Jick Y. Wong

Analysis of False-Negative Diagnoses on Endoscopic Brush Cytology of Biliary and Pancreatic Duct Strictures The Experience at 2 University Hospitals

CONTEXT Endoscopic brush cytology is a valuable technique for the diagnosis of pancreatobiliary malignancy. Despite its widespread use, the sensitivity of this method has been reported as approximately 50%. The specificity is usually higher than 95%. Few reports have systematically analyzed the reasons for this relatively low sensitivity. OBJECTIVES To determine the rate and reasons for false-negative diagnoses in endoscopic brushing cytology of biliary and pancreatic ducts based on the results of sensitivity, specificity, accuracy, and positive and negative predictive values. DESIGN Retrospective analysis of laboratory data and slide review of false-negative cases. SETTING Two tertiary care state university hospitals. PATIENTS A total of 183 pancreatobiliary brushing specimens obtained from patients undergoing endoscopic retrograde cholangiopancreatography for biliary or pancreatic duct disease for a 4- to 5-year period. INTERVENTION Endoscopic retrograde cholangiopancreatography brushings. MAIN OUTCOME MEASURES Determination of sensitivity, specificity, accuracy, and positive and negative predictive values. Analysis of false-negative results. RESULTS The sensitivity, specificity, accuracy, and positive and negative predictive values, overall, were 48%, 98%, 79%, 92%, and 76%, respectively. Sampling error was a major cause of false-negative diagnoses (67%), followed by interpretive (17%) and technical errors (17%). CONCLUSIONS Improvements in sensitivity and diagnostic accuracy for cancer of the pancreatobiliary tract can be achieved by optimizing slide preparatory techniques. Also, enhancement of the cytologists diagnostic skills enables the identification of the morphologic features of premalignant lesions. Repeat brushings are indicated for suspicious or negative results not consistent with the clinical or radiologic findings.

Cytologic diagnosis of syphilitic pleuritis: a case report.

We report on a case of a 68‐yr‐old man with secondary syphilis diagnosed by biopsy of skin lesions, who concomitantly suffered from left lower lobe pneumonia with associated pleuritis. Cytologic examination of the pleural fluid was diagnostic of syphilis, not only by the characteristic cytomorphology but also by demonstration of spirochetes by the May‐Grünwald‐Giemsa (MGG) and Steiner staining methods. This suggests that the pneumonia was also syphilitic. The patient was seropositive for HIV‐1, but this probably did not contribute to the thoracic manifestations of syphilis, as there was no evidence of immunodeficiency by the CD4/CD8 T lymphocyte count. This is the second reported demonstration of Treponema pallidum in a pleural fluid, and the first diagnosed by cytopathologic examination. Diagn. Cytopathol. 16:35–38, 1997.

Membranous lamellar cytoplasmic inclusions in histiocytes and mesothelial cells of serous fluids. Their relationship to phagocytosis of red blood cells.

OBJECTIVE To define the composition of cytoplasmic inclusions forming stacks and concentric whorls in histiocytes and mesothelial cells of serous fluids, imparting to them a resemblance to Gaucher cells, and to draw conclusions on the mechanism of their formation. STUDY DESIGN Three serous fluids (one pleural and two pericardial) containing a fair number of the cells referred to were progressively subjected to the following studies: (1) cytochemistry for mucopolysaccharides, proteins, phospholipids and hemoglobin; (2) immunocytochemistry for immunoglobulins IgA, IgG, IgM and lysozyme; (3) transmission electron microscopy (TEM), and (4) scanning electron microscopy-based energy dispersive X-ray microanalysis (SEM-EDAX). RESULTS All three specimens were blood stained and contained large numbers of histiocytes and mesothelial cells, arranged singly and in groups, with abundant cytoplasmic inclusions. The inclusions stained strongly positive for phospholipids, weakly positive for hemoglobin and negative for all other substances examined by cytochemistry and immunocytochemistry. By TEM the inclusions had a concentric lamellar membranous structure, reminiscent of myelinosomes or lamellar bodies of lipid-forming or -storing cells. There was also phagocytosis by histiocytes and mesothelial cells of red blood cells, which were mostly in a degenerated state. SEM-EDAX of inclusion-bearing cells showed a modest peak for phosphorus and a variable but small peak for iron, which corroborated the cytochemical and TEM findings. CONCLUSION Since there was not metabolic or other systemic disease in the patients to account for these cells, we posit that phospholipids derived from cell membranes of phagocytized cells, especially red blood cells, provide the building blocks for the formation of such inclusions as they enter the metabolic pathway of phagocytic cells (mesothelial cells and histiocytes) and appear in their lysosomal structures. It is advantageous for cytologists to be familiar with significance of such changes and not to mistake them for metabolic or other systemic disease.

