Introduction: Hamartomas of the bile duct named von Meyenburg complex are benign liver lesions consisting of dilated bile duct structures with a surrounding fibrous stroma. Their incidence is age-dependent and they are observed about 1% in children and 5%-6% in adults. Von Meyenburg complexes are infrequently observed lesions, characterized by multiple small nodular lesions located below the Glisson’s capsule, and ranging from 0.1 to 1.0 centimeters in diameter. Von Meyenburg complex of the liver are usually detected during laparotomy or autopsies an incidental finding. Multilocular occurrence is possible although they are rarely spread throughout the whole liver, as it was observed in our patient. They are normally asymptomatic, and are incidental findings in asymptomatic patients. They may be found in normal liver tissue, but also in association with Caroli’s syndrome, congenital hepatic fibrosis, autosomal dominant polycystic renal diseas, cholangiocarcinomas and cholangitis. Cholangiocarcinoma which arise from these lesions are usually lower stage and better differentiations than other type of cholangiocarcinoma. The sonographic findings of von Meyenburg complex are variable, including multiple, small, hyperechogenic images, with poorly delimited margins, or even hypoechogenic images with a “target” pattern with a hyperechogenic center and a hypoechogenic periphery, and well delimited margins. A magnetic resonance cholangiography is the best imaging examination of hamartomas of the bile duct, which can distinguish the different forms of dilatation of the bile duct. Histology of von Meyenburg complexes consists of a variable number of dilated small bile ducts, embedded in a fibrous, sometimes hyalinizing stroma. Microscopically, they are characterized by cystic dilatations of the bile duct or clusters of mature bile duct of various sizes, peri-ductal glands, and encompassed by fibrous stroma. The ductules are lined by small cuboidal or flattened cells, with round to oval nuclei. Bile duct hamartomas contain cysts that are more irregularly shaped then normal ducts, and they may also contain eosinophilic debris or inspissated bile. Case report: A 68-year-old male patient with multiple hepatic lesion which ultrasonic and MSCT appearance suggestive of multiple liver metastases was accepted for surgical exploration and liver biopsy. The patient had one mounts symptoms of vomits and weight loss. During surgery numerous whitish irregular lesions of various sizes scattered in the hepatic surface imitating metastatic deposits were noted trough both liver lobe and trough all liver quadrants. Explorations of the rest of abdominal cavity not found any pathological changes or peritoneal carcinomatosis. Liver biopsy was done and taken three samples for analysis. Tissue was brown-yellow-gray color and medium-firm consistency. Histological analysis demonstrated multiple lesions composed of biliary ducts incorporated in fibrotic tissue (Figure 1).There are usually cystic dilatations of some intrahepatic biliary ducts with irregular shape lined with uniform epithelium (Figure 2). The epithel of biliary ducts in von Meyenburg complex were immunohistochemicaly Epithelial Membrane Antigen positive, Pan-Cytokeratin positive, Cytokeratin 7 negative, Cytokeratin 5/6 negative and Carcinoembryonic antigene negative. Also present were signs of cholestasis with small lakes of bile.Conclusion: Von Meyenburg complexes are an important differential diagnosis of liver metastases. Differential diagnosis of liver metastases also includes other benign liver lesions, including hemangiomas, adenomas or infectious lesions e.g. miliary tuberculosis. As the existence of liver metastases is crucial for therapeutic decision making in malignant diseases, this differential diagnosis must be carefully clarified. Since VMC are usually less than 5 mm in size, they can escape preoperative radiologic diagnostics. The macroscopic appearance of von Meyenburg complexes can mimic liver metastasis as demonstrated in our reported patients.

