Faculty of Medicine

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SQUAMOUS CELL CARCINOMA ARISING IN A KELOID SCAR: A CASE REPORT AND LITERATURE REVIEW
(Macedonian Association of Pathology and North Macedonia Division of IAP, 2025)
Boshkova E
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Angelovska T
Introduction: Keloids are characterized by abnormal fibroblast proliferation and excessive collagen deposition. While typically benign, they have been recognized as potential predisposing factors for cutaneous neoplasia. Case Presentation: We present a rare case of squamous cell carcinoma (SCC) arising within a keloid scar in a 38-year-old female with a history of exuberant keloid formation on the feet. Histopathological examination of the excised lesion revealed moderately differentiated SCC developing within keloid tissue, marked by invasive nests of atypical squamous cells and keratin pearl formation embedded in dense keloidal stroma. Conclusion: Although exceedingly rare, malignant transformation of keloid scars into SCC can occur, particularly in lesions exposed to chronic irritation, inflammation, ulceration, repeated trauma, or ultraviolet radiation. Clinicians should maintain a high index of suspicion when evaluating morphological changes in long-standing keloids. Early biopsy of suspicious lesions is crucial for timely diagnosis and appropriate management.
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INCIDENTAL STUMP DURING CESAREAN SECTION IN IVFEGG DONATION PREGNANCY: A CASE EMPHASIZING THE IMPERATIVE OF ROUTINE HISTOPATHOLOGICAL EVALUATION OF MYOMAS
(Македонско лекарско друштво = Macedonian medical association, 2024-12)
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Onur Dika
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Uterine myomas are commonly benign tumors of the female reproductive system. Although many are diagnosed preoperatively, some are incidentally discovered during obstetric surgery, such as the cesarean section. This case illustrates the necessity of routinely sending any excised uterine myoma for histopathological evaluation to determine its true biological potential and guide further management. We report the case of a 45-year-old primiparous woman (G1P0A1) with a history of in vitro fertilization (IVF) and egg donation, admitted at 37+4 weeks of gestation for elective cesarean section. The procedure was uncomplicated, yet multiple small intramural and subserous myomas were incidentally observed and excised. Histopathological analysis revealed a Smooth Muscle Tumor of Uncertain Malignant Potential (STUMP), characterized by areas of focal necrosis, mild cytologic atypia, and low mitotic activity-features straddling benign leiomyoma and malignant leiomyosarcoma designations. STUMP comprises a rare histologic category representing 0.3-0.9% of presumed fibroids, with unpredictable behavior. Recurrence rates vary from 7% to 36%, with occasional progression to leiomyosarcoma (median time to recurrence ~79 months) [1-5]. Because of this uncertain prognosis, we recommended followup imaging and multidisciplinary consultation. A postoperative MRI followed by hysterectomy revealed additional subserous leiomyomas and chronic granulomatous inflammation. Given the potential risk of progression, the patient underwent definitive hysterectomy with ovarian preservation. This case highlights the crucial role of histopathological evaluation in incidental uterine myomas. Even small lesions may harbor atypical or borderline features warranting close monitoring or definitive treatment. Early detection and accurate classification influence patient prognosis and enable timely surgical and therapeutic interventions. When STUMP is diagnosed, hysterectomy is often recommended as definitive management to reduce recurrence or malignant transformation risk.
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PLACENTAL SITE NODULE : A RARE CASE REPORT
(Македонско лекарско друштво = Macedonian medical association, 2025-09)
Nurxhan Ajeti
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Arta Islami Zulfiu
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Ilirjan Zulfiu
Placental site nodule is a rare, benign non neoplastic lesion of intermediate trophoblastic origin which is thought to represent incomplete involution of the placental implantation site. It is often discovered incidentally in women in reproductive period during evaluation for abnormal uterine bleeding. Although typically not harmful, they can sometimes mimic more serious condition, requiring careful diagnosis.It can be associated with recurrent pregnancy loss , infertility, history of prior intrauterine instrumentation and chronic endometritis. We present a case, 30- year old women who developed abnormal uterine bleeding one year after a full term vaginal delivery. From obstetric history,one pregnancy ended with vaginal delivery of the fetus in term without complication.She had no other interventions on the uterus.Transvaginal ultrasound revealed an intrauterine lesion suspected to be an endometrial polyp. A diagnostic endometrial curettage was performed to evaluate for the endometrial pathology. The obtained tisssue was sent for histopathology analysis . According to the described morphology and immunohistochemical analysis during the histopathological examination of the endometrial tissue, finding corresponds to a placental site noule : a small 4 mm nodule composed of intermediate trophoblastic cells of chorionic type embedded in markedly hyalinized stroma. The trophoblastic cells very in size, from relatively small with uniform nuclei to cells with abundant eosinophilic to ampholphilic cytoplasm (PLAP +,BHCG-). At the next check-up immediately after curettage, the endometrium was 10 mm , without pathological lesions intracavitary. Serum B - human chorionic gonadotropin was negative. On follow - up, the patient had regular menstruation and serum B-human chorionic gonadotrpin was negative. Placental site nodule should be considered in the differential diagnosis of intrauterine lesions, especially in women with recent pregnancy history .Timely and accurate diagnosis is essential to distinguish Placental Site nodule from malignant conditions,avoiding unnecessary interventions. Appropriate clinical management ensures optimal outcomes and reduces the risk of complication or misdiagnosis. Early recognition and follow - up are the key to minimizing long term consequences for women's reproductive health.
