Dr J. H. F. Smith
Prior to the establishment of an organised cervical screening programme in the UK in 1988 there was little formal training of laboratory non-medical staff, apart from the efforts of some enthusiasts in a few training centres. However critical incidents in the screening programme highlighted the need for comprehensive training and since the late 1980s ten training centres have been established principally to provide introductory and update training for cytology screeners and biomedical scientists (BMSs). Recently the National Health Service Cervical Screening Programme (NHSCSP) has produced guidance on the qualifications and training for non-medical laboratory staff, and an accreditation process for the training centres has been instituted.
Trainee cytology screeners and trainee BMSs who wish to specialise in cervical cytology must complete a laboratory based training programme lasting two years or 18 months respectively during which time there are expected to screen under supervision a minimum number of smears and complete a training log which encompasses the syllabus for the WSCSP Certificate in Cervical Cytology examination. In addition they must attend an introductory course, which is designed to complement and consolidate their in-house training and prepare them for the Certificate in Cervical Cytology examination. Successful completion of the training programme and examination is mandatory for promotion to the cytology screener and BMS grade and permits individuals to undertake independent primary screening, double screening and rapid review of cervical smears. Subsequent career progression for BMSs is based on experience and acquisition of further qualifications.
Postgraduate medical trainees in histopathology and cytology undertake a one-year period of basic specialist training (BST) at senior house officer grade on successful completion of which they apply for a specialist registrar (SpR) post in open competition. SpR posts last for 5 years and provide comprehensive training in gynaecological and non-gynaecological cytology. Appointment to a consultant post requires completion of the SpR training and acquisition of the Membership of the Royal College of Pathologists (MRCPath) examination. The MRCPath examination is in two parts: a written test of knowledge, including a compulsory cytology question, and a practical test of competence. Trainees who wish to demonstrate particular competence in cytopathology may also take the RCPath Diploma in Cytopathology examination.
Recently, in response to an escalating national problem with consultant staffing in histopathology and cytology, the Advanced Practitioner in Cervical Cytology (AP) grade has been established. APs are permitted to independently report abnormal cervical smears and give clinical advice in much the same way as a consultant pathologist. APs are recruited from experienced biomedical scientists who have successfully completed a training programme of 'shadow reporting' under consultant supervision and the WSCSP Certificate in Advanced Practice in Cervical Cytology examination.
Reference
Qualifications and Training for Non-medical Laboratory Staff in the UK Cervical Screening Programmes. NHSCSP Publication No. 12, Sheffield 2000
Dr Harold Neal, Mrs Diane Casey
The continuing development of a competent and capable cytology workforce for the National Cervical Screening Programme is vital to maximising benefits for the women of New Zealand. Workforce development is one of the key areas for action in the National Screening Unit's (NSU) Strategic Plan 2003 - 2008. Linked to this is the Draft NSU Workforce Development Strategy 2002 - 2007, which was presented at the last conference. The Workforce Development Strategy includes a number of initiatives to support the cytology workforce.
The Laboratory Workforce Advisory Group considered the proposed initiatives and has identified three initial priorities. The first of these relates to new cytology trainees. Harold Neal will present the Draft Standard Orientation Programme in Cervical Cytology and incorporate sector feedback from the June consultation. The other priorities and laboratory initiatives will be highlighted in the first part of this presentation by Diane Casey.
Ms Jane McEntee, Dr Hazel Lewis
The National Cervical Screening Programme (NCSP) has evolved since its introduction in 1990 through significant changes to the health sector and to the legislative landscape. As Dr Euphemia McGoogan stated in her latest report "It can be likened to a jigsaw puzzle. We know how many pieces we should have, we may have put some together but we do not achieve the completed picture until each is connected properly to the other pieces and only then do we recognise if there are some pieces missing or defective."
Since the Gisborne Inquiry report in 2000 there have been significant changes in the NCSP and the laboratory sector. This was initiated with the introduction of the NCSP Operational Policy and Quality Standards, routine monitoring and evaluation and more recently with direct contractual relationships between the NCSP and Laboratories.
There are still many developments to be progressed over the next few years. Dr McGoogan identified some including the establishment of a national external quality assurance scheme to monitor continuing competence, lack of appropriate training for laboratory staff screening and reporting liquid based cytology, or the development of specific standards and monitoring of outcome measures for these tests. These and other future developments will be highlighted throughout this presentation.
