Information, discrimination and divergence in cytology. III. Optimization of classification of Papanicolaou smears

The performance of a cytology laboratory can be objectively quantitated as the total discrimination, a defined quantity of information. The total discrimination is dependent on the number of categories used in gynecologic cytology and on the corresponding histologic states; over-classification results in a higher rate of misinformation and reduced total discrimination. Total divergence is another measure of the association between cytologic categories and histologic states; in contrast to the total discrimination, the total divergence does not require a one-to-one correspondence between the cytologic categories and the histologic states. Using data from the Gynecologic Cytology Laboratory of the University of Minnesota, the total discrimination was maximized when gynecologic cytology used three categories of diagnosis, consisting of (1) normal, atypical benign or reactive atypia, (2) cervical intraepithelial neoplasia (CIN) and (3) all malignancies. The use of four categories, (1) normal, atypical benign or reactive atypia, (2) mild or moderate dysplasia, (3) severe dysplasia or squamous carcinoma in situ and (4) all malignancies, was almost equally informative. Observations on the total divergences resulted in similar conclusions. These findings generally support the recommendation of the consensus workshop sponsored by the National Cancer Institute (the Bethesda System nomenclature) to group all degrees of CIN into two large categories.     

Information, discrimination and divergence in cytology. IV. Quality control in diagnostic cytology

The performance of diagnostic cytology on Papanicolaou smears can be periodically monitored by calculating the total discrimination or the total divergence of the cytologic diagnoses against the histologic diagnoses on samples obtained by colposcope-directed biopsies. Using these measures, the annual performances of the Gynecologic Cytology Laboratory of the University of Minnesota between 1980 and 1988 were retrospectively analyzed. For those years, the total discrimination and total divergence behaved similarly and were sensitive to the performance of the total system, including specimen sampling errors and laboratory precision. The lowest limits of the permissible range of the total discrimination and total divergence were 0.15 and -1.21 decits, respectively, for a single-slide Papanicolaou test if an 80% "hit" rate was accepted as the lowest threshold for each category. The optimal numbers of category-states were not a sensitive indicator of the quality of a laboratory; i.e., the optimal number of diagnostic categories remained at three throughout the period studied.     

Information, discrimination and divergence in cytology. V. General symmetry of total discrimination and total divergence.

Total discrimination and divergence are derived from Baye's theorem and based on backward (a posteriori) probabilities. Total forward (a priori) discrimination and divergence can be computed from a test matrix from which total backward discrimination and divergence were calculated for optimization of the classifications of gynecologic cytology (Papanicolaou smears) and quality control in a laboratory. The total forward discrimination and divergence appears to behave in parallel with the total backward discrimination and divergence, and the discrepancies in the backward and forward discrimination/divergence were the smallest near the optimum classification scheme. Conversely, the discrepancies between backward and forward discrimination and divergence may be helpful in finding the best classification scheme for gynecologic cytology. The general symmetries of the total backward and forward discrimination/divergence may be related to the human cognitive process of preferring symmetry and to the historic process in which cytologic classification followed histologic classification and continuously checked for matches in two directions--i.e., from histology to cytology and vice versa--thus resulting in the preservation of symmetry.     

Information, discrimination and divergence in cytology. I. Theoretical aspects and definitions

The results of medical tests update the probability of diagnosis (diagnosability) of a patient from the population prevalence of a disease. This paper demonstrates a method of combining several mutually dependent tests as the sum of log odds ratios, and of separating the log odd ratios of the test results and those of prevalences. Extending Kullback's discriminant function between two states to m states (m greater than or equal to 2), it is shown that the information of a test can be measured by discrimination and divergence, which are well-defined measures in information theory and test theory. The performance of diagnostic cytology can then be compared to the results of histopathologic diagnoses or to a peer-reviewed consensus without the use of arbitrarily given scores or without unfounded assumptions about underlying continuous variables. They can also provide a way to optimize the categorization (classification) of Papanicolaou smears and a means of quality control for morphologic tests. These methods can be used to evaluate the performances of cytology laboratories that use two classifications consisting of different numbers of categories (classes) and states.     

Morphologic scales and relative distances between lesions identified on Papanicolaou smears.

