Combined Small and Squamous Transformation in EGFR-mutated Lung Adenocarcinoma

Abstract

Histologic transformation has been described as an acquired mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We herein report the case of a woman with stage IV lung adenocarcinoma harboring EGFR exon 19 deletions who was initially treated with EGFR-TKIs; several cytotoxic chemotherapeutic regimens were used when resistance developed. A lymph node re-biopsy revealed histologic transformation of the tumor to combined small-cell lung cancer and squamous cell carcinoma with retained EGFR exon 19 deletions. Following sequential chemotherapy appropriate for transformed histology, a clinical response was achieved.

Keywords: EGFR mutation; acquired resistance; histologic transformation; non-small-cell lung cancer.

Figure 1.

A cytology specimen from a primary tumor confirmed the diagnosis of adenocarcinoma. A repeated evaluation did not reveal any component of small-cell or squamous cell lung carcinoma. (A) Hematoxylin and Eosin staining (200×). (B) Thyroid transcription factor-1 (TTF-1) (200×).

Figure 2.

Chest computed tomography at the time small-cell and squamous cell transformation was detected (A-C). After four cycles of carboplatin+etoposide (D-E).

Figure 3.

Morphologic features and immunohistochemical staining of a biopsy specimen from a right hilar lymph node obtained by endobronchial ultrasound transbronchial needle aspiration confirming histologic transformation to both small-cell and squamous cell lung carcinoma. (A) Hematoxylin and Eosin staining (200×). (B) Synaptophysin (200×). (C) p40 (200×). (D) Cytokeratin AE1/AE3.