Pancreatic neuroendocrine tumor and solid-pseudopapillary neoplasm: Key immunohistochemical profiles for differential diagnosis

Abstract

AIMTo reveal better diagnostic markers for differentiating neuroendocrine tumor (NET) from solid-pseudopapillary neoplasm (SPN), focusing primarily on immunohistochemical analysis.METHODSWe reviewed 30 pancreatic surgical specimens of NET (24 cases) and SPN (6 cases). We carried out comprehensive immunohistochemical profiling using 9 markers: Synaptophysin, chromogranin A, pan-cytokeratin, E-cadherin, progesterone receptor, vimentin, α-1-antitrypsin, CD10, and β-catenin.RESULTSE-cadherin staining in NETs, and nuclear labeling of β-catenin in SPNs were the most sensitive and specific markers. Dot-like staining of chromogranin A might indicate the possibility of SPNs rather than NETs. The other six markers were not useful because their expression overlapped widely between NETs and SPNs. Moreover, two cases that had been initially diagnosed as NETs on the basis of their morphological features, demonstrated SPN-like immunohistochemical profiles. Careful diagnosis is crucial as we actually found two confusing cases showing disagreement between the tumor morphology and immunohistochemical profiles.CONCLUSIONE-cadherin, chromogranin A, and β-catenin were the most useful markers which should be employed for differentiating between NET and SPN.

Immunocytochemistry for SOX‐11 and TFE3 as diagnostic markers for solid pseudopapillary neoplasms of the pancreas in FNA biopsies

“…Two additional immunohistochemical markers commonly used to differentiate SPNs from NETs are synaptophysin and chromogranin; however, studies have shown that although these stains are highly sensitive for NETs, they lack specificity. Synaptophysin, in particular, though reported to be positive in up to 100% of NETs, has also been seen in the majority of SPNs . Chromogranin, though showing increased specificity for NETs in comparison with synaptophysin in some studies, has also been reported to show at least focal expression in up to 100% of SPNs and in more than 30% of acinar cell carcinomas in others …”

“…4,22 Chromogranin, though showing increased specificity for NETs in comparison with synaptophysin in some studies, 22,23 has also been reported to show at least focal expression in up to 100% of SPNs and in more than 30% of acinar cell carcinomas in others. 4,24 We recently identified 2 additional immunohistochemical stains, SOX-11 and TFE3, that appear to be both sensitive and specific for SPNs on surgical resection. 6 In this study, we explore these 2 stains in the context of cytology and suggest that SOX-11 may be a useful adjunct in the differential diagnosis of SPN with EUS-FNA.…”

“…Immunocytochemical staining can help: the majority of SPNs exhibit aberrant nuclear β‐catenin staining, which has become one of the most useful markers in the diagnosis of this neoplasm. However, up to 12% of acinar cell carcinomas, 8% of NETs, and 100% of pancreatoblastomas have also been reported to exhibit nuclear expression of β‐catenin, decreasing its specificity for SPNs …”

“…However, up to 12% of acinar cell carcinomas, 8% of NETs, and 100% of pancreatoblastomas have also been reported to exhibit nuclear expression of bcatenin, decreasing its specificity for SPNs. [3][4][5] Because of the potential overlap, the diagnosis of SPN often relies on the integration of clinical and morphological features as well as a panel of immunohistochemical stains; even so, a definitive diagnosis can be difficult to make in selected cases, especially if there is little material for evaluation or if the morphologic features are not considered classic for this diagnosis. We recently identified 2 immunohistochemical stains, SRY-related high-mobility group box 11 (SOX-11) and transcription factor E3 (TFE3), that in combination were found to be highly sensitive and specific for the diagnosis of SPNs on surgical resection.…”

An Unusual Presentation of a Solid Pseudopapillary Tumor of the Pancreas Mimicking Adenocarcinoma

“…With regards to IHC assays, positive results with the beta-catenin stain and negative results with neuroendocrine markers, such as chromogranin A or synaptophysin, are important indicators that distinguish SPTs from pancreatic neuroendocrine tumors. 13 SPTs typically show indolent behavior and are associated with long survival rates (even in patients with disseminated disease) secondary to slow tumor doubling time (765 days). 14 Unfortunately, rapid tumor progression led to our patient's mortality 5 months after being diagnosed with this tumor.…”