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Small bowel (small intestine)

Superpage - Tumor

Revised: 8 January 2013
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

Benign tumors and tumor-like conditions

Adenoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare compared to colon
● Often present in patients with familial adenomatous polyposis or Gardner’s syndrome
● Single or multiple, sessile or pedunculated, tubular or villous or mixed
● May become malignant, particularly if large, villous, multiple

Additional references
=========================================================================

HPB Surg 2000;11:339, J Clin Pathol 2004;57:1219



Benign tumors and tumor-like conditions

Amyloidosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare in duodenum (Int J Clin Exp Pathol 2012;5:46)
● Typically diagnosed with rectal biopsy that includes submucosa
Primary: GI involvement in 70% of cases, amyloid in blood vessel walls and muscularis propria
Secondary: GI involvement in 50% of cases, often deposits in blood vessel walls in lamina propria

Micro images
=========================================================================



Amyloidosis of duodenum



Benign tumors and tumor-like conditions

Angiomyolipoma


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update May 2010
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See also Kidney-benign chapter

Definition
=========================================================================

● Benign triphasic tumor composed of dysmorphic, thick walled blood vessels, smooth muscle that appears to spin off from vessel walls, and mature lipid-distended cells

Etiology
=========================================================================

● Member of PEComa family, a concept first proposed by Bonetti (Am J Surg Pathol 1992;16:307), which comprises mesenchymal tumors with perivascular clear cells and epithelioid features that coexpress melanocytic and muscle markers
● Occasionally associated with tuberous sclerosis (OMIM #191100)

Clinical description
=========================================================================

● Usually arises in the kidney (eMedicine), or occasionally in the liver (Arch Pathol Lab Med 2008;132:1679)
● Gastrointestinal angiomyolipoma is very rare

Case reports
=========================================================================

● First documented case of symptomatic ileal angiomyolipoma was in a 60 year old woman suffering from intermittent periumbilical pain (Korean J Gastroenterol 2000;36:250)
● Second case of ileal angiomyolipoma occurred in a 48 year old woman with vague abdominal pain and bloody stool (J Gastroenterol 2005;40:200)
● 25 year old man with 25 cm small bowel mass (Case of the Week #177)
● 28 year old man with with ileal intussusception (World J Gastroenterol 2009;15:1398)

Treatment and prognosis
=========================================================================

● Typically benign behavior at other sites, but occasionally is invasive with metastases (Am J Surg Pathol 1991;15:1083)

Clinical images
=========================================================================



25 cm mass

Gross images
=========================================================================



25 cm mass


Various images

Micro description
=========================================================================

● Benign triphasic tumor composed of dysmorphic, thick walled blood vessels, smooth muscle that appears to spin off from vessel walls, and mature lipid-distended cells
● Tumors occasionally have bizarre epithelioid smooth muscle cells (Int J Surg Pathol 2000;8:67) and possible multinucleation

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● HMB45 and MelanA / A103, SMA, calponin, CD117, S100 (Am J Surg Pathol 2002;26:493)

Negative stains
=========================================================================

● Keratin

Differential diagnosis
=========================================================================

● Theoretically broad, encompassing smooth muscle and lipogenic tumors, but narrowed when one carefully identifies the components of the tumor; few other tumors are immunoreactive for both smooth muscle and melanocytic markers
● Leiomyomas and leiomyosarcomas have a prominent smooth muscle component, but lack a prominent vascular or adipose component
● Melanomas have prominent atypia, necrosis and infiltrative borders



Benign tumors and tumor-like conditions

Barium granuloma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● May occur after barium enema if barium penetrates mucosal tear and stimulates a granulomatous reaction
● More common in colon than small intestine
● Crystals visible under polarized light
● Rarely produces polypoid or ulcerated lesion resembling a neoplasm

Micro description
=========================================================================

● Barium is green and crystalline
● Crystals are within clusters in macrophages or connective tissue



Benign tumors and tumor-like conditions

Benign cystic mesothelioma


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called multicystic mesothelioma
● Rare tumor NOT associated with asbestos, occurs most frequently in women of reproductive age, difficult to diagnose preoperatively (J Med Case Reports 2010;4:385)

Clinical features
=========================================================================

● Often associated with prior pelvic surgery, endometriosis or pelvic inflammatory disease (J Obstet Gynaecol Res 2011;37:1126)
● Some cases may be neoplastic, others may be caused by inflammation and adhesions (Int J Gynecol Pathol 2011;30:163).
● Complete surgical resection recommended; follow up is necessary, because 50% of tumors recur after excision

Case reports
=========================================================================

● 36 year old woman with multiple small cystic lesions in small bowel mesentery and pelvic peritoneum (Case of the Week #205)

Gross description
=========================================================================

● Usually large, may be multifocal or unilocular; free floating cysts may also occur

Gross images
=========================================================================



23 year old woman: multiple adherent cysts

Micro description
=========================================================================

● Cysts are thin-walled, may contain eosinophilic fluid
● Mesothelial cells lining the cysts vary from flattened to endothelial-like to cuboidal
● Inflammatory cells are often present within stroma between cysts
● Foci of mesothelial hyperplasia may be present

Micro images
=========================================================================


       

       
Various images from Case of Week #205


23 year old woman


72 year old woman

   
Left: CD31, Right: MNF-116

Positive stains
=========================================================================

● Mesothelial cells lining cyst are keratin+, calretinin+ (Hum Pathol 2003;34:369).

Differential diagnosis
=========================================================================

Ascitis, loculated: usually has irregular borders, is surrounded by bowel loops or abdominal / pelvic organs
Cystic teratoma: usually contains adipose and calcifications
Lymphangioma: younger patients, may contain chylous fluid grossly, often lymphoid aggregates and smooth muscle within walls, D2-40+
Other mesenteric / omental cysts / pseudocysts: usually unilocular, no distinct cyst wall or internal septa, keratin-, calretinin-
Pseudomyxoma peritonei (mucinous peritoneal metastasis): may have coexisting omental caking, soft-tissue peritoneal nodules, and scalloping of the serosal margins of the liver or spleen



Benign tumors and tumor-like conditions

Blue rubber bleb nevus syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Autosomal dominant or sporadic syndrome of skin or visceral hemangiomas
● Elevated expression of c-kit has been noted in small venous malformations

Case reports
=========================================================================

● 14 year old girl with multiple recurrent hemangiomas of skin and GI tract (Korean J Intern Med 2008;23:208)
● 19 year old man with severe syndrome (Rare Tumors 2010;2:e36)



Benign tumors and tumor-like conditions

Brown bowel syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Prominent dark brown or orange-brown discoloration of bowel wall on serosa and cut surfaces due to lipofuscin (Mayo Clin Proc 1979;54:251)
● Also called ceroidosis
● Associated with malabsorption, pseudo-obstruction (Rofo 2003;175:1143)

Micro description
=========================================================================

● Prominent lipofuscin granules in smooth muscle cells (Arch Pathol Lab Med 1990;114:76)

Differential diagnosis
=========================================================================

● Melanosis coli: pigment within mucosa



Benign tumors and tumor-like conditions

Brunner’s gland hamartoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare benign lesion of duodenum composed of adipose tissue, hyperplastic Brunner’s glands, cystic ducts lined by ciliated cells (World J Gastroenterol 2004;10:2616)

Case reports
=========================================================================

● 43 year old man with Brunner gland hamartoma of the duodenal bulb with multiple ciliated cysts (Arch Pathol Lab Med 2002;126:734)

Clinical images
=========================================================================



Various images

Gross description
=========================================================================

● Pedunculated tumor of submucosa

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Adipose tissue, hyperplastic Brunner’s glands, cystic ducts lined by ciliated cells

Micro images
=========================================================================



Various images



Benign tumors and tumor-like conditions

Brunner’s gland nodule


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Nodular proliferation of normal Brunner’s glands, ducts, stroma
● Also called Brunner’s gland hyperplasia or adenoma
● Usually in mid duodenum
● Associated with erosions and duodenitis
● May cause melena or obstruction
● Probably not neoplastic

Case reports
=========================================================================

● 16 year old boy with upper GI hemorrhage (Singapore Med J 2008;49:81)
● 40 year old man with upper GI bleeding (Turk J Gastroenterol 2011;22:419)

Micro images
=========================================================================



Various images



Benign tumors and tumor-like conditions

Clofazimine toxicity


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Clofazimine is drug for leprosy, Mycobacterium avium complex in HIV patients, graft versus host disease
● Poorly soluble but orally bioavailable small molecule drug that massively accumulates in macrophages when administered over prolonged periods of time (PLoS One 2012;7:e47494)
● May cause severe abdominal pain, red skin discoloration and ichthyosis

Case reports
=========================================================================

● 11 year old boy with severe enteropathy 2 years after beginning clofazimine treatment for graft versus host disease after bone marrow transplant (J Pediatr 2001;138:574)
● 45 year old woman with lepromatous leprosy (Indian J Pathol Microbiol 2004;47:281)

Micro description
=========================================================================

● Red crystals in frozen section with bright-red birefringence, but clear in routinely processed histologic sections
● Causes histiocytosis resembling lymphoma, plasmacytosis (Am J Surg Pathol 2000;24:129)

Micro images
=========================================================================



Crystal-storing histiocytosis: numerous large epithelioid eosinophilic cells intermingle with a mild plasmacytic infiltrate within a fibrous stroma; at high power, cells contain numerous needlelike crystals; D-birefringence under polarized light microscopy


Mononuclear epithelioid cells are strongly CD68+ (KP1) and CD68+ (PG-M1), supporting a histiocytic lineage; plasma cells are CD138+; note the weak cytoplasmic positivity in histiocytes and stronger cytoplasmic positivity in plasma cells for IgG, κ light chain and λ light chain

Electron microscopy description
=========================================================================

● Clear spaces with some osmiophilic bodies



Benign tumors and tumor-like conditions

Colchicine toxicity


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Colchicine is an alkaloid with antimitotic ability used to treat various medical conditions; toxicity can result in multiorgan failure and death (Am J Surg Pathol 2001;25:1067)

Micro description
=========================================================================

● Abundant epithelial mitotic figures with metaphase arrest
● Often enlarged epithelial cells with condensed chromatin in a ring formation within center of cell
● Associated with epithelial loss of polarity and pseudostratification
● Nuclei small, hyperchromatic and compressed to periphery of cell



Benign tumors and tumor-like conditions

Common variable immunodeficiency syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Primary immune defect (usually genetic) causing reduction in B cells and most immunoglobulin classes; also frequent bacterial infections (eMedicine)

Clinical features
=========================================================================

● Chronic diarrhea, malabsorption, recurrent GI giardiasis

Microscopic description
=========================================================================

● Mucosa may resemble celiac sprue or be normal, but always has reduced plasma cells and no IgA plasma cells
● May have lymphoid hyperplasia or apoptotic bodies in crypts
● Histologic patterns: lymphocytic colitis, collagenous enterocolitis, celiac disease, granulomatous disease, acute GVHD and IBD (Am J Surg Pathol 2007;31:1800)



Benign tumors and tumor-like conditions

Cowden's syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Autosomal dominant disorder with facial tricholemmomas, acral keratosis, oral mucosal papillomas, small intestinal and colorectal polyps
● Also called multiple hamartoma syndrome
● Increased risk of malignancy (breast and thyroid cancer), but not in polyps
● Polyps have same histology as mucosal prolapse syndromes (colitis cystica profunda)

Micro description
=========================================================================

● Hamartomatous features with disorganization and proliferation of muscularis mucosa

Micro images
=========================================================================



Colorectal tumors: glands in lobular groupings embedded with relatively dense fibrous stroma

Differential diagnosis
=========================================================================

Peutz-Jeghers polyp



Benign tumors and tumor-like conditions

Cronkhite-Canada syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Noninherited condition associated with high morbidity, characterized by GI hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation, diarrhea (Dig Dis Sci 2012;57:496)

Clinical features
=========================================================================