Presenting Author - Karin Bradshaw, Other Authors - Dr David Roche
A retrospective study of 100 cases
Litigation cells is a term defined as benign cells, which may mimic dysplasia or cancer. The finding of such cells may imply that a cytotechnologist or pathologist missed an abnormality in a woman who subsequently developed cervical cancer.
We reviewed the last smear of 100 patients who had hysterectomies for benign reasons. All smears reviewed were performed within 12 months prior to hysterectomy. None of the uteri contained dysplasia or cancer on histologic examination.
On the slides reviewed we looked for cells or groups of cells with appearances that mimicked low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, squamous cell carcinoma, and all glandular abnormalities.
Experienced screeners and pathologists should have no problem in distinguishing between litigation cells and true abnormalities.
This retrospective study highlights the effect of hindsight bias that may be present when reviewing smears when the clinical outcome is known.
Presenting Author - Karin Bradshaw
Adult Granulosa Cell Tumours are rare findings and can wrongly diagnosed as Follicular cysts resulting in false negative results.
This case is of particular interest as it highlights the definitive features of this ovarian neoplasm, which accounts for only 1.5% of all ovarian neoplasms and only 6% of all malignant ovarian tumours.
Presenting Author - Martina Chai, Other Author - Joyce Lee
Cervical cancer is the second most common cancer among women worldwide and human papillomavirus (HPV) DNA has been found in 99% of cervical cancers and high-grade cervical lesions. About 40 of the 100 or so strains of HPV are transmitted sexually, but 70% of cervical tumors are caused by just 2 strains: HPV-16 and HPV-18. These discoveries have raised the possibility that cervical cancer might be prevented by HPV testing and vaccines.
HPV DNA and expression of viral transforming proteins (E1 and E2) have been found in virtually all cervical cancer cells, indicating an important role of this virus in the pathogenesis of the disease. Thus, a test for HPV DNA can predict the risk of cervical cancer among women with normal Pap smears. This new technology has been introduced by the Digene's Hybrid Capture System (HC2), which uses the DNA/RNA probes and monoclonal antibodies to allow rapid detection of the high-risk HPV DNA in cervical cells.
in recent years, work on HPV vaccines has also progressed rapidly. The vaccines for HPV-16 and HPV-18 are currently being studied in clinical trials. The vaccine contains virus-like particles (VLPs), which are proteins from the virus' outer shell and no genetic material that can cause the disease. The vaccines against HPV-16 and HPV-18 produce high levels of neutralizing and apparently productive antibody. Researchers also are testing other types of vaccines, including a fusion protein, which combines one of the coat proteins with a portion of an HPV protein that is not normally in the virus particle. Also under development are naked DNA vaccines, created by combining one or more genes that encode HPV surface proteins with plasmid DNA. Currently, at least six vaccines are under development worldwide.
Presenting Author - Muna Bulbul, Other Author - Regan Kendrick
The purpose of this poster is to illustrate the rare case of 'Progressive Disseminated Histoplasmosis'.
This was diagnosed on an FNA sub mental lymph node at LabPlus. It sparked a lot of interest within the Laboratory, and in an effort to learn more about the infection, we researched its etiology and its known history within New Zealand.
What we discovered is that Progressive Disseminated Histoplasmosis is rarely heard of in New Zealand, although very common the United States of America. The fact that it is an opportunistic infection with a very high mortality rate, and given that increased incidence of HIV within New Zealand, it is an important finding for all cytologists to be aware of.
Presenting Author -Amy Y. Ou Yang
Cytological specimens often contain large amounts of blood, inflammatory cells that disturb the cytological appearance on a slide. ThinPrep processors employ a new technology that may enhance the cellular content on the slide.
