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Journal of Cancer Research and Therapeutics, Vol. 7, No. 2, April-June, 2011, pp. 205-207 Case Report Multiple cutaneous malignancies in a patient of xeroderma pigmentosum Vandana U Grampurohit, US Dinesh, Ravikala Rao Department of Pathology, SDM College of Medical Sciences and Hospital, Dharwad, Karnataka, India PMID: 21768716 Abstract Xeroderma pigmentosum is a genodermatosis characterized by photosensitivity and the development of cutaneous and internal malignancies at an early age. The basic defect underlying the clinical manifestations is a nucleotide excision repair defect, leading to defective repair of DNA damaged by ultraviolet radiation. These patients exhibit enhanced sensitivity to ionizing radiation. Patients with xeroderma pigmentosum who are younger than 20 years of age have a greater than 1000-fold increased risk of developing skin cancer. Early detection of these malignancies is necessary because they are fast growing, metastasize early and lead to death. Although, early detection and treatment of cutaneous malignancies will reduce the morbidity and mortality, genetic counseling remains the most important measure for preventing xeroderma pigmentosum. We report a case of xeroderma pigmentosum in an 18-year-old male presenting with multiple cutaneous malignancies: squamous cell carcinoma, malignant melanoma and pigmented basal cell carcinoma.Keywords: Cutaneous malignancies, multiple, xeroderma pigmentosum Introduction Xeroderma pigmentosum (XP) was first described in 1874 by Hebra and Kaposi. In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to the characteristic dry, pigmented skin seen in these patients. [1],[2] XP is a genodermatosis characterized by photosensitivity, cutaneous pigmentary changes, premature skin aging and the development of cutaneous and internal malignancies at an early age. These patients exhibit enhanced sensitivity to ionizing radiation. [1],[3],[4] We report a case of XP presenting with squamous cell carcinoma (SCC), malignant melanoma and pigmented basal cell carcinoma (BCC). Synchronous occurence of multiple cutaneous malignancies in a patient of XP is extremely rare. Case Report An 18-year-old male presented with multiple swellings at the inner canthus of the right eye, the left side of the neck, and the lower lip. These swellings had been present for 4-6 months. He gave history of photosensitivity and diminished vision in the right eye. There was history of first-degree consanguinity and his brother and sister suffered from similar complaints. He had been operated earlier in another hospital for a lesion on the upper lip, which was diagnosed as malignant melanoma. On examination, there were hypo and hyperpigmented macules all over the body. The crusted lesions were more over the sun-exposed areas. The findings were consistent with classic type-A XP. There were swellings at the inner canthus of the right eye, on the lower lip intraorally and below the angle of mandible on the left side [Figure - 1] a, b. All the swellings were nodular, firm-to-hard and nontender. The right eye showed corneal opacification due to exposure keratitis. Systemic examination showed no abnormality. The patient underwent wide excision of all the lesions. The mass from the inner canthus of the right eye measured 7 × 3 × 1 cm [Figure - 2]a, with areas of hemorrhage and necrosis seen on the cut section. Microscopic examination was consistent with pigmented BCC. The mass from the lower lip measured 2 × 1 × 1 cm [Figure - 2]a. Histopathologically, it showed features of SCC. The mass from the neck was 5 × 3 × 3 cm size. The cut surface showed dark black /brown pigmentation [Figure - 2]b. Histopathology, showed metastatic melanoma in the skin, with cystic degeneration of metastatic melanoma of the lymph node. Nine months later, the patient returned with complaints of nodular lesions over the right upper lip, the left cheek and the right ala of the nostril. On examination, all the lesions were nodular, firm-to-hard and had raised and everted margins. Once again, wide excision of the lesions was carried out. The growth over the right ala of the nostril measured 1.5 × 1 × 0.4 cm and showed features of pigmented BCC [Figure - 3]. The growth from the left cheek was 3 × 2 × 1.5 cm in size, with a cut surface that was a homogenous gray/white in color. Microscopically, it showed SCC [Figure - 4]. The nodular growth over the right upper lip measured 1.5 × 1.5 × 0.6 cm, with the cut surface showing grayish-black areas. Microscopically, it showed spindle cell melanoma [Figure - 5], with the margins showing sebaceous hyperplasia and BCC in situ. Since the histopathological features were diagnostic immunohistochemical markers were not done. After 10 months, again the patient has inguinal lymphadenopathy with metastatic malignant melanoma but has refused further treatment. Discussion XP is inherited as an autosomal recessive trait. It is a rare pigmentary atrophic disease that begins in childhood and progresses to early development of senile changes in sun-exposed skin. [5] Parental consanguinity is common. XP occurs with an estimated frequency of 1:250000 in the US and, according to Robbins et al., is more common in Japan. The incidence in the Indian population is insignificant. XP shows no sex preference. [1],[3],[6] Intensive research is performed on XP patients because the disease is a model for sun-induced cancer. Determination of defective nucleotide excision repair (NER) mechanisms in ultraviolet (UV)-irradiated skin fibroblasts from XP patients allows the distinction of seven complementation groups (A-G) of the disease. [7] The basic defect in XP is in NER, leading to deficient repair of DNA damaged by UV radiation. NER involves removal and the replacement of damaged DNA with new DNA. Two types of NER exist: global genome NER (GG-NER) and transcription-coupled NER (TC-NER). In addition to defects in the NER genes the immunosuppressive effects of UV-B radiation may also be involved in the pathogenesis of XP. XP patients below 20 years of age have a >1000-fold increased risk of developing skin cancer. [6],[8] The median age of onset of non-melanoma skin cancers reported in patients with XP is 8 years, compared to 60 years in the healthy population. This difference is an indication of the importance of DNA repair in protecting against the development of skin cancer in normal individuals. Variations in the type of malignancies in XP appears to be related to the degree of sun exposure and genetic heterogeneity. [7] The two most common types of cancer found in XP patients are BCC and SCC, mainly occurring on the face, head, and neck. Melanomas occur in one-fourth of cases, and one-third of these occur in the head and neck. [4] A patient presenting with any two of these malignancies is a rare occurrence, with only a few cases reported in the literature; the presence of all the three types of malignancies in one patient is extremely unusual. [6] Early detection of these malignancies is necessary because they are fast growing, metastasize early and lead to death. Two important causes of mortality are metastatic melanoma and SCC. Most patients with XP do not live beyond the third decade because of the development of tumors. [4] Cutaneous neoplasms in XP patients cannot be prevented but early protection from UV radiation should be advised. Premalignant skin lesions may be treated with cryosurgery or topical antimitotic agents. Early removal of neoplasms should be accomplished with excision, chemosurgery or intralesional IFN-α. In selected XP patients, oral isoretinoin has been shown to significantly reduce the incidence of skin cancers. [9] A recent clinical trial by Yarosh et al. [10] found that the enzyme T4 endonuclease V, applied regularly as a topical agent, significantly reduced the onset of both BCC and actinic keratoses, thus giving a little hope to XP patients, who suffer from much psychological trauma and face many socioeconomic problems. Although, early detection and treatment of cutaneous malignancies will reduce morbidity and mortality, genetic counseling remains the most important measure for preventing XP. Acknowledgements We, the authors thank our medical director DR. NiranjanKumar for his support. References
Copyright 2011 - Journal of Cancer Research and Therapeutics The following images related to this document are available:Photo images[cr11050f5.jpg] [cr11050f2.jpg] [cr11050f1.jpg] [cr11050f4.jpg] [cr11050f3.jpg] |
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