The role of endobronchial ultrasound guided transbronchial needle aspiration cytology in the investigation of mediastinal lymphadenopathy and masses, the North Tees experience.

AIM: To assess the diagnostic role of endobronchial ultrasound (EBUS) guided transbronchial fine needle aspiration (TBNA) cytology, in the investigation of mediastinal lymphadenopathy and masses, with emphasis on pathology, criteria for adequacy, and use of liquid based cytology (LBC). METHODS: In January 2008, EBUS guided TBNA was introduced for the staging of lung cancers and for the investigation of unexplained mediastinal lymphadenopathy and masses. Initially, the material was processed conventionally. In May 2008, the laboratory procured the Cytyc T2000. RESULTS: 250 specimens (229 patients) were included from January 2008 to August 2009. The overall inadequate rate was 12%; 16.6% with the conventional method, 17.2% when both conventional and LBC were used, and 9.8% with LBC. With the conventional method, an average of 7.5 slides and one cell block were received per case. With LBC, one slide and one cell block were used for diagnosis. In 72 cases (28.8%) the aspirate showed no evidence of malignancy. In 122 cases (48.8%), there was metastatic disease. In five cases (2%), a diagnosis of atypia, suspicious for non-small cell malignancy, was made. One case (0.4%) each of amyloidosis and mediastinal goitre, 3 cases (1.2%) of lymphoma, 14 cases (5.6%) of sarcoidosis and 1 case (0.4%) each of sarcoma and mesothelioma were seen. CONCLUSIONS: EBUS guided TBNA, in our experience, is a reliable technique for staging of lung cancers, and investigation of unexplained mediastinal lymphadenopathy and masses. LBC reduces the number of slides from 7.5 per case to 1 slide, reducing time required for diagnosis.

The NHS breast screening programme (pathology) EQA: experience in recent years relating to issues involved in individual performance appraisal.

BACKGROUND: The original role of the National Health Service breast screening programme (pathology) external quality assessment (EQA) scheme was educational; it aimed to raise standards, reinforce use of common terminology, and assess the consistency of pathology reporting of breast disease in the UK. AIMS/METHODS: To examine the performance (scores) of pathologists participating in the scheme in recent years. The scheme has evolved to help identify poor performers, reliant upon setting an acceptable cutpoint. Therefore, the effects of different cutpoint strategies were evaluated and implications discussed. RESULTS/CONCLUSIONS: Pathologists who joined the scheme improved over time, particularly those who did less well initially. There was no obvious association between performance and the number of breast cancer cases reported each year. This is not unexpected because the EQA does not measure expertise, but was established to demonstrate a common level of performance (conformity to consensus) for routine cases, rather than the ability to diagnose unusual/difficult cases. A new method of establishing cutpoints using interquartile ranges is proposed. The findings also suggest that EQA can alter a pathologist's practice: those who leave the scheme (for whatever reason) have, on average, marginally lower scores. Consequently, with the cutpoint methodology currently used (which is common to several EQA schemes) there is the potential for the cutpoint to drift upwards. In future, individuals previously deemed competent could subsequently be erroneously labelled as poor performers. Due consideration should be given to this issue with future development of schemes.

Impact of a national external quality assessment scheme for breast pathology in the UK.

BACKGROUND: This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology. AIMS/METHODS: The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using kappa statistics. RESULTS: Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high-this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit-this included histological grading; (3) where consistency could be improved but only by changing the system of classification-this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved-this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming. CONCLUSIONS: These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.

All radial scars/complex sclerosing lesions seen on breast screening mammograms should be excised.

AIM: To determine the incidence of pre-malignant and malignant conditions in radial scars identified from screening mammograms in women taking part in the UK NHS breast cancer screening programme. METHODS: All women in our screening population from 1988 to 2002 with a radiological diagnosis of radial scar or complex sclerosing lesion confirmed on subsequent histopathology were included in this study. Patients were investigated with fine needle aspiration cytology then localisation biopsy (n=46) or straight to localisation biopsy (n=78). Patients where divided into two groups, one with pure RS/CSL with no associated epithelial features and the second with associated ADH, DCIS or invasive cancer. RESULTS: One hundred and twenty-four lesions were confirmed histologically as radial scar or complex sclerosing lesions. The median age was 58 years. Of the 124 patients, 82 were pure RS/CSL. Forty-two had associated epithelial lesions, 22 patients had ADH and 20 patients had either in situ or invasive carcinoma. Where FNA was performed (n=46), mammograms had shown three lesions suspicious of cancer, which were not proven histologically. Mammograms picked up five malignancies out of the nine RS/CSL with associated cancers. Of these, FNA confirmed malignancy in only two patients. Where FNA was not done (n=78), mammogram had read five pure RS/CSL as cancers. It picked up only four cancers in RS lesions with DCIS/Ca out of 11. CONCLUSION: All screen-detected stellate lesions should be excised due to their association with pre-malignant and malignant conditions.

