April 2021 — Genitourinary Pathology
A 79-year-old man with a left testicular mass underwent left radical orchiectomy. On cut section, there is a 4.5 cm indurated, yellow-white solid mass at testicular hilum extending to epididymis and tunica vaginalis. Histological sections show an invasive, biphasic, malignant neoplasm with round to spindle cells with moderate pleomorphism and focal tubular formation. The tumor cells have vesicular nuclei and prominent nucleoli. There is variable mitotic activity and increased apoptosis.
Which of the following staining patterns is seen with BAP1 immunohistochemical stain in this entity?
- Membraonus staining
- Nuclear staining
- Loss of nuclear staining
- Nuclear and cytoplasmic staining
The correct answer is ...
The correct answer is: loss of nuclear staining.
This is a biphasic type malignant mesothelioma (MM) with epithelioid and sarcomatoid components. The epithelioid component is characterized by tubule formation and sarcomatoid component by spindle cell differentiation.
BRCA-1 related protein-1 (BAP1) is a deubiquitinase enzyme that functions as a tumor suppressor gene. BAP1 deletion or loss of function mutation prevents damaged cells from undergoing apoptosis resulting in proliferation of cells harboring deleterious mutations. In MM, BAP1 somatic mutations or deletions are found in 60% of cases and germline mutations in <1% of cases.
By immunohistochemistry BAP1 protein has a nuclear expression in normal cells. In MM, there is either a loss of nuclear expression with cytoplasmic accumulation or a complete loss of BAP1 protein expression. Cytoplasmic accumulation is seen as a result of loss of nuclear localization sequence. Membranous expression is not seen with BAP1 protein expression.
Most studies have described 100% loss of nuclear staining in BAP1 mutated MM. Partial loss of BAP1 nuclear staining is uncommon in MM; extensive loss with a small fraction of cells with retained BAP1 nuclear expression is considered as loss of BAP1 staining.
- Churg A, Naso JR. The Separation of Benign and Malignant Mesothelial Proliferations: New Markers and How to Use Them. Am J Surg Pathol. 2020 Nov;44(11):e100-e112.
Sarwat Gilani, M.B.B.S.
Fellow, Surgical Pathology
Pingchuan Zhang, M.D., Ph.D.
Senior Associate Consultant, Anatomic Pathology
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science