Diagnostic Dilemma: Kaposi’s Sarcoma

Case Study A 94-year-old Caucasian man presented with an ulcer on the medial side of his left foot. His past medical history was significant for an 18-year history of Kaposi’s sarcoma on his hands and feet. Seven months prior to presentation, the patient developed an ulcer on the plantar surface of his left foot with cellulitis. The infection cleared with oral antibiotics and the ulcer healed approximately two months prior to his presentation, but recurred approximately four weeks prior to the visit. The ulcer was painful. He denied anesthesia, paresthesia, claudication, or previous deep vein thrombosis. His past medical history included arthritis, hypertension, hernia, prostate cancer, depression, and cutaneous basal and squamous cell carcinomas. He had been treating the wound with alternating mupirocin and silver sulfadiazine creams and a dry gauze bandage. His other medications include doxorubicin for his Kaposi’s sarcoma, fosinopril, digoxin, and multivitamins. He was previously treated with paclitaxel. His son noticed that the ulcer increased in size while on paclitaxel, but after starting doxorubicin for his Kaposi, the ulceration had improved. Physical examination revealed a pleasant elderly gentleman with extensive photodamage and multiple seborrheic keratoses and actinic keratoses on the upper extremities, chest, and back. Peripheral pulses of the lower extremities were normal. The ankle brachial pressure index was 1.0. There were numerous superficial, clean appearing ulcers over the medial aspect of his left foot, surrounded by hyperkeratotic tissue. There was background violaceous discoloration of the foot (Figure 1). Laboratory Investigations Bacterial cultures grew out moderate Pseudomonas aeruginosa and Enterococcus species. Fungal cultures were negative. Diagnosis and Discussion Our patient has classic type Kaposi’s sarcoma. The four types of Kaposi’s sarcoma are classic, African-endemic, iatrogenic/immunosuppressive/drug associated, and AIDS-associated/epidemic and are compared in Table 1. The four types are likely different manifestations of the same pathological process. The etiology remains to be elucidated, but there is strong evidence that Kaposi’s sarcoma is the result of infection with Kaposi’s sarcoma-associated herpes virus (KSHV) or human herpes virus 8 since DNA fragments can be identified in tissue samples of greater than 95 percent of all variants of Kaposi's sarcoma lesions.1,9 We will focus the discussion in this article to the classic type Kaposi’s sarcoma. Classic Kaposi’s sarcoma primarily affects elderly men of Eastern European, Jewish, or Mediterranean descent. Most lesions of classic Kaposi’s begin after the sixth decade.5 Median age at diagnosis is 64 years (range is 26 years to 90 years old).2 Men are affected up to 15 times more commonly than women.2 Homosexual habits increase the risk for classic Kaposi’s sarcoma, even if patients are not immunosuppressed.2 The typical histology of Kaposi’s sarcoma include spindle-shaped cells with vascular channels lined by abnormal endothelial cells.13 Extravasated erythrocytes, hemosiderin, and fibrosis can often be seen.2 Early lesions of classic Kaposi’s sarcoma appear as firm, violaceous, bluish black, or reddish-brown plaques on the feet that may become nodular and coalesce. Macular lesions are often palpable and hard in consistency. They often begin as oval shaped and are arranged parallel to skin tension lines. Lesions may appear in sites of trauma, such as the acral regions.13 The lesions often coalesce, and tumor formation, erosion, crusting, hyperkeratosis, and ulceration can occur. Lymphedema may occur secondary to deeper involvement of lymph nodes and lymphatics.13 It may progress to the genitals and, in some cases, the face.13 Areas of tense edema may have a peau d’ orange appearance. Persistent lymphatic disease may result in fibrosis, contracture, and loss of use of a limb.13 Periods of remission may occur, in which case the lesion involutes, leaving an atrophic hypopigmented scar. Patients who experience significant edema, ulcerated lesions on the lower extremities, or lesions that are nodular may complain of moderate to severe pain. Lesions classically occur on the lower extremities or hands and slowly spread centripetally.13 Rarely, the tip of the nose, ears, scalp, periorbital areas, and genital areas may become involved. The trunk is rarely affected.13 Visceral and/or mucosal involvement occurs in 10 percent of patients.2 Mucosal lesions often occur on the hard palate and initially appear as a violaceous stain. Soft palate, pharynx, uvula, gingival, and tongue may also be involved.13 The small intestine, liver, and spleen may become involved, but are usually asymptomatic, particularly in classic Kaposi’s sarcoma.13 Lungs, heart, liver, conjunctiva, adrenal glands, and lymph nodes of the abdomen may also be involved. Characteristic and diagnostic skeletal changes include cysts and cortical erosion.12 Urethral or anal canal involvement may result in obstruction. If there is pulmonary involvement, patients may complain of bronchospasm, progressive coughing, or shortness of breath.13 The disease course tends to be chronic, and patients usually survive for 10 to 15 years after diagnosis. Over 35 percent of patients with the disease develop secondary malignancies, such as leukemia, myeloma, and lymphomas.7,8,13 Patient Management Classic Kaposi’s sarcoma is often multifocal, but may occur in localized areas. For patients who are immunocompetent and demonstrate slow progression of disease, observation may be acceptable. Occasionally, the disease will regress spontaneously.9 Goals of therapy are to control symptoms.13 Classic type Kaposi’s sarcoma responds well to radiation treatment.13 One benefit of this method of treatment is its limited depth of penetration. Local therapy reduces bleeding, debulks, and reduces lymphatic obstruction.13 Localized and recurrent lesions may be managed by excisional biopsy, laser, cryosurgery, and electrosurgery.9 For patients with widespread visceral involvement, a combination of surgery, chemotherapy, and/or radiation may be necessary. Systemic treatment is recommended if the patient is developing greater than 10 new lesions per month, or if there is symptomatic lung disease, lymphedema, or visceral involvement.12 Chemotherapeutic agents found to be successful in treating Kaposi’s sarcoma include vinblastine, bleomycin, doxorubicin, and dacarbazine. Vinblastine has been noted to cause the least myelosuppression.9 Intralesional interferon is considered experimental. One study found intralesional interferon alfa-2b at a dose of 1 million to 3 million U gave satisfactory results.6,11 Cryotherapy has also been utilized with 70-percent cosmetic improvement and is useful for small localized lesions only.3 In our patient, the ulcers healed in three weeks with conservative care using topical antibiotics, offloading of pressure from the foot with orthotics, and physical therapy. The patient continued on his chemotherapy regimen (Figure 2).