Kaposi's sarcoma

Background

• Different classifications of Kaposi’s sarcoma based on patient population
• Associated with HHV-8
• Most common cancer in HIV/AIDS patients
• Kaposi’s Sarcoma can be unmasked or induced by initiation of steroids or HAART
• Cutaneous lower extremity lesions most common presentation
• Kaposi’s sarcoma is an AIDS-defining illness
• Treat with HAART and/or chemo

History

• First described by Hungarian Dr. Moritz Kaposi in 1872; rare until 1980s with emergence of HIV/AIDS (1981 cluster of Kaposi’s sarcoma in young men in NYC and California; 1982 listed as AIDS-defining illness by CDC)
• Human Herpesvirus 8 (HHV8)
  • Large, double-stranded DNA virus
  • Necessary but NOT sufficient to cause disease
  • Also associated with body-cavity based lymphomas, multicentric Castleman’s disease (angiofollicular lymph node hyperplasia)

Classifications

• Classic Kaposi’s (CK)
  • Indolent, chronic form, rarely disseminated
  • Skin most commonly effected, lower extremities
  • ~3:1 Male:Female, Age > 60 years old with Mediterranean, Eastern European or Middle Eastern origin

• Endemic Kaposi’s sarcoma (Africa)
  • Male adults or children of both sexes
  • Equatorial/Sub-Saharan Africa
  • Aggressive form with lymph node involvement (lymphedema)
  • 27%, 35%, and 24% of total cancer burden in Uganda, Zimbabwe and Mozambique, respectively

• AIDS-KS
  • Developed countries: Men who have sex with men
  • Developing countries: Heterosexual men and women (Africa)
  • Aggressive disease – most commonly in lungs, gastrointestinal tract, mouth, and genitalia
  • Most common cancer in HIV/AIDS patients

• Iatrogenic due to immunosuppression – Most commonly organ transplant-associated
  • Increased risk after solid organ transplantation
  • Transplant itself may transmit HHV-8 infection
  • Male > Female (3.3:1), average age 43 yo
  • Cutaneous lesion presentation most common
  • More common in liver than kidney transplant patients

• Immune Reconstitution Inflammatory Syndrome (IRIS) Phenomenon
  • Initiation of retroviral therapy can cause the development of KS
  • True unmasked KS-IRIS begins within 6 months of initiating therapy, and the rates remain unclear

Clinical Features

Kaposi's sarcoma skin lesion

• Cutaneous
• Heterogeneous appearance
  • Color – dark blue, reddish, purple, violaceous, dark brown/black
  • Location – extremities, most commonly the feet
  • Lesions: macules, plaques, nodules
  • Associated lymphedema
• Pulmonary
  • Gradual Onset (2-4 weeks)
  • Cough
  • Dyspnea
  • Fever
  • Hemoptysis
  • Asymptomatic
• Gastrointestinal
  • Bleeding
  • Obstruction

Differential Diagnosis

• Cutaneous Lesions:
  • Bacillary angiomatosis
  • Purpura
  • Hematomas
  • Angiomas
  • Dermatofibromas
  • Nevi
• Pulmonary Lesions in HIV/AIDs:
  • Bacterial Pneumonia
  • PCP
  • TB
  • Fungal Infections
• Anorectal Lesions in HIV/AIDs:
  • Common: Anal fissure, Abscess and/or fistula, Hemorrhoid, Pilonidal disease
  • STDs: Gonorrhea, Chlamydial infection, Herpes, Chancroid, Syphilis, Condyloma acuminatum
  • Infectious: TB, CMV infection, actinomycosis, cryptococcosis
  • Neoplastic: Lymphoma, Kaposi’s sarcoma, squamous cell carcinoma

HIV associated conditions

• HIV neurologic complications
  • Toxoplasmosis
  • Cryptococcosis
  • AIDS Dementia
  • Seizures in patients with HIV-AIDS
• HIV pulmonary complications
  • Pneumocystis jirovecii pneumonia (PCP)
  • Tuberculosis (TB)
• Ophthalmologic complications
  • CMV Retinitis
  • Herpes Zoster Ophthalmicus
• Other
  • AIDS fever of unknown origin
  • Immune reconstitution inflammatory syndrome
  • HIV diarrhea
  • Kaposi's sarcoma
  • Pruritic papular eruption of HIV
• HAART medication side effects
  • Lactic acidosis
  • Neuropyschiatric effects
  • Hepatic toxicity
  • Renal toxicity
  • Steven-Johnson's
  • Cytopenias
  • GI symptoms
  • Endocrine abnormalities

