Low-grade dysplasia in Barrett's esophagus: A problematic diagnosis / Displasia de bajo grado en el esófago de Barrett: un diagnóstico problemático

Although low-grade dysplasia (LGD) in Barrett's esophagus (BE) is a histopathological diagnosis based on different histological abnormalities, it is still problematic for different reasons. Patients without confirmed diagnosis of LGD undergo unnecessary and intensified follow-up where the risk of progression is low in the majority of cases. In contrast, the presence of confirmed LGD indicates a high risk of progression. In this article we try to address these reasons focusing on re-confirmation of LGD diagnosis, interobserver agreement, and persistent confirmed LGD. The progression risk of LGD to high-grade dysplasia and esophageal adenocarcinoma will also be reviewed. (AU)

Aunque la displasia de bajo grado (DBG) en el esófago de Barrett (EB) es un diagnóstico histopatológico basado en diferentes anomalías histológicas, este no deja de ser problemático por diferentes razones. Los pacientes sin diagnóstico confirmado de DBG se someten a un seguimiento innecesario e intensificado donde el riesgo de progresión es bajo en la mayoría de los casos. Por el contrario, la presencia de DBG confirmada indica un alto riesgo de progresión. En este artículo tratamos de abordar estas razones centrándonos en la reconfirmación del diagnóstico de la DBG, la concordancia entre observadores y la DBG confirmada y persistente. También se revisará el riesgo de progresión de la DBG a displasia de alto grado y adenocarcinoma esofágico. (AU)

CD44-SNA1 integrated cytopathology for delineation of high grade dysplastic and neoplastic oral lesions.

The high prevalence of oral potentially-malignant disorders exhibits diverse severity and risk of malignant transformation, which mandates a Point-of-Care diagnostic tool. Low patient compliance for biopsies underscores the need for minimally-invasive diagnosis. Oral cytology, an apt method, is not clinically applicable due to a lack of definitive diagnostic criteria and subjective interpretation. The primary objective of this study was to identify and evaluate the efficacy of biomarkers for cytology-based delineation of high-risk oral lesions. A comprehensive systematic review and meta-analysis of biomarkers recognized a panel of markers (n: 10) delineating dysplastic oral lesions. In this observational cross sectional study, immunohistochemical validation (n: 131) identified a four-marker panel, CD44, Cyclin D1, SNA-1, and MAA, with the best sensitivity (>75%; AUC>0.75) in delineating benign, hyperplasia, and mild-dysplasia (Low Risk Lesions; LRL) from moderate-severe dysplasia (High Grade Dysplasia: HGD) along with cancer. Independent validation by cytology (n: 133) showed that expression of SNA-1 and CD44 significantly delineate HGD and cancer with high sensitivity (>83%). Multiplex validation in another cohort (n: 138), integrated with a machine learning model incorporating clinical parameters, further improved the sensitivity and specificity (>88%). Additionally, image automation with SNA-1 profiled data set also provided a high sensitivity (sensitivity: 86%). In the present study, cytology with a two-marker panel, detecting aberrant glycosylation and a glycoprotein, provided efficient risk stratification of oral lesions. Our study indicated that use of a two-biomarker panel (CD44/SNA-1) integrated with clinical parameters or SNA-1 with automated image analysis (Sensitivity >85%) or multiplexed two-marker panel analysis (Sensitivity: >90%) provided efficient risk stratification of oral lesions, indicating the significance of biomarker-integrated cytopathology in the development of a Point-of-care assay.

Use of Immunohistochemical p53 Mutant-Phenotype in Diagnosis of High-Grade Dysplasia of Esophageal Squamous Epithelia.

