A male case of dermatofibrosarcoma protuberans in the breast presenting as gynecomastia

Introduction. Dermatofibrosarcoma protuberans (DFSP) is a very rare 
 mesenchymal tumor that accounts for approximately 0.1% of all malignancies. It is a locally aggressive fibrous tumor, with a high recurrence rate, which 
 sometimes gives rise to distant metastases, usually to the bones and lungs. 
 DFSP usually occurs on the trunk and extremities with only a small number of 
 cases in the breast, especially in men. Case report. This paper analyzes a 
 rare case of DFSP in the male breast. A 66-year-old man presented with 
 gynecomastia of the left breast. The diagnostic work-up comprised of 
 clinical examination, ultrasonography, core biopsy, and mammography. 
 Immunohistochemistry revealed diffuse and strong positivity for vimentin, 
 CD99, and CD34, while the tumor cells were completely negative for keratin, 
 S100 protein, STAT6, CD31, and factor VIII, highly suggestive for DFSP. 
 Subsequently, a radical mastectomy was performed and preoperative diagnosis 
 of dermatofibrosarcoma protuberans was confirmed by pathological examination 
 and immunohistochemistry. The patient was still disease-free six months 
 after the surgical treatment. Conclusion. DFSP is a soft tissue sarcoma that 
 rarely occurs in the breast, especially in men. The most common clinical 
 presentation in the breast is a mass, but it can also present as 
 gynecomastia, as in our case. The diagnosis of DFPS is based on 
 anatomopathology with immunohistochemistry analysis since there are no 
 specific imaging features for this rare entity. Surgical excision with wide 
 and negative margins is optimal for reducing the risk of recurrence.


Introduction
Dermatofibrosarcoma protuberans (DFSP) is an uncommon mesenchymal tumor that accounts for approximately 0.1% of all malignancies (1) and represents less than 5% of all soft tissue sarcomas occurring in adults aged 30 to 40 years (2). The overall incidence is five cases in every 1 million persons annually (3).
This sarcoma usually arises in the dermis and can also extend to the deeper subcutaneous tissues (3). Rare cases of deep-seated DFSP have been reported (4). It is a locally aggressive fibrous tumor, with a high recurrence rate (3). Therefore, it is important to achieve negative margins to minimize disease recurrence (5). DFSP can give rise to distant metastases, usually to the bones and lungs (incidence is less than 5%) (6).
The most common presentation in a male's breast is a mass with extensive nodules on the surface (7). The tumor tends to spare adnexal structures and is commonly superficially located, but in recurrent cases and untreated tumors, it can spread to more deeply situated structures (8,9).
The early symptoms are often non-specific. Consequently, diagnosis is challenging, with a high incidence of misdiagnosis (10). Due to the lack of pathognomonic clinical and imaging findings, DFSP can be mistaken for a keloid, hypertrophic scar, sebaceous cyst or lipoma. In cases with prior trauma, suspicion of DFSP must be raised in the differential diagnosis (11). 5 DFSP usually occurs on the trunk and extremities with only a small number of cases in the breast, especially in men (1,2,5,7,12,13,14). We report a rare case of DFSP in the male breast that clinically presented as gynecomastia.

Case report
A 66-year old man presented with gynecomastia of the left breast that was slowly growing over the past year. In his personal history, there were no risk factors for breast cancer. There was no information about recent trauma, scars in the breast area. Family history was unremarkable for breast cancer. Physical examination was delayed due to the patient's psychological discomfort. It showed an enlarged breast with a palpable nodule beneath the skin without any skin changes on the surface. One year after the breast enlargement was observed, the patient finally underwent ultrasound (US) investigation that showed a welldefined hypoechoic lesion with sharp and smooth edges, located in the superior medial quadrant, between 10 and 12 o'clock, measuring 45 x 22 mm in diameter (Fig. 1). The distance from the skin was 9 mm. Ipsilateral axillary lymph nodes were inconspicuous.  (Fig. 6), CD31 and factor VIII. Such a combination of morphology and immunophenotype was highly suggestive for DFSP regardless of its subcutaneous localization. Subsequently, a radical mastectomy was performed without any adjuvant treatment. Pathologic examination revealed a firm, tan, well-circumscribed oval tumor just beneath the skin, measuring 40 x 30 mm (Fig. 7). Histological and immunohistochemical analyses confirmed the biopsy findings and the diagnosis remained the same. The 6 postoperative care was uneventful without any additional treatment. The patient is diseasefree six months after the surgical treatment.

