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Herein we evaluated a series of 21 embryonal rhabdomyosarcomas of the uterine corpus (ucERMS), a rare neoplasm, to characterize their morphology, genomics, and behavior. Patients ranged from 27 to 73 (median 52) years and tumors from 4 to 15 (median 9) cm, with extrauterine disease noted in two. Follow-up (median 16 months) was available for 14/21 patients; nine were alive and well, four died of disease, and one died from other causes. Most tumors (16/21) showed predominantly classic morphology, comprised of alternating hyper- and hypocellular areas of primitive small cells and differentiating rhabdomyoblasts in a loose myxoid/edematous stroma. A cambium layer was noted in all; seven had heterologous elements (six with fetal-type cartilage) and eight displayed focal anaplasia. The remaining five neoplasms showed only a minor component (

Enteral tubes are necessary for certain patients; however, medication absorption can be affected by this route of administration potentially resulting in decreased efficacy. All first-line treatments for Hepatitis C Virus (HCV) infection are only available as tablets and may have decreased absorption if administered via an enteral tube. This report describes the first case of a pegylated interferon and ribavirin treatment-experienced patient who successfully achieved HCV cure after 12 weeks of elbasvir/grazoprevir administered via percutaneous gastrostomy tube. We further review the available pharmacokinetic and clinical literature regarding administration via enteral feeding tubes for all first-line direct-acting antivirals (DAAs). The literature suggests that crushed administration can be considered for DAAs in patients with gastric access. However, caution should be exercised in patients with extragastric enteral tubes and in those with altered gastrointestinal tract anatomy.

We report 10 cases of a previously undescribed lesion within ovarian teratomas which we designate bronchus-like structures. The lesions occurred in patients aged 16 to 56 yr (mean: 36) and involved the left ovary (n=5) or right ovary (n=5). Nine cases were mature teratomas (dermoid cysts/mature cystic teratomas or mature solid teratomas), 1 with somatic malignant transformation, and 1 was an immature teratoma. The bronchus-like structures ranged in size from 2.5 to 10 mm and were unifocal (7 cases) or multifocal (3 cases). The morphology was relatively constant in all cases and characterised by a well-formed bronchus surrounded by glandular structures, some of which were dilated, separated by stroma containing a variable amount of smooth muscle. In all but 1 case, a proportion of the glands contained abundant foamy cytoplasm. There was little or no nuclear atypia or mitotic activity. At low-power, the glands often had a somewhat "infiltrative" appearance and one case was originally diagnosed as a "pulmonary-type" adenocarcinoma arising in a dermoid cyst. In all cases, there was diffuse staining of the bronchus and glands with TTF1 and Napsin A, confirming the cell lineage. Follow-up in 4 cases (18-130 mo; median: 64 mo) showed no evidence of recurrence; 1 patient died from an unrelated malignancy. In reporting this apparently rare but possibly underrecognized benign lesion arising within ovarian teratomas, we discuss the differential diagnosis and stress that pathologists should be aware of this phenomenon in order to avoid an erroneous diagnosis of malignancy.

A female in her 80's presented to our Emergency Department following a fall. She reported general malaise, weight loss and raised inflammatory markers. Background included renal cell carcinoma 21 years previous, managed with radical nephrectomy. During her inpatient stay she had an episode of haematemesis. Upper GI endoscopy revealed a 3cm polypoidal lesion on the greater curve of the upper stomach. This had an irregular pit pattern endoscopically and was friable. Multiple biopsies revealed metastatic clear cell carcinoma of renal origin; the same sub-type as her previous renal tumour. This is a rare manifestation of metastatic renal cell carcinoma and from literature review, is only the 2

Background HIV-1 transmitted drug resistance (TDR) remains a global challenge that can impact care, yet its comprehensive assessment is limited and heterogenous. We longitudinally characterized statewide TDR in Rhode Island. Methods Demographic and clinical data from treatment-naïve individuals were linked to protease, reverse transcriptase, and integrase sequences routinely obtained over 2004–2020. TDR extent, trends, impact on first-line regimens, and association with transmission networks were assessed using the Stanford Database, Mann-Kendall statistic, and phylogenetic tools. Results In 1123 individuals, TDR to any antiretroviral increased from 8% (2004) to 26% (2020), driven by non-nucleotide reverse transcriptase inhibitor (NNRTI; 5%–18%) and, to a lesser extent, nucleotide reverse transcriptase inhibitor (NRTI; 2%–8%) TDR. Dual- and triple-class TDR rates were low, and major integrase strand transfer inhibitor resistance was absent. Predicted intermediate to high resistance was in 77% of those with TDR, with differential suppression patterns. Among all individuals, 34% were in molecular clusters, some only with members with TDR who shared mutations. Among clustered individuals, people with TDR were more likely in small clusters. Conclusions In a unique (statewide) assessment over 2004–2020, TDR increased; this was primarily, but not solely, driven by NNRTIs, impacting antiretroviral regimens. Limited TDR to multiclass regimens and pre-exposure prophylaxis are encouraging; however, surveillance and its integration with molecular epidemiology should continue in order to potentially improve care and prevention interventions.

