|Year : 2015 | Volume
| Issue : 3 | Page : 670
Metastatic dermatofibrosarcoma protuberans: A rare case report from North India
BB Mahajan1, Kumar Sumir1, Monika Singla2
1 Department of Dermatology, Guru Gobind Singh Medical College and Hospital, Faridkot, Punjab, India
2 Department of Dermatology, Government Medical College and Hospital, Chandigarh, India
|Date of Web Publication||9-Oct-2015|
Department of Dermatology, Government Medical College and Hospital, Sector - 32, Chandigarh
Source of Support: None, Conflict of Interest: None
Dermatofibrosarcoma protuberans (DFSP) is a low-grade tumor with rare metastasis. A 26-year-old male presented with multiple cutaneous nodular lesions of DFSP since 3 months along with distant metastasis to the brain, pleura, and muscles that were detected on investigations. The case is being reported due to its rare disseminated cutaneous with systemic metastasis.
Keywords: Dermatofibrosarcoma protuberans, metastasis, brain, pleura, muscle
|How to cite this article:|
Mahajan B B, Sumir K, Singla M. Metastatic dermatofibrosarcoma protuberans: A rare case report from North India. J Can Res Ther 2015;11:670
| > Introduction|| |
Dermatofibrosarcoma protuberans (DFSP) is a rare neoplasm accounting for <0.1% of all cancers and <2% of all soft tissue sarcomas.  DFSP is a low-grade neoplasm of mesenchymal origin, which typically develops in the dermis with a tendency to recur locally and rarely metastasizes to vital organs. We report a case of a young Punjabi boy with this tumor who developed widespread fatal metastasis.
| > Case report|| |
A 26-year-old male patient presented in the outpatient department with a complaint of appearance of multiple discrete nodules on face, scalp, and upper torso for the last 3 months. The lesions started as multiple pea-sized nodules, which gradually enlarged to form ulcerative masses. There was a history of a nodular lesion on the upper back about 2 years back for which he underwent surgical excision followed by skin grafting from a different institution. At the time of presentation, he had multiple (about 10-15) erythematous nodules of variable sizes ranging from 1 to 10 cm diameter [Figure 1] and [Figure 2]. Two large subcutaneous nodules of size 7-8 cm diameter were present in the left hypochondrium and left infrascapular region. A few of these lesions were ulcerated [Figure 3].
|Figure 2: Multiple erythematous nodules of dermatofibrosarcoma protuberans on upper chest|
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|Figure 3: Large nodulo-ulcerative lesion with purulent discharge on scalp|
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There was a history of mild fever, malaise and decreased appetite since last 2 months along with progressive dyspnea. Patient also complained of severe pain in the left hypochondrial region and intermittent hiccups. There was significant weight loss of about 15 kg in last 3 months. On examination, patient looked cachectic. There was no lymphadenopathy. Respiratory examination revealed decreased breath sounds and dullness in the left lung region. Rest of the systemic examination was normal.
Patient was severely anemic with hemoglobin 7 g/dl. Rest of the biochemical investigations were within normal limits. Serum Venereal Disease Research Laboratory test, ELISA for HIV and viral markers were negative. Chest X-ray showed haziness in the left lower lung field. Contrast enhanced computed tomography (CECT) of the thorax showed extensive nodular pleural thickening in the left mid and lower hemithorax with compressive atelectasis of the underlying lung and associated infiltration of the left hemidiaphragm extending to the subdiaphragmatic region [Figure 4]. CECT of the head showed presence of nodular enhancing lesions in left occipital and parietal lobes [Figure 5] and [Figure 6]. CECT pelvis showed hypodense mass in the right iliacus muscle [Figure 7].
|Figure 4: Computed tomography showing metastatic nodules of dermatofibrosarcoma protuberans in left thoracic region|
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|Figure 5: Computed tomography scan of brain showing metastatic deposits in left occipital lobe|
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|Figure 6: Computed tomography scan of brain showing metastatic deposits in left parietal lobe|
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|Figure 7: Computed tomography scan of pelvis showing metastasis in iliacus muscle|
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Biopsy was taken from two different sites (chest and wrist), and its histopathological examination showed a tumor in the dermis and subcutis and was composed of interwoven bundles of spindle cells with plump nuclei arranged in a storiform pattern. The tumor cells were inundated between fat cells. Scattered mitoses, including abnormal ones were seen [Figure 8] and [Figure 9]. The mitotic activity was high with mitotic count of 8/10 HPF. Immunohistochemical staining with CD34 was found to be positive [Figure 10]. Biopsy was diagnostic of DFSP.
|Figure 8: Histopathology of tumor showing spindle cells with plump nuclei arranged in storiform pattern along with multiple mitotic figures|
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Patient was put on antibiotics, analgesics and antiemetics. Chemotherapy with tablet imatinib mesylate 400 mg daily was given. Palliative radiotherapy was given for brain, pleural, and subdiaphragmatic masses. However, the patient continued to deteriorate and died despite the best treatment available within 15 days.
| > Discussion|| |
The incidence of DFSP worldwide range from 0.8 to 5 cases/million population/year.  Clinically, it presents as asymptomatic papule or plaque that develops into lumpy nodule that is usually ignored. The most common site of the tumor is trunk (62%), followed by the extremities (25%), and head and neck regions (13%).  It usually occurs in the adults in the age group of 20-50 years with male predominance  but may occasionally occur in children. 
