Gastric biomarkers: a global review.

BACKGROUND: Gastric cancer is an aggressive disease with a poor 5-year survival and large global burden of disease. The disease is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Despite the many prognostic, predictive, and therapeutic biomarkers investigated to date, gastric cancer continues to be detected at an advanced stage with resultant poor clinical outcomes. MAIN BODY: This is a global review of gastric biomarkers with an emphasis on HER2, E-cadherin, fibroblast growth factor receptor, mammalian target of rapamycin, and hepatocyte growth factor receptor as well as sections on microRNAs, long noncoding RNAs, matrix metalloproteinases, PD-L1, TP53, and microsatellite instability. CONCLUSION: A deeper understanding of the pathogenesis and biological features of gastric cancer, including the identification and characterization of diagnostic, prognostic, predictive, and therapeutic biomarkers, hopefully will provide improved clinical outcomes.

Diagnostic and prognostic features in adrenocortical carcinoma: a single institution case series and review of the literature.

BACKGROUND: Adrenocortical carcinoma is a rare cancer, with an incidence in the literature of 0.5 to 2 cases per million population per year. Adult adrenocortical carcinoma has a poor prognosis, underscoring the importance of identifying diagnostic and prognostic markers. METHODS: We searched our laboratory database for all cases in the past 15 years with a diagnosis of adrenocortical carcinoma. The original slides were then reviewed for their histopathological features. A representative paraffin block was subjected to further immunohistochemical staining for Ki-67, inhibin, steroidogenic factor-1 (SF-1), p53, and Β-catenin. These slides were scored by the study pathologist who was blinded to all clinicopathological data. In addition, a comprehensive review of the relevant English literature in the past 15 years was conducted. RESULTS: Eight cases were identified, including two adrenal sarcomatoid carcinomas. Seven of the eight cases had a disrupted reticulin network. Six of the eight tumors had >10% Ki-67 expression. Five of the eight tumors had >10% p53 expression. Positive inhibin immunohistochemical staining was seen in three of the eight tumors, and positive SF-1 staining was seen in five of the seven stained tumors. Abnormal Β-catenin intracellular accumulation was noted in four of the eight tumors. The two tumors in our series with sarcomatoid histology did not stain positively for SF-1 or inhibin. CONCLUSIONS: Eight cases of adrenocortical carcinoma, including two with sarcomatoid features are presented. The two sarcomatoid adrenocortical carcinomas in our series did not stain for SF-1 which suggests a possible de novo pathway of tumorigenesis for this rare variant. The reticulin staining method was a useful tool for rapid differentiation of adrenocortical adenomas and carcinomas. Diffuse p53 staining showed a trend for positive correlation with increased Ki-67 expression. Inhibin staining was inconsistently expressed in our cases of adrenocortical carcinoma. In conclusion, as adrenocortical carcinoma is a rare disease, we recommend future multicenter studies with appropriate sample sizes to further evaluate the efficacy of these diagnostic and prognostic markers.

Expression of Toll-like receptor 9 in mouse and human lungs.

Toll-like receptors (TLR) recognize conserved molecular motifs of microorganisms, and constitute an important part of the innate immune system. Numerous studies have shown the importance of these receptors, including TLR9, in establishing effective immune responses to a broad range of infections, and in disorders such as COPD. TLR9 detects unmethylated DNA and is expressed in a wide range of immune cells in mice and humans, as well as other species. Most TLR9 expression studies have been done on cultured or isolated cells, but none that we know of on intact lung. Because cell-specific expression of TLR9 is important to understand its precise role in lung physiology, we tested mouse and human lung tissues for expression of TLR9 mRNA and protein with in situ hybridization and immunohistochemistry, respectively. We found TLR9 mRNA and protein expression in bronchial epithelium, vascular endothelium, alveolar septal cells and alveolar macrophages in both species. Immuno-electron microscopy delineated TLR9 expression in plasma membrane, cytoplasm and the nucleus of various lung cells. Lungs from human cases of COPD had significantly increased numbers of TLR9-positive cells. These are the first data showing TLR9 mRNA and protein expression in intact human and mouse lungs. The data may be useful for clarifying the role of TLR9 in the contributions of specific cells to lung physiology.

