Dermatofibrosarcoma Protuberans of the Breast: A Rare Case Report.

This case report presents a rare case of DFSP in the breast. Despite the high local recurrence rate associated with DFSP, the patient in this case remained free of recurrence. The case highlights the importance of early diagnosis, appropriate treatment, and long-term follow-up for patients with DFSP. This case also emphasizes the need for continued research into the optimal treatment approaches for DFSP, particularly in unusual locations like the breast.

This case report presents a 43-year-old female diagnosed with DFSP in her right breast. DFSP is a rare soft tissue tumor that typically affects individuals aged 20 to 59 [ 1 ]. DFSP is a rare tumor arising from dermis and subcutaneous mesenchymal tissue. In 1924, Darier and Ferrand were the first to describe the progressive recurrent dermatofibroma, and DFSP was later described by Hoffmann in 1925. DFSP grows slowly and has a low malignancy potential; however, if the tumor is not adequately resected, local recurrence may occur, resulting in aggressive sarcoma. In DFSP patients, the most commonly affected site is the trunk, but neck, head, and extremities are also reported to be frequently affected. However, the occurrence of DFSP in the breasts is rare [ 5 ]. The clinical presentation and management of DFSP can be highly variable, as illustrated by two recent case reports. The first describes a 40-year-old pregnant female with an intramammary DFSP, underscoring the diagnostic challenge it poses. Despite a negative genetic test for the classic *COL1A1-PDGFB* fusion, the diagnosis was secured through characteristic histology and CD34 positivity, leading to successful wide local excision during the second trimester [ 6 ]. This case highlights that a high clinical suspicion is paramount, even with atypical genetic findings. In stark contrast, a second report details a 32-year-old male with a neglected DFSP of the breast that progressed to a massive, metastatic tumor following an initial incomplete resection [ 7 ]. This case tragically demonstrates the consequences of positive margins and loss to follow-up. Fortunately, it also powerfully reinforces the established role of imatinib in the advanced setting as the patient achieved a significant clinical and radiological response, including a 50% reduction in tumor bulk, upon treatment initiation. Together, these cases provide a compelling clinical spectrum: the first emphasizes the importance of a definitive initial resection with clear margins to achieve a cure, even in complex situations like pregnancy, while the second serves as a sobering reminder of the disease’s potential for aggressive local recurrence and the life-saving efficacy of targeted therapy with imatinib in the metastatic context, perfectly illustrating the treatment principles outlined in our own case. DFSP on ultrasound can present with a nonspecific appearance on ultrasound, often resembling other common skin lesions, which may contribute to delayed diagnosis [ 8 ]. DFSP is often misdiagnosed because of inadequate tissue sampling caused by shallow biopsies. It is strongly recommended that a punch or incisional biopsy sample the subcutaneous layer in order to distinguish DFSPs from benign lesions. In the event of an indeterminate biopsy or persistent clinical suspicion, a repeat biopsy is advised. Breast surgery to remove the breast masses was performed on the patient with periodic follow-up. Treatment is mainly surgical, with the aim of achieving complete resection of the tumor [ 1 ]. In order to reduce the recurrence rate, the treatment of choice for DFSP seems to be Mohs’ micrographic surgery (MMS) and related variants [ 9 ]. In hospitals where only standard histopathological procedures are available, standard excision with a lateral safety margin of 3 cm is advisable [ 10 ]. The main treatment objective remains complete surgical excision with 3D techniques, which prevents both local recurrence and metastasis [ 11 ]. Having the lesion in the breast allowed for adequate margins to be taken, which contributed to the patient’s long-term survival. Since DFSP is historically associated with high local recurrence rates, ongoing clinical monitoring should include a focus on the primary site every 6–12 months as well as re-biopsy of the suspicious lesions. Over the following years, the patient, in our case, developed several benign breast masses, predominantly located in the right breast. These masses were characterized by an oval morphology and hypoechoic appearance on ultrasound, suggestive of fibroadenoma. Additionally, a solid cyst and other benign lesions were identified in the left breast. A comparative study evaluating four cases of DFSP revealed a similar ultrasonographic presentation, with two cases exhibiting hypoechoic masses and two demonstrating mixed echogenicity [ 8 ]. Other auxiliary, uterine (endometriosis), and flank (lipoma) benign lesions were identified in the patient. DFSP is a rare soft tissue sarcoma subtype characterized by a locally aggressive, infiltrative growth pattern and a low rate of metastatic disease, affecting only 1−4% of cases. The tumor’s rarity means patients affected with metastatic DFSP generally have a poor prognosis. The molecular hallmark of DFSP is the t(17;22)(q22;q13) translocation, which fuses the COL1A1 gene