Pediatric Helicobacter pylori gastropathy demonstrates a unique pattern of gastric foveolar hyperplasia.

OBJECTIVES: Helicobacter pylori (Hp) are the most common agents causing gastric mucosal injury worldwide. Foveolar hyperplasia is a key component of the stomach's reaction to injury. This study examines histopathologic characteristics associated with Helicobacter pylori and with non- Helicobacter pylori-associated gastropathy in children and adolescents, and compares the prevalence of foveolar hyperplasia among these disease subgroups and normal control subjects. METHODS: Eighty-one gastric antral and corpus biopsies from subjects 2-19 years of age were studied. Twenty-two subjects with Helicobacter pylori gastritis were compared to 23 with non-Helicobacter pylori gastropathy and to 36 controls (normal biopsies). Foveolar length, full mucosal thickness, and the foveolar length: full mucosal thickness ratio were derived by a morphometric technique previously developed to analyze adult gastric tissue. RESULTS: Compared to controls, Helicobacter pylori gastritis demonstrated significant increases in antral foveolar length (P < .0001), full mucosal thickness (P < .0001), as well as corpus foveolar length (P < .05) and corpus full mucosal thickness (P < .05). Non-Helicobacter pylori-associated gastropathy also was characterized by increased antral foveolar length (P < .0001) and full mucosal thickness (P < .001) but corresponding corpus measurements did not differ from controls. Antral foveolar length in non-Helicobacter pylori gastropathy was increased, when compared to Helicobacter pylori gastritis (P < .05), while corpus values were not. The non-Helicobacter pylori gastropathy group demonstrated increased antral foveolar length: full mucosal thickness ratios, compared with Helicobacter pylori gastritis (P < .001) and with normal controls (P < .0001). DISCUSSION: An objective, quantitative approach to measuring foveolar hyperplasia in adults was successfully applied to pediatric biopsies and yielded a richer characterization of gastric pathology in children. Foveolar hyperplasia appears to be a generalized phenomenon in the presence of pediatric Helicobacter pylori gastritis but is limited to the antrum in non-Helicobacter pylori gastropathy.

Sclerosing Polycystic Adenoma: Conclusive Clinical and Molecular Evidence of Its Neoplastic Nature.

Sclerosing polycystic adenosis, initially considered a non-neoplastic salivary gland lesion and classified as such in the 2017 WHO Classification of Head and Neck Tumors, has been the subject of controversy regarding its possible neoplastic nature. The reporting of recurrent PI3K pathway alteration represents evidence to support these lesions as being neoplastic and more appropriately referred to as sclerosing polycystic adenoma (SPA). Herein, we provide additional evidence that supports the classification of SPA as a true neoplasm. Eight cases of SPA were identified in our database and consultation files. All cases were subjected to PTEN immunohistochemistry (IHC) and next-generation sequencing (NGS). In addition, one patient underwent genetic counseling and germline testing. The cases included 5 men and 3 women with a mean age of 41 years (range 11-78) and all tumors arose in the parotid gland. One patient had multiple recurrences over a period of 2 years. Morphologically the tumors were circumscribed and characterized by an admixture of acini, ducts and cysts embedded in a fibrotic/sclerotic stroma. The cells lining the ducts and cysts showed variable granular, vacuolated, foamy and apocrine cytoplasmic features, as well as acinar cells contained intracytoplasmic brightly eosinophilic granules. The apocrine intraductal proliferations showed mild to moderate atypia in 6 cases. One case showed overt malignant morphology that ranged from intraductal carcinoma to invasive salivary duct carcinoma. Seven cases tested for PTEN IHC showed loss of nuclear expression in the acinar and ductal cells with retained PTEN expression in the myoepithelial cell and stroma. NGS detected PIK3CA or PIK3R1 genetic alterations in 7 cases, including a novel TFG-PIK3CA fusion. Coexisting PTEN mutations were seen in 4 cases, including in a patient with clinical stigmata of Cowden syndrome and confirmed by germline genetic testing. Our findings herein documented including recurrence of tumor, malignant transformation, high prevalence of PI3K pathway oncogenic alterations and the possible heretofore undescribed association with Cowden syndrome add support to classifying SPA as true neoplasms justifying their designation as adenoma, rather than adenosis.

Frankly Invasive Carcinoma Ex-intraductal Carcinoma: Expanding on an Emerging and Perplexing Concept in Salivary Gland Tumor Pathology.