Estrogen/Progesterone Receptor Loss, CTNNB1 and KRAS Mutations Are Associated With Local Recurrence or Distant Metastasis in Low-Grade Endometrial Endometrioid Carcinoma.

A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be associated with loss of expression of ER-alpha (ER-α) as well as with ß-Catenin-1 ( CTNNB1 ) and Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations. This study reports on institutional experience with the incidence of recurrence in low-grade EEC and their association with CTNNB1 and KRAS mutations as well as estrogen/progesterone receptor (ER/PR) expression. Forty-eight (8.5%) out of 568 cases of low-grade EEC with biopsy-proven recurrence were identified; and were analyzed by immunohistochemistry for ER, PR, p53, MMR protein, and mutation analysis for exon 3 of the CTNNB1 and exon 2 of KRAS in relation to recurrence type, local or distant metastasis/recurrence. Twenty-three patients (4%) developed local, and 25 patients (4.4%) developed distant metastases/recurrence. Decreased expression or loss of ER/PR was found in 17/44 (38.6%) patients with recurrence. Eighty-four percent of patients with low-grade EEC and local recurrence had CTNNB1 mutations. Seventy-three percent of patients with distant metastasis/recurrence had KRAS mutations. The association of these mutations with the type of recurrence was statistically significant for both. Five cases with the morphology of low-grade EEC were reclassified as mesonephric-like carcinoma and were universally characterized by distant metastasis/recurrence, loss of ER/PR expression, large tumor size, absence of CTNNB1 mutations, and the presence of KRAS mutations. In low-grade EEC, CTNNB1 and KRAS mutations are associated with local recurrence and distant metastasis/recurrence, respectively, suggesting that these 2 different progression types may be conditioned by tumor genotype. ER/PR immunohistochemistry may be helpful in identifying poor performers in low-grade EEC. Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRAS mutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.

A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences.

Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERα, ERß1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phenotype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95% CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95% CI = 0.46-1.26) and both 5 (P = 0.04, HR = 0.37, 95% CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95% CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ERß1/2 clusters. A striking feature was the occurrence of ERα on distinct clusters between genders. In female breast cancer, ERα clustered with PR and its isoforms; in male breast cancer, ERα clustered with ERß isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study.

Three uncommon adrenal incidentalomas: a 13-year surgical pathology review.

BACKGROUND: The discovery of adrenal incidentalomas due to the widespread use of sophisticated abdominal imaging techniques has resulted in an increasing trend of adrenal gland specimens being received in the pathology laboratory. In this context, we encountered three uncommon adrenal incidentalomas.The aim of this manuscript is to report in detail the three index cases of adrenal incidentalomas in the context of a 13-year retrospective surgical pathology review. METHODS: The three index cases were investigated and analyzed in detail with relevant review of the English literature as available in PubMed and Medline. A 13-year retrospective computer-based histopathological surgical review was conducted in our laboratory and the results were analyzed in the context of evidence-based literature on adrenal incidentalomas. RESULTS: A total of 94 adrenal specimens from incidentalomas were identified, accounting for 0.025% of all surgical pathology cases. In all 76.6% were benign and 23.4% were malignant. A total of 53 females (56.4%) and 41 males (43.6%) aged 4 to 85 years were identified. The benign lesions included cortical adenoma (43.1%), pheochromocytoma (29.3%) and inflammation/fibrosis/hemorrhage (8.3%). Metastatic neoplasms were the most common malignant lesions (50%) followed by primary adrenocortical carcinomas (31.8%) and neuroblastoma (13.6%). These cases were discovered as adrenal incidentalomas that led to surgical exploration.The three index cases of adrenal incidentalomas with unusual pathologies were encountered that included (a) adrenal ganglioneuroma, (b) periadrenal schwannoma and (c) primary adrenal pleomorphic leiomyosarcoma. These cases are discussed, with a literature and clinicopathological review. CONCLUSIONS: Adrenal lesions are uncommon surgical specimens in the pathology laboratory. However, higher detection rates of adrenal incidentalomas aided by the ease of laparoscopic adrenalectomy has resulted in increased adrenal surgical specimens leading to unsuspected diagnostic and management dilemmas. Accurate pathological identification of common and uncommon adrenal incidentalomas is essential for optimal patient management.

