TUMOR SISTEM ENDOKRIN

BLOCK 21

LABORATORY WORK GUIDE

FOR THE PATHOLOGY OF
ENDOCRINOLOGY

I.PITUITARY GLAND
II. PARATHYROID GLAND
III. THYROID GLAND
IV. ENDOCRINE PANCREAS
V. ADRENAL GLAND
pituitary gland
pituitary gland
 pituitary gland

• The normal gross appearance of the pituitary gland removed from

the sella turcica is shown here. The larger portion, the anterior
pituitary (adenohypophysis), is toward the top. The image at the left
shows the superior aspect of the pituitary with the stalk coming from
the hypothalamus entering it. The inferior aspect of the pituitary is
shown at the right. The posterior pituitary (neurohypophysis) is the
smaller portion at the bottom.
 the pituitary gland

• The normal microscopic appearance of the pituitary

gland is shown here. The adenohypophysis is at the right
and the neurohypophysis is at the left.
The neurohypophysis shown here resembles neural tissue, with glial cells,
nerve fibers, nerve endings, and intra-axonal neurosecretory granules. The
hormones vasopressin (antidiuretic hormone, or ADH) and oxytocin made in
the hypothalamus (supraoptic and paraventricular nuclei) are transported into
the intra-axonal neurosecretory granules where they are released.
 the pituitary gland

• The normal microscopic appearance of the adenohypophysis is

shown here. The adenohypophysis contains three major cell types:
acidophils, basophils, and chromophobes. The staining is variable,
and to properly identify specific hormone secretion,
immunohistochemical staining is necessary.
 adenohypophysis
A simplistic classification is as follows:
• The pink acidophils secrete growth hormone
(GH) and prolactin (PRL)
• The dark purple basophils secrete corticotrophin
(ACTH), thyroid stimulating hormone (TSH), and
gonadotrophins follicle stimulating hormone-
luteinizing hormone (FSH and LH)
• The pale staining chromophobes have few
cytoplasmic granules, but may have secretory
activity.
Pituitary Neoplasma
 a pituitary adenoma

• The circumscribed mass lesion present here in the sella turcica is a

pituitary adenoma. Though pituitary adenomas are benign, they can
produce problems either from a mass effect (usually visual problems
from pressing on the optic chiasm and/or headaches) or from
production of hormones such as prolactin or ACTH.
 The microscopic appearance of the pituitary
adenoma is shown here. Note the monotonous
appearance of these small round cells.
 pituitary adenoma

• Description : Feinnadelpunktat der Hypophyse: Die hypophysären

Zellen mit erhaltenem Zytoplasma sind alle positiv für Prolaktin
chromophobe pituitary adenoma
 PARATHYROID
HYPERPARATHYROIDISM
Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism
HYPOPARATHYROIDISM
Surgically induced
Congenital absence of all glands
Pimary (idiopathic) atrophy of the glands 
autoimmune disease
Familial hypoparathyroidism
PSEUDOHYPOPARATHYROIDISM
Type 1: Gs deficiency  diminished cAMP response
to PTH  Albright hereditary osteodystrophy
Type 2: normal PTH-induced cAMP, with blunted
response to the second messenger
HYPERPARATHYROIDISM
Primary hyperparathyroidism
• Adenoma – 75 to 80%
• Primary hyperplasia (diffuse or nodular) – 10 to 15 %
• Parathyroid carcinoma – less than 5 %
Secondary hyperparathyroidism
• Overactivity of parathyroid gland (hyperplastic) due to
chronic depression in Ca serum level (i.e. renal failure
 renal osteodystrophy  bone abnormality)
Tertiary hyperparathyroidism
• Parathyroid activity may become autonomous and
excessive  hypercalcemia
• Parathyroidectomy is necessary
Parathyroid hyperplasia
PARATHYROID
Parathyroid: chief cell hyperplasia
PARATHYROID
PARATHYROID
 PARATHYROID
GLAND

