Inheritance of proliferative breast disease in breast cancer kindreds.

Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer.

A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors.

Standard treatment for neoplastic meningitis requires frequent intrathecal (IT) injections of chemotherapy and is only modestly effective. DepoCyt is a sustained-release formulation of cytarabine that maintains cytotoxic concentrations of the drug in the cerebrospinal fluid (CSF) for more than 14 days after a single 50-mg injection. We conducted a randomized, controlled trial of DepoCyt versus methotrexate in patients with solid tumor neoplastic meningitis. Sixty-one patients with histologically proven cancer and positive CSF cytologies were randomized to receive IT DepoCyt (31 patients) or IT methotrexate (30 patients). Patients received up to six 50-mg doses of DepoCyt or up to sixteen 10-mg doses of methotrexate over 3 months. Treatment arms were well balanced with respect to demographic and disease-related characteristics. Responses occurred in 26% of DepoCyt-treated and 20% of methotrexate-treated patients (P = 0.76). Median survival was 105 days in the DepoCyt arm and 78 days in the methotrexate arm (log-rank P = 0.15). The DepoCyt group experienced a greater median time to neurological progression (58 versus 30 days; log-rank P = 0.007) and longer neoplastic meningitis-specific survival (log-rank P = 0.074; median meningitis-specific survival, 343 versus 98 days). Factors predictive of longer progression-free survival included absence of visible central nervous system disease on neuroimaging studies (P<0.001), longer pretreatment duration of CSF disease (P<0.001), history of intraparenchymal tumor (P<0.001), and treatment with DepoCyt (P = 0.002). The frequency and grade of adverse events were comparable between treatment arms. In patients with solid tumor neoplastic meningitis, DepoCyt produced a response rate comparable to that of methotrexate and significantly increased the time to neurological progression while offering the benefit of a less demanding dose schedule.

Identification of fungal casts in a patient with renal candidiasis.

Since the treatment of fungal infections with amphotericin B may result in significant nephrotoxicity, better methods for discriminating between life-threatening and more benign fungal infections are needed. Recently numerous fungal casts were identified in the urine of a patient who had undergone renal allograft transplantation. The recognition of fungal casts permitted an unequivocal diagnosis of systemic fungal infection. Successive examinations of the patient's urinary sediment provided an excellent monitor of the response to treatment. The cytologic features of fungal casts are described. Since systemic fungal infections often involve the kidney, screening for fungal casts may have significant clinical applicability.

Usefulness of macroscopic urinalysis as a screening procedure. A preliminary report.

The macroscopic examination (physicochemical testing) is a sufficient laboratory screening procedure for routine urinalyses when accurately assessed. Only in those patients for whom routine urine specimens are macroscopically positive or in symptomatic patients with or without known renal or urinary-tract disease should a microscopic examination be necessary. Results of this study of more than 900 consecutive routinely screened urine specimens indicate that there is less than a 3% diagnostic yield when the urine sediment is examined after a negative macroscopic examination.

Comparison of Papanicolaou's stain with the Gomori methenamine silver (GMS) stain for the cytodiagnosis of Pneumocystis carinii in bronchoalveolar lavage (BAL) fluid.

The cytodiagnosis of Pneumocystis carinii (PC) in bronchoalveolar lavage (BAL) fluids has traditionally required a special stain such as Gomori's methenamine silver (GMS) stain. Recent reports indicate that identification of foamy alveolar casts (FACs) with Papanicolaou's (Pap) stain may provide a sensitive and less complicated way of making the diagnosis. To confirm these observations, results on a series of 318 BALs were reviewed. PC was identified on 65 (20%) specimens from 54 patients. Pap stains and GMS stains were positive on 56 (86%) of these BALs. Pap stains were positive on seven (11%) specimens that had negative GMS stains. PC was later confirmed on these specimens by other methods. Only two (3%) BALs had positive GMS stains and negative Pap stains. The results of this study confirm other reports that show that PC can be sensitively diagnosed with the Pap stain. The authors suggest that routine special stains for PC are unnecessary on BALs.

An improved technic for examining urinary casts and a review of their significance.