on chromosome 17 with the PDGFB gene on chromosome 22. This fusion results in the constitutive, powerful overexpression of the platelet-derived growth factor beta (PDGFRβ) protein, driving the tumor’s growth. However, approximately 8% of patients with DFSP may not have the common COL1A1-PDGFB fusion. Researchers have discovered novel fusion genes, such as COL1A2-PDGFB , that similarly lead to the constitutive expression of PDGFB, suggesting a shared tumorigenesis mechanism across DFSP subtypes, likely arising from a mesenchymal cell type expressing CD34, nestin, and PDGFRβ. The mainstay of management for localized disease is surgical resection, typically using MMS or wide surgical resection to ensure negative margins due to the tumor’s infiltrative nature. Adjuvant treatment, such as radiation therapy, is generally considered unnecessary if a negative margin is achieved. However, radiation therapy can be administered following resection with close or positive margins (if re-excision is impossible) and can be the primary therapy for patients with inoperable disease. Targeting the upregulated PDGFRβ with imatinib mesylate is a viable therapeutic option, but it is generally reserved for patients with unresectable, recurrent, or metastatic DFSP. Conventional chemotherapy has limited activity in this disease. In cases of inoperable or metastatic disease, imatinib therapy is warranted following confirmation of a PDGFB fusion (e.g., COL1A1-PDGFB or COL1A2-PDGFB ). A starting dose of 400 mg once daily is typically sufficient and better tolerated. For patients with imatinib-resistant disease, alternative options include sorafenib and sunitinib, with enrollment in clinical trials strongly encouraged for these challenging cases [ 12 , 13 ]. In the present case, a chest, abdominal, and pelvic CT scan performed following the lumpectomy revealed no evidence of metastatic disease, making targeted therapy unnecessary for initial management. The majority of recurrences are observed within a 3-year time frame following primary surgical excision [ 14 ]. Follow-up examinations primarily target the early detection of local recurrences. Clinical examinations every 6 months for 5 years are advised, thereafter in yearly intervals because of infrequent late events until the end of the tenth year after surgery [ 15 ]. Clinical and imaging follow-up is recommended for at least 5 years for early detection and management of potential local recurrence [ 10 ]. In the recent systematic review of MMS in DFSP [ 10 ], the mean time to recurrence was 68 months. Imaging examinations are generally not required during follow-up, except for recurrent DFSP and DFSP with fibrosarcomatous transformation. The diagnostic and management challenges of DFSP are further highlighted by its potential to present in diverse clinical scenarios. Our case of a primary breast DFSP in a middle-aged woman from Syria underscores the critical need for considering this rare tumor even in common anatomical locations for masses. This is particularly relevant in regions like Syria, where healthcare systems are strained by conflict, potentially leading to delays in diagnosis and specialized care. The diagnostic challenge is universal, as evidenced by a recent report by Hanna et al. [ 16 ] of DFSP occurring in the finger of an infant, an exceptionally rare site and age-group. Together, these cases – spanning different continents, age-groups (infant vs. adult), and anatomical locations (finger vs. breast) – emphasize that DFSP can mimic more common benign conditions anywhere on the body. This reinforces the indispensable role of a high index of clinical suspicion, accurate biopsy with histopathological examination, and vigilant long-term follow-up to ensure local control, regardless of the patient’s demographics or the tumor’s initial presentation.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor, with an estimated annual incidence ranging from 0.8 to 4.5 cases per million individuals [ 1 ]. It is characterized by its propensity for local recurrence and invasive growth. However, distant metastasis is uncommon [ 1 ]. There is a relatively equal distribution between genders, with a male-to-female ratio approximating 1:1. Recent population-based studies have demonstrated consistently high 5-year relative survival rates of more than 90% [ 2 ]. Clinical suspicion of DFSP is typically confirmed through histological examination [ 3 ]. This tumor exhibits a locally invasive pattern of growth, and local recurrence rates can vary significantly depending on the treatment approach. Surgical excision with clear margins is widely considered the optimal treatment approach. Follow-up is primarily focused on early detection of local recurrences. The reported incidence of local relapse following treatment for DFSP exhibits significant heterogeneity within the literature, ranging from 0% to 40%. Recent studies generally indicate a trend toward lower recurrence rates [ 3 ]. However, there are very few cases documented in the literature of DFSP in the breast [ 4 ]. In this report, we present a case of primary DFSP of the breast, treated surgically with long-term disease-free survival. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000549386 ).

The authors have no conflicts of interest to declare.

This study was not supported by any sponsor or funder.

