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Analysis of Histologic Features Suspecting Anaplastic Lymphoma Kinase (ALK)-Expressing Pulmonary Adenocarcinoma
In Ho Choi1, Dong Won Kim1, Sang Yun Ha2
1Department of Pathology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
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.
Insights
Histologic features can predict anaplastic lymphoma kinase (ALK) rearrangements in lung adenocarcinoma, potentially speeding up diagnosis and treatment. This offers an alternative to the costly and time-consuming ALK-FISH test.
Area of Science:
- Oncology
- Molecular Pathology
- Cancer Genetics
Background:
- Anaplastic lymphoma kinase (ALK) rearrangements are key in non-small cell lung cancer treatment.
- ALK-targeted therapies show significant benefits for patients with EML4/ALK translocations.
- ALK-fluorescence in situ hybridization (FISH) is standard but has limitations: cost, time, interpretation skill, and tissue prep.
Purpose of the Study:
- To identify histologic findings that can predict ALK rearrangements in pulmonary adenocarcinoma.
- To find potential complements to the limitations of ALK-FISH testing.
Main Methods:
- Reviewed 205 ALK-positive and 101 ALK-negative pulmonary adenocarcinoma cases (2007-2013).
- Compared histologic findings and ALK immunohistochemistry with ALK-FISH and EGFR/KRAS mutation status.
Main Results:
- ALK-positive cancers showed higher rates of acinar, cribriform, and solid growth patterns.
- Mucin production, signet-ring cells, and psammoma bodies were more frequent in ALK-positive cases.
- Goblet cell-like cells and nuclear inclusions/grooves (resembling papillary thyroid carcinoma) were common in ALK-positive tumors.
Conclusions:
- Specific histologic parameters can predict ALK-rearranged pulmonary adenocarcinoma.
- These findings may enable faster FISH analysis and prompt treatment initiation.
