Polyp A protrusion from a surface Polyps of the Gut Pedunculated Sessile An All-inclusive Classification of Colonic Polyps 1. Developmental a. Juvenile b. Hamartomatous (Peutz-Jeghers) 2. Inflammatory “pseudo-” 3. Neoplastic a. Adenoma b. Carcinoma 4. The Serrated bunch including hyperplastic polyp 5. Recently named: transitional mucosal, fibroblastic 6. Mixed, hybrid, unclassifiable, pimples, etc. 7. Normal mucosa A lot of the information for this discussion comes from the WHO 2010 book Developmental Polyps 1. Juvenile 2. Peutz-Jeghers Smooth, eroded surface Lots of pink lamina propria Cystic crypts Expanded, inflamed lamina propria and crypt distortion: cystic, branched Eosinophils are common Normal or regenerative epithelium Juvenile Polyps Class: Hamartoma Excess cellular lamina propria Hardly any muscularis mucosae: a few branching fibers at the base Distortion: budding, cystic tubules (crypts or pits) Distribution: colon> small intestine & stomach What are the minimal criteria for diagnosing the smallest juvenile polyp? There are none! In fact, there are no diagnostic criteria for juvenile polyps of any size. Every definition is a description that seems to assume that we all know what juvenile polyps look like and how to diagnose them. How do juvenile polyps develop? The best place to look for the smallest changes is in the flat mucosa between the polyps in a colon from a patient with juvenile polyposis Distorted crypts Expanded lamina propria 2 1 Progressively larger polyps in Juvenile polyposis: Even the smallest polyps have excess lamina propria and crypt distortion 3 Juvenile Polyposis Definition: WHO (2010) A familial cancer syndrome…autosomal dominant…characterized by multiple juvenile polyps of the GI tract, predominantly the colorectum, but also stomach, duodenum, biliary tree and pancreas. (total cancer risk may be around 80%) Juvenile Polyposis Diagnostic criteria: WHO (2010) 1. More than 3-5 juvenile polyps of the colorectum or 2. Juvenile polyps throughout the GI tract or 3. Any number of juvenile polyps with a family history of JP 4. Other syndromes involving hamartomatous GI polyps should be ruled out clinically or by pathological examination (P-J, Cowden’s) Some polyps are atypical lobulated or branched Classic JP Atypical JP Genetics of Juvenile Polyposis Classic JP Atypical JP 50-60% of JPS patients have mutations of SMAD4 or BMPR1A. In the rest of the patients, the genetic changes are not known. One JPS patient, 2 different types of polyps: Typical juvenile polyp Not sure of the genetic defect but may be SMAD4 mutation Dysplastic branched polyp Developmental Polyps 1. Juvenile 2. Peutz-Jeghers The Peutz-Jeghers Syndrome Definition WHO (2010) An inherited cancer syndrome (autosomal dominant) characterized by mucocutaneous melanin pigmentation and hamartomatous gastrointestinal polyposis, which preferentially affects the SI.…extra-intestinal neoplasms …. include tumors of the ovary, uterine cervix, testis, pancreas, breast. Mucocutaneous PJS Diagnostic Criteria (WHO, 2010) 1. 3 or more histologically confirmed PJ polyps, or 2. any number of PJ polyps with a family history of PJS, or 3. characteristic prominent mucocutaneous pigmentation with a family history of PJS, or 4. any number of PJ polyps and characteristic prominent mucocutaneous pigmentation Peutz-Jeghers Polyps Class: Hamartoma Branched muscularis mucosae redundant, distorted mucosa normal or regenerative epithelium Genetics: mutation of LKB1/STK11 on 19p in the syndrome SI > stomach and colon The Peutz-Jeghers Syndrome Definition WHO (2010) An inherited cancer syndrome (autosomal dominant) characterized by mucocutaneous melanin pigmentation and hamartomatous gastrointestinal polyposis, which preferentially affects the SI There are no specific written minimal criteria for diagnosing these hamartomatous polyps. Peutz-Jeghers Syndrome Cancer risk in LKB1/STK11 mutation carriers All cancers: 63% by age 60 GI & Panc carcinomas: 42% by age 60 Lim, et al, Gastroenterol. 126:1788, 2004 A typical small intestinal PeutzJeghers polyp A core of branching muscularis mucosae Branching muscularis mucosae The mucosa covering this branching muscle may be close to normal Gastric P-J polyps usually have little branching smooth muscle, and they are composed mainly of cystic pits with hardly any glands. Gastric polyp from a patient with the PeutzJeghers syndrome Colonic P-J polyps are not well characterized. Some may have a muscle core covered by distorted mucosa Colonic polyp from a patient with the PeutzJeghers syndrome Do sporadic PJ polyps exist? Study from Hopkins: 3 patients with solitary typical SI polyps had clinical features suggesting the syndrome, but they didn’t meet the diagnostic requirements for the syndrome. However, 2 of 3 developed cancers like typical PJ syndrome patients. So, if sporadic PJ polyps exist, they do not do so at Hopkins. I have never seen a case either. Burkart, et al. Am J Surg Pathol. 31:1209, 2007 Multiple polyposis syndromes all have a high cancer risk, most of which is colorectal, but other GI and non-GI cancers also occur Juvenile polyposis Peutz-Jeghers syndrome Familial adenomatous polyposis Lynch Syndrome (Hereditary nonpolyposis colorectal carcinoma) Serrated (hyperplastic) polyposis Polypoid prolapsed diverticulosisassociated mucosal fold (Kelly polyp) The next slide is one of these Thick distorted mucosa with prolapse changes An endoscopic polyp composed of transitional mucosa: a transitional mucosal polyp Not all GI polyps have names some are hybrids some don’t fit some are pimples some have obscure literature These will make you crazy! No polyp should take more than 30 seconds to be classified Branching muscularis mucosae (like a P-J polyp) covered by redundant serrated mucosa (like a HP) Polyps due to excess lamina propria These have no name! Colonic polyp with excess lamina propria and a coarse villous or nodular surface and striking crypt distortion This one has no name! If we can’t name things like this in 30 seconds, we make up a harmless name, most recently: Or BUMP Maybe 5-10% of endoscopic polyps contain histologically normal mucosa on the first cuts. If we serial section them or turn the block around and start cutting from the back side, some of them will turn out to be something like……. Start with normal mucosa. Many serial cuts later, a small hyperplastic polyp appears Normal Hyperplastic polyp Start with normal mucosa. Many serial cuts later, a small adenoma appears Normal Adenoma Most often,when we recut it, nothing changes. It is still normal. Dx: normal or no significant abnormality. What made the polyp? Who knows. When we see normal mucosa in a biopsy of an endoscopic polyp, we do not do anything additional, and we just call it normal. Our GI colleagues recognize that this happens, and they have neve disputed our interpretation in such cases.