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Detection of human epidermal growth factor receptor 2 protein and gene in fine needle aspiration cytology specimens and tissue sections from invasive breast cancer: can cytology specimens take the place of tissue sections?

Overexpression of HER2 protein and HER2 gene amplification in breast cancer are prognostic factors for the response to specific medical treatments such as trastuzumab, endocrine therapy, and chemotherapy. Whereas HER2 expression and gene amplification are generally examined in tissue sections, we investigated whether specimens from fine needle aspiration cytology (FNAC) are adequate for these analyses. HER2 protein overexpression and HER2 gene amplification were assessed in both FNAC specimens and tissue sections from 58 cases of invasive breast cancer. Immunohistochemistry assay for HER2 protein expression was performed according to the HercepTest protocol, and HER2 gene amplification was examined with the Spot-light CISH (chromogenic in situ hybridization) Detection kit. There was a significant positive correlation between assessments of HER2 protein status in the cytology specimens and tissue sections. The sensitivity, specificity, and accuracy of HER2 gene amplification detection in cytology specimens in relation to those in tissue sections were 84.0% (21/25 cases), 87.9% (29/33 cases), and 86.2% (50/58 cases), respectively. FNAC specimens are suitable for detection of HER2 overexpression and HER2 gene amplification in invasive breast cancer.

Adult↗

[Cytological and immunocytochemical study of prostatic carcinoma cell in voided urine. Usefulness of prostate-specific antigen in cytology specimen].

The presence of prostatic carcinoma cells in voided urine was seldom noticed and these cells might be hardly distinguished from transitional cell carcinoma cells of the urinary tracts on the Papanicolaou-stained slides. We investigated the cytological findings and the localizations of prostate-specific antigen (PSA) in 7 cases of prostatic carcinomas (4 adenocarcinomas, 2 squamous cell carcinomas, and 1 undifferentiated carcinoma) which showed tumor cells in voided urine. The cytological findings of each histological types were as follows: adenocarcinoma cells were observed in small clusters of round or columnar cells with eccentric nuclei and prominent nucleoli with occasion, squamous cell carcinoma cells were characteristically well-differentiated keratinizing ones varying in shape and in staining reaction, and undifferentiated carcinoma cells were polyhedral and large ones with dense cytoplasm. After destaining of the Papanicolaou-stained slides, the positivity for PSA was demonstrated by immunocytochemical stain with PSA antiserum in cytoplasms of the tumor cells of 6 cases except for 1 undifferentiated carcinoma. We recognized that immunocytochemical detection of PSA was a useful mean in cytological detection for prostatic carcinomas in voided urine.

Adenocarcinoma↗

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.

Female↗

Detection of sexually transmitted diseases by urethral cytology, the ignored male counterpart of cervical cytology.

The detection of sexually transmitted diseases by urethral cytology was investigated in 270 men examined by urethral swabbing smears. Each sample was used to prepare a wet mount smear and smears for staining by the Papanicolaou, Gram and methylene blue techniques. A fifth smear was used for direct staining with fluorescein-conjugated monoclonal antibodies for the detection of Chlamydia trachomatis. The smears were examined for cytoplasmic and nuclear changes as well as for pathogenic organisms and inflammatory changes. Infections with Chlamydia trachomatis, Neisseria gonorrhoeae and human papillomavirus (HPV) produced distinctive cytologic patterns similar to those seen in cervicovaginal smears from women. The patterns in candidiasis, trichomoniasis and herpes simplex virus infection were not as diagnostic. Particularly noteworthy were the nuclear alterations, which appeared to be proplastic in HPV infection but retroplastic in Chlamydia infection. The results of this study indicate that urethral cytology would be an invaluable addition in diagnosing sexually transmitted diseases in men, particularly in the case of Chlamydia and HPV infections. The monomorphic structure of urethral columnar epithelium, as compared to the cervical epithelium, seems to result in a clearer and more constant response to pathogenic infections, as seen in the resulting smears.

