Chennagiri S. Premalata, md#82, 2nd main, 4th phase, 7th block Banashankari 3rd stage Bangalore Karnataka-560085 India E-mail: firstname.lastname@example.org
We report a case of myxoinflammatory fibroblastic sarcoma in a thirteen year old gilrl who presented with a tender swelling in the left upper back. The tumor consisted of varying proportions of inflammatory, myxoid and hyalinized areas. Large bizarre cells with virocyte like inclusions and lipoblast like cells were present. To the best of our knowledge this is the first reported case of myxoinflammatory fibroblastic sarcoma of the back, the extremities being the commonest site of involvement. Due to its varied histologic appearance, the tumor should be differentiated from various benign and malignant soft tissue lesions.
Myxoinflammatory fibroblastic sarcoma (MIFS), or acral MIFS, is a recently described low-grade sarcoma characterized by a poorly defined lobulated tumor with myxoid, inflammatory, and fibrous or hyalinized areas, and large bizarre ganglion-like cells with huge inclusion-like nucleoli and multivacuolated lipoblast-like cells. The tumor predominantly involves the subcutaneous tissues of the hands and feet and, to a lesser extent, the wrists and ankles.1 A few cases have been described in more proximal regions, such as the neck, thigh, and shoulder,2–4 and the term acral was dropped in the 2002 World Health Organization (WHO) classification.5 The tumor is seen most frequently in adults, with a wide age range of 4–81 years, and an equal sex distribution.6 We describe a case of MIFS in a 13-year-old girl, which occurred at an unusual site: the upper back over the scapula. This location has not been described previously in the world literature.
A 13-year-old girl presented with a painful swelling over the left scapular region of 4 months’ duration, with a gradual increase in size. There was no history of trauma. On examination, a soft to firm, tender, 7 × 6 × 6-cm subcutaneous swelling was seen in the left scapular region. The overlying skin showed a scar from a previous biopsy and was freely mobile. There was no regional lymphadenopathy. The underlying bone was free. Chest X-ray and abdominal ultrasound were normal. Fine needle aspiration of the lesion was performed using a 24G needle, and smears were stained with May–Grunwald–Giemsa and Papanicolaou stains. Cytology smears were cellular and were characterized by the following: (i) large, ganglion-like cells, some bi- and multinucleated, with huge inclusion-like nucleoli and intranuclear inclusions (Fig. 1); (ii) many small, uniform, mononuclear, polygonal to spindle cells, often encircling the ganglion-like cells (Fig. 1); (iii) lipoblast-like cells with vacuolated cytoplasm and hyperchromatic scalloped nuclei; and (iv) a background of myxoid matrix with blood vessels and fat cells and scattered pigment-laden macrophages. The possibility of a sarcoma was suggested, and wide excision of the lesion was advised. Aspirated material was also sent for cytogenetic analysis which, however, failed to show metaphases. Histopathology slides of an earlier biopsy performed elsewhere were also reviewed, and showed scattered multivacuolated cells and inflammatory cells in a predominantly myxoid background. The possibility of a benign soft tissue lesion was considered and, in view of the aggressive cytologic findings, a wide excision of the tumor was performed and the specimen was sent for histopathologic examination.
Grossly, an ill-defined lesion measuring 5 × 5 × 4.5 cm was seen in the subcutaneous tissue, composed of lobules of gelatinous material. The overlying skin was free. Microscopically, a lobulated infiltrating tumor was seen in the subcutaneous tissue, focally infiltrating the dermis, showing a variable admixture of myxoid (Fig. 2), inflammatory, and fibrous (Fig. 3) areas. The myxoid nodules showed scattered, large, multivacuolated lipoblast-like cells with scalloped nuclei and vacuolated mononuclear cells lying in pools of mucin (Fig. 4a). The inflammatory areas showed dense infiltrates of lymphocytes, plasma cells, neutrophils, eosinophils, and macrophages. Scattered amongst them were large ganglion-like cells, some multinucleated, with huge eosinophilic inclusion-like nucleoli resembling virocytes (Fig. 4b) and striking intranuclear vacuoles (Fig. 4c). Emperipolesis, with inflammatory cells within the cytoplasm of the large tumor cells, was also seen (Fig. 4a). Occasional multinucleated Touton-type giant cells, synovitis-like areas with groups of uniform mononuclear cells, foci of hemorrhage, and hyalinized areas were also noted. Lipoma-like areas with lobules of fat were seen intricately admixed with the tumor, which has not been described previously.
The tumor cells were positive to immunohistochemical stains for vimentin (1 : 50; Dako, Glostrup, Denmark), S-100 (Fig. 4d) (1 : 75; Novocastra, Newcastle, UK), CD31 (1 : 50; Dako), and CD34 (1 : 50; Dako), and negative for cytokeratin (1 : 50; Novocastra), epithelial membrane antigen (1 : 50; Novacastra), desmin (1 : 20; Novocastra), and HMB45 (1 : 50; Dako). The small mononuclear cells were positive for CD68 (1 : 80; Novocastra), and the large bizarre tumor cells were negative. Immunostaining for latent membrane protein 1 (LMP1) of the Epstein–Barr virus was negative (1 : 50; Dako).