Antiviral therapy continues to be one of the many challenges facing the healthcare provider. This chapter describes viruses that parasitize host cell enzymes and structures to varying degrees and discusses the difficulty of designing or discovering drugs that specifically target viral enzymes without affecting host cell machinery. The chapter examines viruses that establish a latent infection in the host, during which time they are essentially quiescent. It reviews some serious viral infections that stem from the reactivation of latent viruses during periods of impaired cell-mediated immunity. It discusses the development of drug resistance due to viral mutagenicity as an ongoing challenge in antiviral therapy.

The ovary is a common site of metastatic mucinous adenocarcinoma. In most, but not all, cases the presence of a primary neoplasm elsewhere is already known and the metastasis is picked up at diagnosis or is discovered a relatively short time following the diagnosis of the primary neoplasm. We report 2 cases of metastatic gallbladder adenocarcinoma involving the ovaries of women aged 65 and 59 after long time periods of 8 and 5 yr following diagnosis of high-grade dysplasia or early adenocarcinoma of the gallbladder, respectively. In both cases, a review of the original operative notes suggested the possibility of intraoperative gallbladder rupture or bile leakage suggesting that the metastatic disease may have developed secondary to "seeding." In both cases, p53 immunohistochemistry revealed identical null mutation-type immunoreactivity within the gallbladder and ovarian neoplasms, assisting in confirming the ovarian disease as a metastasis from the gallbladder. The possibility of late ovarian metastasis of gallbladder dysplasia or adenocarcinoma secondary to rupture/bile leakage should be borne in mind.

Pneumococcal and herpes zoster - shingles - vaccination prevent a great deal of morbidity, particularly in elderly and immunocompromised hosts. Vaccination of children with conjugate pneumococcal vaccine in recent years has greatly reduced illness in older individuals as well. This article will review the historical and current recommendations for pneumococcal and herpes zoster vaccination and the rationale for changes at the level of the CDC's Advisory Committee on Immunization Practices.

Moderate‐certainty evidence shows that comprehensive legislative smoking bans probably improve overall cardiovascular health. Results for the impact of such bans on respiratory health are less certain.

We report 3 cases of primary extraovarian unclassifiable malignant sex cord-stromal tumors. In all cases, the tumors involved the pelvis, peritoneum, and/or omentum and the morphologic features were essentially those of a poorly differentiated malignant neoplasm. A diagnosis of sex cord-stromal tumor was made on the basis of expression of several markers of ovarian sex cord-stromal tumors and exclusion of other neoplasms. In 1 case, an elevated serum testosterone was present at tumor progression. In reporting these cases, we draw attention to the problems in establishing a diagnosis that can be attributed to the extreme rarity of sex cord-stromal tumors in an extraovarian location and the rarity of unclassifiable malignant sex cord-stromal tumors in general, resulting in pathologists not considering this diagnosis. We review sex cord-stromal tumors occurring in an extraovarian location.

Ovarian Carcinoma (with comments on Fallopian Tube Carcinoma): this chapter outlines the incidence, risk factors, clinical presentation, investigations, treatments and prognosis of cancer at this anatomical site. These features are correlated with the core data that are required to make corresponding histopathology reports of a consistently high quality, available in an appropriate timeframe, and clinically relevant to patient management and prognosis. Summary details of the common cancers given at this site include: gross description, histological types, tumour grade/differentiation, extent of local tumour spread, lymphovascular invasion, lymph node involvement, and the status of excision margins. Current WHO Classifications of Malignant Tumours and TNM8/FIGO are referenced. Notes are provided on other associated pathology, contemporary use of immunohistochemistry, updates on the role of evolving molecular tests, and the use of these ancillary techniques as biomarkers in diagnosis, and prediction of prognosis and treatment response. A summary is given of the more common non-carcinoma malignancies that are encountered at this site in diagnostic practice.

