Pathology and probability. Likelihood ratios and receiver operating characteristic curves in the interpretation of bronchial brush specimens.

Diagnoses in pathology often are qualitative, such as atypical or suspicious, and consequently are thought to have limited clinical value. To investigate the utility of a qualitative diagnostic system, seven pathologists retrospectively evaluated 100 bronchial brush specimens using the following categories: definitely benign, probably benign, possibly malignant, probably malignant, and definitely malignant. The likelihood ratio (LR) and receiver operating characteristic (ROC) curve, two statistical probabilistic measurements, were used to calculate diagnostic accuracy among individuals and groups. The results show: (1) the LR for individual diagnostic categories varied among observers, resulting in different clinically malignant probabilities; (2) observer experience did not appear to play a role in overall diagnostic accuracy, except in the diagnosis of small cell carcinoma; (3) observers operate at higher levels of diagnostic accuracy with, rather than without, clinical history. The authors conclude that qualitative diagnoses contain important information and can be interpreted effectively with LR and ROC.

Cytologic features of villous adenoma of the ampullary region.

Villous adenoma of the ampulla of Vater is a rare but distinct pathologic entity. We studied seven brush cytology specimens from four patients with this unusual lesion all of whom had surgical pathologic confirmation and clinical follow-up. The distinguishing cytologic appearance includes the presence of slender, elongate columnar cells arranged singly or in small sheets and clusters. Long, thin, basally oriented nuclei occupy about one third of the cell and have fine, granular chromatin with one or more nucleoli. Although brushings of villous adenoma of the ampullary region may reveal a relatively benign but distinctive morphologic pattern, the aggressive nature of these lesions has been well documented, including those in our patients.

Paranuclear blue inclusions in small cell undifferentiated carcinoma: a diagnostically useful finding demonstrated in fine-needle aspiration biopsy smears.

In a study of bone marrow aspiration smears, Wittchow et al. (Mod Pathol 1992;5:555-558) described a highly characteristic finding, paranuclear blue inclusions (PBIs), found almost exclusively in cases of metastatic small cell undifferentiated carcinoma (SCUC). PBIs are 1-4 microns, light blue, cytoplasmic inclusions best visualized with Romanowsky-type stains. These inclusions are most easily found indenting the nuclei within clusters of closely opposed tumor cells. In the current study air-dried fine-needle aspiration biopsy (FNAB) smears from 146 primary and metastatic small cell and non-small cell adult and childhood malignancies were reviewed. PBIs were found in 28/32 (88%) of SCUC but were observed in only 4/44 (9%) non-small cell carcinomas, 2/21 (9.5%) lymphomas, 1/8 (12.5%) melanomas, 0/14 sarcomas, and 6/27 (22%) small round cell neoplasms. These results suggest that the presence of PBIs in air-dried FNAB smears of adult neoplasms, while not pathognamonic of SCUC, are a diagnostically useful finding. PBIs may be seen in a variety of different childhood small round cell neoplasms which limits their utility in this setting. The recognition of PBIs is most important to the cytologist who may not have access to ancillary studies, such as immunohistochemistry and electron microscopy.

Brush cytology of the extrahepatic biliary tract: comparison of cytologic features of adenocarcinoma and benign biliary strictures.

Malignant strictures of the extrahepatic biliary tract are difficult to discern from benign strictures solely by clinical and/or radiographic findings. Endoscopic retrograde wire-guided brushings of strictures have proven to be useful in evaluating such lesions. Because the reported sensitivity of diagnosing adenocarcinoma of the extrahepatic biliary tract by this technique has varied considerably (44 to 100%), we undertook a retrospective study to determine if the diagnostic accuracy could be increased by identifying key cytologic features by reviewing a series of 90 biliary tract brushings from 80 patients. The cytologic diagnosis was confirmed either by additional pathologic material and/or clinical follow-up. Utilizing a multiple logistic regression analysis, three key cytologic features were identified that were useful in separating benign from malignant strictures; these features included: nuclear molding, chromatin clumping, and increased nuclear-cytoplasmic ratio. The presence of two of these three features resulted in a sensitivity of 83%; the corresponding specificity was 98%. The use of these key features should aid the cytologist in better recognizing malignant cells in biliary tract brushings.

Oncogene amplification screening by labeled primer multiplex polymerase chain reaction.

This paper describes an improved procedure for rapid detection of amplified genes in fresh or formalin-fixed, paraffin-embedded tissues. Utilizing a multiplex differential polymerase chain reaction with radioactively labeled primers and electrophoresis of the products through thin gels, it is possible to screen for oncogene amplification more rapidly and reproducibly than has been previously demonstrated. This procedure takes advantage of thin vertical gels with external cooling, which allows sharp band resolution. Four separate gels can be electrophoresed at the same time in a single gel box. Because each gel slab contains 10 or more lanes, 40 or more samples can be assayed for gene amplification simultaneously. The entire procedure can be carried out from formalin-fixed, paraffin-embedded tissue to finish in 8 h when combined with a sonication technique for DNA extraction.