Postoperative Polyp Scale (POPS): Development of a New Sinonasal Polyp Grading Scale.

OBJECTIVE: Commonly used endoscopic grading scales, such as the nasal polyp scale, inadequately describe the degree of polyposis found postoperatively in the paranasal sinus cavities. The purpose of this study was to create a novel grading system that more accurately characterizes polyp recurrence in postoperative sinus cavities, the Postoperative Polyp Scale (POPS). METHODS: A modified Delphi method was utilized to establish the POPS using consensus opinion among 13 general otolaryngologists, rhinologists, and allergists. Postoperative endoscopy videos from 50 patients with chronic rhinosinusitis with nasal polyps were reviewed by 7 fellowship-trained rhinologists and scored according to the POPS. Videos were rated again 1 month later by the same reviewers, and scores were assessed for test-retest and inter-rater reliability. RESULTS: Overall inter-rater reliability for the first and second reviews of the 52 videos was Kf = 0.49 (95% CI 0.42-0.57) and Kf = 0.50 (95% CI 0.42-0.57) for the POPS. Intra-rater reliability showed near-perfect test-retest reliability for the POPS with Kf = 0.80 (95% CI 0.76-0.84). CONCLUSION: The POPS is an easy-to-use, reliable, and novel objective endoscopic grading scale that more accurately describes polyp recurrence in the postoperative state which will be useful in the future for measuring the efficacy of various medical and surgical interventions. LEVEL OF EVIDENCE: 5 Laryngoscope, 133:2885-2890, 2023.

Glycogenic hepatopathy is associated with type 1 diabetes mellitus in only a minority of cases in a contemporary adult population.

OBJECTIVES: This study examines the clinical-pathological profiles of patients with glycogenic hepatopathy in a contemporary cohort of patients at an adult acute care hospital. METHODS: Liver biopsies with glycogenic hepatopathy were retrieved from the departmental surgical pathology database, the histological findings were studied, and the clinical findings were reviewed. RESULTS: Five cases of glycogenic hepatopathy were found, including cases associated with type 1 diabetes mellitus (n = 1), type 2 diabetes mellitus (n = 1), corticosteroids (n = 2), and anorexia (n = 2, including the patient with type 1 diabetes). AST and ALT were normal to mildly elevated (13-115 U/L and 7-126 U/L, respectively). Trace ascites was present in two patients. Hepatomegaly was only present in the patient with type 1 diabetes at the time of diagnosis. CONCLUSIONS: Four of five cases were associated with etiologies other than type 1 diabetes, which is widely reported as the most common etiology of glycogenic hepatopathy. This study suggests that etiologies currently only rarely recognized may actually be more common causes of glycogenic hepatopathy than type 1 diabetes in a contemporary adult population. It is important not only to recognize that these rarely reported causes of glycogenic hepatopathy may be underrecognized, but that the clinical presentation may also be mild.

Claudin-18.

