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A commercially available polyclonal antiserum (Dakopatts) raised against bovine neuron specific enolase (NSE) was reacted with 197 sarcomas, 32 carcinomas, 11 carcinoid tumours and 20 malignant melanomas to assess its specificity for neuroendocrine tumours. All the tumours had been fixed in formalin and embedded in paraffin. Positive tumour cells were found in two of 11 squamous cell carcinomas, one of 11 adenocarcinomas, 10 of 10 oat cell carcinomas, 11 of 11 carcinoid tumours, 16 of 20 malignant melanomas, four of seven clear cell sarcomas, nine of 25 leiomyosarcomas, four of 22 rhabdomyosarcomas, one of seven angiosarcomas and one of 20 synovial sarcomas. [ABSTRACT FROM PUBLISHER]

A considerably raised serum alpha-fetoprotein concentration was found in a patient with an ileal adenocarcinoma. alpha-fetoprotein was shown in both the primary tumour and the hepatic metastases by an immunoperoxidase technique. A raised alpha-fetoprotein concentration in association with ileal adenocarcinoma has not been described previously, and it is notable that the first such case should occur as a complication of longstanding Crohn's disease. [ABSTRACT FROM PUBLISHER]

Presents several abstracts on cervical cytology. 'FHIT gene loss of heterozygosity is a feature of preinvasive and microinvasive lesions in squamos cervical cancer'; 'Detection of false negative smears from women with CIN 3 by rapid rescreening'; 'Cervical intraepithelial neoplasia grade 3 (CIN3) and invasive cancer.'

Atypical mycobacteria have been recognised as saprophytic organisms for many years, but it was only with the development of better microbiological culture techniques that they became recognised as potentially pathogenic to man. Infections of tendon sheaths and joints by these organisms may present diagnostic problems, and we report here 3 cases in which Mycobacterium kansasii was responsible for disease at the hand and wrist. [ABSTRACT FROM AUTHOR]

A rare case of moderately differentiated neuroendocrine carcinoma (atypical carcinoid) of the larynx is presented. The role of immunohistochemistry in the diagnosis of the lesion is described. The importance of considering the diagnosis in a patient with prolonged cervical pain with features of glossopharyngeal neuralgia, is discussed. [ABSTRACT FROM AUTHOR]

Aneurysmal fibrous histiocytoma is a rare variant of cutaneous fibrous histiocytoma that results from blood vessel proliferation and haemorrhage into a fibrous histiocytoma. The resulting lesion has a very different clinical appearance, hence the potential confusion with other skin lesions. This report describes the case of a 48 year old woman with a recurrent fibrous histiocytoma with prominent vasculature, which over a three year period recurred on two occasions, showing more progressive features of the aneurysmal variant. In addition, squamous lined cysts were present within this tumour, a finding that has not been described previously. The histological features of this rare lesion and the importance of the differential diagnosis from other similar appearing malignant lesions will be discussed. [ABSTRACT FROM AUTHOR]

The finding of abnormal mitoses is a helpful feature in differentiating between benign and malignant neoplasia and has prognostic significance for some tumours. As the use of a histopathological variable is limited by the reproducibility of its recognition, we tested the interobserver agreement in the classification of abnormal mitoses among histopathologists. Ten practising histopathologists were shown 30 potential mitotic figures and were asked to classify these as ‘normal mitoses’, ‘abnormal mitoses’ or ‘not mitoses’ according to the criteria each pathologist used in their routine practice. The results were analysed using kappa statistics. Overall agreement was only fair with a combined kappa of 0.31 and there was unanimous categorization of only four of 30 test items, none of which was called abnormal. The poorest result was obtained for the category ‘abnormal mitosis’ with only slight agreement (kappa 0.19). Agreement for the other categories varied from moderate (kappa = 0.45) for ‘not a mitosis’ to fair (kappa = 0.26) for ‘normal mitosis’. Comparison of the results for observer pairs showed that for 12 out of the 45 possible pairings, there was no more agreement than might be expected by chance alone. Agreement is poor among practising histopathologists in the recognition of abnormal mitoses. A standardized and robust definition is needed if diagnostic and prognostic significance is accorded to the finding of an abnormal mitosis in the context of neoplasia. [ABSTRACT FROM AUTHOR]

