Analysis of Histologic Features Suspecting Anaplastic Lymphoma Kinase (ALK)-Expressing Pulmonary Adenocarcinoma

Abstract

Background:Since 2007 when anaplastic lymphoma kinase (ALK) rearrangements were discovered in non-small cell lung cancer, the ALK gene has received attention due to ALK-targeted therapy, and a notable treatment advantage has been observed in patients harboring the EML4/ALK translocation. However, using ALK-fluorescence in situ hybridization (FISH) as the standard method has demerits such as high cost, a time-consuming process, dependency on interpretation skill, and tissue preparation. We analyzed the histologic findings which could complement the limitation of ALK-FISH test for pulmonary adenocarcinoma.Methods:Two hundred five cases of ALK-positive and 101 of ALK-negative pulmonary adenocarcinoma from January 2007 to May 2013 were enrolled in this study. The histologic findings and ALK immunohistochemistry results were reviewed and compared with the results of ALK-FISH and EGFR/KRAS mutation status.Results:Acinar, cribriform, and solid growth patterns, extracellular and intracellular mucin production, and presence of signet-ring-cell element, and psammoma body were significantly more often present in ALK-positive cancer. In addition, the presence of goblet cell-like cells and presence of nuclear inclusion and groove resembling papillary thyroid carcinoma were common in the ALK-positive group.Conclusions:The above histologic parameters can be helpful in predicting ALK rearranged pulmonary adenocarcinoma, leading to rapid FISH analysis and timely treatment.

Clinicopathological Features and Therapeutic Responses of Chinese Patients with Advanced Lung Adenocarcinoma Harboring an Anaplastic Lymphoma Kinase Rearrangement

“…There were 3 cases with nuclear inclusion in our study. This finding is supported by the study from Ho et al [21] who reported the notable finding that the presence of nuclear inclusion was more often observed in ALK -positive compared to ALK -negative lung cancer cases.…”

“…It has been reported that the combination of IHC and suspicious histological findings can improve on the shortcomings of FISH [21]. Similar to previous reports, histopathological analysis of the ALK -rearranged cases in our study found the presence of cribriform structure, mucous cells, and extracellular mucus as well as the absence of significant nuclear pleomorphism [22,26].…”

“…However, in our study, a total of 8 (6.67%) patients were ALK-IHC-positive, but further FISH examination found that only 5 (62.5%) patients were ALK -positive. These results suggest that IHC cannot replace FISH in determining ALK arrangement status [21]. …”

“…The first classic pattern was the presence of 1 fusion signal, along with 2 isolated signals showing as red and green color. The second pattern was the presence of 1 fusion signal accompanied by an isolated red signal [21]. …”

Ciliated muconodular papillary tumor of the lung harboring ALK gene rearrangement: Case report and review of the literature

“…Second, our case confirmed that CMPT have an ALK gene rearrangement. Previous studies have demonstrated that histologic features of ALK ‐rearranged lung adenocarcinoma were more likely to show extracellular and intracellular mucin production, and presence of signet‐ring‐cell element . Not only that, but ALK ‐rearranged tumors were also associated with frequent nodal metastasis, higher stage of disease at diagnosis .…”