PIK3R1, HRAS and AR Gene Alterations Associated with Sclerosing Polycystic Adenoma of the Parotid Gland.

Sclerosing polycystic adenoma (SPA) is a rare neoplasm occurring in the salivary glands, mainly the parotid gland. Although it was originally thought to represent a non-neoplastic process, recent genetic data have proven its monoclonality, supporting its neoplastic origin. We report a case of a 73-year-old woman who presented with left neck swelling and pain. A 3 cm hypoechoic, heterogeneous, solid mass was identified on neck ultrasonography within the left parotid gland. Fine needle aspiration revealed benign acinar cells and lymphocytes. Left partial superficial parotidectomy was performed and a diagnosis of SPA was made. Targeted next-generation sequencing (NGS) revealed three clinically significant alterations in the PIK3R1, HRAS, and AR genes. Alterations in the PIK3R1 gene have been previously reported in cases of SPA; however, this study is the first to report two novel clinically significant genomic alterations in the HRAS and AR genes. AR protein expression by immunohistochemistry was strongly and diffusely positive in the neoplastic epithelial cells compared to the adjacent normal salivary gland tissue, which was dead negative for AR. This molecular profile will enhance our understanding of the molecular pathways underlying the development of this tumor. Although this entity was initially thought to be a reactive process, evidence from our case and similar cases strongly support the notion that it is neoplastic due to the presence of specific genetic alterations linked to it.

Clinical Significance of SOX10 Expression in Human Pathology.

The embryonic development of neural crest cells and subsequent tissue differentiation are intricately regulated by specific transcription factors. Among these, SOX10, a member of the SOX gene family, stands out. Located on chromosome 22q13, the SOX10 gene encodes a transcription factor crucial for the differentiation, migration, and maintenance of tissues derived from neural crest cells. It plays a pivotal role in developing various tissues, including the central and peripheral nervous systems, melanocytes, chondrocytes, and odontoblasts. Mutations in SOX10 have been associated with congenital disorders such as Waardenburg-Shah Syndrome, PCWH syndrome, and Kallman syndrome, underscoring its clinical significance. Furthermore, SOX10 is implicated in neural and neuroectodermal tumors, such as melanoma, malignant peripheral nerve sheath tumors (MPNSTs), and schwannomas, influencing processes like proliferation, migration, and differentiation. In mesenchymal tumors, SOX10 expression serves as a valuable marker for distinguishing between different tumor types. Additionally, SOX10 has been identified in various epithelial neoplasms, including breast, ovarian, salivary gland, nasopharyngeal, and bladder cancers, presenting itself as a potential diagnostic and prognostic marker. However, despite these associations, further research is imperative to elucidate its precise role in these malignancies.

Routine elastin staining improves venous invasion detection in colorectal carcinoma.

BACKGROUND: Colorectal carcinoma is the second most common cause of cancer-related deaths in North America. Invasion of tumor cells into lymphatic and blood vessels is an imperative step in the metastatic progression of colorectal carcinoma. OBJECTIVES: This is a before-and-after study conducted by the Department of Pathology and Laboratory Medicine of Mount Sinai Medical Center of Florida to assess the impact on venous invasion (VI) detection by implementing routine elastin staining on all tumor-containing blocks per case, where feasible, in colorectal carcinoma (CRC) resection specimens. METHODS: Clinicopathological parameters of CRC specimens were collected from January until December 2021 (n = 93) for the pre-implementation cohort and from January until December 2022 (n = 61) for the post-implementation cohort. RESULTS: VI detection was significantly increased in the post-implementation cohort at a rate of 50.8 % compared to only 18.6 % in the pre-implementation cohort. The majority of VI identified in the pre-implementation cohort was extramural (61.5 %), whereas in the post-implementation cohort it was intramural (41.9 %). On univariate analysis, implementation of routine elastin stain was associated with strikingly increased VI detection rates (OR = 4.5, p-value < 0.001). On multivariate analysis, after adjusting for other clinicopathologic variables, elastin staining retained its independent statistically significant impact on VI detection (OR = 2.6, p-value = 0.034). Of note, there were no significant differences in the pre- and post-implementation cohorts in the frequency of nodal metastases, tumor extent, histologic grade, perineural invasion, T stage or M stage. CONCLUSION: Based on our results and what has been published recently, we confirm an increase in the VI detection rate after implementing routine elastin staining on all tumor-containing blocks in CRC resection specimens.

The Usefulness of Elastin Staining to Detect Vascular Invasion in Cancer.

