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
  • 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

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

External Links

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.
  • Gutteridge, David L MD, MPH, Egan, Daniel J. MD. The HIV-Infected Adult Patient in The Emergency Department: The Changing Landscape of the Disease. Emergency Medicine Practice: An Evidence-Based Approach to Emergency Medicine. Vol 18, Num 2. Feb 2016.