
lymphoma appears only rarely as a primary renal neoplasm. More often,
renal involvement is secondary to disseminated lymphoma. We report a
case of a 69-year-old man who presented with a right kidney mass. Two
and a half years earlier, he was treated with high-dose methotrexate
and brain irradiation for primary cerebral diffuse large B-cell
lymphoma. Pelvic computed tomography scan revealed a 5.2 cm expansive
mass in the right kidney. Right nephrectomy specimen showed renal cell
carcinoma (RCC) of clear cell type, nuclear grade III with IVLBCL.
Intravascular tumor cells inside the RCC were centroblasts with
aberrant B-cell phenotype (CD20+, CD5+, MUM1+, CD79a-, Bcl6+/-, CD3−,
CD10−). Diagnostic stereotactic biopsy of the brain was reviewed and
showed only perivascular tumor cell infiltrate (immunohistochemically
CD20+, CD5-) with no evidence of intravascular lymphoma dissemination.
On clinical examination, the patient did not have peripheral
lymhadenopathy or hepatosplenomegaly. No skin changes were noted. No
additional disease sites were identified by PET. Bone marrow biopsy was
free from lymphoma, but a monoclonal infiltrate consisting of small
B-cells was identified by flow cytometry. The patient was started on
the R-CHOP21 immunochemotherapy protocol. A repeated bone marrow flow
cytometry analysis performed after 3 cycles was normal. In conclusion,
this report describes an unusual case of IVLBCL coexisting with RCC in
a patient with a history of primary central nervous lymphoma. Systemic
dissemination of malignant lymphoma to a concurrent visceral primary
neoplasm is extremely rare. There are only few reports of these
collision tumors in the English literature.

PP4.

THE ROLE OF CD44
IMMUNOHISTOCHEMICAL EXPRESSION IN GLIOBLASTOMA

J. Mihić1, M. Vučić2, K. Rotim3,
L. Lugović-Mihić4

1Department of Surgery, Dr Josip Benčević
General
Hospital, Slavonski Brod, 2Ljudevit Jurak University
Department of Pathology, 3University
Department
of Neurosurgery, 4University Department of
Dermatovenereology, Sestre
milosrdnice University Hospital Center,
Zagreb, Croatia

Glioblastoma multiforme (GBM) is
the most lethal brain tumor with an
extremely poor prognosis and low survival rate, due to limited
therapeutic possibilities. Establishing the factors responsible for its
development and prognosis can help identify potential diagnostic
markers and targets for new therapeutic regimens. The aim of this study
was to show the role of CD44 in GBM. As recent studies have
demonstrated that CD44 expression in some tumors has a prognostic
value, there is some evidence that increased CD44 expression is linked
to the less favorable prognosis in GBM patients. It is known that CD44
is a widely distributed transmembrane cell-surface adhesion protein
involved in many physiological and pathological processes (matrix
adhesion, lymphocyte homing and activation, wound healing, growth
promotion, cell survival and migration, tumor growth and metastasis,
etc.). There are a number of potential mechanisms by which CD44 might
promote malignancy, e.g., CD44 modulates factors that could allow a
tumor to initiate a metastatic cascade (adhesiveness, motility, matrix
degradation, proliferation and cell survival). Specifically, CD44 binds
to several extracellular matrix components (hyaluronic acid, collagen,
fibronectin, osteopontin) that could facilitate the arrest and
subsequent growth of CD44-expressing tumor cells at secondary sites. On
the other hand, it was also found that lower CD44 expression might
correlate with a greater likelihood of recurrence and consequently
worse outcome overall, which is supported by the observation that
patients with recurrent GBM have better survival outcomes if their CD44
expression levels are higher. Thus, although higher levels of CD44
expression are seen in more severe tumors, lower CD44 levels could
indicate that the malignant cells are more resistant to
chemotherapeutic agents.

PP5.

EXPRESSION OF CADHERIN-CATENIN
COMPLEX IN CLEAR CELL RENAL CELL
CARCINOMA

M. Vučić1, Š. Šoipi2, B. Ružić2,
Z. Kojundžić3, D. Tomas4

 1Department
of Anesthesiology, 2University
Department of Urology, Sestre milosrdnice University Hospital Center, 3School
of Medicine, University of Zagreb, 4Ljudevit
Jurak
University Department of Pathology, Sestre milosrdnice University
Hospital Center, Zagreb, Croatia

Renal cell carcinoma (RCC) accounts
for approximately 3% of all adult
malignancies with the clear-cell type (CC-RCC) comprising 80% of RCC.
Currently, prediction of patient survival is based on traditional
pathomorphological parameters, including tumor size, Fuhrman nuclear
grade and UICC pTN classification. The cadherin-catenin complex
influences migration and modifies cell growth and survival of
neoplastic cells. The aim of this study was to determine
immunohistochemical expression of E-cadherin, N-cadherin and
beta-catenin in CC-RCC and compare it with currently used prognostic
parameters. Forty-two paraffin embedded tumor samples of CC-RCC from
the archive of Ljudevit Jurak University Department of Pathology were
examined. For each case, the percentage of stained tumor cells was
estimated for all three markers and the staining pattern was also
noted. MedCalc software (Mariakerke, Belgium) was used for statistical
analyses. Results were analyzed using Mann-Whitney test and Spearman’s
rank correlation coefficient; p<0.05 was considered to be
statistically significant. At the time of diagnosis, the median patient
age was 65.4 (range 46-80) years, with tumor size median of 3.3 (range
0.9-8.0) cm. All samples of CC-RCC showed positive membrane
immunohistochemical reaction for E-cadherin (median 4.98%) and
N-cadherin (median 25.48). Staining for beta-catenin was membranous
(median 20.36%) and cytoplasmic (median 20.60%). The relationship
between membranous beta-catenin and membranous N-cadherin and
cytoplasmic beta-catenin and membaranous N-cadherin was significant
(p=0.026 and p=0.001, respectively). Comparison of the prognostic
factors with the immunohistochemical expression of study markers showed
that there was significant positive correlation between pT stage and
expression of E cadherin, as well as between tumor size and N-cadherin
expression. In conclusion, our study showed a correlation of N-cadherin
and beta-catenin expression, indicating the potential role of
N-cadherin in tumor progression

PP6.

