Review of cytology and histopathology as part of the NHS Cervical Screening Programme audit of invasive cervical cancers.

OBJECTIVE: To audit pathology slide reporting in the Cervical Screening Programme in England by reviewing cytology and histology slides from women subsequently diagnosed with invasive cervical cancer. METHODS: Between April 2007 and March 2010, 6113 women diagnosed with cervical cancer were identified. Cervical cytology and histology slides taken within 10 years of diagnosis were identified and where possible reviewed after a nationally agreed protocol. Reviewers were not blinded to the original reading of each sample. Most cytology samples before 2005 were conventional, most after 2007 liquid based. RESULTS: Of 13,745 cytology results from women developing cervical cancer, 55% were reviewed. The review result was identical for 55% of slides. Of 3759 originally normal slides, only 45% were normal on review: 11% were inadequate, 21% low grade (borderline or mild dyskaryosis) and 23% high grade (moderate dyskaryosis or worse). Of tests originally normal taken over 5.5 years before diagnosis, 14% were upgraded to high grade compared with 37% within 3.5 years of diagnosis. Of 5159 histology specimens recorded within 10 years of diagnosis of a cancer, 3895 were reviewed. Overall, 94% of samples reviewed retained the original diagnosis. One per cent (33/3012) of cancers were downgraded and 5% (6/112) of negative samples were upgraded to cancer upon review (four of which were taken within 2 months of diagnosis). In comparison, 15% (14/91) of cervical glandular intraepithelial neoplasia (CGIN) and 12% (38/314) of cervical intraepithelial neoplasia grade 3 (CIN3) were upgraded to cancer. CONCLUSIONS: In spite of the excellent quality of cytology in England, a high proportion of negative cytology taken up to three and a half years before diagnosis were considered to contain abnormal cells by reviewers informed of the subsequent cancer. Continuing these reviews, with a strong focus on education, will ensure a clear understanding of these slides and further reduce the risk of developing cervical cancer.

Telomerase expression of malignant epithelial cells correlates with Dukes' stage in colorectal cancer.

BACKGROUND: The ribonucleoprotein telomerase has been proposed as a potential prognostic marker for malignancy. Whether telomerase activity of clinical specimens correlates with other clinico-pathological variables, however, remains controversial. This is at least in part due to the varying contribution that nonmalignant cells will make to the net activity when extracts are assayed for telomerase activity. We therefore designed experiments to assay telomerase activity of isolated malignant cells of primary colorectal cancers. METHODS: Thirty colorectal cancer and 20 corresponding specimen taken from macroscopically normal regions of the colon were mechanically disaggregated and digested with collagenase, DNase and hyaluronidase. The epithelial cell population was separated using Ber-EP4 pan-epithelial antibody and Magnetic Activated Cell Sorting technique. Haematoxylin and eosin staining was used to assess the proportion of recovered epithelial cells which were malignant. Telomerase activity was assayed by the Telomeric Repeat Amplification Protocol, which was quantified by PhosphorImager with Image Quant software. RESULTS: Epithelial cells of three of 20 normal mucosa specimens were telomerase positive with weak activity (mean 3.7 TPGs, Total Product Generated, range 1.4-5.1TPGs). In the cancer group the vast majority (>95%) of the epithelial cells recovered were malignant by cytological criteria. Epithelial cells were telomerase positive in all the cancers, with a wide range of telomerase activity values (mean 22.7 TPGs, range 0.19-308 TPGs). Telomerase activity correlated with Dukes' stage (r = 0.52, P=0.004, Spearman's rank). CONCLUSIONS: Pathological stage correlates with telomerase activity of the malignant cell population of the primary tumour in colorectal cancer. This suggests that telomerase activity increases during the progression of a cancer and may have implications for the design of anticancer (antitelomerase) agents.

Vasculitis of the female genital tract with clinicopathologic correlation: a study of 46 cases with follow-up.

Forty-six cases of vasculitis affecting the female genital tract are described; only 41 similar cases have been previously reported, either as case reports or small series. The age range of the patients was from 22 to 80 years, and most of them presented with abnormal bleeding or were being treated conditions unrelated to the vasculitis. There were 39 hysterectomy specimens (26 of which were derived from total abdominal hysterectomies) and seven specimens of the cervix only. The vasculitis was confined to the cervix in 30 of the 46 cases; in 24 of these, the entire uterus was available for examination. In 23 cases, only a single vessel was involved, and in the other 23 there was more extensive vessel involvement. In all cases, the involved vessels were arterioles and small arteries. In 42 cases, the arteritis was of the polyarteritis nodosa (PAN) type, and in four, of the giant cell type (GCA). Follow-up ranged from < 1 year to 23 (mean, 3) years. Systemic manifestations were previously diagnosed or subsequently developed in only four patients, three with PAN and one with GCA; in each of them, the genital tract vasculitis was found only in the cervix (in one of these, however, the specimen was a loop excision of the cervix and the rest of the uterus was not assessable). The three patients with PAN subsequently developed extragenital PAN (one case), PAN and rheumatoid arthritis (one case), or PAN and polymyalgia rheumatica (one case). The patient with GCA had previously documented temporal arteritis and temperomandibular arthritis. The findings in this series and in previously reported cases indicate that vasculitis of the female genital tract is only rarely associated with systemic vasculitis.

