Definition/General
Introduction:
Kaposi sarcoma (KS) is a multifocal vascular neoplasm caused by Human Herpesvirus-8 (HHV-8/KSHV)
It demonstrates variable clinical behavior from indolent to aggressive
It shows predilection for skin and mucosa
It can involve visceral organs
It represents AIDS-defining malignancy in HIV patients.
Origin:
Arises from lymphatic endothelial cells
Shows endothelial and smooth muscle differentiation
Involves dermis and subcutis
May extend to deeper structures
Associated with HHV-8 infection
Shows angiogenic and proliferative properties.
Classification:
WHO recognizes four clinical variants
Classical (Mediterranean) KS (elderly men)
Endemic (African) KS (young adults/children)
Epidemic (AIDS-associated) KS (most common)
Iatrogenic KS (immunosuppression-related)
Patch, plaque, nodular stages histologically.
Epidemiology:
Geographic variation with Mediterranean and African predominance
Male predominance (10:1 in classical type)
Peak age 5th-6th decades (classical)
Young adults (AIDS-associated)
Indian population shows low incidence except in HIV patients.
Clinical Features
Presentation:
Red to purple plaques or nodules
Multifocal lesions
Lower extremities commonly affected (classical)
Anywhere on body (AIDS-associated)
Non-blanching lesions
Lymphedema may develop.
Symptoms:
Usually asymptomatic
Cosmetic concerns
Pain or discomfort (uncommon)
Lymphedema (advanced cases)
Bleeding from oral lesions
Dysphagia (GI involvement)
Respiratory symptoms (pulmonary KS).
Risk Factors:
HIV infection (most important)
Immunosuppression
Male gender
Mediterranean or African origin
Age >50 years (classical)
Organ transplantation
HHV-8 seropositivity
MSM population.
Screening:
HIV testing in appropriate patients
HHV-8 serology
Complete skin examination
Oral cavity examination
Lymph node assessment
Systemic evaluation for visceral disease.
Master Kaposi Sarcoma Pathology with RxDx
Access 100+ pathology videos and expert guidance with the RxDx app
Gross Description
Appearance:
Red to purple macules, plaques, or nodules
Non-blanching lesions
Variable size (few mm to several cm)
Multifocal distribution
May show ulceration
Cut surface appears hemorrhagic.
Characteristics:
Well-demarcated to ill-defined lesions
Soft to firm consistency
Purple-red color
May show central depression
Hemorrhagic appearance
Cut surface shows spongy texture.
Size Location:
Size varies from few mm to 10 cm
Lower extremities (classical KS)
Face and trunk (AIDS-associated)
Oral cavity (common in AIDS)
Lymph nodes
GI tract (25% of AIDS-KS).
Multifocality:
Multifocal disease characteristic
Bilateral involvement common
Regional clustering
Lymph node involvement frequent
Visceral involvement (AIDS-associated)
Mucocutaneous distribution.
Microscopic Description
Histological Features:
Three histological stages: patch, plaque, nodular
Spindle cell proliferation with slit-like vascular spaces
Extravasated red blood cells
Hemosiderin deposition
Plasma cell infiltrate
Hyaline globules (PAS-positive).
Cellular Characteristics:
Spindle-shaped cells with elongated nuclei
Mild nuclear pleomorphism
Amphophilic cytoplasm
Endothelial-like cells
Mitotic activity variable
Multinucleated cells may be present.
Architectural Patterns:
Patch stage: Subtle vascular proliferation
Plaque stage: Prominent spindle cell proliferation
Nodular stage: Well-formed nodules
Slit-like vascular spaces characteristic
Fascicular growth pattern
Irregular vascular channels.
Grading Criteria:
Low-grade malignancy by definition
Patch stage: Minimal atypia
Plaque stage: Moderate cellularity
Nodular stage: High cellularity
Mitotic rate variable
Cellular atypia mild to moderate.
Immunohistochemistry
Positive Markers:
HHV-8 LANA (95-100%, nuclear)
CD31 (85-90%)
CD34 (80-85%)
D2-40 (lymphatic marker, 70-80%)
Factor VIII (60-70%)
Smooth muscle actin (subset)
VEGFR-2 (80-85%).
Negative Markers:
Cytokeratins (usually negative)
EMA (negative)
S-100 (negative)
Desmin (negative)
CD68 (negative)
Melanoma markers (negative).
Diagnostic Utility:
HHV-8 LANA pathognomonic (nuclear staining)
CD31/CD34 confirm vascular nature
D2-40 suggests lymphatic origin
Essential for early patch stage diagnosis
Useful in differential diagnosis.
Molecular Subtypes:
HHV-8 positive (all cases by definition)
VEGF overexpression
IL-6 production
bFGF activation
Angiogenic pathway activation
Viral oncogenes (vGPCR, vCyclin).
Molecular/Genetic
Genetic Mutations:
HHV-8 infection (obligate)
Viral integration
p53 alterations (rare)
Rb pathway disruption
VEGF overexpression
IL-6 dysregulation
mTOR pathway activation.
Molecular Markers:
HHV-8 LANA (latency-associated nuclear antigen)
vGPCR (viral G-protein coupled receptor)
vCyclin (viral cyclin)
VEGF overexpression
IL-6 production
bFGF activation.
Prognostic Significance:
HHV-8 viral load correlates with disease extent
CD4 count in HIV patients (prognostic)
Clinical subtype determines prognosis
Visceral involvement indicates poor prognosis
Response to HAART in AIDS-KS.
Therapeutic Targets:
Antiretroviral therapy (AIDS-KS)
Interferon-alpha
Liposomal doxorubicin
Paclitaxel
Anti-angiogenic agents (bevacizumab)
mTOR inhibitors (sirolimus)
Pomalidomide.
Differential Diagnosis
Similar Entities:
Angiosarcoma (high-grade vascular malignancy)
Bacillary angiomatosis (Bartonella infection)
Pyogenic granuloma (benign vascular lesion)
Hemangioendothelioma
Fibrosarcoma (spindle cell)
Dermatofibroma.
Distinguishing Features:
Kaposi sarcoma: HHV-8 LANA positive
KS: Slit-like vessels
Angiosarcoma: High-grade cytology
Bacillary angiomatosis: Neutrophilic infiltrate
Pyogenic granuloma: Lobular capillaries
Fibrosarcoma: No vascular differentiation.
Diagnostic Challenges:
Early patch stage vs reactive changes
Spindle cell vs other sarcomas
Well-differentiated vs benign vascular lesions
HHV-8 staining essential for diagnosis
Clinical correlation important.
Rare Variants:
Anaplastic KS (high-grade)
Keloidal KS (fibrotic)
Ecchymotic KS (bruise-like)
Hyperkeratotic KS
Bullous KS
Lymphangioma-like KS.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Skin biopsy/excision from [site], measuring [X x Y x Z] cm
Diagnosis
Kaposi Sarcoma
Histological Stage
Stage: [patch/plaque/nodular/mixed]
Microscopic Features
Shows spindle cell proliferation with slit-like vascular spaces and [specific features]
Extent of Involvement
Involves: [dermis/subcutis/deeper structures]
Margins
Margins: [involved/uninvolved/not applicable] (distance if applicable)
Immunohistochemistry
HHV-8 LANA: [positive/negative] (nuclear pattern); CD31: [positive/negative]; CD34: [positive/negative]
Clinical Correlation
Clinical correlation recommended for staging and management
Final Diagnosis
Kaposi Sarcoma, [stage], HHV-8 positive