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Article: Sonographic Appearance of Lacrimal Glands in Sjögren's Syndrome at High Risk for Lymphoma Development.

Giovannini, Ivan / Pegolo, Enrico / Longhino, Simone / Quartuccio, Luca / Zabotti, Alen

2023 Volume 15, Issue 12, Page(s) e50047

Abstract: Primary Sjögren's syndrome (pSS) is an autoimmune systemic disease characterized by the destruction of exocrine glands, mainly salivary and lacrimal glands. The diagnosis is generally made upon objective tests aimed at assessing salivary and lacrimal ... ...

Abstract	Primary Sjögren's syndrome (pSS) is an autoimmune systemic disease characterized by the destruction of exocrine glands, mainly salivary and lacrimal glands. The diagnosis is generally made upon objective tests aimed at assessing salivary and lacrimal glandular function, autoantibody assays, and the results of labial salivary gland biopsies. A major salivary gland biopsy is usually reserved to assess lymphoproliferative complications. Recently, the sonographic evaluation of the major salivary glands has gained a crucial role in assessing the glandular parenchyma and early detecting abnormalities, while the role of ultrasonography in the assessment of lacrimal glands is still secondary. Our case report is about a male patient who presented parotid gland swelling and purpuric lesions, with preserved salivary and lacrimal glandular function. Considering the presence of risk factors associated with lymphoproliferative development and the peculiar characteristics detected by salivary and lacrimal gland ultrasonography, we performed a parotid gland biopsy, confirming Sjögren's syndrome. Our case demonstrates that lacrimal gland ultrasonography could be implemented, along with major salivary gland ultrasonography, as a routine procedure in evaluating patients with suspected or definite diagnoses of pSS.
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.50047
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Article ; Online: A multinodular and vacuolating neuronal tumor of the cerebrum (MVNT) with glioma-like appearance.

Bagatto, Daniele / Ius, Tamara / Pegolo, Enrico / Morassi, Mauro

Acta neurologica Belgica

2020 Volume 121, Issue 6, Page(s) 1851–1854

MeSH term(s)	Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/pathology ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/pathology ; Female ; Glioma/diagnostic imaging ; Glioma/pathology ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Seizures/diagnostic imaging ; Seizures/etiology
Language	English
Publishing date	2020-07-06
Publishing country	Italy
Document type	Case Reports ; Letter
ZDB-ID	127315-2
ISSN	2240-2993 ; 0300-9009
ISSN (online)	2240-2993
ISSN	0300-9009
DOI	10.1007/s13760-020-01426-y
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Article ; Online: Clinical, laboratory and immunohistochemical characterization of in situ pulmonary arterial thrombosis in fatal COVID-19.

Quartuccio, Luca / Sonaglia, Arianna / Casarotto, Letizia / McGonagle, Dennis / Di Loreto, Carla / Pegolo, Enrico

Thrombosis research

2022 Volume 219, Page(s) 95–101

Abstract: Background: COVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with ... ...

Abstract	Background: COVID-19 patients carry an increased rate of thrombosis. It is controversial to which extent thrombi in the pulmonary arterial tree really contribute to disease severity with hypoxemia secondary to microvascular/lung parenchymal damage with viral alveolitis considered to play the main role in critical disease. Objectives: The primary objective was to compare post-mortem lung disease from fatal COVID-19 pneumonia in patients with macroscopically evident pulmonary arterial tree thrombosis and patients without, by characterizing the immunohistochemical nature of thrombi, and by comparing clinical and laboratory features of these patients with other COVID-19 patients who died but without evidence of pulmonary arterial thrombosis (controls). Patients and methods: 13 COVID-19 pneumonia cases (mean age ± standard deviation: 74 ± 6.5 years) with macroscopically visible pulmonary arterial thrombosis were compared to 14 controls. Hematoxylin and Eosin stained slides were reviewed choosing those with visible pulmonary thrombi which were further characterized by immunohistochemistry, in particular for the inflammatory infiltrates. Ante mortem serum markers relevant to pulmonary embolism were evaluated in both groups. Results: Twenty arterial thrombi (5 cases with multiple thrombi) were selected for study and were composed by white blood cells (WBC) [median, IQR range: 10 % (5-12.25)], mainly neutrophils [58 % (35.2-64.5)]. Cases with thrombosis showed significantly higher levels of platelet count [median, IQR range: 195000/mmc (157750-274,500) vs 143,500 (113000-175,250), p = 0.011], LDH [854 U/L (731-1315) vs 539 (391.5-660), p = 0.003] at admission, and D-dimer at ICU transfer [25,072 FEU (6951-50,531) vs 1024 (620-5501), p = 0.003]. Conclusions: Immunothrombotically driven arterial thrombi in COVID-19 patients are associated with D-Dimer and LDH elevations, thus linking inflammation, coagulopathy and organ damage in fatal COVID-19.
MeSH term(s)	Biomarkers ; COVID-19/complications ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans ; Hypertension, Pulmonary ; Lung ; SARS-CoV-2 ; Thrombosis/complications
Chemical Substances	Biomarkers ; Eosine Yellowish-(YS) (TDQ283MPCW) ; Hematoxylin (YKM8PY2Z55)
Language	English
Publishing date	2022-09-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2022.09.012
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Article: Thyroglossal Duct Lipoma: A Case Report and a Systematic Review of the Literature for Its Management.