Tumor prognosis hinges on accurate cancer staging, a pivotal process influenced by the identification of lymphovascular invasion (LVI), i.e., blood vessel and lymphatic vessel invasion. Protocols by the College of American Pathologists (CAP) and the World Health Organization (WHO) have been established to assess LVI in various tumor types, including, but not limited to, breast cancer, colorectal cancer (CRC), pancreatic exocrine tumors, and thyroid carcinomas. The CAP refers to blood vessel invasion as "angioinvasion" (vascular invasion) to differentiate it from lymphatic vessel invasion (lymphatic invasion). For clarity, the latter terms will be used throughout this review. The presence of lymphatic and/or vascular invasion has emerged as a pivotal prognostic factor; therefore, its accurate identification is crucial not only for staging but also for providing the patient with an honest understanding of his/her prognosis. Given the prognostic importance of the correct identification of LVI, specific staining techniques are employed to distinguish lymphatic vessel invasion from angioinvasion and to differentiate true LVI from artifact. These encompass hematoxylin and eosin (H&E) staining, elastic staining, Factor VIII staining, Ulex europaeus I agglutinin staining, CD31, CD34, D2-40, ERG, and D2-40 (podoplanin) immunohistochemical (IHC) stains among others. Based on a review of numerous publications regarding the efficacy of various methods for LVI detection, elastin staining demonstrated superior accuracy and prognostic value, allowing for more targeted treatment strategies. The clinical significance of accurately detecting LVI cannot be overstated, as it is strongly linked to higher cancer-related mortality and an increased risk of tumor recurrence. This review aims to examine the existing literature on the use of elastin stains in the detection of vascular invasion among different types of tumors and its prognostic value.

Clinicopathological analysis of recurrence and progression of low-grade papillary urothelial carcinoma of the urinary bladder: Predicting the outcome.

BACKGROUND: Urothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined. OBJECTIVES: In our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC. METHODS: Using a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 258 patients included, 157 (60.9 %) had "no recurrence", 85 (32.9 %) had ≥1 "recurrence of LGPUC", and 16 (6.2 %) had "grade progression to HGPUC". The mean follow-up time was 31.5 ± 32 months. Patients with "grade progression" and "recurrence of LGPUC" had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with "no recurrence." Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively. CONCLUSION: Since the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.

Analysis of Genetic Alterations in Cutaneous Malignant Melanomas Unveils Unique Loco-Regional Variations and Novel Predictors of Metastatic Potential.

ABSTRACT: Cutaneous malignant melanoma is an aggressive cancer that contributes significantly to cancer-related mortality. Over the years, a deeper scrutiny of melanoma biology has led to identification of diverse evolutionary patterns involving various genetic pathways. This study attempts to further understand the genetic landscape of cutaneous malignant melanoma in terms of loco-regional variations and malignant potential. Thirty-five cases of cutaneous malignant melanoma were retrieved from the archives and were classified based on location of the primary tumor and presence or absence of metastatic disease. Next-generation sequencing data consisting of base substitutions, copy number variations, indels, and rearrangements in a total of 324 genes were analyzed for recurrent genetic alterations. Statistical analysis was performed using IBM SPSS26 software. Mutations in KDM gene family were found in 62.5% of the melanomas in the head and neck as compared with 10% in melanomas of the extremity and trunk (P = 0.03). Mutations in the RAS gene family were found in 70% of melanomas in the extremities as compared to 12.5% in melanomas of the head and neck (P = 0.003). BTK gene mutations were found exclusively in melanomas of the head and neck (P = 0.032). CREBBP mutations were seen in 50% of the nonmetastatic melanomas as compared with 3.57% of metastatic melanomas (P = 0.005). This study highlights the loco-regional variations in cutaneous malignant melanoma for genetic alterations involving the KDM, RAS, and BTK gene family. In addition, the CREBBP mutational status is identified as a potential prognostic marker for predicting metastatic potential in cutaneous malignant melanomas.

Bronchiolar adenomas (BA) - A detailed radio-pathologic analysis of six cases and review of literature.

