Can cytology reliably subtype non-small cell lung carcinomas?

Cytology specimens play an important role in the diagnosis and predictive testing of lung cancer. While morphological characterisation of small cell and non-small cell lung carcinomas (NSCLC) on cytology is possible, further subtyping of NSCLC into adenocarcinoma and squamous cell carcinoma morphology is also mandatory in the current era of personalised medicine. Notably, cytology specimens in different forms (fine needle aspiration, exfoliative, and cell block) with or without immunocytochemistry are reliable sources for accurate diagnosis of adenocarcinoma and squamous cell carcinoma as evidenced by numerous studies present in the literature. However, there are instances where subtyping of NSCLC based on morphology alone is challenging on cytology samples, especially non-cell block preparations. In this paper, we will discuss current concepts, advances, and challenges of subtyping NSCLC in cytology specimens.     

The role of brushing cytology in the diagnosis of gastric malignancy

The results of endoscopic biopsy and brushing cytology in 234 consecutive patients with established histologic diagnoses of discrete gastric lesions were analyzed. A histopathologic diagnosis of malignancy, established by independent means, was made in 74 patients. Brushing cytology was positive for malignancy in 63, a diagnostic sensitivity of 85%. Endoscopic biopsy was positive in 64, a diagnostic sensitivity of 86%. The sensitivity for combined cytology and biopsy was 91%, which was not significantly greater than for biopsy alone (P = .6). Cytology yielded false-positive results in 5 of 160 patients (3.1%) with confirmed benign disease. There were no false-positive biopsy reports. Although both brushing cytology and biopsy have high diagnostic sensitivities, based on the findings of this study, the routine addition of cytology to biopsy in the endoscopic evaluation of gastric lesions is not recommended. Cytology could be reserved for situations in which difficulty is encountered in obtaining adequate tissue for histologic examination and for cases with a high suspicion of malignancy that have yielded negative biopsies.     

Urinary cytology and the Paris system for reporting urinary cytology: Implications for urological management

By reducing the rate of indeterminate (atypical) diagnoses and standardising reporting terminology, The Paris System for Reporting Urine Cytology helps focus the application of cytology towards the detection primarily of high‐grade urothelial carcinoma. We present a urology‐based perspective of how the new system has influenced clinical decision‐making.     

BSCC,Bethesda or other? Terminology in cervical cytology European panel discussion

The European panel agreed that reproducibility and translatability of terminology in cervical cytology were essential, arguing well for harmonization of reporting systems. The majority at this meeting use a modification of the Bethesda system (BS). Local modifications involved reporting subcategories within high grade and low grade lesions, which would not alter the overall translatability of their systems both with each other and BS. The majority agree that low grade lesions with and without koilocytosis should be managed similarly as should high grade lesions (moderate dysplasia/CIN2 or worse). Those systems linking moderate dysplasia with mild rather than severe dysplasia would need to define moderate dysplasia as such, if their results were to be translatable, which would be preferable to their using a different definition of low grade and high grade lesions. Translation between systems might anyway be facilitated by reporting moderate dysplasia as a subcategory within high grade, which was favoured by most of those present. Therefore, there is no need for exact agreement of terminology if broad principles are agreed. This useful discussion adds weight to the British Society for Clinical Cytology recommendation that the new classification should be adopted by the UK National Health Service Cervical Screening Programme. If the new classification is adopted, the UK would join the European consensus opinion on terminology.     

The big problem of the missing cytology slides

Cytology slides are often unique and irreplaceable. Unlike surgical pathology cases, where additional paraffin sections can be cut, cytology slides often cannot be duplicated because there are only a few direct smears or the diagnostic material is present on a single slide. Cytology slides are often "sent out" to other physicians, laboratories or hospitals, typically so that the pathologist at the institution where the patient will receive treatment can review the slides. Less often, a cytology lab sends out the slides for a second opinion or as part of the discovery process in a lawsuit, where they may or may not be defendants. Rarely, unique and irreplaceable cytology slides are lost. This article presents a hypothetical scenario that is based on reported state appellate court decisions. The article discusses some of the legal issues that will affect the defendant cytologist/cytology lab and the "expert cytologist," and suggests some steps a cytologist/cytology lab can take to minimize the risk of repercussions from a lost unique and irreplaceable cytology slide.     