Introduction: A pleural effusion describes an excess of fluid in the pleural cavity, usually resulting from an imbalance in the normal rate of pleural fluid production or absorption, or both. Pleural effusions are associated with a number of pathological medical conditions. In the vast majority of these cases the cellular response is quite nonspecific and will show varying proportions of mesothelial cells, macrophages, erythrocytes, lymphocytes, neutrophils and other leukocytes. Certain diseases may occasionally show cellular changes in the effusion that will reflect their presence. Examples of these include infections such as tuberculosis, blastomycosis, aspergillosis, viral infections, echinococcosis and cryptococcosis. Noninfectious, nonneoplastic diseases diagnosable by cytopathologic methods include rheumatoid arthritis, luAPSTRAKTI 89 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. pus erythematosus, eosinophilic pleural effusion, pleural endometriois and sickle cell disease. In spite of these occasional specific cytopathologic diagnoses which can be rendered for the nonneoplastic diseases named above, the most significant role of cytopathology by far is in the examination of effusion fluid for the presence of cancer cells. Cytologic examination of pleural effusions is an important initial step in management of malignant effusions. Although most patients with a malignant effusion have a known history of cancer, a positive effusion may be the first sign of an unsuspected malignancy. Cytologic examination of a serous effusion may offer the possibility of an early and accurate diagnosis by using a minimal intervention. The presence of pleural effusions typically signals an advanced stage of disease so it is associated with poor prognosis. The accuracy of cytologic examinations of malignant pleural effusion is in high range (from 40% to 87%). Lung, breast, ovarian, and gastrointestinal cancers are most likely to cause malignant effusions. The histologic type of cancer most commonly seen in serous effusions is adenocarcinoma but a variety of other cancers can cause effusions. Less common malignancies are squamous cell carcinoma, small cell carcinoma (SCC), hematopoietic malignancies, melanoma, germ cell tumours and sarcomas. Mesotheliomas often present with recurrent serous effusions. One of the most important diagnostic doubts in pleural effusion analysis is distinguishing adenocarcinoma from mesothelioma and mesothelioma from benign mesothelial cells. In most cases the diagnose is based on regular cytomorphology analysis and immunocytochemistry is necessary in low percent of cases to establish the diagnose. The specimens are collecting by thoracentesis, processing in a routine fashion and staining by hematoxylin-eosin (H&E) and Papanicolaou stain after wet fixation with 95% ethanol and May-Grunwald-Giemsa stain after air drying. It is important to evaluate the same cells when constructing coordinate immunoreactivity pattern for various immunomarkers. Since the same cells cannot be followed on different cytology smears, they are not ideally suited for routine immunocytochemical evaluation of effusion fluids. Serial sections of cell-blocks show the same cells in adjacent levels which allow proper evaluation of the coordinate immunoreactivity pattern. Conclusion: Pleural fluid cytological analysis has important diagnostic role in most cases so primary aim should be to establish the correct diagnosis with minimal investigation. Cytology is the only method by which one may retrieve cells from fluid, often in the absence of solid lessions or when obtaining a biopsy from the latter is more difficult and costly and entails much greater discomfort or risk for the patient. Effusion cytology is important for: primary diagnosis of cancer, staging, diagnosis of recurrence or disease progression. Evaluation of effusion cytology is one of the most challenging areas in diagnostic cytopathology. A remarkably wide cytomorphological spectrum of reactive mesothelial cells overlaps with various benign and malignant processes. Due to these limitations, a significant proportion of effusion fluids are difficult to interpret with objective certainty by cytomorphology alone. The use of immunocytochemical panel of antibodies with combination of high sensitivity and specificy is the only way for precise distinguishing of adenocarcinomas from mesothelioma, especially in cases with scant tumor cells particularly in metastatic disease from well differentiated carcinoma, and reactive mesothelial cells from mesothelioma. Other stains are used to confirm pulmonary origin and should be selected as a complement to the panel once adenocarcinoma is confirmed. Molecular diagnostics are feasable on routine cytopreparations, primary diagnostics as well as molecular monitoring during targeted therapy.

The skin is the largest organ in our body.Receiving information from the environment allows the role barrier between the human organism and the environment. The histological structure of the skin is variable depending on the part of the organism. The diseases of skin also vary depending on the region. The reason is the local immune status and the external physical, chemical and microbiological environment. The histopathological diagnosis of skin lesions request detailed clinical information. On the other side the histopathological diagnosis of skin lesions provides information on local disease , as well as potential other associated pathological conditions.˝ Extramammary Paget‘s vulvar disease is rare. The pathology of the skin of the vulva is specific both for specific localization, as well as for specific friction and microbiological flora. It is clinically presented as erythematosus or eczematous lesion. It can be local or extensive. Histopathologically, it is characterized by relatively large glandular atypical Paget cells, which are pathognomonic for this disease. These cells have abundant cytoplasm that is granular or vacuolated. Tumor cells are typically localized individually or in groups in the basal and parabasal layers. Immunochemical analyzes are necessary in the diagnosis of Paget‘s disease. The main reason is that Paget‘s disease can be a primary skin disease or associated with non-cutaneous carcinoma primarily of the urothelial or rectal carcinoma . Therefore, it is necessary to recommend that a detailed clinical trial of a patient be conducted in all diagnosed cases of vulvar Paget‘s disease. Mycobacterium marinum is etiological factor of Fish tank granuloma.This Mycobacterium more often causes diseases of fish, both marine and river fish. The humans become infected with Mycobacterium marinuim after contact with skin after micro/trauma Infection is usually localized to the skin.In immunocompromised patients the infection may disseminate or spread to the subcutis and bone. After incubation of few weeks after infection the lesion appear as solitary nodules or plaques.In some cases the disease progresses like suppurative ulcers. Histopathologically there is a wider range of histopathological presentations. Most often you can see abscess, necrosis of wheat and fatty tissue. However, granuloma inflammation is a key morphological substrate. After granuloma inflammation, fibrosis occurs. Since the microscopic image may be somewhat non-specific, clinical data are of great importance for the diagnosis. Multidisciplinarity in the final diagnosis includes microbiological confirmation of the presence of Mycobacterium marinum.

