a 55-year - old female presented with 6-month history of progressively worsening right posterior calf pain . on physical exam , the right posterior calf appeared erythematous and warm with decreased range of motion .
core needle biopsy of the right calf mass demonstrated diffuse - type giant cell tumor [ also known as diffuse - type tenosynovial giant cell tumor ( tgct ) ] and the patient underwent surgical resection .
approximately 7 weeks after surgery , the patient noticed swelling and warmth of the right lower extremity with associated slow growth of friable red soft tissue , approximately 1 cm lateral to the incision .
the patient returned to the operating room for resection of suspected recurrent tgct and debridement of devitalized tissue , ultimately followed by amputation .
the slowing of disease was short - lived and , despite multiple subsequent systemic therapies first with imatinib , followed by adriamycin 
ifosfamide , the patient developed extensive metastatic disease with significant tumor burden in the chest and right inguinal region .
radiographs taken on presentation revealed mild osteoarthritis in bilateral knees , with fullness posterior to the right knee [ figure 1 ] .
post - operative ultrasound performed 7 weeks after initial resection showed a complex cystic and solid mass with hypervascular solid components [ figure 2 ] .
mri demonstrated a large , well - circumscribed , mixed - density soft tissue 20-cm mass , with both solid and cystic components extending from the popliteal fossa to the mid - calf [ figure 3 ] .
ct of the chest , abdomen , and pelvis showed no evidence of metastatic disease .
55-year - old female with right posterior calf pain diagnosed with tenosynovial giant cell tumor .
lateral radiograph of the knee reveals soft tissue fullness in the popliteal fossa ( arrow ) .
55-year - old female with right posterior calf pain diagnosed with tenosynovial giant cell tumor .
doppler ultrasound shows prominent vascularity within the solid , echogenic components of the lesion ( arrow ) .
55-year - old female with right posterior calf pain diagnosed with tenosynovial giant cell tumor .
sagittal t1-weighted mr post - contrast imaging reveals enhancement of solid areas ( arrow ) .
mri done 7 weeks after initial resection showed a heterogeneous lobulated lesion with enhancement of the solid components , centered within the gastrocnemius and extending 7 cm superior to the tibiofemoral joint [ figure 4 ] .
low - volume lymph nodes in the right inguinal region were unchanged . given the aggressive appearance of the lesion , the patient underwent a below the knee amputation .
55-year - old female 7 weeks post - resection of tenosynovial giant cell tumor with complaints of pain and friable tissue growth at the incision site .
( a ) coronal t1-weighted post - contrast mri of the right knee shows a heterogeneous lobulated lesion extending to the mid - calf .
margins of soft tissue components of the lesion are ill - defined and somewhat infiltrative in some areas ( arrowhead ) .
( b ) sagittal t2-weighted mr of the right knee shows both cystic ( thick arrow ) and solid ( thin arrow ) areas within the heterogeneous lesion .
core needle biopsy of the right calf mass demonstrated diffuse - type giant cell tumor ( also known as diffuse - type tgct ) with a heterogeneous cell population consisting of sheets of larger , epithelioid cells with round nuclei and discrete cell borders in a background of histocytes , lymphocytes , and scattered hemosiderin [ figure 5a ] , the characteristic appearance of diffuse - type tgct .
numerous giant cells and focal necrosis were also present . although the cytology of the tumor was atypical with a high mitotic rate of 27 per 10 high - power fields ( hpfs ) , a diagnosis of malignant diffuse - type tgct was not warranted in this limited sample as the sample did not meet five out of the eight criteria needed for a diagnosis of malignancy ( see discussion ) .
immunohistochemical stains were negative for smooth muscle actin ( sma ) , desmin , cd34 ( cluster of differentiation protein ) , pan - k , and s100 protein in the small amount of tissue present .
55-year - old female with right posterior calf pain initially diagnosed with tenosynovial giant cell tumor with subsequent resection demonstrating malignant tenosynovial giant cell tumor .
( a ) core biopsy sample of the mass stained with hematoxylin and eosin , 400 , shows epithelioid cells with round nuclei and a background of lymphocytes , histiocytes , several multinucleated giant cells ( thick arrows ) , and scattered mitoses ( thin arrow ) .
