위장관용종의분류와감별진단 고싞대학교복음병원병리과 장희경 Gastrointestinal Polyp A circumscribed nodular lesion or tumor that protrudes above the surrounding mucosal surface. The role of pathologist is to establish a diagnosis or at least to be able to put it into one of the general polyp categories, and to determine whether the lesion has been adequately excised. 1
The rules for dealing with polyp If you can t name a polyp in 20 seconds then is probably does not have a name or the reference to it is so obscure that you do not know it exists, or you have had poor training. If you think you can name it after 20 and before 30 seconds, then you had better be sure that you are not putting it in the wrong place. If you still can t name it by 30 seconds, make up a name: Benign mucosal polyp is acceptable. Pathologic features of healing biopsy site Time Features Immediate Blood clot with coagulum Hours Acute inflammation; granulation tissue reaction 2 days* Reepithelialization of inflammed biopsy site via ingrowth of epithelial cells from adjacent preserved epithelium; early formation of submucosal scar 1-4 weeks Restoration of mucosa with rudimentary glandular architecture, maturation of submucosal scar months Residual minmal mucosal architectural distortion, submucosal scar * Longer with deep biopsies involving the muscularis propria (Odze, Surgical pathology of the GI tract, liver, biliary tract, and pancreas) 2
Healing mucosal biopsy site 2 days after colon polypectomy, ulceration, inflammation, and granulation tissue reaction ( R.D. Odze, Surgical pathology of the GI tract, liver, biliary tract, and pancreas) 용종의육안적분류 ( 내시경적분류 ) 3
Generic classification of Gastrointestinal polyps Epithelial Non-neoplastic Hyperplastic Inflammatory Hamartoma(sporadic, familial) Cysts/Duplication Heterotopia(embryonic rests) Miscellaneous(tags,stumps,stalks) Epithelial Neoplastic Adenoma(sporadic, familial) typical, flat, serrated Polypoid dysplasia in IBD Carcinoma Neuroendocrine tumors Metastasis(epithelial/non-epithelial) Non-epithelial Lamina propria infiltrates(pneumatosis,xanthoma,endometriosis, etc) Lymphoid (hyperplasia, neoplasia) Mesenchymal(benign, malignant) neural, adipose, vascular, smooth muscle derived inflammatory fibroid polyp Contents Esophagus squamous papilloma glycognesis acanthosis granular cell tumor Stomach fundic gland polyp hyperplastic polyp : nothing like the colonic polyp Colorectum hyperplastic : nothing like the colonic polyp mucosal prolapse-polyp All organs adenoma juvenile Peutz-Yegher polyp carcinoid tumor (polypoid carcinoid tumor) 4
식도용종 염증성용종이가장많으며, 식도낭 - 망 (webs), 이소성폴립 (heterotopias), 평활근종순으로발생한다. 증상이있는식도용종의대부분은악성이다. 최근편평상피유두종의발생이증가하고있다. 과립세포종 (Granular cell tumor) 슈반세포기원의양성종양 식도하부에서호발 단일또는다발성으로발생. 내시경소견 : 50% 이상에서 5mm이하이고, 단단한노란또는연노란색의점막하병변으로관찰된다. PASD, S-100 양성 풍부한과립상의세포질과작고진한핵을가진세포들로구성되며, 이는매우특징적으로, 편평상피하부의몇개의세포만으로도진단이가능하다. 5
The tumor is composed of sheets of uniform histiocyte-like cells with finely granular eosinophilic cytoplasm and small nuclei 위용종 (Gastric Polyps) 궤양주위나 gastroenterostomy stoma 등의염증부위에서이루어짂생검들은실지로용종을형성하지않은경우에도증식성용종이나심지어샘종등과유사하게보일수있다. 내시경시술의 3-5%, 위용종의 75% 가증식성 / 염증성용종이다. 그외바닥샘용종 (fundic gland polyp), 샘종, 위장관간질종양 (GIST), 이소성용종들이관찰된다. 6
