Pancreatic duct stenosis secondary to small endocrine neoplasms: a manifestation of serotonin production?

Abstract

Purpose: To determine if serotonin production by pancreatic endocrine neoplasms is associated with the pancreatic duct stenosis seen in patients with stenosis that is out of proportion to the size of the tumors seen on computed tomographic images.

Materials and methods: Institutional approval was obtained for this HIPAA-compliant study. Informed consent was waived. Clinical and radiologic findings in six patients were reviewed. Gross and histologic findings in the resected pancreata were also assessed. Formalin-fixed paraffin-embedded tumor sections were immunolabeled with antibodies to serotonin. Tissue microarrays constructed from 47 pancreatic endocrine neoplasms from the institutional tissue bank served as controls. Histologic and serotonin immunoreactivity findings were compared between the two groups. The Fisher exact test was used to compare serotonin immunoreactivity.

Results: Only one of the six study patients had a large dominant tumor (4 cm in the pancreatic head). All others were 2.5 cm or smaller. Four of the six pancreatic endocrine neoplasms with associated pancreatic duct stricture had prominent stromal fibrosis. Serotonin immunoreactivity was present in five (83%) patients, and this labeling was strong and diffuse in the four patients with prominent fibrosis. By contrast, stromal fibrosis was minimal in the nonimmunoreactive case. Only three (6%) of the 47 control pancreatic endocrine neoplasms were immunoreactive for serotonin (P < .01, Fisher exact test).

Conclusion: These data suggest that serotonin produced by pancreatic endocrine neoplasms may be associated with local fibrosis and stenosis of the pancreatic duct. Clinicians should be aware that small pancreatic endocrine neoplasms can produce pancreatic duct stenosis resulting in ductal dilatation and/or upstream pancreatic atrophy out of proportion to the size of the tumor.

Figure 1a:

Contrast material–enhanced CT images in patient 1 (29-year-old woman). (a) Axial arterial phase image shows marked atrophy of the pancreatic body (arrowheads) (anteroposterior dimension = 5 mm). Arrow = small enhanced liver mass (metastasis). (b) Venous phase anterior volume-rendered image shows enhanced mass (arrow) with upstream pancreatic atrophy (arrowheads). A separate small cystic lesion (pathologic finding: oligocystic serous cystadenoma) is incidentally shown in the inferior aspect of the pancreatic head.

Figure 1b:

Contrast material–enhanced CT images in patient 1 (29-year-old woman). (a) Axial arterial phase image shows marked atrophy of the pancreatic body (arrowheads) (anteroposterior dimension = 5 mm). Arrow = small enhanced liver mass (metastasis). (b) Venous phase anterior volume-rendered image shows enhanced mass (arrow) with upstream pancreatic atrophy (arrowheads). A separate small cystic lesion (pathologic finding: oligocystic serous cystadenoma) is incidentally shown in the inferior aspect of the pancreatic head.

Figure 2:

Venous phase contrast-enhanced oblique anterior volume-rendered CT image in patient 4 (57-year-old woman) shows enhanced mass (arrows) with marked main pancreatic duct dilatation (arrowheads).

Figure 3a:

(a) Oblique axial arterial phase, (b) axial venous phase, and (c) oblique coronal CT images in patient 5 (64-year-old woman) show minimally dilated main pancreatic duct (arrowheads) in a pancreatic tail with an atrophic truncated appearance. No discrete mass is shown. There is a subtle hypoenhanced area (arrows) in the pancreatic tail.

Figure 3b:

(a) Oblique axial arterial phase, (b) axial venous phase, and (c) oblique coronal CT images in patient 5 (64-year-old woman) show minimally dilated main pancreatic duct (arrowheads) in a pancreatic tail with an atrophic truncated appearance. No discrete mass is shown. There is a subtle hypoenhanced area (arrows) in the pancreatic tail.

Figure 3c:

(a) Oblique axial arterial phase, (b) axial venous phase, and (c) oblique coronal CT images in patient 5 (64-year-old woman) show minimally dilated main pancreatic duct (arrowheads) in a pancreatic tail with an atrophic truncated appearance. No discrete mass is shown. There is a subtle hypoenhanced area (arrows) in the pancreatic tail.

Figure 4:

Image of the gross specimen from patient 6 (47-year-old man) shows a marked dilated pancreatic duct that mimicks a cystic lesion. Mass is indistinct.

Figure 5:

Photomicrographs in patients 3 (A, B), 6 (C, D), and 2 (E, F). A, Sample shows well-differentiated endocrine neoplasm with marked stromal fibrosis. (Hematoxylin-eosin [H-E] stain.) B, D, Samples show strong serotonin immunoreactivity of neoplastic cells, with no labeling in stromal cells. C, Sample from downstream dilatation of the pancreatic duct shows well-differentiated endocrine neoplasm with marked stromal fibrosis extending into a main pancreatic duct (arrows). (H-E stain.) E, Sample shows a hypercellular well-differentiated endocrine neoplasm with minimal stromal fibrosis. (H-E stain.) F, Sample shows negative serotonin immunoreactivity of neoplastic cells. (Original magnification in A, ×200; in B, D, E, F, ×100; in C, ×20.)

Figure 6:

Photomicrographs in 47 controls. A, Tissue microarray shows 47 well-differentiated endocrine neoplasms. Yellow circle = hyalinized stroma, red circle = prominent stromal fibrosis. (H-E stain.) B, Immunohistochemical labeling shows partial serotonin immunoreactivity (yellow circle) in two cases and strong serotonin immunoreactivity (red circle) in one case. (Original magnification in A and B, ×200.)

Figure 7a:

Photomicrographs of the control case with marked stromal fibrosis at higher magnification. (a) Well-differentiated endocrine neoplasm with prominent stromal fibrosis. Note marked stromal fibrosis extending into pancreatic duct (arrows). (H-E stain.) (b) Serotonin labeling shows strong immunoreactivity. (Original magnification in a and b, ×200.)

Figure 7b:

Photomicrographs of the control case with marked stromal fibrosis at higher magnification. (a) Well-differentiated endocrine neoplasm with prominent stromal fibrosis. Note marked stromal fibrosis extending into pancreatic duct (arrows). (H-E stain.) (b) Serotonin labeling shows strong immunoreactivity. (Original magnification in a and b, ×200.)