Sheehan K M, Steele C, Sheahan K, O'Grady A, Leader M B, Murray F E&Kay E W(2005)Histopathology46,287–295Association between cyclooxygenase-2-expressing macrophages, ulceration and microvessel density in colorectal cancer: In colorectal carcinomas, cyclooxygenase-2 (COX-2) is expressed predominantly by epithelial cells and is implicated in tumour progression. Tumour-associated macrophages may influence tumour growth, proliferative rate and angiogenesis and also express COX-2 when activated. Thus they may play an important stromal-epithelial role in carcinogenesis.Τhe aim of this study was to define the relationship between microvessel density (MVD), tumour COX-2 and macrophage COX-2 expression.: Sixty-five cases of formalin-fixed paraffin-embedded colorectal cancer were included in the study. Tissues were immunostained for COX-2, CD68 (macrophage marker) and CD34 (endothelial marker to assess MVD). Thirty-six cases were grossly ulcerated cancers and 29 cases showed focal/microscopic ulceration. Macrophages were in high concentration at the base of ulcerated areas, and were also diffusely dispersed within tumoral stroma. However, the pattern of macrophage COX-2 expression revealed two populations of macrophages—those deep within the tumour (negative for COX-2) and those at the base of ulcers (positive for COX-2). In all cases, the tumour epithelial cells expressed COX-2. MVD was higher at the base of ulcers, adjacent to COX-2+ macrophages, and was lower deep within the tumour.: In colorectal cancers, macrophages may have a dual role. Those concentrated at the base of the ulcers, where there is an associated high MVD, may induce angiogenesis, but their function may be in a healing/repair process. The lack of COX-2+ macrophages and lower MVD deep within the tumour suggests that it may be the epithelial COX-2 component that is important in tumour progression. [ABSTRACT FROM AUTHOR]

Gulmann C, Counihan I, Grace A, Patchett S, Leen E, Leader M & Kay E (2003) Histopathology 43, 453–461 Cytokeratin 7/20 and mucin expression patterns in oesophageal, cardia and distal gastric adenocarcinomas The current study examined cytokeratin (CK)7 and 20 as well as MUC1–6 immunoprofiles in oesophageal, gastric and gastro–oesophageal junction (GOJ) adenocarcinomas. The aim was to compare expression patterns in these locations as aids to accurate classification of these morphologically similar carcinomas which all may involve the GOJ. Tissue microarrays were constructed using tissue from 14 oesophageal, 78 gastric and 39 GOJ adenocarcinomas. Sections were immunostained with CK7, CK20, MUC1, MUC2, MUC5AC and MUC6. The results of this study showed no differences in CK7 and CK20 expression patterns in the three locations. MUC2 expression was higher proximally (43% of oesophageal, 28% of GOJ and 17% of gastric carcinomas) and MUC6 expression was higher distally (7% of oesophageal, 28% of GOJ and 15% of gastric carcinomas). MUC1 expression was associated with higher pTNM-stage. CK 7/20 profiles have no role in distinguishing tumours of the three locations. Mucin expression patterns differed in oesophageal and gastric adenocarcinomas, although not sufficiently to classify individual cases. GOJ adenocarcinomas showed a mucin expression pattern that was partly ‘gastric’, and partly ‘oesophageal’. MUC1 expression was associated with a higher pTNM stage. [ABSTRACT FROM AUTHOR]

