Serological and immunohistochemical detection of human herpesvirus 8 in Kaposi's sarcoma after immunosuppressive therapy for bullous pemphigoid

Kaposi's sarcoma (KS) developed in an 87-year-old human immunodeficiency virus-negative woman from Hokkaido island 4 months after oral administration of prednisolone for the treatment of bullous pemphigoid (BP), and rapidly disseminated to almost the entire body within 2 months. The open reading frame (ORF) 59 and ORF73 proteins encoded by human herpesvirus 8 (HHV-8) were detected immunohistochemically in the nuclei of the tumour cells of KS. The protein coded by ORF73, latent protein, was detected in most of the nuclei of the tumour cells, but only a few tumour nuclei were positive for the ORF59 protein, a lytic protein expressed during active infection. The antibodies against both lytic and latent proteins of HHV-8 were detected retrospectively in the serum 4 months before the appearance of KS and before prednisolone therapy had been started. Immunosuppression associated with the treatment for BP possibly activated latent HHV-8 infection and induced the development of KS.     

艾滋病相关型卡波西肉瘤1例

报告以左手背暗红色半球状结节为表现的艾滋病相关型卡波西（Kaposi）肉瘤1例。患者男,31岁。发热、双侧耳后肿痛18天,入院前10天左手背出现暗红色圆形结节,渐增大为2个半球状结节。抗HIV抗体（＋）。皮肤组织病理检查示：Kaposi’s肉瘤。诊断：艾滋病相关型卡波西肉瘤。拉米夫定（3TC）、司他夫定（D4T）、克力芝（洛匹那韦／利托那韦）抗病毒治疗3个月后,皮损逐渐消退。     

The influence of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma

To assess the clinical and biological benefit of highly active antiretroviral therapy on AIDS-associated Kaposi's sarcoma (KS), 13 patients with AIDS-associated Kaposi's sarcoma (five pulmonary KS and eight cutaneous KS) were prospectively followed for a mean duration of 12 months. Six patients were treated with specific anti-KS chemotherapy before or simultaneously with the introduction of antiretroviral therapy. Clinical response was assessed according to the AIDS Clinical Trial Group (ACTG) criteria. CD4 cell counts, plasma HIV-1 RNA and human herpesvirus 8 (HHV-8) viraemia were measured at baseline and at different points. Among patients with pulmonary KS, we observed three complete responses (CR), one partial response (PR) and one progression. The median survival time after the diagnosis of pulmonary KS was 15 months with a median duration of the response after the discontinuation of specific chemotherapy for KS of 8 months. Among patients with cutaneous KS, we observed four CR, three PR and one stable response. A complete response was significantly associated with a reversal in HHV-8 viraemia (five of six vs. one of six; P = 0.02, Mann-Whitney test).     

Radiotherapy of classic and human immunodeficiency virus-related Kaposi's sarcoma: results in 1482 lesions

Background The lesions of the various forms of Kaposi's sarcoma (KS), which are relatively radiosensitive, have been treated with different modalities of radiotherapy, with heterogeneous aims and results. Objective To verify the effectiveness and safety of radiotherapy on a large number of lesions endowed (classic KS) with a prolonged follow‐up. Methods A retrospective study was done on 711 lesions of classic KS and 771 lesions of human immunodeficiency virus (HIV)‐related KS, treated with traditional X‐ray therapy. Results In classic KS, a cure rate of 98.7% resulted after 13.5 years from the end of radiotherapy. In three lesions (0.42%) in the same patient, an acute radiodermatitis occurred after traumatic action. In HIV‐related KS, a complete remission was obtained in 91.43% of the lesions, partial remission in 6.74% and non‐response in 0.51% at 1 to 46 months from the end of radiotherapy. Conclusion Radiotherapy showed to be a safe and effective method, with relevant importance in the therapeutic strategy of KS.     

Docetaxel in anthracycline-pretreated AIDS-related Kaposi's sarcoma: a retrospective study

