Kaposi Sarcoma is a solitary or multifocal lymphatic tumor, initially described as Classic Kaposi Sarcoma almost 140 years ago, in elderly men of Middle Eastern and Mediterranean descent [6, 7]. No recent report has evaluated the demographics and clinical presentations of CKS patients in Morocco. The current study represents a large retrospective review of 56 patients with a diagnosis of CKS seen at our institution over 11-year period (1998-2008) and is to our knowledge the largest series in our context focusing on this particular population.
Most of demographic and clinical features of our study group are not totally in accordance with previous findings in the literature.
As the analysis of our results indicates, CKS in Morocco exhibits some special clinico-epidemiological characteristics including nodular lesions as first presentation, a more frequent association with lymphedema, disseminated skin lesions at diagnosis, unusual visceral or lymph node involvement and rare coexistence of second primary neoplasm.
The National institute of oncology, Rabat, is the most important cancer center in Morocco, to which are referred patients from the sixteen regions of the country.
In Morocco, we do not possess a national cancer registry, however the local cancer registry of Rabat in 2005, reported a standardized incidence rate of 0,39/100000 habitants. CKS is not uncommon in Morocco, with sporadic cases all over the country. Geographical distribution of CKS according to the region of origin supposes that the disease is more common in northern Morocco. However statistical data regarding the place of birth in general Moroccan population are lacking and no genetic or environnemental factors can be defined.
The incidence of CKS varies greatly with ethnic and geographic factors. The predisposition of Jews has been described in the literature. In Israel, rates of CKS of 2.07 in men and 0.75 in women per 100,000 were calculated . The risk for Jews to develop CKS is 10 times higher than for non-Jews . CKS is rare in North America and North Europe. Low rates were reported in England and Wales as well as in Denmark; intermediate rates were reported in Sweden, whereas higher rates were reported in Italy . The highest incidence rates in Europe were reported in two Mediterranean Italian islands: Sardinia and Sicily. At the National Institute of Oncology, Rabat, CKS accounts 0,1% of all new cases of cancer with a mean of 5 cases diagnosed each year.
The identification of HHV-8 as the causative agent of KS has greatly enhanced our understanding of the pathogenetic events that lead to the development of this tumor . A strong direct correlation between HHV-8 prevalence and CKS incidence was documented. HHV-8 now is known to be the primary cause of all types of KS , but CKS occurs in only a small fraction of HHV-8 infected people. In the Mediterranean area, classical KS develops annually in only 0.03% of the HHV-8 infected men older than 50 years and in 0.01%-0.02% of the HHV-8-infected women older than 50 years . Various cofactors have been implicated in the pathogenesis of KS, including genetic susceptibility, immunologic alterations, and endocrine factors [13, 14]. It has been hypothesized that the abundant expression of various proinflammatory cytokines in early KS lesions may create an immunologic microenvironment that stimulates the growth of HHV-8 and promotes the development of clinical lesions.[15, 16].
One study is available about HHV-8 frequency among CKS patients in Morocco. Kassemi et al reported the seroprevalence of anti-HHV8 antibodies in 2 groups of HIV negative Moroccan patients. Among the 26 patients, 24 (92%) presented with anti-HHV8 antibodies, whereas the 26 donors were seronegative for HHV-8 . In our series, the seroprevalence of anti-HHV8 were not explored. However the serology of anti HHV-8 was done in 5 patients in which it was positive.
The mean age of onset in our series is mainly in accordance to other similar reports  . In fact, CKS is a disease of the elderly with a median age at diagnosis reported variously from 50 to 80 years [19, 20]. Population-based incidence studies from the United States and Europe reported that the median age at time of diagnosis is the seventh decade of life and only 4-8% of cases were reported in individuals younger than 50 years [10, 21]. In the current study, 10 patients were younger than 50 years and the youngest patient was a 15 years old. Worldwide, only sporadic cases occurring before the age of 30 years and occasional cases of CKS have been reported in children . In Israel the median age at onset of CKS is 67 years (range,11-91 years) with no significant variation noted between people from different countries of origin [23, 24]. From 1961 until 1989, 13% of the cases of CKS reported in Israel involved people age, 55 years; 0.3% were age, 15 years, with no variation reported during the period.
Interestingly, 90% women in our study were of postmenopausal age (49-84 years), providing additional support to the speculation that female sex hormones may act prophylactically to CKS development .