Parathyroid adenoma arising

from the left lower
parathyroid gland
 PARATHYROID GLAND

Gross appearance of two parathyroid adenomas, note the roundish

shape, the homogenous appearance interrupted by a few foci of
fresh hemorrahgic or cystic changes, and the brown to yellowish color
PARATHYROID
PARATHYROID
PARATHYROID
PARATHYROID
PARATHYROID
 PARATHYROID CARCINOMA

Sharply outlined fibrous band incompletely dividing tumor into lobules

PARATHYROID CARCINOMA
THYROID
 THYROID
• Normally weighs between 20 and 30 g.
• Follicle is the functional unit of the thyroid 
composed of an epithelium-lined sac filled with
colloid  stores thyroid hormones in the form of
thyroglobulin  T4 (thyroxine) and T3 (triiodo-
thyronine)  regulated by TSH
• Serum T4 and T3 are bound to thyroid-binding
globulin (TBG)
Pathology of
Pathology of the
the thyroid
thyroid

A. HYPOTHYROIDISM
B. HYPERTHYROIDISM
C. THYROIDITIS
D. BENIGN TUMORS (ADENOMAS)
E. MALIGNANT TUMORS
Colloid Goiter
 Pathology of thyroid
C. HYPOTHYROIDISM

Clinical syndromes
Hypothyroidism is manifest as Myxedema in
adults or as Cretinism in children
Non-toxic goiter
Irregular
nodules

Marked variation in the size of follicles

 Nodular (non-toxic) Goiter

The gland is coarsely nodular and contains areas of fibrosis and cystic change.
Euthyroid goiter
Graves Disease
 Pathology of thyroid
HYPERTHYROIDISM (THYROTOXICOSIS)

B. Graves Disease
General Charcteristics
1. Hyperthyroidism caused by diffuse toxic goiter
2. Associated with striking exophthalmos  autoimmune?
3. More in women
4. incidence increased in HLA-DR3 and HLA-B8 positive individual
Mechanism
1. Thyroid-stimulating-immunoglobulin (TSI) reacts with TSH
receptors  stimulates thyroid hormone production
2. Thyroid-growth-immunoglobulin (TGI)  stimulates glandular
hyperplasia and enlargement
3. Antimicrosomal and other autoantibodies are characteristic
Graves disease, hyperthyroidism

Exophthalmos

Thyroid mass
 Major clinical
manifestations
of
Graves disease
 Graves Disease

Diffusely hyperplastic thyroid follicle are lined by tall,

columnar epithelium, and scalloped (“moth eaten”) appearance of
the edge of the colloid.
Graves disease, hyperthyroidism

The follicles are lined by hyperplastic, tall columnar cells

 THYROIDITIS
Inflammation of the thyroid gland
(encompasses a heterogenous group of inflammatory disorders of the
thyroid gland, including those that are caused by autoimmune
mechanisms and infectious agents)

A. Acute suppurative thyroiditis: a bacterial infection,

usually occurs in young children or debilitated patients. It is rare
B. Subacute granulomatous thyroiditis (De Quervain thyroiditis)
C. Chronic thyroiditis (Hashimoto thyroiditis, Struma lymphomatosa,
autoimmune thyroiditis)
D. Riedel’s struma (Riedel’s disease)
 Chronic autoimmune (Hashimoto)
thyroiditis
• Autoimmune disorder that occur more often in women
• Common cause of hypothyroidism, may occasionaly
have an early transient hyperthyroid phase
• Characterized histologically by massive infiltrates of
lymphocytes with germinal center formation, thyroid
follicles are atrophic, and Hurthle cells are prominent
• Associated with various antibodies (antithyroglobulin,
antithyroid peroxidase, anti TSH-receptor, anti-iodine
receptor antobodies)
• May be associated with other autoimmune disorders:
pernicious anemia, DM, Sjogren syndrome  the
incidence is increased in HLA-DR5 and HLA-B5 positive
 Chronic autoimmune (Hashimoto)
thyroiditis

The thyroid gland is symmetrically enlarged and coarsely nodular.

