Invasive cervical cancer after treatment of CIN.

INTRODUCTION: A historical audit of 30 post-treatment cervical cancers (10% of 289 cancers, 1999-2016) compared with a one-year-equivalent control group treated for cervical intraepithelial neoplasia (CIN) grade 3 (n = 164). MATERIALS AND METHODS: We compared history and follow up of cancer patients and controls and reviewed initial excision biopsies preceding cancer and, in 41% of controls, high-grade recurrence (n = 17) or consistently negative follow-up (n = 51). RESULTS: Either abnormal post-excision cytology without high-risk human papillomavirus (hrHPV) tests or immediate re-excision was recorded in 70% (19 of 27) of patients with squamous cell carcinoma (SCC). Negative investigations including cytology, colposcopy, re-excision, hysteroscopy, hrHPV, and/or treatment default were recorded in 83% (25 of 30) of all cancers. The mean interval between initial excision and cancer diagnosis was 79.8 ± 30.1 months versus 11.2 ± 30.1 months for CIN3 recurrence. Eight, 13, and 9 patients with cancer had initial excision at age 20-34, 35-49, and 50+ years, respectively, compared with 71%, 23%, and 5% of controls. CIN3 more often preceded SCC than CIN2 (22:1); 5 of 30 initial excisions were originally reported as negative after severe dyskaryosis. No SCC or CIN3 recurrence followed complete excision. Depth of CIN3 2+ mm (20 of 82 reviewed) was strongly associated with cancer/high-grade recurrence or early stromal invasion on review (18 of 20; 90%). Discrepancies were found on review in 10% of biopsies and as occasional abnormal cells in 9 of 34 cytology slides. CONCLUSIONS: Residual disease may be inconspicuous or absent on cytology, colposcopy, and/or histology. Management taking account of risk of recurrence (age, CIN3 depth, incomplete initial excision) could avoid some post-treatment cancers.

Fertility-sparing surgery for early cervical cancer-approach to less radical surgery.

OBJECTIVE: To evaluate whether certain patients with early-stage cervical cancer are candidates for less radical surgery when considering fertility-sparing surgery. DESIGN: Prospective cohort study. SETTING: Two gynecologic cancer centers (St Thomas' Hospital, London; and West Kent Gynaecological Cancer Centre, Maidstone). POPULATION: Women with early-stage cervical cancer (n = 66) undergoing fertility-sparing surgery, either simple (SVT) or radical vaginal trachelectomy (RVT). METHODS: Prospective clinical data collection and review of patient notes, pathology and radiology data, and pregnancy outcomes. MAIN OUTCOME MEASURES: Postoperative complications, surgical specimen histologic analysis, follow-up data, and obstetric outcome. RESULTS: A total of 66 women underwent either SVT (n = 15) or RVT (n = 51), with pelvic lymphadenectomy, for stage IA2 or IB1 cervical cancer. There was no residual disease in the SVT specimen in 53% versus 29% after RVT. Clear surgical margins in 100% of SVT specimens with residual disease versus 94% after RVT. Two patients had positive lymph nodes after RVT; one of these declined adjuvant treatment until after egg harvesting and subsequently died of disease (1.5%). Median follow-up was 96 months (range, 12-120 months). One patient had a mid vaginal recurrence (1.5%). Twenty-four women have tried to conceive to date, with 14 women having 17 live births. Live birth pregnancy rate was 70.8%. CONCLUSIONS: It is possible to select patients for a less radical fertility-sparing procedure through identification of measurable low-risk factors and thus reduce the morbidity caused by conventional RVT. The selection criteria should be stringent and applied within the setting of a cancer center.

Human papillomavirus testing with conventional Pap smear screening in three inner London community clinics.

