Herbert B. Allen, MD

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

Case Report

A 60-year-old Cambodian woman presented with recurrent fever (temperature, up to 38.8°C) 7 months after receiving a kidney transplant secondary to polycystic kidney disease. Fever was attributed to recurrent pyelonephritis of the native kidneys while on mycophenolate mofetil, tacrolimus, and prednisone. As a result, she underwent a bilateral native nephrectomy and was found to have peritoneal nodules. Pathology of both native kidneys and peritoneal tissue revealed caseating granulomas and acid-fast bacilli (AFB) diagnostic for kidney and peritoneal tuberculosis (TB). She had no history of TB, and a TB skin test (purified protein derivative [PPD]) upon entering the United States from Cambodia a decade earlier was negative. Additionally, her pretransplantation PPD was negative.

Treatment with isoniazid, ethambutol, pyrazinamide, and levofloxacin was initiated immediately upon diagnosis, and all of her immunosuppressive medications—mycophenolate mofetil, tacrolimus, and prednisone—were discontinued. Her symptoms subsided within 1 week, and she was discharged from the hospital. Over the next 2 months, her immunosuppressive medications were restarted, and her TB medications were periodically discontinued by the Tuberculosis Control Program at the Department of Health (Philadelphia, Pennsylvania) due to severe thrombocytopenia. During this time, she was closely monitored twice weekly in the clinic with blood draws performed weekly.

Approximately 10 weeks after initiation of treatment, she noted recurrent subjective fever (temperature, up to 38.8°C) and painful lesions on the right side of the flank, left breast, and left arm of 3 days’ duration. Physical examination revealed a warm, dull red, tender nodule on the right side of the flank (Figure 1) and subcutaneous nodules with no overlying skin changes on the left breast and left arm. A biopsy of the lesion on the right side of the flank was performed, which resulted in substantial purulent drainage. Histologic analysis showed an inflammatory infiltrate within the deep dermis composed of neutrophils, macrophages, and giant cells, indicative of suppurative granulomatous dermatitis (Figure 2). Ziehl-Neelsen stain demonstrated rare AFB within the cytoplasm of macrophages, suggestive of Mycobacterium tuberculosis infection (Figure 3). A repeat chest radiograph was normal.

Comment

Clinical Presentation
Cutaneous TB is an uncommon manifestation of TB that can occur either exogenously or endogenously.¹ It tends to occur primarily in previously infected TB patients through hematogenous, lymphatic, or contiguous spread.² Due to their immunocompromised state, solid organ transplant recipients have an increased incidence of primary and reactivated latent TB reported to be 20 to 74 times greater than the general population.^3,4 One report stated the total incidence of posttransplant TB as 0.48% in the West and 11.8% in endemic regions such as India.⁵ The occurrence of cutaneous TB is rare among solid organ transplant recipients.¹ On average, a diagnosis of latent TB is made 9 months after transplantation because of the opportunistic nature of M tuberculosis in an immunosuppressed environment.⁶

TB Subtypes
Cutaneous TB can be in the form of localized disease (eg, primary tuberculous chancre, TB verrucosa cutis, lupus vulgaris, smear-negative scrofuloderma), disseminated disease (eg, disseminated TB, TB gumma, orificial TB, miliary cutaneous TB), or tuberculids (eg, papulonecrotic tuberculid, lichen scrofulosorum, erythema induratum).⁷ Due to the pustular epithelioid cell granulomas and AFB positivity of the involved cutaneous lesions, our patient’s TB can be classified as a metastatic TB abscess or gummatous TB.⁷

Metastatic TB abscess, an uncommon subtype of cutaneous TB, generally is only seen in malnourished children and notably immunocompromised individuals.^2,8,9 In these individuals, systemic failure of cell-mediated immunity enables M tuberculosis to hematogenously infect various organs of the body, resulting in alternative forms of TB, such as gummatous-type TB.¹⁰ One study reported that of the 0.1% of dermatology patients presenting with cutaneous TB, only 5.4% of these individuals had the rarer gummatous form.⁷ These metastatic TB abscesses begin as a single or multiple nontender subcutaneous nodule(s), which breaks down and softens to form a draining sinus abscess.^2,8,9 Abscesses are most commonly seen on the trunk and extremities; however, they can be found nearly anywhere on the body.⁸ The pathology of cutaneous TB lesions demonstrates caseating necrosis with epithelioid and giant cells forming a surrounding rim.⁹

