Giant exophytic dermatofibrosarcoma protuberans of the breast: A case report with the analysis of clinical and therapeutical issues : Il Giornale di Chirurgia - Journal of the Italian Surgical Association

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Case Report

Giant exophytic dermatofibrosarcoma protuberans of the breast

A case report with the analysis of clinical and therapeutical issues

D’Onghia, Giulianoa,*; Sanguinetti, Alessandrob; Macciò, Tizianac; Cirocchi, Robertob; Avenia, Stefanob; Avenia, Nicolab; Izzo, Paoloa; Izzo, Lucianoa; Gabriele, Raimondoa; Miccini, Michelangeloa; D’Ermo, Giuseppea; Polistena, Andreaa,b

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Il Giornale di Chirurgia – Journal of the Italian Surgical Association: October 2022 - Volume 42 - Issue 3 - p e08
doi: 10.1097/IA9.0000000000000011
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Abstract

Introduction

Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade cutaneous fibrohistiocytic neoplasm first described by Taylor in 1890 and named by Hoffman1 in 1925. DFSP of the breast is an extremely rare occurrence2,3 with a median age at diagnosis typically between 20 and 59 years.2 DFSP is characterized as low- to intermediate-grade neoplasm with high recurrence rate but low metastatic potential.3 Gold standard treatment for DFSP is complete surgical excision with histologically negative margins in order to reduce local relapse.3

Herein, we describe a case of giant, exophytic and ulcerated DFSP occurred in female breast analyzing the clinical features and the therapeutical issues of this rare tumor very seldom located in the breast.

Case presentation

A 35-year-old patient was referred to breast unit outpatient clinic presenting with a huge lump of the right breast noticed 1 year before and with a massive increase in the last few weeks and progressive ulceration with exophytic pattern. The patient has not undergone for several months any medical examination despite the increasing size of the lump for an evident psychological disorder. At the first examination, the mass showed evident features of malignancy, easy bleeding and continuous serum discharge (Figure 1). The patient underwent ultrasound and computed tomography (CT) scan examination (Figure 2) that confirmed a huge mass occupying the subcutaneous and glandular tissues without infiltration of the chest wall, and no suspicious or enlarged lymph nodes were detected in the ipsilateral axilla. A preoperative core needle biopsy was performed with minimal bleeding. The histological examination described features of malignant tumor of mesenchymal origin. Therefore, breast multidisciplinary meeting decided to apply an upfront surgery aiming the radical excision of the tumor. Based on the absence of suspicious or pathological axillary nodes, and the mesenchymal origin of the tumor, no indication to axillary lymph node biopsy neither lymphadenectomy was given. The patient refused the proposal of breast reconstruction. Considering the wide excision required, the small size of the breast and relative low body mass index (BMI), a precautionary hypothesis of thoracoepigastric pedicled flap was designed preoperatively (Figure 1) to ensure the coverage of the skin defect. A radical mastectomy (Figure 3) with primary direct wound closure (Figure 4) was carried out, and no pedicled flap was needed. Histology showed a 13.5 cm × 8.2 cm mesenchymal neoplasm with a 20 mm free margin, composed of uniform spindle cells arranged in fascicles with monotonous pattern. The tumor was highly cellular with little nuclear pleomorphism and relatively few mitoses. Secondary elements such as giant cells, siderophages, and chronic inflammatory cells were infrequent. Immunohistochemistry showed diffuse, strong, staining for antigen CD34 in the spindle cells tumor, no staining using antibodies directed against S100, smooth muscle actin or cytokeratins Ae1/Ae3 was observed (Figure 5A–D). According to the histopathological and immunohistochemical features, a dermatofibrosarcoma protuberans of the breast was diagnosed. The postoperative course was uneventful and the wound showed a primary healing. At the current follow-up, the patient is doing well with no signs of recurrence or of systemic disease.

F1
Figure 1.:
Preoperative tumor appearance. A precautionary hypothetical thoracoepigastric pedicled flap plan was drown preoperatively for the reconstructive phase.
F2
Figure 2.:
CT study showing a huge mass not infiltrating the chest wall and no distant metastases or axillary pathological lymph nodes.
F3
Figure 3.:
Gross specimen after surgical excision, the mass was radically resected with no macroscopic residual.
F4
Figure 4.:
Operative field after mastectomy. The pectoralis major muscle was shaved off to allow radicality on the deep margin.
F5
Figure 5.:
Histopathology of dermatofibrosarcoma protuberans. Histopathology showed: (A and B) low-power view of skin and subcutis infiltration by cellular spindle cell neoplasia with fascicular pattern of growth, intermingled with blood vessels. C, High-power view of relatively monotonous neoplastic proliferation with storiform pattern; only mild atypia is seen, with little nuclear pleomorphism. D, Strong and diffuse positivity for anti-CD34 immunostaining.

Discussion

DFSP is a slowly progressive, painless cutaneous lesion typically appearing as an indurate, violaceous, or red plaque, with a hard thickness and fixed to the skin that arises in the dermis.4 DFSP grows asymmetrical with multiple “protuberant” nodules into the plaque, which develops over years.5

DFSP most commonly develops on the trunk (50% to 60% of cases)6 but it is extremely rare in the breast.7–9

DFSP is mostly diagnosed between 20 and 59 years,10 with a slight male preponderance.11

The etiology of DFSP remains unknown but past trauma, vaccination sites, and radiotherapy have been implicated as predisposing factor in the growth of this malignancy.12

Chromosomal translocation t(17;22)(q22;q13) between chromosome 17 and chromosome 22 and a supernumerary ring chromosome, r(17,22) is found in most of DFSP cases. The translocation results in the fusion of the alpha chain type 1 of collagen (COL1A1) gene with the platelet-derived growth factor beta (PDGFbeta) gene.

