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Biomedical subjects

C A Horwitz

Publications and source records attributed to C A Horwitz.

At least 19 recordsLinked to original sources

Cellular follicular cyst of the ovary: fluid cytology mimicking malignancy.

We report three ovarian cysts studied by aspiration cytology. The fluids obtained were highly cellular, with numerous groups of atypical cells featuring a high nuclear-cytoplasmic ratio, nuclear hyperchromasia, and prominent nucleoli. In each case, these features were considered evidence of a low-grade malignant neoplasm. All three patients underwent oophorectomy, which revealed benign follicular cysts. Possible means of resolving the diagnostic dilemma posed by these cellular follicular cysts are discussed.

Adult

Granulomatous prostatitis: a spectrum including nonspecific, infectious, and spindle cell lesions.

Most granulomas of the prostate are nonspecific; infectious, post-operative, and allergic lesions are much less common. Fine-needle aspiration findings in the typical case are distinctive and easily recognized. Several series have been reported, but few have included histologic follow-up. We describe three cases of granulomatous prostatitis (GP) which showed a spectrum of findings confirmed by histologic sections. In all cases, carcinoma was suspected clinically. Case 1 represents typical nonspecific GP with epithelioid and multinucleated histiocytes. In case 2, aggregates of epithelioid histiocytes alternated with areas of necrosis and neutrophils. Histologically, the granulomas showed purulent centers. Silver stains revealed budding yeast in smears and sections. Cultures of FNA material subsequently revealed Cryptococcus. In case 3, the histiocytes were predominantly spindled and occurred singly and in groups. The differential diagnosis included reactive and neoplastic spindle cell lesions. Histologic sections showed GP with spindled histiocytes. Appreciation of the broad cytologic spectrum of GP will facilitate accurate cytologic diagnosis.

Aged

Negative images of bacilli and mycobacterial infection: a study of fine-needle aspiration smears from lymph nodes in patients with AIDS.

In patients with the acquired immunodeficiency syndrome (AIDS), four cases of mycobacterial infection in which bacilli appeared as cylindrical, nonstaining "negative images" have been previously described. These may have been extracellular or within histiocyte cytoplasm, and they have been described in aspirations from liver, lymph node, and bone marrow and in bronchoalveolar lavage fluid. We report three additional examples of this finding in fine-needle aspirations from lymph nodes in AIDS patients infected with Mycobacterium avium-intracellulare. Our findings support the concept that these negative images of bacilli are diagnostic of mycobacterial infection. Air-dried Romanovsky-stained material is required for their identification.

Acquired Immunodeficiency Syndrome

Fine-needle aspiration of lymph nodes in patients with acute infectious mononucleosis.

We studied lymph node fine-needle aspirations from 10 patients with primary Epstein-Barr virus (EBV) infections (infectious mononucleosis). There were five males and five females, aged 15-54 yr. The diagnoses were confirmed by blood morphology and heterophil antibody (HA) and EBV-specific serologic studies. Nine patients were HA-positive, nine were viral capsid antigen (VCA)-IgM-positive, and all 10 were VCA-IgG-positive and anti-EBV nuclear antigen (EBNA)-negative. Five patients were referred for fine-needle aspiration biopsies for clinically suspected malignant lymphoma (ML). Four of these patients had been tested for HA prior to fine-needle aspiration, with negative results in three cases. The heterophil-positive patient was referred for fine-needle aspiration due to very impressive unilateral cervical adenopathy. Cytologically, all cases showed atypia consisting of greater numbers of large immunoblastic lymphocytes than are usually seen in the reactive lymph node. Two cases were cytologically suspicious for malignant lymphoma but included a considerable background of polymorphic immunoblasts. We suggest that polymorphic immunoblastic proliferations in lymph node cytology are suggestive of infectious mononucleosis. Since several reactive and neoplastic processes mimic this pattern, cases not followed by both confirmatory serologic studies and resolution of adenopathy should be pursued by excisional lymph node biopsy.

