Case Study
Diagnosing And Treating Kaposi’s Sarcoma
April 2014
These authors present key pearls on treating a 26-year-old patient with AIDS, who presented with papules on his lower extremity, chest, back, oral mucosa and genitalia.
A 26-year-old Hispanic male presented to the Maricopa Medical Center in Phoenix with numerous well-circumscribed red to purple colored papules on his chest, back, oral mucosa, genitalia and lower extremity. Beginning below the right knee, the lesions become abundant and coalesce to form woody, indurated dark purple, brown and black plaques that cover most of the lower leg, ankle and foot.
A large fungating nodule is visible protruding from the medial aspect of the leg. The skin on the sole of the right foot is friable and exophytic. The patient has an ulceration on the plantar forefoot. Drainage from the ulceration is clear and malodorous. There is non-pitting edema to the right lower extremity. Pedal pulses are audible via handheld Doppler. Sensation is grossly intact. The patient is unable to walk on the right foot secondary to pain.
His past medical history is remarkable for human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) with treatment of antiretroviral therapy (ART). The right fourth toe was previously amputated following an infection. His past medical history is otherwise unremarkable. The patient has no history of illicit drug use, alcohol abuse or smoking. His family history is unremarkable.
The patient’s vitals included blood pressure of 120/55, a pulse of 111 per minute, respirations of 20 per minute and a temperature of 100ºF. The patient was admitted to the hospital and started on broad-spectrum antibiotics. We took a multidisciplinary approach and solicited opinions from internal medicine, hematology/oncology, infectious disease, dermatology, podiatry and plastic surgery.
The initial workup included a complete blood count with differential, chemistry panel, tuberculosis and coccidioidomycosis screens, Cryptococcus screens, rapid plasma reagin, hepatitis panel, CD4 count, viral load, blood culture, wound culture, venous duplex and X-ray of the right foot. The findings included macrocytic anemia, thrombocytopenia, a CD4 of 89 and a viral load of 119. Wound cultures were positive for Escherichia coli, Pseudomonas putida and Enterococcus faecalis. Imaging studies included chest X-ray and computed tomography scan of his chest, abdomen and pelvis, which helped rule out visceral involvement.
A biopsy of the left shoulder and right leg lesions confirmed the diagnosis of AIDS-associated Kaposi sarcoma. The patient started on antiretroviral therapy and liposomal doxorubicin (Doxil, Janssen Products).
Iatrogenic (transplant-related) Kaposi’s sarcoma is associated with drug-induced immunosuppression.1 It originally arose in the 1970s after patients received long-term corticosteroids following solid organ transplantation. It has since been associated with other immunosuppressive therapies, including chemotherapy. Iatrogenic Kaposi’s sarcoma is slightly more common in men than women and may include mucocutaneous tissue, lymph node or visceral involvement. Approximately one in 200 transplant recipients develops Kaposi’s sarcoma in the United States.1 Usually, these patients were already infected with Kaposi’s sarcoma herpes virus prior to the transplant. They subsequently became vulnerable with the initiation of immunosuppressive medications.
Epidemic (AIDS-associated) Kaposi’s sarcoma is the most common variant of the disease. It is one of several “AIDS defining” illnesses that help to differentiate HIV infection from AIDS. The clinical presentation ranges from minimal disease to widely disseminated mucocutaneous lesions.3 Skin lesions are visible most frequently on the lower extremities, face and genitalia. Involvement of the viscera, particularly the gastrointestinal tract and lungs, may occur in 25 to 50 percent of patients.2,7 Before the introduction of highly active antiretroviral therapy (HAART), the prevalence of Kaposi’s sarcoma in AIDS patients was more than 20,000 times that of the general population.4 Kaposi’s sarcoma has since become less common in the United States with approximately six cases per million people annually. The thought is that aggressive antiretroviral therapy prevents further weakening of immunological function and thereby prevents reactivation of latent Kaposi’s sarcoma herpes virus infection.5
While the populations affected by Kaposi’s sarcoma are different, some of the basic pathological processes are quite similar. In Kaposi’s sarcoma, the endothelial cells of blood and lymphatic vessels are infected with Kaposi’s sarcoma herpes virus. The viral genes are responsible for stimulating cell proliferation, inhibiting apoptosis, inducing angiogenesis and releasing inflammatory cytokines. Virtually all patients with Kaposi’s sarcoma are infected with Kaposi’s sarcoma herpes virus although not all individuals infected with the virus develop Kaposi’s sarcoma. The development of Kaposi’s sarcoma appears to require additional cofactors that in theory are genetic, immunologic and environmental.5 This remains an area of ongoing research.
