1 / 72

The Pathologic classification of Neuroendocrine Tumors

The Pathologic classification of Neuroendocrine Tumors. A.Sadeghipour M.D. Associate Professor of Pathology and Lab. Medicine Iran University of Medical sciences. Why Neuroendocrine Tumors?. 50% OF THE NEUROENDOCRINE TUMORS ARE DIAGNOSED WHEN IN ADVANCED STAGES.

dupre
Download Presentation

The Pathologic classification of Neuroendocrine Tumors

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. The Pathologic classification of Neuroendocrine Tumors A.Sadeghipour M.D. Associate Professor of Pathology and Lab. Medicine Iran University of Medical sciences

  2. WhyNeuroendocrine Tumors?

  3. 50%OF THE NEUROENDOCRINE TUMORSARE DIAGNOSED WHEN IN ADVANCED STAGES

  4. Incidence of NETs isRapidly Increasing

  5. Complexities of Organ Specific Classification of NETs Could Lead to Confusion inDiagnosis and Management

  6. Neuroendocrine TumorsOverview of the Presentation • Definition and history • Epidemiological aspects • Clinical presentation • Paraclinical diagnosis • Immunohistochemistry • Pathological classification, staging and grading • Role of Pathologist in multidisciplinary approach to diagnosis and management

  7. Neuroendocrine TumorsDefinition • Neoplasms originating from the neuroendocrine cell system characterized by cytoplasmicneurosecretory granules Enterochromaffin Cell

  8. Embryology • Embryologic data have now refuted the neural crest origin of most neuroendocrine cells.

  9. Cells of Origin

  10. Neuroendocrine TumorsEpidemiological Aspects

  11. NETs • NETs arise from cells which produce and secrete hormones • Most NETs are slow growing and malignant, with metastatic potential • Common sites of origin are: • GI tract • Lungs • Pancreas

  12. 600 6.00 Incidence of all malignant neoplasms 5.25 Incidence of neuroendocrine tumors 500 5.00 400 4.00 Incidence of all malignant neoplasms per 100,000 Incidence of NETs per 100,000 300 3.00 2.00 200 1.00 100 0 0 76 78 80 82 84 86 88 90 92 94 96 98 00 02 04 74 Year Incidence of Neuroendocrine Tumors Is Increasing • The incidence and prevalence of NETs has increased approximately 500% over the past 30 years (better diagnosis?) Source: US SEER database. Adapted with permission from Yao JC, et al. J Clin Oncol. 2008 26:3063-3072.

  13. NETs Are the Second Most Prevalent Type of GI Malignancy in the US 1,200, 000 1,100, 000 2x more prevalent than pancreatic cancer 2x more prevalent than pancreatic cancer 100, 000 [ ] [ 0 Colorectal1 GEP-NET2 Stomach1 Pancreas1 Esophagus1 Hepatobiliary1 Prevalence in SEER Database 1. National Cancer Institute. SEER Cancer Statistics Review, 1975-2004. http://seer.cancer.gov/csr/1975_2004. 2. Modlin IM, Lye KD, Kidd M. Cancer. 2003;97(4):934-959.

  14. NET Neuroendocrinetumours (NETs) are derived from cells that have the unique ability to synthesise, store and secrete a variety of metabolically active substances, peptides and amines, which can cause distinct clinical syndromes.

  15. Tumours regarded as NETs on the basis of the immunohistochemical expression of markers of NE differentiation Endocrine-Related Cancer (2010) 17 R173–R193

  16. Neuroendocrine TumorsClinical Presentations • Asymptomatic cases (50%) • Initial clinical symptoms are often non-specific and variable • Carcinoid syndrome (symptoms mistaken with other more common problems) • Most NETs are non-secretory and their clinical presentation before metastasis is non-specific

  17. GI NETsClinical Presentation • Clinical presentation of GI NETs varies widely • Often discovered incidentally • Symptoms due to: • Mechanical bulk • Fibrosis • Secretion of various hormones • Serotonin is most common substance secreted from GI NET • Serotonin release can cause carcinoid syndrome Serotonin-producing GI NET (ileum)

  18. Hypotension Flushing Rapid heart beat Heart disease Wheezing Diarrhea GI NETsCarcinoid Syndrome • Symptoms of carcinoid syndrome include: Carcinoid syndrome is associated with metastatic disease

  19. Natural History of Neuroendocrine Tumours Estimated time to diagnosis: 5 to 7 years Death * Diarrhea Vague abdominal symptoms * Flushing Metastases Primary tumour growth 1 2 3 4 5 6 7 8 9 Time, years *Symptoms of carcinoid syndrome Vinik A, et al. Pancreas. 2009 Nov;38(8):876-89 19

  20. Nonspecific Symptoms Are Commonto Multiple Diagnoses Menopause Functional Bowel Disease Symptoms • Sweating • Flushing • Diarrhea • Intermittent abdominal pain •Hypoglycemia• Confusion • Bronchoconstriction • Dyspepsia •GI bleeding • Cardiac disease Food Allergy Irritable Bowel Syndrome Neurosis Alcoholism NET Peptic Ulcer Asthma Anxiety Thyrotoxicosis 20 Aggarwal G, et al. Cleve Clin J Med. 2008;75(12):849-855.