Gastric polyps in practice Hyperplastic polyp: confused anatomy Therefore, we probably throw more things into the hyperplastic category than it deserves because we do not know the limits of hyperplastic polyps in the stomach The distal polyp with too much mucosa, maybe with a little prolapse change at the base Gastric polyps in practice Architecture is defined as the relationship between the glands and the lamina propria, and is best assessed at low magnification. Cytology refers to abnormalities of the nucleus and cytoplasm of individual epithelial cells. This feature is best evaluated at high magnification. 7
A. 증식성 / 염증성용종 Hyperplastic/Inflammatory Polyps 위에서발생하는용종중가장흔하다.(1/1000, 위용종의 75%),. 2/3 이단발성병변, 50 개이상의용종 : 증식성용종증 연령에따라발생빈도도증가 ( 평균 :57.3), 여자에호발, 호발부위 : 위방 32.8%, 위바닥과몸통 29-49%, 들문 2.5% 원인 : 1. H.pylori 위염 ( 치료후 71% 에서퇴행 ) : 76% 2. 만성위축성위염, 3. 악성빈혈, 4. 담즙역류성위염, 5. 위 - 공장문합부 ( 특히 Billroth I), 6. 비스테로이드성소염제의장기간복용등 발생기전 : 위상피의염증이나손상에대한과도한재생반응으로, 선와상피증식이기본병변이다. 감별진단 : 1. 이형성과재생상피의감별 : 가장중요한김별점은표면상피의세포의미성숙유무이다. : 점액소실, 핵 - 세포질비윣증가, 큰공포상의핵과뚜렷한핵소체, 입방형상피세포등이관찰되면상피의재생소견이나, 균일하게심한핵농염이나비정형핵분열상은관찰되지않는다. 2. 낭성용종성위염 Gastritis cystic polyposa: GCP): - GCP 는평활근이없는상피구조가근육층이나점막하층으로확장되어결젃이나용종을형성하는경우로 Billroth II 위젃제술이나심한만성위축성위염과관렦되어발생하거나, 크기가큰 GCP 는증식성용종이나유년형용종과감별이어렵다. 3. 과오종성용종 (Peutz-Yegher polyp) - 고유판내의염증이심하지않거나미약하며, 만성염증과의관련성이없다. - 점막근육이나뭇가지모양으로잘발달되어있다. - 대개다발성으로발생한다. 4. 침윢성샘암종 : 특히증식성용종이나 GCP 는세포의비정형성 (atypia), 결합조직증식증 (desmoplasia) 이없고, 침윢된상피구조에고유판이함께관찰된다. 8
Surface maturation - An important feature to consider in the regeneration versus dysplasia - 1. Surface maturation: As cells move from the pits or crypt to the surface, the nuclei become smaller, and the cytoplasm more abundant and differentiated. This is referred to as maturation. Mitotic activity occurs in that region of the gland. 2. Cytologic features : - The nuclei in the crypts may be of moderate size, but the nuclear/cytoplasmic ratio at the surface is small. - The nuclear membranes are smooth, and there is no nuclear pleomorphism. - Nuclei are situated at the basal membrane of the cell. - there should be no loss of nuclear polarity, and only focal nuclear pleomorphism. 3. Cytologically, nuclear atypia is usually seen deep in the glands or on the sides of villiform structures. But the surface epithelium shows less or no atypia. Increased mitotic figures in the gland base or sides of villi may be seen. Biopsy specimen from gastric polyp 9
Regenerative changes 1. Regular glands arranged parallel to one another ; Lamina propria separating the glands 2. Basally located nuclei and basophilic cytoplasm 3. Increased nuclear cytoplasmic ratio: large vesicular nuclei, prominent nucleoli, 4. Increased mitotic activity. 5. with inflammation and ulceration. 6. - the lack of an abrupt transition from atypical to non-atypical epithelium 7. lack of marked uniform hyperchromatism or nuclear pleomorphism, atypical mitotic activity, and loss of cell polarity. 위증식성용종의임상적의의 예후 : 퇴행 (5%) 하거나, 크기의변화가없거나 (67%), 더커질수있다 (27%). 이형성으로의이행 : 1-20% 용종안에서나인접위점막에서악성으로의가능성 : 0.6% - 7.1% ( 평균 : 2.1%). 크기가 2cm 이상, 50 세이상, 유경형일수록높다. 내시경적경과관찰필요 : 위점막젂체를잘살펴보아야하며, H-pylori 위염과관렦된경우는치료후추적내시경을통해폴립의재발유무와치료유무를확인할필요가있다. 특히심한위축과장형화생이있는경우의증식성용종은일종의경고로받아들일필요가있고, 위젃제술부위에서발생한경우는특히주의할필요가있다. 10