Aim: The aim of this paper is to point out the importance and the role of immunohistochemistry in diagnosing rare benign epithelial tumours of the lung and a very similar malignant tumour of well-differentiated lepidic adenocarcinoma. Introduction: In pulmonary pathology diagnostic dilemmas are frequent. One of the most complex challenges is to differentiate between benign tumours of pneumocytes and other forms of similar tumours. In particular, it is difficult to differentiate between the tumours of the same or similar histogenetic origin and morphological characteristics. However, dilemmas can also be related to whether a tumour has benign or malignant potential. In order to be able to have proper diagnostics, we need to have a detailed insight in the morphological and immunohistochemical features of these tumours. One of the best KRATKI KURSEVI APSTRAKTI 85 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. examples of this are two very rare and morphologically very similar benign epithelial tumours: sclerosing pneumocytoma (according to the 2015 World Health Organisation Classification of Lung Tumours; new terms changed or entities added since 2004; the 2004 World Health Organisation Classification called it sclerosing haemangioma)1 and alveolar adenoma on the one hand; and well-differentiated lepidic adenocarcinoma on the other hand. These are most often cited as the most problematic in terms of their differential diagnostics. When it comes to first two tumours, as it can be concluded from their original names, they were considered to be the tumours of completely different histogenetic origin. However, their immunohistochemical profile and all current data show that they have identical structure and origin. Immunohistochemical diagnostics enabled the demystification of neoplastic processes, as is the case with rare benign tumours of pneumocytes. This diagnostics can also point out the biological potential and help differentiate between benign and malign tumours. Additional dilemma is posed by the fact that sclerosing pneumocytoma may even give metastases into regional lymph nodes, which do not affect disease prognosis 2,3. Histopathological differential diagnosis includes, apart for the above mentioned, other benign epithelial tumors, hemangioma, primary and metastatic carcinoma4. Materials and methods: We analysed two very rare and morphologically very similar benign epithelial tumours, (sclerosing pneumocytoma and alveolar adenoma) and welldifferentiated lepidic adenocarcinoma. It was also performed their immunohistochemical analysis using the following markers: Cytokeratin 7 (CK7), Thyroid transcription factor 1 (TTF-1), Epithelial membrane antigen (EMA), Pan-cytokeratin (CK), Carcinoembryonic Antigen (CEA), FVIII, Ki67 and p53. Results: The first tumour, at the microscopic level, showed sclerosing and haemorrhagic arrangement, with ectatic spaces filled by blood and solid areas and papillary-like formations. Basic cell population was epithelial cells, dominantly with eosinophilic and partially with granular cytoplasm. The nucleus was in the centre, round, without prominent nucleoli and mitoses. Stroma was moderately pronounced and centrally it was denser and composed of bundles of oval and spindle-shaped fibroblasts. Some of the cavities within the tumour had wide, cavernous space, lined with endothelium-like attenuated cells. Mainly in the middle part of the tumour, we could see the areas of hyalinisation of connective tissue. The tumour borders were expansive. The tumour did not infiltrate the pleura. On the final histopathological slides, the second tumour had a microcystic appearance. In central parts there was pale amorphous, homogenous content. Spaces were lined with cylindrical cells containing acidophilic and clear cytoplasm. Stroma was scarcely developed and sometimes with more pronounced parts and composed of groups of elongated spindle-like fibrocytes and fibroblasts. Immunohistochemical analysis of both tumours showed very similar reactivity: Ck7, TTF-1, EMA and CK showed diffuse positivity, k67 showed low proliferation index <1%. Cea in the major part of sclerosing pneumocytoma was negative and focally individual cells had reactivity, while alveolar adenoma was negative in its entirety. P53 and FVIII in both cases showed negative results. After all analyses, the definitive diagnosis of the first tumour is pneumocytoma and for the second one alveolar adenoma. The third tumour showed similar morphology as the previous two. At the microscopic hematoxylin eosin stain, it was dominantly composed of alveolar-adenoid formations. Tumour cells were bulky, cubic or polygonal; foamy, pale acidophilic, with homogenous cytoplasm and hyperchromatic roundish nuclei without prominent nucleoli. The immunohistochemical analysis of the third tumour showed positive reactivity with Ck7, TTF-1, CK, Cea, EMA, k67 proliferation index > 32%, while p53 proliferation index ≥1%, while the FVIII had a negative result. Final diagnosis for this tumour is well-differentiated lepidic adenocarcinoma. Conclusion: Due to almost identical histopathological and immunohistochemical characteristic, there may be a diagnostic dilemma: are these two separate tumours or this is the same tumour. Taking into consideration that sclerosing pneumocytoma give positive epithelial immunohistochemical reaction, their earlier name is wrong. Previous examples are good indicators of how we should adapt the names of tumours to their real nature and this is a good recommendation in terms of how we should organise future classifications. All of the above mentioned points to the fact that with these tumours it is necessary to have immunohistochemical evaluation and that we have to introduce new immunohistochemical predictive and prognostic markers. It is necessary to determine the cut off values for proliferative markers.