The British Society For Clinical Cytology Certificate of Competence In Cytology Screening: A Report of the First 3 Years'' Experience

In 1988 the Department of Health (DOH) recognized the cytology screener grade of laboratory staff. Cytology screeners have a 2 year training period after which they must sit a 'competence examination'. The British Society for Clinical Cytology offers an examination to meet the DOH specification. It consists of a written paper, a practical screening test, a spot test and a short viva voce. The screening test is paramount and candidates who miss a dyskaryotic smear cannot be successful. In the first 3 years there have been 22 examinations, 294 candidates and a pass rate of 76%. The majority of candidates were Cytology Screeners of 2-3 years experience but significant numbers of Medical Laboratory Scientific Officers (MLSOs) and senior MLSOs also chose to sit the examination.     

Cytology of pseudomyxoma peritonei

Cytology of pseudomyxoma peritonei
The cytology of five cases of pseudomyxoma peritonei is described. It is characterized by large masses of mucinous material, some of which is wrapped up in a network of elongated fibroblast-like cells. Irregular clusters of flat branching vimentin-positive fibroblast-like cells may be found as the disease progresses. Goblet or tumour cells were not found in the cytology preparations, although they were seen in the histological sections of the one case which was biopsied. The appendiceal origin of pseudomyxoma peritonei could not be traced in three of four male patients, and the cause of the disease remained undetermined. Autopsy of the fourth case demonstrated a complete replacement of the appendix by mucus.     

Disseminated histoplasmosis diagnosed by percutaneous needle biopsy of a retroperitoneal lymph node. A case report.

A case of disseminated histoplasmosis diagnosed by percutaneous needle biopsy cytology is reported. The patient presented with fever and pancytopenia. Computed tomography (CT) revealed retroperitoneal lymphadenopathy. Cytology smears prepared from a CT-guided screw needle biopsy of one of the lymph nodes showed numerous histiocytes with intracytoplasmic yeast forms consistent with Histoplasma capsulatum. Fungal cultures prepared from additional needle biopsy material confirmed the diagnosis. This case illustrates the utility of needle biopsy in the evaluation of radiographically detected retroperitoneal lymphadenopathy and in the rapid diagnosis of infectious disease in certain clinical settings.     

The BSCC Code of Practice – exfoliative cytopathology (excluding gynaecological cytopathology)

Exfoliative cytopathology (often referred to as non‐gynaecological cytology) is an important part of the workload of all diagnostic pathology departments. It clearly has a role in the diagnosis of neoplastic disease but its role in establishing non‐neoplastic diagnoses should also be recognised. Ancillary tests may be required to establish a definitive diagnosis. Clinical and scientific teamwork is essential to establish an effective cytology service and staffing levels should be sufficient to support preparation, prescreening, on‐site adequacy assessment and reporting of samples as appropriate. Routine clinical audit and histology/cytology correlation should be in place as quality control of a cytology service. Cytology staff should be involved in multidisciplinary meetings and appropriate professional networks. Laboratories should have an effective quality management system conforming to the requirements of a recognised accreditation scheme such as Clinical Pathology Accreditation (UK) Ltd. Consultant pathologists should sign out the majority of exfoliative cytology cases. Where specimens are reported by experienced biomedical scientists (BMS), referred to as cytotechnologists outside the UK, this must only be when adequate training has been given and be defined in agreed written local protocols. An educational basis for formalising the role of the BMS in exfoliative cytopathology is provided by the Diploma of Expert Practice in Non‐gynaecological Cytology offered by the Institute of Biomedical Science (IBMS). The reliability of cytological diagnoses is dependent on the quality of the specimen provided and the quality of the preparations produced. The laboratory should provide feedback and written guidance on specimen procurement. Specimen processing should be by appropriately trained, competent staff with appropriate quality control. Microscopic examination of preparations by BMS should be encouraged wherever possible. Specific guidance is provided on the clinical role, specimen procurement, preparation and suitable staining techniques for urine, sputum, semen, serous cavity effusion, cerebrospinal fluid, synovial fluid, cyst aspirates, endoscopic specimens, and skin and mucosal scrapes.     