We fit a Gaussian-type curve to a nonmonotonic transform of initial arbitrarily given scales (pseudoscalar transform) of a two-way discrete classification table by maximizing the likelihood (entropy) and computing morphologic scales of clusters of objects identified by visual judgments. The scales give the relative distance between pairs of categories or states. Morphologic scales of histologic lesions (states) identified on Papanicolaou smears were computed from a confusion matrix consisting of 3,545 matched pairs of observations on Papanicolaou smears and colposcopically directed biopsies available from the Gynecologic Cytology Laboratory, University of Minnesota, between 1985 and 1987. The original (uncollapsed) confusion matrix consisted of eight cytologic categories and histologic states: normal plus atypical benign, reactive atypia (including condylomatous changes); mild, moderate and severe dysplasia; squamous carcinoma in situ; invasive squamous cell carcinoma; and other malignancies. The morphologic scales are expressed numerically, which reflects a degree of confusion between two diagnostic categories or states. Except for malignancies other than squamous cell carcinoma, morphologic scales of histologic states seen from cytology retained the order of clinical severity. We detected a high degree of confusion between severe dysplasia and carcinoma in situ. Malignancies other than squamous cell carcinoma fell between moderate and severe dysplasia. Such a transposition of the scales in this group containing adenocarcinoma was likely due to frequent association of adenocarcinoma with cervical intraepithelial neoplasia. Morphologic scales of cytologic categories seen from histology showed high degrees of confusion and transpositions between mild and moderate dysplasia and between severe dysplasia and carcinoma in situ.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cytology of argyrophilic carcinoma of the breast

Aspirations of breast lesions from 57 patients were studied by evaluating Grimelius-stained smears in order to determine the cytologic features of argyrophilic carcinoma and the reliability of argyrophilia as a characteristic of malignancy. The cytologic preparations were compared with histologic material. Sixteen benign lesions, 24 carcinomas correctly diagnosed by cytology and 5 carcinomas with technically inadequate smears were argyrophil negative. Five of 12 carcinomas with equivocal cytology were argyrophilic. There was perfect to case-to-case correlation between argyrophilia seen on histologic slides and on smears. The smears of the 5 argyrophilic carcinomas and 2 of the argyrophil-negative carcinomas with equivocal cytology shared features in common not seen in the other 50 smears: elongated cells with eccentric, round-to-oval nuclei and granular or opaque cytoplasm. These features can alert the pathologist to the possibility of malignancy in smears with equivocal cytology. A positive stain for argyrophilia will further increase the index of suspicion.     

Papillary breast lesions diagnosed on cytology. Profile of 65 cases

OBJECTIVE: To analyze the cytologic features of nipple discharge and fine needle aspiration (FNA) cytologic smears from breast lesions reported as showing papillary features and to correlate them with histopathologic features. STUDY DESIGN: The study group consisted of FNA smears and/or nipple discharge smears from 65 breast lesions diagnosed on cytology as duct papilloma, papillary lesion, fibrocystic condition, fibroadenoma, papillary neoplasm or papillary carcinoma. Cytomorphologic features assessed included cellularity, cell pattern (clusters, papillary, 3-dimensionality, etc.) and cell characteristics (monomorphism, pleomorphism, apocrine change, plasmacytoid features). Histological material was available for review and cytohistologic correlation in all cases. RESULTS: Forty-six specimens were FNA smears, and 16 were nipple discharge smears; in 3 cases FNA and nipple discharge cytologic smears were available for review. Cytologic study could predict the presence of a papillary pattern in all neoplasms with pure or focal papillary differentiation. There was an overlap in cytomorphologic features between papillary and nonpapillary benign lesions as well as between benign and malignant papillary neoplasms. Frank blood in the aspirate, cell dissociation and atypia, however, were more frequent in the last. CONCLUSION: Overlap of cytologic features in nonneoplastic and neoplastic benign papillary lesions and between benign and malignant papillary neoplasms necessitates histologic evaluation in all cases diagnosed as papillary on cytology. Since 49.2% of lesions showing papillary features on cytology prove to be malignant, all cases reported as papillary on cytology should be excised urgently for histologic assessment.     

Fine needle aspiration cytology of a lipoblastoma.

A lipoblastoma, an uncommon tumor of childhood that can be mistaken for a liposarcoma, was preoperatively diagnosed by fine needle aspiration cytology. The characteristic features on the cytologic smears were the presence of immature fat cells in the form of spindle-shaped cells, stellate cells and vacuolated lipoblasts along with lipocytes. The cytologic diagnosis was confirmed by histologic study of the excised tumor.     