BACKGROUND: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm. Despite the significant decline in the incidence of acquired immune deficiency syndrome (AIDS)-related KS with the use of highly active antiretroviral therapy (HAART), some patients, even those with a good immune restoration, still have aggressive disease. Liposomal anthracyclines or combination chemotherapy are widely used but adverse effects limit their utilization. OBJECTIVES: We studied the efficacy and tolerance of docetaxel in the treatment of AIDS-related KS after pretreatment with anthracycline. PATIENTS/METHODS AND MAIN OUTCOME MEASURE: A retrospective cohort study was done. Nine human immunodeficiency virus (HIV)-infected patients were treated from 1997 to 2002 with docetaxel. Tumour response was evaluated using the AIDS Clinical Trial Group (ACTG) staging criteria. Clinical and biological toxicity was evaluated. AIDS status with HIV viral load and CD4 T-cell count were measured at the beginning and at the end of the treatment. RESULTS: A major (complete or partial) response and a stabilization of the disease were demonstrated in seven and two patients, respectively. Grade 4 neutropenia and thrombocytopenia were observed in four of nine and one of nine patients, respectively. One patient died after sepsis. CONCLUSIONS: Docetaxel has a good and rapid efficacy in anthracycline-pretreated patients with severe AIDS-related KS. Phase II/III trials should be done to compare docetaxel with liposomal anthracyclines as a first-line treatment.     

Lymphangioma-like pattern and anaplastic evolution in a case of classic Kaposi's sarcoma

Background Usually, classic Kaposi's sarcoma (KS) is clinically characterized by maculae, plaques and nodules and histologically by a proliferation of irregularly-shaped blood vessels, spindle cells and extravasated erythrocytes. The course is indolent. Very rarely, cases have been reported in which malignant transformation occurred with subsequent visceral diffusion. Observations A case of classic KS in an 82-year-old man is reported. Clinically, the lesion appeared lo be a nodule which grew rapidly to become an exophytic tumour mass. Histopathologically, it was characterized at the beginning by a lymphangioma-like pattern with subsequent frank anaplasia. The diagnosis of KS was based on lymph node examination which showed typical features. The patient died after 1 year. Conclusions Taking into account these unusual patterns we emphasize their importance in the differential diagnosis of KS from other angiomatous and anaplastic lesions.     

Kaposi's sarcoma: Venous capillary haemangioblastoma

Summary Histochemical and ultrastructural studies in two patients with Kaposi's sarcoma revealed that spindle cells have the pattern of venous capillary endothelium.Dedicated to Professor Dr. Herzberg on his 65th birthday     

Classic Kaposi's sarcoma in two young heterosexual men

Classic Kaposi's sarcoma is primarily a skin disease of the lower extremities affecting predominantly elderly men of Mediterranean origin. We report classic Kaposi's sarcoma first presenting in the third decade in two heterosexual, HIV-negative, males of Greek origin from Albania. Ten years after onset, the disease became aggressive with unusual clinical features that included exophytic tumors, extensive lesions on the hands as well as the legs, and prominent leg edema. One of the patients also presented lesions on the face, trunk and palate, and bubonic lymphadenopathy. In both cases, CD4 counts were normal and HLA-DR5 was positive. Treatment included radiation therapy, subcutaneous interferon (alpha 2b) and combined chemotherapy (ABV). At follow up 1 and 2 years later, both patients remain in partial remission with significant improvement in clinical disease, on maintenance interferon.     

Human herpesvirus 8 (HHV-8) in familial Kaposi's sarcoma

Human herpesvirus 8 (HHV-8) has been detected in various epidemiological forms of Kaposi's sarcoma (KS). Since familial KS cases are exceedingly rare and the occurrence of familial KS in siblings has thought to depend rather on genetic factors than on a viral factor, familial KS has not been investigated for the presence of HHV-8. To investigate whether HHV-8 is present also in this rare form of KS, we examined tumor biopsies of 2 siblings with familial KS for the presence of HHV-8 specific DNA sequences by a nested PCR protocol. HHV-8 DNA sequences could be detected in KS specimens of both patients. Sequence analysis revealed an identical DNA sequence of HHV-8 in KS tissue of both siblings, but the sequence in our cases differs in one base pair at position 67 from the previously published HHV-8 KS330Bam fragment. The findings indicate that besides the yet poorly defined genetical factors involved in the pathogenesis of KS, HHV-8 may act as a cofactor also in familial KS. In addition, our data demonstrate that HHV-8 is found in all epidemiological forms of KS, including the rarely occurring familial KS. Familial KS may act as a further model to study the interaction of an oncogenic virus with genetic host factors in the context of a neoplastic disorder.     

Penile Kaposi's sarcoma preceded by chronic penile lymphoedema

Kaposi's sarcoma localized to the penis with striking lymphoedema is extraordinary. We report a middle-aged Haitian man who was human herpesvirus-8 seropositive, without evidence of immunosuppression or human immunodeficiency virus infection. He was first seen with Kaposi's sarcoma of 6 months duration localized to his penis, preceded by a 3-year history of chronic penile lymphoedema. His tumour regressed completely after radiotherapy. We propose that chronic lymphoedema in this patient predisposed to the development of Kaposi's sarcoma.     

