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Genes Chromosomes Cancer. 2019 Jun;58(6):357-364. doi: 10.1002/gcc.22724. Epub 2019 Jan 23.

Basal cell carcinomas developing independently from BAP1-tumor predisposition syndrome in a patient with bilateral uveal melanoma: Diagnostic challenges to identify patients with BAP1-TPDS.

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Department of Ophthalmology, Division of Ophthalmic Pathology, University Hospital Bonn, Bonn, Germany.
Institute of Human Genetics, University of Bonn, Bonn, Germany.
Center for Hereditary Tumor Syndromes, University of Bonn, Bonn, Germany.
Institute of Experimental Hematology and Transfusion Medicine, University Clinic of Bonn, Bonn, Germany.


Basal cell carcinomas (BCC) have been recently included into the spectrum of BAP1-tumor predisposition syndrome (TPDS). Uveal melanoma (UM) is also a tumor often observed in patients with this hereditary tumor syndrome, in particular bilateral UM is highly suspicious for BAP1-TPDS although no patient has been reported yet. Based on our index patient with BAP1-TPDS with bilateral UM (choroid OD, oculus dexter; iris OS, oculus sinister), several BCCs and thyroid cancer as well as a family history for cancer, this paper analyzes hints and pitfalls to diagnose this syndrome clinically and histologically. A previously undescribed germline variant, namely a heterozygous deletion of a single nucleotide on position 2001 (c.2001delG;p.[Thr668Profs*24] in exon 16 of the BAP1 gene), was identified. Structural changes in the C-terminal of the BAP1 protein were observed by in silico analysis. While the excised iris melanoma showed loss of BAP1 nuclear staining by immunohistochemical staining, the BCCs of our patient (and in the control group, n = 13) were BAP1 positive. Genetic analysis of the BCC of the ocular adnexae confirmed a remaining intact BAP1 copy. The constellation of (bilateral) UM in combination with BCC should raise suspicion for a BAP1-TPDS. As our BCCs probably developed independently from the BAP1-TPDS and UMs frequently show loss of nuclear BAP1 staining, genetic analysis is mandatory to diagnose this syndrome.


BAP1; BAP1-tumor predisposition syndrome; bilateral uveal melanoma; immunohistochemistry; in silico analysis

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