Kaposi's sarcoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Huda A. Karman, M.D.

Kaposi’s sarcoma arises from endothelial cells, which are epithelial cells that normally lines the luminal surface of blood vessels and lymphatic vessels. Kaposi’s sarcoma is mainly caused by an infection with Human herpes virus 8 (HHV-8), which is also known as Kaposi’s sarcoma-associated herpes virus (KSHV). The main gene involved in the pathogenesis of Kaposi’s sarcoma is ORF73 gene, which encodes the viral latency-associated nuclear antigen (LANA-1). Kaposi’s sarcoma is commonly associated with acquired immune deficiency syndrome (AIDS). On gross pathology, reddish, violaceous, or bluish-black macules and patches are characteristic findings of Kaposi’s sarcoma. On microscopic histopathological analysis the presence of spindle cells with minimal nuclear atypia are characteristic findings of Kaposi’s sarcoma. Kaposi’s sarcoma may be classified according to the clinical setting of the disease into five subtypes: Classic Kaposi’s sarcoma, African cutaneous Kaposi’s sarcoma, African lymphadenopathic Kaposi’s sarcoma, Iatrogenic Kaposi’s sarcoma, and AIDS-associated Kaposi’s sarcoma. The epidemiology of Kaposi sarcoma varies depending on its specific subtype. Before the AIDS epidemic, Kaposi’s sarcoma was relatively rare. In the early epidemic of AIDS, the incidence of HIV-related Kaposi sarcoma significantly increased; however, antiretroviral therapy led to a decrease in the incidence of HIV-related Kaposi sarcoma. While endemic African Kaposi sarcoma is more common in African Bantu, classic Kaposi sarcoma is more prevalent in Middle Eastern countries particularly among males and individuals from Jewish descent. The incidence of Kaposi sarcoma is markedly increased in renal transplant patients ranging from 0.5% to 5.3%. Transplant-related Kaposi sarcoma occurs more commonly in individuals who have Jewish, Arabic, Mediterranean, African, or Caribbean ethnicity. In the United States, the age-adjusted prevalence of Kaposi sarcoma is 8.1 per 100,000 in 2011. The most potent risk factor in the development of Kaposi’s sarcoma is an immune deficiency state. There is no established system for the staging of Kaposi’s sarcoma among immune competent patients. However, the staging of AIDS-associated Kaposi’s sarcoma is based on the AIDS Clinical Trials Group (ACTG) staging system. Symptoms of Kaposi’s sarcoma include fever, abdominal pain, hematochezia, hemoptysis, and gradual development of red/violaceous macules and patches over the nose, legs, and feet. The optimal therapy for Kaposi’s sarcoma depends on multiple factors. Management strategies varies depending on the specific variant of Kaposi’s sarcoma. Classic Kaposi’s sarcoma management may range from no treatment to either radiotherapy, local therapeutic interventions, or surgical excision. Iatrogenic Kaposi’s sarcoma management focuses on modifying immunosuppressive therapy in addition to local therapeutic interventions. Endemic Kaposi’s sarcoma is primarily managed by systemic chemotherapy. However, there is no curative treatment for epidemic Kaposi’s sarcoma; the mainstay management for such patients is HAART therapy which aims for the control of Kaposi’s sarcoma progression. Local/regional therapy recommended for the management of Kaposi’s sarcoma patients may include surgical excision, cryotherapy, and sclerotherapy.

Kaposi’s sarcoma was first described by Dr. Moritz Kaposi, a Hungarian dermatologist at the University of Vienna, in the year 1872

Kaposi’s sarcoma may be classified according to the clinical setting of the disease into five subtypess: Classic Kaposi’s sarcoma, African cutaneous Kaposi’s sarcoma, African lymphadenopathic Kaposi’s sarcoma, Iatrogenic Kaposi’s sarcoma, and AIDS-associated Kaposi’s sarcoma.