COMPARISON OF E-CADHERIN AND
N-CADHERIN EXPRESSION IN
CHROMOPHOBE RENAL CELL CARCINOMA AND RENAL ONCOCYTOMA

M. Vučić1, Š. Šoipi2, Z.
Kojundžić3, D. Tomas4, B. Krušlin4

1Department of Anesthesiology, 2University
Department of Urology, Sestre milosrdnice University Hospital Center, 3School
of Medicine, University of Zagreb, 4Ljudevit
Jurak
University Department of Pathology, Sestre milosrdnice University
Hospital Center, Zagreb, Croatia

Cadherins are a class of type-1
transmembrane proteins that play
important roles in cell adhesion. Renal oncocytoma (RO) is a benign
renal epithelial neoplasm composed of large cells with eosinophilic
cytoplasm. Chromophobe renal cell carcinoma (ChRCC) is a subtype of
renal cell carcinoma characterized by large cells with prominent cell
membranes. The eosinophilic variant of ChRCC is purely composed of
intensively eosinophilic cells. In some cases, the distinction of renal
oncocytoma and ChRCC based only on morphological characteristics can be
difficult. The aim of this study was to determine and compare the
immunohistochemical expression of E-cadherin and N-cadherin in RO and
ChRCC. Thirty-one ChRCC samples and 29 RO samples from the archive of
Ljudevit Jurak University Department of Pathology were examined.
For each case, the
percentage of stained tumor cells was
estimated for both markers. The staining pattern was also noted.
Results were analyzed using Mann-Whitney test and Spearman’s rank
correlation coefficient; p<0.05 was considered to be statistically
significant. All samples of RO and ChRCC showed positive membrane
immunohistochemical reaction for E-cadherin; median expression for RO
was 53.45% and for ChRCC 94.71%. The difference in E-cadherin
expression between the tumors was statistically significant. Comparison
of the prognostic markers of ChRCC (size, tumor Fuhrman grades, pTN
classification) with the expression of E-cadherin yielded no
significant correlation. Immunohistochemical expression of N-cadherin
was also only membranous, but very low in analyzed tumors with median
expression for RO of 0.41% and for ChRCC of 0.32%; the expression was
statistically nonsignificant between tumor groups. In conclusion, RO
and ChRCC were positive for E-cadherin, but ChRCC showed distinct
completely membranous staining pattern that was significantly higher
than in RO. However, additional research is needed to explore the
potential diagnostic implications.

PP7.

EPIDIDYMAL LEIOMYOSARCOMA

F. Keršić1, I. Gugić1, Š. Šoipi2,
A. Demirović3

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

Leiomyosarcoma is a malignant tumor
of smooth muscle origin. Its
presentation in epididymis is very uncommon and only 18 cases have been
described to date. Herein, we present a case of epididymal
leiomyosarcoma in a 59-year-old male patient. The patient presented
with a scrotal mass located in the right epididymis. The patient
underwent excision of the mass, which was submitted to histopathologic
analysis. Gross examination revealed an oval, partly encapsulated tumor
mass measuring 3x2x1.5 cm, with solid and whitish cut surface. Light
microscopy examination revealed a tumor composed of spindle cells with
cigar-shaped and blunt-ended nuclei showing variable atypia, arranged
in short bundles and fascicles. There were 8 mitoses per 10
high-power fields. Foci of hemorrhage were also seen. Tumor cells were
immunohistochemically positive for smooth muscle actin, desmin and
vimentin. Proliferative index measured with Ki67 was up to 50%. A
diagnosis of leiomyosarcoma of epididymis was established. The
epididymis represents a rare location for leiomyosarcoma. Its
histologic characteristics are the same as those found in other organs.
The natural course of this tumor depends on its size, grade and
evidence of nodal or distant metastasis. The treatment of choice is
high inguinal orchiectomy. Because of rarity of epididymal
leiomyosarcoma, the true biological behavior and the role of adjuvant
chemotherapy and radiotherapy are not well defined. Long-term follow up
is required for patients with a diagnosis of epididymal leiomyosarcoma.

PP8.

PROGNOSTIC SIGNIFICANCE OF CYCLIN
D1 AND p27 IN PAPILLARY
MICROCARCINOMA OF THE THYROID GLAND

S. Ramić1, N. Ćelap1, M. Perić
Balja1, M. Marušić2, F. Knežević1

1Ljudevit Jurak University Department of
Pathology, 2Department of Radiology, University
Hospital for Tumors, Sestre milosrdnice University Hospital Center,
Zagreb, Croatia

Papillary thyroid carcinoma (PTC)
is the most frequent thyroid
neoplasm. Despite its well-differentiated characteristics, PTC often
spreads to cervical lymph nodes. Favorable features are female sex, age
under 45, small tumor (<2 cm), and tumors limited to the gland.
Thyroid papillary microcarcinoma (PMC) is a papillary carcinoma that
measures 1 cm in maximum dimension. This type is usually found
accidentally, in surgical specimens of benign lesions. On rare
occasions, PMC behaves aggressively. That is the reason why it is
important to identify patients at a high risk. Surgery is the
cornerstone of PTC therapy and total thyroidectomy (TT) is indicated in
patients at higher risk. The NCCN panel members have suggested that
total thyroidectomy in PMC may not be needed. Cyclin dependent kinases
(CDK) play an important role in metastasizing of thyroid carcinomas.
They activate cell cycle through complexes with cyclins. P27 is a tumor
suppressor that acts as a CDK inhibitor. Cyclin D1 overexpression and
p27 underexpression predict a more aggressive behavior of large
papillary carcinomas. We tested the hypothesis that cyclin D1
overexpression and p27 underexpression could identify a subgroup of PMC
with metastatic potential. The study included 65 patients with PMC.
Data on patient age, sex, tumor size (mm), tumor multifocality and
status of regional lymph nodes (LN) were collected from the pathology
reports. Total thyroidectomy was performed in 23 patients and TT with
paratracheal dissection was performed in 39 patients.
Immunohistochemical expression of cyclin D1 and p27 was evaluated as a
percentage of stained nuclei. Results were analyzed with Student’s
t-test. In our study, the female to male ratio was 8.3:1. The median
age of patients was 50 years; 35.5% of patients were younger than 45.
Tumor multifocality was found in 27.4% of patients. LN metastases were
found in nine patients. Younger age (p=0.046) and male sex (p<0.001)
were strong predictors of LN metastases. Cyclin D1 was expressed in
44.6% of PMC. p27 was expressed in 83.1% of cases. Cyclin D1 inversely
correlated with p27 (p=0.049). Overexpression of cyclin D1 did not
correlate with any clinical or histopathologic parameter.
Underexpression of p27 had an influence on tumor multifocality
(p=0.023) and tendency to correlate with LN metastases (p=0.073).
Expressions of cyclin D1 and p27 cannot be used as markers of high risk
PMC although our results indicated that the cell cycle regulation was
disrupted.

PP9.