Granulomatous mastitis can mimic breast cancer on clinical, radiological or cytological examination: a cautionary tale.

In both women and men, breast lumps are the most common presentation of breast cancer. The following cases illustrate the pathological entity of granulomatous mastitis, which can present simulating breast cancer - including the first description of this condition in a male. These cases demonstrate the difficulty in clinical diagnosis and emphasizes that although there may be clues from the history, clinical awareness that this condition can mimic breast cancer in all aspects of the triple assessment process should arouse suspicion. The importance of histological diagnosis by core or excision biopsy is stressed, as with accurate diagnosis of granulomatous mastitis there is a mandate to avoid unnecessary surgery.

Downregulation of nuclear expression of the p33(ING1b) inhibitor of growth protein in invasive carcinoma of the breast.

BACKGROUND/AIMS: The inhibitor of growth gene 1 (ING1) is a modulator of cell cycle checkpoints, apoptosis, and cellular senescence. The most widely expressed ING1 isoform is p33(ING1b), which can modulate p53, a molecule that is frequently altered in breast cancer. Reduced ING1 mRNA expression has been observed in primary breast cancer expressing wild-type p53. METHODS: p33(ING1b), p53, oestrogen receptor (ER), and progesterone receptor (PgR) expression was studied in 86 primary invasive breast cancers using immunohistochemistry. RESULTS: Reduced nuclear expression of p33(ING1b) was found in cancer cells, both in intensity and the proportion of cells staining. This was associated with enhanced cytoplasmic p33(ING1b) expression in a proportion of cases. Analysis of several known biological factors indicated that high grade tumours were of larger size and more often negative for ER and PgR expression. However, larger tumours were more frequently p53 negative. These results provide evidence that p33(ING1b) alterations are associated with more poorly differentiated tumours. Positive correlations were found between nuclear p33(ING1b) expression and both ER and PgR expression. CONCLUSIONS: Optimum function of p53 is dependent on p33(ING1b) so that a reduction of nuclear p33(ING1b) expression, as seen in this series, would be predicted to compromise p53 function. This study showed that p33(ING1b) alterations were associated with more poorly differentiated tumours. Therefore, p33(ING1b) expression could be used as a marker of differentiation in invasive breast cancer. These results support the view that loss of p33(ING1b) may be an important molecular event in the differentiation and pathogenesis of invasive breast cancer.

The use of a standard proforma in breast cancer reporting.

AIM: To determine whether the introduction of a standard reporting proforma has led to an improvement in the completeness of histopathology reports for breast cancer excision specimens. METHODS: A standard reporting proforma was designed using the Royal College of Pathologists' minimum dataset for breast cancer histopathology reports and the national histopathology reporting form of the National Health Service (NHS) breast screening programme. This was introduced into our department in June 1999, with reports generated from the proforma replacing the standard text reports. The pathological information contained in 50 text reports issued before the introduction of the proforma and 50 reports generated using the proforma was compared with the minimum dataset and NHS breast screening programme guidelines. RESULTS: A general improvement in documentation of individual pathological features was noted after introduction of the proforma. This was most significant in relation to documentation of features, such as microcalcification and ductal carcinoma in situ. In addition, important features such as tumour grade, tumour size, and hormone receptor status were documented more frequently in the proforma group. There was an overall increase in the number of reports regarded as complete after introduction of the proforma. CONCLUSIONS: The introduction of a standard proforma led to a significant improvement in the completeness of breast cancer histopathology reports in this centre, but continued vigilance is needed to ensure that standards continue to improve.

Aggressive local treatment for screen-detected DCIS results in very low rates of recurrence.

