Kaposi Sarcoma

Epidemiology and Etiology:

• Uniformly associated with HHV-8 (KS-associated herpesvirus [KSHV])
• AIDS associated KS:
• Very uncommon with use of HAART
• Particularly frequent in men who have sex with men
• Chronic / classic / European KS:
• Older men
• Eastern European (Ashkenazi Jews) or Mediterranean descent
• Not associated with HIV
• Lymphadenopathic / African / endemic KS:
• Africa
• Young Bantu children of South Africa
• Transplant-associated / immunosuppression-associated / iatrogenic KS:
• Several months to a few years postoperatively in organ transplant recipients who receive high doses of immunosuppressive therapy

Common sites:

• Skin
• Distal extremities
• Mucous membranes
• Lymph nodes
• Visceral organs
• Chronic / classic / European KS:
• Skin of arms and legs
• Viscera or mucosa in 10%
• Transplant-associated / Immunosuppression-associated KS:
• Lymph nodes
• Mucosa
• Visceral organs
• Skin lesions may be absent

• AIDS associated KS:
• Head / neck / face
• Trunk
• Genitals
• Lower extremities
• Oral mucosa
• Lymph nodes
• GI tract
• lungs

Gross features:

• skin:
• patches, plaques, nodules
• very small to several centimeters
• mucosa, soft tissues, lymph nodes, viscera:
• hemorrhagic nodules
• spread along vascular structures in organs
• chronic / classic / European KS:
• multiple
• red to purple to brown skin plaques or nodules
• 3 stages – patch to plaque to nodules
• may ulcerate
• lymphadenopathic / African / endemic KS:
• localized or generalized lymphadenopathy

Histologic features:

• similar for all four types
• early lesions (uncharacteristic):
• subtle vascular proliferation
• patch:
• dilated, irregular, angulated blood vessels
• may dissect collagen fibres in the upper reticular dermis
• often parallel to epidermis
• often perivascular and periadnexal
• flattened or oval spindle cells lining them
• little atypia
• interspersed sparse infiltrate of lymphocytes, plasma cells, and macrophages
• difficult to distinguish from granulation tissue
• plaque:
• exaggeration of all characteristics of patch stage
• more extensive angioproliferation
• dermal, dilated, jagged vascular channels
• perivascular aggregates of similar spindled cells
• numerous extravascular red cells and hemosiderin-laden macrophages
• more dense inflammation - lymphocytes, and plasma cells
• pink hyaline globules (?destroyed red cells) in spindle cells and macrophages
• nodule:
• sheets and intersecting fascicles of plump, proliferating spindle cells in the dermis or subcutaneous tissues
• mild atypia
• many mitoses
• scattered small vessels and slit-like spaces are characteristic
• rows of red cells and hyaline droplets within the slit-like spaces

Immunophenotype:

Marker:	Sensitivity:	Specificity:
HHV-8	all
Endothelial lining cells
Vascular markers
Non-lining spindle cells
CD34	Consistently
CD31	Commonly
FLI1
Factor VIII (neg)

Molecular features:

•  growth factors such as VEGF/VPF and FGF most probably play an essential role

Other features:

• Lung involvement adversely affects prognosis, whereas GI involvement does not
• chronic / classic / European KS:
• slowly growing in size and number
• erratic course of lapses and remissions
• may be associated with haematopoetic malignancies
• lymphadenopathic / African / endemic KS:

• protracted course
• lymphadenopathic variant in African children is rapidly progressive and highly lethal

• Transplant-associated / immunosuppression-associated / iatrogenic KS:

• Develops a few months to several years after immunosuppression
• May resolve entirely upon withdrawal of immunosuppressive treatment
• AIDS associated KS:
• most aggressive form
• variable clinical course ranging from very indolent process requiring little if any therapy, to a rapidly progressive and fatal disease
• Natural couse is commonly relentlyess invasion of mucosal surfaces, lymph nodes, and visceral orans

References:

• Robbins 2005
• WHO book 2002
• Cancer Treatment Reviews 2006; 32: 445.