CONTEXT.­: Claudin-18 is expressed in some gastric cancers. Clinical trials are evaluating it as a therapeutic target. OBJECTIVES.­: To evaluate claudin-18 expression in intestinal metaplasia, dysplasia, and adenocarcinoma of the distal esophagus/gastroesophageal junction and stomach and to evaluate claudin-18 expression in gastric and nongastric neuroendocrine tumors as a marker of gastric origin. DESIGN.­: Samples included gastroesophageal junction with intestinal metaplasia (n = 40), dysplasia (n = 54), and adenocarcinoma (n = 20) and stomach with intestinal metaplasia (n = 79), dysplasia (n = 43), and adenocarcinoma (n = 25). Additionally, gastric (n = 40) and nongastric (n = 322) neuroendocrine tumors were included. Claudin-18 expression was evaluated for any staining as positive and by meeting clinical trial inclusion criteria (≥2+ intensity in ≥50% of tumor). RESULTS.­: Claudin-18 staining was not significantly different across dysplasia categories in the gastroesophageal junction (P = .11) or stomach (P = .12). The rate of positive staining was higher in gastroesophageal junction than stomach for intestinal metaplasia (37 of 40 [92.5%] versus 37 of 79 [46.8%]; P < .001) and high-grade dysplasia (33 of 38 [86.8%] versus 9 of 16 [56.3%]; P = .03). Intestinal metaplasia showed staining in 7 of 37 autoimmune gastritis samples (18.9%) compared with 30 of 42 samples without autoimmune gastritis (71.4%) (P < .001). Adenocarcinoma showed similar staining in gastroesophageal junction (15 of 20; 75.0%) and stomach (17 of 25; 68.0%) (P = .85). Eighty percent (32 of 40) of gastric neuroendocrine tumors were positive for claudin-18 expression, with 57.5% (23 of 40) meeting clinical trial inclusion criteria. Comparatively, 0.62% (2 of 322) of nongastric neuroendocrine tumors showed staining (P < .001). CONCLUSIONS.­: Claudin-18 staining was similar in intestinal metaplasia, dysplasia, and adenocarcinoma. Claudin-18 was negative in most cases of intestinal metaplasia in autoimmune gastritis, indicating that intestinal metaplasia in this setting may differ from other forms. Claudin-18 was sensitive and specific for gastric origin in neuroendocrine tumors.

Evaluation of tumor mutational burden in small early hepatocellular carcinoma and progressed hepatocellular carcinoma.

While researchers know that tumor mutational burden (TMB) is low in hepatocellular carcinoma (HCC), prior studies have not investigated TMB in cirrhosis, small early HCC and progressed HCC. HCC (n = 18) and cirrhosis (n = 6) cases were identified. TMB was determined by a 1.7 megabase, 409-gene next-generation sequencing panel. TMB values were defined as the number of nonsynonymous variants per megabase of sequence. There was no significant difference between cirrhosis versus small early HCC or between cohorts when stratified by size, early versus progressed, differentiation or morphology. There was a significant difference between cirrhosis and small early HCC versus progressed HCC (p = 0.045), suggesting TMB may be related to HCC progression. TMB similarities in small early HCC and background cirrhosis suggest TMB is not a useful tool for diagnosing small early HCC. Additional study is needed to address TMB in histological and molecular subsets of HCC.

Clinico-pathologic findings in patients with median arcuate ligament syndrome (celiac artery compression syndrome).

Median Arcuate Ligament Syndrome (MALS) is a rare entity characterized by severe post-prandial epigastric pain, nausea, vomiting, and/or weight loss. Symptoms have been attributed to vascular compression (celiac artery compression syndrome, CACS), but it remains controversial whether they could be secondary to neural compression. Literature review identified rare description of pathologic findings in surgery journals. The clinico-pathologic findings of four MALS patients who underwent robotic or laparoscopic surgery in our hospital are described. All our patients were female with a median age of 32.5 (range 25-55 years), and a median BMI of 23.5 kg/m2. They presented with chronic often post-prandial abdominal pain (4/4), nausea (3/4), emesis (2/4), anorexia (1/4), and weight loss (1/4). Two patients had a history of Crohn's disease. At intraoperative exploration, the celiac artery and adjacent nerves and ganglia were encased and partially compressed by fibrotic tissue in each patient. In each case laparoscopic excision of fibrotic tissue, celiac plexus and ligament division and was performed; celiac plexus nerve block was also performed in one patient. After surgical intervention, symptoms improved in three of the patients whose specimens show periganglionic and perineural fibrosis with proliferation of small nerve fibers. Our findings support neurogenic compression as a contributing factor in the development of pain and other MALS symptoms, and favor the use of MALS rather than CACS as diagnostic terminology. To further study the pathogenesis of this unusual syndrome, surgeons should submit all tissues excised during MALS procedures for histopathologic examination.

