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Introduction: The objective of this study was to compare the length ratios obtained on panoramic radiography and computed tomography (CT) to verify whether the former is adequate for diagnosing coronoid process hyperplasia., Methods: A case series of patients with coronoid process hyperplasia was investigated. Length ratios between the coronoid process and condyle were measured on panoramic radiographs by using the Levandoski method and on CT scans by using the methods described by Tavassol et al. and Stopa et al. The mean length ratios obtained using the three measurement methods were compared., Results: The mean length ratio measured with the Levandoski method was significantly lower than that measured with the method described by Stopa et al. (1.09 [0.09] vs. 1.21 [0.09]; P = 0.0001) and lower than that measured with the method described by Tavassol et al. (1.09 [0.09] vs. 1.34 [0.44]; P = 0.013)., Conclusion: Panoramic measurement of the coronoid process by using the Levandoski method tended to underestimate the length ratio, emphasizing the importance of using a scanographic measurement method at the slightest doubt to confirm the diagnosis of coronoid process hyperplasia., Competing Interests: Declaration of Competing Interest The authors have no financial or non-financial interests to disclose., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: We conducted this study to clarify the magnetic resonance imaging (MRI) characteristics of lobular endocervical glandular hyperplasia (LEGH) and Nabothian cysts., Methods: This study included 48 patients who underwent hysterectomy at our institution between 2016 and 2020 for suspected LEGH. Histopathological studies confirmed the presence of 25 Nabothian cysts and 23 cases of LEGH. We retrospectively analyzed five characteristic MRI findings: (1) located at the upper cervical canal, (2) positioned within the cervical stroma, (3) not circumscribing the cervical canal, (4) low- to iso-intensity on T1-weighted images (T1WI), and (5) "cosmos" or "microcystic" pattern. We compared the diagnostic accuracy of these findings for LEGH and Nabothian cysts using sensitivity, specificity, and predictive values. Combinations of findings were also calculated., Results: The characteristics "cosmos" or "microcystic" pattern, lesion not circumscribing the cervical canal, and low/iso-intensity on T1WI had a sensitivity and specificity greater than 50%. The sensitivity was 73.9% and specificity 84.0% when a combination of "cosmos" or "microcystic" pattern and lesion not circumscribing the cervical canal was present., Conclusion: The coexistence of a "cosmos" or "microcystic" pattern and not circumscribing the cervical canal was the most characteristic finding that distinguished LEGH from Nabothian cysts. When neither of these findings is present, Nabothian cyst can be suspected., (© 2024. The Author(s).)

Objective: To investigate the value of serum dehydroepiandrosterone sulfate (DHEAS) in the differential diagnosis of primary bilateral macronodular adrenal hyperplasia (PBMAH) from nonfunctional adenoma tumors (NFA), adrenocortical adenoma (ADA) and Cushing's disease (CD). Methods: A cross-sectional study. The clinical data of 302 patients with PBMAH, NFA, ADA and CD diagnosed and treated in the First Medical Center of PLA General Hospital from January 2010 to June 2021 were retrospectively analyzed. Among them, 97 were males and 205 were females, aged (45.7±7.2) years. The area under receiver operating characteristic (ROC) curve was used to evaluate the DHEAS ratio (serum DHEAS value divided by the lower limit of normal reference range for the corresponding age and sex) and the 8∶00 adrenocorticotropic hormone (ACTH) level in the differential diagnosis of PBMAH from NFA, ADA and CD. The maximum value of Youden index was cut-off value. Results: Among the 302 patients, 33 were in PBMAH group, 125 were in NFA group, 67 were in ADA group, and 77 were in CD group. The DHEAS ratio in CD group, NFA group, PBMAH group and ADA group decreased successively, with values of 6.34(4.44, 9.93), 3.37(2.24, 4.79), 1.14(1.04, 2.40) and 0.58(0.27, 1.05), respectively. There was statistical significance among all groups (all P <0.01). The area under the ROC curve for distinguishing PBMAH from NFA, ADA and CD were 0.803, 0.741 and 0.930, and the cut-off value were 2.59, 0.99 and 2.92, respectively. The sensitivity was 66.1%, 64.2% and 87.9%, respectively. The specificity was 81.8%, 81.2% and 85.7%. According to the level of 8∶00 ACTH, PBMAH was divided into ACTH-inhibited group (ACTH<2.2 pmol/L, n =18) and ACTH-non-inhibited group (ACTH≥2.2 pmol/L, n =15).The DHEAS ratio in ACTH-non-inhibited PBMAH group was higher than that in ACTH-inhibited PBMAH group( P <0.01).The area under ROC curve of DHEAS ratio for identifying ACTH-non-inhibited PBMAH and CD was 0.877, the cut-off value was 4.55, the sensitivity was 93.3%, and the specificity was 75.3%. If the DHEAS ratio combined with 8∶00 ACTH was used as a differential diagnostic indicator, the area under the ROC curve for distinguishing ACTH-non-inhibitory PBMAH from CD can reach 0.967, with the sensitivity of 100.0% and the specificity of 81.8%. Conclusions: DHEAS ratios is different in PBMAH, NFA, ADA and CD patients, which can assist in the differential diagnosis of PBMAH from NFA、ADA and CD patients, especially in the differential diagnosis of ACTH-non-inhibited PBMAH patients and CD patients.

