Cytokeratin expression in gastrointestinal stromal tumors: morphology, meaning, and mimicry.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are biologically distinctive neoplasms harboring KIT and PDGFRA mutations. Cytokeratin expression in GISTs is an under-recognized diagnostic pitfall, especially in high grade GISTs with limited biopsy material and from metastatic sites. MATERIALS AND METHODS: We evaluated the histomorphology and expression of four 'broad-spectrum' cytokeratin markers, AE1-AE3, CAM 5.2, MNF-116, and 34ßE12 in 64 GISTs diagnosed over a 68-month period. Individual cytokeratins 5, 6, 7, 8, 14, 17, 18, 19, and 20 were investigated in the 'broad-spectrum' cytokeratin-positive GISTs. RESULTS: Of 64 GISTs, 10 (15%) demonstrated cytokeratin immunopositivity. All 10, considered high risk by the National Institutes of Health consensus approach, were immunopositive for CAM 5.2 and MNF-116. Seven were AE1-AE3 immunopositive. Cytokeratins 8 and 18 were confirmed in 10 and 9 GISTs, respectively. One GIST demonstrated biphasic morphology with cytokeratin immunonegativity in low-grade spindle and immunopositivity in high-grade epithelioid foci. KIT and PDGFRA mutational analysis, undertaken in 5/10 cytokeratin-positive GISTs, harbored KIT exon 11 mutations. CONCLUSION: We hypothesize that cytokeratin expression exclusively in high risk GISTs is a consequence of tumor progression. Given the increasing number of commercially available broad-spectrum cytokeratin immunomarkers, including those reacting with cytokeratins 8 and 18, cytokeratin-positive GISTs must be differentiated from carcinomas, melanomas, and a range of cytokeratin-positive sarcomas to ensure optimal patient management and prognostication.

Pediatric plasmablastic lymphoma: a clinicopathologic study.

Plasmablastic lymphoma (PBL) is reported rarely in children. To date, 10 cases are documented in the English-language literature. This study, based on 13 biopsies from 11 HIV-positive children (9 males, 2 females), documents the clinicopathologic features of PBL. The CD4 count ranged from 9 to 800 cells/mm(3). All biopsies demonstrated exclusive plasmablastic morphology; CD20 immunonegativity; and VS38c, EMA, CD31, MUM-1, CD45, and CD79a immunopositivity. B-cell monoclonality was confirmed in all biopsies. Of 3 biopsies subjected to FISH investigation, 2 had a t(8,14) translocation. Nine patients with follow-up details were treated exclusively with HAART (highly active antiretroviral therapy) or with combinations of HAART, chemotherapy, and radiotherapy. Seven patients died. PBL histomorphology, disease stage, and treatment modalities employed were not predictive of outcome. The survival of 2 stage 4 patients for 3 and 8 years each, managed on HAART, chemotherapy, and radiotherapy, however, may justify a role for combined therapeutic modalities for PBL.

Infantile donovanosis presenting as external auditory canal polyps: a diagnostic trap.

Two infants, 6 months and 4 months of age, presented with bilateral or unilateral external auditory canal polyps and otorrhea, respectively. Additional findings on examination included otitis media and mastoiditis. Tympanic membrane perforation was noted in one patient and a postauricular abscess in the other. Incisional biopsies of the polyps and abscess were reported as nonspecific mixed inflammation and abscess wall, respectively. There was a limited response to an empirical 5-day course of trimethoprim sulfamethoxazole. The children were referred to the academic hospital, and excision of the polyps and biopsies of the middle ear, mastoid, and postauricular abscess was undertaken. All the biopsies demonstrated donovanosis. Reappraisal of the initial incisional biopsies also confirmed donovanosis. Trimethoprim sulfamethoxazole was administered to both patients for 3 weeks, with resolution of the lesions. Subsequent investigations confirmed genital tract donovanosis, human immunodeficiency virus seropositivity, acquired immunodeficiency syndrome, and pulmonary tuberculosis in both mothers. Heightened awareness of the occurrence of donovanosis at unusual sites and improved recognition of the histomorphological features of the disease, especially in small and superficial biopsies, are pivotal not only for its correct diagnosis in extragenital cutaneous and extracutaneous locations but also for timely and adequate therapy and an improved infant and maternal outcome.

