Diagnostic accuracy of squamous cervical lesions studied in spatula-cytobrush smears

The cytologically positive cases found in 25,300 cervical smears of spatula samples and 6,168 smears prepared by combined spatula-Cytobrush sampling were analyzed. The diagnostic accuracy (the correlation between the cytologic and histologic diagnoses) was the same for both types of sampling. As to the histologic diagnosis, the rates of severe dysplasia, carcinoma in situ and squamous carcinoma in the spatula-Cytobrush group were more than twice as high as in the spatula group. In the spatula group, the majority of abnormal cells was of the mature type. In the spatula-Cytobrush group, the majority of smears contained a mixture of immature and mature abnormal cells. The more immature lesions, which are often located higher in the endocervical canal, seem to be better sampled by the Cytobrush. The results indicate that the Cytobrush reaches areas that a spatula cannot reach, resulting in a higher diagnostic efficiency.     

Efficacy of the cytobrush versus the cotton swab in the collection of endocervical cells

Cervical smears should contain endocervical cells to be accepted as adequate for a cytologic diagnosis. Before this study was undertaken, one-third of the smears received in the Cytology Laboratory of Odense University Hospital were inadequate. In an attempt to increase the rate of adequate smears, a randomized study was undertaken to compare the efficacy of the combined spatula-Cytobrush method to that of the spatula-cotton swab method traditionally used by doctors in Denmark. The incidence of smears containing cylindrical and/or metaplastic cells was 89% by the spatula-Cytobrush method as compared to 62% by the spatula-cotton swab method (P less than .001). There were large differences between the rates of adequate smears from the various doctors when using the spatula-cotton swab method (range, 14% to 82%); these differences were far less when using the spatula-Cytobrush method (range, 75% to 100%). A large-scale application of the spatula-Cytobrush method should result in fewer repeat smears required and fewer false-negative smears.     

A low-power, "architectural," clue to the follicular variant of papillary thyroid adenocarcinoma in aspiration biopsy

OBJECTIVE: To search for low-power, or "architectural," clues to the diagnosis of the follicular variant of papillary thyroid adenocarcinoma (FVP) in Diff-Quik-stained aspiration biopsy smears in order to aid in the rapid diagnosis of FVP, especially as a complement to frozen sections. STUDY DESIGN: The smears of 23 cases, each with tissue-proven FVP, were compared to those of 23 cases of classic papillary thyroid adenocarcinoma (PTA), 23 cases of tissue-proven follicular neoplasms (FN) (i.e., adenoma or well-differentiated adenocarcinoma) and 23 samples of colloid nodules (CN). The low-power (10x) features of the four groups were studied and compared. RESULTS: Our study showed that FVP exhibited monolayered cellular sheets with branched, irregular contours, which can be distinguished from the uniform microfollicles with smooth contours formed in FN and the large, round or oval monolayered sheets of follicular cells found in CN. FVP shared all of the features of classic PTA except for the larger, complex sheets of epithelial cells and psammoma bodies found in the latter. CONCLUSION: The branched sheets of epithelial cells evident during low-power examination of Diff-Quick-stained smears of thyroid aspirates are a ready first clue to the rapid diagnosis of FVP. The diagnosis can be confirmed by subsequent careful evaluation of nuclei in Papanicolaou-stained smears and sections of tissue.     

Consequences of the introduction of combined spatula and Cytobrush sampling for cervical cytology. Improvements in smear quality and detection rates