Kaposi’s sarcoma arises from endothelial cells, which are epithelial cells that normally lines the luminal surface of blood vessels and lymphatic vessels. Kaposi’s sarcoma is mainly caused by an infection with Human herpes virus 8 (HHV-8), which is also known as Kaposi’s sarcoma-associated herpes virus (KSHV). The main gene involved in the pathogenesis of Kaposi’s sarcoma is ORF73 gene, which encodes the viral latency-associated nuclear antigen (LANA-1). Kaposi’s sarcoma is commonly associated with acquired immune deficiency syndrome (AIDS). On gross pathology, reddish, violaceous, or bluish-black macules and patches are characteristic findings of Kaposi’s sarcoma. On microscopic histopathological analysis the presence of spindle cells with minimal nuclear atypia are characteristic findings of Kaposi’s sarcoma

Kaposi’s sarcoma is caused by an infection with HHV-8. The term Kaposi’s sarcoma associated virus(KHSV) was coined in order to name the viral causes.

Kaposi’s sarcoma must be differentiated from other diseases that cause similar cutaneous, pulmonary, and gastrointestinal involvement, such as bacillary angiomatosis, AIDS-related lymphoma, and seborrheic keratosis

The epidemiology of Kaposi sarcoma varies depending on the specific subtype. Before the AIDS epidemic, Kaposi’s sarcoma was relatively rare. In the early epidemic of AIDS, the incidence of HIV-related Kaposi sarcoma significantly increased; however, antiretroviral therapy led to a decrease in the incidence of HIV-related Kaposi sarcoma. While endemic African Kaposi sarcoma is more common in African Bantu, classic Kaposi sarcoma is more prevalent in Middle Eastern countries particularly among males and individuals from Jewish descent. The incidence of Kaposi sarcoma is markedly increased in renal transplant patients ranging from 0.5% to 5.3%. Transplant-related Kaposi sarcoma occurs more commonly in individuals who have Jewish, Arabic, Mediterranean, African, or Caribbean ethnicity. In the United States, the age-adjusted prevalence of Kaposi sarcoma is 8.1 per 100,000 in 2011

The most potent risk factor in the development of Kaposi’s sarcoma is an immune deficiency state. Other risk factors include multiple sexual partners, homosexual males, and medical procedures such as blood transfusions and organ transplantation .

According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for Kaposi’s sarcoma.

The prognosis of Kaposi’s sarcoma depends on its histological type, whether the cancer has spread, and the general health status of the patient. When stratified by age, the 5-year relative survival of patients with Kaposi sarcoma was 68.6% and 87.5% for patients <65 and ≥ 65 years of age respectively.

There is no established system for the staging of Kaposi’s sarcoma among immune competent patients. However, the staging of AIDS-associated Kaposi’s sarcoma is based on the AIDS Clinical Trials Group (ACTG) staging system. According to the ACTG staging system, there are 2 groups of AIDS-associated Kaposi’s sarcoma based on the tumor size, patients immune status, and the presence of any systemic illness

Symptoms of Kaposi’s sarcoma include fever, abdominal pain, hematochezia, hemoptysis, and gradual development of red/violaceous macules and patches over the nose, legs, and feet

Kaposi’s sarcoma lesions are nodules or patches that may be purple, red, blue, or black in color and are usually located on the nose, legs, and feet.

Laboratory findings consistent with the diagnosis of Kaposi’s sarcoma include decreased hemoglobin level, positive HIV tests, and positive HHV-8 antigen on immunohistochemistry.

Chest X-ray may be helpful in the diagnosis of Kaposi’s sarcoma lesions that are located in the lungs. Findings on chest X-ray suggestive of Kaposi’s sarcoma include parenchymal nodular or reticular opacities, pleural effusion, and mediastinal/hilar lymphadenopathy.

CT scan may be helpful in the diagnosis of Kaposi’s sarcoma lesions. Findings on CT scan of the chest suggestive of Kaposi’s sarcoma include ill-defined (flame-shaped) nodular lung opacities, interlobular septal thickening, and hilar lymphadenopathy.

Scintigraphy may be helpful in the diagnosis of Kaposi’s sarcoma.

