Publications by authors named "Andrea Palicelli"

59 Publications

Eosinophilic Angiocentric Fibrosis of the Nasal Cavities: A Report of an Uncommon Lesion with Emphasis on the Etiology and Differential Diagnosis.

Medicina (Kaunas) 2022 Jun 28;58(7). Epub 2022 Jun 28.

Department of Medical and Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Anatomic Pathology, University of Catania, 95123 Catania, Italy.

: Eosinophilic angiocentric fibrosis (EAF) is an indolent but sometimes locally destructive lesion with a predilection for the sinonasal tract. Although it was first described in 1983, its etiology remains unknown. Some authors initially attributed EAF to trauma, hypersensitivity, and/or surgical manipulation, while it has been recently suggested to include EAF within the spectrum of IgG4-related systemic diseases. : We report an uncommon case of idiopathic EAF in a 76-year-old male who developed two bilateral tumefactive masses in the nasal cavities. : As the histological examination showed a subepithelial proliferation of fibroblasts along with sclero-hyaline fibrosis around small-sized vessels (an "onion skin-like" pattern) and an eosinophils-rich inflammatory infiltrate, a diagnosis of EAF was rendered. The differential diagnosis included granuloma faciale, Wegener's granulomatosis, and Churg-Strauss syndrome. : Pathologists should be aware of the possibility that this lesion can be part of the wide spectrum of IgG4-related systemic diseases by performing IgG4 investigations to assess adherence to IgG4-related systemic disease criteria.
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http://dx.doi.org/10.3390/medicina58070865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319830PMC
June 2022

Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 2: Subtypes and Divergent Differentiation.

Int J Mol Sci 2022 Jul 16;23(14). Epub 2022 Jul 16.

Department of Urology and Renal Transplantation, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy.

Following several attempts to achieve a molecular stratification of bladder cancer (BC) over the last decade, a "consensus" classification has been recently developed to provide a common base for the molecular classification of bladder cancer (BC), encompassing a six-cluster scheme with distinct prognostic and predictive characteristics. In order to implement molecular subtyping (MS) as a risk stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The second part of this review deals with the pathological and clinical features of the molecular clusters, both in conventional and divergent urothelial carcinoma, with a focus on the role of IHC-based subtyping.
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http://dx.doi.org/10.3390/ijms23147844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317362PMC
July 2022

Are We Ready to Implement Molecular Subtyping of Bladder Cancer in Clinical Practice? Part 1: General Issues and Marker Expression.

Int J Mol Sci 2022 Jul 15;23(14). Epub 2022 Jul 15.

Department of Urology and Renal Transplantation, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy.

Bladder cancer (BC) is a heterogeneous disease with highly variable clinical and pathological features, and resulting in different outcomes. Such heterogeneity ensues from distinct pathogenetic mechanisms and may consistently affect treatment responses in single patients. Thus, over the last few years, several groups have developed molecular classification schemes for BC, mainly based on their mRNA expression profiles. A "consensus" classification has recently been proposed to combine the published systems, agreeing on a six-cluster scheme with distinct prognostic and predictive features. In order to implement molecular subtyping as a risk-stratification tool in routine practice, immunohistochemistry (IHC) has been explored as a readily accessible, relatively inexpensive, standardized surrogate method, achieving promising results in different clinical settings. The first part of this review deals with the steps resulting in the development of a molecular subtyping of BC, its prognostic and predictive implications, and the main features of immunohistochemical markers used as surrogates to stratify BC into pre-defined molecular clusters.
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http://dx.doi.org/10.3390/ijms23147819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319819PMC
July 2022

Molecular subclassification of vulvar squamous cell carcinoma: reproducibility and prognostic significance of a novel surgical technique.

Int J Gynecol Cancer 2022 Aug 1;32(8):977-985. Epub 2022 Aug 1.

Division of Gynecologic Pathology, University of Leipzig, Leipzig, Germany.

Objectives: Vulvar squamous cell carcinoma is subclassified into three prognostically relevant groups: (i) human papillomavirus (HPV) associated, (ii) HPV independent p53 abnormal (mutant pattern), and (iii) HPV independent p53 wild type. Immunohistochemistry for p16 and p53 serve as surrogates for HPV viral integration and mutational status. We assessed the reproducibility of the subclassification based on p16 and p53 immunohistochemistry and evaluated the prognostic significance of vulvar squamous cell carcinoma molecular subgroups in a patient cohort treated by vulvar field resection surgery.

Methods: In this retrospective cohort study, 68 cases treated by vulvar field resection were identified from the Leipzig School of Radical Pelvic Surgery. Immunohistochemistry for p16 and p53 was performed at three different institutions and evaluated independently by seven pathologists and two trainees. Tumors were classified into one of four groups: HPV associated, HPV independent p53 wild type, HPV independent p53 abnormal, and indeterminate. Selected cases were further interrogated by (HPV RNA in situ hybridization, sequencing).