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Computer system for data processing in a histopathology and cytopathology laboratory
(Science Printers and Publishers, 1990-06)
Stavrik, George
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Zografski, George
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Ivkovski, Ljube
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Trpkov, Kiril
A computer system for data processing in a histopathology and cytopathology laboratory handling about 16,000 new specimens a year is described. The system is used for storing all data, producing the reports, identifying unfinished cases, retrieving previous reports for patients with new specimens, tabulating specific findings, making monthly reports of diagnoses of malignancy, correlating histologic and cytologic diagnoses, surveying findings according to organ and morphology, and billing. The introduction of the computer system has provided significant augmentation of productivity and a basis for quality control, scientific research and cytopathologic correlations.
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Endometrial adenocarcinoma occuring in young women
(Hellenic Division of International Academy of Pathology, 2003-05)
Kubelka-Sabit, Katerina
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Prodanova, Irina
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Yashar, Genghis
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Zografski, George
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Background: Endometrial adenocarcinoma (EA) primarily occurs in postmenopausal women. Only 1-8% of the cases are diagnosed in women under forty years of age, while this neoplasm is extremely rare in the third decade. Hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy (HSOPL) is the treatment of choice for older or patients with invasive EA. However, in young women with non-invasive well-differentiated EAs, who wish to preserve their fertility, conservative treatment with progestins can be tried. Aims: The purpose of this retrospective study is to present the clinical and morphologic characteristics, as well as the immunohistochemical profile of 3 cases of well-differentiated EAs, that occurred in women in their third decade of life. Since the neoplasms were non-invasive, an attempt to preserve their fertility has been made. Methods and patients: Six of the 1081 cases (0.5%) of EA diagnosed at the Department of Histopathology and Clinical Cytology in the last 14-year period (1989-2002), occurred in patients younger than 35 years. Three of them (1.4%, 3/206), have been diagnosed in the last two years (2001-2002). The youngest of the last three patients (age 21), had a genetic abnormality (45X/47XXX) and experienced prolonged and heavy uterine bleedings that required explorative curettage. The second patient (age 25) had a history of diabetes and infertility. The neoplasm was found in the endometrial biopsy that was taken for evaluation of the endometrial response to hormonal stimulation. In the third patient (age 27) the neoplasm was an accidental finding in the cervical curettage material that was submitted to our department, for histopathologic reevaluation of the previously diagnosed moderate dysplasia of the epithelium of the uterine cervix. The materials, obtained either by dilatation and curettage (3 cases) or HSOPL (one case), were submitted to our department and were routinely processed. Standard hematoxylin and eosin (H&E) stained slides were prepared from paraffin blocks, whereas additional histochemical (PAS, alcian blue, azan, silver by Jones) and immunohistochemical stains (estrogen-ER, progesterone-PgR, p53, Ki-67) were performed on selected paraffin blocks that contained the neoplastic tissue. Results: In the curettage materials of the three patients, fragments of endometrial polyp were identfied, that contained areas of simple, complex and atypical hyperplasia. In each of these cases, only few small (1-3-millimetre in diameter) foci of well-differentiated EA were detected. Fragments of functional endometrium were also present. All three patients had hormone (ER, PgR) responsive neoplasms, whereas Ki-67 proliferative index was significantly higher in the neoplastic tissue (30-40%), compared to the zones of atypical hyperplasia (10-20%). The suppressor gene protein product p53 was negative in all three EAs. Subsequent dilatation and curettage to remove the residual parts of the polyp was performed in two of the patients. Conservative 5-6-month treatment with progestins led to regression of the disease in all patients, documented by endoscopy and curettage in two patients. As for the youngest patient, clinical decision for HSOPL has been made, and multiple sections of the operative material did not show any residual EA. Conclusions: Even though extremely rare, EAS may occur in asymptomatic patient and/or in young women without clinical evidence of polycystic ovary disease. In these patients careful histopathologic evaluation of the curettage material is essential, in order to select the ones to whom conservative fertility-preserving treatment can be offered.
