Morphological and morphometric analysis of cutaneous squamous cell carcinoma in patients with recessive dystrophic epidermolysis bullosa: a retrospective study

Abstract

Background Recessive dystrophic epidermolysis bullosa is a highly disabling genodermatosis characterized by skin and mucosal fragility and blistering. Cutaneous squamous cell carcinoma (cSCC) is one of the most devastating complications, having a high morbidity and mortality rate. Patients with recessive dystrophic epidermolysis bullosa were reported to have up to a 70-fold higher risk of developing cSCC than unaffected individuals. Immune cells play a role in cancer evolution. Objective The aim of our study was to evaluate immunohistological differences between cSCC in patients with and without recessive dystrophic epidermolysis bullosa. Methods A retrospective study of 25 consecutive cases was performed; five were biopsies of cSCC taken from five patients with recessive dystrophic epidermolysis bullosa; as controls we analysed 10 cSCC in subjects without recessive dystrophic epidermolysis bullosa (5 primitive, 3 postburns and 2 postradiotherapy), 5 cSCC in renal transplant recipients and 5 cutaneous pseudoepitheliomatous hyperplasia in patients with recessive dystrophic epidermolysis bullosa. Results A significant reduction of CD3+, CD4+ and CD68+ between the cSCC in patients with recessive dystrophic epidermolysis bullosa compared to primary cSCC and a significant reduction of CD3+, CD4+, CD8+ and CD20+ were observed in cSCC in patients with recessive dystrophic epidermolysis bullosa compared to secondary cSCC. On the contrary, there was no difference in CD3+, CD8+, CD20+ and CD68+ expression when comparing cSCC in patients with recessive dystrophic epidermolysis bullosa to cSCC in renal transplant recipients. No significant difference was found in size, histopathology, grading, number of mitoses and EGFR expression between the different groups. Conclusions Our data show a reduction in immune cell peritumoral infiltration. Considering the well-known evolution of cSCC in patients with recessive dystrophic epidermolysis bullosa, as well as the younger age at diagnosis, it can be assumed that immune dysfunction might contribute to the cSCC aggressiveness in these patients.

lncRNA HCP5 acts as a ceRNA to regulate EZH2 by sponging miR‑138‑5p in cutaneous squamous cell carcinoma

“…CSCC is an immense clinical and economic problem given its incidence has increased over 200% in the last three decades ( 25 , 26 ). The mortality of high-risk and metastatic CSCC is 40% within 3 years ( 27 ).…”

Immune Disregulation in Cutaneous Squamous Cell Carcinoma of Patients with Recessive Dystrophic Epidermolysis Bullosa: A Single Pilot Study

“…The recessive form, so-called RDEB, is characterized by the presence of bullae that, usually, are present at birth or appear in early infancy [3,4], later-onset being exceptional. Other pathological manifestations are determined at the level of the cornea (corneal erosions) and nail (nail dystrophy), but the most fearful sequela is represented by squamous skin carcinoma [4][5][6][7]. These forms of cSCC sometimes are multiple and may appear well differentiated histologically, but, in keeping with other scar carcinomas, clinically, these tumors behave aggressively, recur locally and often metastasize [8][9][10][11][12][13].…”

“…In fact, scientific evidence points to the role of recurrent bacterial infections [2], lack of collagen VII [3], as well as general [4] and local [5] impairment of the immune defenses, creating a favorable microenvironment for the growth of this tumor. In recent work, we demonstrated a reduced immune cell peritumoral infiltration in patients with RDEB, with a significant reduction in CD3+, CD4+ and CD68+ in RDEB patients with cSCC compared to primary cSCC in patients without RDEB, as well as a significant reduction in CD3+, CD4+, CD8+ and CD20+ in RDEB patients with cSCC compared to non-RDEB patients with secondary cSCC (post-burns and post-radiotherapy) [5]. Recently, new molecules, such as high mobility group box 1 (HMGB1), T cell immunoglobulin, mucin domain 3 (TIM-3) and Heme oxygenase-1 (HO-1), have been shown to play a role in antitumoral immunity.…”

HMGB1-TIM3-HO1: A New Pathway of Inflammation in Skin of SARS-CoV-2 Patients? A Retrospective Pilot Study

“…For HMGB1, TIM-3 and HO-1 a score was assigned, given by the sum of a score related to the different degrees of staining intensity (degree 0 = no staining; degree 1 = weak; degree 2 = moderate; degree 3 = intense staining) and a score related to the percentage of extension (score 0: <1%; score 1: 1-25%; score 2: 26-50%; score 3: 51-74%; score 4: ≥75%). The final score was considered high if the sum of the two scores exceeded 3 [29][30][31].…”