The co-occurrence of distinct lung cancer types within the same lobe is an exceedingly rare phenomenon. Here, we present a unique case wherein primary invasive squamous cell carcinoma and invasive adenocarcinoma concurrently manifested in the identical lung lobe. Additionally, we provide a comprehensive overview of the diagnosis and treatment approaches for multiple primary lung cancers, along with highlighting existing challenges based on the most recent guidelines. Our case underscores the importance of sampling each lesion individually, conducting separate diagnostic procedures, and determining the histological subtype for effective treatment planning irrespective of their location or size.

Synchronous multiple lung cancers are rare and refer to the simultaneous presence of two or more primary lung tumors, which present significant challenges in terms of diagnosis and treatment.

We report a case of multiple synchronous lung cancers with hilar lymph node metastasis of small cell carcinoma of unknown origin in a 73-year-old man. Transbronchial lung biopsy revealed squamous cell carcinoma. Although enlargement of lymph node 12u was detected, no distant metastases were observed. The patient was preoperatively diagnosed with T1cN0M0 and underwent thoracoscopic right upper lobectomy with nodal dissection (ND2a). Based on histopathological findings, the primary lesion was squamous cell carcinoma. A microinvasive adenocarcinoma was also observed on the cranial side of the primary lesion. Tumors were detected in two resected lymph nodes (#12u and #11s). Both tumors were pathologically diagnosed as small cell carcinomas. The primary lesion of the small cell carcinoma could not be identified even by whole-body imaging; however, chemotherapy was initiated for hilar lymph node metastasis of the small cell carcinoma of unknown origin.

Multiple synchronous lung cancers can be accompanied by hilar lymph node metastasis of small cell carcinomas of unknown origin.

The incidence of synchronous multiple primary malignancies is low. The presence of different lung tumor types in one patient is rare. Here, we report a rare case of synchronous lung squamous cell cancer and small cell lung cancer in a 60-year-old man. Because of the presence of two different tumor types, the proper treatment must be determined. To identify treatment targets, the genetic features of primary tumor tissues from the lungs were analyzed by next-generation sequencing (NGS). The objective was to analyze the origin and evolution of multiple primary lung cancers. NGS can find the genetic mutation sites of patients to guide treatment and promote the advancement of precision medicine. The effects of standard treatments were evaluated by response evaluation criteria in solid tumors. The results suggest that early treatment of synchronous multiple primary malignancies is a favorable outcome.