54/F, antral polyp with 1.5cm in size 11
Hyperplastic polyp with dysplastic change Morphological variants of gastric hyperplastic polyp = 용종성선와증식 (Polypoid foveolar hyperplasia) = 증식성폴립의초기병변으로이시기에는악성변환은없다. 1-2mm 크기의무경형융기 현미경소견 : 위와 (gastric pits) 가일정한길이로길어지면서나선형모양을유지하고일부에서는미약한낭성변화를보임. 이때는위선와의수의증가와낭성변화등선와의심한구조적변화는없다. 33% 에서장형화생을보인다. 12
= Polypoid hyperplasia or hyperplastic polyp of gastric cardia/ gastroesophageal junction= 1. 현미경소견 : 들문형점막으로구성되며, 편평상피와의 hybrid-epithelium 이관찰될수도있다. 장형화생은다양한정도로나타나며, 이형성 (<3%) 도관찰될수있다. 2. 원인 : H.pylori-carditis, gastroesophageal refluxassociated carditis 등의주위점막의손상으로인한재생과정에서발생.: 이때편평상피와원주상피의 multilayered or hybrid epithelium 은원인의감별에큰도움이된다. Features that help differenitate intestinal metaplasia in the reflux carditis from H-pylori carditis Feature Intestinal Metaplasia reflux carditis H-pylori carditis GERD + - clinical profile + - Irregular Z-line + - Esophagitis(histologic) + - Gastritis(histologic) - + H.Pylori - + Eosinophils ++ + Neut.Plasma.Lymphocytes + + + Multilayered epithelium + - HID stain positive + - (non-goblet cells) MUC 1,6 positive + - BE CK 7/20 pattern + +/- Complete>Incomplete IM - + IM=intestinal metaplasia, BE=Barrett's esophagus, Neut.=neutrophils, Plasma.=plasma cells, CK=cytokeratin (Odze, Surgical pathology of the GI tract, liver, biliary tract, and pancreas), (AJG, 2005:100:1853-1867) 13
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B. 과오종성폴립 1) 위바닥샘용종 (Fundic gland polyp) 2) 가족성과오종성용종 i. 유년성폴립증 (Juvenile polyposis) ii. Peutz-Yegher 증후군 iii. Cronkhite-Canada Syndrome 증후군 15
소장의용종 소장의악성용종 : 매우드물게발생 ( 위장관악성종양의 1-2%) 대개원위부에서발생, 용종형카르시노이드, 림프종, 악성간엽성종양 소장의양성용종 : 대부분은십이지장에서발생, 소장의용종성병변의 40-50% 차지 : Brunner s gland hyperplasia/hamartoma, reactive lymphoid hyperplasia, nodular duodenitis, heterotopia adenoma 염증성섬유소모양용종 (Inflammatory fibroid polyp) - 섬유모세포모양의간질세포, 소혈관, 염증세포특히호산구의증식을특징으로하는양성점막하종양. - 모든연령층에서발생, 남녀동일핚비윣로발생. - 발생위치에따라증상을나타냄 : 위 - 폐색, 소장 - 장중첩증 - 호발부위 : 위의원위부 (pylorus), 회장원위부. 그외식도, 대장, 소장근위부에서는드물게발생 - 위에서발생핚경우 : 주로 3cm 이하의크기로위축성위염, 궤양과관련되고, 무경형이대부분이며, 고유근육층과는경계가뚜렷. - 소장의경우는. 대개 3cm 이상이며, 가끔유경형도있으며, 궤양을형성하거나, transmural tumors 를형성. 전형적인경우는점막침범은없다. - 감별진단 1. 섬유종증 2. 염증성위종양 임상적의의 : 악성이행의위험성은없다. 16
The mass consists of proliferating fibroblasts-like stromal cells, small blood vessels and inflammatory cells, particularly eosinophils. tending to form concentric layers around the small thin walled blood vessels Polyposis syndrome with non-neoplastic polyps syndrome Histologic features distribution Cancer risk Genetic abnormality Peutz-Yegher 1.Arborizing muscular framework with mucosa containing gastrointestinal epithelium 2.little inflammation 3.misplaced glands mainly small intestine, also stomach and large intestine 2-3% SKT11 Juvenile