|Ahead of print publication
Dermatofibrosarcoma protuberans: Clinicopathological spectrum with emphasis on lymph node metastasis and fibrosarcomatous transformation
Sakshi Dahiya, Reena Tomar, Manisha Ahuja, Varuna Mallya, Shramana Mandal, Nita Khurana, Arun Kumar Rathi
Department of Pathology, Maulana Azad Medical College, Delhi, India
|Date of Submission||07-Apr-2020|
|Date of Decision||31-May-2020|
|Date of Acceptance||23-Aug-2020|
|Date of Web Publication||15-Oct-2021|
Department of Pathology, Maulana Azad Medical College, Delhi
Source of Support: None, Conflict of Interest: None
Introduction: Dermatofibrosarcoma protuberans (DFSP) is an uncommon skin tumor with a low-to-intermediate grade of malignancy, characterized by progressive growth and a propensity for local recurrence. In this series, we are analyzing the clinicopathological spectrum of DFSP cases.
Materials and Methods: A retrospective study of 12 patients with DFSP who were diagnosed at our institute over the last 2 years (2018–2020) was performed.
Results: The clinicopathological spectrum and immunohistochemistry of DFSP cases were studied with one case with lymph node metastasis, which is a rare entity, and two cases of the fibrosarcomatous DFSP were also diagnosed and warrant a special mention.
Conclusion: Pathologists should be aware of metastasis and unusual variants while reporting dermatofibrosarcoma.
Keywords: Dermatofibrosarcoma protuberans, fibrosarcomatous, nodal metastasis
|How to cite this URL:|
Dahiya S, Tomar R, Ahuja M, Mallya V, Mandal S, Khurana N, Rathi AK. Dermatofibrosarcoma protuberans: Clinicopathological spectrum with emphasis on lymph node metastasis and fibrosarcomatous transformation. J Can Res Ther [Epub ahead of print] [cited 2021 Dec 5]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=328261
| > Introduction|| |
Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous soft-tissue sarcoma that was first described by Taylor in 1890, clinically was classified by Darier and Ferrand, and later named by Hoffman. It clinically often masquerades as a benign, indolent tumor, but microscopically, it extends far beyond clinically assessed margins, and spreads locally in the dermis, subcutaneous tissue, and muscles. The gross appearance may vary. Initially, it may present as a slowly growing indurated plaque that can eventually transform into a violaceous to red-brown painless nodule, most commonly on the trunk (50%–60%) or upper limbs (25%) and less often on the head and neck. Clinical differential diagnosis includes keloids, large dermatofibroma, epidermal cyst, and morphea. DFSP diffusely infiltrates the dermis and subcutaneous tissue with peripheral tentacle-like projections; furthermore, invasion of fascia and muscle can also occur.
Even though DFSP is a low-grade malignant tumor, it is associated with multiple recurrences. Fibrosarcomatous (FS) areas in the DFSP are associated with a higher recurrence rate and are more aggressive and have the ability to metastasize regionally and distally. In this series, we are analyzing the clinicopathological spectrum of DFSP cases. We are presenting one case that had spread into axillary lymph nodes, which is a rare phenomenon. Furthermore, we are presenting two cases diagnosed as FS-DFSP.
| > Materials and Methods|| |
Between January 2018 and January 2020, a total of 6440 skin and soft-tissue biopsies were submitted to the Histopathology Section at the Department of Pathology at Maulana Azad Medical College, New Delhi. They were studied retrospectively. Twelve cases of DFSP were identified. Clinical details of patients comprising age, gender, site, and clinical symptoms along with past history were recorded. Radiological findings were also noted. Apart from the gross features of the tumor, H and E slides were analyzed to look for morphological features such as extent, pattern, and presence of pleomorphism, mitosis, and necrosis. Furthermore, the presence of any other cells such as lymphocytes, plasma cells, and collagen entrapment was looked for. Positive immunohistochemistry (IHC) markers such as CD34 and vimentin were used for confirmation of diagnosis. Other markers which were put to rule out differential diagnoses and came out to be negative included smooth muscle actin, desmin, CD31, S100, and HMB45. Important features to diagnose DFSP include storiform/cartwheel arrangement of cells, high cellularity, monomorphic cells, diffuse infiltration of subcutis, and lack of foamy histiocytes, giant cells, and peripheral collagen entrapment.
