Faculty of Medicine

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Incidental gonadal germ cell tumours at the time of prophylactic gonadectomy in patients with Swyer syndrome - a report of 3 cases
(Springer, 2018-08-24)
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Ognenoska-Jankovska, Biljana
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Veljanoska, Slavica
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Plasheska-Karanfilska, Dijana
Background & Objective: Swyer syndrome (46,XY pure gonadal dysgenesis) is an uncommonly encountered condition in which gonadectomy is recommended upon diagnosis due to a significant risk of malignant transformation of the dysgenetic gonads. The aim of this study was to present our experience with incidentally found germ cell tumours in patients with Swyer syndrome. Method: We report the clinico-pathological characteristics of 3 cases of female phenotypic patients presenting with primary amenorrhea who underwent prophylactic bilateral laparoscopic gonadectomy with salpingectomy following a diagnosis of Swyer syndrome. At the time of diagnosis, they were 17 to 20 years old. The presenting features were hypogonadotropic hypogonadism and 46, XY karyotype. A hypoplastic uterus with normal looking fallopian tubes and bilateral gonads were detected by ultrasonography and confirmed during laparoscopy. The patients with dysgerminoma underwent postoperative chemotherapy. All three patients are alive and well 70, 115 and 144 months following surgery. Results: The histopathological examination of the streak gonads which were completely sampled and embedded revealed the presence of bilateral predominantly “burnt out” gonadoblastoma in all patients. In addition, in two patients, a coexisting dysgerminoma of 1.5 and 3.8 cm in diameter FIGO stage IC1 in the right gonad was confirmed. The sequencing of the SRY gene of the patient with bilateral gonadoblastoma without dysgerminoma overgrowth revealed a C/G substitution at the first nucleotide of codon 133, leading to Arg/Gly replacement in the SRYprotein. Conclusion: Our data suggest that patients with gonadal dysgenesis and 46, XY karyotype should be referred for bilateral gonadectomy and their operative specimens should undergo meticulous histopathological examination because of the high risk of neoplastic transformation.
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Correlation between PD-L1 expression and clinicopathological characteristics in triple-negative breast cancer patients
(Springer, 2020-12)
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Ognenoska-Jankovska, Biljana
Background & objectives: While immunotherapy is emerging as an effective treatment option for advanced triple-negative breast carcinoma (TNBC) patients, the clinicopathological significance of PD-L1 expression in TNBC remains unclear. Our objective was to investigate the association between PD-L1 expression and clinicopathological characteristics in TNBC. Methods: The study group comprised 47 TNBC patients in which PD-L1 status was evaluated by immunohistochemistry with SP142 assay on the Ventana BenchMark. All PDL1(+) tumour-associated immune cells (IC) were quantified as % of the tumour area. Tumours were classified as PDL1(+)(>=1%) or PD-L1(-)(<1%). The statistical significance of the correlation between PD-L1 status and clinicopathological characteristics was determined by chi-square test. Results: PD-L1(+) were 24(51.1%) of the 47 TNBC patients whose median age at diagnosis was 59 (range, 39-79). 53.5% (23/43) of the primary and 25%(1/4) of the metastatic TNBC cases were PD-L1(+). 21(87.5%) of the PD-L1(+) TNBC had IC1( 1 and <5%), 2(8.3%) had IC2( 5 and <10%), and 1(4.2%) had IC3( 10) score. The PD-L1(+) status significantly associated with high histological grade (G3, P=0.022), and higher proliferative index (Ki-67>35%, P=0.004), while the correlation with larger tumour size (>2 cm, P=0.055) did not reach statistical significance. No significant relationship was found between PD-L1 status and other variables such as patients` age, postoperative stage, tumour status, lymph nodal status, tumour type, vascular invasion, and p53 expression. Conclusion: Our preliminary results suggest that PD-L1 expression is associated with several high-risk clinicopathological parameters in TNBC patients. Further larger studies are warranted to clarify the clinical relevance of PD-L1 expression in TNBC patients.