ECTOPIC ADRENAL TISSUE IN THE
SPERMATIC CORD OF A PATIENT WITH
SEMINOMA

M. Dubravčić1, Š. Šoipi2, A.
Gubo1, I. Tomašković2, M. Ulamec1,3

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

Ectopic adrenal tissue is not an
uncommon clinical finding. Papers have
been published locating ectopic adrenal tissue at various sites, most
frequently in relation to the kidney, but the existence of ectopic
adrenal tissue in structures around the spermatic cord is rather rare.
We present a patient with adrenal tissue inside the spermatic cord. A
26-year-old man underwent orchidectomy due to testicular tumor.
Epididymis with the testis measuring 7x5x2.5 cm and funicular
structures 8×2.5 cm were sent for histopathologic analysis. On the cut
surface inside testicular parenchyma, a tumor measuring up to 2 cm,
histologically pure seminoma, was found. Inside the resected edge of
the spermatic cord, an organoid structure was noticed. Microscopically,
cortical layers of the adrenal gland were visible and calcifications
were seen in medullar area. Ectopic adrenocortical nodule along the
spermatic cord is a far more common finding than has previously been
reported; it is found in 2% of pediatric patients having surgery in
inguinal or testicular area, its origin being attributed to an
embryologic defect. The clinical significance of ectopic adrenal tissue
is usually minimal but in certain situations, it may be of importance.
It can become functional and result in Conn’s syndrome, extreme
virilization or Cushing’s syndrome. It may also cause relapse of
disease in patients having undergone adrenalectomy because of Cushing’s
syndrome. Also, abnormality in the ectopic tissue may mimic
lymphadenopathy or tumors in other abdominal organs. We describe
ectopic adrenal tissue as a secondary finding in a patient with
testicular seminoma. To our knowledge, it is the second such case
reported in English literature.

PP10.

PSEUDOCARCINOMATOUS EPITHELIAL
HYPERPLASIA OF THE URINARY
BLADDER FOLLOWING THE TREATMENT OF ENDOMETRIAL CARCINOMA

N. Golec1, Z. Marušić2, A.
Reljić3, T. Džombeta1

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

Pseudocarcinomatous epithelial
hyperplasia is a rare phenomenon mostly
associated with prior irradiation and chemotherapy, but also with
ischemia and chronic irritation. It can easily be confused with
invasive carcinoma of the urinary bladder because of the infiltrative
appearance and the fact that hematuria is also the main symptom.
According to some authors, carcinomatous hyperplasia develops after
prolonged period of time (range 9 months to 13 years). Most of the
cases occur after irradiation for prostate cancer in men and for
endometrial or colon cancer in women. We report a case of
pseudocarcinomatous hyperplasia of the urinary bladder in a 55-year-old
woman following irradiation for endometrial carcinoma. Three years
after therapy, the patient presented with symptoms suggestive of
urinary bladder carcinoma. The suspected lesion was biopsied.
Microscopically, samples were covered with regular urothelium, while
lamina propria contained nested invaginations of urothelium surrounded
by blood vessels. Some of these nests showed squamous metaplasia, but
without atypia. Urothelial nests did not invade muscularis propria,
which is frequently found in carcinoma. The characteristic features of
stromal edema, congestion, chronic inflammation and exuberant deposits
of fibrin were found in lamina propria, especially in blood vessel
walls, which were thickened. Differentiation of pseudocarcinomatous
epithelial hyperplasia from urothelial carcinoma can be challenging,
but attention must be paid to stromal tissue where hemorrhage, fibrin
and vascular changes can be seen. Although current studies show no
short-term risk of development of urinary bladder carcinoma, follow up
is necessary because irradiation therapy itself increases the risk of
urothelial carcinoma.

PP11.

ATYPICAL OSSIFYING FIBROMYXOID
TUMOR

N. Friščić1, R. Hatvalić1, Z.
Puljiz2, D. Tomas1,3

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

Ossifying fibromyxoid tumor of soft
parts (OFMT) is a rare soft tissue
tumor displaying an uncertain line of differentiation. OFMT presents as
painless and well-circumscribed small subcutaneous or muscular nodule
on the extremities or on the trunk. It occurs in both males and females
at the average age of 50 years, although there is a slight male
predominance. Some immunohistochemical and ultrastructural features
suggest that this tumor is an unusual form of neural tumor, myoid, or
even that it is of myofibroblastic origin. A 70-year-old patient
presented with a tumor mass on the right gluteal region. The size of
the tumor was 4×3.5×2.5 cm. It was an oval, well-circumscribed mass
with an area of partial calcification. Microscopically, the tumor was
composed of solid, partially cellular clusters of uniform epithelioid
cells showing mitotic activity (in some areas 3 mitoses/1 HPF). The
clusters of tumor cells were surrounded with osteoid, while other parts
of the tumor contained bone trabeculae of various sizes, which were
spreading towards the surface creating a bone shell. The tumor was
partially surrounded with a fibrous pseudocapsule.
Immunohistochemically, tumor cells were diffusely positive for CD-10
and vimentin and focally for S-100 and SMA. Proliferative activity
measured by Ki67 was 15%. Based on histologic and immunohistochemical
analysis, the diagnosis of atypical OFMT was established. In
conclusion, OFMT is usually defined as a neoplasm of intermediate
malignant potential. However, a criterion for malignancy in OFMT has
not yet been clearly defined. Although most malignant OFMT may be
recognized histologically, a small number of otherwise typical OFMT may
behave in a clinically malignant fashion. Recognition of malignant OFMT
should assist in the clinical management of patients with this rare
soft tissue neoplasm.

PP12.

EXPRESSION OF CD133 IN FIBROTIC
KIDNEYS

S. Kostadinova-Kunovska1, R.
Jovanović1, L. Grchevska2, M.
Bogdanovska-Todorovska1, G. Petrushevska1

1Institute of Pathology, Faculty of
Medicine, St. Cyril
and Methodius University, 2Department of Nephrology,
Mother Theresa Clinical Center, Skopje, Macedonia

We report results of the
immunohistochemical and morphometric study of
the expression of CD133 as a putative stemcell marker, in formalin
fixed, paraffin embedded kidney biopsies with primary glomerulopathies,
with interstitial fibrosis comprising more than 10% of the sections, in
comparison to normal kidney tissue. In the group of glomerulopathies,
we found positive parietal epithelial cells in the glomeruli and some
proximal tubular segments in the vicinity of the glomeruli, which was
not related to interstitial fibrosis. On the other hand, in fibrotic
foci, we found positive apical or apico-lateral signal in the
epithelial cells of the atrophic tubules, as well as the presence of
CD133 positive luminal casts. Few interstitial cells in the fibrotic
foci were also positive. In the normal adult kidneys, the parietal
epithelial cells in the glomeruli were positive, as well as some
proximal cortical tubular segments. Quantitative analysis showed the
number of positive tubules to be significantly higher in the fibrotic
kidneys in comparison to normal kidneys (p<0.01). Strong statistical
correlation was found between the extent of interstitial fibrosis and
the number of positive atrophic tubules per 10 high-power
fields (R=0.51; p<0.01), as well as between interstitial fibrosis
and the number of positive interstitial cells (R=0.69; p<0.01).
Although stem cells are known for their role in the regenerative
processes, this study also pointed to the participation of CD133
positive cells in the process of fibrosis, and indicated the necessity
of applying a broader panel of antibodies for further investigation and
elucidation of the nature, origin and role of these cells.

PP13.

