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Volume 39, Issue 1, 2025

Online ISSN: 3042-3511

ISSN: 3042-3503

Volume 39 , Issue 1, (2025)

Published: 31.03.2025.

Open Access

Welcome to Issue 39, No. 1 – the first of our two annual publications for this year. Inside, you'll find a curated selection of articles. Start your year with the essential knowledge and perspectives offered in this timely edition

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01.05.2019.

Original Articles

Dve decenije Ehokardiografskog udruženja Srbije

Na početku 21. veka, u vremenu društveno-političkih i ekonomskih previranja, u tadašnjoj Jugoslaviji nije bilo organizovanih naučnih i edukativnih aktivnosti u oblasti ehokardiografije. Zahvaljujući entuzijazmu nekoliko srpskih kardiologa, koji su prepoznali potrebu za promenom, aprila 2001. godine u Beogradu je osnovano ehokardiografsko udruženje, sa ciljem da postavi standarde ehokardiografskog pregleda, podrži naučne aktivnosti u oblasti ehokardiografije i osnaži saradnju sa međunarodnim ehokardiografskim organizacijama. Nakon raspada bivše Jugoslavije, prvobitan naziv «Jugoslovensko ehokardiografsko udruženje» (YUECHO), 2006. godine promenjen je u Ehokardiografsko udruženje Srbije (ECHOS).

Milica Stefanović, Aleksandar N. Nešković, Ivan Stanković

01.05.2019.

Original Articles

Inverted Meckel diverticulum as a lead-point of ileo-ileal double intussusception: A case report

Adult intussusception caused by inverted Meckel diverticulum is infrequent but important clinical entity, presenting with nonspecific symptoms. It may be observed in any age. We report a 26-year-old male patient with intussusception, who was examined several times for abdominal pain accompanied with nausea and vomiting. Basic diagnostics were inconclusive, so the patient was discharged each time with conservative therapy. After the last episode, CT scan showed suspicious intussusception, so the patient was admitted to general surgery ward. The next day there was a complete regression of all difficulties, and he was free of them in the month ahead. Finally, NMR enterography verified the presence of intussusception, and the operative procedure was performed. At laparotomy, ileo-ileal double intussusception was observed and the affected segment was resected with T-T anastomosis. Histopathological examination demonstrated an inverted Meckel diverticulum, measuring 8cm, with ectopic gastric antral type mucosa and ectopic pancreatic tissue. Postoperatively, the patient made an uneventful recovery.

Slobodan Radmilovic, Branko Lukic, Nemanja Jovanovic, Nikola Djukic, Ivana Blazic, Lidija Prijic Plecevic, Dejan Stevanovic

01.05.2019.

Original Articles

Therapeutic Plasma Exchange in the Treatment of Retrobulbar Neuritis Attacks in Patients with Multiple Sclerosis

The aim of this case report was to review the therapeutic effect of therapeutic plasma exchange in the treatment of retrobulbar neuritis in relation to its side effects, in the absence of the desired therapeutic response to previously applied immunomodulatory therapy, as a justification of therapeutic plasma exchange in the treatment of patients suffering from central nervous system demyelinating diseases. Optic neuritis is an inflammatory optic nerve lesion that may lead to partial or complete loss of vision. Therapeutic plasma exchange was performed on the SPECTRA OPTIA apheresis apparatus, according to a predefined disease diagnosis (RN), which according to the 2016 AFSA criteria belongs to the III category of disease in which apheresis is accepted as the second line of treatment. Three procedures were analyzed and an average of 5050ml of blood was processed. In conclusion, this therapeutic method is absolutely justified, with the appropriate prior preparation of the patient.

Dragoslava Jovanović, Sonja Krmek

01.05.2019.

Original Articles

The risk of using a Class I medical device with the example of prescription reading glasses

The aim of the study was to investigate the degree of exposure to the health risk of the user by using a medical prescription reading goggles, which are classified as low risk, and whether the data from the package leaflet are correctly applied. Medical devices are instruments, apparatus, materials and other products intended to be used for humans and which do not achieve its basic purpose on the basis of pharmacological, immunological or metabolic activity, but are used alone or in combination, including the software required for proper use. Depending on the categories to which they belong, medical devices have greater or lesser risk of adverse health effects on patients. Medical devices are classified to classes according to the degree of risk for the user ranging from low risk to high risk. Research was conducted in retail stores: pharmacies, optical stores and facilities for selling consumer goods. The survey questionnaire methodology collected data on habits of customers - users of diopter reading glasses. The survey was conducted among the masters of pharmacies, opticians and retailers in the period from March to June 2019. Twenty-five facilities were included in the survey in the area of Tuzla, Sarajevo and Zenica.Statistical data processing was done in Microsoft Excel. Study showed that 35% of the respondents answered that patients visited ophthalmologists and brought medical report with needed corrective diopter, while significantly larger number of respondents – 65% answered that patients didn’t visit ophthalmologists and didn’t have a medical report with needed corrective diopter. Research has shown that 73.75% of patients don’t read the instructions for use, while only 26.25% of patients read instructions for use.

