I. NORMAL ANATOMY
A. The small intestine is 6 to 7 m long and divided into the duodenum, jejunum, and ileum. It begins at the distal gastric pylorus and ends at the ileocecal valve and is lined throughout its length by villous mucosa. The individual villus is a slender, fingerlike projection with a variable length-to-crypt ratio ranging from 3:1 to 5:1 (e-Fig. 14.1).* The epithelium consists predominantly of tall, columnar absorptive cells that have basally situated nuclei, eosinophilic cytoplasm, and an apical brush border. The absorptive cells rest on a visible, refractile terminal bar. Other cell types of the intestine include goblet cells, crypt cells, basal cells, Paneth cells, and endocrine cells; the granules of Paneth cells are refractile, eosinophilic, and supranuclear, whereas those of endocrine cells are smaller, eosinophilic but nonrefractile, and infranuclear. The lamina propria contains mixed inflammatory cells including plasma cells, although neutrophils are restricted to vascular channels. Peyer’s patches, which are lymphoid aggregates, are distributed throughout the small intestine mucosa. Intraepithelial lymphocytes (IELs) are normally rare (no more than one per five enterocytes at the tips of the villi), although an increased IEL density may be seen in epithelium overlying lymphoid aggregates or Peyer’s patches in the distal ileum where the associated villi may be shortened or even flattened. Shortened and broadened villi may also be seen in duodenal mucosa overlying Brunner’s glands.
B. The large intestine, or colon, is 1 to 1.5 m long and consists of the right and left colon. The right colon is further subdivided into the cecum, ascending, and proximal transverse colon; the left colon consists of the distal transverse, descending, and sigmoid colon, and the rectum. The mucosa contains evenly spaced, nonbranching crypts arranged perpendicularly to the lumen and extending from the surface to the muscularis mucosae (e-Fig. 14.2). Occasional branching crypts or slight crypt architectural distortion may be seen in the rectum and sigmoid colon, and in areas adjacent to lymphoid aggregates. Paneth cells may be seen until the mid-transverse colon and, as noted earlier, IELs can be prominent in epithelium overlying lymphoid aggregates. However, there are no villi, the lining epithelium has no microvilli and does not rest on a terminal bar, and goblet cells are more numerous (particularly in the left colon). The lamina propria components are similar to those of the small intestine, although the lamina propria is denser in the right colon, and muciphages (mucin-containing macrophages) are more common in the lamina propria of the left colon.
The entire small and large bowel mucosa rest on muscularis mucosae. This smooth muscle layer delineates the lamina propria from the submucosa which comprises loose fatty tissue with a rich angiolymphatic supply. The inner and outer layers of the muscularis propria lie below the submucosa and are separated by the ganglio-neuronal Auerbach plexus. The entire surface of the
intestines is covered by visceral peritoneum (serosa) up to the distal portion of the rectum.
C. The appendix is a tubular organ that extends from the cecum. It has an average length of 7 to 10 cm and has a mucosa that is similar to the large intestine, except for the presence of more prominent lymphoid aggregates which often have well-formed germinal centers. The appendix also has a poorly developed muscularis mucosae that may be interrupted by lymphoid aggregates.
D. The anal canal, the terminal 3 to 4 cm of the gastrointestinal (GI) tract, is an anatomically complex area (e-Fig. 14.3). This chapter employs the surgical anal canal terminology as defined by the most current WHO classification of tumors (discussed later). The mucosa lining the upper portion of the anal canal is a direct extension of the rectal mucosa (colorectal mucosa). The mucosa lining the middle portion of the anal canal (the so-called anal transitional zone (ATZ), a 0.5- to 1-cm segment above the dentate line) has the features of both metaplastic squamous mucosa and urothelium. Submucosal and intramuscular anal glands open into the ATZ via anal ducts that are also lined by ATZ epithelium. The mucosa of the distal anal canal, which extends from the dentate line to the anal verge, consists of specialized nonkeratinizing squamous mucosa with melanocytes. It is distinguished from the perianal skin by the lack of skin appendages.