Other diagnostic studies for Kaposi’s sarcoma include endoscopy, bronchoscopy, and biopsy.

The optimal therapy for Kaposi’s sarcoma depends on multiple factors. Management strategies varies depending on the specific variant of Kaposi’s sarcoma. Classic Kaposi’s sarcoma management may range from no treatment to either radiotherapy, local therapeutic interventions, or surgical excision. Iatrogenic Kaposi’s sarcoma management focuses on modifying immunosuppressive therapy in addition to local therapeutic interventions. Endemic Kaposi’s sarcoma is primarily manage by systemic chemotherapy. However, there is no curative treatment for epidemic Kaposi’s sarcoma; the mainstay management for such patients is HAART therapy which aims for the control of Kaposi’s sarcoma progression.

Local/regional therapy recommended for the management of Kaposi’s sarcoma patients may include surgical excision, cryotherapy, and sclerotherapy.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Huda A. Karman, M.D.

• Kaposi’s sarcoma was first described by Dr. Moritz Kaposi, a Hungarian dermatologist at the University of Vienna, in the year 1872.

• Kaposi’s sarcoma was first described by Dr. Moritz Kaposi, a Hungarian dermatologist at the University of Vienna, in the year 1872.^[1]
• The association between AIDS and Kaposi’s sarcoma was made during the 1980s.
• In 1994, the first discovery of the oncogenic Kaposi’s sarcoma-associated herpesvirus (HHV-8) occurred following the genetic analysis of a Kaposi’s sarcoma lesion by Dr. Yuan Chang, Dr. Patrick S. Moore, and Dr. Ethel Cesarman at Columbia University.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Huda A. Karman, M.D.

Kaposi’s sarcoma may be classified according to the clinical setting of the disease into five subtypes include Classic Kaposi’s sarcoma, African cutaneous Kaposi’s sarcoma, African lymphadenopathic Kaposi’s sarcoma, Immunosuppression-associated Kaposi’s sarcoma, and AIDS-associated Kaposi’s sarcoma.

• According to the clinical setting of the disease, clinical presentation, epidemiology, and prognosis Kaposi’s sarcoma may be classified into five different subtypes^[1][2][3]
• African cutaneous Kaposi’s sarcoma and African lymphadenopathic Kaposi’s sarcoma could be classified under the term of endemic Kaposi’s sarcomas.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Huda A. Karman, M.D.

Kaposi’s sarcoma arises from endothelial cells, which are epithelial cells that normally lines the luminal surface of blood vessels and lymphatic vessels. Kaposi’s sarcoma is mainly caused by an infection with Human herpes virus 8 (HHV-8), which is also known as Kaposi’s sarcoma-associated herpes virus (KSHV). The main gene involved in the pathogenesis of Kaposi’s sarcoma is ORF73 gene, which encodes the viral latency-associated nuclear antigen (LANA-1). Kaposi’s sarcoma is commonly associated with acquired immune deficiency syndrome (AIDS). On gross pathology, reddish, violaceous, or bluish-black macules and patches are characteristic findings of Kaposi’s sarcoma. On microscopic histopathological analysis, the presence of spindle cells with minimal nuclear atypia are characteristic findings of Kaposi’s sarcoma.

• Kaposi’s sarcoma arises from endothelial cells, which are epithelial cells that normally lines the luminal surface of blood vessels and lymphatic vessels.
• Kaposi’s sarcoma is mainly caused by an infection with Human herpes virus 8 (HHV-8), which is also known as Kaposi’s sarcoma-associated herpes virus (KSHV).^[1][2]
• HHV-8 is usually transmitted through both saliva and semen via close sexual contact.
• Another minor routes of transmission for HHV-8 are through organ transplantation and blood transfusion.
• A state of immunosuppression facilitates the development of Kaposi’s sarcoma among patients infected with the virus.^[1]
• Kaposi’s sarcoma is a widely disseminated malignancy that may involve the skin, oral cavity, gastrointestinal tract, and respiratory airways.
• Kaposi’s sarcoma is characterized by abnormal proliferation of endothelial cells, neoangiogenesis, and inflammation.^[3][4]
• Cutaneous manifestations of Kaposi’s sarcoma are due to:

