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Sequential development of dermatofibrosarcoma protuberans in the forehead and eyelid

      Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma that constitutes 1% of all soft tissue sarcomas and <0.1% of all malignancies.
      • Mendenhall W.M.
      • Zlotecki R.A.
      • Scarborough M.T.
      Dermatofibrosarcoma protuberans.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      The distinguishing features are slow growth, local aggressiveness, low metastatic potential, and elevated rates of local recurrences.
      • Mendenhall W.M.
      • Zlotecki R.A.
      • Scarborough M.T.
      Dermatofibrosarcoma protuberans.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      The tumour occurs on the trunk, particularly on the chest and shoulders, in 40%–50% of cases; on the proximal parts of the limbs in 30%–40% of cases; and on the scalp, cheeks, and supraclavicular area in 10%–15% of patients.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      Eyelid DFSP is exceedingly rare with few well-documented cases in the literature.
      • Brazzo B.G.
      • Saffra N.
      Dermatofibrosarcoma protuberans of the brow and eyelid.
      • Chawla B.
      • Pushker N.
      • Sen S.
      • et al.
      Recurrent bilateral dermatofibrosarcoma protuberans of eyelids.
      This report describes the clinical, imaging, and histopathological characteristics of 2 distinct DFSP developing on the forehead and lower eyelid in a middle-aged female.
      This study adhered to the tenets of the Declaration of Helsinki. The patient subject to this study gave informed consent for the use of all medical information documented in the hospital chart and all imaging studies pertaining to the ocular disease, for scientific purposes including but not limited to presentations, journal articles and book chapters.

      Case Report

      A 58-year-old female presented with a painful left lower eyelid mass that gradually enlarged within 3 months. She had a similar lesion on her forehead for many years, for which she had undergone radiotherapy a year earlier at another institution (Fig. 1A). On ocular examination, her visual acuity was 20/30 in each eye. There was an immobile, indurated, and tender nodular lesion measuring approximately 3 cm × 2 cm × 2 cm on an erythematous base on her left lower eyelid (Fig. 1B). The rest of ocular examination was noncontributory. Orbital magnetic resonance imaging (MRI) study disclosed a cutaneous lesion on the left lower eyelid with heterogeneous signal intensity and diffuse contrast enhancement without orbital extension (Fig. 1C). Incisional biopsy was performed from both lesions and the diagnosis of DFSP was established. The patient gave consent for wide local excision only for the eyelid tumour. Histopathological evaluation of the whole-eyelid lesion showed a cellular dermal neoplasm with infiltrative borders into the muscle and fat, forming a “honeycomb” pattern (Fig. 2A). The tumour had a prominent storiform pattern at high magnification and was composed of spindle cells with scant pale cytoplasm and elongated nuclei with minimal pleomorphism (Fig. 2B). Mitotic activity was lower than 5 per 10 high-power fields. Immunohistochemically, the neoplastic cells stained positive for CD34 (Fig. 2C) and vimentin, and negative for factor XIIIA, EMA, S100, desmin, myogenin, HHV8, CD31, and bcl-2. The Ki-67 index was 5%. There were no areas of necrosis or fibrosarcomatous transformation. The surgical margins of the eyelid specimen were reported to be free of tumour cells.
      Fig. 1
      Fig. 1(A) The forehead lesion at presentation, which was biopsied and then treated with radiotherapy a year earlier. (B) The eyelid tumour was densely vascular and hard on palpation.
      (C) Orbital T1-weighted axial magnetic resonance imaging scan showed diffuse enhancement of the relatively well-delineated tumour after contrast agent administration.
      Fig. 2
      Fig. 2(A) The cellular spindle cell neoplasm involved the whole dermis extending into the subcutaneous fat and sparing the skin appendages (H&E, ×40). (B) The monomorphic tumour cells formed prominent storiform patterns and had scant eosinophilic cytoplasm and hyperchromatic nuclei. The entrapped fat cells displayed honeycomb pattern (H&E, ×100). (C) Neoplastic cells were CD34 positive (CD34, ×100).
      The forehead tumour received adjunct radiotherapy at 60 Gy in fractionated doses, and at 20 months of follow-up, the eyelid remained recurrence-free and the forehead tumour was stable.