Kaposi’s sarcoma skin lesions typically vary in color from pink to red, purple and brown. There are three progressive stages: patches, plaques and nodules. The nodular lesions can be exophytic or fungating with breakdown of overlying skin and ulceration. Lymphedema is a common complication resulting from obstruction of lymphatics and may be extensive.4
The differential diagnosis for Kaposi’s sarcoma includes nevi, hematoma, angioma, dermatofibroma, hemangioma, pyogenic granuloma, acroangiodermatitis, angiosarcoma, extrapulmonary Pneumocystis jirovecii, bacillary angiomatosis, Sporothrix schenckii, atypical mycobacterial or fungal infections. Definitive diagnosis requires a biopsy with histopathological tissue evaluation. Histological features characteristic of Kaposi’s sarcoma include whorls of spindle-shaped cells, leukocytic infiltration and neovascularization with aberrant proliferation of small vessels. Microhemorrhaging and hemosiderin deposition are also evident due to a lack of basement membrane within the small vessels. Bacillary angiomatosis may mimic early Kaposi’s sarcoma histology and thus requires Warthin-Starry silver staining to differentiate it.2
Local treatments entail the management of localized Kaposi’s sarcoma lesions and include radiotherapy, topical alitretinoin gel (Panretin, Eisai), cryotherapy, intralesional chemotherapy or biological agent injections, laser treatment, photodynamic treatment and excisional surgery.4
Systemic therapy is indicated for more advanced, extensive or rapidly progressive Kaposi’s sarcoma. Systemic treatment includes cytotoxic chemotherapy and HAART for AIDS-associated Kaposi’s sarcoma.6 Previous chemotherapeutic agents include bleomycin, vinblastine, vincristine (Oncovin, Pfizer), doxorubicin and etoposide (Etopophos, Bristol-Myers Squibb). These have had limited use recently since the development of liposomal anthracyclines such as pegylated liposomal doxorubicin and liposomal daunorubicin (Cerubidine, Bedford Laboratories) and taxanes like paclitaxel (Taxol, Bristol-Myers Squibb), which are now considered the primary treatment modalities of choice for systemic cytotoxic chemotherapy.
Both protease inhibitor and non-nucleoside reverse transcriptase inhibitor types of HAART are associated with a significant decrease in the incidence and size of lesions for AIDS-associated Kaposi’s sarcoma.8 If fact, without antiretroviral therapy, attempts to treat AIDS-associated Kaposi’s sarcoma via chemotherapy or radiotherapy have demonstrated poor overall survival with minimal palliative benefits.4 Combined treatment using antiretroviral therapy and liposomal doxorubicin is considered the standard of care for AIDS-associated Kaposi’s sarcoma.
A 26-year-old Hispanic male presented to the Maricopa Medical Center in Phoenix with numerous well-circumscribed red to purple colored papules on his chest, back, oral mucosa, genitalia and lower extremity. Beginning below the right knee, the lesions become abundant and coalesce to form woody, indurated dark purple, brown and black plaques that cover most of the lower leg, ankle and foot.
A large fungating nodule is visible protruding from the medial aspect of the leg. The skin on the sole of the right foot is friable and exophytic. The patient has an ulceration on the plantar forefoot. Drainage from the ulceration is clear and malodorous. There is non-pitting edema to the right lower extremity. Pedal pulses are audible via handheld Doppler. Sensation is grossly intact. The patient is unable to walk on the right foot secondary to pain.