Results: Final subclassification yielded 22 (32.4%) HPV associated, 41 (60.3%) HPV independent p53 abnormal, and 5 (7.3%) HPV independent p53 wild type tumors. Interobserver agreement (overall Fleiss' kappa statistic) for the four category classification was 0.74. No statistically significant differences in clinical outcomes between HPV associated and HPV independent vulvar squamous cell carcinoma were observed.

Conclusion: Interobserver reproducibility of vulvar squamous cell carcinoma subclassification based on p16 and p53 immunohistochemistry may support routine use in clinical practice. Vulvar field resection surgery showed no significant difference in clinical outcomes when stratified based on HPV status.
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http://dx.doi.org/10.1136/ijgc-2021-003251DOI Listing
August 2022

Robotic versus Laparoscopic Gastrectomy for Gastric Cancer: An Updated Systematic Review.

Medicina (Kaunas) 2022 Jun 20;58(6). Epub 2022 Jun 20.

Surgical Oncology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

: Gastrectomy with D2 lymphadenectomy is the standard surgical treatment with curative intent for patients with gastric cancer (GC). Over the last three decades, surgeons have been increasingly adopting laparoscopic surgery for GC, due to its better short-term outcomes. In particular, laparoscopic gastrectomy (LG) has been routinely used for early gastric cancer (EGC) treatment. However, LG suffers from technical limitations and drawbacks, such as a two-dimensional surgical field of view, limited movement of laparoscopic tools, unavoidable physiological tremors and discomfort for operating surgeon. Therefore, robotic surgery has been developed to address such limitations. : We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines in order to investigate the benefits and harms of robotic gastrectomy (RG) compared to the LG. PubMed/MEDLINE, Scopus, Cochrane Library (Cochrane Database of Systematic Re-views, Cochrane Central Register of Controlled Trials-CENTRAL) and Web of Science (Science and Social Science Citation Index) databases were used to search all related literature. : The 7 included meta-analyses covered an approximately 20 years-study period (2000-2020). Almost all studies included in the meta-analyses were retrospective ones and originated from Asian countries (China and Korea, in particular). Examined overall population ranged from 3176 to 17,712 patients. If compared to LG, RG showed both operative advantages (operative time, estimated blood loss, number of retrieved lymph nodes) and perioperative ones (time to first flatus, time to restart oral intake, length of hospitalization, overall complications, Clavien-Dindo (CD) ≥ III complications, pancreatic complications), in the absence of clear differences of oncological outcomes. However, costs of robotic approach appear significant. : It is impossible to make strong recommendations, due to the statistical weakness of the included studies. Further randomized, possibly multicenter trials are strongly recommended, if we want to have our results confirmed.
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http://dx.doi.org/10.3390/medicina58060834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231199PMC
June 2022

Malignant Clinical Course of "Proliferative" Ovarian Struma: Diagnostic Challenges and Treatment Pitfalls.

Diagnostics (Basel) 2022 Jun 7;12(6). Epub 2022 Jun 7.

Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

Struma ovarii (SO) is a monodermal teratoma predominantly composed of thyroid tissue (TT) showing benign, "proliferative", or malignant histology. By imaging, a 38-year-old patient with lower backache revealed a 6.2-cm vertebral lesion (L5). Core biopsy showed well-differentiated TT without features of papillary carcinoma. A 3.5-cm left ovarian mature teratoma (lacking TT) and peritoneal nodules (showing well-differentiated TT) were also identified and surgically removed. Thyroid ultrasound and cytological examination resulted negative. Four years before, left ovarian cystectomy was performed for a histologically "proliferative" SO. According to the malignant clinical course and WHO classification, this case was overall reassessed as a recurring well-differentiated follicular carcinoma arising in SO (WD-FC-SO), despite lacking malignant histological features in any specimens. Immunophenotype: TTF-1+/PAX-8+/thyroglobulin+/CK7+/chromogranin-/synaptophysin-/inhibin-/calretinin-/HNF1B-; Ki-67 index < 5%. Polymerase chain reaction analysis resulted negative for mutation. The patient refused further treatments, without recurrence after 17 months. The clinical behavior of SO may be unpredictable. Histologically benign or proliferative strumas extraordinarily metastasize, while SO with malignant features may not recur. The exceptional evidence of peritoneal implants of well-differentiated TT (peritoneal strumosis) in patients with histologically benign SO represents a metastasis of WD-FC-SO (like in our case). A multidisciplinary approach including clinical, laboratory, radiologic, and histopathological data is required.
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http://dx.doi.org/10.3390/diagnostics12061411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222151PMC
June 2022

Should Endometrial Cancer Treatment Be Centralized?

Biology (Basel) 2022 May 18;11(5). Epub 2022 May 18.

Unit of Surgical Gynecol Oncology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.

