Metastatic Kaposi Sarcoma

Carlos E. Bueso-Ramos, MD, PhD

Key Facts

Etiology/Pathogenesis

HHV8 infection plays critical role in most cases
- Interacts with other factors

Clinical Issues

Multiple presentations of KS
- Sporadic (Mediterranean countries)
- Endemic (equatorial Africa)
- Iatrogenic (e.g., post transplantation)
- Epidemic (HIV-associated)
Common sites: Skin, lymph nodes, gastrointestinal tract
- Often multifocal

Microscopic Pathology

Wide histologic spectrum
- Lacework of thin-walled capillaries
- Ectatic vessels without pericytes
- Cleft-like vascular spaces, nonbranching
- Well-formed bundles and whorls of spindle cells
Extravasated erythrocytes
Intracytoplasmic eosinophilic hyaline globules
Plasma cells and small lymphocytes common
Hemosiderin-laden macrophages common

Ancillary Tests

Immunohistochemistry
- HHV8(+), CD31(+), CD34(+)
- FVIIIRAg(+) in well-differentiated tumors

Top Differential Diagnoses

Bacillary angiomatosis
Vascular transformation of lymph node sinuses
Angiosarcoma

Kaposi sarcoma (KS) associated with multicentric Castleman disease. In the center of the field, focal KS is present among hyaline-vascular follicles. KS is predominantly sinusoidal.

Lymph node involved by Kaposi sarcoma (KS). Note spindle cells and histiocytes with cytoplasmic, eosinophilic hyaline globules

. The globules stain a lighter color than erythrocytes.

TERMINOLOGY

Abbreviations

Kaposi sarcoma (KS)
Human herpes virus type 8 (HHV8)

Definitions

Kaposi sarcoma (KS): Distinctive type of vascular neoplasm that can involve any body site
- Almost always associated with HHV8 infection
- Occurs sporadically at low frequency but is much more frequent in setting of immunosuppression

ETIOLOGY/PATHOGENESIS

Infectious Agents

HHV-8, a Gammaherpesviridae, is uniformly expressed in KS
- a.k.a. Kaposi sarcoma-associated herpes virus (KSHV)
HHV8 establishes latent infection in most infected KS cells; lytic replication occurs in small subset of KS cells
Transmission via sexual and nonsexual routes
- Saliva contains shed epithelial cells infected by HHV-8

Pathogenesis

KS may be multicentric neoplasm at time of conception
HHV8 interacts with other factors in pathogenesis
- e.g., HIV TAT protein has mitogenic and modulating effects on KS cells
Angiogenic factors and cytokines are likely to be involved
Viral proteins expressed during both latent and lytic phases of viral life cycle contribute to KS pathogenesis

Cell of Origin

KS involves progenitor cell from either blood vessel or lymphatic endothelia
- CD34(+) suggests progenitor endothelial cells

CLINICAL ISSUES

Epidemiology

Incidence
- Varies greatly depending on presentation
Age
- Varies depending on presentation
Gender
- Male predominance in all types of KS
Ethnicity
- Sporadic cases more common around Mediterranean sea

Site

Skin, mucosal surfaces, lymph nodes, and all internal organs
- Skin most common site
- Oral mucosa and gastrointestinal tract are frequent sites
- Lymph node involvement usually associated with skin disease
  - Rare patients reported with only lymph node disease

Presentation

Presentation of KS can be divided into 4 clinical subsets
- Sporadic (classic)
  - Involves distal extremities of elderly patients
  - Common in men of Mediterranean and Jewish Ashkenazi origin
  - Clinically indolent
  - Subset of cases can be clinically aggressive; associated with coexistent non-Hodgkin lymphoma
  - In USA, 0.2 per 100,000 tumors
- African (endemic)
  - Sub-Saharan central Africa
  - 9% of malignant neoplasms in Uganda
  - Children often have generalized lymphadenopathy and aggressive clinical course
  - Subset of aggressive cases likely related to HIV infection
  - Middle-aged adults have KS on extremities; more indolent
- Iatrogenic immunosuppression
  - KS arises more frequently after organ transplantation or steroid therapy
  - 128x increased incidence after kidney transplantation
  - Usually clinically indolent; can be aggressive
- AIDS-associated (epidemic)
  - 451x increased incidence in setting of AIDS infection
  - More common in homosexuals; less frequent in IV drug users and hemophiliacs