Background and AimsTo compare endoscopy and pathology sizing in a large population-based series of colorectal adenomas and to evaluate the implications for patient stratification into surveillance colonoscopy.MethodsEndoscopy and pathology sizes available from intact adenomas removed at colonoscopies performed as part of the Northern Ireland Bowel Cancer Screening Programme, from 2010 to 2015, were included in this study. Chi-squared tests were applied to compare size categories in relation to clinicopathological parameters and colonoscopy surveillance strata according to current American Gastroenterology Association and British Society of Gastroenterology guidelines.ResultsA total of 2521 adenomas from 1467 individuals were included. There was a trend toward larger endoscopy than pathology sizing in 4 of the 5 study centers, but overall sizing concordance was good. Significantly greater clustering with sizing to the nearest 5 mm was evident in endoscopy versus pathology sizing (30% vs 19%, p

Background There are many emerging diagnostic technologies that provide rapid identification (ID) and antimicrobial susceptibility testing (AST) of blood cultures after initial microbial growth is detected. The clinical utility of having these results sooner than standard of care (SOC) ID/AST testing is less clear; one potential advantage would be shorter hospital admissions for those patients with less severe infections whose discharge planning is delayed while waiting for ID/AST results. Methods The Accelerate Pheno™ rapid ID/AST system (AP) was implemented in the clinical microbiology lab at two hospitals within our academic hospital system to run in parallel with our SOC ID/AST diagnostics for all blood cultures with Gram-negative rod (GNR) bacterial growth on initial Gram stain. Results of both diagnostic assays were uploaded to the medical record when available; our antimicrobial stewardship (AS) team discussed the AP results with clinical care teams during working hours. Length of stay (LOS) data was compared between a cohort with GNR bacteremia before and after the implementation of AP testing with AS review. Results There were 207 patients with GNR bacteremia admitted to the hospital during the first six months after implementation of AP testing with AS review (12/2019 – 05/2020). A historical cohort of 96 patients with GNR bacteremia (admitted 01/2018 – 08/2018) with SOC testing without AS review was used for comparison. Median LOS was 5.28 and 5.84 days for the AP and SOC cohorts, respectively; the distribution in the two groups differed significantly (Mann-Whitney U = 8728.5, p = 0.0446). There was also an increase in the percent of admissions shorter than 2 days between the AP and SOC cohorts (12.5% v. 5.2%, p = 0.024) [Figure1]. Figure 1 Conclusion The use of a rapid ID/AST diagnostic technology with AS review may lead to shorter hospitalizations in select patient populations. Disclosures Kimberle Chapin, MD, genmark (Scientific Research Study Investigator)

Introduction There is a lack of evidence to inform guidelines for the management of pre-malignant colorectal sessile serrated lesions (SSL). Northern Ireland (NI) is the only UK region where pathologists have diagnosed SSL (or synonyms) during reporting of Bowel Cancer Screening (BCS) specimens since inception of the programme. The aim of this study is to profile SSL diagnoses, and their risk stratification for surveillance, within BCS in NI. Methods The NI BCS programme was initiated in April 2010, targeting 60–74 year olds through faecal occult blood testing (FOBt). Characteristics of SSL diagnoses were evaluated within the enhanced pathology database completed by all histopathologists reporting BCS specimens in NI. Data up to end March 2017 were considered for analysis, incorporating data on over 17 000 histopathological BCS specimens reviewed at one of four pathology laboratories. Individuals who received a colorectal cancer diagnosis were excluded from analysis. Results SSL were reported in 337 individuals, representing 6.7% of all 5041 individuals who had a non-malignant histopathological BCS specimen reviewed. One male met criteria for serrated polyposis syndrome, and was excluded from further analysis. Of the remaining 336 SSL cases, 208 (61.9%) were male and 81% had only right-sided SSL detected. Large (≥10 mm) SSL or SSL with dysplasia accounted for 82 cases (24.4%), of which only 22 (6.5% of SSL and 0.4% of total 5041 individuals) did not have concurrent conventional adenomas that would already warrant more frequent surveillance. Conclusions SSL cases within this FOBt screening population were predominantly male and right-sided. Of all cases of large or dysplastic SSL, 93.5% also had high or intermediate risk adenomas, which would already require follow-up colonoscopy surveillance at one or three years according to adenoma surveillance guidelines. Therefore, the 2017 British Society of Gastroenterology position statement on serrated polyps will have limited impact in this clinical setting. The clinical significance of concurrent adenomas and SSLs remains to be established.

