Pathology of Endocrine Glands - III

Adrenals

Jaroslava Dušková Inst. Pathol. 1st Med. Fac. Charles Univ. Prague

Endocrine Pancreas

Adrenals cortex

– definitive– fetal (90% regression by 6 months of age)

neonate 8g (3,5kg) 0,002

healthy adult 9g (70kg) 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 cortical carcinoma Adrenal cortical adenoma

Adrenal medullary tumours malignant phaeochromocytoma benign phaeochromocytoma composite phaeochromocytoma/paraganglioma

Extra-adrenal paraganglioma carotid body jugulotympanic vagal laryngeal aorticopulmonary cauda equina…..

Adrenal Cortical Carcinoma M8370/3

two peaks of incidence – middle to old age & preschool children

mostly hormonally active – 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 cortical carcinoma Adrenal cortical adenoma

Adrenal medullary tumours malignant phaeochromocytoma benign phaeochromocytoma composite phaeochromocytoma/paraganglioma

Extra-adrenal paraganglioma carotid body jugulotympanic vagal laryngeal aorticopulmonary cauda equina…..

PheochromocytomaDef.:benign tumour deriving from chromaffin cells

(intraadrenal paraganglioma)

Clin.: resistence, hypertensionMacro: 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

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 score222222221111 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 predilectionIncidence: most common solid extracranial malignant tumours during

the first two years of lifeHistogenesis: see definitionClinic: palpable mass (retroperit, abd., cervical), X-ray - thoracicMacro: soft gray-tan mass, regressive changesMicro: 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. if hormonally active – insulinoma, gastrinoma, glucagonoma, somatostatinoma, VIPoma… /Mitoses <2/10HPF, Ki67 <2%/

2. NET G2 - formerly well diff. neuroendocrine carcinoma - M 8249/3 /Mitoses >2/10HPF, Ki67 >20%/

2. NeuroEndocrine Carcinoma NEC1. large cell NEC - M8013/32. small cell NEC - M8041/3

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)

Other – secondary- pancreatic disease, drugs, chemicals

Gestational - GDM

Diabetes - detailed classification1. Type I Diabetes

1. beta cell destruction

2. Type II- Diabetes1. beta +insulin resistence

3. 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. Insulin Receptor Mutations

5. Exocrine Pancreas Diseases1. Chronic pancreatitis

2. Pancreatectomy

3. Neoplasia

4. Cystic fibrosis

5. Hemochromatosis

6. Fibrocalculous pancreatopathy

6. Endocrinopaties1. Acromegaly

2. Cushing syndrome

3. Hyperthyroidism

4. Pheochromocytoma

5. Glucagonoma

7. Infections1. CMV

2. Coxsackie B

3. Congenital rubella

8. Drugs1. Glucocorticoids

2. Thysroid hormones

3. Beta-adremergic agonists

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

well differentiated endocrine carcinoma of pancreas headmetastasizing into peripancreatic lymph nodes.

T 99 M 81503

Dg.:

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 - 2.

explorative 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 - 3.

hormonal activity of the neoplasm

reappeared

cytostatics administered into a. hepatica

death 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

ComplicationesMetastases 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