Hürthle cell tumors (HCT) remain difficult to treat because some which appear non-malignant on light microscopy later metastasize. In order to improve diagnostic accuracy, the value of ras mutations and nuclear DNA analysis was determined in 65 patients with HCT. Rapid nuclear DNA cytometry (MicroTICAS system) was performed. Mutations of H-ras, K-ras, and N-ras genes were analyzed by oligonucleotide probe hybridizations to polymerase chain reaction (PCR) amplified DNA. HCT were classified by light microscopy as benign (n = 22), intermediate (n = 30), and malignant (n = 13). After a mean follow-up of 7 years, 1 (4.5%) of 22 benign tumors and 4 (13%) of 30 intermediate tumors had metastasized, leading to tumor death in 3 of these 5 patients. Six of the 13 cancers diagnosed by light microscopy also resulted in tumor-related deaths. Aneuploidy was found in 83% of all Hürthle cell cancers, including 3 (60%) of the 5 cancers not diagnosed microscopically. However, 49% of non-malignant HCT also demonstrated aneuploidy. A nuclear area of less than 55 square microns was found in 83% of all Hürthle cell cancers and in 100% of those cancers not diagnosed by light microscopy. However, 47% of non-malignant HCT also demonstrated a "small" nuclear area. Aneuploidy correctly identified 8 of 9 cancers that resulted in tumor death and each of 3 other tumors that developed metastases. However, 1 patient with a diploid tumor died of metastatic cancer. A nuclear area of less than 55 square microns identified each cancer that resulted in a tumor death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

p53 immunohistochemistry for distinguishing reactive mesothelium from low grade ovarian carcinoma.

OBJECTIVE: To determine the utility of immunohistochemical staining for p53 in cell block material for distinguishing reactive mesothelium from borderline or low grade ovarian carcinoma. STUDY DESIGN: Paraffin-embedded cell blocks from paracentesis and pelvic wash fluid of 44 cases of ovarian carcinoma and 20 cases containing only reactive mesothelium were immunostained for p53 using monoclonal antibody DO-7. Tumor grades ranged from borderline to high grade and were serous papillary (33), clear cell (3), mucinous (2), endometrioid (2), mixed serous papillary/clear cell (3) and undifferentiated (1). The three authors independently evaluated the staining, including estimation of the percentage and intensity of positive nuclear staining. RESULTS: A separation of positive from negative cases was seen when staining intensity was considered the critical parameter; moderate to strong staining was considered truly positive. Seventy-three percent (8/11) of borderline tumors, 80% (8/10) of low grade tumors and 65% (15/23) of intermediate to high grade tumors showed moderate to strong positivity. Percentage of staining was a less-reliable parameter as 25% of negative cases were positive by this assessment. CONCLUSION: p53 Immunohistochemistry, using monoclonal antibody DO-7 combined with standard morphologic evaluation, may be useful in distinguishing benign reactive mesothelium from borderline or low grade ovarian carcinoma.

Antibodies, Monoclonal↗

PubMedDate not supplied

George L. Weid, M.D., D.Sc. (hon), F.I.A.C. A tribute on his 80th birthday.

Explore the source record for details and available documents.

Awards and Prizes↗

PubMedDate not supplied

Processing liquid-based gynecologic specimens: comparison of the available techniques.

OBJECTIVE: To develop a cytopreparation protocol suitable for satisfactory processing by the AutoCyte PREP System with the gynecologic specimens collected in PreservCyt fluid for the ThinPrep machine. STUDY DESIGN: The residue of a number of gynecologic specimens collected in PreservCyt and processed by ThinPrep were processed by AutoCyte PREP. Some modifications were made in the cytopreparatory protocol in order to obtain satisfactory specimens. RESULTS: The ThinPrep and AutoCyte PREP specimens were examined independently. The results were comparable, with a high degree of concordance between the two techniques. CONCLUSION: Gynecologic specimens collected in PreservCyt and following the ThinPrep specimen collection protocol can be processed using the AutoCyte PREP System. Minor protocol modifications provided comparable diagnostic material. Additional studies are needed to explore the feasibility of this approach and fulfill the various U.S. regulatory agency requirements for the liquid-based Pap test.

Cytological Techniques↗

PubMedDate not supplied

Cyclin E expression and early cervical neoplasia in ThinPrep specimens. A feasibility study.