Lymphogranuloma venereum (LGV) of the anorectum: evaluation of clinicopathological associations and the utility of a novel RNA in-situ hybridisation stain.

AIMS: Recent studies from multiple global regions have reported a resurgence of lymphogranuloma venereum (LGV) proctitis, which is caused by Chlamydia trachomatis (CT). LGV proctitis is histologically indistinguishable from other forms of sexually transmitted proctitis and is difficult to differentiate from inflammatory bowel disease. While immunohistochemical stains are available for syphilis, there is no commonly available stain for the tissue identification of CT. MATERIALS AND METHODS: From 200 positive CT nucleic acid tests (NAT) from anorectal swabs, we identified 12 patients with biopsies collected from the distal colorectum or anus within 90 days of the positive NAT. We collected basic demographic information and tabulated clinical and histological findings. We examined the performance of a novel RNA in-situ hybridisation (ISH) stain targeting CT 23s rRNA on these 12 cases and 10 controls from the anorectum. RESULTS: All 12 patients were male; nine were HIV+, two had concurrent gonococcal infection, one had concurrent syphilis and one had cytomegalovirus co-infection. The majority of biopsies (11 of 12) showed mild or moderate acute inflammation, had a prominent lymphoplasmacytic infiltrate (eight of 11) and lacked marked crypt distortion (10 of 10). The RNA ISH stain was positive in 10 of 12 cases (sensitivity 83%). One case showed equivocal staining. No controls showed definitive positive staining (specificity 100%). One had equivocal staining. CONCLUSION: Our series showed that anorectal LGV had similar histological findings to those of prior STI proctitis series predominantly comprised of syphilis. The novel RNA ISH stain was sensitive and specific and may show utility in differentiating types of STI proctitis.

Ovarian mucinous neoplasms, intestinal type, in premenopausal patients, develop in abnormal ovaries.

Although several studies have addressed different aspects of mucinous neoplasms arising in the ovary, such as their clinicopathologic features, immunohistochemical profile, and molecular characteristics, no study has presented an analysis of the ovarian tissue where these neoplasms arise. In this study, we included 196 cases of intestinal-type ovarian mucinous neoplasms in premenopausal patients. Our main goal was to perform a rigorous examination of the ovarian tissue surrounding these neoplasms. We also reviewed the clinicopathologic features of these cases. For comparison, the background ovarian tissue in 85 cases of ovarian serous neoplasm and in 29 cases of metastatic neoplasms to the ovary, as well as 57 normal ovaries, was examined. All the patients in this study, which included those with mucinous and with serous neoplasms primary in the ovary, those with metastatic tumors to the ovaries, and those with normal ovaries, were also premenopausal. Patients affected by ovarian mucinous neoplasms ranged in age from 13 to 52 years (median = 36 years). Nulligravidity was seen in 50%, 32%, and 22% of patients with mucinous carcinomas, mucinous borderline neoplasms, and mucinous cystadenomas, respectively. Ovarian mucinous intestinal neoplasms arise in abnormal ovaries characterized by two important features: (1) an abnormal ovarian cortex, seen in 95% of the cases, which is hypocellular or with no distinction between the cellular cortex and medulla, and (2) a remarkable paucity of primordial follicles. The abnormalities detected in the background ovarian tissue might provide insights into the tumorigenesis of these neoplasms and might facilitate their distinction from metastasis to the ovary, in premenopausal patients.

Low-Grade Appendiceal Mucinous Neoplasms: A Single Institution Experience of 64 Cases With Clinical Follow-up and Correlation With the Current (Eighth Edition) AJCC Staging.