Casts represent an important, diagnostic component of urinary sediment, and may signal renal parenchymal disease in asymptomatic individuals. Accurate, precise identification of certain casts may be difficult due to poor visualization by current technics. Casts from freshly voided urine specimens, cytocentrifuged and stained by the Papanicolaou method, can be visualized optimally from permanent slide preparations. The genesis of these casts and their diagnostic potential related to renal disease and acute renal allograft rejection are discussed.

Leukocyturia in cyclosporine-treated renal allograft recipients.

Five hundred eighty-seven daily urine specimens were examined from 179 consecutive renal allograft recipients with the use of quantitative cytodiagnostic urinalysis. Specimens were divided between those patients receiving cyclosporine (CyA) and steroid immunotherapy (73 patients) and those receiving standard azathioprine (Aza) and steroid immunotherapy (106 patients). When patients with urinary tract infections were excluded, an increase in leukocyturia was observed in the CyA-treated patients. Ninety-three percent of the CyA-treated patients had at least one specimen with more than 1,000 neutrophils/10 high-power fields (HPFs) versus 62% of the 106 Aza-treated patients. Sixty-four percent of the specimens examined from the CyA-treated group had more than 1,000 neutrophils/10 HPFs compared with only 18% of specimens from Aza-treated patients. It appears that CyA is a cause of sterile leukocyturia in renal allograft recipients. The significance of leukocyturia in CyA nephrotoxicity needs further definition.

Prevalence of hematuria in urothelial neoplasia.

Voided urine specimens from 82 cases of histologically verified urothelial neoplasia (transitional cell carcinoma grades I, II, III, and carcinoma in situ [CIS] ) were evaluated for the presence of gross and microhematuria (MH). Microhematuria was assessed macroscopically with the reagent-strip blood test and evaluated microscopically with enumeration of erythrocytes using a standardized semiquantitative Papanicolaou-stained urine sediment examination. The authors' retrospective study indicated that gross hematuria rarely was present in urothelial neoplasia, however, occult blood (greater than 5 RBC/HPF) was present in four out of five cases when one sample was examined. In some cases there was an overlap between the number of erythrocytes excreted by control population and those with urothelial neoplasms. Urine sediment examination was more sensitive than reagent-strip testing for MH in patients with urothelial neoplasia.

Ultraviolet spectrophotometric analysis of barbiturates. Current assessment as an emergency screening procedure.

Several laboratory methods are currently available for the detection of barbiturates, but few are suitable for emergency use, The authors evaluated use of an ultraviolet spectrophotometric method as a screening procedure and compared the results with results obtained by other barbiturate methods (colorimetric, gas-liquid chromatographic, and immunochemical), Procedure time was approximately 40 minutes, sensitivity 0.2 mg/dl, precision (coefficient of variation) 5.4%, recovery 97.8% for phenobarbital, and there was good correlation with results obtained by gas-liquid chromatography and the EMIT system for phenobarbital. The authors recommend ultraviolet spectrophotometry as an excellent screening procedure for assessing the severity of barbiturate intoxication.

Prostatic acid phosphatase. Current assessment in vaginal fluid of alleged rape victims.

Although elevated prostatic acid phosphatase activity (ACP) in vaginal fluid is compatible with recent coitus, the finding of spermatozoa in vaginal fluid is usually considered the diagnostic indicator for semen. When 80 alleged rape cases during an 18-month period were reviewed and the results of cytologic examination for the presence of spermatozoa compared with quantitative ACP determinations, the latter appeared to be a more reliable and sensitive indicator of semen. The normal range of ACP in semen, as well as persistence of ACP in vaginal fluid, was also defined. It is concluded that vaginal fluid ACP is a reliable and sensitive method for identification of semen. Furthermore, the results confirm that quantitative ACP determination of vaginal fluid specimens may substantiate the allegation of rape with respect to time.

Differentiation of renal tubular epithelium in renal transplantation cytology.

Increased numbers of renal tubular epithelial cells are present in the urinary sediments of renal transplant recipients during acute rejection. Few investigators have described characteristics of renal tubular epithelial cells in cytologic preparations. This study compiles morphologic characteristics of various tubular epithelial cells and determines the type of the tubular cells present during acute allograft rejection. The results demonstrate that cuboidal forms from the small collecting ducts are the predominent tubular epithelial cells exfoliated in voided urine during acute allograft rejection.

