Tenosynovial giant cell tumor explained

Tenosynovial giant cell tumor
Synonyms:Localized: Localized pigmented villonodular synovitis (L-PVNS), Giant cell tumor of the tendon sheath (GCT-TS), Nodular tenosynovitis, Localized nodular tenosynovitis, and L-TGCT
Diffuse: Pigmented villonodular synovitis (PVNS), Conventional PVNS, and D-TGCT
Field:Oncology
Symptoms:Swelling, pain, stiffness, sensitivity, and/or limited range of motion
Complications:Osteoarthritis
Onset:Most patients are diagnosed between the age of 30-50.
Types:Diffuse and localized
Diagnosis:MRI, biopsy, surgery
Differential:Fibromas, Baker’s cyst, tophaceous gout, synovial sarcoma, hemangioma, synovial chondromatosis, hemorrhagic synovitis
Treatment:Surgery, CSF1R inhibitors
Medication:Imatinib, Pexidartinib, vimseltinib

Tenosynovial giant cell tumor (TGCT) is a group of rare, typically non-malignant tumors of the joints. TGCT tumors often develop from the lining of joints (also known as synovial tissue).[1] [2] [3] .

Common symptoms of TGCT include swelling, pain, stiffness and reduced mobility in the affected joint or limb. This group of tumors can be divided into different subsets according to their site, growth pattern, and prognosis.[4] Localized/nodular TGCT is sometimes referred to as giant cell tumor of the tendon sheath; diffuse TGCT is also called pigmented villonodular synovitis (PVNS).These two distinct subtypes determined by radiographic appearance.[5] Localized TGCT is defined as a well circumscribed tumor while diffuse TGCT exhibits a locally aggressive and infiltrative behavior.[6]

Classification

Classification for TGCT encompasses two subtypes that can be divided according to site – within a joint (intra-articular) or outside of the joint (extra-articular) – and growth pattern (localized or diffuse) of the tumor(s). Localized and diffuse subsets of TGCT differ in their prognosis, clinical presentation, and biological behavior, but share a similar manner of disease development.

Localized TGCT

Localized TGCT is sometimes referred to as localized pigmented villonodular synovitis (L-PVNS), giant cell tumor of the tendon sheath (GCT-TS), nodular tenosynovitis, localized nodular tenosynovitis, and L-TGCT.

The localized form of TGCT is more common. Localized TGCT tumors are typically 0.5 cm-4 cm), develop over years, are benign and non-destructive to the surrounding tissue, and may reoccur in the affected area. The most common symptom is painless swelling. Localized TGCT most often occurs in fingers, but can also occur in other joints.[2]

Diffuse TGCT

Diffuse TGCT is sometimes referred to as pigmented villonodular synovitis (PVNS), conventional PVNS, and D-TGCT.

Diffuse TGCT occurs less frequently and is locally aggressive (in some cases, tumors may infiltrate surrounding soft tissue).[7] It most commonly affects people under 40 years old, though the age of occurrence varies. Diffuse TGCT may occur inside a joint (intra-articular) or outside of a joint (extra-articular). Intra-articular tumors typically occur in the knee (approximately 75% of cases) and hip (approximately 15% of cases). Extra-articular tumors are usually found in the knee, thigh, and foot. Symptoms include swelling, pain, sensitivity, and/or limited range of motion. The rate of reoccurrence is estimated to be 18-46% for intra-articular tumors and 33-50% for extra-articular tumors.

Complications

Diffuse TGCT is locally aggressive and can spread to surrounding tissues, causing bone erosion and tissue damage. If not treated early, it can spread to areas outside the joint, extra-articular, and potentially cause permanent loss of range as well as intense pain.[8] [9]

Mechanism

TGCT tumors grow due to genetic overexpression of colony stimulating factor 1. This causes colony-stimulating factor-1 receptor (CSF1R) cells to accumulate in the joint tissue.[10] [11]

Diagnosis

TGCT can be diagnosed by magnetic resonance imaging (MRI), by biopsy, or during surgery.[12] [13] The disorder is difficult to identify and is often not diagnosed for years due to nonspecific symptoms or a general paucity of symptoms.[14] TGCT cases are often misdiagnosed as osteoarthritis,[15] localized trauma,[16] sports injuries,[17] [18] xanthomas,[19] or other conditions.[20] One study of 122 diffuse TGCT patients found that the average delay in diagnosis was 2.9 years.[21]

To identify or monitor using MRI, the minimum techniques required include T1 weighted images, T2 weighted images, and a fluid sensitive sequence.[22]