Adolescent

Identical IgM antibodies recognizing a glycine-alanine epitope are induced during acute infection with Epstein-Barr virus and cytomegalovirus.

We studied antibody production in serial serum samples from patients with acute Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Sera were analyzed both by enzyme-linked immunosorbent assay (ELISA) using a synthetic peptide (P62) derived from the glycine-alanine repeating region of the Epstein-Barr nuclear antigen (EBNA-1) and by immunoblotting. In prior studies, we have shown that patients with acute EBV infection make IgM antibodies that react with this peptide, that recognize a viral-specific protein (EBNA-1), and that bind with a number of proteins present in uninfected cells; however, antibody binding to these autoantigens was inhibited by the peptide. IgG antibodies reactive with the peptide did not appear until months after the disease and were specific for the EBNA-1 protein. We now find that patients with acute CMV infection but not those with acute infections from a variety of other nonherpes organisms also produce IgM antibodies that recognize the EBV-derived peptide P62. These antibodies also appear to recognize the same cellular proteins as the EBV-induced IgM antibodies. The IgM antibodies appeared in all acutely infected CMV patients studied and occurred both in patients with previous EBV infections and in one patient studied who had not previously been exposed to EBV. It appears that infection with EBV or CMV can induce the synthesis of a very similar or identical set of IgM antibodies.

Amino Acid Sequence

The spectrum of clinical and laboratory findings resulting from human herpesvirus-6 (HHV-6) in patients with mononucleosis-like illnesses not resulting from Epstein-Barr virus or cytomegalovirus.

Recently, the morphologic, immunologic, and molecular makeup of a new virus designated human herpesvirus-6 (HHV-6) has been described. Because cell cultures of HHV-6-infected mononuclear cells showed prominent lymphocytic changes, it could be anticipated that mononucleosis-like illnesses or lymphoproliferative disorders would turn out to be manifestations of active HHV-6 infection. In the present study, blood samples from 27 patients previously categorized as having non-Epstein-Barr virus (non-EBV)/noncytomegalovirus (non-CMV) heterophil-negative mononucleosis-like illnesses were tested for IgM and IgG antibodies to HHV-6. Eight of these patients (30%) had serologic evidence of active HHV-6 infection. The clinical spectrum includes a short-lived febrile illness, mild cervical lymphadenopathy, laboratory data suggestive of active viral hepatitis in two patients, and a prolonged febrile illness in a single patient with previously documented positive anti-HIV serology. The viral studies revealed the presence of fourfold HHV-6-specific IgG titer increases by immunofluorescent assay (IFA) in seven serially studied cases and positive IgM serology on one or more samples tested by IFA or enzyme-linked immunosorbent assay (ELISA) in all eight cases. The authors could not determine whether the illnesses represented primary HHV-6 infections in susceptible individuals or reactivation of latent virus. HHV-6 serologic studies may be indicated in patients with mononucleosis-like illnesses with atypical lymphocytosis when EBV and CMV test results are nondiagnostic.

Adolescent

Oligoclonal T cell receptor gene rearrangements in blood lymphocytes of patients with acute Epstein-Barr virus-induced infectious mononucleosis.

Gene rearrangement studies were performed on blood lymphocytes from eight patients with acute Epstein-Barr virus-induced infectious mononucleosis. The diagnosis in each case was based on characteristic clinical, hematologic, and serologic findings. The blood lymphocytes in each patient consisted predominantly of CD8+ T cells. EBV DNA was detected in seven patients by Southern blot analysis (EBV Bam HI W probe, Bam HI). A germline configuration was found for the immunoglobulin heavy and light chain genes (JH probe, Bam HI and Eco RI; C kappa probe, Bam HI; and C lambda probe, Eco RI). T cell receptor gene rearrangements were detected with J gamma and J beta 1 + 2 probes. Using a J gamma probe with two different restriction enzymes (Bgl II and Eco RI), the blood from each patient showed several bands corresponding to the polyclonal pattern previously described in the blood of normal individuals. Using J beta 1 + 2 probes with two different restriction enzymes (Bgl II and Bam HI), each case showed from 3 to about 12 extragermline bands of varying intensity and in different locations from case to case. In addition, each case showed relative deletion of the J beta 1 germline band. This oligoclonal pattern of T cell receptor gene rearrangements has not been previously reported in benign or malignant T cell populations.

