Metastatic bone lesions of men in combination with an increase in serum PSA from the point of view of diagnosing carcinomas of unknown primary localization

Abstract

In cases of “malignant neoplasm of unknown origin” of men with bone metastases, it is the serum PSA level that can be crucial for further treatment. The literature describes carcinomas with bone metastases and an increase in the prostate-specific antigen, which were twice refuted by a prostate biopsy but had a positive dynamic during anti-androgen therapy (bicalutamide) in combination with chemotherapy (zoledronic acid). The aim of the work is to improve diagnostic algorithms, to investigate a complex of morphological, morphometric and immunohistochemical characteristics of metastatic foci in the bones, which are represented by adenocarcinomas of unknown primary localization in men with increased serological marker PSA, compared with primary carcinomas of the prostate gland. Materials and methods. A retrospective analysis of clinical data, histological and immunohistochemical characteristics of 21 observations of biopsy material from patients with primary carcinoma of the prostate gland (group 1, men aged 56 to 82 years, average 66.00 ± 7.76; median 65) and 10 patients with bone carcinoma metastases without primary localization and increased serum marker PSA (group 2, men aged 43 to 57 years, mean 50.00 ± 9.89; median 46.5) on the basis of the morphological department of diagnostic center “Pharmacy of Medical Academy” for the period 2015–2017. Results. Morphological, morphometric and immunohistochemical changes of carcinomas of unknown primary site in men with metastatic bone lesions and increased serum marker PSA associated with the acquisition of more aggressive properties were identified in comparison with the primary carcinomas of the prostate gland, which tend to local distribution. There were prevalence of poorly differentiated histological forms of metastatic adenocarcinomas, an objective reduction in the area and perimeter of nuclei (P = 0.00002, P < 0.0001, respectively), possible loss of immunohistochemical markers AMACR (p504s) and AR (androgen receptors) specific for acinar prostate carcinomas (P = 0.008). Conclusion. The use of minimal primary immunohistochemical panel from cytokeratin, Pan AE1/AE3 (+) / Vimentin(-) / CD45(-) / S100(-) and secondary – cytokeratin 8(+) / PSA(+) / AMACR (p504s)(+) panels / AR(+/-) will allow to prove the conformity of the carcinoma phenotype with unknown primary site in men with metastatic bone lesions and an increase in the PSA serological marker to the form of disseminated prostate carcinoma with justification for the use of appropriate therapy in cases of non-informative prostate biopsy.