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WHO Classification of Tumours
Secondary tumours of the small intestine


Definition
Tumours of the small intestine that originate from an extra-intestinal neoplasm or that are discontinuous with a primary tumour elsewhere in the gastrointestinal tract.

Epidemiology
In autopsy studies, secondary tumours of the small intestine are 2.5 times more common than primary small-bowel carcinoma

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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



. Metastatic spread to the small intestine from either an intra- or extra-abdominal primary site is more frequent than to any other site in the tubular gastrointestinal tract
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Gill SS, Heuman DM, Mihas AA (2001)
Small intestinal neoplasms.
J Clin Gastroenterol 33: 267-82




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Idelevich E, Kashtan H, Mavor E, Brenner B (2006)
Small bowel obstruction caused by secondary tumors.
Surg Oncol 15: 29-32



.

Origin
The routes by which secondary neoplasms reach the small bowel include direct extension (i.e. colonic, pancreatic and gastric cancers), intraperitoneal spread (i.e. ovarian cancer) and lymphohaemato - genous embolization (i.e. melanoma, lung and breast cancer). Melanoma is the most common malignancy to metastasize to the small intestine, although testis, lung, breast and ovarian cancers also frequently involve the small intestine by metastatic spread

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




Click to access Pubmed
Idelevich E, Kashtan H, Mavor E, Brenner B (2006)
Small bowel obstruction caused by secondary tumors.
Surg Oncol 15: 29-32



. Melanoma, lung, breast and ovarian cancers also more frequently metastasize to the small intestine than to the stomach or colorectum
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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



. Primary melanomas of the intestine are very rare. Although most melanomas found in the small bowel have no history of a primary tumour, the general consensus is that they are virtually all metastases from a misdiagnosed or regressed primary melanoma
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Elsayed AM, Albahra M, Nzeako UC, Sobin LH (1996)
Malignant melanomas in the small intestine: a study of 103 patients.
Am J Gastroenterol 91: 1001-6




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Lens M, Bataille V, Krivokapic Z (2009)
Melanoma of the small intestine.
Lancet Oncol 10: 516-21



.

Clinical features
Small intestinal metastases can cause obstruction, perforation, intussusception, malabsorption and/or gastrointestinal bleeding

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Cicin I, Ozyilmaz F, Karagol H, Yalcin F, Uzunoglu S, Kaplan M (2009)
Massive upper gastrointestinal bleeding from pure metastatic choriocarcinoma in patient with mixed germ cell tumor with subclinical intestinal metastasis.
Urology 73: 443.e15-7




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Garwood RA, Sawyer MD, Ledesma EJ, Foley E, Claridge JA (2005)
A case and review of bowel perforation secondary to metastatic lung cancer.
Am Surg 71: 110-6




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Horiuchi A, Watanabe Y, Yoshida M, Yamamoto Y, Kawachi K (2007)
Metastatic osteosarcoma in the jejunum with intussusception: report of a case.
Surg Today 37: 440-2




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Idelevich E, Kashtan H, Mavor E, Brenner B (2006)
Small bowel obstruction caused by secondary tumors.
Surg Oncol 15: 29-32




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Rosato FE, Rosato EL (2008)
Current surgical management of intestinal metastases.
Semin Oncol 35: 177-82




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von Holzen U, Viehl CT, Hamel CT, Oertli D (2009)
Ileal intussusception due to visceral malignant melanoma metastasis.
Surgery 145: 339-40



. Obstruction is more commonly seen in association with metastatic lobular breast carcinoma
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Idelevich E, Kashtan H, Mavor E, Brenner B (2006)
Small bowel obstruction caused by secondary tumors.
Surg Oncol 15: 29-32



. Nonspecific symptoms associated with metastasis to the small intestine include abdominal discomfort, gas distension, and diarrhoea
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Gifaldi AS, Petros JG, Wolfe GR (1992)
Metastatic breast carcinoma presenting as persistent diarrhea.
J Surg Oncol 51: 211-5



.