One of the most important yardsticks for evaluating sampling for the detection of premalignant and malignant cervical lesions is the percentage of smears that contain cells from the transformation zone. Until February 1985, all smears made by around 500 different general practitioners were taken with a modified Ayre spatula. In the period February to October 1985, 24,496 smears of spatula samples and 5,716 smears prepared by combined spatula-Cytobrush sampling were analyzed. With the introduction of the combined spatula-Cytobrush method, the rate of smears containing cells from the transformation zone (adequate smears) rose from 84% to 98%. With the spatula-alone method, there were large differences between the rates of adequate smears from the various doctors; with the combined spatula-Cytobrush method, all participating doctors were without exception highly successful. The positive cytology rate was significantly higher in the combined spatula-Cytobrush smears (0.75%) as compared with the spatula-alone smears (0.38%). There was also a change in the diagnostic pattern in that more premalignant changes of the glandular epithelium of the endocervix were detected. One case of early invasive adenocarcinoma of the endocervix, in which the combined spatula-Cytobrush smears was positive and the repeat spatula-alone smear made by the gynecologist was negative, is discussed in detail. We anticipate that, with the large-scale introduction of the Cytobrush sampling method, fewer repeat smears will be required and, in addition, the observed relative increase of endocervical adenocarcinoma of the endocervix will be halted. In addition, there will be fewer false-negative smears.     

Cytodiagnosis of 112 salivary gland lesions. Correlation with histologic and frozen section diagnosis.

Aspirates of 112 cases of salivary gland lesions with histologic correlation were reviewed. Fifty-five cases (49%) had frozen sections made. The 112 cases included 76 cases of benign lesions (31 cases of pleomorphic adenoma, 19 of Warthin's tumor and 26 of nonneoplastic lesions), 22 of primary salivary gland malignancy and 14 of metastatic malignant lesions. The overall accuracy in diagnosing benign and malignant lesions was 95%. The accuracy in diagnosing the exact category of neoplastic lesions was 70%. The diagnostic sensitivity for malignant lesions was 86% and the specificity, 99%. There was one false positive, in which a pleomorphic adenoma was diagnosed as small cell carcinoma. Five false-negative cases were encountered that were due to underdiagnosis of mucoepidermoid carcinoma and adenoid cystic carcinoma. The smears were reviewed, and the diagnostic pitfalls are discussed. A comparison of the cytodiagnosis and frozen section diagnosis was made. In frozen sections there were two false negatives, and two diagnoses were deferred. The overall diagnostic accuracy was 91%. The accuracy in diagnosing the exact category of neoplastic disease was 77%. The diagnostic sensitivity for malignant disease was 70% and specificity, 100%. Frozen section, however, did supplement the fine needle aspiration diagnosis in 13 cases.     

Comparison of cytohistologic techniques in diagnosis of gastroesophageal malignancy

OBJECTIVE: To evaluate the diagnostic performance of various endoscopic cytologic techniques, namely, brushing cytology, touch smear cytology and crush cytology, and comparison with concurrent biopsy results in diagnosis of gastroesophageal malignancy. STUDY DESIGN: This prospective study was conducted on 100 patients, with 78 clinically suspected cases of esophageal malignancy and 22 cases of gastric malignancy. RESULTS: The diagnostic accuracy of touch smear in esophageal malignancy was significantly higher (94.12%) than brushing and crush smears (89.71% each), and endoscopic biopsy had the diagnostic accuracy of 88.24%. The diagnostic accuracy of combined brushing and biopsy was 100%; it was 97.06% for touch smears combined with biopsy. In comparison, the diagnostic accuracy in gastric malignancy was 75% for brushing alone, which was significantly lower than touch smear (87.5%) and endoscopic biopsy (87.5%). The diagnostic yield for crush smear was 81.25%. A combination of touch smears and biopsy had a diagnostic yield of 100%; it was 93.75% for combined brushings and biopsy. CONCLUSION: A combination of cytohistologic techniques resulted in a statistically significant increase in the diagnostic yield of gastroesophageal malignancies and thus cytologic techniques may act as adjunct to biopsy histology to increase the diagnostic efficiency.     

Fine needle aspiration cytology of eyelid tumors

Fine needle aspiration (FNA) biopsy was performed on 19 patients with eyelid masses. Six of the patients also had preauricular/submandibular nodal enlargements aspirated. Histopathologic study was performed in ten of the cases. FNA cytology made the diagnosis of an epithelial malignancy in 17 cases (10 sebaceous carcinomas, 4 poorly differentiated carcinomas, 2 squamous cell carcinomas and 1 malignant melanoma). The diagnostic accuracy of FNA cytology in evaluating eyelid masses was thus 89.4%; there were two false-negative cases. All nodal FNA smears revealed metastases of the respective primary tumors. This study indicated that FNA cytology is a simple and efficient method for making the diagnosis of malignancy in eyelid masses, especially in those patients who are not suitable candidates for surgery. Subsequent nodal metastases and tumor recurrence were detected without difficulty using FNA smears.     