• The high vascularity of the tumor that leads to the leakage of RBC and haemosiderin into the surrounding tissue
• The inflammatory process that surrounds the tumor leads to a mild painful swelling of the area

• The oncogenesis of HHV-8 infection is due to a number of human cellular genes that have been incorporated through molecular piracy into the viral DNA sequence.
• The genes acquired by HHV-8 will augment the cellular proliferation pathways of infected cells through various mediators and DNA synthesis proteins such as:

• Complement-binding protein
• IL-6
• BCL-2
• Cyclin D
• vcyclin ^[5]
• VEGF
• PDGF
• FGF
• TGF β
• Interferon regulatory factor
• Flice inhibitory protein (FLIP)
• Dihydrofolate reductase
• Thymidine kinase
• Thymidylate synthetase
• DNA polymerase

• The augmentation of such cellular proliferation pathways will protect the virus from the immune system and allow a continuous viral replication during the latency period.
• During the latent period, HHV-8 will express a viral latency-associated nuclear antigen (LANA-1) that acts as transcriptional modulator.^[6]
• The functions of HHV-8 viral latency-associated nuclear antigen (LANA-1) include:

• A tethering molecule that stabilize the viral DNA to the cellular chromosome
• An inhibitor of p53 tumor suppressor protein
• An inhibitor of retinoblastoma (Rb) tumor suppressor protein
• A suppressor of the viral lytic phase of replication

• The main gene involved in the pathogenesis of Kaposi’s sarcoma is ORF73 gene^[7], which encodes the viral latency-associated nuclear antigen (LANA-1).^[3]
• Other viral latent genes involved in the induction of malignant cellular proliferation include:

• vCyclin gene^[5]
• vFLIP gene^[8]
• ORF K12 gene (kaposins gene)^[9]
• KSHV miRNAs^[10][11]

• Kaposi’s sarcoma is associated with a number of conditions that include:^[1]

• Acquired immune deficiency syndrome (AIDS)
• Patients receiving immunosuppressive therapy

• On gross pathology, reddish, violaceous, or bluish-black macules and patches are characteristic findings of Kaposi’s sarcoma.^[11]
• The cutaneous lesions start to develop distally then progressively spread and coalesce to form nodules or plaques.

• On microscopic histopathological analysis the presence of spindle cells with minimal nuclear atypia are characteristic findings of Kaposi’s sarcoma.
• Other findings of Kaposi’s sarcoma on light microscopy may include:^[11]

• Excessive vascular proliferation
• Abundant red blood cells
• Red blood cell and hemosiderin extravasation
• Abundant lymphocytes and monocytes
• Premonitory sign (a neovascular lesion wrapped around a pre-existing space)
• Intracytoplasmic PAS +ve hyaline globules (pale pink globs that are paler than red blood cells)

• The table below differentiates between the four main lesion stages of development for Kaposi’s sarcoma:^[2]

• On immunohistochemistry Kaposi’s sarcoma is characterized by:^[11]

• Positive CD31
• Positive CD34
• Positive HHV-8
• Positive D2-40
• Positive Ki-67
• Positive ERG

• Detection of the LANA protein antigen in tumor cells confirms the diagnosis.

• The following images show the different gross pathological findings and different sites:

• 
  Intraoral lesion depicting Kaposi Sarcoma. Source: Wikimedia Commons ^[12]
• 
  Violaceous lesions on the nose of Kaposi sarcoma. Source: Wikimedia Commons^[13]
• 
  Pulmonary lesion of Kaposi sarcoma. Source: Wikimedia Commons ^[14]
• 
  Lesion in a foot. Source: Wikimedia Commons.^[15]
• 
  Kaposi sarcoma lesion Source: Wikimedia Commons.^[16]
• 
  Kaposi sarcoma lesion Source: Wikimedia Commons.^[17]

• Illustrated below is a series of microscopic images demonstrating Kaposi’s sarcoma:

• 
  Kaposi sarcoma observed under low magnification^[11]
• 
  Kaposi sarcoma observed under high magnification^[11]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Farima Kahe M.D. [2] Haytham Allaham, M.D. [3] Amandeep Singh M.D.[4] Huda A. Karman, M.D.

