High-grade soft tissue sarcoma arising in a desmoid tumor: case report and review of the literature

Desmoid tumors (DT) are rare benign monoclonal fibroblastic tumors representing less than 5 % of all soft tissue tumors [1]. Also called aggressive deep-seated fibromatosis, they typically arise from muscular or aponeurotic structures. Their location may be extra-abdominal [2] or in the abdominal wall, usually sporadic, or intra-abdominal [3], often associated with familial adenomatosis polyposis (FAP) [1]. The mammary location is very rare (<10 % of all cases), the literature being limited to case reports and three retrospective series totalizing 81 patients [4‐6]. Such location does not seem to differ in term of clinical outcome than other locations.

Desmoid tumors grow slowly. Their aggressiveness is local with no potential for metastasis or dedifferentiation. In the last 2012 World Health Organization (WHO) classification of sarcomas, they are classified as tumors with intermediate malignancy potential. Locally, they can damage vital structures and threaten life [7], notably in intra-abdominal locations, and have a high rate of recurrence even after complete resection. Their treatment remains challenging, based on diverse strategies [7, 8]: “wait-and-see policy”, non-steroidal anti-inflammatory drugs (NSAIDs), hormone therapy, chemotherapy and recently investigational targeted therapies (imatinib, sorafenib, pazopanib), and surgery and/or radiation therapy. Their natural history is not well-defined and poorly understood, including long periods of stabilization, or even spontaneous regression.

The arising of a soft tissue sarcoma in a DT is an exceptional event, with only three cases reported to date [9‐11]. Here we report on a 61-year patient who presented a locally advanced breast DT refractory to multiple systemic therapies and in which arose a rapidly lethal high-grade undifferentiated soft tissue sarcoma.

We report an exceptional case of soft tissue sarcoma arising in a refractory and locally advanced DT. As usually observed at the time of diagnosis of mammary DT [5], our patient was older than patients with abdominal location and the stage was advanced. Given the tumor volume, the initial treatment was medical, and during almost 2 years, the patient received successively NSAIDs, two regimens of hormone therapy, two regimens of chemotherapy and three targeted therapies without success. After 2 years of treatment, a suspect modification of the clinico-radiological aspect led to surgery. Pathological analysis of the operative specimen discovered a high-grade undifferentiated soft tissue sarcoma within the DT. Such pleomorphic sarcomas (ex-MFH, malignant fibrous histiocytoma) are typically deep-seated and aggressive tumors with both local and metastatic risks [12]. Four months after surgery, the patient showed locoregional relapse by the sarcoma, initially sensitive to gemcitabine-docetaxel, followed by multimetastatic progression refractory to several therapeutic lines, leading to the death 25 months after the surgery.

To our knowledge, this is the fourth case of sarcoma arising within a DT reported in the literature, and the first one in a breast DT. In the first case report published more than 50 years ago [9], a 19-year-old woman, without medical history, was operated for an inguinal 13-cm DT. During follow-up, she presented a local relapse treated with a total of four courses of radiotherapy over an 18-month period. Nine years after the last course, she presented a sudden increase in growth and cutaneous ulceration of the locally recurrent DT. Biopsy of this 15-cm mass identified a fibrosarcoma. Histopathologic examination of the surgical resection specimen showed a 5-cm high-grade fibrosarcoma surrounded by the DT. Six months after surgery, a local relapse of the fibrosarcoma occurred, requiring amputation. Following the amputation, several local recurrences were observed treated with surgery, then radiotherapy. Twenty months after amputation, the patient died. The second case [10] is a 53-year-old man, with significant history of Milroy’s disease (chronic hereditary lymphedema of unknown origin). He presented a non-tender 14-cm DT in the medial malleolar region, without any functional limitation, diagnosed by open biopsy. Given the infiltrative nature of the lesion and the minimal clinical symptoms, observation was decided. Two weeks after the biopsy, a small raised skin lesion appeared posterior to the open biopsy incision. A punch biopsy showed aspect consistent with DT. Three months later, a dramatic increase in the posterior mass occurred with a fungating and necrotic aspect; the radiological evaluation showed the previously-identified DT, as well as the new large fungating mass associated to one additional small area of abnormal signal within the DT. Biopsy of the fungating tumor identified a high-grade undifferentiated pleomorphic sarcoma, leading to below-knee amputation. The pathological analysis of the operative specimen showed the DT, which contained the two nodular masses corresponding to the undifferentiated sarcoma. Surgical margins were negative for sarcoma but microscopically positive for DT. Ten years after amputation, the patient was alive with no evidence of disease. The third case [11] is extracted from a series of eight patients in which the morphologic changes seen after radiotherapy in desmoid-type fibromatosis were retrospectively studied. The patient was a 12-year-old boy with initially a 9.5-cm DT of the proximal part of the upper limb treated by surgery. He presented a local relapse 36 months later that was treated with external radiotherapy (dose between 50 and 60 Gy). Sixteen years later, he underwent forequarter amputation because of a clinical progression of the tumor: the pathological analysis of the operative specimen demonstrated areas of fibrosarcoma with zonal necrosis, hypercellularity, severe nuclear atypia, and increased mitotic activity, adjacent to the locally recurrent DT. Three months after amputation, the patient was alive with no evidence of disease.

In summary, in all informative cases, the diagnosis of sarcoma was suspected by clinical modifications of the DT (volume increase, ulceration, multilobulated aspect) associated with radiological modifications with appearance of nodular masses within the DT. But these signs are not specific, and given the very exceptional character of sarcomatous degeneration of DT, the pre-therapeutic diagnostic confirmation was attempted in only one case, the diagnostic being done after surgery in the three other cases. Like for any soft tissue sarcoma, the treatment was margin-free monobloc surgery.

In pathophysiological term, in all cases, the sarcoma appeared within the DT and a specific risk factor for developing sarcoma was present: Milroy’s disease in one case [9], and radiotherapy in the three others ones with an interval between radiotherapy and sarcoma diagnosis of 9 years [9], 16 years [11], and 22 years (our case). In the two first cases, the radiotherapy was delivered in order to treat the DT, whereas in our case, it was delivered after surgery of breast cancer 20 years before the diagnosis of DT. In the absence of molecular analyses, it is not possible to know whether a common genetic mutation could explain the coexistence of DT and soft tissue sarcoma. Classically, the pleomorphic undifferentiated sarcomas display a complex genetic profile without specific structural alteration, whereas DTs display a simple genomic profile with specific mutation. The search for a common molecular alteration in both entities might benefit from the new next-generation sequencing techniques. Regarding the cell of origin, the embryologic derivation of the fibroblast (the mesoderm) renders it capable of giving rise, under appropriate oncogenic influences, to a wide range of proliferative manifestations [13] including for example aggressive fibromatosis, fibrosarcoma arising in a keloid, dermatofibrosarcoma protuberans, malignant fibrous histiocytoma, and also one case of aggressive fibromatosis progressing over 3 years to poorly differentiated sarcoma with widespread metastases, which may suggest a progressive increase in the malignant potential of the fibroblasts in the patient’s tumor.

We report the fourth case of soft tissue sarcoma arising in a DT. This case reinforces the need for timely and accurate diagnosis when a desmoid tumor modifies its clinical or radiological aspect, notably in presence of associated risk factors such as history of radiotherapy. Given the exceptional nature of such diagnosis, case reports such as this one serve as the only reference for clinicians taking care of these patients.

Written informed consent was obtained from the patient’s husband after her death for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.