Clinical significance of atypical glandular cells by the 2001 Bethesda System in cytohistologic correlation

OBJECTIVE: To evaluate incidence, cytology findings and pathology outcome of atypical glandular cells (AGC) in Pap smears according to the 2001 Bethesda criteria. STUDY DESIGN: From 103,073 consecutive Pap smears, 113 (0.1%) AGC cases were identified. Of these, 91 (80%) had adequate histologic evaluation included in this study. RESULTS: Abnormal histology findings were seen in 38 patients (42%). Final pathology results revealed 14 endometrial adenocarcinomas, 5 endocervical adenocarcinomas, 1 cervical squamous cell carcinoma, 1 endometrial stromal sarcoma, 6 other malignancies, 4 endocervical adenocarcinomas in situ, 4 cases ofendometrial complex byperplasia, 1 case of endocervical glandular dysplasia and 2 cases of cervical intraepithelial neoplasia 3 with glandular involvement. Women with AGC, favor neoplasia, were more likely to have significant pathology than those with AGC, not otherwise specified, 74% vs. 33% (p = 0.002). Some characteristic background cytologic findings were also noticed in most cases of endometrial, fallopian tube and endocervical adenocarcinoma. CONCLUSION: A diagnosis of AGC is more clinically significant by the 2001 Bethesda System, especially the "AGC, favor neoplastic" category. Some background cytologic features are important because they are indicators of malignancy.     

The cytologic diagnosis of adenocarcinoma in situ of the cervix uteri and related lesions. II. Microinvasive adenocarcinoma

Criteria for the cytologic diagnosis of microinvasive adenocarcinoma of the cervix have not been previously established. Such cytologic criteria were evolved through the detailed analysis of cervical smears from 40 histologically confirmed cases. The cellular features of cervical adenocarcinoma in situ (AIS) were always associated with microinvasion. Syncytia of glandular cells, small cells in very crowded sheets and papillary groupings of cells, when seen in conjunction with AIS, were suggestive of microinvasion. Dissociation of cells was common. Nuclear pleomorphism with an irregular chromatin pattern and inconspicuous-to-prominent nucleoli was frequently present. In some cases, a tumor diathesis was seen in the smear background. Using these criteria, our predictive accuracy for diagnosing microinvasive cervical adenocarcinoma is improving steadily and now approaches 50%. Ongoing investigation of these cases must include a diagnostic come biopsy to further improve the predictive accuracy for this lesion.     

High diagnostic accuracy of cytologic smears of central nervous system tumors. A 15-year experience based on 4,172 patients

OBJECTIVE: To investigate the diagnostic accuracy and current role of intraoperative cytologic smears of central nervous system tumors. STUDY DESIGN: Retrospective analysis of 4,172 patients operated on during 1985-1999, with 3,541 intraoperative smears performed during open procedures and 631 during stereotactic biopsies. RESULTS: Complete correlation with the final diagnosis was achieved in a mean of 89.8% (range, 83-93.7% per year). Diagnostic accuracy increased to 95% on average (range, 91.5-96.7% per year) when cases of partial correlation, mainly due to grading deviations, were included. The most accurate intraoperative diagnoses were obtained in cases of meningioma (97.9%), metastasis (96.3%) and glioblastoma (95.7%). A significant reduction in diagnostic accuracy was observed in cases of oligodendroglioma (80.9%) and ependymoma (77.7%). Besides diagnosis and grading, smear cytology provided resection guidance in cases of well-delineated tumors. CONCLUSION: Intraoperative smears in neurosurgery are easy to obtain and inexpensive and have high diagnostic accuracy. In addition to stereotactic biopsy procedures, intraoperative smears permit reliable intraoperative guidance during lesion targeting and resection.     

