Kaposi's sarcoma

Kaposi's sarcoma is an angiosarcoma consisting of multiple endothelial channels surrounded by spindle cells. There are four types. The second two are related to HIV.

Classical Kaposi's sarcoma (rare) affects elderly men in the industrial world. It has a variable behaviour, and is often indolent, but not always so.

Endemic Kaposi's sarcoma (KS) has been recognized in equatorial Africa since at least the 1940's. It has an adult and a paediatric form, and is much more common in males (10:1). The patient is typically a male labourer of about 40, who has had symptoms for 18 months before the growth of his lesions forces him to seek treatment.

His symptoms start with oedema of his leg(s), usually at the end of the day, which is gone by the morning. At first his oedema is intermittent; later, it becomes more constant, and eventually ceases to pit on pressure. Once locally progressive disease has developed, the normal temperature gradient of his affected limb is reversed, so that it is warmer peripherally than it is proximally.

The indolent form (common) occurs after a variable period of oedema, as 3 to 5 mm nodules which are more easily felt than seen, and are the typical lesions of endemic Kaposi's sarcoma. They form in or under the skin of his feet and legs and less often his hands and lower arms, usually in more than one limb, and on his right arm more often than his left. Involvement is usually asymmetrical, and one limb may be normal. The nodules are usually the same colour as the surrounding skin, but may be purple. He may also have larger subcutaneous nodules along his superficial vessels. Nodules may persist unchanged for years, and disappear spontaneously, only to reappear at new sites. Traditional practitioners sometimes excise them, usually with good results. Less commonly, he has asymmetrically distributed plaques, millimetres to centimetres in diameter, starting on the sides and dorsum of his feet, and later on his palms and soles. These have a palpable edge and are darker than the surrounding skin.

The nodes at the root of his most diseased limbs are often enlarged, but he has no generalized lymph node enlargement. He loses some weight and becomes moderately anaemic. After several years he may have pleural effusions (see below), but is unlikely to have more than an occasional lesion in unusual sites (his conjunctiva, mouth, head, neck, or trunk).

The infiltrating form (common) appears in a previously oedematous limb as a diffuse, ill-defined, dark thickening of his skin and deeper tissues, with some hyperkeratosis. It is a hot ''woody' infiltration which creeps proximally to cause joint deformity, stiffness, and disability. This infiltration is more widespread than the plaques described above, and has no raised edge. It may occur alone, but is usually accompanied by nodules, or aggressively growing tumours. The bones of his infiltrated feet or hands may show periarticular osteoporosis, followed by multiple erosions, which may enlarge until his phalanges and metatarsals can no longer be seen on an X-ray. No new bone is formed, except in response to successful treatment.

The locally aggressive form (fairly common) presents as one or more rapidly growing, cauliflower-like tumours, anywhere on his feet, legs, or hands; they arise from existing nodules, which may have been unchanged for months or years. These aggressive lesions ulcerate, and discharge quantities of offensive fluid with a characteristic smell. He has other unchanged nodules proximal to the tumour and around it, and there is always the infiltration described above, somewhere in the same or another limb. If he presents earlier, you may see one of these aggressive lesions before it has started to ulcerate.

The lymphadenopathic form (uncommon) presents in an African child or adolescent as symmetrically enlarged, slightly irregular, fleshy, firm (but not hard), nodes in all sites. He may also have a few atypical skin lesions.

There are two HIV-related varieties of Kaposi's sarcoma:

HIV-related Kaposi's sarcoma of Caucasians in the industrial world. This differs somewhat from that in sub- Saharan Africa.

Atypical African Kaposi's sarcoma (AAKS) was first recognized in the early 1980s. More than 90% of patients are HIV positive, and the sex ratio is more nearly equal (males to females 5:1). At presentation men have a mean age of 35 and women of 25. The patient is likely to have had symptoms for about 8 months, which include loss of weight, and almost always a completely symmetrical generalized lymph node enlargement. You can usually find skin lesions somewhere. Look for irregular 3 to 30 mm easily palpable dark plaques, which are more common on his face, head, neck, trunk, and proximally on his limbs. You may also find them in his throat, or anywhere in his mouth (50% of cases), where they are most often seen on his palate.

The lesions on his mucosa start as a flat purple stain, which becomes raised and then nodular, before it finally ulcerates, sometimes covered by a layer of thrush. Occasionally, his entire gums are infiltrated. Sometimes, he has nodules, particularly on his insteps, and on his thighs along the line of his long saphenous veins, where there may be oedema and infiltration. He may also have oedema of his extremities, which can be severe and resemble the endemic form of the disease, but unlike the latter, it may also involve his trunk, head, and neck. There is a 5% chance that he will have no skin or mucosal changes, and if so, his prognosis seems to be better. He usually has at least one opportunist infection. In spite of all this, he may respond to chemotherapy, and return to work for months, or even years, so it is well worth giving.

Bayley Anne C, ''Atypical African Kaposi's Sarcoma'. Report to the conference ''AIDS in Africa; Naples 1987'. In press. Karger, Basle.

KAPOSI'S SARCOMA ENDEMIC AFRICAN KAPOSI'S SARCOMA DIAGNOSING ENDEMIC KAPOSI'S SARCOMA. Look carefully for typical nodules, which you will almost certainly find somewhere. Feel for a reversed temperature gradient, especially in the patient's legs (see above).

If he has multiple nodules, and mycetoma is rare, biopsy is unnecessary, because the lesions are so typical.