Aims: Tissue microarrays offer an efficient way of examining a large number of tumour cases on a single glass slide. A major concern, however, is tumour heterogeneity. Also, the use of tissue microarrays in biopsy material is unexplored. The purpose of the present study was to assess the possibility and validity of arraying three 0.6-mm cores per case in endoscopic gastric cancer biopsies for immunophenotyping. Methods and results: Thirty-eight cases were studied with immunohistochemical staining for p53, CD44v6 and vascular endothelial growth factor. Full tissue sections were compared with triple core-tissue microarrays. Thirty-six cases contained three cores with tumour, one case contained two cores with tumour and one case contained only a single core with viable tumour and was excluded. Three further cores had been lost from three separate cases on the sections for immunohistochemistry. κ values for whole-sections versus tissue microarrays ranged between 0.77 and 0.94. p53 immunohistochemical staining (interpretation as + or –) yielded the best result with only 1/37 mismatches, whereas CD44v6 (graded both for intensity and extent) showed 3/37 mismatches. The small depth of tissue in cores from biopsies necessitates all cores being arrayed flush with the face of the recipient wax block for maximizing the number of sections available. Compared with the first section over 30 additional 4-µm sections were available before the first case (with one core left) had to be excluded and 80 sections before half the tissue cores were lost. Conclusions: It is impracticable to array more than 120–150 cores per block. Tissue microarray with three cores per case is feasible and valid for studying biopsy material. [ABSTRACT FROM AUTHOR]

Background Ultraviolet radiation (UVR) damages keratinocytes. Direct DNA damage may undergo enzymatic repair followed by resumption of the normal cell cycle. Cells may also be eliminated without inflammation by the error-free process of programmed cell death or apoptosis. Necrosis of cells can occur after overwhelming damage. Failure of apoptosis leads to retention of cells with persistent mutations. Objectives This study investigates p53-dependent apoptotic responses in normal skin following solar-simulated radiation (SSR). Methods Sun-protected buttock skin from normal volunteers with no history or clinical evidence of skin cancer was exposed to graded doses of SSR, 0·5, 1, 2 and 3 times the minimal erythema dose (MED). Biopsies taken at a range of time points (4·5, 9, 24, 33, 48 and 72 h) after UVR, quantified the time course and dose-response of apoptosis and the expression of the relevant proteins, p53, p21[sup waf1 / Cip1] and Bax, by single and double labelling techniques. Results Apoptosis was upregulated in a dose-dependent manner as was the expression of p53, p21[sup waf1/Cip1] and Bax in response to SSR. Following exposure to 3 MEDs it was found that: (i) the maximum number of apoptotic cells occurred at 48 h; (ii) p53 protein expression was upregulated from 4 to 72 h preceding peak p21[sup waf1/Cip1] protein expression (9-48 h) and peak Bax protein expression (33 h). Conclusions These results suggest that, following SSR, normal human skin induces apoptosis by the p53, p21[sup waf1/Cip1], Bax pathway in vivo. In addition, induction of apoptosis and expression of p53, p21[sup waf1/Cip1] and Bax occurs in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

A method of generating nucleic acid probes by polymerase chain reaction (PCR) for the detection of Epstein-Barr virus (EBV)-DNA by in situ hybridization in oral hairy leukoplakia (OHL) lesions is described. This method has the advantage over older methods of being cheaper, quicker and retaining sensitivity and specificity. Purified PCR products of Epstein-Barr virus DNA of 110 bp and 328 bp were labelled with biotin by nick translation or random primer labelling and were compared in in situ hybridization experiments with probes prepared by incorporation of biotin-labelled nucleotides in the PCR reaction mixture, with EBV viral DNA as a template. These probes were applied to 18 OHL tongue biopsies known to be positive for EBV-DNA, using a commercially available biotin-labelled BamHI "V" fragment EBV-DNA probe. To determine the specificity of the probes, we applied them to 20 normal tongue tissue samples and to 12 biopsies taken from keratotic tongue lesions from patients without risk factors for HIV infection and known to be negative for EBV-DNA. Clear positive signals for EBV-DNA were detected in all 18 cases of OHL biopsies using the amplimer of 328 bp labelled by PCR and random primer labelling. However, nick translation labelling was less efficient and sensitive. All control specimens were negative for EBV-DNA. [ABSTRACT FROM AUTHOR]

Claire Urwin, Principal Lead for Pre-Registration Developments in London/Programme Leader M Nurse, University of Sunderland (claire.urwin@sunderland.ac.uk), reviews the development of the registered nursing associate role and considers factors relating to professional development for role holders.