The aim of this comparative study was to look at two different processing methods used for nongynaecologic specimens in order to achieve the optimal appearance on a monolayer cellular yield. Also, to compare the expense in terms of materials consumed when processing the samples by either using a liquid-based ThinPrep® preparation versus the cytocentrifuge technique. The results showed that in nongynaecologic the ThinPrep® preparation performed better in most of the categories compared to the cytocentrifuge technique. However, for urine specimens, the cytocentrifuge technique performed equally if not better than the ThinPrep® preparation in all categories. In diagnostic categories, both processing methods performed almost as good as each other, but the ThinPrep® preparation cannot match the cost effectiveness of the cytocentrifuge technique. Therefore, the ThinPrep® preparations are best adapted for nongynaecologic specimen (except for urine), and that would provide an optimal diagnostic sensible monolayer cellular yield.
David Roche
FNA has a key role in the investigation of head and neck masses. Most organs and structures in the head and neck are not too far from the skin and mucosal surfaces, and vital structures are well tucked away, making FNA a relatively simple and safe procedure to perform. However although the sample may be easy to procure, interpretation is not always straightforward.
Dilemmas and pitfalls include benign and malignant lesions that have similar cytologic features, nonrepresentative samples, cystic lesions, and occasional unusual and rare lesions. In many cases the correct diagnosis can be reached by careful attention to cytologic detail, clinical history, and ancillary tests. However in a number of cases the cytologic features will not allow confident distinction between several possibilities.
The workshop will consist of 10 everyday cases from salivary gland, thyroid, lymph node, and soft tissue, which illustrate areas of particular diagnostic difficulty. Cases to illustrate the differential diagnoses will also be presented, with discussion of the cytologic features and ancillary tests, which may be useful in arriving at a correct diagnosis.
Dr Noreen Tracey - BreastScreen Auckland and North
Breast cancer screening internationally was initiated mainly on the results of two major randomised control trials, namely the HIP study and the Swedish Two Counties trial. The latter was published in 1985. Subsequently Finland and Sweden launched their Screening Programmes in 1986, England & Wales in 1988, the Netherlands in 1989 and Australia in 1992.
BreastScreen Aotearoa was launched in December 1998 offering free mammograms every two years to eligible women in the 50 to 64 age range. It is controlled centrally by the National Screening Unit but provided locally by six Lead Providers.
Women either self refer into the programme or are enrolled via their GP. They then attend for a screening mammogram, which commences them on the screening pathway. They continue along this pathway until a final diagnosis is reached.
Multiple debates surround screening for breast cancer. Is it worthwhile? Is the eligible age range sufficient? Is the screening interval appropriate? Is mammography the right screening tool? These will be the main areas of development in all of the Breast Screening Programmes, which exist worldwide. Meanwhile data published from the well established Programmes do show a reduction in mortality from breast cancer, which is the primary aim of all the Programmes. How much of this reduction is purely due to screening and how much is due to the associated increased awareness in the population and advances in treatment is less certain.
Dr Elizabeth Salisbury
The advent of breast screening has revolutionized the radiological and pathological diagnosis of breast disease. The multiclisciplinary approach to diagnosis and management has undoubtedly improved patient management and outcome and has increased the communication and understanding between radiologist, surgeon and pathologist. However, breast screening has also brought with it many challenges. Fine needle aspiration of breast is not longer limited to palpable lesions. We are now seeing numerous biopsies from impalpable, small lesions, many of which represent hyperplastic, atypical or preinvasive lesions. The line between a malignant and benign diagnosis has been blurred and this, combined with increasing surgical pressure to perform one stage, definitive therapeutic procedures has, by necessity, produced a rapid expansion in our knowledge of breast cytology. New technologies (e.g. vacuum assisted core biopsies) have at times partially replaced FNAB as a diagnostic tool, however, in our experience at Breastscreen Western, FNAB remains a central diagnostic procedure in the work up of women with screen detected lesions. The ability of FNAB to provide a fast, cheap, reliable and minimally invasive diagnostic result has ensured its continuing use in our clinics.
This lecture does not aim to provide a comprehensive discussion of breast cytology, as there are many excellent texts on this topic. Instead, I wish to focus on the problem areas of breast cytology, particularly within a breast screening setting. There are many pitfalls in breast cytology and by looking at some of the clinical and cytological scenarios I will try and outline how these pitfalls can be best avoided.
