Indeterminate fine-needle aspiration of the breast. Image analysis-assisted diagnosis.

BACKGROUND: Fine-needle aspiration (FNA) of the breast, although effective for the diagnosis of breast carcinoma, has a significant drawback. A minority of cases cannot be classified as benign or malignant. These FNAs are assigned an inconclusive diagnosis, often prompting surgical biopsy. Surgery is justified in some of these cases, but many of these lesions are benign. If these inconclusive FNAs could be accurately diagnosed as benign or malignant, many of these patients might avoid having to undergo surgical biopsy. METHODS: An image analysis and an automated learning system that was developed at the University of Wisconsin (Xcyt) was used to categorize 56 (37 benign and 19 malignant) breast FNAs diagnosed as "indeterminate" and the computer diagnosis compared with the surgical biopsy. For each case, an operator chose a group of cells within a single field on the FNA slide and digitized this image using a video camera. The outline of each nucleus was manually outlined, and the exact border was delineated by the computer. Based on the analysis of three nuclear features (area, texture, and smoothness), the Xcyt system computed a benign or malignant diagnosis and a corresponding probability of malignancy for each case. RESULTS: Probabilities of malignancy for the respective cases ranged from 0.0-1.0. Benign cases were defined as those having probabilities of malignancy < 0.3; those with probabilities above this limit were considered malignant. Using these criteria, the computer identified 33 cases as benign and 23 cases as malignant. When compared with the surgical biopsy, 42 of the cases (75%) were correctly classified with a sensitivity and specificity of 73.7% and 75.7%, respectively. There were only 5 false-negative cases with a false-negative rate of 13.5% and a predictive value of a negative test of 84.8%. CONCLUSIONS: When faced with inconclusive diagnoses of FNAs of breast masses, the authors believe that image analysis may be used as an aid in the further classification of such lesions, thereby providing a more appropriate triage for surgical biopsy.

A simple splenic reticuloendothelial function test: counting erythrocytes with argyrophilic inclusions.

The presently accepted methods for evaluation of splenic reticuloendothelial (RE) function include 99mTc sulfur colloid spleen scan, antibody-coated autologous erythrocyte clearance, and pocked erythrocyte count. All methods involve special equipment and/or risk and inconvenience to patients. A simple method of assessing splenic RE function was developed by counting erythrocytes with argyrophilic inclusions using a simple silver stain and an ordinary microscope. To test the validity of this method, blood samples were collected from patients suspected of having hyposplenia or asplenia, including patients with history of splenectomy, sickle cell disease or trait, and newborns. Blood samples were also collected from normal adults and from patients without hyposplenia or asplenia as controls. The samples were tested by this method and compared to the pocked erythrocyte count that served as a gold standard. The results obtained by the two methods were found to be very comparable with little overlap between those from controls and patients with definite hyposplenia or asplenia. With the pocked erythrocyte count as the gold standard, this method has a sensitivity of 88.9% and a specificity of 97.1%. However, this method requires no special equipment. Staining can be applied to fresh blood smears as well as to Wright-stained smears, and the silver-stained smears are permanent.

Low-grade transitional cell carcinoma of the urinary bladder: application of select cytologic criteria to improve diagnostic accuracy [corrected].

The cytologic diagnosis of low-grade transitional cell carcinoma of the bladder is difficult, and the reported sensitivity of a positive diagnosis ranges from 0 to 73%. Using regression analysis, our laboratory previously reported the criteria of increased nuclear/cytoplasmic ratios, irregular nuclear membranes, and cytoplasmic homogeneity as indicative of low-grade transitional cell carcinoma. To examine the validity of these criteria, six observers examined 88 bladder-wash specimens (39 transitional cell carcinomas and 49 benign) and, using the selected criteria, graded each wash for the probability of malignancy. Diagnostic accuracy was measured using the receiver operating characteristic curve and the likelihood ratio. Overall observer accuracy was 76%, the sensitivity of a definitive negative diagnosis was 82%, and the specificity of a definitive positive diagnosis was 96%. We conclude that key cytologic criteria can be learned and effectively applied with high accuracy. Observer variation in diagnostic categories might reflect different confidence levels and probabilities of transitional cell carcinoma.

p53 gene mutations and steroid receptor status in breast cancer. Clinicopathologic correlations and prognostic assessment.

BACKGROUND: There is increasing evidence linking development and progression of cancer to an accumulation of mutations at the genomic level. The most frequently mutated gene known to date in sporadic breast cancer appears to be the tumor suppressor gene p53. This study was designed to determine the frequency of p53 gene mutations in primary breast cancer, to correlate the presence of p53 mutations with established clinicopathologic parameters, including the estrogen receptor (ER) and progesterone receptor (PR) status, and to assess the prognostic significance of p53 mutations regarding patient survival. METHODS: We examined the p53 gene in genomic DNA samples from 192 primary breast cancers. Using denaturant gradient gel electrophoresis, the authors analyzed exons 5-9 in all tumors for mutations and performed DNA sequencing in 20 tumors to identify the exact nature of the p53 mutations. RESULTS: p53 gene alterations were identified in 43 of the 192 tumors (22%), the majority localized in exons 5 and 6. DNA sequencing showed mostly missense mutations resulting from G or C substitutions. p53 mutations were found more often in tumors of younger women (P = 0.002), Afro-American women (P = 0.05), and in tumors lacking ER (P = 0.03), PR (P = 0.04), or both (P = 0.06). There were no significant correlations with family history, tumor size, histologic grade or type, nodal status, or disease stage. The overall survival rates showed no significant difference between patients with mutant and wild-type p53 tumors. The same was true when the comparison was limited to node-negative patients or patients with ER-positive or ER-negative tumors. Finally, there was no significant difference in survival between patients with tumors harboring mutations in exons 5 and 6 versus exons 7-9. CONCLUSIONS: The results of this and other studies demonstrate a consistent relationship between ER-positive tumors and wild-type p53 on one hand and ER-negative cancers and p53 mutations on the other. Our data do not support a significant prognostic role for p53 mutations in predicting survival.

Adenovirus infection of the kidney: mass formation in a patient with Hodgkin's disease.

Adenovirus (AV) infection usually has a benign course in normal hosts; however, in immunocompromised patients, AV may cause pneumonia, cystitis, or disseminated disease with substantial morbidity and even mortality. Although pulmonic AV involvement is common, infection of the kidney is unusual. The histologic findings previously described include tubular necrosis with interstitial inflammation and glomerulonephritis. We report a case of an AV-induced unilateral mass lesion in the kidney of a patient with Hodgkin's disease (HD) following bone marrow transplantation.

Pulmonary veno-occlusive disease. Fatal progression of pulmonary hypertension despite steroid-induced remission of interstitial pneumonitis.

This report describes a 28-yr-old patient with pulmonary veno-occlusive disease (PVOD). She presented with pulmonary hypertension, hypoxemia, and interstitial pneumonitis. We report the discordance between the response of her hypoxemia and interstitial pneumonitis, which resolved with corticosteroid therapy, and her progressive pulmonary hypertension, which caused fatal right heart failure. This report emphasizes that the radiographic interstitial shadowing of PVOD may be caused by either (1) an inflammatory interstitial pneumonitis (which may be responsive to anti-inflammatory therapy) or (2) interstitial pulmonary edema, or both.