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Biomedical subjects

J F Silverman

Publications and source records attributed to J F Silverman.

At least 91 records · Page 5Linked to original sources

Negative images due to clofazimine crystals simulating MAI infection in a bronchoalveolar lavage specimen.

"Negative images" of bacilli in mycobacterial infections have been recently described in air-dried, Romanovsky-stained cytologic material. We report a case of negative images due to crystalline deposition of clofazimine, a drug used to treat Mycobacterium avium-intracellulare complex infection in AIDS patients. The negative images of clofazimine crystals seen in bronchoalveolar lavage (BAL) macrophages resemble the negative images of mycobacterial infection due to the pseudogaucher appearance of the cells. Crystals are distinguished by their refractile reddish appearance in unfixed, unstained smears, and by their birefringence on polarization. Crystals were found in both Pap-stained and Diff-Quik-stained smears and were negative with Ziehl-Neelsen stains. Clofazimine crystals in BAL specimens must be distinguished from the pseudogaucher type cells of mycobacterial infection in this patient population. We believe that this is the first report of clofazimine crystal deposition diagnosed in a BAL specimen along with electron microscopic examination of the cytologic material.

AIDS-Related Opportunistic Infections↗

Systematization of primary histopathologic and fine-needle aspiration cytologic features and description of unusual histopathologic features of neuroblastic tumors: a report from the Pediatric Oncology Group.

On the basis of a detailed review of the primary histopathologic features of 239 cases and the fine-needle aspiration cytologic features of seven cases, a systematized schema of differentiation, progressive maturation and organization, and biologic behavior in neuroblastic tumors (NTs) is presented. The differentiation is of the gangliocytic and schwannian lineages. Maturation occurs in differentiating neuroblasts, leading to the formation of various stages of ganglion cells and Schwann cells. Organization is characterized by nesting pattern, rosette formation, parallel arrangement of neuropil, and alignment of Schwann cells along the neurites. According to this schema the NTs can be arranged in the following order: undifferentiated, poorly differentiated, and differentiating neuroblastoma; nodular, intermixed, and borderline ganglioneuroblastoma; and ganglioneuroma. Formulation of such a schema is helpful in gaining a better understanding of the complex pathologic features and in defining the criteria for various types of NTs. Therefore, the schema also would be helpful in achieving uniformity and reproducibility of the diagnosis of various types of NTs. Previously unreported features related to shape, size, nucleus, and cytoplasm of neuroblasts; secondary changes and patterns; changes in the fibrovascular septa; and other morphologic aspects of NTs and features (such as large tumor cells, karyorrhectic cells in fine-needle aspiration biopsy, tumor giant cells, anaplasia, and nesting pattern of tumor cells that have not been sufficiently emphasized) also are described. The importance of these previously unreported and insufficiently emphasized features relates to the histologic and cytologic diagnosis of NTs. For example, some of the features, such as starry sky appearance and spindle-shaped neuroblasts, may be misleading if seen in a small biopsy specimen. Others, such as tumor giant cells resembling ganglion cells and nesting pattern, will provide clues to the correct diagnosis. Some of the features, such as sclerosing pattern, hyalinization, and dense lymphoplasmacytic infiltration, may be related to the phenomenon of regression exhibited by neuroblastomas.

Biopsy, Needle↗

Fine-needle aspiration biopsy of pulmonary coccidiodomycosis. Spectrum of cytologic findings in 73 patients.

Coccidioides immitis, the causal agent of coccidiodomycosis, is endemic in the arid desert regions of Mexico and the southwestern United States. Individuals may acquire the disease through the inhalation of conidia. The majority of infected patients are asymptomatic or exhibit flu-like symptoms. Two percent of infected individuals ultimately demonstrate a solitary pulmonary nodule that may be radiographically indistinguishable from neoplasms or other infectious lesions. This report describes the spectrum of cytologic findings in 73 patients who were diagnosed with pulmonary coccidiodomycosis by fine-needle aspiration (FNA) biopsy. The patients ranged in age from 30 to 92 years. Ten had a previous history of malignancy. The smears were characterized by a large amount of granular, eosinophilic debris with a paucity of acute or chronic inflammation. Granulomatous inflammation was present in only three cases. The diagnosis was confirmed by the cytologic observation of C. immitis spherules that ranged in size from approximately 20 to 200 microns. Many of these spherules had a crushed or fractured appearance, and occasional calcified forms were seen. Endospores were observed in intact spherules and were rarely observed outside these spherules. Mycelial elements occasionally were present. C. immitis were cultured in 9 of 44 cases in which fungal cultures were obtained. The cytologic differential diagnosis, which includes contaminant, other infectious diseases and malignancies, is discussed.