PRIMARY RENAL LEIOMYOSARCOMA:
CASE REPORT

A. Pačić1, J. Bacalja1, G.
Bedalov2, Č. Tomasović-Lončarić1, P.
Šenjug1, S. Bulimbašić1

1Department of Pathology, 2Department
of Urology, Dubrava University Hospital, Zagreb, Croatia

Renal leiomyosarcoma is a rare
tumor accounting for only 0.5% of all
primary renal tumors and 50%-60% of renal sarcomas. Most tumors are
grade 2 or 3, and prognosis is generally poor. We present a case of a
patient with renal leiomyosarcoma and metastases to the pancreas and
lungs. A 62-year-old man presented with dull pain in the left thorax
and abdomen. Computed tomography scan showed expansive mass in the
upper pole of the right kidney, multiple lesions in both lungs and a
solitary lesion in the pancreas. Provisional diagnosis of renal cell
carcinoma with lung and pancreatic metastases was made. Bronchoscopy
and transbronchial biopsy were done. Histologic and basic
immunohistochemical (IHC) analysis showed spindle cell proliferation of
the possible myofibroblastic origin; however, the material was
insufficient for detailed IHC and prediction of biological potential.
Metastatic renal cell carcinoma was ruled out. Right radical
nephrectomy and adrenalectomy were performed. Surgical specimen was
referred to the pathology unit for routine histologic analysis and
ancillary tests: IHC and electron microscopy. Gross examination showed
a 5.5x4x4 cm tumor in the upper pole of the kidney. The cut surface was
white and firm; infiltration of both outer renal parenchyma and
perirenal fat was noted. Histologically, tumor cells had features of
smooth muscle cell with high mitotic rate and areas of necrosis. On
IHC, the tumor showed diffuse positivity for smooth muscle actin and
caldesmon, and focal for desmin. Immunostains for cytokeratin, S100,
HMB 45 and CD 117 were negative. Ki-67 was positive in 30% of tumor
cells. Additional electron microscopy analysis confirmed smooth muscle
differentiation and diagnosis of primary renal leiomyosarcoma was made.
In conclusion, although most high-grade renal tumors with spindle cell
morphology represent sarcomatoid renal cell carcinomas, primary renal
sarcomas do exist and they have to be included in the differential
diagnosis of renal tumors with aggressive behavior and distant
metastasis.

PP14.

GLOMERULONEPHRITIS AFTER RENAL
TRANSPLANTATION

J. Bacalja1, S. Bulimbašić1, A.
Pačić1, K. Mihovilović2, P.
Šenjug1, M. Knotek2, D. Galešić Ljubanović1

1Department of Pathology, Dubrava
University Hospital, 2Department
of Nephrology, Merkur University Hospital, University of Zagreb, School
of Medicine, Zagreb, Croatia

Glomerulonephritis (GN) after renal
transplantation can be caused by
recurrent disease, development of de novo GN in the
transplanted organ, or transplanted GN from a donor with unrecognized
disease. It is an underlying cause of end-stage renal failure in
30%-50% of kidney transplant recipients. We analyzed clinical data and
histopathologic findings of patients who had biopsy proven
glomerulonephritis after renal transplantation diagnosed at Department
of Pathology, Dubrava University Hospital. Clinicopathologic data of
six patients with biopsy proven GN after renal transplantation were
collected to assess the prevalence, clinical course and outcome of the
disease. Five males and one female (age range 29-47, mean 37.6 years)
had biopsy proven GN, diagnosed 6-525 days after transplantation. Four
patients presented with abnormal and two with normal clinical and
laboratory data. Focal segmental glomerulosclerosis (FSGS) was
diagnosed in three patients. IgA nephropathy, membranoproliferative GN
type I and pauci-immune GN (PI-GN) were diagnosed in one patient each.
Five patients had recurrence of primary disease (3 patients with FSGS,
one membranoproliferative GN and one PI-GN). IgA nephropathy developed de
novo in a patient with
autosomal dominant polycystic kidney
disease. At the end of follow up (1.5-7 years after transplantation),
three patients were on chronic dialysis, two had normal and one
abnormal graft function. In conclusion, in our study FSGS was the most
common GN after transplantation. The graft loss in our transplant
patients with GN was 50%.

PP15.

NINE-YEAR REGISTRY OF NATIVE
RENAL BIOPSY AT DEPARTMENT OF
PATHOLOGY, DUBRAVA UNIVERSITY HOSPITAL IN ZAGREB 

J. Bacalja1, S. Bulimbašić1,
P.Šenjug1, A. Pačić1, I.
Horvatić2, M. Knotek3, K. Galešić2, D. Galešić Ljubanović1

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

The aim of the study was to assess
the incidence of native renal
diseases diagnosed by biopsy at Department of Pathology, Dubrava
University Hospital. Renal biopsy registry kept at the Department was
reviewed over a nine-year period (from April 2003 to December 2012),
with retrospective statistical analysis of data on native renal
diseases. During the study period, a total of 1981 native renal
biopsies were performed, with patient age range 1-88 (mean 47.1) years.
Biopsies originated from 11 Croatian hospitals and Mostar University
Hospital (Bosnia and Herzegovina). Men had 1.3 times more biopsies than
women (M:F=1085:806). Glomerular diseases were the most frequent
diagnosis (70.9%), followed by diseases of the blood vessels (8.8%) and
tubular interstitium (5.0%). Primary glomerular diseases were 1.4 times
more frequent than secondary ones. IgA nephropathy was the most common
disease diagnosed in 18.9% of biopsies, followed by focal segmental
glomerulosclerosis (12.1%) and membranous glomerulonephritis (8.4%).
Pauci-immune glomerulonephritis was the most common secondary
glomerular disease in our sample (6.9%), followed by lupus nephritis
(5.6%) and diabetic nephropathy (5.5%). Normal renal parenchyma was
found in 3.7% of biopsies. End stage renal disease of unknown cause was
found in 0.8% of biopsies. Some diseases were more frequently diagnosed
in women than in men and vice
versa. IgA nephropathy was 2.7
times (M:F=263:96), diabetic nephropathy 2.4 times (M:F=73:31) and FSGS
1.9 times more frequently diagnosed in men than in women. Lupus
nephritis was 2.8 times more frequently diagnosed in women than in men
(F:M=78:28). In conclusion, currently two-thirds of renal biopsies
performed in Croatia are processed by our laboratory. We believe that
the data presented are representative and provide detailed information
on the incidence, prevalence and trends in the epidemiology of renal
diseases in Croatia.

PP16.

