Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Kaposi's Sarcoma Kaposi's sarcoma (KS) was first described in 1872 by Dr. Moritz Kaposi. He described five new cases of an indolent purplish skin tumor of the lower extremities in elderly men. Until recently it has remained an obscure, poorly understood malignancy. There are four recognized forms of KS: the classic variety, as described by Dr. Kaposi; the endemic form; those cases seen in transplant patients; and the epidemic form. Classic KS is an indolent, purplish skin neoplasm of the lower extremities seen in elderly white males of Ashkenazic or Mediterranean descent in their sixth to eighth decades. The endemic form, representing 10% of the adult malignancies in Africa, was initially described in 1934 by Smith and Elmes. It is the second most prevalent African malignancy. There are two clinical types: cutaneous and lymphoproliferative. Ninety percent are of the cutaneous variety. Both types show male predominance and are more aggressive tumors than the classic variety. This is especially true of the lymphoproliferative type, which has a poor prognosis, with death usually occurring secondary to disease in two to three years. Clinical presentation of endemic KS is rarely seen in the head and neck. A 200% to 400% increase in risk of developing KS has been noted in transplant patients on immunosuppressive chemotherapy, with the first sign of KS noticed typically 9 to 16 months into therapy. Head and neck locations for KS lesions are frequent and these lesions tend to be aggressive. Interestingly, with the removal of the immunosuppressive therapy most of these KS lesions spontaneously involute. Epidemic KS (EKS) presents in AIDS patients, and, after non-Hodgkin's lymphoma, is the most common malignancy in AIDS. It is noted predominantly in the homosexual and bisexual male population. Its incidence is less among those who have contracted AIDS from intravenous drug usage. EKS is seen in all anatomic regions, and is the cause of death in around 11% of effected AIDS patients. The most common cause of death remains opportunistic infection. A study by Marcussen and Sooy looked at 399 patients with AIDS. Head and neck manifestations were noted in 165 (41%) of these patients. Of that group, 58 (35%) had cutaneous, oral, or pharyngeal evidence of Kaposi's sarcoma. Intraoral sites of EKS represent the most common site of head and neck disease. The most common site was the hard palate (53%), followed by the oropharynx (13%), gingiva (11%), tongue (9%), lips (4%), and buccal mucosa (3%). Extraoral KS lesions can be seen in any location on the head and neck. Areas of particular note include the tip of the nose, the scalp, and periorbital region. Additionally reported sites in the head and neck include the parotid, thyroid, pharynx, tonsils, lung, trachea, and brain. KS lesions are classically described as red to purple lesions varying from macules to nodules. In the AIDS population, apigmented lesions can be seen, and a higher degree of suspicion is warranted. Most KS tumors are nontender and do not blanch. In mucosal locations lesions are more likely to be painful or asymptomatic. These pigmented tumors are often grouped in clusters that may coalesce into a larger single lesion. Very large tumors have a tendency to ulcerate and bleed. This has been noted in both pulmonary and gastrointestinal lesions at endoscopy, and presents a potential emergency situation. The staging system currently used for EKS was originally described in 1984 by Mitsuyasu and Groopman from UCLA. It is as follows: Stage I one anatomic area with <10 lesions A asymptomatic The differential diagnosis of Kaposi's sarcoma includes virtually all pigmented lesions of the dermis and epidermis. Diagnosis of KS is made by clinical history, a thorough physical exam, and histologic confirmation. A cutaneous core biopsy or mucosal biopsy is usually sufficient for diagnosis. In certain centers an FNA may be adequate as well. If the lesion is small enough, and there is no contraindication, simple excisional biopsy is both diagnostic and therapeutic. Kaposi's sarcoma is most often not a local disease. In a patient with oral mucosal disease, visceral disease is likely. Visceral involvement is usually clinically silent, but bowel obstruction and pulmonary hemorrhage have been reported. Early endoscopic verification is recommended. Barium swallow or gastrointestinal intraluminal contrast studies are not helpful. Even in the face of Stage II cutaneous KS, over half of patients will have evidence of gastrointestinal disease at endoscopy. Biopsy of gastrointestinal or pulmonary mucosal lesions is not prudent since severe bleeding can result. KS is quoted as a cause of AIDS-related death in only 11% of cases, with a median survival time of 14 months when KS was the initially defining illness of AIDs. A history of a previous opportunistic infection, a T4 to T8 ratio of less than 0.5, an absolute T4 count of less than 200, and "B" symptoms correlate with a poorer prognosis. Five-year survival is estimated at 10%. The treatment goals for KS must be balanced between the expected course of the disease versus the toxicity of therapy. The following criteria represent the consensus amongst KS investigators: dysphagia, airway obstruction, pain or ulceration, hemorrhage, disfigurement, or rapid growth of a lesion. Treatment options include radiation therapy, systemic chemotherapy, surgical