DLE Progressing to Squamous Cell Carcinoma : A Case Report

A 90 years female diagnosed as a case of Discoid lupus erythematosus (DLE) developed Squamous cell carcinoma from the lesions over a period of 5 years due to treatment gap and late follow up. Diagnosis was based on clinical aspects (erythematous, nodular and scanty bleeding), dermoscopic features and histopathological examination, the absence of systemic involvement and routine laboratory parameters, which registered all within normal range. SCC in a patient with DLE is rare in Nepalese patients. It is every essential to counsel the diagnosed cases of DLE and warn all patients about all the possible outcomes and compliance with medications should be ensured. Nepal Journal of Dermatology, Venereology & Leprology, Vol.14(1) 2016, pp.51-55


Introduction
D iscoid lupus erythematosus (DLE) is a benign, autoimmune disorder of the skin, clinically characterized by red scaly patches which heal with atrophy, scarring and pigmentary changes, and histopathologically by stratum corneum hyperkeratosis and follicular plugging, thinning and fl a ening of stratum malpigii, hydropic degenera on of the basal layer also referred to as liquiefac on degenera on, which is characterised by vacuolar spaces beneath and between basilar kera nocytes which shows individual cell necrosis (apoptosis) and acquire elongated contours like their superfi cial counterparts rather than their normal columnar appearance (squama sa on).Frequently, the undula ng rete ridge pa ern is lost and is replaced by a linear array of squama zed kera nocytes.
Thickening and tortuosity of the basement membrane correlate with deposi on of immune reactants.The stromal layer shows a predominantly lymphocy c infi ltrate arranged along the dermal-epidermal junc on, around the hair follicles and other appendages, and in an inters al pa ern; inters al mucin deposi on; edema, vasodilata on, slight extravasa on of erythrocytes.
Disease commonly aff ects the sun-exposed areas of the skin.DLE is subdivided into a localized form in which lesions are confi ned to the face and neck or a disseminated form in which lesions also occur elsewhere on the body.Malignant transforma on is a rare complica on of this condi on.This is a case of squamous cell carcinoma (SCC) developing over lesions of disseminated DLE.The paucity of reports of this complica on in literature search warrants its men on. 1 Subjects with DLE have high-levels of plasmacytoid dendri c cells -derived interferon-a, which mediates both loss of immune tolerance to self-an gens and exaggerated infl ammatory state, and supports prolifera on and diff eren a on of hyperac ve B-cells.In a few cases, DLE of the lips, scalp, ears or nose may eventually progress to squamous cell carcinoma (SCC).Photosensi vity and the long-standing immunemediated chronic infl amma on and dysregulated healing characterized by atrophy, hypopigmenta on or scarring inherent to DLE are risk factors for progression to SCC. 2

Report
A 90 years female was diagnosed with localised type DLE 6years ago.She had lesions only over the face.She was undergoing treatment with oral hydroxychloroquine, topical hydrocor sone and sunscreen.However she was lost to follow up.A er a late follow up period of 5years and treatment gap there was complaint of few of the older lesion over the le temporal region becoming more erythematous, nodular [Figure 1] and scanty bleeding was noted.The nodules had adherent scaling also.On the le temporal area the nodules were around 2x1, 2x3 cm in size [Figure 1].There was no lymphadenopathy.Systemic examina on was normal.Haematological inves ga on, chest X-ray, ECG was unremarkable.
Based on clinical examina on and dermospcopic features Figure1, 2 the lesions were suspected to have malignant transforma on, hence, a skin punch biopsy for histopathological evalua on was advised.The histopatological reading was Squamous cell carcinoma, moderately diff eren ated.Histopathology showed acantho c epidermis with papillomatosis and parakeratosis.The epidermis shows loss of polarity involving full thickness.The squamous cells were pleomorphic having hyperchroma c nucleus with nuclear rim irregularity.Mitosis cons tuted 1-3/HPF.Nests of atypical squamoid cells surrounded by large number of lymphocytes infi ltrated the upper dermis was seen Figure .3-6.Hence, excisional biopsy was advised.
Pa ent was advised and underwent a thorough workup to see for metastasis.CBC (complete blood count), LFT (liver func on test), RFT (renal func on test), TFT (thyroid func on test), Thyroid Ultrasound, ECG (electrocardiogram), ANA, An -single-stranded DNA done were unremarkable.She underwent WLE (wide lesional excision) with Rhomboid fl ap for closure (Figure 7).A er excision frozen sec on were evaluated and the reports was all the margins (anterior, posterior, superior, inferior) free from carcinomatous changes.There was epidermal dysplasia with foci of dermal invasion by atypical squamous cells.Full thickness dysplasia in the epidermis in the form of loss of polarity, moderate to marked atypia, enlarged vesicular nuclei, prominent nucleoli and eosinophilic cytoplasm were seen.Frequent mitosis (2-4/HPF) upto the surface layer was seen.Invasive foci were surrounded by dense desmoplas c reac on.Papillomatosis, parakeratosis, hyperkeratosis, occasional kera n pearl forma on and dense lymphocy c infi ltrates was noted.Deepest resected base included in the biopsy was free of tumor.

