Carcinoid Tumor - MColey

Carcinoid Tumor - MColey - Carcinoid Tumor Marcelyn Coley...

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Unformatted text preview: Carcinoid Tumor Marcelyn Coley Surgery IV Conference Mount Sinai School of Medicine History History 1888 – First described by Labarsch 1907 – Oberndorfer coined term “Karzinoide” (carcinoma­like, lack of malignant potential or particularly benign features) Carcinoid Tumor Carcinoid Tumor 5th to 7th decade of life Incidence 2.47 and 2.58 per 100,000 for men and women, respectively (series reported to NCI 4.48 and 3.98/100,000 Black M/F Occurrence rate 1:300 autopsies Reported in a number of organs – Lungs, bronchi, GI tract, ovaries Carcinoid Tumor Arises from enterochromaffin cells (Kulchitsky cells) type of enteroendocrine cell distributed throughout the digestive tract. – Ability to stain with potassium chromate (chromaffin), a feature of cells that contain serotonin Found in crypts of Lieberkuhn (intestinal glands) secretes serotonin among other peptides PICTURE/GRAPH of secretions Secretory products of carcinoid Secretory products of carcinoid Amines Tachykinins Peptides 5HT Kallikrein Pancreatic polypeptide (40%) Prostaglandins 5­HIAA Substance P (32%) Chromogranins (100%) 5­HTP Neuropeptide K (67%) Neurotensin (19%) Histamine Other HCGα (28%) HCGβ Dopamine Motilin HCG, Human chorionic gonadotropin; 5­HIAA, 5­Hydroxyinoleacetic acid; 5­HT, 5­Hydroxytryptamine; 5­HTP, 5­Hydroxytryptophan Classified by embryologic origin – Foregut (respiratory tract, thymus, stomach) – Midgut (small intestine, appendix, prox colon) – Hindgut (distal colon, rectum, GU tract) 1/3 of midgut tumors symptomatic – 10% assoc with carcinoid syndrome Hindgut rarely cause carcinoid, asymptomatic, even when metastatic Characteristics of carcinoids Characteristics of carcinoids Foregut Midgut Hindgut Histology Stomach, duodenum, pancreas, bronchus Trabecular Jejunum, ileum, appendix, ascending colon Solid mass of cells Transverse and descending colon, sigmoid, rectum Mixed Silver Staining Argyrophil Argentaffin Variable Secretory products 5­HT, serotonin, histamine, multiple polypeptides Stomach 20­25% Serotonin, prostaglandins, polypeptides Small intestine 35% None Localization Metastasis to liver Asc colon 60% Carcinoid syndrome Atypical Rectum <10% of tumors >2cm Appendix 2% Classical Rare Pathology Pathology Grossly, small, firm submucosal nodules, yellow­tan on cut surface Grow slowly Pathology Pathology After serosal invasion often an intense desmoplastic reaction producing mesenteric fibrosis, intestinal kinking, and intermittent obstruction Small bowel – multicentric 20­30% patients (multicentricity exceed other malignant neoplasms of GIT) 10­20% 2nd primary neoplasm – Commonly large intestine synchronous adenocarcinoma Associated with MEN I ~10% cases HISTOLOGY HISTOLOGY Typical – Well­differentiated, containing small regular cells with rounded nuclei Atypical or anaplastic – Increased nuclear atypia, mitotic activity, areas of necrosis Five distinct patterns recognized – Insular, trabecular (ribbon like), glandular, undifferentiated, and mixed\ Biologic behavior does not always correspond to histologic characteristics – Distinction between benign and malignant is based upon presence or absence of metastasis – correlates to size and site of primary tumor The two types of silver staining used to histologically identify neuroendocrine cells are argyrophil and argentaffin in addition to immunohistochemical stains such as chromogranins, synaptophysin and enolase Poorly differentiated gastric Poorly differentiated gastric carcinoid •sheets of poorly differentiated tumors cells with areas of necrosis (arrow). •marked nuclear pleomorphism and hyperchromasia. Lewin, KJ, Appelman, HD. Tumors of the esophagus and stomach. Atlas of tumor pathology (electronic fascicle), 1996. Variable malignant potential – Related to size, location, depth of invasion, and growth pattern Gastrointestinal Carcinoid Gastrointestinal Carcinoid Most common site (Sabiston) – 1. Appendix (45%)** – 2. Small intestine (28%) (last 2ft of ileum) – 3. Rectum (16%) (Cheek RC et al) According to SEER database of 11,427 carcinoids 1973­ 1997 – – – – Small intestine (45%)** Rectum (20%) Appendix (16%) Colon (11%) Similar results database study from a Swedish registy – 5,184 carcinoid tumors 1958­1998 Appendix Appendix Most common location Majority in 40s to 50s F>M Majority asymptomatic, located distal 1/3 of appendix Symptomatic case tend to larger tumor, at the base of the appendix (10%) and metastatic disease – Obstruction, appendicitis, or carcinoid syndrome with tumor mets to liver 5­yr survival overall 71%; 10 to 30% with distant metastasis Appendix: Surgery Appendix: Surgery Depends on the site of primary tumor