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Clinicopathological analysis of incidentally detected blue nevi of the uterine cervix in biopsy and curettage specimens. A report of 7 cases.
(Springer, 2019-09)
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Ognenoska-Jankovska, Biljana
Background & Objectives: Blue nevi (BN) of the uterine cervix (UC) are rare incidental lesions; they are often found in hysterectomy specimens from middle-aged women, or rarely in specimens obtained during more conservative diagnostic procedures (e.g. biopsy, curettage). The objective of our study was to analyse the clinicopathological features of 7 incidentally detected cases of the BN of the UC in biopsy or curettage specimens. Methods: Among a total of 60 BN of the UC diagnosed on operative and biopsy specimens in our Department between 2000-2019, in 7 (7/60, 11.7%) cases BN were found in biopsy or curettage specimens that had been taken for an examination of a clinically or cytologically suspicious cervical lesion (3/7, 42.9%) or a dysfunctional uterine bleeding (4/7, 57.1%), respectively. The mean age of the patients was 44 years (range, 29-57 years). In addition to routine hematoxylin&eosin, histochemical and immunohistochemical stainings were also performed. Results: Histologically, all cases showed loose aggregates of pigmented, spindle-shaped, dendritic or nevoid, epithelioid cells in the superficial stroma in one (4/7, 57.1%) or >2 fragments of cervical mucosa (3/7, 42.9%). The lesions ranged in size from 0.5 to 6mm (mean, 2.4mm), while their thickness ranged between 0.5-4mm (mean, 1.5mm). In one case the BN was presenting as an endocervical polyp. The pigmented cells in all tested cases were positive for melanin (Fontana-Masson), S100, Melan-A, as well as for HMB45 in 3 cases. Conclusion: Although the BN of the UC seem to be lesions of low clinical significance, they require careful differential diagnosis with other pigmented lesions including malignant melanoma, especially because they are rarely detected and might easily be missed or misinterpreted in scanty endocervical curettage or cervical biopsy specimens due to their small size, more frequent endocervical localization and occasional discrete findings.
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Benign granular cell tumor of the uterine corpus: A case report
(The Arab Division of the International Academy of Pathology In Collaboration with the Jordanian Society of Pathologists, 2018-10)
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Krstevska, Iskra
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Ognenoska-Jankovska, Biljana
Objective: Granular cell tumors (GCTs) are relatively uncommon soft tissue tumors that are usually benign (0.5-2.0% malignant). They have been described in many sites and organs, although cases with genital involvement have rarely been reported. We present the clinicopathological features of a case of a uterine corpus GST. Methods: A 37-year-old woman with secondary infertility was admitted at the University Clinic of Gynecology and Obstetrics for a hysteroscopic examination during which a polypoid isthmico-cervical lesion was detected. Results: The biopsy excision specimen consisted of one smaller fragment of the endometrium and two larger semispherical fragments measuring 0.7x0.5x0.4 and 0.8x0.6x0.4 cm. Upon microscopic examination of the larger fragments under the partly pseudodecidualized endometrial or isthmic type of surface mucosa, a benign mesenchymal neoplasm was found composed of nests of large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei lacking conspicuous nucleoli or mitotic figures. In addition to PAS positivity, upon immunohistochemical staining, the large cells also showed vimentin, S-100, neuron-specific enolase, CD56, CD57, calretinin and Wilms tumor 1 positivity. The proliferative index determined by Ki-67 staining was <5%. Based on the pathological and immunohistochemical examinations, the diagnosis of a benign GCT was established. Due to the fact that the neoplasm was incompletely excised a wide local excision was recommended along with a careful follow-up of the patient. The patient refused the excision and is being well and preparing for in vitro fertilization 24 months following biopsy. Conclusion: GCTs of the uterus and especially of the uterine corpus are extremely rare. To the best of our knowledge, this is a second reported case of uterine corpus GCT in the English-language literature. It is important for gynecologists as well as pathologists to be aware of the possibility of uterine corpus GCTs, for which accurate diagnosis, complete resection and long-term follow-up are crucial.