长链非编码RNA在Kaposi肉瘤组织中的表达

目的：检测长链非编码RNA(lncRNA)在Kaposi肉瘤组织和瘤旁正常组织中的表达。方法：利用高通量lncRNA芯片技术检测5例Kaposi肉瘤组织及其瘤旁正常组织的lncRNA 表达谱,筛选差异表达的lncRNA,并利用实时荧光定量PCR(qRT-PCR)方法进一步验证芯片结果,同时采用生物信息学分析差异lncRNA靶基因KEGG通路注释。结果：与正常组织相比,Kaposi肉瘤组织中共筛选出717个差异表达的lncRNA,其中上调表达408个,下调表达309个;与正常组织相比,lnc-PXDN-3:3和lnc-PERP-10:2在Kaposi肉瘤组织中均表达上调,与芯片结果一致。生物学过程注释集中在Wnt信号通路、泛素化代谢、TGF-beta信号通路、P53信号通路。结论：lncRNA可能与Kaposi肉瘤发病有关。     

Epidemiological study of classic Kaposi's sarcoma: a retrospective review of 125 cases from Northern Israel

BACKGROUND: The morphology of Kaposi's sarcoma is clinically and histologically the same in all clinical forms of the disease. However, there is a difference in the clinical and biological behaviour of the different forms of the disease. The behaviour also differs among individuals with the same form. The factors involved in the initiation and prognosis of the disease are still unknown. The classical form is more common in middle-aged Jews of East European or Mediterranean origin, people of Italian and southern Greek origin. Classic Kaposi's Sarcoma is seen relatively more frequently in Israel than in many other countries. OBJECTIVE: The aim of this study was to examine risk factors that influence the development and course of the disease. METHODS: This retrospective study includes 125 patients with Kaposi's sarcoma, all diagnosed and followed in the Department of Dermatology at Rambam Medical Center in Haifa. RESULTS: The group included 85 (68%) men and 40 (32%) women. Fourteen subjects received corticosteroid therapy and three were kidney transplant recipients. Age at onset of the disease was 21-87 years, with a mean age of 67. A total of 121 patients (96.8%) were Jews and four (3.2%) were non-Jews. A majority (61.6%) were of East European origin. The number of new cases each year was constant in relation to the general population, except for two peaks, one in 1970 and another in 1986-89. The lower limbs were involved in most patients. Extracutaneous involvement was present in 18.4%. Of all the subjects, 28 (22.4%) had diabetes mellitus and 21 (16.8%) had a second primary malignancy. The malignancies were of lymphoreticular origin in 10 patients, four in the urinary bladder, three had carcinoma of the large bowel and one of the pancreas. CONCLUSION: Our study shows similar clinical findings to those described in other series. The relatively high frequency of carcinomas of the colon and urinary bladder was not reported elsewhere. We observed a consistent rate of new cases each year with two peaks in 1970 and 1986-1989, the cause of which deserves explanation. Of interest is the relative rise in the number of females with Kaposi's sarcoma. A relative high risk for developing Kaposi's sarcoma has been found among Jews of Ashkenazi origin compared to those of other ethnic groups. Israeli-born subjects presented a relatively more aggressive course of disease than others.     

Systemic treatment modalities in the management of AIDS-related Kaposi's sarcoma

Background Kaposi's sarcoma (KS) is the most common neoplasm in patients with AIDS: in some cohorts of homosexual men with AIDS, the lifetime risk of KS approaches 50%. Prognosis is either ‘good risk’ or ‘poor risk’ according to recommended staging criteria. Objective In the present study we treated a good risk AIDS-KS group of patients with low dose of alpha-2 interferon (alpha-21FN) plus AZT, and a poor risk AIDS-KS group of patients with chemotherapy. Study design Prospective, non-randomized trial. Subjects Forty-four homosexual or bisexual male patients between 21 and 45 years old with positive ELISA for HIV, and KS, were included in the study. Intervention Ten patients received alpha-2 1FN plus AZT, 12 bleomycin, 12 doxorubicin-bleomycin-vincristine (ABV), and ten patients did not receive treatment. Results One patient achieved complete remission, two partial remission (PR), six stable disease (SD) and one progression (P) during alpha-2 IFN plus AZT treatment. Seven patients showed SD and five P during bleomycin treatment; and four patients achieved PR and eight SD during ABV treatment. Outcome Despite the fact that the different systemic treatment modalities employed allowed us to achieve clinical responses, there was no significant improvement in survival.     