● 80% present at age 50+
● Polyps present in stomach or colorectum; rarely small bowel
● Less pedunculated than other juvenile polyps
● May develop adenomas, adenocarcinoma

Symptoms:
● Diarrhea, weight loss, abdominal pain, weakness, anorexia
● 50% die of cachexia

Case reports
=========================================================================

● 78 year old man with weight loss, diarrhea, and altered sense of taste (Gastroenterol Hepatol (NY) 2012;8:197)

Micro description
=========================================================================

● Juvenile-type polyps, with cystically dilated glands in polyp and nonpolypoid mucosa
● No dysplasia



Benign tumors and tumor-like conditions

Decidual reaction


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare lesion of decidual cells, usually in terminal ileum (Arch Pathol Lab Med 2010;134:378)
● May cause obstruction, severe bleeding

Micro description
=========================================================================

● Decidual cells (“glassy” with abundant eosinophilic cytoplasm) infiltrate bowel wall

Micro images
=========================================================================



Decidual cells with abundant eosinophilic cytoplasm, central nucleus, and no atypia

Differential diagnosis
=========================================================================

● Metastatic carcinoma
● Peritoneal malignant deciduoid mesothelioma
● Placental site trophoblastic tumor



Benign tumors and tumor-like conditions

Endometriosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Endometrial glands, stroma and hemosiderin in small bowel

Clinical features
=========================================================================

● Mean age 44 years, range 28 to 56 years
● Presents with pain, mass or incidental findings
● May cause obstruction or mimic other diseases
● Rarely complicated by neoplasms or precancerous changes (Am J Surg Pathol 2000;24:513)
● Endometriosis associated tumors include endometrioid carcinoma, MMT (Hum Pathol 2000;31:456)
● Alterations in N-cadherin expression may cause deep tissue invasion (Mod Pathol 2010;23:38)

Case reports
=========================================================================

● 44 year old woman with diffuse abdominal pain (World J Gastroenterol 2008;14:3430)
● 51 year old woman with clinical diagnosis of pancreatitis due to high amylase (J R Soc Med 1999;92:17)

Gross description
=========================================================================

● Serosal and subserosal nodules < 5 cm
● Smooth muscle hypertrophy
● Gray cut surface with minute areas of hemorrhage

Micro description
=========================================================================

● Endometrial glands, stroma (may show decidualization), hemosiderin in deeper layers
● Fibrosis of bowel wall, neuronal hypertrophy (Am J Surg Pathol 2001;25:445)
● Mucosal changes similar to those in Crohn disease, prolapse, ischemia

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD10 (endometrial stroma)



Benign tumors and tumor-like conditions

Enteritis cystica profunda


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Mucosal glands and mucinous cysts in submucosa or deeper layer (J R Soc Med 2004;97:29, Arch Pathol Lab Med 2010;134:378)
● Usually asymptomatic, but may cause obstruction or intussuception
● Pathogenesis: herniation, implantation after ulceration, mucosal microdiverticula, and reepithelialization of fistulae (eg, in Crohn disease)

Micro description
=========================================================================

● Mucosal glands and mucinous cysts in submucosa or deeper (subserosa) layer with hemosiderin, foreign body giant cells, and lamina propria around the epithelium

Micro images
=========================================================================



Mucin filled cysts (PAS-diastase)



Benign tumors and tumor-like conditions

Fibromatosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Uncommon in small bowel, rarely adheres to or penetrates bowel wall
● Usually in mesentery or retroperitoneum
● Also called intraabdominal desmoid tumor

Clinical features
=========================================================================

● Mean age 34 years old (younger than GIST patients)
● May be associated with trauma, familial polyposis coli, Gardner’s syndrome, hormonal stimulation
● Characterized by mutations in beta-catenin gene, CTNNB1 or APC gene (Oncologist 2011;16:682)
● Benign, but may recur

Case reports
=========================================================================

● 73 year old woman with tumor in jejunal pouch (World J Surg Oncol 2006;4:27)

Treatment
=========================================================================

● Surgical excision, radiation therapy, possibly chemotherapy

Gross description
=========================================================================

● Firm, tan, homogenous
● Usually large (6 to 25 cm) with infiltrative margins

Micro description
=========================================================================

● Broad, sweeping fascicles of bland spindle cells with minimal mitotic activity (mean 4 mitoses/50 HPF), bland nuclear features, finely collagenous stroma
● Infiltrative borders, evenly spaced blood vessels
● May involve muscularis propria but no necrosis, no hemorrhage, no myxoid degeneration, no epithelioid cells, no pleomorphism, no foam cells, no inflammatory cells

Micro images
=========================================================================



Other images

Positive stains
=========================================================================

● Vimentin, smooth muscle actin, desmin (50%)

Negative stains
=========================================================================

● CD34, S100, CD117 (some antibodies give CD117+ results)

Electron microscopy description
=========================================================================

● Myofibroblastic/fibroblastic differentiation

Differential diagnosis
=========================================================================

GIST:: CD117+ with all antibodies, often CD34+, often malignant histologic features (Am J Surg Pathol 2000;24:947, Mod Pathol 2003;16:366)



Benign tumors and tumor-like conditions

Gangliocytic paraganglioma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See also Ampulla"

General
=========================================================================

● Rare tumor of periampullary region and second portion (middle) of duodenum
● Rarely in jejunum or ileum
● May derive from endodermal-neuroectodermal complexes in the embryonic ventral pancreas, due to totipotential nature of adult stem cells that differentiate along different lineages

Clinical features
=========================================================================

● Presents with GI bleed, abdominal pain or anemia
● May be multiple or associated with neurofibromatosis 1 or carcinoid syndrome
● Usually benign, 7% had nodal metastases at presentation (BMC Cancer 2011;11:187), rarely has metastases of endocrine component

Case reports
=========================================================================

● 42 year old man with obstructive jaundice (Rev Col Bras Cir 2011;38:288)
● 56 year old man with melana (World J Surg Oncol 2010;8:42)
● 61 year old man with nodal metastasis (Diagn Pathol 2010;5:27)
● 67 year old man (Chin Med J (Engl) 2012;125:388)
● 67 year old woman with metastatic tumor in regional lymph nodes containing spindle cell, epithelial and ganglion components (Arch Pathol Lab Med 2003;127:e139)

Gross description
=========================================================================

● Usually 1-3 cm, sessile or polypoid

Clinical images
=========================================================================



Periampullary submucosal tumor and surface ulcer bleeding

Gross images
=========================================================================



Tumor near ampulla


Malignant tumor

Micro description
=========================================================================

● Submucosal lesion(s) with overlying ulcerations
● Organoid pattern
● Triphasic with endocrine (carcinoid like cells in compact nests and trabeculae), spindle cell (Schwann cell like), and ganglion type cells of varying proportions resembling carcinoid, paraganglioma and ganglioneuroma
● Variable stromal amyloid

Micro images
=========================================================================



Various images


Malignant tumor

Positive stains
=========================================================================

● Pancreatic polypeptide (in endocrine cells, not specific to this tumor)
● Keratin (epithelial cells)
● S100 (spindle cells)
● Neuron specific enolase (ganglion cells)

Differential diagnosis
=========================================================================

Carcinoid tumor
Carcinoma
Ganglioneuroma
● Paraganglioma



Benign tumors and tumor-like conditions

Ganglioneuroma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 19 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Neural tumor, usually arises from nerves within bowel wall, may be mucosal
● Multiple tumors are associated with neurofibromatosis type 1, MEN 2b/3; sporadic tumors are usually solitary

Case reports
=========================================================================

● 32 year old man with neurofibromatosis type 1 (Ann Diagn Pathol 2009;13:50)
● 42 year old man with benign solitary small intestinal ganglioneuroma presenting with perforation peritonitis (Indian J Gastroenterol 2001;20:31)
● Primary mesentery ganglioneuroma (J Pediatr Surg 2007;42:573)

Gross description
=========================================================================

● Polypoid

Micro description
=========================================================================

● Proliferation of ganglion cells and Schwann cells in mucosa and deeper layers
● May see accentuation of submucosal and myenteric plexus in MEN 2b/3

Micro images
=========================================================================



Ganglioneuroma and ganglioneuromatosis: A-solitary ganglioneuroma presents as a single polyp, but C-diffuse ganglioneuromatosis forms a flat, ill-defined mass lesion; both solitary (B) and diffuse (D) ganglioneuromatosis contain ganglion and neoplastic Schwann cells

Positive stains
=========================================================================

● S100, NSE



Benign tumors and tumor-like conditions

Hemangioma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare single or multiple benign vascular tumors, often in ileum and mid-jejunum
● Either diffuse, circumscribed or papillary growths
● May cause anemia, hemorrhage, intussusception, melena, obstruction, perforation (Zhonghua Bing Li Xue Za Zhi 2005;34:275)
● May be associated with hemangiomas elsewhere

Types of hemangiomas
=========================================================================

Capillary: usually asymptomatic, small, solitary, composed of tightly packed capillaries
Cavernous: localized or diffuse; blood filled sinuses with minimal connective tissue; often symptoms of a mass or bleeding
Arteriovenous: Most common type; abnormal veins and arteries, but otherwise resembles cavernous hemangioma

Case reports
=========================================================================

● 9 year old girl with melena, anemia and cavernous hemangioma (Gastroenterol Clin Biol 2008;32:15)
● 14 year old boy with solitary cavernous hemangioma in proximal small intestine that caused iron deficiency anemia beginning at age 3 years (Arch Pathol Lab Med 1993;117:939)
● 81 year old woman with jejunal hemangioma (J Korean Surg Soc 2011;80:362)
● Combined hemangioma and angiodysplasia (Am J Surg 2010;200:e30)

Micro images
=========================================================================



Proliferation of dilated vessels and small capillaries



Benign tumors and tumor-like conditions

Hereditary hemorrhagic telangiectasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Autosomal dominant syndrome of multiple vascular lesions of mucous membrane, skin and internal organs (Endoscopy 2008;40:23, Am J Gastroenterol 1993;88:1116)
● Associated with severe GI hemorrhage
● Difficult to identify vascular lesions at time of surgical resection



Benign tumors and tumor-like conditions

Hyperplastic Pacinian corpuscle


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Intraabdominal Pacinian corpuscles up to 1 cm

Micro description
=========================================================================

● Resembles cutaneous counterpart
● Central blood vessel and nerve ending surrounded by 14-45 tortuous, concentric lamellae

Micro images
=========================================================================



Digital lesion: A-relationship between pacinian corpuscle (P) and nerves (arrows); these two structures are interspersed with vascular and nervous twigs (double arrowheads) with surrounding loose connective and fatty tissues; B-normal structures of pacinian corpuscle are seen (outer capsule continuous with perineurium, lamellated inner and outer core, nerve fibers terminating center of inner core)


Digital lesion following dog bite: a-diffuse swelling; b-Pacinian hyperplasia with inner nerve fiber surrounded by concentric fibrous lamellae; c-inner core cells are S100+; d-outer lamellae are vimentin+; e-outer core cells are EMA+

Differential diagnosis
=========================================================================

Strongyloides: has cuticle, internal structures



Benign tumors and tumor-like conditions

Idiopathic retractile mesenteritis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, idiopathic, nonneoplastic condition usually affecting small bowel, which can cause thickening and shortening of mesentery
● Also called mesenteric panniculitis
● Usually men age 40+, associated with intestinal obstruction but no other systemic symptoms
● Despite some reports, not strongly associated with trauma or surgery (World J Gastroenterol 2009;15:6139)

Case reports
=========================================================================

● 36 year old man with fever, chills and weight loss (Clinics (Sao Paulo) 2008;63:843)
● 37 year old woman with chronic abdominal pain and thickened colonic wall (Tunis Med 2010;88:950)
● 74 year old man with acute abdominal pain (World J Gastroenterol 2009;15:117)

Clinical images
=========================================================================



Small bowel obstruction from area of localized thickening

Gross images
=========================================================================



Colon (sigmoid): normal mucosa with wall thickening

Micro description
=========================================================================

● Fibrosis, fat necrosis, chronic inflammation, variable focal calcification
● Minimal atypia or mitotic figures

