Kaposi's Sarcoma is a multicentric vascular neoplasm-associated with the Kaposi's sarcoma associated herpes virus. The KSHV virus is also known as the human herpes virus 8. Studies have shown that KSHV-infected cells of vascular endothelial origin secrete cytokines, chemokines, and growth factors that allow for angiogenesis and further cancer pathogenesis [1
]. The KSHV viral genome encodes several viral genes. One of the viral genes encodes for a constitutively active intramembranous viral G-protein coupled receptor (vGPCR). This vGPCR is present in only a small number of infected cells and causes a signaling cascade which allows for the downstream transcription of genes which encode for cytokines, chemokines, and growth factors which are ultimately secreted from the cell and have paracrine effects on neighboring cells causing further cell proliferation and cancer growth [2
There are four types of KS seen clinically. These include classic variant KS, endemic KS, transplant-associated KS, and AIDS-associated KS. Classic variant KS is slow growing, often limited to the skin, and often found in people of Mediterranean descent. Endemic KS is found in Africa in HIV negative patients. This form is aggressive and can affect children. Transplant-associated KS is seen in patients who are on immunosuppressive therapy. The last type is AIDS-associated KS, which can develop in HIV positive patients [3
]. It is unknown why people of Mediterranean descent or of African descent are susceptible to the KSHV; however, it is known that HIV positive patients and patients who are on chronic immunosuppressive drugs have a compromised immune system which can make them susceptible to the KSHV and subsequently to the development of KS. Thus, it can be deduced that the classic and endemic variants are caused by genetic susceptibilities to the KSHV.
Our patient is of Mediterranean descent and is HIV negative, and the classic variant of KS in these patients tends to be more indolent in nature, these patients are often elderly as was our patients and occurs in men more often than women in a 15 to 1 ratio. The cancer often begins in the hands or feet and progresses towards the body, potentially taking several years to decades before the cancer metastasizes to the viscera [4
]. KS most often metastasizes to lymph nodes, the gastrointestinal tract, and to the lungs [5
]. The lesions begin as multiple firm reddish/brown or purple/blue plaques and nodules [4
]. The lesions are initially flat and if left untreated will become confluent and raised. Although of Mediterranean descent, our patient had a rare type of KS known as lymphangioma-like KS, which can occur in each of the four KS variants and is less than 5% of all KS cases [6
]. These patients usually present similar to KS, with blue/purple solid lesions; however, our patient also had severe lymphedema and soft tissue swelling as well as bulla-like vascular lesions characteristic of LLKS [7
]. Bulla-like lesions are the most common clinical feature seen in LLKS. Also, LLKS usually presents in the lower extremities, as was the case in our patient [8
The diagnosis of LLKS can be made based on clinical presentation and on histological examination of the lesions. LLKS is typified histologically by lymphangioma-like spaces. Often these patients also histologically show patterns associated with the other forms of KS. These patterns include spindle and endothelial cell proliferation, red blood cell extravasation, hemosiderin-laden macrophages, and other signs of an inflammatory reaction [5
]. In addition, biopsy samples can be stained for immunohistochemistry with anti-HHV8 antibodies in order to detect the KSHV in the tumors themselves, which can be detected in all four KS variants. shows the staining that was performed on our patient's biopsy sample. shows immunohistochemical staining for HHV8, and Figures and show the classic lymphangioma-like spaces.
Figure 2 (a) Patient's skin biopsy showing immunohistochemical stain for HHV8. There is a strong nuclear reactivity in the endothelial cells as well as some of the stromal spindle cell component. (b) and (c) H and E staining of skin biopsy from the patient. Within (more ...)
Treatment of KS includes simple excision of a single lesion and a combination of surgery, radiation, and chemotherapy for multiple and metastasized KS.
Herein we describe a patient with an extremity lesion that was initially believed to be a necrotic gangrenous foot. Cultures from his left foot biopsy from one of his lesions grew Gram-positive cocci and Gram-negative rods. We began the patient on systemic broad-spectrum antibiotics to treat his superinfected gangrenous foot. It was only after a biopsy was attained and histological and immunohistochemical examination was performed that we discovered that the patient had LLKS and it was at that time when the oncology team was able to begin management with chemotherapy, radiation, and surgery. It is important to recognize the typical skin lesions of KS and not to overlook Kaposi's sarcoma within the differential of a patient who presented as ours did, especially in a patient who is of Mediterranean descent, elderly, and HIV negative.