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WHO Classification of Tumours
Secondary tumours of the stomach


Definition
Tumours of the stomach that originate from an extra-gastric neoplasm or that are discontinuous with a primary tumour elsewhere in the stomach.

Epidemiology
Metastatic disease involving the stomach is unusual. In a series of 771 patients with gastric neoplasms found at endoscopy, only 2.6% were secondary tumours

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Campoli PM, Ejima FH, Cardoso DM, Silva OQ, Santana Filho JB, Queiroz Barreto PA, Machado MM, Mota ED, Araujo Filho JA, Alencar Rde C, Mota OM (2006)
Metastatic cancer to the stomach.
Gastric Cancer 9: 19-25



. The incidence of gastric metastasis found in autopsy cases is 0.2–1.4%, whereas that seen in autopsies performed specifically in cancer patients is 1.7–5.4%
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DAVIS GH, ZOLLINGER RW (1960)
Metastatic melanoma of the stomach.
Am J Surg 99: 94-6




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Disibio G, French SW (2008)
Metastatic patterns of cancers: results from a large autopsy study.
Arch Pathol Lab Med 132: 931-9




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Green LK (1990)
Hematogenous metastases to the stomach. A review of 67 cases.
Cancer 65: 1596-600




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Menuck LS, Amberg JR (1975)
Metastatic disease involving the stomach.
Am J Dig Dis 20: 903-13




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Telerman A, Gerard B, Van den Heule B, Bleiberg H (1985)
Gastrointestinal metastases from extra-abdominal tumors.
Endoscopy 17: 99-101



.

Clinical features
Gastric metastases are symptomatic in half of the patients affected. The most common clinical presentations include anaemia and gastrointestinal bleeding, abdominal pain or dyspepsia

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Campoli PM, Ejima FH, Cardoso DM, Silva OQ, Santana Filho JB, Queiroz Barreto PA, Machado MM, Mota ED, Araujo Filho JA, Alencar Rde C, Mota OM (2006)
Metastatic cancer to the stomach.
Gastric Cancer 9: 19-25




Click to access Pubmed
De Palma GD, Masone S, Rega M, Simeoli I, Donisi M, Addeo P, Iannone L, Pilone V, Persico G (2006)
Metastatic tumors to the stomach: clinical and endoscopic features.
World J Gastroenterol 12: 7326-8




Click to access Pubmed
Green LK (1990)
Hematogenous metastases to the stomach. A review of 67 cases.
Cancer 65: 1596-600




Click to access Pubmed
Wu MH, Lin MT, Lee PH (2007)
Clinicopathological study of gastric metastases.
World J Surg 31: 132-6



. The time interval between the diagnosis of a primary neoplasm and its metastasis to the stomach varies according to the tumour type. For example, in most patients with lung or oesophageal carcinomas that had metastasized to the stomach, the metastases were diagnosed within 2 years of diagnosis of the primary malignancy. In contrast, half of melanoma or breast carcinoma metastases to the stomach are diagnosed > 2 years after diagnosis of the primary tumour
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De Palma GD, Masone S, Rega M, Simeoli I, Donisi M, Addeo P, Iannone L, Pilone V, Persico G (2006)
Metastatic tumors to the stomach: clinical and endoscopic features.
World J Gastroenterol 12: 7326-8



. In some patients, the development of gastric metastasis leads to the initial diagnosis of their cancer. As metastases to the stomach are frequently limited to the submucosa and seromuscular layers, the results of endoscopic evaluation may be normal. The most common endoscopic appearance of a gastric metastasis is of a nodule resembling a submucosal tumour, seen as a mass with a smooth surface, normalcoloured mucosa and a central depression or ulceration (“volcano-like” lesion). In some patients, the presence of metastatic lobular breast cancer may resemble an advanced gastric cancer with features of linitis plastica
Click to access Pubmed
De Palma GD, Masone S, Rega M, Simeoli I, Donisi M, Addeo P, Iannone L, Pilone V, Persico G (2006)
Metastatic tumors to the stomach: clinical and endoscopic features.
World J Gastroenterol 12: 7326-8




Click to access Pubmed
Green LK (1990)
Hematogenous metastases to the stomach. A review of 67 cases.
Cancer 65: 1596-600




Click to access Pubmed
Taal BG, Peterse H, Boot H (2000)
Clinical presentation, endoscopic features, and treatment of gastric metastases from breast carcinoma.
Cancer 89: 2214-21



. Imaging is particularly useful in cases of submucosal tumours for which mucosal biopsies give negative results. Radiography –computed tomography (CT) scan and/or double- contrast barium meal – or endoscopic ultrasonography may show pathological thickening of the gastric wall
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Shah SM, Smart DF, Texter EC, Morris WD (1977)
Metastatic melanoma of the stomach: the endoscopic and roentgenographic findings and review of the literature.
South Med J 70: 379-81



.

