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Case Reports
. 2024 May 31;13(5):1150-1162.
doi: 10.21037/tlcr-24-352. Epub 2024 May 24.

A rare case report of a primary lung cancer comprising adenocarcinoma and atypical carcinoid tumor, with the carcinoid component harboring EML4-ALK rearrangement

Wenbin Hu  1 , Jiaming Zhao  1 , Guoxia Wang  1 , Qihao Wang  1 , Mingming Deng  2 , Jie Shen  3 , Paul Hofman  4 , Edyta Maria Urbanska  5 , Eric Santoni-Rugiu  6 , Petros Christopoulos  7 , Robert A Ramirez  8 , Toyoaki Hida  9 , Xiaoqing Lu  10 , Binjun He  1
Affiliations
Case Reports

A rare case report of a primary lung cancer comprising adenocarcinoma and atypical carcinoid tumor, with the carcinoid component harboring EML4-ALK rearrangement

Wenbin Hu et al. Transl Lung Cancer Res. .

Abstract

Background: The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of EML4-ALK fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown. The advances of therapy development in such patients are still limited and there is no standard treatment. We present a case of collision tumor in the lung consisting of atypical carcinoid and adenocarcinoma to better understand the clinical characteristics of this disease.

Case description: We report an extremely rare case of EML4-ALK rearrangement in a pulmonary atypical carcinoid tumor that coexisting with adenocarcinoma. A 58-year-old woman, who was asymptomatic, underwent pulmonary lobectomy due to the detection of a gradually enlarging solitary pulmonary nodule in the right upper lung. Histological examination of the resected tumor revealed the presence of both atypical carcinoid (approximately 80%) and adenocarcinoma (approximately 20%) components. Metastases by the carcinoid component were observed in mediastinal lymph nodes (station 2R and 4R) and in the primary tumor. Anaplastic lymphoma kinase (ALK) rearrangement was detected in both the primary and metastatic lesions of the carcinoid tumor. Four cycles of chemotherapy with etoposide and carboplatin were dispensed after surgery.

Conclusions: This is the first reported case of coexisting pulmonary adenocarcinoma and atypical carcinoid tumor with an ALK fusion only detected in the carcinoid component. The presence of ALK rearrangement in pulmonary carcinoid tumor is very uncommon, and there is currently no standard treatment for advanced stages. Therefore, comprehensive molecular testing, including ALK rearrangement analysis, should be recommended for mixed tumors exhibiting features of atypical carcinoid. ALK inhibitors could represent a potential treatment strategy for selected patients.