Prediction of recurrent disease by cytology and HPV testing after treatment of cervical intraepithelial neoplasia

Objective: To assess the role of human papillomavirus (HPV) testing and cytology as predictors of residual/recurrent disease after treatment of high‐grade cervical intraepithelial lesions. Methods: One hundred and thirty‐eight women with cervical intraepithelial neoplasia (CIN) grade 2/3 lesion on biopsy were included in a prospective follow‐up study in Belgium and Nicaragua. All women were treated with loop electrosurgical excision procedure (LEEP) and follow‐up visits took place at 6 weeks, 6 months, 1 year and 2 years. During these visits, a Papanicolaou (Pap) smear test was taken, colposcopy was performed and specimens were collected for HPV testing. Cytology, high‐risk (HR) HPV presence, persistent HR HPV infection and combinations of these tests at different time points during follow‐up were correlated with histologically confirmed residual/recurrent disease. Results: Thirteen patients (9%) developed residual/recurrent disease during follow‐up. Abnormal cytology at 6 weeks after treatment was significantly correlated with residual/recurrent disease. Nine of thirty‐seven patients with abnormal cytology at 6 weeks had recurrent disease versus three of seventy with a normal cytology [odds ratio (OR): 7.2; 95% confidence interval (CI): 1.8–28.5; P = 0.003). Sensitivity of this test was 75.0%, specificity 70.5%. Combining abnormal cytology and the presence of HR HPV within the first 6 months after treatment gave the best correlation with residual/recurrent disease: of the 54 women with abnormal cytology and/or HR HPV presence within the first 6 months, 11 developed residual/recurrent disease (OR 10.2; 95% CI: 2.2–48.3). Sensitivity of this combination was 84.6% and specificity 65.0%. Conclusion: Cytology remains the cornerstone in the early follow‐up after LEEP for CIN lesions of the cervix. HPV testing can add value as it increases the sensitivity of cytology in concomitant testing within the first 6 months.     

Cytopathological diagnosis of alveolar soft part sarcoma,a rare soft tissue neoplasm

S. Agarwal, R. Gupta, V. K. Iyer, S. R. Mathur and R. Ray Cytopathological diagnosis of alveolar soft part sarcoma, a rare soft tissue neoplasm Objective: Alveolar soft part sarcoma (ASPS) is a rare soft tissue neoplasm, having various morphological mimics, especially on fine needle aspiration cytology (FNAC). Because no definite immunohistochemical markers are available to aid a correct diagnosis, knowledge of the cytomorphological features is essential for correct patient management. Cytological features of five cases of ASPS are discussed, along with the ultrastructural findings available in one of them. Methods: Cytology records from 1997 to 2009 were reviewed for cases with a diagnosis of ASPS on cytology. The histology slides of the cases were also assessed for confirmation of the diagnosis. All the slides were reviewed by three pathologists. Results: There were five cases of ASPS diagnosed on FNAC. Their cytological features were noted in detail. The diagnoses in all the cases were confirmed on histology, and ultrastructural findings available in one of them were also assessed. Conclusions: The knowledge of cytological features may aid in diagnosing this rare tumour correctly on FNA smears, thus enabling correct patient management.     