Bronchiolar adenomas (BAs)/ciliated muco-nodular papillary tumors (CMPTs), are small, peripheral lung nodules arising predominantly in the elderly that follow a benign course. They can be mistaken for adenocarcinomas on frozen section. Immunohistochemistry (IHC) for basal cell markers highlights the continuous layer of basal cells underlying the tumor cells in BAs. BAs are further subdivided into proximal-type and distal type. Six BAs were retrieved from the pathology archives. The cases were classified based on morphology into proximal and distal BAs. The clinical and radiological features were reviewed. Immunohistochemistry and special stains were performed. The most common radiological picture of BA/CMPT was of a solid nodule with SUVmax < 3 as seen in 60% cases. 40% cases showed cavitation on CT. On histological examination, four cases were morphologically classified as proximal BAs and two as distal BAs. In proximal BAs, TTF1 was focally positive only in the basal cells in three of four. The mucin stained acidic. In distal BAs, TTF1 was diffusely positive in both basal and luminal cells. There was scant intracellular neutral mucin. Both the distal BAs had concomitant neuroendocrine tumors in the same lobe. Though the number of cases evaluated in this study is too low to be statistically significant, this study provides additional evidence to the concept of BA classification based on site specific histology and supplementary immunohistochemistry and reiterates the radiological features that may help distinguish it from malignant lesions.

Rising incidence of appendiceal neoplasms over time: Does pathological handling of appendectomy specimens play a role?

BACKGROUND: Appendectomy is the most common emergent surgical procedure. Primary appendiceal neoplasms are rare entities that are usually detected incidentally in less than 2% of all appendectomies. The increase in the incidence rates of appendiceal neoplasms over time raises the question whether there is an actual change in the disease occurrence or is it a matter of increased recognition and reporting of what would have been previously missed and undiagnosed. OBJECTIVES: In our study, we aimed to review the archived tissue specimens of patients who were diagnosed with appendiceal neoplasms during the past decade at our institution and compare our clinical experience with published data to identify possible reasons that contribute to the increase in incidence rates of such neoplasms over the past few years. METHODS: Using a pathological database of surgical specimens from patients who underwent appendectomies between January 01, 2010 and September 30, 2020 at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 1568 patients included, 102 (6.5%) had appendiceal neoplasms divided between primary (79.4%) and secondary/metastatic (20.6%) neoplasms. Annual incidence of appendiceal neoplasms over the past 10 years in our institution demonstrated an increasing trend from 5.6% in 2010 to 12.7% in 2020, which we hypothesize might be attributed to submitting more representative sections of the appendix for pathological examination than we had previously. Our results also showed that 2.8% of patients initially presenting with a typical clinical picture of acute appendicitis had appendiceal neoplasms as a truly incidental finding, while 20.3% of patients who underwent elective appendectomies for a suspicious appendiceal mass were found to be neoplastic. Interestingly, among the 80 cases of epithelial neoplasms, more non-carcinoid neoplasms were detected than carcinoid tumors. CONCLUSION: Based on our results and what has been published recently, we confirm an additional increase in incidental appendiceal neoplasms found in appendectomies performed for a clinical picture of acute appendicitis, which may be related to more thorough specimen assessment. Whether this is clinically impactful remains to be determined. However, these data support a modification in the way appendectomy specimens are handled in pathology labs post-operatively.

Morphological and immunophenotypical analysis of the spindle cell component in adenomyomatous hyperplasia of the gallbladder.

BACKGROUND: Adenomyomatous hyperplasia (AMH) of the gallbladder, reported in 1-8.7% of cholecystectomies, consists of cystically dilated sinuses/glands with a surrounding spindle cell proliferation which is thought to be composed of smooth muscle cells. Myofibroblasts are contractile cells that secrete a variety of biochemical modulators causing a "field-effect". Myofibroblasts can be immunohistochemically distinguished from smooth muscle cells by their desmin negativity. METHODS: Eighteen cases of AMH and five cases each of chronic follicular cholecystitis, chronic cholecystitis, gallbladder carcinoma and 10 colonic diverticular disease were stained with actin and desmin. The percentage of myofibroblasts was estimated by the difference between actin and desmin staining in the same field. Statistical anlysis was performed using SPSS 22.0. RESULTS: The percentage of actin staining was significantly higher in AMH and gallbladder carcinoma compared to chronic follicular and chronic cholecystitis (p = 0.04). The percentage of desmin staining did not show any significant difference between the four groups. The estimated myofibroblastic population was significantly higher in AMH when compared to chronic follicular and chronic cholecystitis (p = 0.005). CONCLUSION: The spindle cell proliferation around cystically dilated glands in AMH is composed predominantly of myofibroblasts and of smooth muscle cells as previously described. This finding suggest a derangement in epithelial-stromal interactions as the underlying pathophysiology in AMH.

Clinical, histopathologic, and immunoarchitectural features of dermatopathic lymphadenopathy: an update.