Discussion
DFSP represents a low-grade malignant soft tissue tumor that arises from the dermis and extends to the deeper structures. There are several histopathological variants of DFSP that have been described, including pigmented DFSP or Bednar tumor, myxoid, juvenile DFSP or giant cell fibroblastoma, atrophic, sclerosing and myoid, occurring in pure form or admixed with one of the others creating hybrid lesions. A small subset of DFSP patients present with fibrosarcomatous progression that is more aggressive and has higher rates of recurrence and metastasis (11).
The distribution of DFSP between genders shows that women have higher incidence rates than men except among the elderly (15), which is in opposition to statements of other reports in which men are slightly more commonly affected than women (9). In our case, the tumor on the male breast appeared much later, at the age of 66, compared to the recently The pathogenesis of DFSP is poorly explained. DFSP was observed to occur in pretraumatic areas, including vaccination sites, burn scars, tattoos, surgical scars, and radiotherapy (11). Almost all molecularly characterized cases have been found to have a COL1A1-PDGFB fusion gene. It was found that dermatofibrosarcoma protuberans with the new COL6A3-PDGFD fusion variant has a predilection for breast and also has typical histologic and immunohistochemical features (8). Several case reports and epidemiologic studies suggest that hormones may also be involved in the pathogenesis of DFSP. Kreicher Immunohistochemically, DFSP usually shows strong positivity for CD34 (in 97% of the patients (1)), vimentin and negative staining for cytokeratin, S-100, epithelial membrane antigen and variable staining for smooth muscle actin (SMA) (12). The present case showed positivity for CD34 along with negativity for S-100 and only focal positivity for SMA, similar to the most recent reported DFSP case in the male breast (7).
The main differential diagnosis of DFSP of the breast includes primary breast tumors with spindle cell differentiation like benign fibrous histiocytoma, phyllodes tumor, cellular fibroadenoma, dermatofibrosarcoma, neurofibroma, nodular fasciitis, fibrosarcoma, and inflammatory myofibroblastic tumor (12).
It was found that older age and male sex were significant predictors of mortality (19). Factors like histologic subtype, high mitotic index, cellularity, size, location of the tumor, and recurrent lesions are reportedly associated with higher recurrence rates (14). The treatment of DFSP is primarily surgical. In our case, the more radical approach was made, and the patient underwent a mastectomy, like in the recent similar published case (7). In our case, following the patient's desire, a left mastectomy was performed.
Lesions with positive margins after surgery or in cases where resection is limited due to anatomical location, adjuvant radiotherapy is suggested (2). Prognostic factors that are shown to be significant are tumor location, surgical margins, and the presence of a highgrade component (20). However, these factors are identified for DFSP in locations other than breast. No impact on survival was found in patients undergoing radiation therapy (21). Imatinib mesylate, a protein tyrosine kinase inhibitor, is used for the treatment of 8 unresectable, recurrent and/or metastatic DFSP in adult patients because it inhibits the overactivity of PDGF receptor in these tumor cells (11). A response rate of approximately 65% has been achieved among DFSP patients treated with imatinib. A small subset of DFSP lacking the classic translocation t(17:22) seems to have no response to imatinib (14).
Long-term follow-up requires strict ultrasonographic monitoring every 6 to 12 months with biopsy in cases of suspected recurrence. The 5-year survival rate of patients with DFSP is higher than 99% (2).

Conclusion
DFSP is a soft tissue sarcoma that rarely develops in the breast of male patients. The clinical presentation includes a firm, erythematous, subcutaneous lump that has an indolent growth pattern. The diagnosis of DFPS is based on anatomopathology with immunohistochemistry because there are no specific signs for this rare entity. Surgical excision with wide and negative margins is optimal for reducing the risk of recurrence.