Primary intranodal Warthin-like variant of mucoepidermoid carcinoma.

This report describes a rare case of primary intranodal Warthin-like mucoepidermoid carcinoma (WL-MEC) presenting as a left level II lymph node mass in a 48-year-old man. Warthin-like mucoepidermoid carcinoma is a recently defined variant of MEC that bears a close histologic resemblance to Warthin tumor. Whereas MEC has readily identifiable key histologic features that render diagnosis relatively straightforward, WL-MEC is a challenging diagnosis due to overlapping histologic features and only limited case reports in the literature. This case was initially diagnosed as primary intranodal MEC after the exclusion of metastasis by imaging. It was not until years later, upon review of historic cases, that the diagnosis of WL-MEC was established. This diagnosis was further supported by molecular testing that was not available at the time of the original diagnosis.

Cytokeratin 7 and 19 expression in oropharyngeal and oral squamous cell carcinoma.

PURPOSE: The precise etiopathogenesis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), and reasons for predilection for crypt epithelium, remain uncertain. The purpose of this study is to investigate the interaction between HPV and specific cytokeratins 7 (CK7) and 19 (CK19) in crypt epithelium. METHODS: This is a retrospective cohort study of patients presenting between 1999 and 2015 at a tertiary referral center. CK7 and CK19 positivity and H Scores were determined by immunohistochemistry. Disease-specific and overall survival rates were analyzed. RESULTS: There were 253 patients presenting with OPSCC (134), squamous cell carcinoma (SCC) of unknown primary site (22), and oral tongue SCC (97). Primary tumor CK7 and CK19 positivity and H Scores were significantly higher in HPV-positive OPSCC than HPV-negative OPSCC and oral tongue SCC. Higher CK19 Scores, but not CK7 Scores, were also seen in regional metastases from HPV-positive OPSCC than other sites. No impact on disease-specific or overall survival was identified on multivariate analysis. CONCLUSION: The increased expression of CK7 and CK19 in HPV-positive OPSCC compared to HPV-negative disease supports the theory for a role for these cytokeratins in the etiopathogenesis of HPV-related OPSCC.

MDS/MPN-Unclassifiable with t(X;17)(q28;q21) and KANSL1-MTCP1/CMC4 Fusion Gene.

Myelodysplastic/myeloproliferative neoplasm, unclassifiable (MDS/MPN-U) is a poorly characterized entity among overlap myeloid syndromes. Recent studies have shown heterogeneous mutational profiles in this group being able to subclassify them into entities closely related to the more well-established disorders under the umbrella term of the MDS/MPN group. Recurrent cytogenetic alterations are, nonetheless, rare in MDS/MPN-U. Here, for the first time, we report a case of MDS/MPN-U with a t(X;17)(q28;q21) chromosomal rearrangement leading to the KANSL1-MTCP1 fusion gene.

The role of tumour morphology in assigning HPV status in oropharyngeal squamous cell carcinoma.

OBJECTIVES: There is no consensus on the optimal approach to human papilloma virus (HPV) testing in oropharyngeal squamous cell carcinoma (OPSCC). Our objective was to classify OPSCC as HPV positive or negative based on (1) morphology alone, (2) p16 status alone, (3) combined morphology and p16 status with additional HPV testing in discordant cases in keeping with 2012 College of American Pathologists (CAP) guidelines (combined approach), and to evaluate and compare survival outcomes. MATERIALS AND METHODS: Retrospective review of 168 patients, 146 with OPSCC and 22 with cervical SCC of unknown primary site (SCCUP). Morphology was classified as keratinizing or non-keratinizing, p16 immunohistochemistry (IHC) performed and additional HPV DNA PCR testing undertaken in cases in which morphology and p16 status were discordant. Survival statistics were evaluated and compared for the 3 different approaches to classification. RESULTS: On univariate analysis all 3 classification methods significantly predicted for overall survival (OS). Both p16 status and the combined approach also predicted for disease specific survival (DSS), whereas morphology fell just outside significance (p = 0.06). On multivariate analysis only the combined approach retained significance for both OS and DSS, whilst morphology was also significant for DSS. CONCLUSIONS: Our findings confirm that tumour morphology significantly predicts for survival in OPSCC. However, we found combined tumour morphology and p16 IHC, with additional testing for discordant cases to be superior to either morphology or p16 IHC alone. Further study is required to establish the optimal testing method for HPV in OPSCC particularly in low prevalence populations.

Tumour Cell Anaplasia and Multinucleation as Prognosticators in Oropharyngeal Squamous Cell Carcinoma.

Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCC) tend to have good outcomes, however a subset does not share this favourable prognosis. The aim of this paper is to investigate the utility of tumour cell anaplasia and multinucleation as prognostic markers in oropharyngeal squamous cell carcinoma. Retrospective review of 104 patients with OPSCC or squamous cell carcinoma of unknown primary site (SCCUP) who underwent primary resection and/or lymph node dissection. Slides of both primary and nodal metastatic disease were assessed for the presence of anaplasia and multinucleation. 53 patients were HPV-positive. Anaplasia was more frequent in males (p = 0.005), smokers (p = 0.003), and HPV-negative disease (p = 0.04). HPV status and > 10 pack-year smoking history were independent predictors of recurrence-free survival (RFS) and disease-specific survival (DSS). Neither anaplasia, nor multinucleation, at the primary site or in cervical metastases, had any significant impact on RFS or DSS. We did not find either anaplasia or multinucleation to have any significant prognostic impact in OPSCC. However, given the small number of adverse events in the HPV-positive cohort, we may have lacked sufficient power to detect significance in what was the subgroup of primary interest. Our study highlights the challenge of identifying markers of poor prognosis in HPV-positive OPSCC.

Large loop excision of the transformation zone and preterm delivery over a decade in a major women's hospital.

BACKGROUND: The success of cervical screening relies on assessment and treatment of pre-malignant disease. Large loop excision of the transformation zone (LLETZ) has been the mainstay of treatment for cervical intraepithelial neoplasia (CIN). Preterm delivery (PTD) in subsequent pregnancy is a long-term complication of the intervention. AIMS: To describe the characteristics of women who had LLETZ treatment(s) followed by PTD in the Rotunda Hospital over a 10-year period. METHODS: The pathology and the obstetric databases were searched to identify women who had LLETZ followed by PTD from 1 January 2007-31 December 2016. Details including gestation at delivery, depth of LLETZ and grade of CIN were extracted. Exclusion criteria included multiple pregnancy, and deliveries due to current pregnancy indications. RESULTS: There were 97 women eligible for inclusion. Mean gestation at delivery was 33+2 weeks. CIN 1 was diagnosed in 16, CIN 2 in 24, CIN 3 in 53, and four were negative for CIN. No microinvasive or invasive disease was identified. The average depth of excision was 9.9 mm, 11.4 mm and 8.5 mm for CIN 1, 2 and 3, respectively. The difference in depth between excisions with CIN 2 and 3 was significant (p = 0.019). CONCLUSIONS: Despite having a lower mean depth of excision, women with CIN 3 comprised the majority of those who experienced PTD, suggesting that factors other than mechanical weakness are implicated in PTD for these women. This is in keeping with recent suggestions that the common denominator in high grade CIN and PTD is an altered vaginal microbiome.

Impact of positive margins on outcomes of oropharyngeal squamous cell carcinoma according to p16 status.

BACKGROUND: Currently, positive surgical margins in head and neck cancer are considered to be an indicator for postoperative chemoradiotherapy (CRT) over radiotherapy (RT) alone. However, there are less data regarding the impact of margin status on human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC). METHODS: We performed a retrospective review of 55 patients with oropharyngeal SCC undergoing primary surgical treatment. The impact of margin status on disease-specific survival (DSS) was studied according to p16 status. RESULTS: Twenty-one patients had positive margins. Adjuvant treatment in these cases was CRT (n = 6), RT alone (n = 14), and none (n = 1). Among p16-negative patients, positive margins and dysplasia at margins predicted significantly worse DSS. Among patients with p16-positive disease, margin status had no impact on DSS. CONCLUSION: Patients with p16-positive oropharyngeal SCC and positive margins after excision maintain a low risk of recurrence despite most receiving RT alone as adjuvant treatment. These findings raise questions regarding the additional benefit of postoperative CRT in this group.

Distant melanoma causing small bowel obstruction.

Small bowel obstructions (SBOs) are common. Adhesions make up the majority of cases at 84.9%, followed by abdominal herniae and malignancies. A 71-year-old female presented with total constipation, abdominal distension, on a background of resected cutaneous melanoma nine years prior. A CT-scan showed small bowel intussusception and disseminated mucosal-enhancing lesions consistent with metastases. She was brought to the operating theatre where six areas of intussusception were identified and manually reduced. Biopsies confirmed the diagnosis of melanoma. Melanoma of the gastrointestinal tract (GIT) is rare, with most cases occurring as metastasis from cutaneous lesions. Melanomas of the GIT are usually asymptomatic in their early stages, and are often diagnosed when complications, such as obstruction or perforation occur. Management of such cases consists mainly of surgical intervention to resolve the complication. In people who present with SBO without previous surgeries or herniae, a malignant cause must be considered.