Micro images
=========================================================================



Various images



Benign tumors and tumor-like conditions

Idiopathic retroperitoneal fibrosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Fibrosis which develops in retroperitoneum, often at aortic bifurcation
● Associated with drug methylsergine, other fibrotic lesions (sclerosis of major bile ducts, Riedel’s thyroiditis, inflammatory pseudotumor of orbit)
● IgG4 often involved in pathogenesis of idiopathic sclerosing lesion; associated with male gender
● Associated with lymphoma, which developed in 15% of patients

Case reports
=========================================================================

● 58 year old man with idiopathic sclerosing mesenteritis and retroperitoneal fibrosis (Korean J Gastroenterol 2011;58:221)
● With previous sclerosing mesenteritis and small bowel obstruction (Eur J Gastroenterol Hepatol 2006;18:1285)

Gross description
=========================================================================

● Not well circumscribed

Micro description
=========================================================================

● Widely scattered germinal centers and plasma cells in background of dense fibrosis
● Eosinophilic infiltration and oblitertaive phlebitis in IgG4 related cases (Am J Surg Pathol 2009;33:1833)



Benign tumors and tumor-like conditions

Inflammatory fibroid polyp


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Uncommon, benign polypoid submucosal mass with CD34+ spindle cells and granulation tissue, usually in distal stomach or terminal ileum (Arch Pathol Lab Med 2011;135:1311)
● Presents as obstructive mass or causing intussusception (Radiographics 1999;19:539)
● True neoplasms, usually with PDGFRA mutation (Pathologe 2009;30:117)

Case reports
=========================================================================

● 35 year old woman with concurrent appearance of Crohn's disease and inflammatory fibroid polyp (Ann Ital Chir 2005;76:395)
● 39 year old woman presenting with small intestinal obstruction (Case of the Week #86)

Treatment
=========================================================================

● Excision (does not recur)

Gross description
=========================================================================

● Polypoid (without stalk), submucosal mass, dumbbell shape in small intestine due to intussuception, mucosal ulceration and splitting and atrophy of muscularis propria

Gross images
=========================================================================



Case of the Week #86


Inflamatory fibroid polyp

Micro description
=========================================================================

● Submucosal mixture of prominent capillaries, spindle cells (occasionally concentrically arranged around vessels / onion-skinning) and inflammatory cells (particularly eosinophils, plasma cells and mast cells) in granulation tissue-like stroma (Arch Pathol Lab Med 2010;134:378)
● May be transmural
● May have lymphoid follicles
● Rare multinucleated giant cells, no atypia, no/rare mitotic figures
Histologic patterns: classical, edematous, fibrovascular, nodular, sclerotic

Micro images
=========================================================================





Various images


Case of the Week #86

Positive stains
=========================================================================

● CD34+ spindle cells
● Variable calponin, cyclin D1, fascin, smooth muscle actin, vimentin, CD35

Negative stains
=========================================================================

● CD117 (although mast cells are positive)

Differential diagnosis
=========================================================================

Inflammatory myofibroblastic tumor: usually children, may recur, plasma cells and lymphocytes with few eosinophils, mitotic activity in cellular areas, less prominent blood vessels, smooth muscle actin+, desmin+, ALK+/-, CD34- (Hum Pathol 2002;33:307)
GIST: malignant in 30-50%, plump spindle cells with eosinophilic cytoplasm, variable skenoid fibers and muscular infiltration, CD117+ (Mod Pathol 2000;13:1134, Mod Pathol 2003;16:366)
Inflammatory polyp of Crohn’s or ulcerative colitis: similar histology but different clinical history and findings in remainder of bowel



Benign tumors and tumor-like conditions

Inflammatory myofibroblastic tumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called inflammatory pseudotumor; previously called inflammatory fibrosarcoma
● Often in children but can occur at any age
● No clinical associations
● Benign, but may recur; rarely has malignant behavior
● Rarely behaves malignant
● ALK+ tumors (22% of patients age 40 years or younger) have a more favorable prognosis (Am J Surg Pathol 2001;25:761)
● Complications: obstruction, intussusception

Case reports
=========================================================================

● 2 month old infant with intestinal obstruction (J Med Assoc Thai 2009;92:114)
● 2 year old girl with jejunal tumor (Pathol Int 2001;51:47)
● 29 year old woman with intramural ileal tumor showing ALK/TPM3 fusion using FISH (Hum Pathol 2006;37:112)

Gross description
=========================================================================

● Mean 3-4 cm, submucosal sessile polypoid mass or multiple masses with broad base
● Tan-gray-yellow
● Overlying mucosa may be ulcerated

Micro description
=========================================================================

● Usually limited to submucosa
● Plump ovoid myofibroblastic spindle cells with inflammatory infiltrate including plasma cells and lymphocytes
● May be sparsely cellular with myxoid stroma
● May have rarefaction around muscular walled blood vessels
● May be infiltrative
● Cellular areas may have up to 2 mitotic figures/HPF
● Variable vascular component

Micro images
=========================================================================



Plump, ovoid myofibroblastic cells with pale eosinophilic cytoplasm in collagenous background with numerous lymphocytes and plasma cells


CD117- (endothelial cells are positive internal control)

Positive stains
=========================================================================

● Vimentin, muscle specific actin, smooth muscle actin, anaplastic lymphoma kinase (variable)

Negative stains
=========================================================================

● S100, desmin (Mod Pathol 2000;13:1134), CD117 (endothelial cells may be CD117+), CD34

Electron microscopy description
=========================================================================

● Myofibroblasts

Differential diagnosis
=========================================================================

Fibromatosis: invades bowel secondarily



Benign tumors and tumor-like conditions

Inflammatory polyp


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Polypoid inflammatory mucosa associated with Crohn’s disease or ulcerative colitis
● Also amebiasis, schistosomiasis, ulcers, anastomotic sites

Micro description
=========================================================================

● Solitary small polyps of inflamed regenerating mucosa in a fibroblastic or granulation tissue stroma
● No/few mitotic figures, no atypical mitotic figures, often zonation
● May have bizarre stromal changes resembling sarcoma



Benign tumors and tumor-like conditions

Intussusception


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Portion of bowel (intussuscipiens) swallows another length of bowel (intussusceptum)
● Usually occurs during first 5 years of life, 50% within first year (BMC Pediatr 2012;12:36)
● May be due to lymphoid hyperplasia in ileocecal region secondary to adenovirus or other viral infections
● In older patients, may be associated with HIV or due to pedunculated intraluminal lipoma or leiomyoma that serves as point of traction
● Complications: ischemic necrosis due to compression of vessels


Diagram

Case reports
=========================================================================

● 75 year old man with giant ileal lipoma (Int J Surg Case Rep 2012;3:382)

Treatment
=========================================================================

● Manual reduction, barium enema, resection

Clinical images
=========================================================================



Gentle reduction of the ileoileal intussusception



Benign tumors and tumor-like conditions

Ischemia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Mucosal damage (initially) due to vascular occlusion or reduced blood flow associated with shunting
● Usually not due to atherosclerosis because of widely anastomosing blood supply
● Damage varies from none to hemorrhagic infarction
● Also ulceration, mucosal plaque, strictures
Grossing bowel specimens with possible ischemia: dissect blood vessels and submit several sections to detect inflammation and thrombosis

Gross images
=========================================================================



Various images

Micro description
=========================================================================

Early: lamina propria hemorrhage, superficial epithelial necrosis, preservation of deep crypts
Later: ulceration with minimal inflammation, villous distortion, pyloric gland metaplasia progressing to full thickness infarct
Late: strictures affecting muscularis propria

Micro images
=========================================================================



Various images

Differential diagnosis
=========================================================================

Crohn’s disease: marked inflammatory infiltrate, no stricture of muscularis propria, no hemosiderin

Additional references
=========================================================================

J Med Case Rep 2012;6:48, Histol Histopathol 2010;25:277



Benign tumors and tumor-like conditions

Kayexelate damage


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Kayexelate (sodium polystyrene sulfonate) in sorbitol is used to treat hyperkalemia, but may crystallize in small intestine (also elsewhere in GI tract) and produce endoscopic findings resembling ulcer or erosion (Am J Surg Pathol 2001;25:637)
● Also causes intestinal necrosis (South Med J 2009;102:493, Hum Pathol 2007;38:527)

Case reports
=========================================================================

● 87 year old man (Case Rep Gastroenterol 2007;1:144)

Micro description
=========================================================================

● Crystals are lightly basophilic with a faint crystalline mosaic pattern, better seen with PAS/Alcian blue
● Crystals are refractile but not polarizable, luminal and adherent to intact surface epithelium or mixed with inflammatory exudates in patients with ulcer or erosion

Micro images
=========================================================================



Various images


Figure a-Kayexalate crystals are variable sizes, all showing a mosaic “cracking” pattern; patient had severe cardiovascular compromise and received kayexalate for hypokalemia; bowel was necrotic and ischemic
Figure b-Cholestyramine crystals resemble kayexalate, but are red; larger cyrstals show some mosaic “cracking,” but smaller cholestyramine crystals do not




Benign tumors and tumor-like conditions

Klippel-Trenaunay-Weber syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Hemangiomas, somatic and bony hypertrophy, port wine stains, urinary bladder hemangiomas

Case reports
=========================================================================

● Patient with severe anemia due to extensive jeujenal varices (Am J Gastroenterol 1998;93:2274)
● 60 year old man with colonic varices (Radiographics 2005;25:1694)

Clinical images
=========================================================================



Jejunal varices



Other / benign tumors and tumor-like conditions

Leiomyoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Benign smooth muscle tumors that arise from small bowel muscularis propria or muscular mucosa
● Duodenal leiomyomas of muscular mucosa are incidental, 1-2 mm, merge with muscularis mucosa; those not from muscularis mucosa are also often incidental but larger, 2-4 cm, with firm, white, whorled cut surface

Micro description
=========================================================================

● Low cellularity, no/rare mitotic figures, resembles esophageal leiomyoma

Micro images
=========================================================================



Esophageal leiomyomas

Positive stains
=========================================================================

● Smooth muscle actin, desmin

Negative stains
=========================================================================

● CD117, CD34

Differential diagnosis
=========================================================================

GIST: often cytologically malignant in small bowel; CD117+, often CD34+ (Rom J Morphol Embryol 2011;52:1121, Am J Surg Pathol 2003;27:625)



Benign tumors and tumor-like conditions

Lipoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, usually submucosal
● May cause ulceration or intussusception
● Lipohyperplasia often found near ileocecal valve

Case reports
=========================================================================

● 45 year old man with ileocecal Intussusception due to lipoma (N Engl J Med 2009;361:e55)
● 52 year old woman with pedunculated lesion of terminal ileum (J Med Case Rep 2010;4:51)
● 77 year old man with ileocecal valve lipoma (JSLS 2009;13:80)

Gross description
=========================================================================

● Bright yellow, round, encapsulated
● Bulges into lumen, 5% multiple
● May have hemorrhage or necrosis

Gross images
=========================================================================



Large pedunculated polypoid lipoma

Micro images
=========================================================================



Circumscribed collection of mature adipocytes

Differential diagnosis
=========================================================================

● Lipomatosis: bowel infiltrated by mature fat



Benign tumors and tumor-like conditions

Lymphangioma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually children, associated with similar tumors elsewhere

Micro images
=========================================================================



Lymphagioma of duodenum

Differential diagnosis
=========================================================================

● Lymphatic cysts: incidental finding in elderly



Benign tumors and tumor-like conditions

Lymphoid hyperplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called lymphoid polyp; formerly called pseudolymphoma
● Most common site is ileocecal region
● Causes intussusception in children
● Nodular lymphoid hyperplasia: nodules throughout bowel, associated with giardiasis or childhood viral infection

Case reports
=========================================================================

● 60 year old woman with florid reactive lymphoid hyperplasia of terminal ileum (BMJ Case Rep. 2010;2010 Epub 2010 Jan 13.)