Neural tumours of the neck presenting as thyroid nodules: a report of three cases

OBJECTIVES: Neural tumours of the neck may at times secondarily involve the thyroid and manifest clinically as thyroid nodules. On cytological evaluation these nodules may be confused with other spindle lesions of the thyroid. We report two cases of schwannoma and one case of a malignant peripheral nerve sheath tumour (MPNST) of the neck, which presented as thyroid nodules and evaluate the role of cytology in identifying these tumours. METHODS: The thyroid nodules in all the three cases were sampled by the non-aspiration technique using a 23-gauge needle. Both alcohol-fixed and air-dried smears were prepared and stained by the Papanicolaou and May-Grünwald-Giemsa stains. Cytology smears and histology sections from the resected specimens were reviewed, and the findings noted. RESULTS: Both the cases of schwannoma were correctly identified on cytology while the case of MPNST could only be typed as a spindle cell tumour. However, on cytology it was not possible to state whether the tumours were thyroidal or extrathyroidal in origin. CONCLUSIONS: Schwannomas of the neck are easily identifiable on cytology compared with MPNST. However, cytology alone is not helpful in identifying the origin of these tumours. As primary neural tumours of the thyroid are rare, the possibility of a soft tissue neural tumour extending into the thyroid should always be ruled out while evaluating these cases.     

A software system to record and analyze digitized cell images

This paper describes basic software for digitization and processing of microscopic cell images used at the Department of Clinical Cytology at Uppsala University Hospital. A family of programs running on a PDP-8 minicomputer which is connected to a Leitz Orthoplan microscope with two image scanners, one diode-array scanner and a moving-stage photometer, is used for data collection. The digitized image data is converted by converted by conversion program to IBM compatible format. The data structures for image processing and statistical evaluation on the IBM system are also described. Finally, some experiences from the use of the software in cytology automation are discussed.     

Papillary serous carcinoma of the peritoneum with paraaortic lymph node metastasis despite minimal intraperitoneal involvement: a case report

BACKGROUND; Papillary serous carcinoma of the peritoneum (PSCP) is a tumor that produces widespread intraperitoneal lesions. Unlike serous ovarian adenocarcinoma, many aspects of its mode of progression and biologic characteristics are unclear. CASE: A 46-year-old woman with PSCP had no detectable ascites and minimal intraperitoneal involvement at the time of the diagnosis, but a paraaortic lymph node metastasis was present. Preoperative endometrial cytology was positive (suspicion of adenocarcinoma). The histologic diagnosis was poorly differentiated serous adenocarcinoma. Cytology of the peritoneal washings demonstrated positive findings, similar to those of endometrial cytology. After cytoreductive surgery, including lymph node dissection and platinum-based chemotherapy, the patient achieved long-term survival. CONCLUSION: PSCP can present with an early paraaortic lymph node metastasis. Endometrial cytology can be valuable in the diagnosis.     

Emperipolesis as a key feature in imprint cytology of the thymus. A report of two cases

BACKGROUND: Imprint cytology of the thymus has not received much attention. Cytology of the thymus is important because the uninvolved thymus may be needled during aspiration procedures. CASES: In two cases, during surgery for carcinoma of the thyroid, we received thymic tissue mistakenly sampled as a pretracheal lymph node for frozen section to rule out metastasis. Imprint smears were studied. The presence of thymocytes in the cytoplasm of thymic epithelial cells (emperipolesis) was the most significant feature in the imprints. However, it was not detected on histology. CONCLUSION: Thymic epithelial cells provide mechanical support and play a major role in the maturation of lymphocytes (thymocytes). They are observed as emperipolesis on imprint cytology. Its utility in identifying thymic cells in aspiration cytology needs to be investigated.     

Cytomorphology of verrucous carcinoma of the cervix. A case report

BACKGROUND: Verrucous carcinoma of the uterine cervix is rare. Cytology is thought not to be helpful in the diagnosis of this lesion due to its bland morphology. The cytologic features of this lesion remain poorly defined. CASE: The cytologic findings in a Pap smear facilitated the diagnosis of verrucous carcinoma of the cervix. The features included atypical polygonal and spindle cells with abundant, keratinizing cytoplasm; atypical squamous cells with pearl formation; and frequent, nonkoilocytic cytoplasmic vacuolization. CONCLUSION: There are 30 published reports on verrucous carcinoma involving the cervix and vagina that include the cytologic findings. In 70% of these cases, cytology was abnormal. Recognition of the cytologic characteristics may help in identifying this lesion on cytology, prevent delays in diagnosis and ensure that patients receive appropriate therapy.     

