Paget disease is characterized by an intense lymphocytic response, devoid of the immune-suppressive impact of the PD-L1 pathway, but with occasional CTLA-4 expression.

BackgroundBrain metastases (Bmets) are frequent; however, limited data exist on the efficacy of immunotherapy in these lesions. The aims of the study were to analyze the immunohistochemical expressions of programmed death ligand 1 (PD-L1) and CD8 in Bmets and to compare them with their expressions in paired primary tumors, as well as correlate the results with clinicopathological features.MethodsThis is a retrospective study of 233 patients with Bmets and 111 paired primaries. Clinical, histological, and molecular data were recorded and compared with the immunohistochemical results of PD-L1 and CD8 expressions. The statistical analysis included χ2 test, Cramer’s V test, factorial analyses of variance, simple regression analysis, and Kaplan-Meier analysis with log-rank product limit estimation.ResultsPD-L1 expression was found in 23.6% of Bmets and in 29.0% of primary tumors with concordant expression between them in 75.5% of cases. Bmets PD-L1 expression was associated with primary tumor PD-L1 expression and the primary tumor type. Significant CD8 peritumoral expression was found in 68.6% of Bmets and in 87.7% of primary tumors. CD8 expression was concordant between primary and metastatic tumors in 73.3% of cases. Bmets CD8 expression was associated with primary tumor CD8 expression and primary tumor type. PD-L1 expression was associated with CD8 expression in both primary and metastatic tumors. The concordance between primary and metastatic tumor PD-L1 expression was independent of all factors studied. The concordance between primary and metastatic CD8 expressions was marginally associated to the time of Bmets development. No prognostic role for PD-L1 and CD8 expression in Bmets was found.ConclusionPD-L1 and CD8 Bmets expressions are associated with the primary tumor type and its PD-L1 and CD8 expressions. No factor predicts the discordance for PD-L1 expression, while time to Bmets development is associated with CD8 expression discordance.

Although the spread of extragenital tumors to individual female genital tract organs, particularly the ovary, has been much studied, histologic data with regard to secondary tumors involving the whole gynecologic tract are largely lacking. Thus, the aim of the study was to investigate the pathologic and clinical features of these tumors in order to better understand their features. This is a retrospective study of 196 secondary lesions involving the gynecologic tract. The parameters studied were the primary site, its histologic type and grade, the presence of mucous production, the type of secondary involvement, defined as distant metastasis, direct extension or locoregional recurrence, and the time to metastasis. Organs involved were the ovary (50%), the vagina (22%), the myometrium (10.7%), the cervix (10.2%), the endometrium (3.6%), the vulva (2%), and the Fallopian tube (1.5%). Most often, primary tumors were colorectal (39.8%), endometrial (15.3%), breast (12.7%), ovarian (10.7%), and gastric (5.6%). Secondary tumors were metachronous in 43.9% of the cases with a mean time to recurrence of 55.5 mo. Distant metastases were the most common type of secondary involvement (64.8%), followed by direct extension (19.9%) and local recurrence (15.3%). Gastrointestinal tumors involved mostly the ovaries, endometrial tumors the vagina, ovarian tumors the myometrium, and urothelial tumors the cervix/vagina (P<0.0001). Vaginal lesions endometrial origin presented with only superficial invasion (P=0.0002). The primary tumor's features dictate a different pattern of secondary involvement of the gynecologic tract. Endometrial tumors produce mostly superficial vaginal recurrences, mucus-producing gastrointestinal tumors present with ovarian metastases, whereas breast tumors affect the entire gynecologic tract and present the tumors with the most late recurrences.

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