Page 845 - Textbook of Pathology, 6th Edition

Gastrinoma 2. Pancreatic islet cells: Hyperplasia or adenoma seen in 80% 829
(G-Cell Tumour, Zollinger-Ellison Syndrome) cases; frequently with Zollinger-Ellison syndrome.
3. Pituitary: Hyperplasia or adenoma in 65% cases; manifest
Zollinger and Ellison described diagnostic triad consisting
of the following: as acromegaly or hypopituitarism.
Fulminant peptic ulcer disease 4. Adrenal cortex: Uncommonly involved by adenoma or
Gastric acid hypersecretion pheochromocytoma.
5. Thyroid: Less commonly involved by adenoma or
Presence of non-β pancreatic islet cell tumour. hyperplasia.
Such non-β pancreatic islet cell tumour is the source of
gastrin, producing hypergastrinaemia and hence named 2. MEN type 2 syndrome (Sipple’s syndrome) is
gastrinoma. Definite G cells similar to intestinal and gastric characterised by medullary carcinoma thyroid and
G cells which are normally the source of gastrin in the body, pheochromocytoma. Genetic abnormality in these cases is
have not been identified in the normal human pancreas but mutation in RET gene in almost all cases. MEN 2 has two
neoplastic cells of certain islet cell tumours have major syndromes:
ultrastructural similarities. MEN type 2A is the combination of medullary carcinoma
thyroid, pheochromocytoma and hyperparathytroidism.
MORPHOLOGIC FEATURES. Majority of gastrinomas MEN type 2A has further three subvariants:
occur in the wall of the duodenum. They may be benign i) MEN 2A with familial medullary carcinoma thyroid
or malignant. Gastrinomas are associated with peptic ii) MEN 2A with cutaneous lichen amyloidosis
ulcers at usual sites such as the stomach, first and second iii) MEN 2A with Hirschsprung’s disease.
part of the duodenum, or sometimes at unusual sites such MEN type 2B the combination of medullary carcinoma
as in the oesophagus and jejunum. About one-third of thyroid, pheochromocytoma, mucosal neuromas, intestinal
patients have multiple endocrine neoplasia—multiple ganglioneuromatosis, and marfanoid features.
adenomas of the islet cells, pituitary, adrenal and 3. Mixed syndromes include a variety of endocrine
parathyroid glands.
neoplastic combinations which are distinct from those in
MEN type 1 and type 2. A few examples are as under: CHAPTER 27
MISCELLANEOUS ENDOCRINE TUMOURS von Hippel-Lindau syndrome from mutation in VHL
gene is association of CNS tumours, renal cell carcinoma,
MULTIPLE ENDOCRINE NEOPLASIA (MEN) pheochromocytoma and islet cell tumours.
SYNDROMES Type 1 neurofibromatosis from inactivation of neurofibro-
min protein and activation of RAS gene, is associated with
Multiple adenomas and hyperplasias of different endocrine MEN type 1 or type 2 features.
organs are a group of genetic diorders which produce
heterogeneous clinical features called multiple endocrine POLYGLANDULAR AUTOIMMUNE (PGA) SYNDROMES
neoplasia (MEN) syndromes. Presently, 4 distinct types of
MEN syndromes are distinguished. These are briefly outlined Immunologic syndromes affecting two or more endocrine The Endocrine System
below along with major disease associations: glands and some non-endocrine immune disturbances
produce syndromic presentation termed polyglandular
1. MEN type 1 syndrome (Wermer’s syndrome) includes autoimmune (PGA) syndromes. PGA syndromes are of two
adenomas of the parathyroid glands, pancreatic islets and types:
pituitary. The syndrome is inherited as an autosomal
dominant trait. There is 50% chance of transmitting the PGA type I occurring in children is characterised by
predisposing gene, MEN 1 (or menin) gene, to the child of an mucocutaneous candidiasis, hypoparathyroidism, and
affected person. MEN 1 is characterised by the following adrenal insufficiency.
features: PGA type II (Schmidt syndrome) presents in adults and
1. Parathyroid: Hyperplasia or adenoma; hyperparathy- commonly comprises of adrenal insufficiency, autoimmune
roidism is the most common (90%) clinical manifestation. thyroiditis, and type 1 diabetes mellitus.

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