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Multifocal Hurthle cell (oxyphilic) variant of papillary thyroid carcinoma associated with Hashimoto`s thyroiditis: A case report
(Macedonian Association of Pathology, 2016-09)
Qerimi, Adelina
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Ognenoska-Jankovska, Biljana
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Stojkoska, Elena
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Objective: Oxyphilic (Hurthle cell) variant of papillary thyroid carcinoma (OVPTC) is a rare subtype accounting for 1-11% of all cases of papillary thyroid carcinomas (PTCs). The clinicopathological features and biological behavior of OVPTC have not yet been thoroughly characterized. We present a case of multifocal OVPTC with concurrent Hashimoto`s thyroiditis. Material and Methods: A 51-year-old female patient with multinodular goiter underwent a fine-needle aspiration biopsy which was reported as negative, followed by a subtotal thyroidectomy procedure. Results: The surgically obtained material consisted of two oval fragments designated as right and left thyroid lobe with the largest diameter of 5 cm and 4.5 cm, respectively. Grossly, on the cut section of the left lobe two well-circumscribed, white to grey-tanned foci with the largest diameter of 1.3 cm and 0.6 cm, respectively, were found. Microscopically, in a background of Hashimoto`s thyroiditis, the two foci revealed a neoplasm with predominantly insular growth pattern and focally follicular or papillary structures composed of large polygonal cells with abundant eosinophilic granular cytoplasm and optically clear nuclei with the characteristic intranuclear pseudoinclusions and nuclear grooves. Psammoma bodies and areas of calcification were also present. Mitoses were rare and no vascular or capsular invasion was encountered. Immunohistochemically, tumor cells showed diffuse positivity for low-molecular-weight cytokeratin and cytokeratin 19 and focal positivity for thyroid transcription factor-1. Conclusions: This case confirms that although OVPTC remains controversial, it usually displays the morphological and immunohistochemical features of the classical type of PTC, which can aid in avoiding the diagnostic pitfalls in distinguishing this subtype of PTC from other benign or malignant Hurthle cell lesions.
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Warthin-like papillary carcinoma of the thyroid: A case report
(Macedonian Association of Pathology, 2016-09)
Stojkoska, Elena
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Qerimi, Adelina
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Ognenoska-Jankovska, Biljana
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Objective: Warthin-like variant of papillary carcinoma (WLPCT) is an uncommon variant, first described in 1995, with a clinical presentation and prognosis similar to the classic papillary thyroid carcinoma (PTC). We report a case of WLPCT focusing on the histopathological and immunohistochemical features. Material and Methods: A 60-year old female, with no remarkable past medical history, underwent surgical treatment of an enlarged multinodal goiter with previous negative fine-needle aspiration biopsy findings. A left total and right subtotal thyroidectomy was performed. The patient is alive and well 4 months after the surgery. Results: On gross examination, the right lobe of the thyroid gland measured 4.5x1.5x1 cm, and the left lobe with adjoined isthmic lobe measured 5x3.5x2 cm. In the right lobe an oval, firm, grey, 0.8 cm large nodule was found, while in the left lobe another well-circumscribed, pale-brown, 2.5 cm large nodule was present. The left lobe nodule was diagnosed as an atypical follicular adenoma with no capsular or vascular invasion. Histology of the right lobe nodule showed an encapsulated tumor composed of papillary structures lined by oncocytic cells and rich lymphoid stroma, with germinal centers in the papillary stalks, typical for WLPCT. Immunohistochemically, tumor cells of WLPCT showed positive expression for cytokeratin 19, thyroid transcription factor-1 and thyroglobulin. Conclusions: Warthin-like variant is one of the rarest variants of PTC (less than 100 reported cases in the literature) with as favorable prognosis as the classic PTC. Morphology and immunohistochemistry are of decisive significance in differentiating these neoplasms from benign lymphoepithelial lesions, Hurthle cell carcinoma and tall cell variant of PTC.
