PMC6854169_01
Magnetic resonance imaging (MRI) confirmed a 4.6 cm relatively well circumscribed, hypervascular, enhancing mass (circled) in the distal pancreatic body with no associated pancreatic ductal dilatation.
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Right upper quadrant ultrasonography (US) and magnetic resonance imaging (MRI) studies confirmed a 4.6 x 4.2 x 3.5 cm mass lesion in the distal pancreatic body with no pancreatic duct dilatation (Figure 1).
Endoscopic Ultrasound (EUS) examination demonstrated an oval, hypoechoic mass with well-defined borders and no evidence of associated regional lymphadenopathy. No invasion of regional vasculature was present.
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This confirmed a greater than 40 mm oval mass lesion with well-defined endosonographic borders in the distal pancreatic body (Figure 2).
Three-dimensional microbiopsy tissue particles predominated. These show homogenous magenta spheroids with intimately associated spindled cells and collections of intervening, high nuclear/cytoplasmic ratio, small to intermediated sized cells with crush artifact (Modified Giemsa stain, 200X).
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The majority of the cellular material in the ROSE slides consisted of three-dimensional microbiopsy tissue particles which were present predominantly in the central areas of the direct smears. These microbiopsy particles contained homogenous magenta spheroids with intimately associated spindled cells and collections of intervening, high nuclear/cytoplasmic ratio, small to intermediated sized cells with crush artifact (Figure 3).
Large, cohesive, three-dimensional aggregates of cellular material predominate in the direct smears. These show spheroidal globules of eosinophilic to amphophilic extracellular material with intimately associated small to intermediate sized spindled and epithelioid cells. While appliqueed spindled cells are noted on the spheroids, true intrinsic fibrovascular cores are not identified (Papanicolaou stain, 200X).
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While appliqueed spindled cells were noted on the globules, true intrinsic fibrovascular cores were not identified (Figure 4).
Cyanophilic homogenous spheroid with adherent or intrinsic bland spindled cells (fibroblasts) and collections of small, high nuclear/cytoplasmic ratio round to oval smears intervening between (Papanicolaou stain, 400X).
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At higher magnification in less complex cell groups, individual globular spheroids appeared cyanophilic in the Papanicolaou stained slides, and these structures showed either adherent or intrinsic small bland spindled nuclei (Figure 5).
(a) Scattered loosely cohesive collections of epithelioid cells were noted in the direct smear backgrounds (Modified Giemsa stain, 400X). (b) These cells varied in shape from round to oval to plasmacytoid with finely granular chromatin and occasional minute nucleoli (Papanicolaou stain, 400X). (c) These cells appeared similar to the cells between the globules in the cell block but were dyscohesive (Hematoxylin & eosin stain, 400X).
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These cells had minimal cytoplasm, were small to intermediate in size and varied from round to oval to occasionally plasmacytoid (Figure 6).
The cell block showed loose collections of small epithelioid cells and in some areas connected disc-like spheres of hyalinized fibrous tissue with adherent/intrinsic bland spindle cells, suggesting a possible papillary/arborizing morphology (Hematoxylin & eosin stain, 200X).
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In some areas of the cell block the spheroids were minimally associated with the small epithelioid cells and appeared as hyalinized discs with intimately associated bland spindled cells, possibly interpreted as a papillary architectural pattern (Figure 7).
(a) Cell block showing cytoplasmic immunoreactivity for scattered small to intermediate sized, high nuclear/cytoplasmic ratio cells present between spheroids (CK AE1-3 immunohistochemistry, 400X). (b) Cell block with similar pattern of immunoreactivity (beta-catenin immunohistochemistry, 400X). (c) Cell block with patchy/weak cytoplasmic immunoreactivity (Chromogranin A immunohistochemistry, 400X). (d) Cell Block with diffuse and strong immunoreactivity in epithelioid cells, while spheroids and intrinsic spindled nuclei appear nonreactive (Synaptophysin immunohistochemistry, 400X).
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AE1-3, chromogranin, synaptophysin and beta-catenin (Figure 8). A diagnosis of neoplasia, favor a PanNEN was given with a comment stating that a pancreatic solid pseudopapillary neoplasm could not be entirely excluded.
(a) Histologic sections from the pancreatectomy specimen confirmed a solid neoplasm with a low power pattern reminiscent of pulmonary alveolar edema or proteinosis with peripheral rims of epithelial cells surrounding eosinophilic spaces (Hematoxylin & eosin, 100X). (b) At greater magnification, the collagenized nature of the eosinophilic cobblestones is apparent with lesional epithelial cells in ribbons between the spheroids (Hematoxylin & eosin, 200X). (c) At highest magnification, the small, bland, tapering and spindled nuclei (black arrow) within the spheroids can be readily distinguished from the lesional epithelial cells between the cobblestones (white arrow) (Hematoxylin & eosin, 600X).
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The majority of the histologic sections showed an exaggerated gyriform pattern of growth resulting in a cobblestone pavement-like architectural pattern with eosinophilic discs of fibrous stroma surrounded by neoplastic cells (Figure 9).
(a) Absence of brick red staining and no evidence of apple-green birefringence on polarized light excludes amyloid protein deposition in the cobblestones (Congo red stain, 200X). (b) Orange-pink staining with intrinsic fibrils in sections of the cobblestones supports the impression of spheroids of fibrous tissue (Movat stain, 200X). (c) Azure blue staining with intrinsic fibrils further indicates that the homogenous and paucicellular spheroids are comprised of fibrous tissue (Trichrome stain, 200X).
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Trichrome stains were performed. These helped to exclude amyloid deposition and to confirm that the spheroids were truly comprised of fibrous tissue (Figure 10).
(a) Diffuse granular cytoplasmic immunoreactivity is present in the ribbons of lesional epithelial cells between fibrous spheroids (Chromogranin A immunohistochemistry, 400X). (b) Diffuse and strong homogenous cytoplasmic immunoreactivity is confirmed in the epithelial cells (Synaptophysin immunohistochemistry, 400X). (c) Very rare epithelial nuclei (<3% of lesional cells) show immunoreactivity with the proliferation marker (Ki-67 immunohistochemistry, 400X).
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Ancillary immunohistochemical studies undertaken on sections from the resected tumor confirmed diffuse immunoreactivity with chromogranin and synaptophysin with a nonreactive result for beta-catenin and with a low (<3%) proliferation index on Ki-67 testing (Figure 11).