ABC3 Part I: a review of the guidelines for terminology,classification and management of cervical cytology in England

J. H. F. Smith ABC3 Part I: a review of the guidelines for terminology, classification and management of cervical cytology in England The provision of guidance on cytology reporting and evaluation, first outlined in 1995 with the publication of Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology (ABC), and subsequently revised and expanded in a second edition in 2000, has been pivotal to the success of the National Health Service Cervical Screening Programme (NHSCSP), ensuring that standards are upheld, and that rigorous evaluation and quality assurance take place. In the last decade, major changes to the NHSCSP, notably the adoption of revised age ranges and screening intervals for all women in England, implementation of liquid‐based cytology and, most recently, the decision to introduce high‐risk human papillomavirus (HR‐HPV) testing for triage of low‐grade and borderline (equivalent to 'atypical') cytological abnormalities and test of cure after treatment of cervical intraepithelial neoplasia (CIN) determined that an updated version of ABC was required. The third edition of ABC recommends adoption, with minor modification, of the revised British Society for Clinical Cytology terminology and provides guidance on the management of abnormal cytology results linked to this terminology taking account of HR‐HPV testing. To accommodate these changes, expanded result codes, which are electronic codes used to transfer management information to central computers for follow‐up, call and recall of individual women, have been developed. Further guidance on specimen adequacy is also provided. Revised performance indicators are described and explained in a separate article by R. Blanks in this issue of Cytopathology. All the changes in ABC3 are designed to support the mission statement of the NHSCSP that ‘the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity’.     

Diagnostic value of cytology and colposcopy for squamous and glandular cervical intraepithelial lesions

The main objective of work was to determine a diagnostic value of cytology and colposcopy as a method of screening and differential diagnosis, as well as to determine the relative value of some colposcopic features of squamous and glandular cervical intraepithelial lesions. Cytological diagnosis and colposcopy findings is compared with histological ones for 187 patients with intraepithelial lesions (142 squamous and 45 glandular ones with or without squamous components) and determined the sensitivity and positive predictive value of cytology and colposcopy, including the types of colposcopic abnormalities associated with squamous/glandular intraepithelial lesions. The sensitivity of cytology as a screening method for SIL (squamous intraepithelial lesions) is 89% and for GIL (glandular intraepithelial lesions) 98%. Positive predictive value of differential cytology for SIL is 59% and for GIL 53%. Sensitivity of colposcopy for both lesions' type is 87%. Acetowhite epithelium occurs for more often with SIL, whereas atypical vessels and unequal, dilated gland openings with GIL (p < 0.05). Cytology and colposcopy as screening methods have a high sensitivity. Nevertheless, cytology is far more accurate in determining differential diagnosis of SIL than GIL and some colposcopy abnormalities suspicious of GIL should be further tested in praxis.     

European guidelines for quality assurance in cervical cancer screening: recommendations for cervical cytology terminology

There are many different systems of cytology classification used in the member states of the European Union (EU) and many different languages. The following short annexe to Chapter 3 of the European Guidelines for Quality Assurance in Cervical Cancer Screening provides a framework that will allow different terminologies and languages to be translated into standard terminology based on the Bethesda system (TBS) for cytology while retaining the cervical intraepithelial neoplasia (CIN) classification for histology. This approach has followed extensive consultation with representatives of many countries and professional groups as well as a discussion forum published in Cytopathology (2005;16:113). This article will describe the reporting of specimen adequacy, which is dealt with in more detail elsewhere in Chapter 3 of the guidelines, the optional general categorization recommended in TBS, the interpretation/cytology result and other comments that may be made on reports such as concurrent human papillomavirus testing and the use of automation review and recommendations for management. The main categories in TBS will be described in the context of CIN, dyskaryosis and dysplasia terminologies so that all may be translated into the same framework. These guidelines should allow European countries to adapt their terminology in such a way as to make their screening programmes comparable with each other as well as with programmes elsewhere in the world.