Aim: The aim of this study is to present a case of benign lymphadenitis that cytologically was interpreted as suspicios for malignant lymphoma. Introduction: This study represents a case of a patient with cervical lymph node swelling in which the cyto-diagnosis performed by fine needle aspiration cytology was suspicious for lymphoma. The correct diagnosis was assessed by subsequent histology after the removal of the enlarged cervical lymph node. Material and Methods: For cytologic study the material was obtained by fine needle aspiration biopsy and syringe washings, air-dried smears and alcohol-fixed smears, which were prepared and appropriately stained by PAP and May Gruenwald-Giemsa stains. For correct diagnosis an extirpated lymph node was properly fixed and processed with routine haematoxylin eosin staining as well as with an additional immunohistochemical analyses. Results: The cyto-histologic features were characterized by a polymorphous population of cells, germinal center cells with large nuclei, a few epithelioid-type cells and histiocytes with intracellular inclusions The cytological diagnosis implied suspicion for malignant lymphoma probably of Hodgkin type. Histologic features revealed a reactive lymph node architecture that immunohistochemically revealed the diagnosis of Toxoplasma lymphadenitis. Serologic testing for toxoplasma in other institution revealed elevated titres that established the histopathological diagnosis. Conclusion: Lymphadenitis due to Toxoplasma infection is common and should be considered in the diagnosis of unexplained lymphadenopathy at all sites, especially the cervical region. Serologic confirmation should be recommended for all suspected cases and unlike in this case, fine needle aspiration cytodiagnosis can eliminate the need for hospitalization and surgery.

Introduction: Pancreatic lesions, made of spindle cells, are a heterogeneous group of lesions, ranging from reactive, inflammatory changes to tumors. Differentiation of an individual lesion is difficult and requires the use of additional analytical methods (histochemical, immunohistochemical and molecular), and a comparison of morphological characteristics with other characteristics of the changes (radiologic and laboratory characteristics). We will present two cases of benign spindle cell lesions of the pancreas, with reference to the differential diagnosis. Material and Metods: The first patient was a female, aged 51 years, with a change localized in the pancreatic head, diameter of 9.5 cm. The second patient was a male, aged 35 years, with a change in the pancreatic tail, with maximum diameter of 5.5 cm. Results: In a female patient, the lesion was an inflammatory myofibroblastic pancreatic tumor, built of fascicles of mostly spindle cells (fibroblasts/myofibroblasts). The cells had uniform, elongated, spindle nuclei and eosinophilic cytoplasm. They were arranged in short fascicles that occasionally made storiformn formations. Mitotic activity of spindle cells was low (0 - 2 mitosis/ HPF 10, FD 0.65). In the stroma, there was a mixed inflammatory infiltrate, consisting of lymphocytes, plasma cells, histiocytes, eosinophils and neutrophils. In between, there were fascicles of collagen, together with the parts of the pancreas (excretory ducts, lobules, acini, and parts of the endocrine pancreas) (Figure 1). Immunohistochemically, spindle cells showed a diffuse immunohistochemical positivity to: Vimentin, SMA and Desmin. Negative immunohistochemical reaction was showed to S-100, p53, CDX2 and ALK-1.