The classic form of DFSP is a low-grade tumor constituting approximately 85-90% of cases with very low risk of metastasis (approximately 5%) and local recurrence rate of about 26%. The remaining patients present with a fibrosarcomatous variant, which is associated with increased risk for the development of local recurrence (approximately 58%) as well as metastasis to vital organs (approximately 15%).  The spread by hematogeneous route is seen in 4-6% of cases.  The most common site of metastasis is a lung but metastasis to brain, bone, heart, lymph nodes, pancreas, orbit, and testis have also been reported [Table 1]. ,,,, Our case also presented high grade DFSP with metastasis to multiple organs, including brain, pleura, and iliacus muscle.
Diagnosis of DFSP is confirmed by histopathology in which proliferation of spindle cells embedded in collagen and arranged in storiform or cartwheel pattern is characteristic.  There are several variants of DFSP, for example, Bednar tumor (pigmented DFSP), fibrosarcomatous DFSP, myxoid variant, indeterminate fibrohistiocystic variant. Risk factors for developing metastatic DFSP include tumor located on head and neck region, on histopathological examination, fibrosarcomatous variant, increased mitotic rate (>8 mitoses per 10 HPF), more spindle cells, more number of nuclei, myxoid change, giant rosettes, hyalinization and pigmented melanocytes, etc.
The mainstay of treatment for DFSP is wide surgical excision. However in case of multiple, unresectable and metastatic DFSP, who are not eligible for surgery, chemotherapy with tyrosine kinase inhibitors like imatinib can be started. Imatinib mesylate is a selective low molecular weight inhibitor of the platelet-derived growth factor (PDGF) receptor tyrosine kinase, which controls tumor growth by inhibiting the PDGF-mediated autocrine or paracrine loop of tumor growth.  Newer tyrosine kinase inhibitors such as sunitinib, duratinib, and multikinase inhibitors like nilotinib have also been developed. Radiotherapy is recommended postoperatively for residual tumors, for large unresectable tumors and with a history of multiple recurrences. In our case, chemotherapy with imatinib as well as radiotherapy was given.
Development of systemic metastasis portends a poorer prognosis. In our patient, increasing cachexia, dyspnea, loss of appetite, and nonresponsiveness to treatment was suggestive of an unfavorable outcome.
It seems that current published rate of metastasis underestimated the metastatic risk. Lack of prior accurate diagnosis and thorough evaluation were contributing factors in making the prognosis poor in our patient. Finding high-risk factors associated with metastasizing potential will sensitize clinicians to subclassify those patients having potential risk for development of metastasis. Periodic examination along with periodic scanning of organs is advisable in selected cases having high risk. To the best of our knowledge, we are reporting second case of DFSP with distant muscle metastasis worldwide until now.
| > References|| |
Labropoulos SV, Razis ED. Imatinib in the treatment of dermatofibrosarcoma protuberans. Biologics 2007;1:347-53.
Garcia C, Clark RE, Buchanan M. Dermatofibrosarcoma protuberans. Int J Dermatol 1996;35:867-71.
Westermann GW, Buerger H, Kappes U, Matzkies F, Kisters K. Dermatofibrosarcoma protuberans with lung metastasis in a patient with progressive systemic sclerosis. South Med J 2002;95:363-5.
Bowne WB, Antonescu CR, Leung DH, Katz SC, Hawkins WG, Woodruff JM, et al.
Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution. Cancer 2000;88:2711-20.
Peschos D, Dallas P, Doulis A, Agnantis N, Vougiouklakis T. Dermatofibrosarcoma protuberans occuring in a child. J Exp Clin Cancer Res 2005;24:135-8.
Mentzel T, Beham A, Katenkamp D, Dei Tos AP, Fletcher CD. Fibrosarcomatous ("high-grade") dermatofibrosarcoma protuberans: Clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance. Am J Surg Pathol 1998;22:576-87.
Mbonde MP, Amir H, Kitinya JN. Dermatofibrosarcoma protuberans: A clinicopathological study in an African population. East Afr Med J 1996;73:410-3.
Chryssogonidis IA, Vorkas G, Papadopoulos C, Lytras C. Testicular metastasis of dermatofibrosarcoma protuberans: A case report (an ultrasonography approach). Arch Oncol 2002;10:33-4.
Yokoyama Y, Murakami Y, Sasaki M, Morifuji M, Hayashidani Y, Kobayashi T, et al.
Pancreatic metastasis of dermatofibrosarcoma protuberans. J Gastroenterol 2004;39:798-800.
Gupta AK, Singh H, Manalel AM, Jaiswal NK. A rare case of scalp dermato-fibrosarcoma protuberans with intracranial extension and distant soft tissue and liver metastasis. Calicut Med J 2011;9:E8.
Lal P, Goel A, Mandal AK. Dermatofibrosarcoma protuberans of scalp with cervical lymph node metastasis. Sarcoma 2004;8:43-5.
Nakra T, Cook T, Douglas RS, Goldberg RA. Dermatofibrosarcoma protuberans metastatic to the orbit. Arch Ophthalmol 2004;122:1240-1.
Ugurel S, Utikal J, Mohr P, Helmbold P, Pfoehler C, Schiller M et al
. Imatinib in locally advanced dermatofibrosarcoma protuberans: A phase 2 trial of the Dermatologic Cooperative Oncology Group (DeCOG). J Clin Oncol 2006;24 Suppl: 535s.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]