Appendix Prognosis best predicted by size <1cm – Simple appendectomy adequate >2cm – right hemicolectomy 1 to 2 cm decide by location – Base of appendix or invading mesentery Right hemicolectomy – Appendectomy alone if tumor can be fully resected Mesoappendiceal invasion regardless of tumor size – Right hemicolectomy Studies show that recurrence unlikely with small tumors with this feature treated by appendectomy alone. (Kulke. N Engl J Med 1999) – Tumor size Metastasis <1cm 2% 1­2cm 50% >2cm 80% Small Intestine Small Intestine ~1/3 of small intestine neoplasms Commonly within 60cm of ileocecal valve 6th and 7th decade, present with abdominal pain or SBO Carcinoid syndrome in 5 to 7% of patients Multiple tumors in up to 30% 5­yr survival 36% with distant metastasis Small intestine Small intestine Often metastasis to lymph nodes or liver Treatment – Resection of involved segment and mesentery – Even in known metastasis Carcinoid of ileum Carcinoid of ileum Colon Colon 7th decade Presenting with abdominal pain, anorexia, or weight loss Carcinoid syndrome uncommon Majority in right colon – Cecum Asymptomatic until tumor becomes large – – In 2 studies, at diagnosis, average tumor size – 5cm 2/3 patients had local nodal or distant metastasis Colon Colon 5­yr survival based on metastasis – Local ­ 76% – Regional ­ 72% – Distant ­ 30% Small localized tumors likely cured by resection Rectum Rectum 6th decade Majority found incidentally on rectal exam or endoscopy Uncommon presentation includes rectal bleeding or pain Carcinoid syndrome rare Size correlates with metastasis – Often to lymph nodes or liver Size Metast asis 1cm Rare 1­ 1.9cm ~10% >2cm >70% Rectum Rectum Treatment – <1cm – Local excision (clear margins) – 1­2cm – more controversial, some recommend more extension resection in those with muscular invasion or symptoms – >2cm – Low anterior resection or abdominoperineal resection (similar to txt for adenocarcinoma) This aggressive approach has been challenged since survival is not consistently improved Prospective study FIGURE 2. Berkson–Gage survival analysis for tumor size and distant metastasisfree survival of the 31 patients presenting without metastasis. Increasing tumor size was associated with significantly decreased metastasis free survival. Tumor size was not available for three patients. Koura et al. Carcinoid tumors of the rectum. Cancer 1997; 79:1294 5­yr survival rates – Localized (90%) – Regional (49%) – Distant metastasis (26%) SEER database Stomach Stomach Three Categories – Type 1 70 to 80% of gastric carcinoids Associated with chronic atrophic gastritis and often pernicious anemia Derived from enterochromaffin­like (ECL) cells Hypothesized that ECL cells develop into carcinoid after chronic stimulation by high gastric levels i.e. pts with atrophic gastritis Gastric Carcinoids Gastric Carcinoids Type 1 – 6th and 7th decade, F>M – Carcinoid syndrome rare – Usually indolent and generally benign condition – Metastases <10% of tumors <2cm – ~20% present in larger tumors – Type 2 Associated with gastrinomas (Zollinger­Ellison syndrome) or MEN type 1 <5% of gastric carcinoids ECL cells MEN1 gene locus (11q13) appears to be involved in the pathogenesis of many of these tumors (Debelenko et al.) Behave similar to type 1 – Type 3 “sporadic carcinoids” – not associated with any other disease process 20% of gastric carcinoids Most aggressive – local or hepatic metastases up to 65% of patients May be associated with carcinoid syndrome – Often produce 5­Hydroxytryptophan in contrast to type 1 and 2, often produce serotonin Other sites Other sites Lung Ovary – **produce carcinoid syndrome without metastases secondary to direct drainage into the systemic circulation – Often arise in cystic terotoma or dermoid tumor – In one report, 189 or 329 ovarian carcinoids(57%) coexisted with cystic teratomas/dermoid tumors. – Compared to carcinoids without associated germ cell tumors, these were significantly smaller, less likely to have metastases or carcinoid syndrome Clinical Manifestations Clinical Manifestations Majority are asymptomatic and found incidentally at time of surgery, endoscopy, or autopsy [80%] When present—correlate with location and extent of tumor Carcinoid Syndrome Malignant Carcinoid Syndrome Malignant Carcinoid Syndrome Occurs in <10% with tumors Commonly tumors of gi tract, esp. small bowel Other locations described >90% with carcinoid syndrome have metastatic disease, exceptions are bronchial and ovarian tumors Patients with the syndrome almost invariably have hepatic metastases – venous drainage from a metastatic tumor in the liver goes directly into the systemic circulation and bypasses hepatic inactivation Liver metastases Liver metastases icine/pulmonar/images/hussain1/scan1.jpg Malignant Carcinoid Syndrome