Discussion
SCC and, less commonly, basal cell carcinoma (BCC) are the most feared complica ons of CCLE.In one study by Millard et al., the incidence was 3.3% among 120 white pa ents with CCLE. 4 The scalp is the most common site involved followed by the lips.Heavy smoking could also be a contribu ng factor.The scalp is the most common site involved as seen in our pa ent, followed by the lips. 4Squamous cell carcinoma usually arises in skin damaged by ac nic rays.Exposure to chemicals such as coal tar, soot, arsenic and a variety of oils and dis lla on products is also implicated in its pathogenesis.It occasionally occurs in scars following infl ammatory or degenera ve processes.It is an endstage complica on of a wide array of infl ammatory skin condi ons. 5 Due to muta on in p53 tumor suppressor gene, there will be defect in apoptosis of kera nocytes that have sustained UV-radia on-induced DNA damage which ul mately lead to SCC. 6 Usually SCC in DLE develops a er about two decades 3 but earlier onset has also been reported. 7,8Cutaneous squamous cell carcinomas that arise secondary to infl ammatory and degenera ve processes have a much higher rate of metastasis than those developing in sun damaged skin.SCC of lower lip also has a higher incidence of metastasis. 9ere have been sporadic reports of neoplas c change in DLE which range from SCC and basal cell carcinoma to malignant fi brous his ocytoma and atypical fi broxanthoma. 10The interval between development of DLE and SCC has varied from 4 to 20 years. 5,7,11recipita ng factors for SCC are age more than 40 years, male sex, sun/ultraviolet ray exposure, skin pigmenta on, and chronic infl ammatory processes.There is an inverse rela on between skin pigmenta on and development of SCC because of the protec ve eff ect of melanin. 6e long-term prognosis of such cases is varied.SCC arising in DLE is regarded as a locally aggressive but lowgrade carcinoma with recurrences.One study reported local recurrences in about 20% and metastasis in 30% cases. 2 1 death has also been reported from mul ple metastases. 13e risk of a pa ent with DLE developing systemic lupus erythematosus (SLE) is small.It varies from 1.3% to about 6.5%.The risk is higher with disseminated DLE (22%) than in DLE confi ned to head and neck (1.2%). 3Here, pa ent did not have any features of SLE, despite having localised DLE for more than 5 years.The presence of laboratory abnormali es in DLE does not itself appear to predispose to the development of SLE. 3 DLE pa ents showing signs of nephropathy, presence of arthralgias and elevated ANA ters (> or=1:320) should be carefully monitored, because they may be at risk of developing systemic LE. 14 An -single-stranded DNA an bodies in a pa ent with DLE may indicate an increased risk of development of SLE. 15 To conclude SCC in a pa ent with DLE is rare in Nepalese pa ents.It is every essen al to counsel and warn all pa ents about all the possible outcomes and compliance with medica ons should be ensured.Our pa ent had a successful outcome with local excision of the tumor.
Excisional biopsy microscopic fi ndings: Sec ons examined show skin ssue comprising of epidermis, dermis and subcu s.The epidermis is dysplas c with foci of dermal invasion by atypical squamous cells.Full thickness dysplasia in the epidermis in the form of loss of polarity, moderate to marked atypia, enlarged vesicular nuclei, prominent nucleoli and eosinophilic cytoplasm are seen.Frequent mitosis (2-4/HPF) upto the surface layer are seen.Invasive foci are surrounded by dense desmoplas c reac on.Papillomatosis, parakeratosis, hyperkeratosis, occasional kera n pearl forma on and dense lymphocy c infi ltrates are noted.Deepest resected base included in this biopsy is free of tumor.Impression: moderately diff eren ated squamous cell carcinoma; temporal region.

Figure 1 :
Figure 1: Arrows show previous DLE lesion and the new lesion which developed over the DLE lesion, erythematous, nodules with adherent scaling and scanty bleeding, Biopsy site; 4mm Skin Punch Biopsy was done

Figure 2 :
Figure 2: Dermoscopic features showing scale, crusts and bleeding; typical malignant changes were not viewed due to the presence of secondary changes

Figure 3 :
Figure 3: Low power view showing acanthosis papilomatosis and invasion into the dermis

Figure 4 :
Figure 4: The squamous epithelium showing loss of polarity involving full thickness

Figure 6 :
Figure 6: Tumor nests surrounded by large number of lymphocytes.