NASAL GLOMUS TUMOR: CASE REPORT

D. Didović1, I. Babić2, M. Vučić3

13rd grade student, School of Medicine,
University of Zagreb, 2Children’s Hospital, Zagreb, 3Ljudevit Jurak University
Department of Pathology,  Sestre milosrdnice University
Hospital, Zagreb, Croatia

Glomus tumors or glomangiomas are
rare benign neoplasms (2% of all soft
tissue neoplasms) first described by Masson in 1924. They represent a
vascular hamartomatous derivative of the glomus body, a normal
intradermal arteriovenous anastomosis surrounded by connective tissue.
Glomus bodies are present in the whole body but most numerous are in
fingers and toes. They have an abundant sympathetic innervation, which
is very important for their function of preventing blood flow to the
upper skin layers when the body is exposed to cold temperature. Glomus
tumors are more common in women between 30 and 50 years of age and are
not associated with any other condition. Glomus tumors usually appear
as solitary lesions. However, a multiple glomus tumor syndrome has been
described. Glomangiosarcoma is an exceptionally rare malignant variant
of the glomus tumor. Here we report a case of a 9-year-old patient with
clinically diagnosed apical nasal tumor. The material was an irregular
skin specimen (0.4 cm in diameter) with a yellowish formation on its
surface (0.1 cm in diameter). Microscopically, the epidermal layer was
intact and a formation built of vascular spaces covered with several
layers of regular cuboid glomus cells was present in the dermal layer.
The tumor was well circumscribed. Malignancy features such as
infiltrative growth, necrosis, nuclear pleomorphism or mitotic activity
were not found. Immunohistochemically, the tumor cells were positive
for smooth muscle actin (SMA), negative for S100 and CD31 +/-. The
tumor was completely removed. In conclusion, glomangiomas are usually
located subungually on fingers and toes and extremely hurt when
pressed. The SMA positivity was crucial for this diagnosis although the
tumor was not located at its most common site and occurred at a very
young age.

PP17.

AMELOBLASTOMA OF THE SINONASAL
TRACT: CASE REPORT

I. Veliki Dalić1, L.
Labinac-Peteh2, B. Grdinić3, I.
Grgorinić4, B. Krušlin1

1Ljudevit Jurak University Department of
Pathology, Sestre
milosrdnice University Hospital Center, Zagreb, 2Department
of Pathology, 3ENT Department, 4Department
of Radiology, Pula General Hospital, Pula, Croatia

The aim is to present a case of a
rare tumor, sinonasal ameloblastoma.
A 61-year-old patient was admitted to Pula General Hospital with a
history of right-sided nasal obstruction associated with epistaxis from
the right nostril after blowing. Nasal endoscopy showed the right nasal
cavity filled with a polypoid mass that was attached to the bottom of
the nasal cavity. MSCT showed the right maxillary sinus homogeneously
filled with a soft tissue tumor that destroyed the tuber and
anterolateral wall of the nasal cavity. Surgery was performed and the
tissue specimens were sent to pathology. On microscopic examination,
the tumor consisted of the cords and islands of odontogenic epithelium,
without cytologic atypia, within edematous, myxoid, hypocellular
stroma. Columnar cells displaying a palisading pattern with classic
basaloid appearance and reverse polarity lined the periphery of the
epithelium. On immunohistochemical examination, tumor cells showed
positive reaction to CK-PAN and CK 5/6. According to history data,
histologic finding and immunohistochemical analysis, we concluded it to
be a case of sinonasal ameloblastoma.

PP18.

Diffuse large B-cell lymphoma WITH
RENAL INVOLVEMENT: CASE REPORT

V. Šimić1, S. Ostojić Kolonić2,4,
B. Jelić Puškarić3, I.
Kardum-Skelin3,4

1Zadar General Hospital, Zadar, 2Department
of Hematology, 3Department of Clinical Cytology and
Cytogenetics, Merkur University Hospital, Zagreb, 4School
of Medicine, University of Zagreb, Zagreb, Croatia

Diffuse large B-cell lymphoma
(DLBCL) is the most common form of
non-Hodgkin’s lymphoma. There is a slight male predominance. It usually
arises de novo, but it can also be transformation or
progression of a less aggressive tumor. DLBCL involvement of the kidney
is rare and uncommon, although there are some autopsy reports that
confirm renal involvement with DLBCL as a relatively common finding. We
present a case of renal involvement with DLBCL in an 81-year-old woman.
Abdominal computerized tomography and ultrasonography showed a mass in
the right kidney on which fine needle aspiration (FNA) was done and a
sample for cytomorphological, immunocytochemical analysis and flow
cytometry (clonality) was obtained. Microscopically, the tumor was
composed of monomorphous medium sized to large lymphoid cells with oval
to round vesicular nuclei. The cytoplasm was scanty to moderately
abundant, basophilic, somewhere with vacuoles. Immunocytochemically,
neoplastic cells were positive for CD 20 and the majority of these
cells showed increased proliferation activity detected by Ki67 of up to
52%. The cytologic diagnosis was NHL B large cell CD 20 positive. Flow
cytometry phenotype and clonality analysis confirmed infiltration of
the right kidney with CD 20 positive large cells B-NHL. In conclusion,
the kidney involvement with DLBCL is very rare either as a primary or
secondary process and is often without any symptoms. Although unlikely,
it is important for physicians who deal with these kinds of
patients to be aware of the possibility of lymphoma arising in the
kidney. Accurate recognition of DLBCL kidney involvement has an
important implication for the outcome prediction and further clinical
management, as these patients tend to have poorer prognosis and a
higher frequency of central nervous system involvement when relapsing.

PP19.

MUCINOUS TUBULAR CELL CARCINOMA
OF THE KIDNEY: CASE REPORT

E. Lovrić, A. Skrtić, A.
Borovečki, S. Gašparov

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

Mucinous tubular and spindle cell
carcinoma of the kidney (MTSCC-K) is
a rare variant of renal cell carcinoma. It has recently been described
for the first time, in 2004, in the World Health Organization
classification of renal cell carcinoma as a specific type of tumor.
There are small series of this entity in the literature described as a
low-grade renal epithelial neoplasm that rarely metastasizes, with
mucinous, tubular and spindle cell features. It accounts for less than
0.8% of renal neoplasms and has a strong female predominance. We
present a case of MTSCC-K for its rarity and diagnostic algorithm
complexity. A 48-year-old woman was hospitalized due to the right
kidney tumor. The tumor was visualized by abdominal computed tomography
and ultrasonography. Macroscopically, the tumor was present in the
lower pole and middle portion of the kidney and showed a
well-circumscribed, regular, solid, yellow-white cut surface. The
longest axis measured about 9 cm without hemorrhage or necrosis and did
not extend to the pelvis. There was no invasion of the renal vein and
perinephric fat. Tissue samples were fixed in 10% neutral buffered
formalin, embedded in paraffin and stained with H&E, periodic
acid-Schiff and Alcian blue. Histologic examination of the tumor showed
tubular and trabecular structures consisting of monomorphous, cuboid
cells with relatively uniform nuclei without nuclear atypia and with
rare mitoses. There was no evidence of sarcomatoid differentiation. A
single lymph node of the renal hilum without metastasis tissue was
observed. Immunohistochemically, the tumor cells were positive for
renal cell carcinoma, cytokeratin (CK)18, CK7, vimentin, CD15; rarely
cells were CD10 positive and CK HMW negative. MTSCC-K is a tumor with
relatively indolent behavior. It must be differentiated from other
types of renal cell carcinomas, which are more aggressive. Differential
diagnosis includes papillary renal cell carcinoma, papillary renal cell
carcinoma with sarcomatoid changes, metanephric adenoma, sarcomatoid
renal cell carcinoma, collecting duct carcinoma and angiomyolipomas.
Most MTSCCs-K have a favorable prognosis although some cases with
regional lymph node involvement and intra-abdominal recurrences have
been reported. MTSCC-K without sarcomatoid change but with metastasis
to the liver and retroperitoneal lymph nodes has been described. Kuroda
et al. describe a high-grade mucinous tubular
and spindle cell
carcinoma with nuclear pleomorphism and propose it to be a high-grade
counterpart of a typical low-grade MTSCC-K, as in our patient. It is
essential to report new cases to determine the prevalence and prognosis
of MTSCC-K. A precise differential diagnosis between MTSCC-K and other
types of renal carcinomas is important for predicting patient
prognosis. Pathologists should be aware of the histologic spectrum of
MTSCCs-K to ensure an accurate diagnosis.