COL1A1 is the most abundant and ubiquitously distributed collagen among collagen family proteins, PDGF is a potential mitogen for a variety of cells. Chimeric COL1A1-PDGFbeta gene removes the upstream sequences of PDGFbeta exon 2, which are noted as elements negatively controlling PDGFbeta gene transcription. This possibly causes the formation of an autocrine growth factor involved in the development of DFSP.13

The main histologic differential diagnoses for DFSP are fibromatosis, myoepithelioma, metaplastic carcinoma, and phyllodes tumor.14

The diagnosis of DFSP is established on histopathological features characterized by proliferation of plump, uniform spindle cells arranged in fascicles with monotonous storiform pattern. The cells have little nuclear pleomorphism and few mitoses.13 Immunohistochemical positive expression of CD34 and negative expression of S-100, and smooth muscle actin or cytokeratins Ae1/Ae3 are considered diagnostic markers for DFSP.15

First-line therapy for DFSP is standard surgical excision with a safe margin from 2 to 3 cm. A full thickness resection including skin, subcutaneous tissue, and underlying fascia is required.16,17 Despite its low malignant potential, incomplete surgical resection may lead to a local recurrence sometimes associated to a more aggressive sarcomatous evolution.18,19

For small DFSP with adequate breast volume, breast-conserving procedure with large surgical margins can be considered an appropriate treatment.20–22

For large DFSP of the breast mastectomy with primary reconstruction or in cases similar to the one reported, considering the impossibility of skin-sparing procedures, a two-stage prosthetic breast reconstruction, with initial insertion of a tissue expander followed by changeover to a definitive implant, are the primary options of treatment.23–25

Large skin defects after excision of DFSP often require a plastic reconstruction with skin grafts and local, pedicled, or microvascular flaps.17 When DFSP is located in the thorax or, as in the presented case, in the breast a thoracoepigastric pedicled flap can be adopted. This is a rotational advancement flap that can be used to lift up to the chest the skin located in the lateral region of the abdomen. It is mainly indicated in the coverage of surgical defect after excision of the tumor in the inferior inner quadrant of the breast or following mastectomies.26,27

More complex reconstruction using a latissimus dorsi flap or according to patient’s BMI and after CT scan evaluation a deep inferior epigastric artery perforator (DIEP) flap can also be considered.

Latissimus dorsi flap, first described by Schneider et al,28 can be used in order to cover a large skin defect, in immediate or delayed breast reconstruction.29 DIEP flap is probably the best choice in autologous breast reconstruction because better cosmesis can be achieved with skin and soft tissue, without sacrifice abdominal or dorsal musculature.30,31 However, DIEP flap requires adequate abdominal tissue to replace the breast and adequate blood vessel supply.32

Some authors suggest the use of Mohs micrographic surgery as a first-line treatment for maximum tissue preservation and low recurrence rates.33,34

The local recurrence rate for DFSP in literature ranges from 10% to 60%,35 instead the rate of development of regional or distant metastatic disease is respectively only 1% and 4% to 5%,36 and usually they occur in regional lymph nodes and the lung.37

According to the Sarcomatous Tumors guidelines by the Italian Association of Medical Oncology (AIOM),38 National Comprehensive Cancer Network (NCCN)39,40 and to the data of the literature41 axillary surgery is generally not recommended in the sarcomatous tumor of the breast. If axillary lymph node metastases are suspected at the preoperative study, a fine needle aspiration or a biopsy is recommended prior to surgery. Guidelines recommend that if histological examination confirms metastatic lymph nodes an axillary lymphadenectomy should be performed. Otherwise, there is no indication for routine sentinel lymph node biopsy or axillary lymphadenectomy.39,40 In the reported case, ultrasounds and CT scan examination showed no evidence of suspicious or pathological axillary nodes, and therefore no axillary surgery was carried out.

Radiation has occasionally been used as a primary treatment for DFSP.42 It could be an option of treatment in patients with DFSP that cannot obtain negative margins after surgery.43 If a negative margin is acquired, no adjuvant treatment is needed.39,40

Imatinib mesylate, a tyrosine kinase inhibitor, is the first-line systemic therapy for DFSP and was established into clinical practice in 2006. In 2010, the National Comprehensive Cancer Network (NCCN) guidelines recommended imatinib for metastasis and/or recurrences when disease is unresectable or unacceptable functional or cosmetic outcomes with resection are predicted.39 In Imatinib Target Exploration Consortium Study (B2225),44 Imatinib mesylate showed clinical activity against localized and metastatic DFSP with t(17;22) but did not show clinical response in fibrosarcomatous variants of DFSP with lacking t(17;22).

An adequate follow-up must be always applied for a precocious detection of local recurrences but standardized follow-up of DFSP has not been established. Some authors suggest a minimum of 3 years follow-up, every 6-month intervals.45

Conclusions

DFSP of the breast is a rare malignancy with slow and painless growth. Immunohistochemistry for CD34 is necessary to confirm the diagnosis. Despite DFSP low malignant potential, inadequate surgical excision may lead to a local more aggressive recurrence. Breast-conserving surgery can be adopted for small DFSP of the breast but in case of large tumor mastectomy is the treatment of choice associated to an appropriate plastic reconstruction. If a negative axilla is detected in the preoperative study, there is no indication for further axillary surgery. A multidisciplinary approach and a long-term follow-up are always recommended for DFSPs high recurrence rate.

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Keywords:

Breast; Dermatofibrosarcoma protuberans; Exophytic; Mastectomy; Treatment

Copyright © 2022 The Authors. Published on behalf of the Associazione Chirurghi Ospedalieri Italiani and Wolters Kluwer.