Faculty of Medicine

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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 clinico-pathological characteristics, Ki67 and p53 expression in triple negative and non-triple negative breast cancer – A single center experience
(Klinicko bolnicki centar Zemun - Beograd, 2016)
Ognenoska-Jankovska, Biljana
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Stojkoska, Elena
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Qerimi, Adelina
Aim: The aims of our study were to compare clinicopathological characteristics, Ki-67 and p53 expression between triple-negative (TN) and non-TN invasive breast carcinomas. Introduction: TN breast cancer is associated with a higher histologic grade, shorter survival, and a higher recurrence rate. TN tumors usually express high levels of p53 and Ki67 that is currently considered prognostic markers for patients with breast cancer. Materials and Methods: A total of consecutive 189 breast carcinoma cases analyzed in our department in 2013 were included in this study. Clinicopathological characteristics such as age, tumor (pT), nodal status (pN), and grade, and Ki-67 and p53 expression were compared between the TN and non-TN groups using Pearson's chi-square and Student's t-test. Results: Mean age for the two groups was 59 years, and vary between 36 and 84, and there was no significant difference in the groups. There was no significant difference in the pT between TN and non-TN group. G (p<0.05) and pN (p<0.01) were significantly higher than that in the non-TN group. Ki-67 expression in the TN group was significantly higher than that in the non-TN group (p<0.01), and significantly correlated with the G (p<0.01), but not with pT and pN. p53 expression in the TN group was significantly higher (p<0.01), but was not significantly correlated with pT, pN and G. Conclusions: TN breast carcinomas have higher grade and nodal status, and they are associated with significantly higher expression of Ki-67 and p53 compared with non-TN tumors.
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Superficial leiomyoma of the gastrointestinal tract with interstitial Cajal-like cells
(Springer, 2015-09)
Qerimi, Adelina
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Stojkoska, Elena
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Ognenoska-Jankovska, Biljana
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Objective: Some authors suggest common origin of all gastrointestinal stromal tumours from stem cells, which may show diverse differentiation. There are reports in which cells with a morphology of interstitial Cajal-like cells are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. Method: We have analyzed 9 cases of superficial leiomyomas, received in our institutions as endoscopically or surgically obtained material. The tumour sections were immunohistochemically stained with CD117, CD34, NSE, S 100, α-S MA and desmin. Results: There were one esophageal and 8 colonic superficial leiomyomas, 2 of which rectal. Histological analysis showed presence of stellate cells morphologically similar to the interstitial cells of Cajal. Immunohistochemical analysis showed that in addition to diffuse positivity for -SMA and desmin, all leiomyomas showed presence of CD117, CD34 and NSE positive cells between smooth muscle cells, while six of them showed presence of S-100 positive cells. The cells were found in different quantity, usually were scarce and diffusely scattered through the tumours without predilection site. Conclusion: The presence of CD177, CD 34, S-100 and NSE positive cells in superficial leiomyomas may suggest a common origin of GI stromal tumours.

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