Treatment

Patients affected by TGCT should be managed within expert centers or reference networks, by a dedicated, experienced sarcoma multidisciplinary treatment team, including a pathologist, radiologist, orthopaedic surgeon, pain specialist, surgical, radiation and medical oncologists.[23] Patients initially treated at cancer centers have lower recurrence rates than those initially treated by community centers.[24]

Surgery has been the most common form of treatment for both localized and diffuse TGCT. After surgery, patients may receive physical therapy in order to help rehabilitate affected joints. However, recurrence of TGCT after surgery is common, with a higher rate of recurrence for diffuse TGCT than for localized TGCT. In cases of recurrent or resistant disease, multiple surgeries, total joint arthroplasties, or amputation may be required.

A multidisciplinary approach, supplementing surgery or other treatments, can also improve outcomes in cases of recurrent TGCT.[25] In the late 2010s, treatment with CSF1R inhibitors emerged as an option[26] that may help improve functionality for patients with recurrent TGCT or TGCT that is not easily managed by surgery.An oral CSF-1R inhibitor pexidartinib is approved in the US and only available through a Risk Evaluation and Mitigation Strategy (REMS) Program,[27] and two other oral CSF-1R inhibitors, pimicotinib and vimseltinib are being developed in phase 3 trials.[28] [29]

There is insufficient and contradictory evidence on radiation therapy, in the form of radiosynoviorthesis (yttrium injections) or external beam, before or after surgery and thus no recommendation for its use in TGCT can be made. [30]

For asymptomatic patients, active surveillance is the preferred method.[31] [32] Active surveillance includes monitoring with MRI in intervals (e.g., every 6 months) to ensure the delay in treatment does not pose a potential harm.[33] This should be carefully weighed against the potential for over treatment.

Epidemiology

A study conducted in the Netherlands estimated that the worldwide incidence of TGCT is 43 cases per million person-years. The majority – 39 cases per million person-years – were estimated to be localized TGCT; the remaining 4 cases per million person-years were estimated to be diffuse TGCT.[34] TGCT can occur in patients of any age, but people with localized TGCT are typically between 30 and 50 years old, while diffuse TGCT tends to affect people under the age of 40.

