Wild-Type Anaplastic Lymphoma Kinase Expression in Solitary Pulmonary Nodules: A Potential Marker for Primary Lung Squamous Cell Carcinoma in Patients With Previous Neck Squamous Cell Carcinoma

TL;DR

This paper explores using wild-type ALK as a marker to distinguish primary lung SCC from metastatic HNSCC in patients with a history of neck cancer.

Contribution

The study presents two cases where wild-type ALK IHC helped diagnose primary lung SCC in patients with prior HNSCC.

Findings

Wild-type ALK positivity was observed only in lung lesions, not in metastatic SCC from HNSCC.

ALK IHC combined with FISH can aid in differentiating primary LSCC from metastatic SCC.

This approach may guide postoperative strategies in patients with solitary pulmonary nodules.

Abstract

In patients with a history of head and neck squamous cell carcinoma (HNSCC), distinguishing between primary lung squamous cell carcinoma (LSCC) and pulmonary metastasis of HNSCC is critical when a solitary pulmonary nodule is observed. However, differentiation in clinical practice remains challenging because no golden-standard immunohistochemical (IHC) marker has been established to identify the primary organ of squamous cell carcinoma (SCC). The anaplastic lymphoma kinase (ALK) gene harbors rearrangements in approximately 4-6% of non-small cell lung cancer (NSCLC) cases. The detection of ALK rearrangements is well-established through anti-ALK IHC. While anti-ALK IHC is primarily positive in adenocarcinoma within NSCLC, wild-type ALK without rearrangements is occasionally detected in other histological types, such as SCC. We report two surgical cases with a history of laryngeal cancer that exhibited solitary pulmonary SCC, in which only the lung lesions demonstrated positivity for wild-type ALK through IHC and fluorescence in-situ hybridization method, allowing for the diagnosis of primary LSCC and following postoperative strategy.

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