CKS has an overwhelming male predominance, with a male-to-female ratio of approximately 10:1 to 15:1 [10, 18]. However, in more recent studies, the sex ratio is much lower: 8:1 in Colombia , and 3:1 in Italy . The 4:1 male-to-female ratio found in our study has been reported previously [10, 27].
Cutaneous KS is often first evident as discrete erythematous or violaceous bilaterally symmetric patches, most commonly on the lower extremities. A study of Sardinian CKS found this initial lower extremity location evident in 155 of 200 patients . Patches may evolve into plaques and nodules. Nodules and/or plaques were the most common type of lesion in our series.
Associated lymphedema, especially of the feet, is not uncommon and it occurred particularly in a high proportion (42%) of our patients.
KS is a multicentric neoplasm frequently evident as a multiple vascular cutaneous and mucosal nodules [29, 30]. Lesions may be limited to skin or sometimes arises to oral cavity, lymph nodes, or viscera in 10-15% . The gastrointestinal tract is the most common extracutaneous site of involvement. An endoscopic upper gastrointestinal tract evaluation of 87 Greek CKS patients showed that 71 (81.6%) had gastrointestinal lesions . Other visceral organs that may be affected include liver, heart and lung [23, 33].
Our study reveals more locations in upper extremities, lymph nodes, and visceral sites than previously reported for CKS [33, 34]. Unusual sites, as seen in 14 of our patients, include penis, ear, mouth, eyelids, conjunctiva, and nose. They are often associated with poor prognosis . The findings of a large number (n = 5) of CKS in the penis in the current study may relate to an aggressive form of the disease.
Prognosis appears to correlate with the degree of immunosuppression and older age among classic KS patients[35, 36]. Localized nodular KS has the best prognosis, with few deaths directly attributable to KS. Clinical classification of KS may be the best prognosticator, comparing localized nodular disease, locally aggressive disease, and generalized KS.
Several staging systems have been proposed for the classification of CKS [37, 38]. A recently proposed staging system is often followed, which is based on objective criteria that more closely follow the clinical variability of CKS, and thereby makes therapeutic choices easier. We elected this staging classification because it allows a better distinction between early (skin-localized) and advanced (disseminated) CKS.
CKS by itself is rarely the cause for the patient's demise. In the current study CKS is more aggressive than reported in the literature, with 29 (51,7%) having multicentric disease and classified in stage III and IV and 16% with widespread disseminated disease. Furthermore, the proportion of patients with systemic involvement in our cohort was slightly higher to that seen in other series of patients with CKS, ranging from 4% to 10% of patients.[10, 36]. Also, in this work, we found that men were more likely to have advanced stage at diagnosis. Such observations were not previously noted. For example, Stratigos and al reported a series of Sixty-eight patients. Mean age and sex did not differ significantly by clinical stage (I-II vs IV)
It is not a novel observation that CKS is associated with other primary malignancies, often of the reticuloendothelial system, that may precede, coincide with or follow the occurrence of CKS . CKS is reportedly more commonly a primary than a secondary neoplasm . However, information was obtained in several cases indicating CKS arose subsequent to other malignancy, offering the suggestion of a common etiology. The current study found that only 10,7% of CKS patients with complete follow-up data available had associated a second primary malignancy, a lower occurrence than previously reported in the literature, 9-42%.[33, 40–42]. This lower frequency of second primary malignancies is similar to the 18% found in a previous study on Israeli patients by Feurman and al .
The association between aggressive clinical course of CKS and immunosuppression has previously been suggested. The immunological dysfunction underlying CKS is unknown and may result from advanced age or chronic infection . Its induction by immunosuppressive therapy and its subsequent regression on removal of immunosuppression provided early clinical recognition of the reversibility of CKS. However, none of our patients reported an immunologic dysfunction supporting the previous report of an immunological etiology of CKS .
Diabetes mellitus seems to occur more frequently among CKS patients than in the general population . The high frequency of non-insulin dependent diabetes mellitus has been reported repeatedly among American  and Israeli  subjects but was not found in subjects with endemic form of CKS . The frequency 3,9% of non-insulin dependent diabetes mellitus in our series is lower than reported in the literature.
Only a small number of familial cases of CKS have been reported[35, 46, 47]. Among Ninety CKS subjects described by Di Giovana , only one was familial. Similarly, in a series of 56 CKS patients from north-east Sardinia, no familial cases were reported.