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Malignant diffuse peritoneal leiomyomatosis: A case report
(Expansion Scientifique Publications, 1998-10)
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Ivkovski, Ljube
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Yashar, Genghis
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Veljanovska, Slavica
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Vuzevski, Vojislav
Diffuse peritoneal leiomyomatosis (DPL) is a rare condition characterized by the presence of multiple abdominal smooth muscle nodules. Malignant transformation appears to be extremely rare. This report presents the eighth case with proven malignancy. The patient is a 43 year old, Caucasian, non-pregnant female, with no history of hormonal therapy, presented with a few months old history of intermittent and increasing right lower abdominal pain. In October 1996, explorative laparatomy was performed. Innumerable subperitoneal gray-white masses with firm to rubbery consistency, varying in size from 0.2 to 11.5 cm, were found scattered over the parietal peritoneum, omentum and mesentery. Several of these nodules were removed. Their microscopic appearance was variable. Most of the lesions appeared to consist of subperitonel nodules of benign-appearing smooth muscle cells. Nevertheless, some of them showed malignant characteristics, marked cellularity, and numerous mitoses. Immunohistochemical and ultrastuctural studies proved the smooth muscle origin of the tumors. During the next few months the abdominal tumors increased in size and the patient's condition progressively deteriorated. A second laparotomy was performed in March 1997. More than 40 nodules were removed together with a small bowel segment where inflammatory fistula was found. After receiving three courses of chemotherapy, the patient refused further treatment. In December 1997, the patient was admitted to the hospital with acute abdominal pain due to ileus, and the third laparotomy was performed. This additional case indicates that DPL has a low, but definite malignant potential, and suggests that meticulous examination of histologic material and careful follow up are required.
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Small and large cell neuroendocrine carcinomas of the uterine cervix. A report of 10 cases.
(Springer, 2005-08)
Kubelka-Sabit, Katerina
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Plaseska-Karanfilska, Dijana
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Prodanova, Irina
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Yashar, Genghis
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Hadzi-Nicheva, Biljana
BACKGROUND: Small (SCC) and large cell (LCC) neuroendocrine carcinomas of the uterine cervix are rare and highly aggressive neoplasms. Their association with the integration of human papilloma virus (HPV) DNA of the types 16 or 18 has been documented in many studies. AIMS: The purpose of this study is to present the clinical, histopathological, immunohistochemical characteristics and the presence of HPV DNA in ten cases of SCCs and LCCs of the uterine cervix. METHODS: Seven patients with primary SCCs and three patients with LCCs of the uterine cervix were diagnosed at our department between 1989 and 2004. Clinical data were retrieved from the patients’ files and included age, recurrence and survival. Routinely processed operative and/or biopsy specimens were used for immunohistochemical stains and hybridization procedures. Primary antibodies against several epithelial, neuroendocrine, mesenchimal and proliferative markers were included. The presence of HPV DNA was assessed by conventional in situ hybridization (ISH) using probes for HPV 16/18 and 31/33/51 and polymerase chain reaction (PCR), using three primers (MY09/11, GP5+/GP6+, E6). Six of the patients were surgically treated. Postoperatively, four received chemo and/or radiotherapy, two rejected further treatment and one patient was lost to follow-up. The other four patients underwent conservative treatment due to advanced disease. RESULTS: The patients’ age ranged from 25 to 71 years. Histologically, the tumors showed trabecular, nesting or a sheet-like pattern, with areas of necrosis and frequent mitoses. Their neuroendocrine nature was confirmed by diffuse positive immunostaining for neuron-specific enolase and low-molecular weight cytokeratins. Focal positivity for chromogranin, synaptophysin and S100, together with pancytokeratin and EMA, was evident in the majority of the tumors. Their aggressive potential was confirmed by high Ki-67 proliferative index (50-90%). HPV types 16/18 were found in 4 tumors using ISH, and HPV 16 in additional 3, using PCR (type 16). 3 of the patients developed distant metastases and died 7-48 months after receiving partial or full treatment, while 6 are alive and without evidence of disease after 4-38 months. CONCLUSIONS: SCCs and LCCs are highly aggressive neoplasms. However, early diagnosis and combined therapy may improve survival in some patients. Although mainly a morphologic diagnosis, immunohistochemistry may help in the diagnosis of SCC and LCC.
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Benign and malignant pigmented lesions of the female genital tract (FGT). Report of 15 cases.