Endometrial cancer (EC) is the most common malignancy of the female genital tract in Western and emerging countries. In 2012, new cancer cases numbered 319,605, and 76,160 cancer deaths were diagnosed worldwide. ECs are usually diagnosed after menopause; 70% of ECs are diagnosed at an early stage with a favorable prognosis and a 5-year overall survival rate of 77%. On the contrary, women with advanced or recurrent disease have extremely poor outcomes because they show a low response rate to conventional chemotherapy. EC is generally considered easy to treat, although it presents a 5-year mortality of 25%. Though the guidelines (GLs) recommend treatment in specialized centers by physicians specializing in gynecologic oncology, most women are managed by general gynecologists, resulting in differences and discrepancies in clinical management. In this paper we reviewed the literature with the aim of highlighting where the treatment of EC patients requires gynecologic oncologists, as suggested by the GLs. Moreover, we sought to identify the causes of the lack of GL adherence, suggesting useful changes to ensure adequate treatment for all EC patients.
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http://dx.doi.org/10.3390/biology11050768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9138425PMC
May 2022

Cutaneous Involvement in Diseases with Plasma Cell Differentiation: Diagnostic Approach.

Curr Oncol 2022 04 24;29(5):3026-3043. Epub 2022 Apr 24.

Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.

Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient's work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed.
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http://dx.doi.org/10.3390/curroncol29050246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139249PMC
April 2022

S-100 Immunohistochemical Positivity in Rhabdomyoma: An Underestimated Potential Diagnostic Pitfall in Routine Practice.

Diagnostics (Basel) 2022 Apr 2;12(4). Epub 2022 Apr 2.

Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

A 66-year-old man presented with a 2.8 cm lesion of the left vocal cord. On contrast-enhanced computed tomography scans, the tumor extended to the supraglottis, subglottis, paraglottic space and anterior commissure, causing partial obstruction of the laryngeal lumen. At another hospital, a fragmented incisional biopsy was diagnosed as a granular cell tumor, as to the S-100 immunohistochemical positivity. After excision, the tumor revealed to be an adult-type laryngeal rhabdomyoma. The typical cytoplasmic rod-like inclusions and cross striations were more evident in the second specimen. We confirmed the unusual S-100 immunohistochemical positivity (variable intensity, >90% of tumor cells). Muscle markers were not performed on the previous biopsy, resulting positive in our specimen (Desmin: strong, diffuse expression; Smooth Muscle Actin: strong staining in 10% of tumor cells). Melan-A, CD68, GFAP, pan-cytokeratins, CEA, calretinin and neurofilaments resulted negative. To our brief, systematic literature review, S-100 positivity (usually variable, often weak or patchy/focal) was globally found in 19/34 (56%) adult-type rhabdomyomas of the head and neck region. Especially on fragmented biopsy material, the differential diagnoses of laryngeal rhabdomyomas may include granular cell tumors, oncocytic tumors of the salivary glands or of different origin, and paragangliomas.
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http://dx.doi.org/10.3390/diagnostics12040892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030831PMC
April 2022

Visceral Leishmaniasis Associated with B-Cell Chronic Lymphocytic Leukemia: Report of a Case and Review of the Literature.

Life (Basel) 2022 Jan 27;12(2). Epub 2022 Jan 27.

Pathology Unit, Azienda Ospedaliera "Santa Maria" di Terni, University of Perugia, 05100 Terni, Italy.

Infections often complicate the course of hematological diseases and may represent a diagnostic challenge. In particular, visceral leishmaniasis diagnosis may be missed in lymphoma patients, as lymphoma-related immunosuppression can lead to a misleadingly negative serology and to atypical clinical manifestations, including the lack of fever, considered a common symptom in leishmaniasis. Herein, we report a case of visceral leishmaniasis in a patient with a long history of B-cell chronic lymphocytic leukemia presenting with increasing fatigue and diarrhea, in the absence of fever. serology was negative. Bone marrow biopsy performed with the clinical suspicion of transformation to high-grade lymphoma disclosed intracytoplasmic inclusion bodies resembling within the cytoplasm of macrophages, and CD1a immunohistochemical expression helped to confirm the diagnosis of leishmaniasis. Liposomal amphotericin B was administered with complete symptom resolution. The correct identification of is critical as visceral leishmaniasis represents a severe disease with an often fatal outcome, particularly in frail patients, unless promptly recognized and adequately treated. A review of the literature of visceral leishmaniasis cases occurring in B-cell chronic lymphocytic leukemia patients is performed.
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http://dx.doi.org/10.3390/life12020185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880775PMC
January 2022

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review (Part 6): Correlation of PD-L1 Expression with the Status of Mismatch Repair System, , , and Other Genes.

Biomedicines 2022 Jan 22;10(2). Epub 2022 Jan 22.

Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

Pembrolizumab (anti-PD-1) is allowed in selected metastatic castration-resistant prostate cancer (PC) patients showing microsatellite instability/mismatch repair system deficiency (MSI-H/dMMR). loss-of-function is linked to hereditary PCs and homologous recombination DNA-repair system deficiency: poly-ADP-ribose-polymerase inhibitors can be administered to -mutated PC patients. Recently, docetaxel-refractory metastatic castration-resistant PC patients with or somatic mutations had higher response rates to pembrolizumab. regulates cell cycle/proliferation/apoptosis through pathways including the AKT/mTOR, which upregulates PD-L1 expression in PC. Our systematic literature review (PRISMA guidelines) investigated the potential correlations between PD-L1 and MMR/MSI/ statuses in PC, discussing few other relevant genes. Excluding selection biases, 74/677 (11%) PCs showed dMMR/MSI; 8/67 (12%) of dMMR/MSI cases were PD-L1+. dMMR-PCs included ductal (3%) and acinar (14%) PCs (all cases tested for MSI were acinar-PCs). In total, 15/39 (39%) PCs harbored aberrations: limited data are available for PD-L1 expression in these patients. 13/137 (10%) PTEN- PCs were PD-L1+; 10/29 (35%) PD-L1+ PCs showed PTEN negativity. mutations may increase PD-L1 levels, while the potential correlation between PD-L1 and ERG expression in PC should be clarified. Further research should verify how the efficacy of PD-1 inhibitors in metastatic castration-resistant PCs is related to dMMR/MSI, DNA-damage repair genes defects, or PD-L1 expression.
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http://dx.doi.org/10.3390/biomedicines10020236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868626PMC
January 2022

Primary Diffuse Large B-Cell Lymphoma of the Urinary Bladder: Update on a Rare Disease and Potential Diagnostic Pitfalls.

Curr Oncol 2022 02 10;29(2):956-968. Epub 2022 Feb 10.

Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.

Diffuse large B-cell lymphoma (DLBCL) represents the most frequent type of non-Hodgkin lymphoma. Globally, DLBCL is an aggressive disease, requiring an accurate diagnosis and prompt treatment. The diagnosis is often made on biopsy samples of a nodal mass, however, approximately 40% of DLBCL cases arise at extranodal sites. The most common extranodal site is the gastrointestinal tract, however any extranodal area may be primarily involved. Primary urinary bladder lymphoma represents only 0.2% of extranodal non-Hodgkin lymphomas, whereas secondary involvement of the urinary bladder by a systemic lymphoma is a more common event. Despite being rare, DLBCL is considered to represent the predominant primary urinary bladder lymphoma. The majority of cases reported in the bladder belong to the DLBCL, NOS group, and there are only rare cases of EBV-positive DLBCL, NOS. In this review, we summarize the current knowledge on DLBCL primarily occurring in the urinary bladder, with the aim of increasing clinician and pathologist awareness on this aggressive lymphoma rarely arising in the urinary bladder. Additionally, we focus on those entities which should be taken into consideration in the differential diagnosis, highlighting potential diagnostic pitfalls.
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http://dx.doi.org/10.3390/curroncol29020081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8870454PMC
February 2022

Long-Term Outcomes of Surgical Resection of Pathologically Confirmed Isolated Para-Aortic Lymph Node Metastases in Colorectal Cancer: A Systematic Review.

Cancers (Basel) 2022 Jan 28;14(3). Epub 2022 Jan 28.

Surgical Oncology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

Background: Para-aortic lymph node (PALN) metastases represent patterns of initial recurrence in only 2-6% CRC patients, after an estimated 23-28 month time interval. An increasing trend towards curative surgery has been witnessed in patients presenting with controlled PALN recurrence. Nevertheless, lack of consensus has impaired an unambiguous statement for PALN recurrence resection.

Methods: We performed a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, which led us to gain deeper insight into the prognostic factors and long-term outcomes after resection for synchronous or metachronous pathologically confirmed CRC isolated para-aortic lymph node metastases (PALNM). Pubmed/MEDLINE, Embase, Scopus, Cochrane Library and Web of Science databases were used to search all related literature.

Results: The nine articles included covered a study period of 30 years (1988-2018), with a total of 161 patients. At presentation, most primary CRCs were located in the colon (74%) and 95.6%, 87.1% and 76.9% patients had T3-T4, N1-N2 and well/moderately differentiated CRC, respectively. We identified a 59.4-68% 3-year OS rate and 53.4-87.5% 5-year OS rate, with a 25-84 months median OS, 26.3-61% 3-year DFS rate and 0-60.5% 5-year DFS rate, with a 14-24 month median DFS. Overall, 62.1% re-recurrence rate ranged from 43.8% to 100%.

Conclusions: Although PALNMs resection in CRC patients may be considered a feasible and beneficial option, no conclusions or recommendations can be made taking into account the current evidence. Therefore, further randomized, possibly multicenter trials are strongly recommended and mandatory if we want to have our results confirmed and patient selection criteria clearly identified.
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http://dx.doi.org/10.3390/cancers14030661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833834PMC
January 2022

The classification of neuroendocrine neoplasms of the lung and digestive system according to WHO, 5th edition: similarities, differences, challenges, and unmet needs.

Panminerva Med 2022 Jun 11;64(2):259-264. Epub 2022 Feb 11.

Institute of Thoracic Surgery, University of Foggia, Foggia, Italy.