polyposis 1.widely spaced, variably cystically dilated glands lined by normal or hyperplastic epithelium 2.inflammed edematous stroma 3.littel or no smooth muscle colon and rectum always, and/or stomach and small intestine increased SMD4 BMPR1A Cronkite- Canada Cowden s 1.Similar to Juvenile polyposis 2.interpolypoid mucosa shows variably cystically crypts 1.variable 2.mucosal hamartoma :similar to Juvenile polyposis with abundant lamina propria or fibrosis 3.esophagus: glycogenic acanthosis colon: lipoma, fibroma, etc. entire GI tract Controversi al/ maybe increased(?) entire GI tract unknown PTEN Nonhereditar y, Unknown etiology 17
25Months/M, Rectal polyp, 0.7x0.5cm 1.widely spaced, variably cystically dilated glands lined by normal or hyperplastic epithelium 2.inflammed edematous stroma 3.littel or no smooth muscle 18
Juvenile polyp with dysplastic change Peutz-Jeghers Polyps Sporadic Peutz-Jeghers Polyps(PJP): Extremely rare, ㅡmorphologically same as the familial PJP. Small intestine: characteristic - smooth muscle bundles of varying thickness extending in an aborizing arrangement up into the head of polyp. Stomach: indistinguishable from that of hyperplastic polyps(ddx. point: nonpolypoid gastric mucosa: gastritis Generally, PJP is not diagnosed in the setting of gastritis. Colon, mucosal prolapse polyp display smooth muscle proliferation that may mimmic a PJP. 19
smooth muscle bundles of varying thickness extending in an aborizing arrangement up into the head of polyp Gastric PJP 20
대장용종증식성용종 (hyperplastic or metaplastic polyp) - 대장에서가장흔한용종 - 대개다발성병변 - 좌측대장에서호발 - 발생기젂 : 표면상피와상부에위치하는선와 (crypt) 의과성숙과선와간의융합과관렦이있을것으로추측 Hyperplastic polyp DDx point: 1. serration of crypts only at the surface 2. the base of crypts are narrow, lined with undifferentiated cells 21
감별진단 1. sessile serrated adenoma(ssa): 우측대장에서호발하고, 점막근판을따라서선와가 lateral growth 하고, dilation 되고, branching 하는소견이특징적이며, 증식성용종에비해선와세포의비정형성, 위중층이다소심하고, 점액소실과호산성의세포질이관찰된다. 2. traditional serrated adenoma: serrated adenoma 는저배율에서는증식성폴립과유사하게보이나, 고배율에서표면상피의미성숙소견을보인다 Sessile serrated adenoma (SSA) 48/F, colon polyp, 0.8x0.6x0.5cm Major pathologic findings 1. sessile growth 2. hyperplastic background 3. serration of crypts down to the muscularis mucosae 4. dilatation and branching of basal crypt with/without horizontal crypt and dystrophic goblet cells 5. in areas, eosinophilic cytoplasm 6. focal dysplasia of epithelial cells 22
Polyps due to excess lamina propria Sometimes, they are likely to be called inflammatory pseudopolyp Caution! : An inflammatory pseudopolyp diagnosis might leads to an assumation that the patient has UC. 점막탈출증 - 관련염증성용종 (Mucosal prolapse-associated with inflammatory polyp) 정의 : 점막이탈출되어육안적인이상소견을보이는병변을통칭하며, 발생부위, 조직학적소견, 임상소견에따라, 유사한병리소견을갖는 entity 들을통칭하여 mucosal prolapse syndrome 이라한다. 치료 : 용종절제술이나외과적절제술후에도재발을잘한다. 만성변비등의근본원인을제거하는것이치료에도움이된다. 23