Animals↗

Epidemiological data, cytology and colposcopy in IUD (intrauterine device), E-P (estro-progestogens) and diaphragm users. Study of cytological changes of endometrium IUD related.

The author compares the epidemiological, cytological and colposcopical data found in IUD users, with a control population of estro-progestogens and condom users. The age, parity and clinical symptomatology, mainly leukorrhea, was higher in IUD users. At the colposcopic examination a normal pattern was found in condom users more frequently, but the suspect colposcopic signs were frequently associated with the use of the IUD. The oncologic evaluation of smears showed a slight dysplasia in 17.65% and 10.53% in IUD users and estro-progestogen users respectively. The only case of carcinoma in situ was found in the IUD users group. The bacteriological diagnosis on the smears did not reveal a quantitative difference in the three groups, while a qualitative difference was found, particularly with a high frequency of Trichomonas vaginalis and Corynebacterium vaginalis, and one case of Actinomyces in IUD users. The cytological study of the endometrium obtained by mono-use devices, revealed an aspect of aspecific non plasmacellular endometritis in 75% of the cases; a dysfunctional hormonal cytological aspect in 32.50%, and the oncological evaluation in 60% of the cases revealed atypical endometrial cells IUD related. No neoplastic lesion was found. The author concludes that the use of IUD must be prudent and accurate follow up must be carried out.

Abortion, Spontaneous↗

[Determination of circulating immune complexes in the serum of patients with cytologically suspected and cytologically positive cervix smears].

In a pilot study there was taken away venous blood from 26 women for quantitative examination of circulating immune complexes because of cytologic suspected or positive diagnosis of the cervix uteri before planned conization. The concentration of immune complexes would be opposed to the colposcopic, cytologic and histologic diagnoses. In comparison to 26 women with cytological inconspicuous cervix diagnoses there is a light increase of immune complex concentration, but there is no significant difference between both groups.

Antigen-Antibody Complex↗

Aspiration cytology of intramuscular myxoma. A comparative clinical, cytologic and histologic study of ten cases.

Soft-tissue tumors are a fairly new area for aspiration cytology. As part of the correlation between the cytology and histology in these tumors, a retrospective study of ten intramuscular myxomas was conducted. All of the patients presented with a firm, painless intramuscular mass that was excised with different surgical margins; no recurrences were found at follow-up. The cytologic findings corresponded well with the histologic ones. Droplets of a highly viscous fluid typically characterized an aspirate from an intramuscular myxoma. The fluid was generally not very cellular. The cells had elongated cytoplasm and spindle-shaped nuclei. They varied in size and shape, and cellular atypia was minimal. Aspirates from low-grade myxofibrosarcoma and myxoid liposarcoma presented the main differential diagnostic problems.

Adult↗

Fine needle aspiration biopsy cytology of paragangliomas. Cytologic, light microscopic and ultrastructural studies of three cases.

Paragangliomas are uncommon tumors arising in paraganglion tissue, which is especially well represented in the head and neck. In our hospital three head and neck masses recently proved to be paragangliomas on aspiratory biopsy cytology, with subsequent histologic confirmation. One was an apparently benign carotid body tumor, while the others were metastatic nasopharyngeal paragangliomas. The latter two tumors were clearly malignant, with roentgenographically proven pulmonary metastases in one and widespread lymph node involvement in the other. Histologically all were vascular tumors composed of large cells with abundant cytoplasm and pleomorphic, sometimes bizarre nuclei. These characteristic chief cells were clearly evident on cytology, with pleomorphic nuclei, prominent nucleoli, clumped chromatin and generally eosinophilic, finely granular or reticular cytoplasm. However, the distinction between benign and malignant tumors depended on the presence of mitoses or a tumor diathesis. Cytology seems to be able to provide a diagnosis of paraganglioma and, in these cases at least, an estimation of the biologic behavior.

Biopsy, Needle↗

Brush cytology of the extrahepatic biliary tract: comparison of cytologic features of adenocarcinoma and benign biliary strictures.

