Search PubMed⌕ Search

Biomedical subjects

Liron Pantanowitz

Publications and source records attributed to Liron Pantanowitz.

At least 55 records · Page 3Linked to original sources

Histological characterization of regression in acquired immunodeficiency syndrome-related Kaposi's sarcoma.

BACKGROUND: Kaposi's sarcoma (KS) is an angioproliferative lesion that may regress or progress. Progression is related to spindle cell proliferation and the expression of human herpes virus-8 latency genes, including latent nuclear antigen-1 (LNA-1), cyclin-D1, and bcl-2. KS regression has not been well characterized histologically. Therefore, this study was undertaken to characterize the histopathology of pharmacologically induced regressed cutaneous KS. METHODS: Skin punch biopsies from eight patients with acquired immunodeficiency syndrome (AIDS)-related KS, that regressed following chemotherapy with paclitaxel or the angiogenesis inhibitor Col-3, were investigated by light microscopy. Comparative immunophenotyping on pre- and post-treatment specimens for CD31, LNA-1, cyclin-D1, bcl-2, and CD117 (c-kit) was performed. RESULTS: Clinical and histologic features of regression were similar for paclitaxel and Col-3 treatment. On clinical examination, lesions flattened, became smaller, and lost their purple-red appearance, resulting in an orange-brown macule. Histological regression was divided into partial (n = 3) and complete (n = 5) regression. Partially regressed lesions had a significant reduction of spindle cells in the dermal interstitium, with residual spindle cells arranged around superficial and mid-dermal capillaries. Complete regression was characterized by an absence of detectable spindle cells, with a slight increase in capillaries of the superficial plexus. All regressed samples exhibited a prominent, superficial, perivascular, lymphocytic infiltrate and abundant dermal hemosiderin-laden macrophages. This clinicopathologic picture resembled the findings of pigmented purpura. CD31 staining correlated with the reduction of spindle cells. Regression was accompanied by a quantitative and qualitative decrease in LNA-1 and cyclin-D1 immunoreactivity, but no change in bcl-2 or c-kit expression. CONCLUSIONS: Pharmacologically induced regression of AIDS-related cutaneous KS is characterized by a complete loss or decrease of spindle cells, increased lymphocytes, and prominent dermal siderophage deposition. Without any prior knowledge of the history of KS regression following therapy, regressed KS lesions may be misdiagnosed clinically and histologically as pigmented purpuric dermatitis.

Acquired Immunodeficiency Syndrome↗

Inflammatory fibroid polyps of the gastrointestinal tract: evidence for a dendritic cell origin.

Inflammatory fibroid polyps (IFPs) are rare mesenchymal tumors of the gastrointestinal tract that consist of spindle-shaped stromal cells and an inflammatory infiltrate rich in eosinophils. Their etiology and histogenesis remain unknown. Based on previous reports of their immunoreactivity for CD34 and c-kit biomarkers, IFPs have been thought to be related to gastrointestinal stromal tumors (GISTs). After reviewing the current literature and examining IFPs at the light microscopic level, we evaluated a series of IFPs using an extensive panel of immunohistochemical and in situ hybridization markers in an effort to gain insight into their etiology and histogenesis and to determine their true relationship to GISTs. Sixteen routinely processed IFP specimens (14 gastric, 1 ileal, and 1 rectal) were immunohistochemically stained for antibodies to CD34, HMB-45, desmin, smooth muscle actin, calponin, h-caldesmon, anaplastic lymphoma kinase, S-100 protein, epithelial membrane antigen, c-kit (CD117), stem cell factor (SCF/N19 or kit ligand), p53, bcl-2, cyclin D1, and human herpesvirus-8 (HHV8). In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was also performed. Ten cases were further evaluated for the dendritic cell markers fascin, CD21, CD23, and CD35. Stromal cells were diffusely positive for CD34 and fascin in all (100%) cases, and these stromal cells were, in addition, immunoreactive for calponin and smooth muscle actin in 88% and 25% of cases, respectively. CD35 was also found to be focally reactive in the stromal cells. Cyclin-D1 was overexpressed in all (100%) IFPs. All other immunohistochemical markers and EBER were negative in the stromal cells. These findings suggest that the proliferating stromal cells in IFPs are of dendritic cell origin, with some cases also exhibiting myofibroblastic features. Absence of c-kit, SCF, and h-caldesmon immunoreactivity fails to support a relationship to GISTs. We also conclude that Epstein Barr virus and HHV8 are unlikely etiologic agents of IFPs. Overexpression of cyclin D1 in all cases suggests that a defect in cell-cycle regulation may be involved in the growth of IFPs.

