Reticulin stains are commonly used in surgical pathology to assess mass lesions for the possibility of
hepatocellular carcinoma. The loss of normal
reticulin staining can help support a diagnosis of
hepatocellular carcinoma, and this
stain has proven to be particularly helpful on limited biopsies and fine-needle aspirates. However, an underappreciated diagnostic pitfall is that non-neoplastic liver tissue can also show
reticulin loss when there is fatty change. To further characterize this important diagnostic pitfall,
reticulin staining was studied in cases of nonalcoholic steatosis,
nonalcoholic steatohepatitis, and hepatic
adenomas with fatty change. A total of 112 cases with varying degrees of steatosis were collected from 4 academic centers, including 49 cases of steatosis, 49 cases of
steatohepatitis, and 14 hepatic
adenomas with fatty change. Steatosis was graded as mild (5% to 30% macrovesicular steatosis), moderate (31% to 60%), and marked (>60%).
Reticulin stains were scored as the number of foci with diminished
reticulin staining in 10 hpf. A focus of diminished
reticulin was scored when the extent of
reticulin loss was similar to that seen in
hepatocellular carcinomas. In the total study set, 28 cases showed mild steatosis, 40 cases showed moderate steatosis, and 44 cases showed marked steatosis. Interestingly, increasing amounts of fat were associated with decreased
reticulin staining. For mild steatosis,
reticulin loss was rare, with the number of foci of
reticulin loss per 10 hpf averaging 0.8 (range, 0 to 3); however, this increased for moderate steatosis, which showed a mean of 3.0 foci per 10 hpf (range, 0 to 5), and was most prominent with marked steatosis, which showed an average of 5.8 foci of
reticulin loss per 10 hpf (range, 5 to 8). An almost identical pattern was seen in cases of
nonalcoholic steatohepatitis. Overall,
reticulin loss was not associated with the degree of
inflammation or with the presence or absence of balloon cell change.
Reticulin loss also did not correlate with
fibrosis stage. In hepatic
adenomas,
reticulin loss was seen only in areas of fatty change, and decreased
reticulin again paralleled the amount of steatosis, with more prominent
reticulin loss in those cases with marked steatosis. In conclusion,
reticulin loss that reaches levels seen in
hepatocellular carcinoma can be seen focally in benign liver tissues with fatty change. Overall, loss of
reticulin is more common and more extensive with marked fatty change and does not seem to be linked to
inflammation or
fibrosis stage. Loss of
reticulin can also be seen in hepatic
adenomas with fatty change. Increased awareness of this important diagnostic pitfall will help prevent overcalling of
reticulin loss when evaluating biopsies and resections of
hepatic neoplasms with fatty change.