Squamous cell carcinoma arising within discoid lupus erythematous lesions: A systematic review

To the Editor: Discoid lupus erythematosus (DLE) is the most common form of chronic cutaneous lupus erythematosus, characterized by erythematous, atrophic plaques with scale.1Shapera E.A. Kim P.D. Squamous cell cancer arising in an African American male cheek from discoid lupus: a rare case and review of the literature.Case Rep Surg. 2016; 2016: 9170424PubMed Google Scholar An infrequently reported complication of DLE is the development of squamous cell carcinoma (SCC).1Shapera E.A. Kim P.D. Squamous cell cancer arising in an African American male cheek from discoid lupus: a rare case and review of the literature.Case Rep Surg. 2016; 2016: 9170424PubMed Google Scholar The aim of this systematic review was to summarize the characteristics and outcomes of SCC arising within DLE lesions. Embase and MEDLINE searches were conducted on June 27, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Fig 1). A total of 118 patients from 45 studies were included following the screening process (Tables I and II). Of the 118 patients (mean age: 50.4 years) who developed SCC within DLE lesions, the majority were males (55.9%, n = 66/118). Localized DLE was present in 73.7% (n = 87/118) of the patients and generalized DLE (DLE lesions below the neck) in 21.2% (n = 25/118); 5.1% (n = 6/118) did not report DLE distribution. A positive smoking history and prior immunosuppressant use were reported in 14.4% (n = 17/118) and 12.5% (n = 5/40) of the patients, respectively. The most common sites of SCC development were the lip (53.3%, n = 65/122), forearm (11.5%, n = 14/122), and scalp (7.4%, n = 9/122). The lower lip (41.8%, n = 51/122) was more affected than the upper lip (11.5%, n = 14/122).Table ICharacteristics and outcomes of patients with squamous cell carcinoma arising within discoid lupus erythematosus lesionsCharacteristics and outcomesNo. (%)Age Mean age ± SD50.4 ± 11.4 Range24-85Sex Female49 (42.6) Male66 (57.4) Unknown3Race Black or African American16 (18.6) White6 (7.0) Asian64 (74.4) NR32Prior smoking history Yes17 (14.4) No101 (85.6)Prior history of squamous cell carcinoma Yes2 (1.7) No116 (98.3)Prior history of BCC Yes2 (1.7) No116 (98.3)Prior immunosuppressant use Yes5 (12.5) No35 (87.5) Unknown78Age at DLE onset (years) Mean age ± SD33.2 ± 7.4 Range7-58Type of DLE Localized87 (77.7) Disseminated25 (22.3) NR6Hypertrophic Yes10 (90.9) No1 (9.1) NR107Duration of DLE disease (years) Mean duration ± SD19.0 ± 10.9 Range2-44Location of SCC Lower lip51 (41.8) Upper lip14 (11.5) Forearm14 (11.5) Scalp9 (7.4) Groin1 (0.8) Cheek9 (7.4) Hand7 (5.7) Extremities2 (1.6) Ear2 (1.6) Neck2 (1.6) Nose3 (2.5) Face3 (2.5) Lower limb2 (1.6) Preauricular area2 (1.6) Infra-auricular region1 (0.8) Total reported SCCs122Treatment for SCC Surgical excision alone47 (81.0) Surgical excision with chemotherapy1 (1.7) Surgical excision with radiation8 (13.8) Surgical excision with combined chemotherapy and radiation2 (3.4) Unknown60Biopsy Yes110 (99.1) No1 (0.9) Unknown7Period between DLE and initial SCC lesion (years) Mean period ± SD15.0 ± 7.0 Range0.5-41SCC metastasis Yes29 (26.9) No79 (73.1) Unknown10Recurrent SCC Yes41 (40.2) No61 (59.8) Unknown16Mortality Yes23 (25.0) No69 (75.0) Unknown26No. = number; % = percentage.BCC, Basal cell carcinoma; DLE, discoid lupus erythematosus; NR, not reported; SCC, squamous cell carcinoma; SD, standard deviation. Open table in a new tab Table IIPatients with mortality outcomeOutcomesNo. (%)SCC metastasis Yes10 (90.9) No1 (9.1) Unknown12Recurrent SCC Yes11 (100.0) No0 (0.0) Unknown12Cause of death