Background : Inflammatory lesions and cysts are the most common Bartholin glands pathologic diagnoses. There have been very few reports of benign solid lesions of Bartholin glands such as nodular hyperplasia. Materials and methods : Thirty-two lesions diagnosed as Bartholin duct cyst in the gynecologic specialized institute were reviewed by two expert gynecological pathologists. Results : Using specific criteria, 7 qualified as nodular hyperplasia, 25 as Bartholin duct cyst. The average age of the patients with nodular hyperplasia was 31 years (range, 24 to 43). These lesions were solid, solid and cystic or purely cystic, had a mean maximal dimension of 3.3 cm, and were frequently thought to be Bartholin cysts on clinical examination. Four lesions were diagnosed as Bartholin duct cysts, while in the review they were considered as nodular hyperplasia. Conclusion : Nodular hyperplasia of Bartholin gland may be more common than is reported in the literature. This study showed that the diagnosis of nodular hyperplasia has been overlooked due to limited literature sources., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Snapping of fingers can be caused by pathologies such as stenosing flexor tenosynovitis. However, snapping symptoms in the metacarpophalangeal (MP) joint caused by hypertension and hyperplasia of the lateral band are rare. We present a 26-year-old female with symptoms of painful snapping of the middle finger. When the finger was actively flexed from the hyperextension of the MP joint, the ulnar lateral band was prominent, and a snapping phenomenon occurred. The cause of the snapping finger was considered to be tightness of the ulnar lateral band, and surgery was planned. Intraoperatively, the ulnar lateral band was tense and hyperplastic. The snapping phenomenon disappeared immediately after the resection of the lateral band. It is important to consider this condition as one of the differential diagnoses of snapping finger when the patient complains of an atypical snapping phenomenon., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We offer a comprehensive depiction of the cytomorphological characteristics of lobular endocervical glandular hyperplasia (LEGH) as observed in SurePath™ liquid-based cytology (LBC), subsequently confirmed on cone biopsy. Lobular endocervical glandular hyperplasia (LEGH), a precursor to gastric-type adenocarcinoma (GAE) of the endocervix, is rare and reports of it in cervical cytology are scarce. We provide a thorough description of the cytomorphological features of LEGH observed in SurePath™ liquid-based cytology (LBC), later confirmed by cone biopsy. To the best of our knowledge, this is the first report documenting cytology of LEGH in LBC of a Pap sample., (© 2024 John Wiley & Sons Ltd.)

