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In recent years there have been many advances that have changed approaches to the pathophysiology and treatment of Kaposi’s Sarcoma (KS). Described initially in 1872 by a Hungarian dermatologist, a distinction is today made between four epidemiological forms of Kaposi’s sarcoma.
Classic KS corresponds to the first description of the disease and it is characterised by purplish papules and nodules developing predominantly on the lower limbs together with lymphoedema. It has a predilection for elderly males with a sex ratio of around 10:1. In most cases it is a low-grade disease that progresses slowly and only rarely is specific treatment needed.
Endemic KS, described in sub-Saharan Africa, is often more aggressive entailing nodular ulcerated lesions to the extremities, localisation to the internal organs, and paediatric forms with lymphadenopathy and a very poor prognosis. Endemic KS predominantly affects mostly males with a sex ratio of 2 or 3:1.
In the 1970s, iatrogenic KS was distinguished. This is when KS develops in patients who have been under long-term immunosuppressant treatments, possibly following organ transplants. When iatrogenic KS first appeared, this underscored the opportunistic nature of this tumour for the first time, a feature which, with the coming HIV epidemic, would really come to the forefront.
This was played out when, during the early 1980s, KS was beginning to be reported in young homosexuals who also presented opportunistic infections, especially PCP. This was how the fourth epidemiological form of KS, known as epidemic KS, appeared, and we now know that it is connected to the immune system damage caused by HIV. AIDS-related KS was almost exclusively seen among HIV-positive homosexuals. These cases were generally more aggressive than the other epidemiological forms of KS with, notably, more widespread skin involvement and the possibility of localisation to the internal organs, mainly the gastrointestinal and respiratory systems, which led to patients dying in spite of specific treatments
While the different epidemiological forms present specific clinical characteristics, they have certain essential points in common that allow the pathophysiology of the disease to be defined:
• Mostly affects males, especially classic KS and epidemic KS
• Common histological features with differentiation as follows:
— The early lesions are macules with ectasia and/or dilated vascular spaces and an infiltrate of lymphocytes and plasma cells.
— The later lesions are papules, consisting also of a moderate proliferation of spindle cells, which are today recognised by all authors to originate from endothelium. These cells show endothelial cell markers such as CD34 and CD31 and they express lymphatic and/or vascular endothelial growth factor receptors.
— Nodules comprised almost exclusively of a dense spindle cell infiltrate.
• A consistent association with human herpesvirus-8 (HHV-8 or KSHV for Kaposi’s sarcoma associated-herpesvirus) .
This last point has transformed the field of research into KS. Since it was discovered, the evidence has built up to suggest that HHV-8 is the causal agent in KS. While serology techniques need to be improved in order for the seroprevalence of HHV-8 infection in the general population to be appreciated, the techniques for genome detection and morphological techniques have led to the link between HHV-8 and KS being more firmly established and have meant that it is recognised today that:
— HHV-8 is connected to all epidemiological forms of KS
— This virus is implicated in multicentric Castleman disease and in serous lymphomas
— There is a relationship between infection with HHV-8 and the later development of KS
— The HHV-8 genome holds a large number of genes that could potentially be involved in regulating cell division, cell transformation and also angiogenesis.
There is much that needs further clarification, such as the various modes of viral contamination and the true place that should be accorded to HHV-8 in the therapeutic management of KS.
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