| > Results|| |
Overall, 12 cases were identified in analysis of data in the last 2 years. The age of patients ranged between 22 and 55 years. Seven patients were female and five were male. Sites of involvement were thigh (3 cases), hypochondriac area (3 cases), chest (2), back (2), and neck and arm (1 each). The size of the lesions varied from 2 cm × 1 cm to 15 cm × 10 cm. Contrast-enhanced computed tomography description for a typical lesion was reported as a heterogeneously enhancing lesion of varying sizes in subcutaneous planes. Other features varied with cases. Initially, trucut biopsy was performed in eight cases. The other four were direct excisions in toto.Resected margins were positive in just one patient and skin infiltration was seen in one case as well [Figure 1]a. On histomorphology, tumor comprised highly cellular sections with spindle cells arranged in storiform pattern [Figure 1]b and also in fascicles in two cases. There was an infiltration of these cells in the fat lobules [Figure 1]c, appearing to form a honeycomb-like pattern. Fascicular arrangement along with increased atypia [Figure 1]d indicates a sarcomatous change. One case presented with axillary lymph node metastasis, which is a rare entity, and we highlight its importance. On H & E, lymphoid tissue is visible at the periphery with replacement of centre by the tumor cells. [Figure 2]. Although mitotic activity [Figure 3] is not defined, mitotic activity in the sarcomatous area averages between 7 and 15/10 high-power field (HPF). Two cases in our series demonstrated the FS DFSP variant. In a typical case of DFSP, cells are monomorphic and spindly with scant eosinophilic cytoplasm and hyperchromatic nuclei. IHC was performed in all cases, out of which the tumor cells were positive for both vimentin [Figure 4] and CD34 [Figure 5] in all cases except two where vimentin was focal. Four cases were those with a re-occurrence. The time of re-occurrence varied from 1 to 10 years. [Table 1] and [Table 2] show DFSP cases with gross and morphologic features, fat infiltration, and skin involvement.
|Figure 1: (a) H and E ×20: Dermatofibrosarcoma protuberans tumor reaching the skin; (b) H and E ×40 showing storiform arrangement of spindle cells; (c) Fat infiltration; (d) Pleomorphism|
Click here to view
|Figure 2: H and E ×4: Section shows lymphoid tissue in periphery with areas of dermatofibrosarcoma protuberans in center (inset: ×10)|
Click here to view
|Figure 3: H and E ×20: Mitosis in fibrosarcomatous area in DSFP cases (inset: ×40)|
Click here to view
| > Discussion|| |
DFSP presents as an asymptomatic papule or plaque that is usually ignored. Later on, it can develop into a nodule or big mass. The most common site of the tumor is trunk (62%), followed by the extremities (25%) and head-and-neck regions (13%). In our study, thigh and hypochondriac areas were the most common sites, accounting for 3 cases each. It usually occurs in adults in the age group of 20–50 years with male predominance but may occasionally occur in children. Age presentation in our study was similar, but female preponderance was seen instead of males. 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%. FS transformation of DFSP was first described in 1951 by Penner who presented a case of metastasizing DFSP containing areas indistinguishable from fibrosarcoma. The definition of this transformation is morphologic representing a transition of typical DFSP to a fascicular proliferation of spindle cells with increased cytologic atypia and usually increased mitotic activity. For diagnosing FS-DFSP, the FS proliferation should occupy at least 5%–10% of the tumor. In our study, two cases had a mitotic rate >10/10 HPF, areas of necrosis, and had significant mild-to-moderate pleomorphism. Two cases with high mitotic rate had a fascicular pattern of cells, with necrosis in one case representing the FS-DFSP cases in our study. FS variant is associated with increased risk for the development of local recurrence (approximately 58%) as well as metastasis to vital organs (approximately 15%). One of our FS-DFSP cases had a re-occurrence after 1 year. The spread by hematogenous route is seen in 4%–6% of cases. Necrosis, high mitotic rate (>10 mitoses per 10 hpf), and the presence of pleomorphic areas in FS-DFSP tend to be related to poor clinical outcome, but no statistically significant association was detected.
Lymph node metastasis was seen in one case only. The swelling was on the arm and presented with re-occurrence. The axillary node was involved and primarily diagnosed on biopsy. Interestingly, there were no FS areas in this case.
CD34 was used in distinguishing CD34+ dermal neoplasms such as Kaposi's sarcoma, DFSP (both CD34+), and epithelioid sarcoma (often CD34+) from dermatofibroma (CD34−). We ruled out other CD34 + lesions from DFSP based on morphology. All cases of DFSP were positive for CD34 and vimentin except two cases which had focal vimentin positivity. CD34 positivity is usually less intense or completely lost in FS areas, possibly explained by the progression of DFSP to CD34-negative fibrosarcoma. We did not find CD34 loss in FS areas of our two cases of FS-DFSP.
