Cutaneous balamuthiasis: A clinicopathological study.

INTRODUCTION: Balamuthia mandrillaris, a free-living amoeba, causes an uncommon infection that is characterized by cutaneous and neurological involvement, which carries a poor prognosis. METHODS: This is a retrospective observational study including patients with clinical suspicion of cutaneous balamuthiasis, their skin biopsies, and/or a positive direct immunofluorescence test. The data were collected from the Dermatology and Pathology service of the Hospital Cayetano Heredia and the Instituto Tropical Alexander von Humboldt, Lima, Peru, from January 1985 to June 2007. We identified 60 biopsies from 35 patients, from which clinical data were available in 30. RESULTS: Twenty-two (73%) patients had centrofacial lesions, mostly located on the nose. The classical lesion was an asymptomatic, erythematous, or violaceous infiltrated plaque. Twenty-two (73%) patients had neurologic involvement. Fifty (83%) biopsies showed granulomatous dermatitis and 75% showed ill-defined tuberculoid granulomas without caseous necrosis. Multinucleated giant cells were observed in 52 (87%) biopsies. Trophozoite forms were identified in the biopsies of 25 (71%) patients. Direct immunofluorescence was positive in 25 (71%) patients. CONCLUSION: B. mandrillaris is a pathogen that is capable of inducing a characteristic skin lesion with a reaction pattern of ill-defined tuberculoid granulomas and many giant cells.

Level of tumor-infiltrating lymphocytes and density of infiltrating immune cells in different malignancies.

Aim: To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. Methods: 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3+, CD4+, CD8+, CD20+, CD68+ and CD163+ cells by digital analysis. Results: TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Conclusion: Standardized evaluation of TIL levels may provide valuable prognostic information in a spectrum of different malignancies.

Dermal xanthomatous infiltrates after brentuximab vedotin therapy in mycosis fungoides with large-cell transformation: A novel histologic finding.

Mycosis fungoides (MF) is the most common variant of cutaneous T-cell lymphomas. Large-cell transformation of MF has been associated with disease progression and overall poor outcome. The expression of CD30, which defines anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis, might also occur in a subset of patients with MF, with or without large-cell transformation. Brentuximab vedotin is an anti-CD30 monoclonal antibody which has been proven to be a safe and effective therapeutic agent in the treatment of CD30-positive lymphomas, such as Hodgkin lymphoma and ALCL. Recently, brentuximab vedotin has been shown to have a significant clinical activity in treatment-refractory or advanced MF or Sezary syndrome with a wide-range of CD30 expression levels. We report a patient with MF tumor stage with large-cell transformation and low CD30 expression with good response to brentuximab vedotin and unusual extensive xanthomatous changes in the follow-up biopsy.

Coccidioidomycosis Involving Lungs and Skin: A Mimicker of Metastatic Disease.

Coccidioidomycosis is the major systemic mycoses, considered to be 1 of the most infectious fungal diseases. In symptomatic patients, the most common manifestation is pulmonary disease, but many other organs can be affected. Disseminated disease occurs in 1%-5% of all patients affected by coccidioidomycosis and can affect any organ, with the skin, central nervous system, and musculoskeletal system being reported as the most prevalent. Here, we report a 42-year-old male farmer from the west Texas who presented with an approximately 2-month history of progressive shortness of breath and dyspnea on exertion, weight loss, and night sweats. He was treated with various antibiotics for possible upper respiratory tract infection without symptomatic improvement. Computed tomography of the chest revealed numerous subcentimeter noncalcified pulmonary nodules scattered throughout both lungs with extensive mediastinal and bilateral hilar lymphadenopathy. The patient was referred to our hospital for further evaluation of suspected metastatic lung disease. Physical examination revealed an erythematous 1.2 cm nodule on his left medial eyebrow. Skin biopsy of the lesion revealed prominent squamous epithelial hyperplasia with basal keratinocytic atypia and associated mixed inflammatory infiltrate and scattered large thick-walled spherules containing variable-sized endospores, predominantly within the multinucleated giant cells. Special stain Periodic acid-Schiff tissue culture studies confirmed these to be Coccidioides immitis. After appropriate treatment with antifungal therapy for 5.5 months, his symptoms have improved with complete disappearance of lung nodules and a partially cavitated (1.1 × 1.1 cm) lesion in the left upper lung confirmed by follow-up chest computed tomography. With this report, the authors highlight disseminated coccidioidomycosis, a great mimicker of metastatic lung disease, which was diagnosed by skin biopsy, to ensure its prompt recognition and appropriate antifungal therapy.

Immunophenotypic Shifts in Primary Cutaneous γδ T-Cell Lymphoma Suggest Antigenic Modulation: A Study of Sequential Biopsy Specimens.

