色素性乾皮症

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder resulting from mutations in nucleotide excision repair. It is characterised by severe photosensitivity, cutaneous pigment changes, malignant tumour development, and occasionally progressive neurologic degeneration. The aim is to report three cases of XP with cutaneous malignancies with emphasis on the importance of prevention of malignant transformation in these patients. Three adults within their 3rd and 4th decades with XP were managed for cutaneous malignancies: two males and one female, two of whom were siblings. Two had fungating lesions on the forehead, and one had multiple scalp lesions. The histology in all the three patients revealed squamous cell carcinoma (SCC). All underwent wide local excision, followed by full and split thickness skin grafting to cover the defects, except the one that had transposition flap at a second surgery, and were co-managed with a dermatologist. Skin malignancies especially SCC and basal cell carcinoma are common in the facial regions of patients with XP. Adequate education of the patients on the importance of protection from the ultraviolet radiation radiations will prevent malignant transformation, and early presentation with appropriate treatment will improve prognosis.

Patients with genodermatoses, such as nevoid basal cell carcinoma syndrome, recessive dystrophic epidermolysis bullosa, familial atypical multiple mole and melanoma syndrome, xeroderma pigmentosum and ichthyosis with confetti, face a high risk of skin malignancies. While dermoscopy significantly improves diagnostic accuracy compared to clinical examination, its specificity remains limited when evaluating ambiguous lesions in these complex patients. This narrative review examines the role of reflectance confocal microscopy and line-field confocal optical coherence tomography in high-risk populations. By enabling the in vivo visualization of histologic-like features at cellular resolution, these noninvasive imaging technologies overcome the limitations of dermoscopy. The analysis of illustrative cases demonstrates that integrating these tools enhances both sensitivity and specificity, allowing for a precise differentiation between true malignancies and benign mimics. While reflectance confocal microscopy remains the standard for melanocytic criteria, line-field confocal optical coherence tomography complements it by overcoming depth limitations. Consequently, the use of combined noninvasive imaging supports a more conservative management strategy, potentially reducing the number of unnecessary excisions while ensuring the timely detection of skin cancer in patients with rare genetic syndromes.

INTRODUCTION: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by defective DNA repair, leading to extreme photosensitivity Affected individuals have a profoundly elevated risk estimated to be more than 10,000-fold greater than the general population of developing cutaneous malignancies, primarily squamous cell carcinoma (SCC). Management requires rigorous photoprotection and prompt, often repeated, surgical excisions. This is critically challenging in resource-limited settings with high ultraviolet exposure and limited surgical/oncological infrastructure. CASE PRESENTATION: We report a 7-year-old female from rural Somaliland, born to consanguineous parents, She presented with a 6-month history of an ulcerated, bleeding plaque on her right temple. Two younger siblings also exhibited milder dermatological symptoms, raising suspicion of familial XP with a 2-year history of progressive photosensitivity, xerosis, and freckling. Examination revealed characteristic XP findings including diffuse poikiloderma and ocular involvement (conjunctival growths, dry eyes). A clinical diagnosis of XP with suspected SCC was made. The lesion was initially excised with a 2mm margin; however, the SCC recurred within three months. A second, more extensive wide local excision with a 4mm margin and flap reconstruction was successful. Histopathology confirmed well-differentiated SCC invading the deep dermis. CONCLUSION: This case highlights the aggressive and recurrent nature of cutaneous SCC in XP patients, It underscores the necessity of standard 4mm surgical margins even in anatomically challenging areas to prevent recurrence. Even in childhood. It underscores the immense challenges of managing this life-threatening genodermatosis in settings with limited access to specialized multidisciplinary care, advanced reconstructive surgery, and lifelong photoprotective resources. The iterative surgical approach, complicated by graft failure, illustrates the need for robust primary excision and highlights the role of pragmatic, adaptive surgical planning in low-resource contexts.

The XPG endonuclease is crucial for nucleotide excision repair (NER) and other genome maintenance pathways. Precise regulation of XPG recruitment and activity during DNA repair is essential to avoid erroneous DNA incisions and genomic instability. In this study, we employed live-cell imaging to investigate how XPG is regulated during NER, focusing on its dynamic interactions with key factors involved in the pre- and post-incision steps. We found that TFIIH and XPA facilitate recruitment and association of XPG with DNA damage and that XPG localizes separately from TFIIH to UV-induced lesions. Furthermore, our results show that XPG's dissociation from DNA damage is triggered by its own incision activity as well as by that of XPF. Additionally, the exonuclease EXO1 promotes XPG dissociation, likely by processing incised DNA, even in the absence of XPG-mediated incision. Our findings help to better understand the regulatory mechanisms that control XPG activity during NER and provide important insights into the complex dynamics of the repair process.