mucosal prolapse syndrome 발생부위 : 위장관어디서나발생이가능하나, 직장과 S 자결장의하부에서흔히발생. 임상특징 : 남녀비슷하게발생, 어린이부터성인까지발생, 임상증상 : 무증상에서부터직장출혈, 직장항문동통, 소양증, 급작스런복부통증, 배변장애, 설사, 직장종괴등다양함 내시경소견 : 단발또는다발의점막충혈, 궤양, 용종성병변 발생기전 : 1. cystic fibrosis, acute diarrheal disease, IBD, chronic constipation, motility disorder 등에합병되어나타날수있다. 2. 배변시직장내압증가, 비정상적인항문괄약근기능, 골반근육기능부전, 방사선조사등의여러원인에의한조직상해와궤양 ( 외상 ) 의발생 - 점막의용종형태로재생 - 점막하혈관의허혈 - 괴사, 궤양 - 점막재생의과정이반복됨으로서발생. 병리소견 1. 최초병변 : 비특이염증 2. 용종 : 1. 다양한크기 (0.5-4cm) 2. 무경형, 일부유경형 3. 표면은매끈하나유두상 / 융모상을보이는경우가많다. 4. 궤양이나괴사가가끔괸찰될수있다. 5. 반복되는출혈소견과괴사와염증소견 : 용종과인접점막에서관찰될수있다. 24
3. 특징적현미경소견 : (1) 섬유모세포와평활근섬유의점막근판에서점막고유판내로의증식 : 점막근판이두터워지고, 근육섬유가갈라져서나뭇가지모양으로관찰된다. (2) 상피의재생소견 : 선와가길어지고구조가변형되기도하며, 증식성으로톱니모양의내강표면이관찰된다. 부분적으로기저막직하의교원질판이두터워져서 collagenous colitis 와유사하게보일수도있다. 점액이소실되고재생성소견을보이므로이형성과혼돈하기쉽다. (3) 다양핚정도의궤양또는미란형성 : 궤양은대개표면적이다. 호중구가선와내로침윢하기도하며, 염증성삼출물이점막표면을덮기도한다 subtypes (1) inflammatory cap polyp: 표면미란을덮고있는모자모양의뚜렷한육아조직이나섬유소원이부각되는경우이다. S자결장과직장에서주로호발. 섬유근육의발달은심하지않는경우도많다. (2) inflammatory cloacogenic polyps : 항문이행부에서발생. 편평상피와원주상피가혼재될수있고, 표면이융모형태로보이기도함. (3) solitary rectal ulcer syndrome-associated polyp : 내시경에서주로직장전벽에서궤양이나충혈된 patch형태로관찰됨. (4) diverticular disease-associated polyp(kelly polyp) (5) prolapsing redundant mucosa : 점막의만성손상상태에서급성염증이병발하는경우에주로발생하며, 고유근육층과점막근판이융합되어점막과잉상태를보이는경우로염전이나장중첩증을유발할수도있다. 현미경소견 : 점막의키높이증가와변형되거나길어진선와, 혈관울혈과출혈, 혈전, 혈색소침착, 미란, 육아조직, 섬유화와점막근판섬유의고유판내로유입. (6) colitis cystica profunda/proctitis cystica profunda(hamartomatous inverted polyp, enterogenous cyst): 25
감별진단 1. 특발성염증성장질환 : 초기병변, IBD 때보이는 basal plasmacytosis 는관찰되지않는다. 2. 포이츠예거용종 : 점막근판에서평활근섬유가용종간질내로유입되는소견이비슷하므로특히산발성포이츠예거용종의짂단에앞서점막탈출 - 용종산발성을반드시고려해야한다. 가족력과임상소견의확인이필요. 3. 융모상샘종 : 표면이융모형태를보이는경우는이형성과재생성상피를감별해야한다. 표면상피세포의성숙도로감별. 4. 침윢성암종 : colitis cystica profunda/proctitis cystica profunda 아형경우에주의를요한다. : - 세포없는점액푸울이점막하층이나심부에서관찰될때는특히염증의졲재, 육아조직, 간질의섬유화를 stromal desmoplasia 와혼돈해서는앆된다. 이때는낭을구성하는상피의특성에준하여결정한다. 27/M Multiple polyps at rectosigmoid area with from 0.5cm to 4cm in size 26
Mucosal prolapse polyp; Inflammatory cap polyposis 1. Surface of polyp covered by inflammatory exudates associated granulation tissue 2. Numerous elongated dilated crypts with lobular arrangements 3. Polyp base: proliferating smooth muscle fibers from lamina propria 27
28
Neuroendocrine tumor (Carcinoid tumor) of gastrointestinal tract Neuroendocrine tumor (NET) -spectrum: from traditional carcinoid tumor to small cell carcinoma -acccording to site, the biologic bahavior is different Carcinoid tumor: traditionally low-grade, potentially malignant tumor. : recommend as well-differentiated neuroendocrine tumor by 2000 WHO. The 2000 WHO classification of GI-NET (grade I-IV) 1. Well-differentiated neuroendocrine tumor, (carcinoid tumor) Grade I (usually or probably benign behavior) - Nonfunctioning, cytologically bland - tumor size < 1cm - confined to the mucosa/submucosa - without angioinvasion 2. Well-differentiated neuroendocrine tumor (carcinoid tumor) Grade II (uncertain malignant behavior) - Nonfunctioning, cytologically bland - tumor size : 1-2cm - confined to the mucosa/submucosa - with angioinvasion noted in some cases * Grade I,II: is also as Grade Ia, Ib 29
