title: Malignant tenosynovial giant cell tumor with CDKN2A/B genomic alteration: a histological, immunohistochemical, and molecular study.
abstract: Diffuse-type tenosynovial giant cell tumor (D-T TSGCT) is regarded as a benign but locally aggressive neoplasm with significant recurrent potential. We report a case of malignant D-T TSGCT with pleural metastases arising in the left knee in a 57-year-old man. The tumor demonstrated atypical features, including a solid infiltrative pattern with spindling of the tumor cells, nuclear pleomorphism with prominent nucleoli, and markedly increased mitotic activity (>20 mitoses/10 high-power fields). The immunoprofile demonstrated clusterin+, D2-40+, CD68+, p63+, MDM2+, and p16+ tumor. The next-generation sequencing-based assay demonstrated loss of the CDKN2A/B gene. Pleural metastases with identical histologic and immunohistochemical features were identified 2 years later after primary tumor resection. To the best of our knowledge, this is the first reported case of D-T TSGCT with CDKN2A/B genomic alteration, MDM2 expression, and p16 loss. Clinicians and pathologists should be aware of the morphologic variability and the metastatic propensity of this entity.
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL 60611, USA. Electronic address: Borislav.Alexiev@northwestern.edu.
authors.forename: Borislav A
authors.initials: BA
authors.lastname: Alexiev
authors.affiliation: Department of Radiology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL 60611, USA.
authors.forename: Yanki
authors.initials: Y
authors.lastname: Tumer
authors.affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL 60611, USA.
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Yang
mesh_terms: D000671:Amputation, Surgical; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000032:analysis / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000032:analysis / Q000235:genetics; D000070779:Giant Cell Tumor of Tendon Sheath / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary / Q000601:surgery; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D007719:Knee Joint / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D010997:Pleural Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000556:secondary; D000072078:Positron Emission Tomography Computed Tomography; D011237:Predictive Value of Tests; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: CDKN2A/B loss; Giant cell tumor; Metastases