Publications by authors named "Paola Parente"

63 Publications

Evaluation of Micro Satellite Instability and Mismatch Repair Status in Different Solid Tumors: A Multicenter Analysis in a Real World Setting.

Cells 2021 Jul 24;10(8). Epub 2021 Jul 24.

Unit of Pathology, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo, 71013 Foggia, Italy.

Immune-checkpoint inhibitors (ICIs) play a key role in the treatment of advanced stage colorectal cancer (CRC) patients featuring a deficient DNA mismatch repair (dMMR) system or a high microsatellite instability (MSI-H) profile. However, beyond the established role in CRC patients, ICIs have highly proven efficacy in other solid tumors featuring MSI-H/dMMR status represented by endometrial, gastric, ovarian, prostatic, and pancreatic carcinomas (EC, GC, OC, PrC, and PaC). Our aim was to compare the concordance rates among the Idylla™ MSI test, TapeStation 4200, and immunohistochemical (IHC) analysis in assessing MSI-H/dMMR status in EC, GC, OC, PrC, and PaC patients. The Sanger sequencing-based Titano MSI test was used in discordant cases. One hundred and eighty-five cases ( = 40 PrC, = 39 GC, = 38 OC, = 35 PaC, and = 33 EC) were retrospectively selected. MMR protein expression was evaluated by IHC. After DNA quality and quantity evaluations, the Idylla and TapeStation 4200 platforms were adopted for the evaluation of MSI status. Remarkably, compared to IHC, the Idylla™ platform achieved a global concordance rate of 94.5% (154/163) for the microsatellite stable (MSS)/proficient MMR (pMMR) cases and 77.3% (17/22) for the MSI-H/dMMR cases. Similarly, a global concordance rate of 91.4% (149/163) and 68.2% (15/22) for MSS/pMMR and MSI-H/dMMR cases was also identified between IHC and the TapeStation 4200 microfluidic system. In addition, a global concordance of 93.1% (148/159) and 69.2% (18/26) for MSS/pMMR and MSI-H/dMMR cases was observed between the Idylla™ and TapeStation 4200 platforms. Discordant cases were analyzed using the Titano MSI kit. Overall, our data pinpointed a central role for molecular techniques in the diagnostic evaluation of dMMR/MSI-H status not only in CRC patients but also in other types of solid tumors.
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http://dx.doi.org/10.3390/cells10081878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391221PMC
July 2021

The histomorphological and molecular landscape of colorectal adenomas and serrated lesions.

Pathologica 2021 Jun;113(3):218-229

Department of Translational Medicine, University of Ferrara, Ferrara, Italy.

The 2019 WHO classification of digestive system tumors significantly reformed the classificatory definition of serrated lesions of the colorectal mucosa and added new essential diagnostic criteria for both conventional adenomas and hereditary gastrointestinal polyposis syndromes. Histopathological examination of colorectal adenocarcinoma precursors lesions represents an important segment of daily clinical practice in a pathology department and is essential for the implementation of current colorectal adenocarcinoma secondary prevention strategies. This overview will focus on a schematic histopathological and molecular classification of precursor lesions arising within colorectal mucosa.
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http://dx.doi.org/10.32074/1591-951X-270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299322PMC
June 2021

Synchronous primary gastric triple-hit high-grade B-cell lymphoma and gastric adenocarcinoma: endoscopic and pathological findings.

BMJ Case Rep 2021 Jul 20;14(7). Epub 2021 Jul 20.

Pathology Unit, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.

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http://dx.doi.org/10.1136/bcr-2021-244643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292813PMC
July 2021

Which are the limiting factors in lung tissue sampling and diagnostic accuracy for a new Interventional Pulmonology Unit? From expert consensus-based evidence to results of a new-born Unit.

J Thorac Dis 2021 May;13(5):2942-2951

Pathology Unit, Fondazione IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo, (FG), Italy.

Background: There is a gap of knowledge about the factors that may determine the quality and the accuracy of diagnostic bronchoscopic procedures when setting up a new Interventional Pulmonology Unit. As little evidence-based medicine is available on this matter, an online consensus opinion of experts was gathered and compared with real-life data coming from a new Interventional Pulmonology (IP) Unit.