Coronal section  irregular nodules and an intact capsule
Hashimoto thyroiditis
 Chronic autoimmune (Hashimoto)
thyroiditis

Atrophic thyroid follicles with conspicuous chronic inflammatory infiltrate

(the inflammatory cells form prominent lymphoid follicles with germinal centers)
 Hashimoto Thyroiditis

Dense lymphocytic infiltrates with germinal centers

Residual thyroid follicle lined by Hurthle cells are also seen
 BENIGN TUMORS
(ADENOMAS)
• Are most often solitary
• Present clinically as nodules
• Can occur in a variety of histologic
pattern (follicular, Hurthle cell)
• Are most often nonfunctional but can
occasionally cause hyperthyroidism
• Female:male is 7:1
FOLLICULAR ADENOMA

• Embryonal adenoma
• Fetal adenoma
• Simple adenoma
• Colloid adenoma
• Hurthel cell adenoma
• Atypical adenoma
 Follicular adenoma
Embryonal adenoma

The tumor features a trabecular pattern with poorly formed follicles

that contain little if any colloid
 Follicular Adenoma
COLLOID ADENOMA
The cut surface of an encapsulated mass reveals:

Hemorrhage

Fibrosis

Cystic change
 Follicular Adenoma

Cystic

A solitary, well-circumscribed nodule is seen.

 Follicular Adenoma

Well-differentiated follicles resembling

normal thyroid parenchyma.
 Follicular adenoma
FETAL ADENOMA

Regular pattern of small follicles

 Follicular adenoma

Hurthle cell Adenoma

Cells with abundant eosinophilic cytoplasm and small regular nuclei.

MALIGNANT TUMORS

• Papillary Carcinoma
• Follicular Carcinoma
• Medullary Carcinoma
• Anaplastic Carcinoma
 G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

• Is the most common thyroid cancer (90%)

• Most frequent between ages 20 – 50 years
• Female:male is 3:1
• Papillary growth pattern with ground glass nuclei
• Better prognosis than other forms of thyroid cancer ,
even when adjacent lymph nodes is involved
• Can be long-term consequence of prior radiotherapy to
the neck
• Typically invades lymphatics and spreads to regional
lymph nodes
 G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

Macroscopic appearance with FNAB

grossly discernible papillary structure
 G. MALIGNANT TUMORS

Papillary
Thyroid
Carcinoma
(PTC)

Cut surface diplays a circumscribed

pale tan mass with foci of
cystic change
Papillary Thyroid Carcinoma (PTC)

Well-formed papillae
Papillary Thyroid Carcinoma (PTC)

“Orphan Annie eye”, or ground-glass nuclei, or empty appearing nuclei

Papillary Thyroid Carcinoma (PTC)
the most common thyroid cancer

Branching papillae are lined by neoplastic columnar epithelium with

clear nuclei. A calcospherite (psammoma body) is evident..
 Papillary Thyroid Carcinoma (PTC)
CYTOLOGY, MMG stain

Frosted glass
nucleus
 G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma

(FTC)

Cut surface of follicular carcinoma

with the substantial replacement
of the lobe of the thyroid.

The tumor has a light-tan

appearance and contains small foci
of hemorrage
Tumor infiltration (thyroid carcinoma)
 G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

Glandular lumen contains recognizable colloid

 G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

ADENOMA CARCINOMA

Capsular integrity in follicular neoplasm is critical in distinguishing follicular

adenoma from carcinoma.
Follicular adenoma: capsule is usually thin, occasionally more prominent;
no capsular invasion is seen (arrows).
Follicular carcinoma: capsular invasion (arrows)
 G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

A microfollicular tumor has invaded veins in the thyroid parenchyma.