Nuclear protrusions in cells from cytologic specimens. Mechanisms of formation.

OBJECTIVE To explore the mechanisms of formation of nuclear protrusions (NPs) encountered in cytologic specimens and specifically the possibility of their being the result of an aberrant division of the cell and to determine how widespread the NP phenomenon is in cells from various tissues. STUDY DESIGN Six hundred fifty-four cervical smears out of 5,000 with abundant cervical columnar epithelium examined were found to have many cells with NPs (group A). These cells were studied: (A) by light microscopy to define the structure and stages of formation of NPs, (B) by transmission electron microscopy (TEM), (C) by tubulin immunostaining for detection of mitotic spindle-associated microtubular structures, (D) by fluorescence in situ hybridization (FISH) utilizing X chromosome probes to monitor chromosomal movement into NPs, and (E) by direct fluorescence microscopy to examine autofluorescence patterns in cells with NPs. Also, tissue sections of 240 cervical cone biopsies, many including intraepithelial neoplasia (group B), were examined for NPs, and sections containing NPs were subjected to TEM. Last, 390 nongynecologic cytologic specimens from various lesions and organs obtained by fine needle aspiration or brushing methods were examined for the presence of NPs. RESULTS NPs were found in a variety of tissues, epithelial and nonepithelial. Their formation in the cases examined appeared to be related to cell division, as indicated by: the light microscopic findings; the TEM findings (centriole at their tip, indication of spindle formation, nucleolar movement into the NP and suggestion of chromosomal movement as well); positive tubulin immunostaining of centrosome-centriole in NPs and also of the underlying region of the nuclear pole, indicating the presence of microtubules consistent with mitotic spindle; and movement of one X chromosome into NPs, as shown by FISH. CONCLUSION NPs are formed in cells from a variety of tissues, epithelial and nonepithelial. In many cases they appear to result from aberrant cell division--namely, unipolar mitosis--occurring before prophase events are completed. Another possible mechanism of NP formation not involving cell division is through alteration or remodeling of the cytoskeleton of the cell; that was shown experimentally to produce nuclear volume and shape changes, including formation of protrusions.

Enhancing Recovery of Endocervical Component on Gynecologic Cytology Specimens Processed by Thin-Layer Technology

OBJECTIVE To address the causes and report the corrective measures required for resolving the initial problem of high rates of cervical vaginal cytology specimens reported as having no endocervical component on SurePath (AutoCyte, Inc., Burlington, North Carolina, U.S.A.) liquid-based, thin-layer technology at an academic center cytology laboratory. STUDY DESIGN Analysis of 511 cases lacking endocervical/transformation zone component out of 9,221 SurePath thin-layer gynecologic specimens processed in a one-year period. The study encompassed a review of sample collection techniques by physicians and nurses, specimen processing, cytologic features of endocervical/squamous metaplastic cells processed by the SurePath method and statistical analysis of endocervical cell recovery rates after implementation of corrective measures. RESULTS Absence of endocervical/transformation zone component varied from an initial 18% in the first month to an average of 5.3% after corrective actions were implemented. Current rates of SurePath thin-layer specimens having no endocervical component are lower than those for conventional smears. CONCLUSION Since SurePath was only recently introduced to the market, there are no previously published data addressing how to optimize the recovery of endocervical component on liquid-based, thin-layer specimens processed by this methodology.