Methods: A survey was emailed to the heads of all Italian IP Units to investigate the factors influencing the success of the diagnostic yield of a new IP Unit. The survey consisted of 24 items grouped by topic; the level of agreement ranged from 1 (no influence) to 7 (strong influence). After responses were collected, we submitted the data on the accuracy of the endoscopic procedures performed during the first two years of our new IP Unit to the attention of the participants for a second round of survey; the level of consistency between the first and second round of responses was assessed.

Results: After having been shown the results of the first two years of activity of our Unit, in the second round of the survey the responders indicated the personal skills of the Interventional Pulmonologist, the availability of echoendoscopic technology and the expertise in evaluating cytological samples as the factors able to positively influence the performance of a newly established IP Unit. Neither the role of dedicated nursing assistance, the availability of a rapid on-site evaluation, nor the presence of anesthesiology assistance were considered to be limiting factors for the final accuracy results.

Conclusions: A consensus of opinion of a group of expert interventional pulmonologists highlighted the factors that may be responsible for the diagnostic success of a newly established Italian IP Unit. These factors are mainly three: personal skills of the interventional pulmonologist, the availability of echoendoscopic technology, and the expertise in reading cytological samples.
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http://dx.doi.org/10.21037/jtd-20-2990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182518PMC
May 2021

A diminutive polyp with synchronous liver metastasis: Luck or skill?

Dig Liver Dis 2021 Jun 16. Epub 2021 Jun 16.

Gastroenterology and Endoscopy Units, Fondazione "Casa Sollievo della Sofferenza", IRCCS, San Giovanni Rotondo, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.dld.2021.05.019DOI Listing
June 2021

Inverted colonic diverticulum (ICD): report of two cases and literature review of a not that unusual endoscopic challenge.

Clin Res Hepatol Gastroenterol 2021 Apr 27;45(5):101711. Epub 2021 Apr 27.

Gastroenterology and Endoscopy Units, Fondazione "Casa Sollievo della Sofferenza", IRCCS, San Giovanni Rotondo, Italy. Electronic address:

Inverted colonic diverticulum (ICD) is a rare intraluminal lesion occurring in about 0.7-1.7% of people, often endoscopically indistinguishable from polyps. Some unspecific endoscopic features may assist to distinguish polypoid ICD from true polyps. This differentiation bears relevance for the therapeutic approach, as colonic polyps require snare polypectomy, a practice which may be associated with colonic perforation in case of true ICD. The endoscopist, therefore, should be aware of the likelihood of detecting these lesions during colonoscopy. A close inspection and a gentle probing could assist in a correct diagnosis and avoid risky procedures such as biopsy or polypectomy. Rarely, a neoplasm arising over an ICD and its treatment has been described. We reported two cases, one of which with dysplasia, and their treatment, and reviewed all the ICD endoscopic cases so far reported in the literature, remarking the possibility of finding pedunculated ICDs or neoplasm arising over an ICD.
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http://dx.doi.org/10.1016/j.clinre.2021.101711DOI Listing
April 2021

Histopathology of non-IBD colitis practical recommendations from pathologists of IG-IBD Group.

Dig Liver Dis 2021 Aug 10;53(8):950-957. Epub 2021 Mar 10.

Institute of Pathology, ASST Spedali Civili, Brescia, Italy.

Pathologists are often called upon to diagnose colitides that differ from the two main forms of inflammatory bowel disease (IBD). These non-IBD colitides include infectious colitis, microscopic colitis, ischemic colitis, eosinophilic colitis, autoimmune enterocolitis, segmental colitis associated with diverticulosis, drug-induced colitis, radiation colitis and diversion colitis. The diagnosis of these different disease entities relies on the histopathological examination of endoscopic biopsies of the gastrointestinal tract. This paper reviews the main histomorphological characteristics of the various Non-IBD colitides.
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http://dx.doi.org/10.1016/j.dld.2021.01.026DOI Listing
August 2021

Histopathology of Non-IBD Colitis. A practical approach from the Italian Group for the study of the gastrointestinal tract (GIPAD).

Pathologica 2021 Feb;113(1):54-65

University Hospital "San Giovanni di Dio e Ruggi D'Aragona", Salerno, Italy.

Non-IBD colitides (NIBDC) are intestinal diseases clinically and endoscopically overlapping with Inflammatory Bowel Diseases (IBD), sometimes with a similar histological picture. NIBDC include entities such as infectious colitis, ischemic colitis, pseudomembranous colitis, eosinophilic colitis, autoimmune enterocolitis, segmental colitis associated with diverticulosis, drug-induced colitis, radiation-induced colitis, diversion colitis, and microscopic colitis, this last including two entities: collagenous and lymphocytic colitis. The knowledge of the most useful histological features and the main clinical data for each entity is mandatory in daily clinical practice, for correct pathological diagnosis and clinical management.
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http://dx.doi.org/10.32074/1591-951X-234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138693PMC
February 2021

Histopathology of IBD Colitis. A practical approach from the pathologists of the Italian Group for the study of the gastrointestinal tract (GIPAD).

Pathologica 2021 Feb;113(1):39-53

Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), Italy.

Inflammatory bowel diseases (IBDs) are lifelong disorders in which an interaction between genetic and environmental factors is involved. IBDs include two entities: Crohn's disease (CD) and ulcerative colitis (UC); these can be adequately diagnosed and distinguished with a correct methodological approach based on communicating exhaustive clinical, endoscopic and laboratory information to the pathologist and performing adequate bioptic sampling and precise morphological signs including crypt architecture, distribution of inflammation and granulomas, when present. IBD needs to be distinguished from non-IBD colitis, mostly at its onset. Moreover, IBDs are associated with an increased risk of developing colorectal adenocarcinoma. In daily pathological practice, correct diagnosis of IBD and its subclassification as well as a correct detection of dysplasia is imperative to establish the best therapeutic approach.
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http://dx.doi.org/10.32074/1591-951X-235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138698PMC
February 2021

Neuroendocrine neoplasms of the duodenum, ampullary region, jejunum and ileum.

Pathologica 2021 Feb;113(1):12-18

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Neuroendocrine neoplasms of the small intestine are some of the most frequently occurring along the gastrointestinal tract, even though their incidence is extremely variable according to specific sites. Jejunal-ileal neuroendocrine neoplasms account for about 27% of gastrointestinal NETs making them the second most frequent NET type. The aim of this review is to classify all tumors following the WHO 2019 classification and to describe their pathologic differences and peculiarities.
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http://dx.doi.org/10.32074/1591-951X-228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138699PMC
February 2021

Neuroendocrine neoplasms of the esophagus and stomach.

Pathologica 2021 Feb;113(1):5-11

Institute of Pathology, University Hospital and University of Lausanne, Switzerland.

Esophageal neuroendocrine neoplasms (E-NENs) are much rarer than other gastro-entero-pancreatic neuroendocrine neoplasms, the majority showing aggressive behavior with early dissemination and poor prognosis. Among E-NENs, exceptionally rare well differentiated neuroendocrine tumors (E-NET) and more frequent esophageal poorly differentiated neuroendocrine carcinomas (E-NEC) and mixed neuroendocrine-non neuroendocrine neoplasms (MiNEN) can be recognized. E-NECs usually exhibit a small cell morphology or mixed small and large cells. Esophageal MiNEN are composed of NEC component admixed with adenocarcinoma or squamous cell carcinoma. Gastric (G) NENs encompass a wide spectrum of entities ranging from indolent G-NETs to highly aggressive G-NECs and MiNENs. Among G-NETs, ECL-cell NETs are the most common and, although composed of histamine-producing cells, are a heterogeneous group of neoplastic proliferations showing different clinical and prognostic features depending on the patient's clinico-pathological background including the morphology of the peri-tumoral mucosa, gastrin serum levels, presence or absence of antral G-cell hyperplasia, and presence or absence of MEN1 syndrome. In general, NET associated with hypergastrinemia show a better outcome than NET not associated with hypergastrinemia. G-NECs and MiNENs are aggressive neoplasms more frequently observed in males and associated with a dismal prognosis.
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http://dx.doi.org/10.32074/1591-951X-229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138695PMC
February 2021

Accuracy and inter-observer agreement of the nice and kudo classifications of superficial colonic lesions: a comparative study.

Int J Colorectal Dis 2021 Jul 1;36(7):1561-1568. Epub 2021 Mar 1.

Gastroenterology and Endoscopy Units, Fondazione "Casa Sollievo della Sofferenza", IRCCS, San Giovanni Rotondo, Italy.