Keywords: ALK rearrangement; case report; pulmonary adenocarcinoma; pulmonary atypical carcinoid.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-352/coif). R.A.R. and T.H. serve as unpaid editorial board members of Translational Lung Cancer Research from January 2024 to December 2025. J.S. is from Dagong Law Firm. E.M.U. received grants from Merck and AstraZeneca; honoraria from Janssen, Amgen, AstraZeneca, Novartis; support for attending meetings and travel from AstraZeneca and Roche; payment for participation in Advisory Board from Roche, Takeda, Pfizer, AstraZeneca. E.S.R. received grants from Sanofi and Takeda; honoraria from Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Roche, Takeda; payment for participation in Advisory Board from Roche and Takeda. P.C. has received research funding from AstraZeneca, Amgen, Boehringer Ingelheim, Merck, Novartis, Roche, and Takeda, speaker’s honoraria from AstraZeneca, Gilead, Janssen, Novartis, Roche, Pfizer, Thermo Fisher, Takeda, support for attending meetings from AstraZeneca, Eli Lilly, Daiichi Sankyo, Janssen, Gilead, Novartis, Pfizer, Takeda, and personal fees for participating to advisory boards from AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda and Roche, all outside the submitted work. R.A.R. has consulting agreements with several companies (TerSera Therapeutics, ITM Radiopharma, Regeneron, Advanced Accelerator Applications, Novartis, Ipsen, Amgen, Astra-Zeneca, Curium, Exelexis, EMD Serono) that manufacture products to treat neuroendocrine tumors and lung cancers, all outside the submitted work. R.A.R. is a Board of Directors member of the North American Neuroendocrine Tumor Society. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Preoperative chest CT scan images. (A) The CT scan shows a round 6 millimeter solid nodule located in the peripheral region of the right upper lobe (posterior segment); (B) the CT scan shows that the nodule has increased to 14 millimeter after 20 months; (C) coronal view of the nodule; (D) sagittal view of the nodule; (E) mediastinal window reveals the pulmonary nodule; (F) the enhanced CT scan shows mild to moderate enhancement of the nodule, and no enlargement of hilar or mediastinal lymph nodes. The red arrows in the image indicate the primary tumor. CT, computed tomography.
Figure 2
Figure 2
3D reconstruction of pulmonary nodule. (A) 3D reconstruction imaging shows the blood supply of the nodule; (B) maximum intensity projection of the nodule; (C) the reconstructed image shows the location of the nodules; (D) 3D reconstruction imaging shows the location relationship between the nodules and bronchus; (E) 3D reconstruction imaging shows the location relationship between the nodules and pulmonary arteries; (F) 3D reconstruction imaging shows the location relationship between the nodules and pulmonary veins. 3D, 3-dimensional.
Figure 3
Figure 3
Histopathological image of the surgical specimen. (A) H&E of the atypical carcinoid tumor component, ×10; (B) H&E of the adenocarcinoma component, ×10; (C) H&E reveals indistinct boundary between the tumor components of atypical carcinoid and adenocarcinoma, ×10; (D) H&E reveals mitosis of the carcinoid cell, ×20; (E) H&E reveals mitosis of the carcinoid cell, ×20; (F) H&E reveals the carcinoid component with necrosis, ×20; (G) elastic fiber staining shows elastic fiber breakage, ×10; (H) H&E reveals lymphovascular invasion by the carcinoid component, ×10; (I) H&E reveals metastasis of carcinoid cells in lymph nodes, ×10. The yellow line indicates the boundary between two tumor components. The yellow arrows indicate the mitosis in (D)-(E), the necrosis in (F), the elastic fiber breakage in (G). H&E, hematoxylin and eosin.
Figure 4
Figure 4
Immunohistochemical staining results of lymphovascular invasion and lymph node metastasis of carcinoid component. (A-C) The lymphovascular invasion of atypical carcinoid component stains positive for CgA (A), Syn (B), and CD56 (C). Magnification ×40. (D-F) The metastasis of carcinoid cells in lymph nodes stains positive for CgA (D), Syn (E), and CD56 (F). Magnification ×10. CgA, chromogranin A; Syn, synaptophysin; CD56, cluster of differentiation 56.
Figure 5
Figure 5
The results of immunohistochemistry and FISH. (A) The adenocarcinoma component stains partially positive for napsin A, ×10; (B) the adenocarcinoma component stains positive for TTF-1, ×10; (C) the atypical carcinoid component stains positive for CgA, ×10; (D) the atypical carcinoid component stains positive for Syn, ×10; (E) the atypical carcinoid component stains positive for CD56, ×10; (F) the atypical carcinoid component stains positive for ALK, ×40; (G) the adenocarcinoma component stains negative for ALK, ×40; (H) the Ki-67 index of the mixed tumor is approximately 10%, ×20; (I) FISH analysis reveals that the atypical carcinoid component from the primary tumour harbors ALK gene rearrangement (shown by the arrows), ×100; (J) FISH analysis of the metastatic lymph nodes reveals ALK gene rearrangement in tumor cells (shown by the arrows), ×100. FISH, fluorescence in situ hybridization; TTF-1, thyroid transcription factor-1; CgA, chromogranin A; Syn, synaptophysin; CD56, cluster of differentiation 56; ALK, anaplastic lymphoma kinase; Napsin A, novel aspartic proteinase A.
Figure 6
Figure 6
NGS showing the EML4-ALK fusion. NGS, next-generation sequencing; EML-4, echinoderm microtubule associated protein like 4; ALK, anaplastic lymphoma kinase.
See this image and copyright information in PMC

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