Background. In this single-institution study, we applied the current (eighth edition) American Joint Committee on Cancer pathologic staging criteria to 64 low-grade mucinous neoplasms of the appendix (LAMNs), examined their histopathologic features, and studied the patients' clinical outcomes. Design. Sixty-four LAMNs, with a median follow-up of 52 months, were reviewed. Results. The distribution of pathologic stages was pTis (n = 39), pT3 (n = 1), pT4a (n = 5), pT4aM1a (n = 8), and pT4aM1b (n = 11). Recurrence was observed in only 2 patients (both with pT4aM1b disease), one of whom died of disease. All remaining patients were disease-free after a median clinical follow-up of 60 months. Conclusions. Our study confirms that pTis LAMNs have an excellent prognosis and suggests that pT4a and pT4aM1a LAMNs may also have a low risk of developing progressive disease.

Intravascular B-cell lymphoma: case report of a rare cause of pulmonary arterial hypertension.

BACKGROUND: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease characterized by proliferation of malignant lymphoid cells within the small vessels of various organs resulting in diffuse thrombosis. It most commonly affects the central nervous system and the skin, but if it involves the pulmonary arteries it can cause acute severe pulmonary hypertension (PH) and right heart failure. Early diagnosis is essential as the clinical course is extremely aggressive. In this report, we present a case of rapidly progressive PH and subsequent right ventricular (RV) failure secondary to IVLBCL. We review the important differential diagnoses and diagnostic evaluation needed to make a correct and early diagnosis. CASE SUMMARY: A 53-year-old, previously healthy man developed 2 months of progressive shortness of breath. After being treated for presumptive pneumonia, he was admitted with hypoxic respiratory failure, altered mental status, and severe PH. He developed RV failure and subsequent liver failure. He was ruled out for pulmonary embolism. Despite aggressive management with inhaled nitric oxide and epoprostenol, inotropes, and continuous renal replacement therapy, the patient passed away. Post-mortem examination revealed the presence of IVLBCL with extensive involvement notable of the brain, heart, lungs, and pulmonary arteries. DISCUSSION: The acute development of severe PH and RV failure in the absence of pulmonary emboli is uncommon and represents a challenging diagnostic and management clinical scenario. When accompanied by altered mental status, constitutional symptoms and an elevated lactate dehydrogenase, clinicians should have a high index of suspicion for intravascular lymphoma, as early diagnosis is critical to maintain a reasonable chance of survival.

Pathology and Pathogenesis of Chagas Heart Disease.

Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of people infected with the protozoan parasite Trypanosoma cruzi. One way T. cruzi is transmitted to people is through contact with infected kissing bugs, which are found in much of the Western Hemisphere, including in vast areas of the United States. The epidemiology of T. cruzi and Chagas heart disease and the varied mechanisms leading to myocyte destruction, mononuclear cell infiltration, fibrosis, and edema in the heart have been extensively studied by hundreds of scientists for more than 100 years. Despite this wealth of knowledge, it is still impossible to predict what will happen in an individual infected with T. cruzi because of the tremendous variability in clonal parasite virulence and human susceptibility to infection and the lack of definitive molecular predictors of outcome from either side of the host-parasite equation. Further, while several distinct mechanisms of pathogenesis have been studied in isolation, it is certain that multiple coincident mechanisms combine to determine the ultimate outcome. For these reasons, Chagas disease is best considered a collection of related but distinct illnesses. This review highlights the pathology and pathogenesis of the most common adverse sequela of T. cruzi infection-Chagas heart disease-and concludes with a discussion of key unanswered questions and a view to the future.

Heterogeneity of Fibrosis in Liver Biopsies of Patients With Heart Failure Undergoing Heart Transplant Evaluation.

