Jungsuk An Department of Pathology, Samsung Medical Center 09-39)Metastatic Gastric Cancer from Pancreatic Ductal Adenocarcinoma

Clinical History 66-year-old male patient with postprandial abdominal pain (one month ago) Abdomen + Pelvic CT ( ) - Diffuse wall thickening from duodenum 2nd portion to proximal jejunum  R/O Angioedema vs. nonspecific enteritis. Esophagogastroduodenoscopy ( ) STOMACH : 1. Irregular shaped hyperemic flat elevated lesion on posteroGC of high body (1cm) : R/O flat adenoma 2. Hyperemic flat elevated lesion on GC of high body (0.5cm) 3. Flat elevated lesion on anterior wall of proximal antrum (0.4cm) 4. Reddish polypoid lesion on GC of lower body (0.3cm) 5. Diffuse mucosal atrophy on antrum and LC of body DUODENUM : 1. Irregular shaped flat mucosal lesion on 2 nd portion 2. Elevated lesion with intact mucosa on GC side of 2 nd portion (0.6cm) CA19-9 : 186

Abdomen + Pelvic CT ( )

Initial Endoscopy – Stomach ( )

Initial Endoscopy – Duodenum ( )

Stomach, high body, greater curvature, posterior, biopsy :. A few atypical glands, consistent with tubular adenocarcinoma Note: After deep sections, a few atypical glands were identified in the deep mucosa adjacent to muscularis mucosa. For confirmation, please perform multiple deep biopsies. Biopsy of Initial Endoscopy (S )

1. Reddish flat elevated lesion on GC of high body (2.5cm) 2. Reddish flat elevated on posterior of #1 (2.0cm) #1 #2 Secondary Endoscopy – Stomach ( )

1. Stomach, high body, greater curvature, biopsy :. A few atypical glands (see note) 2. Stomach, "posterior aspect of #1", biopsy :. Atypical glands (see note) Note: Based on histology, malignancy (tubular adenocarcinoma) is suspected. Biopsy of Secondary Endoscopy (D09-929)

- CA19-9 : 186 Mildly increased FDG uptake in pancreatic tail and soft tissue lesion around celiac axis.  R/O Pancreas cancer with metastasis around celiac axis Positron Emission Tomography ( )

No Diffuse wall thickening from duodenum 2nd portion to proximal jejunum Low attenuated lesion in pancreatic tail (1.9cm) with invasion of surrounding fatty tissue  R/O Pancreatic carcinoma Soft-tissue density lesion around celiac axis and proximal part of common hepatic artery and splenic artery  R/O Tumor infiltration Pancreas CT ( )

Tertiary Endoscopy – Stomach ( ) Not indicated for endoscopic submucosal dissection

Biopsy of Tertiary Endoscopy (D ) 1. Stomach, high body, greater curvature, biopsy:. Tubular adenocarcinoma, moderately differentiated, with multiple endolymphatic tumor emboli 2. Stomach, high body, greater curvature, posterior, biopsy:. Atypical glands, highly suggestive of tubular adenocarcinoma, poorly differentiated Cytokeratin 7

Cytokeratin immunohistochemical stain Hypoechoic area in pancreatic tail (1.5cm) : EUS-FNA Soft tissue mass invasion around celiac axis

Pancreas, EUS-guided aspiration: A few atypical cells with many normal acinar cells, suspected malignancy, DUCTAL ADENOCARCINOMA FNA of EUS (P )

Initial discordant results - Endoscopy : Two hyperemic elevated lesions, R/O flat adenoma - Pathology : Atypical glands, consistent with adenocarcinoma - CT : Diffuse wall thickening in duodenum - CA19-9 : 186 PET, Pancreas CT, EUS-guided FNA, rebiopsy with immunostaining  Metastatic gastric carcinoma from pancreatic adenocarcinoma  Chemotherapy Summary and Progress

Review Hematogenous Metastases to the Stomach. A Review of 67 cases Green LK. Cancer. 1990;65: SiteType Cases at Endoscopy Case at Necropsy Total (%) LungAdenocarcinoma-1827 Small cell carcinoma11016 Squamous cell carcinoma1610 Mixed cell carcinoma-11 PancreasAdenocarcinoma2510 Carcinoid113 EsophagusSquamous cell carcinoma4310 ColonAdenocarcinoma147 LiverHepatocellular carcinoma113 Choloangiocarcinoma-11 SkinMelanoma-34 KidneyRenal cell carcinoma-11 ProstateAdenocarcinoma-11 TestesSeminoma-11 Head and neckSquamous cell carcinoma-11

Review Nonspecific symptoms - Weight loss, anorexia, abdominal discomfort, nausea, and vomiting. - Less commonly, epigastric pain, melena, dysphagia, and postprandial bloating - Gastrointestinal bleeding and hypovolemic shock Upper gastrointestinal radiographs of metastatic lesions - Characteristic single or multiple “bulls’ eye” or “target” lesion Endoscopy : three main morphologic types of lesions 1. Multiple nodules of varying size with tip ulceration 2. Submucosal masses elevated and ulcerated at apex, “volcano-like’’ lesions 3. Nonulcerated masses - Rarely, polyps, flat ulcers, raised plaques or linitis plastica Histologic examination - Submucosal growth pattern without transition from gastric mucosa at lesion’s edge - Distinctive characteristics such as melanin pigment, keratinization, and patterns similar to primary malignancies Hematogenous Metastases to the Stomach. A Review of 67 cases Green LK. Cancer. 1990;65:

Review Metastatic Tumors to the Stomach: Analysis of 54 Patients Diagnosed at Endoscopy and 347 Autopsy Cases Oda I, et al. Endoscopy 2001;33:

Review Metastatic Gastric Tumor Secondary to Pancreatic adenocarcinoma Takamori H et al. J Gastroenterol. 2005;40(2):

Review Of particular interest to the pathologist is that adenocarcinomas of gastrointestinal or pancreatobiliary origin may adhere to the gastric glands and pits, preserving this morphology even as pits themselves are destroyed mimicking an in-situ ‘pseudoprimary' gastric lesion. Uncommon Mucosal Metastases to the Stomach Kanthan R et al. World J Surg Oncol. 2009;7:62 Lung adenocarcinoma Colon adenocarcinoma

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Organ-specific immunostaining profiles using multiple markers - Colorectal : TTF-1-/CDX2+/CK7-/CK20+ or TTF-1-/CDX2+/CK7-/CK20-/(CEA+ or MUC2+) - Ovarian : CK7+/MUC5AC+/TTF-1-/CDX2-/CEA-/GCDFP Breast : GCDFP-15+/TTF-1-/CDX2-/CK7+/CK20- or ER+/ TTF-1-/CDX2-/CK20-/CEA-/MUC5AC- - Lung : TTF-1+ or TTF-1-/CDX2-/CK7+/CK20-/GCDFP-15-/ER-/CEA-/ MUC5AC- - Pancreaticobiliary : TTF-1-/CDX2-/CK7+/ CEA+/MUC5AC+ - Stomach : TTF-1-/CDX2+/CK7+/ CK20- IHC profiles Panels of Immunohistochemical Markers Help Determine Primary Site of Metastatic Adenocarcinooma Park SY et al. Arch Pthol Lab Med. 2007;131: