Investigating a clinically actionable BRAF mutation for monitoring low-grade serous ovarian cancer: A case report.

Low-grade serous ovarian cancer (LGSOC) poses a specific clinical challenge due to advanced presentation at diagnosis and the lack of effective systemic treatments. The aim of this study was to use a precision medicine approach to identify clinically actionable mutations in a patient with recurrent LGSOC. Primary, metastatic and recurrence tissue, and blood samples were collected from a stage IV LGSOC patient. Single-gene testing for clinically actionable mutations (BRAF V600, KRAS and NRAS) and subsequent whole-exome sequencing (WES) were performed. Droplet digital PCR was used to evaluate the presence of an identified BRAF D594G mutation in the matched plasma cell-free DNA (cfDNA). No clinically actionable mutations were identified using single-gene testing. WES identified a BRAF D594G mutation in six of seven tumor samples. The patient was commenced on a MEK inhibitor, trametinib, but with minimal clinical response. A newly designed ddPCR assay detected the BRAF alteration in the matched tissues and liquid biopsy cfDNA. The identification and sensitive plasma detection of a common "druggable" target emphasises the impact of precision medicine on the management of rare tumors and its potential contribution to novel monitoring regimens in this field.

Gastrointestinal Erdheim-Chester disease.

We report a rare case of Erdheim-Chester Disease, a non-Langerhans cell histiocytosis. A 60-year old female presented with a seven-month history of vague abdominal symptoms. A large retroperitoneal mass was detected on computed tomography (CT), but multiple CT-guided biopsy samples were inconclusive. Laparoscopy revealed a mass in the distal ileum, which was resected. Histology and immuno-histochemistry supported a diagnosis of Erdheim-Chester Disease.

Sudden unexplained death in childhood. An audit of the quality of autopsy reporting.

Cases of sudden unexplained death in childhood (SUDC) in Ireland in children aged > 1 year and < 5 years were examined in order to assess the quality of autopsy reporting. All SUDC cases are notified to and documented by the National Sudden Infant Death Register (NSIDR) in Ireland along with all cases of sudden infant death syndrome (SIDS) referring to sudden infant deaths less than one year of age. The database of the NSIDR in Ireland was interrogated and cases of SIDS and SUDC were compared over a fifteen-year period (1995-2009). SIDS cases whose autopsies were conducted in the same hospital in the same year as the index SUDC case were used for comparison. The autopsy report for each case was examined and modified Rushton (MR) score(s1) calculated. MR scores were compared along with the number of paediatric pathology prosectors and the year of autopsy examination between the two groups. 45 cases were registered as SUDC (age 52 - 152 weeks) between 1995-2009. Autopsy reports were available for 43/45 (95%) of these. 43 SIDS cases from the same year and site of autopsy were used for comparison. Overall MR scores were higher in the SIDS cases, with 29/43 (67%) cases obtaining the minimum arbitrary score (MAS) of > 300 compared to 25/43 (58%) of SUDC cases. Paediatric pathologists in specialist centres carried out similar numbers of SIDS autopsies and SUDC autopsies (46% SIDS, 44% SUDC). Autopsies carried out by paediatric pathologists in specialist centres met the MAS in 19/21 (90%) SIDS cases and 18/19 (95%) SUDC cases. Based on our findings we recommend referral of all SUDC cases to specialist centres for optimal autopsy examination and investigation, and that cases of sudden unexpected death in children over 1 year of age are investigated according to the same guidelines as are used for unexpected death under one year of age.

Schwannosis induced medullary compression in VACTERL syndrome.

A 7-year-old boy with a history of VACTERL syndrome was found collapsed in bed. MRI had shown basilar invagination of the skull base and narrowing of the foramen magnum. Angulation, swelling and abnormal high signal at the cervicomedullary junction were felt to be secondary to compression of the medulla. Neuropathologic examination showed bilateral replacement of the medullary tegmentum by an irregularly circumscribed cellular lesion which was composed of elongated GFAP/S 100-positive cells with spindled nuclei and minimal atypia. The pathologic findings were interpreted as intramedullary schwannosis with mass effect. Schwannosis, is observed in traumatized spinal cords where its presence may represent attempted, albeit aberrant, repair by inwardly migrating Schwann cells ofperipheral origin. In our view the compressive effect of the basilar invagination on this boy's medulla was of sufficient magnitude to have caused tumoral medullary schwannosis with resultant intermittent respiratory compromise leading to reflex anoxic seizures.

Has the ThinPrep method of cervical screening maintained its improvement over conventional smears in terms of specimen adequacy?

