Reticulin Loss in Benign Fatty Liver: An Important Diagnostic Pitfall When Considering a Diagnosis of Hepatocellular Carcinoma.
Aatur D Singhi, Dhanpat Jain, Sanjay Kakar, Tsung-Teh Wu, Matthew M Yeh, Michael Torbenson. Johns Hopkins, Baltimore, MD; Yale, New Haven, CT; UCSF, San Francisco, CA; Mayo, Rochester, MN; U. of Wash., Seattle
Background: Reticulin stains are commonly used when diagnosing hepatocellular carcinomas (HCC) and typically demonstrate diminished or loss of reticulin fibers. Reticulin is particularly helpful on small biopsies and difficult cases. However, an under-recognized diagnostic pitfall is that non-neoplastic liver tissues can show decreased staining in areas of fatty change. To better clarify the histological correlates of this diagnostic pitfall, we evaluated the extent of reticulin loss in a variety of non-cancerous settings.
Design: 96 cases with varying grades of macrovesicular steatosis (mild, 5-33%; moderate, 34-66%; and marked, >66%) were collected from 5 academic centers: 49 cases had steatosis alone, 35 cases with NASH and 12 hepatic adenomas with fatty change. The following were evaluated: steatosis grade, inflammation, ballooning, and fibrosis. The number of foci with diminished reticulin staining in 10 high power fields (hpf) was calculated. A focus was scored positive when the extent of reticulin loss was similar to that seen in HCC.
Results: Diminished reticulin staining was observed in steatosis, NASH, and fatty adenomas. In hepatic steatosis without NASH, the extent of reticulin loss was associated with the grade of steatosis. For mild steatosis, reticulin loss was rare with the number of foci of reticulin loss per 10 hpf averaging 0.8 (range 0-3), but increased for moderate steatosis, mean 3.0 (range 0-5), and most prominent with marked steatosis, mean 5.8 (range 5-8). The same overall pattern was more evident in cases of NASH: mild steatosis had an average of 1 hpf, moderate 2.9, and marked steatosis 5.8. Overall, reticulin loss was not associated with inflammation, balloon cell change and fibrosis stage. In hepatic adenomas, decreased reticulin staining paralleled the amount of steatosis with marked steatosis showing the highest with an average of 6.0 hpf. Reticulin loss in hepatic adenomas was seen only in areas of fatty change and normal reticulin patterns were retained in the non-fatty areas.
Conclusions: Reticulin loss that focally reaches the levels seen in HCC can be seen in benign liver tissues with fatty change. Overall, reduction of reticulin is more common and more extensive with marked fatty change and does not appear to be linked to inflammation or fibrosis. Increased awareness of this important diagnostic pitfall will help prevent over-calling reticulin loss when evaluating specimens with fatty change.
Category: Liver & Pancreas
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 202, Monday Morning