Growth disturbances of the temporomandibular Joint are characterized by mandibular asymmetry, sometimes with secondary maxillar disturbances. Although the clinical symptoms are sometimes quite severe, patients usually have no pain. There are several growth disturbances, but in this article we discuss three particular causes of facial asymmetry, namely hemimandibular growth defects; overdevelopment, underdevelopment and neoplasms of the mandibular joint. Hemimandibular overdevelopment (hyperplasia) is a growth disorder characterized by progressive asymmetry of the mandibula. Hemimandibular hypoplasia, on the other hand, is a growth disorder involving underdevelopment of the condyle mandibulae due to impingement of the growth center and ankylosing. A pronounced asymmetrical face can cause aesthetic problems and always requires diagnostics, because in addition to the hyperplasia and hypoplasia mentioned above, other causes can explain the asymmetry such as, for example, an osteoarthritis or even a tumor emanating from the base of the skull, mandibula or soft tissues.

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., (© 2023 Wiley Periodicals LLC.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sunny et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., (© 2023. The Author(s) under exclusive licence to The Japanese Society for Clinical Molecular Morphology.)

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.

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., (© 2023 College of American Pathologists.)

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., (© 2023 S. Karger AG, Basel.)

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.

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 Fırat 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., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Classification of the putative flat preneoplastic and neoplastic lesions of the urothelium with features subthreshold for urothelial carcinoma in situ remains a challenging, indeed, vexing problem in diagnostic surgical pathology. This area, subtending lesions including flat urothelial hyperplasia, urothelial dysplasia, and atypia of unknown significance, has struggled under evolving classifications, changing criteria, and limited clinical actionability, all confounded by the recognized lack of diagnostic reproducibility. Herein, we review the state of the literature around these lesions, reviewing contemporary criteria and definitions, assessing the arguments in favor and against of retaining hyperplasia, dysplasia, and atypia of unknown significance as diagnostic entities. We clarify the intent of the original definitions for dysplasia as a lesion felt to be clearly neoplastic but with morphologic features that fall short of the threshold of urothelial carcinoma in situ. While several pathologists, including some experts in the field, conflate the term dysplasia with urothelial atypia of unknown significance, the latter is defined as a descriptive diagnosis term to express diagnostic uncertainty of a lesion of whether it is clearly reactive or neoplastic. Both molecular studies and clinical needs are considered, as we outline our approach on diagnosing each of these lesions in clinical practice. Recommendations are made to guide consistency and interoperability in future scholarship, and the place of these lesions in context of evolving trends in the field is considered., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background. The interpretation of histopathological changes of endometrial hyperplasia with or without atypia can be challenging. We aim to investigate the role of specific immunohistochemical markers in the endometrial stroma to classify endometrial hyperplasia in difficult cases. Methods and Results. We retrospectively reviewed and reclassified (WHO 2014): 47 specimens with endometrial hyperplasia without atypia, 33 with atypical hyperplasia (AH), and 13 endometrioid adenocarcinomas. We performed IHC for B-catenin, E-cadherin, p16, estrogen receptors and progesterone receptors, and B-cell lymphoma 2 (BCL2). Percentage of positive stromal cells was calculated. B-catenin was equally expressed in the stroma of both hyperplasia and AH (mean 60%, 50%; P  = .17) and was absent from adenocarcinoma (0%, hyperplasia vs adenocarcinoma; P  < .0001, AH vs adenocarcinoma; P  < .0001). E-cadherin was not expressed in the stroma of any lesion, while p16 expression levels were not statistically different (hyperplasia vs AH; P  = .46, hyperplasia vs adenocarcinoma; P  = .22, AH vs adenocarcinoma; P  = .48). Estrogen and progesterone were highly identified in stromal cells of hyperplasia (80%) and diminished in AH (respectively, at 30% and 60%, hyperplasia vs AH; P  < .0001), and in adenocarcinoma (0% and 40%, respectively). Finally, BCL2 was not differentially expressed (hyperplasia vs AH; P  = .33, hyperplasia vs adenocarcinoma; P  = .17, AH vs adenocarcinoma; P  = .36). Conclusion . Estrogen and progesterone were strongly expressed in stroma exclusively of hyperplasia, while B-catenin was particularly expressed in hyperplasia and AH. Use of these markers can be useful in the differential diagnosis of hyperplasia from AH, and AH from adenocarcinoma in challenging cases.

