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Histologic and Clinical Features

July 25, 1994

Histogenesis

The cell of origin (histogenesis) for KS still remains controversial. KS is characterized by the proliferation of spindle-shaped cells ("KS cells," Ensoli 1991). The histogenesis of these spindle cells, however, is still undefined. Mesenchymal cells, vascular and lymphatic endothelial cells (Rutgers 1986; Way 1993) and smooth muscle cells (Weich 1991) have all been proposed as potential KS cell progenitors.

Most researchers contend that these spindle-shaped KS cells are considered to be the "tumor" element of the lesions, which are associated with slit-like vascular channels lined by endothelial cells, fibroblasts and inflammatory cells; the vascular channels extend themselves in the process of new blood vessel formation (neo-angiogenesis) in the early stage lesions. In the later stage of the lesions, neo-angiogenesis continues, but the KS spindle-cells now make up larger, three-dimensional tumor masses.

Two methods have been developed to study the histogenesis and pathogenesis of KS: 1) the establishment of long-term cell cultures derived from KS lesions; and 2) the development nude mice into which cultured KS-derived cells are injected.

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Pathology

Three characteristic histologic stages have been described for cutaneous KS: patch, plaque and nodular. While some lesions appear to rise de novo as nodules (Susan E. Krown, personal communication), the patch stage is often the earliest pattern of KS lesions, which arise in the reticular dermis as a clinically macular (non-palpable) lesion (Gottlieb 1992). Patch stage lesions are characterized by a proliferation of small interweaving bands of spindle cells with irregular slit-like vascular channels surrounding normal dermal vessels and adnexal structures accompanied by a variable, inflammatory lymphocytic infiltrate (Tappero 1993 b).

In plaque-stage, KS there is expansion of the spindle-cell and vascular process. These spindle cells, now dispersed in the reticular dermis, are comprised within a network of reticular and collagen fibers (Levine 1993). Clinically, such lesions are palpable (i.e., they have depth).

Nodular-stage KS lesions are mostly composed of sheets of spindle cells with mild to moderate cytologic atypia, single cell necrosis, and trapped erythrocytes (Tappero 1993 b). The irregular, slit-like, vascular channels of the spindle cells tend to coalesce in larger tumor masses.


Clinical Features

AIDS-KS has a wide variety of clinical presentations. Lesions composed of various colors and shapes are usually defined as macules, papules, nodules or plaques.

Macular lesions are often innocuous looking, faint pink, red or purple, and small in size. At this stage they are usually asymptomatic. They are most commonly seen on sole, hard palate and tip of the nose.

Lesions on the trunk of a patients can start out as macules, but they are usually papular at presentation. When they are on the trunk, neck or the penis, they are frequently oblong and 1 to 2 cm in longest dimension (Tappero 1993 b). When lesions occur on the face they are most often round and less than 1 cm in size.

Papular lesions or plaques are often found in the distal extremities, whereas larger plaques with nodules frequently occur around the elbows and knees of patients. The plaques and nodules on the legs are often associated with painful edema. Lymphatic infiltration alters the course and dimension of cutaneous KS as well as cause extreme pain, maceration and ulceration. Lymphedema is also thought to be associated with a release of multiple cytokines which are central to the pathogenesis of KS.

Oral lesions are much harder to categorize and measure. Oral lesions are the first clinical manifestation in approximately 22% of patients with KS, and are seen in approximately 45% of patients who have concomitant skin lesions (Ficarra 1988). They are usually asymptomatic, but can produce obstructive symptoms such as difficulty in swallowing, loosening of teeth and pain.

Gastrointestinal tract lesions, which are usually asymptomatic, occur in almost 50% of patients with KS (Mitsuyasu 1993). They most commonly appear in the bowel, liver and spleen. They often appear as raised, red lesions and are not easy to biopsy because of their submucosal location.

Pulmonary KS is the most severe and life threatening form of AIDS-KS (Garay 1987). Dyspnea (difficulty in breathing) with or without fever and sometimes hemoptysis (coughing up blood) are the presenting symptoms of pulmonary KS. To definitively diagnose pulmonary KS, a transbronchial or open lung biopsy is necessary. Pulmonary lesions, however, are not usually biopsied because of the risk of bleeding. A chest radiograph can detect subtle, diffuse reticulo-nodular infiltrates and pleural effusion (fluid around the lung in the pleural space) (Mitsuyasu 1993).

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This article was provided by Treatment Action Group. It is a part of the publication The KS Project Report: Current Issues in Research & Treatment of Kaposi's Sarcoma.
 

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