Guidelines for anal cytology--to make cytological diagnosis and follow up much more reliable.

Anal intraepithelial neoplasia is a difficult diagnostic and management problem, particularly when it occurs in women with synchronous or metachronous genital intraepithelial neoplasia. Diagnosis and follow up by colposcopy is too specialized for widespread use, and although anal cytology has been used before it has been thought of as too inconsistent for practical application. This study standardized collection of specimens and investigated interobserver variation. The aim of the study was to determine whether observers could reliably distinguish high grade anal intraepithelial neoplasia from other conditions. Standardized collection of anal preparations was achieved in the host centre. A meeting of experienced cytopathologists was convened to agree guidelines for anal cytology. These guidelines were sent to the panel of six observers who were subsequently circulated with 30 cytopathological preparations in random order and asked to report them all. The results were collected and processed centrally. Four individuals were in complete agreement about those preparations which were inadequate for reporting, but two others had a lower threshold for rejecting preparations as inadequate. There was agreement between the observers in over 95% of cases in distinguishing high grade intraepithelial neoplasia from other cytological conditions. Kappa values range from 0.66 to 1.00. This study demonstrates that the provision of guidelines for the interpretation of anal cytopathological preparations can result in a high degree of interobserver agreement about the clinically important distinction between high grade anal intraepithelial neoplasia and other conditions. Anal cytology is a more useful technique for diagnosis and follow up of 'at risk' individuals than has previously been suggested, and should be utilized more widely in this group of patients.

Studies on the innervation of human renal allografts.

Kidneys are innervated by a plexus of nerves around the renal artery, which is disrupted by transplantation. This is a report of a comparison of the nerves in human renal allografts and normal kidneys. There were many sympathetic ganglia around normal renal arteries but none around transplanted vessels, although equal numbers of ganglia were present in hilar tissues of normal and transplanted kidneys. An immunohistological study with an antibody to synaptophysin showed that the number of synapses in transplanted ganglia was severely reduced. Immunohistological studies on allograft kidneys using antibodies to various neurofilament proteins and the Schwann cell marker S100 showed a marked reduction in neurofilament proteins shortly after transplantation with subsequent partial recovery, and a lesser reduction in S100. Renal allografts have structurally abnormal innervation but are not completely denervated.

Pathology of the uterine body.

In this review we look at recent developments in the pathology of the uterine body. Factors influencing the growth of leiomyomas are evaluated together with response to medical therapy and consequent histopathological changes. Further work on carcinosarcomas tends to support the common stem-cell theory of origin, which may also be true of other sarcomas, as common chromosomal abnormalities have been found. There has been continued work on prognostic factors in endometrial carcinomas with ploidy, hormone receptor status, HER-2/neu expression, and coexistent hyperplasia confirmed as independent prognostic factors, while clear cell and serous papillary carcinomas are confirmed as poor prognostic types. Finally, recent 'tumors' associated with tamoxifen are reviewed.

Successful treatment of invasive pulmonary aspergillosis in chronic granulomatous disease with orally administered itraconazole suspension.

A 3-yr-old boy with known chronic granulomatous disease presented with a left-sided chest wall mass. Extensive intrathoracic and extrathoracic aspergillosis was confirmed by CT scan-guided percutaneous biopsy. Initially, he was treated intravenously with liposomal amphotericin and subcutaneous gamma-interferon, but his clinical condition deteriorated over 7 wk of treatment. The amphotericin was therefore discontinued, and itraconazole in an oral suspension was begun. There was progressive clinical improvement after 3 months of this regime, and marked radiologic clearing was apparent after 8 months of treatment. A multicenter trial of this mode of therapy in patients with invasive aspergillosis is indicated.

Patterns of CEA-related antigen expression in invasive squamous carcinoma of the cervix.

The recognition of an adhesive role for the CEA-related antigens emphasizes the need for clear demonstration of the changes in CEA expression and subcellular localization between normal and neoplastic tissues. Using a panel of monoclonal and polyclonal antibodies, membranous and cytoplasmic CEA expression was seen in 50 invasive cervical squamous carcinomas in four distinct patterns dependent on tumour type and differentiation. Membranous CEA expression is a marker of differentiation in squamous carcinomas and may influence tumour behaviour and hence patient survival. Strong CEA positivity was seen on the endothelium of vessels containing tumour in ten cases where vascular metastases were prominent. Staining of these ten cases revealed concomitant sialated Lewis X positivity in tumour cells with weak endothelial positivity in three cases; cervical squamous tumour cells may localize to vascular endothelium, and hence disseminate, through specific binding of CEA and/or sialated Lewis X.