Leopold G. Koss

Small cell (OAT cell) carcinoma of minor salivary gland origin

Fourteen anaplastic, small cell cancers of minor salivary glands, histologically akin to oat cell carcinoma of the bronchus, were presented. Half of the patients had neck node metastases; four patients survived 5 years or longer. The possibility of minor salivary gland primaries must be kept in mind whenever small cell carcinomas are found in neck nodes. A speculative comment on the possible common cellular origin of these minor salivary gland tumors and oat cell carcinoma of the lung is offered.

Prevalence Rates of Uterine Cervical Carcinoma in situ for Women Using the Diaphragm or Contraceptive Oral Steroids

Study of the prevalence rates of uterine cervical carcinoma in situ among women attending centres of Planned Parenthood of New York City, Inc., showed a small but statistically significant difference between the population choosing and using the diaphragm and the population choosing and using oral steroids for contraception. This can be attributed either to a decreased prevalence rate for women using the diaphragm or to an increased rate for women using oral steroids. The reason for the difference is not apparent from these data.

Primary choriocarcinoma of the urinary bladder. Report of a case with probable epithelial origin

The seventh case of primary choriocarcinoma of the urinary bladder is presented. The results of initial bladder biopsies on this 82‐year‐old male patient revealed a poorly differentiated urothelial carcinoma and carcinoma in situ. The diagnosis of choriocarcinoma was established at autopsy, and confirmed by the demonstration of chorionic gonadotropin by immunoperoxidase technique. The literature is reviewed and a possible epithelial origin of this rare tumor is discussed.

CARCINOGENESIS IN THE HUMAN URINARY BLADDER: OBSERVATIONS AFTER EXPOSURE TO PARA-AMINODIPHENYL.

EXPOSURE of industrial workers to potent urinary-bladder carcinogens is a quasi-experimental situation that offers a unique opportunity to study the natural history of human cancer. Crabbe and his co-workers1 , 2 adopted periodic cytologic examinations of the urinary sediment as the principal means of follow-up study of these unfortunate people. They demonstrated the reliability and practical value of this technic in the diagnosis of early bladder cancer. Since 1957 we have been studying the cellular makeup of the urinary sediment of a large group of workers exposed to para-aminodiphenyl (xenylamine). This substance was identified as a urinary-bladder carcinogen in dogs by Walpole, .xa0.xa0.

Association of human papillomavirus with neoplastic processes in the genital tract of four women with impaired immunity

Abstract The presence of papillomavirus particles was documentd by electron microscopy in atypical squamous epithelium of the cervix, vagina, and vulva, and in cells derived therefrom in four women with compromised immune status who were being followed in our clinics. Three of the patients had treated Hodgkins disease, and one a dermatologic disorder, perhaps akin to epidermodysplasia verruciformis. Initially, all four patients developed treatment-resistant condylomata acuminata of the vulva and adjacent areas. Subsequently, one of the patients was shown to harbor in the vagina a focus of markedly atypical epithelium, perhaps a flat condyloma. Two other patients, followed for several years, developed multiple epidermoid carcinomas in situ affecting the cervix, vagina, and vulva. In one of these two latter patients the disease progressed to multiple foci of superficially invasive carcinoma. The possible role of the human papillomavirus in the genesis of these lesions is discussed.

Quality control of cervical cytology in high-risk women. PAPNET system compared with manual rescreening

OBJECTIVEnTo compare the effectiveness of the PAPNET System with conventional rescreening of negative cervical smears in a high-risk population.nnnSTUDY DESIGNnThree thousand ninety-seven negative cervical smears from women with past history of cervical abnormalities were rescreened manually and with the PAPNET System. There were two reviews of PAPNET images: the first by two cytotechnologists with limited exposure to the instrument, and the second, limited to smears with discrepant diagnoses, by an expert in the use of the system. The remaining discrepant smears were submitted to a blinded microscopic review by a third party. The a priori consensus diagnosis was arbitrarily established when the result of two of the three reviews--manual, PAPNET and the independent third review--were concordant. The results of rescreening were compared with available biopsies.nnnRESULTSnOn manual rescreening of the 3,097 smears, 2,901 (93.66%) were reported as negative and 170 (5.49%) as abnormal. On the first PAPNET review, 2,938 (94.87%) were reported as negative and 150 (4.84%) as abnormal. There were 144 smears with discrepant diagnoses. After the second PAPNET review of these discrepant smears, the agreement between manual and PAPNET rescreening rose from 94.27% to 95.58%. A final, blinded review of 89 residual discrepant smears was used to establish consensus diagnoses. The diagnoses made by PAPNET-assisted rescreening agreed much better with the consensus diagnoses than did manual rescreening (Kappa = .61 vs. Kappa = -.32, P < .001). When compared with the results of 50 available biopsies, PAPNET-assisted rescreening also had a somewhat lower false negative rate (sensitivity 58.82% vs. 41.18%, P = .17) and a statistically significant lower false positive rate (specificity 63.64% vs. 36.36%, P = .01).nnnCONCLUSIONnPAPNET-assisted rescreening, when carried out by an experienced person, is more efficient than manual rescreening.