Neuroendocrine neoplasms (NENs) are a group of disease entities sharing common morphological, ultrastructural and immunophenotypical features, yet with distinct biological behavior and clinical outcome, ranging from benign to frankly malignant. Accordingly, a spectrum of therapeutic options for each single entity is available, including somatostatin analogues (SSA), mTOR-inhibitors, peptide receptor radionuclide therapy (PRRT), non-platinum and platinum chemotherapy. In the last few decades, several attempts have been made to better stratify these lesions refining the pathological classifications, so as to obtain an optimal correspondence between the scientific terminology and, the predictive and prognostic features of each disease subtype, and achieve a global Classification encompassing NENs arising at different anatomical sites. The aim of this review was to analyze, compare and discuss the main features and issues of the latest WHO Classifications of NENs of the lung and the digestive system, in order to point out the strengths and limitations of our current understanding of these complex diseases.
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http://dx.doi.org/10.23736/S0031-0808.22.04602-XDOI Listing
June 2022

Second Trimester Fetal Loss Due to Infection: A Rare Cause of Preterm Premature Rupture of Membranes (PPROM).

Diagnostics (Basel) 2022 Jan 10;12(1). Epub 2022 Jan 10.

Clinical Microbiology Laboratory, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

is a facultative anaerobic, motile, non-spore-forming Gram-negative bacillus, which belongs to the family of Enterobacteriaceae. Severe infections due to spp. have been reported in the urinary tract, respiratory airways, intra-abdominal organs, skin and soft tissue, eye, bone, bloodstream, and central nervous system. In newborns, is a well-known cause of meningitis, cerebral abscesses, brain adhesions, encephalitis, and pneumocephalus. Infection can be acquired through vertical maternal transmission or horizontal hospital settings; however, in many cases, the source is unknown. Preterm premature rupture of membranes (PPROM), caused by , has rarely been described. Herein, we describe a case of PPROM at 16 weeks and 3 days of gestation, leading to anhydramnios. The parents opted for legal termination of the pregnancy, as the prognosis was very poor. was isolated postmortem from a placental subamniotic swab and parenchymal sample, as well as fetal blood and lung. To the best of our knowledge, this is the first case of early second-trimester PPROM in which infection was demonstrated.
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http://dx.doi.org/10.3390/diagnostics12010159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774530PMC
January 2022

Surgical resection versus radiofrequency ablation for the curative treatment of intrahepatic recurrent hepatocellular carcinoma: an unsolved question.

HPB (Oxford) 2022 Jun 20;24(6):994-995. Epub 2021 Dec 20.

Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.

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http://dx.doi.org/10.1016/j.hpb.2021.12.011DOI Listing
June 2022

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 7: PD-L1 Expression in Liquid Biopsy.

J Pers Med 2021 Dec 6;11(12). Epub 2021 Dec 6.

Fertility Center, Department of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

Liquid biopsy is an accessible, non-invasive diagnostic tool for advanced prostate cancer (PC) patients, potentially representing a real-time monitoring test for tumor evolution and response to treatment through the analysis of circulating tumor cells (CTCs) and exosomes. We performed a systematic literature review (PRISMA guidelines) to describe the current knowledge about PD-L1 expression in liquid biopsies of PC patients: 101/159 (64%) cases revealed a variable number of PD-L1+ CTCs. Outcome correlations should be investigated in larger series. Nuclear PD-L1 expression by CTCs was occasionally associated with worse prognosis. Treatment (abiraterone, enzalutamide, radiotherapy, checkpoint-inhibitors) influenced PD-L1+ CTC levels. Discordance in PD-L1 status was detected between primary vs. metastatic PC tissue biopsies and CTCs vs. corresponding tumor tissues. PD-L1 is also released by PC cells through soluble exosomes, which could inhibit the T cell function, causing immune evasion. PD-L1+ PC-CTC monitoring and genomic profiling may better characterize the ongoing aggressive PC forms compared to PD-L1 evaluation on primary tumor biopsies/prostatectomy specimens (sometimes sampled a long time before recurrence/progression). Myeloid-derived suppressor cells and dendritic cells (DCs), which may have immune-suppressive effects in tumor microenvironment, have been found in PC patients circulation, sometimes expressing PD-L1. Occasionally, their levels correlated to clinical outcome. Enzalutamide-progressing castration-resistant PC patients revealed increased PD-1+ T cells and circulating PD-L1/2+ DCs.
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http://dx.doi.org/10.3390/jpm11121312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709072PMC
December 2021

EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 3).

Cancers (Basel) 2021 Nov 30;13(23). Epub 2021 Nov 30.

Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.

EBV is the first known oncogenic virus involved in the development of several tumors. The majority of the global population are infected with the virus early in life and the virus persists throughout life, in a latent stage, and usually within B lymphocytes. Despite the worldwide diffusion of EBV infection, EBV-associated diseases develop in only in a small subset of individuals often when conditions of immunosuppression disrupt the balance between the infection and host immune system. EBV-driven lymphoid proliferations are either of B-cell or T/NK-cell origin, and range from disorders with an indolent behavior to aggressive lymphomas. In this review, which is divided in three parts, we provide an update of EBV-associated lymphoid disorders developing in the gastrointestinal tract, often representing a challenging diagnostic and therapeutic issue. Our aim is to provide a practical diagnostic approach to clinicians and pathologists who face this complex spectrum of disorders in their daily practice. In this part of the review, the chronic active EBV infection of T-cell and NK-cell type, its systemic form; extranodal NK/T-cell lymphoma, nasal type and post-transplant lymphoproliferative disorders are discussed.
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http://dx.doi.org/10.3390/cancers13236021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8656853PMC
November 2021

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables.