See also

Notes and References

  1. 10.5858/arpa.2012-0165-CR. Tenosynovial Giant Cell Tumor: Case Report and Review. 2012. Lucas. David R.. Archives of Pathology & Laboratory Medicine. 136. 8. 901–906. 22849738. free.
  2. Book: Fletcher . C. D.M. . Bridge . J.A. . Hogendoorn . P. . Mertens . F. . 2013 . WHO Classification of Tumours of Soft Tissue and Bone. Fourth Edition . https://web.archive.org/web/20160719223451/http://apps.who.int/bookorders/WHP/detart1.jsp?sesslan=1&codlan=1&codcol=70&codcch=4005 . dead . July 19, 2016 . . 9789283224341 .
  3. 10.1016/j.ijscr.2016.12.019. Giant cell tumor of soft tissues: A case report of extra-articular diffuse-type giant cell tumor of the quadriceps. 2017. Rateb. Kochbati. Hassen. Ben Ghozlen. Leila. Abid. Faten. Farah. Med Samir. Daghfous. International Journal of Surgery Case Reports. 31. 245–249. 28199932. 5310176.
  4. 10.1097/CCO.0b013e328347e1e3. Treatment of tenosynovial giant cell tumor and pigmented villonodular synovitis. 2011. Ravi. Vinod. Wang. Wei-Lien. Lewis. Valerae O.. Current Opinion in Oncology. 23. 4. 361–366. 21577109. 1608847.
  5. Stacchiotti . Silvia . Dürr . Hans Roland . Schaefer . Inga-Marie . Woertler . Klaus . Haas . Rick . Trama . Annalisa . Caraceni . Augusto . Bajpai . Jyoti . Baldi . Giacomo Giulio . Bernthal . Nicholas . Blay . Jean-Yves . Boye . Kjetil . Broto . Javier-Martin . Chen . Wei-Wu Tom . Dei Tos . Paolo Angelo . January 2023 . Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts . Cancer Treatment Reviews . en . 112 . 102491 . 10.1016/j.ctrv.2022.102491. 36502615 . 10067/1923310151162165141 . free .
  6. Palmerini . Emanuela . Staals . Eric L. . Maki . Robert G. . Pengo . Stefano . Cioffi . Angela . Gambarotti . Marco . Picci . Piero . Daolio . Primo Andrea . Parafioriti . Antonina . Morris . Carol . Antonescu . Cristina R. . Gronchi . Alessandro . Casali . Paolo Giovanni . Donati . Davide M. . Ferrari . Stefano . January 2015 . Tenosynovial giant cell tumour/pigmented villonodular synovitis: Outcome of 294 patients before the era of kinase inhibitors . European Journal of Cancer . en . 51 . 2 . 210–217 . 10.1016/j.ejca.2014.11.001. 25465190 .
  7. 10.1155/2017/7402570. Limb Amputation after Multiple Treatments of Tenosynovial Giant Cell Tumour: Series of 4 Dutch Cases. 2017. Mastboom. Monique J. L.. Verspoor. Floortje G. M.. Gelderblom. Hans. Sande. Michiel A. J. van de. Case Reports in Orthopedics. 2017. 1–6. 28744388. 5506462. free.
  8. Web site: Clinical Study. The Stone Clinic. web journal. 2007-08-07 . https://web.archive.org/web/20070701034540/http://www.stoneclinic.com/PVNS.htm . 2007-07-01.
  9. 4313448. 2014. Jabalameli. M. Surgical outcomes of 26 patients with pigmented villonodular synovitis (PVNS) of the knee at a mean follow-up of 4 years: Introducing a novel technique. Medical Journal of the Islamic Republic of Iran. 28. 123. Jamshidi. K. Radi. M. Hadi. H. Bagherifard. A. 25679002.
  10. 10.1073/pnas.0507321103. A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. 2006. West. R. B.. Rubin. B. P.. Miller. M. A.. Subramanian. S.. Kaygusuz. G.. Montgomery. K.. Zhu. S.. Marinelli. R. J.. De Luca. A.. Downs-Kelly. E.. Goldblum. J. R.. Corless. C. L.. Brown. P. O.. Gilks. C. B.. Nielsen. T. O.. Huntsman. D.. Van De Rijn. M.. Proceedings of the National Academy of Sciences. 103. 3. 690–695. 16407111. 1325107. 2006PNAS..103..690W . The CSF1 translocations result in overexpression of CSF1. In cases of TGCT and PVNS carrying this translocation, it is present in a minority of the intratumoral cells, leading to CSF1 expression only in these cells, whereas the majority of cells express CSF1R but not CSF1, suggesting a tumor-landscaping effect with aberrant CSF1 expression in the neoplastic cells, leading to the abnormal accumulation of nonneoplastic cells that form a tumorous mass.. free.