(Springer, 2001-09)
Kubelka, Katerina
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Yashar, Genghis
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Prodanova, Irina
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Ivkovski, Ljube
Introduction: Benign and malignant pigmented lesions (PL) of the FGT are uncommon, predominantly affecting the vulva. Methods: We report the clinical and pathological features of the 15 PL of the FGT retrieved in a 12-year, retrospective analysis at our Department. Patient records and archival pathology specimens of 7 benign and 8 malignant PL of the FGT, were reviewed. Results: The mean age of all patients was 47 (range, 28-67). Three patients had vulvar nevi (2 intradermal and 1 dysplastic), while blue nevi ranging 2-10 mm in diameter were accidentally discovered in the endocervix of the hysterectomy specimens in four other patients. Vulvar primary malignant melanomas (PMMs) were uncommon (4 cases), comprising 2.5% of female PMMs and 4.3% of all vulvar malignancies diagnosed between 1989 and 2000. Contrary to other studies, all vulvar PMM in our series were of nodular type, ranging 3-13 mm in depth according to Breslow and III-IV level according to Clark. Within the same period, two patients with malignant PL of the uterine cervix were detected, accounting for 0.13% of all females with malignant cervical neoplasms. One of them had a PMM diagnosed in advanced clinical stage (FIGO III), and the other patient had an unusual pigmented squamous cell carcinoma in liB postoperative stage. There were also 2 cases of delayed unilateral ovarian metastases of cutaneous PMM. The diagnosis in all cases of non-vulvar pigmented lesions was confirmed by immunohistochemistry. Conclusions: Although uncommon, PL especially those affecting rare localizations must be considered as diagnostic possibility in FGT.
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Myoepithelial carcinoma of the breast arising in adenomyoepithelioma. A case report.
(Springer, 2001-09)
Yashar, Genghis
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Ivkovski, Ljube
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Kubelka, Katerina
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Zografski, George
Introduction: Adenomyoepithelioma (AME), and especially myoepithelial carcinoma (MC), the malignant variant of this tumor, is a rare breast neoplasm. This report comprises the pathological features of a breast MC arising in AME with an aggressive clinical course. Case report: A 48-year old woman with a palpable mass in the right breast was admitted in November 1998. A month later following FNAB, surgical excision was performed. During the follow-up period of 17 months, until the patient's death, two local recurrences developed. Despite the aggressive chemotherapy, administrated after the first recurrence, subsequently bone, pulmonary and brain metastases appeared. Results: The primary tumor was an ovoid, white-grey, encapsulated mass measuring 4x3,5x1,5 cm. Microscopically, this biphasic tumor was composed of rare tubules surrounded by interlacing bundles of spindle cells exhibiting mild atypia. It was initially classified as a benign phyllodes tumor. The immunohistochemical analyses performed after the second recurrence proved the myoepithelial origin of the neoplasm (S-100, cytokeratin and alpha-SMA positive cells), with a high mitotic index (11 MF/10 HPF), and an immunophenotype indicating aggressive biological potential (steroid receptor negative, 50% Ki-67 and 30% p53 positive cells). Therefore, it was reclassified as MC arising in spindle cell type of AME. Conclusion: The histopathological diagnosis of AME could be very difficult, especially when a distinction from other spindle cell breast neoplasms must be done. Immunohistochemistry is essential to confirm the diagnosis, having in mind the reported pathological characteristics and the immunohistochemical profile of recurrent and malignant tumors of this type.
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Immunohistochemical study of phyllodes tumor of the breast
(Springer, 1999-09)
Yashar, Genghis
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Kubelka, Katerina
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Zografski, George
Phyllodes tumor ('PT) is a rare, fibroepithelial breast neoplasm with unpredictable prognostic and controversial therapeutic aspects. Aims: The aim of this retrospective study is to evaluate Ki-67 and CD34 antigen expression, as well as estrogen (ER) and progesterone receptor (PgR) status in stromal cells, as additional diagnostic criteria in assessing different types of PT. Methods: Routinely processed, formalin-fixed and paraffin-embedded surgical specimens from 47 cases of PT were stained by immunoperoxidase technique using Ki-67, CD34, ER and PgR monoclonal antibodies. On the basis of histopathological criteria proposed by Azzopardi, 6 malignant, 12 borderline and 29 benign PT have been evaluated. The mean size of the tumour was 9.4 cm (range 2.8-20 era). During the follow-up period (mean 50, range 2-127 months), recurrences were observed in 8 patients (17%). Results: The proliferating index determined by Ki-67 antigen expression was significantly different between histologically benign PT (19%), borderline PT (25%) and malignant PT (50%). There was a difference of the human progenitor cell CD34 antigen expression in malignant PT (50%), borderline PT (50%) and benign PT (30%). As expected, the stromal cells in various types of PT were mostly ER negative and PgR positive. Conclusions: Our preliminary results suggest that CD34 positivity and high proliferative index of Ki-67 antigen in stromal cells are more frequently associated with high grade PT. Therefore, the immunohistochemical features could provide better discrimination between different PT types. The prognostic implications of these observations should be evaluated in additional studies.

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