OBJECTIVE: To investigate cyclin E expression as a possible marker for early cervical neoplasia using ThinPrep gynecologic specimens from premenopausal women. STUDY DESIGN: Archived ThinPrep liquid-based cervical/endocervical specimens (Cytyc Corporation, Boxborough, Massachusetts, U.S.A.) diagnosed as human papillomavirus infection (HPV) (20), atypical squamous cells of undetermined significance (ASCUS) (48) and within normal limits (WNL)/benign cellular changes (BCC) (21) were resampled in duplicate, fixed in 95% ethanol, subjected to immunocytochemical staining with the cyclin E antibody (clone 13A3, Novocastra Laboratories Ltd., Newcastle upon Tyne, U.K.) and HPV antibody (clone K1H8, Dako Corporation, Carpinteria, California, U.S.A.) and the expression scored by two pathologists and correlated with the cytologic diagnosis. A case was scored as positive if it contained > 10 abnormal squamous cells with nuclear immunocytochemical staining. RESULTS: The cylin E antibody assay was positive in 20 (100%) cases cytologically diagnosed as HPV. These cases were also anti-HPV antibody positive. Four cases (19%) cytologically diagnosed as WNL/BCC were cyclin E positive. Of these, two were anti-HPV antibody positive. Thirty-four (73%) cases cytologically diagnosed as ASCUS were positive for the cyclin E assay and for anti-HPV antibody staining. CONCLUSION: Cyclin E expression correlates strongly with morphologic features of HPV in ThinPrep specimens and may serve as a surrogate marker for HPV infection and early cervical preneoplastic lesions.

Adult↗

PubMedDate not supplied

Does use of the AutoPap assisted primary screener improve cytologic diagnosis?

OBJECTIVE: To correlate the ranked review slides by the AutoPap Assisted Primary Screener with the final cytologic diagnosis and to assess whether the ranking of slides improves diagnostic accuracy. STUDY DESIGN: A total of 5,865 consecutive conventional and suitable cervical/vaginal smears, including high-risk (HR) cases, were processed by the AutoPap System. All slides designated Review were manually screened by two cytotechnologists using the Ranked Review Report. All abnormal findings and reactive/reparative changes were referred to two attending cytopathologists for a final diagnosis. After screening, the Review slides called Within Normal Limits (WNL) were selected according to rank for a further Quality Control (QC) review by the supervisor. All HR cases not selected by AutoPap for QC review were also rescreened. The final diagnoses of the possibly abnormal/reactive/reparative referred slides were recorded and distributed in five ranks according to the Ranked Review Report assignment. RESULTS: Of 5,865 slides, 5,120 (87%) qualified for scanning. The AutoPap System designated 3,840 (75%) slides for manual review. One thousand three hundred forty-five slides were assigned for QC review. After elimination of nonqualified slides, 763 remained. Rescreening detected 1 high grade squamous intraepithelial lesion (HSIL), 2 low grade squamous intraepithelial lesions (LSIL), 5 atypical squamous cells of undetermined significance (ASCUS) and 5 Benign Reactive Changes (BRC). QC of 364 HR cases revealed 1 LSIL, 2 ASCUS and 3 BRC. Ultimately, 313 (8.1%) smears were diagnosed as ASCUS or a more severe abnormality, 262 (6.8%) as reactive/reparative changes, 3,259 (84.8%) as WNL and 6 (0.1%) as unsatisfactory. Of 313 abnormal slides, 181 were ranked by the system in the 1st rank, 61 in the 2nd, 38 in the 3rd, 19 in the 4th and 14 in the 5th. No HSIL or more severe lesions occurred in the fourth and fifth ranks. CONCLUSION: Our study validated the claim by the manufacturer that a significant epithelial abnormality is more likely to be present if a high score is assigned to a slide. The preliminary results support use of the AutoPap Assisted Primary Screener to improve cytologic diagnosis.

Female↗

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Performance of the AutoPap primary screening system at Jefferson University Hospital.

OBJECTIVE: To evaluate the performance of the AutoPap System for primary screening of cervical/vaginal cytologic smears at the 25% no review rate at Jefferson University Hospital. STUDY DESIGN: A total of 5,865 consecutive conventional and suitable cervical/vaginal smears, including high-risk cases, were processed by the AutoPap System. Slides designated "no further review" (NFR) were manually screened by a cytopathologist (rapid screening) and a cytotechnologist (detailed screening) to detect epithelial abnormalities and assess the slide adequacy. The presence of Candida or Trichomonas was noted. Three cytopathologists determined the final diagnosis of all epithelial abnormalities by majority agreement. RESULTS: Of 5,865 slides, 5,120 (87%) qualified for scanning. The system classified 1,280 slides as NFR (25%) and 3,840 (75%) as review. Manual screening of 1,280 slides classified as NFR revealed 1,252 cases within normal limits, 10 atypical squamous cells of undetermined significance (4, favor low grade squamous intraepithelial lesion, 6 favor reactive) and 18 benign cellular changes. Adequacy assessment discrepancies were detected on 98 (19%) of 515 cases of satisfactory but limited by lack of endocervical component (SBLBLEC) and 15 (14%) of 105 cases on satisfactory but limited by inflammation/obscuration. Twenty-five percent of cases classified as SBLBLEC were vaginal smears. Trichomonas vaginalis was noted in 12 slides and Candida in 29. CONCLUSION: These preliminary results show that in our patient population, the AutoPap primary screener selected as NFR mostly slides within normal limits. The adequacy assessment discrepancies were comparable to those found in routine laboratory practice.