II. GROSS EXAMINATION AND SPECIMEN HANDLING
A. Endoscopic biopsy. When processing the specimen, it is important to record pertinent clinical history and endoscopic findings. Biopsies are typically small fragments of mucosal tissue in the range of 1 to 5 mm in greatest dimension that do not need to be inked or subdivided. Important gross descriptors are the number, size, and the size range of the biopsy fragments. In cases where numerous fragments are present, an estimate for the number and the dimensions in aggregate should be given (documentation of the number and size is important to ensure that the biopsies are adequately represented on the slides). Routine microscopic examination of endoscopic biopsies usually entails examination of three hematoxylin and eosin (H&E)-stained levels.
B. Suction biopsy of the rectum, which makes possible sampling of the submucosa, is used for evaluation of Hirschsprung’s disease. After processing, the tissue is serially sectioned in its entirety, but initially only every third level is H&E-stained; if no ganglion cells are identified in these slides, the remaining sections are stained and examined. In some labs, frozen sections are performed for histochemical staining by the acetylcholinesterase reaction to identify proliferating nerve fibers in the lamina propria and muscularis mucosae.
C. Polypectomy specimens should be described and measured. The need for inking of the resection margin is a controversial topic; in practice, it is often difficult to do since the stalk retracts and thus may be hard to identify grossly (although the cauterized base can be easily identified microscopically). The specimen is bisected or serially sectioned depending on its size, and entirely submitted. Sectioning should follow the vertical plane of the stalk to maximize the evaluation of the polypectomy margin. At least three H&E levels are examined.
D. Endoscopic mucosal resections can be single or multiple fragments. All dimensions are recorded and the mucosal surface described. Inking of the margins is a matter of choice since cautery artifact will be noted at the time of microscopic evaluation for deep and mucosal margins, and since ink may actually artifactually extend along non-marginal mucosa. The entire specimen is serially sectioned, and the fragments are oriented and entirely submitted.
E. Bowel resection.
1. Neoplastic. Tumor resections include segmental resection of a portion of small or large bowel, ileocolectomy, low anterior resection (LAR), abdominoperineal resection (APR), total colectomy, and total mesorectal
excision (TME). The portion of resected bowel is oriented, and the length, diameter (or circumference), and wall thickness are measured. The length and diameter of the appendix and the dimensions of mesentery are also measured, if present. The external surface (serosa in most cases) of the bowel is inspected for tumor involvement, perforation, adhesion, and fat wrapping. For TME specimens, the grossly observable completeness of the mesorectum is evaluated as “complete,” “near complete,” or “incomplete” before opening the bowel (see College of American Pathologists Cancer Protocols for Colon and Rectum at www.cap.org). The bowel is opened longitudinally along the antimesenteric border, unless this would mean cutting through the tumor.
The maximal size of the tumor and the distance to the proximal and distal resection margins, or to the closest margin in unoriented specimens, are documented. After fresh tissue is collected for biobanking (as needed), the specimen is pinned out on a wax board (mucosal side up) and fixed by submerging in 10% formalin overnight. The tumor is then sectioned to assess the depth of invasion; blocks for microscopic examination are taken to include the area of deepest penetration and the relationship to adjacent, grossly nonneoplastic mucosa. Additional sections include proximal and distal resection margins; if tumor approximates the margin, such as in APR or LAR specimens, the margin should be inked and multiple sections perpendicular to the margin submitted; if the inked radial margin is not included in the tumor sections, one separate radial margin section should be submitted. One random section from normal-appearing bowel, and sections from any additional gross lesions (such as separate polyps), should also be submitted. If the appendix is present, it is handled as an appendectomy specimen as described later.