Kaposi’s sarcoma must be differentiated from other diseases that cause similar cutaneous, pulmonary, and gastrointestinal involvement, such as bacillary angiomatosis, AIDS-related lymphoma, and seborrheic keratosis.

• Kaposi’s sarcoma must be differentiated from other diseases that cause similar cutaneous, pulmonary, and gastrointestinal involvement.^[1][2][3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]Amandeep Singh M.D.[3] Huda A. Karman, M.D.

In the United States, the age-adjusted prevalence of Kaposi sarcoma is 8.1 per 100,000. The age-adjusted incidence of Kaposi sarcoma was 0.64 per 100,000 persons in the United States in 2011. Male are more commonly affected by Kaposi’s sarcoma than female. The male to female ratio is approximately 10-15:1.

• In 2011, the age-adjusted incidence of Kaposi sarcoma was 0.64 per 100,000 persons in the United States.^[1]
• Shown below is an image depicting the incidence of Kaposi sarcoma versus all types of cancers in the United States from 1975 to 2011.

• In the United States, the age-adjusted prevalence of Kaposi sarcoma is 8.1 per 100,000 in 2011.^[1]

• AIDS-related Kaposi sarcoma usually occurs in young to middle aged patients aged 20-54 years.^[2]
• Classic Kaposi sarcoma generally seen in patients aged 50-70 years.^[3]
• African Kaposi sarcoma occurs in younger age around 35-40 years old.^[4]

• AIDS-related Kaposi sarcoma usually occurs in homosexual males, bisexual men, and in the female sexual partners of bisexual men.^[4][5][6]
• African Kaposi sarcoma seen in heterosexual men and women equally.
• Male are more commonly affected by Kaposi’s sarcoma than female. The male to female ratio is approximately 10-15:1.^[7]

• Shown below is a table depicting the age-adjusted prevalence of Kaposi sarcoma by race in 2011 in the United States.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Amandeep Singh M.D.[3] Huda A. Karman, M.D.

Common risk factor in the development of Kaposi’s sarcoma is immune deficiency state, multiple sexual partners, homosexual males, and medical procedures such as blood transfusions and organ transplantation.

• Common risk factors in the development of kaposi’s sarcoma include:^[1][2]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]Amandeep Singh M.D.[3] Huda A. Karman, M.D.

• According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for Kaposi’s sarcoma.

• According to the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for Kaposi’s sarcoma.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2] Amandeep Singh M.D.[3] Huda A. Karman, M.D.

The prognosis of Kaposi’s sarcoma (KS) depends on its histological type, whether the cancer has spread, and the general health status of the patient. When stratified by age, the 5-year relative survival of patients with Kaposi sarcoma was 68.6% and 87.5% for patients <65 and ≥ 65 years of age respectively.

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection does not always lead to KS; it is still unclear what other factors may be required, such as preexisting immune system damage, or a specific interaction with HIV or other viruses. However, research in Africa has shown that even in the absence of HIV/AIDS, KS is more common in men than women although KSHV infection is equal between both sexes. This suggests that sex hormones may either protect from or predispose to KS in persons infected with the virus. Growth can range from very slow to explosively fast, and be associated with significant mortality and morbidity.^[1]

The prognosis of Kaposi’s sarcoma depends on the following:

• The type of Kaposi sarcoma
• Whether the cancer has spread
• Whether the cancer has just been diagnosed or has recurred
• The patient’s general health, especially the immune system

• Between 2004 and 2010, the 5-year relative survival of patients with Kaposi sarcoma was 72%.^[1]

• When stratified by age, the 5-year relative survival of patients with Kaposi sarcoma was 68.6% and 87.5% for patients <65 and ≥ 65 years of age respectively.^[1]

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