Candidiasis↗

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Differential diagnosis of oncocytic lesions of the breast and thyroid utilizing a semiquantitative approach.

OBJECTIVE: To assess whether a light microscopic, semiquantitative approach could reliably distinguish between benign nonneoplastic, benign neoplastic and malignant oncocytic lesions of the breast and thyroid. STUDY DESIGN: Alcohol-fixed, Papanicolaou-stained fine needle aspiration smears of histologically proven goiter and chronic thyroiditis (18 cases), Hürthle cell adenomas (7 cases), Hürthle cell carcinomas (6 cases), fibrocystic disease (17 cases), papillomas and papillomatosis (7 cases) and apocrine carcinomas (6 cases) were rated by three independent observers using the following 10 cytologic criteria: cellularity, nuclear-cytoplasmic ratio, multinucleation, nuclear size, nuclear shape, anisonucleosis, multinucleolation, nucleolar-nuclear ratio, nucleolar size and nucleolar shape. Each of these 10 cytologic criteria was rated using a 1-3 scale. The scores for all 10 features were summed to give a total score for each case. The total scores were statistically analyzed to determine the validity and reproducibility of the summed criteria. RESULTS: The summed criteria of the total scores were reproducible between the three observers, with standard deviations ranging from 1.36 to 2.88 for thyroid and 1.72 to 2.00 for breast oncocytic lesions. The ability of the total scores to differentiate benign from malignant oncocytic lesions of the breast and thyroid was confirmed by a positive predictive value for malignancy of 67% for thyroid and 72% for breast and a negative predictive value for malignancy of 100% for nonneoplastic oncocytic lesions and > 90% for benign oncocytic neoplasms in both. The Kruskal-Wallis test revealed that the total scores were able to distinguish three diagnostic categories of nonneoplastic, benign neoplastic and malignant oncocytic breast and thyroid lesions, with P < .005. CONCLUSION: Without the expenditures of additional time, costs or materials, this semiquantitative approach compared favorably with contemporary morphometric studies involving the differential diagnosis of oncocytic cell pathology in fine needle aspiration cytology.

Breast Neoplasms↗

PubMedDate not supplied

Diagnostic utility of sialosyl-Tn in discriminating carcinomatous cells from benign mesothelium in body cavity effusions.

OBJECTIVE: Detecting malignant cells in the setting of reactive mesothelium can be difficult. Several techniques have been tried but without widespread acceptance. Sialosyl-Tn (STn) is an aberrantly glycosylated precursor of the MN blood group antigen frequently expressed in carcinomas and dysplastic epithelium. We investigated the STn monoclonal antibody for its clinical utility as an isolated stain to discriminate benign mesothelium from malignant cells. STUDY DESIGN: Cell block material from 72 cases of body cavity fluids were immunostained for STn using the avidin-biotin complex method without antigen retrieval. Slides were incubated overnight at 4 degrees C in a humidified chamber. RESULTS: Strong immunoreactivity was noted in 31/40 (77%) carcinomatous cases. Only moderate staining was noted in 1 of 28 (4%) benign effusions and weak staining in 5 (18%) additional benign cases. Specificity was 100%, sensitivity 78%, positive predictive value 100% and negative predictive value 76%. No staining was noted in four noncarcinomatous malignant effusions. CONCLUSION: STn may have diagnostic value in this cytologic setting as part of a diagnostic panel but not as an isolated stain.

Antigens, Tumor-Associated, Carbohydrate↗

PubMedDate not supplied

Computerized screening devices and performance assessment: development of a policy towards automation. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The 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. CONSENSUS POSITION: The 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. ONGOING ISSUES: Guidelines 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.

Automation↗

PubMedDate not supplied

Fine needle aspiration diagnosis of a pulmonary metastasis from a cutaneous adenoid cystic carcinoma. A case report.

BACKGROUND: Primary cutaneous adenoid cystic carcinomas (CACC) rarely metastasize to the lung. The few documented cases have been diagnosed by surgical biopsy. CASE: An 82-year-old female presented with an enlarging lung mass 15 years after being diagnosed with CACC. The diagnosis of metastatic adenoid cystic carcinoma was made following a computed tomography-guided fine needle aspiration (FNA) biopsy. CONCLUSION: Metastatic CACC in the lung can be diagnosed by FNA. Knowledge of the patient's clinical history and morphologic variants of CACC is important in making the diagnosis.

Aged↗