Cells 2021 11 14;10(11). Epub 2021 Nov 14.

Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

Immunotherapy targeting the PD-1-PD-L1 axis yielded good results in treating different immunologically ''hot'' tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pembrolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11-41% (depending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in <200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41-50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases.
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http://dx.doi.org/10.3390/cells10113166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625301PMC
November 2021

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 2: Clinic-Pathologic Correlations.

Cells 2021 11 14;10(11). Epub 2021 Nov 14.

Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

Many studies have investigated the potential prognostic and predictive role of PD-L1 in prostatic carcinoma (PC). We performed a systematic literature review (PRISMA guidelines) to critically evaluate human tissue-based studies (immunohistochemistry, molecular analysis, etc.), experimental research (cell lines, mouse models), and clinical trials. Despite some controversial results and study limitations, PD-L1 expression by tumor cells may be related to clinic-pathologic features of adverse outcome, including advanced tumor stage (high pT, presence of lymph node, and distant metastases), positivity of surgical margins, high Grade Group, and castration resistance. Different PD-L1 positivity rates may be observed in matched primary PCs and various metastatic sites of the same patients. Over-fixation, type/duration of decalcification, and PD-L1 antibody clone may influence the immunohistochemical analysis of PD-L1 on bone metastases. PD-L1 seemed expressed more frequently by castration-resistant PCs (49%) as compared to hormone-sensitive PCs (17%). Some series found that PD-L1 positivity was associated with decreased time to castration resistance. Treatment with ipilimumab, cyclophosphamide/GVAX/degarelix, or degarelix alone may increase PD-L1 expression. Correlation of PD-L1 positivity with overall survival and outcomes related to tumor recurrence were rarely investigated; the few analyzed series produced conflicting results and sometimes showed limitations. Further studies are required. The testing and scoring of PD-L1 should be standardized.
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http://dx.doi.org/10.3390/cells10113165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618408PMC
November 2021

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.

Int J Mol Sci 2021 Nov 15;22(22). Epub 2021 Nov 15.

Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients' serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.
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http://dx.doi.org/10.3390/ijms222212330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618001PMC
November 2021

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1.

Int J Mol Sci 2021 Nov 15;22(22). Epub 2021 Nov 15.

Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

Epigenetic alterations (including DNA methylation or miRNAs) influence oncogene/oncosuppressor gene expression without changing the DNA sequence. Prostate cancer (PC) displays a complex genetic and epigenetic regulation of cell-growth pathways and tumor progression. We performed a systematic literature review (following PRISMA guidelines) focused on the epigenetic regulation of PD-L1 expression in PC. In PC cell lines, CpG island methylation of the promoter negatively regulated PD-L1 expression. Histone modifiers also influence the PD-L1 transcription rate: the deletion or silencing of the histone modifiers MLL3/MML1 can positively regulate PD-L1 expression. Epigenetic drugs (EDs) may be promising in reprogramming tumor cells, reversing epigenetic modifications, and cancer immune evasion. EDs promoting a chromatin-inactive transcriptional state (such as bromodomain or p300/CBP inhibitors) downregulated PD-L1, while EDs favoring a chromatin-active state (i.e., histone deacetylase inhibitors) increased PD-L1 expression. miRNAs can regulate PD-L1 at a post-transcriptional level. miR-195/miR-16 were negatively associated with PD-L1 expression and positively correlated to longer biochemical recurrence-free survival; they also enhanced the radiotherapy efficacy in PC cell lines. miR-197 and miR-200a-c positively correlated to PD-L1 mRNA levels and inversely correlated to the methylation of PD-L1 promoter in a large series. miR-570, miR-34a and miR-513 may also be involved in epigenetic regulation.
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http://dx.doi.org/10.3390/ijms222212314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619683PMC
November 2021

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).

Int J Mol Sci 2021 Nov 14;22(22). Epub 2021 Nov 14.

Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy.

In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapy-resistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ T-cells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223).
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http://dx.doi.org/10.3390/ijms222212297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618402PMC
November 2021

Management of colovesical fistula: a systematic review.

Minerva Urol Nephrol 2022 Aug 18;74(4):400-408. Epub 2021 Nov 18.

Unit of Surgical Oncology, Azienda USL-IRCCS Reggio Emilia, Reggio Emilia, Italy.

Introduction: Colovesical fistulas (CVFs) account for approximately 95% enterovesical fistulas (EVFs). About 2/3 CVF cases are diverticular in origin. It mainly presents with urological signs such as pneumaturia and fecaluria. Diagnostic investigations aim at confirming the presence of a fistula. Although conservative management can be chosen for selected individuals, most patients are mainly treated through surgical interventions. CVF represents a challenging condition, which records high rates of morbidity and mortality. Our systematic review aimed at achieving deeper knowledge of both indications, in addition to short- and long-term outcomes related to CVF management.