Purpose: For superficial colonic lesions, the NICE and Kudo classifications are used in the in vivo prediction of histology and as guide to therapy. The NICE system derives information from unmagnified NBI endoscopic images. The Kudo one necessitates a magnification, but, as this tool is not commonly available, it is applied also to characterize unmagnified pictures to compare their diagnostic performances.

Methods: We conducted a prospective comparison of the NICE versus the Kudo classification for the differential diagnosis of colonic polyps taking histology as the gold standard. The inter-observer agreement for both classifications among 11 colonoscopists was also evaluated. Short unmagnified NBI videoclips of 64 colonic polyps were sent twice to the participants. In the first round, they classified the lesions according to the NICE classification; 4 months later, the same videos were assessed with the Kudo system. The diagnosis provided by the participants was grouped in non-neoplastic, non-invasive neoplasia, invasive neoplasia.

Results: Overall, the diagnostic accuracy was 82% (95%CI: 79-85) with the NICE system and 81% (95%CI: 78-84) with the Kudo one (ρ = 0.78). The accuracy of the NICE classification for non-neoplastic lesions was greater compared with the Kudo's (ρ = 0.03). Sensitivity sub-analyses revealed a higher ability of the NICE in distinguishing between neoplastic vs. non-neoplastic lesions (ρ = 0.01). The overall inter-rater agreement did not differ when the classifications were compared.

Conclusion: The NICE and the Kudo classifications might be considered comparable. Our data could allow the use of the NBI Kudo classification even in those centers where magnification is not available.
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http://dx.doi.org/10.1007/s00384-021-03897-8DOI Listing
July 2021

Transabdominal ultrasound-guided pancreatic biopsy: a neglected but safe, effective and inexpensive procedure that needs to be re-juvinalized.

J Ultrasound 2021 Jun 1;24(2):175-182. Epub 2021 Feb 1.

Division of Gastroenterology and Endoscopy, IRCCS, Fondazione Casa Sollievo della Sofferenza, Viale Cappuccini 1, 71024, San Giovanni Rotondo, Italy.

Background: For solid pancreatic masses, ultrasound endoscopic fine-needle biopsy is suggested as the front-line investigation for tissue achievement, notwithstanding the optimal performance of transabdominal ultrasound (TUS)-guided biopsy.

Purpose: To reassess the efficacy and effectiveness of TUS-guided sampling and to determine the factors predictive of accurate histology.

Methods: In total, 142 patients with an indication for a TUS-guided biopsy of a pancreatic mass were analyzed. A single pass of an 18-gauge Biomol needle was carried out by the Menghini technique. The accuracy, sensitivity, and specificity of the procedure in terms of correctly diagnosing an inflammatory or neoplastic lesion were determined. The patients' characteristics, the size and location of the mass, and the sonographers' experience in performing TUS were recorded.

Results: The sampling was unsuccessful in 24 cases, owing to the deep localization of lesions (57%), bloating (33%), or low patient compliance (10%). The accuracy, sensitivity, and specificity of the 118 successful biopsies were 81%, 79%, and 100%, respectively. A biopsy core was obtained in 90 of the 118 patients (76%) in whom the procedure was attempted. In the multivariate analysis, lesion size (≤ 20 mm vs. > 20 mm) (OR = 5.3 [1.7-17.0]) and operator experience (OR = 4.4 [1.6-12.1]) predicted the acquisition of adequate samples. With an expert sonographer, the accuracy, sensitivity, and specificity were 87%, 85%, and 100%, respectively. Two adverse events were registered: mild abdominal pain and a hypotensive crisis.

Conclusions: The present investigation highlights the optimal performance of a TUS-guided biopsy of a pancreatic mass. Because of its simplicity and safety, the procedure needs to be included among the recommended investigative options.
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http://dx.doi.org/10.1007/s40477-020-00542-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137799PMC
June 2021

Primary Epithelioid Hemangioma of the Central Nervous System: A Case Report and Review of the Literature.

J Neuropathol Exp Neurol 2021 Aug;80(7):717-719

Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.

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http://dx.doi.org/10.1093/jnen/nlaa163DOI Listing
August 2021

Hodgkin Reed-Sternberg-Like Cells in Non-Hodgkin Lymphoma.

