AG, 64-year-old gentleman of Greek descent, presents with a 6-month history of rash that started on his upper extremities and now includes his lower extremities.
• Rash apparent on arms and legs; it appears raised and red in color, and is more pronounced on his legs, which contains red and blue papules with some lesions appearing to have been recently bleeding
appearing to have been recently bleeding
• Decrease in appetite over the last several weeks
• Occasional diarrhea
• Weight loss of 10 lbs
• Afebrile, stable vital signs
Relevant Medical History
• Up-to-date with all of his vaccinations and cancer screenings (colonoscopy, prostate-specific antigen)
• Results show borderline pancytopenia; however, blood cell counts are within normal limits for his yearly trends
• Negative viral panel (HIV, Parvovirus B19, CMV, HSV)
Relevant Social History
• Married for 40 years and denies any extra-marital affairs
• No recent travel, sick contacts, or illicit drug use
• The decision is made to biopsy the lesions on his legs
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Answer C: These would be the expected pathology findings for Kaposi Sarcoma (“classic” subtype).
Kaposi Sarcoma (KS) is a malignancy that is most often associated with HIV infection; however this represents only one of four different subtypes. The patient described in this case was HIV-negative along with a history that did not coincide with HIV exposure. Therefore, it is important to keep KS on the differential diagnosis for certain skin rashes, even if the patient has tested negative for HIV.
The four types of KS include 1) the “classic” type; 2) HIV-associated (and AIDS defining); 3) endemic (African-born patients); and 4) iatrogenic, which is secondary to administration of immunosuppressive therapy, (eg, transplant patients). Classic KS is male dominant, and typically occurs in patients from Middle Eastern, Mediterranean, or Central European descent.1 (Slide 2)
One common link between all four subtypes is the association with human herpes virus-8 (HHV-8). In order to develop KS, the patient must have been exposed to HHV-8. However, an infection with HHV-8 does not necessarily lead to KS in all infected patients. In patients living in the Mediterranean, less than 1% of all HHV-8 infected patients will develop classic KS each year.2 Consequently, there are additional risk factors that place patients with HHV-8 exposure at increased risk for developing classic KS.
One such risk factor is immunosuppression, which also appears to be a common risk factor amongst all KS types. In classic KS, there is mixed data as to what exactly defines immunosuppression, although there is some data suggesting increasing age and ingestion of oral steroids is associated with classic KS.1,2 Additional risk factors include anemia and concurrent cancers (eg, hematologic and lymphomas). Interestingly, there is some data showing that the risk of developing KS in cigarette smokers decreases by 20% for every 10-pack year history.3
Patients presenting with classic KS will typically have skin lesions that can be red, blue, or purple in color and are maculopapular and nodular with the potential to bleed.4 The lower extremities are most commonly involved, although the upper extremities can be affected as well.1 (Slide 3) The rash usually develops over a longer period of time (months to years) and not acutely. Although the skin represents the primary manifestations of classic KS, it can also involve the gastrointestinal tract (Slide 4) and oral mucosa.4 This occurs less than 10% of the time, and is less frequent than with AIDS-associated KS.4
The differential diagnoses (aside from the other KS variants) for the type of skin lesions seen in classic KS include carcinomas of the skin (squamous cell, basal cell), bacillary angiomatosis, and peripheral vascular disease. The diagnosis can be made largely by history and physical examination with confirmation from a skin biopsy. The pathology from the skin biopsy can show extensive inflammatory cells including lymphocytes and plasma cells along with extensive spindle cell proliferation and angiogenesis with a positive HHV-8 polymerase chain reaction.
There are several treatment modalities for classic KS including surgery, radiation therapy, chemotherapy (systemic and local), and topical medications.5 If the skin lesions are in a very limited distribution, surgery is an option although the recurrence rate is high.6 Classic KS is sensitive to radiation therapy; however, the best dosing for the radiation remains to be determined.
In addition, new lesions often develop in fields that were not irradiated, so determining the best radiation field is often very difficult. Local chemotherapy regimens include vinblastine, vincristine, and bleomycin, although the injections into KS lesions are relatively painful and may leave behind scar tissue.5 Topical treatments include imiquimod and cis-retinoic acid, although there is not substantial data studying these treatments. Systemic chemotherapy is usually reserved for patients with diffuse lesions or those that have failed other treatment regimens such as radiation or local therapy. There does not appear to be an optimal regimen; however, doxorubicin, the taxanes, and etoposide have been used with some reported success.5
Classic KS is a condition that does share some similarities with the other subtypes of KS, but there are important differences to keep in mind when evaluating patients that do not fit the typical profile of AIDS-related KS. Once diagnosed, classic KS does have several treatment options, however, additional clinical data is needed in order to develop a more robust treatment algorithm.
1. Goedert JJ, Vitale F, Lauria C, et al. Risk factors for classical Kaposi’s sarcoma. J Natl Cancer Inst. 2002;94(22):1712.
2. Vitale F, Briffa DV, Whitby D, et al. Kaposi’s sarcoma herpes virus and Kaposi’s sarcoma in the elderly populations of 3 Mediterranean islands. Int J Cancer. 2001;91(4):588.
3. Anderson LA, Lauria C, Romano N, et al. Risk factors for classical Kaposi sarcoma in a population-based case-control study in Sicily. Cancer Epidemiol Biomarkers Prev. 2008;17(12):3435.
4. Balachandra B, Tunitsky E, Dawood S, et al. Classic Kaposi’s sarcoma presenting first with gastrointestinal tract involvement in a HIV-negative Inuit male–a case report and review of the literature. Pathol Res Pract. 2006;202(8):623.
5. Brambilla L, Bellinvia M, Tourlaki A, et al. Intralesional vincristine as first-line therapy for nodular lesions in classic Kaposi sarcoma: a prospective study in 151 patients. Br J Dermatol. 2010;162(4):854.
6. Brenner B, Rakowsky E, Katz A, et al. Tailoring treatment for classical Kaposi’s sarcoma: comprehensive clinical guidelines. Int J Oncol. 1999;14(6):1097.