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Idiopathic myointimal hyperplasia of the mesenteric veins is a segmental ischemia associated with noninflammatory hyperplasia of the intimal smooth muscle of the mesenteric veins. Owing to its rarity, timely diagnosis is often difficult., Objective: The goal of this study was to improve clinical practice in terms of the diagnosis of idiopathic myointimal hyperplasia of the mesenteric veins., Design: This was a retrospective observational study., Settings: This study was conducted in a single institution with case collection from clinical archives., Patients: Data from 12 cases of idiopathic myointimal hyperplasia of the mesenteric veins were retrieved from 2006-2020. Most patients were elderly men, with a male-to-female ratio of 10:1., Main Outcome Measures: Clinical, endoscopic, radiologic, and pathologic characteristics of idiopathic myointimal hyperplasia of the mesenteric veins served as outcome measures., Results: Radiologically, marked segmental mural thickening and poor enhancement involved the sigmoid colon and rectum in most cases, with extension to the descending colon in some cases. Typical cases showed obliteration of the inferior mesenteric veins and collateral vessels. Colonoscopic findings were reminiscent of ischemia or ulcerative colitis, but sharp demarcation from the uninvolved segment was the most distinguishing feature. Surgically resected specimens showed marked segmental mural thickening, edema, and mucosal discoloration grossly. Microscopically, thick-walled, tortuous veins were observed mainly in the submucosa and subserosa, and the submucosa was markedly thickened in all cases. The subserosal large veins showed myointimal hyperplasia, and pericolic fat necrosis was invariably observed. The most useful histologic finding in biopsy material was tortuous, arteriolized mucosal capillaries with occasional fibrinoid necrosis., Limitations: This study was limited by its small number of cases and selection bias; there was also no prospective external validation., Conclusions: Radiologic and pathologic features of idiopathic myointimal hyperplasia of the mesenteric veins are distinct from those of ulcerative colitis or nonspecific ischemic colitis. Careful interpretation of endoscopic and radiologic images and generous biopsies with interpretation by experienced pathologists might lead to an early diagnosis and prevent unnecessary medical treatment. See Video Abstract at http://links.lww.com/DCR/B806., La Hiperplasia Miointimal Idioptica De Las Venas Mesentricas Es Una Peculiar Isquemia Venosa Que Puede Diagnosticarse Antes De La Ciruga: ANTECEDENTES:La hiperplasia miointimal idiopática de las venas mesentéricas es una isquemia segmentaria asociada con hiperplasia no inflamatoria del músculo liso de la íntima de las venas mesentéricas. Debido a su rareza, el diagnóstico oportuno suele ser difícil.OBJETIVO:Mejorar la práctica clínica con respecto al diagnóstico de hiperplasia miointimal idiopática de venas mesentéricas.DISEÑO:Estudio observacional retrospectivo.AJUSTES:Institución única, colección de casos de archivos clínicos.PACIENTES:Se recuperaron datos de 12 casos de hiperplasia miointimal idiopática de las venas mesentéricas durante el período 2006-2020. La mayoría de los pacientes eran hombres de edad avanzada, con una proporción de hombres a mujeres de 10:1.PRINCIPALES MEDIDAS DE RESULTADO:Características clínicas, endoscópicas, radiológicas y patológicas de la hiperplasia miointimal idiopática de las venas mesentéricas.RESULTADOS:Radiológicamente, se vio marcado engrosamiento mural afectando de manera segmentaria y escaso realce que comprometieron al colon sigmoides y al recto en la mayoría de los casos, con extensión al colon descendente en algunos casos. Los casos típicos mostraron obliteración de las venas mesentéricas inferiores y vasos colaterales. Los hallazgos colonoscópicos recordaban a la isquemia o la colitis ulcerosa, pero la demarcación nítida del segmento no afectado fue la característica más distintiva. Las piezas quirúrgicas mostraron un marcado engrosamiento mural de manera segmentaria, edema y decoloración de la mucosa de forma macroscópica. Microscópicamente, se observaron venas tortuosas de paredes engrosadas principalmente en la submucosa y subserosa y la submucosa se encontraba marcadamente engrosada en todos los casos. Las grandes venas subserosas mostraban hiperplasia de la mioíntima e invariablemente se observaba necrosis grasa pericólica. El hallazgo histológico más útil en el material de biopsia fueron los tortuosos capilares arteriolizados de la mucosa con necrosis fibrinoide ocasional.LIMITACIONES:Pequeño número de casos; sesgo de selección; sin validación externa prospectiva.CONCLUSIONES:Las características radiológicas y patológicas de la hiperplasia miointimal idiopática de las venas mesentéricas son distintas a las de la colitis ulcerosa o la colitis isquémica no específica. La interpretación cuidadosa de las imágenes endoscópicas y radiológicas y múltiples biopsias de manera generosa con la interpretación de patólogos experimentados pueden conducir a un diagnóstico temprano y prevenir tratamientos médicos innecesarios. Consulte Video Resumen en http://links.lww.com/DCR/B806. (Traducción-Dr Osvaldo Gauto)., (Copyright © The ASCRS 2021.)