Computer-Based Diagnostic Analysis of Cells in the Urinary Sediment

Evaluation of images of cells from the urinary sediment by a computer-based microscope has yielded important preliminary results. Computer identification of benign and malignant urothelial cells can now be accomplished with a small margin of error. Furthermore, 2 categories of atypical urothelial cells can be identified. This information has been applied successfully to the study of 12 patients with bladder cancer, including 3 with non-papillary carcinoma in situ. Computer-generated diagnostic profiles based on a relatively modest number of urothelial cells (60 to 150 per patient) proved to be of diagnostic value. It is anticipated that within a few years a practical computerized system of identification of cells in the urinary sediment can be made available for general laboratory use.

Esophageal carcinoma metastatic to the retina. Diagnosis of a case by cytologic examination of intraocular vitreous washings.

BACKGROUNDnThe most common primary tumors of the eye are melanomas in adults and retinoblastomas in children. Although generally not recognized, metastases to the eye are more frequent than primary tumors.nnnRESULTSnOccult esophageal carcinoma metastasized to the retina in a 51-year-old woman. The cytologic diagnosis of carcinoma was established on intraocular vitreous washings. Further workup disclosed an adenocarcinoma of the esophagus, confirmed by brushings and biopsy.nnnCONCLUSIONnThe cytologic features of the intraocular aspirate allowed a rapid and reliable diagnosis that led to further investigation.

A study of factors affecting choice of contraceptives.

A systematic long-range study of 40000 women begun in 1965 by Planned Parenthood of New York City Inc. analyzed data to determine if choice of contraceptive is affected by factors (age ethnic origin early sexual experience number of children and economic status) that influence development of cervical carcinoma. Data were obtained from annual cytological specimens of all women and from initial interviews when contraceptive choice was made. Preliminary cytological and pathological findings are given. Population characteristics include low economic level with more than 50% between 21-30 years and 53% Negro. Differences were found according to ethnic group in (1) age at first pregnancy (47% Puerto Rican/Spanish and 51% Negro women pregnant by age 19 compared to 15% whites) and (2) size of families (larger families more common among Negroes and Puerto Ricans). A comparison of choice of oral contraceptives and the diaphragm revealed a great preference for orals in all ethnic groups especially among Puerto Ricans and in women under 30 years. No difference in choice of contraceptive was found with respect to family size while a preference for orals was found among women in the lower income group and among those pregnant before 20 or never pregnant. The choice and use of contraceptives varies in groups of women according to factors that influence probability of developing cervical carcinoma. An evaluation of any possible effect of the contraceptive itself is thus much more complicated than might first appear. Any consideration of the problem must take into account the biased choice of contraceptives among population groups with different probabilities of developing carcinoma of the uterine cervix. Such a study is underway. Evaluations of initial prevalence of and developing incidence of cervical carcinoma are also planned.

Computerized Screening Devices and Performance Assessment: Development of a Policy Towards Automation

ISSUESnThe extension of automation to the diagnostic assessment of clinical materials raises issues of professional responsibility, on the part of both the medical professional and designer of the device. The International Academy of Cytology (IAC) and other professional cytology societies should develop a policy towards automation in the diagnostic assessment of clinical cytologic materials.nnnCONSENSUS POSITIONnThe following summarizes the discussion of the initial position statement at the International Expert Conference on Diagnostic Cytology Towards the 21st Century, Hawaii, June 1997. 1. The professional in charge of a clinical cytopathology laboratory continues to bear the ultimate medical responsibility for diagnostic decisions made at the facility, whether automated devices are involved or not. 2. The introduction of automated procedures into clinical cytology should under no circumstances lead to a lowering of standards of performance. A prime objective of any guidelines should be to ensure that an automated procedure, in principle, does not expose any patient to new risks, nor should it increase already-existing, inherent risks. 3. Automated devices should provide capabilities for the medical professional to conduct periodic tests of the appropriate performance of the device. 4. Supervisory personnel should continue visual quality control screening of a certain percentage of slides dismissed at primary screening as within normal limits (WNL), even when automated procedures are employed in the laboratory. 5. Specifications for the design of primary screening devices for the detection of cervical cancer issued by the IAC in 1984 were reaffirmed. 6. The setting of numeric performance criteria is the proper charge of regulatory agencies, which also have the power of enforcement. 7. Human expert verification of results represents the gold standard at this time. Performance characteristics of computerized cytology devices should be determined by adherence to defined and well-considered protocols. Manufacturers should not claim a new standard of care; this is the responsibility of the medical community and professional groups. 8. Cytology professionals should support the development of procedures that bring about an improvement in diagnostic decision making. Advances in technology should be adopted if they can help solve problems in clinical cytology. The introduction of automated procedures into diagnostic decision making should take place strictly under the supervision and with the active participation and critical evaluation by the professional cytology community.nnnONGOING ISSUESnGuidelines should be developed for the communication of technical information about the performance of automated screening devices by the IAC to governmental agencies and national societies. Also, guidelines are necessary for the official communication of IAC concerns to industry, medicolegal entities and the media. Procedures and guidelines for the evaluation of studies pertaining to the performance of automated devices, performance metrics and definitions for evaluation criteria should be established.