Radiation-Induced Morphea Following Treatment of Myofibroblastic Sarcoma – A Case Report

Dear Editor, A 54-year-old male with painful swelling of the left knee, diagnosed as myofibroblastic sarcoma involving the left distal femur, underwent wide local excision of the tumour and adjuvant radiotherapy. Following radiotherapy, he developed left leg swelling, skin thickening, and stiffness of the knee, which was attributed to lymphedema and treated conservatively. Three years later, he sought a dermatology consultation for persistent skin hardening and discolouration. Examination revealed an irregular, shiny, hyperpigmented, indurated, alopecic plaque, extending from the medial to posterolateral aspect of the lower one-third of his left thigh and knee [Figure 1]. High-frequency ultrasound (HFUS) imaging of the affected region, done using a 15 MHz probe, showed increased thickness with hypoechogenicity of the dermis and hyperechogenicity of the subcutis [Figure 2]. Histopathologic examination of the affected skin revealed an unremarkable epidermis, vertical streaking of collagen in the papillary dermis, collagen deposition in the deep dermis and subcutis, perivascular inflammatory infiltrate, and adnexal atrophy [Figure 3a]. The clinicopathological features and imaging were consistent with the diagnosis of radiation-induced morphea (RIM), which was further confirmed by the decrease in CD34+ stromal cells in the dermis [Figure 3b]. The patient was treated with topical tacrolimus 0.1% due to the localized nature of the disease; however, he was lost to follow-up.Figure 1: Induration and hyperpigmentation of skin with loss of hair over the (a) medial, posterior and (b) lateral aspect of lower one-third of left thigh and kneeFigure 2: (a) High-frequency ultrasound (15 MHz) showing an increase in thickness with hypoechogenicity of the dermis and hyperechogenicity of the subcutis. (b) High-frequency ultrasound of the adjacent normal skin showing hyperechoic dermis and hypoechoic subcutisFigure 3: (a) Square biopsy sign with thickened collagen bundles in the dermis, extending into the subcutaneous tissue (H and E, 4×). (b) Immunohistochemistry: Decreased CD34 positive stromal cells in the dermis (IHC, 4×)RIM is a rare complication of radiotherapy, characterized by inflammation and sclerosis of skin, often developing within a year of receiving radiotherapy, as evident in our case.[1-3] Radiation can trigger an increase in Th2 cytokines and activate transforming growth factor-beta, causing upregulation of collagen synthesis in susceptible individuals.[1,3] There are no definite patient, disease, or treatment-related risk factors for RIM.[1-3] Interestingly, most reports in the literature are of females with breast cancer undergoing radiotherapy, with approximately 0.2% developing RIM. The proximity of irradiated tissue to the skin could explain this strong association.[1] Many, including our patient, underwent surgery before radiotherapy, which by itself is a risk factor for morphea.[1] RIM manifests as an erythematous indurated plaque at the site of irradiation, which later evolves into a pigmented sclerotic plaque. Though it may extend outside the irradiated field, generalized morphea is extremely rare.[2,3] Like idiopathic morphea, thick homogenized collagen bundles in the dermis, perivascular and periadnexal inflammatory infiltrate, and loss of periadnexal adipose tissue are seen in the histopathology of RIM.[1-4] Histopathology is important to establish the diagnosis and to rule out tumour recurrence. HFUS is a useful diagnostic tool that enables assessment of disease activity. The findings in our patient fulfilled the sonographic criteria for active morphea suggested by Wortsman et al.[5] The clinical differentials for RIM include post-irradiation fibrosis, radiation dermatitis, radiation recall dermatitis [Table 1], and cellulitis.[1,4] In our case, RIM was mistaken for lymphoedema-associated skin changes, which lead to a delay in treatment. Depending on the location, RIM could be disfiguring, disabling, or painful, thus affecting the patient’s quality of life. Though topical or systemic immunomodulators and photochemotherapy have been used to treat RIM, it has an unpredictable disease course and variable treatment response.[1,3,4]Table 1: Comparison of radiation-induced morphea with its major clinical differential diagnosesIn conclusion, RIM needs to be differentiated from other radiation-induced skin reactions to ensure appropriate management and better outcomes. Along with histopathology, HFUS and CD34 immunohistochemistry can aid in diagnosis. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.