Vinicio Boneschi

Treatment of classical Kaposi's sarcoma with gemcitabine

Background: Several drugs are active in aggressive classical Kaposi’s sarcoma (CKS); chemotherapeutic agents with fewer side-effects, more rapid response and able to overcome resistance to previous treatment are advisable when treating patients in a second line. Gemcitabine, an analogue of deoxycytidine with cytotoxic activity in the treatment of solid tumours, has been found to have no serious side-effects. Objective: To evaluate the usefulness of treating patients affected by aggressive CKS with gemcytabine. Methods: Twelve patients with a recurrent aggressive form of CKS previously treated with chemotherapy were treated with gemcitabine. The drug was administered intravenously at the dose of 1.2 g/week for 2 weeks, followed by a 1-week interval, until maximal response was reached. Objective responses and toxicity were evaluated according to WHO criteria. Results: Eleven evaluable patients achieved an objective response: CR in 1/11 and PR in 10/11. Toxicity was limited. Conclusion: This study shows the usefulness of treating patients affected with aggressive CKS with gemcitabine, in order to obtain control of the disease and to reduce the related symptoms as well as to overcome a possible resistance to previous treatments.

Human herpesvirus 8 DNA in the skin and blood of patients with Mediterranean Kaposi's sarcoma: clinical correlations

Background: Kaposi’s sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi’s sarcoma by confirmational display analysis and polymerase chain reaction. Objective: As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi’s sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease. Methods: By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi’s sarcoma. Results: HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi’s sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I–II disease as opposed to 73.6% of those with stage III–IV. Conclusion: The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi’s sarcoma.

Intralesional Chemotherapy for Kaposi’s Sarcoma

Over a period of 36 months we treated 12 patients with skin localizations of Kaposis sarcoma with intralesional chemotherapy. Local administration of vincristine (usual dose 0.1 mg per site) or bleomycin appeared to be very effective: in 93 injected nodules we obtained 74 complete and 19 partial regressions. No significant local or systemic toxicity has so far been observed.

Human immunodeficiency virus negative Kaposi sarcoma and lymphoproliferative disorders

The concomitant occurrence of more than one primary neoplasm in the same individual has led researchers to seek possible common etiopathogenetic factors. Kaposi sarcoma (KS) is a multicentric neoplasm of vascular origin and perhaps viral etiology. Four forms of KS are known: classic or Mediterranean, endemic or African, posttransplant, and epidemic or acquired immunodeficiency syndrome‐associated KS. In its classic form KS mainly affects elderly people and often has a long and indolent course that occasionally allows other malignancies to appear. Previous studies of the possible association between human immunodeficiency virus (HIV) negative KS and lymphoproliferative disorders (LDs) have produced discordant results.

ERK-Dependent Downregulation of the Atypical Chemokine Receptor D6 Drives Tumor Aggressiveness in Kaposi Sarcoma

Savino, Caronni, and colleagues report that D6 expression was inversely correlated with increased tumor-associated M2-macrophages and aggressiveness in ERK pathway–activated Kaposi sarcoma (KS), and suggest targeting of CCR2 and the ERK pathway as a therapeutic option for patients with KS. D6 is an atypical chemokine receptor acting as a decoy and scavenger for inflammatory CC chemokines expressed in lymphatic endothelial cells. Here, we report that D6 is expressed in Kaposi sarcoma (KS), a tumor ontogenetically related to the lymphatic endothelium. Both in human tumors and in an experimental model, D6 expression levels were inversely correlated with tumor aggressiveness and increased infiltration of proangiogenic macrophages. Inhibition of monocyte recruitment reduced the growth of tumors, while adoptive transfer of wild-type, but not CCR2−/− macrophages, increased the growth rate of D6-competent neoplasms. In the KS model with the B-Raf V600E–activating mutation, inhibition of B-Raf or the downstream ERK pathway induced D6 expression; in progressing human KS tumors, the activation of ERK correlates with reduced levels of D6 expression. These results indicate that activation of the K-Ras–B-Raf–ERK pathway during KS progression downregulates D6 expression, which unleashes chemokine-mediated macrophage recruitment and their acquisition of an M2-like phenotype supporting angiogenesis and tumor growth. Combined targeting of CCR2 and the ERK pathway should be considered as a therapeutic option for patients with KS. Cancer Immunol Res; 2(7); 679–89. ©2014 AACR.

Multiple miliary osteomas of the face.

We report an exceptional case of multiple miliary osteomas of the face in an elderly woman, which developed in the absence of previous inflammatory or neoplastic skin disease. Excellent aesthetic results were achieved by surgical removal of about 90 miniature stones present in the facial skin of the patient.

Lymphogranuloma venereum: the Italian experience

An epidemic of lymphogranuloma venereum (LGV) has been described in men who have sex with men (MSM) in the western world, particularly in western Europe. The first Italian case was reported by the authors in 2006, and up to March 2008 there have been 13 symptomatic cases, all in MSM. Ten cases had LGV proctitis and three cases had inguinal adenopathy as their clinical presentation. The initial three cases reported receptive anal intercourse in metropolitan areas of northern Europe, Turkey and eastern Europe, whereas the later cases were infections acquired locally. Diagnosis was by LGV-specific real-time PCR in nine cases, by symptoms and PCR for Chlamydia trachomatis in three cases, and in one case clinically and epidemiologically.

Granulomatous tattoo reaction induced by intense pulse light treatment

Cosmetic tattooing involves implantation of pigments into the dermis in order to create a permanent makeup. Here, we report a case of sarcoidal granulomatous reaction to old cosmetic tattoos after an intense pulsed light (IPL) treatment for facial skin rejuvenation. We consider this case as a peculiar example of photo‐induced reaction to tattoo. In addition, we hypothesize that an underlying immune dysfunction was present, and acted as a predisposing factor for this unusual response, as the patient had suffered from an episode of acute pulmonary sarcoidosis 15 years before. Overall, our observation suggests that IPL treatment should be used cautiously in patients with tattoos, especially when a history of autoimmune disease is present.

Vinorelbine therapy for Kaposi's sarcoma in a kidney transplant patient

We report the case of a patient with Kaposis sarcoma after kidney transplantation. Despite the discontinuation of azathioprine and a reduction in the cyclosporin dosage, the disease continued to evolve, and antineoplastic treatment became necessary. After 14 cycles of vinorelbine chemotherapy, there was a 75% regression of the initial lesions, despite the continuation of cyclosporin A.

Syphilis with a lichen planus-like pattern (hypertrophic syphilis)

To the Editor, A 52-year-old Caucasian man presented with a 1-month history of a widespread pruritic cutaneous eruption. Physical examination revealed multiple violaceous plaques with verrucous surfaces asymmetrically distributed on the trunk and upper limbs, thus resembling hypertrophic lichen planus (Fig. 1). A centrally eroded nodule was also present on the scalp, while the interdigital spaces were involved by serous crusted lesions with fissures (Fig. 2). No mucosal lesions, genital ulcers, alopecia or lymphadenopathy was found. The patient denied the use of drugs. Histopathologic examination with hematoxylin– eosin staining showed irregular psoriasiform hyperplasia of epidermis with wedge-shaped hypergranulosis (Fig. 3). The dermis contained a lichenoid infiltrate composed of lymphocytes and plasma cells, and the latter were numerous around vessels (Fig. 4). Polymerase chain reaction and immunohistochemistry (Fig. 5) revealed the presence of Treponema pallidum in the epidermis and papillary dermis. Additionally, venereal disease research laboratory titers were