Five cases of melanoma in HIV positive patients

ARTICLE

According to the CDC staging criteria classification, Kaposi's sarcoma, high grade B-cell non-Hodgkin lymphoma and invasive carcinoma of the cervix are the only AIDS-defining neoplasms [1-3]. A number of other malignancies, such as Hodgkin's disease, cancers of the rectum, anus, germ-cell tumours, and rhabdomyosarcoma, which are not traditionally considered to be HIV-associated, appear to occur more frequently than would be expected in these patients [4, 5].

At present there are no data on the prevalence of cutaneous cancers in HIV/AIDS population. Since 1994 we have observed 5 cases of cutaneous malignant melanoma (CMM) diagnosed in patients with HIV/AIDS disease.

Patient 1

A 54-year-old homosexual man presented in June 1994 with a 6-month history of a red nodule on his left leg, which had enlarged in the last 2 months (Fig. 1). At the moment of our observation the patient, diagnosed as having HIV positive antibodies in 1989, was in B2 stage (CDC stage classification). He had been treated with zidovudine and didanosine. A wide surgical excision was performed and histology revealed a nodular melanoma (tumour thickness 9-mm). Abdominal sonography, performed for melanoma staging, revealed a mass, 11 cm in size, on the right kidney which was confirmed by total body TC scans. The patient underwent right nefrectomy and histopathological examination revealed a tubulopapillary adenocarcinoma. The patient is still free from disease and being treated with HAART including a protease inhibitor.

Patient 2

A 31 year-old male drug addict, who had been diagnosed with HIV infection since 1984, was referred to our Department in June 1995 because of the enlarging and chromatic changing of a congenital melanocytic nevus on his left pectoral region (Fig. 2). His past medical history was significant for viral hepatitis B, and at the moment of admission he was in treatment with zidovudine and didanosine. The lesion was excised with 1 cm safety margin. Histological examination showed a superficial spreading melanoma (SSM): the tumour thickness was 0.85 mm. The patient is now in HAART therapy and there are no signs of HIV or melanoma progression.

Patient 3

A 64-year-old homosexual man, found HIV-seropositive in 1995, consulted us in March 1996 because of the appearance on his abdomen of a sharply limited oval brownish-black pigmented plaque, 8 x 6 mm in size, which had been enlarging for the previous 12 months (Fig. 3). For treatment of his HIV infection, the patient was under indinavir, zidovudine, and lamivudine. The lesion was excised with a wide safety margin and histological examination revealed a SSM, the Breslow thickness was 2.3 mm. At present, after a 5-year follow-up, the patient's general condition is still good and there is no evidence of metastases.

Patient 4

A 28 year-old man with a history of drug addiction and homosexuality, known to have been HIV-seropositive since 1997, presented because of the onset of a nevus in his scrotum. The patient reported that a maternal uncle had died from CMM one year earlier. The lesion was surgically excised and histologic examination confirmed the clinical diagnosis of SSM (tumour thickness 0.4 mm). At the moment the patient, classified in C3 stage, is on HAART and his general condition is good.

Patient 5

A 46 year-old homosexual male with a diagnosis of AIDS since 1998 presented with a history of a black nodule on his scalp. The lesion had appeared four months before our observation and had rapidly expanded; successively, other blue-brown macules and papules developed around it (Fig. 4). A wide resection of the scalp lesions was performed. The histologic evaluation revealed a SSM, penetrating to a depth of 4.5 mm with satellitosis. Chest X-ray, abdominal sonography and total body TC scans had initially ruled out visceral metastases. Five months later, new brown-black hypodermic nodules appeared in proximity to the surgical scar. The patient refused any additional surgery and was therefore treated with dacarbazine (800 mg intravenously) and 2alpha-interferon (3 million units subcutaneously, three times a week). In January 2000 abdominal ultrasound revealed massive ascite and multiple liver metastasis. The patient died 2 months later.

Discussion

Including our patients, only 31 cases of HIV-infected subjects who subsequently developed CMM have been described in the literature so far (Table I). Twenty-eight of them were male (90.3%), 3 female (9.7%); the average age at diagnosis was 38.4 years, (range 23-64 years). The average Breslow thickness was of 1.6 mm (range 0.0-9 mm). The trunk was the main area involved (66.6%), followed by the limbs (13.3%) and head and neck (10%). Family history of CMM, presence of dysplastic nevi, photo-type, sun exposure and sunburns were only rarely detailed.

CD4⁺ lymphocyte cell counts, reported in 21 patients, ranged from 15 to 1,162 cells/mm³. Little is known about the patient's antiretroviral therapy. Interestingly no dysplastic nevi were observed in our HIV patients. By contrast, dysplastic nevi are observed in 33.9% of the immunocompetent patients affected with sporadic melanoma. Whether CMM occurs more frequently or whether it is more likely to metastasise in persons with HIV than in the general population remains an unanswered question at the moment. In fact, the data collected to date do not allow a definitive evaluation of the real incidence of CMM in HIV-infected patients. Nor can they confirm the more aggressive clinical behaviour of HIV-associated CMM. It is noteworthy that homosexual men who account for 80% of the survey (20 out of 25 patients whose risk category for HIV infection was reported), seem to represent the category at major risk for CMM. Homosexual practice is high-risk behaviour for HIV disease in developed countries. Its overall seroprevalence varies considerably with geographic location, race, and economic status and is approximately 15.6% in Italy [26] and ranges from 30% to 53% in USA [27, 28]. The role of sun-induced immunosuppression in the development of CMM is currently under evaluation [28]. Ultraviolet radiation may promote the initiation and the progression of CMM by depletion of cellular tumour suppressor genes, i.e. p53 and pRb, thus resulting in increased mutations, induction of oxidative DNA damages and defective DNA-repair enzymes [29]. Excessive exposure to ultraviolet B may impair the functional activity of epidermal Langerhans cells, and provide further reason for the reduction in skin tumour surveillance [29, 30].

As patients' life expectancy appears to be prolonged after the advent of the HAART therapy, skin cancers will probably become more frequent in the next future. Clinicians should keep close medical surveillance to promptly diagnose new cases of melanoma and non-melanoma skin cancers and advise their HIV-infected patients on the risk of prolonged sun exposure and severe sun burns for the development of skin cancers. *

Article accepted on 26/4/01

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