  11. 10.1097/PAS.0b013e31802b86f8. Translocation and Expression of CSF1 in Pigmented Villonodular Synovitis, Tenosynovial Giant Cell Tumor, Rheumatoid Arthritis and Other Reactive Synovitides. 2007. Cupp. John S.. Miller. Melinda A.. Montgomery. Kelli D.. Nielsen. Torsten O.. o??Connell. John X.. Huntsman. David. Rijn. Matt van de. Gilks. Cyril B.. West. Robert B.. The American Journal of Surgical Pathology. 31. 6. 970–976. 17527089 . 29544370. As the CSF1 translocation is postulated to play an important role in the biology of PVNS/TGCT, the consistent presence of CSF1 expression in translocation-negative cases implies that other mechanisms can lead to CSF1 up-regulation..
  12. 10.3944/AOTT.2011.2442. Long-term results of surgical treatment of pigmented villonodular synovitis of the knee. 2011. Akinci. Orhan. Akalin. Y.. Incesu. M.. Eren. A.. Acta Orthopaedica et Traumatologica Turcica. 45. 3. 149–155. 21765227. free.
  13. 10.1093/rheumatology/keu230. Long-term follow-up results of primary and recurrent pigmented villonodular synovitis. 2014. Verspoor. Floortje G. M.. Zee. Aniek A. G.. Hannink. Gerjon. Van Der Geest. Ingrid C. M.. Veth. Rene P. H.. Schreuder. H. W. Bart. Rheumatology. 53. 11. 2063–2070. 24917565. free.
  14. Frassica FJ, Bhimani MA, McCarthy EF, Wenz J . Pigmented villonodular synovitis of the hip and knee . Am Fam Physician . 60 . 5 . 1404–10; discussion 1415 . October 1999 . 10524485 . 2020-08-06 . 2011-06-06 . https://web.archive.org/web/20110606011227/http://www.aafp.org/afp/991001ap/1404.html . dead .
  15. 10.1016/j.arth.2016.12.053. Prognosis of Advanced Tenosynovial Giant Cell Tumor of the Knee Diagnosed During Total Knee Arthroplasty. 2017. Lei. Pengfei. Sun. Rongxin. Liu. Hao. Zhu. Jianxi. Wen. Ting. Hu. Yihe. The Journal of Arthroplasty. 32. 6. 1850–1855. 28161138.
  16. 10.1186/1752-1947-3-9331. Tenosynovial giant cell tumors as accidental findings after episodes of distortion of the ankle: Two case reports. 2009. Illian. Christian. Kortmann. Horst-Rainer. Künstler. Hans Otto. Poll. Ludger W.. Schofer. Markus. Journal of Medical Case Reports. 3. 9331. 20062758. 2803852 . free .
  17. 10.2519/jospt.2008.2934. Postoperative Management of Pigmented Villonodular Synovitis in a Single Subject. 2008. Hegedus. Eric J.. Theresa. Kristen. Journal of Orthopaedic & Sports Physical Therapy. 38. 12. 790–797. 19047769.
  18. 10.5435/JAAOS-22-04-223. Oncologic Conditions That Simulate Common Sports Injuries. 2014. Krych. Aaron. Odland. Andrew. Rose. Peter. Dahm. Diane. Levy. Bruce. Wenger. Doris. Stuart. Michael. Sim. Franklin. Journal of the American Academy of Orthopaedic Surgeons. 22. 4. 223–234. 24668352. 37108679.
  19. 23185646. 2012. Adams. E. L.. Yoder. E. M.. Kasdan. M. L.. Giant cell tumor of the tendon sheath: Experience with 65 cases. ePlasty. 12. e50. 3499005.
  20. 10.4132/jptm.2015.11.15. Intramuscular Tenosynovial Giant Cell Tumor, Diffuse-Type. 2016. Lee. Yoo Jin. Kang. Youngjin. Jung. Jiyoon. Kim. Seojin. Kim. Chul Hwan. Journal of Pathology and Translational Medicine. 50. 4. 306–308. 26755356. 4963964.
  21. 10.1016/j.semarthrit.2010.07.005. Pigmented Villonodular Synovitis: A Retrospective Single-Center Study of 122 Cases and Review of the Literature. 2011. Ottaviani. Sébastien. Ayral. Xavier. Dougados. Maxime. Gossec. Laure. Seminars in Arthritis and Rheumatism. 40. 6. 539–546. 20884045.
  22. Stacchiotti . Silvia . Dürr . Hans Roland . Schaefer . Inga-Marie . Woertler . Klaus . Haas . Rick . Trama . Annalisa . Caraceni . Augusto . Bajpai . Jyoti . Baldi . Giacomo Giulio . Bernthal . Nicholas . Blay . Jean-Yves . Boye . Kjetil . Broto . Javier-Martin . Chen . Wei-Wu Tom . Dei Tos . Paolo Angelo . January 2023 . Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts . Cancer Treatment Reviews . en . 112 . 102491 . 10.1016/j.ctrv.2022.102491. 36502615 . 10067/1923310151162165141 . free .
  23. Stacchiotti . Silvia . Dürr . Hans Roland . Schaefer . Inga-Marie . Woertler . Klaus . Haas . Rick . Trama . Annalisa . Caraceni . Augusto . Bajpai . Jyoti . Baldi . Giacomo Giulio . Bernthal . Nicholas . Blay . Jean-Yves . Boye . Kjetil . Broto . Javier-Martin . Chen . Wei-Wu Tom . Dei Tos . Paolo Angelo . January 2023 . Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts . Cancer Treatment Reviews . en . 112 . 102491 . 10.1016/j.ctrv.2022.102491. 36502615 . 10067/1923310151162165141 . free .
