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Published on: January 19, 2019
Poorly differentiated lung adenocarcinomas with concurrent ALK and CD30 expression: a diagnostic pitfall mimicking
Jietian Jin1, Wenjian Cen2, Qin Yan1
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.
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.