Evidence Acquisition: We performed a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. Pubmed/MEDLINE, Embase, Scopus, Cochrane Library and Web of Science databases were used to search all related literature.

Evidence Synthesis: The 22 included articles covered an approximately 37 years-study period (1982-2019), with a total 1365 patient population. CVF etiology was colonic diverticulitis in most cases (87.9%). Pneumaturia (50.1%), fecaluria (40.9%) and urinary tract infections (46.6%) were the most common symptoms. Abdomen computed tomography (CT) scan (80.5%), colonoscopy (74.5%) and cystoscopy (55.9%) were the most frequently performed diagnostic methods. Most CVF patients underwent surgery (97.1%) with open approach (63.3%). Almost all patients had colorectal resection with primary anastomosis with or without ostomy and 53.2% patients underwent primary repair or partial/total cystectomy. Four percent anastomotic leak, 1.8% bladder leak and 3.1% reoperations rates were identified. In an average 5-68-month follow-up, overall morbidity, overall mortality and recurrences rates recorded were 8-49%, 0-63% and 1.2%, respectively.

Conclusions: CVF mainly affects males and has diverticular origin in almost all cases. Pneumaturia, fecaluria and urinary tract infections are the most characteristic symptoms. Endoscopic tests and imaging are critical tools for diagnostic completion. Management of CVFs depends on the underlying disease. Surgical treatment represents the final approach and consists of resection and reanastomosis of offending intestinal segment, with or without bladder closure. In many cases, a single-stage surgical strategy is selected. Perioperative and long-term outcomes prove good.
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http://dx.doi.org/10.23736/S2724-6051.21.04750-9DOI Listing
August 2022

Cutaneous Localization of Classic Hodgkin Lymphoma Associated with Mycosis Fungoides: Report of a Rare Event and Review of the Literature.

Life (Basel) 2021 Oct 11;11(10). Epub 2021 Oct 11.

Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.

Mycosis fungoides and nodal classic Hodgkin lymphoma (cHL) have been reported to occur concurrently or sequentially in the same patient. A long-lasting mycosis fungoides more often precedes the onset of nodal cHL, although few cases of nodal cHL followed by mycosis fungoides have been observed. Skin involvement is a rare manifestation of cHL that may be observed in the setting of advanced disease. The decrease in skin involvement in cHL is mainly due to the improved therapeutic strategies. The concurrent presence of mycosis fungoides and cutaneous localization of classic Hodgkin lymphoma represents a very uncommon event, with only two cases reported so far. Herein, we describe the case of a 71-year-old man, with a history of recurrent nodal cHL, who developed MF and, subsequently, the cutaneous localization of cHL. The clinicopathological features of the two diseases are described focusing on the main differential diagnoses to be taken into consideration, and a review of the literature is performed.
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http://dx.doi.org/10.3390/life11101069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537882PMC
October 2021

Mixed chorangioma and leiomyoma of the placenta, with a brief review of nontrophoblastic placental lesions.

Pediatr Dev Pathol 2022 May-Jun;25(3):316-320. Epub 2021 Oct 4.

Department of Pathology & Laboratory Medicine, Rutgers-New Jersey Medical School, Newark, New Jersey.

Chorangioma is the most common type of primary non-trophoblastic tumor of the placenta, usually identified incidentally on ultrasound or at delivery. Leiomyomas within the placenta have been described, though they are rare and usually of maternal origin. We present an unusual case of a placental tumor with combined histopathologic and immunohistochemical features of both chorangioma and leiomyoma. A 39-year-old woman was found to have an echogenic placental mass at 33 weeks of gestation on ultrasound, that was thought to be a chorangioma. They followed up weekly, and performed a cesarean section at 39 weeks, due to concern for intrauterine growth restriction. No fetal or maternal complications occurred. Grossly, a 9-cm, red-brown mass with a broad-based stalk was identified on the fetal surface of the placenta near the periphery. Microscopically, the lesion was found to display characteristic features of chorangioma, with vascular proliferation, which stained positive for CD34 and CD31. SMA and caldesmon immunohistochemical staining was also positive, highlighting the proliferation of smooth muscle throughout the neoplasm. Literature review revealed a single additional case with similar characteristics.
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http://dx.doi.org/10.1177/10935266211047775DOI Listing
June 2022

Fetal Presentation of Mediastinal Immature Teratoma: Ultrasound, Autopsy and Cytogenetic Findings.

Diagnostics (Basel) 2021 Aug 25;11(9). Epub 2021 Aug 25.

Obstetric Unit, Department of Medical and Surgical Sciences, Sant'Orsola-Malpighi Hospital, 40138 Bologna, Italy.