BACKGROUND: Mild cellular atypia of esophageal squamous epithelial dysplasia has a risk of progressing to cancer that poses great confusion for pathological diagnosis. There is no research on the diagnosis and differential diagnosis of esophageal squamous dysplasia by the expression of immunohistochemical (IHC) p53. The study aims to conduct a graded diagnosis of esophageal squamous epithelial hyperplasia by combining p53 expressions and microscopic histomorphological characteristics. METHODS: The study was conducted from January 2021 to January 2022 and included a total of 208 cases including 262 specimens with atypical hyperplasia or dysplasia of squamous epithelia discovered by esophageal mucosal biopsy. HE staining was used to grade the epithelial hyperplasia degree, and all cases underwent p53 IHC evaluation. RESULTS: Benign lesions: we did not find any p53 IHC mutant-phenotype (0/12 cases) in 12 cases of esophagitis. We found 10 cases (10/80 cases) of p53 IHC mutant-phenotype in 80 cases of low-grade dysplasia, and 158 cases (158/170 cases) of p53 IHC mutant-phenotype of high-grade lesions in 170 cases of high-grade dysplasia and early cancer based on the χ2 test results. We found statistically significant differences in p53 IHC mutant-phenotype between the high-grade squamous epithelial lesions and benign lesions. The sensitivity and specificity of p53 in detecting high-grade squamous epithelial lesions were 92.9% and 89.1%, respectively. The positive predictive value was 94.0%, and the negative predictive value was 87.2%. CONCLUSION: In this study, we found that p53 IHC had high sensitivity and specificity in detecting high-grade esophageal squamous epithelial lesions. Therefore, it has potential to be used as a routine item in pathological detection for auxiliary risk stratification of esophageal squamous epithelial lesions.

Intraductal papilloma with atypical ductal hyperplasia and neuroendocrine differentiation as a possible precursor lesion of solid papillary carcinoma.

Breast papillary neoplasms include a wide range of tumor types, and their pathological diagnosis is sometimes difficult. Furthermore, the etiology of these lesions is still not fully understood. We report the case of a 72-years-old woman referred to our hospital with bloody discharge from the right nipple. An imaging study detected a cystic lesion, including a solid component contiguous with the mammary duct, in the subareolar region. The lesion was then removed by segmental mastectomy. Pathological examination of the resected specimen revealed an intraductal papilloma with atypical ductal hyperplasia. Moreover, the atypical ductal epithelial cells expressed neuroendocrine markers. The presence of an intraductal papillary lesion with neuroendocrine differentiation suggests solid papillary carcinoma. Thus, this case suggests that intraductal papilloma could be a precursor of solid papillary carcinoma.

Pacinian corpuscle hyperplasia in a 6-year-old girl.

We present a rare case of Pacinian corpuscle hyperplasia (PCH) presenting with typical finger pain in a 6-year-old girl. As appendages in children are smaller than those in adults, diagnostic criteria are needed for pathological confirmation of PCH in pediatric patients.

Pulmonary Nodular Lymphoid Hyperplasia Evaluated with Bronchoalveolar Lavage Fluid Findings: A Case Report and Review of the Literature on Japanese Patients.

Pulmonary nodular lymphoid hyperplasia (PNLH) is a very rare disease, and it is difficult to diagnose PNLH and distinguish it from mucosa-associated lymphoid tissue (MALT) lymphoma. In addition, information on bronchoalveolar lavage fluid (BALF) analyses is lacking. We herein report a 36-year-old Japanese woman diagnosed with PLNH by a surgical biopsy and analysis of BALF. The BALF showed an increase in B-cell marker-positive lymphocytes, normal patterns of B-cell clonality, mucosa-associated lymphoid tissue 1 gene, and immunoglobulin heavy chain at 14q32 translocations. We also reviewed Japanese cases of PNLH described in Japanese or English to explore the characteristics of such cases.

Polypoid-Type Adenomyomatous Lesion of the Cystic Duct: Report of a Case and Review of Literature.

Adenomyomatous hyperplasia, a common non-neoplastic lesion in the gallbladder, is rarely identified in the extrahepatic bile duct. Typically, these lesions appear as a nodule or mural thickening/elevation. However, in exceptional circumstances, pedunculated/polypoid adenomyomatous lesion occurs in the biliary tract; two cases in the gallbladder and only one case in the common bile duct have been reported. Despite their benign nature, adenomyomatous lesions, especially those with a polypoid appearance, are clinically difficult to exclude a possibility of malignant neoplasms. We describe a case of polypoid-type adenomyomatous lesion of the cystic duct in a 72-year-old man, which was considered as a cystic duct neoplasm preoperatively. Gross examination of the resected specimen revealed that the 9 mm-sized cystic duct polyp. Histologically, the polypoid lesion consisted of glands without atypia, fibrous stroma, smooth muscle bundles, and accompanying stromal inflammation, leading to the diagnosis of benign adenomyomatous lesion. The lesion might be considered as adenomyomatous hyperplasia arising in the valve of Heister, while true nature of the lesion is uncertain. Recognition and accumulating for this rare disease will contribute to better clinical management in the future.

Urine Cytology Findings in Cases of Pseudocarcinomatous Urothelial Hyperplasia of the Bladder Often Represent a Diagnostic Challenge.

CONTEXT.­: Pseudocarcinomatous urothelial hyperplasia (PCUH) architecturally and cytologically mimics cancer. The urine cytology features of PCUH have not been described. OBJECTIVE.­: To describe PCUH features in urine cytology. DESIGN.­: We reviewed urine cytology cases with concurrent PCUH tissue specimens from 5 academic institutions and classified them by using The Paris System criteria. RESULTS.­: Thirty-nine patients included 31 men and 8 women with a mean age of 67 years (range, 39-87 years). All patients had prior pelvic irradiation, and most presented with hematuria (n = 27). The specimens included voided urine (n = 16); bladder washing (n = 11); and urine, not otherwise specified (n = 12). The specimen preparation included cytospin (n = 29) and ThinPrep (n = 10). Original interpretations were negative for high-grade urothelial carcinoma (n = 28), atypical urothelial cells (AUCs; n = 10), and high-grade urothelial carcinoma (HGUC; n = 1). Twenty-five urine specimens (64%) had findings of PCUH. These specimens were moderately cellular and composed of sheets, cohesive groups, or isolated urothelial cells. Nucleoli were present in 23 cases. The nuclear membrane was smooth to irregular (n = 9), smooth (n = 8), and irregular (n = 8). The chromatin was glassy (n = 8), vesicular (n = 7), hyperchromatic (n = 7), and vesicular to finely granular (n = 3). The cytoplasm varied from dense squamoid, to finely vacuolated, to vacuolated. Nucleomegaly was observed in all 25 specimens, and nuclear-cytoplasmic ratio greater than 0.5 was seen in 11 of 25 cases (44%). The background contained acute inflammation (n = 14), was clean (n = 9), and contained red blood cells (n = 2). All cases originally interpreted as AUCs and HGUC had PCUH features. CONCLUSIONS.­: PCUH urine features can overlap with AUCs, HGUC, and other nonurothelial malignancies. In our cohort, 44% (11 of 25) of urine specimens with PCUH changes were initially misclassified. Recognition of cytologic features of PCUH is important to avoid overcalling reactive changes.

Screening for unilateral aldosteronism should be combined with the maximum systolic blood pressure, history of stroke and typical nodules.

To determine factors associated with lateralization in primary aldosteronism (PA). The clinical data for PA patients hospitalized at the First Affiliated Hospital of Guangxi Medical University from October 2016 to March 2021 were included in this study. They were classified according to results derived from computed tomography (CT): bilaterally normal nodules (no typical nodules were found in either adrenal glands, only changes in unilateral adrenal hyperplasia thickening or bilateral adrenal hyperplasia thickening), unilateral nodules (typical nodule appears in unilateral adrenal gland, and there are no abnormalities in the contralateral adrenal gland or only thickening of unilateral adrenal hyperplasia) and bilateral nodules (typical nodule like changes in bilateral adrenal glands). Multivariate logistic regression and receiver operating characteristic (ROC) were used to analyze the factors associated with lateralization of PA and consistencies between adrenal CT images and adrenal venous sampling (AVS) results. A total of 269 patients with PA were recruited, with an average age of 46 years and 112 cases had typical nodules. Results from CT scans revealed that there were 49 bilateral normal cases, 177 cases were unilateral abnormal and 43 cases were bilateral abnormal. In all of the PA patients, multifactorial logistic regression analysis showed that the maximum systolic blood pressure (OR = 1.03, P < .001), history of stroke (OR = 2.61, P = .028), and typical nodules (OR = 1.9, P = .017) were all relevant factors in unilateral primary aldosteronism (UPA). In the unilateral nodule group, multivariate logistic regression analysis suggested that maximum systolic blood pressure (OR = 1.03, P < .001) and typical nodules (OR = 2.37, P = .008) were the related factors for UPA. However, the consistency between adrenal CT and AVS was only 40.68%, while maximum systolic blood pressure (OR = 1.02, P < .001) and plasma aldosterone renin ratio (OR = 1.001, P = .027) were the relevant consistent factors between AVS and CT results. Maximum systolic blood pressure, typical nodules, and history of stroke are important factors to consider when screening for UPA. It is recommended to combine medical history and imaging findings when looking at different subgroups before a clinical decision is made. Patients with PA in the absence of lesions or bilateral lesions on CT should be diagnosed by AVS as far as possible.

Giant hyperplastic gastric polyp: A diagnostic dilemma!!

Gastric hyperplastic polyps (GHP) account for a majority of benign gastric polyps. Most of the GHPs are <2 cm, asymptomatic, and incidentally detected on endoscopy or radiologically. With increasing size, these polyps manifest as upper gastrointestinal bleeding, iron deficiency anemia, and gastric outlet obstruction (GOO). We report an unusual case of giant GHP simulating gastric carcinoma and posing as a diagnostic challenge for the surgeons emphasizing the diagnostic role of histopathology. A 46-year-old female presented with clinical features of progressive GOO for 1 year. Endoscopy revealed an eccentric proliferative lesion in the antrum. Computed tomography showed a polypoidal, enhancing mural thickening involving distal body and antro-pyloric region measuring 8.4 cm × 6.6 cm × 1.8 cm. Subtotal gastrectomy was done in view of clinical features of GOO and having a clinical suspicion of malignancy. Gross examination showed a giant sessile hyperplastic polyp with lobulated surface. Microscopy revealed features of a large, sessile hyperplastic polyp without any evidence of dysplasia. The patient was symptomatically relieved and is on follow-up. To conclude, giant GHPs can mimic gastric carcinoma on endoscopy and radiology. The possibility of giant GHP should be kept in mind in the presence of an intensely contrast-enhancing polypoidal lesion in the gastric antrum. Long-term endoscopic follow-up is recommended.

New candidates in the differential diagnosis of malignant mesothelioma from benign mesothelial hyperplasia and adenocarcinoma; DARS2 and suprabasin.

OBJECTIVES: Malignant mesothelioma (MM) is a primary malignant tumour with a very bad prognosis, which develops from the mesothelial cells lining the serosal surfaces. Because MM can show a wide variety of histological patterns and its cytomorphological features are quite extensive, it is often confused with lung adenocarcinomas (LAC) and reactive mesothelial hyperplasia (RMH). The immunohistochemical examination method is the most useful method for discrimination. In this study, we aimed to determine the value of suprabasin and DARS2 markers in the differential diagnosis of RMH, MM and LAC. METHODS: Thirty MM, 30 LAC and 30 RMH samples selected from the archive of Firat University Hospital Pathology Department Laboratory were included in this study. Suprabasin and DARS2 markers were applied to the samples immunohistochemically and their place in the differential diagnosis was examined. RESULTS: Although DARS2 expression was observed in RMH, MM and adenocarcinoma samples, Suprabasin expression was only observed in adenocarcinoma. There was a significant difference between the groups in terms of DARS2 and Suprabasin expression. No suprabasin expression was detected in MM and RMH. CONCLUSION: Suprabasin and DARS2 may be proposed as new biomarkers to differentiate MM from LAC.

French national cohort of neuroendocrine cell hyperplasia of infancy (FRENCHI) study: diagnosis and initial management.

Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current practice, a clinical and radiological approach is more and more preferred (NEHI syndrome). This national study aimed to address diagnosis and initial management of patients followed up for a NEHI pattern in pediatric centers for rare lung diseases (RespiRare, France). Data on neonatal and familial events, symptoms at diagnosis, explorations performed and results, and therapeutic management were collected by questionnaire. Fifty-four children were included (boys 63%). The mean onset of symptoms was 3.8 ± 2.6 months. The most frequent symptoms at diagnosis were tachypnea (100%), retraction (79.6%), crackles (66.7%), and hypoxemia (59.3%). The mean NEHI clinical score, evocative when ≥ 7/10, was 7.9 ± 1.4 (76% with a score ≥ 7). All chest CT-scans showed ground glass opacities evolving at least the middle lobe and the lingula. Lung biopsy was performed in 38.9% of the cases and was typical of NEHI in only 52.4%, even when the clinical presentation was typical. Initial treatments were oxygen (83.6%) and more curiously intravenous pulses of steroids (83.3%) and azithromycin (70.2%). CONCLUSION: This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs. WHAT IS KNOWN: •Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy. WHAT IS NEW: •In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively. •Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI.

Hiperplasia sebácea ectópica en mucosa oral de neonatos: reporte de tres casos / Ectopic sebaceous gland hyperplasia in neonates oral mucosa: 3 case studies / Hiperplasia sebácea ectópica na mucosa oral de recém-nascidos: relato de 3 casos

La hiperplasia de glándulas sebáceas es un hallazgo benigno y transitorio, común en el período neonatal. Secundariamente al estímulo hormonal androgénico se produce un hipercrecimiento de las glándulas, con mayor frecuencia en nariz y mejillas, donde existen en mayor densidad. La hiperplasia de glándulas en una localización ectópica, llamada gránulos de Fordyce (GF), es excepcional en el período neonatal. Se han reportado en aproximadamente 1% de los recién nacidos, y con frecuencia se localizan en la mucosa oral. Los GF se describen como lesiones papulares de aspecto vesiculoso blanco amarillentas de 1-3 mm2, que podrían confundir al neonatólogo o al pediatra con entidades infecciosas, dando lugar a pruebas invasivas y tratamientos innecesarios. Se describen tres casos clínicos de neonatos con diagnóstico de hiperplasia sebácea ectópica localizada en mucosa oral, con el objetivo de revisar la etiología, las características clínicas, los diagnósticos diferenciales y la evolución de esta entidad benigna. Conclusiones: la hiperplasia sebácea ectópica en mucosa oral de neonatos es un hallazgo benigno autolimitado que se presenta con baja frecuencia. El reconocimiento clínico de esta entidad es importante para evitar diagnósticos incorrectos y tratamientos innecesarios.

Sebaceous gland hyperplasia is a common transient and benign finding in neonates. After androgenic hormonal stimulation, there is a gland overgrowth mainly in the nose and cheeks where there is a greater density of glands. Ectopic sebaceous gland hyperplasia, called Fordyce's Granules (FG), is exceptional in neonates and it is reported in approximately 1% of newborns and frequently located in the oral mucosa. FGs are described as 1-3mm2 yellowish-white papular and vesicular lesions. Neonatologists or pediatricians may confuse these clinical features with infectious diseases, leading to invasive tests and unnecessary treatment. We describe three clinical cases of neonates with diagnosis of ectopic sebaceous gland hyperplasia located in the oral mucosa, with the aim of reviewing the etiology, clinical characteristics, differential diagnoses and evolution of this benign entity. Conclusions: ectopic sebaceous gland hyperplasia of the lips is a self-limited benign finding occurring infrequently in newborns. The clinical recognition of this entity is important to avoid inaccurate diagnoses or unnecessary treatment.

A hiperplasia das glândulas sebáceas é um achado benigno e transitório comum nos neonatos. Secundário ao estímulo hormonal androgênico, há um hipercrescimento das glândulas com mais frequência no nariz e nas bochechas onde há uma maior densidade das glândulas. A hiperplasia das glândulas num local ectópico, chamado Fordyce Granules (FG), é excepcional no período neonatal, e ela é relatada em aproximadamente 1% dos recém-nascidos e muitas vezes está localizada na mucosa oral. Os FGs são descritos como lesões vesiculares brancas amareladas de 1-3mm2, o que poderia confundir o neonatologista ou pediatra com entidades infecciosas, levando a testes invasivos e tratamentos desnecessários. Descrevemos três relatos clínicos de recém-nascidos com diagnóstico de hiperplasia sebácea ectópica localizada na mucosa oral, com o objetivo de rever a etiologia, características clínicas, diagnósticos diferenciais e evolução desta entidade benigna. Conclusões: hiperplasia sebácea ectópica na mucosa oral de recém-nascidos é um achado benigno autolimitante que ocorre com baixa frequência. O reconhecimento clínico desta entidade é importante para evitar diagnósticos incorretos e tratamentos desnecessários.