Liver biopsies are commonly performed in heart transplant candidates to confirm congestive hepatopathy (CH) and to assess the degree of fibrosis. Heterogeneity of fibrosis is frequent in CH, making it difficult to stage fibrosis. In this study, we evaluated the prevalence of heterogeneity of fibrosis and nodular regenerative hyperplasia (NRH) in liver biopsies with CH secondary to heart failure. Fifty liver biopsies with CH secondary to heart failure were reviewed. The fibrosis was scored on trichrome stain as follows: stage 0 for no fibrosis, stage 1 for zone 3 fibrosis, stage 2 for zone 3 and portal fibrosis, stage 3 for bridging fibrosis, and stage 4 for cirrhosis. Both stage 3 and stage 4 fibrosis were classified as advanced fibrosis. A predominant pattern of fibrosis and a secondary pattern of fibrosis, defined as a different stage of fibrosis seen in at least 10% of the biopsy material, if present, were recorded. A biopsy was considered to show heterogenous fibrosis if there was at least a 2 stage difference between the predominant and secondary patterns. Thirteen biopsies (26%) showed heterogenous fibrosis. Sixteen biopsies (32%) showed some evidence of advanced fibrosis: 5 had uniform advanced fibrosis, 4 had predominant pattern of advanced fibrosis, and advanced fibrosis was focal in 7 biopsies from 6 patients. NRH-type changes were seen in 9 of 50 biopsies (18%). In conclusion, our study showed heterogenous fibrosis in the liver biopsy of a quarter of patients with CH due to heart failure, highlighting the limitations of fibrosis assessment in the biopsies, and suggests that correlation with the complete clinical information is essential for management decisions.

The Use of Screencasts with Embedded Whole-Slide Scans and Hyperlinks to Teach Anatomic Pathology in a Supervised Digital Environment.

BACKGROUND: There is an increasing interest in using digitized whole-slide imaging (WSI) for routine surgical pathology diagnoses. Screencasts are digital recordings of computer screen output with advanced interactive features that allow for the preparation of videos. Screencasts that include hyperlinks to WSIs could help teach pathology residents how to become familiar with technologies that they are likely to use in their future career. MATERIALS AND METHODS: Twenty screencasts were prepared with Camtasia 2.0 software (TechSmith, Okemos, MI, USA). They included clinical history, videos of chest X-rays and/or chest computed tomography images, links to WSI digitized with an Aperio Turbo AT scanner (Leica Biosystems, Buffalo Grove, IL, USA), pre- and posttests, and faculty-narrated videos of the WSI in a manner closely resembling a slide seminar and other educational materials. Screencasts were saved in a hospital network, Screencast.com, YouTube.com, and Vimeo.com. The screencasts were viewed by 12 pathology residents and fellows who made diagnoses, answered the quizzes, and took a survey with questions designed to evaluate their perception of the quality of this technology. Quiz results were automatically e-mailed to faculty. Pre- and posttest results were compared using a paired t-test. RESULTS: Screencasts can be viewed with Windows PC and Mac operating systems and mobile devices; only videos saved in our network and screencast.com could be used to generate quizzes. Participants' feedback was very favorable with average scores ranging from 4.5 to 4.8 (on a scale of 5). Mean posttest scores (87.0% [±21.6%]) were significantly improved over those in the pretest quizzes (48.5% [±31.2%]) (P < 0.0001). CONCLUSION: Screencasts with WSI that allow residents and fellows to diagnose cases using digital microscopy may prove to be a useful technology to enhance the pathology education. Future studies with larger numbers of screencasts and participants are needed to optimize various teaching strategies.

Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation.

Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well-differentiated neuroendocrine tumors often showed immunoreactivity for site-specific markers. Although the histologic and immunohistochemical features of a breast tumor may raise the suspicion of a metastatic neuroendocrine neoplasm, the pathologic findings should be interpreted in the context of the clinical history and imaging findings in order to establish an accurate diagnosis.

Metastatic hepatocellular carcinoma presenting as a pancreatic mass by computed tomography scan and mimicking a primary neuroendocrine tumor: a potential pitfall in aspiration cytology.