BACKGROUND : Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2)., Methods: We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria., Results: The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%)., Conclusions: With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making., (© 2022. The Author(s).)

Objective: To evaluate exposure-response between 1,3-butadiene, styrene and lymphohaematopoietic cancers in an updated cohort of workers at six North American plants that made synthetic rubber polymers., Methods: Employees were followed from 1943 through 2009 to determine mortality outcomes. Cox regression analyses estimated rate ratios (RRs) and 95% CIs by quartile of cumulative exposure to butadiene or styrene, measured in parts per million-years (ppm-years), and exposure-response trends for all leukaemia, lymphoid leukaemia, myeloid leukaemia, acute myeloid leukaemia, non-Hodgkin's lymphoma (NHL), multiple myeloma and all B-cell malignancies., Results: Among 21 087 workers, adjusted RRs for butadiene and all leukaemia (132 deaths) rose with increasing exposure, with an RR of 2.53 (95% CI 1.37 to 4.67) in the highest exposure quartile (≥363.64 ppm-years), and the exposure-response trend was statistically significant for all leukaemia (p=0.014) and for lymphoid leukaemia (52 deaths, p=0.007). Styrene exposure-response trends for all leukaemia and lymphoid leukaemia were less consistent than those for butadiene. Cumulative exposures to butadiene and styrene were not associated consistently with myeloid leukaemias or the B-cell malignancies, NHL and multiple myeloma., Conclusions: We confirmed a positive exposure-response relationship between butadiene and all leukaemia among workers, most of whom had coexposure to styrene. Results supported an association between butadiene and lymphoid leukaemia, but not myeloid leukaemia, and provided little evidence of any association of butadiene or styrene exposures with major subtypes of B-cell malignancies other than lymphoid leukaemia, including NHL and multiple myeloma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: - To evaluate exposure-response relationships between 1,3-butadiene and styrene and selected diseases among synthetic rubber polymer workers., Methods: - 21,087 workers (16,579 men; 4508 women) were followed from 1943 through 2009 to determine mortality outcomes. Cox regression models estimated rate ratios (RRs) and 95% confidence intervals (CIs) by quartile of cumulative exposure to butadiene or styrene and exposure-response trends for cancers of the bladder, lung, kidney, esophagus and pancreas, and for all nonmalignant respiratory disease (NMRD), chronic obstructive pulmonary disease (COPD) and pneumonia., Results: - Bladder cancer RRs were 2.13 (95% CI = 1.03 to 4.41) and 1.64 (95% CI = 0.76 to 3.54) in the highest quartiles of cumulative exposure to butadiene and styrene, respectively, and exposure-response trends were positive for both monomers (butadiene, trend p = 0.001; styrene, trend p = 0.004). Further analyses indicated that the exposure-response effect of each monomer on bladder cancer was demonstrated clearly only in the subgroup with high cumulative exposure (at or above the median) to the other monomer. Lung cancer was not associated with either monomer among men. Among women, lung cancer RRs were above 1.0 in each quartile of cumulative exposure to each monomer, but exposure-response was not seen for either monomer. Male workers had COPD RRs slightly above 1.0 in each quartile of cumulative exposure to each monomer, but there was no evidence of exposure-response among the exposed. Monomer exposure was not consistently associated with COPD in women or with the other cancer outcomes., Conclusions: - This study found a positive exposure-response relationship between monomer exposures and bladder cancer. The independent effects of butadiene and styrene on this cancer could not be delineated. In some analyses, monomer exposure was associated with lung cancer in women and with COPD in men, but inconsistent exposure-response trends and divergent results by sex do not support a causal interpretation of the isolated positive associations., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The coronavirus disease 2019 (COVID-19) has greatly impacted health-care systems worldwide, leading to an unprecedented rise in demand for health-care resources. In anticipation of an acute strain on established medical facilities in Dallas, Texas, federal officials worked in conjunction with local medical personnel to convert a convention center into a Federal Medical Station capable of caring for patients affected by COVID-19. A 200,000 square foot event space was designated as a direct patient care area, with surrounding spaces repurposed to house ancillary services. Given the highly transmissible nature of the novel coronavirus, the donning and doffing of personal protective equipment (PPE) was of particular importance for personnel staffing the facility. Furthermore, nationwide shortages in the availability of PPE necessitated the reuse of certain protective materials. This article seeks to delineate the procedures implemented regarding PPE in the setting of a COVID-19 disaster response shelter, including workspace flow, donning and doffing procedures, PPE conservation, and exposure event protocols.