Acute Disease

Antibodies to an Epstein-Barr virus nuclear antigen synthetic peptide in infectious mononucleosis. Report of two cases.

The Epstein-Barr virus nuclear antigen (EBNA-1) contains a region of repeating glycine and alanine amino acids. It has been shown that this region contains a major epitope of EBNA-1. With well-characterized sequential sera from two cases of acute infectious mononucleosis, a specific IgM response was detected to the EBNA-1 synthetic peptide by enzyme-linked immunosorbent assay (ELISA). Conversely, an IgG response was observed in the convalescent phase of the illness with a progressive decline of the IgM antibodies. This response was observed with heterophil-positive and heterophil-negative EBV/IM. The peptide-specific serologic response was confirmed by immunoblotting, the serial serum samples on extracts of EBV transformed B-cells. There was excellent correlation between the antipeptide ELISA and blotting techniques.

Acute-Phase Reaction

Severe thrombocytopenia in Epstein-Barr virus-induced mononucleosis.

Severe thrombocytopenia is a rare complication of Epstein-Barr virus-induced infectious mononucleosis. We evaluated the clinical and laboratory data from seven patients seen between 1976 and 1985 whose lowest platelet counts varied from 3 to 25 x 10(9) per liter. Five of the seven patients were initially thought to have either acute leukemia or idiopathic thrombocytopenic purpura; eventually, however, primary Epstein-Barr virus infections were confirmed in all patients. Two of six patients tested had antiplatelet antibodies during the acute phase of their illnesses. Eight additional patients with acute disease who had only mild thrombocytopenia (94 to 144 x 10(9) per liter) were also tested for platelet antibodies with negative results. Steroid therapy was administered to three patients and platelet transfusions to one. All seven patients recovered with no serious hemorrhagic sequelae.

Adolescent

Primary spindle-cell sarcomas of the breast: diagnosis by fine-needle aspiration.

Primary breast sarcomas (excluding cytosarcoma phyllodes and its sarcomatous recurrences) are rare neoplasms. Few have been described in the aspiration cytology literature. We report the cytologic features of two cases of stromal sarcoma (both with the pattern of malignant fibrous histiocytoma) and two cases of angiosarcoma. The dominant cytologic features included individual atypical spindle cells and fragments of collagenous stroma. Tumor giant cells were present in one stromal sarcoma. Features of possible significance in the diagnosis of angiosarcoma include obvious vessel formation by atypical spindle cells, bridging of adjacent tumor fragments by spindle cells, and microacinar structures lined by atypical spindle cells. The differential diagnostic considerations in spindle-cell breast aspirations are discussed.

Adult

Basal-cell adenoma of the salivary gland: a benign adenoma that cytologically mimics adenoid cystic carcinoma.

We describe the fine-needle aspiration cytology of two cases of basal-cell adenoma (BCA) of the parotid gland. Both consisted of groups of small uniform cells with scant cytoplasm and occasional single cells. Small amounts of metachromatic stroma were present in smears from one case. The cytologic and histologic similarities between (BCA) and the solid type of adenoid cystic carcinoma are emphasized. Unequivocal distinction between these two entities may not be possible by cytologic criteria alone.

Adenoma

Transrectal fine needle biopsy of the prostate: combined histological and cytological technique.