Macroscopy
Typical features of intestinal metastases include intestinal-wall thickening, submucosal spread, and ulcers

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Idelevich E, Kashtan H, Mavor E, Brenner B (2006)
Small bowel obstruction caused by secondary tumors.
Surg Oncol 15: 29-32



. Melanomas and sarcomas may appear as nodules or polyps
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Panizo-Santos A, Sola I, Lozano M, de Alava E, Pardo J (2000)
Metastatic osteosarcoma presenting as a small-bowel polyp. A case report and review of the literature.
Arch Pathol Lab Med 124: 1682-4



.

Histopathology
Metastases are typically located deep within the submucosa or the muscularis propria of the small bowel, with little involvement of the mucosa. The lack of an in situ component within the mucosa may also serve as also a clue that the neoplasm is a metastasis, although metastatic carcinoma may grow on the lumenal surface and mimic an in situ neoplasm. Obtaining appropriate clinical information about possible primary sites should be the first step in the evaluation of a metastasis. When a possible primary tumour site has been identified, histological, immunohistochemical and molecular comparision of the metastasis with the primary tumour may help to confirm the origin of the metastasis. In difficult cases, immunohistochemistry may help to differentiate between primary small-bowel cancer (positive for keratin 20 and CDX2), metastatic melanoma (positive for Melan A and S100 protein), metastases from ovary and breast (typically positive for keratin 7 and estrogen/progesterone receptors), lung (typically positive for keratin 7 and thyroid transcription factor 1/TTF1) and those from liver, kidney and prostate (typically negative for keratins 7 and 20 and positive for hepatocyte-paraffin- 1 antibody/HepPar1, PAX8 and prostatespecific antigen [PSA], respectively)

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




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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



. In contrast, the distinction between multiple primary small-bowel carcinoids and their metastases may not be possible. This also applies to leiomyo - sarcomas and other mesenchymal neoplasms of the small intestine.

Prognosis and predictive factors
Intestinal metastases usually represent a late stage of disease at which other haematogenous metastases are also frequently found. However, the prognosis for patients with small-bowel metastasis varies widely, partly according to the primary tumour type and patient-specific factors

Click to access Pubmed
Idelevich E, Kashtan H, Mavor E, Brenner B (2006)
Small bowel obstruction caused by secondary tumors.
Surg Oncol 15: 29-32



. Metastatic melanoma or renal carcinomas with isolated metastasis to the small intestine may be associated with prolonged survival after resection
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Albert JG, Gimm O, Stock K, Bilkenroth U, Marsch WC, Helmbold P (2007)
Small-bowel endoscopy is crucial for diagnosis of melanoma metastases to the small bowel: a case of metachronous small-bowel metastases and review of the literature.
Melanoma Res 17: 335-8



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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
Click to contact editor
Gabriel M. Groisman
Department of Pathology
Hillel Yaffe Medical Center
Hadera
ISRAEL





High-grade retroperitoneal sarcoma metastatic to the small intestine, gross micrograph.
High-grade retroperitoneal sarcoma metastatic to the small intestine, gross micrograph.

Metastatic high-grade serous ovarian carcinoma within the serosa of the small intestine secondary to intraperitoneal spread.
Metastatic high-grade serous ovarian carcinoma within the serosa of the small intestine secondary to intraperitoneal spread.

Frequency of metastasis to the small intestine by site of the primary neoplasm. Data shown are based on findings of 3827 autopsies
Frequency of metastasis to the small intestine by site of the primary neoplasm. Data shown are based on findings of 3827 autopsies

Metastatic malignant melanoma in the small intestine.
Metastatic malignant melanoma in the small intestine.

Metastatic malignant melanoma in the small intestine, microscopic view.
Metastatic malignant melanoma in the small intestine, microscopic view.

Metastatic adenocarcinoma in the small intestine.
Metastatic adenocarcinoma in the small intestine.

Metastatic adenocarcinoma in the small intestine.
Metastatic adenocarcinoma in the small intestine.

Metastatic adenocarcinoma, small intestine.
Metastatic adenocarcinoma, small intestine.

Metastatic breast carcinoma in the colon.
Metastatic breast carcinoma in the colon.