Retinoid receptors are expressed in mouse and human lungs.

Retinoid receptors are members of nuclear receptor superfamily consisting of two distinct families: RARs (retinoic acid receptors) and RXRs (retinoid X receptors). Each family contains three receptor subtypes α, ß, and γ. Retinoids transduce their effects through binding to retinoid receptors and inhibit transcription factors such as activator protein-1 and nuclear factor-κB (NF-κB) both of which regulate the transcription of several inflammatory genes. Considering the role of retinoid receptors in lung physiology, we need a precise understanding of their expression in normal and inflamed lungs. We used light and electron microscopic immunohistochemistry and Western blot to determine the expression of retinoid receptors in a murine model of endotoxin-induced (E. coli; 055:B5, 80 µg intranasal) acute lung inflammation and normal human lungs. Western blot showed expression of all six retinoid receptor subtypes in normal and inflamed mouse lungs. Immunohistology localized differential expression of retinoid receptors in airway epithelium, alveolar/septal macrophages, vascular endothelium, and alveolar septum in mouse lungs. Intranasal LPS challenge in mice resulted in increased expression of RXRα in airway epithelium compared to control animals. All six retinoid receptor subtypes were expressed in normal human lungs. Immunoelectron microscopy further confirmed the localization of all the receptors in various lung cells including the nucleus of these cells. The basal and altered expression of retinoid receptors in normal and inflamed lungs, respectively, may suggest their roles in lung pathophysiology.

Outcomes of Patients with Small Intestine Adenocarcinoma in a Canadian Province: A Retrospective Multi-Center Population-Based Cohort Study.

Background: Small intestine adenocarcinoma is a rare cancer. The current study aims to determine the outcomes of patients with small intestine adenocarcinoma in a Canadian province. Methods: This retrospective population-based cohort study assessed patients with small intestine adenocarcinoma who were diagnosed from 2008 to 2017 in Saskatchewan. A Cox proportional multivariate regression analysis was performed to determine the correlation between survival and exploratory factors. Results: 112 eligible patients with a median age of 73 years and M:F of 47:53 were identified. Overall, 75% had a comorbid illness, and 45% had a WHO performance status >1. Of the 112 patients, 51 (46%) had early-stage disease and 61 (54%) had advanced-stage disease. The median overall survival (mOS) was as follows: stage one, 59 months; stage two, 30 months; stage three, 20 months; and stage four, 3 months (p < 0.001). The median disease-free survival of patients with stage three disease who received adjuvant chemotherapy was 26 months (95% CI:23.1−28.9) vs. 4 months (0.0−9.1) with observation (p = 0.04). Patients who received chemotherapy for advanced disease had a mOS of 10 months (3.5−16.5) vs. 2 months (0.45−3.6) without chemotherapy (p < 0.001). In the multivariate analysis, stage four disease, hazard ratio (HR), 3.20 (1.84−5.40); WHO performance status >1, HR, 2.22 (1.42−3.45); lack of surgery, HR, 2.10 (1.25−3.50); and a neutrophil:lymphocyte ratio of >4.5, HR, 1.72 (1.10−2.71) were significantly correlated with inferior survival. Conclusions: Most patients with small intestine adenocarcinoma were diagnosed with advanced-stage disease. Advanced-stage disease, poor performance status, lack of surgery and a baseline neutrophil:lymphocyte ratio >4.5 were correlated with inferior survival.

A review of duodenal metastases from squamous cell carcinoma of the cervix presenting as an upper gastrointestinal bleed.