Transrectal fine needle biopsy was performed on 50 patients with suspicious prostatic examinations using the Surecut and Chiba needles. The 21 gauge Surecut needle provided a core of tissue for routine histology in 42 of 50 patients (84 per cent) as well as cells for cytology in 46 of 50 (92 per cent). This was in contrast to positive cytology results with the 22 gauge Chiba needle in 44 of 50 patients (88 per cent). Fourteen cancers were detected: 12 by Surecut histology, 11 by Surecut cytology and 10 by Chiba cytology testing, for sensitivity rates of 86, 79 and 71 per cent, respectively. Our results indicate that the 21 gauge Surecut needle provides cytology results equivalent to the 22 gauge Chiba needle. However, the Surecut needle has the added advantage of providing a core of tissue for routine histological study, and it can be used safely as an outpatient procedure on unprepared bowel.

Biopsy, Needle

Heterophil-negative mononucleosis-like illnesses with atypical lymphocytosis in patients undergoing seroconversions to the human immunodeficiency virus.

The authors present data from four patients with acute heterophil-negative mononucleosis-like illnesses who were initially thought to have primary Epstein-Barr virus (EBV) infections but eventually were shown to be seroconverting to the human immunodeficiency virus (HIV). Widespread lymphadenopathy and blood smears indistinguishable from those typically encountered in the acute phase of infectious mononucleosis were present in all cases. There were also varying combinations of fever, sore throat, and malaise, as well as mild abnormalities of hepatic function and elevated cold agglutinins (anti-I). Anti-HIV was detected by both enzyme-linked immunosorbent assay and Western blot techniques in all cases, with increasing titers noted in two of three serially studied cases. In one patient, a dual infection with the hepatitis B virus was also documented. Diagnostic possibilities in patients with acute mononucleosis-like illnesses dominated by prominent lymphadenopathy should include primary seroconversions to HIV.

Antibodies, Heterophile

Cytostructural localization of peanut lectin binding in fine-needle aspirates of benign and malignant breast lesions.

Numerous studies have employed lectin binding patterns to investigate alterations in cell surface polysaccharide expression associated with malignant transformation. Cytostructural relocalization of peanut lectin (Arachis hypogaea) binding sites from the cell surface to the cytoplasm has been described in breast carcinomas. To investigate the possible utility of peanut lectin binding patterns in the diagnosis of breast fine-needle aspirations, the PNA immunoperoxidase method was applied to smears from a group of 15 benign and malignant breast lesions. Cytostructural relocalization of PNA binding was seen in both benign and malignant breast lesions, indicating that it is of little diagnostic utility in the assessment of malignancy. This finding was noted in both cytologic and histologic preparations.

Binding Sites

Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection.

Five distinct Epstein-Barr virus (EBV)-determined nuclear antigens (EBNA-1 to EBNA-5) were recently identified. Antibody responses to these antigens could conceivably differ, and thus prove of serodiagnostic value, in EBV-associated disease processes. As a first step, murine or human cell lines transfected with appropriate EBV DNA fragments and stably expressing either EBNA-1 or EBNA-2 were used to determine the frequency and time of emergence of antibodies to these two antigens in the course of acute and chronic infectious mononucleosis (IM) and to assess their titers in so-called chronic active EBV infections. Following IM, antibodies to EBNA-2 arose first and, after reaching peak titers, declined again in time to lower persistent or even nondetectable levels. Antibodies to EBNA-1 emerged several weeks or months after anti-EBNA-2 and gradually attained the titers at which they persisted indefinitely. The ratios between the anti-EBNA-1 and anti-EBNA-2 titers therefore were generally well below 1.0 during the first 6-12 months after IM and turned to well above 1.0 during the second year. In clear cases of chronic IM, the inversion of this ratio was delayed or prevented. In the less well-defined chronic EBV infections, low ratios were observed in only some of the patients. Because many of these illnesses were not ushered in by a proven IM and often showed EBV-specific antibody profiles within the normally expected range, a causal role of the virus in these cases remains doubtful.

Acute Disease

Carcinoid tumors of the middle ear.