  21. Spectrum of paraneoplastichumoral syndromes secondary to NETs

  22. Functional NETs: Secrete active substances , peptides and amine • Non-Functional NETs: Mass effect

  23. Neuroendocrine Tumors Pathological classificationStaging/Grading

  24. ClassificationTraditional Method • NETs have been traditionally classified as foregut, midgut, or hindgut, depending on site of origin • Replaced by new tumor-based classification method developed by World Health Organization (WHO)

  25. Classification World Health Organization Method • WHO classification defines NETs by degree of tumor differentiation, with specific clinicopathological features • The WHO classification system is based on the following criteria: • Biological behavior (malignancy) • Metastases • Ki-67 index • Angioinvasion • Tumor size • Histological differentiation • Hormonal syndrome

  26. WHO Classification 2000 • The nomenclature used in this classification is considers the following factors: • Histomorphology (degree of differentiation) • Presence / absence of local invasion / metastasis (Stage) • Proliferation index (grade)

  27. Well differentiated endocrine tumors - low grade malignancy Well differentiated endocrine carcinomas Poorly differentiated endocrine carcinomas - small cell carcinomas Mixed exocrine and endocrine carcinomas Tumor-like lesions WHO Classification 2000

  28. WHO Classification

  29. WHO Classification 2000

  30. Well differentiated neuroendocrine tumor grade 1

  31. WHO Classification 2000

  32. Neuroendocrine tumor grade 2 RadioGraphics March 2002 vol. 22 no. 2 351-365

  33. WHO Classification 2000

  34. Small cell neuroendocrine carcinoma grade 3 Cesar A. Moran etal. Am J Clin Pathology, 2009; 131: 206-221.

  35. Large cell neuroendocrine carcinoma Grade 3 Cesar A. Moran etal. Am J Clin Pathology, 2009; 131: 206-221.

  36. WHO Classification 2010: NeuroendocrineNeoplasms of the Digestive System • Working principles • “Neuroendocrine” defines the peptide hormoneproducing tumors and share neural-endocrine markers • “Neuroendocrine neoplasm” includes well- and poorly differentiated tumors • Premise: All neuroendocrineneoplasmshave a malignant potential • This premise has an influence on the incidence data because NENs that were regarded as benign and not considered in the incidence data (eg, SEERS data) now have to be included

  37. WHO Classification 2010: NeuroendocrineNeoplasms of the Digestive System • Main criteria determining the malignant potential –Tumor histopathology o Well differentiated o Poorly differentiated –Proliferative activity G1, G2, G3 –Site, size, infiltration/invasion, metastasis (TNM) o Esophagus, stomach, duodenum, ileum, appendix, colorectum,pancreas

  38. NeuroendocrineNeoplasms: NENs of the Gastroenteropancreatic (GEP) System Bosman FT, et al. WHO Classification of Tumours of the Digestive System. Lyon, France: IARC Press; 2010.

  39. NeuroendocrineNeoplasms: NENs of the Gastroenteropancreatic (GEP) System Bosman FT, et al. WHO Classification of Tumours of the Digestive System. Lyon, France: IARC Press; 2010.

  40. Systems of Nomenclature for Neuroendocrine Tumors (Pancreas & Volume 39, Number 6, August 2010) The grade of the tumor MUST be included in the pathology report, along with a reference to the specific grading system being used. Unqualified terms such as neuroendocrine tumor or neuroendocrine carcinoma without reference to grade do not provide adequate pathology information.

  41. Diagnostic Standards for NENs • Mandatory: • Histopathology―well or poorly differentiated • Expression of neuroendocrine markers synaptophysin and chromogranin A • Proliferative activity: G1–G3 • Stage: pTNM (ENETs 2007 and UICC 2009)

  42. Differentiated Stem Cell Origin of GEP-NENs

  43. Expression of neuroendocrine markers

  44. NE-Cells

  45. Neuroendocrine TumorsIHC for Diagnosis • Cytosolic (NSE, PGP 9.5) • Related to secretory granules (chromogrnins) • Related to synaptic vesicles (synaptophysin, VMAT) • Intermediate filaments (NF, High molecular weight CK) • Adhesion molecules (N-CAM)

  46. IHC Markers in Diagnosis of NETs

More Related