Teratomas are the most common congenital tumors, occurring along the midline or paraxial sites, or uncommonly, the mediastinum. Teratomas are classified as mature, containing only differentiated tissues from the three germinal layers; and immature, which also present with neuroectodermal elements, ependymal rosettes, and immature mesenchyme. Herein, we describe a new case of fetal mediastinal immature teratoma detected at 21 weeks of gestational age (wga) + 1 day with thorough cytogenetic analysis. Ultrasound (US) showed a solid and cystic mass located in the anterior mediastinum, measuring 1.8 × 1.3 cm with no signs of hydrops. At 22 wga, US showed a mass of 2.4 cm in diameter and moderate pericardial effusions. Although the prenatal risks and available therapeutic strategies were explained to the parents, they opted for termination of pregnancy. Histology showed an immature teratoma, Norris grade 2. Karyotype on the fetus and tumor exhibited a chromosomal asset of 46,XX. The fetal outcome in the case of mediastinal teratoma relies on the development of hydrops due to mass compression of vessels and heart failure. Prenatal US diagnosis and close fetal monitoring are paramount in planning adequate treatment, such as in utero surgery, ex utero intrapartum therapy (EXIT) procedure, and surgical excision after birth.
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http://dx.doi.org/10.3390/diagnostics11091543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468681PMC
August 2021

EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 1).

Cancers (Basel) 2021 Sep 12;13(18). Epub 2021 Sep 12.

Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.

EBV is the most common persistent virus in humans. The interaction of EBV with B lymphocytes, which are considered the virus reservoir, is at the base of the life-long latent infection. Under circumstances of immunosuppression, the balance between virus and host immune system is altered and hence, EBV-associated lymphoid proliferations may originate. These disorders encompass several entities, ranging from self-limited diseases with indolent behavior to aggressive lymphomas. The virus may infect not only B-cells, but even T- and NK-cells. The occurrence of different types of lymphoid disorders depends on both the type of infected cells and the state of host immunity. EBV-driven lymphoproliferative lesions can rarely occur in the gastrointestinal tract and may be missed even by expert pathologists due to both the uncommon site of presentation and the frequent overlapping morphology and immunophenotypic features shared by different entities. The aim of this review is to provide a comprehensive overview of the current knowledge of EBV-associated lymphoproliferative disorders, arising within the gastrointestinal tract. The review is divided in three parts. In this part, the available data on EBV biology, EBV-positive mucocutaneous ulcer, EBV-positive diffuse large B-cell lymphoma, not otherwise specified and classic Hodgkin lymphoma are discussed.
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http://dx.doi.org/10.3390/cancers13184578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465149PMC
September 2021

EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 2).

Cancers (Basel) 2021 Sep 8;13(18). Epub 2021 Sep 8.

Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.

Epstein-Barr virus (EBV) is a common pathogen infecting people primarily early in life. The virus has the ability to persist throughout a person's life, usually in B lymphocytes. Conditions of immunodeficiency as well as the introduction of immunosuppressive therapies and the advent of transplant technologies has brought immunodeficiency-associated lymphoproliferative disorders into view, which are often driven by EBV. The group of EBV-associated lymphoproliferative disorders includes different entities, with distinct biological features, ranging from indolent disorders, which may even spontaneously regress, to aggressive lymphomas requiring prompt and adequate treatment. These disorders are often diagnostically challenging due to their overlapping morphology and immunophenotype. Both nodal and extra-nodal sites, including the gastrointestinal tract, may be involved. This review, divided in three parts, summarizes the clinical, pathological, molecular features and treatment strategies of EBV-related lymphoproliferative disorders occurring in the gastrointestinal tract and critically analyzes the major issues in the differential diagnosis. In this part of the review, we discuss plasmablastic lymphoma, extra-cavitary primary effusion lymphoma and Burkitt lymphoma.
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http://dx.doi.org/10.3390/cancers13184527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469260PMC
September 2021

Gastrointestinal Manifestations in Systemic Mastocytosis: The Need of a Multidisciplinary Approach.

Cancers (Basel) 2021 Jul 1;13(13). Epub 2021 Jul 1.

Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy.

Mastocytosis represents a heterogeneous group of neoplastic mast cell disorders. The basic classification into a skin-limited disease and a systemic form with multi-organ involvement remains valid. Systemic mastocytosis is a disease often hard to diagnose, characterized by different symptoms originating from either the release of mast cell mediators or organ damage due to mast cell infiltration. Gastrointestinal symptoms represent one of the major causes of morbidity, being present in 60-80% of patients. A high index of suspicion by clinicians and pathologists is required to reach the diagnosis. Gastrointestinal mastocytosis can be a challenging diagnosis, as symptoms simulate other more common gastrointestinal diseases. The endoscopic appearance is generally unremarkable or nonspecific and gastrointestinal mast cell infiltration can be focal and subtle, requiring an adequate sampling with multiple biopsies by the endoscopists. Special stains, such as CD117, tryptase, and CD25, should be performed in order not to miss the gastrointestinal mast cell infiltrate. A proper patient's workup requires a multidisciplinary approach including gastroenterologists, endoscopists, hematologists, oncologists, and pathologists. The aim of this review is to analyze the clinicopathological features of gastrointestinal involvement in systemic mastocytosis, focusing on the relevance of a multidisciplinary approach.
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http://dx.doi.org/10.3390/cancers13133316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269078PMC
July 2021
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