An Appraisal of Immunohistochemical Stain Use in Hepatic Metastasis Highlights the Effectiveness of the Individualized, Case-Based Approach: Analysis of Data From a Tertiary Care Medical Center.

CONTEXT.­: Liver biopsy plays an important role in the clinical management of metastases and often requires workup using immunohistochemical (IHC) markers, but the approach varies among institutions. OBJECTIVE.­: To evaluate the utility of a morphologic pattern-based, individualized approach in the workup of hepatic metastases. DESIGN.­: All liver biopsies with metastasis between 2015 and 2018 were identified from our institutional database and were reviewed. The morphologic pattern of the metastasis and IHC markers used in each case were recorded. The final identification of primary site of the tumor was assessed based on all the available clinicopathologic data. The academic ranking and practice pattern of the pathologist signing out the case were also recorded. RESULTS.­: A total of 406 liver biopsies with metastasis were identified, and the cases were classified as adenocarcinoma (253 of 406; 62%), carcinoma not otherwise specified (12 of 406; 3%), neuroendocrine neoplasm (54 of 406; 13%), poorly differentiated carcinoma (43 of 406; 11%), nonepithelial tumor (24 of 406; 6%), and squamous cell carcinoma (20 of 406; 5%). The primary site was unknown in 39% (158 of 406) at the time of liver biopsy. A primary site was determined in 97% (395 of 406) of all cases, and only 3% (11 of 406) remained true carcinoma of unknown primary. The average number of IHC markers/case in patients with known primary was 2.6, compared with 5.9 with an initial unknown primary and 9.5 in cases of true carcinoma of unknown primary. CONCLUSIONS.­: An individualized, case-based approach seems to be highly cost-effective and uses fewer IHC markers compared with preset panels that often comprise 10 or more IHC markers.

Proapoptotic protein BIM as a novel prognostic marker in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma. Numerous studies have demonstrated many genetic aberrations in MCL in addition to the characteristic t(11:14), including frequent biallelic deletions of Bim, a proapoptotic member of the BCL-2 family. In mice, Bim deletion coupled with cyclin D1 overexpression generates pathologic and molecular features of human MCL. Since the regulation of apoptosis is crucial in MCL pathogenesis, we hypothesize that BIM expression may be associated with tumor cell survival. Clinical data and tissue from 100 nodal MCL cases between 1988 and 2009 were collected from three large academic medical centers. The average patient age of our MCL cohort was 65.5 years old (range, 42-97) with a 2:1 male to female ratio. Immunohistochemistry was performed with a validated anti-BIM antibody. Patients were separated into low and high BIM-expressing categories with a cutoff of 80%. As expected for a proapoptotic tumor suppressor, patients with high BIM expression were less likely to have progressive disease and more likely to have a complete response (P = .022). In addition, high BIM-expressing MCL tumors revealed a trend toward increased overall survival with this trend persisting in sub-analysis of Ann Arbor stages III and IV. No correlation between BIM expression, Ki-67 index, and MIPI score was observed, suggesting a role for BIM as a novel independent prognostic factor. While BIM is only one member of a complex family of apoptosis-regulating proteins, these findings may yield clinically relevant information for the prognosis and therapeutic susceptibility of MCL.