Anaplastic lymphoma kinase (ALK) rearranged lung adenocarcinoma is frequently characterised by prominent mucin secretion and a heterogeneous population of mucinous cells. These histological features may result in misdiagnosis as invasive mucinous adenocarcinoma.

We conducted a comprehensive analysis of 4 cases of ALK-rearranged lung adenocarcinoma, focusing on the clinicopathological features, genetic mutations, and clinical outcomes. Among these cases, 3 cases were initially diagnosed as invasive mucinous adenocarcinoma, while one case was identified as recurrent invasive mucinous adenocarcinoma. The cohort comprised 3 female and 1 male patient/s, with ages ranging from 47 to 63 years (mean age 54.8 years).

The tumour cells exhibited sieve-like tubular and solid signet ring structures, with evidence of intracytoplasmic and extracellular mucin secretion. Immunohistochemical analysis demonstrated diffuse expression of TTF-1, Napsin A, and ALK(D5F3) in tumour cells, while HNF4a, CK20, and MUC5AC were consistently negative.

Next-generation sequencing analysis confirmed ALK rearrangements in 3 cases. Accurate identification of this specific subtype of lung adenocarcinoma is essential for administering appropriate treatment and reducing the risk of potential misdiagnosis.