Pigmented villonodular synovitis

Classification according to ICD-10
M12.2	Villonodular Synovitis (pigmented)
ICD-10 online (WHO version 2019)

The pigmented villonodular synovitis is the outdated and in German-speaking countries often used term for the tenosynovial giant cell tumor , a rare disease of the mucous membrane in joints or tendon sheaths . Common abbreviations are PVS and PVNS . This disease should not be confused with the giant cell tumor of the bone .

causes

The tenosynovial giant cell tumor is a benign tumor from the group of soft tissue tumors. As a rule, there is overexpression of the growth factor CSF1 , which is often triggered by a t (1; 2) translocation typical of this sarcoma . Parts of the first and second chromosomes are exchanged in such a way that the gene for CSF1 in section 1p13 of the first chromosome is linked to a gene for collagen type VI ( COL6A3 ) in section 2q35 of the second chromosome.

This translocation occurs spontaneously in synovial cells that form the tumor and attract histiocytes , hemosiderin- laden macrophages and other inflammatory cells , which are responsible for the often reddish-brown pigmentation of these synovial tumors . In addition to the circumscribed (nodular) form, there are diffuse forms that spread throughout the joint or the entire tendon sheath.

frequency

In the literature, the incidence of PVS is given as 1.8 per million. The main age of the disease is the 3rd and 4th decade of life. The joint most affected is the knee .

Symptoms

The affected joints or tendon sheaths are swollen - on the one hand due to the thickened mucous membrane, on the other hand often due to an inflammatory joint effusion . This is often bloody, sometimes repeated punctures are performed before the diagnosis is made . Involvement of several joints or locations is possible but an absolute rarity. In these cases, the rare malignant giant cell tumor of the tendon sheaths must be considered, which is itself a controversial entity.

Diagnosis

Arthroscopic image of a shoulder with pigmented villonodular synovitis

It is not uncommon for the PVS to be discovered by chance during a joint endoscopy . Brownish-yellow mucous membrane villi are found in the diffuse forms. The localized disease is a circumscribed tumor.

Nodules PVS of the knee joint

The diagnosis is confirmed by microscopic examination . The magnetic resonance imaging shows characteristic findings.

therapy

In the case of corresponding complaints, the tumor must be removed (nodular) or, in the case of diffuse forms, the removal of the joint mucosa (synovectomy) . A radiation therapy or Radiosynoviorthesis (adjunct to surgery) can be successful. Cortisone injections or the administration of non-steroidal anti-inflammatory drugs , on the other hand, are not disease-related, at most symptomatically effective.

Complete removal of the tumor is often difficult, especially if it is diffuse. Then there is sometimes only an endoprosthesis as a therapeutic alternative .

PVS cells show overexpression of "Colony stimulating factor-1" (CSF1). Only a few cells of the lesion show this, but inflammatory cells are attracted, which in turn increasingly express CSF1 receptors. Imatinib , a tyrosine kinase inhibitor that is used very successfully in certain cancers, blocks these CSF1 receptors. Accordingly, one tries to use it at the PVS. Five of 27 patients showed tumor regression, one complete, 4 partial. 20 of the 27 had no further disease progression. Other authors used an antibody against certain parts of the vascular wall, which they injected directly into the joint ( bevacizumab , a humanized monoclonal antibody against the vascular endothelial growth factor (VEGF)). In one case of a multiple recurrence in the knee joint, they achieved a clear clinical and radiological improvement.

In an American phase I study in 2015, a dose escalation study with a specially developed selective CSF1 receptor inhibitor (PLX3397) was carried out on 41 patients; In a subsequent phase II study on 23 patients, the response rate was 52%. This receptor antagonist was developed on the basis of a crystallographic structure analysis in such a way that, like imatinib, it binds to phenylalanine in position 797 (phe797) in the catalytic pocket of the protein, but unlike imatinib, it also binds the juxtamembrane domain and thus stabilizes the receptor in the closed inactive form . A randomized study with PLX3397 vs. Placebo takes place. All local measures, especially the competently performed tumor removal, should be exhausted. How the disease behaves after discontinuation of the antibody is still unclear.

literature

• tumororthopaedie.org
• Carl Joachim Wirth: Practice of orthopedics. Georg Thieme Verlag, Stuttgart / New York 2001, ISBN 3-13-125683-4 .
• HR Dürr et al: The pigmented villonodular synovitis (PVS). (PDF; 399 kB)

Individual evidence

1. ↑ RB West, BP Rubin, MA Miller, S. Subramanian, G. Kaygusuz, K. Montgomery, S. Zhu, RJ Marinelli, A. De Luca, E. Downs-Kelly, JR Goldblum, CL Corless, PO Brown, CB Gilks, TO Nielsen, D. Huntsman, M. van de Rijn: A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. In: Proceedings of the National Academy of Sciences . Volume 103, Number 3, January 2006, pp. 690-695, doi: 10.1073 / pnas.0507321103 . PMID 16407111 , PMC 1325107 (free full text).
2. ^ PA Cassier et al.: Efficacy of imatinib mesylate for the treatment of locally advanced and / or metastatic tenosynovial giant cell tumor / pigmented villonodular synovitis. In: Cancer. 118 (6), Mar 15, 2012, pp. 1649-1655.
3. ↑ MJ Nissen et al .: Efficacy of intra-articular bevacizumab for relapsing diffuse-type giant cell tumor. In: Ann Rheum Dis. 73 (5), May 2014, pp. 947-948.
4. ↑ WD Tap, ZA Wainberg, SP Anthony, PN Ibrahim, C. Zhang, JH Healey, B. Chmielowski, AP Staddon, AL Cohn, GI Shapiro, VL Keedy, AS Singh, I. Puzanov, EL Kwak, AJ Wagner, DD Von Hoff, GJ Weiss, RK Ramanathan, J. Zhang, G. Habets, Y. Zhang, EA Burton, G. Visor, L. Sanftner, P. Severson, H. Nguyen, MJ Kim, A. Marimuthu, G. Tsang , R. Shellooe, C. Gee, BL West, P. Hirth, K. Nolop, M. van de Rijn, HH Hsu, C. Peterfy, PS Lin, S. Tong-Starksen, G. Bollag: Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. In: N Engl J Med. 373 (5), Jul 30, 2015, pp. 428-437. (PDF)
5. ↑ Bruce Chabner, Victoria Richon: Structural Approaches to Cancer Drug Development. In: New England Journal of Medicine. Volume 373, Issue 5, July 30, 2015, pp. 402-403, doi: 10.1056 / NEJMp1503567

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