The significance of pathohistological analysis of operative material and tumor immunophenotype in differential diagnosis of sarcomatoid carcinoma and carcinosarcoma rare malignant lung neoplasms. Introduction: Lung carcinosarcoma, biphasic tumor, composed of non-small caracinomatous and sarcomatous heterogeneous components, is a rare neoplasm and represents less than 1% of all malignant lung tumors. Case report: A 64-year old man reported to physician complainig of fever that lasted for two months. Chest CT showed signs of right lung infiltration, close to the hilus and mediastinal lymphadenopathy. After bronchoscopy and biopsy of the suspected changes pathohistological finding was: carcinoma squamosum invasivum. Lobectomy of upper right lobe and mediastinal lymphadenectomy were performed. On gross examination, distanced 5 mm from the resection margin, withish tumor (22x7x5mm) infiltrating the wall of the lobar bronch was found. Histological analysis found that tumor tissue was partly consisted of atypical epithelial cells, with larger, mitotically active nuclei with focuses of keratinization and partialy of atypical oval and spindle cells,with hyperchromatic, pleomorphic nuclei, with high mitotic index. Lymph nodes were negative for tumor tissue. Results of immunohistochemical tumor tissue analysis: Cytokeratin - positive in carcinomatous component, Vimentin - positive in sarcomatous component, Actin, Desmin and S100 - negative. According to the results of morphological and immunohistochemical analysis of the tumor tissue lung carcinomsarcoma was diagnosed. Conclusion: For establishing definitive pathohistological diagnosis in biphasic tumor cases, a pathohistological examination of operative material is necessary, and morphological assessment should be suported by immunohistochemical analysis.

Sarcomatoid differentiation in renal cell carcinoma (sarcomatoid renal cell carcinoma – sRCC) represents a dedifferentiated high grade neoplasm of the kidney that contains carcinomatous and sarcomatous component. sRCC is an uncommon tumor, with the incidence of 5-8% of renal carcinoma. Sarcomatoid differentiation is a result of divergent differentiation of malignant epithelial cells. During this process tumor cells lose their epithelial features, and acquire mesenchymal characteristics, which provides them higher APSTRAKTI 79 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. capacity for migration and metastasis.This phenotype can be encountered in all RCC subtypes, including clear cell, papillary, chromophobe RCC, and carcinomaof collecting duct. Sarcomatoid component may resemble fibrosarcoma or undifferentiated pleomorphic sarcoma. Less often heterologous differentiation can be found, with histologic patterns resembling rhabdomyosarcoma, chondrosarcoma, or osteosarcoma. Rhabdoid phenotype is an aggressive form of divergent differentiation which has been described in clear cell RCC, papillary RCC, as well as in chromophobe RCC (CRRCC). CRRCC comprise about 6% of RCC, and has better prognosis compared to other RCC subtypes. Sarcomatoid differentiation is found in 8% of these tumors, and is an indicator of poor prognosis, as it is in other RCC types. Sarcomatoid component may represent terminally dedifferentiated clone which can arise from any RCC subtype, or can develop from a special clone. Although sRCC is most frequently found in high grade tumors, the occurrence of sarcomatoid differentiation in RCC, Fuhrman 1/2, detected in 30% of the cases, denies the claim that sarcomatoid differentiation is a continual process of classic RCC dedifferentiation, but a consequence of sarcomatoid stem cell activation within the tumor. In a case of sarcomatoid differentiation in renal carcinoma it is necessary to detect focuses of any morphological type of renal cell carcinoma, and to verify the immunohistochemical positivity of sarcomatoid component to epithelial and mesenchymal markers. Their epithelial origin is confirmed by the expression of cytokeratins, and EMA. PAX8, CAIX, and CD10 can be used to confirm the renal origin, which is of particular importance in finding of sarcomatoid cells in needle biopsy, as well as in metastatic RCC. CAIX, p53, and Bcl-2 can play a major role in transformation of RCC to highly malignant neoplasm with sarcomatoid differentiation. The expression of CAIX, p53, and Bcl-2 is indicator of poor prognosis and worse survival of the patients with sRCC. Significant micromorphological parameters that may influence the clinical course of the disease comprise percentage of sarcomatoid differentiation (>50%), presence of vascular invasion, extent of necrosis, and advanced TNM stage. Type and grade of sarcomatoid component, as well as RCC subtype do not influence the clinical outcome. The prognosis of patients with sRCC is worse compared to prognosis of other histologic forms of RCC. Sarcomatoid differentiation in RCC is a significant cause of mortality, with average survival of 4-9 months after diagnosis. The majority of unclassified RCCs contains variable percent of tumor cells with sarcomatoid morphology, without recognizable epithelial component. About 3% of RCC are exclusively sarcomatoid. These tumors are larger, more often invade adrenal glands and other adjacent organs, metastasize more frequently into regional lymph nodes and bones, and have significantly shorter survival (average is 4.3 months). Differential diagnosis of sRCC should exclude primary renal sarcoma, sarcomatoid urothelial carcinoma, and angiomyolipoma. Micromorphologically sRCC may resemble classic sarcoma, however it should be taken into account that primary renal sarcomas are extremely rare in adults, and comprise less than 1% of renal malignancies. The half of primary renal sarcomas are leiomyosarcomas, consisting of smooth muscle component, which is extremely rare in sRCC. In sarcomatoid urothelial carcinoma, the location of tumor is of significance, also the presence of carcinoma in situ, recurrence of urothelial carcinoma, and immunohistochemical positivity to CKhmw and p63. In angiomyolipoma, immunoreactivity to HMB45, as well as the presence of focuses with classic morphology, excludes sarcomatoid RCC. Conclusion: Sarcomatoid differentiation in renal cell carcinoma is a result of divergent differentiation of malignant epithelial cell, and can be found in all renal cell carcinoma subtypes. During this process tumor cells lose their epithelial features, and acquire mesenchymal characteristics, which provides them higher capacity for migration and metastasis. It is very important to recognize the presence of sarcomatoid differentiation in renal cell carcinoma, since it is an indicator of poor prognosis irrespective of RCC subtype.

