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

Hermans, B. C. M., Derks, J., Groen, H. J. M., Stigt, J. A., van Suylen, R. J., Hillen, L. M., van den Broek, E. C., Speel, E-J. M. & Dingemans, A-M. C., Dec-2019, In : Endocrine Connections. 8, 12, p. 1600-1606 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Bregtje C M Hermans
  • Jules Derks
  • Harry J M Groen
  • Jos A Stigt
  • Robert Jan van Suylen
  • Lisa M Hillen
  • Esther C van den Broek
  • Ernst-Jan M Speel
  • Anne-Marie C Dingemans

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.

Original languageEnglish
Pages (from-to)1600-1606
Number of pages7
JournalEndocrine Connections
Issue number12
Early online date1-Nov-2019
Publication statusPublished - Dec-2019

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