Diffuse signet ring-type gastric adenocarcinoma. (a) EUS-FNA yielded this material from a gastric lesion. This pattern is classic for signet ring gastric cancer, in which some cells take on the appearance of a signet ring (see the cell at 2 o’clock) – the “hole” of the ring is a mucin vacuole, which appears mostly white and the “ring” is the thin rim of cytoplasm. The malignant nucleus is large, is eccentrically placed, and appears to bulge out of the cell, completing the picture of a signet ring. These carcinomas often diffusely involve the stomach as single cells, and thus FNA often produces numerous discohesive single cells rather than tissue fragments. Note the nuclear size differences, the coarse chromatin, and the irregular nuclear borders seen in these cells. These cells may resemble histiocytes, and a high degree of suspicion may be required for their detection. In this direct smear (DS), inflammatory cells partially obscure cell detail (Pap-stained DS). (b) Isolated signet ring cells with the crescentic-shaped nuclei compressed toward the periphery by large intracytoplasmic mucinous vacuole, characteristic of the tumor. Mucinous cytoplasmic condensation is evident in the cell on the left. Background is clean (TP). If cell block material is present, keratin markers or special stain for mucicarmine can differentiate the cells from histiocytes, which express CD68 or KP-1 [1]

EUS-FNA of gastrointestinal stromal tumor (GIST). (a) This aspirate shows numerous uniform spindle cells with monotonous, slender, well-aliened nuclei with pale chromatin, no nucleoli, and delicate wispy basophilic cytoplasm. The cytoplasmic borders are indistinct, giving a syncytial appearance. The fragment is too cellular to be a fragment of normal connective tissue, which is sometimes seen when a lesion is not properly sampled during the procedure. Note the myxoid stromal quality. Mitoses were not evident (TP). (b) GIST on a conventional smear shows similar nuclear morphology. The myxoid stroma is more diffuse (Pap-stained DS). (c) Same case of GIST as above processed as SP specimen. Main differences are that the stroma appears denser and cells are more compact than TP (SP). (d) Positive immunostain for c-kit (a cell-surface transmembrane tyrosine kinase also known as CD117). Immunostain for DOG1 was also positive (CB). (e) The resection shows fascicles of uniform, bland spindle cells with pale, eosinophilic cytoplasm and myxoid stroma (H&E). Radiologically, this lesion was submucosal, distal, well marginated, heterogeneous, and enhancing. GISTs are the most common mesenchymal neoplasms of the gastrointestinal tract and should be differentiated from other mesenchymal tumors. They harbor specific activating mutations in the KIT or platelet-derived growth factor receptor-α (PDGFRA) which makes them responsive to pharmacologic inhibitors, such as imatinib mesylate, and sunitinib malate. Overall, it is difficult to completely distinguish GIST from other spindle-shaped neoplasms in this region, and immunohistochemical studies are often critical for a definitive diagnosis. Approximately 90 % of GISTs are positive for c-kit and 95 % are positive for DOG-1 [2]. S-100 positivity is suggestive of a nerve sheath tumor, such as schwannoma, whereas smooth muscle actin (SMA) reactivity is seen in smooth muscle neoplasms, such as leiomyoma. Clinical suspicion for GIST may arise from imaging studies showing a submucosal location of the tumor. (f and g) Gastric duplication cyst; a second lesion was identified as a well-defined, 3-cm hypoechoic lesion with a heterogeneous internal structure, along the greater curvature of the stomach/peripancreatic by a previously performed computed tomography (CT) scan. It was suspected to be a lymph node suspicious for non-Hodgkin lymphoma. The cystic nature of the lesion was not diagnosed due to the solid-tissue appearance of the lesion, presumably, because of the mucinous nature of the fluid (DQ). The images demonstrate thick mucin with embedded ciliated columnar epithelial cells. Mucin is more diffuse and stains magenta on DQ and clumped and pale basophilic on TP (f, DQ-stained DS; g, TP). Histologically, the cysts were lined with pseudostratified ciliated columnar as seen on subsequent resection

Benign gastric and duodenal mucosa. (a) Benign gastric foveolar cells showing a honeycomb arrangement with an apical mucin cup (TP). (b) Benign gastric mucosa with branching mucus glands with vacuolated cytoplasm (H&E). (c) Benign duodenal mucosa appears as flat, two-dimensional sheet with an organized honeycomb configuration. Cells are polarized and uniform with low nucleus-to-cytoplasmic ratios. The nuclei are monotonous with bland chromatin. Most importantly, duodenal mucosa shows goblet cells, which appear as evenly distributed “eosinophilic holes” in the fragments which are not seen in pancreatic mucinous neoplasms (TP). EUS-FNA of the pancreas must transverse the normal GI tract mucosa and may be seen as contaminants in pancreatic FNA specimens. EUS-FNA for pancreatic head and body/tail lesions are performed via the duodenum and the stomach, respectively. Because the GI contaminants are also mucin-secreting epithelium, one must carefully distinguish them from cystic mucinous tumors