The mesentery and soft tissue are also dissected for lymph nodes (many nodes are located along large vessels), and the number and size range of identified nodes are recorded. Small lymph nodes can be submitted in toto without sectioning. Larger nodes are serially sectioned and the cut surfaces examined; if metastatic carcinoma is grossly appreciated, as evidenced by a white and hard cut surface, the size of the metastatic deposit should be recorded, and one representative section from each grossly positive node should be submitted. If the cut surfaces of the nodes are tan, soft, homogeneous, and lack gross evidence of metastasis, the entire node should be submitted for microscopic evaluation. Although a minimum of 12 nodes is required by established staging criteria, all nodes that can be found should be submitted. Fewer nodes may be acceptable for small specimens, for cases that have received preoperative chemoradiation, and for APR or LAR specimens (because lymph nodes are less numerous below the peritoneal reflection). However, when fewer than 12 nodes are identified, a second attempt to dissect lymph nodes is strongly recommended (and should be documented in the pathology report).
2. Nontumor bowel resections
a. For polyposis specimens, pinning and gross examination are similar as for tumor specimens. Sampling focuses on the largest lesions, lesions with a distinct or worrisome gross appearance (including firmness, ulceration, and adherence to the wall), and flat and depressed areas of mucosa.
b. Resections for inflammatory bowel disease (IBD), particularly for ulcerative colitis (UC), require sequential sections spaced every 10 cm. The sections include transition regions between normal-appearing and diseased segments, distal and proximal margins, and representative inflammatory polyps. Any focal lesions (such as areas with raised mucosa), fistula tracts, and strictures are sampled. The appendix, if present, is handled
as an appendectomy specimen, as described later. Representative lymph nodes are submitted, but there is no need for extensive sampling unless a carcinoma is suspected or identified.
c. Miscellaneous resections. In the case of ischemic necrosis, the mesenteric vessels should be carefully examined and sampled to evaluate the possibility of thrombosis, embolization, or vasculitis. For penetrating traumatic injuries, inspection for possible entry and exit wound sites is important. It is also important to grossly and microscopically examine the proximal and distal resection margins for tissue viability.
When proctectomy or rectosigmoid resection is performed for Hirschsprung’s disease, the distal margin is usually indicated by the surgeon. Sequential sections every 1 to 2 cm from distal to proximal should be submitted to achieve an accurate estimation of the aganglionic region.
F. For appendectomy specimens, the length, diameter, surface appearance, and dimensions of the specimen, including the mesoappendix, are recorded. For a nonneoplastic appendix, one half of the longitudinally bisected tip, the proximal margin, and two cross-sections are submitted in a single cassette, to include the mid-portion and any possible perforation. For a neoplastic appendix, after photography and gross description, the specimen is bread loafed and submitted in its entirety. In cases of pseudomyxoma peritonei, any associated mucin is also submitted in toto.
G. Anal biopsy is treated similarly to other GI biopsies.
H. Endomucosal resection (EMR) specimens are processed as are esophageal EMR specimens (as discussed earlier).
I. Hemorrhoidal excision requires one section.
III. DIAGNOSTIC FEATURES OF NONNEOPLASTIC CONDITIONS OF THE SMALL INTESTINE
A. Congenital anomalies
1. Heterotopic gastric mucosa typically presents as a small nodule or sessile polyp in the duodenal bulb and consists of full-thickness fundic-type oxyntic mucosa. It differs from foveolar surface metaplasia in which the surface epithelium of the duodenal mucosa is replaced by gastric foveolar cells (e-Fig. 14.4), and which is often associated with duodenitis secondary to Helicobacter pylori infection.
2. Heterotopic pancreas presents as a mass lesion in the duodenum and is composed of ducts and acini, with or without islets.
3. Meckel’s diverticulum results from persistence of the proximal portion of the vitelline duct and is always located on the antimesenteric border of the ileum. Associated heterotopic pancreatic tissue or gastric mucosa is common. Congenital diverticulum is a rare occurrence in the duodenum and jejunum (e-Figs. 14.5 and 14.6).
4. Malrotation, stenosis, atresia, duplication, and defects of the musculature are rare. Duplications can be cystic or tubular; about 75% are not contiguous with the lumen of the associated bowel segment. Duplications contain all the layers of the segment from which they have arisen, although mucosal heterotopias may occur. Any segment of the GI tract may be involved, and duplications are not associated with other anomalies. Neuroenteric remnants most commonly occur in the cervicothoracic or lumbosacral regions and also contain all the layers of the originating segment; however neuroenteric remnants originate from the dorsal midline and are associated with other congenital anomalies. Neural elements may be observed, primarily in lesions approximating the spinal cord.
B. Malabsorptive disorders
1. Celiac disease, also known as gluten-sensitive enteropathy, celiac sprue, or nontropical sprue, is an immune-mediated disorder secondary to hypersensitivity to α-gliadin. Classic histologic features include villous atrophy, crypt
hyperplasia, intraepithelial lymphocytosis, a dense lamina propria lymphoplasmacytic infiltrate, and enterocyte damage. Villous atrophy ranges from partial blunting or broadening to complete flattening, but the overall thickness of the mucosa may not be reduced significantly due to crypt hyperplasia (e-Figs. 14.7 and 14.8). Eosinophils and neutrophils may be present in the infiltrate but are usually not prominent. Enterocyte damage is evidenced by flattening and/or cytoplasmic vacuolization. The Marsh-Oberhuber classification scheme describes five histologic lesions of gluten-sensitive enteropathy but is not widely used in routine practice.
TABLE 14.1 Conditions That Can Mimic Gluten-Sensitive Enteropathy
Celiac disease/gluten-sensitive enteropathy
Tropical sprue
Autoimmune enteropathy
HIV enteropathy
Common variable immunodeficiency
Viral enteritis
Giardiasis
Bacterial overgrowth
Infectious enteritis
Food allergies
Crohn’s disease
Zollinger-Ellison syndrome
Systemic autoimmune diseases
Dermatitis herpetiformis
Nonsteroidal anti-inflammatory drugs
Helicobacter pylori infection
An increased number of IELs in villous tips is an important diagnostic feature that has also been described as “loss of the decrescendo pattern.” Although the increase is defined as >40 lymphocytes per 100 enterocytes, a formal count or immunostaining for T lymphocytes is usually unnecessary since lymphocytosis is typically diffuse and evenly distributed along the entire length of the villi (if the mucosa is not completely flattened).
Increased IELs may be the only histologic finding in early, latent, or partially treated celiac disease; serologic tests should be suggested in these cases. However, since many other conditions in addition to celiac disease can result in IEL, the pathologic diagnosis should remain descriptive (Table 14.1). The vast majority of patients with celiac disease have HLA-DQ2 or HLA-DQ8 and their absence almost excludes the diagnosis (Arch Pathol Lab Med. 2010;134:826).
2. Refractory sprue refers to unresponsiveness to a gluten-free diet or relapse of symptoms despite gluten restriction. It is histologically indistinguishable from classic celiac disease; some gastroenterologists regard it as a type of T-cell lymphoma. Neutrophils may be more numerous.
3. Collagenous sprue is characterized by villous flattening and subepithelial collagen deposition.
4. Autoimmune enteropathy shares many clinical and histopathologic features with celiac disease but often involves both the small and the large intestines. A biopsy typically exhibits villous flattening and dense lamina propria lymphoplasmacytic infiltrates (e-Figs. 14.9 and 14.10). In contrast to celiac disease, intraepithelial lymphocytosis and crypt hyperplasia may not be evident, and neutrophils may be more numerous. Apoptotic bodies may be
apparent. A complete lack of goblet cells and/or Paneth cells may be seen in some cases. Although some patients have anti-enterocyte and/or antigoblet cell antibodies, serologic tests are not routinely employed. A clinical response to steroids may help establish the diagnosis.
5. Eosinophilic gastroenteritis involving the small intestine exhibits histologic features similar to those described for eosinophilic gastritis (e-Fig. 14.11). There may or may not be villous blunting, but IELs are usually not increased. Parasitic infestations, food allergy including cow’s milk protein intolerance, a drug reaction, connective tissue disorders, and a neoplasm should be excluded.
6. Common variable immunodeficiency is characterized by the absence of lamina propria plasma cells (e-Fig. 14.12). Other features may include a variable degree of villous blunting, intraepithelial lymphocytosis, and lymphoid aggregates. Infectious agents, particularly Giardia, should be searched for in these biopsies.
7. Microvillus inclusion disease is a rare autosomal recessive disease causing intractable diarrhea in infancy. The hallmark of the disease is the loss of a normal brush border on the luminal surface of the enterocytes. Instead, the brush border is incorporated into the cytoplasm as apical microvillus inclusions. The microscopic features can be best demonstrated by periodic acid-Schiff (PAS) stain, electron microscopy, and immunostains for carcinoembryogenic antigen, CD10, or villin. Diffuse villous atrophy is also present, but an inflammatory response and intraepithelial lymphocytosis are not evident.
8. Lymphangiectasia, either primary (congenital) or secondary (due to obstruction), may present as a localized mass lesion or diffusely involve the bowel (e-Fig. 14.13). The presence of secondary lymphangiectasia is concerning for an unsampled underlying mass lesion as the source of obstruction, which should be mentioned in the report.
9. Abetalipoproteinemia features lipid accumulation in enterocytes giving rise to a clear or foamy appearance. The normal villous architecture is well preserved.
C. Infectious diseases
1. Tropical sprue and bacterial overgrowth simulate celiac disease but may involve the entire small intestine with more severe disease distally. Clinical history, including any travel history, is important in establishing the diagnosis.
2. Giardiasis does not induce significant villous architectural change or an inflammatory response. The diagnosis is based on the identification of pearshaped trophozoites at the luminal surface of normal-appearing mucosa (e-Fig. 14.14), which can be mistaken as cytoplasmic debris. The organisms can be highlighted by trichrome and Giemsa stains.
Whipple disease exhibits distended villi due to lamina propria accumulation of foamy macrophages stuffed with the diastase-resistant, PAS-positive (e-Fig. 14.15), rod-shaped bacterium Tropheryma whippelii. The microorganisms can also be detected by polymerase chain reaction (PCR) analysis and electron microscopy. Gomori’s methenamine silver (GMS), acid-fast bacilli (AFB), or Fite stains should be performed on these biopsies to rule out fungal (histoplasmosis) or mycobacterial (due to Mycobacterium avium intracellulare) infections because the morphology of these infections are quite similar to Whipple disease on H&E stain.
3. Cryptosporidiosis is characterized by uniform, spherical, 2- to 4-μm bodies attached to the brush border that appear bluish on H&E stain (e-Fig. 14.16). The organisms may be confused with mucin droplets.
4. Strongyloidiasis is diagnosed by identification of larvae, eggs, and adult worms embedded in the crypts (e-Fig. 14.17). Eosinophils, sometimes with Charcot-Leyden crystals, may be prominent. The nematodes most commonly infect the small intestine, but also rarely infect the stomach and colon. Gastric strongyloidiasis may sometimes be associated with infection by human T-lymphotropic virus type 1, a virus that causes adult T-cell lymphoma/leukemia.
IV. DIAGNOSTIC FEATURES OF POLYPS AND NEOPLASMS OF THE SMALL INTESTINE. The WHO classification scheme of tumors of the small intestine is given in (Table 14.2)
A. Brunner’s gland hyperplasia, hamartoma, and adenoma may actually be variants of the same process and consist of expanded lobules of benign Brunner’s glands separated by delicate fibrous septa. They are typically located in the submucosa, but penetration into the mucosa is common. Cystic degeneration may occur, which has been termed Brunner’s gland cyst.
B. Peutz-Jeghers polyp, while most common in the small intestine, also occurs in the colon and stomach. It is a hamartomatous polyp characterized by an arborizing network of smooth muscle supporting benign-appearing mucosa that may be hyperplastic (e-Fig. 14.18). Most polyps occur as part of an inherited cancer syndrome, but sporadic cases may be encountered. Because syndromic polyps carry an increased risk of cancer, they should always be assessed for dysplasia.