Gross images
=========================================================================



Terminal ileum exhibiting shows mucosal ulcers due to nodular lymphoid hyperplasia

Micro description
=========================================================================

● Numerous lymphoid follicles with germinal centers in lamina propria or submucosa

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD20, CD45; do not confuse BCL2 expression in marginal zone cells with BCL2 expresion of germinal center cells in follicular lymphoma (Am J Surg Pathol 2003;27:888)

Differential diagnosis
=========================================================================

● Low grade lymphoma: often infiltrative, light chain restriction



Benign tumors and tumor-like conditions

Mastocytosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare systemic disorder with mast cells in skin, bones, lymph nodes, other organs
● 50% involve GI tract and may cause malabsorption
● Rarely involves small bowel without skin involvement
● Consider diagnosis if 6+ mast cells present per high power field
● Immunoreactivity for CD25 in GI mucosal mast cells is specific for Systemic Mastocytosis and can be used to confirm the diagnosis (Am J Surg Pathol 2007;31:1669)

Case reports
=========================================================================

● Mast cell sarcoma of small intestine (J Clin Pathol 2011;64:1035)
● Systemic mastocytosis mimicking inflammatory bowel disease (Am J Surg Pathol 2006;30:1478)

Micro description
=========================================================================

● Variable villus abnormality with increased mast cells or eosinophils

Micro images
=========================================================================



Various images (not necessarily small bowel)

Positive stains
=========================================================================

● Mast cell tryptase, CD117, CD25

Additional references
=========================================================================

World J Gastroenterol 2008;14:7005, Am J Clin Pathol 2004;122:560



Benign tumors and tumor-like conditions

Myxoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Extremely rare in small intestine
● May be part of Carney complex (familial myxoma syndrome), an autosomal dominant syndrome with 17q2 mutation and cardiac and cutaneous myxomas, lentigines, myxoid fibromas of the breast, pituitary adenomas, primary adrenocortical micronodular hyperplasia with Cushing syndrome, psammomatous melanotic schwannoma, testicular large cell calcifying Sertoli cell tumor (Medicine (Baltimore) 1985;64:270)

Case reports
=========================================================================

● 47 year old woman with simultaneous cardiac and small bowel myxoma (Arch Pathol Lab Med 2003;127:481)

Gross description
=========================================================================

● Intraluminal, pedunculated, firm round nodule with smooth and ulcerated mucosal surface, myxoid and gelatinous cut surface

Micro description
=========================================================================

● Bland, stellate stromal cells and small, mature capillaries widely separated by myxoid material
● Scattered lymphocytes and plasma cells
● No mitotic activity, no atypia

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Vimentin

Negative stains
=========================================================================

● CD117/KIT, CD31, smooth muscle actin, S100



Benign tumors and tumor-like conditions

Neurofibroma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Associated with multiple endocrine adenomatosis or von Recklinghausen’s disease (neurofibromatosis 1)
● With NF1, also associated with hyperplasia of submucosal and myenteric nerve plexuses, mucosal ganglioneuromatosis, GI stromal tumors, gangliocytic paraganglioma
● GISTs arising in NF1 do not express the typical sporadic GIST mutations of KIT exon 9, 11, 13, or 17 or PDGFRA exon 12 or 18; suggesting a different pathogenesis (Am J Surg Pathol 2006;30:90)

Case reports
=========================================================================

● 52 year old woman with isolated intestinal neurofibromatosis in colon (World J Gastroenterol 2008;14:6569)
● 73 year old man with intestinal neurofibromatosis and small-bowel adenocarcinoma (Eur J Cancer Care (Engl) 2009;18:466)

Micro images
=========================================================================



Colonic neurofibroma



Benign tumors and tumor-like conditions

Neuromuscular and vascular hamartoma of small bowel


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called small bowel hamartoma
● Similar to diaphragm disease (annular constrictions causing small bowel obstruction associated with NSAIDs), but without NSAID association (Am J Surg Pathol 1999;23:1414)

Case reports
=========================================================================

● 32 year old man with obstruction (J Lab Physicians 2010;2:109)
● Neuromuscular and vascular hamartoma arising in a Meckel's diverticulum (Pathology 2006;38:173)

Gross description
=========================================================================

● Multiple circumferential indentions of serosa corresponding to discrete ridges on mucosal surface

Micro description
=========================================================================

● Ridges composed of submucosa only, contain proliferating blood vessels surrounded by smooth muscle fibers originating from a frayed muscularis mucosa
● Variable nerve and ganglionic cells present in fibrous collagenous tissue
● No/minimal inflammatory infiltrate

Micro images
=========================================================================



Various images



Benign tumors and tumor-like conditions

Peutz-Jeghers polyp


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Polyp supported by broad bands of muscularis mucosa smooth muscle, thicker centrally, resembling “Christmas tree” at low power
● Also called hamartomatous polyp

Peutz-Jeghers syndrome:
=========================================================================

● Autosomal dominant disorder (1 per 200,000) with variable penetrance, usually diagnosed at age 20-30
● Hamartomatous polyps in small bowel (100%), stomach and colon (25%) - polyps may occur without other features of syndrome, may be associated with enteritis cystica profunda, may cause intussusception and bleeding
● Polyps are benign, but adenocarcinoma may arise from associated adenomatous lesions
● Melanotic pigmentation of digits, genitalia, lips, oral mucosa, palms, soles
● Also sex-cord tumor with annular tubules (almost all patients); adenocarcinomas of stomach, large or small bowel; adenoma malignum of cervix, ovarian mucinous tumors, carcinomas of breast, lung, pancreas, uterus

Pathophysiology
=========================================================================

● Aberrant intestinal stem cell lineage dynamics in Peutz-Jeghers syndrome leads to protracted clonal evolution in the crypt (Gut 2012;61:839)

Clinical features:
=========================================================================

● Sporadic Peutz Jeghers polyp have a cumulative lifetime risk of cancer similar to those with syndrome (Am J Surg Pathol 2007;31:1209)
● Large polyps (>15 mm) may cause intussusception and GI bleeding (Am J Gastroenterol 2011;106:940)
● Misplaced dysplastic epithelium may resemble malignancy (Am J Surg Pathol 2000;24:34)

Case reports
=========================================================================

● 13 year old girl with solitary ileal polyp (Case Rep Gastroenterol 2010;4:452)
● 76 and 84 year old men (J Med Case Rep 2011;5:240)

Gross description
=========================================================================

● Adenomatous-like polyps
● Pedunculated, large, lobulated

Clinical images
=========================================================================



Various images

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Polyp supported by broad bands of muscularis mucosa smooth muscle, thicker centrally
● “Christmas tree” appearance at low power
● Columnar and goblet cells superficially
● Paneth and endocrine cells at base
● Epithelial misplacement (pseudoinvasion) in 10%

Micro images
=========================================================================



Various images

Virtual slides
=========================================================================



Small intestine, duodenum

Differential diagnosis
=========================================================================

Enteritis cystica profunda
● Invasive carcinoma



Benign tumors and tumor-like conditions

Pneumatosis cystoides intestinalis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Submucosal gas-filled cysts in GI tract
● Called mucosal pseudolipomatosis if it resembles lipomatosis

Clinical features
=========================================================================

● Part of differential diagnosis of acute abdomen (World J Gastroenterol 2012;18:453)
● In infants, associated with necrotizing enterocolitis and may be fatal; also associated with cystic fibrosis, congenital heart defects
● In adults, either idiopathic or varied clinical settings including chemotherapy, chronic lung disease, drugs, ischemic colitis, obstruction, scleroderma (World J Gastroenterol 2011;17:4932, Arch Pathol Lab Med 2010;134:378)
● Often indolent clinical course, although radiographically resembles carcinoma
● Considered a finding, not a diagnosis

Case reports
=========================================================================

● 6 year old girl with ulcerative colitis (Arch Pathol Lab Med 1999;123:354)
● 73 year old woman with dysplasia in perforated intestinal pneumatosis (World J Gastroenterol 2009;15:4189)
● Idiopathic myointimal hyperplasia of mesenteric veins and pneumatosis intestinalis (J Crohns Colitis 2011;5:239)

Gross description
=========================================================================

● Polypoid grapelike masses protrude through mucosa
● Soft, bluish, and often sessile,‘‘bubble wrap’’ crackling noise while handling the specimen

Clinical images
=========================================================================



Endoscopy

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Submucosal cysts lined by multinucleated giant cells
● Mucosa contains cryptitis, crypt abscesses, granulomas
● May also resemble lipomatosis

Micro images
=========================================================================



Various images

Differential diagnosis
=========================================================================

Crohn’s disease



Benign tumors and tumor-like conditions

Pseudomelanosis duodeni


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Brown-black pigment in lamina propria macrophages of proximal duodenum
● Also known as melanosis duodeni
● Due to iron and sulfur (J Formos Med Assoc 1995;94:632), and may be associated with oral iron intake, hypertension, diabetes or end stage renal disease (Endoscopy 2008;40:165, World J Gastroenterol 2012;18:1414)
● Not associated with laxative abuse (J Clin Gastroenterol 1988;10:127)
● Not associated with lipofuscin pigment, which is identified in melanosis coli.
● Often identified at endoscopy
● Pigment may originate in atmosphere or diet
● No known clinical significance

Case reports
=========================================================================

● 94 year old woman with GI bleed and spotty hyperpigmentation at endoscopy (Case of the Week #231)

Micro images
=========================================================================



Various images

               
Case of Week #231



Benign tumors and tumor-like conditions

Reactive nodular fibrous pseudotumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● First described in 2003 in 5 patients (4 men), mean age 56 years (Am J Surg Pathol 2003;27:532)
● May present as obstruction (Am Surg 2011;77:790), but otherwise benign clinical course

Gross description
=========================================================================

● Firm, tan-white, 4-6 cm, solitary/multiple, in small bowel or colon

Micro description
=========================================================================

● Low/moderate cellularity
● Spindled fibroblasts arranged haphazardly or in intersecting fascicles
● Often infiltrative borders
● Stroma rich in wire-like, keloidal or hyalinized collagen
● Peripheral lymphoid aggregates

Positive stains
=========================================================================

● Vimentin, CD117 or muscle specific actin (80%), smooth muscle actin or desmin (60%) (Int J Surg Pathol 2004;12:365)

Negative stains
=========================================================================

● CD34, S100, ALK1

Differential diagnosis
=========================================================================

Fibromatosis



Benign tumors and tumor-like conditions

Sclerosing peritonitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Inflammatory and fibrosing process affecting visceral peritoneum that can encase small bowel (World J Gastroenterol 2012;18:1999)
● Infiltrates mesentery at attachment site with peritoneum
● Usually spares retroperitoneum
● Associated with dry eyes and itchy scaly skin lesions

Clinical features
=========================================================================

● Associated with beta blockers; chronic peritoneal dialysis
● Rare causes include abdominal surgery, abdominal tuberculosis, cirrhosis, dermoid cyst rupture, endometriosis, familial Mediterranean fever, fibrogenic foreign material, GI malignancy, intraperitoneal chemotherapy, liver transplantation, luteinized ovarian thecomas, pertioneoventricular shunting, protein S deficiency, recurrent peritonitis, sarcoidosis, subclinical primary viral peritonitis

Case reports
=========================================================================

● Sclerosing peritonitis associated with luteinized adult granulosa cell tumor (Int J Gynecol Pathol 2012;31:141)

Clinical images
=========================================================================



Encapsulating thick, white adherent membrane encasing small bowel



Benign tumors and tumor-like conditions

Selective IgA deficiency


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Nodular lymphoid hyperplasia, reduced IgA plasma cells, otherwise normal (Pathol Res Pract 2009;205:876)



Other / benign tumors and tumor-like conditions

Tufting enteropathy


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Intractable diarrhea syndrome, sometimes familial, beginning in neonates
● Also called intestinal epithelial dysplasia (Orphanet J Rare Dis 2007;2:20)
● Due to Epithelial cell adhesion molecule gene (EpCAM) (Gastroenterology 2008;135:429, Gut Liver 2010;4:407)

