171. Adrenal Pathology Cortex-Medulla

Question 1

Inner most zone

Cells produce androgens (15% of cortical volume)

Cells are more haphazardly arranged, appear smaller than cells of the other zones, have granular, eosinophilic cytoplasm

Answer 1

Zona reticularis

Question 2

Gross:

• solitary, unilateral masses
• Well circumscribed gray white mass, often large

Microscopically:

• Zellballen
• nested in a ball of cells
• Rich vascular network surrounding zellballens
• salt and pepper nuclei
• may have scattered bizzare (pleomorphic) nuclei

Answer 2

Pheochromocytoma

Question 3

10% tumor:

• 10% are bilateral
• 10% are paragangliomas
• 10% in children
• 10% are malignant
• 10% are familial (MEN2A or 2B or NF-1)

Combination of adrenal mass on imaging with elevated urine and/or serum catechomalines or their metabolites

• VMA support the diagnosis

Answer 3

Pheochromocytoma

Question 4

Gross:

• unilateral and solitary
• classically bright yellow in color

Microscopically:

• Often unencapsulated, mixture of growth patterns (nests, cords, solid)
• Most cells have vesicular/vacuolated clear cytoplasm (contains lipid) with scattered cells exhibiting eosinophilic cytoplasm
• DO NOT see mitoses or necrosis

Answer 4

Adrenal cortical adenoma

Question 5

Gross:

• brown to gray color
• very thin
• 2 mm thick

Microscopically composed of:

• pheochromocytes
• sustentacular cells
• nerves and ganglion cells

Answer 5

Adrenal medulla

Question 6

Tumor of the adrenal medulla pheochromocytes that has metastasized 10% of pheochromocytomas

Answer 6

malignant pheochromocytoma

Question 7

Benign tumor of adults

Two components:

• myelo: bone marrow elements
• lipoma: mature adipose

Grossly:

• red (marrow)
• yellow (fat)

Answer 7

Adrenal myelolipoma

Question 8

Can be epithelial, endothelial, or parasitic

Involve the cortex and/or medulla

Answer 8

Cystic lesions

Question 9

> 100 g and > 6.5 cm

Answer 9

Adrenal cortical carcinoma in adult

Question 10

Prototypical example of primary (acute) adrenal insufficiency

Occurs in the setting of an overwhelming bacterial infection

• Neisseria meningitidis –> sepsis

Characterized by hypotension, shock, and widespread purpura of the skin

Patients have rapidly developing adrenal insufficiency associated w/ massive bilateral adrenal hemorrhage

Answer 10

Waterhouse-Friderichsen Syndrome

Question 11

Gross:

• large, firm, gray to white
• hemorrhage, necrosis, cystic changes

Microscopically:

• small cells with hyperchromatic (dark) nuclei
• very little cytoplasm
• high mitotic rate and abundant apoptotic nuclear debris *** small round blue cell tumor
• stroma made up of pink fibrillary material
• neuropil
• Homer-Wright pseudorosettes

Answer 11

Neuroblastoma

Question 12

> 400 g and > 10.5 cm

Answer 12

Adrenal cortical carcinoma in child

Question 13

Normal adrenal cortical tissue in an abnormal location

Answer 13

Adrenal cortical heterotopia

Question 14

Most ___ are sporadic and are not associated with inherited syndromes

Answer 14

Adrenal cortical neoplasms

Question 15

Catecholamine secreting tumor arising from the adrenal medulla composed of neoplastic chromaffin cells

Most common in 5th decade of life

Symptoms:

• HTN
• HA
• Anxiety
• Palpitations
• Nausea
• Diaphoresis

Answer 15

Pheochromocytoma

Question 16

Malignant tumor composed of neural crest derived neuroblastic cells

Relatively common malignancy in CHILDREN - 6% of childhood malignancies

Present as an abdominal pass with pain and catecholamine metabolites in urine

• VMA and HVA

Answer 16

Neuroblastoma

Question 17

Zone closest to the adrenal capsule (outer most zone)

Cells produce mineralcorticoids (15% of cortical volume)

Cells are arranged in clusters, high nuclear to cytoplasm ratio versus other zones

• cytoplasm is pink to purple
• cytoplasm is finely vaculated

Answer 17

Zona glomerulosa

Question 18

Stroma in a classic neuroblastoma is composed of pink fibrillary material called ___

Composed of neurotic processes of the primitive neuroblasts

Surrounded by Homer-Wright pseudorosettes

Answer 18

Neuropil

Question 19

Is it possible to tell whether a tumor is functional or nonfunctional from microscopic morphology?