  24. Ottaviani . Sébastien . Ayral . Xavier . Dougados . Maxime . Gossec . Laure . June 2011 . Pigmented Villonodular Synovitis: A Retrospective Single-Center Study of 122 Cases and Review of the Literature . Seminars in Arthritis and Rheumatism . en . 40 . 6 . 539–546 . 10.1016/j.semarthrit.2010.07.005. 20884045 .
  25. 10.1302/0301-620X.94B7.28927. The management of diffuse-type giant cell tumour (Pigmented villonodular synovitis) and giant cell tumour of tendon sheath (Nodular tenosynovitis). 2012. Van Der Heijden. L.. Gibbons. C. L. M. H.. Dijkstra. P. D. S.. Kroep. J. R.. Van Rijswijk. C. S. P.. Nout. R. A.. Bradley. K. M.. Athanasou. N. A.. Hogendoorn. P. C. W.. Van De Sande. M. A. J.. The Journal of Bone and Joint Surgery. British Volume. 94-B. 7. 882–888. 22733940.
  26. 10.1186/s40425-017-0257-y. The tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) have fueled interest in therapeutically targeting these cells. In this context, the colony-stimulating factor 1 (CSF1)/colony-stimulating factor 1 receptor (CSF1R) axis has gained the most attention, and various approaches targeting either the ligands or the receptor are currently in clinical development.. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy. 2017. Cannarile. Michael A.. Weisser. Martin. Jacob. Wolfgang. Jegg. Anna-Maria. Ries. Carola H.. Rüttinger. Dominik. Journal for Immunotherapy of Cancer. 5. 1. 53. 28716061. 5514481 . free .
  27. FDA approves pexidartinib for tenosynovial giant cell tumor . FDA . 20 December 2019 .
  28. Web site: CTG Labs - NCBI .
  29. Web site: CTG Labs - NCBI .
  30. Stacchiotti . Silvia . Dürr . Hans Roland . Schaefer . Inga-Marie . Woertler . Klaus . Haas . Rick . Trama . Annalisa . Caraceni . Augusto . Bajpai . Jyoti . Baldi . Giacomo Giulio . Bernthal . Nicholas . Blay . Jean-Yves . Boye . Kjetil . Broto . Javier-Martin . Chen . Wei-Wu Tom . Dei Tos . Paolo Angelo . January 2023 . Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts . Cancer Treatment Reviews . en . 112 . 102491 . 10.1016/j.ctrv.2022.102491. 36502615 . 10067/1923310151162165141 . free .
  31. Spierenburg . Geert . Staals . Eric L. . Palmerini . Emanuela . Randall . Robert Lor . Thorpe . Steven W. . Wunder . Jay S. . Ferguson . Peter C. . Verspoor . Floortje G.M. . Houdek . Matthew T. . Bernthal . Nicholas M. . Schreuder . Bart H.W.B. . Gelderblom . Hans . van de Sande . Michiel A.J. . van der Heijden . Lizz . February 2024 . Active surveillance of diffuse-type tenosynovial giant cell tumors: A retrospective, multicenter cohort study . European Journal of Surgical Oncology . en . 50 . 2 . 107953 . 10.1016/j.ejso.2024.107953. 38215550 . free . 1887/3748215 . free .
  32. Stacchiotti . Silvia . Dürr . Hans Roland . Schaefer . Inga-Marie . Woertler . Klaus . Haas . Rick . Trama . Annalisa . Caraceni . Augusto . Bajpai . Jyoti . Baldi . Giacomo Giulio . Bernthal . Nicholas . Blay . Jean-Yves . Boye . Kjetil . Broto . Javier-Martin . Chen . Wei-Wu Tom . Dei Tos . Paolo Angelo . January 2023 . Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts . Cancer Treatment Reviews . 112 . 102491 . 10.1016/j.ctrv.2022.102491 . 10067/1923310151162165141 . 0305-7372. free .
  33. Stacchiotti . Silvia . Dürr . Hans Roland . Schaefer . Inga-Marie . Woertler . Klaus . Haas . Rick . Trama . Annalisa . Caraceni . Augusto . Bajpai . Jyoti . Baldi . Giacomo Giulio . Bernthal . Nicholas . Blay . Jean-Yves . Boye . Kjetil . Broto . Javier-Martin . Chen . Wei-Wu Tom . Dei Tos . Paolo Angelo . January 2023 . Best clinical management of tenosynovial giant cell tumour (TGCT): A consensus paper from the community of experts . Cancer Treatment Reviews . en . 112 . 102491 . 10.1016/j.ctrv.2022.102491. 36502615 . 10067/1923310151162165141 . free .
  34. 10.1080/17453674.2017.1361126. Higher incidence rates than previously known in tenosynovial giant cell tumors. 2017. Mastboom. Monique J L.. Verspoor. Floortje G M.. Verschoor. Arjan J.. Uittenbogaard. Daniël. Nemeth. Banne. Mastboom. Walter J B.. Bovée. Judith V M G.. Dijkstra. P D Sander. Schreuder. H W Bart. Gelderblom. Hans. Van De Sande. Michiel A J.. TGCT study group. Acta Orthopaedica. 88. 6. 688–694. 28787222. 5694816.

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