Locatello, Luca Giovanni / Graziadio, Marilena / D'Orlando, Elena / Vallone, Alfredo / Miani, Cesare / Pegolo, Enrico / Rugiu, Maria Gabriella

Diagnostics (Basel, Switzerland)

2023 Volume 13, Issue 5

Abstract: Thyroglossal duct (TGD) remnants in the form of cysts or fistulas usually present as midline neck masses and they are removed along with the central body of the hyoid bone (Sistrunk's procedure). For other pathologies associated with the TGD tract, the ... ...

Abstract	Thyroglossal duct (TGD) remnants in the form of cysts or fistulas usually present as midline neck masses and they are removed along with the central body of the hyoid bone (Sistrunk's procedure). For other pathologies associated with the TGD tract, the latter operation might be not necessary. In the present report, a case of a TGD lipoma is presented and a systematic review of the pertinent literature was performed. We present the case of a 57-year-old woman with a pathologically confirmed TGD lipoma who underwent transcervical excision without resecting the hyoid bone. Recurrence was not observed after six months of follow-up. The literature search revealed only one other case of TGD lipoma and controversies are addressed. TGD lipoma is an exceedingly rare entity whose management might avoid hyoid bone excision.
Language	English
Publishing date	2023-03-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662336-5
ISSN	2075-4418
ISSN	2075-4418
DOI	10.3390/diagnostics13050932
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Article ; Online: The protean role of Val804Met RET mutation in thyroid neoplasms: An example of a "MEN2C" syndrome?

Miani, Cesare / Locatello, Luca Giovanni / Rugiu, Maria Gabriella / Antonio, Jamile Karina / Di Loreto, Carla / Pegolo, Enrico

Pathology, research and practice

2023 Volume 244, Page(s) 154388

Abstract: Background: Val804Met RET is one of the most common genetic alterations in Multiple Endocrine Neoplasia 2 and is considered to confer only a moderate risk for familial medullary thyroid carcinoma (MTC). The associated phenotype can however be much more ... ...

Abstract	Background: Val804Met RET is one of the most common genetic alterations in Multiple Endocrine Neoplasia 2 and is considered to confer only a moderate risk for familial medullary thyroid carcinoma (MTC). The associated phenotype can however be much more complex in some cases. Methods: A clinical, genetic, and pathological analysis was conducted on a family cluster of thyroid neoplasms associated with Val804Met RET mutation. Results: All the kindreds who are carriers of the mutated RET received total thyroidectomy + /- VI level dissection. The proband presented with a pT1bN0 MTC, her 29-yo brother showed a concomitant papillary thyroid carcinoma (PTC) and MTC, their father had a pT1a PTC plus a follicular adenoma, while the uncle of the proband showed C-cell hyperplasia. None had clinical or biochemical evidence of parathyroid disorders or pheochromocytoma. Conclusions: In the presence of Val804Met RET several types of thyroid premalignant and malignant should be screened for, and without limiting to MTC.
MeSH term(s)	Male ; Female ; Humans ; Proto-Oncogene Proteins c-ret/genetics ; Multiple Endocrine Neoplasia Type 2a/genetics ; Multiple Endocrine Neoplasia Type 2a/pathology ; Thyroid Neoplasms/genetics ; Thyroid Neoplasms/pathology ; Mutation/genetics ; Adrenal Gland Neoplasms
Chemical Substances	Proto-Oncogene Proteins c-ret (EC 2.7.10.1) ; RET protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-02-24
Publishing country	Germany
Document type	Case Reports
ZDB-ID	391889-0
ISSN	1618-0631 ; 0344-0338
ISSN (online)	1618-0631
ISSN	0344-0338
DOI	10.1016/j.prp.2023.154388
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Article: Multimodal Assessment Shows a Mostly Preserved Cognitive Status in Incidentally Discovered Low Grade Gliomas: A Single Institution Study.