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Follicular variant of papillary thyroid carcinoma arising in struma ovarii: A case report
(Macedonian Association of Pathology, 2016-09)
Stojkoska, Elena
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Qerimi, Adelina
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Ognenoska-Jankovska, Biljana
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Objective: Struma ovarii is a rare form of ovarian mature teratoma and is the most common type of monodermal teratoma (3% of all ovarian teratomas). 5-10% of such tumors are malignant with papillary carcinoma as the most common type (70%) while 26% of them are a follicular variant of papillary thyroid carcinoma (FVOPTC). We report a case of FVOPTC arising in struma ovarii focusing on the clinical, histopathological and immunohistochemical features. Material and Methods: A 29-year old nulliparous female underwent laparoscopic surgery of a 7 cm a large right ovarian cyst, diagnosed by ultrasound. Clinically and biochemically she was euthyroid with normal serum TSH level, and without previous significant medical or gynecological history. Results: Grossly, a laparoscopically obtained material consisted of 8x3 cm fragment of cyst wall measuring 0.2 to 0.6 cm in thickness with a focus of 5 mm large grayish-white tumor. Histology of the cyst wall showed thyroid tissue characteristic of cystic struma ovarii while the tumor showed typical nuclear features of papillary thyroid carcinoma with follicle formation and minimal presence of papillary structures typical for FVOPTC arising in thyroid tissue. Immunohistochemical staining showed positive expression for thyroglobulin, TTF-1, and cytokeratin-19 in the tumor cells. Conclusions: FVOPTC arising in struma ovarii is difficult to assess because it is a rare tumor with about 60 published cases and lacking standard criteria for diagnosis. Thus, the morphological criteria for the diagnosis of this tumor are based on classical criteria for primary thyroid carcinoma. Prognostically, FVOPTCs measuring less than 2 cm arising in struma ovarii are considered as low-risk lesions with a low rate of recurrence and metastasis.
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Ovarian Leydig cell tumor (hilus cell tumor): A case report
(Macedonian Association of Pathology, 2016-09)
Qerimi, Adelina
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Stojkoska, Elena
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Ognenoska-Jankovska, Biljana
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Trajanova, Milka
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Objective: Leydig cell tumor is a rare ovarian tumor that belongs to the group of sex-cord stromal tumors. They produce testosterone leading to hyperandrogenism. As a subtype of steroid cell tumors of the ovary characterized by the presence of Reinke crystals, it comprises 19% and affects mainly young women. Material and Methods: A 24-year old nulliparous patient clinically presented with hirsutism, oligomenorrhea, and infertility. Ultrasonography showed a left ovarian tumor mass with the greatest diameter of 4.3 cm. The patient underwent a laparoscopic tumorectomy followed by gradual withdrawal of the symptoms at the first check-up after 6 months follow-up. Results: The laparoscopically obtained material consisted of 15 yellow to orange-tanned, soft and solid fragments with a diameter ranging from 0.5 to 5.5cm. Microscopically, the tumor was solid, relatively well-circumscribed, and composed of cellular areas with clustering of nuclei separated by eosinophilic anuclear zones. Some of the tumor cells had scant and others abundant eosinophilic or clear cytoplasm with lipid-rich, oil Red O-positive vacuoles and oval, hyperchromatic or bizarre nuclei. Mitotic figures were scarce, while Reinke crystals were found after a prolonged search. Immunohistochemically, tumor cells showed diffuse positivity for vimentin, focal for cytokeratin AE1/AE3, alfa-smooth muscle actin, S100, CD99, calretinin, inhibin-alpha, melan A, CD56 and were steroid hormone receptor negative. Conclusions: Although idiopathic hirsutism and other benign androgen excess disorders like polycystic ovarian syndrome are common, the presence of an ovarian mass in younger patients should raise suspicion of Leydig cell tumor or other steroid cell tumors. This case confirms that Reinke crystal quest should always be tenacious.
