Merkel hücreli karsinomda tanısal ve prognostik belirteçler

Objective: Merkel cell carcinoma (MCC), also known as primary neuroendocrine carcinoma of the skin, is a rare but aggressive tumor. Its diagnosis is based on histopathological and immunohistochemical examinations, and perinuclear punctate staining with Cytokeratin 20 (CK20) is an unexpected diagnostic finding in other neuroendocrine carcinomas. In the light of the discovery of Merkel cell polyomavirus (MCPyV) by Feng et al. in 2008 and molecular studies, it is now known that sun damage and MCPyV play the major role in tumor development. According to geographical region and viral pathogen identification technique, the rate of MCPyV positive cases varies between 49-89% in the literature. Recently, it has been suggested that virus-associated (MCPyV (+)) and sun-damage-related (MCPyV (-)) cases may differ from each other in terms of morphology, immunohistochemistry, and prognosis. Our aim is to divide cases into MCPyV (+) and (-) subgroups with the help of immunohistochemical markers and to investigate the differences between them. Material and Methods: Between 2002 and 2022, patients diagnosed with MCC in the Department of Pathology of Istanbul Faculty of Medicine were identified by scanning the archive records created in the computer environment. Slides of biopsy and excision material of 67 patients were re-evaluated. A total of 13 cases, whose paraffin block material could not be reached or considered unsuitable for the study, were excluded from the study and the study was continued with 54 cases. Appropriate blocks were selected so that the immunohistochemical evaluation could be performed properly. Antibodies to CK20 (clones Ks20.8 and SP33), MCPyV (clones Ab3 and CM2B4), p53 (DO-1), Rb1 (358) and Ki67 (MIB-1) were administered. The clinical parameters of the cases were obtained through the hospital automation system, oncology file archives and, in cases that could not be accessed in this way, one-on-one contact with the patient or patient relatives. Results: Fifty-four patients' ages at the time of diagnosis ranged from 24-91 years, with a mean of 67. 26 patients were female, 28 patients were male. 42 cases demonstrated extremity, head-neck and trunk distribution, and 12 cases were MCC cases with primary nodal involvement without a cutaneous lesion. Tumor diameters of the patients at the time of diagnosis ranged from 0.6-20 cm, and the mean tumor diameter was 3.8 cm. At admission, 10 (18.5%) patients were stage I, 14 (25.9%) patients were stage II, 25 (46.3%) patients were stage III, and 5 (9.3%) patients were stage IV. On histopathological examinations, tumor cells were often round shaped, with narrow cytoplasm and clear chromatin. Cases were rich in mitosis and the number of mitoses per mm2 ranged from 4 to 85. Lymphovascular invasion was detected in 37% of the patients. Immunohistochemical study with MCPyV (clone Ab3) revealed 44 (81.5%) cases with positive results. When we investigated the clinical characteristics of MCPyV (+) and (-) patients, there was no significant difference between them in terms of age and location, while MCPyV (-) cases were male at a rate of 90%. There was no significant difference between MCPyV (+) and (-) cases in terms of morphology, other than larger cytoplasm that is detected more often in MCPyV (-) cases. There were 5 cases which the CM2B4 clone did not stain and 8 cases which it stained weakly and/or at low percentages while they were positive with the Ab3 clone. Only 2 cases were negative with CK20 Ks20.8 and SP33 clones and these cases were MCPyV (-) (p=0.031). Staining compatible with mutation of p53 was found to be 70% and 50% in the MCPyV (-) group and 31.8% and 11.4% in the MCPyV (+) group at the cut-off values of 20% and 50%, respectively (p=0.025 and 0.013). Loss of expression of Rb1 was detected at a rate of 40% in the MCPyV (-) group and 22.7% in the MCPyV (+) group (p=0.020). ≥20% staining with Rb1 was seen only in the MCPyV (+) cases. Ki67 scores of the cases ranged from 15 to 95%, and when we assess the mean of the MCPyV (+) and MCPyV (-) groups in terms of Ki67 scores, it was 54.7% in MCPyV (+) and 71.3% in MCPyV (-) (p=0.020). In our series, disease-related death was observed at a rate of 39.6%, and the mean expected survival time in MCPyV (+) patients was calculated as 111.5±12.8 months, and in MCPyV (-) patients as 50±12.7 months (p=0.393). When the mean Ki67 scores of patients with and without distant metastasis were evaluated, 65.9% and 54.3% values were found (p=0.048). With a threshold value of 50%, patients whose Ki67 score was below 50% was found to have a significantly longer survival (p=0.030). Cox regression analysis showed that male gender and advanced stage (III - IV) shortened the survival (p=0.041 and 0.005). Conclusion: No significant difference was found between 44 MCPyV (+) and 10 MCPyV (-) cases in our series in terms of age and location; nevertheless, it was observed that MCPyV (-) cases were mostly male. Morphologically, no distinctive morphological finding was found between MCPyV (+) and (-) cases, except for cytoplasmic features. Clone Ab3 was found to be more successful in identifying MCPyV (+) and (-) groups compared to CM2B4. It was determined that CK20 negativity, staining compatible with p53 mutation, loss of expression of Rb1 and high Ki67 score were the distinguishing features of MCPyV (-) compared to MCPyV (+) group. Ki67 score was found to be useful in predicting distant metastasis and determining survival times when we set the threshold value of 50%. It was also determined that male gender and advanced stage (III - IV) had an effect on disease-related survival. It was shown that MCPyV status did not have a significant effect on survival.