Diagnostics (Basel) 2020 Nov 27;10(12). Epub 2020 Nov 27.

Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

Reed-Sternberg cells (RSCs) are hallmarks of classic Hodgkin lymphoma (cHL). However, cells with a similar morphology and immunophenotype, so-called Reed-Sternberg-like cells (RSLCs), are occasionally seen in both B cell and T cell non-Hodgkin Lymphomas (NHLs). In NHLs, RSLCs are usually present as scattered elements or in small clusters, and the typical background microenviroment of cHL is usually absent. Nevertheless, in NHLs, the phenotype of RSLCs is very similar to typical RSCs, staining positive for CD30 and EBV, and often for B cell lineage markers, and negative for CD45/LCA. Due to different therapeutic approaches and prognostication, it is mandatory to distinguish between cHL and NHLs. Herein, NHL types in which RSLCs can be detected along with clinicopathological correlation are described. Moreover, the main helpful clues in the differential diagnosis with cHL are summarized.
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http://dx.doi.org/10.3390/diagnostics10121019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760963PMC
November 2020

Correction to: A New Intraepithelial γδ T-Lymphocyte Marker for Celiac Disease Classification in Formalin-Fixed Paraffin-Embedded (FFPE) Duodenal Biopsies.

Dig Dis Sci 2020 Nov 25. Epub 2020 Nov 25.

Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.

The original version of the article unfortunately contained an error in the first name and the surname of the all authors in the author group. Below is the corrected first name and the surname of the authors.
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http://dx.doi.org/10.1007/s10620-020-06731-3DOI Listing
November 2020

Current prognostic and predictive biomarkers for gastrointestinal tumors in clinical practice.

Pathologica 2020 Sep;112(3):248-259

Anatomic Pathology, San Martino IRCCS Hospital,, Genova, Italy.

The pathologist emerged in the personalized medicine era as a central actor in the definition of the most adequate diagnostic and therapeutic algorithms. In the last decade, gastrointestinal oncology has seen a significantly increased clinical request for the integration of novel prognostic and predictive biomarkers in histopathological reports. This request couples with the significant contraction of invasive sampling of the disease, thus conferring to the pathologist the role of governor for both proper pathologic characterization and customized processing of the biospecimens. This overview will focus on the most commonly adopted immunohistochemical and molecular biomarkers in the routine clinical characterization of gastrointestinal neoplasms referring to the most recent published recommendations, guidelines and expert opinions.
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http://dx.doi.org/10.32074/1591-951X-158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931577PMC
September 2020

Gastrointestinal lymphoproliferative lesions: a practical diagnostic approach.

Pathologica 2020 Sep;112(3):227-247

Department of Medical Biotechnology, Section of Pathology, University of Siena, Italy.

The gastrointestinal tract (GI) is the primary site of lymphoproliferative lesions, spanning from reactive lymphoid hyperplasia to overt lymphoma. The diagnosis of these diseases is challenging and an integrated approach based on clinical, morphological, immunohistochemical and molecular data is needed. To reach to confident conclusions, a stepwise approach is highly recommended. Histological evaluation should first assess the benign neoplastic nature of a given lymphoid infiltrate. Morphological and phenotypic analyses should then be applied to get to a definite diagnosis.

This review addresses the key histological features and diagnostic workup of the most common GI non-Hodgkin lymphomas (NHLs). Differential diagnoses and possible pitfalls are discussed by considering distinct groups of lesions ( small to medium B-cell NHLs; medium to large B-cell NHLs; T-cell NHLs; and mimickers of Hodgkin lymphoma). The key clinical and epidemiological features of each entity are also described.
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http://dx.doi.org/10.32074/1591-951X-161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931576PMC
September 2020

Malignant epithelial/exocrine tumors of the pancreas.

Pathologica 2020 Sep;112(3):210-226

Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy.