Upper gastrointestinal bleeding due to duodenal metastases is extremely uncommon. Extra-pelvic spread of squamous cell carcinoma (SCC) of the cervix to the small bowel is rare with only 6 reported cases in the English literature since 1981(PubMed, Medline).We report the case of a 49-year-old woman who presented with upper-gastrointestinal bleeding two years after the diagnosis of SCC of the cervix. At esophagogastroduodenoscopy, there was a stricture in the second part of the duodenum which was biopsied for a suspected neoplastic lesion. Histologic and immunohistochemical examination showed a malignant lesion with characteristics identical to her original tumor in the cervix confirming the duodenal metastases.The clinical presentation of a 'malignant' upper-gastrointestinal bleed due to duodenal metastases from SCC of the cervix is unusual. Awareness of such infrequent patterns of metastases in cervical cancer confirmed by histopathological diagnosis is important for best practice therapeutic decisions in these patients.

An appraisal of students' awareness of "self-reflection" in a first-year pathology course of undergraduate medical/dental education.

BACKGROUND: Self-reflection and reflective practice are increasingly considered as essential attributes of competent professionals functioning in complex and ever-changing healthcare systems of the 21st century. The aim of this study was to determine the extent of students' awareness and understanding of the reflective process and the meaning of 'self-reflection' within the contextual framework of their learning environment in the first-year of their medical/dental education. We endorse that the introduction of such explicit educational tasks at this early stage enhances and promotes students' awareness, understanding, and proficiency of this skill in their continuing life-long health professional learning. METHODS: Over two years, students registered in first-year pathology at the University of Saskatchewan were introduced to a self-reflection assignment which comprised in the submission of a one-page reflective document to a template of reflective questions provided in the given context of their learning environment. This was a mandatory but ungraded component at the midterm and final examinations. These documents were individually analyzed and thematically categorized to a "5 levels-of-reflection-awareness" scale using a specially-designed rubric based on the accepted major theories of reflection that included students' identification of: 1) personal abilities, 2) personal learning styles 3) relationships between course material and student history 4) emotional responses and 5) future applications. RESULTS: 410 self-reflection documents were analyzed. The student self-awareness on personal learning style (72.7% level 3+) and course content (55.2% level 3+) were well-reflected. Reflections at a level 1 awareness included identification of a) specific teaching strategies utilized to enhance learning (58.4%), b) personal strengths/weaknesses (53%), and c) emotional responses, values, and beliefs (71.5%). Students' abilities to connect information to life experiences and to future events with understanding were more evenly distributed across all 5 levels of reflection-awareness. CONCLUSIONS: Exposure to self-reflection assignments in the early years of undergraduate medical education increases student awareness and promotes the creation of personal meaning of one's reactions, values, and premises in the context of student learning environments. Early introduction with repetition to such cognitive processes as practice tools increases engagement in reflection that may facilitate proficiency in mastering this competency leading to the creation of future reflective health professionals.

Recovery of borderline oxacillin-resistant Staphylococcus pseudintermedius (BORSP) from bone and soft tissue of a rheumatoid arthritis patient with severe osteoporosis: transmission from the family dog.

We report a case of borderline oxacillin-resistant S. pseudintermedius (BORSP) in a rheumatoid arthritis patient with severe osteoporosis. The organism is also resistant to erythromycin and clindamycin. We also present clear evidence on transmission from the family dog.

Gastrointestinal schwannoma: an unusual colonic lesion mimicking adenocarcinoma.

Gastrointestinal schwannoma is a rare, benign pathological entity that can mimic colonic adenocarcinoma and cause diagnostic dilemmas for treatment. A case of a 68-year-old woman with colonic adenocarcinoma who was discovered to have an incidental synchronous bowel lesion that proved to be a gastrointestinal schwannoma and not a synchronous adenocarcinoma is described. Gastrointestinal schwannomas are uncommon in the colorectal region; they are most often located in the stomach. These spindle cell lesions are distinct from gastrointestinal stromal tumours because the tumour cells have a distinct immunophenotype, with strong diffuse positivity for S-100, glial fibrillary acidic protein and vimentin, and corroborative negative staining of CD34, CD117 and smooth muscle markers. Accurate diagnosis and recognition of this benign entity is, therefore, of immense clinicopathological value for accurate planning of therapeutic strategies.

