Pulmonary Sarcomatoid Carcinoma with ALK Rearrangement: Frequency, Clinical-Pathologic Characteristics, and Response to ALK Inhibitor

Abstract

PURPOSE: The incidence of anaplastic lymphoma kinase (ALK) rearrangement in pulmonary sarcomatoid carcinoma (PSC) is controversial. In this study, we aimed to reveal the reliable frequency and the clinical-pathologic characteristics of pulmonary sarcomatoid carcinoma (PSC) with ALK rearrangement in Chinese population, and to provide insight into the translatability of anti-ALK treatment in this treatment-refractory disease. METHODS: Immunohistochemistry (IHC) using a Ventana anti-ALK (D5F3) rabbit monoclonal antibody was performed in 141 PSC specimens collected from multiple medical centers. IHC-positive cases were then confirmed using ALK fluorescent in situ hybridization (FISH). The incidence rates and clinical-pathologic characteristics of ALK-rearranged PSC were then analyzed. Response to ALK inhibitor crizotinib in a patient with ALK-rearranged PSC was evaluated according to the response evaluation criteria for solid tumors (RECIST) version 1.1. RESULTS: Five of 141 (3.5%) of PSCs showed ALK rearrangement-positive by IHC and then were confirmed by FISH. Two were carcinosarcomas and the other three were pulmonary pleomorphic carcinoma (PPC). Strong positive ALK rearrangement was observed in both the epithelioid and sarcomatoid components. The median age of ALK-positive patients was younger than that of ALK-negative patients. PSCs in never-smokers were more likely to harbor ALK rearrangement than those in former or current smokers (P < .05). A 40-year-old woman diagnosed with ALK-rearranged PPC experienced a partial response (−32%) to the ALK inhibitor crizotinib. CONCLUSIONS: The incidence rates of ALK rearrangement in PSC in the Chinese population are similar to those of other subtypes of NSCLC. PSCs in younger never-smokers are more often to harbor ALK rearrangement. ALK inhibitors may serve as an effective treatment for ALK-rearranged PSC.

Anaplastic lymphoma kinase (ALK)-rearranged pulmonary pleomorphic carcinoma successfully treated with crizotinib

“…[12][13][14] These findings suggest that ALK-positive PPC patients may be older than patients with ALK-positive lung adenocarinoma. 10 Moreover, it is notable that the epithelial components of our patients and those of the three aforementioned patients were all adenocarcinomas, consistent with the findings of Chen et al 15 that 4 of 5 ALK-positive patients with PSC had adenocarcinomas with epithelial components. These results indicate that ALK rearrangements in patients with PPC may likely arise in those with an adenocarcinoma epithelial component.…”

Uncommon Types of Lung Carcinoma With Mixed Histology: Sarcomatoid Carcinoma, Adenosquamous Carcinoma, and Mucoepidermoid Carcinoma

“…20,21,27 To date, targeting of oncogenic KRAS has not been successful. Other targetable mutations, such as ALK translocations, are rare but encountered, 28,29 as are BRAF V600E mutations. 2 ALK and MET amplifications are also seen.…”

<p>Poor prognosis of pulmonary sarcomatoid carcinoma with <em>KRAS</em> mutation and <em>ALK</em> fusion</p>

“…There is no experience of success or guideline for treatment of such disorders in clinical practice. Referring to the commonly used treatment for NSCLC, the patient should be treated with crizotinib because of positive EML4- ALK fusion 19. However, NSCLC may fail to respond to molecular targeted therapy because of adverse TP53 and KRAS mutations 13.…”

“…Advanced PSC always has a very poor prognosis and responds poorly to conventional platinum-based chemotherapy 14,20. It has been reported that ALK inhibitors may be an effective treatment for ALK rearrangement in PSC 19. However, KRAS mutations can result in a detrimental impact on prognosis and responsiveness to platinum-based chemotherapy in NSCLC18,21 as well as in PSC 14–16.…”