THE DIFFERENTIAL DIAGNOSIS of endemic Kaposi's sarcoma includes leprosy (30.5), fungal infections of his feet with brawny oedema, and chronic osteitis (7.13) of his feet and legs (sometimes secondary to ulceration in leprosy, 30.5), tropical ulcer (31.2), mycetoma (31.3), the hyperkeratosis of lymphedema (31.4), and onchocerciasis.

PROGNOSIS UNTREATED. The indolent type: lesions grow slowly and cause little morbidity. The aggressive type: lesions grow steadily and lead to an early death; the superficial ones ulcerate and cause considerable distress. In the lymphadenopathic type lesions also grow steadily.

MANAGEMENT. [f41]If he has the indolent form of the disease, he needs no treatment. Follow him up carefully, because other types may develop.

If he has any other form of the disease, he needs chemotherapy and, rarely, surgery.

AAKS [s7]ATYPICAL AFRICAN KAPOSI'S SARCOMA DIAGNOSIS. If he has visible masses of symmetrical nodes, each 3[nd]4 cm, AAKS is likely, so search his skin and mouth carefully for characteristic lesions, and if necessary biopsy one.

BIOPSY. is unnecessary if: (1) The diagnosis is obvious clinically. (2) He has symmetrically enlarged nodes [lt]2 cm, because it will probably only show the reactive hyperplasia of HIV infection.

Biopsy is useful because it may reveal a treatable condition if: (1) He has symmetrical nodes (5%) [mt]2 cm without the characteristic skin or mucosal lesions which allow you to diagnose AAKS clinically. (2) He has large asymmetric nodes (e.g. large nodes one side of his neck, and small ones, or none, on the other). If so, expect to find tuberculosis or lymphoma.

PROGNOSIS AND STAGING. In Lusaka a staging scheme has been proposed for prospective testing based on about 500 patients followed for 2 years.

Stage One. Lymphadenopathy alone (diagnosis proved by biopsy). No oral or skin lesions. A normal chest X-ray. Little or no weight loss.

Stage Two. Any combination of lymph node enlargement, skin lesions, and oral disease, without oedema of his head, neck, trunk, or bikini area. No CNS signs. A normal chest X-ray, and only moderate weight loss.

Stage Three. As for Stage Two, but with any of the following: gross weight loss, cough, dyspnoea, bilateral basal infiltration or pleural effusions, neurological symptoms (without evidence of cryptococcal or tuberculous meningitis at lumbar puncture), oedema of the trunk, face or bikini area.

SURGERY [s7]BOTH TYPES Kaposi's sarcoma has a multicentric origin, so that radical excision is impossible. Chemotherapy can cause quite large tumours to disappear; debulking excision is unnecessary.

Amputation may be indicated ([lt]5% of patients) if: (1) He is unresponsive to the available drugs and his tumour is still growing. (2) He arrives with advanced destructive disease of one limb, and is too septicaemic, or cachectic, to tolerate chemotherapy.

CAUTION ! Beware of bleeding. Check his platelets, always use a tourniquet, and have diathermy available.

CHEMOTHERAPY [s7]BOTH TYPES When indicated give him:

Vincristine 1.4 mg/m['2] intravenously on day 1, and weekly for 6 weeks. Beware of ileus if he has AAKS and stop weekly injections if it occurs.

And, actinomycin D as a bolus intravenous injection of 1 to 1.5 mg/m['2] on Day 1, and then every 21 days for 6 doses. Warn him that he may lose several kilos during the first 3 or 4 weeks as his oedema resolves.

The first signs of a satisfactory response (90% of patients) are cooling of the affected limb, and diminished itching, pain, and oedema. At about 3 weeks nodules and florid tumours begin to flatten, and shrink, and many may finally disappear, to leave only a small scar. Continue treatment for 3 to 6 courses, until no tumour remains, or it ceases to respond. To distinguish infiltration from residual fibrosis, remember that fibrosis is cool, but infiltration is hot.

See him regularly, and warn him that his disease may recur, usually in 1[nd]2 years. If so, treat him as before, and he will usually respond. If he ceases to respond and needs a second-line drug, use adriamycin (preferably), bleomycin, or daunorubicin.

If radiotherapy is available, it will speed the resolution of localized tumours, but chemotherapy is probably also necessary.

If he is sputum-positive for AAFB (only seen with AAKS), start antituberculous treatment 10 days before chemotherapy.

RESPONSE on treatment. KS: 87%. AAKS: 61%.

SURVIVAL after treatment. KS: unknown, but probably [mt]8 years. AAKS: Stage One unknown but several patients have survived [mt]3 years. Stage Two [mt]3 years. Stage Three 7.5 months.

DIFFICULTIES [s7]WITH AAKS If he has a DRY COUGH, which does not produce sputum, but produces streaky haemoptyses after a few weeks, suspect PULMONARY AAKS (this is commonly misdiagnosed as tuberculosis). He rapidly becomes progressively breathless, and may be breathess and cyanosed even while receiving oxygen at rest, fighting to oxygenate himself with every accessory muscle. Early, the only radiographic signs are mildly increased bronchovascular markings. Soon, he has reduced air entry at his bases, with fine crepitations that do not disappear on coughing, and a bilateral symmetrical fluffy infiltrate, most marked in his perihilar and basal zones, which usually spares his apices completely (unlike tuberculosis, which usually involves the apices and is asymmetrical). The infiltrate resembles pulmonary oedema, but does not respond to digoxin, diuretics, or steroids. Chemotherapy for AAKS will usually improve his dyspnoea rapidly, so that he can discontinue oxygen in 3[nd]4 days, and be out of bed in a week. His X-ray lesions will start to resolve in 3[nd]4 weeks, and may resolve completely, if he survives long enough.