Treatment
=========================================================================

● Total parental nutrition

Micro description
=========================================================================

● Variable villus abnormality, epithelial crowding, disorganization and focal tufting
● No epithelial lymphocytosis

Micro images
=========================================================================



Various images

Electron microscopy description
=========================================================================

● Basement membrane abnormalities; increase in desmosome length and number; decreased number of microvilli of surface enterocytes with structural disorganization

Electron microscopy images
=========================================================================



Various images



Benign tumors and tumor-like conditions

Turner’s syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● XO karyotype of females with short stature, webbed neck, streak gonads, shield chest
● Often telangiectasias in bowel (J Pediatr Endocrinol Metab 2009;22:759) and increased prevalence of celiac disease; testing for anti-endomysial antibody is suggested before starting hormone treatment (Eur J Endocrinol 2009;160:675)



Benign tumors and tumor-like conditions

Vascular diseases-general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See also enterocolic (lymphocytic) phlebitis

General
=========================================================================

● May mimic Crohn’s disease due to mucosal ulceration or gangrene, submucosal edema, perforation and stenosis
● Usually due to atherosclerosis (Radiol Clin North Am 2008;46:877)
● Also adhesions, fungal infection, periarteritis nodosa, radiation therapy, rheumatoid arthritis, thromboangiitis obliterans



Carcinoma

General


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● 2% of malignancies of GI tract occur in small bowel
● 5,000 cancers and 1,200 deaths per year in US
● Most tumors are adenocarcinomas, often associated with adenomas
● Metastases to liver, peritoneal surfaces, regional lymph nodes



Carcinoma

Adenocarcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See also Ampullary adenocarcinoma

General
=========================================================================

● Much less common in small intestine than in colon
● Men or women, ages 40-70, any site in small bowel
● Also associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer), Crohn’s disease, Peutz-Jegher’s syndrome, von Recklinghausen’s disease, cholecystectomy, cystic fibrosis, Meckel’s diverticulum (Hum Pathol 2010;41:1087)
● May cause obstruction
● Usually advanced stage at diagnosis with deep wall penetration, nodal metastases
● Nodal metastases and distal location (jejunum and ileum) of tumor are most important independent prognostic factors (Hum Pathol 2010;41:1087)
● Presence of adenomatous component may be favorable prognostic factor

Case reports
=========================================================================

● 36 year old woman, also with intestinal duplication of ileum (Rev Med Chil 2009;137:1341)
● 48 year old man, also with Crohn’s disease (World J Gastroenterol 2009;15:1774)
● 64 year old woman with synchronous adenocarcinoma and carcinoid tumor of the terminal ileum (BMC Cancer 2005;5:157)
● 68 year old woman with ileal adenocarcinoma arising from multifocal gastric heterotopias (Med Oncol 2011;28:1023)
● 72 year old Japanese man with intramucosal adenocarcinoma of the ileum after ileosigmoidostomy (World J Surg Oncol 2009;7:41)
● Small bowel carcinoma mimicking relapse of Crohn’s disease (J Crohns Colitis 2011;5:152)

Gross description
=========================================================================

● Papillary or polypoid, may have napkin ring appearance (encircles lumen), proximal bowel dilation

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Often moderately well differentiated, mucin producing
● Scattered endocrine cells

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Mucin staining varies based on site of lesion (Mod Pathol 2003;16:403)
● Mucin, CEA, lysozyme
Duodenum: positive for MUC1
Jejunum/ileum: positive for CK20

Negative stains
=========================================================================

Duodenum: negative for CK20
Jejunum/ileum: negative for MUC1

Electron microscopy description
=========================================================================

● Prominent microvilli

Additional references
=========================================================================

Int J Clin Exp Pathol 2012;5:203, Nihon Shokakibyo Gakkai Zasshi 2011;108:429, World J Gastroenterol 2010;16:1527



Carcinoma

Adenosquamous carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare

Case reports
=========================================================================

● 55 year old man with tumor of ileum (Arch Pathol Lab Med 1999;123:739)
● 65 year old woman with squamous cell carcinoma arising from ileum (BMJ Case Rep 2011 May 12)
● 80 year old woman with tumor of jejunum (Pathol Int 2005;55:590)

Micro description
=========================================================================

● Malignant glandular and squamous elements

Micro images
=========================================================================



Left: adenosquamous carcinoma; right: squamous cell carcinoma



Carcinoma

Anaplastic carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Aggressive behavior

Micro description
=========================================================================

● Bizarre tumor cells, often multinucleated, with abundant cytoplasm



Carcinoma

Neuroendocrine carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually fatal

Case reports
=========================================================================

● 52 year old man with collision tumor of primary adenocarcinoma and neuroendocrine carcinoma of duodenum (Rare Tumors 2012;4:e20)

Micro description
=========================================================================

● Marked pleomorphism, large irregular hyperchromatic nuclei, prominent nucleoli, tumor necrosis, frequent mitotic figures

Micro images
=========================================================================



Nests of small cells with uniform round nuclei with classic salt and pepper chromatin



Carcinoma

Sarcomatoid carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 55 year old man with sarcomatoid carcinoma in the jejunum (Arch Pathol Lab Med 2004;128:918)

Micro description
=========================================================================

● Sheets of spindle cells; anaplastic component (tumor giant cells with bizarre nuclei) may be present (Pathologica 1997;89:425)

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CK7, cytokeratin AE1/AE3, vimentin, epithelial membrane antigen

Negative stains
=========================================================================

● CK20



Carcinoma

Signet ring cell carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Gross images
=========================================================================



Tumor with stricture in distal duodenum

Micro description
=========================================================================

● Marked cytologic atypia, mitotic figures, intracytoplasmic lumina, invasion of lamina propria, extracellular mucin pools

Micro images
=========================================================================



Figure 4

Differential diagnosis
=========================================================================

● Artifacts from trauma, particularly if tissue is fragmented or crushed (Arch Pathol Lab Med 2001;125:1473, figure 2)

Additional references
=========================================================================

Case Rep Gastroenterol 2009;3:49, Korean J Gastroenterol 2007;50:51



Carcinoma

Small cell carcinoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, in few cases reported, prognosis better than for small cell lung tumors

Micro description
=========================================================================

● Sheets and nests of small, round cells with scanty cytoplasm, hyperchromatic nuclei, stippled chromatin, indistinct nucleoli, numerous mitotic figures and apoptotic cells
● Foci of necrosis and vascular invasion common
● Resembles pulmonary tumor
● Pure or mixed with adenocarcinoma

Micro images
=========================================================================



Tumor of proximal ileum; figure 4 is synaptophysin

Positive stains
=========================================================================

● Neuroendocrine markers, CK8, may be TTF1 positive

Electron microscopy description
=========================================================================

● Membrane-bound dense core granules

Additional references
=========================================================================

Arch Pathol Lab Med 2003;127:e357, J Clin Oncol 2004;22:2730, J Clin Pathol 2010;63:620



Lymphoma

Lymphoma-general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● One of most common malignant tumors in small bowel
● GI tract is most common site of primary extranodal lymphoma, but also a site of secondary disease in 10% with non-Hodgkin’s lymphoma at presentation
● Usually solitary, 50% have nodal metastases at diagnosis
● 2 year actuarial survival is 42%
● If biopsy shows atypical lymphoid proliferation, recommend rebiopsy to obtain fresh tissue for flow cytometry, PCR or gene rearrangement studies
● 2/3 are B cell, 1/3 are T cell lymphomas

Gross description
=========================================================================

● Diffusely infiltrating mass with garden hose appearance OR bulky tumor mass with ulceration OR polypoid growth pattern

Additional references
=========================================================================

Int J Hematol 2008;87:375, J Int Med Res 2007;35:406, Histopathology 2003;43:135



Lymphoma

Burkitt’s lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● High grade lymphoma, usually in children
● Endemic cases in Africa usually do not present with GI involvement
● Sporadic cases in Western world and Middle East may present with ileocecal involvement, pain or obstruction

Case reports
=========================================================================

● 16 year old boy with acute abdomen (Cases J 2009;2:9322)
● 24 year old man with Burkitt's lymphoma of ileum and renal cell carcinoma.(Can J Surg 2008;51:E77)

Gross images
=========================================================================



Ileocecal valve tumor contributed by Dr. Kaveh Naemi, Irvine, California


Terminal ileum tumor

Micro description
=========================================================================

● Small, noncleaved, monomorphic cells with round nuclei, prominent multiple nucleoli, basophilic cytoplasm
● Vacuoles on touch prep
● Starry sky appearance on low power

Micro images
=========================================================================



Ileocecal valve tumor (courtesy of Dr. Kaveh Naemi, Irvine, California)


Above ileocecal valve tumor (left to right): CD20+, CD10+, Ki-67 strong, bcl2- (contributed by Dr. Kaveh Naemi, Irvine, California)


Terminal ileum tumor (left to right): H&E, CD10+, Ki-67 (strong)

Cytology images
=========================================================================



Touch prep

Positive stains
=========================================================================

● CD20, CD10

Negative stains
=========================================================================

● CD5, CD23

Molecular description
=========================================================================

● c-myc translocations of t(8;14) and others

Molecular images
=========================================================================



Terminal ileum tumor: c-myc by FISH



Lymphoma

Diffuse large B cell lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare lymphoma subtype in intestine - intestinal lymphomas are usually MALT-type
● Cases may have MALT or non-MALT origin

Prognostic factors
=========================================================================

● Diffusely dense BCL6 expression (suggest germinal center B cell origin aod favorable prognosis, Am J Surg Pathol 2003;27:790)
● CD10+ tumors suggest favorable prognosis (Arch Pathol Lab Med 2002;126:956)
● Perforation is associated with a poorer prognosis (Histopathology 2008;53:432)

Case reports
=========================================================================

● 69 year old Japanese woman with simultaneous gastric MALT lymphoma and ileal diffuse large B-cell lymphoma (Int J Clin Exp Pathol 2012;5:260)

Micro images
=========================================================================



Various images



Lymphoma

Enteropathy-associated T cell lymphoma (EATL)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Intestinal tumour of intraepithelial T lymphocytes composed of large, often polymorphic lymphoid cells, which are negative for CD56 (WHO)
● Associated with long standing malabsorption (mean 28 years) that ceases to be gluten-sensitive
● 14% incidence in celiac sprue patients
● Abdominal pain, clubbing, fever, hemorrhage, intestinal obstruction, perforation, ulceration of bowel, weight loss; also sustained increase in serum IgA
● Ulceration may coincide with or precede detectable lymphoma, but it is difficult to rule out lymphoma (unless have multiple biopsies) since it may be focal
● 75% dead within 2 years

Gross description
=========================================================================

● Widespread patchy involvement, often of small bowel, associated with ulceration, stricture, perforation

Micro description
=========================================================================

● May require 20 tissue sections to diagnose malignancy since tumor is so focal

WHO classification:

Type I (celiac associated):
● Variable lymphomatous infiltrate with neoplastic large cells with conspicuous nucleoli
● May have pleomorphic, multinucleated cells
● Also small to medium-sized lymphocytes, histiocytes and eosinophils
● Adjacent mucosa shows villous atrophy, crypt hyperplasia, increased inflammatory cells in lamina propria, intraepithelial lymphocytosis

Type II (no history of celiac sprue):
● Lymphomatous infiltrate is homogeneous and composed of small to medium-sized lymphocytes with a rim of pale or clear cytoplasm, slightly irregular nuclei and small nucleoli; CD8+, CD56+
● Villous atrophy, blunting and intraepithelial lymphocytosis confined to area of lymphoma
● More distant nonlymphomatous mucosa is unremarkable

Micro images
=========================================================================





Various images

Positive stains
=========================================================================

● CD3, CD7, CD30

Negative stains
=========================================================================

● CD4, CD8, CD22, CD68

Additional references
=========================================================================

Arch Pathol Lab Med 2011;135:1283



Lymphoma

Follicular lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Common low grade lymphoma, often arises in terminal ileum or as small polypoid masses throughout bowel (lymphomatoid polyposis, which may also represent mantle cell lymphoma)
● Either primary or secondary