Bartonella quintana-induced vulval bacillary angiomatosis.

Bacillary angiomatosis (BA) is an increasingly reported infection, mainly in patients with acquired immunodeficiency syndrome. Different epidemiological risk factors are associated with the transmission of the causative agents, Bartonella henselae and B. quintana. Vulval BA is described rarely. Two patients presented with a vulval mass (Patient 1) and a verrucous vulval growth (Patient 2), which were diagnosed clinically as tuberculosis and carcinoma, respectively. Patient 1 also had pulmonary tuberculosis and Kaposi sarcoma. Biopsy of the vulval lesions confirmed BA, characterized by a multilobular proliferation of blood vessels that were lined by epithelioid endothelial cells. There were prominent intervascular neutrophils, karyorrhectic debris, and clumps of paravascular argyrophilic organisms. The biopsy from Patient 1 was deep dermal/subcutaneous in location and displayed foci of confluent suppuration. There was florid pseudoepitheliomatous hyperplasia in the biopsy from Patient 2. Molecular investigations confirmed intralesional B. quintana, hitherto unreported in vulval BA, as the causative agent in both biopsies. On follow-up, Patient 2 had developed additional lesions in the vulva and thigh, but all her lesions and the vulval mass (Patient 1) responded to erythromycin treatment. Patient 1 succumbed to tuberculosis. Heightened recognition of BA underpins rapid and optimal clinicopathological diagnosis, even in uncommon locations. Identification of the causative Bartonella species is important for appropriate, interventive social management.

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.

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.

Langerhans cells in anaplastic Kaposi sarcoma with a paucivascular phenotype: a potential diagnostic pitfall.

Anaplastic Kaposi sarcoma (AKS), a rare variant of Kaposi sarcoma, has a poorly recognized histomorphologic spectrum, including a paucivascular phenotype, that mimics a range of undifferentiated malignancies. This study, that highlights the hitherto undocumented phenomenon of S100-protein-positive Langerhans cells (SLCs) as a potential diagnostic pitfall in paucivascular AKS, involved review of nine such AKS that required diagnostic immunohistochemical (IHC) work-up. All biopsies had a predominant or exclusive spindle or epithelioid cell infiltrate. The first three tumors were diagnosed as malignant peripheral nerve sheath tumor (2) and metastatic melanoma (1), based on S100-protein immunopositivity. Biopsy of a co-existent pigmented sole lesion (patient 3) demonstrated nodular KS. Subsequent IHC investigation of these three tumors demonstrated an endothelial phenotype and HHV8 immunopositivity, confirming AKS. CD1a and langerin staining of the S100-protein-positive cells confirmed Langerhans cells as the cause of the diagnostic pitfall. Subsequently, six further paucivascular AKS with intratumoral SLCs were recognized on histomorphological and IHC appraisal. In conclusion, heightened awareness of the histomorphologic spectrum, appropriate IHC investigation, and informed appraisal thereof, are critical to the diagnosis of AKS with an undifferentiated phenotype, and the avoidance of IHC pitfalls, such as those caused by under-recognition and misinterpretation of bystander SLCs in AKS.

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.

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.

Cutaneous colesional acquired immunodeficiency syndrome associated Kaposi sarcoma and cryptococcosis.