( b ) although the majority of the resection specimen appears similar to the core biopsy , select areas of the resection stained with hematoxylin and eosin ( 400 ) , display pleomorphic cytology with large , highly atypical cells ( arrow ) and atypical mitoses ( arrowhead ) , consistent with the diagnosis of malignant diffuse - type tgct .
the right lower extremity amputation specimen , which was received 7 weeks after the initial resection , revealed a large , cystic and solid mass extending from the popliteal fossa to the mid - calf [ figure 6 ] .
microscopic examination showed areas of large , bizarre , and anaplastic epithelioid cells , warranting a diagnosis of malignant tgct .
atypical mitoses were also present , and the tumor showed an infiltrative pattern , with invasion of the skin , associated ulceration and necrosis , and a mitotic rate of 23 per 10 hpfs [ figure 5b ] .
hemosiderin deposition and characteristic cleft - like spaces were readily apparent , along with widespread areas with relatively bland cytology , the characteristic appearance of benign diffuse - type tgct .
55-year - old female who initially presented with progressive right posterior calf pain now status post right leg amputation for malignant tenosynovial giant cell tumor . gross pathology of the amputated right lower extremity reveals a heterogeneous tumor with cystic ( thick arrow ) and solid ( thin arrow ) components extending from the popliteal fossa to the mid - calf .
immunohistochemical stains for sma , d2 - 40 ( focal ) , and desmin ( rare ) were positive in lesional cells , with cd163-positive histiocytes , while s100 , pan - k , cd34 , and leukocyte common antigen ( lca or cd45 ) immunostains were negative .
these differences from the original immunoprofile were minor and also likely due to tumor heterogeneity .
core needle biopsy of the right calf mass demonstrated diffuse - type giant cell tumor ( also known as diffuse - type tgct ) with a heterogeneous cell population consisting of sheets of larger , epithelioid cells with round nuclei and discrete cell borders in a background of histocytes , lymphocytes , and scattered hemosiderin [ figure 5a ] , the characteristic appearance of diffuse - type tgct .
numerous giant cells and focal necrosis were also present . although the cytology of the tumor was atypical with a high mitotic rate of 27 per 10 high - power fields ( hpfs ) , a diagnosis of malignant diffuse - type tgct was not warranted in this limited sample as the sample did not meet five out of the eight criteria needed for a diagnosis of malignancy ( see discussion ) .
immunohistochemical stains were negative for smooth muscle actin ( sma ) , desmin , cd34 ( cluster of differentiation protein ) , pan - k , and s100 protein in the small amount of tissue present .
55-year - old female with right posterior calf pain initially diagnosed with tenosynovial giant cell tumor with subsequent resection demonstrating malignant tenosynovial giant cell tumor .
( a ) core biopsy sample of the mass stained with hematoxylin and eosin , 400 , shows epithelioid cells with round nuclei and a background of lymphocytes , histiocytes , several multinucleated giant cells ( thick arrows ) , and scattered mitoses ( thin arrow ) .
( b ) although the majority of the resection specimen appears similar to the core biopsy , select areas of the resection stained with hematoxylin and eosin ( 400 ) , display pleomorphic cytology with large , highly atypical cells ( arrow ) and atypical mitoses ( arrowhead ) , consistent with the diagnosis of malignant diffuse - type tgct .
the right lower extremity amputation specimen , which was received 7 weeks after the initial resection , revealed a large , cystic and solid mass extending from the popliteal fossa to the mid - calf [ figure 6 ] .
microscopic examination showed areas of large , bizarre , and anaplastic epithelioid cells , warranting a diagnosis of malignant tgct .
atypical mitoses were also present , and the tumor showed an infiltrative pattern , with invasion of the skin , associated ulceration and necrosis , and a mitotic rate of 23 per 10 hpfs [ figure 5b ] .
hemosiderin deposition and characteristic cleft - like spaces were readily apparent , along with widespread areas with relatively bland cytology , the characteristic appearance of benign diffuse - type tgct .
55-year - old female who initially presented with progressive right posterior calf pain now status post right leg amputation for malignant tenosynovial giant cell tumor . gross pathology of the amputated right lower extremity reveals a heterogeneous tumor with cystic ( thick arrow ) and solid ( thin arrow ) components extending from the popliteal fossa to the mid - calf .
immunohistochemical stains for sma , d2 - 40 ( focal ) , and desmin ( rare ) were positive in lesional cells , with cd163-positive histiocytes , while s100 , pan - k , cd34 , and leukocyte common antigen ( lca or cd45 ) immunostains were negative .
these differences from the original immunoprofile were minor and also likely due to tumor heterogeneity .
tgct was first described in 1852 by chassaignac as synovial membrane proliferation involving the flexor tendons of the fingers and was later redefined by jafee et al . , to encompass lesions involving the synovium , tendon sheath , bursa , and joint .
