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Soft Tissue Tumors

Fibrohistiocytic tumors

Giant cell tumor of tendon sheath - diffuse type


Reviewer: Vijay Shankar, M.D. (see Reviewers page)
Revised: 27 October 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See malignant tumors below

General
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● Extra-articular, destructive villonodular hyperplasia with synovial mononuclear cells mixed with multinucleated giant cells, foam cells, siderophages and inflammatory cells
● Considered the soft tissue counterpart of pigmented villonodular synovitis - may represent extension of articular tumor since often occurs near a joint

Terminology
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● Also called tenosynovial giant cell tumor-diffuse type
● Called pigmented villonodular synovitis (PVNS) when occurs near a joint
● Note: terminology of giant cell tumors is inconsistent in literature

Epidemiology
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● Rare; less frequent than localized type
● Usually < age 40 years, with female predominance

Clinical features
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● Develops in synovial lining of joints, tendon sheaths and bursae
● Usually knee (80%); also ankle, hip, shoulder, elbow, foot
● Almost always monoarticular, painful swelling
● May actually be hyperplastic, not neoplastic (Hum Pathol 2003;34:65)
● Occasionally invades underlying bone; may cause bone cyst formation, loss of bone and cartilage
● Locally aggressive; often recurs, but only rarely has malignant behavior (see below)

Case reports
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● 26 year old woman with tumor of subcutaneous thigh (Skeletal Radiol 2007;36:327)
● Arising in bursa of knee (Knee 2007;14:402)

Treatment and prognosis
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● Excision; may recur if inadequate excision; radiation therapy for recurrences
● See below for cases with malignant behavior

Gross description
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● Brown-yellow spongy tissue, firm and nodular, often 5 cm or larger

Gross images
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Diffuse type of tenosynovial giant cell tumor consisting of mottled brown-yellow-red villonodular mass


Hemosiderin pigment on surface


Knee synovectomy shows diffuse involvement with villous areas and a few nodules; flat shiny surface is normal synovium


Multinodular red-brown tumor (Univ Alabama)


White gray cartilage (arrow) and brown villous tissue

Micro description
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● Diffuse expansive sheets of cells with infiltrative borders and variable cellularity; tumor margins are more cellular
● Also hyperplastic synovium with papillary projections composed of foamy histiocytes and hemosiderin containing macrophages
● Large clefts, pseudoglandular or alveolar spaces lined by synovial cells, osteoclast-like multinucleated (10-70 nuclei) giant cells, epithelioid cells
● Abundant collagen may be present, but lymphocytes and plasma cells are sparse
● Also giant hemosiderotic granules (2-3x diameter of RBC), giant siderophages (Pathologe 2005;26:96)
● May have 5+ mitotic figures/10 HPF, rarely chondroid metaplasia (Mod Pathol 2007;20:545)
● Malignant if nodular and solid invasive growth plus large cells with large nuclei, prominent nucleoli, necrotic areas and atypical mitotic figures (see below)

Micro images
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Multiple synovial lined clefts and hemosiderin deposits in the subsynovial layer


Low power: sheets of small histiocytes, hyalinization and giant cells; high power: abundant hemosiderin pigment is seen


Villi have cellular cores, variable width and shape


Villi lined by synovial cells and histiocytes; giant cells and lymphocytes are also present


Various images


Papillary tumor


Multinucleated giant cells, synovial cells, fibroblasts and inflammatory cells


CD68+, S100+ cells in chondroid areas

Other images: shoulder tumor #1; #2; #3; #4; #5; histiocytes and giant cells in dense connective tissue stroma #1; #2; iron deposits (Prussian blue stain); foam cells

Cytology description
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● Round, spindled and multinucleated cells without atypia
● Round cells have minimal cytoplasm and eccentric nuclei, occasional cytoplasmic hemosiderin, no mitotic figures

Cytology images
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Various images

Positive stains
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● CD68 (stromal and giant cells, Hum Pathol 2003;34:65)
● Also CD31 (75%), calretinin (63%, Pathologe 2005;26:96), desmin (35-40%), CD14
● HAM56, CD45, and lysozyme (Arkh Patol 2010;72:34)

Negative stains
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● S100 (but chondroid areas are S100+), CD45/LCA, EMA, keratin, HMB45, CD34, smooth muscle actin

Electron microscopy description
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● Features of histiocytes and fibroblasts (Ultrastruct Pathol 2002;26:15)

Molecular/cytogenetics description
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● Clonal with neoplastic and reactive features
● Neoplastic due to CSF1 overexpression (Am J Surg Pathol 2007;31:970) or 1p13 (CSF1) rearrangements, often with COL6A3 at 2q35 (Proc Natl Acad Sci USA 2006;103:690)
● Also reactive features (Hum Pathol 2003;34:65)
● Translocations, t(2;3) and der(8) t(8;12) (Ultrastruct Pathol 2002;26:15)
● Some show trisomy of chromosome 5 & 7

Differential diagnosis
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● Hemosiderotic synovitis: associated with hemophilia and intraarticular bleeding, no mononuclear or giant cell nodular proliferation, hemosiderin primarily in synovial lining cells

Additional references
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eMedicine #1, #2, Am Fam Physician 1999;60:1404


Malignant giant cell tumor of tendon sheath-diffuse type

General
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● Rare tumor with coexisting or prior benign giant cell tumor plus sarcomatous areas
● Not a WHO diagnosis

Clinical features
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● Mean 61 years, no gender preference
● Usually extra-articular, near large joints or extremities
● Most common location is knee joint
● Often metastasizes or recurs, but variable outcome (Am J Surg Pathol 2008;32:587, Zhonghua Wai Ke Za Zhi 2008;46:1645)

Case reports
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● 72 year old woman with hip tumor (Jpn J Clin Oncol 1993;23:317)

Gross description
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● Mean 9 cm

Micro description
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● Benign areas with gradual or abrupt change to frank sarcoma containing pleomorphic, spindle or enlarged oval cells resembling MFH, fibrosarcoma, myxosarcoma or giant cell tumor with large nuclei and prominent nucleoli (Am J Surg Pathol 1997;21:153)
● Also necrosis and atypical mitotic figures
● Higher Ki 67 index

Micro images
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Various images

Molecular / cytogenetics description
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● Malignant cases may have trisomy 5 and 7 (Arch Pathol Lab Med 2000;124:1636)
● Deregulated CFS1 overexpression is frequent
● Cyclin A mRNA is up-regulated
● Aberrations of cyclin A, p53, 15q (Clin Cancer Res 2008;14:6023)

End of Soft Tissue Tumors > Fibrohistiocytic tumors > Giant cell tumor of tendon sheath - diffuse type


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