J Pathol Transl Med.  2016 Jul;50(4):258-263. 10.4132/jptm.2016.04.19.

Transformation to Small Cell Lung Cancer of Pulmonary Adenocarcinoma: Clinicopathologic Analysis of Six Cases

• Ahn S
• Hwang SH
• Han J
• Choi YL
• Lee SH
• Ahn JS
• Park K
• Ahn MJ
• Park WY

• KMID: 2345547
• DOI: http://doi.org/10.4132/jptm.2016.04.19

Abstract

BACKGROUND
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first line treatment for a subset of EGFR-mutated non-small cell lung cancer (NSCLC) patients. Although transformation to small cell lung cancer (SCLC) is one of the known mechanisms of resistance to EGFR TKIs, it is not certain whether transformation to SCLC is exclusively found as a mechanism of TKI resistance in EGFR-mutant tumors.
METHODS
We identified six patients with primary lung adenocarcinoma that showed transformation to SCLC on second biopsy (n = 401) during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were compared between initial and second biopsy samples.
RESULTS
Six patients showed transformation from adenocarcinoma to SCLC, of which four were pure SCLCs and two were combined adenocarcinoma and SCLCs. Clinically, four cases were EGFR-mutant tumors from non-smoking females who underwent TKI treatment, and the EGFR mutation was retained in the transformed SCLC tumors. The remaining two adenocarcinomas were EGFR wild-type, and one of these patients received EGFR TKI treatment.
CONCLUSIONS
NSCLC can acquire a neuroendocrine phenotype with or without EGFR TKI treatment.

Keyword

Lung neoplasms; Receptor, epidermal growth factor; Tyrosine kinase inhibitor; Small cell lung carcinoma; Adenocarcinoma

MeSH Terms

Adenocarcinoma*
Biopsy
Carcinoma, Non-Small-Cell Lung
Female
Humans
Lung
Lung Neoplasms
Phenotype
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor
Small Cell Lung Carcinoma*
Protein-Tyrosine Kinases
Receptor, Epidermal Growth Factor

Figure

• 

  Fig. 1. Three cases showing transformation from non-small-cell lung cancer to small-cell lung cancer. (A) Initial biopsy of case 3 shows adenocarcinoma. Second biopsy after Iressa treatment, mediastinal lymph node specimen shows small cell carcinoma (B) and tumor cells are strongly positive for CD56 (C). (D) In case 4, second biopsy after gefetinib treatment reveals combined small-cell and adenocarcinoma histology. (E) Adenocarcinoma is identified in the brain tissue of case 2 at the time of initial diagnosis. (F) Second biopsy after afatinib treatment from this patient has combined small-cell and adenocarcinoma histology. (G) CD56 is expressed in the small cell component of the tumor sample.

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