Comparison of dysmorphic erythrocytes with other urinary sediment parameters of renal bleeding.

Dysmorphic erythrocytes have been described in the urine sediment of patients with renal parenchymal bleeding. This study compares the prevalence of dysmorphic erythrocytes in 5,128 urine specimens with blood, erythrocytic, or fibrin casts, proteinuria, and significant numbers of exfoliated renal tubular cells (RTCs). Of the 510 samples containing pathologic casts, 15% had dysmorphic erythrocytes, 60% had proteinuria, 71% had RTCs, and 12% had no other urinalysis abnormality. Of the 186 samples containing dysmorphic erythrocytes, 55% had pathologic casts, 42% had proteinuria, 71% had RTCs, and 13% had no other abnormality. Renal hematuria can best be evaluated by examination of all four of these urinalysis abnormalities rather than using a single entity for diagnosis. Patients with urinalysis evidence of renal hematuria should be evaluated further for renal disease rather than lower urinary tract disorders.

The urinary myeloma cast. Frequency of detection and clinical correlations in 30 patients with multiple myeloma.

The authors examined urine specimens from 30 patients with multiple myeloma (MM) to determine the usefulness of cytodiagnostic urinalysis in evaluating such patients. Nine patients had clinical evidence of renal failure. In six of these nine patients (67%), or 20% of all patients, the urine sediment contained unique "MM-casts." These were characterized by a waxy to granular matrix surrounded by reactive, syncytial, giant cells with occasional renal cells embedded in the cast matrix. These casts were not observed in urine specimens from patients with normal renal function. Renal biopsy in two patients with MM-casts confirmed that cytologic diagnosis of "MM-kidney." The patient groups with or without MM-casts were comparable with respect to age, sex, and clinical stage of disease. In contrast, those with MM-casts were more likely to have clinical evidence of renal disease (100% vs. 13%), Bence Jones proteinuria (100% vs. 35%), hypercalcemia (50% vs. 8%), and hyperuricemia (50% vs. 4%). The two groups could not be distinguished reliably by urine physicochemical determinations. However, there were marked differences in the frequency of microscopic abnormalities. All patients with MM-cast formation excreted other pathologic casts as well and had evidence of tubular injury, while five of six had evidence of ischemic necrosis. This compared with 17%, 13%, and 21%, respectively, of those without MM-casts. Thus, cytodiagnostic urinalysis is of value in distinguishing MM-kidney from the numerous other causes of renal failure in patients with MM.

Identification of a toxoplasma cyst by fine-needle aspiration.

In the course of evaluating the fine-needle aspiration technic a toxoplasma cyst was identified in a lymph node excised from a patient in whom toxoplasmosis subsequently was confirmed serologically. This is the first reported case in which a cyst was identified by this method. The recognition of a cyst and characteristic cytologic features in the aspirate demonstrates the utility of fine-needle cytologic examination in diagnosing toxoplasmic lymphadenitis.

Inclusion-bearing cells in industrial workers exposed to lead.

Histochemical and microscopic studies have shown that a characteristic renal response to lead exposure is the formation of discrete, dense, staining intranuclear inclusion bodies in renal tubular epithelial cells. Cytologic examination of urinary sediment showed that four of 19 (21%) lead workers had exfoliated inclusion-bearing cells of proximal renal tubular origin. These lead-induced inclusion-bearing cells appeared distinctly different from viral-induced inclusions, degenerative or nonspecific intranuclear inclusions seen with tubular necrosis, or macronucleoli seen in reparative renal tubular epithelium. While their presence indicates cytologic evidence of tubular injury, the clinical significance of these cells and their application to medical monitoring is not clearly understood.

Urinary cytodiagnosis of acute renal allograft rejection using the cytocentrifuge.