Azra Hodzic, Senada Dzebo, Dusan Djuric, Vladimir Biocanin, Samra Trtak, Amra Colic, Jovanka Trifunovic

01.04.2018.

Abstracts

Granulomatous inflammation in the thyroid gland

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.

Bozidar Kovacevic

01.04.2018.

Abstracts

Tumori graničnog maligniteta gastrointestinalnog i hepatobilijarnog trakta

Ova mala kliničko-patološka kategorija tumora se odlikuje nepredvidljivošću kliničkog toka i/ili ishoda bolesti, a tome u prilog često govore i patohistološka obeležja tumora koja pružaju samo neke odlike maligniteta, sugerišu mogući maligni potencijal ili pokazuju odlike između benignih i malignih proliferacija1. Boljim definisanjem dijagnostičkih kriterijuma danas su ovi tumori smanjeni na manje od 5% svih tumora u GI i HBP sistemima, a njihov maligni potencijal se često posredno izražava kao proliferativni, recidivni ili metastatski potencijal2,3. Najveći broj njih odnosi se na dobro diferentovane neuroendokrine tumore (NET), gastrointestinalne stromalne tumore (GIST) i mucinozne cistične neoplazije (MCN). Od epitelnih neoplazija nejasnog malignog potencijala u digestivnoj cevi se posebno izdvajaju mucinozne neoplazije apendiksa i cekuma (do 0,2% tumora GIT) često praćene rupturom i peritonealnim pseudomiksomom kao tzv. „diseminovana peritonealna mucinoza“4. One se odlikuju „cistadenomskom“ morfologijom, ponekad kompleksne acinusne i mikrocistične organizacije sa displastičnim epitelom i mucinoznom (pseudo)invazijom zida, ali bez invazivnosti epitelnih elemenata5. Slična histološka obeležja vide se u kod mucinoznih cističnih neoplazija (MCN) u biliopankreatičnom traktu i jetri, gde se displastične epitelne promene duktusa pankreasa (analogne pankreasnoj intraepitelnoj neoplaziji PanIN I-III), i bilijarnih duktusa (analogne bilijarnoj intraepitelnoj neoplaziji BilIN I-III) u perifernim zonama razgranavanja moraju jasno razlikovati od rane invazije, tj. od adenokarcinoma6. Kad su u pitanju adenomatozni polipi sa pseudoinvazijom u digestivnom traktu, oni se moraju razlikovati od pravih „malignih polipa“ tj. adenomatoznih polipa sa ranom invazijom koji pokazuju disekciju stromalnih elemenata mukoze i submukoze i izazivaju dezmoplastičnu reakciju. Pseudoinvazija se odlikuje odsustvom infiltrativnog tipa rasta, dezmoplazije, uočavanjem strome (lamine proprije) oko prolabiranih glandularnih struktura, hemoragijom, hemosiderofagijom, a nekada i invertnim rastom, bilo pulzionim ili limfovaskularnim, kao i stvaranjem limfoglandularnih kompleksa sa fokalnim limfoidnim agregatima7. Kada su u pitanju dobro diferentovani NET, danas se pored klasične i imunohistohemijske dijagnostike obavezno moraju odrediti i korelirati mitotski indeks (MI) izražen na 10 polja velikog mikroskopskog uveličanja, ali određen na najmanje 50 polja, kao i procentualni proliferativni Ki-67 indeks određen u području najveće aktivnosti na najmanje 500 ćelija. Na taj način određuje se stepen maligniteta NET koji po novoj klasifikaciji iz 2017. godine koji pored NET-G1 i NET-G2 podrazumeva i novouvedeni dobro diferentovani NET visokog stepena (NET-G3) za tumore sa MI preko 20 /10HPF i Ki-67 indeks preko 20%, ali koji se moraju razlikovati od slabo diferentovanih neuroendokrinih karcinoma (NEC) istih ili viših vrednosti ovih parametara8. Značajna je i grupa visceralnih mezenhimalnih tumora nejasnog malignog potencijala koji se pojavljuju u digestivnom sistemu, posebno za GIST kao najčešći od njih i koji čini oko 2% klinički značajnih tumora u abdomenu. Danas su jasno definisani AFIP kriterijumi malignog potencijala (Miettinen, 2005) i NIH kriterijumi metastaskog potencijala (Fletcher, 2002) koji čine i sastavni deo aktuelnih TNM klasifikacija. Oni uključuju obavezne podatke o preciznoj lokalizaciji i veličini tumora i mitotskom indeksu izraženom na 50 polja velikog mikroskopskog uveličanja9. Na osnovu toga se prepostavljaju stepeni rizika malignog toka bolesti i uključivanja adjuvantnih terapijskih protokola, dok je