Diagnosis
Diagnosis may be difficult because of the vast number of dermatologic conditions that resemble cutaneous TB, including mycoses, sarcoidosis, leishmaniasis, leprosy, syphilis, other non-TB mycobacteria, and Wegener granulomatosis.⁹ Thus, confirmatory diagnosis is made via clinical presentation, detailed history and physical examination, and laboratory tests.¹¹ These tests include the Mantoux tuberculin skin test (PPD or TST) or IFN-γ release assays (QuantiFERON-TB Gold test), identification of AFB on skin biopsy, and isolation of M tuberculosis from tissue culture or polymerase chain reaction.¹¹Given our patient’s history, clinical presentation, and the identification of mycobacteria with AFB stain, the diagnosis of cutaneous gummatous TB was confirmed.

At-Risk Populations
The recommendation for the identification of at-risk populations for latent TB testing and treatment have been clearly defined by the World Health Organization (Table).¹² Our patient met 2 of these criteria: she had been preparing for organ transplantation and was from a country with high TB burden. Such at-risk patients should be tested for a latent TB infection with either IFN-γ release assays or PPD.¹²These recommendations are supported by the American Thoracic Society, which specifies that a positive PPD test in a solid organ transplant recipient is defined as having induration greater than 5 mm.¹³ However, even with a high index of suspicion, it has been reported that as many as 75% to 80% of organ recipients who developed TB had a false-negative pretransplantation PPD due to anergy from immunosuppression.¹⁴ Given the notable risk for TB in organ transplant recipients on immunosuppressive medications, these patients should receive screening tests with high sensitivity and specificity, while controlling for possible anergy. Unfortunately, the role of anergy testing in the diagnosis of latent TB is not well defined, and thus not recommended at this time.^13,15 It is recommended to repeat PPD testing 7 to 10 days after the first test as a booster effect to rule out false-negative results.¹⁵

Finally, thrombocytopenia is an infrequent, life-threatening complication that can be acquired by immunocompromised patients on anti-TB therapy.¹⁷ Drug-induced thrombocytopenia can be caused by a variety of medications, including rifampicin, isoniazid, ethambutol, and pyrazinamide. Diagnosis of drug-induced thrombocytopenia can be confirmed only after discontinuation of the suspected drug and subsequent resolution of the thrombocytopenia.¹⁷ Our patient initially became thrombocytopenic while taking isoniazid, ethambutol, pyrazinamide, and levofloxacin. However, her platelet levels improved once the pyrazinamide was discontinued, thereby suggesting pyrazinamide-induced thrombocytopenia.

Conclusion

The risk for infectious disease reactivation in an immunocompromised patient undergoing transplant surgery is notable. Our findings emphasize the value of a comprehensive pretransplant evaluation, vigilance even when test results appear negative, and treatment of latent TB within this population.^16,18,19 Furthermore, this case illustrates a noteworthy example of a rare form of cutaneous TB, which should be considered and included in the differential for cutaneous lesions in an immunosuppressed patient.

An 88-year-old Caucasian man of Italian ancestry came into our clinic with multiple, painful purple-red “growths” on his left foot that he’d had for several years (FIGURE 1).

The patient had no systemic complaints (no fever, chills, weight loss, night sweats). He had a history of hypertension, a cardiac valve replacement, and chronic back pain (secondary to a motor vehicle accident). He was taking warfarin and nadolol.

The patient had multiple, 0.1– to 0.5-cm purple-red papules and nodules on the dorsal and plantar surfaces of the left foot, with associated moderate lower extremity edema and mottled dyspigmentation.

We did a punch biopsy, which showed a nodular neoplasm composed of moderately plump, spindle-shaped cells in short interweaving fascicles and numerous extravasated erythrocytes in the spaces (“vascular slits”) between the spindle-shaped cells (FIGURE 2).

FIGURE 1
Painful papules and nodules

FIGURE 2
Hematoxylin/eosin stain

What is your diagnosis?
How would you manage this condition?

Diagnosis: Kaposi’s sarcoma

Classic Kaposi’s sarcoma is a rare mesenchymal tumor most often seen in elderly men of Mediterranean or Ashkenazi Jewish origin with an annual incidence in the United States of between 0.02% and 0.06%, with a peak occurring in the 5th to 8th decade of life.¹ (Two-thirds of cases develop after the age of 50.) Population-based studies in the United States have shown a male-to-female ratio of 4:1.¹

First described by the Hungarian dermatologist Moritz Kaposi in 1872, Kaposi’s sarcoma assumed prominence during the emerging HIV epidemic and is now the most common tumor in patients with acquired immune deficiency syndrome (AIDS).²

Recent research has implicated the human herpes virus–8 (HHV–8) as an inductive agent (necessary though not sufficient) in all epidemiologic subsets of the disease.²

There are 4 principal clinical variants of Kaposi’s sarcoma:

1. classic (or chronic),
2. African endemic (includes childhood lymphadenopathic),
3. transplant-associated, and
4. AIDS-related.

