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High-grade nuclear atypia associated with invasive lung adenocarcinoma, aided diagnosis
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High-grade nuclear atypia was correlated significantly with invasive lung adenocarcinomas, which advocates caution in diagnosis if tumors with high-grade nuclear atypia are observed, even if they are small in maximum dimension, according to study results published online.
In previous studies, nuclear area and nuclear major dimension were observed to be practical independent markers for assessing the prognosis of lung adenocarcinomas. Under the newly proposed histological classification of lung adenocarcinoma, pathological T1a tumors with a pure lepidic growth pattern — adenocarcinoma in situ — are linked with excellent prognosis, yet patients exhibiting pathological T1a tumors with invasion experience poorer outcomes. To aid the diagnosis of early invasive carcinomas, it is vital to accurately assess the invasive features, even in subcentimeter tumors.
To determine the clinicopathological characteristics of subcentimeter (≤10 mm) adenocarcinomas, with special reference to stromal invasion, the researchers retrospectively reviewed 595 patients with adenocarcinomas that were surgically resected at Fukuoka University Hospital, Japan, from January 2003 to December 2009.
Of the 595 adenocarcinomas, 66 tumors were identified as subcentimeter tumors, including 36 invasive tumors and 30 adenocarcinoma in situ.
According to study results, of the 36 invasive carcinomas, 20 (56%) were minimally invasive adenocarcinomas and 16 (44%) showed more than 5 mm invasion, five (14%) of which had no lepidic growth portions and were classified as entirely invasive carcinoma; all entirely invasive carcinomas were more than 5 mm in diameter. Invasive adenocarcinomas with more than 5 mm invasion were classified into papillary predominant and acinar predominant carcinomas, and neither micropapillary predominant nor solid predominant carcinoma was found in subcentimeter tumors.
“To the best of our knowledge, this is the first histopathological report to examine subcentimeter adenocarcinomas with special reference to early invasive features,” the researchers wrote. “More than half of adenocarcinomas ≤10 mm in diameter (36/66) were invasive, and 55% (20/36) of these were minimally invasive. Moreover, just over half (19/36) of invasive carcinomas had no localized fibrous area. It was occasionally difficult to detect invasion in such tumors, and nuclear atypia was an important variable in suggesting invasiveness.”
Based on the findings, high-grade nuclear atypia was always associated with invasive carcinomas and aided the diagnosis. In addition, invasive carcinoma with more than 5 mm invasion was significantly associated with presence of metastasis in sensitivity analysis in patients followed for more than 2 years. Compared with adenocarcinomas of 11 mm to 20 mm in diameter, subcentimeter carcinomas included significantly more adenocarcinoma in situ, fewer entirely invasive carcinomas and fewer invasive carcinomas with localized fibrous area.
According to the researchers, “This report is the first to demonstrate the importance of nuclear grading in subcentimeter adenocarcinomas, and in our cases, all carcinomas with high-grade nuclear atypia were determined to be invasive. These results strongly suggested that diagnosis should proceed with care if tumors with high-grade nuclear atypia are observed, even if they are small in maximum dimension (≤10 mm).”
Disclosure: The researchers report no relevant financial disclosures.