His past medical history is remarkable for human immunodeficiency virus and acquired immunodeficiency syndrome (HIV/AIDS) with treatment of antiretroviral therapy (ART). The right fourth toe was previously amputated following an infection. His past medical history is otherwise unremarkable. The patient has no history of illicit drug use, alcohol abuse or smoking. His family history is unremarkable.
The patient’s vitals included blood pressure of 120/55, a pulse of 111 per minute, respirations of 20 per minute and a temperature of 100ºF. The patient was admitted to the hospital and started on broad-spectrum antibiotics. We took a multidisciplinary approach and solicited opinions from internal medicine, hematology/oncology, infectious disease, dermatology, podiatry and plastic surgery.
The initial workup included a complete blood count with differential, chemistry panel, tuberculosis and coccidioidomycosis screens, Cryptococcus screens, rapid plasma reagin, hepatitis panel, CD4 count, viral load, blood culture, wound culture, venous duplex and X-ray of the right foot. The findings included macrocytic anemia, thrombocytopenia, a CD4 of 89 and a viral load of 119. Wound cultures were positive for Escherichia coli, Pseudomonas putida and Enterococcus faecalis. Imaging studies included chest X-ray and computed tomography scan of his chest, abdomen and pelvis, which helped rule out visceral involvement.
A biopsy of the left shoulder and right leg lesions confirmed the diagnosis of AIDS-associated Kaposi sarcoma. The patient started on antiretroviral therapy and liposomal doxorubicin (Doxil, Janssen Products).
A Primer On The Different Varieties Of Kaposi’s Sarcoma
Kaposi sarcoma is an angioproliferative disorder of the vascular endothelium affecting mucocutaneous tissues with the potential to involve viscera. Its pathogenesis is multifactorial and hinges on immune dysfunction with simultaneous infection of the human herpes virus 8, also known as Kaposi’s sarcoma herpes virus. There are four distinct types that are grouped according to the natural history of the disease as well as the population in which the disease occurs.1 Classic Kaposi’s sarcoma develops in individuals of Mediterranean, Eastern European or Middle Eastern heritage. It usually affects men older than 50 years who develop slow growing, purple-red lesions on the lower legs and feet. It may also spread to the arms and trunk. Disseminated disease and visceral involvement are uncommon. African endemic Kaposi’s sarcoma occurs in sub-Saharan indigenous African populations.2 It typically arises in younger men under the age of 40 years but may also affect women and children. The clinical course ranges from indolent skin lesions on the extremities to more pronounced visceral involvement. There is a less common, aggressive subtype that can progress quickly in children and involves the lymph nodes and organs with potentially fatal sequelae.
Iatrogenic (transplant-related) Kaposi’s sarcoma is associated with drug-induced immunosuppression.1 It originally arose in the 1970s after patients received long-term corticosteroids following solid organ transplantation. It has since been associated with other immunosuppressive therapies, including chemotherapy. Iatrogenic Kaposi’s sarcoma is slightly more common in men than women and may include mucocutaneous tissue, lymph node or visceral involvement. Approximately one in 200 transplant recipients develops Kaposi’s sarcoma in the United States.1 Usually, these patients were already infected with Kaposi’s sarcoma herpes virus prior to the transplant. They subsequently became vulnerable with the initiation of immunosuppressive medications.
Epidemic (AIDS-associated) Kaposi’s sarcoma is the most common variant of the disease. It is one of several “AIDS defining” illnesses that help to differentiate HIV infection from AIDS. The clinical presentation ranges from minimal disease to widely disseminated mucocutaneous lesions.3 Skin lesions are visible most frequently on the lower extremities, face and genitalia. Involvement of the viscera, particularly the gastrointestinal tract and lungs, may occur in 25 to 50 percent of patients.2,7 Before the introduction of highly active antiretroviral therapy (HAART), the prevalence of Kaposi’s sarcoma in AIDS patients was more than 20,000 times that of the general population.4 Kaposi’s sarcoma has since become less common in the United States with approximately six cases per million people annually. The thought is that aggressive antiretroviral therapy prevents further weakening of immunological function and thereby prevents reactivation of latent Kaposi’s sarcoma herpes virus infection.5
While the populations affected by Kaposi’s sarcoma are different, some of the basic pathological processes are quite similar. In Kaposi’s sarcoma, the endothelial cells of blood and lymphatic vessels are infected with Kaposi’s sarcoma herpes virus. The viral genes are responsible for stimulating cell proliferation, inhibiting apoptosis, inducing angiogenesis and releasing inflammatory cytokines. Virtually all patients with Kaposi’s sarcoma are infected with Kaposi’s sarcoma herpes virus although not all individuals infected with the virus develop Kaposi’s sarcoma. The development of Kaposi’s sarcoma appears to require additional cofactors that in theory are genetic, immunologic and environmental.5 This remains an area of ongoing research.