za lečenje metastatske i/ili neresektabilne bolesti neophodno određivanje mutacionog statusa KIT, PDGFRA, SDHA i SDHB gena. Takođe je značajno prepoznavanje i nalčin dijagnostike inflamatornog miofibroblastnog tumora (IMT) koji najčešće zahvata adolescente i mlade ženske odrasle osobe (75% intra-abdominalno i ponekad multinodularno), a histološki se odlikuje karakterističnom mešavinom inflamatornih (posebno limfoplazmocitnih i histiocitnih) i stromalnih (posebno miofibroblastnih) elemenata10. Karakteristična nuklearna imunoreaktivnost za ALK-1 protein se vidi samo u oko 50% slučajeva. Ovaj tip tumora ima nepredvidiv tok, ali se recidivi (29%) i metastaze (4%) češće javljaju kod epiteloidnih hipercelularnih i mitotski aktivnijih tumora sa pojavom nuklearne atipije stromalnih ćelija11. Hepato-biliopankreatični tumori nejasnog malignog potencijala osim pomenutih MCN podrazumevaju i intraduktalne papilarne mucinozne neoplazme (IPMN) sa teškom epitelnom displazijom (analogne BilIN III, PanIN III) ali bez pridružene mikroinvazije ili jasnih adenokarcinoma12. Takođe, hepatomi nejasnog malignog potencijala su hepatoidni tumori koji odgovaraju hepatocelularnim adenomima (HCA) s ati- 75 MATERIA MEDICA • Vol. 34 • Issue 1, suplement 1 • april 2018. pijom neoplastičnih ćelija i koji ne ispunjavaju sve ostale parametre maligniteta (elementi invazivnosti, trabekularna dezorganizacija i povećanje broja gredica, evidentna mitotska aktivnost) a po pravilu su “beta-katenin aktivišući tip” HCA koji se imunohistohemijski može dokazati i koji pokazuje visok stepen maligne transformacije13. Usled toga je neophodno ekstezivno uzorkovanje velikih HCA tumora da se ne bi previdela fokalna maligna alteracija. U jetri se retko može videti i epiteloidni hemangioendoteliom (EHE), nepredvidivog kliničkog toka, koji se često pogrešno interpretira kao (adeno)karcinom. Po pravilu se javlja kod osoba srednjeg životnog doba, kao multipla nodularna promena (80%) i javlja se s ekstrahepatičnim širenjem u 50% slučajeva. Neophodno je da se kod mladih jasno razlikuje od infantilnog hemangioendotelioma. Mikroskopski se odlikuje zonalnošću sa centralnom miksohondroidnom i sklerotičnom promenom u kojoj se vide dendritične tumorske ćelije, dok se periferno uočavaju delom obliterisani a delom prošireni sinusoidi sa papilarnim projekcijama atipičnog endotela14. Često se u tumorskim ćelijama vide intracitoplazmatske vakuole koje mogu sadržati eritrocite. Mora se razlikovati od dobro diferentovanog angiosarkoma visokom celularnošću i jačom atipijom, što je povezano i sa malignom alteracijom EHE. Pankreasna solidno-pseudopapilarna neoplazija se odlikuje češćim benignim kliničkim tokom nego recidivima i veoma retkim metastaziranjem. Opisala ju je Virginia Franz (1959) kao pedijatrijski benigni tumor, ali se danas izdvaja boljom mikroskopskom karakterizacijom kod adolescenata i mladih (10-45 god.). Obilno se javlja u distalnom pankreasu, promera od 3-15 cm kao jasno ograničen, lobuliran, hemoragičan tumor. Histološki ga odlikuju papilarnost, pseudorozete, holegranulomi i fokalna hijalinizacija15. Maligni potencijal i rizik metastaziranja se povezuju sa hipercelularnošću, atipijom i izraženijom mitotskom aktivnošću. 

Marjan Micev

01.04.2018.

Abstracts

Androgen insensitivity (testicular feminization) syndrome and XY gonadal dysgenesis (Swyer syndrome)

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. 

Neli Basheska

01.04.2018.

Abstracts

Sarcomatoid differentiation in renal carcinoma

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.

Ljubinka Jankovic Velickovic

01.04.2018.

Abstracts

The von Meyenburg complex

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.

Filip Vukmirovic, Ljiljana Vuckovic, Mileta Golubovic

01.04.2018.

Abstracts

Differential diagnosis of benign spindle cell pancreatic lesions: report of two cases

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.

Radoslav Gajanin

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