A Case of ALK‐Rearranged Combined Lung Adenocarcinoma and Neuroendocrine Carcinoma with Diffuse Bone Metastasis and Partial Response to Alectinib

We report a rare case of stage IV pulmonary combined large-cell neuroendocrine carcinoma
(LCNEC) and adenocarcinoma (ACA), both demonstrating anaplastic lymphoma kinase (ALK)
rearrangement by IHC and FISH. This 61-year-old lifelong nonsmoking Asian woman presented with
a cough, and after diagnosis and surgical treatment, completed four cycles of adjuvant cisplatin and
etoposide chemotherapy. She subsequently developed recurrence with bony metastases of exclusively
ALK-positive LCNEC. Alectinib was started, and the patient experienced a partial response READ ARTICLE

Current Oncology DOI:10.3390/curroncol29020072

Authors: Chloe A. Lim, Norbert Banyi, Tracy Tucker, Diana N. Ionescu, Barbara Melosky

Case StudyKirk SmithFebruary 3, 2022neuroendocrine, adenocarcinoma, driver mutation, ALK, LCNEC

Heterogeneous Tumor-Immune Microenvironments between Primary and Metastatic Tumors in a Patient with ALK Rearrangement-Positive Large Cell Neuroendocrine Carcinoma

We present a case study of a 32-year-old female patient with ALK-rearrangement-positive LCNEC, who had multiple distant metastases including mediastinal lymph-node, bilateral breasts, multiple bones, liver and brain. Multiple biopsy samples obtained from primary lung and three metastatic tumors were analyzed by fluorescent multiplex immunohistochemistry. Tissue localizations of tumor-infiltrating lymphocytes in the tumor nest and surrounding stroma were evaluated. T cell and B cell infiltrations were decreased with distance from primary lung lesion. Although each tumor displayed a unique TIME, all tumors exhibited concomitant regression after treatment with an ALK-inhibitor. This study provides the first evidence of the coexistence of distinct TIME within a single individual with ALK-rearrangement-positive LCNEC. The present study contributes to our understanding of heterogeneous TIMEs between primary and metastatic lesions and provides new insights into the complex interplay between host-immunity and cancer cells in primary and metastatic lesions. READ ARTICLE

International Journal of Molecular Science DOI: 10.3390/ijms21249705

Authors: Tashiro T, Imamura K, Tomita Y, Tamanoi D, Takaki A, Sugahara K, Sato R, Saruwatari K, Sakata S, Inaba M, Ushijima S, Hirata N, Sakagami T

Case StudyKirk SmithDecember 19, 2020B cell, ALK, heterogeneity, immune checkpoint, large cell neuroendocrine carcinoma, LCNEC, neuroendocrine tumors, NET, PD-L1, regulatory T-cells, Tregs, tumor-immune microenvironments, TIME, tumor-infiltrating lymphocyte, TIL