Objective: To evaluate 1943 to 2009 mortality among 22,785 synthetic rubber industry employees., Methods: Standardized mortality ratio (SMR) and internal Cox regression analyses., Results: Among hourly employees with more than or equal to 10 years worked and more than or equal to 20 years since hire, SMRs were elevated for leukemia (SMR = 139, 95% confidence interval [CI] = 106 to 179), non-Hodgkin lymphoma (NHL) (SMR = 136, CI = 102 to 177), bladder cancer (SMR = 148, CI = 110 to 195) and, for women only, lung cancer (SMR = 225, CI = 103 to 427). Butadiene and styrene exposure-response trends were positive for leukemia and bladder cancer but not for NHL or for lung cancer among women., Conclusions: Results support a causal relationship between butadiene and leukemia. Interpretation of results for lung cancer among women and for bladder cancer is uncertain because of inability to control for smoking and inadequate or inconsistent support from other studies for an association between butadiene or styrene and the latter cancers.

We describe a novel gene fusion, EWSR1-CREM, identified in 3 cases of clear cell carcinoma (CCC) using anchored multiplex polymerase chain reaction, a next-generation sequencing-based technique. CCC is a low-grade salivary tumor recently characterized to have EWSR1-ATF1 fusions in the majority of cases. Three cases of malignant tumor presenting in the base of tongue, lung, and nasopharynx were studied. All cases shared a clear cell morphology with hyalinized stroma, presence of mucin and p63 positivity and were initially diagnosed as mucoepidermoid carcinoma but were negative for evidence of any of the expected gene fusions. Anchored multiplex polymerase chain reaction demonstrated a EWSR1-CREM fusion in all 3 cases to confirm a diagnosis of CCC. This finding is biologically justified as CREM and ATF1 both belong to the CREB family of transcription factors. EWSR1-CREM fusions have not been previously reported in CCC and have only rarely been reported in other tumors. We show that the ability to discover novel gene variants with next-generation sequencing-based assays has clinical utility in the pathologic classification of fusion gene-associated tumors.

