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Published on: January 19, 2019
Histomorphologic features of lung adenocarcinomas exhibiting ALK gene rearrangement
Daniel S Grosser1, Haiying Zhang1
1Department of Pathology, Baylor University Medical CenterDallasTexas.
Abstract:
With the advent of tyrosine kinase inhibitors, the identification of tumors with alterations in tyrosine kinase genes has become important to guide treatment. Lung adenocarcinomas harboring ALK translocations may be targeted with drugs such as crizotinib. We undertook a retrospective review of our institution's pathology records from January 2015 through September 2017 and identified 10 lung adenocarcinomas with ALK rearrangements. We reviewed the histomorphologic features and immunohistochemical results from these 10 cases. Morphologic features included patterns such as acinar, papillary, micropapillary, and solid, as well as features such as cribriform, signet ring, and extracellular mucin. Acinar (including simple and cribriform) was the most common pattern, followed by papillary. Solid and signet ring features were the least common. These findings were consistent with prior histomorphologic studies of ALK-positive lung adenocarcinomas. Certain histomorphologic patterns are associated with ALK positivity. However, histomorphologic features are neither absolutely sensitive nor absolutely specific in suggesting ALK rearrangement. Thus, identification of lung adenocarcinomas that may benefit from treatment with tyrosine kinase inhibitors requires comprehensive molecular testing.
Insights
Identifying ALK rearrangements in lung adenocarcinoma is crucial for targeted therapy. While certain histomorphologic patterns suggest ALK positivity, molecular testing is essential for accurate diagnosis and treatment selection.
Area of Science:
- Oncology
- Pathology
- Genetics
Background:
- Tyrosine kinase inhibitors (TKIs) have revolutionized cancer treatment, necessitating precise identification of targetable genetic alterations.
- Anaplastic lymphoma kinase (ALK) gene rearrangements are key biomarkers in a subset of lung adenocarcinomas, predicting response to specific TKIs like crizotinib.
Observation:
- This study retrospectively reviewed 10 lung adenocarcinoma cases with confirmed ALK rearrangements.
- Histomorphologic features, including acinar, papillary, micropapillary, and solid patterns, along with cribriform, signet ring, and extracellular mucin, were analyzed.
- Acinar patterns (simple and cribriform) were most prevalent, followed by papillary patterns.
Findings:
- The study observed that specific histomorphologic patterns are associated with ALK rearrangements in lung adenocarcinoma.
- Acinar and papillary patterns were the most common histomorphologic features in ALK-positive cases.
- However, histomorphologic features alone are not sufficiently sensitive or specific for definitive ALK rearrangement diagnosis.
Implications:
- Histomorphology can serve as a preliminary indicator for potential ALK rearrangements in lung adenocarcinoma.
- Comprehensive molecular testing remains indispensable for accurate diagnosis and guiding TKI therapy selection.
- Accurate identification of ALK-positive lung adenocarcinomas ensures optimal patient management and therapeutic outcomes.
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