Clinical Challenge: Purplish Patches and Plaques on the Legs

The lesion identified in this patient is an example of classic or classical Kaposi's sarcoma (KS). KS is a multifocal tumor of endothelial cell origin with stage-dependent characteristic histopathology, which is classified into four clinical variants: classical, AIDS-associated, immunosuppression-associated, and...

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The lesion identified in this patient is an example of classic or classical Kaposi’s sarcoma (KS). KS is a multifocal tumor of endothelial cell origin with stage-dependent characteristic histopathology, which is classified into four clinical variants: classical, AIDS-associated, immunosuppression-associated, and the African-endemic subtype.

Epidemiology

Classical KS is typically seen in Mediterranean or Jewish male patients in their sixties. The annual incidence rates for classic KS vary in different geographic regions, ranging from 0.14 per million inhabitants (for both male and female patients) in Great Britain to 10.5 per million in males and 2.7 per million in females in Italy. Most regions demonstrate a KS male to female prevalence ratio of 3:1.

Presentation and Course

These tumors begin on the skin as unilateral or bilateral bluish-red macules on the distal portions of the lower extremities that can resemble hematomas. They generally progress slowly both horizontally and vertically, developing into firm plaques and later into nodules. 

As the tumor progresses, its color may change to a more brownish hue, with the skin overlying the tumor becoming hyperkeratotic and ulcerated, particularly on the lower extremities.

The surrounding areas frequently are characterized by pitting edema, which may evolve into fibrosis. Multiple lesions at different stages of evolution are often observed, as early lesions may regress while others develop.

The course of classical KS is usually prolonged and benign, with patients often living with the slowly progressing disease for decades. Eventually, progression and dissemination to other body sites is typically seen.

The tumors may spread to the lymph nodes, mucous membranes, and inner organs such as the gastrointestinal tract, although these manifestations are rarely symptomatic. Since most patients with classical KS are elderly, death from other causes often precedes extensive spread.

Other Variants

AIDS-associated KS is a rapidly progressive form seen in HIV-infected patients that is characterized by early involvement of extracutaneous sites. Early lesions appear as small oval violaceous macules that can develop rapidly into plaques and nodules. 

These lesions frequently occur on the face, especially the nose, eyelids, ears, and trunk. Oral mucosa is frequently involved. Spread to the lymph nodes, gastrointestinal tract, and lungs is common. 

Transplantation-associated KS (also termed iatrogenic KS) is observed predominately in kidney allograft recipients and more rarely in recipients of other solid organ and bone marrow allografts. 

Iatrogenic KS has also been reported in patients receiving immunosuppressive therapy for other reasons, notably the treatment of autoimmune diseases. Skin lesions are prominent, and progression can be either slow as is seen in the classical variant, or rapidly disseminating, as is seen in AIDS-associated KS.

African endemic KS occurs in some African countries. Lesions may occur as nodular-, florid-, infiltrative-, and lymphadenopathic types. Florid/vegetating and infiltrative variants are often aggressive, and lesions may extend deeply into the dermis, subcutis, muscle and bone.

Lymphadenopathic African KS mostly affects children and young adults, and it may run a fulminant courses with rapid progression. 

Pathogenesis

Although there is some debate regarding the question as to whether KS is a reactive proliferative disorder or a true malignant neoplasm, it is accepted that all KS subtypes are caused by infection with human herpesvirus (HHV)-8, also known as KS-associated herpesvirus (KSHV), a member of the γ-Herpesviridae subfamily, genus Rhadinovirus. The viral genome is detectable in lesions at all stages regardless of the clinical subtype.   

HHV-8 primarily invades vascular and lymphatic endothelial cells, stimulating their proliferation, as well as inflammation, angiogenesis, and the inhibition of apoptosis. 

The routes of HHV-8 transmission are not completely known, however both sexual and non-sexual salivary modes of transmission, as well as blood product and organ transplantation-associated transmission are accepted.

Differentials

The differential diagnosis of cutaneous KS depends on the clinical stage and includes:hematoma, melanoma, pyogenic granuloma, spindle cell hemangioendothelioma, arteriovenous malformations (pseudo-KS), severe stasis dermatitis (pseudo-KS), bacillary angiomatosis, angiosarcoma, angiokeratoma, and nodal myofibromatoma.

When lesions are observed in the oral mucosa, practitioners should consider non-Hodgkin’s lymphoma, squamous cell carcinoma, bacillary angiomatosis, and melanoma.

Treatment

Initial treatment of the cutaneous manifestations of classical KS is often managed by local therapies aimed at eliminating individual lesions. Recurrence rates are high, but these local therapies are often satisfactory for several years in slowly progressing classical KS.  

These treatments include surgical excision, local destruction with liquid nitrogen, laser or photodynamic therapy, and topical therapy with 9-cis-retinoic acid.

Radiation therapy may be useful in the oral mucosa and other less accessible body areas. Patients with rapidly progressive or widespread manifestations of classical KS may respond well to chemotherapies such as doxorubicin, bleomycin, vincristine, etoposide, and dacarbazine, either alone or in combination.

Jonathan Whitehouse, BS, is a medical student at Baylor College of Medicine.

Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine in Houston.