Transcript Pigmenty
Pathology of Endocrine Glands - III Adrenals Endocrine Pancreas Jaroslava Dušková Inst. Pathol. 1st Med. Fac. Charles Univ. Prague Adrenals cortex – definitive – fetal (90% regression by 6 months of age) neonate 8g healthy adult 9g (3,5kg) (70kg) 0,002 0,0001 – zones G,F,R 20x medulla norm hypoplasia congenitalis Adrenals - syndromes hypofunction - panhypocorticalism – acute – chronic – Adison – peripheral – central hyperfunction – AGS – Cushing – hyperaldosteronism Conn, Bartter m Adison: peripheral central Adrenals - syndromes hypofunction - panhypocorticalismus – acute – chronic – Adison – periferic – central hyperfunction – Cushing – hyperaldosteronism Conn, Bartter – AGS WHO Clasification of Tumours of the Adrenal Gland (WHO 2004) Adrenal cortical tumours Adrenal medullary tumours Adrenal cortical carcinoma Adrenal cortical adenoma malignant phaeochromocytoma benign phaeochromocytoma composite phaeochromocytoma/paraganglioma Extra-adrenal paraganglioma carotid body jugulotympanic vagal laryngeal aorticopulmonary cauda equina….. Adrenal Cortical Carcinoma M8370/3 peaks of incidence – middle to old age & preschool children mostly hormonally active two – androgens only – androgens + glucocorticoids – androgens + glucocorticoids+mineralocorticoids – estrogens (exceptional) Adrenal Cortical Carcinoma M8370/3 Malignancy criteria high nuclear grade (Fuhrman) mitoses incl. atypical diffuse architecture necrosis invasion into veins, capsule m. Cushing periph. hypothalamic m. Cushing paraneopl.15% pituitary C.>50% Androgen overproduction AGS WHO Clasification of Tumours of the Adrenal Gland (WHO 2004) Adrenal cortical tumours Adrenal medullary tumours Adrenal cortical carcinoma Adrenal cortical adenoma malignant phaeochromocytoma benign phaeochromocytoma composite phaeochromocytoma/paraganglioma Extra-adrenal paraganglioma carotid body jugulotympanic vagal laryngeal aorticopulmonary cauda equina….. Pheochromocytoma Def.: benign tumour deriving from chromaffin cells (intraadrenal paraganglioma) Clin.: resistence, hypertension Macro: whittish, solid, regressive changes Micro: solid alveolar (Zellballen) Behaviour: benign (15% bilateral, 10% children,10% malignant) part of MEN II and von Hippel-Lindau disease Biology Behaviour of Pheochromocytoma Diffuse growth Central necroses High cellularity Monotonous Fusocellular Mitoses >3/10 HPF Atypical mitoses Invasion into fatty tissue Invasion to vessels Transcapsular invasion Pleomorphic cells Nuclear hyperchromasia 2 2 2 2 2 2 2 2 1 1 1 1 PASS score Thompson L.D.R.: Phaeochromocy toma of the Adrenal Gland Scoring Scale (PASS) to separate benign from malignant neoplasms. A clinicopathologic and immunophenotypic study of 100 cases. Am. J. Surg. Pathol. 26(5), 2002, 551-566 PASS score <4/20 benign Neuroblastoma (WHO: Neuroblastic tumours of adrenal gland and sympathetic nervous system) Def.: childhood embryonal tumours of migrating neuroectodermal cells derived from the neural crest and destined for the adrenal medulla and sympathetic nervous system Age /sex – 96% in the 1st decade , no sex predilection Incidence: most common solid extracranial malignant tumours during the first two years of life Histogenesis: see definition Clinic: palpable mass (retroperit, abd., cervical), X-ray - thoracic Macro: soft gray-tan mass, regressive changes Micro: undiff. + differentiating neuroblasts Variants: neuroblastoma (undiff.), ganglioneuroblastoma intermixed, ganglioneuroblastoma nodular, ganglioneuroma Behaviour: malignant, dependent on age and histology variant Islets of Langerhans (1869) adults 100 000 -1000 000 cell types: B - insulin A - glucagon D – somatostatin PP – pancreatic polypeptide D – vasoactive intestinal polypeptide Islets of Langerhans - regressive changes fibrosis (postinflamm.) - DM I mucoviscidosis DM frequency 10x hyalinosis, amyloidosis Islets of Langerhans - progressive changes hyperplasia – diabetic embryopathy nesidioblastosis Islets of Langerhans - tumours nesidioma ( event. in MEN I) insulinoma, glucagonoma, somatostatinoma,VIPoma, PP-oma, G cells - gastrinoma, EC – serotonin - carcinoid neuroendocrine carcinoma New classification of GastroEnteroPancreatic NeuroEndocrine Neoplasms GEP –NEN (2010) 1. NeuroEndocrine Tumour NET 1. NET G1 (carcinoid) - M8240/3 1. 