Case 1: Clinical History -The patient was an 18-year-old woman with a history of primary amenorrhea. The physical examination revealed normal female external genitalia, moderate breast development, scarce pubic hair, and scant axillary hair. Pelvic examination revealed an absence of a uterus. The vagina ended in a blind pouch and measured 6cm in length. An abdominal ultrasonogram showed solid bilateral gonadal structures measuring 31x15mm right, and 30x 6mm left in the pelvic cavity without any evidence of a uterus. These findings were confirmed by MRI scan. Serum levels of estradiol and testosterone were 45.7pg/mL and 7.5nmol/L, respectively. FSH and LH levels were 8.46mlU/ml and 20.2mlU/ml. Cytogenetic analysis of peripheral blood lymphocytes revealed a 46,XY karyotype, with translocation t(13,14) inherited from her father. The molecular investigation confirmed active SRY with amplification of 6 nonpolymorphic loci on AZFa, AZFb, and AZFc regions on Y chromosome. Three months after her first referral the patient underwent bilateral prophylactic laparoscopic gonadectomy. The patient is being followed up regularly and she has no complaints after five years. Pathological Findings- Grossly, the right gonad was 4.3x1.8x1.8cm and the left gonad was 4.5x2.0x1.7cm. The right fallopian tube was 3.8cm long and 0.2cm in diameter, while the left one was 1.5cm long and 0.2cm in diameter. In addition, 4 cysts measuring 0.3- 1cm in diameter were found in the fat tissue on the surface of the left fallopian tube. The cut surface of the right gonad resembled testicular tissue showing two discrete, firm, well-demarcated, slightly bulging, homogenous, light grey-tan colored nodules, measuring 0.1 and 0.9cm in maximal dimension. Three similarly looking nodules were present in the left gonad measuring 0.4-0.5cm in diameter. In addition, a white whorled, firm, smooth muscle body fused to one pole of the gonad was found bilaterally measuring 1.2cm right, and 1.3cm left. Microscopically, both gonads were composed of varying proportions of small and solid, or less frequently larger, with early lumen formation seminiferous tubules lined by immature Sertoli cells, surrounded with fibrous, focally edematous stroma in which prominent Leydig cells were present. Rare tubules contained Sertoli cells with abundant cytoplasm filled with coarse, eosinophilic granules. The nodules were composed of solid immature tubules lined by cylindrical immature Sertoli cells separated by fibrous stroma containing fewer Leydig cells. Fallopian tubes were hypoplasic, while the cysts were lined by a single layer of cuboidal to columnar cells some of which had cilia. Thus, the clinical, laboratory, imaging, genetic and histological findings confirmed the diagnosis of complete androgen insensitivity syndrome with bilateral testicular hamartomas.Discussion Androgen insensitivity syndrome (AIS) is a disorder where there is resistance to androgen actions influencing both the morphogenesis and differentiation of androgen-responsive body structures. It is the most common type of male pseudohermaphroditism, characterized by an absence of androgen receptor activity due to a mutation at Xq11–q12 localization on the androgen receptor gene. the. In the largest series of 43 patients with the AIS published by Rutgers and Scully hamartomas were present in 63% of the cases, while Sertoli cell adenomas were reported in 23% and malignant tumors including two seminomas, one intratubular germ cell neoplasm with early stromal invasion and a malignant sex cord tumor in 9% of the cases. Case 2: Clinical History- The patient was a 17-year-old girl with primary amenorrhea. On external examination, she had an unambiguous female phenotype albeit with poor breast development. Her external genitalia had a normal appearance but internal examination showed a hypoplastic uterus. Ultrasonography failed to show follicular activity in the gonads. Her gonadotropins were high (FSH, 55.6mU/ml; LH, 18.3mU/ml) and estradiol was low (20.0pg/ml). Nonmosaic 46,XY karyotype was detected in patient’s leukocytes by cytogenetic analysis. Under the tentative clinical diagnosis of pure gonadal dysgenesis, a prophylactic bilateral laparoscopic gonadectomy with bilateral salpingectomy was performed. A biopsy specimens from the gonads were sent for cytogenetic analysis. The sequencing of the SRY gene of the proband revealed a C/G substitution at the first nucleotide of codon 133, leading to Arg/Gly replacement in the SRY protein. The mutation was also present in patient’s father, who is a phenotypically normal