General-primary follicular lymphoma of small bowell
=========================================================================

● Median age 54 years, 2/3 female
● Small bowel is most common site in GI tract; duodenum > ileum > colon; often transmural involvement
● Disease localized to bowel and regional lymph nodes in most cases (Am J Surg Pathol 2011;35:1255)
● Indolent with occasional relapses but no/rare deaths, median disease free survival of 69 months (Am J Surg Pathol 2002;26:216)
● Duodenal cases may be more common in women, are usually periampullary (Am J Surg Pathol 2000;24:688)
● Distal small bowel involvement is more likely to present as bowel obstruction requiring resection

Gross description
=========================================================================

● Bowel thickening with multiple elevated nodules or plaques, possible bowel obstruction

Micro description
=========================================================================

● Usually follicular growth pattern of small, cleaved, bland appearing lymphocytes
● May transform to higher histologic grade

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD20, CD10, BCL2; also CD75, CD79

Negative stains
=========================================================================

● CD3, CD5, CD23, BCL1/Cyclin D1

Molecular description
=========================================================================

● t(14;18) in 80% (Cancer 2010 Dec 29. [Epub ahead of print])

Additional references
=========================================================================

Hepatogastroenterology 2012;59:751, J Gastroenterol 2010;45:370, J Clin Gastroenterol 2008;42:997



Lymphoma

Histiocytic lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare tumor that resembles sinus histiocytosis with massive lymphadenopathy, but has aggressive clinical course (Am J Surg Pathol 2004;28:1133, Am J Clin Pathol 1993;100:285)

Prognostic factors
=========================================================================

● Tumor size may be prognostic factor

Positive stains
=========================================================================

● CD68, LCA, CD4, CD31



Lymphoma

Hodgkin’s lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Stringent criteria suggested due to rarity of primary disease and possible confusion with secondary spread
● Associated with inflammatory bowel disease or longstanding chronic inflammation, combined with chronic immunosuppression; in these cases, may be due to Epstein-Barr virus associated lymphoproliferation (Am J Surg Pathol 2000;24:66)

Case reports
=========================================================================

● 38 year old man with Crohn's disease for 24 years (Arch Pathol Lab Med 2001;125:424)
● 79 year old man with low grade fever (J Cancer Res Ther 2010;6:342)

Treatment
=========================================================================

● Discontinuation of immunosuppressive therapy may be helpful

Gross description
=========================================================================

● Transmural involvement of bowel wall, often multifocal, associated with fissuring ulcers, diverticula with abscesses

Micro description
=========================================================================

● Reed-Sternberg cells in background of lymphoid hyperplasia, occasional granulomas

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD15, CD30

Negative stains
=========================================================================

● CD45 (LCA)



Lymphoma

Lymphoplasmacytic lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Low-grade B-cell lymphoma characterized by proliferation of small and plasmacytoid lymphocytes and plasma cells containing monoclonal intracytoplasmic immunoglobulins
● Often associated with serum viscosity syndrome due to IgM
● Formerly called immunocytoma

Laboratory
=========================================================================

● Monoclonal serum gammopathy

Case reports
=========================================================================

● 57 year old woman with obstructive tumor (Arch Pathol Lab Med 2001;125:677)

Micro description
=========================================================================

● Nodular or diffuse transmural infiltrate of small lymphocytes, mature plasma cells, lymphoplasmacytoid cells associated with extracellular PAS+ material

Micro images
=========================================================================



Various images



Lymphoma

MALT lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Tumor of Mucosa Associated Lymphoid Tissue; a type of marginal cell lymphoma
● More common in stomach than small bowel
● Often relapses in GI tract only
● In adults, occurs anywhere in gut but only rarely in appendix and esophagus
● Initially a type of hyperplasia, then monoclonal T cell dependent (from H. pylori infection), then T cell independent
● Initial stages may be “cured” by antibiotics or surgery

Case reports
=========================================================================

● 38 year old man with ileal MALT lymphoma with large-cell component that regressed spontaneously (Gut Liver 2010;4:117)
● 50 year old woman with MALT related multiple lymphomatous polyposis (World J Gastroenterol 2007;13:1453)
● Ileal MALT lymphoma causing massive gastrointestinal haemorrhage (Postgrad Med J 2009;85:163)

Micro description
=========================================================================

Low grade:
● Small or monocytoid lymphocytes with irregular nuclei that form lymphoepithelial lesions
● Reactive germinal centers and plasmacytoid cells are common

High grade:
● Resembles diffuse large B cell lymphoma, but may have Reed-Sternberg like cells

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD20

Negative stains
=========================================================================

● CD3, CD5, CD10, CD23, BCL1

Molecular description
=========================================================================

● t(11;18) involving c-myc is common



Lymphoma

Mantle cell lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Uncommon in small bowel; often presents as multiple lymphomatoid polyposis (Arch Pathol Lab Med 2011;135:1283)
● Also involves stomach and colon

Clinical features
=========================================================================

● 88% males, mean age 61 years
● Weight loss, fatigue, diarrhea, abdominal pain, often iron deficiency
● Mean survival less than 3 years
● May begin as single lesion or with disseminated multiple mucosal involvement (Mod Pathol 2001;14:811)

Case reports
=========================================================================

● 38 year old man with intussusception (J Clin Oncol 2002;20:4397)
● 85 year old man with coexistent adenocarcinoma (Arch Pathol Lab Med 2003;127:E64)

Gross description
=========================================================================

● Nodular, sessile or polypoid lesions, widely spaced with confluent studded or cobblestone appearance
● Each polyp 2 mm to 2 cm
● May be dominant tumor mass in ileocecum

Gross images
=========================================================================



Mass of terminal ileum is partially necrotic

Micro description
=========================================================================

● Infiltrative mantle cells (small lymphocytes with cleaved irregular nuclei) with invasion of submucosa, sparing of mucosa
● Epithelial invasion and ulceration occurs late in disease
● Secondary intestinal dissemination by lymph node based mantle cell lymphoma is exceedingly common; has a lymphomatous polyposis pattern with involvement of colon (Am J Surg Pathol 1996;20:442)

Micro images
=========================================================================



Early tumors


Tumor of terminal ileum / clon (figures 2/3)


Left to right: H&E, cyclin D1, CD20


Various images

Positive stains
=========================================================================

● CD20, CD5, cyclin D1/BCL1 rearrangement with t(11;14)(q13;q32)

Negative stains
=========================================================================

● CD3, CD10, CD23

Differential diagnosis
=========================================================================

Nodular lymphoid hyperplasia: benign, associated with common variable immunodeficiency syndrome or other infections
● Multiple lymphoid polyps: benign germinal centers in children, patients with Gardner’s syndrome



Lymphoma

Mediterranean lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called immunoproliferative small intestinal disease, Middle Eastern lymphoma
● More common among non-European Jews, Middle Eastern Arabs, South African blacks
● B cell lymphoma that arises in background of chronic diffuse mucosal plasmacytosis, with IgA heavy chain synthesis (no variable chain synthesized)

Clinical features
=========================================================================

● Many have pre-existing malabsorption
● May initially respond to antibiotics
● Often due to Campylobacter jejuni, another human pathogens responsible for immunoproliferative states (N Engl J Med 2004;350:239)

Case reports
=========================================================================

● 53 year old woman with immunoproliferative small intestinal disease (Turk J Gastroenterol 2012;23:91)

Gross description
=========================================================================

Low grade: non flattened mucosa
High grade: diffusely thickened folds with small nodules in distal duodenum / proximal jejunum

Micro description
=========================================================================

Low grade:
● Heavy lymphoplasmacytic infiltrate by mature cells

High grade:
● Resembles diffuse large cell lymphoma with plasmacytoid features
● May have starry sky pattern, follicular hyperplasia

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Monoclonal kappa or lambda (not both), syndecan1, IgA heavy chain
● BCL6 and p53 expression associated with advanced stage and aggressive behavior (World J Gastroenterol 2006;12:3602)



Lymphoma

Natural killer cell (NK cell) lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 36 year old man without gluten sensitive enteropathy (Arch Pathol Lab Med 2003;127:e142)
● NK like T cell lymphoma misdiagnosed as Behcet's enteritis of terminal ileum (Korean J Gastroenterol 2011;57:365)

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD3 epsilon, CD7, CD16, CD56, CD103

Flow cytometry images
=========================================================================






Lymphoma

Post-transplant lymphoproliferative disorders


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● May primarily involve the small bowel
● Either polymorphic or monomorphic (low grade or high grade)
● Also EBV associated smooth muscle tumors (Am J Surg Pathol 2006;30:75, Case of the Week #210)

Gross images
=========================================================================



Post-liver transplant patient with 4 cm mass causing intussusception

Micro images
=========================================================================



Post-liver transplant patient: various images



Lymphoma

Primary effusion lymphoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● HIV patient with small bowel mass (Am J Surg Pathol 2002;26:1363)



Lymphoma

Waldenström macroglobulinemia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare but distinctive involvement of small bowel

Gross description
=========================================================================

● Small white nodules, variably distended serosal lymphatics
● Mucosa is white, nodular or granular

Micro description
=========================================================================

● Marked mucosal and submucosal lymphangiectasia and short, broad villi (Medicine (Baltimore) 2007;86:210)
● Coarse eosinophilic material (macroglobulin) in lymphatics, macrophages, lamina propria



Other malignancies

Carcinoid tumor


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Low grade malignancy arising from epithelial stem cells in crypts
● Also called Neuroendocrine G1 (NET G1) tumor (WHO)

Clinical features
=========================================================================

● 50% of small bowel tumors
● Usually adults in 50’s, also children
● Most common in ileum (including Meckel’s diverticulum); also jejunum and distal duodenum
● Associated with celiac disease, bowel duplication, von Recklinghausen’s disease, inflammatory polyps
● 15-35% are multiple
● Slow growing, but can metastasize to regional lymph nodes, liver, bone, skin, thyroid
● Usually occur as small, dispersed nodules
Carcinoid syndrome in 1% (20% with widespread metastases)
● 5 year survival: 50-65% (85% if confined to bowel wall vs. 5% if serosal invasion)

Clinical features by Site
=========================================================================

Ileum:
● Patients with multiple tumors have higher incidence of carcinoid syndrome (22% vs. 2%) and poorer prognosis (Am J Surg Pathol 2003;27:811)

Duodenum:
● 2/3 express gastrin, 1/3 of these are associated with Zollinger-Ellison syndrome and are almost always metastatic
● May be associated with MEN1
● Duodenal carcinoids are less aggressive, usually don’t cause death vs. ampullary carcinoids (Hum Pathol 2001;32:1252)

Case reports
=========================================================================

● 55 year old man with angiomatous polyps simulating Crohn’s disease (Arch Pathol Lab Med 2000;124:450)
● 59 year old woman with metastases to cardiac conducting system (Arch Pathol Lab Med 2002;126:1538)

Treatment
=========================================================================

● Surgical excision of tumor and regional lymph nodes, excise solitary liver metastases

Gross description
=========================================================================

● Tumor protrudes through mucosa as small, polypoid lesion, intact or ulcerated overlying mucosa, buckling of bowel wall
● Bright yellow after formalin fixation, mean 2 cm

Gross images
=========================================================================



Carcinoid tumors

Micro description
=========================================================================

● Submucosal tumor that infiltrates muscularis propria
● Solid, insular (nesting), trabecular or glandular masses of monotonous small round cells with peripheral pallisading
● Moderate finely granular cytoplasm, small nucleoli, salt and pepper chromatin
● Angiolymphatic invasion common, mitotic figures rare
● Mucin present if glandular pattern
● Amphicrine cell pattern rare (endocrine and exocrine cells)
● Adjacent mucosa in ileal tumors shows angiomatous polyposis (mucosal edema, capillary ectasia, muscularis mucosa hypertrophy, fibrosis / smooth muscle proliferation in lamina propria, club-shaped villi, intramucosal capillary proliferation, although this is not specific for carcinoid tumors, Mod Pathol 2001;14:821)

