Laboratory Studies
The following studies are indicated in patients with intestinal polyposis syndromes:
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CBC count with differential and platelets
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Stools for occult blood
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Prothrombin time/activated partial thromboplastin time (if significant bleeding is present)
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Serum albumin levels (if weight loss is present)
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Genetic testing, including band 5q21-22 for Gardner syndrome (ie, familial adenomatous polyposis [FAP]), band 7p22, 5q21-22, and 3p21.3 for Turcot syndrome, band 19q13.3-13.4 for Peutz-Jeghers syndrome (PJS), band 10q23.3 for Bannayan-Riley-Ruvalcaba syndrome (BRR) and Cowden disease, band 9q22.3-q31 for Gorlin syndrome (GS)
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Fecal alpha1-antitrypsin or fecal calprotectin (if albumin is low and weight loss is present; to evaluate for protein-losing enteropathy)
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Levothyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), thyroid antimicrosomal or thyroid peroxidase antibody to exclude Hashimoto thyroiditis in individuals with symptomatic BRR syndrome
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Liver function tests and alpha-fetoprotein level to screen for hepatoblastoma in patients with suspected Gardner syndrome and an abdominal mass; electrolytes, plasma or urine cortisol, and adrenocorticotropic hormone (ACTH) in patients with suspected Gardner syndrome if Cushing syndrome is present
Imaging Studies
The role of imaging studies in favor of endoscopic examination has not been well established for individuals with intestinal polyposis syndromes. [60] Examples of endoscopic findings are shown in the images below.
Multiple large polyps in the colon. The polyp in the center of the image is situated on a stalk. (Endoscopic image).
For those individuals with small bowel polyposis, double balloon enteroscopy (DBE), both antegrade and retrograde, can be successful in reaching and resecting targeted polyps. [61]
Upper GI with small bowel follow through (SBFT) can be used to evaluate for polyps but incurs radiation exposure.
Thus, video capsule endoscopy is an emerging modality used to evaluate for small bowel polyps that spares radiation for the patient (see the image below). [62, 63] It has been shown to be better than UGI with SBFT for polyp detection rate, comfort, and patient preference. [64]
Air-contrast barium enema (BE) can be used to evaluate for colonic polyps in patients who are not candidates for colonoscopic examination.
Magnetic resonance enterography can be used for small bowel surveillance of polyps as well and serves as a complementary study to video capsule endoscopy, especially because the capsule can overestimate polyps secondary to retrograde flow. [64]
Air-contrast barium enema (BE) can be used to evaluate for colonic polyps in patients who are not candidates for colonoscopic examination.
Contrast-enhanced ultrasonography is emerging as a noninvasive technique to characterize vascular patterns of polyps with the aim of recognizing neoangiogenic traits of colorectal adenomas and carcinomas. This imaging modality may help differentiate hamartomatous polyps from adenomatous polyps, which may have malignant potential, especially in PJS. [65]
Additional imaging studies in patients with Gardner syndrome may include the following:
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Radiographs of the skull, teeth, and mandible to screen for osteomas and plan management of dental anomalies
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CT scanning, ultrasonography, or MRI of the abdomen to evaluate abdominal masses (hepatoblastoma, adrenal carcinoma, mesenteric fibromas/desmoids)
In patients with Turcot syndrome, CNS imaging, GI imaging, and other imaging modalities are indicated if Gardner syndrome is suspected, as clinically warranted.
For patients with known PJS, perform routine screening, mammogram, and breast ultrasound for early detection of occult neoplasms. Perform ultrasonography or CT scanning of the pelvis or testicles to screen for possible malignancies in patients with conditions such as gynecomastia and precocious puberty.
For patients with known PTEN- hamartomatous syndrome imaging studies include the following:
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Routine breast imaging to screen for neoplasia (Seventy five percent of females develop breast neoplasia.)
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Imaging of the thyroid, if suggestive of malignancy
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Imaging of the ovaries, if suggestive of malignancy
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MRI of the head, if symptomatic
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Radiography of the spine to monitor for scoliosis
For patients with known GS, perform radiography of the mandible, ribs, and spine to diagnose and treat anomalies. Perform CNS imaging to exclude hydrocephalus and medulloblastoma if warranted by clinical evaluation. Perform imaging of the ovaries to exclude pathologic conditions of the ovaries in women with suggestive symptoms.
Patients with GS should not require SBFT or BE for detection of polyps (only gastric polyps have been reported). In a series of 105 patients with GS, Kimonis et al reported the following radiologic findings: [38]
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Calcification of the falx cerebri (65%)
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Bridged sella (68%)
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Flame-shaped lucencies in the phalanges, carpals, and metacarpals (30%)
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Bifid ribs (26%)
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Calcification of the tentorium cerebri (20%)
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Hemivertebrae (15%)
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Fused vertebral bodies (10%)
Procedures
All patients with polyposis syndromes require serial endoscopy and colonoscopy to evaluate for the degree of polyposis and survey for malignant transformation.
In patients who have PJS and chronic sinusitis, endoscopic evaluation for possible nasal polyposis may be required. Squamous cell carcinoma has been reported in a patient with PJS and nasal polyps.