Dermatopathic lymphadenopathy is a distinctive form of paracortical lymph node hyperplasia that usually occurs in the setting of chronic dermatologic disorders. The aim of this study is to update our understanding of the clinicopathologic and immunophenotypic features of dermatopathic lymphadenopathy. The study cohort was 50 lymph node samples from 42 patients diagnosed with dermatopathic lymphadenopathy. The patients included 29 women and 13 men with a median age of 49 years (range, 12-79). Twenty-two (52%) patients had a dermatologic disorder, including mycosis fungoides (n = 6), chronic inflammatory dermatoses (n = 13), melanoma (n = 1), squamous cell carcinoma (n = 1), and Kaposi sarcoma in the context of human immunodeficiency virus infection (n = 1). Twenty (48%) patients did not have dermatologic manifestations. Lymph node biopsy specimens were axillary (n = 22), inguinal (n = 21), cervical (n = 4), and intramammary (n = 3). All lymph nodes showed paracortical areas expanded by lymphocytes; dendritic cells, including interdigitating dendritic cells and Langerhans cells; and macrophages. Melanophages were detected in 48 (98%) lymph nodes. Immunohistochemical analysis provided results that are somewhat different from those previously reported in the literature. In the paracortical areas of lymph node, S100 protein was expressed in virtually all dendritic cells, and CD1a was expressed in a significantly greater percentage of cells than langerin (80 vs. 35%, p < 0.0001). These results suggest that the paracortical regions of dermatopathic lymphadenopathy harbor at least three immunophenotypic subsets of dendritic cells: Langerhans cells (S100+, CD1a+(high), langerin+), interdigitating dendritic cells (S100+, CD1a+(low), langerin-), and a third (S100+, CD1a-, langerin-) minor population of dendritic cells. Furthermore, in more than 60% of dermatopathic lymph nodes, langerin highlighted trabecular and medullary sinuses and cords, showing a linear and reticular staining pattern, which could be a pitfall in the differential diagnosis with Langerhans cell histiocytosis involving lymph nodes.

Understanding the histogenesis of a HRAS-PIK3R1 co-driven metastatic metaplastic breast carcinoma associated with squamous metaplasia of lactiferous ducts.

Metaplastic breast carcinoma (MBC) represents a heterogeneous group of aggressive primary breast cancers that can show differentiation into carcinomatous and sarcomatous elements. Due to its rapid growth, this malignancy can replace precursor lesions, which remain unknown in most cases. Herein, we describe a MBC presenting as a deceptive post-biopsy hematoma. Histopathological and immunohistochemical evaluation of the primary tumor revealed a squamous cell carcinoma arising in a background of squamous metaplasia of lactiferous ducts (SMOLD). In the absence of ductal carcinoma in situ, we consider SMOLD as a nonobligatory precursor of MBC. The tumor showed 'dedifferentiation' into spindle, mucin-producing, osteoclast-like giant cell and fibromatosis-like carcinoma. Next-generation sequencing revealed the driver mutations HRASQ61R and PIK3R1c.1738_1745+2del in addition to MYH11S638L and amplification of ERCC5 and FGF14, which were potential contributors to tumor phenotype. Tumor dedifferentiation was probably facilitated by epithelial-to-mesenchymal transition (EMT) with aberrant expression of platelet and endothelial adhesion molecule-1, leading to early metastasis via hematogenous route rather than lymphatic. The co-occurrence of phosphoinositide 3-kinase and mitogen-activated protein kinase pathway abnormalities along with EMT could mediate divergent growth in breast cancer.

Primary sebaceous carcinoma of the male breast: Case report and review of literature.

Primary sebaceous carcinoma of the breast is an exceedingly uncommon neoplasm that is defined as primary invasive carcinoma of the breast with sebaceous differentiation in more than 50% of cells. All confirmed cases have been reported in women. Herein, we report the case of a 70-year-old man with a primary sebaceous breast carcinoma, the first unequivocal case to be reported thus far in a man.

Severe Myocardial Steatosis: Incidental Finding or a Significant Anatomic Substrate for Sudden Cardiac Arrest?

