Clinicopathologic features and diagnostic challenges of small cluster pattern appendiceal neuroendocrine tumors.

Appendiceal neuroendocrine neoplasms (NENs) can present with various growth patterns including the traditional triad of histologic patterns-insular, trabecular and tubular. A small cluster pattern was also found in this study and the literature on this specific morphology is limited. In this study, we conducted a comprehensive review of appendiceal NENs from our institution over a ten-year period. Clinical and demographic data were obtained from medical records. Immunohistochemical stains were performed with antibodies specific for synaptophysin, chromogranin, INSM1, CD56, serotonin and peptide YY. The small cluster pattern was found in 29.4 % of all cases evaluated. The tumor cells in these cases were predominantly located at the distal tip of the appendix, associated with fibrous obliteration. These tumors were smaller in size and tended towards less advanced tumor stage, with reduced incidence of lymphovascular and/or perineural invasion. Chromogranin expression was identified in 76 % of these cases. There is a heterogeneous hormone profile with 46.7 % serotonin and 33.3 % peptide YY. In conclusion, the small cluster pattern NENs present with unique histological features and hormone expression profile. Among the various neuroendocrine markers, INSM1 showed superior diagnostic performance, with high sensitivity and minimal non-specific staining.

Mast cell infiltration and activation in the gallbladder wall: Implications for the pathogenesis of functional gallbladder disorder in adult patients.

BACKGROUND: Functional gallbladder disorder (FGD) is characterized by recurrent biliary colic with a decreased gallbladder ejection fraction on cholescintigraphy but absence of visible gallbladder abnormalities on ultrasonography. FGD is generally regarded as a primary gallbladder motility disturbance, however, the underlying pathophysiology remains largely unknown. In this study, we investigated the potential role of mast cells in the pathogenesis of FGD by examining mast cell density and activation in the gallbladder wall. DESIGN: Twenty adult patients with FGD undergoing cholecystectomy were included in the study. Seven patients with no gallbladder disease were served as controls who were subject to incidental cholecystectomy during abdominal surgery such as partial hepatectomy. The density of mast cells in the gallbladder wall was assessed by immunohistochemistry and by toluidine blue special stain. Mast cell activation was evaluated by calculating the percentage of degranulated mast cells on toluidine blue stain. RESULTS: Compared to the controls, patients with FGD showed a significant increase in mast cell infiltration in the gallbladder walls. Peak mast cell accumulation was predominantly located in the inner muscular layer of the gallbladder wall. Mast cell activation was also markedly increased in the FGD group as evidenced by significantly enhanced mast cell degranulation. CONCLUSIONS: Mast cell infiltration and activation were significantly increased in the muscular wall of gallbladders from FGD patients, suggesting potential involvement of mast cells in the compromised gallbladder motility in adult patients with FGD.

Outcomes using a single tapered dilator for Micra leadless pacemaker implant.

OBJECTIVES: Comparison of outcomes, device deployment time (DT), and total time (TT) using a single tapered Coons dilator versus sequential serial dilation for implantation of the Micra leadless pacemaker. BACKGROUND: Micra leadless pacemaker placement requires a 23 French Micra introducer sheath (MIS) for percutaneous delivery. We sought to evaluate outcomes with use of a single tapered Coons dilator (CD) versus sequential serial dilatation (SD) method to facilitate insertion of the Micra introducer sheath. METHODS: 35 patients were included in the SD arm and 49 in the CD arm. DT and TT were recorded in minutes and cost in dollars. Analysis was performed using independent t-test between two groups and one-way ANOVA to evaluate inter-operator variability in the CD arm. RESULTS: Both DT and TT were significantly lower for the CD arm (15.1 ± 5.1 vs 23.5 ± 9.3, p < 0.0005 and 29.9 ± 14 vs 39.3 ± 13.5 min, p = 0.000374; respectively). The cost was also significantly lower using a CD versus SD. There was no inter-operator variability in the CD arm between 6 operators (p = 0.177 for DT and p = 0.304 for TT). No complications occurred in the SD arm. There were 3 vascular access site complications in the CD arm, all of which occurred early in the operator's experience. CONCLUSION: Coons dilator is an efficient and cost-effective method for vascular dilatation to facilitate Micra leadless pacemaker insertion. Rate of complications is low and expected to improve with greater experience.

Confined Low Grade Appendiceal Mucinous Neoplasm With Coexisting Distant Metastasis.

BACKGROUND/AIM: Appendiceal mucinous neoplasms (AMNs) are tumors with dysplastic mucinous epithelium, a pushing growth pattern but no infiltrative invasion to the appendiceal wall. Some AMNs are associated with pseudomyxoma peritonei, characterized by intraperitoneal mucinous involvement. Recent studies have demonstrated that LAMNs confined to the appendix have low or no risk for disease recurrence, progression, and peritoneal involvement during follow up. CASE REPORT: Here, we present two extremely rare cases with confined low grade appendiceal mucinous neoplasm (pTis and pT3) and simultaneous extraperitoneal subcutaneous or ovary involvement at the time of diagnosis. CONCLUSION: Our cases demonstrate that although the primary tumor is limited to the appendix, coexisting distant metastasis may occur on very rare occasions.

The Angiopoietin Signaling Pathway Is Involved in Inflammatory Processes in Hospitalized COVID-19 Patients.