Origin
Cancers can metastasize to the stomach by lymphohaematogenous spread (i.e. melanoma, breast cancer or lung cancer), by direct extension (pancreatic or oesophageal cancer) or by intraperitoneal dissemination (i.e. ovarian cancer)

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Feczko PJ, Collins DD, Mezwa DG (1993)
Metastatic disease involving the gastrointestinal tract.
Radiol Clin North Am 31: 1359-73



. Although virtually all primary neoplasms can metastasize to the stomach, large series of autopsy studies indicate that gastric metastases most often originate from malignant melanomas or carcinomas of the breast, oesophagus and lung
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Green LK (1990)
Hematogenous metastases to the stomach. A review of 67 cases.
Cancer 65: 1596-600



. In patients who present with gastric metastasis in the clinical setting, the most common primary neoplasms of origin are also malignant melanomas or carcinomas of the breast, as well as carcinomas of the oesophagus, lung, and pancreas
Click to access Pubmed
De Palma GD, Masone S, Rega M, Simeoli I, Donisi M, Addeo P, Iannone L, Pilone V, Persico G (2006)
Metastatic tumors to the stomach: clinical and endoscopic features.
World J Gastroenterol 12: 7326-8




Click to access Pubmed
Oda , Kondo H, Yamao T, Saito D, Ono H, Gotoda T, Yamaguchi H, Yoshida S, Shimoda T (2001)
Metastatic tumors to the stomach: analysis of 54 patients diagnosed at endoscopy and 347 autopsy cases.
Endoscopy 33: 507-10




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Washington K, McDonagh D (1995)
Secondary tumors of the gastrointestinal tract: surgical pathologic findings and comparison with autopsy survey.
Mod Pathol 8: 427-33



. Metastases from primary neoplasms of the kidney, testis, uterus, ovary and colon have also been described
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Campoli PM, Ejima FH, Cardoso DM, Silva OQ, Santana Filho JB, Queiroz Barreto PA, Machado MM, Mota ED, Araujo Filho JA, Alencar Rde C, Mota OM (2006)
Metastatic cancer to the stomach.
Gastric Cancer 9: 19-25




Click to access Pubmed
Green LK (1990)
Hematogenous metastases to the stomach. A review of 67 cases.
Cancer 65: 1596-600



. Two thirds of breast-cancer metastases to the stomach are lobular carcinomas
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McLemore EC, Pockaj BA, Reynolds C, Gray RJ, Hernandez JL, Grant CS, Donohue JH (2005)
Breast cancer: presentation and intervention in women with gastrointestinal metastasis and carcinomatosis.
Ann Surg Oncol 12: 886-94




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Taal BG, Peterse H, Boot H (2000)
Clinical presentation, endoscopic features, and treatment of gastric metastases from breast carcinoma.
Cancer 89: 2214-21



.

Macroscopy
Solitary metastases to the stomach are more common than multiple metastases. However, whether single or multiple, most gastric metastases are located in the upper two thirds of the stomach. Metastases are typically seen as a raised nodule covered by normal mucosa that may have a central ulceration. In some instances the metastasis forms a polypoid mass or a necrotic ulcer reminiscent of a primary gastric carcinoma. Metastatic lobular carcinoma of the breast may diffusely infiltrate the wall of the stomach, simulating linitis plastica. Pigmented metastatic melanoma may be seen as small black mucosal spots

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Campoli PM, Ejima FH, Cardoso DM, Silva OQ, Santana Filho JB, Queiroz Barreto PA, Machado MM, Mota ED, Araujo Filho JA, Alencar Rde C, Mota OM (2006)
Metastatic cancer to the stomach.
Gastric Cancer 9: 19-25




Click to access Pubmed
De Palma GD, Masone S, Rega M, Simeoli I, Donisi M, Addeo P, Iannone L, Pilone V, Persico G (2006)
Metastatic tumors to the stomach: clinical and endoscopic features.
World J Gastroenterol 12: 7326-8




Click to access Pubmed
Green LK (1990)
Hematogenous metastases to the stomach. A review of 67 cases.
Cancer 65: 1596-600




Click to access Pubmed
Shah SM, Smart DF, Texter EC, Morris WD (1977)
Metastatic melanoma of the stomach: the endoscopic and roentgenographic findings and review of the literature.
South Med J 70: 379-81



.