Kaposi’s sarcoma skin lesions typically vary in color from pink to red, purple and brown. There are three progressive stages: patches, plaques and nodules. The nodular lesions can be exophytic or fungating with breakdown of overlying skin and ulceration. Lymphedema is a common complication resulting from obstruction of lymphatics and may be extensive.4
The differential diagnosis for Kaposi’s sarcoma includes nevi, hematoma, angioma, dermatofibroma, hemangioma, pyogenic granuloma, acroangiodermatitis, angiosarcoma, extrapulmonary Pneumocystis jirovecii, bacillary angiomatosis, Sporothrix schenckii, atypical mycobacterial or fungal infections. Definitive diagnosis requires a biopsy with histopathological tissue evaluation. Histological features characteristic of Kaposi’s sarcoma include whorls of spindle-shaped cells, leukocytic infiltration and neovascularization with aberrant proliferation of small vessels. Microhemorrhaging and hemosiderin deposition are also evident due to a lack of basement membrane within the small vessels. Bacillary angiomatosis may mimic early Kaposi’s sarcoma histology and thus requires Warthin-Starry silver staining to differentiate it.2
Pertinent Pearls On The Workup And Treatment
The initial workup should involve a complete exam of the skin, oral cavity, genitalia and rectum with a chest X-ray to rule out pulmonary involvement. Additional procedures may be required to assess the extent of pulmonary or gastrointestinal involvement.2 With AIDS-associated Kaposi’s sarcoma, the severity of the disease and immunosuppression will also need assessment of the CD4 count and viral load, and ascertaining the presence of other systemic HIV-associated illnesses. The major treatment goals for Kaposi’s sarcoma are symptom palliation, decreasing tumor size and edema, management of organ compromise and prevention of disease progression. Treatments are categorized as local or systemic.
Local treatments entail the management of localized Kaposi’s sarcoma lesions and include radiotherapy, topical alitretinoin gel (Panretin, Eisai), cryotherapy, intralesional chemotherapy or biological agent injections, laser treatment, photodynamic treatment and excisional surgery.4
Systemic therapy is indicated for more advanced, extensive or rapidly progressive Kaposi’s sarcoma. Systemic treatment includes cytotoxic chemotherapy and HAART for AIDS-associated Kaposi’s sarcoma.6 Previous chemotherapeutic agents include bleomycin, vinblastine, vincristine (Oncovin, Pfizer), doxorubicin and etoposide (Etopophos, Bristol-Myers Squibb). These have had limited use recently since the development of liposomal anthracyclines such as pegylated liposomal doxorubicin and liposomal daunorubicin (Cerubidine, Bedford Laboratories) and taxanes like paclitaxel (Taxol, Bristol-Myers Squibb), which are now considered the primary treatment modalities of choice for systemic cytotoxic chemotherapy.
Both protease inhibitor and non-nucleoside reverse transcriptase inhibitor types of HAART are associated with a significant decrease in the incidence and size of lesions for AIDS-associated Kaposi’s sarcoma.8 If fact, without antiretroviral therapy, attempts to treat AIDS-associated Kaposi’s sarcoma via chemotherapy or radiotherapy have demonstrated poor overall survival with minimal palliative benefits.4 Combined treatment using antiretroviral therapy and liposomal doxorubicin is considered the standard of care for AIDS-associated Kaposi’s sarcoma.