UNLABELLED: Liquid-based cytology (LBC) has replaced conventional smear assessment in many centers over recent years. In our laboratory this transfer took place in 1999. At that time we performed a split sample study comparing the conventional method of cervical smear evaluation with the ThinPrep system. This split sample study identified a dramatic improvement in specimen adequacy with LBC. While 11% of conventional preparations were reported as unsatisfactory and almost 9% were reported as suboptimal, evaluation of the same cases using LBC saw this combined figure reduced to 2.3%. AIM: To evaluate whether this dramatic fall in unsatisfactory smears has been maintained with the use of LBC. The database for all smears reported for 2005 (100% LBC) was interrogated. The number of unsatisfactory reports was calculated. The reason for an unsatisfactory report was recorded for each case. The overall unsatisfactory rate was compared with that reported in the 1999 split sample study. A total of 41,312 smear tests were reported in 2005. 1,342 (3.25%) were reported as unsatisfactory. Our findings support the ongoing value of LBC in a routine cervical screening laboratory in terms of continuing to maintain a low rate of unsatisfactory smears.

Cutaneous T-cell lymphoma presenting as a ten month history of unilateral facial swelling.

A 25-year-old fisherman presented with a ten-month history of unilateral facial swelling involving his lower lip and eyelids. The differential diagnosis for oro-facial swelling is extensive including congenital, infective, inflammatory and neoplastic processes. Biopsies revealed a cutaneous T cell lymphoma.

Primary bone lymphoma: single institution case series.

BACKGROUND: Primary bone lymphoma (PBL) is a rare condition and accounts for less than 2% of adult lymphomas and 3% of all primary bone malignancies. Because of the rarity of this disease, there is a lack of prospective randomised clinical trials and hence optimal treatment is uncertain. AIM: We report on our experience of treating PBL over 20 years. METHODS: Using our hospital database, we identified all patients with PBL, their treatment, and long-term follow-up. RESULTS: From January 1989 to July 2007, we identified 12 patients with PBL. Long extremity bones were the most common presenting sites. Multifocal disease was present in three cases. Treatment modalities included surgery, chemotherapy, and radiotherapy. Median follow-up was 8 years (range 0.5-18.5 years), and overall survival was 100%. CONCLUSIONS: Combined modality therapy, i.e. chemotherapy followed by radiotherapy, is the preferred treatment option unless adverse neurology or an unstable fracture presents first.

Understanding operative intervention in childbirth: a patient perspective.

A study was undertaken to ascertain patients' understanding of the operative interventions in labour and to assess follow-up by the operator. A total of 200 consecutive women who had undergone caesarean section or instrumental delivery were selected. These women were questioned postoperatively. Questions were asked to ascertain the patients' understanding of the procedure and to assess follow-up by the operator. Seven patients had a forceps delivery, 64 had a ventouse delivery and 129 had a caesarean section. The majority of patients felt that the reason for the operative delivery had been explained to them at delivery and that they fully understood the need for this intervention. A total of 26 women were not seen postoperatively by the doctor who delivered them. Women who underwent forceps or ventouse delivery were less likely to be seen post-delivery, although this difference did not reach statistical significance.

Opportunistic cervical screening at a sexual health clinic.

Women attending sexual health services may be higher risk for cervical cancer than the general population. In the United Kingdom, where a national cervical screening programme is underway, sexual health clinics no longer routinely offer their attendees cervical smears. Abnormal cervical smears add considerably to the workload of a sexual health service. In the absence of an organised national cervical screening programme in Ireland opportunistic screening is heavily relied upon. Opportunistic screening is performed in primary care, sexual health services and other women's health services. In the absence of this opportunistic cervical screening treatable pre-cancerous lesions may go unrecognised.

Pregnancy outcome in immigrant women in the Rotunda Hospital.

In recent years the numbers of immigrants attending maternity hospitals has risen. The amount of antenatal care these women receive varies widely. Analysis was performed of deliveries to immigrant women in the Rotunda Hospital in 2002. Women were sub-divided depending on antenatal care received in Ireland. Women who received no antenatal care were 'unbooked', those who attended the hospital two to 28 days before delivery were 'late bookers'. The remaining women were 'booked'. There were 1,954 deliveries to immigrant women; 1,1 73 (60%) 'booked', 391 (20%) 'late bookers' and 390 (20%) 'unbooked'. 'Unbooked' women had a higher rate of spontaneous vertex delivery (63%) (p < 0.01). 'Late bookers' had a higher rate of caesarean section (27.6%) (p < 0.01). The 'late bookers' infants were more likely to be preterm, low birth weight and had a higher rate of neonatal ICU (NICU) admissions (p < 0.01). This study has identified 'late booker' immigrants as a high-risk group.

Perinatal outcome in unbooked women at the Rotunda Hospital.

To determine the incidence and outcome of unbooked pregnancies in women at the Rotunda Hospital Retrospective case control study. All unbooked deliveries in the Rotunda Hospital over a two year period were identified and matched with a control. Control patients were selected as the next delivery after each case and were regular antenatal attenders. Demographic and obstetric data was collected from each case and control and compared using the Chi-square test. There were 101 unbooked women in the study, during this time there were 11522 deliveries giving an incidence of unbooked pregnancies of 0.88%. Unbooked women were found to be young, multiparous, unemployed and unmarried. They were more likely to deliver by spontaneous vaginal delivery to preterm, low birth weight infants and were at greater risk of a stillbirth and neonatal death. Unbooked pregnancies account for a small proportion of our antenatal population. However, perinatal outcome is significantly worse in unbooked patients compared to those who are regular antenatal attenders.