Evaluation

• Clinical impression
• Biopsy is gold standard for definitive diagnosis
• WHO Clinical Staging of HIV/AIDS
  • Stage 4: Presumptive Diagnosis of HIV/AIDS can be made from clinical signs of Kaposi’s
• GI manifestations
  • Unlikely visible on XR; can be seen on flex sig or colonoscopy
• Pulmonary Manifestations
  • Heterogeneous on XR - nodular, interstitial and/or alveolar infiltrates, pleural effusion, hilar and/or mediastinal adenopathy, or an isolated nodule

Staging

• Classic Kaposi's Sarcoma
  • No staging system. It is excluded in TNM Staging of soft tissue sarcomas by American Joint Committee on Cancer (AJCC)

• AIDS-KS Staging

	Good Risk (all of the following)	Poor Risk (any of the following)
Tumor, T	T0: Skin and/or lymph nodes and/or minimal oral disease	TI: Tumor-associated edema or ulceration, extensive oral KS, GI KS, KS in other non-nodal viscera
Immune System, I	CD4 > 200	CD4 < 200
Systemic Illness, S	S0: No history of OI or thrust, No "B" Symptoms (fever, night sweats, weight loss, diarrhea > 2 weeks) Karnofsky performance > 70	SI: History of OI and/or thrush, "B" symptoms, Karnofsky performance <70, Other HIV-related illness

Management

• Highly Active Anti-retroviral therapy (HAART):
  • Can achieve remission in 60-90% remission in stage T0 disease
  • Can combine with chemotherapy
• Chemotherapy:
  • First-line: Pegylated liposomal doxorubicin (PLD) 20mg/m2 every three weeks (unless cardiac contraindication)
  • Second-line: Vinblastine, Bleomycin, Paclitaxel, Etoposide, Gemcitabine
• Cutaneous Specific Treatment:
  • Alitretinoin (9-cis-retinoic acid) topical gel 0.1% FDA-approved for cutaneous AIDS-associated KS
  • Intralesion Injection: Vinblastine or Bleomycin or INF-alpha
  • Vinblastine 0.2 – 0.3mg/mL solution with a volume of 1 mL per 0.5 cm2 of lesion
  • IFNa - FDA approved for AIDS-associated KS
• Radiation Therapy
  • 30 Gy in 15 daily 2 Gy fractions
• Other Drug Trials:
  • Bevacizumab - an anti-VEGF-A
  • Imatinib - monoclonal antibody tyrosine kinase receptor
• Steroids
  • Associated with generation and exacerbation of KS
  • Important implications because of the high use of steroids in this patient population (HIV/AIDS, transplant)
  • Once steroids are removed, KS can regress

See Also

• HIV - AIDS (Main)

External Links

• http://www.ncbi.nlm.nih.gov/pubmed/25256409
• http://www.ncbi.nlm.nih.gov/pubmed/20413015

References

• Farge, D. "Kaposi's Sarcoma in Organ Transplant Recipients. The Collaborative Transplantation Research Group of Ile De France." The European Journal of Medicine 2.6 (1993): 339-43.
• Fenig, Eyal, Baruch Brenner, Erica Rakowsky, Moshe Lapidoth, Alan Katz, and Aaron Sulkes. "Classic Kaposi Sarcoma." American Journal of Clinical Oncology 21.5 (1998): 498-500.
• Krown, SE, C. Metroka, and JC Wemz. "Kaposi's Sarcoma in the Acquired Immune Deficiency Syndrome: A Proposal for Uniform Evaluation, Response and Staging Criteria." Journal of Clinical Oncology 7.9 (1989): 1201-207.
• Krown, SE, MA Testa, and J. Huang. "AIDS-related Kaposi's Sarcoma: Prospective Validation of the AIDS Clinical Trials Group Staging Classification. AIDS Clinical Trials Group Oncology Committee." Journal of Clinical Oncology 15.9 (1997): 3085-092.
• Moosa, M.r. "Kaposi's Sarcoma in Kidney Transplant Recipients: A 23-year Experience." QJM 98.3 (2005): 205-14.
• Osawa, R., N. Kato, T. Yanagi, and N. Yamane. "Clearance of Recurrent, Classical Kaposi’s Sarcoma Using Multiple Paclitaxel Treatments." Acta Derm Venereol Acta Dermato-Venereologica 87.5 (2007): 435-36. Web.
• Robey, Rebecca C., and Mark Bower. "Facing up to the Ongoing Challenge of Kaposiʼs Sarcoma." Current Opinion in Infectious Diseases 28.31 (2015).
• Rosen, Peter, and John A. Marx. Rosen's Emergency Medicine: Concepts and Clinical Practice. 8th ed. Philadelphia: Elsevier Saunders, 2014.
• Safai, B., and R. A. Good. "Kaposi's Sarcoma: A Review and Recent Developments." CA: A Cancer Journal for Clinicians 31.1 (1981): 2-12.

Authors

Natalie Sciano, Ross Donaldson, Daniel Ostermayer, Neil Young