Malignant strictures of the extrahepatic biliary tract are difficult to discern from benign strictures solely by clinical and/or radiographic findings. Endoscopic retrograde wire-guided brushings of strictures have proven to be useful in evaluating such lesions. Because the reported sensitivity of diagnosing adenocarcinoma of the extrahepatic biliary tract by this technique has varied considerably (44 to 100%), we undertook a retrospective study to determine if the diagnostic accuracy could be increased by identifying key cytologic features by reviewing a series of 90 biliary tract brushings from 80 patients. The cytologic diagnosis was confirmed either by additional pathologic material and/or clinical follow-up. Utilizing a multiple logistic regression analysis, three key cytologic features were identified that were useful in separating benign from malignant strictures; these features included: nuclear molding, chromatin clumping, and increased nuclear-cytoplasmic ratio. The presence of two of these three features resulted in a sensitivity of 83%; the corresponding specificity was 98%. The use of these key features should aid the cytologist in better recognizing malignant cells in biliary tract brushings.

Adenocarcinoma↗

Improving accuracy in gynecologic cytology. Results of the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

The College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP) is a quarterly mailed glass-slide quality improvement program. This growing program started as a pilot in 1989 with 207 laboratories. In 1991, 605 laboratories participated. The diagnostic menu is modified from the Bethesda System and divides referenced slides into a negative series (normal, infectious, and reactive) and a positive series of epithelial lesions. A facsimile option facilitates immediate educational feedback. The 1989 through 1991 major discrepancy rate averaged 5%. The consensus laboratory response had higher concordance than either pathologist or cytotechnologist responses. Low-grade squamous intraepithelial lesion was the leading cause of false-negative participant response, while reactive/reparative change was the leading cause of false-positive response. Pathologist false-negative and false-positive responses from group or large case-volume practices were significantly lower than those from solo or small case-volume practices. Cytotechnologists in multiple-technologist or large-volume laboratories had significantly lower false-negative responses than solo technologists or those in low case-volume laboratories, but false-positive rates did not differ. Experienced participants had fewer major discrepancies. The Interlaboratory Comparison Program in Cervicovaginal Cytology illustrates the feasibility of a large, mailed glass-slide program, and offers laboratories a continuous method for monitoring and improving performance in gynecologic cytology.

Cytodiagnosis↗

[Nuclear DNA ploidy pattern and cytological atypia in aspiration cytology of breast cancer].

The relationship between nuclear DNA ploidy pattern and cytological atypia in aspiration cytology of breast cancer was studied in 40 cases of primary breast cancers (T1: 14 cases; T2: 26 cases). They were divided into two groups, according to cytological specimens, high degree (H group) and low degree (L group). Twelve of 40 cases were classified into H group and 28 cases into L group. Fresh frozen materials were obtained from mastectomy specimens and nuclear DNA analysis was carried out by flow cytometry (FCM). Estrogen receptor (ER) and progesterone receptor were measured with the DCC method. Lymph node metastases were histologically seen in 17 cases; the ER positive rate was 55.0%, and the PgR positive rate was 42.5%. FCM revealed 21 cases (52.5%) with diploidy pattern and 19 cases (47.5%) with aneuploidy pattern. S-phase fraction in 17 cases (48.6%) exceeded 20%. L group had more diploid cases and ER positive cases than H group (p < 0.05, p < 0.01). No differences in other factors were seen between the two groups. In diploid cases, L group had more ER positive cases than H group (p < 0.02).

Biopsy, Needle↗

[Evaluation of the role of cytology in the diagnosis of cancer of the lung. Comparison between cytology and pathological anatomy in 330 cases of proximal cancers].

This retrospective study was performed to evaluate the interest of cytology in the diagnosis of pulmonary carcinomas. Bronchial samples were collected from 330 patients known to display a macroscopic lesion which was detected by bronchoscopy. Cytological analysis of the bronchial brushings and washings, removed at the first fibroscopy, allowed the diagnosis of malignancy in 92% of the cases analyzed whereas the biopsy confirmed the malignancy in 77% of the cases. In conclusion cytological studies gave information on malignity and classification in 90% of the cases. However histological classification only could guarantee the choice of the best treatment regimen.