Guarracino, Ilaria / Ius, Tamara / Pegolo, Enrico / Cesselli, Daniela / Skrap, Miran / Tomasino, Barbara

Cancers

2020 Volume 12, Issue 1

Abstract: Incidentally discovered low-grade gliomas (iLGGs) are poorly reported in the literature. Still less is known about iLGG patients' neuropsychological profile: It is unclear whether iLGG patients are cognitively proficient, thus further confirming the ... ...

Abstract	Incidentally discovered low-grade gliomas (iLGGs) are poorly reported in the literature. Still less is known about iLGG patients' neuropsychological profile: It is unclear whether iLGG patients are cognitively proficient, thus further confirming the concept of asymptomatic. From our monoinstitutional cohort of 332 patients operated for LGG from 2000 to 2017 we selected those who underwent a neuropsychological testing (
Language	English
Publishing date	2020-01-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12010156
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Article ; Online: Machine learning to improve interpretability of clinical, radiological and panel-based genomic data of glioma grade 4 patients undergoing surgical resection.

Dal Bo, Michele / Polano, Maurizio / Ius, Tamara / Di Cintio, Federica / Mondello, Alessia / Manini, Ivana / Pegolo, Enrico / Cesselli, Daniela / Di Loreto, Carla / Skrap, Miran / Toffoli, Giuseppe

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 450

Abstract: Background: Glioma grade 4 (GG4) tumors, including astrocytoma IDH-mutant grade 4 and the astrocytoma IDH wt are the most common and aggressive primary tumors of the central nervous system. Surgery followed by Stupp protocol still remains the first-line ...

Abstract	Background: Glioma grade 4 (GG4) tumors, including astrocytoma IDH-mutant grade 4 and the astrocytoma IDH wt are the most common and aggressive primary tumors of the central nervous system. Surgery followed by Stupp protocol still remains the first-line treatment in GG4 tumors. Although Stupp combination can prolong survival, prognosis of treated adult patients with GG4 still remains unfavorable. The introduction of innovative multi-parametric prognostic models may allow refinement of prognosis of these patients. Here, Machine Learning (ML) was applied to investigate the contribution in predicting overall survival (OS) of different available data (e.g. clinical data, radiological data, or panel-based sequencing data such as presence of somatic mutations and amplification) in a mono-institutional GG4 cohort. Methods: By next-generation sequencing, using a panel of 523 genes, we performed analysis of copy number variations and of types and distribution of nonsynonymous mutations in 102 cases including 39 carmustine wafer (CW) treated cases. We also calculated tumor mutational burden (TMB). ML was applied using eXtreme Gradient Boosting for survival (XGBoost-Surv) to integrate clinical and radiological information with genomic data. Results: By ML modeling (concordance (c)- index = 0.682 for the best model), the role of predicting OS of radiological parameters including extent of resection, preoperative volume and residual volume was confirmed. An association between CW application and longer OS was also showed. Regarding gene mutations, a role in predicting OS was defined for mutations of BRAF and of other genes involved in the PI3K-AKT-mTOR signaling pathway. Moreover, an association between high TMB and shorter OS was suggested. Consistently, when a cutoff of 1.7 mutations/megabase was applied, cases with higher TMB showed significantly shorter OS than cases with lower TMB. Conclusions: The contribution of tumor volumetric data, somatic gene mutations and TBM in predicting OS of GG4 patients was defined by ML modeling.
MeSH term(s)	Adult ; Humans ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/genetics ; Brain Neoplasms/surgery ; DNA Copy Number Variations/genetics ; Phosphatidylinositol 3-Kinases/genetics ; Glioma/diagnostic imaging ; Glioma/genetics ; Glioma/surgery ; Astrocytoma ; Prognosis ; Biomarkers, Tumor/genetics ; Genomics ; Mutation/genetics
Chemical Substances	Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Biomarkers, Tumor
Language	English
Publishing date	2023-07-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-04308-y
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Article ; Online: Eosinophilic myocarditis: comprehensive update on pathophysiology, diagnosis, prognosis and management.