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Apocrine carcinoma in situ with microinvasion – A case report
(Macedonian Association of Pathology, 2016-09)
Ognenoska-Jankovska, Biljana
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Qerimi, Adelina
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Stojkoska, Elena
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Objective: Invasive apocrine carcinoma is a very rare type of breast malignancy, with an incidence of 0.5-4%, which presumably develops from apocrine precancerous lesions. We report a case of microinvasive apocrine carcinoma which was diagnosed by fine needle aspiration cytology (FNAC) and confirmed by histopathology. Material and Methods: A 45-year-old woman following a routine mammography that showed irregular spiculated mass measuring approximately 2.5cm in the upper outer quadrant of the left breast was referred to our Department for FNAC. The patient subsequently underwent left-sided quadrantectomy and axillary lymph node dissection, followed by postoperative adjuvant chemotherapy and radiotherapy. After 3 years of follow-up, no local recurrence or metastases were found. Results: FNAC yielded moderately cellular smears composed of loosely cohesive clusters of large, polygonal cells with abundant, basophilic and granular cytoplasm suggestive of malignant neoplasm with apocrine features. On gross examination of the quadrantectomy specimen, a grayish-white, solid growth with pushing borders measuring 2.5x1.7x1.5 cm was identified. Twenty-one lymph nodes measuring from 0.3 to 1.3 cm were dissected. Histologically atypical apocrine adenosis, low- and high-grade apocrine ductal carcinoma in situ (ADCIS) and 9 foci of microinvasive apocrine carcinoma (0.1-0.5mm) were found. Apocrine metaplasia was identified in the surrounding ducts. No nodal involvement was observed and the surgical margins were tumor free. Immunohistochemistry revealed that malignant cells (ADCIS and microinvasive carcinoma) were strongly positive for gross cystic disease fluid protein-15, Her2, and androgen receptor, and negative for estrogen and progesterone receptors. Ki67 proliferative index was approximately 15-20%, while 20-25% of the tumor cells were immunoreactive for p53. Conclusions: Here we report a case in which all of the stages involved in apocrine carcinoma progression were identified, from benign metaplasia to hyperplasia, atypia, ADCIS, to microinvasive cancer.
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Correlation between cytopathology and histopathology in women with squamous cell abnormalities of the uterine cervix
(Macedonian Association of Pathology, 2016-09)
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Objective: The objective of our study was to investigate the correlation between cytology and cervical biopsy findings in women with squamous cell abnormalities on cervical cytology. Material and Methods: A comparative retrospective study was conducted in the period from September 2015 to March 2016 in a series of 184 sexually active women, aged from 20 to 60 years, with squamous cell abnormalities in the liquid-based cytology test. In all women, cervical biopsy with endocervical curettage was performed colposcopically for histopathological analysis. Results: Cytologically, there were 118 (64.13%) atypical squamous cells of undetermined significance (ASC-US), 22 (11.96%) low-grade squamous intraepithelial lesions (LSIL), 38 (20.65%) high-grade squamous intraepithelial lesions (HSIL) and 6 (3.26%) invasive squamous cell carcinoma cases. According to the histopathological findings in the cervical biopsy and/or endocervical curettage material in 108 (58.70%) women only nonneoplastic lesions were diagnosed. Twenty-four (13.04%) women had histologically confirmed LSIL, 42 (22.83%) had HSIL and in 10 (5.43%) cases invasive SCC was confirmed. For all squamous cell abnormalities, the sensitivity of the liquid-based cytology test in LSIL and higher grade lesions was 58.70% (108/184) and false positivity was 41.30% (76/184). Excluding ASC-US lesions, the sensitivity of the liquid-based cytology test was 78.80% (52/66) and the false positivity was 21.21% (14/66). The positive predictive value was 100% (6/6) for invasive SCC, 68.42% (26/38) for HSIL and 31.82% (7/22) for LSIL. Conclusions: The high sensitivity of the liquid-based cytology test for HSILs shows that it is an effective screening test for cervical cancer and its precursor lesions.

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