Adult↗

The utility of ancillary studies in pediatric FNA cytology.

We evaluated the diagnostic contribution of adjunct studies performed on aspirated material in the work-up of pediatric fine-needle aspiration (FNA) biopsies. Ancillary studies were performed on 54 of 136 (39.7%) pediatric FNA biopsies during a 5-year period. In 23 (16.9%) cases, immunocytochemical (ICC) studies, consisting of immunoperoxidase staining of direct smears and/or cell blocks or flow cytometric immunophenotyping, were performed. The studies were adequate in 14 cases (60.9%), suboptimal in five cases (21.7%), and inadequate in four cases (17.4%). Of the adequate and suboptimal cases, the ICC data helped to narrow the differential diagnosis or classify the disease process in eight cases (42.1%), confirmed cytologic impression in nine cases (47.4%), and gave contradictory results in two cases (10.5%). Adequate material for electron microscopy (EM) was obtained in 14/19 cases (73.7%). Ultrastructural studies were diagnostic, or helped classify the disease process in five cases (35.7%), confirmed the cytologic impression in four cases (28.6%), helped exclude diagnostic considerations in three cases (21.4%), and were judged to be non-contributory in two cases (14.3%). Cytogenetic studies revealed six of seven cases (all neoplasms) to have abnormal karyotypes. Special stains for organisms performed on smears from 25 cases including Ziehl-Neelsen, Gomori methenamine silver (GMS), Gram, and Warthin-Starry (WS) were negative except for 1/16 GMS and 4/9 Gram stains. In summary, we found that with appropriate case selection, ancillary studies performed on aspirated material can provide useful information in pediatric FNA cytology.

Abdominal Neoplasms↗

The utility of ancillary techniques in effusion cytology.

We believe that, in general, immunocytochemical studies when used as a panel are the most helpful of the ancillary techniques in the workup of a difficult effusion cytology case. Routine histochemical stains for mucin should also be employed due to their low cost and simplicity, but suffer from lack of sensitivity and specificity. EM examination is especially helpful in the differentiation of metastatic carcinoma from mesothelioma, but lacks specificity due to overlapping ultrastructural features, and is both costly and labor intensive. Immunophenotyping by flow cytometry is useful in the workup of problematic lymphoid proliferations, but DNA analysis by flow cytometry is not useful as a screening technique. Fortunately, most effusion cytology cases will not need the use of ancillary studies, since the diagnosis will be accurately rendered based on the cytomorphologic findings. However, occasional cases will benefit from the use of specific ancillary studies, which can aid in making an accurate, specific, and rapid diagnosis in an otherwise challenging case.

Cytological Techniques↗

Fine-needle aspiration cytology of spindle cell neoplasms of the adrenal gland.

Three spindle cell neoplasms were encountered in a series of 46 FNA of the adrenal performed between 1984 and 1991. These neoplasms included a recurrent undifferentiated adrenal cortical carcinoma (ACC) with a predominant spindle cell pattern, a pheochromocytoma (PC), and a metastatic desmoplastic malignant melanoma (DMM). Cytologically, the ACC was characterized by the presence of numerous microtissue fragments composed of spindle-shaped malignant cells with oval to spindle-shaped nuclei, one or more nucleoli, and bipolar cytoplasmic processes. In some areas the tumor cells were dissected by vascular channels. The background contained abundant metachromatic stroma as well as individually scattered tumor cells. The PC was composed predominantly of loosely cohesive spindle-shaped cells along with more polygonal shaped cells with delicate faintly staining granular cytoplasm. The tumor cells exhibited mild anisonucleosis. The tumor fragments were well vascularized by arborizing delicate capillary channels. The DMM was composed of microtissue fragments, interlacing fascicles and loose aggregates of spindle-shaped malignant cells with hyperchromatic nuclei, small nucleoli, and an absence of cytoplasmic pigment. In each case ancillary studies including immunocytochemistry and electron microscopy (EM) were helpful in the differential diagnosis. The ACC was negative for cytokeratins, neuron-specific enolase (NSE), and muscle-specific actin (HHF), but displayed strong positivity for vimentin as well as characteristic whorls of smooth endoplasmic reticulum by EM. The PC was positive for NSE and chromogranin with no EM performed. The DMM stained for S-100 and vimentin but was negative for HMB-45, cytokeratin, and HHF. EM examination revealed rare atypical premelanosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗

Electron microscopy of fine-needle aspiration biopsies of the mediastinum.

Twenty cases of fine-needle aspiration (FNA) biopsy of mediastinal tumors with ultrastructural studies of the aspirated material were reviewed. The cases were classified according to the cytologic and ultrastructural diagnosis. A specimen insufficient for ultrastructural study was obtained in five cases (25%). Refinement of the cytologic diagnosis was made in three cases (15%) and good correlation between the initial cytologic impression and the ultrastructural studies was seen in the remaining cases (60%). Comparison of different sites of FNA biopsy revealed a higher rate of ultrastructural examination in the cases involving the mediastinum. Illustrative cases of the use of electron microscopy in FNA biopsies of mediastinal tumors are presented.

Adult↗

Fine needle aspiration biopsy cytology as an adjunct in the diagnosis of childhood sarcoidosis.

Fine needle aspiration biopsy cytology performed in three children with sarcoidosis expedited clinical investigation and diagnosis of their disease. Each patient had a different clinical presentation; in two of them lymphoma was part of the initial differential diagnosis. Aspiration cytology in all cases revealed collections of epithelioid histiocytes, and multinucleate foreign body-type giant cells, without accompanying necrosis or acute inflammation. A diagnosis of non-caseating granulomas consistent with sarcoidosis was made in all aspirates. Special stains for identification of organisms performed on the smears of one case, and culture of aspirate material from one case were negative. Subsequent serum angiotensin converting enzyme levels in all patients were elevated. Chest x-ray films in all patients showed mediastinal and hilar lymphadenopathy. One patient had an interstitial pulmonary infiltrate. All patients responded to steroid therapy. Fine needle aspiration biopsy can be a useful diagnostic tool in the evaluation of children with suspected sarcoidosis.

Adolescent↗

Ornithine decarboxylase activity during gastric ulcer healing in dogs.

Ornithine decarboxylase (ODC) activity has been associated with mucosal growth and injury, yet, little information is available on ODC activity during gastric ulcer healing. We measured ODC activity in the ulcer base submucosa and the surrounding mucosa at 1 cm and 2 cm and assessed ulcer surface healing and a histologic score in experimentally induced ulcers (Quinton ulcer-maker) at 0 and 5 hr and at one, two, three, four, and seven days. A total of 26 dogs were studied, eight of which received 2% difluoromethylornithine (DFMO, a specific inhibitor of ODC) in drinking water. Ulcer healing was assessed by digitizing initial (plug size), and final ulcer surface area and was expressed as percent ulcer surface reduction. A histologic score was assessed by two independent pathologists unaware of the treatment. ODC induction was observed in the submucosa of the ulcer base but not in the surrounding mucosa. The baseline submucosal ODC activity was measured at 0.2 +/- 0.1 pmol (14CO2)/mg protein/hr, and at one day the ODC activity increased to 4.0 +/- 0.7, at three days to 15.2 +/- 5.5, and at seven days to 2.6 +/- 1.0 (P less than 0.001). DFMO treatment delayed GU healing significantly up to three days, but no difference was noted at seven days. The assessed histologic parameters did not correlate with ODC activity, and DFMO treatment did not alter the histologic score. These data suggest that polyamine biosynthesis occurs in the ulcer base submucosa during the first seven days of experimentally placed gastric ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparative DNA analysis of solid tumors by flow cytometric and image analyses of touch imprints and flow cell suspensions.