5-hmC loss is another useful tool in addition to BAP1 and MTAP immunostains to distinguish diffuse malignant peritoneal mesothelioma from reactive mesothelial hyperplasia in peritoneal cytology cell-blocks and biopsies.

The differentiation between reactive mesothelial hyperplasia (RMH) and diffuse malignant peritoneal mesothelioma (DMPM) is challenging especially when applied on peritoneal small samples. The use of BRCA-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) immunostains is familiar to identify malignant mesothelial proliferation. Recently, nuclear 5-hydroxymethylcytosine (5-hmC) was reported to be a new recognition tool of pleural mesothelial malignancy on surgical specimens. However, application of 5-hmC immunostaining has not yet studied in peritoneal specimens from small biopsies or cytology cell-blocks. The aim was to assess the diagnostic accuracy of this new marker combination to distinguish DMPM from RMH in biopsies and cell-blocks. Seventy-five cases were analyzed; among which, 38 were of cytological specimens including 6 RMH and 32 DMPM, and 37 tissue biopsies with 7 RMH and 30 DMPM. BAP1, MTAP, and 5-hmC immunostains were performed on all cases. RMH cases exhibited a retained staining with all immunostains. Among DMPM, BAP1 was lost in 71.8% of cytology cell-blocks and 66.7% of biopsies. MTAP was lost in 40.6% of cytology cell-blocks and 33.3% of biopsies. 5-hmC was lost in 40.6% of cytology cell-blocks and 30% of biopsies. The combination of BAP1, MTAP, and 5-hmC showed the best accuracy in differential diagnosis between RMH and DMPM (sensitivity = 0.84, specificity = 1 in cytology cell-blocks; sensitivity = 0.90, specificity = 1 in biopsy). The best diagnostic combination in peritoneal cytology effusion fluids and biopsies samples provided by BAP1, MTAP, and 5-hmC should be applied on a diagnostic step-wise algorithm by pathologists involved into the management of DMPM, because of their therapeutic implications.

The role of hematological parameters in distinguishing acute appendicitis from lymphoid hyperplasia.

BACKGROUND: One of the most misdiagnosed appendicular pathologies is lymphoid hyperplasia (LH) that can be managed con-servatively when identified early and is self-limiting. The aim of this retrospective study was to compare acute appendicitis (AA) with LH in terms of hematological parameters to determine whether there is a hematological predictor to distinguish the two diseases. METHODS: Complete blood cell counts of patients with AA were compared with those having LH. RESULTS: One-hundred-ninety-five patients (118 male/77 female) underwent appendectomy. Histopathological examination re-vealed acute AA in 161 patients (82.6%), and negative appendectomy (NA) in 19 patients (9.7%). Of the NA specimens, 16 were LH (8.2%). Thirteen patients (6.7%) had AA with simultaneous LH. White blood cell count (p=0.030, neutrophil (p=0.009), neutrophil per-centage (p=0.009), and neutrophil/lymphocyte ratio (p=0.007) were significantly higher in AA whereas lymphocyte count (p=0.027), lymphocyte percentage (p=0.006) were significantly higher in LH. Multi logistic regression analysis revealed white blood cell count as the only independent predictor in distinguishing AA from LH with a 69.1% sensitivity, 80.0% specificity, 77.5% positive predictive value, and 72.1% negative predictive value. The cut-off value for white blood cell count was 11.3 Ku/L, and every one unit (1000/mm3) increase in white blood cell count raises the risk of AA by 1.24 times, while values below this value will increase the likelihood of LH. CONCLUSION: The most predictive complete blood count parameter in distinguishing LH from AA appears to be as white blood cell count.