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., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to disclose.

Background: Computer-aided examination of digital tissue images has attracted attention in recent years. Application in the field of parathyroid pathology has not been studied previously. It holds a potential to assist in the examination of parathyroid gland adenoma or hyperplasia., Objectives: To explore parathyroid cell detection of slide images by digital tissue analysis and compare the results to standard human processing., Methods: 47 incisional biopsies of healthy appearing parathyroid glands were evaluated for their cellularity level. First, by the standard examination using microscopy by three independent pathologists. We compared the mean cellularity grading of the pathologists to the output of a computerized cell detection software., Results: A disagreement was found between the standard human cellularity grading and the digital analysis output. However, the digital analysis reaches a 94% specificity and 48% sensitivity to predict high cellularity (>60% parenchymal cells)., Conclusions: Digital analysis of parathyroid tissue can be used as a tool for hypercellularity elimination, therefore assisting in the diagnosis of parathyroid cell hyperplasia. Additional studies using more advanced algorithms are necessary for further precision enhancement., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: PRAME (PReferentially expressed Antigen in MElanoma) is an antigen that shows marked overexpression in melanoma compared to normal skin melanocytes. PRAME immunohistochemistry has proven effective in distinguishing melanocytic nevi from melanoma, but it is unclear if it may be used to distinguish melanoma in situ from other benign pigmented lesions. In particular, differentiating from melanocytic hyperplasia in sun-damaged skin is sometimes clinically and histopathologically challenging. We hypothesized that PRAME staining of solar lentigo, sun-damaged skin, and melanoma in situ would aid in setting a threshold of positivity that could be useful in evaluating such conditions., Methods: We collected and stained typical examples of solar lentigo, melanoma in situ, and non-lesional sun-damaged skin by PRAME immunohistochemistry to assess a potential cutoff of PRAME positivity., Results: Solar lentigo and non-lesional sun-damaged skin had 10 or fewer PRAME-positive cells per millimeter (mean 1.2), on the other hand melanoma in situ had at least 16 (mean 75.1)., Conclusions: PRAME immunostaining appears sensitive and specific in the current series. This could be clinically useful for distinguishing melanoma in situ from benign melanocytic hyperplasia in sun-damaged skin. However, further studies are required to determine if 10 cells per millimeter is an acceptable threshold of positivity., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: Distinction between well-differentiated endometrial carcinoma (EMCA) with microglandular/mucinous features and benign endocervical microglandular hyperplasia (MGH) can be a diagnostic challenge, especially when tissue is limited. The immunostains used to distinguish endocervical and endometrial carcinoma are less useful when the differential diagnosis is MGH. Here, we investigate the utility of p63 and phosphatase and tensin homologue (PTEN) to aid accurate classification., Methods and Results: Cases obtained from our pathology archives included 25 EMCA with mucinous/microglandular features, 26 MGH and nine atypical microglandular proliferations. Cases were assessed for glandular architecture, presence of mucinous and/or eosinophilic luminal secretions, subnuclear vacuoles, foamy histiocytes, inflammation, squamous metaplasia, cytological atypia and mitotic activity. The presence and pattern of immunohistochemical staining for p63 and PTEN was recorded. Microglandular proliferations with cytological atypia, mitotic activity, foamy histiocytes and complex glandular architecture were more commonly seen in EMCA, while small glands, bland nuclei and subnuclear vacuoles were enriched in MGH. All MGH cases displayed p63-positive subcolumnar reserve cells and retained PTEN expression. Four EMCA cases showed non-specific focal p63 staining either at the surface of the tumour or in areas of squamous differentiation. p63 and PTEN immunostains accurately predicted the final diagnosis for 3 atypical microglandular proliferation cases with follow-up., Conclusions: While there are morphological characteristics that differentiate EMCA and MGH, there is frequent overlap between these entities. Nonetheless, the pattern and extent of p63 and PTEN can aid accurate classification. Consistent p63-positive subcolumnar reserve cells were seen only in MGH., (© 2022 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Papillary endothelial hyperplasia (PEH) is a rare soft tissue lesion arising from excessive reactive endothelial cell proliferation described in humans, dogs, and horses. PEH is considered a diagnostic challenge in humans, in which it is frequently misdiagnosed as angiosarcoma. We describe here PEH that developed at injection sites in 2 cats that were initially misdiagnosed as feline injection-site sarcoma by cytology and as subcutaneous angiosarcoma by histopathology. Morphologic features included sharp demarcation from surrounding tissues, and a layered microscopic architecture with an outer fibrous capsule from which emerged fibrovascular stalks covered by a monolayer of factor VIII-related antigen and CD31-positive flat-to-plump endothelial cells. Both lesions had a cystic core containing abundant erythrocytes and fibrin. PEH lesions did not recur in either case. Immunohistochemistry for α-smooth muscle actin and desmin demonstrated that the capsule was devoid of smooth muscle cells, excluding an intravascular origin. PEH in these cats was hypothesized to have developed extravascularly following trauma related to injection. We wish to provide awareness of PEH in domestic cats and of the risk of misdiagnoses leading to overtreatment.

