FIBROADENOMA OF THE BREAST

Definition

Epidemiology / Age Group

• Most common in females between 20-30 years of age.
• Growth is hormonally influenced - tumors may enlarge rapidly during pregnancy and regress after menopause.

Clinical Features

• Presents as a palpable, freely movable, well-circumscribed mass.
• The characteristic mobility on examination earns it the name "breast mouse."
• Usually solitary, but may be multiple or bilateral.
• Non-tender, smooth, rubbery consistency.

Morphology

Gross Appearance

Microscopy

1. Neoplastic epithelial component - Ducts lined by a double layer of epithelium ranging from normal lobules to varying degrees of hyperplasia; ducts may be simple/round or elongated/branching.
2. Neoplastic stromal component - Fibrous connective tissue stroma that is uniform, delicate, myxoid, and of low cellularity; resembles normal intralobular (peritubular) stroma; contains spindle cells without atypia.

Growth Patterns (Two Types)

• Pericanalicular pattern: Epithelium forms round or oval tubules with patent lumen; proliferating stromal cells grow around open ducts in a circumferential fashion.
• Intracanalicular pattern: Stromal growth compresses ducts into curvilinear slits (clefts); ducts appear distorted.

Both patterns may coexist and have no prognostic significance.

Hormonal Changes

• Pregnancy: Epithelial component may show lactational changes; glands increase in size.
• Post-menopause: Stroma becomes more fibrous and densely hyalinized; may calcify forming "popcorn" calcifications on mammography.

Variants

Malignant Potential

• Malignant transformation is extremely rare (<0.3%).
• Fibroadenoma is considered a benign lesion with an excellent prognosis.

Treatment

• Surgical excision (lumpectomy) is the treatment of choice.
• Does not recur after complete excision.

Exam Tip: Remember the key triad - young woman + freely mobile breast lump ("breast mouse") + biphasic (epithelial + stromal) histology = Fibroadenoma.

ADDISON'S DISEASE (PRIMARY CHRONIC ADRENOCORTICAL INSUFFICIENCY)

Definition

First described by Thomas Addison in 1855 as a syndrome of "general languor and debility, remarkable feebleness of the heart's action, and peculiar changes in the skin."

Etiology / Causes

Autoimmune Polyendocrinopathy Syndromes (APS)

• APS-1: Adrenalitis + hypoparathyroidism + mucocutaneous candidiasis; caused by AIRE gene mutation (chr 21q22)
• APS-2 (Schmidt syndrome): Adrenal insufficiency + autoimmune thyroiditis ± T1D; starts in 4th decade
• APS-4: Adrenalitis + gastritis/vitiligo/pernicious anemia but no thyroiditis or T1D

Pathogenesis

• Autoimmune destruction of steroidogenic cells in all three zones of the adrenal cortex (zona glomerulosa, fasciculata, reticularis)
• Results in loss of all three classes of adrenocortical hormones
• Low cortisol removes negative feedback on the hypothalamo-pituitary axis → ACTH rises markedly
• ACTH is derived from POMC, which also yields melanocyte-stimulating hormone (MSH) - this causes the characteristic hyperpigmentation

Morphology

Gross

• Autoimmune adrenalitis: Irregularly shrunken glands, difficult to identify within perirenal fat
• Tuberculous / fungal: Adrenals enlarged, architecture effaced by granulomatous inflammation
• Metastatic: Adrenals enlarged, normal architecture obscured by infiltrating neoplasm

Microscopy

• Tuberculous cases: Classic caseating granulomas
• Metastatic cases: Neoplastic cells replacing cortical tissue

Clinical Features

Due to Glucocorticoid (Cortisol) Deficiency

• Progressive weakness and easy fatigability (most common initial symptom)
• Anorexia, nausea, vomiting, weight loss, diarrhea
• Hypoglycemia (loss of gluconeogenic effect)

Due to Mineralocorticoid (Aldosterone) Deficiency

• Hyponatremia and hyperkalemia (Na loss, K retention)
• Metabolic acidosis
• Hypotension and volume depletion
• Salt craving

Due to ACTH / MSH Excess (Pathognomonic)

• Hyperpigmentation - most characteristic sign
• Affects sun-exposed areas, pressure points (neck, elbows, knees, knuckles), nail beds, nipples, areolae, buccal mucosa, and recent scars
• Absent in secondary adrenal insufficiency (pituitary/hypothalamic disease) - key differentiating point

Due to Androgen Deficiency (in females)

• Decreased pubic and axillary hair
• Decreased libido

Laboratory Findings

Key differentiator: In secondary adrenal insufficiency (pituitary failure), ACTH is low and there is NO hyperpigmentation.

Addisonian Crisis (Acute Adrenal Insufficiency)

• Precipitated by stress (infection, surgery, trauma) in a patient with chronic insufficiency
• Features: Severe hypotension/shock, vomiting, abdominal pain, fever, profound hyponatremia, hyperkalemia
• Medical emergency - treat with IV hydrocortisone immediately

Treatment

• Replacement therapy: Oral hydrocortisone (glucocorticoid) + fludrocortisone (mineralocorticoid)
• Dose must be doubled or tripled during illness/stress ("sick day rules")
• Patient education regarding crisis prevention

Exam Tip - Key triad of Addison's disease: Hyperpigmentation + Hypotension + Hyponatremia/Hyperkalemia. Remember: HIGH ACTH = hyperpigmentation = PRIMARY adrenal failure. Low ACTH = no pigmentation = SECONDARY failure.