With the above distinctive morphologic features, a diagnosis of MIFS was made.
MIFS is a recently described low-grade sarcoma. Montgomery et al.6 first described 51 cases mainly occurring in the wrists, digits, and ankle regions, with an equal sex distribution, and seen over a wide age range of 4–81 years; they named it “inflammatory myxohyaline tumor of the distal extremities with virocyte or Reed–Sternberg-like cells.” At about the same time, Meis-Kindblom and Kindblom1 described a series of 44 similar tumors as acral MIFS, and also noted a relation to tendon sheaths and joints. Five similar tumors were described by Michal7 under the heading “inflammatory myxoid tumor of the soft parts with bizarre giant cells.” The tumor commonly presents as a painless, slowly growing mass in the extremities, but also occurs in the more proximal soft tissues, such as the neck and shoulder.3,4 Most of the tumors were diagnosed as inflammatory or benign lesions on biopsy because of the varied histologic appearance of this tumor.1 Our case is the first to be reported in the scapular region, with an unusual presentation of a painful, tender, slowly growing mass in a 13-year-old girl.
The cytomorphologic features of this tumor are also very distinctive, and a diagnosis of MIFS is possible on fine needle aspiration biopsy provided that all the distinctive features are sampled.8
Gross examination usually shows an ill-defined multinodular mass with myxoid areas in the subcutis. Histologically, MIFS shows a striking admixture of myxoid, inflammatory, and hyalinized areas. The myxoid areas show vacuolated, large, lipoblast-like cells and scattered mononuclear cells. The inflammatory areas show lymphoid aggregates, neutrophils, eosinophils, and plasma cells admixed with large ganglion-like cells, with huge inclusion-like nuclei resembling virocytes or Reed–Sternberg cells, sometimes showing emperipolesis9 and areas of hyalinization. Synovitis-like areas with infiltration by bland mononuclear cells have been described.1 In our case, in addition to the typical features of MIFS, there were lipoma-like areas intimately admixed with other areas. Ultrastructurally, the bizarre tumor cells show features of modified fibroblasts, with an abundance of intermediate filaments and dilated rough endoplasmic reticulum.1 Clonal chromosomal changes have been described in one case, which showed a complex karyotype with reciprocal translocation t(1;10)(p22;q24) in addition to the loss of chromosomes 3 and 13, supporting the neoplastic nature of MIFS.10 Immunostains show consistent positivity for vimentin and variable positivity for CD34, cytokeratin, CD68, and smooth muscle actin (SMA).1,2,6,11 The presence of virocyte-like cells raises the possibility of an infectious etiology. Montgomery et al.6 analyzed 10 cases of MIFS by polymerase chain reaction for Epstein–Barr virus, and found that four patients were positive; they suggested the possibility of a latent rather than active infection. Immunostaining for LMP1 of the Epstein–Barr virus was negative in our case.
Our case of MIFS showed certain unique features: (i) location in the left upper back in the lower scapular region; (ii) presentation as a painful, tender mass, which is not surprising considering the rich inflammatory component of the tumor; and (iii) presence of lipoma-like areas closely associated and admixed with the tumor.
The differential diagnosis of MIFS includes inflammatory and benign entities, such as nodular and proliferative fasciitis, tenosynovitis, inflammatory myofibroblastic tumor, and benign myxoid lesions such as myxoma and ganglion cyst, especially in small biopsy specimens. The typical large bizarre cells with huge virocyte-like inclusions within inflammatory and myxoid areas are not seen in these lesions. MIFS should be differentiated from malignant tumors, such as myxoid malignant fibrous histiocytoma, myxoid liposarcoma, and epithelioid sarcoma. Myxoid malignant fibrous histiocytoma shows focal areas of high-grade pleomorphic sarcoma with a storiform pattern and lacks virocyte-like cells. Myxoid liposarcoma usually occurs in deep soft tissues and lipoblasts contain fat rather than the mucin seen in the neoplastic cells of MIFS. Epithelioid sarcoma is characterized by necrosis and immunoreactivity for cytokeratin, and lacks inflammatory cells and bizarre neoplastic cells.
In conclusion, MIFS is a low-grade sarcoma with a high rate (22–67%) of local recurrence, sometimes leading to amputations.1 Metastasis to the lungs and liver has been reported, but is very rare and can occur rapidly.1,11 We describe the cytologic and histologic features of a rare case of MIFS of the back, in the subcutaneous tissue over the scapula, the first such tumor to be described at this site. The patient underwent wide excision of the lesion and was free of disease 10 months after surgery.