First-Line Lorlatinib for ALK-Rearranged Pulmonary Large-Cell Neuroendocrine Carcinoma with Brain Metastases and Suspected Leptomeningeal Involvement: A Case Report and Literature Review
Abstract
We report a case of ALK-rearranged pulmonary large-cell neuroendocrine carcinoma (LCNEC) with brain metastases and radiologically suspected leptomeningeal involvement, successfully treated with first-line lorlatinib. A 58-year-old woman was diagnosed with LCNEC, and molecular testing revealed an EML4-ALK fusion. Lorlatinib achieved a partial response, with regression of the primary lesion, brain metastases, and suspected leptomeningeal lesions. Our literature review showed that ALK-positive LCNEC occurs more often in younger, female, and never- or light-smoking patients. In such cases, molecular testing should be actively pursued. In LCNEC harboring actionable driver alterations, molecularly guided treatment, as used for NSCLC, may be a reasonable option.
Related
- Subdural Hematoma During Lorlatinib-Induced Regression of Leptomeningeal Carcinomatosis with Suspected Dural Involvement in ALK-Positive Lung Adenocarcinoma
- Beyond the blood-brain barrier: amivantamab plus lazertinib in EGFR-mutant non-small cell lung cancer with brain and leptomeningeal metastases.
- Amivantamab and lazertinib in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer with brain and leptomeningeal metastases: an editorial on efficacy, challenges in assessment, and future directions.
- Complete remission with single agent lorlatinib in children with ALK+ anaplastic large cell lymphoma and central nervous system involvement: a case report
- Cerebral Attack With Cortical-Leptomeningeal Involvement and Seizures in AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder
BibTeX
@article{nakano2026firstline,
title = {{First-Line Lorlatinib for ALK-Rearranged Pulmonary Large-Cell Neuroendocrine Carcinoma with Brain Metastases and Suspected Leptomeningeal Involvement: A Case Report and Literature Review}},
author = {Yoshio Nakano and Kazuya Nishimura and Hiroka Serizawa and Yusuke Kuze and Gen Masuda and Norio Okamoto and Iwao Gohma and Yumiko Yasuhara},
journal = {Internal Medicine},
year = {2026},
month = aug,
doi = {10.2169/internalmedicine.7727-26},
url = {https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_7727-26/_article},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - First-Line Lorlatinib for ALK-Rearranged Pulmonary Large-Cell Neuroendocrine Carcinoma with Brain Metastases and Suspected Leptomeningeal Involvement: A Case Report and Literature Review
AU - Yoshio Nakano
AU - Kazuya Nishimura
AU - Hiroka Serizawa
AU - Yusuke Kuze
AU - Gen Masuda
AU - Norio Okamoto
AU - Iwao Gohma
AU - Yumiko Yasuhara
PY - 2026
DA - 2026/08/19
JO - Internal Medicine
DO - 10.2169/internalmedicine.7727-26
UR - https://www.jstage.jst.go.jp/article/internalmedicine/advpub/0/advpub_7727-26/_article
AB - We report a case of ALK-rearranged pulmonary large-cell neuroendocrine carcinoma (LCNEC) with brain metastases and radiologically suspected leptomeningeal involvement, successfully treated with first-line lorlatinib. A 58-year-old woman was diagnosed with LCNEC, and molecular testing revealed an EML4-ALK fusion. Lorlatinib achieved a partial response, with regression of the primary lesion, brain metastases, and suspected leptomeningeal lesions. Our literature review showed that ALK-positive LCNEC occurs more often in younger, female, and never- or light-smoking patients. In such cases, molecular testing should be actively pursued. In LCNEC harboring actionable driver alterations, molecularly guided treatment, as used for NSCLC, may be a reasonable option.
SN - 1349-7235
SN - 0918-2918
ER -