The 2000 WHO classification of GI-NET 3. Well-differentiated neuroendocrine carcinomas (malignant carcinoid tumor ) Grade III (low-grade malignancy) - nonfunctioning, cytologically bland - tumors > 2cm either with or without angioinvasion, - with extension beyond the submucosa - all functioning well-differentiated tumors of any size 4. Poorly-differentiated neuroendocrine carcinomas Grade IV (high-grade malignant potential) - cytologically poorly-differentiated tumors, - either functional or non-functional - tumors >2cm either with or without angioinvasion, - These tumors have been variously called oat-cell carcinoma, and small-cell carcinoma, large cell neuroendocrine carcinoma(lcnec) 30
Criteria for generic assessing the prognosis of neuroendocrine tumors of the Gastrointestinal tract The site and classification of GI-NET 31
Carcinoid tumor (=well differentiated neuroendocrine tumor) 용어 : Carcinoid tumor 보다는 well differentiated neuroendocrine tumor 사용을권장함 All GI carcinoid tumor except appendix and rectum Appendix Carcinoid tumor = well differentiated neuroendocrine tumor (Size < 1cm, no invasion) Carcinoid tumor (= well differentiated neuroendocrine carcinoma) (Any size, Mesoappendix invasion, metastasis, angioinvasion) Rectum Carcinoid tumor = well differentiated neuroendocrine tumor (Size < 1cm, no invasion) Carcinoid tumor (= well differentiated neuroendocrine carcinoma) (Any size, Muscle invasion, angioinvasion, node or distant metastasis) /3 /1 /3 /1 /3 Angioinvasion 의경우는면역염색을통해증명하는것이필요함 Pancreas Well-differentiated endocrine tumor, Confined to the pancreas, no angioinvasion, size <2cm, <2 mitosis/10hpf & <2% Ki-67 index Well-differentiated endocrine tumor, Confined to the pancreas (one or more of >2cm, 2-10 mitosis/10hpf, >2% Ki-67 index Neuroendocrine carcinoma, well-differentiated (atypical carcinoid) & poorly differentiated (Any size with metastasis or distinct malignant evidence) /1 Ki-67 면역염색은선택사항 /2 /3 직장카르시노이드종양 아시아에서백인에비해유병율이높으나, 전체직장암에서 1-2% 만을차지한다. 5 년생존율이 88.3% 로좋은편이다. 진단시 80% 정도가 1cm 미만으로, 국소절제가가능하다. 평균전이율이 4-18% 로, 지름이 1cm 이하일때 3%, 1.0-1.9cm 인경우는 10-15%, 2cm 이상인경우는 60-80% 로전이한다. 그러나일본의보고는 5mm 이하인경우가전이하는예가 3.7% 였다. 32
References 1. Odze RD, Goldblum JR, Crawford JM. Surgical Pathology of the GI tract, liver, biliary tract, and pancreas. W.B. Sauders, Philadelphia, 2004. 2. Fenoglio-Preiser CM. Gastrointestinal pathology. 3rd ed.. Solotion, Philadelphia, 2008 3. Goldman H, Antonioli DA. Mucosal biopsy of the esophagus, stomach, and proximal duodenum. Human Pathol 13;423-448, 1982 4. Appelman HD. Localized and extensive expansions of the gastric mucosa.pathology of the Esophagus, stomach, and duodenum. Churchill Livingstone, New York, 1984. 5. Kim YH, Kim WH. Inflammatory fibroid polyps of gastrointestinal tract. Am J Clin Pathol 89: 721-727, 1988 6. Hattori T. Morphological range of hyperplastic polyps and carcinomas arising in hyperplastic polyps of stomach. J Clin Pathol 38:622-630, 1985 7. Ming SC, Goldman H. Pathology of the gastrointestinal tract.. 2nd ed. Williams&Wilkins. Philadelphia.1998 8. Williams GT. Endocrine tumors of the gastrointestinal tract-selected topics. Histopathol. 50:30-41, 2007 33