Epstein-Barr virus-positive ileal carcinomas associated with Crohn’s disease

Vanoli, Alessandro; Sabatino, Antonio Di; Martino, Michele; Dallera, Elena; Furlan, Daniela; Mescoli, Claudia; Macciomei, Maria Cristina; Biancone, Livia; Neri, Benedetto; Grillo, Federica; Biletta, Elena; Sessa, Fausto; Paulli, Marco; Corazza, Gino Roberto; Solcia, Enrico

doi:10.1007/s00428-017-2209-9

Cited by 14 publications

(17 citation statements)

References 9 publications

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“…In keeping with that, overexpression of the Wnt-related transcription factor and stem cell marker Sex-determining Region Y-Box (SOX) 9 has been observed in hyperplastic crypts of untreated CD patients [59], as well as in CD-SBC tumour cells, in direct continuity with SOX-9 + adjacent dysplastic and hyperplastic crypts ( carcinogenesis [62], has been documented in two microsatellite-stable T-cell rich CrD-SBC [63,64]. In both cases EBV has been also found in dysplastic lesions associated with CrD-SBC and in small foci of iuxta-tumoral epithelium apparently in the absence of dysplasia [63,64]. 63 On this basis we support that rarely EBV latent infection might be a very early, crucial event during carcinogenesis in those patients.…”

Section: Pathogenesis and Preneoplastic Lesionsmentioning

confidence: 53%

“…stage. EBV latent infection should be considered in SBC irrespective of their histologic type, in light of the better prognosis of the only two EBV + CrD-SBC cases reported so far [63,64]. Funding: San Matteo Hospital Foundation, Pavia, Italy.…”

Section: Discussionmentioning

confidence: 99%

“…High TILs in SBC can be induced by additional factors besides MSI status, such as oncogenic viruses. As this regards, it is interesting to note that two non-MSI high-TIL SBC with EBV latent infection described in CrD seem to be associated with a favourable outcome [63,64], probably due to the anti-tumour immune response induced by abnormal peptide production from EBV. Therefore, although these findings need to be confirmed by further evidences, EBV latent infection should be considered in CrD-SBC for a better prognostic evaluation.…”

Section: Prognosis and Treatmentmentioning

confidence: 99%

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Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: the Current Knowledge

Giuffrida¹,

Vanoli²,

Arpa³

et al. 2018

Preprint

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Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders, including coeliac disease (CD) and Crohn’s disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumor-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.

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Section: Pathogenesis and Preneoplastic Lesionsmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Prognosis and Treatmentmentioning

confidence: 99%

See 1 more Smart Citation

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: the Current Knowledge

Giuffrida¹,

Vanoli²,

Arpa³

et al. 2018

Preprint

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“…This retrospective study included 47 patients with primary non-ampullary CrD-SBCs, mostly from the ileum [n = 44], two from the jejunum, and one from the duodenum. The patients, some of whom have been partly studied in previous series, 1,2,14 had surgical resection and complete survival data from 15 tertiary referral Italian inflammatory bowel disease centres participating in the Small Bowel Cancer Italian Consortium. Neuroendocrine neoplasms were excluded.…”

Section: Study Populationmentioning

confidence: 99%

Separation of Low- Versus High-grade Crohn’s Disease-associated Small Bowel Carcinomas is Improved by Invasive Front Prognostic Marker Analysis

Arpa

Grillo

Giuffrida

et al. 2019

Journal of Crohn's and Colitis

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Background and Aims Crohn’s disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favourable behaviour, thus outlining the need to improve the histopathological prediction of Crohn’s disease-associated small bowel carcinoma prognosis. Methods As in recent studies on colorectal cancer, a substantial improvement in prognostic evaluations has been provided by the histological analysis of the tumour invasive front; we therefore systematically analysed the tumour budding and poorly differentiated clusters in the invasive front of 47 Crohn’s disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium. Results Both tumour budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn’s disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers [12/47, 25%] characterised by combined invasive front low grade coupled with a glandular histology and a low stage [I or II] and showing no cancer-related death during a median follow-up of 73.5 months. Conclusions The improved distinction of lower- from higher-grade Crohn’s disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms.

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“…This subtype of GC is frequently associated with EBV, with reported rates varying from 22% to 100% [13]. Approximately 90% of the world population is infected by EBV, which has been reported to be associated with several tumor types such as lymphomas and nasopharyngeal, parotid, gastric, and ileal carcinomas [13][14][15]. The reasons why neoplastic transformation occurs only in a small number of patients, while most subjects are spared, are unknown, as are the mechanisms of infection of the gastric epithelium.…”

Section: Discussionmentioning

confidence: 99%

Bilateral Breast Metastases from Epstein-Barr Virus-Associated Gastric Cancer during Pregnancy: Is There a Method to Its Madness?

et al. 2020

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Breast metastases of extramammary malignant neoplasms are rare, with an incidence of 0.3%-2.7% among all malignant mammary tumors. Breast metastases from gastric carcinoma are very rare (<0.1%), and this event is even rarer during pregnancy. Herein, we describe a 39-year-old Caucasian woman with a history of an Epstein-Barr virus-associated gastric carcinoma (EBVaGC) that was characterized by prominent tumor infiltrating lymphocytes. Three years after undergoing radical surgery, the patient developed bilateral breast nodules during her pregnancy. A breast biopsy was performed, and histology confirmed a diagnosis of EBVaGC; tumor cells showed positivity for cytokeratin 8/18 and E-cadherin, and negativity for cytokeratin 7, cytokeratin 20, cytokeratin 5/6, caudal type homebox 2, androgen receptor, mammaglobin, gross cystic disease fluid protein-15, and estrogen and progesterone receptors. We also discuss the main diagnostic pitfalls. To our knowledge, this is the first report of an EBVaGC with lymphoid stroma that developed breast metastases during pregnancy.

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Epstein-Barr virus-positive ileal carcinomas associated with Crohn’s disease

Cited by 14 publications

References 9 publications

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: the Current Knowledge

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: the Current Knowledge

Separation of Low- Versus High-grade Crohn’s Disease-associated Small Bowel Carcinomas is Improved by Invasive Front Prognostic Marker Analysis

Bilateral Breast Metastases from Epstein-Barr Virus-Associated Gastric Cancer during Pregnancy: Is There a Method to Its Madness?

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