A few years ago there was an editorial in Diagnostic Cytopathology, which examined the causes of successful litigation in breast cytology. The authors stated that one of the most problematic areas was that of unsatisfactory/non-diagnostic aspirates which were reported as benign, thus leading to false reassurance of both clinician and patient. Closely related to this is the issue of an aspirate, which contains abundant benign cellular material, but is non-representative of the lesion. In this context, lack of clinical, radiological and pathological correlation leads to mismanagement of the patient. The authors found that true false negative reports were very uncommon and that when malignancy was present in smears it was rarely reported as an unqualified benign finding. How may the pathologist and clinician avoid this trap?
This requires good communication between radiologist/surgeon and pathologist. There are clear advantages in having the pathologist perform the aspirate if the lesion is palpable as the pathologist is able to examine the material at the time of the procedure and determine if diagnostic material is being obtained. For impalpable lesions, attendance by a pathologist or scientist at the aspirate will also increase the diagnostic yield and provide an opportunity for discussion with the radiologist as to the nature of the lesion. Once the pathologist is aware of the type of lesion, which is being aspirated, they can assess whether the material is likely to be representative. For example it may be entirely appropriate to obtain only fat and blood if the radiologist or surgeon believe the abnormality to be an island of entrapped fat or an intramammary lipoma. Conversely, abundant benign material should not be viewed as an adequate aspirate if the radiologist believes the lesion to be malignant. This may sound like a basic principle, but patients have been under investigated and under treated as a result of nonrepresentative, falsely reassuring benign results.
Whilst one pass yielding cellular material may be enough to make a positive diagnosis of malignancy or fibro adenoma, when one is dealing with an abnormality which is vague in clinical and/or radiological presentation, the degree of confidence in a negative report increases with the number of passes. In our practice, we tend to make more passes into lesions which come with the clinical history of "?prominent breast tissue ?other" or "?scar tissue ?cancer" as one has to ensure that the cytological examination of the lesion has been thorough. A negative result is more meaningful if three or four (or more) passes have been made into a number of areas of the lesion, rather than one or two. But once again, correlation with the clinical and radiological features is necessary. FNA is often used to reassure the patient who presents with high anxiety regarding an indistinct abnormality. While some may argue that this in an inappropriate use of the test, we nevertheless have to ensure that any reassurance given is well founded.
As in all areas of cytology, the acceptance and over interpretation of technically unsatisfactory material should be avoided.
Lobular carcinoma and low grade infiltrating duct carcinomas may cause diagnostic difficulties. Remember too that sometimes a small carcinoma may be overshadowed by a larger, adjacent benign lesion, creating a confusing cytological appearance.
The aspirate of a typical fibroadenoma in a young woman does not usually produce too much diagnostic difficulty and it is somewhat surprising for our clinical colleagues to learn that fibroadenomas, particularly in older age groups can be a significant cause of false positive results. The other area of difficulty is the separation of fibroadenomas, particularly cellular fibroadenomas from phyllodes tumours.
The three classic cytological components of fibroadenomas are:
Diagnostic difficulties are caused by alterations in the appearance of each of these components. Increased ceilularity or atypia within the epithelia] sheets may lead to a diagnosis of hyperplasia or a papillary lesion. Fibroadenomas in pregnancy may also be a cause of false positive results due to lactational change and cellular dispersion. Myxoid alteration of the stromal component may lead to an over diagnosis of mucinous carcinoma, particularly in an older woman. Overzealous smearing may give the impression of cellular dispersion, and is a common cause of over interpretation of atypia in fibroadenomas.
Separation from phyllodes tumours can be particularly difficult. There is a spectrum between fibroadenoma, cellular fibroadenoma, benign phyllodes and malignant phyllodes. It may be difficult histologically to determine the precise classification of some fibroepithelial lesions, and in some cases it may be cytologically impossible. Close attention to the degree of stromal cellularity, atypia and the presence of any mitoses may provide useful clues, but the overlap between cellular FA and benign PT may be great. Some authors state that the degree of atypia within the stromal cells provides the most useful cytological clue.
We have seen cases of phyllodes tumour in which only the epithelial component was obtained at aspiration, leading to a diagnosis of epithelial hyperplasia. This is also a recognized pitfall. it is important to remember also that fibroadenomas may have secondary changes within them, which will cause difficulties. Hyperplasia, apocrine metaplasia, sclerosing adenosis, LCIS and DCIS have all been reported in fibroadenomas and may produce confusing cytological patterns. Recognition of bare oval nuclei in the background and appreciation of the overall fibroepithelial architecture should hold the pathologist back from making a definitive malignant diagnosis.
