Poorly differentiated lung adenocarcinomas with concurrent ALK and CD30 expression: a diagnostic pitfall mimicking ALK‐positive anaplastic large‐cell lymphoma
- 1Department of Pathology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of China
- 2Department of Molecular Diagnostics, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer Sun Yat‐Sen University Cancer Center Guangzhou People's Republic of China
- 3Department of Pathology The Eighth Affiliated Hospital, Sun Yat‐Sen University Shenzhen People's Republic of China
Abstract
Aims: Although ALK rearrangement is a well‐established alteration in lung adenocarcinoma (LUAD), CD30 expression in this setting remains poorly characterized. We analysed a series of poorly differentiated LUADs with concurrent ALK and CD30 expression that closely resemble ALK‐positive anaplastic large‐cell lymphoma (ALCL), focusing on their clinicopathological and molecular features as well as potential diagnostic and therapeutic implications.
Methods and results: We retrospectively searched multi‐institutional case databases and the published literature, ultimately identifying eight cases of poorly differentiated LUAD with concurrent ALK and CD30 expression. Clinical, histomorphological, immunohistochemical and molecular features, along with treatment responses and outcomes, were systematically recorded and analysed. Patients had a median age of 47.5 years (range, 26–67 years), with equal sex distribution and all presented with advanced‐stage disease (stage III–IV). The diagnostic challenge posed by these tumours was substantial: four cases were initially radiologically suspected to represent aggressive lymphoma, and one patient had been misdiagnosed and actively treated as ALCL at an outside institution before referral. Histologically, all tumours consisted of diffuse sheets of markedly pleomorphic large cells with prominent nucleoli and brisk mitotic activity, a morphology strikingly reminiscent of ALCL hallmark cells. Most cases showed diffuse or focal expression of epithelial markers, with variable TTF‐1 positivity. The Ki‐67 proliferation index ranged from 50% to 95%. All cases co‐expressed ALK and CD30, lacked lymphoma‐associated immunophenotypic markers and showed no evidence of clonal T‐cell receptor gene rearrangement (TCR). Molecular sequencing confirmed that all ALK fusion breakpoints corresponded to previously described LUAD‐associated variants, and all patients achieved marked responses to ALK‐directed therapy.
Conclusions: Poorly differentiated LUAD with dual ALK and CD30 expression is a rare but diagnostically challenging entity that can closely simulate ALK‐positive ALCL. Awareness of this mimic is critical to ensure accurate diagnosis and timely initiation of appropriate targeted therapy.
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BibTeX
@article{jin2026poorly,
title = {{Poorly differentiated lung adenocarcinomas with concurrent ALK and CD30 expression: a diagnostic pitfall mimicking ALK‐positive anaplastic large‐cell lymphoma}},
author = {Jietian Jin and Wenjian Cen and Qin Yan and Yangshan Chen and Chaoyun Huang and Yanfeng Feng and Neng Jiang},
journal = {Histopathology},
year = {2026},
month = jul,
doi = {10.1111/his.70257},
url = {https://doi.org/10.1111/his.70257},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Poorly differentiated lung adenocarcinomas with concurrent ALK and CD30 expression: a diagnostic pitfall mimicking ALK‐positive anaplastic large‐cell lymphoma
AU - Jietian Jin
AU - Wenjian Cen
AU - Qin Yan
AU - Yangshan Chen
AU - Chaoyun Huang
AU - Yanfeng Feng
AU - Neng Jiang
PY - 2026
DA - 2026/07/31
JO - Histopathology
DO - 10.1111/his.70257
UR - https://doi.org/10.1111/his.70257
AB - Aims: Although ALK rearrangement is a well‐established alteration in lung adenocarcinoma (LUAD), CD30 expression in this setting remains poorly characterized. We analysed a series of poorly differentiated LUADs with concurrent ALK and CD30 expression that closely resemble ALK‐positive anaplastic large‐cell lymphoma (ALCL), focusing on their clinicopathological and molecular features as well as potential diagnostic and therapeutic implications. Methods and results: We retrospectively searched multi‐institutional case databases and the published literature, ultimately identifying eight cases of poorly differentiated LUAD with concurrent ALK and CD30 expression. Clinical, histomorphological, immunohistochemical and molecular features, along with treatment responses and outcomes, were systematically recorded and analysed. Patients had a median age of 47.5 years (range, 26–67 years), with equal sex distribution and all presented with advanced‐stage disease (stage III–IV). The diagnostic challenge posed by these tumours was substantial: four cases were initially radiologically suspected to represent aggressive lymphoma, and one patient had been misdiagnosed and actively treated as ALCL at an outside institution before referral. Histologically, all tumours consisted of diffuse sheets of markedly pleomorphic large cells with prominent nucleoli and brisk mitotic activity, a morphology strikingly reminiscent of ALCL hallmark cells. Most cases showed diffuse or focal expression of epithelial markers, with variable TTF‐1 positivity. The Ki‐67 proliferation index ranged from 50% to 95%. All cases co‐expressed ALK and CD30, lacked lymphoma‐associated immunophenotypic markers and showed no evidence of clonal T‐cell receptor gene rearrangement (TCR). Molecular sequencing confirmed that all ALK fusion breakpoints corresponded to previously described LUAD‐associated variants, and all patients achieved marked responses to ALK‐directed therapy. Conclusions: Poorly differentiated LUAD with dual ALK and CD30 expression is a rare but diagnostically challenging entity that can closely simulate ALK‐positive ALCL. Awareness of this mimic is critical to ensure accurate diagnosis and timely initiation of appropriate targeted therapy.
SN - 0309-0167
SN - 1365-2559
ER -