A 29-year-old female presented with a one year history of swelling at the medial side of her left knee. Ultrasound examination reveals a subcutaneous isoechoic to hypoechoic lesion measuring 2.1 x 1.5 x 2 cm, with internal vascularity.

 

Authors

• Sophia Liu, University of Pennsylvania, Philadelphia, PA
• Daisy Sun, MD PhD, Miami Valley Hospital, Dayton, OH

Diagnosis & Discussion
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Figure 1	Figure 2	Figure 3
Figure 4	Figure 5	Figure 6

Images 1-6:

• Figure 1: Rapid on-site evaluation (ROSE) FNA material of left knee soft tissue mass, smear, Diff-Quik stain, 40x magnification
  
  
• Figure 2: Rapid on-site evaluation (ROSE) FNA material of left knee soft tissue mass, smear, Diff-Quik stain, 400x magnification
  
  
• Figure 3: Rapid on-site evaluation (ROSE) FNA material of left knee soft tissue mass, smear, Diff-Quik stain, 400x magnification
  
  
• Figure 4: Rapid on-site evaluation (ROSE) FNA material of left knee soft tissue mass, smear, Diff-Quik stain, 400x magnification
  
  
• Figure 5: Core biopsy of left knee soft tissue mass, H&E, 100x magnification
  
  
• Figure 6: Core biopsy of left knee soft tissue mass, CD163, 100x magnification

Questions:

1. What is the best diagnosis based on the cytomorphology, histomorphology and immunohistochemical findings in Figures 1 through 6?
   
   
1. Melanoma
2. Pyogenic granuloma
3. Tenosynovial giant cell tumor, diffuse type
4. Granular cell tumor
5. Tenosynovial giant cell tumor, localized type



2. Which of the following is true regarding tenosynovial giant cell tumor, localized type?
   
   
   1. Most commonly occur in the knee and hip
   2. Diagnosis can be made even in the absence of osteoclast-like giant cells
   3. Highly infiltrative lesion, which leads to recurrence in the majority of cases
   4. It is the most common tumor of the hand
   5. The patient always reports a history of trauma
      
      
3. Which of the following is true regarding malignant tenosynovial giant cell tumor?
   
   

1. Malignant tumor located around a large joint
2. Patient may have a prior history of tenosynovial giant cell tumor
3. Often occurs in upper extremities
4. Usually affects young people

Answers:

Question 1: Correct answer is C
The smears (Figs 1-3) show a cellular specimen with cells in clusters or singly, composed of mostly hemosiderin-laden foamy macrophages and mononuclear cells, some of which display mild nuclear enlargement and occasional binucleation. A possible multinucleated giant cell (Fig 4) is identified. Core biopsy material (Fig 5) shows diffuse sheet-like growth of cells forming blood filled pseudoalveolar and cleft-like spaces. No/minimal giant cells are seen. Immunohistochemistry (IHC) (Fig 6) shows that the mononuclear cells are positive for CD163 and CD68 while negative for AE1/3 and SOX10. Iron staining highlights abundant hemosiderin. The cytomorphology and immunohistochemical profile are most consistent with tenosynovial giant cell tumor (TGCT), diffuse type.

Question 2: Correct answer is B
TGCTs encompass a group of lesions that involve synovium-lined tendon sheaths, synovial joints, and adjacent soft tissue. They are divided into intra- or extra-articular based on site, and localized or diffused (D-TGCT) based on growth pattern. The localized forms mainly involve small joints, and are systematically benign, while D-TGCTs are more aggressive and destructive, typically monoarticular and affect large joints.  Extra-articular D-TGCTs are very rare. Grossly, localized TGCTs are well circumscribed and partially encapsulated while D-TGCTs are poorly demarcated from adjacent tissue. Microscopically, the lesion is composed of a polymorphous cell population including mononuclear cells, foamy macrophages, multinucleated giant cells, and hemosiderin. Multinucleated giant cells serve as a major diagnostic clue. Multinucleated giant cells are less common in D-TGCTs than the localized form and may be absent or extremely rare in 20% of the cases. IHC studies can be helpful. Clusterin stains larger mononuclear cells and Desmin can be positive in cells with dendritic features in 45-80% of cases. The histiocyte-like cells are positive for CD68, CD163, and CD45.
Question 3: Correct answer is B
Originally thought of as a non-neoplastic reactive process, the etiology for TGCT is now related to overexpression of colony stimulation factor 1 (CSF-1), which is a hemopoietic growth factor and results in soft tissue hyperplasia in synovial cells. The nonspecific symptoms and radiographic and histological findings make the diagnosis a challenge.

Malignant TGCT is extremely rare, with high local recurrence rate and high potential for  distant metastasis. Based on criteria defined by Enzinger and Weiss, malignant TGCT are either benign TGCT coexisting with sarcoma (primary malignant TGCT) or sarcomatous recurrence of a previously diagnosed benign TGCT (secondary malignant TGCT). Most of these malignant TGCTs occur in lower extremities of middle aged to older adults, with a male predominance.