Carcinoid tumors of the middle ear are rare, with only three previously reported cases. The authors report the light and electron microscopic and immunohistochemical features of two carcinoid tumors that occurred in a 34-year-old female and a 21-year-old male. Both presented with unilateral hearing loss. By light microscopic examination, both were characterized by trabecula of tall columnar cells with basal nuclei and no mitotic activity. Electron microscopic examination demonstrated large numbers of pleomorphic neurosecretory granules, perinuclear aggregates of intermediate filaments, cell junctions, and surface microvillous processes. Some cells contained intermediate filaments forming tonofilaments and lacked secretory granules. These cells stained for cytokeratin by immunoperoxidase and separated the neuroendocrine cells from the underlying basal lamina. The cells in this tumor stained for the molluscan cardioexcitatory peptide. Cells in both tumors also stained for pancreatic polypeptide. Neither case stained for lysozyme, insulin, glucagon, somatastatin, gastrin, substance P, thyroid-stimulating hormone, adrenocorticotropic hormone, Met-enkephalin, Leu-enkephalin, neuropeptide Y, peptide YY, neurotensin, Bombesin, serotonin, neuron-specific enolose, glial and neural filaments, S-100 protein, cholecystokinin, beta-endorphin, beta-human chorionic gonadotropin, luteinizing hormone/follicle-stimulating hormone, vasoactive intestinal polypeptide, prolactin or calcitonin. Carcinoid tumor of the middle ear can be distinguished from paraganglioma and middle ear adenoma.

Adult

Marked hyperbilirubinemia in infectious mononucleosis. Analysis of laboratory data in seven patients.

While mild to moderate hepatic dysfunction is commonly encountered in infectious mononucleosis induced by Epstein-Barr virus (EBV), clinical jaundice with high bilirubin levels (greater than or equal to 6.0 mg/dL [greater than or equal to 103 mumol/L] is only occasionally encountered. In this study, seven patients with primary EBV infections had peak bilirubin levels of 10.2 to 23.0 mg/dL (174 to 393 mumol/L) and, for the most part, presented initial diagnostic problems. Complications included the virus-associated hemophagocytic syndrome and acute respiratory distress syndrome in one patient and transient renal failure in another. The laboratory data suggested that a combination of hemolysis and viral-induced cholestasis was responsible for the intense hyperbilirubinemia in at least five patients. Physicians should be aware that marked hyperbilirubinemia can occur with EBV-induced infectious mononucleosis and, thereby, obviate the need for costly diagnostic laboratory tests and, occasionally, invasive procedures.

Adolescent

Selected aspects of acute and chronic infectious mononucleosis and mononucleosis-like illnesses for the practicing allergist.

The diagnosis of EBV-IM or a heterophil-negative mononucleosis-like syndrome is best approached by combining morphologic and serologic data. The minimal hematologic criteria should always be searched for before accepting a case as IM or an IM-like illness. If minimal morphologic data are not rigidly adhered to, the number of heterophil-negative cases included under the umbrella of IM or an IM-like illness will swell and include a variety of other illnesses where early diagnosis may be important for treatment purposes. When EBV studies are indicated, the entire profile (VCA-IgM, VCA-IgG, and anti-EBNA) should be performed. Anti-VCA-IgG titers alone, for example, are of very limited usefulness unless they are negative (less than 1:10), in which case the diagnosis of EBV-IM is excluded. The main problems connected with the diagnosis of the CMS center about the nonspecificity of both clinical and EBV serologic data. Thus, a significant effort must be made to rule out underlying disease, especially those chronic illnesses with immunosuppressive effects that are capable of reactivating the EBV latency state and producing EBV serology similar to that seen in CMS. Other dilemmas relate to diagnostic cut-off levels for particular EBV-related tests, including antibodies to EA and the relative unavailability of several tests for detection of subtle immunodeficiency or T-cell dysfunction in individual patients with suspected CMS. Future efforts will be directed to the diagnostic usefulness of antibody responses to well-defined recombinant fragments of the EBV genome (ie, anti-EBNA1 vs. -EBNA2 titers).

Acute Disease