Comparative DNA analysis by flow cytometric (FCM) and image analyses (IA) has shown a high concordance rate. When present, discordance has been attributed to the presence of aneuploid cell populations detected only by IA, yet missed by FCM. This phenomenon has been explained by loss of aneuploid cells during FCM cell processing, differences in sampling area, or misinterpretation of the DNA histograms. To determine which factors are responsible for the discordance between IA and FCM, 82 fresh solid tumors from various sites were examined. Flow cytometric analysis was performed on cell suspensions isolated from the tumors, whereas IA was performed on touch imprints (IAT) and on cytosmears of the same cell suspension used for FCM (IAF). Comparison between IAT and IAF (IAT/IAF) assessed cell processing and sampling area differences, whereas IAF/FCM comparison assessed differences in apparatus and methodology as possible contributing factors to discordance. Furthermore, DNA histograms of IAT, IAF, and FCM were analyzed in the discordant cases to determine whether the discordance was due primarily to different cell populations detected (true discordance) or due to differences in histogram interpretation of the same cell populations (false discordance). IAT/IAF and IAF/FCM concordance rates (90% and 88%) were not significantly different from that of IAT/FCM (87%). False discordance accounted for most of the discordant cases in IAT/FCM comparison (six cases, 67%), whereas true discordance was seen in three cases. In all three truly discordant cases, the DNA-aneuploid cell populations detected only by IAT yet missed by FCM were also detected by IAF. This study demonstrates that discordance between IA and FCM is probably not due to cell loss during FCM cell processing or sampling area differences, but may be due to differences in assessing DNA ploidy in the interpretation of IA histograms and/or dilution of aneuploid cells by normal diploid cells in FCM.

Cell Separation↗

The size of small cell lung carcinoma cells. Ratio to lymphocytes and correlation with specimen size and crush artifact.

The size of small cell lung carcinoma (SCLC) cells has often been ambiguously defined as one and a half to four times that of a lymphocyte. The purpose of this study was to determine the ratio of nuclear diameter (ND) of SCLC cells to that of lymphocytes in the same tissue sections and to assess whether the size of SCLC cells correlates with the size of tumor specimens and crush artifact. The overall mean ND (microns +/- SD) of SCLC cells was 9.2 +/- 2.1, found in 36 oat cell carcinomas (OAT, 1,800 nuclei) and 16 intermediate cell carcinomas (INT, 800 nuclei). The mean ND of OAT and INT cells was 8.1 +/- 1.3 and 11.6 +/- 1.5, respectively. The mean ND of lymphocytes (2,600 nuclei) was 5.2 +/- 0.3. The overall mean of ND ratios (+/- SD) between SCLC cells and lymphocytes was 1.8 +/- 0.4 (median, 1.7), 1.6 +/- 0.2 for OAT and 2.2 +/- 0.3 for INT. The mean size of the 52 SCLC biopsy specimens was 0.6 +/- 0.9 cm. Of all the biopsies, 84.6% (n = 44) showed various degrees of tissue crushing. The ND of SCLC cells was associated with specimen size (P = .004) and the degree of tissue crushing (P = .001). Therefore, our findings further support the hypothesis that OAT should be considered the effect of artifact rather than a true variant of SCLC and that the ND of SCLC cells is approximately two times that of lymphocytes.

Analysis of Variance↗

Fine-needle aspiration cytology of the adrenal gland. Fifty biopsies in 48 patients.

Fine-needle aspiration biopsy of 50 adrenal masses from 48 patients was performed between 1984 and 1991. The series consisted of 28 males and 20 females, with an age range of 12 months to 79 years (mean age, 55 years). Clinical and/or pathologic follow-up was available in 37 patients. Fine-needle aspiration was diagnostic in all 29 malignant cases having follow-up, with no false-positive diagnoses. There were six primary malignancies (three neuroblastomas, two pheochromocytomas, and one adrenal cortical carcinoma) and 23 metastatic lesions. Of these, the lung was the most frequent primary malignancy (60%), followed by melanoma and renal cell carcinoma (8.6% each). The remaining nonmalignant fine-needle aspiration diagnoses were adrenal cortical neoplasms (most likely adenoma), adrenal cortical hyperplasia, myelolipoma, benign adrenal tissue, and abscess. Based on clinical follow-up, three other adrenal adenomas were not diagnosed by fine-needle aspiration. Six biopsy specimens (12%) were insufficient for diagnosis. Ancillary studies including electron microscopy and/or immunocytochemistry were performed on 13 malignant aspirates and provided additional confirmation of the cytology diagnosis in 12 cases. This study confirms that fine-needle aspiration is a sensitive and highly specific procedure for the evaluation of primary and metastatic malignancies involving the adrenal gland. The technique is less useful in the workup of benign processes but, in some instances, can provide specific diagnostic information.

Adolescent↗

The effect of tissue disaggregation methods on the clonogenicity of solid human tumor cells.