The viral agent SARS-CoV-2 clearly affects several organ systems, including the cardiovascular system. Angiopoietins are involved in vascular integrity and angiogenesis. Angiopoietin-1 (Ang1) promotes vessel stabilization, while angiopoietin-2 (Ang2), which is usually expressed at low levels, is significantly elevated in inflammatory and angiogenic conditions. Interleukin-6 (IL-6) is known to induce defective angiogenesis via the activation of the Ang2 pathway. Vasculitis and vasculopathy are some of the defining features of moderate to severe COVID-19-associated systemic disease. We investigated the serum levels of angiopoietins, as well as interleukin-6 levels and anti-SARS-CoV2 IgG titers, in hospitalized COVID-19 patients across disease severity and healthy controls. Ang2 levels were elevated in COVID-19 patients across all severity compared to healthy controls, while Ang1 levels were decreased. The patients with adverse outcomes (death and/or prolonged hospitalization) had relatively lower and stable Ang1 levels but continuously elevated Ang2 levels, while those who had no adverse outcomes had increasing levels of both Ang1 and Ang2, followed by a decrease in both. These results suggest that the dynamic levels of Ang1 and Ang2 during the clinical course may predict adverse outcomes in COVID-19 patients. Ang1 seems to play an important role in controlling Ang2-related inflammatory mechanisms in COVID-19 patients. IL-6 and anti-SARS-CoV2 spike protein IgG levels were significantly elevated in patients with severe disease. Our findings represent an informative pilot assessment into the role of the angiopoietin signaling pathway in the inflammatory response in COVID-19.

Russell Body Gastroesophagitis Concurrent With Barrett's Esophagus.

BACKGROUND: Russell body gastroesophagitis is a rare entity characterized by the accumulation of immunoglobulins within the cytoplasm of plasma cells. CASE REPORT: Here, we present the case of a 41-year-old male with history of gastroesophageal reflux disease who presented with nausea, vomiting, and altered mental status. Candida esophagitis was noted on upper endoscopy. After treatment, a surveillance endoscopy revealed salmon colored mucosa in the distal esophagus and mild gastric erythema. The biopsy confirmed Barrett's esophagus that was negative for dysplasia and mild chronic inactive gastritis. Interestingly, diffusely infiltrating Russell body-containing plasma cells (Mott cells) were present in the distal esophagus and extending into the gastric cardia. The Mott cells were highlighted on CD138 immunostaining and Periodic acid-Schiff stain. Immunostaining for cytokeratin AE1/AE3 was negative. There was no evidence of Helicobacter pylori organisms on the gastric mucosa. CONCLUSION: This is the first report on Russell body-containing plasma cells diffusely involving both esophagus and gastric cardia with concurrent Barrett's esophagus.

Rapid Sarcomatoid Transformation of Lung Squamous Cell Carcinoma After Neoadjuvant Therapy: A Case Report.

Pulmonary sarcomatoid carcinoma is a rare variant of non-small cell lung cancer. Here, we report on the case of a 67-year-old male with a diagnosis of biopsy-proven moderately differentiated squamous cell carcinoma of the left lower lobe of the lung. The tumor cells on biopsy had epithelioid morphology with strong immunoreactivity for CK7 and p40. The mass was surgically removed one year later due to its poor response to stereotactic radiotherapy and chemotherapy. The lobectomy specimen revealed pleomorphic mitotically active spindle cell neoplasm with scattered foci of epithelial component. The tumor cells showed diffuse immunopositivity for vimentin, as well as focal immunoreactivity for CK7, p40 and S100 in the epithelial component. To the best of our knowledge, this is the first documented case of histopathologic sarcomatoid transformation of lung squamous cell carcinoma after neoadjuvant therapy. The clinical course, diagnosis and a review of literature are presented.

In-Hospital Outcomes and Trends of Tricuspid Valve Surgery in Heart Transplant Patients.

INTRODUCTION: Tricuspid valve (TV) regurgitation is the most common valvular pathology after orthotopic heart transplant (OHT). The number of transplants being performed is increasing with patients living longer after heart transplant. Data on TV surgery in OHT recipients is limited. METHODS: We sought to analyze the outcomes of patients undergoing TV surgery from a large diverse, multicentric, nationwide cohort using the Nationwide Inpatient Sample (NIS) database. RESULTS: A total of 42,766 TV repair or replacement (bioprosthetic and mechanical) involving adult patients (age ≥18 years) between 2007 and September 2015 were identified. Of these, 366 were performed in patients with OHT. TV repair was the most common surgery performed in both groups (OHT group and native heart group). Compared to the native group, patients with OHT had a significantly higher incidence of cardiogenic shock (20 vs. 11%, p = 0.024), acute kidney injury (AKI) (59 vs. 30%, p < 0.001), and AKI requiring hemodialysis (13 vs. 4%, p < 0.001). Also, the mean length of stay for the index admission was significantly longer in the OHT group (27 vs. 17 days, p = 0.008). The mortality rate was similar between the two groups (7 vs. 8%, p = 0.753). The number of TV surgeries performed in OHT patients from 2007 to 2014 have remained stable (p = 0.803) compared to those in native heart patients which showed a significantly increasing trend (p = 0.019) during the same time period. CONCLUSIONS: TV surgery remains an important treatment modality among the OHT population and carries a similar mortality during index hospitalization as that in native heart patients undergoing TV surgery.