Evaluation Of Colonic Polyps Kathia E. Rosado Orozco MD GI and Liver Pathologist Hato Rey Pathology Associates

► Disclosure:  I have no financial disclosures to make.  I will suggest texts and websites for reference and study, but receive no financial gain from these.

Colonic Adenomas ► Benign premalignant proliferation of colonic epithelium—all have dysplasia (low grade) and are dysplastic. ► Precursor lesions to colorectal carcinoma.

Classification ► Tubular: less than 25% villous ► TVA: between 20-80% villous ► Villous Adenoma:  Less than 5% of adenomas  More than 30% have high grade dysplasia  2% have carcinoma

Low grade dysplasia

Colonic Adenomas ► 60-70% of all endoscopically removed colonic polyps ► Lifetime prevalence: % ► 50% increase in size with time ► Only some (5-10%) progress to carcinoma ► 3-5% have invasive carcinoma at diagnosis ► Size of adenoma is BEST predictor of carcinoma risk ► High grade dysplasia and villous component more likely with increase in size of polyp

Chromosomal Instability Pathway

High Grade Dysplasia ► Also known as carcinoma in situ ► Present in 5-7 % of adenomas at initial diagnosis ► More likely if:  villous  larger (>1cm)  older than 60 yrs

Intramucosal Carcinoma ► Neoplastic cells extend through gland basement membrane and into lamina propria BUT NOT through muscularis mucosae. ► NOT shown to have metastatic risk:  Paucity of lymphatics in colonic mucosa  Classified same as high grade in TNM

Pseudoinvasion in Adenomas ► Misplaced or herniated epithelium in submucosa. ► Can be mistaken for invasive carcinoma ► Most in left colon, particularly sigmoid— almost never seen proximal to transverse colon ► Pedunculated polyps, more than 1 cm with at least 1 cm stalk. ► Peristalsis related torsion/twisting

Adenoma with Invasive Adenocarcinoma

Distinguishing Pseudoinvasion vs. Invasion 1. Compare the epithelium to epithelium you are confident is adenoma in the same polyp. 2. Compare the stroma to stroma you are confident is the benign stroma of adenoma in the same polyp. 3. Look for evidence of definite vascular or lymphatic space invasion. 4. Cut levels. This will at least buy you a little time, and you may find more definitive evidence of submucosal invasion in the deeper sections. 1. Compare the epithelium to epithelium you are confident is adenoma in the same polyp. 2. Compare the stroma to stroma you are confident is the benign stroma of adenoma in the same polyp. 3. Look for evidence of definite vascular or lymphatic space invasion. 4. Cut levels. This will at least buy you a little time, and you may find more definitive evidence of submucosal invasion in the deeper sections. Yerian, L USCAP short course

-You can call the clinician to discuss the endoscopic findings and management plan. -Benign misplaced epithelium is uncommon in sessile lesions. If the polyp was not completely excised and is not endoscopically resectable, then the patient may need to undergo a resection irrespective of your assessment of the submucosal epithelium. Yerian, L USCAP 2010 Short course

Pseudoinvasion ► Occasionally a definite distinction between invasion and pseudoinvasion is not possible and consensus cannot be reached, even among experienced GI paths ► Giving a descriptive diagnosis is best and a phone call to the clinician may be helpful. The pathologist may choose to describe the finding ("deep neoplastic glands of uncertain significance"), and elaborate in a comment as to the diagnostic problems. ► Yerian, L USCAP 2010 short course

Carcinomas arising in Adenomas ► ► Surgical resection if:   Poorly differentiated   at or near margin   lymphovascular invasion ► ► Endoscopic polypectomy is adequate if:   carcinoma is low grade (well or moderately differentiated)   margin is free or carcinoma, more than 1 cm away from margin   no evidence of lymphovascular invasion

-Up to 30% in asxs adults over 50 y/o -Prevalence increases with age -Usually less than 5mm -Smooth, sessile -Typically do not increase in size with time (left sided)

Serrated Adenomas ► Controversial entity only recently recognized (1990) as a pathologic lesion distinct from hyperplastic polyps ► Recognition due to:  Pts with hyperplastic polyposis have an increased risk for neoplasia  Sporadic right-sided hyperplastic polyps more commonly contain a variety of genetic alterations NOT present in left-sided counterparts

Serrated adenomas ► Formal evaluation of their clinical features and incidence is lacking due to discrepancies in literature in terms of nomenclature--called by numerous names ► Are thought to represent 20% of all lesions with serrated architecture encountered at endoscopy

Serrated adenomas: Facts ► Epithelial neoplasm with a distinctive serrated architecture associated with abnormal proliferation and associated risk for colorectal neoplasia ► Slightly more common in left colon  If Small, endoscopic removal ► In right side:  Large (more than 1cm), flat  Remove entirely  Can present as an enlarged fold

Serrated polyp neoplasia pathway ► Proposed to represent an alternative molecular pathway to colorectal cancer ► Hp-- > atypical HP-- > serrated adenoma -- > cancer -- > cancer ► Predominant carcinomas of this pathway: show defective DNA mismatch repair (MMR)—can be MSI high or low ► 10 to 15% of all colorectal cancers

MSI and Cancer ► MSI is a key factor in several cancers including colorectal, endometrial, ovarian and gastric cancers. Colorectal cancer studies have demonstrated two mechanisms for MSI occurrence. ► The first is in hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch Syndrome, where an inherited mutation in a mismatch-repair gene causes a microsatellite repeat replication error to go unfixed. ► The second mechanism whereby MSI causes colorectal cancer is an epigenetic change which silences an essential mismatch-repair gene. ► In both cases, microsatellite insertions and deletions within tumor suppressor gene coding regions result in uncontrolled cell division and tumor growth.

Traditional serrated, usually left-sided

Eosinophilic cytoplasm

Sessile serrated adenoma, right-sided

Sessisle serrated adenoma, right-sided

Neoplasia in serrated polyp pathway ► Most if not all sporadic MSI carcinomas have a serrated histogenesis ► Epidemiological association with smoking but typical in elderly females ► Can have several histologic patterns:  Well to poorly differentiated  Undifferentiated  Lymphocytic response

-lymphocytic infiltrate -solid -signet ring cells -mucinous