Pituitary Gland Pathology

8/6/2019 Pituitary Gland Pathology

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u ary an a o ogy

Anatomy

Small Bean-Shaped Organ

Located at Base of Brain

Within Sella Turcica

Close proximity to Optic Chiasm

Beneath Hypothalamus, attached by Pituitary Stalk

1cm in GD

0.5 gm in weight

Anterior Lobe

(Adenohypophysis) (80% of Gland)

Posterior Lobe

(Neurohypophysis)

Cell Types

Somatotrophs (GH)

Lactotrophs (Prolactin)Corticotrophs (ACTH)

Thyrotrophs (TSH)

Gonadotrophs (FSH, LH)

Modified Glial cells (Pituicytes),

Axonal Processes

OxytocinVasopressin (ADH)

Acidophilic (A) Pink

Secrete GH, Prolactin

Basophilic (B) Dark Purple

Secrete ACTH, TSH, Gonadotrophins

Chromophobe (C) Pale Staining

Few Secretary Activities

Resemble Neural Tissue

Glial cells

Nerve Fibers

Nerve Endings

Intra-Axonal Neurosecretory Granules

Anterior Pituitary Posterior Pituitary

Larger Portion Smaller Portion

NH Neurohypophysis (Posterior) AH Adenohypophysis (Anterior)

Functions of Hormones

Symptoms of Pituitary Diseases

Hyperpituitarism

Excessive Secretion of Trophic Hormones

Functional Adenoma of Anterior Pituitary

Hyperplasia of Anterior Pituitary

Carcinomas of Anterior Pituitary

(Rare, Non-Functional, Metastasis Lymph Nodes, Bones, Liver)Secretion of Hormones by Non-Pituitary Tumours

Certain Hypothalamic Disorders

Hypopituitarism

Deficiency of Tropic Hormones due to Destructive process of Pituitary Gland

Local Mass Effects

On Optic Chiasm resulting visual field abnormalities

Cranial Nerve compression

Intracranial Pressure

Pituitary Apoplexy (Haemorrhage)

Multiple Endocrine Neoplasia Syndrome (MENSyndrome)

Group ofGenetically Inherited Diseases resulting in Proliferative lesions

(Hyperplasia/ Adenoma/ Carcinoma) ofMultiple Endocrine Organs

MEN I MEN IIa MEN IIb

Pituitary Adenoma

Parathyroid Hyperplasia

Adenoma

Hyperplasia

Pancreas Hyperplasia

Adenoma/ Ca

Adrenal Cortical Hyperplasia Pleochromocytoma Pleochromocytoma

Thyroid C-Cell Hyperplasia

Medullary Ca

C-Cell Hyperplasia

Medullary Ca


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yperp u ar sm - u ary enoma

Definition

10% of Intracranial Neoplasm

Adult 30-50 y/o

Isolated Lesions (mostly)

Most common cause ofHyperpituitarism

Functional, Non-Functional (Silent)

3% - Associated with MEN Type I

Associated with Gene Abnormalities

Genetic Abnormalities

Monoclonal in origin (Single Somatic Cells)

G-Protein Mutation

Mutation in -subunit of G-Protein (Signal Transduction)Interferes with its GTPase activity

Activation of cAMP generation, Unchecked Cellular Proliferation

Association with MEN-I Syndrome

Aggressive Pituitary Adenoma

Mutation ofRAS oncogene

Over Expression ofc-MYC oncogene

Gross Morphology

Soft, Well-circumscribed lesion, confined to Sella Turcica

Larger lesions

Extend into Suprasellar region

Compress Optic Chiasm

Compress adjacent structures Cranial Nerves

Invasive Adenoma (30%)

Nonencapsulated

Infiltrate Adjacent Bone, Dura, Brain, Nasopharynx, Nasal Cavity

Pituitary Adenoma

Circumscribed Mass Lesion

(in Sella Turcica)

Brain, Pituitary Adenoma

Compressing Optic Chiasm

Pituitary Adenoma

Massive, Nonfunctional Adenoma

Grow beyond confines of Sella Turcica

Distorted the overlying brain

Histology

Monomorphic, Uniform, Polygonal cells arrayed in Sheets/ Cords

Supporting Connective Tissue/ Reticulin is sparse (soft gelatinous consistency)

Nuclei U niform, Pleomorphic

Cytoplasms (depending on type, amount of secretary product)

Acidophilic

Basophilic

Chromophobic

Cellular monomorphism, Absence of significant Reticulin Network distinguish

from Non-Neoplastic Anterior Pituitary Parenchyma (Pituitary Hyperplasia)

Classification based on Hormones Produced by Neoplastic Cells

detected by Immunohistochemical (IHC) stains on tissue sections

Adenohypophyseal Adenoma

Small round cells

Small round Nuclei

Pink to Blue cytoplasm

Cells are monotonously arranged

Absence of Reticulum Network

Reticulin Stain

Normal Hyperplasia Adenoma

Normal Acinararchitecture

Expanded Acini ofHyperplasia

Total breakdown ofReticulin Fiber network

Types of Pituitary Adenoma

Prolactin Cel l Adenoma (20-30%)

Growth Hormone Cell Adenoma (5%)

Mixed GH-Prolactin Adenoma (5%)

ACTH Cell Adenoma (10-15%)

Gonadotroph Cell Adenoma (10-15%)

Null Cell Adenoma (20%)

TSH Hormone Cell Adenoma (1%)

Other Pleurihormonal Adenoma (15%)

Pituitary Adenoma H&E

Growth Hormone (GH) +ve ACTH +ve

Prolactin +ve PIT-1 +ve

(Pituitary specific transcription factor responsiblefor pituitary development, hormone production in

mammals)


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Prolactinoma (Lactotroph Adenoma)

Hyperfunctioning Adenoma (most common)

Female - 20-40 y/o

Amenorrhea, Galactorrhea, Loss of Libido, Infertility

Microscopic

Weakly Acidophilic/ Chromophobic cells

IHC

Within secretory granules in cytoplasm of cells

Corticotroph Cell Adenoma (ACTH)

Basophilic or Chromophobic

ACTH Hypersecretion of Adrenal CortisolHypercortisolism Cushing Syndrome

(Due to excess ACTH by Pituitary)

24h Urine Free Cortisol Level

Loss of Normal Diurnal pattern of Cortisol Secretion

Hypercortisolism (Cushing Syndrome)

Central Obesity

Moon Face

Weakness, Fatigability

Hirsutism

Plethora

Hypertension

Glucose Intolerance

Osteoporosis

Neuropsychiatric Abnormalities

Menstrual Abnormalities

Skin Striae

IHC

Other Pituitary Adenoma

Gonadotroph Adenoma (LH, FSH)

Thyrotroph Adenoma (TSH)

Nonfunctioning Adenoma (25%)

Null cell Adenoma (Hormone ve Adenoma)

Clinically Silent counterparts of functioning Adenomas

Growth Hormone Adenoma (Somatotrophic Adenoma)

2nd

most common functioning Adenoma

Microscopic

Granulated cells which are Acidophilic or Chromophobic

IHC

GH within Cytoplasm of cells

Gigantism/ Acromegaly

Persistent Hypersecretion ofGH

Stimulate Hepatic Secretion of

Insulin-like Growth Factor-I (IGF-I/ Somatomedin C)

Gigantism Acromegaly

Children before Closure of Epiphyses After Closure of Epiphyses

Due to GH, IGF-1 GH

Generalized in body size Growth most conspicuous in

Skin, Soft Tissue, Viscera (Thyroid,

Heart, Liver, Adrenal), Bones of Face,

Hands, Feet

Disproportionately Long Arms, Legs

Bone Density (Hyperostosis)

Spine, Hips

Enlargement of Jaw

Protrusion (Prognathism)

Broadening of Lower Face

Enlarged Hands, Feet

Broad, Sausage-like Fingers

Gonadal dysfunction

Diabetes Mellitus

Generalised Muscle WeaknessHypertension

Arthritis

CHF

Risk of GI Bleeding

Diagnosis

Serum GH, IGF-1 Level

Failure to suppress GH Production in

response to oral load of glucose

Broadening of Lower Face

Protrusion of Jaw (Prognathism)Mandibular overgrowth

Hand of Acromegaly

Widen

Thickened

Stubby


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ypop u ar sm

Definition

Secretion of Pituitary Hormones

result from diseases of Hypothalamus, Pituitary

Destructive Lesions of Pituitary (mostly)

75% of Parenchyma is Lost, Absent

Hypopituitarism + (Evidence of) Posterior Pituitary Dysfunction

in form ofDiabetes Insipidus

Almost always Hypothalamic origin

Causes

1. Tumours, Other Mass Lesions2. Pituitary Surgery, Radiation3. Pituitary Apoplexy

Sudden haemorrhage into glandResults in rapid enlargement of gland

Neurosurgical emergency

Cause sudden death

4. Ischaemic Necrosis of Pituitary (Sheehan Syndrome)Post-partum necrosis of Anterior Pituitary

5. Rathke Cleft CystLined by Ciliated Cuboidal Epithelium

with occasionally Goblet cells, Anterior Pituitary Cells

6. Empty Sella SyndromeDestruction of Part/ All of Pituitary Gland in Ablation by Surgery,

Radiation

7. Genetic DefectsMutation in Pit-1 Transcription factor

8. Tumours in HypothalamusCraniopharyngiomas

Malignant tumours that Metastasize to Pituitary

9. Inflammatory disorders, InfectionsSarcoidosis, TB Meningitis

Posterior Pituitary Syndromes

Diabetes Insipidus

Deficiency of ADH Polyuria

Inability of Kidneys to Reabsorb H2O properly from urine

Result from

y Head Traumay Tumoursy Surgeryy Inflammatory disorders Hypothalamus, Pituitary2 Forms

y Centraly Nephrogenic (renal tubular unresponsiveness to circulating ADH)Syndrome of Inappropriate ADH Secretion (SIADH)

Resorption of excessive amounts of free H2Oy Hyponatremiay Cerebral OedemaEctopic ADH secretion by Malignant Neoplasms

Hypothalamic Suprasellar Tumours

Tumour/ Tumour-like lesions in Sellar region

Induce Hypofunction/ Hyperfunction of Anterior Pituitary, Diabetes Insipidus

Gliomas sometime arising in the Chiasm

Craniopharyngiomas

Derived from Vestigial Remnants ofRathke pouch

Epithelial neoplasm confined to region of Sella Turcica

Comprising 3-5% of all Intracranial Neoplasms

Admantinomatous Papillary

Nest/ Cords ofStratified Squamous

Epithelium embedded in Spongy

Reticulum

Composed of both Solid, Papillae

lined by Well Differentiated

Squamous Epithelium

Documents

Pituitary Gland Pathology