Pulmonary lymphangitic carcinomatosis from squamous cell carcinoma of the cervix.

INTRODUCTION: Pulmonary metastasis presenting as lymphangitic carcinomatosis arising from squamous cell carcinoma (SCC) of the cervix is a rare event. Poorly represented in the literature, this event is associated with a) difficulty in accurate diagnosis, b) grave prognosis, and the c) lack of recognized predisposing risk factors. CASE REPORT: A 50 year-old female presented at our practice with a three-month history of a productive cough associated with dyspnoea and shortness of breath. A chest x-ray and computed tomography (CT) scan revealed multiple bilateral patchy areas with subsegmental atelectasis in both lungs which was investigated with a bronchoscopy, left thoracoscopy, and a left lung biopsy. Pathological examination of the wedge biopsy of the left upper lobe revealed neoplastic sheets of cell disturbed along the septal vessels, perivascular/peribronchial lymphatics, and the subpleural lymphatics. This lymphangitic carcinomatosis was confirmed to be metastatic from SCC of the cervix that had been diagnosed and treated two years ago. She was treated with systemic Carbo/Taxol chemotherapy and corticosteroids as a palliative measure. Despite temporary improvement, she died 13 months later. CONCLUSION: Pulmonary lymphangitic carcinomatosis is a rare manifestation of metastatic SCC of the cervix. As clinical presentations including radiographic imaging mimics other pulmonary entities, accurate diagnosis remains a challenge. Increased clinical awareness of such patterns of metastases in cervical cancer supported by accurate pathological diagnosis is imperative to guide appropriate therapy in these patients.

Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins.

AIM: The aim of our study was to evaluate survival outcomes in malignant mixed Mullerian tumors (MMMT) of the uterus with respect to the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components. METHODS: 23 cases of uterine MMMT identified from the Saskatchewan Cancer Agency (1970-1999) were evaluated. Immunohistochemical expression of Bad, Mcl-1, bcl-x, bak, mdm2, bax, p16, p21, p53, p27, EMA, Bcl-2, Ki67 and PCNA was correlated with clinico-pathological data including survival outcomes. RESULTS: Histopathological examination confirmed malignant epithelial component with homologous (12 cases) and heterologous (11 cases) sarcomatous elements. P53 was strongly expressed (70-95%) in 15 cases and negative in 5 cases. The average survival in the p53+ve cases was 3.56 years as opposed to 8.94 years in p53-ve cases. Overexpression of p16 and Mcl-1 were observed in patients with longer survival outcomes (>2 years). P16 and p21 were overexpressed in the carcinomatous and sarcomatous elements respectively. Cyclin-D1 was focally expressed only in the carcinomatous elements. CONCLUSIONS: Our study supports that a) cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis and b) p53 is an important immunoprognostic marker in MMMT of the uterus.

Expression of cell cycle proteins in male breast carcinoma.

INTRODUCTION: Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints. METHODS: 75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS). RESULTS: Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07). CONCLUSION: Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future.

Multiple colonic and ileal perforations due to unsuspected intestinal amoebiasis-Case report and review.

Amoebiasis, caused by the intestinal protozoan Entamoeba histolytica, though a relatively common parasitic disease in the tropical and subtropical regions, is uncommon in the developed countries. In these countries, as amoebic colitis shares similar clinical symptoms and endoscopic features with inflammatory bowel disease (IBD), these cases can be easily unrecognized and misdiagnosed. In this case report, we discuss the case of an adult patient with invasive intestinal amoebiasis, who was initially managed as Crohn's disease on corticosteroid treatment and subsequently rapidly deteriorated and developed multiple perforations in the colon and ileum. Despite total colectomy followed by resection of the small bowel, he died of multiple organ failure and sepsis within two months of his initial clinical presentation of diarrhea with abdominal pain. The learning point of this case is that invasive intestinal amoebiasis should be considered as a differential diagnosis at the first clinical adult presentation of IBD-like symptoms despite suggestive endoscopic findings of Crohn's like ulcers. Regardless of negative endoscopic biopsies, due to the low sensitivity of microscopic examination, serology test for antibody and molecular test for Entamoeba DNA are recommended for accurate detection and identification of Entamoeba species, especially in the high risk populations with recent travel to endemic zones and for patients with immunosuppression and comorbidities such as diabetes mellitus, tuberculosis, alcoholism, HIV/AIDS and in pregnant women. Amoebiasis should be completely ruled out prior to corticosteroid administration, to avoid severe complications such as fulminant intestinal amoebiasis which is associated with an inherently high mortality.

