The spectrum of HIV-related nephropathy in children.

BACKGROUND: Despite the burden of human immunodeficiency virus (HIV) disease in Southern Africa, there have been few reports of HIV-related nephropathy in children. This study outlines the spectrum of HIV-1-related kidney diseases of children in KwaZulu-Natal, South Africa. METHODS: A review of the clinical presentation, laboratory and histopathological findings of children diagnosed with HIV-related nephropathy. RESULTS: Forty-nine out of 71 children (1-16 years old) with HIV-1 related nephropathy underwent kidney biopsy. The most common histopathological finding was focal segmental glomerulosclerosis (FSGS), which was present in 32 (65.3%) children; 13 (26.5%) having collapsing glomerulopathy and 19 (38.8%) classic FSGS. The majority of patients showed haematological (86.4%) and electrolyte abnormalities (69.4%). Renal impairment was present in 41% of patients on initial presentation. However, end-stage kidney disease was present in only 4% of these patients. All patients were treated with highly active anti-retroviral therapy (HAART), the majority (79.6%) showed decreased proteinuria with 38.8% having complete remission. CONCLUSIONS: This study, one of the largest series of children reported from Africa, demonstrates that nephrotic syndrome due to HIV-associated nephropathy (HIVAN) is the commonest presentation of HIV-related nephropathy in childhood. Highly active anti-retroviral therapy in combination with angiotensin-converting enzyme antagonists is highly effective in decreasing proteinuria and preserving renal function.

Extra-uterine myoid tumours in patients with acquired immunodeficiency syndrome: a clinicopathological reappraisal.

AIMS: AIDS-associated myoid tumours (AIDS-MTs), often Epstein-Barr virus (EBV)-associated (EBV-positive MTs), include smooth muscle tumors (SMTs) and the relatively recently recognized myopericytomas (MPCTs). The myoid immunophenotype of AIDS-MTs has been documented inconsistently. The aim of this study was to reappraise the phenotypic and immunophenotypic features of extra-uterine AIDS-MTs and the clinical profile of afflicted patients. METHODS AND RESULTS: EBV early RNA in-situ hybridization testing on 27 AIDS-MTs from 25 patients identified 19 of 27 (70.4%) EBV-positive MTs and eight of 27 (29.6%) EBV-negative MTs. EBV-positive MTs comprised 12 of 19 EBV-positive SMTs [six leiomyomas, one smooth muscle tumour of uncertain malignant potential (STUMP), five leiomyosarcomas] and seven of 19 EBV-positive MPCTs [benign (five), malignant (two)]. The EBV-negative MTs, made up exclusively of EBV-negative SMTs, included angioleiomyoma (one), leiomyoma (one), STUMP (one) and leiomyosarcomas (five). Malignant AIDS-MTs demonstrated hypercellularity, pleomorphism, increased mitoses and necrosis. EBV-positive leiomyosarcomas retained a conspicuous fascicular architecture. Four of five EBV-negative leiomyosarcomas demonstrated marked pleomorphism. All EBV-positive MPCTs and two EBV-positive leiomyosarcomas contained aggregates of desmin-negative round and oval cells. Seventeen of 25 patients died, mainly from comorbid diseases. CONCLUSION: While the reappraised spectrum of AIDS-MTs does not demonstrate divergent subtype-determined clinical behaviour, heightened awareness/recognition of this expanded spectrum will not only promote improved diagnosis of pleomorphic and myopericytic variants, which may be the sentinel clue to AIDS and its comorbidity, but will also facilitate distinction from histopathological mimics in specific anatomic locations.

Dermal Epstein Barr virus--associated leiomyosarcoma: tocsin of acquired immunodeficiency syndrome in two children.

Although rare in childhood, a relatively high incidence of smooth muscle tumors are recognized in patients with AIDS, mainly in association with Epstein Barr virus (EBV) infection. Although EBV-associated smooth muscle tumors have been documented rarely in the subcutis of AIDS patients, dermal involvement has not been described to date. This report describes dermal EBV-associated leiomyosarcomas (EBV-LMS) with a nodular but superficial plaque-like appearance on the lower limbs of 2 males, 9 and 12 years old. Histopathological assessment of the excised lesions demonstrated hypercellular mitotically active dermal tumors with hyperchromatic spindle and round cells, arranged in short fascicles and sheets, with microfoci of necrosis. A smooth muscle immunophenotype, including prominent desmin immunopositivity, and positive EBV-encoded RNA in situ hybridization investigation confirmed a diagnosis of EBV-LMS. Subsequent HIV seropositivity and AIDS were confirmed in both patients. Both patients also had pulmonary tuberculosis and received antituberculous therapy. Patient 1 had a 3 cm re-excision of the prior tumor site. He received highly active antiretroviral therapy, completed 6 months of antituberculous therapy, achieved immune reconstitution and viral suppression and is tumor-free 2 years after tumor excision. Patient 2 died before further therapy. The immune status, presence, and appropriate therapy of co-existent systemic infection and highly active antiretroviral therapy in AIDS patients with EBV-LMS are crucial to a favorable outcome.