Micro images
=========================================================================





Carcinoid tumors


With adjacent angiomatous polyposis


Ileal biopsy (courtesy of Dr. Hanni Gulwani)


Ileal biopsy (courtesy of Dr. Hanni Gulwani) - synaptophysin

Positive stains
=========================================================================

● Keratin, CEA, chromogranin, synaptophysin, Leu7, Fontana-Masson (argentaffin reaction)
● Also neuroendocrine secretory protein 55, Ghrelin, somatostatin receptor, CDX2, xenin, CK19 (Arch Pathol Lab Med 2008;132:1285)
● PAX8 (paired box) is expressed in duodenal carcinoids and negative in ileal carcinoids (Am J Surg Pathol 2010;34:723)
● Ileal carcinoid are positive for CDX2 and duodenal carcinoid are positive for PDX-1 (duodenal homeobox factor-1, Am J Surg Pathol 2009;33:626)
● Rarely PAP

Negative stains
=========================================================================

● Mucin, S100, CK7, CK20, TTF1

Electron microscopy description
=========================================================================

● Well formed, membrane bound, dense core secretory granules with dense (osmophilic) cores



Other malignancies

Carcinoid syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Occurs in 1% with carcinoid tumors, 20% with widespread metastases
● Elevated levels of 5 hydroxy-indoleacetic acid (5-HIAA), a metabolite, are found in blood and urine
● Normally liver deactivates vasoactive amines (serotonin, histamine, bradykinin, others) released from carcinoid tumors
● Clinical symptoms occur if liver metastases are present or if tumor venous blood flow bypasses the liver

Symptoms
=========================================================================

● Vasomotor disturbances (cutaneous flushes, cyanosis of face and anterior chest, intermittent hypertension), palpitations, intestinal hypermotility (nausea, vomiting, diarrhea, cramps)
● Also asthmatic attacks with bronchospasm, fibrosclerosis of AV and tricuspid valves, elastotic sclerosis of mesenteric vessels causing ischemia, dermal sclerosis, hepatomegaly

Carcinoid heart disease
=========================================================================

● Right sided focal or diffuse plaques of thickened valvular or mural endocardium that may extend to the great veins, coronary sinus, pulmonary trunk and main pulmonary arteries
● Tricuspid and pulmonic valves are usually affected by plaque formation
● Left heart and left sided valves are less frequently affected
● Endocardial fibrosis is a reaction to serotonin or kinin peptide exposure
● Plaques are composed of fibroblasts, myofibroblasts and smooth muscle cells embedded in a collagenous matrix, covered by a layer of endothelium
● No elastic tissue is present within the plaque



Other malignancies

Duodenal endocrine tumors


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Aggressive tumors - metastases common at diagnosis (21%)
● G cell (gastrin) tumors are associated with Zollinger-Ellison syndrome, MEN1 syndrome
● D cell (somatostatin) tumors are associated with neurofibromatosis 1 in blacks

Case reports
=========================================================================

● Duodenal gastrinoma with multiple gastric neuroendocrine tumors secondary to chronic Helicobacter pylori gastritis (Am J Surg Pathol 2012;36:935)

Gross description
=========================================================================

● 0.5 to 2 cm, smooth, round

Micro description
=========================================================================

● Features of carcinoid tumors
● Often G-cells or D-cells
● Usually glandular component present; psammoma bodies often present in D cell tumors



Malabsorption

Enteroendocrine cell dysgenesis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Enteroendocrine cells are part of body's largest endocrine system; secrete multiple regulatory molecules which control physiological and homeostatic functions, particularly postprandial secretion and motility (Therap Adv Gastroenterol 2008;1:51)
● Enteroendocrine cell dysgenesis is extremely rare (1 known paper) congenital life threatening malabsorptive condition (Stanford University)
● Defect is secondary to point mutations in NEUROG3, causing arrest of endocrine cell development in small intestine and colon (Hum Pathol 2007;38:570)

Micro images
=========================================================================



Various images



Other malignancies

Follicular dendritic cell sarcoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare tumor, first described in 1986 (Am J Pathol 1986;122:562)
● Usually presents as painless, indolent mass (occasionally pain but without constitutional symptoms)
● May be associated with Castleman’s disease-hyaline vascular type
● Need immunostains for diagnosis

Sites
=========================================================================

● Usually lymph nodes, predominantly cervical, axillary or mediastinal (Am J Hematol 1998;59:161)
● Extranodal sites include oral cavity, spleen, liver, small intestine, pancreas, peritoneum, soft tissue, skin

Poor prognostic factors
=========================================================================

● Large tumor size (6 cm or more), intraabdominal location and coagulative necrosis (Cancer 1997;79:294)

Case reports
=========================================================================

● 36 year old man with nausea, vomiting, diarrhea and abdominal pain (Case of the Week #81)

Treatment
=========================================================================

● Excision; often recurs locally, occasional distant metastases to liver or lung

Gross images
=========================================================================



Duodenal mass 10.5 x 10 cm

Micro description
=========================================================================

● Storiform arrangement of oval or spindled cells, lymphocytic infiltrate

Micro images
=========================================================================



Various images


CD35

Positive stains
=========================================================================

● CD21, CD35; occasionally S100

Negative stains
=========================================================================

● Desmin, smooth muscle actin, CD117/c-kit

Differential diagnosis
=========================================================================

● Fibroblastic reticulum cell sarcoma: vimentin+, smooth muscle actin+, desmin+, CD21-, CD35-
Gastrointestinal stromal tumor: CD117+, CD34+, CD21-, CD35-
● Interdigitating dendritic cell tumor: S100+, vimentin+, CD21-, CD35-
● Melanoma or other sarcomas



Other malignancies

Gastrointestinal autonomic tumor (GANT)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Variant of gastrointestinal stromal tumors with ultrastructural neural differentiation (Am J Surg Pathol 2001;25:979)
● Requires EM for diagnosis
● Mean age 55 years, usually men
● Usually small bowel, mesentery, retroperitoneum
● Usually malignant

Case reports
=========================================================================

63 year old woman (Chirurg 2001;72:600)

Gross description
=========================================================================

● >10 cm, well circumscribed, transmural involvement of bowel wall
● Tan-pink, lobulated, hemorrhagic with necrosis and cystic degeneration

Micro description
=========================================================================

● Interlacing spindle cells with minimal pleomorphism, skenoid fibers and myxoid change, 1-2 mitoses/10 HPF

Positive stains
=========================================================================

● CD117, CD34 (variable), vimentin, NSE

Negative stains
=========================================================================

● Muscle markers

Electron microscopy description
=========================================================================

● Neuron like cells with axonal cytoplasmic processes
● Synapse like structures
● Dense core neurosecretory granules

Electron microscopy images
=========================================================================



Various images



Other malignancies

Gastrointestinal stromal tumor (GIST)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Tumor which differentiates along line of interstitial cell of Cajal, the gut’s pacemaker cell

Clinical features
=========================================================================

● Median age 67 years, usually > 50 years
● May occur in HIV+ children
● 30-50% are malignant with 5 year survival of 50%; malignant tumors metastasize to liver and peritoneum
● Note: don’t call GIST if CD117 negative without expert concurrence
Types: spindle cell GIST (70%), epithelioid cell GIST (20%), mixed (10%)
● CD117- GIST: 5% predilection for stomach or omentum/peritoneum, exhibit epithelioid or mixed type
● Dedifferentiated GIST: rare, CD117- with marked anaplasia

Sites
=========================================================================

● GI sites: stomach (60%), jejunum and ileum (30%), duodenum (5%) and colorectum (<5%, Mod Pathol 2003;16:366)

Prognostic factors
=========================================================================

● Poor prognosis (malignant): over 5 cm, fresh tumor necrosis, extensive hemorrhage unrelated to surgery, hypercellular, marked atypia, 5+ mitotic figures/HPF, smaller cells
High risk: > 1 cm and > 5 MF/50 HPF; also infiltrative border within muscularis propria
Intermediate risk: 1-5 MF/50 HPF and > 1 cm
Low risk: < 1 cm (often are serosal)

Case reports
=========================================================================

● 45 year old woman with mid-jejunal mass and malignant GIST (Case of the Week #237)

Treatment
=========================================================================

● Gleevec (STI571) inhibits tyrosine kinases including CD117/KIT and Abl protein in CML

Gross description
=========================================================================

● Often large, well circumscribed, bulky, intramural masses
● Fish-flesh or tan-brown appearance, hemorrhage, necrosis, cystic softening

Gross images
=========================================================================



Case of Week #237 (pelvic mass was attached to the mid-jejunum)

Micro description
=========================================================================

● Usually histologically malignant, usually transmural, usually plump spindle cells with eosinophilic cytoplasm within variably hyalinized or edematous stroma
● Skenoid fibers (extracellular collagen globules) common
● Muscle infiltration is common but not predictive of behavior
● May have epithelioid morphology

Micro images
=========================================================================



Various images (H&E)


Case of Week #237


Low power jejunal GIST, ulcerated surface, few entrapped glands inside (courtesy of Dr. Hanni Gulwani)




Various immunostains

Positive stains
=========================================================================

● CD117 (Am J Surg Pathol 2003;27:625), CD34, vimentin
● Variable alpha smooth muscle actin, DOG1, Carbonic anhydrase II (Am J Surg Pathol 2009;33:1401)
● DOG1 and PKC8 can be used in the diagnosis of KIT negative GIST (Mod Pathol 2011;24:866)

Negative stains
=========================================================================

● S100, desmin

Electron microscopy description
=========================================================================

● Long interdigitating cytoplasmic processes, intercellular junctions, dense core granules

Molecular description
=========================================================================

● Activating mutations in KIT or platelet-derived growth factor receptor &alpha receptor tyrosine kinases (Arch Pathol Lab Med 2011;135:1298)

Differential diagnosis
=========================================================================

Fibromatosis: may be CD117+ with some antibodies (Am J Surg Pathol 2000;24:947, Am J Surg Pathol 2001;25:549)
Inflammatory fibroid polyp: spindle and stellate cells with onion skinning around blood vessels, eosinophils, lymphocytes and plasma cells; CD34+ spindle cells are KIT-, DOG1-)
Leiomyoma-uterine type: attached to colon without wall involvement, resemble benign leiomyoma, actin+, desmin+, CD117-
Leiomyosarcoma: atypical histology, smooth muscle actin OR desmin positive, CD117-, CD34-, no KIT mutations


GIST-duodenum

General
=========================================================================

● Median age 56 years (range 10-88 years)
● Associated with neurofibromatosis type 1 (often with multiple tumors)
● Often long period to recurrence or metastases

Prognostic factors
=========================================================================

Poor prognostic factors:
● >5 cm, > 5 mitoses/50 HPF
● Epithelioid pattern with mucosal invasion

Good prognostic factors:
● <2 cm and <5 mitoses/50 HPF
● Organoid pattern with low cellularity

Gross description
=========================================================================

● Small intramural or external nodules or large masses extending into retroperitoneum

Micro description
=========================================================================

● Usually spindle cell tumors, often with skenoid fibers

Positive stains
=========================================================================

● CD117, CD34 (54%), smooth muscle actin (39%), S100 (20%)

Negative stains
=========================================================================

● Desmin (trapped smooth muscle fibers are positive)

Molecular description
=========================================================================

● KIT mutations in exon 11 (30%) and exon 9 (13%) are common



Other malignancies

Granulocytic sarcoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Myeloid leukemic cells that may present initially as small bowel mass causing abdominal pain and obstruction (Arch Pathol Lab Med 2006;130:1570)

Case reports
=========================================================================

● 28 year old woman with primary isolated myeloid sarcoma of GI tract (Intern Med 2010;49:853)
● 36 year old man with small bowel obstruction as presenting sign (Isr Med Assoc J 2011;13:507)
● 50 year old woman with aleukaemic myeloid sarcoma of small intestine (J Clin Pathol 2009;62:757)

Gross images
=========================================================================