male. APSTRAKTI 77 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. The patient is alive and well 12 years after the operation without any evidence of disease. Pathological Findings- Macroscopically, both fallopian tubes were 4cm long and 0.4cm in diameter, while the gonads were measuring 3x2.2x1.2cm the right, and 2.2x0.8x1cm the left. Upon dissection, both gonadal streaks had a similar, variegated appearance with multiple areas of microcalcification. The histological evaluation of the gonads confirmed a gonadoblastoma of 3cm in diameter in the right gonad and a predominantly “burnt-out” gonadoblastoma of 2.2cm in the left gonad with only a microscopic focus of recognizable gonadoblastoma less than 1mm in diameter. The tumors were composed of primordial germ cells intimately admixed with sex cord elements, which surrounded round spaces filled with eosinophilic basement membrane-like material. The atypical germ cells had abundant clear or pale, slightly granular cytoplasm and round vesicular nuclei with prominent nucleoli. The small, often fusiform sex cord element cells had uniform round or oval nuclei with indiscernible nucleoli and scant cytoplasm. The uninvolved gonadal tissue bilaterally had the morphology of a streak gonad composed largely of ovarian-type stroma, with extended calcification and small germinal inclusion cysts present, without any follicles. The fallopian tubes were infantile. Therefore, the histopathological findings confirmed the diagnosis of bilateral gonadoblastoma in streak gonads, FIGO Stage IB, in a patient with a XY gonadal dysgenesis (Swyer syndrome). Discussion: XY gonadal dysgenesis (GD) is a result of abnormal testis development in utero. Pure 46,XY GD should be considered when an adolescent presents as a phenotypic female with delayed puberty and primary amenorrhea. Rarely, they may present with a detectable abdominal or pelvic gonadoblastoma mass. When the presumptive diagnosis suggests GD, further criteria may strengthen the diagnosis, while ultimately, the most definitive diagnosis is through biopsy of the gonads. Bilateral streak gonads are seen in pure XY GD. The risk of otherwise undetected gonadoblastoma in XY GD patients is high, and prophylactic or therapeutic gonadectomy is therefore often indicated when XY GD is diagnosed. 

To present pathological processes of the TG with histological detection of granulomas, analysis of morphological forms of granulomas, and their diagnostic significance. This paper is based on literature review and insight into the archival materials of the Institute of Pathology and Forensic Medicine of the Military Medical Academy.The presence of granulomas in the thyroid gland (TG) includes specific pathological processes such as subacute thyroiditis (SAT) and palpation thyroiditis (PT). The clinical manifestations of the granulomas may be accompanied by symmetrical or asymmetrical enlargement and palpatory pain in the gland, which requires further clinical examination. Granulomas in the TG can be associated with various benign and malignant processes. There are two large groups of granulomas: foreign-body giant cell granulomas (FBG) and immune granulomas (IGR). FBG are histiocytic reactions to chemically inert, exogenous or endogenous materials. Etiologically, IGRs arise in the framework of infectious, autoimmune, toxic, drug-induced or pathological processes of unknown etiology. According to the presence of necrosis IGRs can be further divided as necrotizing or non-necrotizing type. TG granulomas of the infectious, autoimmune or inflammatory nature of the unknown etiology are extremely rare. 1. Granulomas in specific pathological processes of the TG Subacute (de Quervain’s) thyroiditis or granulomatous thyroiditis is an inflammatory process that is clinically presented as enlarged and painful TG. In most cases, the result is a complete recovery of the TG function. Permanent hypothyroidism is found in about 5% of patients. SAT is usually preceded by upper respiratory tract infection. The disease is etiologically related to viral infections, genetic predisposition and the use of immuno therapy. Macroscopically, TG is usually symmetrically enlarged, but there are also localized forms with nodular morphology, which imitate neoplastic lesions. The microscopic characteristic is the presence of multifocal and diffusely distributed folliculocentric granulomas. They are found in different phases and consist of epitheloid histiocytes, lymphocytes, plasma cells, neutrophils, and multinuclear giant cells (MGC). At the center of the granuloma, the colloid is reduced