What you’ll see

Clinically, classic Kaposi’s sarcoma often first manifests as blue-red, well-demarcated, painless macules confined to the distal lower extremities.³ These slow-growing lesions may enlarge to forms papules and plaques, or progress to nodules and tumors. Unilateral involvement is often observed at the outset of the disease, with potential centripetal spread occurring late-in-course.³

Early lesions are generally soft, spongy, and “angiomatous,” while in the advanced state, lesional skin becomes hard, solid, and brown in color.³ Edema of the surrounding tissue is common. In addition to the skin, classic Kaposi’s sarcoma also involves mucosal sites (especially the oral and gastrointestinal mucosae).

Differential includes melanocytic nevus

A differential diagnosis for classic Kaposi’s sarcoma includes stasis dermatitis (“acroangiodermatitis”), melanocytic nevus, pyogenic granuloma, hemangioma, granuloma annulare, arthropod assault, and dermatofibroma/dermatofibrosarcoma protuberans (DF/DFSP).

Melanocytic nevi, pyogenic granuloma, hemangioma, granuloma annulare, and DF/DFSP ordinarily feature single lesions, while Kaposi’s sarcoma has multiple lesions. An arthropod assault is pruritic, and stasis dermatitis typically has dilated/varicose veins.

Histology will confirm your suspicions

While epidemiological and clinical factors may suggest classic Kaposi’s sarcoma, a final diagnosis ultimately rests on confirmatory histology. The pathology of classic Kaposi’s sarcoma (like all of the variant subtypes) is based solely on stage of the lesion.

Early patch-stage lesions exhibit papillary dermal proliferation of small, angulated vessels lined by bland endothelial cells with an accompanying sparse infiltrate of lymphocytes and plasma cells.

As the disease progresses to the plaque stage, the vascular proliferation expands into the reticular dermis and subcutis. The transition to nodular Kaposi’s sarcoma develops when a population of spindle cells expressing endothelial markers occurs between the “vascular slits” (FIGURE 2).

Chemotherapy for rapidly progressive disease

There is minimal evidence-based data for the treatment of Kaposi’s sarcoma. Treatment options for limited disease include surgical excision, cryotherapy, laser ablation, topical retinoids (alitretinoin), interferon-alpha, and radiation.¹

If rapidly progressive disease (>10 new lesions per month) exists, the most effective treatment remains systemic chemotherapy (vincristine, doxorubicin, vinblastine,⁴ bleomycin,⁴ or paclitaxel⁵). The benefits of chemotherapy can last for months—and even years.

Liquid nitrogen cryotherapy does the trick

We treated our patient with liquid nitrogen cryotherapy that was applied at regular 4- to 6-week intervals over several months. After 3 months, our patient’s lesions were nearly resolved. We followed him monthly thereafter.

Correspondence
John Patrick Welsh, MD, Associates in Dermatology, 4727 Friendship Avenue, Suite 300, Pittsburgh, PA 15224-1778; jp_welsh@hotmail.com.

An 88-year-old Caucasian man of Italian ancestry came into our clinic with multiple, painful purple-red “growths” on his left foot that he’d had for several years (FIGURE 1).

The patient had no systemic complaints (no fever, chills, weight loss, night sweats). He had a history of hypertension, a cardiac valve replacement, and chronic back pain (secondary to a motor vehicle accident). He was taking warfarin and nadolol.

The patient had multiple, 0.1– to 0.5-cm purple-red papules and nodules on the dorsal and plantar surfaces of the left foot, with associated moderate lower extremity edema and mottled dyspigmentation.

We did a punch biopsy, which showed a nodular neoplasm composed of moderately plump, spindle-shaped cells in short interweaving fascicles and numerous extravasated erythrocytes in the spaces (“vascular slits”) between the spindle-shaped cells (FIGURE 2).

FIGURE 1
Painful papules and nodules

FIGURE 2
Hematoxylin/eosin stain

What is your diagnosis?
How would you manage this condition?

