Immunohistochemical expression and prognostic value of PD-L1 in Extrapulmonary small cell carcinoma: a single institution experience.

BACKGROUND: Extrapulmonary small cell carcinomas (ESCC) are rare but aggressive tumors. Relapses are common despite treatment with chemotherapy and/or radiotherapy. Prospective data for treatment of ESCC are lacking; treatment of these cancers usually incorporates lung small cell carcinoma treatment recommendations. Cancer staging remains the most important prognostic factor. Cancer immunotherapy targeting the PD-1/PD-L1 pathway has shown efficacy in multiple tumor types, and could be an appealing treatment strategy for these rare tumors. METHODS: We investigated PD-L1 expression by immunochemistry (IHC) in ESCCs diagnosed at University of Massachusetts Medical Center, from 1999 to 2016. 34 cases with sufficient material were selected for PD-L1 IHC analysis using clone E1L3N. PD-L1 expression was evaluated using the combined positive score (CPS). Retrospective chart review was performed. We evaluated the incidence and prognostic value of PD-L1 expression in ESCC at our institution. RESULTS: Twelve out 34 cases (35%) had PD-L1 CPS scores ≥1. Ten cases had CPS scores ranging 1-5, whereas 2 cases had CPS scores > 80. The overall response rate to the standard chemotherapy with/without radiotherapy in the PD-L1 positive group was 80% versus 67% for the PDL-1 negative group (p-value 0.67). The median overall survival for the PD-L1 positive group, regardless of stage, was 11.5 months versus 7 months for PD-L1 negative group (p-value 0.34). Patients with limited stage disease with positive PD-L1 had a median survival of 53 months compared to 15 months for patients with PD-L1 negative limited stage (p-value 0.80). CONCLUSIONS: This study showed that at least one third of our ESCC tissue samples expressed PD-L1. There was a trend for higher response rates to the standard chemotherapy with/without radiotherapy and improved survival in PD-L1 positive patients. Further studies are required to understand the implications of immune dysregulation in these aggressive tumors. PD-L1/PD-1 inhibitors should be investigated in this group of patients.

Carcinoma de células pequeñas en la unión gastroesofágica / Gastroesophageal junction small cell carcinoma

Resumen Los tumores de células pequeñas extrapulmonares pueden aparecer en múltiples órganos y forman una rara afección clínico-patológica de tumores neuroendocrinos, con gran proliferación epitelial y con comportamiento biológico agresivo. El tubo gastrointestinal es la fuente más común de tumores de células pequeñas extrapulmonares. Nuestro caso clínico describe un paciente con carcinoma de células pequeñas en la unión gastroesofágica, que fue diagnosticado en el contexto de sangrado de tubo digestivo alto. Se excluyó un tumor pulmonar primario; el paciente recibió quimioterapia, quimiorradioterapia y radioterapia cerebral profiláctica, con buena evolución clínica. Nuestro caso se trata de una rara afección clínica, lo que evidencia la importancia de diagnosticar enferemedades poco frecuentes. Existe poca evidencia en la bibliografía de cómo deben tratarse estos pacientes.

Abstract Extrapulmonary small cell carcinomas (EPSCC) can arise in multiple organ sites and form a rare clinicopathological entity of high proliferative epithelial neuroendocrine tumors with aggressive biological behavior. Gastrointestinal is the most common source of EPSCC. We report a case of gastroesophageal junction small cell carcinoma, which was diagnosed in the context of upper gastrointestinal bleeding. A primary small cell lung carcinoma was excluded. Chemotherapy, neoadjuvant chemoradiotherapy and prophylactic cranial radiotherapy were given, with good clinical outcome. Our case of a very rare condition highlights the importance of recognizing atypical pathologic diagnoses. More research needs to be conducted with EPSCC patients in order to better characterize disease pathogenesis, and an optimal disease management.