FINAL DIAGNOSIS: MYOFIBROBLASTOMA, EPITHELIOID TYPE
Myofibroblastoma is an uncommon tumor of the breast composed of cells having features of both fibroblastic and smooth muscle origins. It is predominantly observed in the male breast, presenting as a solitary, palpable, firm mass that is freely movable. Grossly, it is a well-circumscribed lesion. Microscopically it is characterized by nodular proliferation of plump spindle cells, separated by wide ribbons of collagen. Local excision is curative and to date, there are no reported cases of recurrence or distant metastasis. The importance of diagnosing this lesion accurately is emphasized here to avoid extensive and radical surgery.
Myofibroblasts are spindle shaped or fusiform mesenchymal cells derived from fibroblasts.1 They can be seen in all tissues outside the central nervous system. They can be distinguished from spindled myoepithelial cells on the basis of their distribution, immunohistochemical and ultrastructural characteristics.
Wargotz et al2 in 1987 first described the term "myofibroblastoma". In a series of sixteen patients, the median age was 64 (range 41-85 years) and eleven of the sixteen patients were men. Of the five women, four were post-menopausal. Skin retraction, axillary node enlargement and nipple discharge were absent in all patients.
About 60 cases of myofibroblastoma have been reported in the literature so far.3 Men and women are found to be equally affected. The size of the lesion ranges between 0.9 to 10 cm; the mean diameter being 2.7 cm.
According to the histological composition, myofibroblastomas are divided into five subtypes, i.e. classic type, collagenized, epithelioid, cellular and infiltrative variant. Classically these tumors are composed of bundles of slender, bipolar, uniform, spindle shaped cells typically arranged in clusters separated by broad bands of collagen throughout the tumor. The epithelioid variant shows polygonal or epithelioid cells arranged in alveolar groups. This pattern may co-exist with classical variant or may constitute the predominant growth pattern. The term epithelioid variant is used to describe tumors in which more than 50% of the lesion has this histological pattern.4
The FNA examination revealed a bland cellular appearance, comprising of cells with abundant cytoplasm, centrally placed uniform nucleus & prominent nucleolus. The differential diagnosis of these epitheloid cells includes epithelial lesions like infiltrating ductal carcinoma, apocrine carcinoma and the granular cell tumor of the breast. Absence of single cells, nuclear atypia, pleomorphism and mitosis rules out the possibility of ductal and apocrine carcinoma. Negative staining with AE1/AE3 and positive staining with smooth muscle actin (SMA), desmin and CD34 helps to exclude any epithelial malignancy. It is also important to consider mesenchymal lesions like nodular and proliferative fasciitis, fibromatosis, leiomyoma, spindle cell lipoma, myoepithelioma and peripheral nerve sheath tumors (PNST) in the differential diagnosis.5 Malignant tumors like spindle cell carcinoma, stromal sarcoma and malignant fibrous histiocytoma should also be included in the differential diagnosis.6 The lack of cytologic atypia along with absence of hemorrhage, necrosis and mitotic figures in the present case would help to rule out the malignant spindle cell tumors. The benign stromal tumors can be differentiated by immunohistochemical stains that can be performed on the paraffin embedded cell block material from the FNA biopsy. In our case, we had a simultaneous core biopsy on which the stains were carried out.
PNSTs are S-100 positive and negative for actin, desmin and CD34. Spindle cell lipoma would be composed predominantly of adipose tissue, a feature that was lacking in the present case. Also actin, desmin and CD34 would be negative in these cells. Leiomyoma would yield a more cellular aspirate with appreciable amount of eosinophilic cytoplasm containing blunt ended nuclei. The cells in leiomyoma are positive for actin, desmin and negative for CD34. The lack of keratin and/or S100 expression would rule out myoepithelioma. Fibromatosis, nodular and proliferative fasciitis of the breast would show plump mesenchymal cells in a mucoid and inflammatory background on aspiration cytology. Excisional biopsy of fibromatosis and fasciitis will show infiltrative margins, a feature unusual in myofibroblastomas except in infiltrative variant.
The cell of origin of myofibroblastoma has not been defined so far. Possible precursor cells are thought to be fibroblasts, pericytes and smooth muscle cells.7
To summarize, myofibroblastoma can be diagnosed and differentiated from benign and malignant stromal tumors, both by morphology and immunostaining. This aids in appropriate patient management, by simple excision avoiding radical surgery.
Contributed by Anuradha Murty Dharbhamulla, MD, MSc, MIAC, Dilip Gupta, MD, MIAC and Manju E. Nath, MD