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Calcitonin-Producing Neuroendocrine Neoplasms of the Pancreas: Clinicopathological Study of 25 Cases and Review of the Literature

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Abstract

Increased levels of circulating calcitonin are a clue in the diagnosis of medullary thyroid carcinoma. However, hypercalcitoninemia can also be related to other pathological conditions, including pancreatic neuroendocrine neoplasms (PanNENs). Ectopic hormonal production is not unusual in both functioning and non-functioning PanNENs; however, little is known about the frequency of calcitonin expression in these neoplasms. The aims of this study were to assess the frequency of calcitonin immunoreactivity in PanNENs, independently from serum calcitonin levels, and to evaluate the clinicopathological and prognostic features of calcitonin-immunoreactive (Cal-IR) PanNENs, including a comparison with cases already reported in the literature. We screened 229 PanNENs for the immunohistochemical expression of calcitonin, including both functioning and non-functioning neoplasms, as well as both well-differentiated and poorly differentiated PanNENs. Both the clinicopathological data and the follow-up information were available and were compared with the immunohistochemical results. In addition, we reviewed the features of the calcitonin-producing PanNENs previously reported in the literature. Calcitonin was expressed in 25 of our 229 PanNENs (10.9%). Examples of well- and poorly differentiated, as well as both functioning and non-functioning PanNENs, were found to be calcitonin immunoreactive. Cal-IR PanNENs did not show any significant difference with the whole series of neoplasms included in the study, when the clinicopathological parameters were considered, except for a younger age at diagnosis and for a larger size of the tumor in non-functioning Cal-IR PanNENs. Taken together, our results show that calcitonin immunoreactivity is not an exceptional event in PanNENs. Furthermore, calcitonin expression does not identify a separate clinical entity, in contrast to other PanNENs with ectopic hormone production, such as adrenocorticotropic hormone (ACTH)-producing PanNENs, which show a distinctively more aggressive behavior.

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Authors and Affiliations

  1. Department of Medicine and Surgery, Unit of Pathology, University of Insubria, 21100, Varese, Italy

    Silvia Uccella, Roberta Maragliano & Fausto Sessa

  2. Institute of Pathology, University of Bern, Bern, Switzerland

    Annika Blank & Aurel Perren

  3. Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland

    Stefano La Rosa

Authors
  1. Silvia Uccella
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  2. Annika Blank
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  3. Roberta Maragliano
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  4. Fausto Sessa
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  5. Aurel Perren
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  6. Stefano La Rosa
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Correspondence to Silvia Uccella.

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The study was approved by the Ethical Committee of the AST Sette Laghi, Ospedale di Circolo, Varese, Italy, and Cantonal Ethical Commission, Bern, Switzerland.

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The authors declare that they have no conflict of interest.

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Uccella, S., Blank, A., Maragliano, R. et al. Calcitonin-Producing Neuroendocrine Neoplasms of the Pancreas: Clinicopathological Study of 25 Cases and Review of the Literature. Endocr Pathol 28, 351–361 (2017). https://doi.org/10.1007/s12022-017-9505-4

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