The clinicopathologic features of 4 AIDS patients with cutaneous colesional Kaposi sarcoma (KS) and cryptococcosis, a rare phenomenon, are described. Biopsies from 3 patients who were highly active antiretroviral therapy (HAART)-naive demonstrated predominant KS with a conspicuous spindle cell component and small aggregates of cryptococcal yeasts in 2 biopsies and predominant gelatinous cryptococcosis with attenuated KS spindle cells in 1 biopsy. One patient was HAART exposed. He had childhood pulmonary tuberculosis, was treated for disseminated cutaneous cryptococcosis 18 months earlier and presented with cutaneous lesions, odynophagia and massive cervical lymphadenopathy in the eighth week of HAART, after achieving viral suppression and a CD4 cell increase from 28 to 184 cells/µL. His skin biopsy demonstrated a dense lymphoplasmacytic infiltrate, neutrophils, and granulomas with admixed aggregates and single Cryptococcus neoformans and focal aggregation of human herpes virus 8-immunopositive spindle cells. Acid fast bacilli were not identified and mycobacterial molecular studies were negative. The features were compatible with cutaneous cryptococcal immune reconstitution inflammatory syndrome. His nodal and oropharyngeal biopsies demonstrated dense mixed, including granulomatous, inflammation with few cryptococcal yeasts and acid fast bacilli, confirmed to be Mycobacterium tuberculosis on polymerase chain reaction testing, without KS. These features were also compatible with immune reconstitution inflammatory syndrome, but the exact role of each infection in the extracutaneous sites was unconfirmed. Colesional KS and cryptococcosis served as the sentinel lesion of AIDS in 3 patients and of immune reconstitution inflammatory syndrome in 1 patient.

Gastric plexiform angiomyxoid myofibroblastic tumor.

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a relatively recently described gastric tumor with a peculiar plexiform growth pattern. PAMT is typified by a myofibroblastic immunophenotype that distinguishes it from the more common gastrointestinal stromal tumors and the rarely documented fibromyxomas. We report an additional PAMT, the seventh tumor with this label, which was an incidental finding on abdominal computed tomography scan of a 35-year-old Indian female. The tumor measured 4 x 3 x 2 cm and demonstrated plexiform architecture, myxoid stroma, prominent vasculature and spindled cells with myofibroblastic differentiation. The clinicopathological features, progesterone immunopositivity, hitherto undocumented, and mimicry of other primary and secondary gastric mesenchymal tumors, including endometrial stromal sarcoma, are discussed.

Paediatric intussusception caused by acquired immunodeficiency syndrome-associated Kaposi sarcoma.

PURPOSE: To document the clinicopathological features of paediatric intussusception caused by acquired immunodeficiency syndrome (AIDS)-associated Kaposi sarcoma (KS). METHODS: Clinicopathological features of six patients with AIDS-KS-associated intussusception were obtained retrospectively from departmental and hospital records. RESULTS: Six debilitated male children, without cutaneous KS, were presented with abdominal pain and vomiting for >1 week. Intussusception was the sentinel of HIV infection in five patients. One patient had been on HAART for 13 months. Three patients each had ileal and ileocolic intussusceptions; two had recurrent intussusception. Bowel resection was performed because of failed reduction, infarction and polypoid lead points in all patients, in addition to perforation and peritonitis in three. Five patients died, the immediate cause being massive hematochezia from anorectal KS and/or septic shock. One patient, who received post-surgical chemotherapy and HAART, is currently in remission. Pathologic examination confirmed intussusception due to KS. CONCLUSION: AIDS-KS-associated intussusception occurred without cutaneous KS. Resection of the infarcted segment may relieve the presenting obstruction, but recurrent intussusception may occur because every elevated KS is a potential lead point. AIDS-KS-I is rare but fatal in children, unless timely surgical intervention, optimal histopathological diagnosis, and appropriate medical management, including HAART and chemotherapy, are facilitated.

Granulomas in acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma: evidence for a role for Mycobacterium tuberculosis.

BACKGROUND: Co-lesional acquired immunodeficiency syndrome-associated cutaneous Kaposi sarcoma (AIDS-KS) and Mycobacterium tuberculosis-associated granulomatous inflammation are undocumented. METHOD: Retrospective appraisal of skin biopsies with co-lesional AIDS-KS and microscopic tuberculosis (TB). RESULTS: Sixteen biopsies from nine males and seven females form the study cohort. Histological assessment confirmed nodular and plaque KS in 12 and 4 cases each, respectively. Necrotizing, non-necrotizing and a combination of necrotizing and non-necrotizing granulomatous inflammation were present in nine, two and five biopsies each, respectively. The identification of acid fast bacilli on Ziehl-Neelsen staining and M. tuberculosis on polymerase chain reaction confirmed co-lesional TB in 15/16 biopsies. Co-lesional AIDS-KS and lichen scrofulosorum, hitherto undocumented, were confirmed in one biopsy. The histopathological findings served as a marker of human immunodeficiency virus (HIV) infection, visceral TB, therapeutic noncompliance and multidrug resistant pulmonary TB in nine, eight, five and one patient, respectively. M. tuberculosis was cultured from sputum or nodal tissue of all patients. CONCLUSION: Granulomatous inflammation in KS requires optimal histopathological and molecular investigation to confirm an M. tuberculosis origin. The cutaneous co-lesional occurrence of AIDS-KS and microscopic TB may serve as the sentinel clue to HIV infection, systemic TB, therapeutic noncompliance or multidrug resistant TB.

