Dear Editor, Malignant transformation can occur in long-standing lesions of discoid lupus erythematosus (DLE).[1] This complication is relatively rare in the Indian population due to the protective effects of melanin. We describe here a patient of DLE-systemic sclerosis overlap syndrome, who developed squamous cell carcinoma (SCC) in lesions of DLE, after an intervening period of 10 years. A 45-year-old female patient, non-smoker, and farmer by occupation, presented with complaints of raised lesions over the scalp of 8 months duration, and thickening of the skin over hands and fingers for the past 6 months. The patient was a known case of localized DLE with lesions over the face and scalp for the past 10 years. She had been prescribed tablet hydroxychloroquine 200 mg twice daily, topical tacrolimus, and sunscreen 3 years ago, but defaulted on both topical and systemic treatment. There was no history of any other oral medications intake or radiation therapy and no family history of skin malignancies. In the present visit, the patient also complained of bluish discoloration of fingers on exposure to cold and photosensitivity. She had type V Fitzpatrick skin type. Her general physical and systemic examinations were normal. Cutaneous examination revealed multiple ill-defined hyperpigmented plaques, over malar region/nasal margins, and scalp frontal/temporal/parietal regions, some healing with atrophy/scarring. An irregular hypertrophic nodule 6 × 6 cm in size, was present over the scalp vertex and parietal region, with overlying areas of necrosis, hemorrhage, and scarring. The skin surrounding the tumor showed scarring alopecia with areas of hyper and hypopigmentation [Figure 1]. There was no clinically detectable involvement of lymph nodes or the presence of distant metastases. The tumor was accordingly classified as tumor-node-metastases (TNM) stage 3 as per the Union for International Cancer Control eighth edition (UICC 8) staging system. Skin sclerosis involving both hands extending proximal to metacarpophalangeal joints, pitted scars over fingers, digital tip ulcers, and resorption of the right-hand index and middle fingers were observed [Figure 2].Figure 1: Irregular hypertrophic nodule over the vertex and parietal region of the scalp with overlying areas of necrosis, hemorrhage, and scarring. Scarring alopecia with areas of hyper and hypopigmentation in the skin surrounding the growthFigure 2: Right hand with sclerosis of the skin extending proximal to metacarpophalangeal joints, pitted scars over fingers, digital tip ulcers, and resorption of the index and middle fingersOn investigation, complete blood count, liver and kidney function tests, urine examination, chest X-ray, abdominal ultrasound, and pulmonary function tests were normal. Anti-nuclear antibody (ANA) by immunofluorescence (1:160), anti-U1 ribonucleoprotein (U1RNP), and anti-topoisomerase 1 antibodies were positive. Anti-double-stranded DNA (dsDNA) antibody was negative. Dermoscopy of the scalp lesion surrounding the tumor revealed loss of follicular ostia, a few areas of follicular plugging, arborizing vessels, and white structureless areas. Histopathological examination of a facial lesion showed interface dermatitis with deposition of IgG at the dermoepidermal junction [Figure 3].Figure 3: Photomicrograph of histopathology from the face lesion showing (a) perivascular inflammation with interface dermatitis (H and E, 40×); (b) band-like deposition of IgG at the dermoepidermal junction (direct immunofluorescence IgG, 200×)She was diagnosed as a case of DLE with systemic sclerosis overlap. Head computed tomography scan showed minor punctate erosions on the outer table of skull of the underlying calvaria. On dermoscopy of the tumor on the scalp, white circles, central keratin, and coiled vessels were observed. Histopathology of the tissue from edge of the nodular plaque over the scalp revealed ulcerated epidermis with infiltration of the dermis by tumor lobules and nests. Tumor cells had abundant eosinophilic cytoplasm and nuclear polymorphism with large irregular nuclei and prominent nucleoli, confirming a well-differentiated histological subtype of SCC [Figure 4a]. Immunohistochemistry showed strong nuclear positivity for p63 in infiltrating SCC lobules [Figure 4b].Figure 4: Histopathology from scalp lesion showing (a) squamous cell carcinoma infiltrating the dermis in lobules and nests (H and E, 100×); (b) infiltrating lobules of squamous cell carcinoma with strong nuclear positivity for p63 (immunohistochemistry p63, 100×)Wide local excision of SCC lesion was performed under general anesthesia in the plastic surgery department. The patient was counseled regarding compliance to treatment and avoidance of sun exposure. She was also advised on the management of her digital vasculopathy, avoidance of cold, woolen gloves/socks, and tablet nifedipine 10 mg three times daily. SCC incidence in long-standing chronic DLE cases varies from 2.3% to 3.3% and is higher in males. Earlier studies have documented 7 to 30 years of latency in the development of SCC in DLE lesions; however, recent reports mention it as early as 1 to 3 years.[2] SCC developing in colored skin is rare due to larger and more melanized melanosomes, which filter out harmful UV-B rays. In the Indian population, SCC incidence in DLE lesions ranges from 0.98% to 3.4%, with a latency of 9.59 ± 5.6 years.[3] Our patient developed SCC after a latency of 10 years and the likely predisposing factors were actinic damage due to prolonged sun (UV light) exposure, chronic inflammation, and scarring. Other risk factors for malignant transformation in DLE lesions include long-term immunosuppression and infection by Human Papilloma Virus (HPV).[4] Studies have shown a close link between carcinogenesis and chronic inflammation. Various inflammatory cells promote oncogenic transformation and have anti-apoptotic effects. Mouse model studies have demonstrated the role of pro-inflammatory cytokines in the development of cutaneous malignancies. Some cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, IL-17, and IL-23 act as pro-tumor cytokines, whereas IL-12 and interferon (IFN)-γ exhibit anti-tumorigenic properties.[5] Non-compliance to hydroxychloroquine in our patient, which has anti-inflammatory action, may have aggravated ongoing inflammation, subsequent scarring, and oncogenesis. It may be noted that hydroxychloroquine, an inhibitor of autophagy, and immunomodulator, is being investigated for its anticancer role, in combination with standard therapies in several clinical trials.[6] Co-existence of systemic sclerosis with another connective tissue disorders is reported to deteriorate clinical disease course.[7] Overlap of systemic sclerosis, due to accompanying inflammation and sclerosis, could also promote malignant transformation in our DLE patient although this needs to be substantiated further. SCC associated with DLE lesions behaves as a locally aggressive tumor with a recurrence rate and a metastatic rate of 21% and 31%, respectively. In such a setting, SCC should be differentiated from hypertrophic LE and kerato-acanthoma. The presence of finger-like dermal extensions of atypical keratinocytes and malignant dyskeratosis prompt a diagnosis in favor of SCC.[1] To conclude, malignant change can occur in chronic lesions of DLE, especially in the presence of risk factors such as non-compliance to treatment, chronic sun exposure, and overlap syndrome. Patients with DLE should be monitored closely, as SCC arising in such a scenario is aggressive in nature and warrants urgent intervention. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.