The clinical diagnosis of acute renal allograft rejection in immunosuppressed recipients can often be predicted or confirmed on the basis of characteristic urinary cytologic findings. Use of cytocentrifugation permits a simple, rapid, reproducible and semiquantitative means of preparing cytologic urinary specimens of diagnostic quality from small quantities of urine. The cytodiagnosis of acute renal rejection was established before or on the same day a clinical diagnosis of rejection was made in the majority of renal transplant cases studied over a 12-month period. Renal tubular cells were found to be the exfoliated cells of greatest value in predicting an acute rejection episode, and their persistence has prognostic importance.

Cytologic identification of clinically occult proliferative breast disease in women with a family history of breast cancer.

A cytologic method for sampling the normal breast by fine-needle aspiration (FNA) was used to determine the frequency of clinically inapparent proliferative breast disease (PBD) in women with family histories of breast cancer. The authors attempted to obtain specimens from each quadrant of both breasts in 51 female first-degree relatives of breast cancer patients. The study group had no detectable masses by physical examination or mammography. Samples were prepared on membrane filters, Papanicolaou stained, and evaluated cytomorphologically. Three hundred seventy-eight of 408 (92.6%) possible quadrants were sampled; cellular material was obtained from 290 (76.7%) quadrants. PBD was identified in 20 of the 51 women (39.2%). When epithelium was obtained, nuclear area, perimeter, and diameter were measured with the use of computerized image analysis. Nuclei in samples containing atypical hyperplasia showed significant differences in these parameters when compared with cells from samples containing normal epithelium or benign hyperplasia. The authors' findings indicate that FNA sampling and computerized image analysis are useful in the detection and characterization of clinically inapparent PBD.

Evaluation of asymptomatic microhematuria.

OBJECTIVES: The purpose of this study was to evaluate a comprehensive urine cytodiagnostic assay to assist in localizing the site of origin and the etiology of asymptomatic microhematuria. This analysis, which assesses various qualitative and quantitative aspects of the voided urine, is compared simultaneously with controls obtained from the established routine urologic evaluation. METHODS: One hundred consecutive subjects who presented solely for the evaluation of asymptomatic microhematuria were evaluated by the established routine urologic evaluation and a refined urine cytodiagnostic assay. For the purpose of this study, only calculi and neoplasms were considered significant findings. RESULTS: The incidence of significant urologic disease was 13% (3 renal neoplasms, 2 urothelial bladder carcinomas, and 8 urinary calculi). The refined urine cytodiagnostic assay identified both uroepithelial vesical neoplasms, 7 of the 8 urinary calculi, and none of the 3 renal neoplasms. The presence of dysmorphic urinary red blood cells (RBCs) and RBC casts was strongly suggestive of renal parenchymal bleeding. Overall, 43 of 44 subjects (98%) with dysmorphic RBCs and RBC casts failed to demonstrate any significant urologic etiology. CONCLUSIONS: These preliminary results suggest that the refined cytodiagnostic urine assay may be helpful in distinguishing whether a given patient's microhematuria is of a significant urologic or a renal parenchymal cause. The addition of this specialized urinalysis may prove a useful adjunct in improving the diagnostic yield in patients with asymptomatic microhematuria.

Acute leukemic infiltration of the vitreous diagnosed by pars plana aspiration.

A 30-year-old man with acute lymphoblastic leukemia, null cell, L2 type developed a unilateral dense cellular vitreous infiltrate while in apparent remission. Cytopathologic examination of material aspirated from the vitreous established the diagnosis of lymphoblastic infiltration. Prompt radiotherapy and chemotherapy rapidly reduced the vitreous infiltration and cleared cells from the cerebrospiral fluid. Intraocular involvement by the leukemic process was the initial sign of central nervous system involvement. Acute lymphoblastic leukemia should be added to the list of lymphoproliferative disorders capable of vitreous infiltration, and which can be identified by vitreous aspiration and cytopathologic examination.

Cerebrospinal fluid cytopathology.

Cerebrospinal fluid (CSF) evaluations represent important diagnostic procedures for many pathologic conditions of the central nervous system, such as meningitis, encephalitis, and brain tumors. The authors' discussion of CSF cytopathology includes specimen collection and cytopreparation, microscopic evaluation, cell differential and cell counting methods, and the cellular composition of pathologic CSF. The accuracy of CSF cytopathology is indicated and future trends are noted.