A tenebrous tale: malignant melanoma of the oesophagus.

A 57-year-old man presented with a 4-month history of worsening symptoms of oesophageal obstruction. The physical examination was unremarkable. An oesophagogastroduodenoscopy revealed an exophytic tumour in the distal oesophagus. A biopsy demonstrated malignant melanoma. Staging of the melanoma showed disseminated lymph node and bony-spine metastases. He had no prior history of cutaneous or ocular melanoma. Following full multidisciplinary team input, he was palliated with a metal mesh stent and immunotherapy. He died 3 months later following community management.

Production of Ultracold 87 Rb133 Cs in the Absolute Ground State: Complete Characterisation of the Stimulated Raman Adiabatic Passage Transfer.

We present the production of ultracold 87 RbCs molecules in the electronic, rovibrational and hyperfine ground state, using stimulated Raman adiabatic passage to transfer the molecules from a weakly bound Feshbach state. We measure one-way transfer efficiencies of 92(1)% and fully characterise the strengths and linewidths of the transitions used. We model the transfer, including a Monte Carlo simulation of the laser noise, and find this matches well with both the transfer efficiency and our previous measurements of the laser linewidth and frequency stability.

Association of Extracapsular Spread With Survival According to Human Papillomavirus Status in Oropharynx Squamous Cell Carcinoma and Carcinoma of Unknown Primary Site.

IMPORTANCE: The presence of extracapsular spread (ECS) of metastatic nodes is considered a poor prognosticator in head and neck cancer, with postoperative chemoradiation therapy often recommended over radiation therapy alone in such cases. However, there is less clarity regarding the effect of ECS on human papillomavirus-associated oropharynx squamous cell carcinoma (OPSCC) or carcinoma of unknown primary site (CUP). OBJECTIVE: To investigate the association of ECS according to human papillomavirus status in OPSCC and CUP with survival. DESIGN, SETTING, AND PARTICIPANTS: This investigation was a retrospective cohort study performed between August 1998 and March 2015 at an academic teaching hospital. Participants were 83 patients with OPSCC (n = 62) or CUP (n = 21) undergoing neck dissection as part of initial treatment. MAIN OUTCOME AND MEASURES: Human papillomavirus status was determined by p16 immunohistochemistry. The presence of ECS was extrapolated from pathology reports, and the extent of ECS was determined by rereview of original pathology slides. Disease-specific survival (DSS) and recurrence-free survival (RFS) were assessed. RESULTS: Among 83 patients (71 male), there were 45 p16-positive and 38 p16-negative tumors. Fifty-one patients had ECS, which was graded as extensive in 43 cases. The median follow-up was 31 months for all patients and 50 months for surviving patients. Among the entire cohort, adverse predictors of RFS were p16-negative status (hazard ratio [HR], 9.4; 95% CI, 3.3-27.2) and ECS (HR, 6.5; 95% CI, 2.0-21.6). Adverse predictors of DSS were p16-negative status (HR, 16.8; 95% CI, 3.9-71.2) and ECS (HR, 8.3; 95% CI, 2.0-35.3). Among p16-negative patients, ECS was significantly associated with worse RFS (HR, 9.7; 95% CI, 1.3-72.3) and DSS (HR, 8.7; 95% CI, 1.1-62.7). In contrast, among p16-positive patients, ECS had no effect on RFS (HR, 1.1; 95% CI, 0.2-7.8) or DSS (HR, 1.2; 95% CI, 0.1-18.7). CONCLUSIONS AND RELEVANCE: The presence of ECS appears to be associated with survival in OPSCC and CUP according to p16 status. Our findings raise questions regarding the benefits of postoperative chemoradiation therapy in p16-positive patients with ECS.

Creation of ultracold

We report the creation of a sample of over 1000 ultracold ^{87}Rb^{133}Cs molecules in the lowest rovibrational ground state, from an atomic mixture of ^{87}Rb and ^{133}Cs, by magnetoassociation on an interspecies Feshbach resonance followed by stimulated Raman adiabatic passage (STIRAP). We measure the binding energy of the RbCs molecule to be hc×3811.576(1) cm^{-1} and the |v^{''}=0,J^{''}=0⟩ to |v^{''}=0,J^{''}=2⟩ splitting to be h×2940.09(6) MHz. Stark spectroscopy of the rovibrational ground state yields an electric dipole moment of 1.225(3)(8) D, where the values in parentheses are the statistical and systematic uncertainties, respectively. We can access a space-fixed dipole moment of 0.355(2)(4) D, which is substantially higher than in previous work.