Goblet cell adenocarcinoma and signet-ring cell adenocarcinoma are well-known diagnostic pitfalls of routine appendectomy specimens. Here we present a case of acute appendicitis with prominent neuronal (ganglion cell) hyperplasia and swelling which histologically mimics goblet cell adenocarcinoma and signet-ring cell adenocarcinoma. Attention to the cytologic features of the lesional cells (absence of atypia, mitotic activity) and their close association with nerves and classic ganglion cells, along with the use of a limited panel of immunostains, ensures proper classification of this rare but striking benign process.

Background: Oral epithelial dysplasia (OED) is the presence of cells of an abnormal type within a tissue, which may signify a stage preceding the development of cancer. Our aim was to determine the interrelation between the expression of multiple molecular markers and the histological features of oral dysplasia., Methods: Fifteen samples of OED (five for each severity degree) were analyzed through software assisted image cytometry nuclear morphology. p53 (wild-type and mutated form), Bax and Bcl2 expression was immunohistochemically determined, and the gene expression of MMP1, MMP2, MMP9 and hTERT was determined by RT-PCR. The mean, standard deviation, ANOVA and Fisher's Exact Test (P<0.05) were performed., Results: Our analysis indicated congruence between the software-assisted measurement of nuclear morphology and severity degree. Only five samples were positive to p53-mutated form; and Bax was more expressed than Bcl-2. hTERT expression was significantly expressed in relation to severity, and MMP1 was predominantly expressed, followed by MMP9 and MMP2., Conclusions: Our results reinforce that software-assisted measurement is an alternative to severity degree determination. MMP1 is an important marker for severity dysplasia degree; however, the predominant expression of Bax over Bcl-2 suggests that this pro-apoptotic state could be used to minorize the progression, perhaps, as a future therapeutic target.

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.