Primary cutaneous γδ T-cell lymphoma (PCGD TCL), an aggressive type of lymphoma, accounts for approximately 1% of all primary cutaneous lymphomas. We have occasionally observed changes in T-cell antigen expression (immunophenotypic [IP] shift) over time, a phenomenon that is considered rare in T-cell lymphoma including cutaneous T-cell lymphoma. Therefore, we assessed sequential biopsies of PCGD TCL for possible IP shifts of the lymphoma cells. We searched for cases of PCGD TCL with consecutive biopsies to perform a comprehensive immunohistochemical analysis of paired specimens. A median of 12 markers per case was tested. We evaluated the percentage of neoplastic lymphocytes and determined the differential expression of antigens (gain, loss, increase or decrease). We identified 9 patients with PCGD TCL with consecutive biopsies. All (100%) cases had IP shifts of at least 1 antigen, whereas overall 22 pairs of markers were shifted: gain of reactivity occurred in 7 (31.8%) and loss in 3 (13.6%); increased reactivity in 4 (18.2%) and decreased in 8 (36.4%). Molecular analysis of TCRγ showed identically sized monoclonal rearrangements between biopsy pairs in 4/4 (100%) patients. There was no correlation between IP shifts and the clinical appearance of lesions, histopathologic or cytologic features, or molecular rearrangements. IP shifts are common in PCGD TCL, occurring in all patients in this study and involving a variety of antigens. IP shifts do not seem to be linked to changes in the T-cell clone and are without obvious clinical or morphologic correlates. The occurrence of IP shifts in PCGD TCL suggests that antigen modulation may be involved in pathogenesis. IP shifts are somewhat frequent in T-cell lymphoma; however, it does not suggest a second neoplasm, and molecular studies can be used to determine clonal identity.

EBV-negative Aggressive NK-cell Leukemia/Lymphoma: Clinical, Pathologic, and Genetic Features.

Aggressive natural killer cell leukemia (ANKL) is a systemic NK-cell neoplasm, almost always associated with Epstein-Barr virus (EBV). Rare cases of EBV-negative ANKL have been described, and some reports suggested more indolent behavior. We report the clinicopathologic, immunophenotypic, and molecular characteristics of 7 EBV-negative ANKL. All patients were adults, with a median age of 63 years (range 22 to 83 y) and an M:F ratio of 2.5:1. Five patients were White, 1 Black, and 1 Asian. All patients presented acutely, with fever (6/7), cytopenias (6/7), and splenomegaly (4/7). Four patients had lymphadenopathy, 4 had extranodal disease. Bone marrow involvement was present in 5, with hemophagocytosis in 3. Peripheral blood was involved in 5 with the neoplastic cells containing prominent azurophilic granules. By immunohistochemistry and/or flow cytometry, the tumor cells lacked surface CD3 and were positive for CD56 (7/7), CD2 (5/5), CD8 (3/7), CD30 (4/5), and granzyme-B (6/6). They were negative for CD4, CD5, ßF1, TCRγ, LMP1, and EBV-encoded RNA. Polymerase chain reaction for TCRG clonality was polyclonal. Mutational analysis revealed missense mutations in the STAT3 gene in both cases studied. Median survival was 8 weeks from the onset of disease. One patient received allogeneic bone marrow transplant and is alive with no disease (follow-up 15 mo). EBV-negative ANKL exists but is rare. It tends to occur in older patients and is indistinguishable clinically and pathologically from EBV-positive ANKL, with a similar fulminant clinical course. The high prevalence of Asian patients seen with EBV-positive disease seems less evident with EBV-negative cases.

Sífilis nodular diseminada con fenómeno de prozona asociada a VIH/sida / Nodular syphilis spread associated with HIV/AIDS prozone phenomenon

Los cuadros de sífilis nodular diseminada que se presentan como un pseudolinfoma son muy raros, se ha descrito hasta la actualidad 11 casos publicados. La coinfección con el VIH puede alterar los resultados de las pruebas treponémicas y no treponémicas, lo que resulta en hallazgos falsos negativos y falsos positivos. Se estima que la coinfección sífilis y VIH está en aumento, por lo que se necesitaun diagnóstico acertado para evitar las graves consecuencias de un diagnóstico tardío. Presentamos un caso de sífilis nodular que sepresentó como un pseudolinfoma en un paciente con infección por VIH/sida que inicialmente mostró serología para sífilis negativaatribuida al fenómeno de prozona.

Disseminated nodular syphilis boxes presenting as a pseudo-lymphoma nodular are very rare, to date only 11 reported cases has been described. Co-infection with HIV may alter the results of the tests nontreponemal and treponemal not, resulting in false negative. It is estimated that co-infection HIV and syphilis is on the rise, so a correct diagnosis is needed to prevent the serious consequences of a late diagnosis. We present a case of nodular syphilis which was presented as a pseudolymphoma in a patient with HIV/AIDS infection that initially showed a serology for syphilis negative attributed to the prozone phenomenon.