Interpreting microbiopsies in cervical smears. A cytohistologic approach

OBJECTIVE: To assess interobserver variation in the diagnosis of thick tissue specimens (microbiopsies) in cytology smears and histologic sections taken from them, to evaluate the applicability of MIB-1 in histologic sections from microbiopsies and to evaluate whether processing microbiopsies in inconclusive smears has additional diagnostic value. STUDY DESIGN: Cytologic smears were selected in which there were diagnostic disagreements between pathologists and cytologists and microbiopsies were present. Interobserver variation among three pathologists and three cytologists in the diagnosis of these microbiopsies was investigated. The smears were processed for histologic sections, and interobserver variation between pathologist diagnoses were analyzed. An additional histologic slide stained for MIB-1 was used for consensus diagnosis. The consensus diagnosis was compared with available follow-up and its sensitivity and specificity determined. The value of applying the microbiopsy technique in slides diagnosed as inadequate or atypical squamous cells of undetermined significance (ASCUS) was analysed. RESULTS: From a series of 62,334 cervical smears, 49 with microbiopsies were selected. It was possible to derive histologic slides from 38 cases. Interobserver variability in the diagnosis of microbiopsies and histologic sections from them was moderate--kappa = .44 (SE = .06) and kappa = .44 (SE = .09), respectively. In the consensus meeting for all cases, a conclusive diagnosis was reached. The Pearson correlation coefficient between the consensus diagnosis and MIB-1 staining was r = .62. The sensitivity of the consensus diagnosis for the follow-up diagnosis was 71% and the specificity 60%. Diagnosis on approximately 50% of slides diagnosed as inadequate or ASCUS could be made. CONCLUSION: The histotechnical workup of microbiopsies is not difficult; however, their diagnosis can be a problem. Adequate diagnostic criteria are not available. Aided by MIB-1 staining, histologic sections from microbiopsies can be diagnosed, and the diagnoses correlated with follow-up in most cases. Processing of microbiopsies in smears with an inconclusive cytologic diagnosis or a diagnosis of ASCUS allowed correct diagnosis in 50% of cases in this study.     

Cytologic and DNA cytometric diagnosis and therapy monitoring of squamous cell carcinoma in situ and malignant melanoma of the cornea and conjunctiva

OBJECTIVE: To investigate the diagnostic accuracy of exfoliative cytology of the cornea and conjunctiva and DNA image cytometry for quality control and monitoring of therapy for malignant neoplasms. STUDY DESIGN: Conjunctival or corneal smears from six cases clinically suspicious for malignant melanomas and eight suspicious for carcinomas in situ were investigated. Smears from 18 cases clinically nonsuspicious for neoplastic diseases served as negative controls. Repeated smears were obtained during and after local mitomycin C (MMC) therapy. RESULTS: In none of 18 nonsuspicious cases, cytology revealed abnormal cells. DNA cytometry showed nonaneuploidy in all of these. All smears from patients with histologically proven malignant melanomas (MM) and squamous cell carcinomas in situ revealed abnormal cells. Image cytometry demonstrated DNA aneuploidy in 66.6% of patients with MM and 80% with carcinoma. Sensitivity of cytology thus was 100% for both MM and carcinoma; specificity also was 100%. DNA measurements after MMC therapy revealed euploid polyploidization of nonneoplastic squamous cells. DNA cytometry provided an objective identification of tumor cell regression. CONCLUSION: Cytologic examination of corneal and conjunctival smears is a noninvasive tool with high diagnostic accuracy for detection of epithelial neoplasms. DNA image cytometry can serve for quality control and for objective monitoring of the effect of local chemotherapy.     