As the first node in treatment algorithms for breast disease, pathologists have the potential to play a critical role in refining appropriate therapy for lesions in the atypical ducal hyperplasia-ductal carcinoma in situ (ADH-DCIS) spectrum by conservatively approaching diagnosis of lesions limited in size on core needle biopsy. Appropriate efforts to downgrade the diagnosis of lesions at the borderline of ADH and DCIS will certainly lead to more breast conservation and avoid the common morbidities of mastectomy, sentinel node biopsy, and radiation therapy. Whether results of clinical trials of active surveillance will successfully identify a subset of women who may successfully forgo even limited breast-conserving surgery is eagerly anticipated. Given the increasing concern that a significant number of women with DCIS are overtreated, identification of patients at very low risk for progression who may forgo surgery and radiation therapy safely is of significant interest., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Despite the importance of atypia in diagnosing and classifying breast lesions, the definition of atypia varies depending on the context, with a lack of consistent and objective criteria for assessment. Atypia in breast pathology may be cytonuclear and/or architectural with different applications and implications. Cytonuclear atypia is used to assist the distinction of various intraductal epithelial proliferative lesions including usual ductal hyperplasia (UDH) versus atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS), and to grade DCIS. In invasive carcinoma, nuclear atypia (i.e., nuclear pleomorphism) is a component of the histological grading system. Stromal cell cytonuclear atypia is one of the key features used to distinguish fibroadenoma from phyllodes tumour (PT) and to classify PT as benign, borderline or malignant. Similarly, cytonuclear atypia is used in the evaluation of myoepithelial cell alterations in the breast. Architectural atypia is used to differentiate flat epithelial atypia (FEA) from ADH or DCIS. In addition to the inherent subjectivity in the interpretation of atypia, which presents as a morphological continuum reflecting a biological spectrum, the lack of standardisation in defining atypia augments diagnostic discordance in breast pathology, with potential implications for patient management. Evidence to date suggests that the traditional criteria used to assess atypia may require modification in the era of digital pathology primary diagnosis. This review aims to provide a comprehensive review of atypia in breast pathology with reference to inconsistencies, challenges and limitations., (Copyright © 2021 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Masson's tumor or intravascular papillary endothelial hyperplasia is a rare nonmalignant pseudotumoral disease, arising in different anatomic sites, that can clinically and radiologically mimic various benign and malignant tumors. We report an exceptional case of mediastinal Masson's tumor, mimicking a thymoma, in a 48-year-old man, successfully treated with surgery. Though surgical removal may be technically difficult because of the intrinsic hypervascularized nature of these pseudotumoral benign lesions, resection is generally recommended, as they represent a locus minoris resistentiae of blood vessels, potentially causing fatal bleedings., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Blunt duct adenosis (BDA) is a breast lesion first described by Foote and Stewart in 1945 as a proliferative benign lesion of the terminal duct lobular unit. Throughout recent decades, further literature descriptions of BDA have been confusing. Some consider BDA to be a separate entity, some a growth pattern of columnar cell changes. The WHO 2012 considered BDA and columnar cell changes to be synonyms, while columnar cell lesions, especially those with atypia, are part of a spectrum of early precursors of the low nuclear grade breast neoplasia family. In the updated WHO 2019 version, BDA is mentioned as 'not recommended' terminology for columnar cell lesions without further discussing it, leaving the question open if BDA should be considered a separate entity.Good diagnostic criteria for BDA have however largely been lacking, and its biological background has not yet been unravelled. In this paper, we point out that BDA is mainly associated with benign breast lesions and not with other recognised precursor lesions. Further, 16q loss, which is the hallmark molecular event in the low nuclear grade breast neoplasia family, is lacking in BDA. We therefore hypothesise that BDA may not be a true precursor lesion but a benign polyclonal lesion, and propose morphological diagnostic criteria to better differentiate it from columnar cell lesions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Pacinian disorders are exceedingly rare, and the exact pathogenesis is still unknown. The most common symptoms are pain, sensory changes, and a visible or palpable mass, and diagnosis is usually made by pathological examination after the excision of the painful nodule. In this case report, we present the case of a 49-year-old male with Pacinian corpuscle hyperplasia located on the metacarpophalangeal joint, emerging at the same hand of the patient two years after the treatment due to complex regional pain syndrome (CRPS). To the best of our knowledge, this is the first case report revealing the association of CRPS with hyperplasia of Pacinian corpuscles.