Adenocarcinoma↗

Terminology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Differences in type, structure, quality of health care systems and availability of resources influence reporting systems. In most countries, individual systems have a long history of usage that might preclude adoption of a uniform terminology worldwide. CONSENSUS POSITION: It is desirable but unrealistic at this time to aim for a unified terminology worldwide. It should be the stated objective of the International Academy of Cytology to serve as an umbrella organization for various terminologies and enhance mutual understanding and cooperation. Translation tables of equivalent terms have been created to allow increased communication. Consensus has been achieved in defining essential elements required of any terminology system: (1) the report must be text based: numerical Papanicolaou class designations alone are inadequate; (2) an assessment of the adequacy of the sample should be included; and (3) the diagnosis must address the primary purpose of cervical cytology: to indicate the presence or absence of epithelial abnormalities. Incorporating additional elements within a terminology system may be more or less appropriate, depending on the setting in which the system is used. ONGOING ISSUES: Despite the cited problems in adopting a uniform terminology worldwide, a single system would have many advantages in terms of communication and research and may be a long-term goal worth pursuing. Countries are invited to present their individual national terminology systems and participate in an ongoing dialogue, critically evaluating the advantages and disadvantages of all systems.

Cervix Uteri↗

Quality assurance/control issues. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: General definitions of quality assurance and quality control (QA/C) have existed in many forms for decades, and a new discipline guides their application to diverse industrial and recently medical processes without much fanfare. However, in the field of cervical cytology screening, the range of QA/C options has recently broadened and become controversial. With the advent of new systems of terminology, larger-scale laboratories and new technologies--plus strong governmental and legal pressures in some nations--the range of extremely difficult and sometimes expensive QA/C choices our community faces is greater than ever. CONSENSUS POSITION: At our conference, the basic definitions of QA/C posed little difficulty. Presentation of the range of methods in use today and of those based on new technologies where use is proposed or has just begun also was achieved with little or no dispute. However, there was lack of consensus on exactly how QA/C methods are to be assessed. Indeed, there was little consistency in the use of different outcome measures with which we can judge success or failure of specific QA/C options. In addition, the tension between pressure to adopt sometimes uncertain or expensive method enhancements and pressure to maintain affordability and the widest possible access for populations that most need cervical cytology screening is greater than ever. ONGOING ISSUES: More data are required that would enable assessment of QA/C options with the clearest possible understanding of cost/benefits and current or new assumptions of risk. Other task forces, such as medicolegal, cost/benefit and those devoted to new technologies, are our essential partners in meeting the challenges described above.

Centers for Medicare and Medicaid Services, U.S.↗

Digital imagery/telecytology. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Optical digital imaging and its related technologies have applications in cytopathology that encompass training and education, image analysis, diagnosis, report documentation and archiving, and telecommunications. Telecytology involves the use of telecommunications to transmit cytology images for the purposes of diagnosis, consultation or education. This working paper provides a mainly informational overview of optical digital imaging and summarizes current technologic resources and applications and some of the ethical and legal implications of the use of these new technologies in cytopathology. CONSENSUS POSITION: Computer hardware standards for optical digital imagery will continue to be driven mainly by commercial interests and nonmedical imperatives, but professional organizations can play a valuable role in developing recommendations or standards for digital image sampling, documentation, archiving, authenticity safeguards and teleconsultation protocols; in addressing patient confidentiality and ethical, legal and informed consent issues; and in providing support for quality assurance and standardization of digital image-based testing. There is some evidence that high levels of accuracy for telepathology diagnosis can be achieved using existing dynamic systems, which may also be applicable to telecytology consultation. Static systems for both telepathology and telecytology, which have the advantage of considerably lower cost, appear to have lower levels of accuracy. Laboratories that maintain digital image databases should adopt practices and protocols that ensure patient confidentiality. Individuals participating in telecommunication of digital images for diagnosis should be properly qualified, meet licensing requirements and use procedures that protect patient confidentiality. Such individuals should be cognizant of the limitations of the technology and employ quality assurance practices that ensure the validity and accuracy of each consultation. Even in an informal teleconsultation setting one should define the extent of participation and be mindful of potential malpractice liability. ONGOING ISSUES: Digital imagery applications will continue to present new opportunities and challenges. Position papers such as this are directed toward assisting the profession to stay informed and in control of these applications in the laboratory. Telecytology is an area in particular need of studies of good quality to provide data on factors affecting accuracy. New technologic approaches to addressing the issue of selective sampling in static image consultation are needed. The use of artificial intelligence software as an adjunct to enhance the accuracy and reproducibility of cytologic diagnosis of digital images in routine and consultation settings deserves to be pursued. Other telecytology-related issues that require clarification and the adoption of workable guidelines include interstate licensure and protocols to define malpractice liability.

