Kaposi sarcoma

Epidemiology

Most common malignancy in patients with untreated HIV

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Etiology

• Etiologic Agent: Human Herpesvirus 8 (HHV-8) / Kaposi Sarcoma-associated Herpesvirus (KSHV).
• Subtypes:
  • Epidemic (AIDS-related): Most common in US; occurs with CD4 < 200/mm³ (sexually transmitted route).
  • Classic (Sporadic): Elderly men of Mediterranean or Eastern European Jewish descent.
  • Endemic (African): Sub-Saharan African children and young men; aggressive lymphadenopathic course.
  • Iatrogenic (Post-transplant): Solid organ transplant recipients on chronic immunosuppressive therapy. c

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Pathophysiology

HHV-8 infects vascular and lymphatic endothelial cells, causing them to differentiate into a mixed phenotype thought to increase oncogenic potential. The HHV-8 genome contains several viral oncogenes that inhibit cell cycle regulation and apoptosis, thereby promoting endothelial cell growth and tumorigenesis

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Clinical features

• Cutaneous Lesions:
  • Violaceous (purplish-red to dark brown) macules, papules, plaques, or nodules.
  • Non-tender, non-pruritic, non-blanching. c
    • Slit-like vascular channels, blood leaks into the surrounding interstitial dermis
  • Common sites: Lower extremities, trunk, face, mucosal surfaces (hard palate, gingiva).
• Progression: may disseminate to the organs, particularly the gastrointestinal tract, respiratory tract, and lymph nodes.
  • Gastrointestinal tract involvement: abdominal pain and diarrhea; hemorrhage and bowel obstruction in severe cases
    • Often polypoid nodules
  • Pulmonary: Dyspnea, cough, hemoptysis, fever. CXR shows bilateral interstitial infiltrates and pleural effusions (poor prognosis).

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Diagnostics

• Biopsy and histology of cutaneous or visceral lesions (indicated in all patients)
  • Dermal proliferation of spindle-shaped endothelial cells with slit-like vascular spaces, red blood cell extravasation, and inflammation.

Feature	Bacillary Angiomatosis (BA)	Kaposi Sarcoma (KS)
Etiology	Bartonella spp. (Bacteria)	HHV-8 (DNA Virus)
Histology	Capillary proliferation, plump endothelial cells	Spindle cells, slit-like vascular spaces
Infiltrate	Neutrophilic	Lymphocytic & Plasmacytic
Special Stain	Warthin-Starry stain shows organisms	N/A
Treatment	Antibiotics (Doxycycline, Erythromycin)	ART (first-line), Chemotherapy/Radiation for severe disease

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Differential Diagnostics

• Bacillary Angiomatosis (Bartonella henselae/quintana):
  • Diff by history of cat/flea exposure; lesions are red/purple vascular papules that blanch on pressure.
  • Biopsy shows neutrophilic infiltrate with Warthin-Starry silver stain (+) for bacilli (vs KS: spindle cells, lymphocytic infiltrate, HHV-8 +).
• Melanoma:
  • Diff by ABCDE criteria (asymmetry, border irregularity, color variegation), lack of mucosal predilection, and S-100 / HMB-45 (+) on biopsy.
• Pyogenic Granuloma:
  • Diff by solitary, rapidly growing, friable, highly vascular papule prone to profuse bleeding with minor trauma; lobular capillary proliferation on biopsy.
• Stasis Dermatitis:
  • Diff by location restricted to bilateral lower extremities, association with chronic venous insufficiency/varicosities, and lack of oral/visceral lesions.
• Angiosarcoma:
  • Diff by rapid aggressive growth, history of radiation therapy or chronic lymphedema (Stewart-Treves syndrome), and negative HHV-8 IHC.

Treatment

1. Systemic Antiretroviral Therapy (ART):
   • First-line treatment for all AIDS-related cases. Immune reconstitution often causes regression of cutaneous lesions.
2. Systemic Chemotherapy:
   • Indicated for extensive cutaneous disease, visceral involvement (GI/pulmonary), or progression despite ART.
   • First-line agents: Liposomal doxorubicin or paclitaxel.
3. Local Therapy (Symptomatic or cosmetic lesions only):
   • Intralesional vinblastine, topical alitretinoin, radiation therapy, or cryotherapy.
4. Transplant-related KS:
   • Reduce immunosuppressive therapy (e.g., transition to mTOR inhibitors like sirolimus).

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