Role of bone marrow imprints in haematological diagnosis: a detailed study of 3781 cases

X. Gong, X. Lu, X. Wu, R. Xu, Q. Tang, G. Xu, L. Wang, X. Zhang and X. Zhao Role of bone marrow imprints in haematological diagnosis: a detailed study of 3781 cases Objectives: To explore the role of imprints in routine bone marrow (BM) diagnosis. Methods: The cellularity and diagnostic accuracy of BM imprints, aspirate smears and trephine biopsy sections from 3781 patients were assessed using routine cytochemical staining. Seventy‐nine cases of lymphoma and 114 cases of plasma cell myeloma (PCM) were selected for correlation analysis of tumour cell infiltration patterns. Another 21 cases of lymphoma were selected to detect t(14;18)(q32;q21) and t(11;14)(q13;q32) by fluorescent in situ hybridization (FISH) on BM imprints, and the G‐banding technique was performed for comparison. Results: BM imprints were better than smears for evaluating cellularity. In the BM imprint group, diagnostic accuracy for metastatic carcinoma, myeloproliferative neoplasm, myelodysplastic/myeloproliferative neoplasm and PCM was better than in the smear group, while accuracy for megaloblastic anaemia, acute myeloid leukaemia, refractory cytopenia with unilineage or multilineage dysplasia, refractory anaemia with excess blasts and lymphoplasmacytic lymphoma was higher than in the section group, but not statistically different from the smear group. Good correlation of infiltration patterns of lymphoma and myeloma cells was found between BM imprints and sections (r = 0.90 and 0.78, respectively). Detection of t(11;14)(q13;q32) by FISH on imprints was higher than G‐banding analysis. Conclusions: BM imprints show features of both smears and trephine sections. Imprints are superior to smears for evaluation of cellularity, and are also better than sections for analysis of cytological changes. In addition, FISH on BM imprints markedly improves the identification of chromosomal abnormalities.     

Aspiration cytology of the oncocytic variant of papillary adenocarcinoma of the thyroid gland

OBJECTIVE: To study the cytologic features of the oncocytic variant of papillary adenocarcinoma of the thyroid gland to distinguish this subtype from other oncocytic lesions of the thyroid. STUDY DESIGN: We reviewed the smears from aspiration biopsies of 6 proven cases of oncocytic variant of papillary adenocarcinoma and compared their cytologic features with smears from 19 oncocytic follicular neoplasms (11 adenocarcinomas and 8 adenomas). Smears were stained with a modified Giemsa stain (Diff-Quik). RESULTS: All smears were cellular. Colloid was variable but more abundant in cases of the oncocytic variant of papillary adenocarcinoma. The cells in papillary adenocarcinoma had round to ovoid, overlapped nuclei; prominent intranuclear inclusions; and "grooves." Nucleoli were generally absent. In oncocytic follicular neoplasms, the cells had round nuclei and prominent nucleoli. Nuclear inclusions and grooves were seen but were not as prevalent as in papillary adenocarcinomas. CONCLUSION: The oncocytic variant of papillary adenocarcinoma of the thyroid gland can be distinguished from other oncocytic lesions by fine needle aspiration biopsy, whereas the absence of prominent nucleoli in oncocytes favors the diagnosis of an oncocytic papillary adenocarcinoma.     

The impact of liquid-based oral cytology on the diagnosis of oral squamous dysplasia and carcinoma

OBJECTIVE: Even though diagnostic oral exfoliative cytology is a useful, economical and practical tool in the diagnosis of oral dysplasia and carcinoma, it is not yet extensively used. The results of conventional exfoliative and liquid-based diagnostic cytology in oral potentially malignant lesions (PML) are herein reported and compared with the histological diagnosis. METHODS: Either conventional (89) or liquid-based (384) exfoliative cytology was used for the diagnosis of oral dysplasia/carcinoma in 473 subjects and the results were compared with scalpel biopsy histology. Cells were collected using a Cytobrush device for conventional smears and with a dermatological curette for the liquid-based cytology. The 'curette technique' also allowed for the collection of 'accidental' tissue fragments, utilized as microbiopsies. RESULTS: Histological diagnosis was squamous carcinoma in 96 of 473 cases, high-grade dysplasia (oral intraepithelial neoplasia two to three) in 24 and other lesions in 353 cases. The smears in the conventional cytology group were inadequate in 12.4%, with an 85.7% sensitivity and a 95.9% specificity. There were 8.8% of inadequate specimens in the liquid-based cytology group; sensitivity was 95.1% and specificity was 99.0%. CONCLUSIONS: Although conventional cytology is useful when diagnosing oral PML (better sensitivity and predictive positive value if compared with the cervical smear test with similar specificity) and can improve the accuracy of histological diagnosis, liquid-based cytology gives better results, as it not only enhances both sensitivity and specificity, but also provides material for further investigation (AgNORs, DNA, microbiopsies, etc.).     

