Malignant tenosynovial giant cell tumor with CDKN2A/B genomic alteration: a histological, immunohistochemical, and molecular study

Borislav A Alexiev; Yanki Tumer; Guang-Yu Yang

doi:10.1016/j.humpath.2016.12.003

Malignant tenosynovial giant cell tumor with CDKN2A/B genomic alteration: a histological, immunohistochemical, and molecular study

Hum Pathol. 2017 May:63:144-148. doi: 10.1016/j.humpath.2016.12.003. Epub 2016 Dec 15.

Authors

Borislav A Alexiev¹, Yanki Tumer², Guang-Yu Yang³

Affiliations

¹ Department of Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL 60611, USA. Electronic address: Borislav.Alexiev@northwestern.edu.
² Department of Radiology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL 60611, USA.
³ Department of Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL 60611, USA.

PMID: 27989786
DOI: 10.1016/j.humpath.2016.12.003

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.

Keywords: CDKN2A/B loss; Giant cell tumor; Metastases.

Publication types

Case Reports

MeSH terms

Amputation, Surgical
Biomarkers, Tumor* / analysis
Biomarkers, Tumor* / genetics
Biopsy
Cyclin-Dependent Kinase Inhibitor p15* / analysis
Cyclin-Dependent Kinase Inhibitor p15* / genetics
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p18* / analysis
Cyclin-Dependent Kinase Inhibitor p18* / genetics
Giant Cell Tumor of Tendon Sheath / chemistry
Giant Cell Tumor of Tendon Sheath / diagnosis*
Giant Cell Tumor of Tendon Sheath / genetics
Giant Cell Tumor of Tendon Sheath / secondary
Giant Cell Tumor of Tendon Sheath / surgery
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry*
Knee Joint* / chemistry
Knee Joint* / diagnostic imaging
Knee Joint* / pathology
Knee Joint* / surgery
Magnetic Resonance Imaging
Male
Middle Aged
Molecular Diagnostic Techniques*
Pleural Neoplasms / chemistry
Pleural Neoplasms / diagnosis*
Pleural Neoplasms / genetics
Pleural Neoplasms / secondary
Positron Emission Tomography Computed Tomography
Predictive Value of Tests
Proto-Oncogene Proteins c-mdm2 / analysis
Sequence Analysis, DNA
Sequence Analysis, RNA
Time Factors
Treatment Outcome

Substances

Biomarkers, Tumor
CDKN2A protein, human
CDKN2B protein, human
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16
Cyclin-Dependent Kinase Inhibitor p18
MDM2 protein, human
Proto-Oncogene Proteins c-mdm2