Pancreatic malignant exocrine tumors represent the most important cause of cancer-related death for pancreatic neoplasms. The most common tumor type in this category is represented by pancreatic ductal adenocarcinoma (PDAC), an ill defined, stroma-rich, scirrhous neoplasm with glandular differentiation. Here we present the relevant characteristics of the most important PDAC variants, namely adenosquamous carcinoma, colloid carcinoma, undifferentiated carcinoma, undifferentiated carcinoma with osteoclast-like giant cells, signet ring carcinoma, medullary carcinoma and hepatoid carcinoma. The other categories of malignant exocrine tumors, characterized by fleshy, stroma-poor, circumscribed neoplasms, include acinar cell carcinoma (pure and mixed), pancreatoblastoma, and solid pseudopapillary neoplasms. The most important macroscopic, histologic, immunohistochemical and molecular hallmarks of all these tumors, highlighting their key diagnostic/pathological features are presented. Lastly, standardized indications regarding gross sampling and how to compile a formal pathology report for pancreatic malignant exocrine tumors will be provided.
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http://dx.doi.org/10.32074/1591-951X-167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931574PMC
September 2020

Celiac disease: histology-differential diagnosis-complications. A practical approach.

Pathologica 2020 Sep;112(3):186-196

Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.

Celiac disease is a multi-factorial chronic inflammatory intestinal disease, characterized by malabsorption resulting from mucosal injury after ingestion of wheat gluten or related rye and barley proteins. Inappropriate T-cell-mediated immune response against ingested gluten in genetically predisposed people, leads to characteristic histological lesions, as villous atrophy and intraepithelial lymphocytosis. Nevertheless, celiac disease is a comprehensive diagnosis with clinical, serological and genetic characteristics integrated with histological features. Biopsy of duodenal mucosa remains the gold standard in the diagnosis of celiac disease with the recognition of the spectrum of histological changes and classification of mucosa damage based on updated Corazza-Villanacci system. Appropriate differential diagnosis evaluation and clinical context also for the diagnosis of complications is, moreover, needed for correct histological features interpretation and clinical management.
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http://dx.doi.org/10.32074/1591-951X-157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931573PMC
September 2020

Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes.

Pathologica 2020 Sep;112(3):166-185

Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Italy.

Gastric cancer accounts for about 6% of cancers worldwide, being the fifth most frequently diagnosed malignancy and the third leading cause of cancer related death. Gastric carcinogenesis is a multistep and multifactorial process and is the result of the complex interplay between genetic susceptibility and environmental factors. The identification of predisposing conditions and of precancerous lesions is the basis for screening programs and early stage treatment. Furthermore, although most gastric cancers are sporadic, familial clustering is observed in up to 10% of patients. Among them, hereditary cases, related to known cancer susceptibility syndromes and/or genetic causes are thought to account for 1-3% of all gastric cancers. The pathology report of gastric resections specimens therefore requires a standardized approach as well as in depth knowledge of prognostic and treatment associated factors.
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http://dx.doi.org/10.32074/1591-951X-166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931572PMC
September 2020

Neoplastic and pre-neoplastic lesions of the oesophagus and gastro-oesophageal junction.

Pathologica 2020 Sep;112(3):138-152

Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Italy.

Oesophageal and gastro-oesophageal junction (GOJ) neoplasms, and their predisposing conditions, may be encountered by the practicing pathologist both as biopsy samples and as surgical specimens in daily practice. Changes in incidence of oesophageal squamous cell carcinomas (such as a decrease in western countries) and in oesophageal and GOJ adenocarcinomas (such as a sharp increase in western countries) are being reported globally. New modes of treatment have changed our histologic reports as specific aspects must be detailed such as in post endoscopic resections or with regards to post neo-adjuvant therapy tumour regression grades. The main aim of this overview is therefore to provide an up-to-date, easily available and clear diagnostic approach to neoplastic and pre-neoplastic conditions of the oesophagus and GOJ, based on the most recent available guidelines and literature.
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http://dx.doi.org/10.32074/1591-951X-164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931575PMC
September 2020

Non gastro-esophageal reflux disease related esophagitis: an overview with a histologic diagnostic approach.

Pathologica 2020 Sep;112(3):128-137

Anatomic Pathology, San Martino IRCCS Hospital, Genova, Italy.