AIMS: To review our institution's practice of treatment of a mammographically detected population of ductal carcinoma in situ (DCIS) patients and to determine the outcome. METHODS: Between April 1989 and March 1994, 304 women with median age 59 years (range 51-65) with DCIS detected on screening mammogram, were treated in the Newcastle General and Royal Victoria Infirmary Hospitals, Newcastle-upon-Tyne, UK. More than half of the women (n=176, 57.8%) decided to have mastectomy. Other treatment options were wide local excision (WLE) with radiotherapy (n=97, 32%) and WLE alone (n=31, 10.2%). All except five received adjuvant hormone treatment. RESULTS: Predominant DCIS was comedo in 122 (42%), followed by cribriform in 87 (30%) and micropapillary in 44 (15%) cases. Grade I was found to be commonest grade (54%) followed by grade II (27%) and grade III (11%). With a median follow-up of 88 months, there were six (2%) recurrences, all of which were in women who were given breast conservation treatment, WLE with radiotherapy (n=1, 1%) and without radiotherapy (n=5, 16.6%). Mastectomy in this series was not associated with any recurrence at all. In three cases the recurrence was invasive, one of who also had distant metastasis. CONCLUSIONS: The findings of this study suggest that in women with DCIS suitable for breast conservation, WLE when combined with radiotherapy is associated with a very low recurrence rate.

Granulomatous disease in common variable immunodeficiency: effect on immunoglobulin replacement therapy and response to steroids and splenectomy.

A 40 year old white woman with common variable immunodeficiency of four years duration presented with rapidly increasing splenomegaly. Despite high dose, weekly intravenous immunoglobulin, it was impossible to raise the trough serum IgG concentration to within the normal range. While waiting for a diagnostic splenectomy, low dose corticosteroids were started, leading to a decrease in the size of the spleen and an increase in the trough IgG concentration. Both spleen and liver showed non-caseating granulomas. Following splenectomy, the corticosteroids were tailed off and the trough IgG was maintained well into the normal range on a reduced, fortnightly dose of intravenous immunoglobulin and a low dose of oral corticosteroid.

Tumour bed biopsy detects the presence of multifocal disease in patients undergoing breast conservation therapy for primary breast carcinoma.

This study prospectively examined tumour bed biopsies in 135 consecutive patients undergoing conservative surgery for breast carcinoma. All had wide resection of the primary tumour and histologically clear margins. Twelve patients (9%) had positive tumour bed biopsies. Two subgroups of patients had positive bed biopsies; those with ductal carcinoma in situ, and a second group with more aggressive disease characterized by lymph node involvement, vascular invasion and a higher grade and mitotic count. As the majority of recurrences from breast carcinoma occur in the region of the primary tumour, bed biopsy may aid in the identification of a group of patients with multifocal or aggressive disease who are at increased risk of local recurrence.

Dexamethasone suppression test in dementia and depression. Clinical and biological correlates.

To determine the usefulness of the DST in differentiating depression from dementia, the test was administered to three diagnostic groups of psychogeriatric patients: depression; dementia; and dementia with depression. Clinical assessments were supplemented by ratings on the HRSD and SCAG, as well as by EEG and CT. All three groups showed a high incidence of abnormal DST results unrelated to presence or severity of affective symptoms, but showing a better association with SCAG and its 'organic' subsets. The mechanism(s) underlying these abnormal results may reflect organic brain disease. The usefulness of the DST in differentiating depression from dementia in the elderly was not confirmed.

Dexamethasone suppression test and response to antidepressant therapy in psychogeriatric patients.

Senile dementia patients show a high incidence of abnormal Dexamethasone Suppression Test (DST) which has been suggested to reflect the presence of atypical or subclinical depression; this study was designed to test this hypothesis. Thirty-six patients, diagnosed as suffering from dementia and/or depression on the DSM-III criteria, participated in the study. They were divided into three groups. dementia (12), depression (12) and dementia with depression (12). The results indicated that although patients with depression alone responded well to antidepressant therapy, no improvement occurred in patients with dementia. Demented patients who had clinical depression also showed a poor response. The response to treatment was unrelated to the DST status of the patients. It is concluded that abnormal DST in dementia patients is not indicative of a masked affective state, and antidepressants have no place in the management of dementia patients who have a positive DST but no overt affective symptoms.