Collini, Valentino / Burelli, Massimo / Favaretto, Virginia / Pegolo, Enrico / Fumarola, Francesca / Lepre, Veronica / Pellin, Lisa / Taurian, Marco / Quartuccio, Luca / Imazio, Massimo / Sinagra, Gianfranco

Minerva cardiology and angiology

2023 Volume 71, Issue 5, Page(s) 535–552

Abstract: Hypereosinophilic syndromes are a group of disorders secondary to the accumulation of eosinophils leading to the injury of one or more organs. Among them, eosinophilic myocarditis (EM) is a rare form of inflammatory cardiomyopathy characterized by ... ...

Abstract	Hypereosinophilic syndromes are a group of disorders secondary to the accumulation of eosinophils leading to the injury of one or more organs. Among them, eosinophilic myocarditis (EM) is a rare form of inflammatory cardiomyopathy characterized by eosinophilic infiltration into myocardial tissue and subsequent release of substances with cell membrane damage and cell destruction. The degree of infiltration is thought to depend on the underlying condition, as well as the degree and duration of eosinophil exposure and ranges from mild localized disease to diffuse multifocal infiltrates associated with myocardial necrosis, thrombotic complications and endomyocardial fibrosis. The main causes of EM are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome variants, infections and cancer. Clinical presentation can be variable, ranging from asymptomatic forms to life-threatening conditions, to chronic heart failure due to progression to chronic restrictive cardiomyopathy. Marked eosinophilia in peripheral blood, elevated serum eosinophilic cationic protein concentration and multimodality imaging may suggest the etiology of EM, but in most cases an endomyocardial biopsy must be performed to establish a definitive diagnosis. Systemic treatment varies greatly depending on the underlying cause, however the evidence of an eosinophilic infiltrate allows initiation of immunosuppressive therapy, which is the mainstay of treatment in idiopathic and in most forms of EM. Patients with helminthic infection benefit from anti-parasitic therapy, those with myeloid clone often need a tyrosine kinase inhibitor, while anticoagulant therapy should be undertaken in case of possible thrombotic complications.
MeSH term(s)	Humans ; Myocarditis/diagnosis ; Myocarditis/etiology ; Myocarditis/therapy ; Churg-Strauss Syndrome/complications ; Churg-Strauss Syndrome/diagnosis ; Churg-Strauss Syndrome/drug therapy ; Granulomatosis with Polyangiitis/complications ; Prognosis ; Hypereosinophilic Syndrome/diagnosis ; Hypereosinophilic Syndrome/therapy ; Hypereosinophilic Syndrome/complications
Language	English
Publishing date	2023-05-10
Publishing country	Italy
Document type	Journal Article
ZDB-ID	3059238-0
ISSN	2724-5772
ISSN (online)	2724-5772
DOI	10.23736/S2724-5683.23.06287-7
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Article: Nuts and bolts of salivary gland pathology in primary Sjögren's syndrome.

Zabotti, Alen / Giovannini, Ivan / Longhino, Simone / Manfrè, Valeria / Rizzo, Maria Teresa / De Vita, Salvatore / Di Loreto, Carla / Quartuccio, Luca / Pegolo, Enrico

Clinical and experimental rheumatology

2023 Volume 41, Issue 12, Page(s) 2525–2537

Abstract: Primary Sjögren's syndrome (pSS) is a chronic, systemic, inflammatory autoimmune disease characterised by lymphocyte proliferation and progressive damage to exocrine glands. Salivary gland histopathology based on salivary gland biopsy is relevant for the ...