Extra-anogenital bilharziasis cutanea tarda revisited.

BACKGROUND: Even in schistosomiasis-endemic areas, extra-anogenital bilharziasis cutanea tarda (E-BCT) is rare. To date, the occurrence of E-BCT in pre-existing cutaneous pathology is undocumented. The study was undertaken to document the expanded clinicopathological spectrum and to comment on the putative pathogenetic mechanisms of a Schistosoma hematobium-associated E-BCT. METHODS: Eight-year clinicopathological appraisal of E-BCT. RESULTS: The clinical details are as follows. Seventeen specimens from 16 patients formed the study cohort. All specimens showed granulomatous inflammation with eosinophils, aggregates of terminal-spined S. hematobium ova and variable fibrosis. Copulating worms were identified in three biopsies. In 12/16 patients, E-BCT occurred in pre-existing pathology, including recurrent squamous papilloma (1), bilateral hidradenitis suppurativa (1) and scar tissue (10) with 7 showing a keloidal morphology. Prior and current urinary schistosomiasis was present in nine and seven patients, respectively. CONCLUSION: E-BCT, a reflection of prior, re-infective or inadequately treated urinary schistosomiasis, is deemed to be a function of egg-laying consequent to the aberrant pathway of worms. Based on E-BCT occurrence in pre-existing extra-anogenital cutaneous fibroinflammatory and cicatricial processes and the presence of adult worms in three extra-anogenital biopsies in the present study, it is hypothesized that altered tissue mesenchymal repair reactions may promote extra-anogenital cutaneous worm entrapment and egg-laying.

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.

Molluscum-like cutaneous cryptococcosis: a histopathological and pathogenetic appraisal.

BACKGROUND: Molluscum-like cutaneous cryptococcosis (MLCC) is characterized by hypopigmented or skin-colored papules with central umbilication. The histomorphological nuances of Cryptococcus neoformans infection that effect mimicry of molluscum contagiosum are undocumented. This histopathological study was undertaken to assess the histopathological characteristics of MLCC and to determine potential evolutionary pathogenetic mechanisms and significance. METHODS: A 5-year retrospective re-appraisal of cutaneous cryptococcosis biopsies with a clinical molluscum-like appearance. RESULTS: All 26 specimens with a molluscum-like appearance showed a dome-shaped architecture with central invagination and dermal C. neoformans of varying size and shape, with capsular fragmentation; 20 biopsies had a paucireactive appearance and 6 combined granulomatous and paucireactive foci. Twenty, two and four biopsies showed transepidermal, transfollicular and combined transepidermal and transfollicular elimination (TFE) of fungi, necrobiotic collagen and debris through the central invagination, respectively. Subepithelial neutrophils and collagen necrobiosis were identified in 8 and 14 cases each, respectively. Varying sized and shaped yeasts, capsules of varying width, capsular fragmentation and collagen necrobiosis were ultrastructurally confirmed. CONCLUSION: Transepithelial and TFE of C. neoformans, necrobiotic collagen, inflammatory cells and cellular debris account for the morphological attributes of MLCC. The eliminatory process is a potential public health hazard, serving as a vehicle for C. neoformans transfer to the exterior.

Otic pneumocystosis in acquired immune deficiency syndrome.

