179. Adrenal Pathology, Cortex/Medulla

Question 1

What are the layers of the adrenal gland (5), what %volume do they take up, what hormones do they produce?

Answer 1

Cortex

• Capsule
• Zona glomerulosa (15% volume) - produces MCs
• Zona fasciculata (70% volume) - produces GCs
• Zona reticularis (15% volume) - produces androgens

Medulla (produces catecholamines)

Question 2

Cortical Hypofunction

• Etiology (3)
• sx
• gross
• Waterhouse Friderichsen Syndrome (what is it, path, etiology)

Answer 2

Eti: Pituitary insufficiency, Addison’s Disease (chronic adrenal insufficiency, due to autoimmune inflammation [mainly] or tumors, HIV, TB), Abrupt withdrawal of steroid therapy (iatrogenic)
sx: fatigue, hypotension, hyperpigmentation, hyperkalemia
Gross: atrophic cortex
WFS: acute cortical hypofunction - acute adrenal failure
- path: hemorrhage and necrosis
- eti: meningococcal sepsis, DIC, severe hypotension

Question 3

Cortical Hyperfunction

• Etiology (4)
• sx
• gross (types)

What are the top 3 types of adrenal mass lesions?

Answer 3

E: Cushing’s Disease (ACTH-secreting pit adenoma), Other ACTH-secreting tumors (lung carcinoma), Primary adrenal cortical hyperplasia, cortisol-producing adrenal cortical tumor
Cushing’s syndrome: high cortisol levels, central obesity, moon faces, purple striae, hirsutism
Gross:
1. diffuse hyperplasia - symmetric enlargement (congenital adrenal hyperplasia, Cushing syndrome)
2. Micronodular - all <1.0 cm (Cushing Syndrome)
3. Macronodular - some >1.0cm (uncommon)

Adrenal Mass Lesions
#1 - Non-fx Cortical Adenoma (37-77%)
#2 - PCC (5-20%)
#3 - Metastatic Carcinoma (2-11%)

Question 4

Adrenal Cortical Adenoma

• what is it, prevalence
• types of functional adenoma
• gross
• histo
• assoc syndromes

Answer 4

Benign neoplasm in 1-5% general population = MOST COMMON ADRENAL TUMORS
Most non-fx, discovered incidentally
functional adenoma - may produce a different hormone

Conn Syndrome - aldo-producing
Cushing Syndrome - GC-producing
Androgen producing (assoc with feminization or virilization)
Mixed-hormone producing adenoma

Gross: well-circumscribed mass, golden-yellow color, small <5cm and light <100g, homogenous cut surface, no invasion
Histo: looks similar to normal cells, on background of non-neoplastic adrenal gland

Assoc: MEN I, Hyperparathyroidism Jaw Tumor Syndrome, Li Fraumeni Syndrome

Question 5

Adrenal Cortical Carcinoma

• what is it, prevalence
• gross
• histo: Weiss Criteria

Answer 5

Primary malignant neoplasm, 2-4% all adrenal masses
gross: large (>6.5cm, >100g), tan-grey color (necrosis/hemorrhage), heterogeneous cut surface + invasion to surrounding tissue (into periadrenal fat cells)

Histo: >3 of the following suggest malignant behavior
cytologic atypia
1. Pink cytoplasm
2. difference of pattern
3. necrosis
4. high nuclear grade 
high mitosis
5. >5 mitoses/HPF
6. atypical mitoses
invasion
7. venous invasion
8. capsular invasion
9. extraadrenal invasion

Question 6

PCC

• prevalence
• assoc syndromes
• gross
• histo
• only definitive criteria for malignancy

Answer 6

10% tumor - 10% malignant, 10% bilateral, 10% inherited
syndromes: MEN2A, MEN2B, VHL, NF1, Stuge-Weber
Most cases functional = producing catecholamines
Gross: pink/red/gray, slightly heterogeneous, surrounded by rim of cortex
Histo: ZELLBALLEN (large tumor cells forming nests), purple cytoplasm, sustentacular cells present
ONLY definitive criteria for malignancy = METASTASES

Question 7

Ganglioneuroma

• what is it, derivation, composition
• gross
• histo

Answer 7

Benign tumor, neural crest derived
composed of ganglion cells and Schwannian stroma
NOT hormonally active
Gross: pale grey mass confined in medulla, with rim of intact cortex
Histo: SCHWANNIAN STROMA (spindle cells)

Question 8

Neuroblastoma

• what is it
• pt population
• most common site
• CP, PE
• gross
• histo

Answer 8

Malignant tumor of neural crest-derived cells
Pt: children (1/7000 births, 6% all childhood malignancies)
Most common site = ADRENAL MEDULLA
CP: palpable (advanced) abd mass +/- abd pain, catecholamine metabolites (VMA, HMA) elevated in urine, “Blueberry Muffin Baby” = hemorrhagic spots on abd wall spread all over body/limbs/face skin

Gross: large size, replaces most adrenal gland and kidney
Histo: high density of small round blue cells, Homer-Wright Rosettes (indicates neuroblastoma!)

Question 9

Types of Adrenal Cysts (4) - gross/histo for one

Answer 9

1. Endothelial Cysts - most common (45% adrenal cysts)
Gross: cystic lesion
Histo: endothelial cell lining
2. Epithelial Cysts - epithelial lining
3. Parasitic Cysts 
4. Pseudocysts (39%) - no cell lining

Question 10

TB Granuloma

• histo
• ddx

Adrenal Myelolipoma

• what it is
• components
• gross
• histo

Answer 10

TB: histo: multinucleated giant cell
ddx: fungal cause (granulomas)

Adrenal Myelolipoma - benign tumor of adults
components: bone marrow and mature adipose
Gross: Red (marrow) and yellow (fat) colored mass
histo: adipocytes and bone marrow cells

Question 11

Metastatic Tumors

• prevalence
• cause
• location
• common primary sites
• gross
• histo

Answer 11

P: common (10% all mets)
Can cause adrenal insufficiency
Often bilateral (50%)
>95% mets are carcinomas

Common primary sites: RENAL cell carcinoma, LUNG carcinoma

Gross: yellow/pink color confined in medulla

Histo: immunostain + for primary site tumor cells
lung - invasive gland forming
renal - chicken wire vasculature

Question 12

Heterotopic/Ectopic Adrenal Cortical Tissue

• what it is
• cause
• most common sites
• things you may see on histo

Answer 12

normal adrenal tissue in abnormal location
due to abnormalities in adrenal cortical cell migration during development

Sites: CELIAC AXIS (MOST COMMON), testes/ovaries, intrarenal, hernia sacs

Histo:

• if adrenal tissue in kidney = see adrenal cells with glomeruli/tubular cells (kidney histo)
• if ectopic thyroid in adrenal = see thyroid follicles in adrenal tissue