excision, immune modifier therapy, and local therapy. Kaposi's sarcoma lesions are quire radiosensitive. In small lesions of Stage I or II this is considered to be the treatment of choice. This is especially true for cutaneous lesions where radiotherapy is well-tolerated. AIDS patients are much more likely to encounter mucosal toxicity from XRT. Severe mucositis of the oral cavity, pharynx, and larynx have been noted at relatively low doses. As a result efforts have been made to determine how small of a radiation dose is effective. The optimal dose seems to be 3000 cGy, minimizing recurrence locally, having the highest response rate, and less mucosal toxicity than higher dose regimens. Good responses to chemotherapy have also been noted in KS. Generally single agent regimens are reserved for early disease Stage II or less, and combination therapy is reserved for Stage III and IV. Vinblastine and Etoposide are both agents that have achieved a greater than 75% response rate. A common combination treatment protocol is ABV (adriamycin, bleomycin, and vinblastine). This regimen achieved a slightly higher response rate than either of the two single agents described above; however, an increase in opportunistic infections was also noted. The alternating weekly regimen of Vinblastine and Vincristine has also been successful in achieving greater than 80% response rate. Surgery is an excellent method of control of local disease and is best suited to small cutaneous lesions and pedunculated lesions in the upper aerodigestive tract. Cure has rarely been noted, and it should be noted that brisk bleeding can be encountered during surgical resection. The CO2 and KTP laser have been used with good local response and hemostasis, and are especially useful in obstructive upper airway disease. Alpha interferon 2a and 2b in high doses have shown the greatest promise in immune modifier therapy response rates near 45%. Effectiveness was greatest in those patients without B symptoms and those with CD4 counts greater than 200 cells/mm3. Local therapies are very promising and for the otolaryngologist may be the best tool in the control of Kaposi's sarcoma. Intralesional vinblastine is very effective in controlling local disease, and is a vital office outpatient treatment modality. A study published by Epstein used a 0.2 mg/ml concentration of Vinblastine, with 0.1 ml injected into each 0.5 cm2 of surface area. In this series of 42 patients, 74% showed greater than 50% decrease in the size of the lesion. Mean duration of response was only around 4 months. It is inexpensive and has limited side effects. After the injection the patient notes local discomfort starting at around 24 hours and extending up to three days. This has been tolerated well with pain medications. Numbness, which spontaneously resolves within one month, has been noted in less than 15% of cases. Several other local modalities for treatment exist. Intralesional interferon shows promise but recent studies have been unable to prove a statistically significant response versus placebo. Photodynamic therapy likewise has been effective in eradicating KS lesions. The CO2 laser has been used successfully in the upper aerodigestive tract and offers the benefit of good hemostasis. Cryotherapy is also recognized as an effective means of controlling small local disease. What is the role of the otolaryngologist in KS? Suspicion should always be raised by the diagnosis of AIDS. All lesions should be biopsied. Local treatments with vinblastine, the laser, or excision can easily be undertaken in the office setting. All systemic disease (greater than Stage II) should be treated under the guidance of an experienced oncologist and/or radiation oncologist. They will handle treatment for the vast majority of KS patients. The otolaryngologist's specific expertise in airway management will also be needed in those patients with emergent obstructive symptomatology. In the face of the growing numbers of worldwide AIDS patients we must be prepared to face this disease. Case Presentations A 42-year-old white man was diagnosed with AIDS in 1989. Approximately 8 months prior to this presentation, a cluster of pigmented nodular lesions were noted on the hard palate. Biopsy revealed a histologic pattern consistent with Kaposi's sarcoma. He was subsequently referred to a local dental clinic where he underwent intralesional injections with vinblastine. Complete response was noted. At a recent follow-up visit to the Special Medicine Clinic he was again noted to have a small cluster of purplish lesions in the same site. The Otolaryngology Service was consulted. Given the history of Kaposi's sarcoma in this location, it was felt that this represented a recurrence. Again he was referred to the same dental clinic, where the lesion was treated with approximately 0.4 cc of a 0.1 mg per cc solution of vinblastine (0.04 mg total dose) injected into the lesion. This was repeated after two weeks, and again a complete remission was achieved. The only side effect was a local erythematous reaction noted at 24 hours. The patient reported the feeling of a "pizza burn" at the treatment site at this time which resolved after 48 hours. He is currently in remission without visual signs of Kaposi's sarcoma lesions. Bibliography Abrams DI, Volberding PA. Alpha-interferon therapy of AIDS-associated Kaposi's sarcoma. Semin Oncol 1987;14:43-47. 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