 G. MALIGNANT TUMORS: Medullary Thyroid Carcinoma (MTC)

Clinical Features
• Symptoms related to endocrine secretion: carcinoid
syndrome (calcitonin), Cushing syndrome (ACTH)
• Watery diarhea in 1/3 cases, caused by secretion
of vasoactive intestinal peptide, pros-taglandin, and
several kinins
• Familial MTC: hypertension, episodic hypertension,
symptoms attributable to the secretion of catechol-
amines and phaeochromocytoma
• Therapy: thyroidectomy  local recurrencies 1/3
• 5-year survival rate is 75%
 G. MALIGNANT TUMORS:

Medullary Carcinoma

Solid pattern of growth and do not Coronal section  total (bilateral)

have connective tissue capsule. involvement by a firm, pale tumor.
 G. MALIGNANT TUMORS:

Medullary Thyroid Carcinoma

Nest of polygonal cells embedded in a collagenous framework.

 G. MALIGNANT TUMORS:

Medullary Thyroid Carcinoma

Amyloid: Congo red staining  polarized light microscope

 pale green birefringent
 G. MALIGNANT TUMORS:

Medullary Carcinoma

Typically contain amyloid, visible here as homogenous

extracellular material, derived from calcitonin molecules
secreted by the neoplastic cells
 G. MALIGNANT TUMORS:

Anaplastic Carcinoma of the Thyroid

The tumor in traverse section partially surround the trachea

and extend into the adjecent soft tissue.
 G. MALIGNANT TUMORS:

Anaplastic Carcinoma

The tumor is composed of bizarre spindle and giant cells with numerous mitoses
Endocrine Pancreas
Secretory Products of Islet Cells and Their Physiologic Actions

Cell Secretory Mol. Physiological Action

Product Wt.
Alpha Glucagon 3500 Catabolic, stimulates glycogenolysis &
gluconeogenesis, raises blood glucose

Beta Insulin 6000 Anabolic, stimulates glycogenesis, lipogenesis,

protein synthesis, lowers blood glucose. Inhibits
secretion of alpha, beta, D1, acinar cells

Delta Somatostatin 1600

D
Delta Vasoactive Intestinal 3800 Same as glucagon, regulates tone & GE tract
Polypeptide (VIP) motility, activates cAMP of intestinal epithelium
D1

PP Human pancreatic 4300 Stimulates gastric enzyme secretion, inhibits

polypeptide (ppp) intestinal motility & bile secretion

EC Serotonin, substance 176 Induce vasodilatation, increases vascular

P (motilin) permeability, stimulates motility of gastric
muscle and tone of lower esophageal sphincter
Pancreatic Endocrine Tumors
 Beta cell tumor

Many of the granules have irregular or crystalline content

 Alpha cell tumor

Granules are large and have dense peripheral nucleoid

 G-cell tumor

Granules are similar to those of VIP-producing tumor and

of normal gastrin cells. Most tumors from
Zollinger-Ellison have this appearance
 VIP-producing tumors

This tumor hav larger and more pleomorphic granules

Alpha cell tumor

Gross appearance shown,

required the performance
of a near total
pancreatectomy.
Alpha cell tumor (Glucagonoma)

Gross appearance shown,

exhibits foci of
hemorrhage and necrosis.
 Alpha cell tumor

The tumor showing a prominent gyriform arrangement of the

tumor cells. Tumors of this pattern are usually composed of
either alpha or beta cells
 ISLET CELL TUMOR

Gastrinoma (G-cell tumor)

- is often a malignant tumor, sometimes
occuring in extrapancreatic sites
- results in gastrin hypersecretion and hyper-
gastrinemia
- is associated with Zollinger-Ellison syndrome
(marked gastric hypersecretion of HCl),
recurrent peptic ulcer disease and hypergas-
trinemia
 G-cell tumor

Rosette-like gland formation in G-cell tumor (gastrinoma)