Subcutaneous palisading granulomatous pseudocysts of Echinococcus granulosus origin.

BACKGROUND: Palisading granulomatous reactions are documented in many diseases. Although subcutaneous cystic echinococcosis (CE) is documented rarely, a subcutaneous palisading, granulomatous, pseudocystic (PGP) reaction to elusive Echinococcus granulosus membranous components, in the absence of cutaneous fistulization, is undocumented. METHODS: Seven-year clinicopathological review of subcutaneous echinococcal PGP reactions. RESULTS: Gross: seven thick-walled 'cysts' containing clear or straw-colored fluid were investigated. Histopathology: the pseudocysts contained a palisade of epithelioid histiocytes and giant cells. Focal periodic acid Schiff (PAS)-positive eosinophilic fragments, some resembling keratin 'flakes', were identified within the lumen or within the cellular palisade, consistent with a PGP reaction to fragmented E. granulosus membrane. Clinical correlation: the initial histopathological diagnosis of two patients was ruptured epidermoid cysts with an assumed granulomatous reaction to eosinophilic keratinous debris. Subsequent diagnosis of CE in the liver and cervical soft tissue necessitated review of the 'epidermoid cysts'; PAS-positive E. granulosus membranous fragments masqueraded as keratinous debris. Renal, hepatic and pleuropulmonary CE were confirmed in the remaining patients following confirmation of an echinococcal PGP reaction. CONCLUSION: Heightened awareness and obsessive appraisal of subcutaneous PGP reactions for subtle, focal, PAS-positive and echinococcal membranous fragments are pivotal to the diagnosis that also serves as a clue to visceral CE.

Bilateral lipomastia in men: a side effect of highly active antiretroviral therapy.

Breast enlargement in men and women is a documented feature of the highly active antiretroviral therapy- associated human immunodeficiency virus lipodystrophy syndrome. The exact underlying histomorphological features of this condition are speculative because most cases are diagnosed on clinical grounds with or without radiographic confirmation. The main documented causes of breast enlargement in men on highly active antiretroviral therapy include gynecomastia and lipomastia; however, biopsy-confirmed lipomastia is a rarely described phenomenon, with only 1 such case being described to date. In documenting 2 patients who underwent bilateral mastectomy for clinical gynecomastia of unknown cause, we emphasize the need for a greater degree of clinicopathological awareness of highly active antiretroviral therapy-associated lipomastia and the role of the histopathologist in the informed management of patients afflicted with human immunodeficiency virus infection on highly active antiretroviral therapy.

Pediatric renal cryptococcosis: novel manifestations in the acquired immunodeficiency syndrome era.

Pediatric cryptococcosis has been documented in various organs, but pediatric renal cryptococcosis (RC) remains undocumented to date. The authors report RC in 2 children with AIDS, 7 and 9 years of age, with proteinuria. Both patients, on antiretroviral therapy (ARV) for 28 (patient 1) and 54 (patient 2) weeks each, had secured viral immunosuppression, but immune restoration was realized by patient 1 only. Cryptococcal immune reconstitution inflammatory syndrome (IRIS) was diagnosed on the renal biopsy from patient 1 based on the clinicopathological profile and the presence of segmental glomerular and an interstitial lymphoplasmacytic and granulomatous reaction to Cryptococcus neoformans, with a predominance of capsule-deficient fungal forms. The renal biopsy from patient 2 demonstrated typical HIV-associated nephropathy with focal intratubular and interstitial C neoformans yeasts. Pediatric AIDS-associated renal disease must be expanded to include RC and cryptococcal IRIS, and the kidney must be included as a potential sentinel site of IRIS.

Periampullary Epstein-Barr virus-associated myopericytoma.

Although myopericytoma occurs predominantly in the extremities, a wider anatomical distribution, malignant variant, and association with Epstein-Barr virus have been recognized recently. However, benign, malignant, or Epstein-Barr virus-myopericytoma has not been documented in the gastrointestinal tract to date. We report a periampullary Epstein-Barr virus-myopericytoma in a patient with AIDS who presented with obstructive jaundice. The tumor contained round, oval, and plump spindle cells arranged around and between slit-like, dilated, and staghorn vessels. A malignant variant was favored based on the presence of cellular pleomorphism, 23 mitoses per 10 high-power fields, necrosis, and lymphovascular involvement. Immunohistochemistry confirmed a myoid immunophenotype with h-Caldesmon positivity and desmin negativity. Epstein-Barr virus-encoded RNA was demonstrated by in situ hybridization. Heightened awareness of Epstein-Barr virus-myopericytoma and occurrence in the periampullary location are critical to diagnostic workup and differentiation of myopericytoma from other mesenchymal tumors and pseudotumors especially in small biopsies and in patients with AIDS.