Fibroadenomas may also be involved by infiltrating carcinomas, and the risk here is that the cytology (and radiology) of the fibroadenoma masks the co-existent malignancy.
Typical apocrine cells are usually easy to recognize so it may seem strange that so many people express great difficulty with apocrine lesions. Difficulties are encountered in three main areas:
The differentiation of atypical apocrine metaplasia from apocrine carcinoma may be difficult in some cases. Useful cytological clues include:
Care should always be exercised in diagnosing malignancy in a cystic lesion, no matter how atypical the cells appear.
Other rare lesions, such as histiocytoid variant of lobular carcinoma and granular cell tumours may mimic benign apocrine cells due to the fact that in both lesions the constituent cells may have abundant pale/granular cytoplasm and bland nuclei.
Two main problems exist in the diagnosis of papillary lesions - recognition and assessment of atypia.
Firstly, there is the problem of recognition of papillary lesions and distinction from other look alike lesions such as fibroadenoma and certain malignancies.
Not all papillary lesions will present with classic branching epithelial tissue fragments with fibrovascular cores so the pathologist needs to be aware of some of the more subtle clues which may indicate a papillary lesion. Strips of columnar cells, numerous single columnar cells, hard anatomical edges with palisading at the edges of tissue fragments and large monolayered sheets are all clues which may alert the pathologist to a diagnosis of a papillary lesion.
The finger-like and branched aggregates seen in fibroadenomas may be suggestive of a papillary lesion. Numerous bare oval nuclei and stromal fragments are useful indicators of FA. Similarly, some of the low grade carcinomas may mimic papillary lesions due to the presence of flat monolayered sheets and columnar cells.
The second diagnostic problem is establishing the degree of atypia within a papillary lesion. Histologically benign papillary lesions may display quite marked cytological atypia and some invasive papillary carcinomas may be deceptively bland. In recognition of this, many cytopathologists (including this author) recommend excision and histological examination of all papillary lesions without making a definitive cytological prediction of atypia or malignancy.
Papillary lesions often produce very cellular aspirates displaying marked cellular dispersion. Combine this with a degree of cytological atypia and it is easy to see how these lesions may produce false positive results. In our unit, sclerosing papillomas with atypia have on rare occasions been a cause of false positive FNA results. One of these lesions presented with a palpable, clinically and radiologically malignant lesion with overlying skin tethering. If the subtle signs of a papillary lesion are not recognized at the time of aspirate, the triple test may fail and the patient may be over treated.
Infarcted papillomas are a particular trap as the smears may be cellular and contain a mixture of atypical dispersed cells, often with background necrosis. Again, if the subtle papillary features are overlooked, the triple test may fail, leading to mismanagement.
Extreme care should be exercised in diagnosing malignancy in a papillary lesion. In our unit, we do not report definite malignancy in aspirates which have features suggestive of a papillary lesion.
The cytological diagnosis of ductal carcinoma in situ is a well documented pitfall in fine needle aspiration cytology of the breast and the advent of breast screening has led to an increase in detection of DCIS. Generally speaking it is not possible to reliably predict the presence or absence of invasion in malignant breast lesions on cytological grounds alone. This concept underlines the importance of triple diagnosis in breast disease in which the assessment of the clinical, radiological and cytological features is central to the diagnostic work up of breast lesions. In the majority of cases, a malignant smear pattern associated with an impalpable lesion containing casting calcifications will histologically turn out to be ductal carcinoma in situ. Similarly, a clinically and radiologically malignant mass associated with malignant cells on FNA will usually turn out to be invasive carcinoma. There is, however, a subgroup of patients in whom these generalizations do not apply and in these cases, a lesion which radio logically and clinically was thought to be invasive may contain only DCIS. Cases such as these, although uncommon, demonstrate the limitations of FNA of breast and a significant number of these patients will undergo unnecessary axillary dissection.
High grade DCIS and invasive malignancy have many overlapping cytological features, however, there are some features which should alert the cytologist to the possibility of in situ disease. High grade comedo-type DCIS is characterized by the presence of large, malignant cells with abundant well defined cytoplasm. The cells typically display variable cohesion. Important cytological clues are found in the background of the smears, namely, necrotic debris, macrophages and occasionally calcium. Necrosis is generally uncommon in FNAs of invasive lesions and its presence should alert the cytologist to the possibility of DCIS.