Mixed epithelial endocrine neoplasms of the colon and rectum - An evolution over time: A systematic review.

BACKGROUND: Mixed tumors of the colon and rectum, composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms. These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally. Though they have been a well-documented entity in the pancreas, where the exocrine-endocrine mixed tumors have been known for a while, recognition and accurate diagnosis of these tumors in the colon and rectum, to date, remains a challenge. This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification. Therefore, dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers. Though, most of these tumors are high grade and of advanced stage, intermediate and low grade lesions of these mixed tumors are also increasingly been reported. There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions. AIM: To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape, clinicoradiological features, pathology, treatment, prognosis, the current status of the management of the primary lesions, their recurrences and metastases. METHODS: A comprehensive review of the published English literature was conducted using the search engines PubMed, MEDLINE and GOOGLE scholar. The following search terms ["mixed tumors colon" OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors] were used. Eligibility criteria were defined and all potential relevant items, including full articles and/or abstracts were independently reviewed, assessed and agreed upon items were selected for in-depth analysis. RESULTS: In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review. This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives, nomenclature, clinicoradiological features, pathology, treatment, prognosis and the current status of the management of both the primary lesions, their recurrences and metastases. Gaps in knowledge have also been identified and discussed. An important outcome of this manuscript is the justified proposal for a new, simple, clinically relevant, non-ambiguous terminology for these lesions to be referred to as mixed epithelial endocrine neoplasms (MEENs). CONCLUSION: MEEN of the colon and rectum are poorly understood rare entities that encompass an extensive range of heterogeneous tumors with a wide variety of combinations leading to tumors of high, intermediate or low grade malignant potential. This proposed new revised terminology of MEEN will solve the biggest hurdle of confusion and misclassification that plagues these rare unique colorectal neoplasms thus facilitating the future design of multi institutional prospective randomized controlled clinical trials to develop and evaluate newer therapeutic strategies that are recommended for continued improved understanding and personal optimization of clinical management of these unique colorectal neoplasms.

Bacteremia with Staphylococcus pseudintermedius in a 4 month old pediatric oncology patient.

Staphylococcus pseudintermedius colonizes and is a pathogen of dogs and is being increasingly recognized from specimens from humans with various infections. We describe a case of S. pseudintermedius bacteremia in a 4 month old pediatric oncology patient with clear evidence of transmission from the family pet.

Extrapelvic Metastases in Endometrial Stromal Sarcomas: A Clinicopathological Review With Immunohistochemical and Molecular Characterization.

Endometrial stromal sarcoma is a rare uterine tumor associated with favorable outcomes despite its ability to recur and metastasize to distant sites. Most recurrences are local, being limited to the abdomen/pelvis, but distant metastases can occur. Metastatic endometrial stromal sarcoma can occur many months to years after the original diagnosis or may present prior to the primary, potentially creating a diagnostic challenge. We report a bi-institutional review of 10 cases of endometrial stromal sarcoma with extrapelvic metastases without a prior history of endometriosis. The histologic, immunophenotypic, and molecular characteristics of these tumors are analyzed in the context of a relevant literature review.

Nitrofurantoin-associated bronchiolitis obliterans organizing pneumonia: report of a case.

Bronchiolitis obliterans organizing pneumonia due to nitrofurantoin has rarely been reported and is associated with poor outcomes. A case of nitrofurantoin-associated bronchiolitis obliterans organizing pneumonia responsive to drug withdrawal and corticosteroids is presented.