In patients with Cowden disease, biopsies of suspicious lesions seen on the mammogram are warranted to exclude neoplasia, and biopsies of other suspicious areas are indicated to exclude malignancy.
In patients with GS, skin biopsies may be required to exclude basal cell carcinomas.
Histologic Findings
Adenomatous polyps, found in patients with FAP and its variants, vary in size, ranging from single crypt adenomas to microadenomas of 2-5 crypts in size to sessile tubular adenomas visualized with endoscopy. Adenomas are composed of immature epithelial cells with increased proliferation rates above crypt requirements. Increased growth in size of adenomas enhances the formation of dysplasia. No smooth muscle bundles are present in adenomatous polyps.
Gruber et al characterized PJS hamartomas are exophytic with an elongated frondlike epithelium possessing cystic dilatation of glands that contain hypermucinous goblet cells atop a network of arborizing smooth muscle bundles. [66] PJS polyps show areas of florid epithelial misplacement and dysplasia. [18]
Patients with Cowden disease and BRR syndrome also present with hamartomatous intestinal polyps, which are small and dome-shaped. Polyps in Cowden syndrome are mainly colonic, sessile, and small, without surface erosion and show mildly inflamed fibrotic lamina propria with smooth muscle proliferation and lymphoid follicles. They have the least cystic glands and no thick mucin. Ganglion cells and nerve fibers are present within the lamina propria and mucosal fat. [28]
In contrast, other forms of juvenile polyposis consist of abundant lamina propria without the presence of smooth muscle bundles. Large, inflammatory polyps contain a well-differentiated mature epithelial layer with a smooth dome but lobulated appearance due to cyst formation with thick mucin but without smooth muscle bundles. They have a strikingly edematous, markedly fibrotic and inflamed lamina propria. [28]
Polyps in Cronkhite-Canada syndrome are broad-based, sessile with cryptic features ranging in size from a few mm to 1.5 cm. One can see polyps distributed over other polyps similar to a hydatidiform mole. Specific histology of these polyps exhibits a hamartomatous appearance, an expanded edematous lamina propria, inflammatory cell infiltration, and tortuous, dilated cystic glands or crypts. [29]
Endoscopically, polyps of serrated polyposis syndrome are hyperplastic, which are 2-5 mm in size. They appear pale, glisten, are covered with mucous, look similar to the surrounding mucosa, and have minimal vascularity. Serrated polyps are usually sessile or flat. They are defined as epithelial lesions with serrated appearance on histology secondary to infolding of crypt epithelium. [15]
Examples of histologic findings are shown in the images below.
Pedunculated tubular adenoma. Note the contrast between the goblet cell-rich glands along the pedicle of the polyp and in the underlying normal colonic mucosa at the bottom and the dysplastic glands in the polyp proper. The dysplastic glands are more crowded and exhibit decreased mucin production. (Hematoxylin and eosin stain; 1X magnification).
Sessile tubular adenoma. The glands on the superficial aspect of the specimen are dysplastic and exhibit increased nuclear size, hyperchromasia, crowding, and decreased mucin production. (Hematoxylin and eosin stain, 4X magnification).
Hamartomatous (Peutz-Jeghers) polyp, small bowel. This pedunculated polyp has a cerebriform appearance due to the arborizing frond-like growth with delicate finger-like projections of the stroma. (Hematoxylin and eosin stain, 1X magnification).
Hamartomatous (Peutz-Jeghers) polyp, small bowel. Closer view of the fingerlike projections of the stroma demonstrates prominent smooth muscle fascicles between the glandular elements. (Hematoxylin and eosin stain, 4X magnification).
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Familial adenomatous polyposis, total colectomy specimen. The colonic mucosa is studded with innumerable sessile and small pedunculated polyps, which involve the entire length of the specimen.
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Pedunculated tubular adenoma. Note the contrast between the goblet cell-rich glands along the pedicle of the polyp and in the underlying normal colonic mucosa at the bottom and the dysplastic glands in the polyp proper. The dysplastic glands are more crowded and exhibit decreased mucin production. (Hematoxylin and eosin stain; 1X magnification).
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Sessile tubular adenoma. The glands on the superficial aspect of the specimen are dysplastic and exhibit increased nuclear size, hyperchromasia, crowding, and decreased mucin production. (Hematoxylin and eosin stain, 4X magnification).
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Hamartomatous (Peutz-Jeghers) polyp, small bowel. This pedunculated polyp has a cerebriform appearance due to the arborizing frond-like growth with delicate finger-like projections of the stroma. (Hematoxylin and eosin stain, 1X magnification).
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Hamartomatous (Peutz-Jeghers) polyp, small bowel. Closer view of the fingerlike projections of the stroma demonstrates prominent smooth muscle fascicles between the glandular elements. (Hematoxylin and eosin stain, 4X magnification).
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Hamartomatous polyp, as seen in the stomach. (Endoscopic image).
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Colon in familial adenomatous polyposis (FAP). (Endoscopic image).
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Small bowel polyp. (Video capsule image).
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Multiple large polyps in the colon. The polyp in the center of the image is situated on a stalk. (Endoscopic image).