Myocardial steatosis, also known as lipomatosis cordis, is characterized by adipose tissue within the myocardium without significant fibrosis. Evidence suggests that accumulation of fat can disturb the normal electromechanical physiology of the myocardium. Herein, we discuss the case of a 60-year-old woman with a history of chronic obstructive pulmonary disease who died because of anoxic encephalopathy after a sudden cardiac arrest (SCA). An electrocardiogram showed QRS fragmentation noted as notched R in inferior leads. The autopsy revealed a very small thromboembolus in a distal subsegmental branch of the pulmonary artery, which could not explain the SCA. There was an extensive intramyocardial accumulation of adipose tissue involving the right ventricle and interventricular septum, which split the myocardium into discrete bundles. Arrhythmogenic right ventricular cardiomyopathy was ruled out based on the absence of typical fibrofatty changes. The mechanism of fat replacement was likely secondary to redistribution of visceral fat in the setting of Cushing syndrome. We propose that severe myocardial steatosis can create an anatomic substrate to facilitate the development of SCA. Myocardial steatosis should be reported to identify patients who are at risk for developing cardiovascular events secondary to extreme cardiac adiposity.

Tracheal agenesis with esophageal atresia: an autopsy case report of a variant incompatible with life.

Background: Tracheal agenesis/atresia (TA) presents with respiratory distress at birth and subsequent difficulty in endotracheal intubation. The antenatal course is complicated by polyhydramnios and premature labor. Case report: We present a newborn baby boy with respiratory distress and unsuccessful intubation. Postmortem neck dissection revealed tracheal atresia with esophageal atresia and high tracheoesophageal fistula. Conclusion: In this variant of tracheal atresia, the coexistent esophageal atresia precluded the establishment of a functional air passage. This variant that does not fall into the any of the described categories in accepted classification systems. The lack of any distal communication makes this case inoperable and fatal.

NRF1 motif sequence-enriched genes involved in ER/PR -ve HER2 +ve breast cancer signaling pathways.

Nuclear respiratory factor 1 (NRF1) transcription factor has recently been shown to control breast cancer progression. However, mechanistic aspects by which NRF1 may contribute to susceptibility to different breast tumor subtypes are still not fully understood. Since transcriptional control of NRF1 seems to be dependent on epidermal growth factor receptor signaling, herein, we investigated the role of NRF1 in estrogen receptor/progesterone receptor negative, but human epidermal growth factor receptor 2-positive (ER/PR -ve HER2 +ve) breast cancer. We found that both mRNA and protein levels of NRF1 and its transcriptional activity were significantly higher in ER/PR -ve HER2 +ve breast cancer samples compared to normal breast tissues. This was consistent with our observation of higher NRF1 protein expression in the experimental model of HER2+ breast cancer brain metastasis. To identify network-based pathways involved in the susceptibility to the ER/PR -ve HER2 +ve breast cancer subtype, the NRF1 transcriptional regulatory genome-wide landscape was analyzed using the approach consisting of a systematic integration of ChIP DNA-seq, RNA-Microarray, NRF1 protein-DNA motif binding, signal pathway analysis, and Bayesian machine learning. Our findings show that a high percentage of known HER2+ breast cancer susceptibility genes, including EGFR, IGFR, and E2F1, are under transcriptional control of NRF1. Promoters of several genes from the KEGG HER2+ breast cancer pathway and 11 signaling pathways linked to 6 hallmarks of cancer contain the NRF1 motif. By pathway analysis, key breast cancer hallmark genes of epithelial-mesenchymal transition, stemness, cell apoptosis, cell cycle regulation, chromosomal integrity, and DNA damage/repair were highly enriched with NRF1 motifs. In addition, we found using Bayesian network-based machine learning that 30 NRF1 motif-enriched genes including growth factor receptors-FGFR1, IGF1R; E2Fs transcription factor family-E2F1, E2F3; MAPK pathway-SHC2, GRB2, MAPK1; PI3K-AKT-mTOR signaling pathway-PIK3CD, PIK3R1, PIK3R3, RPS6KB2; WNT signaling pathway-WNT7B, DLV1, DLV2, GSK3B, NRF1, and DDB2, known for its role in DNA repair and involvement in early events associated with metastatic progression of breast cancer cells, were associated with HER2-amplified breast cancer. Machine learning search further revealed that the likelihood of HER2-positive breast cancer is almost 100% in a patient with the high NRF1 expression combined with expression patterns of high E2F3, GSK3B, and MAPK1, low or no change in E2F1 and FGFR1, and high or no change in PIK3R3. In summary, our findings suggest novel roles of NRF1 and its regulatory networks in susceptibility to the ER/PR -ve HER2 +ve aggressive breast cancer subtype. Clinical confirmation of our machine learned Bayesian networks will have significant impact on our understanding of the role of NRF1 as a valuable biomarker for breast cancer diagnosis and prognosis as well as provide strong rationale for future studies to develop NRF1 signaling-based therapeutics to target HER2+ breast cancer.

