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Review
. 2023 Aug 25;12(17):5537.
doi: 10.3390/jcm12175537.

Multidisciplinary Approach to the Diagnosis of Occult Primary Neuroendocrine Neoplasm: A Clinical Challenge

Roberta Elisa Rossi  1 , Francesca Corti  2 , Sara Pusceddu  3 , Massimo Milione  4 , Jorgelina Coppa  5 , Benedetta Masoni  1 , Simone Oldani  3 , Giovanna Sabella  4 , Pietro Cafaro  2 , Alessandro Repici  1   6
Affiliations
Review

Multidisciplinary Approach to the Diagnosis of Occult Primary Neuroendocrine Neoplasm: A Clinical Challenge

Roberta Elisa Rossi et al. J Clin Med. .

Abstract

Approximately 11% to 14% of subjects with neuroendocrine neoplasms (NENs) have metastatic lesions with unknown primary origin (UPO), with the majority of UPO-NENs found in the small bowel. Herein, we assessed the available literature on UPO-NENs, focusing on clinical presentation and diagnostic techniques to identify the primary site. The identification of the primary tumor is important as it affects the prognosis; however, the clinical presentation can be non-specific in non-functioning forms. In the presence of metastatic disease, the histological sample is fundamental to obtain immunohistochemical markers that might orientate the clinician in the search for the primary tumor through radiology, functional imaging and endoscopic techniques. In summary, multidisciplinary management plays a key role in UPO-NENs, even more than in other NENs. Molecular biology and gene-expression profiling represent areas of great interest which might be developed in the near future for both the diagnosis and the treatment of these neoplasms.

Keywords: capsule endoscopy; diagnosis; double-balloon enteroscopy; immunohistochemistry; molecular biology; neuroendocrine neoplasms; treatment; ultrasound endoscopy; unknown primary tumor.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart showing the process of study selection.
Figure 2
Figure 2
Histological and immunohistochemical attributes of a metastatic small-intestinal NET (SI-NET). (A), Characteristic organoid or nested architectural pattern of well-differentiated neuroendocrine tumor. Immunohistochemical expression was noted for Chromogranin (A,B), CDX2 (C) and Serotonin (D).
Figure 3
Figure 3
(A), Characteristic ribbon-like architectural pattern of pancreatic well-differentiated neuroendocrine tumor with site-specific ISLET-1 immunostaining positivity outline pancreatic landscape (B); in contrast, intestinal NENs usually present an organoid morphological pattern (C) with immunoreactivity for site-specific marker CDX2 in an intestinal landscape (D).
Figure 4
Figure 4
A possible diagnostic algorithm for the detection of neuroendocrine neoplasms of unknown origin.
See this image and copyright information in PMC

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