Histopathology
The features of metastases to the stomach are similar to those observed in other organs. In most cases the metastasis is located within the submucosal or muscularis propria layers, with little or no involvement of the mucosa. The lack of an in situ component within the mucosa may also serve as a clue that the neoplasm is a metastasis. In cases with mucosal involvement, the distinction from a primary adenocarcinoma may be difficult. Immunohistochemistry may help to differentiate between a primary gastric cancer (frequently positive for keratin 7, MUC5AC, MUC2, and CDX2), and metastases from a variety of extra-gastric primary sites, such as metastatic melanoma (positive for Melan A and S100 protein), metastases from ovary and breast (positive for keratin 7, gross cystic disease fluid protein and estrogen/progesterone receptors), lung (positive for keratin 7 and thyroid transcription factor-1 [TTF1] and those from liver, kidney and prostate (negative for keratins 7 and 20 and positive for hepatocyte-paraffin-1 antibody [HepPar1], paired box gene 8 [PAX8] and prostatespecific antigen [PSA]

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Chu P, Wu E, Weiss LM (2000)
Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases.
Mod Pathol 13: 962-72




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O'Connell FP, Wang HH, Odze RD (2005)
Utility of immunohistochemistry in distinguishing primary adenocarcinomas from metastatic breast carcinomas in the gastrointestinal tract.
Arch Pathol Lab Med 129: 338-47




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Oien KA (2009)
Pathologic evaluation of unknown primary cancer.
Semin Oncol 36: 8-37




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Park SY, Kim BH, Kim JH, Lee S, Kang GH (2007)
Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma.
Arch Pathol Lab Med 131: 1561-7




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Tong GX, Yu WM, Beaubier NT, Weeden EM, Hamele-Bena D, Mansukhani MM, O'Toole KM (2009)
Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study.
Mod Pathol 22: 1218-27



.

Prognosis and predictive factors
Gastric metastases usually represent a late, disseminated stage of the patient’s disease in which other haematogenous metastases may also be found. The prognosis is poor but varies depending on the source of the metastasis. In one series, overall survival after the diagnosis of gastric metastasis from a variety of primary origins ranged from 0 to 14 months, with a median of 4.75 months

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Campoli PM, Ejima FH, Cardoso DM, Silva OQ, Santana Filho JB, Queiroz Barreto PA, Machado MM, Mota ED, Araujo Filho JA, Alencar Rde C, Mota OM (2006)
Metastatic cancer to the stomach.
Gastric Cancer 9: 19-25



. In patients with breast carcinoma, the median survival after development of gastric metastasis was 10 months, with 23% of patients surviving > 24 months
Click to access Pubmed
Taal BG, Peterse H, Boot H (2000)
Clinical presentation, endoscopic features, and treatment of gastric metastases from breast carcinoma.
Cancer 89: 2214-21



.








Christine Iacobuzio-Donahue
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Christine Iacobuzio-Donahue
Department of Pathology
The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions
Baltimore
USA




Gabriel M. Groisman
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Gabriel M. Groisman
Department of Pathology
Hillel Yaffe Medical Center
Hadera
ISRAEL





Multiple gastric metastases from rhabdomyo sarcoma of the spermatic cord in a boy aged 15 years.
Multiple gastric metastases from rhabdomyo sarcoma of the spermatic cord in a boy aged 15 years.

Metastasis of lobular breast carcinoma to gastric oxyntic mucosa. Differentiation from a primary gastric cancer may be difficult without additional ancillary studies.
Metastasis of lobular breast carcinoma to gastric oxyntic mucosa. Differentiation from a primary gastric cancer may be difficult without additional ancillary studies.

Immunostaining for gross cystic disease fluid protein (GCDFP) demonstrates strong positive labelling, consistent with origin from a breast primary.
Immunostaining for gross cystic disease fluid protein (GCDFP) demonstrates strong positive labelling, consistent with origin from a breast primary.