Identification of Campylobacter pylori in gastric biopsy smears

The use of gastric biopsy imprint smears to diagnose Campylobacter pylori was compared with the use of tissue sections and cultures. Multiple gastric biopsies were taken from the mucosa of 42 patients during endoscopy. Imprint smears were prepared from the samples used to make tissue sections; other samples were used for microbiologic culture. There was a good concordance (93%) between the morphologic diagnosis of C pylori in the air-dried, Giemsa-stained smears and the tissue sections; the cytologic preparations were clearly positive in six cases (14%) whose sections contained low numbers of the organisms. There was a concordance of 83% between the combined morphologic techniques and the bacteriologic culture. Six positive cases were detected only by the morphologic techniques while one positive case was detected only by bacteriologic culture. C pylori was identified in one or more preparations of the antral biopsy specimens in 23 (55%) of the 42 cases, including 23 (74%) of the 31 cases with a final diagnosis of gastritis or ulcer. These results show the usefulness of the cytologic study of gastric biopsy smears in diagnosing C pylori infections.     

Cytologic characteristics of Wilms' tumors in fine needle aspirates. A study of ten cases

The cytologic findings observed in fine needle aspiration (FNA) biopsy smears from ten cases of Wilms' tumor are reported. Blastemal cells, small, round cells with slightly oval nucleoli and fine, evenly dispersed chromatin, were recognized in all cases. Stromal (90%) and epithelial components (40%) were also present. Additional recognizable features were anaplasia (in two of three cases having histologic anaplasia), rosettes (four cases), necrosis (six cases) and inflammatory cells (six cases). In six cases, small fragments of tissue were also recovered for histologic examination after paraffin embedding. There were no complications attributable to the procedure. FNA cytology may be used as the sole diagnostic procedure for Wilms' tumors when preoperative chemotherapy protocols are in use.     

Problems in cervicovaginal cytology: fine structure as an aid to diagnosis

The ultrastructure of cytologically abnormal, thick cell groups and epithelial fragments in cervical and vaginal scrape material was investigated and found to be useful in differentiating between carcinoma in situ, invasive nonkeratinizing squamous carcinoma and adenocarcinoma of the endocervix and also in confirming the presence of cytologically suspected vault deposits of recurrent endometrial adenocarcinoma. It was demonstrated that although accurate evaluation of these thick groups in smear preparations is often not possible, thick sections of similar, plastic-embedded material showed some features which enabled a distinction to be made between squamous and glandular lesions and that these differences were more pronounced at the ultrastructural level. The squamous lesions were characterized by wide intercellular spaces with microvilli and tonofibrils within the cytoplasm while glandular lesions showed narrow intercellular spaces, prominent Golgi zones and endoplasmic reticulum together with mucus droplets in some cells.     

Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer

OBJECTIVE: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma. STUDY DESIGN: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer. RESULTS: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions. CONCLUSION: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.     

Oral exfoliative cytology in the diagnosis of paracoccidioidomycosis

OBJECTIVE: To assess the efficacy of conventional oral exfoliative cytology as a diagnostic tool in paracoccidioidomycosis. STUDY DESIGN: Cytologic smears and incisional biopsies were obtained from 10 patients with a clinical suspicion and oral manifestations of paracoccidioidomycosis. Cytologic smears and sections of the incisional biopsy underwent methenamine silver staining for fungi according to the Gomori-Grocott method. The dry glass slides were examined at 400 or 1,000 x magnification, and the presence and shape of yeasts of Paracoccidioides brasiliensis were investigated. RESULTS: Yeasts of the fungus P brasiliensis were clearly identified in cytologic smears and sections from incisional biopsies in all cases analyzed (100.0%). CONCLUSION: Cytology of oral samples proved an effective diagnostic method for the detection of paracoccidioidomycosis in humans.