C. Adenomyoma of the ampulla of Vater exhibits an orderly arranged lobular pattern of benign pancreaticobiliary ducts in a background of proliferating smooth muscle. It may coexist with heterotopic pancreas.
D. Adenomas are rare in the small intestine and usually occur in the duodenum. Multiple adenomas are almost always associated with familial adenomatous polyposis (FAP). Histologically identical to their colorectal counterparts, they are classified into tubular, tubulovillous, and villous types. The differential diagnosis includes gastric surface metaplasia and reparative change.
E. Adenocarcinoma of the small intestine is rare, accounting for only 2% of all primary GI tumors despite the fact that the small intestine constitutes about 75% of the length and about 90% of the mucosal surface of the GI tract (Table 14.3). Adenocarcinoma of the small intestine is morphologically indistinguishable from colorectal adenocarcinoma, but most cases are cytokeratin 7 (CK7)-positive which may help resolve the differential diagnosis.
F. Ampullary carcinoma is actually a heterogeneous group of tumors. It arises in the vicinity of the ampulla of Vater and includes the most common intestinal-type adenocarcinoma as well as the pancreaticobiliary type. The former has a more favorable outcome than the latter, although the overall survival of ampullary carcinoma is better than that of pancreatic ductal carcinoma (which probably reflects differences in respectability). However, distinguishing the site of origin is sometimes a challenge (Table 14.4).
G. Neuroendocrine tumor (NET) accounts for one-third of small intestinal tumors. Duodenal NETs are derived from endocrine cells of the foregut and tend to be <2 cm in greatest dimension and asymptomatic. Gastrin-producing NETs are associated with ZES (Zollinger-Ellison syndrome) in 40% to 50% of cases. Distal jejunum and ileal NETs are derived from cells of the midgut; 25% to 30% are multifocal, and clinically they are more aggressive than proximal NET.
Microscopically, small intestinal NET are similar to NET arising elsewhere (e-Fig. 14.19) and have a very bland cytomorphology; invasion into or beyond the muscularis propria and/or distant metastasis are the main criteria for determining malignant behavior. In contrast, poorly differentiated NET exhibit overt histologic features of malignancy. Tables 14.5 and 14.6 summarize the current WHO classification and AJCC staging schemes, respectively.
TABLE 14.2 WHO Histologic Classification of Tumors of the Small Intestine
Epithelial tumors
Adenoma
Tubular
Villous
Tubulovillous
Dysplasia (intraepithelial neoplasia), low grade
Dysplasia (intraepithelial neoplasia), high grade
Hamartomas
Peutz-Jeghers polyp
Juvenile polyp
Carcinoma
Adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Squamous cell carcinoma
Adenosquamous carcinoma
Medullary carcinoma
Undifferentiated carcinoma
Neuroendocrine neoplasms
Neuroendocrine tumor (NET)
NET, G1 (carcinoid)
NET, G2
Neuroendocrine carcinoma (NEC)
Large cell NEC
Small cell NEC
Mixed adenoneuroendocrine carcinoma (MANEC)
EC cell, serotonin-producing NET
Gangliocytic paraganglioma
Gastrinoma
L-cell, glucagon-like peptide and PP/PYY-producing NETs
Somatostatin-producing NET
Mesenchymal tumors
Lipoma
Leiomyoma
Gastrointestinal stromal tumor
Leiomyosarcoma
Angiosarcoma
Kaposi sarcoma
Others
Lymphomas
Burkitt lymphoma
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma
Diffuse large B-cell lymphoma
Immunoproliferative small intestinal disease (includes α-heavy chain disease)
Follicular lymphoma
Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)
Mantle cell lymphoma
T-cell lymphoma
Enteropathy associated T-cell lymphoma (EATL)
Secondary tumors
WHO, World Health Organization; EC, enterochromaffin; PP, pancreatic polypeptide; PYY, polypeptide YY.
From: Bosman FT, Carneiro F, Hruban RH, Theise ND, eds. World Health Organization Classification of Tumours of the Digestive System. Lyon: IARC Press; 2010. Used with permission.