AIDS-associated otic pneumocystosis is rare. Of 14 cases documented mainly as case reports up to now, only 1 has been reported in the surgical pathology literature. We report 6 males, mean age of 32.3 years, with external auditory canal masses and otorrhea. Two biopsies contained a predominance of granulation tissue with a mixed inflammatory cell infiltrate and elusive foci of foamy exudate. In contrast, 4 biopsies demonstrated conspicuous angiocentric mantles of stippled, foamy exudate. Fibrin was noted in intravascular, perivascular, and intervascular locations. One biopsy demonstrated bordering of the foamy exudate by a palisaded granulomatous reaction, with adjacent discrete giant cell-containing granulomas. Special stains confirmed trophozoites and cysts within the foamy exudate. Review of 2 initial "nondiagnostic" biopsies confirmed granulation tissue and necrotic debris in which Pneumocystis jiroveci was identified in focal foamy exudate. After the diagnosis of otic pneumocystosis, all patients were initiated on trimethoprim-sulfamethoxazole. One patient also had dapsone. Two patients succumbed to pulmonary tuberculosis and 2 were lost to follow-up. One patient with pneumocystis pneumonia did not return for follow-up after 6 weeks. One patient experienced complete resolution of the mass on medical therapy, and is disease free for 4 years. Heightened recognition of the characteristic foamy exudate in an unconventional location remains the gold standard in the timely diagnosis of this eminently treatable disease. In all patients, otic pneumocystosis served as the sentinel of underlying HIV infection and AIDS.

Concomitant malacoplakia and granuloma inguinale of the cervix in acquired immune deficiency syndrome.

We describe concomitant granuloma inguinale (GI) and malacoplakia of the cervix in 2 acquired immune deficiency syndrome (AIDS) patients aged 27 and 36 years. Both patients presented with a bloody foul-smelling vaginal discharge. Speculum examination confirmed cervical ulceration, prompting the diagnosis of cervical carcinoma in both patients. Cervical punch biopsies confirmed the characteristic features of GI; granulation tissue containing a dense plasma cell infiltrate, aggregates of neutrophils, and vacuolated enlarged histiocytes containing Donovan bodies were noted. Many of these histiocytes and sheets of von Hansemann cells contained intracytoplasmic Michaelis-Gutmann bodies, confirming concomitant malacoplakia. Michaelis-Gutmann bodies were also present in extracellular locations. Ultrastructural examination confirmed these histopathologic findings. One patient died of disseminated tuberculosis before treatment was initiated. The other patient did not return for a follow-up visit of her cervical lesion. Concomitant GI and malacoplakia is unreported in genital and extragenital sites; Klebsiella granulomatis must therefore be added to the list of bacteria associated with malacoplakia. Malacoplakia of the female genital tract is documented rarely and remains unreported, to date, in AIDS patients. Similar to the pathogenetic mechanisms described for AIDS-associated malacoplakia in extragenital sites, it is hypothesized that, in addition to abnormal macrophage functioning and an inability to degrade bacteria, special constituents of K. granulomatis are undigestable by lysosomal enzymes in human immunodeficiency virus-infected patients.

Cryptococcosis masquerading as a tuboovarian abscess.

This report describes a 25-year-old human immunodeficiency virus- seropositive patient who initially presented with clinical features of a tuboovarian abscess. After a poor response to antibiotic therapy, laparotomy and excision of a right-sided, unilocular, pseudocystic ovarian mass measuring 140 x 80 x 60 mm were undertaken. Mucoid gelatinous material, with a glistening appearance and slimy consistency, coated the inner surface of the thick wall. The cyst contained clear, viscid fluid with a similar slimy consistency. Although the macroscopic diagnosis was that of an ovarian mucinous cystadenocarcinoma, histopathologic assessment confirmed a well-circumscribed pseudocystic cryptococcoma with a wall of granulation and fibrous tissue and compressed ovarian stroma. The inner surface was covered by large, paucireactive, extracellular "yeast lakes" of carminophilous Cryptococcus neoformans yeasts of varying shape and size. To the best of our knowledge, this is the first documentation of ovarian cryptococcosis in the English language literature. Despite their rarity in the female genital tract, fungal infections must be considered in the differential diagnosis of patients presenting with pelvic pain of obscure origin and a pelvic mass that is refractory to antibiotic therapy.