      Discussion

      DFSP is usually a slow-growing fibroblastic/myofibroblastic tumour with variable clinical presentations and growth patterns.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      • Mark R.J.
      • Bailet J.W.
      • Tran L.M.
      • et al.
      Dermatofibrosarcoma protuberans of the head and neck. A report of 16 cases.
      It most commonly starts as a violaceus red-blue plaque with small increments of growth over years and then multiple nodules develop over the plaque.
      • Mendenhall W.M.
      • Zlotecki R.A.
      • Scarborough M.T.
      Dermatofibrosarcoma protuberans.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      The tumour may even be present at birth, only to be recognized decades later.
      • Weinstein J.M.
      • Drolet B.A.
      • Esterly N.B.
      • et al.
      Congenital dermatofibrosarcoma protuberans: variability in presentation.
      On rare occasions, DFSP may rapidly arise as a firm, solitary cutaneous nodule.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      Although the 2 lesions in our patient were histologically identical, their clinical courses were distinctly different; the forehead lesion developed over 20 years and the eyelid tumour emerged only in 3 months.
      The MRI findings are not specific and demonstrate a well-delineated tumour that is isointense or mildly hyperintense on T1-weighted images and hyperintense on T2-weighted scans.
      • Zhang L.
      • Liu Q.
      • Cao Y.
      • et al.
      Dermatofibrosarcoma protuberans: computed tomography and magnetic resonance imaging findings.
      However, because DFSP is histologically poorly circumscribed and often extends into the dermis, subcutis, and muscles, it is advisable to resect deeper and wider from the margins that are appreciated clinically or on MRI studies.
      • Mendenhall W.M.
      • Zlotecki R.A.
      • Scarborough M.T.
      Dermatofibrosarcoma protuberans.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      • Mark R.J.
      • Bailet J.W.
      • Tran L.M.
      • et al.
      Dermatofibrosarcoma protuberans of the head and neck. A report of 16 cases.
      • Snow S.N.
      • Gordon E.M.
      • Larson P.O.
      • Bagheri M.M.
      • Bentz M.L.
      • Sable D.B.
      Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature.
      Documented predisposing factors favouring the development of DFSP include surgical scars, radiodermatitis, sites of multiple immunizations, old burns, and sites of central venous lines.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      • Mark R.J.
      • Bailet J.W.
      • Tran L.M.
      • et al.
      Dermatofibrosarcoma protuberans of the head and neck. A report of 16 cases.
      A history of trauma is present in up to 20% of patients.
      • Llombart B.
      • Serra-Guillén C.
      • Monteagudo C.
      • Guerrero J.A.L.
      • Sanmartin O.
      Dermatofibrosarcoma protuberans: a comprehensive review and update on diagnosis and management.
      The tumour may also be associated with acanthosis nigricans, arsenic intoxication, acrodermatitis enterohepatica, and pregnancy.
      • Mark R.J.
      • Bailet J.W.
      • Tran L.M.
      • et al.
      Dermatofibrosarcoma protuberans of the head and neck. A report of 16 cases.
      Our patient had none of these conditions.
      The genetic background of DFSP has recently been elucidated. In more than 90% of patients, the t(17;22) (q22;q13) translocation is present, which leads to the fusion of COL1A1 and PDGFB genes.
      • Noujaim J.
      • Thway K.
      • Fisher C.
      • Jones R.L.
      Dermatofibrosarcoma protuberans: from translocation to targeted therapy.
      • Rutkowski P.
      • Debiec-Rychter M.
      Current treatment options for dermatofibrosarcoma protuberans.
      The gene product acts as an autocrine factor involved in Ras-MAPK, PI3K-AKT-mTOR signalling pathways and is a potent mitogen-stimulating proliferation, differentiation, and migration.
      • Noujaim J.
      • Thway K.
      • Fisher C.
      • Jones R.L.
      Dermatofibrosarcoma protuberans: from translocation to targeted therapy.
      Imatinib mesylate, a tyrosine kinase inhibitor, has been shown to be effective in locally inoperable or metastatic DFSP, and identifying this genetic rearrangement may become mandatory in selected patients.
      • Noujaim J.
      • Thway K.
      • Fisher C.
      • Jones R.L.
      Dermatofibrosarcoma protuberans: from translocation to targeted therapy.
      • Rutkowski P.
      • Debiec-Rychter M.
      Current treatment options for dermatofibrosarcoma protuberans.
      We did not determine the genetic status of the tumour in our patient.
      Securing microscopically negative surgical margins is the cornerstone of treatment in DFSP because recurrence rates after simple excisional biopsy varies between 20% and 70%.
      • Mark R.J.
      • Bailet J.W.
      • Tran L.M.
      • et al.
      Dermatofibrosarcoma protuberans of the head and neck. A report of 16 cases.
      • Rutkowski P.
      • Debiec-Rychter M.
      Current treatment options for dermatofibrosarcoma protuberans.
      Gayner et al.
      • Gayner S.M.
      • Lewis J.E.
      • McCaffrey T.V.
      Effect of resection margins on dermatofibrosarcoma protuberans of the head and neck.
      showed that a margin of ≤2 cm was associated with a recurrence of 60%, whereas a margin of >2 cm was associated with a recurrence rate of 20%. A study on 29 patients suggested that the use of Mohs’ micrographic surgery lowered the recurrence rate to 1% and this may become the treatment of choice in most cases.
      • Snow S.N.
      • Gordon E.M.
      • Larson P.O.
      • Bagheri M.M.
      • Bentz M.L.
      • Sable D.B.
      Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature.
      Because most relapses occur within 2–3 years, it may be early to declare our patient recurrence-free after 20 months of follow-up.
      • Mark R.J.
      • Bailet J.W.
      • Tran L.M.
      • et al.
      Dermatofibrosarcoma protuberans of the head and neck. A report of 16 cases.
      Radiotherapy has re-emerged as a useful adjunct tool in large or incompletely resected tumours, and a recent study on 14 patients with a median follow-up of 10.5 years found that with 55.8–66 Gy radiation dose, 86% of patients became disease-free.
      • Williams N.
      • Morris C.G.
      • Kirwan J.M.
      • Dagan R.
      • Mendenhall W.M.
      Radiotherapy for dermatofibrosarcoma protuberans.
      Our patient is a rare example of DFSP developing consecutively as 2 separate tumours on the forehead and eyelid with identical histology but disparate clinical courses.

      Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

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