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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
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 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
Papillary Thyroid Carcinoma (PTC)
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
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)
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
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 have connective tissue capsule.
Coronal section total (bilateral) 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 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)