PP20.

RENAL SQUAMOUS CELL CARCINOMA:
CASE REPORT

E. Lovrić, A. Skrtić, A.
Borovečki, S. Gašparov

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

Primary solitary squamous cell
carcinoma (SCC) of the kidney has not
yet been reported in the literature. In contrast, SCC of the renal
pelvis has been sporadically reported in the literature as an unusual
tumor with a malignant course. SCC is described in the background of
renal lithiasis and xanthogranulomatous pyelonephritis. We describe a
case of SCC of the kidney. A 63-year-old man presented with right
lumbar pain and a history of renal tuberculosis. Ultrasonography and
computed tomography of the right kidney demonstrated hydronephrosis and
right renal multicystic mass (9.6×7.5 cm). Core biopsy of the tumor
revealed malignant squamous cells. The patient underwent right
nephrectomy with no postoperative complications. Macroscopic
examination of the 730-g weight nephrectomy specimen revealed a 10x12x6
cm tumor mass. Almost the entire kidney parenchyma was replaced by a
white soft tumor with broad necrotic areas. The renal pelvis and
calices were not discerned. The tumor invaded the renal capsule,
perinephric soft tissue and adrenal gland. Light microscopy showed
solid epithelial nests of atypical squamous cells with keratin pearls
and intercellular bridges. Immunohistochemically, the tumor cells were
positive for cytokeratin AE1/AE3 but not for vimentin. The
Ziehl-Neelsen staining was negative. The renal pelvis and calices were
erosive and the remaining urothelium showed no significant atypia.
There was no evidence that the renal SCC derived from the renal pelvis
or calices. The remaining normal renal parenchyma was very scant, only
scattered renal glomeruli were recognized in some areas. The
histogenesis of the renal SCC is controversial. Renal pelvic urothelial
cell carcinoma can transform into SCC or unrecognized renal pelvic SCC
can broadly invade the renal parenchyma. It is believed that chronic
irritation by renal pelvis calculi can cause malignant transformation
of urothelium from metaplasia and dysplasia to carcinoma in situ
and invasive carcinoma. It is presumed that renal SCC can also develop
from metaplastic epithelium of the collecting tubules or distal tubules
if there is no connection with the pelvis. Early diagnosis and
monitoring of patients with long-standing nephrolithiasis are needed
for early detection of renal cancer.

PP21.

ACUTE RENAL FAILURE IN A PATIENT
WITH DIFFUSE LARGE B-CELL
LYMPHOMA

I. Domazetovski1, R. Jovanović1,
S. Kostadinova-Kunovska1, S.
Duganovska1, B. Labachevski1, I. Nikolov2, N. Ivanovski2, A. Sikole2,
G. Petrushevska1

1Institute of Pathology, Medical Faculty,
St. Cyril and
Methodius University, Skopje, 2University Department
of Nephrology, Medical Faculty, Skopje, R. Macedonia

 The aim of the report is to
update the literature concerning this
topic and highlight the importance of renal biopsy for reaching an
accurate diagnosis, selecting appropriate therapy and improving final
outcome. After physical examination, laboratory tests and urine
analysis, abdominal ultrasonography was performed and peripheral blood
smear obtained. Autopsy samples were obtained from the kidneys,
enlarged lymph nodes, and bone marrow, fixed in 10% formalin, sliced
and processed with hematoxylin and eosin (H&E), and
immunohistochemical staining methods for CD20, CD79, Bcl-2, Bcl-6 and
Ki67. Laboratory tests showed high levels of degradation products and
severe anemia, while peripheral blood smear showed the presence of
dysplastic erythroblasts and hypogranular neutrophils. The amount of
proteins in 24-hour urine was 1.5 g/L. Ultrasonography showed enlarged
kidneys, with signs of first-degree urinary obstruction and a swollen,
hypoechogenic parenchyma. At autopsy, diffuse, confluent zones of
necrosis and bleeding were present in both kidneys. Histologically, the
interstitial space was heavily infiltrated with a mononuclear
substrate, mainly in the medullar part. The glomeruli were spared, with
slight capillary congestion, whereas the tubules were atrophic, with
notable focal presence of casts. The vast majority of infiltrating
cells were CD20, CD79 and Bcl-2 positive and Bcl-6 negative. Ki67 was
above 80%. In conclusion, acute renal failure caused by lymphomatous
infiltration of the kidneys is extremely rare and usually occurs due to
bilateral infiltration. The absence of other causes, together with
enlarged, slightly obstructed kidneys with hypoechogenic parenchyma on
ultrasonography strongly suggested an infiltrative process in our
patient. The massive interstitial lymphomatous infiltration, tubular
compression and atrophy in our patient might have been the cause of
acute renal failure.

PP22.

INVASIVE GASTRIC CARCINOMA:
IMMUNOHISTOCHEMICAL EVALUATION OF
HER2 PROTEIN EXPRESSION

E. Lazović Salčin1, M. Dorić1, S.
Radović1, M. Babić1, S.
Kuskunović1, A. Hukić1

 1Department
of Pathology, School of Medicine,
University of Sarajevo, Sarajevo, Bosnia and Herzegovina

 Stomach cancer accounts for
10% of all cancers worldwide and is
the second leading cause of cancer death. Proven prognostic factors
have been shown to be insufficient; therefore, it is necessary to
identify biological prognostic factors that are considered to represent
a key step in the prognosis of this cancer. In gastric cancer, the
presence of HER2 protein was observed, however, the results of its
expression and clinical relevance are still limited and controversial.
The aim of the study was to assess immunohistochemical expression of
HER2 protein in different histologic types of invasive gastric cancer.
In this randomized retrospective study, archive tissue samples of 60
patients diagnosed as invasive gastric cancer were used. Control group
consisted of ten samples of stomach tissue with normal histology. HER2
protein expression was determined using immunohistochemistry. The
expression of HER2 protein was observed in 13.36% of gastric cancer, of
which 11.70% showed overexpression with the most frequent appearance of
the intestinal-type carcinoma by Lauren. Of the total cancer samples
investigation, HER2 protein expression was negative (0) in 69.97% and
weakly positive (+) in 16.67% of cases. There was negative correlation
with histologic type by Lauren, without statistical significance. The
probability test showed, with statistical significance, that Lauren’s
intestinal type compared to the diffuse type was twenty times more
likely to demonstrate overexpression of HER2 protein. In conclusion,
the expression of HER2 protein is present in only some of the gastric
cancers. The reasons for selective expression of HER2 in patients with
intestinal-type gastric cancer are complex and need to be explored in
more detail at the molecular level.