The prognosis of DFSP is generally excellent if completely excised with clear margins of 2.5–3 cm of normal tissue from the gross tumor boundary, with a three-dimensional resection (en bloc removal) that includes skin, subcutaneous tissue, and the underlying investing fascia, achieving negative microscopic margins. The treatment provided to our cases consisted of surgery with margin excision. In the present case series, only one case had a positive deep resected margin. DFSP is also considered to be a radiosensitive tumor. Consequently, radiation therapy can be recommended as adjuvant therapy in cases with positive margins or close margins after maximal resection, in case of a large lesion with negative margins, in case of recurrent lesion or in case that achievement of wide margins would result in a functional or cosmetic deficit. Imatinib is a useful neoadjuvant directed therapy for select patients with DFSP who are not direct candidates for surgery owing to the local extension of the tumor or possible secondary cosmetic or functional impairment. Patients who have DFSP with high-risk features could be followed for 10 years given the high median time to local recurrence or metastases. The ideal frequency of clinical visits remains unclear.
| > Conclusion|| |
In summary, DFSP is a distinct oncological entity which often presents a diagnostic challenge. The proper identification and diagnosis is clinically important. The goal of this retrospective study was to expand on the clinicopathological characterization, to be aware of rare lymph node metastasis, rare presentation, and variants of this unusual neoplasm like FS-DFSP, which has more chances of being aggressive. Exploring the morphological features with IHC and awareness of this entity is important for a prompt diagnosis and a proper management of the disease, preventing both over and undertreatment of this low-to-intermediate grade malignancy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Suit H, Spiro I, Mankin HJ, Efird J, Rosenberg AE. Radiation in management of patients with dermatofibrosarcoma protuberans. J Clin Oncol 1996;14:2365-9.
Zemni I, Sassi I, Boujelbene N, Haddad S, Doghri R, Chargui R, et al
. Vulvar Darier-Ferrand dermatofibrosarcoma: Unusual localization of a rare tumor. Pan Afr Med J 2019;33:46.
Arnaud EJ, Perrault M, Revol M, Servant JM, Banzet P. Surgical treatment of dermatofibrosarcoma protuberans. Plast Reconstr Surg 1997;100:884-95.
Foshee JP, Trofymenko O, Zeitouni NC. Surgical and functional considerations of dermatofibrosarcoma protuberans involving facial nerve danger zones. J Clin Aesthet Dermatol 2019;12:39-43.
Roh MR, Bae B, Chung KY. Mohs' micrographic surgery for dermatofibrosarcoma protuberans. Clin Exp Dermatol 2010;35:849-52.
Stancu B, Mironiuc IA, Crisan M, Mera M. Surgical treatment of dermatofibrosarcoma protuberans using a reversed adipofascial sural flap-Case report. Clujul Med 2014;87:277-83.
Ding JA, Enjoy M: Dermatofibrosarcoma protuberans with fibrosarcomatous areas a clinicopathological study of nine cases and a comparison with allied tumors. Cancer 1989;64:7212.
Goldblum JR, Reith JD, Weiss SW. Sarcomas arising in dermatofibrosarcoma protuberans: A reappraisal of biological behavior in eighteen cases treated by wide local excision with extended clinical follow up. Am J Surg Pathol 2000;24:1125.
Mahajan BB, Sumir K, Singla M. Metastatic dermatofibrosarcoma protuberans: A rare case report from North India. J Cancer Res Ther 2015;11:670.
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.
Achouri L, Triki A, Bouzaiene H, Chemleli M, Laamouri B, Slimen M, et al
. Transformed dermatofibrosarcoma protuberans: A series of nine cases and literature review. J Dermatol Dermatol Sur 2016;20:1-4.
Miettinen M. Fibroblastic and Myofibroblastic Neoplasms with Malignant Potential. In: Miettinen M, editors. Modern Soft Tissue Pathology. Tumors and Non-Neoplastic Conditions. Cambridge: Cambridge University Press; 2010. p. 348-59.
Hayakawa K, Matsumoto S, Ae K, Tanizawa T, Gokita T, Funauchi Y, et al
. Risk factors for distant metastasis of dermatofibrosarcoma protuberans. J Orthop Traumatol 2016;17:261-6.
Sharma S, Kudva R, Valiathan M, Ayachit A. Fibrosarcomatous variant of dermatofibrosarcoma protuberans: An aggressive tumor-a case report. Int J Health Sci Res 2015;5:434-8.
Socoliuc C, Zurac S, Andrei R, Stăniceanu F. Multiple histological subtypes of dermatofibrosarcoma protuberans occurring in the same tumor. Rom J Intern Med 2015;53:79-88.
Archontaki M, Korkolis DP, Arnogiannaki N, Konstantinidou C, Georgopoulos S, Dendrinos P, et al
. Dermatofibrosarcoma protuberans: A case series of 16 patients treated in a single institution with literature review. Anticancer Res 2010;30:3775-9.
Navarrete-Dechent C, Mori S, Barker CA, Dickson MA, Nehal KS. Imatinib treatment for locally advanced or metastatic dermatofibrosarcoma protuberans: A systematic review. JAMA Dermatol 2019;155:361-9.
Huis In 't Veld EA, van Coevorden F, Grünhagen DJ, Smith MJ, van Akkooi ACJ, Wouters MWJM, et al
. Outcome after surgical treatment of dermatofibrosarcoma protuberans: Is clinical follow-up always indicated? Cancer 2019;125:735-41.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]