Fibrosarcomatous change in the background of dermatofibrosarcoma protuberans in male breast: Study of a rare case and review of the entity.

Dermatofibrosarcoma protuberans is a cutaneous soft tissue neoplasm with potential for local recurrence but distant metastasis is rare. Trunk and extremities are most commonly involved. This case presented as left-sided breast lump in a male patient. The patient underwent left-sided modified radical mastectomy. Tissues were subjected to histopathological and immunohistochemical test subsequently. The tumor cells showed storiform arrangement with nuclear pleomorphism and increased mitotic figures at places. They were reactive to CD34 and non-reactive to S-100, smooth muscle actin, desmin, cytokeratin and epithelial membrane antigen. The diagnosis of dermatofibrosarcoma protuberans with areas of fibrosarcomatous change was given. Though trunk is a common site for this tumor but its presentation as male breast lump has made the case unique.

INTRODUCTION

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft tissue neoplasm first described by Taylor in 1890. It is locally aggressive and has an infiltrative growth pattern but distant metastasis is uncommon.[1] It most commonly occurs in adults over the age of 30 and constitutes 2-6% of all soft tissue sarcomas. DFSP most commonly involves trunk and extremities. Male: Female ratio is 1:1. Mainstay of treatment is wide local excision, although Mohs micrographic surgery (MMS) emerges as an alternative approach.[2] Our case highlights two interesting features. First, there is an unusual occurrence of DFSP in breast and second, there is fibrosarcomatous change in the background of DFSP.

CASE REPORT

A 40-year-old male presented with chief complaints of lump in the central part of his left breast for 3 months. It was gradually increasing in size but there was no history of pain. He did not have any significant past history of illness and his family history was unremarkable. On examination, it was a firm, mobile, nodular, non-tender swelling and showed an area of ulceration on the overlying skin. The lump grossly measured 6.5 cm × 4 cm and the area of ulceration measured 3.2 cm × 2 cm. His hematological and biochemical parameters were within normal limit. Fine needle aspiration cytology (FNAC) was done from the swelling and smears showed large number of ovoid- to spindle-shaped cells with mild to moderate nuclear atypia and scanty cytoplasm. The cells were arranged discretely and also in some clusters in a myxoid background [Figure 1]. Impression of FNAC smears was 'mesenchymal lesion, probably intermediate grade neoplasm'. The patient then underwent left-sided modified radical mastectomy [Figure 2]. Gross appearance of the tumor was partly solid and partly cystic. The solid area was grayish fleshy in appearance. Histopathological examination of sections from tumor revealed a tumor composed of spindled-shaped cells having plump nuclei, arranged in intersecting fascicles and storiform pattern [Figure 3]. The tumor cells showed nuclear pleomorphism and increased mitotic figures (8-10/10 high power field) were seen in some areas [Figure 4]. Plexiform capillary network was seen in the background with areas of hemorrhage and myxoid change [Figure 5]. The tumor involved overlying skin, nipple and areola [Figure 6]. Surgical lines of resections were tumor-free and all the 19 lymph nodes dissected from axillary pad of fat showed reactive changes. Impression of histopathological examination was spindle cell sarcoma of left breast, and paraffin blocks of the tumor were subjected to immunohistochemical (IHC) test. On IHC test, tumor cells were reactive to CD34 [Figure 7] and non-reactive to S-100, smooth muscle actin, desmin, cytokeratin and epithelial membrane antigen. So, the final diagnosis of DFSP with areas of fibrosarcomatous change was given.

Figure 1

Ovoid to spindle shaped cells with mild to moderate nuclear atypia and scanty cytoplasm, arranged discretely and also in some clusters in a myxoid background

Figure 2

Mastectomy scar–left

Figure 3

Tumour composed of spindled shaped cells with plump nuclei, arranged in intersecting fascicles and storiform pattern

Figure 4

Mitotic figures and nuclear atypia–high power view

Figure 5

Areas of myxoid change along with a capillary

Figure 6

Tumour involving overlying skin

Figure 7

Tumour cells stain positively for CD34

DISCUSSION

DFSP is classified among the fibroblastic/myofibroblastic tumors of intermediate malignancy (rarely metastasizing). Histologically, it is characterized by diffuse infiltration of dermis and subcutis by neoplastic cells, which grow along the fibrous septa of the subcutaneous tissue and interdigitate with fat lobules, resulting in a honeycomb appearance. The epidermis is usually uninvolved and tumor cells encase skin appendages without destroying them. The cells are uniform spindle-shaped containing plump or elongated wavy nuclei and arranged in predominantly storiform pattern. Mitotic activity is usually low.[3] Occasionally, DFSP may show focal fibrosarcomatous changes with a characteristic herringbone pattern. The cellular atypia is then even more prominent with hyperchromatic nuclei and increased mitotic figures. Histologic subtype, high mitotic index, cellularity, size, location on the head and neck, and recurrent lesions are factors reportedly associated with higher recurrence rates.[4] In our case too, in some areas, cytological atypia was marked and mitotic figures were increased (8-10/10 high power field). Immunohistochemical studies have shown moderate to strong staining of human progenitor cell antigen CD34 in tumor cells. CD34 is a useful marker that allows differentiation of DFSP tumor cells from normal stromal cells and dermatofibroma (DF). In DF, tumor cells are positive for factor XIIIa and are rarely positive for CD34. Additionally, immunostaining using CD34 as a marker is helpful in identifying tumor cells at the surgical margins, particularly when treating recurrent DFSP, in which tumor cell fascicles are often interspersed with the scar tissue. Although CD34 and factor XIIIa can differentiate most cases of DFSP and DF, the overlap of CD34 and factor XIIIa expression in both lesions indicates the need to identify other potential immunohistochemical markers.[5] Recently, Stromelysin-3 (ST3) was found to be a useful marker for the differential diagnosis of DF and DFSP. ST3 is a member of the matrix metalloproteinase (MMP) family, which is believed to play a role in tissue remodeling during various processes, such as wound healing and tumor invasion. ST3 is expressed in the majority of cases of DF, whereas DFSPs are only rarely ST3 positive.[6] Most cases of DFSP feature a specific translocation of chromosomes 17 and 22, which results in constitutive production of platelet-derived growth factor B chain (PDGFB) and stimulation of DFSP growth. Surgical excision remains treatment of choice for DFSP. Most authorities would suggest a margin of 2-3 cm of normal tissue from the gross tumor boundary. Despite optimal surgical management, local and regional recurrences are detected in up to 17% of patients with classic DFSP.[4] Nowadays, MMS has been advocated by several authors as an alternative approach to the use of wide resection surgery with tumor-free margins. Mohs surgical technique allows an immediate microscopic examination of the margins. Imatinib mesylate is a potent inhibitor of PDGFB. On October 19, 2006, the US Food and Drug Administration (FDA) granted approval for imatinib, as a single agent for the treatment of adult patients with unresectable, recurrent, and/or metastatic DFSP. With limited clinical data to date, a response rate of approximately 65% has been achieved among DFSP patients treated with imatinib (recommended dose 800 mg/d). A small subset of DFSP lacking the classic translocation t (17:22) seems to have no response to imatinib.[7] Our case has been treated with left-sided modified radical mastectomy on the basis of FNAC diagnosis but imatinib was not administered in postoperative period. To conclude, though dermatofibrosarcoma can arise in the trunk, its presentation as male breast lump is rare and focal areas of fibrosarcomatous change has made the case more unique. Close follow-up of the patient is required to detect any recurrence at the earliest.

Financial support and sponsorship

Department of Pathology, Chittaranjan National Cancer Institute.

Conflict of interest

There are no conflicts of interest.