PP23.

IMMUNOHISTOCHEMICAL EVALUATION OF
NEOANGIOGENESIS IN GASTRIC
CANCER

A. Hukić, S. Radović, S.
Kuskunović-Vlahovljak, M. Dorić, M.
Babić, E. Lazović Salčin

Department of Pathology, School of
Medicine, University of
Sarajevo, Bosnia and Herzegovina

Neoangiogenesis is a process of
formation of new blood vessels, which
is crucial for survival, further growth and metastasis of the tumor.
Strong evidence has been found supporting the claim that there is
positive correlation between the activity of COX-2, inducible enzyme
included in cyclooxygenase pathways, which under the influence of
various inflammatory stimuli leads to the formation of prostaglandins
from arachidonic acid, neoangiogenesis and primary and metastatic tumor
growth. The aim of the study was to investigate whether there is a
correlation between COX-2 activity in the tissue of gastric cancer and
the formation of new blood vessels. We analyzed 60 samples of gastric
cancer and 20 samples of gastritis from the same patients. We used
immunohistochemical staining with COX-2, CD 34 and CD105 antibodies.
Compared to the control group, significantly higher levels of COX-2
were found in the study group (χ2=15.293; p<0.05). COX-2 exerted
influence on neoangiogenesis visualized by CD105 with statistical
significance (Ro=0.303; p<0.05), but had no effect on MVD that was
shown with CD34, or on the size of primary tumor and invasion of lymph
glands. Expression of CD105, which is used to display the volume of
neoangiogenesis, was statistically significantly higher in the study
group (F=18.429; p<0.05), but had no effect on the size of primary
tumor (Ro=-0.040; p>0.05) or invasion of lymph glands (Ro=-0.032;
p>0.05). The study showed that there were grounds for further
investigation of the role of COX-2 in neoangiogenesis, but it requires
extensive studies to assess the exact mechanism and appropriate method
for it to serve as a prognostic factor.

PP24.

MOLECULAR GENETIC ANALYSIS OF
RENAL ANGIMYOADENOMATOUS TUMOR

 A. Škrtić1,2, E. Lovrić1,
A. Borovečki1,2, S. Peterson3,
J. Hagenkord4, Z. Gatalica3

 1Department
of Pathology, Merkur University
Hospital, 2Department of Pathology, School of
Medicine, University of Zagreb, Zagreb, Croatia, 3Department
of Translational and Clinical Research, Transgenomic Laboratories, Transgenomic,
Inc., 4Creighton University School of Medicine,
Omaha, NE, USA

Three cases initially diagnosed as
renal angiomyoadenomatous tumor
based on morphology and phenotypic results from pathology files of the
Creighton University Medical Center and Creighton Medical Laboratories,
Omaha, Nebraska, USA, were analyzed. Morphologic features were reviewed
and additional immunohistochemical and molecular methods including
virtual karyotyping using SNP arrays and VHL gene sequencing were
performed. Results of the molecular genetic studies were compared to
the control group consisting of eleven cases of various types of renal
carcinomas. Microscopically, all three tumors showed similar features.
Tumors were circumscribed, composed of clear cells forming tubules,
cystic spaces and papillae and had prominent smooth muscle-rich stroma,
all consistent with described histologic features of renal
angiomyoadenomatous tumor. Immunohistochemically, epithelial cells were
positive for CK7, EMA and FHIT, and negative for vimentin, RCC antigen
and CD10. Stromal cells were SMA, vimentin and calponin positive, while
CK AE1/AE3, RCC and CD10 negative. SNP array analysis showed different
karyotypes, one with trisomy 18, and two normal. Specifically, none of
the tumors showed numerical abnormality of chromosome 3. One of the
cases with normal karyotype showed point mutation in exon 1 of the VHL
gene. Control group included seven clear cell renal cell carcinomas
(RCC), two papillary RCC, one chromophobe RCC, and one oncocytoma. SNP
array karyotyping showed 3p loss or whole chromosome 3 losses in all
seven clear cell RCC cases, and no 3p abnormality in chromophobe RCC
and oncocytoma. Uniparental disomy of chromosome 3 was found in two
cases of papillary RCC. VHL gene sequencing revealed VHL gene mutation
only in clear cell RCC cases. In our experience, morphologic and
immunohistochemical characteristics consistent with renal
angiomyoadenomatous tumor are not sufficient for the correct diagnosis.
Our molecular genetic analysis showed these tumors to be heterogeneous.
They differ from the typical clear cell RCC lacking structural or
numerical abnormality of chromosome 3, but when VHL gene sequencing
reveals mutation, it is more appropriately to classify such tumors as a
variant of clear cell RCC with prominent smooth muscle stroma.
Identification of specific gene abnormalities in this variant of kidney
tumor will lead to a more accurate diagnosis and hence better clinical
management and treatment.

PP25.

SFRP1 AND SFRP3 PROTEIN
EXPRESSION IN NORMAL AND IUGR
COMPLICATED HUMAN PLACENTAS

J. Zmijanac Partl1, D.
Fabijanović2, A. Škrtić3,4, T.
Čižmešija2, L. Adrović2, T. Nikuševa Martić2, Lj. Šerman2

1Department of Obstetrics and Gynecology,
Merkur
University Hospital, 2Department of Biology, School
of Medicine, University of Zagreb, 3Department
of
Pathology, Merkur University Hospital, 4Department
of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia

Wnt signaling pathway antagonists
such as SFRP1 and SFRP3 proteins play
an important role in maintaining trophoblast functions. Increased
expression of SFRP1 and SFRP3 was found in the placentas obtained from
complicated pregnancies with fetal intrauterine growth retardation
(IUGR) implicating placental insufficiency. The aim of the present
study was to analyze the distribution of SFRP1and SFRP3 in normal and
IUGR human placentas. Quantitative evaluation of morphological and
immunohistochemical analysis was preformed (control, n=4; IUGR
placenta, n=10). Chorionic plate, syncytiotrophoblast, stromal cells
and blood vessels of stem, intermediate and terminal villi, as well as
intermediate syncytiotrophoblast and decidual cells were observed.
Positively stained cells were analyzed semi quantitatively (0%-25%,
25%-49%, 50%-74%, and >75%), as well as the intensity of staining
(scored 0-3: negative, weak, moderate or strong). A significant
difference was found in SFRP1 and SFRP3 protein expression and
intensity of staining between the group of IUGR placentas and control
group (p<0.05; one-way ANOVA). SFRP1 and SFRP3 proteins showed
cytoplasmic staining of chorionic plate cells, villous
syncytiotrophoblast, decidua and extravillous intermediate
trophoblasts. There was SFRP3 nuclear staining in chorionic villous
stromal cells and nuclear and cytoplasmic vascular smooth muscle cells.
Significant correlation of SFRP3 and SFRP3 protein expression and
intensity of staining was found in IUGR placentas (p<0.05; one-way
ANOVA). In conclusion, overexpression of SFRP1 and SFRP3 in IUGR
placentas may indicate a role in the pathogenesis of IUGR placental
dysfunction and placental morphological changes.

