Cytomorphology of non‐small cell lung carcinoma with anaplastic lymphoma kinase gene rearrangement

Abstract

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase demonstrating activating mutations in several malignancies including a subset (1-5%) of non-small cell lung carcinomas (NSCLC). Prior work examining, the histologic features of these tumors found a spectrum of findings, notably a solid/acinar pattern, as well as a mucinous cribriform pattern. We present the first study to date describing the cytomorphology of NSCLC harboring ALK rearrangements. A retrospective database search was conducted to identify cytologic specimens of NSCLC demonstrating ALK rearrangement. Cytogenetic analysis was performed with fluorescence in situ hybridization. A total of 12 patients were identified, 10 with available material. Cellular morphology and smear background was evaluated in the study group, as well as control cases lacking ALK rearrangement. A total of 25 specimens from 10 patients were obtained. Five patients never smoked, and four patients had a remote smoking history. ALK rearrangements were identified in cells with unique cytologic characteristics. All cases demonstrated moderate to poor differentiation with a predominance of single cells showing anisonucleosis and frequent intracytoplasmic neutrophils. The control cases showed cells with smaller, less pleomorphic nuclei, and smaller nucleoli with more clusters/tissue fragments. Several unique cytomorphologic features were consistently identified in the study population relative to the control population and include a prominence of single, markedly enlarged tumor cells with plasmacytoid features and anisonucleosis, as well as intracytoplasmic neutrophils. Larger studies are warranted to confirm our preliminary findings, as these features may help establish a more cost-effective means to select patients being tested for ALK mutational analysis.

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

“…This observation was consistent with another study, which showed that ALK-positive adenocarcinomas might metastasize to lymph nodes early, despite the small size of the primary tumor (Jokoji et al, 2010;Paik et al, 2012;Takamochi et al, 2013). To date, several small sample studies (Takahashi et al, 2010;Zhang et al, 2014;Toll and Maleki, 2015) have reported that ALK rearrangements were associated with moderate or poor differentiation status; our study further affirmed this finding in a relatively larger sample size.…”

Cytological markers for predicting ALK‐positive pulmonary adenocarcinoma

“…8,14,15 Ha et al reported that ALK-positive cancer was characterized by an individually scattered pattern of SRCC. 8,14,15 Ha et al reported that ALK-positive cancer was characterized by an individually scattered pattern of SRCC.…”

“…4 EGFR-positive tumors are reportedly associated with lepidic growth (visible as a flat or monolayer architecture on cytology) in histological specimens and with the presence of intranuclear inclusions in cytological specimens. [6][7][8][9] Previous histological studies have shown that solid signet ring cell carcinoma (SRCC) and a mucinous cribriform structure are observed in ALK-positive cancers. [6][7][8][9] Previous histological studies have shown that solid signet ring cell carcinoma (SRCC) and a mucinous cribriform structure are observed in ALK-positive cancers.…”

“…[10][11][12][13] In addition, many histological features were also identified, such as solid and acinar growth, papillary and micropapillary patterns, hepatoid feature, lack of lepidic growth, and intra-and/or extra cytoplasmic mucin. 8,[14][15][16] However, SRCC can be difficult to recognize cytologically because SRCC can exhibit various cytoplasmic features and appearance patterns. 8,[14][15][16] However, SRCC can be difficult to recognize cytologically because SRCC can exhibit various cytoplasmic features and appearance patterns.…”

“…8,14,15 Thus, predicting ALK-positivity based only on cytological features is presently difficult. 8,14,15 Thus, predicting ALK-positivity based only on cytological features is presently difficult.…”