Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype.

ABSTRACT: INTRODUCTION:Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (PI) 40-80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up. METHODS:Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1). RESULTS:All patients had N0 or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5-18.5 months). Mean Ki-67 PI was 59% (range 15-100%). In 6/11 LCNEC Ki-67 PI was ?40%. OS was longer for Ki-67 ?40% compared to >40% (17 months (95% CI 11-23 months) vs. 5 months (95% CI 0.7-9 months), p=0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67 ?40%. 8/11 patients could be subclassified and both SCLC-like (n=6) and NSCLC-like (n=2) subtype were present. No MEN1 mutation was found. CONCLUSION:Stage IV LCNEC with a solitary brain metastasis and N0/N1 disease show in the majority of cases Ki-67 PI ?40% and prolonged survival, distinguishing them from general LCNEC. This unique subgroup can be both of the SCLC-like and NSCLC-like subtype.

SUBMITTER: Hermans BCM 

PROVIDER: S-EPMC6933830 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature