TUMOR SISTEM ENDOKRIN

BLOCK 21

LABORATORY WORK GUIDE FOR THE PATHOLOGY OF ENDOCRINOLOGY

I.PITUITARY GLAND II. PARATHYROID GLAND III. THYROID GLANDIV. ENDOCRINE PANCREASV. ADRENAL GLAND

pituitary gland

pituitary gland

pituitary glandThe 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 glandThe 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 glandThe 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.

adenohypophysisA 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 adenomaThe 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 adenomaDescription : Feinnadelpunktat der Hypophyse: Die hypophysren Zellen mit erhaltenem Zytoplasma sind alle positiv fr Prolaktin

chromophobe pituitary adenoma

PARATHYROIDHYPERPARATHYROIDISMPrimary hyperparathyroidismSecondary hyperparathyroidismTertiary hyperparathyroidismHYPOPARATHYROIDISMSurgically inducedCongenital absence of all glandsPimary (idiopathic) atrophy of the glands autoimmune diseaseFamilial hypoparathyroidismPSEUDOHYPOPARATHYROIDISMType 1: Gs deficiency diminished cAMP response to PTH Albright hereditary osteodystrophyType 2: normal PTH-induced cAMP, with blunted response to the second messenger

HYPERPARATHYROIDISMPrimary hyperparathyroidismAdenoma 75 to 80%Primary hyperplasia (diffuse or nodular) 10 to 15 %Parathyroid carcinoma less than 5 %Secondary hyperparathyroidismOveractivity of parathyroid gland (hyperplastic) due to chronic depression in Ca serum level (i.e. renal failure renal osteodystrophy bone abnormality)Tertiary hyperparathyroidismParathyroid activity may become autonomous and excessive hypercalcemiaParathyroidectomy is necessary

Parathyroid hyperplasia

PARATHYROID

Parathyroid: chief cell hyperplasia

PARATHYROID

PARATHYROID

PARATHYROIDGLANDParathyroid adenoma arising from the left lower parathyroid gland

PARATHYROID GLANDGross 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 CARCINOMASharply outlined fibrous band incompletely dividing tumor into lobules

PARATHYROID CARCINOMA

THYROID

T H Y R O I DNormally 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 TSHSerum T4 and T3 are bound to thyroid-binding globulin (TBG)

Pathology of the thyroidHYPOTHYROIDISMHYPERTHYROIDISMTHYROIDITISBENIGN TUMORS (ADENOMAS)MALIGNANT TUMORS

Colloid Goiter

Pathology of thyroid C. HYPOTHYROIDISMClinical syndromesHypothyroidism is manifest as Myxedema in adults or as Cretinism in children

Non-toxic goiterIrregular nodulesMarked variation in the size of follicles

Nodular (non-toxic) GoiterThe gland is coarsely nodular and contains areas of fibrosis and cystic change.

Euthyroid goiter

Graves Disease

Pathology of thyroidHYPERTHYROIDISM (THYROTOXICOSIS)B. Graves DiseaseGeneral Charcteristics1. Hyperthyroidism caused by diffuse toxic goiter2. Associated with striking exophthalmos autoimmune?3. More in women4. incidence increased in HLA-DR3 and HLA-B8 positive individualMechanism1. 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, hyperthyroidismExophthalmos Thyroid mass

Major clinical manifestations of Graves disease

Graves DiseaseDiffusely hyperplastic thyroid follicle are lined by tall, columnar epithelium, and scalloped (moth eaten) appearance of the edge of the colloid.

Graves disease, hyperthyroidismThe follicles are lined by hyperplastic, tall columnar cells

THYROIDITISInflammation of the thyroid gland(encompasses a heterogenous group of inflammatory disorders of thethyroid gland, including those that are caused by autoimmunemechanisms and infectious agents)

A. Acute suppurative thyroiditis: a bacterial infection, usually occurs in young children or debilitated patients. It is rareB. Subacute granulomatous thyroiditis (De Quervain thyroiditis)C. Chronic thyroiditis (Hashimoto thyroiditis, Struma lymphomatosa, autoimmune thyroiditis)D. Riedels struma (Riedels disease)

Chronic autoimmune (Hashimoto) thyroiditisAutoimmune disorder that occur more often in womenCommon cause of hypothyroidism, may occasionaly have an early transient hyperthyroid phaseCharacterized histologically by massive infiltrates of lymphocytes with germinal center formation, thyroid follicles are atrophic, and Hurthle cells are prominentAssociated 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) thyroiditisThe thyroid gland is symmetrically enlarged and coarsely nodular.Coronal section irregular nodules and an intact capsule

Hashimoto thyroiditis

Chronic autoimmune (Hashimoto) thyroiditisAtrophic thyroid follicles with conspicuous chronic inflammatory infiltrate(the inflammatory cells form prominent lymphoid follicles with germinal centers)

Hashimoto ThyroiditisDense lymphocytic infiltrates with germinal centersResidual thyroid follicle lined by Hurthle cells are also seen

BENIGN TUMORS (ADENOMAS)Are most often solitaryPresent clinically as nodulesCan occur in a variety of histologic pattern (follicular, Hurthle cell)Are most often nonfunctional but can occasionally cause hyperthyroidismFemale:male is 7:1

FOLLICULAR ADENOMAEmbryonal adenomaFetal adenomaSimple adenomaColloid adenomaHurthel cell adenomaAtypical adenoma

Follicular adenomaEmbryonal adenomaThe tumor features a trabecular pattern with poorly formed follicles that contain little if any colloid

Follicular AdenomaCOLLOID ADENOMAThe cut surface of an encapsulated mass reveals:Hemorrhage

Fibrosis

Cystic change

Follicular AdenomaA solitary, well-circumscribed nodule is seen.Cystic

Follicular AdenomaWell-differentiated follicles resembling normal thyroid parenchyma.

Follicular adenomaFETAL ADENOMARegular pattern of small follicles

Follicular adenomaHurthle cell AdenomaCells with abundant eosinophilic cytoplasm and small regular nuclei.

MALIGNANT TUMORSPapillary CarcinomaFollicular CarcinomaMedullary CarcinomaAnaplastic Carcinoma

G. MALIGNANT TUMORSPapillary Thyroid Carcinoma (PTC)Is the most common thyroid cancer (90%)Most frequent between ages 20 50 yearsFemale:male is 3:1Papillary growth pattern with ground glass nucleiBetter prognosis than other forms of thyroid cancer , even when adjacent lymph nodes is involvedCan be long-term consequence of prior radiotherapy to the neckTypically invades lymphatics and spreads to regional lymph nodes

G. MALIGNANT TUMORSPapillary Thyroid Carcinoma (PTC)Macroscopic appearance with grossly discernible papillary structureFNAB

G. MALIGNANT TUMORSPapillary 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 cancerBranching papillae are lined by neoplastic columnar epithelium with clear nuclei. A calcospherite (psammoma body) is evident..

Papillary Thyroid Carcinoma (PTC) CYTOLOGY, MMG stainFrosted glass nucleus

G. MALIGNANT TUMORSFollicular 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 TUMORSFollicular Thyroid Carcinoma (FTC)Glandular lumen contains recognizable colloid

G. MALIGNANT TUMORSFollicular 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)ADENOMACARCINOMA

G. MALIGNANT TUMORSFollicular Thyroid Carcinoma (FTC)A microfollicular tumor has invaded veins in the thyroid parenchyma.

G. MALIGNANT TUMORS: Medullary Thyroid Carcinoma (MTC)Clinical FeaturesSymptoms 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 kininsFamilial MTC: hypertension, episodic hypertension, symptoms attributable to the secretion of catechol-amines and phaeochromocytomaTherapy: thyroidectomy local recurrencies 1/3 5-year survival rate is 75%

G. MALIGNANT TUMORS: Medullary CarcinomaSolid 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 CarcinomaNest of polygonal cells embedded in a collagenous framework.

G. MALIGNANT TUMORS: Medullary Thyroid CarcinomaAmyloid: Congo red staining polarized light microscope pale green birefringent

G. MALIGNANT TUMORS: Medullary CarcinomaTypically contain amyloid, visible here as homogenous extracellular material, derived from calcitonin molecules secreted by the neoplastic cells

G. MALIGNANT TUMORS: Anaplastic Carcinoma of the ThyroidThe tumor in traverse section partially surround the trachea and extend into the adjecent soft tissue.

G. MALIGNANT TUMORS: Anaplastic CarcinomaThe tumor is composed of bizarre spindle and giant cells with numerous mitoses

Endocrine Pancreas

Secretory Products of Islet Cells and Their Physiologic Actions

Pancreatic Endocrine Tumors

Beta cell tumorMany of the granules have irregular or crystalline content

Alpha cell tumorGranules are large and have dense peripheral nucleoid

G-cell tumorGranules are similar to those of VIP-producing tumor and of normal gastrin cells. Most tumors from Zollinger-Ellison have this appearance

VIP-producing tumorsThis tumor hav larger and more pleomorphic granules

Alpha cell tumorGross 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 tumorThe 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 TUMORGastrinoma (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 tumorRosette-like gland formation in G-cell tumor (gastrinoma)