Contribution of exfoliative cytology to the diagnosis of laryngeal lesions

OBJECTIVE: To estimate the diagnostic accuracy and reliability of exfoliative laryngeal cytology. STUDY DESIGN: Over three years (1996-1999) cytologic smears were obtained from clinically suspicious laryngeal lesions during laryngoscopy in a total of 31 selected patients (28 males and 3 females with an age range from 28-90 years). The cytologic diagnoses were analyzed and correlated with the histologic and final clinical diagnoses in 17 and 14 cases, respectively. Cytologic identification of the exact histologic type of the lesion was evaluated in 17 patients from whom both cytologic smears and biopsy material were obtained. RESULTS: The overall specificity was 100%, with no false positive diagnoses. The overall sensitivity was 93.3%, with one false negative cytologic diagnosis, in a case of non-Hodgkin's lymphoma. Cytohistologic correlation showed complete agreement between cytologic and histologic diagnoses in five of six benign lesions, in four cases of dysplasia and in six cases of squamous cell carcinoma. The overall diagnostic accuracy of cytology was 96.7% CONCLUSION: Exfoliative cytology by the smear technique is a reliable and accurate method in clinically suspected laryngeal lesions. Moreover, exfoliative cytology may be applied as the only alternative diagnostic method, especially in elderly patients with coexistent cardiorespiratory problems, when biopsy is not advisable or indicated.     

Abrasive bronchial brushing cytology. A preliminary study of 200 specimens for the diagnosis of neoplastic and nonneoplastic bronchopulmonary lesions

Two hundred subjects with chronic respiratory symptoms with a suspicion of malignancy were selected for bronchial brushing cytology. Prior sputum examination had shown malignant squamous cells in two cases only. The cytologic appearances of the brushing smears were divided into five categories: 41 (20.5%) smears with positively malignant cells; 20 (10%) smears predominantly showing chronic inflammatory features; 31 (15.5%) smears with mainly acute inflammatory changes; 60 (30%) smears with normal cytologic features; and 48 (24%) smears unsatisfactory for cytologic interpretation. Thirteen patients with a positive cytology had a positive tissue biopsy for malignancy. Among the group with chronic inflammatory changes, acid-fast bacilli were identified in nine cases, and one smear showed frank tuberculous granuloma. In the unsatisfactory group, two cases showed malignant cells in the postbrushing sputum. There was one false-negative report for malignancy in the entire study. This study confirms the sensitivity and accuracy of bronchial brushing cytology in the diagnosis of various bronchopulmonary lesions, especially malignancy and pulmonary tuberculosis, in India.     

Adult-type rhabdomyoma of the palate. Cytologic presentation of two cases with histologic and immunologic study

The cytologic presentations of two adult-type rhabdomyomas of the soft palate are reported. Fine needle aspiration smears of the lesions contained globular tumor cells that had striations and intracytoplasmic rod-shaped inclusions. These inclusions, corresponding to hypertrophied Z bands, were pathognomonic of rhabdomyoma tissue. The cytologic diagnosis was confirmed by histologic and immunologic studies in both cases. The cytologic preparations fixed in alcohol or air dried did not show the "spiderweb cells" observed in the histologic sections of tissue fragments fixed in formaldehyde; this clearly illustrates that the morphology of the cells of this tumor depends primarily on the specimen preparation technique used. These cases suggest that aspiration cytology can establish the diagnosis of this benign tumor of striated muscle, for which total surgical removal is usually sufficient to effect a cure. The differential diagnosis is discussed in detail.     

Cytology of desmoplastic medulloblastoma in imprint smears: a report of 2 cases

BACKGROUND: Desmoplastic medulloblastoma is a rare subtype of medulloblastoma with astroglial differentiation. The cytomorphologic features in intraoperative imprint smears from 2 cases of desmoplastic medulloblastoma are described. CASE REPORTS: A 22-year-old man and 27-year-old woman with a cerebellar tumor underwent craniotomy and tumor resection. The imprint cytologic smears contained cellular zones and nodular hypocellular areas containing astroglial and oligodendrogliallike elements. The cytology was misinterpreted as glial tumors, while the final histologic diagnosis in both cases were desmoplastic medulloblastoma. CONCLUSION: Desmoplastic medulloblastoma shows distinctive cytology in intraoperative smears. However, the occurrence of this rare type in adults and the presence of astroglial elements in imprint smears may cause a cytologic misinterpretation as gliomas.     