2. if hormonally active – insulinoma, gastrinoma, glucagonoma, somatostatinoma, VIPoma… /Mitoses <2/10HPF, Ki67 <2%/ NET G2 - formerly well diff. neuroendocrine carcinoma - M 8249/3 /Mitoses >2/10HPF, Ki67 >20%/ 2. NeuroEndocrine Carcinoma NEC 1. 2. 3. large cell NEC - M8013/3 small cell NEC - M8041/3 Mixed AdenoNeuroEndocrine Carcinoma MANEC M8244/3 Exceptions: Tubular appendical carcinoid M8245/1; L-cell NET PP/PYY M8152/1 Islets of Langerhans - syndromes hyperfunction - insulinoma – hypoglycemia (weekness , sweating, tremor, coma) – Zollinger-Ellison, Werner Morrison, glucagonoma hypofunction – absolute or relative insulin lack ( DMI/II or glucagonoma) hyperglycemia – acute : polydipsia, ketoacidosis, coma, liver steatosis , brain edema – chronic: diabetes mellitus: microangiopathy, macroangiopathy, neuropathy, retinopathy, embryopathy Diabetes mellitus Def.: group of disorders with glucose intolerance in common --------------Chronic hyperglycemia and disturbances of carbohydrate, protein, and fat metabolism. Diabetes mellitus - types DM I – IDDM – juvenile DM II – NIDDM -(+MODY) – secondary- pancreatic disease, drugs, chemicals Gestational - GDM Other Diabetes - detailed classification 1. Type I Diabetes 6. 1. beta cell destruction 2. 3. beta +insulin resistence Genetic Defects of Beta Cell Function 1. Maturity Onset Diabetes of the Young (type 1-6 with known mutations) 2. Maternaly inherited diabetes and deafness due to mitochondrial mutations 3. Defects in proinsulin conversion 4. Insulin gene mutation 4. 5. 1. 2. 3. 4. 5. Type II- Diabetes 1. 7. Chronic pancreatitis Pancreatectomy Neoplasia Cystic fibrosis Hemochromatosis Fibrocalculous pancreatopathy Acromegaly Cushing syndrome Hyperthyroidism Pheochromocytoma Glucagonoma Infections 1. CMV 2. Coxsackie B 3. Congenital rubella 8. Drugs 1. Glucocorticoids 2. Thysroid hormones 3. Beta-adremergic agonists Insulin Receptor Mutations Exocrine Pancreas Diseases 1. 2. 3. 4. 5. 6. Endocrinopaties 9. Genetic Syndromes Associates with Diabetes 1. Down syndrome 2. Klinefelter syndrome 3. Turner syndrome 10. Gestational Diabetes Diabetes mellitus - complications acute – hypoglycemia (DM I and insulin treatment) – diabetic ketoacidosis : lack of insulin – increased release of fatty acids –increased ketone formation – metabolic acidosis chronic – AGE – Advanced Glycosylation End-products – diabetic micro- and macroangiopathy – neuropathy – infection Pešková M., Hvižď R., Dušková, J. Malignant somatostatinoma (brief overview and a case review) Rozhl Chir. 2007 Dec;86(12):643-7. Czech. Male 73 Dg.: well differentiated endocrine carcinoma of pancreas head metastasizing into peripancreatic lymph nodes. T 99 M 81503 Case Report woman 26 yrs N 571/92 History - 1. mononucleosis in the childhood 2 yrs prior to death during her 9th week of pregnancy repetitive amentia statuses, hospitalized in the Psychiatry Clinic hypoglycemia 1,2mmol/l found transferred to General Medicine Clinic two weeks later gravidity interruption History explorative - 2. laparotomy - tumour of the pancreas with liver metastases no tumour in the biopsy sample taken next two monts – cycles of chemotherapy, the hormonal activity of the neoplasm dissappeared progression of the neoplasm with the gastric wall infiltration History hormonal - 3. activity of the neoplasm reappeared cytostatics death administered into a. hepatica two years from the onset of the disease C- peptide proteolytic phragment of proinsulin secreted (equimollar quantities) by beta-cells of Langerhans islets Diagnosis Morbus principalis Carcinoma neuroendocrinum parvocellulare pancreatis ad parietem ventriculi et reproperitoneum progressum Complicationes Metastases carcinomatosae lnn. mesentericorum, hepaticorum, iliacorum. Hyperinsulinismus. Causa mortis Generalisatio carcinomatis Hyperinsulinism due to pancreatic tumour – mostly B-cell NESIDIOMA (insulinoma) - BENIGN – rare in pregnancy – malignant B-cell tumour neuroendocrine carcinoma / nesidioblastoma extremely rare paraneoplastic hypoglycemia – mesenchymal retroperitoneal, adrenocortical, GIT tumours