Intraductal carcinoma (IDC) of the salivary glands is an uncommon and enigmatic tumor, our understanding of which is rapidly evolving. Recent studies have demonstrated multiple IDC subtypes and consistent gene fusions, most frequently involving RET. Because IDC is a ductal proliferation surrounded by flattened myoepithelial cells, it was previously presumed to be analogous to breast ductal carcinoma in situ, but recent evidence has shown that the myoepithelial cells of fusion-positive IDC harbor the same genetic alterations of the ductal cells and are therefore neoplastic. In addition, there are rare reports of fusion-positive IDC with overt areas of irregular invasion lacking myoepithelial cells, but this phenomenon is not well documented or understood. This study aims to better characterize these frankly invasive carcinoma ex-IDC. All cases of frankly invasive carcinoma ex-IDC were obtained from the authors' files. Inclusion criteria included a component of concurrent or antecedent IDC and/or a fusion known to be associated with IDC. Immunohistochemistry (S100, SOX10, mammaglobin, androgen receptor, p63, p40) and molecular analysis (targeted RNA sequencing or large panel DNA next generation sequencing) was performed. Clinical follow-up was obtained from medical records. Ten cases of frankly invasive carcinoma ex-IDC were identified. The tumors occurred in 8 men and 2 women ranging from 33 to 82 years (mean, 66.3). All but one case arose in the parotid gland. In 4 cases, the IDC component was intercalated duct type. It was mixed apocrine/intercalated duct in two, and in the remaining 4 cases, no residual IDC was identified. The frankly invasive carcinomas were remarkably heterogeneous, ranging from minimally to widely invasive beyond the confines of the IDC, low-grade to high-grade, with morphologies that varied from duct-forming to those having clear cell or sarcomatoid features, to frankly apocrine. The original diagnoses for these cases were (adeno) carcinoma, not otherwise specified (n = 6), salivary duct carcinoma (n = 3), and secretory carcinoma (n = 1). All cases harbored fusions: NCOA4::RET (n = 6), TRIM33::RET (n = 2), TRIM27::RET (n = 1), and STRN::ALK (n = 1). Clinically, one tumor recurred locally, cervical lymph node metastases occurred in five patients, and distant metastasis later developed in four of these patients. Our findings highlight striking diversity in frankly invasive carcinomas that arise from fusion-positive IDC, a tumor which may serve as a precursor neoplasm like pleomorphic adenoma. These carcinomas vary in their extent of invasion, grade, histologic appearances, and clinical behavior. Importantly, in contrast to pure IDC, which is believed to be indolent, many frankly invasive cases were aggressive. Because RET and ALK fusions are targetable, it is important to recognize the broad spectrum of frankly invasive carcinomas that can arise from IDC, particularly because some cases are completely overrun or recur without any recognizable IDC component. These results suggest fusion analysis may be of clinical benefit on any salivary gland (adeno) carcinoma, not otherwise specified or salivary duct carcinoma.

The Most Common Mistake in Laryngeal Pathology and How to Avoid it.

Upper aerodigestive tract (UADT) spindle cell squamous carcinoma (SCSC), also known as sarcomatoid carcinoma, is a high-grade subtype of conventional squamous cell carcinoma (SCC) that is histologically characterized by a combination of differentiated SCC in the form of intraepithelial dysplasia and/or invasive differentiated SCC, and the presence of an invasive (submucosal) undifferentiated malignant spindle-shaped and pleomorphic (epithelioid) cell component. Typically, SCSC presents as a superficial polypoid mass not infrequently with surface ulceration precluding identification of an intraepithelial dysplasia. Further, in many cases an invasive differentiated SCC is not identified. Adding to the complexity in such cases, is that immunohistochemical staining in a significant minority of cases is negative for epithelial-related markers but often the cells express mesenchymal-related markers. In such cases, differentiating SCSC from a reactive (benign) spindle cell proliferation or a mucosal-based sarcoma can be problematic, with treatment implications. Herein, we detail the clinical and pathologic features of laryngeal SCSC and discuss the rationale for diagnosing a carcinoma and avoiding a diagnosis of sarcoma. In our experience, such cases represent one of the more common mistakes made in laryngeal pathology. Yet, virtually all such lesions are SCSCs. The treatment and prognosis relies on the accuracy of this distinction.

Cytology adds value to monoclonal antibody Das-1 testing for detection of high-risk pancreatic cysts.

INTRODUCTION: Determining the risk of malignancy in a pancreatic cyst (PC) is a clinical and diagnostic challenge. Monoclonal antibody (mAb) Das-1 test was shown to have high sensitivity, specificity, and accuracy in detecting high-risk (HR) cysts. Das-1 mAb test detects HR mucinous cysts with high-grade dysplasia (HGD), invasive carcinoma, and/or intestinal-type epithelium. Correlation of mAb Das-1 testing of PC fluids with cytomorphologic findings has not been evaluated. MATERIALS AND METHODS: We correlated cytology with mAb Das-1 test results and resection histology in 26 PCs. There were 18 intraductal papillary mucinous neoplasms (IPMN), 1 intraductal oncocytic papillary neoplasm (IOPN), 4 mucinous cystic neoplasms (MCN), 2 serous cystadenomas, and 1 cystic pancreatic neuroendocrine tumor (PanNET). HR cysts included cysts with high-grade atypia on cytology or HGD on histology, invasive carcinoma, IOPNs, and cystic PanNETs. Intestinal type IPMNs were also HR cysts on histology. RESULTS: In 17 cases (65.38%), cytology and mAb Das-1 test correlated with histology. There were 2 (7.69%) mAb Das-1 test negative HR PCs diagnosed by cytology. Five (19.23%) mAb Das-1 test positive HR PCs had mucin only or cells with low-grade dysplasia on cytology. Two mAb Das-1 test positive HR PCs had nondiagnostic cytology. HR IOPN and cystic PanNET were not detected by mAb Das-1 test. CONCLUSION: The mAb Das-1 is a sensitive and specific biomarker for detecting HR mucinous PCs. Adding cytology to mAb Das-1 testing improves the sensitivity for the detection of nonmucinous HR PC. Together, cytology with mAb Das-1 testing is more accurate than either one alone.