Diagnosis: Kaposi’s sarcoma

Classic Kaposi’s sarcoma is a rare mesenchymal tumor most often seen in elderly men of Mediterranean or Ashkenazi Jewish origin with an annual incidence in the United States of between 0.02% and 0.06%, with a peak occurring in the 5th to 8th decade of life.¹ (Two-thirds of cases develop after the age of 50.) Population-based studies in the United States have shown a male-to-female ratio of 4:1.¹

First described by the Hungarian dermatologist Moritz Kaposi in 1872, Kaposi’s sarcoma assumed prominence during the emerging HIV epidemic and is now the most common tumor in patients with acquired immune deficiency syndrome (AIDS).²

Recent research has implicated the human herpes virus–8 (HHV–8) as an inductive agent (necessary though not sufficient) in all epidemiologic subsets of the disease.²

There are 4 principal clinical variants of Kaposi’s sarcoma:

1. classic (or chronic),
2. African endemic (includes childhood lymphadenopathic),
3. transplant-associated, and
4. AIDS-related.

What you’ll see

Clinically, classic Kaposi’s sarcoma often first manifests as blue-red, well-demarcated, painless macules confined to the distal lower extremities.³ These slow-growing lesions may enlarge to forms papules and plaques, or progress to nodules and tumors. Unilateral involvement is often observed at the outset of the disease, with potential centripetal spread occurring late-in-course.³

Early lesions are generally soft, spongy, and “angiomatous,” while in the advanced state, lesional skin becomes hard, solid, and brown in color.³ Edema of the surrounding tissue is common. In addition to the skin, classic Kaposi’s sarcoma also involves mucosal sites (especially the oral and gastrointestinal mucosae).

Differential includes melanocytic nevus

A differential diagnosis for classic Kaposi’s sarcoma includes stasis dermatitis (“acroangiodermatitis”), melanocytic nevus, pyogenic granuloma, hemangioma, granuloma annulare, arthropod assault, and dermatofibroma/dermatofibrosarcoma protuberans (DF/DFSP).

Melanocytic nevi, pyogenic granuloma, hemangioma, granuloma annulare, and DF/DFSP ordinarily feature single lesions, while Kaposi’s sarcoma has multiple lesions. An arthropod assault is pruritic, and stasis dermatitis typically has dilated/varicose veins.

Histology will confirm your suspicions

While epidemiological and clinical factors may suggest classic Kaposi’s sarcoma, a final diagnosis ultimately rests on confirmatory histology. The pathology of classic Kaposi’s sarcoma (like all of the variant subtypes) is based solely on stage of the lesion.

Early patch-stage lesions exhibit papillary dermal proliferation of small, angulated vessels lined by bland endothelial cells with an accompanying sparse infiltrate of lymphocytes and plasma cells.

As the disease progresses to the plaque stage, the vascular proliferation expands into the reticular dermis and subcutis. The transition to nodular Kaposi’s sarcoma develops when a population of spindle cells expressing endothelial markers occurs between the “vascular slits” (FIGURE 2).

Chemotherapy for rapidly progressive disease

There is minimal evidence-based data for the treatment of Kaposi’s sarcoma. Treatment options for limited disease include surgical excision, cryotherapy, laser ablation, topical retinoids (alitretinoin), interferon-alpha, and radiation.¹

If rapidly progressive disease (>10 new lesions per month) exists, the most effective treatment remains systemic chemotherapy (vincristine, doxorubicin, vinblastine,⁴ bleomycin,⁴ or paclitaxel⁵). The benefits of chemotherapy can last for months—and even years.

Liquid nitrogen cryotherapy does the trick

We treated our patient with liquid nitrogen cryotherapy that was applied at regular 4- to 6-week intervals over several months. After 3 months, our patient’s lesions were nearly resolved. We followed him monthly thereafter.

Correspondence
John Patrick Welsh, MD, Associates in Dermatology, 4727 Friendship Avenue, Suite 300, Pittsburgh, PA 15224-1778; jp_welsh@hotmail.com.

An 88-year-old Caucasian man of Italian ancestry came into our clinic with multiple, painful purple-red “growths” on his left foot that he’d had for several years (FIGURE 1).

The patient had no systemic complaints (no fever, chills, weight loss, night sweats). He had a history of hypertension, a cardiac valve replacement, and chronic back pain (secondary to a motor vehicle accident). He was taking warfarin and nadolol.

The patient had multiple, 0.1– to 0.5-cm purple-red papules and nodules on the dorsal and plantar surfaces of the left foot, with associated moderate lower extremity edema and mottled dyspigmentation.