Fine needle aspiration cytology of breast fibroadenoma. A cytohistologic correlation study of 405 cases.

OBJECTIVE: To evaluate the cytohistologic correlation of breast fibroadenoma (FA) in order to assess the value of cytology in the conservative management of this lesion. STUDY DESIGN: A retrospective analysis of all aspirates diagnosed as FA or fibroadenomatous lesion (n = 1,549) for which a histologic follow-up study was available (n = 362). Forty-three aspirates, including 14 nonrepresentative smears, from histologically proven FAs with a different cytologic report were also included in the study. RESULTS: Cytohistologic agreement was present in 287 of the 362 cytodiagnoses. Lack of correlation was observed in 75 cases. Most diagnostic errors accumulated in the older patient group. The sensitivity of the cytologic diagnosis of FA was 86.9% (90.8% excluding nonrepresentative cases), with a positive predictive value of 79.3%. In 43 cases a histologic diagnosis of FA was given after previous erroneous (n = 29) or nonrepresentative cytodiagnoses (n = 14). The specificity of the cytologic diagnosis of FA reached 93.8%, with a negative predictive value of 96.3% (97.5% excluding nonrepresentative cases). Regarding malignancy, five tumors were diagnosed as FA and were malignant. No false positive diagnoses of malignancy were given, but nine aspirates were included in the category "suspicious for carcinoma." CONCLUSION: FA of the breast remains a diagnostic challenge for the cytopathologist. A considerable amount of benign breast lesions can mimic FA on cytology, and such diagnostic categories as "fibroadenomatous lesion" or "consistent with FA" are associated with low diagnostic accuracy. While the cytologic requisites for entering a program of conservative management of FA are established, it seems that strict diagnostic criteria should be applied even at the expense of diminishing sensitivity.     

Performance of 3 methods for quality control for gynecologic cytology diagnoses

OBJECTIVE: To evaluate performance and viability of internal quality control (QC) strategies in a public health laboratory of the state of S?o Paulo. STUDY DESIGN: A retrospective study was performed with 3 QC strategies to improve internal cytologic diagnoses: morphologic guided-list criteria (MGLC), 100% rapid-rescreening (100% RR) of negative slides ("turret" method) and 10% rescreening (10% R) of negative slides. Cases were examined at Adolfo Lutz Institute, S?o Paulo, Brazil, from 2002 to 2004. Histopathologic results, when available, were considered gold standard; cytologic consensus diagnosis was by 2 pathologists when histologic results were unavailable. RESULTS: MGLC selected 20.7% samples with cytologic atypias, 10% R selected 0.6% and RR selected 2.5%. Cytologic/histologic initial concordance was 57.4%, low-grade squamous intra-epithelial lesion false negative rate was 34.9% and high-grade squamous intraepithelial lesion false negative rate was 12.2%. After diagnosis, consensus concordance was 97.2%. CONCLUSION: The 100% RR and 10% R QC strategies detected more false negative cases in liquid-based cytology than in conventional Pap smears. The 100% RR strategy reduced the false negative results and allowed evaluation of individual staff performance. The 10% R strategy did not offer significant results. We concluded that association of MGLC and 100% RR strategies might improve cytologic diagnostic quality.     

Classification of cervical smears with discordance between the cytologic and/or histologic ratings

The problems of diagnostic variability between certified cytotechnologists was studied. Three cytology laboratories submitted a total of 28 cervical smears that had a discordance between the cytologic and/or histologic ratings. Eight independent cytotechnologists provided blind readings on each slide, expressed as "absence of cervical intraepithelial neoplasia (CIN)" to "CIN III." The median rating was absence of CIN or CIN I for 8 slides, CIN II for 5 and CIN III for 15. With a kappa value greater than 0 reflecting agreement beyond chance expectation and a value of 0.40 indicating fair agreement, the kappa value for 8 X 28 ratings was 0.36 (P = .0001), with a 90% confidence interval (CI) between 0.34 and 0.37. The kappa value was 0.14 (P = .10), with a 90% CI between 0.10 and 0.18, on a subsample of nine smears with two or more positive cytology diagnoses but a negative histology. Sixteen of the 28 slides represented cases of histologically proven cancer. Treating cytologic diagnoses of CIN II and CIN III as positive, the sensitivity of the cytologist with reference to histology varied between 71% and 86% while the specificity ranged from 18% to 62%. The positive predictive value was 1/2.5 to 1/1 and the negative predictive value was 1/6 to 1/1. The predictive power (true positives/false positives) ranged from 1.0 to 2.2. The cytodiagnosis of these cervical smears from cases of discordance thus exhibited limited reliability. Standardization of the relevant cytologic knowledge and its routine application is needed to improve the level of performance.     