Oil red O staining for lipid-laden macrophage index of bronchoalveolar lavage: interobserver agreement and challenges to interpretation.

INTRODUCTION: Oil Red O (ORO) staining on cytologic specimens with calculation of the lipid-laden macrophage index (LLMI) is used as a part of the workup in a number of clinical settings, particularly when aspiration is of concern. As a part of ongoing internal quality improvement measures, the objective of the present study was to evaluate the interobserver agreement of the LLMI calculation and to identify factors that affect the variability of the calculation. MATERIALS AND METHODS: There were 9 study participants, which included 3 trainees, 3 cytotechnologists, and 3 cytopathologists. Each participant reviewed 100 ORO-stained bronchoalveolar lavage slides and assigned an LLMI score to each case. The scores were categorized into 3 groups according to the associated aspiration risk: low, LLMI <40; intermediate, LLMI 40 to 90; and high, LLMI >90. The participants were also requested to note any challenges to the calculation for each case. RESULTS: The interobserver agreement among all participants was fair (κ = 0.23). Stratified by participant group, the interobserver agreement among the trainees was fair (κ = 0.24), among cytotechnologists was fair (κ = 0.32), and among cytopathologists was moderate (κ = 0.60). In 70 cases, at least one participant scored the case at least one category higher than the other participants; in 47 cases there was a two category difference. A primary diagnostic challenge reported by participants was macrophage pigmentation (hemosiderin, anthracosis). CONCLUSIONS: We found only fair interobserver agreement among all 9 participants in the study. Hemosiderin and anthracotic pigmentation was a major factor impeding LLMI calculation resulting in overestimation of the LLMI.

Extranodal Rosai-Dorfman disease arising in the heart: clinical course and review of literature.

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a nonmalignant disease of unknown etiology. It may present as bilateral, massive, painless cervical lymphadenopathy; however, one third of the cases have extranodal involvement. Extranodal sites include soft tissue, skin, upper respiratory and gastrointestinal tracts, and central nervous system, with head and neck being the most common. Here we report a rare case of intracardiac RDD in a 46-year-old, African-American female who presented with worsening shortness of breath and fatigue for 7 weeks. Comprehensive physical examination was within normal limits; the patient had no lymphadenopathy. Echocardiogram revealed a large mass in the left atrium extending into the mitral valve. The mass was resected under the pretext of clinical diagnosis of myxoma, and the patient underwent a radical extended interatrial septectomy with bovine pericardial patch reconstruction. The 8-cm resected mass consisted of areas of fibrosis alternating with sheets of histiocytes enmeshed in a mixed inflammatory infiltrate. Histiocytes contained intact lymphocytes, plasma cells, neutrophils, and erythrocytes suggesting emperipolesis. The diagnosis of RDD was confirmed by immunohistochemistry. This case highlights the extranodal manifestation of RDD in the heart which could be easily mistaken for a myxoma on clinical and radiologic evaluation. RDD must be considered in the differential diagnosis of any patient who presents with a cardiac mass.

Comparison of Knifelight Surgery versus Conventional Open Surgery in the Treatment of Carpal Tunnel Syndrome.

BACKGROUND: A variety of surgical treatment methods for carpal tunnel syndrome are introduced recently, including open surgery, endoscopic and the Knifelight. It is hypothesized that Knifelight method could decrease scar tenderness and time before return to daily activities for patients and is accompanied with less disturbance to fine sensory nerves. OBJECTIVES: To compare the Knifelight instrument and open carpal tunnel release with respect to scar length, operation duration, recovery time needed before return to work and amount of pain three weeks after surgery in patients with neurophysiologically confirmed carpal tunnel syndrome. PATIENTS AND METHODS: FIFTY NINE PATIENTS WITH INDICATION FOR CARPAL TUNNEL RELEASE RANDOMLY ASSIGNED INTO TWO GROUPS: open (n=30) or Knifelight (n=29). The patients compared regarding scar length, operation duration, time to return to daily activities and amount of pain at three weeks after operation based on Visual Analog Scale. RESULTS: There was no significant differences regarding age and sex in the two groups. The scar length, operation duration and time before return to daily activities were significantly lower in the Knifelight group. Although the mean visual analogue scale of Knifelight group found to be lower than the other, it was not statistically significant. CONCLUSIONS: The Knifelight technique is accompanied with advantages over the open surgery regarding operation time, scar length and time to return to daily activities. The pain relieve based on Visual Analog Scale was not statistically different from conventional open surgery.