Introduction: Lobular carcinoma in situ (LCIS), atypical ductal and lobular hyperplasia (AH) increase breast cancer risk. We examined risk management recommendations (RMR) and acceptance in AH/LCIS., Methods: All patients with AH/LCIS on core needle biopsy from 2013 to 2016 at our institution were identified; cancer patients were excluded. Univariate and multivariate analysis examined factors associated with management., Results: 98 % of patients were evaluated by breast surgeons and 53 % underwent risk model calculation (RC). 77 % had new RMR. RMR of MRI screening (MRI), genetic counselling (GC) and medical oncology (MO) referral were 41 %, 18 %, 77 %, respectively. MRI screening was more likely recommended in those with strong family history (p = 0.01), and high RC (p < 0.001). Uptake of at least one RMR did not occur in 84 % of patients. Use of RC correlated with MO acceptance (p = 0.049)., Conclusions: Diagnosis of atypia has the potential to change risk management for most, however only 16 % of patients accepted all RMR., (Copyright © 2021. Published by Elsevier Inc.)

Competing Interests: The authors declare no conflict of interest.

Reparative perineural hyperplasia is an incidental and probably underreported reactive histologic finding thus far only reported in the setting of healing wounds or adjacent to a dermatofibroma in cutaneous specimens. It is characterized by a focal concentric proliferation of cytologically bland spindled perineurial cells and is hence considered a benign histologic mimic of neoplastic perineural invasion. Thus, it may present a diagnostic pitfall and we therefore consider it as a valuable entity to be aware of. To the best of our knowledge, this brief case report is the first to convey that reparative perineural hyperplasia may also occur in the gastrointestinal tract. It may therefore be a ubiquitous reactive histological phenomenon relating to previous surgical or traumatic wounds in various sites, that is, outside the thus far established setting of skin reexcision specimens.

Background: Infant pulmonary function tests (iPFTs) in subjects with neuroendocrine cell hyperplasia of infancy (NEHI) have demonstrated substantial expiratory airflow obstruction and air trapping., Research Question: Can indices from iPFTs be used in the diagnosis of NEHI?, Study Design and Methods: This is an observational case-control study evaluating iPFT results from a registry of patients assessed at the Hadassah Hebrew University Medical Center between 2008 and 2018. iPFTs results in infants with NEHI were compared to two disease control infant groups (infants evaluated for recurrent wheezing and infants evaluated due to prematurity) and a spirometry control group of infants with normal expiratory airflow, using the Kruskal-Wallis test. Receiver operating characteristic (ROC) curves were used to assess the diagnostic accuracy of iPFT indices., Results: We evaluated iPFT data in 481 infants (15, NEHI; 292, wheezing; 128, premature; and 46, spirometry control group). Infants with NEHI had significantly increased trapped air volumes (median functional residual capacity measured with infant whole-body plethysmography [FRC pleth ] was 199% predicted; median ratio of residual volume to total lung capacity was 59% predicted) when compared with results in all evaluated groups of infants (P < .001), including multiple pairwise comparisons. Airflow limitation was demonstrated in infants with NEHI when compared with the infants in the spirometry control group but was similar to the two disease control groups. FRC pleth had the best discriminatory ability for NEHI diagnosis, with an FRC pleth  ≥ 150% predicted demonstrating a ROC of 0.91 (95% CI, 0.82-1.00), sensitivity of 86.7% (95% CI, 59.5%-98.3%), and specificity of 95.5% (95% CI, 93.2%-97.3%)., Interpretation: Findings on iPFTs of markedly increased air trapping, out of proportion to the degree of airflow limitation, are characteristic of infants with NEHI. iPFT results demonstrating an FRC pleth  ≥ 150% predicted are highly specific for NEHI and may aid in early diagnosis. Further research is required to confirm these findings in a prospective cohort and to understand the pathophysiologic explanation for these findings., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)