Abstract	Primary Sjögren's syndrome (pSS) is a chronic, systemic, inflammatory autoimmune disease characterised by lymphocyte proliferation and progressive damage to exocrine glands. Salivary gland histopathology based on salivary gland biopsy is relevant for the diagnosis of pSS and therefore broadly applied in clinical practice. Tissue can be obtained from labial salivary glands (LSG) biopsy or from major salivary glands (MSG) biopsy, namely the parotid; in this latter scenario, the procedure can be either an open surgical biopsy or a US guided core needle biopsy.In this review we will: i) present the histopathological findings that may be encountered by pathologists on biopsies from pSS patients; ii) discuss the advantages and disadvantages of the surgical and/or imaging guided procedures to obtain tissues from LSG or MSG; iii) describe the histopathological features of lymphoma of MSG in pSS patients.
MeSH term(s)	Humans ; Sjogren's Syndrome ; Salivary Glands ; Parotid Gland/diagnostic imaging ; Parotid Gland/pathology ; Salivary Glands, Minor/pathology ; Lymphoma/pathology ; Biopsy
Language	English
Publishing date	2023-11-29
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/fcjoqx
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Article: Secretagogue effect of PDE4 inhibitor apremilast on human salivary gland organoids obtained from primary Sjögren's syndrome patients.

Manfrè, Valeria / Parisi, Salvatore / Caligiuri, Isabella / Repetto, Ombretta / Zabotti, Alen / Pegolo, Enrico / Fabro, Cinzia / De Vita, Salvatore / Canzonieri, Vincenzo / Di Loreto, Carla / Rizzolio, Flavio / Quartuccio, Luca

Clinical and experimental rheumatology

2023 Volume 41, Issue 12, Page(s) 2493–2501

Abstract: Objectives: The aim of the study was to culture vital salivary gland organoids obtained through labial or parotid biopsy of primary Sjögren's syndrome (pSS) patients in order to evaluate their morphological and functional features in basal condition and ...

Abstract	Objectives: The aim of the study was to culture vital salivary gland organoids obtained through labial or parotid biopsy of primary Sjögren's syndrome (pSS) patients in order to evaluate their morphological and functional features in basal condition and after stimulation with Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activator forskolin and phosphodiesterase 4 (PDE4) inhibitor apremilast, their in vitro regenerative capacity and the immune-histological resemblance with original tissue. Methods: Salivary gland tissues from five pSS patients were processed to obtain vital organoids; swelling assay and cell proliferation tests were performed after forskolin and apremilast application. Immunochemistry evaluation on original salivary gland tissue and corresponding organoids was performed, and secretomics analysis was conducted to assess their functional status. Reults: After application of forskolin and apremilast, we observed organoid swelling after 30 minutes, compatible with a positive functional status and enhancement of saliva production. In 3 cases, apremilast induced organoid proliferation. All cases were positive for cytokeratin 14 (CK14) and most for cytokeratin 5 (CK5). All the cases were positive for amylase; its secretion, and thus functional status of organoids, was confirmed by its high concentration in the culture medium. A focal ductal differentiation was found in some cases, highlighted by epithelial membrane antigen (EMA) positivity. The more differentiated EMA positive areas were negative for the staminal marker CK14, showing a sort of "complementary staining". Conclusions: Our data highlighted that differentiated cells and vital functional organoids that recapitulate the development of original salivary glands can be obtained from pSS epithelium. For the first time, the direct stimulating effect of PDE4 inhibitor apremilast on pSS human salivary gland organoids is reported, opening new perspectives on targeting oral dryness with drugs that combine secretagogue and immunomodulatory effects.
MeSH term(s)	Humans ; Sjogren's Syndrome ; Phosphodiesterase 4 Inhibitors/pharmacology ; Secretagogues ; Colforsin ; Salivary Glands ; Organoids/metabolism ; Organoids/pathology
Chemical Substances	Phosphodiesterase 4 Inhibitors ; Secretagogues ; apremilast (UP7QBP99PN) ; Colforsin (1F7A44V6OU)
Language	English
Publishing date	2023-12-23
Publishing country	Italy
Document type	Journal Article
ZDB-ID	605886-3
ISSN	1593-098X ; 0392-856X
ISSN (online)	1593-098X
ISSN	0392-856X
DOI	10.55563/clinexprheumatol/7f4fzu
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