A 43-year-old Arab female, married with 6 children, a nonsmoker, with no significant past medical history, presented to Albairouni University Hospital in July 2018, complaining of a right breast mass measuring 22 × 16 mm. History and physical examination, and CT chest, abdominal, and pelvis in July 2018, revealed no evidence of metastatic disease. A biopsy was performed. The gross examination identified an irregularly outlined ovoid mass measuring 22 × 16 × 12 mm, along with two smaller irregular tissue pieces and a skin stripe. Microscopically, the biopsy revealed a moderately well-demarcated intra-dermal tumorous area made up of intersecting and whorled short bundles of spindled cells and collagen formation, with many, some atypical, mitoses, separated from the skin epidermis by a thin free zone. Immunohistochemistry demonstrated negative for S100 and ACTIN. CD34 staining was focal and weak, presenting in less than 10% of tumor cells. Given the classic morphological features and the specific immunoprofile, which can be seen in DFSP with fibrosarcomatous change, the diagnosis was consistent with DFSP ( Fig. 1 – 6 ). A complete skin examination was performed, which showed no other lesions. A wide local excision was performed with negative margins. Low-to-medium power photomicrograph of the DFSP showing the characteristic feature of the tumor mass being separated from the overlying epidermis (top, outlined) by a thin, cell-poor free zone (Grenz zone). The dermal component shows a dense proliferation of spindled cells. Low-power photomicrograph illustrating the storiform or cartwheel pattern of the neoplastic spindled cells within the deep dermal/subcutaneous tissue. The clear, acellular area (center) may represent an artifact, a myxoid change, or a section of a blood vessel. Low-to-medium power photomicrograph similar to Figure 1 , highlighting the superficial aspect of the tumor, its proximity to the epidermis (top, outlined), and the characteristic appearance of the spindled cell proliferation in the underlying dermis. High-power photomicrograph demonstrating the whorled and intersecting short bundles of spindled cells and associated collagen, typical of the tumor’s architectural pattern. The contrast in the staining intensity may represent different areas of the tumor (e.g., more cellular vs. more collagenous/fibrous). Medium-power photomicrograph showing the deep portion of the tumor invading the dermis/subcutaneous tissue and entrapping an adnexal structure, likely a hair follicle (center-left), a common feature of DFSP. The surrounding tumor cells exhibit the classic fascicular and storiform growth pattern. Medium-power photomicrograph focusing on the dense, monotonous proliferation of spindled tumor cells forming the characteristic storiform pattern (cells radiating out from a central point, like spokes on a wheel). The pale vertical cleft may be an artifact of tissue processing or a vascular space. The patient’s subsequent clinical course was notable for several benign findings, which are summarized in the timeline in Table 1 for clarity: in August 2018, the patient presented with right axillary node enlargement (25 × 20 mm). An ultrasound exhibited a hypoechoic, oval mass in the right axilla and a suspicious mass of the right breast (6 mm) (BIRADS 4). In addition, multiple masses were identified in the left breast. CEA and CA15-3 were at normal levels. Given the recent history of DFSP, these lesions were investigated promptly. A surgery to remove the right and left breast and right axillary masses was performed, and the pathology result was consistent with fibroadenoma with no malignancy. Clinical timeline of the patient's clinical history In February 2021, a soft tissue mass 25 × 20 mm in the left flank was observed; it was resected and was consistent with a lipoma with degenerative changes and no malignancy. A hypoechoic right breast mass with regular margins at 1 o’clock “BIRADS 3” was detected on breast US on May 5, 2021, and consistent with fibroadenoma; it was monitored on periodic follow-up ( Fig. 7 ). In October 2022, a CT scan revealed a mass on the posterior wall of the uterus, 12 × 12 mm, which underwent resection; the pathology result was consistent with benign endometriosis with mild hyperplastic and inflammatory changes. Breast ultrasound (US) shows a distance measurement of 2.24 cm marked by calipers (Dist 2.24 cm), indicating the size of a structure or region of interest within the breast tissue. Also shows typical echogenicity of breast tissue, including the hypoechoic (darker) subcutaneous fat and the glandular/stromal layers. The primary purpose of these images is to visualize the internal structure of the breast, often to screen for or characterize masses, cysts, or other abnormalities. Despite these multiple benign findings, the patient remained free of DFSP recurrence. Long-term follow-up remains essential to monitor for any local recurrence. The patient is doing well and adherent to follow-up every 6 months.

Ethics Committee at Damascus University does not require ethical approval for reporting individual cases or case series. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Ayla Kouli, Razan Alhasan, and Mousa Alali participated in literature review, data analysis, and radiological interpretation; co-wrote the discussion; and helped structure the case presentation. Ahmad Al-Bitar led the clinical assessment, patient follow-up, and surgical planning and contributed significantly to case documentation and manuscript supervision. Maher Saifo provided oncologic expertise; contributed to treatment planning; and critically revised the manuscript for intellectual and clinical accuracy.