Malignant Carcinoid Syndrome CLASSIC SYMPTOMS – – – Vasomotor Cardiac Gastrointestinal Symptoms – Cutaneous flushing (80%) *** (diff erythematosus, violaceous, prolonged flushes, bright­red patchy) – Diarrhea (76%)** episodic, explosive, watery, occur after meals – Hepatomegaly (71%) – Cardiac lesions­Right heart valve (41 to 70%) PS, TR, TS – Asthma/Bronchoconstriction (25%) Malignant Carcinoid Syndrome Malignant Carcinoid Syndrome Metastasis to liver Malabsorption and pellagra (dementia, dermatitis, and diarrhea) occasionally present – thought due to excessive diversion of dietary tryptophan Carcinoid Tumor Carcinoid Tumor In absence of carcinoid syndrome, symptoms of carcinoids tumors in small bowel are similar to other small bowel tumors Abdominal pain ± partial/complete obstruction – often caused by intussusception – Local desmoplastic reaction (caused by humoral agents) Diarrhea (result of PBO) and weight loss Diagnosis Diagnosis Produce serotonin, which is then metabolized in the liver and the lung to the inactive 5­HIAA Elevation of humoral factors basis in those with carcinoid syndrome Urinary excretion of 5­HIAA* ­ end product of serotonin metabolism 75% sensitive and specificity up to 100% Errors induced by certain drugs and foods Normal 2 to 8 mg/day, Most carcinoids >100mg/day (99­2070) (in one study) +tumors, but without carcinoid syndrome 50 to 260 mg/day (not useful in foregut carcinoid bronchial, gastric lack aromatic amino decarboxylase – 5­hydroxytryptophan is produced instead (assays not available in US labs) – – – – – Inc’d 5­HIAA excretion in urine and inc serotonin uptake by platelets Urinary serotonin is normal or slightly increased Diagnosis Diagnosis Chromogranin A – protein made in the secretory granules of a variety of neuroendocrine tissues : (specificity not well established – Elevated in >80% cases (with or without the syndrome?) – Generally parallels 5­HIAA – May be predictor of prognosis (301 pts, >5000µg/L=poor overall survival) Blood Serontonin – Helpful when U5­HIAA testing is equivocal Diagnosis Diagnosis Others Plasma substance P, neurotensin, neurokinin A, and neuropeptide – however, not elevated in all patients Provocative test­ pentagastrin, calcium, or epinephrine to reproduce symptoms, but rarely used today – Useful when biochemical markers are marginally elevated Diagnosis Diagnosis Once syndrome is confirmed, the tumor may be localized (metastasis) – Abdominal CT – Indium­111 octreotide imaging (somatostatin receptor scintigraphy) higher sensitivity than conventional imaging i.e. CT Other tests –Add picture of BE – Barium (filling defects) and endoscopic studies – Video capsule endoscopy, MR, angiography, high­ resolution ultrasonography CT: malignant carcinoid of ileum CT: malignant carcinoid of ileum Small bowel follow through Small bowel follow through Polypoid mass of the terminal ileum Somatostatin receptor scintigraphy Somatostatin receptor scintigraphy Staging Staging No standard system for describing spread of gastrointestinal carcinoids Management Management After localization of the tumor… Surgery is the mainstay of treatment Based on… – Tumor size – Tumor site – Presence or absence of metastatic disease Removal of tumor (if no mets) Control of carcinoid symptoms if present Widespread metastases – palliative resection Metastases Metastases Widespread metastasis – Surgical debulking indicated, in many series, provides symptomatic relief – ? Hepatic resection Wedge resection or hepatic lobectomy – Hepatic artery ligation or percutaneous embolization – Reports of tumor regression with hepatic artery occlusion combined with chemo Multimodal therapy needs further evaluated Carcinoid syndrome – Octreotide and alpha interferons have been effective – In one study of 130 patients with metastatic carcinoid tumor, interferon alpha resulted in decreased urinary 5­HIAA (42%) and regression (15%) Prognosis Prognosis Dependent on size, location of primary tumor Midgut tumors better survival than foregut and hindgut Resection of a carcinoid tumor localized to its primary site approaches a 100% survival rate 5­yr survival ~65 to 67% with regional disease 25 to 35% with distant metastasis Long­term palliation often can be obtain due to slow growing nature Chromogranin A found to be an independent predictor of an adverse prognosis Summary Summary >80% asymptomatic, often incidental finding Initial diagnostic test 24­hr urinary 5­HIAA Treatment and prognosis dependent of size and location of primary tumor Resection is tumor increased overall survival Metastases correlate with location and size of tumor ...
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This note was uploaded on 12/24/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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