PP26.

Immunohistochemical expression of
SFRP1 and SFRP3 proteins in
rat reproductive tissues

A. Šerman1, D. Fabijanović2, T.
Nikuševa Martić2, T.
Čižmešija2, L. Adrović2, J. Zmijanac Partl3, A. Škrtić4,5, L. Šerman2

1Department of Obstetrics and Gynecology,
Sveti Duh
University Hospital, 2Department of Biology, School
of Medicine, University of Zagreb, 3Department
of
Obstetrics and Gynecology, 4Department of Pathology,
Merkur University Hospital, 5Department of
Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia

SFRP1 and SFRP3 act as Wnt
signaling pathway antagonists and play an
important role in rat embryonic development. The aim of the
present study was to analyze the distribution of two SFRP family
proteins, SFRP1 and SFRP3, in rat reproductive tissues. The gestational
days selected for this study cover the period from rat embryo
implantation (day 6; Fischer strain) to the formation of the placenta
(day 15). All tissue samples were stained for SFRP1 and SFRP3
immunohistochemically and their distribution was evaluated. In
the rat, expression of both antigens is more pronounced in
the perimetrium
and myometrium, whereas decidual cells show
only occasional positive cytoplasmic reaction. Three samples
from each selected day of gestation (days 6, 7, 8, 10, 11 and 15) were
analyzed (18 in total). On gestation day 6, SFRP1 and SFRP3 labeling
was seen in endometrial intercellular spaces and in rare cytoplasms and
perivascularly, whereas uterine glands remained unstained. Rare
positive cytoplasms and perivascular expression of both proteins were
seen on the following day as well. On day 8, endometrial border zones,
cytoplasms and intercellular spaces were stained, with the addition of
intercellular spaces in parts near the luminal epithelium. On the
following two days (days 10 and 11), intense intercellular and
cytoplasmic staining of the endometrial periphery became evident, along
with rare cytoplasms in the lateral decidua at the point of their
transition toward the rest of the endometrium. Placenta and trophoblast
giant cells did not show labeling for either of the antigens. Up to
this point, the overall impression of SFRP1 and SFRP3 staining pattern
is that their expression becomes more intense and more frequent as one
moves from the embryo toward the peripheral areas of the uterus.
Finally, the labeling of both proteins diminished during gestation day
15 and was only sporadic compared to the previous days. Our data
indicate that Wnt signaling pathway has an important role in early rat
development.

PP27.

MAST CELLS IN THE HUMAN FETAL
TESTIS

T. Goluža1, V. Kozina2, M. Kos3,
D. Ježek2

1Department of Gynecological Surgery,
Zagreb University
Hospital Center, 2Department of Histology and
Embryology, School of Medicine, University of Zagreb, 3Ljudevit
Jurak University Department of Pathology, Sestre milosrdnice University
Hospital Center, Zagreb, Croatia

In the human testis, mast cells are
located inside the interstitium,
surrounding blood vessels. Their minor population is situated in the
vicinity of seminiferous tubules. Mast cells are a constant cell type
in the connective tissue of the human testis and epididymis from birth
to adulthood. Studies showed that the number of mast cells in the
interstitium, mediastinum and albuginea of the testis as well as in the
epididymal connective tissue increases slightly during infancy,
decreases during childhood, and then increases again at puberty, but
there are no known data on their presence in fetal testis tissue. It
can be assumed that mast cells develop in parallel fashion with sex
cords and interstitial tissue. The main aim of this study was to
investigate the development and presence of mast cells in 19 samples of
human fetuses 15 to 36 weeks of gestation. For overview histology,
paraffin sections were stained with hemalaun and eosin. In order to
visualize and localize mast cells, sections of testis tissue embedded
in Durcopan were stained with toluidine blue. Immunohistochemistry
(detection of mast cell tryptase) was performed in paraffin sections.

Preliminary results showed the
presence of mast cells only in tunica
albuginea of the testis and connective tissue of the mediastinum and
epididymis. No mast cell tryptase positive cells were found inside the
interstitium between the seminiferous tubules. Overview of the slides
did not provide visible evidence for a change in the population of mast
cells in the connective tissue, depending on the gestational age of the
fetus.

PP28.

GIANT CELL EPENDYMOMA OF FILUM
TERMINALE: CASE REPORT

L. Pažanin1, H. Čupić1, C. Lež2,
A. Batoš Tripalo3, DJ Živković4

1Ljudevit Jurak University Department of
Pathology, Sestre
milosrdnice University Hospital Center, Zagreb, 2Department
of Cytology, Zabok General Hospital, Zabok, 3Department
of Radiology, 4University Department of
Neurosurgery, Sestre milosrdnice University Hospital Center, Zagreb,
Croatia

Ependymomas account for up to 6% of
the central nervous system tumors
and up to 70% of spinal cord tumors. Giant cell ependymoma is a
peculiar and especially rare variant of ependymoma with only four cases
reported previously in the region of filum terminale. We describe a
case of a filum terminale giant cell ependymoma occurring in a
17-year-old female. She presented with a 17-month history of right
sciatica distributed in the S1 dermatome. Magnetic resonance imaging
(MRI) revealed intradural expansive mass in the spinal canal (L3 to S1)
showing intensive contrast enhancement. The patient underwent
laminectomy and the tumor was completely removed by use of
microneurosurgical techniques. The postoperative course was uneventful.
Histologic and immunohistochemical findings were consistent with the
diagnosis of giant cell ependymoma displaying a relatively high MIB-1
proliferation index and exceedingly rare mitoses, but no necrosis or
microvascular proliferation. Follow up MRI performed three months later
disclosed a recurrent tumor in the spinal canal. As a result of these
findings, radiation therapy was carried out. Post radiation MRI of the
lumbosacral spine showed no further progression of the process and
three years after the diagnosis the patient had normal neurologic
status. In spite of the relatively high proliferation index, our case
further supports the presumed benign biological nature of giant cell
ependymoma. However, as the number of reported cases is limited, it is
still difficult to draw firm conclusions on the biological behavior of
this particular type of ependymoma.