Tenosynovial giant cell tumor presenting as a parotid gland mass: Expanding the differential diagnosis of giant cell-rich lesions in salivary glands.

Tenosynovial giant cell tumors (TGCT) are rare benign soft tissue tumors affecting mostly young adults. The most common affected sites include the knee, ankle, elbow, shoulder, and fingers. The temporomandibular joint is occasionally affected. Herein, we report a case of a 31-year-old Caucasian male who presented clinically with a parotid gland mass. The initial clinical and radiological work-up failed to reveal any involvement of the adjacent temporomandibular joint. Fine-needle aspiration revealed a cellular tumor composed of mononuclear and multinucleated giant cells with fibrosis and hemosiderin deposition. This was subsequently found to be a TGCT arising from the temporomandibular joint. Giant cell-rich lesions are uncommon in salivary glands. Herein, we describe the cytomorphology and clinico-radiographic features of this tumor with emphasis on the differential diagnosis of giant cell-rich lesions presenting in salivary glands. Despite its rare occurrence, this entity should be considered when giant cells are prominent in specimens acquired from this location.

Introduction

Tenosynovial giant cell tumors (TGCT), also known as giant cell tumors of tendon sheath, are benign locally recurring lesions. They are the prototypical tumors arising from the synovium and are also the most common benign tumors of the tendon sheath and synovium.[1] TGCT usually occur in young to middle-age patients, with women being more affected than men. They are divided into localized and diffuse forms based on their clinical presentation and growth pattern. The localized variant, also called nodular tenosynovitis, is the most common form. They occur predominantly in the hands near the synovium of the tendon sheath or interphalangeal joint. The diffuse form is also known as a pigmented villonodular tenosynovitis which mostly affects larger joints such as the knee, hip, and shoulder.[1] It is very rare for these tumors to be encountered in the parotid gland, and the differential diagnosis can be considerably challenging, especially when involvement of the adjacent joint is inconspicuous. Although histologic features of this entity have been adequately reported in the literature,[23] only a few reports have described the cytology of TGCT involving the parotid gland.[3]

Case Report

A 31-year-old Caucasian male presented with the right facial swelling which had been increasing in size. The patient became aware of the mass following history of trauma to the face. Physical exam revealed a 2-3 cm firm mass in the right parotid gland just anterior to the right tragus. No cervical lymphadenopathy was present. Imaging showed a 3.2 cm × 2.2 cm × 2.2 cm multilobulated, homogenous, solid mass in the superficial parotid gland with extension into the deep lobe, right temporalis, and right lateral pterygoid muscle. This was clinically thought to represent a benign tumor favoring a pleomorphic adenoma.

A fine-needle aspiration (FNA) biopsy of this tumor was performed. Smears and a cell block were prepared. The smears showed a cellular specimen composed of single cells and cohesive groups of mononuclear epithelioid cells with moderate to abundant cytoplasm, round to oval paracentric nuclei and conspicuous nucleoli. Numerous multinucleated giant cells with similar nuclear features were present [Figure 1a and b]. Fibrosis and hemosiderin deposition were noted in the cell block material [Figure 1c]. No significant cytologic atypia, pleomorphism, necrosis or increased mitotic activity, was appreciated. Immunohistochemical analysis showed strong positive staining of the cells for CD68 and vimentin [Figure 2], with negative staining for cytokeratin AE 1/3, S-100 protein, smooth muscle actin (SMA) and p63 (CD68 is used to highlight histiocytes and macrophages; vimentin is often expressed in mesenchymal cells; cytokeratin AE 1/3 is an epithelial marker; S-100 protein is usually positive in melanocytic and nerve sheath tumors; SMA is used to identify normal and neoplastic smooth muscle cells, myofibroblasts and myoepithelial cells; p63 protein is often used to identify myoepithelial and squamous cell neoplasms). Based on the above findings, a giant cell tumor or a reactive/granulomatous process was favored over a primary salivary gland neoplasm. Excision of the lesion was recommended.

Figure 1

(a and b) The smears show a cellular specimen composed of single cells and cohesive groups of mononuclear epithelioid cells with moderate to abundant amount of cytoplasm, round-oval paracentric nuclei and conspicuous nucleoli. Numerous multi nucleated giant cells with similar nuclear features are dispersed in the background (revision g) (Diff-Quick, ×200). (c) Cell block material shows features similar to the aspirate material with focal hemosiderin deposit on (revision g) (H and E, ×200)

Figure 2

Immunostains show the cells of concern being strongly and diffusely positive for CD68 (a) and vimeninn (b) (IHC, ×100)

On gross examination, the resection specimen consisted of two cauterized soft tissue fragments measuring 5 cm × 4 cm ×3.3 cm in aggregate. The cut surface showed tan, white lobulated tissue with focal hemorrhage. Microscopically, the lesion was composed of solid sheets of epithelioid mononuclear and multinucleated giant cells surrounded by thick fibrous bands. Focal hemosiderin pigment deposition was present. The cells exhibited round to oval nuclei with small conspicuous nucleoli. No significantly increased mitotic activity or necrosis was present. The adjacent parotid gland appeared unremarkable. Seven lymph nodes identified were all negative for malignancy. A diagnosis of TGCT was rendered.

Ten months following the initial presentation, a follow-up computed tomography scan revealed a 10 mm residual mass anterior to the mandibular condyle and extended toward the right lateral pterygoid muscle. The right temporomandibular joint showed an irregularity with erosion of the anterior margin of the right glenoid fossa. A repeat aspiration biopsy confirmed the recurrence of the giant cell-forming tumor. The patient underwent resection of the tumor and the temporomandibular joint with identical histologic features to those seen in the prior resection. Follow-up imaging results (brain magnetic resonance imaging) showed no residual tumor.

Discussion

Fine needle aspiration has been a very powerful tool in the diagnosis of primary salivary gland lesions. Many salivary gland lesions can be accurately diagnosed by FNA cytology.[3456] The aspiration smears of TGCT are usually characteristic and show variable numbers of multinucleated giant cells dispersed in the background of the mononuclear histiocytoid cells.[178] The histopathologic differential diagnosis of giant cell-rich lesions in the salivary glands is extensive [Table 1]. One important differential is “giant cell tumor” of the salivary gland. It is a very rare lesion often associated with other primary tumors of the salivary gland. The lesion shows malignant appearing atypical mononuclear and multinuclear cells with high nuclear to cytoplasmic ratios and prominent nuclear pleomorphism. Malignant processes such as malignant fibrous histiocytoma with giant cells should be excluded. They are often larger and show more significant atypia, abundant necrosis, and atypical mitoses. Metastatic melanoma can certainly present in this area and may demonstrate many multinucleated giant cells on cytology and histopathology and should always be excluded.[179]

Table 1

Differential diagnosis of giant cell-rich lesions of the salivary glands

Infectious and inflammatory lesions in the differential diagnosis include granulomatous lesions such as the necrobiotic granuloma or foreign body giant cell reaction. Granulomatous lesions are usually less localized and have more inflammatory cells. Necrobiotic granulomas are characterized by degenerating collagen surrounded by histiocytes and proliferating capillaries. Tendinous xanthomas may also be confused with TGCT; however, the former tend to arise in the setting of hyperlipidemia and are composed predominantly of xanthoma cells with cholesterol clefts and absence of mononuclear cells.[110]

In summary, TGCT of the temporomandibular joint may present clinically and radiologically as a primary parotid gland lesion.[3] It is important to keep this entity in the differential diagnosis of giant cell-rich lesions in the parotid gland sampled by FNA.