TABLE 14.3 Tumor, Node, Metastasis (TNM) Staging Scheme for Small Intestinal Carcinomas
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 submucosaa
T2
Tumor invades muscularis propria
T3
Tumor invades through the muscularis propria into the subserosa, or into nonperitonealized perimuscular tissue (mesentery or retroperitoneum) with extension 2 cm or lessa
T4
Tumor perforates the visceral peritoneum or directly invades other organs or structures (includes other loops of small intestine, mesentery, or retroperitoneum >2 cm, and abdominal wall by way of serosa; for duodenum only, invasion of pancreas or bile duct)
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 4 or more regional lymph nodes
Distant metastasis (M)
M0
No distant metastasis
M1
Distant metastasis
Stage grouping
Stage 0
Tis
N0
M0
Stage I
T1
N0
M0
T2
N0
M0
Stage IIA
T3
N0
M0
Stage IIB
T4
N0
M0
Stage IIIA
Any T
N1
M0
Stage IIIB
Any T
N2
M0
Stage IV
Any T
Any N
M1
a 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 retroperitoneum.
From: Edge SB, Byrd DR, Compton CC, et al., eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010. Used with permission.
H. Gangliocytic paraganglioma occurs almost exclusively in the periampullary region and is benign in the majority of cases. As in other locations, the tumor consists of a mixture of ganglion-like cells, Schwannian cells, and epithelioid endocrine-like cells (e-Fig. 14.20). S-100 positivity is a useful marker to differentiate the neoplasm from a gastrointestinal stromal tumor (GIST).
I. GIST of the small intestine accounts for 30% to 40% of all GISTs of the GI tract and tends to be more aggressive than its gastric counterpart (Table 14.7) (Am J Surg Pathol. 2006;30:477-89). Table 14.8 summarizes the current AJCC staging scheme of GIST arising outside of the stomach.
J. Immunoproliferative small intestinal disease (IPSID) is a distinct type of extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue [MALT] lymphoma), typically seen in young adults in Middle Eastern and Mediterranean countries. About half of patients exhibit characteristic α-heavy
chain paraproteinemia without associated light chains (α-heavy chain disease). Patients present with malabsorption and diarrhea. Some patients progress to diffuse large B-cell lymphoma.
TABLE 14.4 Tumor, Node, Metastasis (TNM) Staging Scheme for Ampullary Carcinoma
Primary tumor (T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
Tis
Carcinoma in situ
T1
Tumor limited to ampulla of Vater or sphincter of Oddi
T2
Tumor invades duodenal wall
T3
Tumor invades pancreas
T4
Tumor invades peripancreatic soft tissues or other adjacent organs or structures
Regional lymph nodes (N)
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Regional lymph node metastasis
Distant metastasis (M)
M0
No distant metastasis
M1
Distant metastasis
Stage grouping
Stage 0
Tis
N0
M0
Stage IA
T1
N0
M0
Stage IB
T2
N0
M0
Stage IIA
T3
N0
M0
Stage IIB
T1
N1
M0
T2
N1
M0
T3
N1
M0
Stage III
T4
Any N
M0
Stage IV
Any T
Any N
M1
From: Edge SB, Byrd DR, Compton CC, et al., eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010. Used with permission.
TABLE 14.5 Classification and Grading of Neuroendocrine Neoplasms of the GI Tract
Classification
Grade
Definition
Neuroendocrine tumor (carcinoid)
I
Cytologically bland, mitotic count <2 per 10 high power fields (HPFs) and/or 2% ≤Ki 67 indexa
II
Cytologically bland, mitotic count 2-20 per 10 HPFs and/or 3-20% Ki 67 index
Neuroendocrine carcinoma (NEC)
III
Mitotic count >20 per 10 HPF and/or >20% Ki 67 index
MANEC
Hyperplastic and preneoplastic lesions
Tumor displaying at least 30% of adenocarcinoma or NEC
GI, gastrointestinal.
a Grading requires mitotic count in at least 50 HPFs and Ki67 percentage in at least 500-2000 cells within the areas of strongest nuclear labeling.