Background Pituitary abscess is less common but life threating which is usually misdiagnosed as pituitary tumor pre operatively in spite of radiological advancement Definite diagnosis is possible only postoperatively Material and methods we report a case of years old woman admitted in our department with symptoms of headache visual impairment and pituitary dysfunction MRI brain revealed sellar and supra sellar mass consistent with pituitary tumor She eventually underwent endoscopic trans sphenoidal removal Per operatively pus was evident A month later she was well and fully recovered pituitary function Results The histopathological examination confirmed presence wall of abscess cavity however Culture showed no growth Conclusion This case report gives emphasis on the importance of considering pituitary abscess as a differential diagnosis in patients with sella supra sellar mass Early diagnosis and surgical management of a pituitary abscess significantly decreases morbidity and mortality and it also helps to establish the definite diagnosis

Aims Involved circumferential resection margin (CRM) (R1) in oesophageal carcinoma (OC) has conflicting definitions. This study aimed to compare two such definitions applied to a cohort of OC resection specimens and also evaluated a novel three-tier CRM stratification. Methods and results OC patients with pT3 disease were classified as R0 or R1 on the basis of Royal College of Pathologists (UK) (RCPath) and College of American Pathologists (CAP) criteria and group survivals were compared. Patients were then stratified into three groups on the basis of tumour distance from the CRM (>1 mm, 0.1–1 mm, 0 mm). A total of 195 patients were included. According to RCPath criteria, 50 resections were R0 and 145 R1; median survival was 72.0 and 18.1 months. Using CAP criteria, 137 resections were R0 and 58 R1; median survival was 30.1 and 12.6 months. Using three-tier stratification, tumour was clear by >1 mm (R0) in 50 cases, 0.1–1 mm from CRM (RCPath R1; CAP R0) in 87 cases and 0 mm (R1) in 58 cases; median survival was 72.0, 24.6 and 12.6 months, respectively. Survival difference was statistically significant using each binary system and also the three-tier system. Conclusions Both RCPath and CAP criteria to define CRM have similar prognostic value. A novel three-tier classification of CRM status provides more detailed prognostication.

We report 3 cases in which endometrial stromal cells exhibited marked nuclear atypia with a symplastic appearance. Two cases involved non-neoplastic endometrial stroma, one within an ovarian endometriotic cyst and the other within normal eutopic endometrium. In the third case, the symplastic change involved the neoplastic cells of an endometrial stromal sarcoma. Symplastic endometrial stromal cells have rarely been described in normal endometrium and in endometrial stromal sarcoma but, as far as we are aware, this phenomenon has not been reported previously in endometriosis. In the 3 cases, the atypical cells were a focal finding. The abnormal nuclei were markedly enlarged, atypical, and hyperchromatic with multilobated forms but without mitotic activity. This unusual phenomenon is a benign change when involving non-neoplastic endometrial stroma and is of no clinical significance. It is analogous to the presence of atypical symplastic nuclei in normal tissues and in other pathologic lesions in the female genital tract. In reporting these cases, we review normal tissues and pathologic lesions in the female genital tract with atypical symplastic nuclei.

Background An extrapulmonary small cell carcinoma is a rare condition. It has similar histological features to pulmonary small cell carcinoma and is equally aggressive. Case presentation We present the case of a 60-year-old woman who presented with right upper quadrant pain. Computerised tomography revealed an appendiceal lesion and multiple liver metastases. Exploratory laparotomy and right hemicolectomy was performed with histopathological analysis confirming a primary small cell carcinoma of her appendix. Conclusion This is the first reported case of a pure extrapulmonary carcinoma arising from the appendix.

Aspergilloma refers to a fungal ball formed by saprophytic overgrowth of Aspergillus species and is seen secondary to cavitatory/cystic respiratory diseases. Paucity of clinical and pathological data of aspergilloma in India prompted us to analyze cases of aspergilloma over 15 years. The clinical features were recorded in all and correlated with detailed pathological examination. Aspergillomas were identified in 41 surgical excisions or at autopsy. There was male predominance; half the patients were in their fourth decade. Episodic hemoptysis was the commonest mode of presentation (85.4%). Forty aspergillomas were complex, occurring in cavitatory lesions (82.9%) or in bronchiectasis (14.6%). Simple aspergilloma was seen as an incidental finding in only one. Tuberculosis was the etiological factor in 31 patients, producing cavitatory or bronchiectatic lesions; other causes were chronic lung abscess and bronchiectasis (unrelated to tuberculosis). Surgical resections are endorsed in view of high risk of unpredictable, life-threatening hemoptysis.