or absent. In later phases, fibrosis can develop perifollicularly. In terms of differential diagnosis (DDG), it is important to differentiate SAT from other granulomatous inflammations. Palpation thyroiditis (Multifocal granulomatous folliculitis) is the most common pathological process in TG with microscopic detection of granulomas. It is an incidental microscopic finding involving individual or minor follicular groups. Changes arise as a result of mechanical microtrauma after the palpation of the TG. Microscopic changes are characterized by damage to the follicles with interfollicular APSTRAKTI 73 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. accumulation mainly of histiocytes in the presence of lymphocytes, plasma cells and MGCs. In the DDG of PT, the following conditions must be considered: SAT, primary and secondary microscopic foci of papillary microcarcinoma, C-cell hyperplasia, and focal forms of Langerhans histiocytosis. 2. Foreign-body giant cell granuloma is frequent incidental microscopic finding in TG. It arises as a reaction to the accumulation of endogenous substances in the areas of spontaneous or degenerations induces by fine-needle aspiration biopsy (FNAB). The most common forms of FBGs on endogenous material are cholesterol granulomas. These FBGs are composed of MGCs, foamy histiocytes, and hemosiderophages arranged around crystal deposits. Depending on how old the lesion is, there may be a focal necrosis, a different degree of fibrosis, extracellular deposits of hemosiderin, and other inflammatory cells. The presence of FBGs and histiocytic aggregates is not only important in the preoperative cytological diagnostics, but also in the post-operative pathohistological analysis of TG nodules. Large nuclei of histiocytes with hypochromasia, nuclear membrane irregularities and the presence of MGC can imitate the cytological features of papillary thyroid carcinoma (PTC). Exogenous biomaterials are rarely cause of FBGs in TG. After thyroidectomy, in cases of diagnosed TG malignancies, the presence of suture FBGs in thyroid bed imitates recurrence or the rest of malignancy and is the cause of repeated surgeries. 3. Necrotizing granulomas (NGR) in TG Granulomas with necrosis may be of infectious and noninfectious etiology. Tuberculosis is the most common cause of NGR in TG. Tuberculosis in TG can be presented as a solitary nodal lesion, diffuse microlesions, nodular goiter, and rarely as an abscess or a chronic skin sinus. As a infectious cause of NGR in TG, sporadically reported cases have been caused by histoplasmosis, coccidioidomycosis and nocardiosis. Rare non-infectious NGR in TG or in the TG bed, of autoimmune etiologies, have been described as part of Wegener’s granulomatosis and rheumatoid arthritis. Post-operative necrotizing granulomas also represent NGR of non-infectious cause. Microscopically, there is a morphology that matches post biopsy granulomas in other organs (prostate, urinary bladder). 4. Non-necrotizing granulomas (NNGR) in TG Sarcoidosis is a multi-systemic chronic granulomatous inflammation of unknown etiology. Thyroid is rarely affected by sarcoidosis. Macroscopically, the gland is diffusely or nodularly enlarged or reduced in volume. Interstitially localized NNGR represent a typical histological presentation. Sarcoidosis of TG should be distinguished from the sarcoid-like stromal reactions of PTC in the gland or regional lymph nodes. In these cases, it is necessary to clinically exclude the systemic disease. 5. Granulomas and histiocytic reactions in neoplastic processes of TG Apart from the described FBGs, PT and sarcoid-like reactions, in epithelial tumors of the TG histiocytic aggregates (not granulomas) may also be seen as secondary changes after FNAB. Interfollicular/ intraluminal presence of MGCs with or without the presence of histiocytes and granuloma-like morphology represents a characteristic finding in PTC. The cytological and histological detection of MGCs is one of the diagnostic criteria for PTC. Their presence in tumors may be due to a reaction to an altered colloid produced by PTC or as a non-specific immune response to due tumor cells. Conclusion: Granulomas in the TG are not rare. Knowing the morphology of granulomas, pathological processes and the circumstances in which they occur is significant in DDG of primary tumors of the TG, their recurrence and metastases in the cervical lymph nodes. The diagnosis of granulomatous inflammation in TG can be based on the histological characteristics of granulomas in correlation with clinical and laboratory findings.