Kaposi's sarcoma after immunosuppressive therapy for bullous pemphigoid

Immunosuppressed patients are at risk of acquiring Kaposi's sarcoma. We describe a 86-year-old man who was receiving steroid therapy for bullous pemphigoid and rapidly developed Kaposi's Sarcoma. The authors review and discuss the role of acquired immunosuppression in the pathogenesis of Kaposi's sarcoma.     

Bleomycin-induced flagellate dermatitis in AIDS patients with Kaposi's sarcoma

Objective To describe and illustrate bleomycin-induced cutaneous toxicity, which may present atypically in AIDS patients with Kaposi's sarcoma. Design and subjects Case note review of all AIDS patients receiving systemic chemotherapy in the preceding year. Setting Combined oncology and HIV out-patient clinic at the Chelsea and Westminster Hospital in London. Outcome measured Cutaneous toxicity associated with intravenous bleomycin therapy. Results We report three cases of bleomycin-induced flagellate dermatitis with atypical presentation of pruritic skin lesions after relatively low doses of bleomycin. Conclusions Bleomycin usage is increasing as an effective agent in the treatment of AIDS-related Kaposi's sarcoma. Awareness that cytotoxic drugs may produce a range of unusual cutaneous adverse effects in this patient population is important for doctors of all specialities who treat HIV-infected patients. The pathomechanism of flagellate dermatitis is discussed.     

Rainbow pattern in Kaposi's sarcoma under polarized dermoscopy: a dermoscopic pathological study

Summary Background We found previously that the features of Kaposi’s sarcoma (KS) under polarized dermoscopy are characterized by a bluish‐reddish coloration, a scaly surface, small brown globules and, most distinctively, the multicoloured ‘rainbow pattern’. Objectives To evaluate the significance of the rainbow pattern on dermoscopy as a diagnostic feature in KS, and to demonstrate that it is associated with the unique vascular structure of the tumour. Methods More than 100 lesions from seven patients with histologically proven KS were examined with polarized light dermoscopy. Sixty‐three patients with various other cutaneous vascular and nonvascular tumours were also examined. KS lesions exhibiting the rainbow pattern and KS lesions lacking the rainbow pattern on dermoscopy were excised, and dermoscopic features were compared with histopathological structures. The dermoscopic patterns of other vascular tumours were also compared with histological features. In addition, the changes in dermoscopic features and histological structures were assessed before and after surgical therapy in one patient with KS. Results On the basis of evaluations with polarized dermoscopy, the rainbow pattern was found to be a highly specific dermoscopic feature for KS. Histology of KS lesions showing the rainbow pattern under polarized light dermoscopy demonstrated a vascular lumen‐rich pattern of closely arranged ‘back‐to‐back’ vascular structures, whereas histology of KS lesions without the rainbow pattern showed a vascular lumen‐poor pattern with vascular lumina separated further apart by intervening stromal and cellular tissue. Other vascular tumours did not exhibit the rainbow pattern and were characterized histologically by variably sized vascular structures separated by substantial amounts of stromal and cellular tissue. In one patient with KS, disappearance of the rainbow pattern was associated with obliteration of the vascular structure following surgical ablation therapy. Conclusions The rainbow pattern in KS is associated with the vascular lumen‐rich histological subtype, is not manifest in the vascular lumen‐poor subtype and disappears following total tumour removal. Therefore, the underlying structural arrangement of the vessels in KS may determine whether or not the rainbow pattern can be seen on polarized dermoscopy.     

Stimulation of Kaposi's sarcoma cell growth by urine from women in early pregnancy,the current source for clinical-grade human chorionic gonadotropin preparations

Clinical-grade preparations of human chorionic gonadotropin (hCG) have been shown to be toxic to Kaposi's sarcoma (KS) cells. However, the results of clinical studies using commercial hCG preparations KS remain highly contradictory. More particularly, some hCG preparations could have a paradoxical growth effect on KS. Such discrepant results may be explained by the fact that the anti-KS activity is not associated with hCG itself but with one or more factors that are co-purified with the hormone. We found here that crude urine from first trimester pregnant women, the current source for commercial hCG, had a growth stimulatory effect on KS cells. By contrast, urine from last trimester pregnant women, from non-pregnant young women, from menopausal women and from men exhibited neither a growth stimulatory nor a growth inhibitory effect on KS cells. The amplitude of this pregnancy urine-associated pro-KS activity/hCG unit was higher than that achieved with clinical-grade hCG preparations. Partial co-purification of pregnancy-associated factors during the extraction procedure of commercial hCG from urine may explain the pro-KS activity achieved with some hCG preparations. We, therefore, suggest a cautious use of hCG purified from pregnancy urine for the treatment of KS.