Several pathological conditions, other than gastro-esophageal reflux disease and its complications, can affect the esophagus. While some of these can present with unspecific lesions (i.e. ulcers and epithelial damage) and require clinico-pathological correlation for diagnosis (i.e. drug-induced esophagitis and corrosive esophagitis) other conditions show distinctive histological lesions which enable the pathologist to reach the diagnosis (i.e. some specific infectious esophagites and Crohn's disease). In this context eosinophilic esophagitis is the condition which has been increasingly studied in the last two decades, while lymphocytic esophagitis, a relatively new entity, still represents an enigma. This overview will focus on and describe histologic lesions which allow pathologists to differentiate between these conditions.
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http://dx.doi.org/10.32074/1591-951X-156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931579PMC
September 2020

Gastro-esophageal reflux disease and Barrett's esophagus: an overview with an histologic diagnostic approach.

Pathologica 2020 Sep;112(3):117-127

Anatomic Pathology, San Martino IRCCS Hospital, Genova, Italy.

The first part of this overview on non-neoplastic esophagus is focused on gastro-esophageal reflux disease (GERD) and Barrett's esophagus. In the last 20 years much has changed in histological approach to biopsies of patients with gastro-esophageal reflux disease. In particular, elementary histologic lesions have been well defined and modality of evaluation and grade are detailed, their sensitivity and specificity has been evaluated and their use has been validated by several authors. Also if there is not a clinical indication to perform biopsies in patient with GERD, the diagnosis of microscopic esophagitis, when biopsies are provided, can be performed by following simple rules for evaluation which allow pathologists to make the diagnosis with confidence. On the other hand, biopsies are required for the diagnosis of Barrett's esophagus. This diagnosis is the synthesis of endoscopic picture (which has to be provided with the proper description on extent and with adequate biopsies number) and histologic pattern. The current guidelines and expert opinions for the correct management of these diagnosis are detailed.
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http://dx.doi.org/10.32074/1591-951X-162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931578PMC
September 2020

Mediastinal Nodular Lesions Synchronous to Lung Carcinoma on Frozen Section: Trap and Lesson.

Diagnostics (Basel) 2020 Oct 31;10(11). Epub 2020 Oct 31.

Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo 71013 (FG), Italy.

Thymoma is the most frequent neoplasm arising in the anterior mediastum. It usually presents as an enlarged central mass. In the literature, multiple thymoma is described as an unusual finding; rare variants have also been described, like the signet ring-like cell variant. Evidence of co-existence of signet ring-like cells and lymphocytes in small biopsies from nodular mediastinal lesions can lead to a diagnosis of metastatic carcinoma, mostly at frozen sections. Thymoma and pulmonary carcinoma are very rarely associated neoplasms. We present a case of two mediastinal lesions discovered during pulmonary carcinoma staging. At frozen section, a diagnosis of 'epithelioid proliferation associated to lymphoid tissue' was advanced on a sample of nodular lesions and of 'carcinoma' on pulmonary biopsy. Double AB Type Thymoma with a signet ring cell-like component, synchronous to pulmonary adenocarcinoma, was the diagnosis made on formalin fixed-paraffin embedded samples. Reporting the coexistence of these two entities can help pathologists and surgeons to establish the best management of similar patients.
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http://dx.doi.org/10.3390/diagnostics10110893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692310PMC
October 2020

A New Intraepithelial γδ T-Lymphocyte Marker for Celiac Disease Classification in Formalin-Fixed Paraffin-Embedded (FFPE) Duodenal Biopsies.

Dig Dis Sci 2021 Oct 3;66(10):3352-3358. Epub 2020 Nov 3.

Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.

Background: The histopathologic diagnosis of celiac disease (CD) may be challenging when the duodenal biopsies mucosal injury is limited. Intraepithelial T-lymphocytes (IELs) can be useful to characterize the degree of mucosal inflammation. A small fraction of IELs expresses the γδ T-cell receptor (named γδ-IELs), whose density, determined by flow cytometry or frozen section immunohistochemistry (IHC), is a specific marker for CD.

Aim: To establish a new IHC assay for γδ-IELs applicable to formalin-fixed paraffin-embedded (FFPE) duodenal biopsies.

Methods: We analyzed γδ-IELs using IHC in 138 duodenal biopsies using a standard IHC staining protocol with a new monoclonal antibody H-41. IELs were quantitated with digital image analysis.