Hepatocellular carcinoma (HCC) is a highly malignant neoplasm, often presenting at late stage and portending a poor prognosis for the patient. The peripancreatic fat is a rare site of extrahepatic metastasis, and metastatic HCC can mimic primary pancreatic neoplasms, even in this location. It is crucial to be aware of this pitfall in the evaluation of aspiration cytology of pancreatic neoplasms and to develop a strategy to reach the correct diagnosis. We present an endoscopic ultrasound fine-needle aspiration diagnosis of metastatic HCC presenting as a pancreatic mass radiologically that had neuroendocrine features on various cytological and histological preparations. The metastatic lesions were located surgically in the peripancreatic adipose tissue with involvement of one peripancreatic lymph node. This case illustrates the utility of FNA for diagnosing uncommon presentations of HCC and the importance of clinical history, cell block, and an immunocytochemical panel in determining the origin of the tumor.

Analysis of ThinPrep cytology in establishing the diagnosis of small cell carcinoma of lung.

BACKGROUND: ThinPrep liquid-based cytology (TP) preparations are being used increasingly in nongynecologic specimens. To the authors' knowledge, few studies to date have evaluated TP cytology in the setting of small cell carcinoma of the lung (SCCL). Accurately differentiating SCCL from other lung tumors has important clinical and therapeutic implications. Herein, the authors evaluated the diagnostic utility and cytomorphology of TP in the setting of SCCL. METHODS: All cases of SCCL with prior or concurrent TP cytologic specimens were identified via computer search. The cytodiagnoses were tabulated. When available, cytologic material was reviewed. Performance parameters of the various cytologic modalities processed with TP were calculated. RESULTS: In 121 patients with SCCL, 261 TP specimens were identified. The cytodiagnoses were: SCCL (119 specimens), suspicious for SCCL (45 specimens), atypical cells-not otherwise specified (22 specimens), negative/nondiagnostic (63 specimens), and nonsmall cell carcinoma (4 specimens). During the same period of time, 3 cases of false-positive diagnoses of SCCL were identified. The positive predictive value for a cytodiagnosis of SCCL on TP was 97.5%, and the sensitivity was 62.8%. Bronchial brush was the most sensitive cytologic modality (78.3%). Immunostaining was found to be contributory to the diagnosis in 10 of the 11 cases in which it was attempted. CONCLUSIONS: TP is a sound alternative to conventional preparations for the cytodiagnosis of SCCL. Cytomorphology of SCCL is altered in TP with less molding, less cell fragility, more discohesion, and tumor cell shrinkage artifact. Immunohistochemical staining of cellblocks is a useful adjunct in challenging cases. A positive cytodiagnosis of SCCL on TP can be used to initiate definitive therapy when biopsy is not possible.

Barbershops as hypertension detection, referral, and follow-up centers for black men.

Barbershops constitute potential sites for community health promotion programs targeting hypertension (HTN) in black men, but such programs have not been evaluated previously. Here we conducted 2 nonrandomized feasibility studies to determine whether an enhanced intervention program of continuous blood pressure (BP) monitoring and peer-based health messaging in a barbershop lowers BP more than standard screening and health education (study 1) and can be implemented by barbers rather than research personnel (study 2). In study 1, we measured changes in HTN treatment and BP in regular barbershop customers with poorly controlled HTN assigned for 8 months to either an enhanced intervention group (n=36) or a contemporaneous comparison group (n=27). Groups were similar at baseline. BP fell by 16+/-3/9+/-2 mm Hg in the enhanced intervention group but was unchanged in the comparison group (P<0.0001, adjusted for age and body mass index). HTN treatment and control increased from 47% to 92% (P<0.001) and 19% to 58% (P<0.001), respectively, in the enhanced intervention group, whereas both remained unchanged in the comparison group. In study 2, barbers were trained to administer the enhanced intervention continuously for 14 months to the entire adult black male clientele (n=321) in 1 shop. Six barbers recorded 8953 BP checks during 11 066 haircuts, thus demonstrating a high degree of intervention fidelity. Furthermore, among 107 regular customers with HTN, treatment and control increased progressively with increasing intervention exposure (P<0.01). Taken together, these data suggest that black-owned barbershops can be transformed into effective HTN detection, referral, and follow-up centers. Further research is warranted.