# 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.

## Key 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.