Adult↗

Advances in the pathobiology and treatment of Kaposi sarcoma.

PURPOSE OF REVIEW: Kaposi sarcoma, which has reached epidemic proportions in parts of Africa and in the Western world, continues to pose a problem in patients with AIDS receiving highly active antiretroviral therapy (HAART). This article reviews the new and important information regarding the epidemiology, biology, and management of Kaposi sarcoma that was published in the last year. RECENT FINDINGS: Worldwide Kaposi sarcoma herpesvirus/human herpesvirus 8 (HHV8) seropositivity has been found to exceed the incidence of Kaposi sarcoma. Therefore, investigators have justifiably implicated other cofactors (eg, blood-sucking arthropods, angiotensin converting enzyme inhibitors, hemodialysis, and iron) in the development of Kaposi sarcoma. In the transplant setting, Kaposi sarcoma lesions have been shown to originate from the engraftment of donor tumor cells. The detection of HHV8 in Kaposi sarcoma lesions has provided a new diagnostic tool to help differentiate Kaposi sarcoma from its mimics. Kaposi sarcoma lesional cells, now confirmed to be of lymphatic origin, have been shown to express several chemokine receptors, some of which may help explain the predilection for skin. Regression of Kaposi sarcoma has been characterized histologically for the first time. The finding that some tumor cells can remain in an atrophic state even in completely regressed lesions suggests that they have the potential to recur. Protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based HAART regimens have been verified to be similarly effective. Although antiretrovirals have been noted to favorably alter the clinical characteristics of Kaposi sarcoma favorably, they seem not to alter the natural history of this disease. In the HAART era, because CD4 cell count was shown no longer to provide prognostic information about AIDS-related Kaposi sarcoma, the traditional classification system for staging AIDS-related Kaposi sarcoma has been refined. Also, a new staging system for classic Kaposi sarcoma has been proposed. SUMMARY: Numerous advances have emerged regarding Kaposi sarcoma during the last year, many of which still need to be translated into clinically useful information. The results of new clinical trials involving antivirals purposely directed against HHV8 and antiretrovirals for HIV-uninfected people are anticipated. Finally, although investigators during this period did provide us with additional potential therapeutic targets, more novel approaches such as RNA interference and gene therapy have been also proposed as options in the future management of Kaposi sarcoma.

Acquired Immunodeficiency Syndrome↗

Ligneous (pseudomembranous) inflammation involving the female genital tract associated with type-1 plasminogen deficiency.

Ligneous (pseudomembranous) inflammation of the female genital tract is a rare and unusual condition characterized by extensive subepithelial fibrin deposition and associated inflammation. Ligneous inflammation in extragenital sites, predominantly the conjunctiva, has been linked to plasminogen deficiency. Individuals with plasminogen deficiency are unable to remove fibrin deposited in injured mucosal tissue. Severe systemic ligneous inflammation involving the female genital tract that is linked to hypoplasminogenemia has not previously been described. We present a patient with ligneous inflammation of her genital, middle ear, and oral mucosa that was associated with type-1 homozygous plasminogen deficiency due to a novel missense mutation in the plasminogen gene.

DNA↗

Analysis of on-line clinical laboratory manuals and practical recommendations.

CONTEXT: On-line clinical laboratory manuals are a valuable resource for medical professionals. To our knowledge, no recommendations currently exist for their content or design. OBJECTIVE: To analyze publicly accessible on-line clinical laboratory manuals and to propose guidelines for their content. DESIGN: We conducted an Internet search for clinical laboratory manuals written in English with individual test listings. Four individual test listings in each manual were evaluated for 16 data elements, including sample requirements, test methodology, units of measure, reference range, and critical values. Web sites were also evaluated for supplementary information and search functions. RESULTS: We identified 48 on-line laboratory manuals, including 24 academic or community hospital laboratories and 24 commercial or reference laboratories. All manuals had search engines and/or test indices. No single manual contained all 16 data elements evaluated. An average of 8.9 (56%) elements were present (range, 4-14). Basic sample requirements (specimen and volume needed) were the elements most commonly present (98% of manuals). The frequency of the remaining data elements varied from 10% to 90%. CONCLUSIONS: On-line clinical laboratory manuals originate from both hospital and commercial laboratories. While most manuals were user-friendly and contained adequate specimen-collection information, other important elements, such as reference ranges, were frequently absent. To ensure that clinical laboratory manuals are of maximal utility, we propose the following 13 data elements be included in individual test listings: test name, synonyms, test description, test methodology, sample requirements, volume requirements, collection guidelines, transport guidelines, units of measure, reference range, critical values, test availability, and date of latest revision.