The cytological diagnosis of intermediate and low grade DCIS is not so straightforward and many of the rare types of DCIS may be particularly problematic. Necrosis and high nuclear grade are generally not features of the lower grades of DCIS. Cellular pleomorphism and dispersion are usually not prominent and particular attention must be paid to the architectural features, nuclear atypia and monomorphic cell population. Some authors have found that the presence of tubular structures and stromal fragments associated with tumour cells are significant indicators of invasive carcinoma, These features may be subtle and separation from atypical proliferative lesions such as atypical ductal hyperplasia and papillary lesions may be difficult. Low grade carcinoma in situ tends to present more of a problem of under diagnosis, however, in some cases there is sufficient atypia and dispersion to be reported as malignant.
It is important to remember that ductal carcinoma in situ of the breast displays a wide range of cytological presentations, reflecting the wide variety of histological subtypes. In a significant number of cases there may be an atypical radiological or clinical presentation, which when interpreted in the light of a malignant FNA result, inadvertently leads to over treatment or mismanagement of the patient.
High grade carcinomas producing cellular smears with numerous dispersed atypical cells do not usually pose a great diagnostic challenge to the experienced eye. The same cannot be said, however, of the low grade carcinomas, particularly tubular carcinoma. The degree of architectural and cytological atypia may be extremely subtle and separation from epithelial hyperplasias and even fibroadenomas may be difficult. Tubular carcinoma is typified by small angular clusters and tubular structures of cells displaying mild atypia. Cellular dispersion may be minimal and small numbers of bare oval nuclei may be identified.
Fragments of fibromyxoid stroma may also be present. In many cases a definitive diagnosis of malignancy may not be possible and histological examination may be needed to establish diagnosis.
Exercise caution in diagnosing malignancy in the following settings:
Exercise caution in issuing a benign report in the following settings:
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J. H. F. Smith
In contrast to the NHS breast screening programme, which was developed and implemented nationally against a clear set of predetermined achievable standards, the NHS cervical screening programme (NHSCSP) developed initially at a local level and subsequently became a national programme in 1988. As a result, the NHSCSP exhibited considerable local variation and different standards, precluding reliable evaluation on a national scale. In response to this problem, the professional bodies produced guidance on smear reporting and programme evaluation1; a code of practice for laboratories 2 and guidelines on quality assurance 3 . The quality standards, which concentrate on smear taking, smear reporting and colposcopy, will be outlined.
In order to ensure that all screening staff screening or reporting smears are competent it was recommended, amongst other things, that staff should participate in a proficiency testing scheme. The initial proficiency testing scheme was based on the New York scheme and provided a numerical score for individuals. However it was variously implemented in the NHS regions such that comparisons could not easily be made and there was little advice about the handling of individual poor performance.
A revised national proficiency test protocol was introduced in 1996, which in part addressed these problems, but this has now been superseded by a national external quality assurance scheme in gynaecological cytopathology4 that has been designed in line with the requirements of other interpretive E0A schemes in cellular pathology5. Operation of the scheme closely follows normal laboratory working practice and evaluation of an individual's performance is measured against 80% consensus opinion of all the participants. The purpose of the scheme is educational rather than punitive. Substandard performance is defined statistically and there is clear guidance on handling persistent substandard performance. The scheme will be described in detail.
1. Achievable standards, Benchmarks for reporting, and Criteria for evaluating cervical cytopathology. NHSCSP Publication No 1. '1 st Edition 1995 [2nd Edition, 20001
2. Recommended Code of Practice for Laboratories Providing a Cytopathology Service. British Society for Clinical Cytology. 1997
3. Quality Assurance Guidelines for the Cervical Screening Programme. NHSCSP Publication No 3. NHSCSP, Sheffield. 1995
4. External Quality Assessment Scheme for Gynaecological Cytopathology. NHSCSP Publication No 15. NHSCSP, Sheffield. 2003
5. Recommendations for the Development of HistopathologylCytopathology External Quality Assessment Schemes. Department of Health. 1998