Foamy Macrophages in Clear Cell Renal Cell Carcinoma are Highly Associated with BAP1Deficient Tumors

Document Type

Conference Proceeding

Publication Date

3-1-2024

Publication Title

Lab Invest

Abstract

Background: Foamy macrophages in a renal tumor are typically associated with papillary renal cell carcinoma (RCC). However, we have occasionally encountered tumors that appear to be of clear cell subtype, yet which contain stromal foamy macrophages, causing diagnostic challenge. Design: Clear cell RCCs that exhibited foamy macrophages in the stroma (between intact tumor cells, excluding areas of hemorrhage or necrosis, identified on H&E stain) were retrieved. The histologic features and immunohistochemistry were evaluated, and after finding that this histology was highly enriched for BAP1 loss, we retrospectively reviewed 28 known BAP1- deficient tumors from a cohort of 112 consecutive clear cell RCC for the presence of foamy macrophages. Results: Fourteen tumors were identified in 12 men and 2 women, including 1 from retrospective review of the known BAP1- deficient tumors. Age ranged from 37 to 79 years (median 63 years). Median tumor size was 5.3 cm, and nuclear grade was either 3 or 4 (n=7 each). Almost all caused a diagnostic challenge (12/14), 4 of which were encountered as consultations for classification, and the remainder triggered the original pathologist to perform immunohistochemistry or other studies. Two were institutional specimens diagnosed as clear cell RCC without ancillary studies. All tested (14/14) showed abnormal negative BAP1 staining at least regionally, and 12/12 were positive for CA9 (although decreased in high-grade areas for a subset). Keratin 7 was focally positive in 3/12, and AMACR was positive in 11/11 but varied in intensity from weak to strong. Cathepsin K was negative in 8/8 tested, and additional evaluations showed negative TFE3/TFEB FISH (n=1), negative TRIM63 RNA ISH (n=1), normal/retained FH staining (n=3), and negative keratin 20 (n=2). Conclusions: Although foamy macrophages are usually considered a feature of papillary RCC, they can rarely be found in clear cell RCC. This morphology appears to be highly associated with BAP1-deficient tumors. For RCC tumors with deceptive morphology including clear cells and foamy macrophages, CA9 and BAP1 are helpful markers to confirm the classification as clear cell type, which may affect treatment selection in the metastatic setting.

Volume

104

Issue

3

First Page

S952

Last Page

S953

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