Objectives  Evaluation of the changing trends in esthesioneuroblastoma in an Irish context and review of management options nationally to clarify the best current therapeutic approach by comparing with international research on this uncommon malignancy. Design  Retrospective review. Setting  Tertiary referral center. Participants  All patients presenting with esthesioneuroblastoma in Beaumont hospital or on the National Cancer Registry of Ireland between 1994 and 2013. Main Outcome Measures  Recurrence-free and overall survival. Results  During the study period, 32 cases of esthesioneuroblastoma were diagnosed (0.4 per million per year). Average age at diagnosis was 57 years; however, two cases were under 20. The majority (62.5%) were male. Patients predominantly presented with epistaxis or nasal congestion (73%), while two cases were identified incidentally on radiological investigations. Twenty-seven cases underwent primary surgical management (two post neo-adjuvant treatment) with seventeen requiring bifrontal craniotomy. Twenty-four of these received postoperative radiation therapy. Overall, 5-year survival was 65%. Kadish A/B patients exhibited 100% 5-year disease-specific survival versus 54% in Kadish C/D ( p  = 0.011). Hyams grade I/II patients exhibited 75% 5-year disease-specific survival versus 63% in Hyams grade III/IV ( p  = 0.005). Patients treated endoscopically exhibited 100% 5-year disease-specific survival versus 51% in those treated via an open approach ( p  = 0.102). Conclusions  Many controversies exist in the diagnosis and management of this condition. Despite this, results from Irish data are mostly concordant with the international literature. The rising incidence of this disease may represent improved pathological recognition. An increasing number of esthesioneuroblastoma cases are being successfully treated via endoscopic surgery.

Objective: The aim of this study was to characterize environmental exposure from Deepwater Horizon oil spill among pre-K to fourth-grade children from six schools in Mobile County, Alabama., Methods: A mail-in survey administered 11 months post-oil spill to children's parents/caregivers elicited information on exposure-related activities. Descriptive and multivariable analyses were performed., Results: Overall, 180 children (coastal schools, 90; inland schools, 90) completed the survey. During the post-oil spill period, children in coastal schools were less likely to reduce their exposure-related activities, including fishing; eating and selling caught fish; visiting beaches; and parental participation in cleanup activities, than children in inland schools. Particularly, fishing and eating caught fish were significantly associated with the coastal group (odds ratio = 2.28; 95% confidence interval = 1.54 to 3.36)., Conclusion: Proximity to the shoreline may serve as an indicator for potential exposure in oil spills among vulnerable populations including children.

Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal tumor of the gastrointestinal tract. The paucity of intracranial metastasis makes treatment strategies difficult. This manuscript presents the first documented case report of a GIST that presented clinically with pituitary symptoms due to a pituitary metastasis.

Background: Posttransplant lymphoproliferative disorders (PTLD) are a common malignancy after renal transplantation with a high incidence of PTLD described in the first posttransplant year. We sought to determine incidence and risk determinants of PTLD in Irish kidney transplant recipients., Methods: Retrospective observational study of 1996 adult first kidney transplant recipients between 1991 and 2010 in the Republic of Ireland. Recipients were cross-referenced with the National Cancer Registry to determine incidence of PTLD. Kaplan-Meier analysis was performed for PTLD-free survival, allograft survival, and patient survival after PTLD. Cox proportional hazards models were used to identify independent risk factors for PTLD in our population., Results: We identified 31 cases of PTLD during the study period. Histological subgroups included: early lesions (n = 1); polymorphic PTLD (n = 1); monomorphic PTLD (n = 27), Hodgkin disease (n = 2). Median time to PTLD diagnosis was 8.3 (range, 1.2-13.9) years. Cumulative incidence (95% CI) of PTLD at 1, 2, 3, 5, 10, and 15 years was 0%, 0.16% (0.05-0.5%), 0.21% (0.08-0.57%), 0.21% (0.08-0.57%), 1.76% (1.15-2.69%), and 3.07% (2.1-4.43%), respectively. Allograft survival after PTLD diagnosis was 94.4% (66.6-99.2%) at 5 years. Patient survival after PTLD diagnosis was 64% at 1 year, 53% at 2 years, 48% at 5 years, and 37% at 10 years. No risk factors for PTLD were identified., Conclusions: We found a paucity of early onset PTLD in our cohort with no cases in the first posttransplant year. Potential contributing factors included a high prevalence of previous Epstein-Barr virus exposure and a relatively low immunological risk profile in our recipient cohort compared with prior studies. Further studies are required to reevaluate the epidemiology of PTLD in the modern era of transplant immunosuppression.