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

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...

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Autores principales: Hermans, B C M, Derks, J L, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933830/
https://www.ncbi.nlm.nih.gov/pubmed/31751303
http://dx.doi.org/10.1530/EC-19-0372
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author Hermans, B C M
Derks, J L
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
author_facet Hermans, B C M
Derks, J L
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
author_sort Hermans, B C M
collection PubMed
description 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) subtypes 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.
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spelling pubmed-69338302019-12-30 Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype Hermans, B C M Derks, J L 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 Endocr Connect Research 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) subtypes 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. Bioscientifica Ltd 2019-11-14 /pmc/articles/PMC6933830/ /pubmed/31751303 http://dx.doi.org/10.1530/EC-19-0372 Text en © 2019 The authors http://creativecommons.org/licenses/by-nc/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Research
Hermans, B C M
Derks, J L
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
Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype
title Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype
title_full Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype
title_fullStr Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype
title_full_unstemmed Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype
title_short Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype
title_sort large cell neuroendocrine carcinoma with a solitary brain metastasis and low ki-67: a unique subtype
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933830/
https://www.ncbi.nlm.nih.gov/pubmed/31751303
http://dx.doi.org/10.1530/EC-19-0372
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