Computer Communication Networks↗

The role of fine needle aspiration cytology and imprint cytology in cervical lymphadenopathy.

OBJECTIVE: To determine the diagnostic accuracy of cervical lymphadenopathy by fine needle aspiration (FNAC) and imprint cytology (IC). METHODS: This study included 94 patients with cervical lymphadenopathy. This study was carried out in the Departments of General Surgery and Pathology, King Fahad Hospital, Hofuf, Kingdom of Saudi Arabia, from June 2001 through to July 2002. They were subjected to clinical examination and FNAC of one of the enlarged lymph nodes. This was followed by IC and histological examination of this lymph node after its excision. RESULTS: Clinical examination was correct in 78% of the cases. The overall accuracy of fine needle aspiration was 93%. It was accurate on all cases of reactive hyperplasia, 93% of tuberculosis lymphadenitis, 90% in Hodgkin's lymphoma, 86% in non-Hodgkin's lymphoma, and 91% of metastasis lymphadenopathy. On the other hand, the overall accuracy of IC was higher than that of fine needle aspiration, being 97%. It diagnosed all cases of reactive hyperplasia and non-Hodgkin's lymphoma, 97% in tuberculosis lymphadenitis, 90% in Hodgkin's lymphoma and 95% in metastasis lymphadenopathy. CONCLUSION: These techniques proved to be reliable, rapid, and inexpensive procedures in diagnosis of lymphadenopathy. They can differentiate well between inflammatory and neoplastic lesions, in cases of lymphoma, cytological diagnosis should be followed by histological diagnosis for accurate classification and grading.

Adult↗

Inclusion-cytology versus smear-cytology in fine needle abdominal biopsy.

1568 patients underwent percutaneous fine needle biopsy (22-23 g. Chiba). 761 of these had histologic type confirmation of malignant disease. Among the latter, 313 cases had adequate samples retrieved from the same lesion for smear cytology (SC) and inclusion cytology (IC), 400 for SC alone (378 performed before the use of IC) and 48 for IC alone. SC was stained by Papanicolaou and MGG, IC by haematoxylin-eosin technique. In SC + IC group typing accuracy was 0.64 for SC and 0.86 for IC, in SC group was 0.66, in IC group was 0.87. IC permitted an easier preparation and interpretation of special stains. In conclusion, IC routine is recommended. Some interesting observations were possible because material was collected from three hospitals.

Abdomen↗

Urine cytology. Part II: renal cytology.

Properly collected urine samples examined by qualified cytologists can aid in the diagnosis and management of various infectious and inflammatory renal parenchymal diseases. Patients with proteinuria, hematuria or bacteriuria will benefit most from renal cytologic examination. Exfoliative cells from renal parenchymal tumors often do not communicate with the collecting system. Some disseminated neoplasms, such as lymphoma or myeloma, can be diagnosed and followed by cytologic study.

Bacterial Infections↗