Kaposi Sarcoma (KS)(Clinical Condition)

OVERVIEW: What every practitioner needs to know

Are you sure your patient has Kaposi sarcoma? What should you expect to find?

Patients with human immunodeficiency virus (HIV)-related Kaposi sarcoma (KS) can have a wide variety of clinical presentations, ranging from localized to diffuse cutaneous disease, mucocutaneous lesions, lymphadenopathy, and/or visceral involvement. The patient may have one or more of the following findings on physical examination:

• Skin: localized or diffuse involvement with hyperpigmented to violaceous macules, papules (Figure 1, Figure 2), patches (Figure 3, Figure 4, Figure 5), and/or plaques. In advanced disease, the patients may also develop friable tumors on the skin (Figure 6, Figure 7).

• Oral mucosa: violaceous patches, papules, or plaques on the palate, buccal mucosa, and/or gingiva; advanced lesions may be friable or ulcerated, and tumors can also develop on mucosal surfaces.

  ---

  Continue Reading

• Other mucosal involvement: lesions can develop on any mucosal site, including the oral, ocular, nasal, and genital mucosa.

• Lymph node involvement: patients may develop localized or diffuse lymphadenopathy, with the inguinal and cervical lymph nodes (Figure 8) being the most commonly involved. Associated lymphedema is often seen in patients with lymph node disease (Figure 9, Figure 10).

• Internal involvement: in advanced disease, patients may develop pulmonary and/or gastrointestinal (GI) involvement, and associated symptoms may include nausea, vomiting, GI bleeding, perforation, ileus, cough, bronchospasm, and/or dyspnea.

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

How did the patient develop Kaposi sarcoma? What was the primary source from which the infection spread?

KS-associated herpesvirus, or human herpesvirus 8 (HHV-8) is the primary underlying factor, in addition to immunosuppression secondary to HIV infection, for the development of HIV-associated KS. The acquisition of HHV-8 varies from sexual transmission (predominantly in the developed world) to early childhood or mother-to-child transmission (more commonly in the developing world). The prevalence rate of HHV-8 varies throughout the world, with infection being very common in sub-Saharan Africa (prevalence rates >50%), to moderately common in Mediterranean countries (prevalence rates 20–30%), to uncommon in Europe, Asia, and the United States (prevalence rates <10%). In the United States, prevalence rates are highest among men who have sex with men (MSM).

In the United States and Europe, KS is most commonly seen in MSM. In this population, a low cluster of differentiation (CD)4 count has been linked to the developed of KS, and acquisition of the HHV-8 virus increases with the number of lifetime sexual partners. In Africa, because HHV-8 is acquired more commonly in early childhood, the development of HIV-related KS may occur in children and young adults as their CD4 count declines. Patients in Africa are also at risk for endemic KS, which is related to HHV-8 infection but is independent of HIV status.

Which individuals are of greater risk of developing Kaposi sarcoma?

Patients with clinical acquired immune deficiency syndrome (AIDS) are at greater risk of developing HIV-related KS. Once patients develop disease, HIV-related KS can have a variable course, but patients may worsen with a decline of the CD4 count. In addition, patients may develop a flare of KS due to immune reconstitution syndrome following initiation of highly active antiretroviral therapy (HAART).

In a study by Shiels and colleagues, the authors report that between 1980 and 2007 in the United States, an estimated 81.6% (95% confidence interval [CI], 81.2–81.9%) of the 83,252 KS cases occurring among persons with HIV. The proportion of KS in persons with AIDS peaked in the early 1990s (1990–1995: KS, 90.5% [95% CI, 90.2–90.8%]).

Beware: there are other diseases that can mimic Kaposi sarcoma:

There are several entities that can mimic cutaneous KS clinically and may require a biopsy for differentiation. These include:

• Lichenoid tissue reactions: lichen planus and lichenoid-type drug eruptions can present with hyperpigmented to violaceous patches, papules, or plaques on the skin. Lichenoid drug eruptions can occur as a result of HAART or antibiotics, which are commonly taken by patients at risk for KS.

• Acroangiodermatitis: this presents as violaceous patches and plaques, typically on the lower extremities of patients with venous hypertension.

• Angiosarcoma: this presents most commonly on the head and neck region of elderly persons as an erythematous or blue-black bruise-like patch or plaque, which may ulcerate or bleed. Patients with chronic lymphedema or a history of radiation therapy are also at risk.

• Other entities in differential diagnosis include: pyogenic granuloma, bacillary angiomatosis, hemangiomas, ecchymosis, or pseudolymphoma/lymphoma.

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

Although clinical examination alone by an experienced clinician may be sufficient for diagnosis, there are numerous entities that can mimic KS in the skin and a biopsy is needed for confirmation. Given the implications of the diagnosis, biopsy is recommended.

Histologic analysis of clinical lesions (i.e., skin, lymph nodes, or visceral organs) can allow for confirmation of the diagnosis. Histology shows a proliferation of slit-like vascular spaces lined by atypical endothelial cells and surrounded by a spindle cell proliferation. The slit-like vascular spaces may dissect among collagen bundles, and a plasmacytic infiltrate may be present. Immunohistochemical staining with antibodies against a latent nuclear antigen (LNA-1) can highlight the presence of HHV-8 within lesional nuclei.

Results that confirm the diagnosis

Histologic analysis of clinical lesions (i.e., skin, lymph nodes, or visceral organs) can allow for confirmation of the diagnosis. Histology shows a proliferation of slit-like vascular spaces lined by atypical endothelial cells and surrounded by a spindle cell proliferation. The slit-like vascular spaces may dissect among collagen bundles, and a plasmacytic infiltrate may be present. Immunohistochemical staining with antibodies against a latent nuclear antigen (LNA-1) can highlight the presence of HHV-8 within lesional nuclei.

What imaging studies will be helpful in making or excluding the diagnosis of Kaposi sarcoma?

Imaging studies are not particularly useful in making or confirming the diagnosis of KS; however, imaging, such as a chest X-ray or computed tomography (CT) scan, may be helpful in staging and estimating the extent of disease once the diagnosis is made on histology.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has Kaposi sarcoma, what therapies should you initiate immediately?

Dermatology may be the most useful service for diagnosing cutaneous KS, since they can assist in clinico-pathologic correlation of skin disease using physical examination and biopsies. If the patient only has oral manifestations, oral medicine may be helpful in performing a confirmatory biopsy. For potential lymph node or visceral disease, the general surgery or gastrointestinal service may assist in making the diagnosis by performing biopsies on the involved tissue.

• Curative therapy is not available, and the goal of treatment is to control symptoms and limit/slow progression.

• Limited, small, or slow growing lesions may only be clinically monitored, unless they are in a cosmetically sensitive area, painful, bleeding, or otherwise symptomatic.

• If patients develop HIV-associated KS and they are not on HAART, HAART should be initiated.

• Limited disease can be treated with conservative therapy, such as cryotherapy, radiation therapy, topical immunotherapy with imiquimod, topical retinoids, or intralesional chemotherapy.

• Systemic chemotherapy:

  Diffuse or disseminated disease is best treated with systemic chemotherapy.

  Side effects for pegylated liposomal doxorubicin most commonly include hematologic toxicity, including leukopenia, lymphopenia, and neutropenia. Significant neutropenia, alopecia, and sensory neuropathy are more commonly seen with paclitaxel than pegylated liposomal doxorubicin.

  Pegylated liposomal doxorubicin and paclitaxel are both active agents for patients with advanced, systemic KS in the HAART era, with response rates ranging from 50 to 60%.

Anti-infective agents (Table I)