Abstracting and Indexing↗

The scratch test.

Explore the source record for details and available documents.

Artifacts↗

Kaposi's sarcoma.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Management of AIDS-related Kaposi sarcoma: advances in target discovery and treatment.

Kaposi sarcoma (KS) is the most common tumor arising in HIV-infected patients and is considered an AIDS-defining illness by CDC guidelines. Recent advances in the elucidation of the pathogenesis of KS continue to uncover potential targets for therapies. Such targets include the KS herpesvirus/human herpesvirus 8 and the processes of angiogenesis and cellular differentiation. Five agents are currently approved by the FDA for the treatment o KS: alitretinoin gel for topical administration and liposomal daunorubicin, liposomal doxorubicin, paclitaxel, and interferon-alpha for systemic administration. Many more agents, particularly angiogenesis inhibitors and other pathogenesis-targeted therapies, are in clinical development. With increasing recognition that effective antiretroviral regimens are associated with both a decreased proportion of new AIDS-defining KS cases and a regression in the size and number of existing KS lesions, most, if not all, patients with KS should be advised to take antiretroviral drugs that will maximally decrease HIV-1 RNA levels.

Acquired Immunodeficiency Syndrome↗

Crohn's disease of the esophagus.

Crohn's disease of the esophagus is rare but is being detected more frequently because of the use of upper endoscopy. Clinicopathologic correlation is required to establish the correct diagnosis. We present a case of esophageal Crohn's disease and review the literature to demonstrate that esophageal involvement is usually associated with disease elsewhere in the gut.

Adult↗

Plasma cell disorders in HIV-infected patients: from benign gammopathy to multiple myeloma.

Plasma cell disorders are not uncommonly reported in young patients with HIV infection. These disorders range from benign polyclonal hypergammaglobulinemia to indeterminate monoclonal gammopathy of unknown significance (MGUS) to malignant dyscrasias, including multiple myeloma and plasma cell leukemia. Hypergammaglobulinemia and oligoclonal banding had been the most frequently reported disorders in the pre-HAART era. In HIV-infected persons, the incidence of MGUS is reported to be around 2.5%, with an approximate 4.5-fold increased risk of multiple myeloma. Many of these HIV-infected patients had been treated with alkylator-based regimens, and these reports predate the current widespread use of thalidomide-dexamethasone combination treatment in multiple myeloma. Although the optimal therapy for an HIV-infected person might with plasma cell dyscrasia is yet to be defined, in the current era of HAART the otherwise healthy HIV-infected patient might be tested like an HIV-negative person. Consequently, treatment with immunomodulatory agents (eg, thalidomide) and proteasome inhibitors (eg, bortezomib) may also be worth considering. High-dose chemotherapy with an autologous peripheral blood stem cell transplant is increasingly being considered as consolidation therapy in the younger non-HIV-infected myeloma patient. In the next few years, it is anticipated that these approaches will be applied more frequently to HIV-infected persons with myeloma.

Adult↗

Charcot-Leyden crystals: pathology and diagnostic utility.

Eosinophilia is associated with several diseases of the upper respiratory tract. The predominance of eosinophils in nasal tissue, secretions, and lavage fluid has been used as an aid in the diagnosis of allergic rhinitis. Charcot-Leyden crystals, considered to be a morphologic hallmark of eosinophil-related disease, are often also found in inflamed nasal tissue and paranasal sinus contents of patients with allergic rhinitis. These bipyramidal-shaped crystals are composed of the enzyme lysolecithin acylhydrolase, one of several eosinophilic proteins that damage respiratory epithelium and contribute to the pathology of allergy in the upper respiratory tract.

Eosinophilia↗

AIDS-related non-Hodgkin lymphoma: still a problem in the era of HAART.

Despite advances in HAART, patients with HIV infection remain at significantly increased risk for intermediate- and high-grade B-cell non-Hodgkin lymphoma. The reasons for this persistent risk and the clinical and molecular correlates that predict outcomes and treatment responsiveness are areas of active investigation. Here we review the epidemiologic and pathobiologic features of AIDS-related lymphoma along with clinical evaluation and treatment options in patients with this disease.

Adult↗