Metastasis14 (60.9) Sepsis secondary to scalp infection1 (4.3) Respiratory failure1 (4.3) Unknown7 (30.4)Time from initial SCC presentation to death (months) Mean time ± SD22.0 ± 16.8 Range3.4-54No. = number; % = percentage.SCC, Squamous cell carcinoma; SD, Standard deviation. Open table in a new tab No. = number; % = percentage. BCC, Basal cell carcinoma; DLE, discoid lupus erythematosus; NR, not reported; SCC, squamous cell carcinoma; SD, standard deviation. No. = number; % = percentage. SCC, Squamous cell carcinoma; SD, Standard deviation. The mean duration between DLE onset and SCC development was 15.0 years (range: 0.5-41). Of 47 patients who reported treatment outcomes for SCC, all had undergone surgical excision. Eight patients had received radiotherapy, 1 had received chemotherapy, and 2 had received combined radiation and chemotherapy. Of those who reported metastasis and recurrences, 26.9% (n = 29/108) experienced SCC metastasis, and 40.2% (n = 41/102) reported SCC recurrences. In addition, 25.0% (n = 23/92) of the patients reported a mortality outcome due to metastasis (60.9%, n = 14/23), sepsis (4.3%, n = 1/23), and respiratory failure (4.3%, n = 1/23) (Table II). Although the pathogenesis of SCC development within DLE lesions is unknown, 2 hypotheses have been proposed. First, hypopigmented DLE plaques may predispose the lesions to actinic damage, which has been implicated in SCC.2Grossman D. Leffell D.J. Squamous cell carcinoma.in: Goldsmith L.A. Katz S.I. Gilchrest B.A. Paller A.S. Leffell D.J. Wolff K. Fitzpatrick's Dermatology in General Medicine. 8th ed. McGraw Hill, 2012: 1283-1294Google Scholar Second, the chronic scarring from DLE, in combination with constant local inflammatory stimuli, might be associated with carcinogenesis.3Cassarino D.S. Derienzo D.P. Barr R.J. Cutaneous squamous cell carcinoma: a comprehensive clinicopathologic classification.J Cutan Pathol. 2006; 33: 191-206Crossref PubMed Scopus (127) Google Scholar We also found that majority of the SCCs occurred on sun-exposed sites, most commonly the lip. This may be due to constant sun exposure, smoking/tobacco use, and irritation from allergens. For instance, 82.3% (n = 14/17) of the patients who reported a smoking history developed an SCC on the lip. SCC with DLE compared with SCC without DLE emphasizes the significance of this association: tumor recurrence (40% vs 20%), metastasis (26.9% vs 6%), and death (26.1% vs 1%).4Clayman G.L. Lee J.J. Holsinger F.C. et al.Mortality risk from squamous cell skin cancer.J Clin Oncol. 2005; 23: 759-765Crossref PubMed Scopus (307) Google Scholar Although limited literature exists to explain the high recurrence, metastasis, and death outcomes, the prolonged duration between DLE onset and SCC diagnosis or prior failed treatments might be implicated. These patients require prompt surgical treatment after diagnostic biopsy, radiological examination, sentinel lymph node biopsy for high-risk tumors, as well as long-term monitoring. Given that this review relied largely on published case reports, our findings should be interpreted with caution. Case reports have been documented to have an increased risk of bias.5Murad M.H. Sultan S. Haffar S. Bazerbachi F. Methodological quality and synthesis of case series and case reports.BMJ Evid Based Med. 2018; 23: 60-63Crossref PubMed Scopus (888) Google Scholar Additionally, reporting bias likely contributed to the high reported rates of tumor recurrence, metastasis, and mortality in the DLE-related SCC group. Further studies focusing on SCC arising within DLE lesions might be warranted.

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