From: Bosman FT, Carneiro F, Hruban RH, Theise ND, eds. World Health Organization Classification of Tumours of the Digestive System. Lyon: IARC Press; 2010. Used with permission.
TABLE 14.6 Tumor, Node, Metastasis (TNM) Staging Scheme for Neuroendocrine Tumors of Duodenum/Ampulla/Jejunum/Ileum
Primary tumor (T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
T1
Tumor invades lamina propria or submucosa and ≤1 cma in size (small intestinal tumors); tumor ≤1 cm (ampullary tumors)
T2
Tumor invades muscularis propria or >1 cm in size (small intestinal tumors); tumor >1 cm (ampullary tumors)
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 nonperitonealized tissues
T4
Tumor invades visceral peritoneum (serosa) or invades other organs For any T, add (m) for multiple tumorsaTumor limited to ampulla of Vater for ampullary gangliocytic paraganglioma
Regional lymph nodes (N)
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Regional lymph node metastasis
Distant metastasis (M)
M0
No distant metastasis
M1
Distant metastasis
Stage grouping
Stage 0
Tisa
N0
M0
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
Any T
Any N
M1
a Tis applies only to stomach.
From: Edge SB, Byrd DR, Compton CC, et al., eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010. Used with permission.
TABLE 14.7 Proposed Guidelines for Assessing the Malignant Potential of Small Intestinal GISTs
Tumor
Predicted biologic behavior
≤2 cm, ≤5 mitoses/50 HPFs
Benign, metastasis rate or tumor-related mortality: 0
>2 ≤5 cm, <5 mitoses/50 HPFs
Low malignant potential, metastasis rate or tumor-related mortality: 4%
>5 ≤10 cm, ≤5 mitoses/50 HPFs
Moderate malignant potential, metastasis rate or tumor-related mortality: 25%
>10 cm, or >5 mitoses/50 HPFs
High malignant potential, metastasis rate or tumor-related mortality: 50-90%
GIST, gastrointestinal stromal tumor; HPFs, high-power fields.
Modified from Am J Surg Pathol. 2006;30:477-89.
TABLE 14.8 Tumor, Node, Metastasis (TNM) Staging Scheme Gastrointestinal Stromal Tumors (Excluding Stomach)
Primary tumor (T)
TX
Primary tumor cannot be assessed
T0
No evidence of primary tumor
T1
Tumor 2 cm or less
T2
Tumor >2 cm but not >5 cm
T3
Tumor >5 cm but not >10 cm
T4
Tumor >10 cm in greatest dimension
Regional lymph nodes (N)
NX
Regional lymph nodes cannot be assessed
N0
No regional lymph node metastasis
N1
Regional lymph node metastasis
Distant metastasis (M)
M0
No distant metastasis
M1
Distant metastasis
M1a
Lung
M1b
Other distant sites
Stage Grouping
Mitotic rate
Stage IA
T1 or T2
N0
M0
Low
Stage II
T3
N0
M0
Low
Stage IIIA
T1
N0
M0
High
T4
N0
M0
Low
Stage IIIB
T2
N0
M0
High
T3
N0
M0
High
T4
N0
M0
High
Stage IV
Any T
N1
M0
Any rate
Any T
Any N
M1
Any rate
Low mitotic rate: 5 or fewer per 50 HPFs; high mitotic rate: over 5 per 50 HPFs.
From: Edge SB, Byrd DR, Compton CC, et al., eds. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010. Used with permission.
K. Enteropathy-type T-cell lymphoma typically develops in the setting of refractory sprue and ulcerative jejunitis or jejunoileitis, and most commonly affects the jejunum. It is characterized by dense infiltration of atypical T lymphocytes in association with epithelial destruction.
V. DIAGNOSTIC FEATURES OF NONNEOPLASTIC CONDITIONS OF THE LARGE INTESTINE
A. Neuromuscular disorders
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
The Intestines, Appendix, and Anus
The Intestines, Appendix, and Anus
ILKe Nalbantoglu
Elizabeth M. Brunt