Results: Compared to those in non-celiac controls (n = 51), γδ-IEL density was significantly increased in newly diagnosed celiac disease patients (n = 22, p < 0.0001). In ROC-curve analysis, the cutoff of 6.5 γδ-IELs/100 enterocytes distinguished optimally active CD patients from non-celiac controls (sensitivity 96%, specificity 95%). γδ-IEL density in CD patients on a gluten-free diet (n = 53) were also higher than in controls (p < 0.0001), but lower than those in newly diagnosed CD (p < 0.0001). The diagnostic value of γδ-IELs outperformed that of CD3 + IELs in both patient groups. γδ-IELs were better than CD3 + IELs distinguishing between celiac disease and conditions histologically mimicking celiac disease (n = 12).

Conclusions: Intraepithelial γδ T-lymphocytes can be stained and quantitated reliably in FFPE duodenal biopsies. The results showed excellent specificity and sensitivity for celiac disease. The new IHC method of detection of γδ-IELs is a promising addition to the routine histopathologic assessment methodology of celiac disease.
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http://dx.doi.org/10.1007/s10620-020-06680-xDOI Listing
October 2021

Diagnosis of Hodgkin Lymphoma from Cell Block: A Reliable and Helpful Tool in "Selected" Diagnostic Practice.

Diagnostics (Basel) 2020 Sep 25;10(10). Epub 2020 Sep 25.

Pathology Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy.

Background: The diagnosis of lymphoma requires surgical specimens to perform morphological evaluation, immunohistochemical and molecular analyses. Ultrasound-guided fine needle aspiration may represent an appropriate first approach to obtain cytological samples in impalpable lesions and/or in patients unsuitable for surgical procedures. Although cytology has intrinsic limitations, the cell block method may increase the possibility of achieving an accurate diagnosis.

Methods: We retrospectively selected a total of 47 ultrasound-guided fine needle aspiration and drainage samples taken from patients with effusion and deep-seated lesions which are clinically suspicious in terms of malignancy.

Results: In 27 cases, both cell block and conventional cytology were performed: 21/27 cell blocks were adequate for the diagnosis of lymphoma and suitable for immunocytochemistry and molecular analyses vs. 12/20 samples to which only conventional cytology was applied. Moreover, in five patients we were able to make a diagnosis of Hodgkin lymphoma with the cell block (CB) technique.

Conclusions: Contrary to conventional cytology, the cell block method may allow immunocytochemistry and molecular studies providing useful information for the diagnosis and subtypization of lymphoma in patients unsuitable for surgical procedure or with deep-seated lesions or extra-nodal diseases; additionally, it is a daily, simple and helpful approach. Moreover, we describe the usefulness of cell blocks in the diagnosis of Hodgkin lymphoma.
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http://dx.doi.org/10.3390/diagnostics10100748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601842PMC
September 2020

Oral plasmablastic lymphoma: A case report.

Medicine (Baltimore) 2020 Sep;99(39):e22335

Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, Terni, Italy.

Introduction: Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency viruses -positive patients. Oral cavity is the most commonly PBL affected site. Most oral PBLs presented as asymptomatic swellings, frequently associated with ulcerations and bleeding. Most cases lacked B-symptoms, suggesting a more local involvement of the disease. No standard treatment is yet for oral PBL. Five-year survival rate recorded no more than 33.5%.

Patient Concerns: A 39-year-old male presented to Dental Clinic with 1 month swelling of the oral cavity, in absence of any other symptoms or signs. He followed antibiotic therapy just on suspicion of an oral abscess and later oral surgical treatment on suspicion of bone neoplasm.

Diagnosis: Surgical specimen analysis highlighted a diffuse infiltrate of large-sized atypical cells with plasmablastic appearance and plasma cell phenotype. Oral cavity PBL was diagnosed. Blood tests recorded mild lymphopenia and positive human immunodeficiency viruses serology.

Interventions: Patient underwent chemotherapy including intrathecal methotrexate prophylaxis, in addition to a highly active antiretroviral therapy.

Outcomes: At 12 months from diagnosis, patient recorded complete hematological remission.

Conclusions: Oral PBL diagnosis requires a high level of suspicion and awareness both by physicians and pathologists. They should be aware of the extent of such disease which is often mistaken as oral abscess or infected tooth, thus leading to delay the most appropriate diagnostic evaluation. As PBL is an aggressive non-Hodgkin lymphoma, a delayed diagnosis might negatively impact on both treatment and survival.
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http://dx.doi.org/10.1097/MD.0000000000022335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523795PMC
September 2020
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