Bowel has 2 concentric exophytic masses

Micro images
=========================================================================



Various images

Differential diagnosis
=========================================================================

● Bacterial infections: may have positive Leder stain



Other malignancies

Kaposi sarcoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Present in GI tract in 50% with AIDS, although symptoms in only 10% (diarrhea, protein-losing enteropathy, abdominal pain)

Case reports
=========================================================================

● 35 year old man with jejunal tumor (Rev Gastroenterol Peru 2005;25:285)
● 37 year old man with tumor of stomach and duodenum (Dig Endosc 2010;22:241)
● 39 year old and 74 year old patients with stomach and small bowel tumors (Pathol Res Pract 2007;203:227)

Gross description
=========================================================================

● Multiple red-brown or purple nodules, 5-15 mm

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Spindle cells that expand lamina propria and obliterate muscularis mucosa, extravasated red blood cells
● Often submucosal involvement

Micro images
=========================================================================



Kaposi sarcoma involving duodenal lamina propri; submucosal involvement is more common


Kaposi sarcoma of stomach, showing characteristic eosinophilic cytoplasmic inclusions (arrowheads), which may represent residua of phagocytosed red cells; inclusions are 60% sensitive for Kaposi sarcoma and relatively specific

Positive stains
=========================================================================

● CD34, CD31

Negative stains
=========================================================================

● S100, desmin, muscle specific actin



Other malignancies

Leiomyosarcoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Duodenal tumors - mean age 54 years (Am J Surg Pathol 2003;27:625)

Case reports
=========================================================================

● 43 year old woman with leiomyosarcoma of small intestine presenting as pelvic mass (Eur J Obstet Gynecol Reprod Biol 1996;66:187)
● 63 year old man with leiomyosarcoma of small intestine presenting as intussusception (Saudi J Gastroenterol 2005;11:170)

Gross description
=========================================================================

● Intraluminal, bulging, polypoid tumor (duodenal tumors - mean 14 cm)

Gross images
=========================================================================



Leiomyosarcoma of small bowel

Micro description
=========================================================================

● Resemble smooth muscle cells
● High grade features (pleomorphism, atypia, mitotic figures, necrosis)

Positive stains
=========================================================================

● Smooth muscle actin, desmin

Negative stains
=========================================================================

● CD34, CD117



Other malignancies

Metastases


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Often appear as multiple polypoid tumors causing obstruction or perforation
● Usually melanoma (see below), lung carcinoma, breast carcinoma, choriocarcinoma

Case reports
=========================================================================

● 21 year old man with osteosarcoma metastases presenting as small bowel polyp (Arch Pathol Lab Med 2000;124:1682)
● 61 year old woman with leiomyosarcoma causing intussusception (Arch Pathol Lab Med 2000;124:169)

Gross images
=========================================================================



Osteosarcoma metastatic to jejunum


Metastasis-site of origin not specified


Gall bladder carcinosarcoma: metastatic to small bowel (courtesy Dr. Semir Vranic, University of Sarajevo, Bosnia and Herzegovina)

Micro images
=========================================================================



Metastatic leiomyosarcoma


Metastatic osteosarcoma


Melanoma metastatic to small bowel

General
=========================================================================

● Often long period between primary and metastatic diagnosis
● Better prognosis if solitary versus multiple metastases

Case reports
=========================================================================

● 17 year old man and 60 year old woman with metastatic cutaneous melanomas (Int J Surg Case Rep 2012;3:395)

Gross images
=========================================================================



Metastatic cutaneous melanoma to jejunum

Micro description
=========================================================================

● Undifferentiated tumor with discohesive cells with pink cytoplasm, pleomorphic nuclei, macronucleoli, frequent mitotic figures
● Spindled or epithelioid cells

Micro images
=========================================================================



Melanoma from thigh of 50 year old Bosnian man metastatic to jejunum (H&E, S100, MelanA), courtesy of Dr. Semir Vranic, University of Sarajevo, Bosnia and Herzegovina


Various images

Positive stains
=========================================================================

● S100, HMB45, MelanA/Mart1

Negative stains
=========================================================================

● CD117, CD34, smooth muscle actin



Other malignancies

Mullerian adenosarcoma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Tumor with benign glandular component and malignan stromal component
● Rare in small bowel; associated with endometriosis and unopposed estrogen therapy (Am J Surg Pathol 2000;24:513)

Micro description
=========================================================================

● Proliferation of endometrioid glands and stroma with stromal condensation around glands, mild to moderate cytologic atypia of stroma and stromal mitoses
● May have stromal pseudodecidualization, focal epithelial atypia
● No definite malignant epithelial features



Other malignancies

Zollinger-Ellison syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Syndrome due to production of gastrin that enters systemic circulation by gastric, pancreatic or peripancreatic carcinoids
● Tumors may be very small and difficult to detect

Micro description
=========================================================================

● Variable villus abnormality with increased chronic inflammatory cells and neutrophils in lamina propria; may have surface erosions
● Also gastric foveolar metaplasia of duodenum
● May be normal by H & E but abnormal by EM



Miscellaneous

Transplantation


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Acute changes associated with transplantation (not rejection) are epithelial denudation, crypt regeneration, mild acute inflammation

Acute cellular rejection
=========================================================================

● Occurs weeks to months after transplantation
● Resembles graft vs. host disease with increase in lymphocytes in lymphoid tissues
● Crypt epithelial damage and apoptosis, chronic inflammation in lamina propria, epithelial lymphocytosis, lymphocytic infiltration of vessels

Chronic rejection
=========================================================================

● Fibrosis of bowel wall, vascular sclerosis
● May develop post-transplantation lymphoproliferative disorders associated with EBV infection
● Rejection is monitored by mucosal biopsy



Miscellaneous

Staging


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Does not apply to carcinoid tumors, GIST, lymphoma or sarcoma OR tumors in ileocecal value, Ampulla of Vater or Meckel’s diverticulum

Primary tumor (T)
=========================================================================

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1a: Tumor invades lamina propria
T1b: Tumor invades submucosa *
T2: Tumor invades muscularis propria
T3: Tumor invades through the muscularis propria into the subserosa or into the nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or less *
T4: Tumor perforates the visceral peritoneum or directly invades other organs or structures (includes other loops of small intestine, mesentery or retroperitoneum more than 2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct)

* Note: the nonperitonealized perimuscular tissue is, for jejunum and ileum, part of the mesentery and, for duodenum in areas where serosa is lacking, part of the interface with the pancreas

Regional lymph nodes (N)
=========================================================================

NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in 1-3 regional lymph nodes
N2: Metastasis in four or more regional lymph nodes

● Note: involvement of the celiac nodes is considered M1 disease for carcinomas of the duodenum, jejunum and ileum

Distant metastasis (M)
=========================================================================

M0: No distant metastasis
M1: Distant metastasis

Stage grouping
=========================================================================

Stage 0: Tis N0 M0
Stage I: T1-2 N0 M0
Stage IIA: T3 N0 M0
Stage IIB: T4a N0 M0
Stage IIIA: Any T N1 M0
Stage IIIB: Any T N2 M0
Stage IV: Any T any N M1



Other malignancies

Staging-GIST


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Staging system also used for GIST of esophagus, colorectum, mesentery and peritoneum

Primary tumor (T)
=========================================================================

TX: Primary tumor cannot be assessed
T0: No evidence for primary tumor
T1: Tumor 2 cm or less
T2: Tumor more than 2 cm but not more than 5 cm
T3: Tumor more than 5 cm but not more than 10 cm
T4: Tumor more than 10 cm in greatest dimension

● For ruptured tumors, use radiologic data to estimate tumor size

Regional lymph nodes (N)
=========================================================================

N0: No regional lymph node metastasis
N1: Regional lymph node metastasis

● Nodal metastases are extremely rare in GIST, so there is no routine indication for lymph node biopsy or lymph node dissection
● Use N0/pN0 if no information on nodal status; do not use NX

Distant Metastasis (M)
=========================================================================

M0: No distant metastasis
M1: Distant metastasis (specify site, if known)

● Most GISTs metastasize to intra-abdominal soft tissue or liver
● Intra-abdominal metastasis refers to tumor involvement in abdominal cavity away from the primary mass, usually to serosal surfaces of abdomen, pelvis, retroperitoneum
● Multiple primary tumors are associated with neurofibromatosis type 1 or familial GIST syndrome and should not be considered intraabdominal metastasis, although rare cases of multiple independent GISTs at different GI locations have been reported
● If no primary GI GIST is identified, solitary omental, mesenteric, pelvic or retroperitoneal GISTs should be considered primary tumors
● A liver metastasis implies metastatic tumor inside the liver parenchyma as 1 or more nodules, but adherence to liver capsule, even if extensive, should not be considered liver metastasis

Anatomic stage / prognostic groups
=========================================================================

Stage IA: T1-2 N0 M0 and low mitotic rate
Stage IB: T3 N0 M0 and low mitotic rate
Stage II: T1-2 N0 M0 and high mitotic rate or T4 N0 M0 and low mitotic rate
Stage IIIA: T1 N0 M0 and high mitotic rate OR T4 N0 M0 and low mitotic rate
Stage IIIB: T2-4 N0 M0 and high mitotic rate
Stage IV: N1 or M1

● Low mitotic rate: 5 or fewer per 50 HPF
● High mitotic rate: over 5 per 50 HPF
● The required total count of mitoses is per 5 mm2 on the glass slide (50 HPF for older microscopes, 20 HPF for newer microscopes)

Tables
=========================================================================



Guidelines for risk assessment of primary gastrointestinal stromal tumor

Additional references
=========================================================================

Protocol for the Examination of Specimens From Patients With GIST (pdf)



Miscellaneous

Staging – neuroendocrine tumors


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Click here for staging for ampullary tumors
● See also PubCan

Primary tumor (T)
=========================================================================

TX: Primary tumor cannot be assessed
T0: No evidence for primary tumor
T1: Tumor invades lamina propria or submucosa and size 1 cm or less
T2: Tumor invades muscularis propria or size > 1 cm
T3: Tumor invades through the muscularis propria into subserosal tissue without penetration of overlying serosa (jejunal or ileal tumors) or invades pancreas or retroperitoneum (ampullary or duodenal tumors) or into non-peritonealized tissues
T4: Tumor invades visceral peritoneum (serosa) or invades other organs

● For any T, add (m) for multiple tumors

Regional lymph nodes (N)
=========================================================================

NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis

● For duodenal tumors, the regional lymph nodes are duodenal, hepatic, pancreaticoduodenal, infrapyloric, gastroduodenal, pyloric, superior mesenteric, pericholedochal nodes
● For ileal and jejunal tumors, the regional lymph nodes are the cecal (for tumors arising in the terminal ileum), superior mesenteric, mesenteric nodes
● Metastases to celiac nodes are considered distant metastases

Distant Metastasis (M)
=========================================================================

M0: No distant metastasis
M1: Distant metastasis

Anatomic stage / prognostic groups
=========================================================================

Stage I: T1 N0 M0
Stage IIA: T2 N0 M0
Stage IIB: T3 N0 M0
Stage IIIA: T4 N0 M0
Stage IIIB: Any T N1 M0
Stage IV: M1 (any T, any N)



Miscellaneous

Features to report for tumors


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 21 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Tumor location
● Histologic type
● Histologic grade if relevant (well differentiated: >95% glands, moderately: 50-95% glands, poorly: 5-49% glands, undifferentiated: <5% glands)
● Tumor size
● Extent / depth of invasion
● Margin involvement (proximal, distal, radial [soft tissue closest to deepest tumor penetration]), and distance of tumor to margin
● Invasion of other structures
● Obstruction, perforation, ulceration, proximal dilation
● Nuclear grade, presence of necrosis
● Angiolymphatic invasion
● Other pathologic findings (polyps, Crohn’s disease, celiac disease)
● Nodal involvement (# involved, # identified)
● Results of special studies

Additional references
=========================================================================

Arch Pathol Lab Med 2000;124:46

End of Small bowel (small intestine) > Superpage > Tumor


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