4a Tumor Sistem Endokrinaaa

TUMOR SISTEM ENDOKRIN

BLOCK 21

LABORATORY WORK GUIDE FOR THE PATHOLOGY OF

ENDOCRINOLOGY

I.PITUITARY GLAND II. PARATHYROID GLAND

III. THYROID GLANDIV. 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 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.

the pituitary gland

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

PARATHYROIDHYPERPARATHYROIDISM

Primary hyperparathyroidismSecondary hyperparathyroidismTertiary hyperparathyroidism

HYPOPARATHYROIDISMSurgically inducedCongenital absence of all glandsPimary (idiopathic) atrophy of the glands

autoimmune diseaseFamilial hypoparathyroidism

PSEUDOHYPOPARATHYROIDISMType 1: Gs deficiency diminished cAMP response

to PTH Albright hereditary osteodystrophyType 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

PARATHYROIDGLAND

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

T H Y R O I D

• 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 the thyroidPathology of the thyroid

A. HYPOTHYROIDISMB. HYPERTHYROIDISMC. THYROIDITISD. BENIGN TUMORS (ADENOMAS)E. MALIGNANT TUMORS

Colloid Goiter

Pathology of thyroid

C. HYPOTHYROIDISM

Clinical syndromesHypothyroidism 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 DiseaseGeneral Charcteristics

1. Hyperthyroidism caused by diffuse toxic goiter2. Associated with striking exophthalmos autoimmune?3. More in women4. incidence increased in HLA-DR3 and HLA-B8 positive individual

Mechanism

1. Thyroid-stimulating-immunoglobulin (TSI) reacts with TSH receptors stimulates thyroid hormone production2. 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


The thyroid gland is symmetrically enlarged and coarsely nodular.Coronal section irregular nodules and an intact capsule

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 centersResidual 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 ADENOMAThe cut surface of an encapsulated mass reveals:

Hemorrhage

Fibrosis

Cystic change

Follicular Adenoma

A solitary, well-circumscribed nodule is seen.

Cystic

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


Macroscopic appearance with grossly discernible papillary structure

FNAB

G. MALIGNANT TUMORS

Papillary Thyroid

Carcinoma (PTC)

Cut surface diplays a circumscribed pale tan mass with foci of

cystic change


Well-formed papillae


“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


Glandular lumen contains recognizable colloid

G. MALIGNANT TUMORS


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)

ADENOMA CARCINOMA

G. MALIGNANT TUMORS


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 have connective tissue capsule.

Coronal section total (bilateral) involvement by a firm, pale tumor.


Medullary Thyroid Carcinoma

Nest of polygonal cells embedded in a collagenous framework.


Medullary Thyroid Carcinoma

Amyloid: Congo red staining polarized light microscope pale green birefringent


Medullary Carcinoma

Typically contain amyloid, visible here as homogenous extracellular material, derived from calcitonin molecules secreted by the neoplastic cells


Anaplastic Carcinoma of the Thyroid

The tumor in traverse section partially surround the trachea and extend into the adjecent soft tissue.


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 Product

Mol. Wt.

Physiological Action

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

DeltaD

Somatostatin 1600

DeltaD1

Vasoactive Intestinal Polypeptide (VIP)

3800 Same as glucagon, regulates tone & GE tract motility, activates cAMP of intestinal epithelium

PP Human pancreatic polypeptide (ppp)

4300 Stimulates gastric enzyme secretion, inhibits intestinal motility & bile secretion

EC Serotonin, substance P (motilin)

176 Induce vasodilatation, increases vascular 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)

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4a Tumor Sistem Endokrinaaa