An approach to the problem of false negatives in gynecologic cytologic screening

A system of quality control for gynecologic cytologic screening designed to minimize the problem of false-negative cytologic reports is proposed. The system involves the harvesting of "quality control" smears, at the time of colposcopic examination, from patients referred to colposcopy because of previous abnormal smears that had been interpreted as representing dysplasia or neoplasia. These quality control smears are then submitted to the cytology laboratory, indistinguishable from bona fide cases, among the routine smears. This appears to be a more effective means of quality control than the current standard system used in the United States, which involves cytology laboratories routinely rescreening 10% of the slides reported out as "negative".     

Paratesticular spindle cell rhabdomyosarcoma diagnosed by fine needle aspiration cytology: a case report

BACKGROUND: Spindle cell rhabdomyosarcoma is a rare, newly identified subtype ofembryonal rhabdomyosarcoma with improved behavior and a predilection for the paratesticular area. Fine needle aspiration (FNA) cytology findings of embryonal rhabdomyosarcoma have been described. However, there is no previous report on the cytologic findings of spindle cell rhabdomyosarcoma at testicular or extratesticular sites. CASE: A 13-year-old boy presented with a large, right sided scrotal mass. Fine needle aspiration (FNA) was performed for rapid diagnosis. The smears revealed numerous spindle cells and large fragments of cytoplasmic processes with cross-striations and were diagnosed as spindle cell rhabdomyosarcoma. The histologic sections were also diagnosed as spindle cell rhabdomyosarcoma. CONCLUSION: The cytologic findings of this rare tumor have not been reported before. The cross-striations were easily identified in FNA smears, so the diagnosis of spindle cell rhabdomyosarcoma was made confidently. The histologic sections showed only spindle cells with different patterns of arrangement, resembling leiomyosarcoma. The cross-striations were not identified in the histologic sections. In this case cytologic diagnosis aided the histologic diagnosis.     

Fine needle aspiration cytodiagnosis of Hodgkin's disease and its subtypes. I. Scope and limitations

The fine needle aspiration (FNA) smears and paraffin-embedded sections from 89 cases with a cytologic and histologic diagnosis of Hodgkin's disease (HD) and 27 cases with minor or major cytohistologic discrepancies were reviewed. The accuracy of the initial cytologic study was found to be 91.8% for diagnosing HD and 58.1% for classifying its subtypes. Following review, 87 of the 89 agreement cases remained classified as HD. Of the 27 cases with initial cytohistologic discrepancies, 12 were classified as HD and 10 were categorized as lymphocytic or non-Hodgkin's lymphoma by both cytology and histology upon review. Following review, the accuracy of FNA cytology for the diagnosis of HD improved to 98.0%, with 71.4% correct subtyping. The greatest limitation of cytologic subtyping was in cases of nodular sclerotic HD: only 3 of 17 cases could be subtyped even after review. The cytomorphologic features of the HD subtypes are described, and the difficulties encountered in the cytodiagnosis of HD are discussed at length. The results of this study indicate that FNA cytology is a useful tool not only for the diagnosis of HD, but also for its subtyping.     

Needle aspiration cytology of a benign and a malignant schwannoma

The histologic and cytologic features of an uncommon solitary, malignant schwannoma and a benign schwannoma are presented. The benign tumor revealed characteristic interlacing fascicles of spindle-shaped cells on both histology and cytology. The malignant schwannoma produced a variable histologic pattern that was selectively sampled from a recurrence in a scar; only obviously malignant, undifferentiated, spindle-shaped cells not capable of further characterization were seen on cytology. Preliminary experience with immunoperoxidase staining for the neural crest marker S-100 protein has been encouraging and may permit identification of these tumors on aspiration smears.