Cholangitis Lenta Causing Bile Cast Nephropathy: A Unique Model of Hepatorenal Failure in Sepsis.

INTRODUCTION: Inadequate perfusion and abnormal cellular metabolism are among the mechanisms of organ dysfunction in sepsis. Concomitant hepatorenal failure during the late phase of sepsis is poorly understood. CASE REPORT: The autopsy of a child who developed sepsis-induced hepatorenal failure revealed bile cast nephropathy, hepatic centrilobular necrosis and cholangitis lenta, a type of sepsis-induced cholestasis, with no biliary obstruction, fibrosis or cirrhosis. The liver and renal function declined at the same rate as procalcitonin increased. DISCUSSION: Failure of resolution and persistent inflammation in sepsis can result in ductular injury and stagnation of bile with subsequent cholemia. The kidney failure was associated with the formation of intratubular bile casts. CONCLUSION: This case illustrates how severe cholestasis in combination with bile cast nephropathy may be potential and unrecognized contributors to hepatorenal failure in sepsis. Whether bile toxicity causes renal failure in the context of cholangitis lenta should be further studied.

Constitutive Notch Signaling Causes Abnormal Development of the Oviducts, Abnormal Angiogenesis, and Cyst Formation in Mouse Female Reproductive Tract.

The Notch signaling pathway is critical for the differentiation of many tissues and organs in the embryo. To study the consequences of Notch1 gain-of-function signaling on female reproductive tract development, we used a cre-loxP strategy and Amhr2-cre transgene to generate mice with conditionally activated Notch1 (Rosa(Notch1)). The Amhr2-cre transgene is expressed in the mesenchyme of developing female reproductive tract and in granulosa cells in the ovary. Double transgenic Amhr2-cre, Rosa(Notch1) females were infertile, whereas control Rosa(Notch1) mice had normal fertility. All female reproductive organs in mutants showed hemorrhaging of blood vessels progressing with age. The mutant oviducts did not develop coiling, and were instead looped around the ovary. There were multiple blockages in the lumen along the oviduct length, creating a barrier for sperm or oocyte passage. Mutant females demonstrated inflamed uteri with increased vascularization and an influx of inflammatory cells. Additionally, older females developed ovarian, oviductal, and uterine cysts. The significant change in gene expression was detected in the mutant oviduct expression of Wnt4, essential for female reproductive tract development. Similar oviductal phenotypes have been detected previously in mice with activated Smo and in beta-catenin, Wnt4, Wnt7a, and Dicer conditional knockouts, indicating a common regulatory pathway disrupted by these genetic abnormalities.

Comparison of Performance Characteristics of Oval Cup Forceps Versus Serrated Jaw Forceps in Gastric Biopsy.

BACKGROUND: Obtaining quality endoscopic biopsy specimens is vital in making successful histological diagnoses. The influence of forceps cup shape and size on quality of biopsy specimens is unclear. AIM: To identify whether oval cup or two different serrated jaw biopsy forceps could obtain specimens of superior size. Secondary endpoints were tissue adequacy, depth of tissue acquisition, and crush artifact. METHODS: A single-center, prospective, pathologist-masked, randomized controlled trial was performed. In total 136 patients with a clinical indication for esophagogastroduodenoscopy with biopsy were randomized to receive serial biopsies with a large-capacity serrated forceps with jaw diameter 2.2 mm (SER1) and either a large-capacity oval forceps with jaw diameter 2.4 mm (OVL) or large-capacity serrated biopsy forceps with jaw diameter 2.4 mm (SER2) in two parallel groups. RESULTS: SER2 provided significantly larger specimens than did the other forceps (SER2 3.26 ± 1.09 vs. SER1 2.92 ± 0.88 vs. OVL 2.92 ± 0.76; p = 0.026), with an average size difference of 0.34 mm greater with SER2 compared to SER1 and OVL. OVL provided significantly deeper biopsies compared to SER1 and SER2 (p = 0.02), with 31 % of OVL biopsies reaching the submucosa. SER2 had significantly less crush artifact than SER1 and OVL (p < 0.0001). CONCLUSION: Serrated forceps provided larger samples compared to oval jaw forceps of the same size, with SER2 providing the largest specimen size. Oval cup forceps had deeper penetration of epithelium, while the larger jaw diameter serrated jaw forceps had less crush artifact. All three forceps provided specimens adequate for diagnostic purposes.