Triple secondary neoplasms

Abstract

Pegylated liposomal doxorubicin (PLD) is a first-line therapy for AIDS Kaposi's sarcoma [1]. Kaposi's sarcoma lesions contain dilated vascular spaces with extravasated erythrocytes; PLD uptake due to extravasation of liposomes was anticipated, offering advantage over conventional formulation. Skin Kaposi's sarcoma biopsies of patients under PLD reached 10–20 times doxorubicin concentrations to that of the normal skin [1]. Complete regression of Kaposi's sarcoma solely with highly active antiretroviral therapy (HAART) has been reported [2–5], questioning the need of chemotherapy for this angioproliferative disease produced by human herpes virus 8, as chemotherapy can increase immunosuppression. Worsening of Kaposi's sarcoma after HAART initiation is a manifestation of immune reconstitution syndrome [6,7], and without visceral involvement, it is a limited phenomenon; as immune function recovers, Kaposi's sarcoma regresses without further therapy. Secondary malignancy is a concern from chemotherapy use, but its role is difficult to demonstrate as other factors can contribute to its development. A substantial high incidence of secondary neoplasms – 9% among Kaposi's sarcoma patients treated with PLD – was recently reported [8], and oral cavity squamous cell carcinoma has also been reported in PLD-exposed patients [9–12], raising concerns of a possible contributing effect of PLD in the development of these neoplasms. Here, we present the case of a 37-year-old man with a 20-year history of cigarette smoking (average 5 cigarettes per day), who was diagnosed with AIDS on May 2011; he presented with wasting syndrome, oropharyngeal-candidiasis, disseminated-Mycobacterium avium Intracelulare and cutaneous Kaposi's sarcoma. His viral load was 631 471 copies/ml and CD4+ 144 cells/ml. The patient was started on Truvada + Kaletra and, 4 months later, the viral load was undetectable and the CD4+ had risen to 196 cells/ml. Following this, he received five monthly cycles with bleomycin 17 units, vincristine 2 mg and dexamethasone 16 mg, after which monthly PLD was started. On October 2012, after eight cycles of PLD, the patient noted multiple erythematous plaques in his penis; his HIV viral load remained undetectable, but he had 73 cells/ml CD4+. A penis biopsy revealed epidermoid carcinoma, which was successfully treated with topical 5% fluouracil. In November 2012, the patient complained of lip and oral mucosa lesions, for which the biopsies reported high-grade dysplasia. Several variants of HPV were identified: in the penis carcinoma and ureteral smear 16, in lips 33 and 35, in oral mucosa 35, in fresh oral mucosal smear 16 and 33, and in perianal condylomas 16 and 11. To our knowledge, there are no reports on adverse effects of PLD in HIV patients with concomitant mucosal HPV infections. However, since PLD concentrates for prolonged periods in mucous membranes, it is likely that it might alter local immunity since. PLD immunosuppression could also increase HPV replication [13], and decrease CD4+ cell counts [8] as for the case herein reported, in whom despite HIV viral suppression, CD4+ cells decrease with PDL administration (Fig. 1).Fig. 1: Temporal events of patient's case.Administration of chemotherapy*: (1) bleomycin 17 mg + vincristine 2 g + dexamethasone 16 mg (5 cycles); (2) pegylated liposomal doxorubicin (PLD) 60 mg + dexamethasone 16 mg (10 cycles). Red line, HIV viral load; blue diamonds, CD4+ cell count; pink bars, accumulated PLD. (a) Hematoxylin and eosin (HE) 40×. Penis mucosa with marked cytological atypia involving the entire epithelium. Note numerous atypical mitosis in the upper zones. *In-situ epidermoid penis carcinoma, human papillomavirus (HPV)16+. (b) HE 10×. Lip mucosa with acanthosis, cytologic atypia involving half epithelium. Note koilocytosis in the upper. High grade dysplasia (HGD) of the lip HPV 33 and 35+. (c) Oral mucosa. HE 4× and Ki67 immunostain. Oral mucosa with irregular acanthosis and cytologic atypia. Involving more than half of the epithelium. Note Ki67 positive in the entire epithelium, HGD of oral mucosa HPV35+.Although there has been an increasing incidence of non-AIDS-defining malignancies in the HAART era, the incidence of cancers of the oral cavity and penis in HIV patients is rare (<1%) [14]. Kaposi's sarcoma remission can be achieved solely with HAART and thus the use of PLD in AIDS Kaposi's sarcoma should be questioned since it can chronically affect the control of HPV infection and thus increase the risk of HPV-related neoplasms. Acknowledgements Conflicts of interest There are no conflicts of interest.