the most common type of localized tgct is also referred to as giant cell tumor of the tendon sheath , which typically occurs as a localized nodule on the tendon sheaths of the fingers or toes . on the contrary
, the diffuse type tends to infiltrate the joint , and more frequently involves large joints , most commonly the knee , followed by the hip .
diffuse - type tgct tends to be more aggressive , often recurring locally ( 856% ) , and is capable of malignant transformation .
enzinger et al . , first described malignant tgct as uncontrolled growth within a benign lesion or as the recurrence of a previously benign lesion . despite aggressive management , including surgical resection , chemotherapy , and radiation , prognosis in malignant tgct is poor .
lesions most commonly metastasize to regional lymph nodes and lungs , with a median survival of 22.5 months after diagnosis .
time to metastatic disease ranges from 4 months to 5 years , with a median of 11 months .
li et al . , and bertoni et al . , described the following histologic characteristics as suggestive of malignancy : nodular and/or solid infiltrative growth pattern , large round or oval cells , cells with large nuclei and nucleoli , areas of necrosis , and atypical mitoses .
criteria for malignant tgct were also developed at the armed forces institute of pathology ( afip ) to include five out of eight characteristics including diffuse pleomorphism , prominent nucleoli , high cytoplasmic to nuclear ratios , mitotic ratio greater than 10 per 10 hpfs , necrosis , discohesion of tumor cells , paucity of giant cells , and a diffuse growth pattern .
our case demonstrated features described by both bertoni et al . , and the afip to be classified as malignant [ figure 5b ] and
the initial biopsy of the lesion was atypical including a mitotic rate greater than 10 per 10 hpfs as well as necrosis ; however , it did not fulfill enough of the criteria to be classified as malignant tgct . radiographic appearance of tgct is non - specific , ranging from soft tissue swelling to soft tissue mass and bony involvement .
radiographs of tgct lesions most commonly demonstrate joint effusion , soft tissue swelling , bony erosion , and lack of calcification in the context of normal bone mineralization and preservation of the joint space . similarly , ultrasound is non - specific ; however , it is useful for characterizing its solid and cystic components .
mri is superior due to its better delineation of soft tissues and its ability to more accurately determine the extent of synovial proliferation , joint effusion , bone erosion , and deposits of hemosiderin .
tgct lesions generally have hemosiderin deposits , which will appear as dark , low - signal regions on t1-weighted and t2-weighted images , with associated susceptibility artifact on gradient echo sequences .
the presence of hemosiderin is characteristic of tgct lesions ; however , it can also be seen in other lesions such as synovial hemangioma or hemophiliac arthropathy and does not correlate with malignant potential .
regions of enhancement can be seen in tgct in the regions of synovial proliferation , but do not predict the aggressiveness of the lesion .
imaging of malignant tgct is rarely reported , and the only description of the mri characteristics suggestive of malignant tgct is reported in the pathology and rheumatology literature and includes frequent lobulation , infiltrative lesions with poorly defined margins , and close association with tenosynovial structures and/or joint spaces .
murphey et al . , suggest that findings most consistent with a malignant lesion are bony invasion and presence of metastases .
our patient 's first post - resection mri included multiple areas of lobulation and close association with the joint ; however , these findings are also often seen in benign disease .
the most concerning feature of the post - resection mri was diffuse involvement of the medial and lateral gastrocnemius muscles with an infiltrative appearance and loss of clear tissue planes , a finding that was not seen on the initial mri .
in all reported cases , the diagnosis of malignant tgct was not made until after histopathologic examination of the biopsied lesion , most likely because of the low incidence of the lesion and the paucity of imaging of malignant tgct in the literature .
this case highlights the appearance of malignant tgct on multiple imaging modalities . while no single clinical , histopathologic , or radiographic feature separates benign from malignant lesions , a compilation of findings including rapid recurrence , and infiltrative appearance on imaging with invasion of adjacent soft tissues suggest malignancy .
therefore , the current standard of practice remains local wide resection of tgct lesions with close follow - up and tissue sampling when clinically indicated .
 malignant tenosynovial giant cell tumor ( tgct ) is a rare clinical entity that can arise as a recurrent lesion or can co - exist with a benign tgct lesion . 
 malignant tgct most commonly arises in the lower extremity and tends to be clinically aggressive , with most patients developing recurrent lesions or dying . 
 much of the literature describes the histopathologic features and classifies this broad group of tumors , with little description of the imaging characteristics of this disease . 
 we present the multimodality appearance of a case of malignant diffuse - type tgct that recurred 2 months after resection with subsequent rapid clinical progression . 
INTRODUCTION
RADIOLOGIC FEATURES
PATHOLOGIC FEATURES
Initial pathology
DISCUSSION
CONCLUSION