We did a punch biopsy, which showed a nodular neoplasm composed of moderately plump, spindle-shaped cells in short interweaving fascicles and numerous extravasated erythrocytes in the spaces (“vascular slits”) between the spindle-shaped cells (FIGURE 2).

FIGURE 1
Painful papules and nodules

FIGURE 2
Hematoxylin/eosin stain

What is your diagnosis?
How would you manage this condition?

Diagnosis: Kaposi’s sarcoma

Classic Kaposi’s sarcoma is a rare mesenchymal tumor most often seen in elderly men of Mediterranean or Ashkenazi Jewish origin with an annual incidence in the United States of between 0.02% and 0.06%, with a peak occurring in the 5th to 8th decade of life.¹ (Two-thirds of cases develop after the age of 50.) Population-based studies in the United States have shown a male-to-female ratio of 4:1.¹

First described by the Hungarian dermatologist Moritz Kaposi in 1872, Kaposi’s sarcoma assumed prominence during the emerging HIV epidemic and is now the most common tumor in patients with acquired immune deficiency syndrome (AIDS).²

Recent research has implicated the human herpes virus–8 (HHV–8) as an inductive agent (necessary though not sufficient) in all epidemiologic subsets of the disease.²

There are 4 principal clinical variants of Kaposi’s sarcoma:

1. classic (or chronic),
2. African endemic (includes childhood lymphadenopathic),
3. transplant-associated, and
4. AIDS-related.

What you’ll see

Clinically, classic Kaposi’s sarcoma often first manifests as blue-red, well-demarcated, painless macules confined to the distal lower extremities.³ These slow-growing lesions may enlarge to forms papules and plaques, or progress to nodules and tumors. Unilateral involvement is often observed at the outset of the disease, with potential centripetal spread occurring late-in-course.³

Early lesions are generally soft, spongy, and “angiomatous,” while in the advanced state, lesional skin becomes hard, solid, and brown in color.³ Edema of the surrounding tissue is common. In addition to the skin, classic Kaposi’s sarcoma also involves mucosal sites (especially the oral and gastrointestinal mucosae).

Differential includes melanocytic nevus

A differential diagnosis for classic Kaposi’s sarcoma includes stasis dermatitis (“acroangiodermatitis”), melanocytic nevus, pyogenic granuloma, hemangioma, granuloma annulare, arthropod assault, and dermatofibroma/dermatofibrosarcoma protuberans (DF/DFSP).

Melanocytic nevi, pyogenic granuloma, hemangioma, granuloma annulare, and DF/DFSP ordinarily feature single lesions, while Kaposi’s sarcoma has multiple lesions. An arthropod assault is pruritic, and stasis dermatitis typically has dilated/varicose veins.

Histology will confirm your suspicions

While epidemiological and clinical factors may suggest classic Kaposi’s sarcoma, a final diagnosis ultimately rests on confirmatory histology. The pathology of classic Kaposi’s sarcoma (like all of the variant subtypes) is based solely on stage of the lesion.

Early patch-stage lesions exhibit papillary dermal proliferation of small, angulated vessels lined by bland endothelial cells with an accompanying sparse infiltrate of lymphocytes and plasma cells.

As the disease progresses to the plaque stage, the vascular proliferation expands into the reticular dermis and subcutis. The transition to nodular Kaposi’s sarcoma develops when a population of spindle cells expressing endothelial markers occurs between the “vascular slits” (FIGURE 2).

Chemotherapy for rapidly progressive disease

There is minimal evidence-based data for the treatment of Kaposi’s sarcoma. Treatment options for limited disease include surgical excision, cryotherapy, laser ablation, topical retinoids (alitretinoin), interferon-alpha, and radiation.¹

If rapidly progressive disease (>10 new lesions per month) exists, the most effective treatment remains systemic chemotherapy (vincristine, doxorubicin, vinblastine,⁴ bleomycin,⁴ or paclitaxel⁵). The benefits of chemotherapy can last for months—and even years.

Liquid nitrogen cryotherapy does the trick

We treated our patient with liquid nitrogen cryotherapy that was applied at regular 4- to 6-week intervals over several months. After 3 months, our patient’s lesions were nearly resolved. We followed him monthly thereafter.

Correspondence
John Patrick Welsh, MD, Associates in Dermatology, 4727 Friendship Avenue, Suite 300, Pittsburgh, PA 15224-1778; jp_welsh@hotmail.com.