Poorly differentiated lung adenocarcinomas with concurrent ALK and CD30 expression: a diagnostic pitfall mimicking ALK-positive anaplastic large-cell lymphoma
In brief
Rare lung adenocarcinoma mimicking lymphoma responds to ALK inhibitors in all eight cases
In a review of eight poorly differentiated lung adenocarcinomas that co-express ALK and CD30 and resembled ALK-positive anaplastic large-cell lymphoma, all patients had advanced disease and were initially misdiagnosed as lymphoma in half of the cases. Molecular testing confirmed lung-type ALK fusions and every patient achieved marked tumor regression with ALK-directed therapy. Recognizing this mimic can prevent diagnostic errors and ensure timely targeted treatment.
- Journal
- Histopathology (Q1)
- Published
- 31 July 2026
- Study design
- Cohort / observational study
- Evidence level
- Level 4, Very Low (CEBM 4)
- Authors
- Jietian Jin, Wenjian Cen, Qin Yan, Yangshan Chen, Chaoyun Huang, Yanfeng Feng, et al.
- PMID
- 42538745
- DOI
- 10.1111/his.70257
Why clinicians should know about it
- Picked for Histology (paper of the day, 2 August 2026).
- Picked for Hematology (paper of the day, 2 August 2026).
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.