The effect of mechanical, enzymatic and combined disaggregations on the same tumor tissue (n = 154) to define variables related to clonogenic efficiency (CE) of human tumor clonogenic assay (HTCA) was examined. Overall, CE was highly associated with the percentage of malignant cells in the inoculative suspensions (P less than 0.001) and the total cell concentration plated (P = 0.03). However, there was no significant correlation between CE and the disaggregation method, type of tumor, cell viability, proportion of macrophages in the inoculum, or length of incubation (10 or 20 days). In addition, a higher CE was found in some nonadherent fractions when comparing the CE of the original plating suspensions to that of their nonadherent fractions. It is concluded that mechanical disaggregation is the simplest technique for obtaining the highest yield of malignant cells, which is a decisive factor for colony growth, and that an incubation time of 10 days and 1 x 10(6) cells per plate is the best condition for the human tumor clonogenic assay.

Gastrointestinal Neoplasms↗

Cytologic diagnosis of aspergillosis in cardiac transplantation.

Fine-needle aspiration of the lung is now widely utilized to diagnose pulmonary neoplasms, but often serologic techniques or open-lung biopsy is relied on for the diagnosis of infectious pulmonary processes. We report a series of four patients in whom the fine-needle aspiration technique was used to make the rapid cytologic diagnosis of pulmonary aspergillosis. Culture confirmation was also obtained on the aspirated material. A discussion of the available techniques for the laboratory diagnosis of pulmonary aspergillosis is presented and the advantages of fine-needle aspiration cytology are stressed. Our favorable results support expanded use of fine-needle aspiration cytology in the evaluation of lung nodules appearing in immunosuppressed populations.

Adult↗

Fine-needle aspiration cytology of Langerhans' cell histiocytosis (eosinophilic granuloma) of bone in children.

Fine-needle aspiration (FNA) cytology of three cases of Langerhans' cell histiocytosis (eosinophilic granuloma [EG]) of bone in children (mean age--8.3 yr; range 5-11 yr) is presented. Two patients presented with vertebral lesions and the third had a femoral mass. Cytomorphologic features of EG were seen in all cases including Langerhans' cell histiocytes having oval to reniform shape nuclei with nuclear grooving and abundant pale cytoplasm. The background showed a polymorphic population of cells including neutrophils, lymphocytes, foamy histiocytes, and osteoclasts. Moderate numbers of eosinophils were seen in two cases, while eosinophils were sparse in the third case. Ancillary immunocytochemical (ICC) studies performed on the aspirated material demonstrated positive staining for S-100 protein (all three cases) and T-6 antigen (one case). Ultrastructural examination (EM) performed in one case demonstrated characteristic Birbeck granules in the histiocytes. A specific cytologic diagnosis was made in all cases, enabling proper chemotherapy in one case, surgical excision in another and spontaneous resolution in the third case. Our experience demonstrates that FNA cytology can make a definitive diagnosis of EG, especially when coupled with ancillary studies such as ICC and EM on the aspirated material.

Biopsy, Needle↗

Pediatric fine-needle aspiration biopsy.

A total of 135 fine-needle aspiration (FNA) biopsies from varying sites were performed in 123 children (mean, 10.5 years; range, one day to 18 years) over a five-year period. One hundred thirty (96.3%) biopsy specimens were satisfactory for evaluation. Seventy-nine cases were nonneoplastic (60.8%); among these cases, a specific diagnosis of infectious disease was made in 17 (13.1%). A diagnosis of neoplastic disease was made in 50 (38.5%) cases, of which 14 (10.8%) were benign, 28 (21.5%) were malignant, and 8 (6.2%) were neoplasms of uncertain biologic potential. The sensitivity of pediatric FNA biopsies was 90.6%, specificity 100%, positive predictive value 100%, negative predictive value 94.7%, and efficiency of the test 96.5%. There were no false-positive diagnoses and there were four false-negative diagnoses, three of which involved aspirates of the central nervous system (CNS). Ancillary studies, including immunocytochemistry (20 cases), electron microscopic examination (18 cases), microbiologic culture (8 cases), cytogenetic studies (7 cases), and flow cytometry (3 cases), were performed on the aspirated material, enabling a more specific diagnosis or supplying additional information in many cases. Definitive diagnosis by FNA biopsy enabled radiation therapy and/or chemotherapy to be administered for unresectable malignant neoplasms, provided material for culture of infectious lesions, identified benign lesions not needing surgery, and aided the surgeon in planning the extent of surgery in resectable malignant neoplasms. These results support the greater use of FNA biopsy in the pediatric population.

Abdominal Neoplasms↗