BACKGROUND AND METHODOLOGY: This observational study aimed to establish prevalence of high-risk human papillomaviruses (hrHPV) in women attending three inner London community clinics for routine screening and to pilot hrHPV testing in the triage of either borderline or negative cytology after previous abnormalities. Hybrid Capture 2 was carried out on brush samples taken alongside conventional smears from 1434 women aged 20-49 years. hrHPV positivity prompted earlier referral of women with previous abnormalities and either low-grade or negative cytology. Outcome at colposcopy was compared with the records of 1871 women aged 20-49 years attending colposcopy during the same period of time (routine colposcopies). RESULTS: hrHPV was detected in 111/161 (68.9%) women with abnormal cytology, 76/460 (16.5%) with negative cytology after previous abnormalities and 105/813 (12.9%) with negative cytology and no previous abnormalities. Overall, hrHPV was detected in 292/1434 (20.4%) women in the study (95% CI 18.3-22.5). hrHPV prevalence increased with severity of cytological abnormality (p<0.001) and decreased with age both with negative and low-grade cytology (p<0.001). High-grade cervical intraepithelial neoplasia (CIN) biopsies were found more frequently in women in the study groups with low-grade (p<0.001) or negative cytology than in routine colposcopies, but more women in the study groups attended colposcopy (8.2% compared with 4.1% routine colposcopies, p<0.001). CONCLUSIONS: hrHPV positivity increased detection of high-grade CIN in the study groups at the expense of more colposcopies. hrHPV negativity could reduce the need for investigation of low-grade cytology in women aged over 35 years and for surveillance after previous abnormalities.

Cytologic diagnosis of pancreatic endocrine tumors by endoscopic ultrasound-guided fine-needle aspiration: a review.

Precise localization and diagnosis of pancreatic endocrine tumors (PETs) is important, because pancreatic PETs have different clinical and biological behavior and treatment modalities than do exocrine pancreatic tumors. In contrast to the much more common exocrine adenocarcinomas, cytologic studies of PET are relatively rare and many cytopathologists lack experience with the cytomorphologic features of these tumors.During the last 10 yr, endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has matured into an accurate, highly sensitive, and cost-effective modality for the preoperative localization of pancreatic PETs. This has resulted in an increased number of PETs first sampled as cytology specimens. This manuscript focuses on the cytomorphologic features most suggestive of pancreatic PETs, differential diagnosis, and diagnostic pitfalls of PETs. The technical development of EUS-guided FNA and the ancillary studies for pancreatic PETs are also reviewed. The data summarized in this review indicate that EUS-FNA is a valuable method in the recognition of pancreatic PETs and in most cases cytopathologists could reach a correct diagnosis of these tumors, including their hormone producing capability on aspirated cytologic material.

Characterization of cells of the B lineage in the human adult greater omentum.

Peritoneal B cells and their omental precursors play an important role in the immune response of the peritoneal cavity and mucosal surfaces in mice. We have previously shown that peritoneal and mucosal B lineage cells are unlikely to be significantly linked in humans. However, the status of the omentum remains unknown. Here, using immunohistochemistry, we observed that sparse, quiescent B cells and occasional clusters of B cells were present in the omentum and that plasma cells, predominantly with cytoplasmic immunoglobulin G (IgG), were present. We analysed sequences of immunoglobulin genes amplified using reverse transcriptase-polymerase chain reaction (RT-PCR) from the normal human greater omentum, and describe the characteristics of variable region genes used by IgG, IgA and IgM. We focused on the properties of IgVH4 and IgVH5 families to allow comparisons of like with like between different Ig isotypes and cells from different immune compartments. We observed that the IgM genes were derived from a mixed population with mutated and unmutated immunoglobulin sequences. All IgVH4 and IgVH5 genes used by IgA and IgG from omental cells showed evidence of somatic hypermutation but the load of mutations was not significantly different to that seen in either the systemic or the mucosal compartments. The trends observed, including the dominance of IgG plasma cells, the IgA1/IgA2 ratio being biased towards IgA1, JH1 usage, and a moderate level of somatic mutations, link omental B lineage cells with the systemic compartment. These observations reinforce previous studies highlighting the difference between human and murine B-cell compartments and their relationship to the mucosal immune system.