Answer 19

No

Question 20

Gross:

• large bulk tumors are typical
• hemorrhage and necrosis are common –> invade liver, kidney, pancreas

Microscopic:

• Highly cellular tumors
• Arranged in variable patterns (solid, gland-like, nested)
• Increased nuclear to cytoplasmic ratio
• clear to pink cytoplasm
• mitotic activity present
• atypical mitoses may be present

Answer 20

Adrenal cortical carcinoma

Question 21

Cell types are prominent in the adrenal medulla

Presence is critical in the process of stimulating release of catecholamines by the pheochromocytes

Answer 21

Nerves and ganglion cells

Question 22

Spindle shaped support cells

Use immunoperoxidase staining with Abs to S100 to highlight these cells

Exact function unknown

Answer 22

Sustentacular cells

Question 23

Also known as medullary or chromaffin cells

Main cell type of the mature adrenal medulla

Synthesize and secrete the main product

• catecholamines

Microscopically:

• large size
• abundant blue cytoplasm
• salt and pepper nuclei with occasional prominent nucleoli
• arranged in clusters and supported by a rich fibrovascular network

Answer 23

Pheochromocytes

Question 24

Gross:

• solitary, unilateral mass
• May be calcified, well-circumscribed, firm, tan-yellow, often large

Microscopically:

• Mixture of mature schwannian stroma with interspersed ganglion cells

Answer 24

Ganglioneuroma

Question 25

Pattern of hyperplasia Glands appear enlarged but the enlargement is characterized by multiple nodules \< 1.0 cm in greatest dimension Nodules lack a capsule 30-40% of Cushing syndrome cases

Answer 25

Micronodular pattern of hyperplasia

Question 26

Most common cause of primary chronic adrenal insufficiency Produce antibodies to cortical cells - most commonly cytochrome p450 enzymes Adrenal glands appear atrophic Microscopically: - cortex is remarkable for atrophy - prominent infiltrate of lymphocytes and plasma cells

Answer 26

Addison Disease (autoimmune adrenalitis)

Question 27

Fairly common, 1-5% of the general population 80% are non-functional, 20% are functional - aldosterone-producing (Conn Syndrome) - glucocorticoid-producing (Cushing Syndrome) - w/ mixed endocrine syndrome or associated virilizing/feminizing (rare) Benign neoplasms with excellent prognosis after surgical removal

Answer 27

Adrenal cortical adenoma

Question 28

Uncommon pattern of hyperplasia Glands appear enlarged but the enlargement is characterized by multiple nodules some of which measure \> 1.0 cm in greatest dimension

Answer 28

Macronodular pattern of hyperplasia

Question 29

Histopathologic criteria to determine if an adrenal cortical neoplasm is benign or malignant 1. Pink cytoplasm 2. Difference pattern 3. Necrosis 4. High nuclear grade 5. \>5 mitoses/50 HPF 6. Atypical mitosis 7. Venous invasion 8. Capsular invasion 9. Extraadrenal invasion \>3 criteria --\> malignancy

Answer 29

Weiss Criteria

Question 30

Benign tumor of neural crest derivation composed of mature ganglion cells and schwannian (neural derived) stroma Embryonal tumors (neuroblastic) of the sympathetic nervous system - most common site is posterior mediastinum 20% of cases occur in the adrenal medulla

Answer 30

Ganglioneuroma

Question 31

Pattern of hyperplasia Glands appear symmetrically enlarged grossly Most common pattern seen in congenital adrenal hyperplasia and Cushing Syndrome

Answer 31

Diffuse pattern of hyperplasia

Question 32

Li Fraumeni Syndrome Carney complex MEN1 (Wermer Syndrome) Beckwith-Wiedemann

Answer 32

Inherited syndromes that predispose patients to adrenal cortical neoplasms

Question 33

Middle zone Cells produce glucocorticoids (70% of cortical volume) Cells are arranged in columns that are perpendicular to the capsule

Answer 33

Zona fasciculata

Question 34

Bilateral increase in adrenal cortical mass d/t a documented endocrine abnormality Diagnosis cannot be made on pathological exam alone, one must correlate with clinical presentation and other lab tests

Answer 34

Adrenal cortical hyperplasia

Question 35

Renal cell carcinoma, lung carcinoma - most common - renal: CA9 - lung: TTF1 HCC, colon, breast cancer

Answer 35

Common primary sites of metastasis

Question 36

Important cause of secondary adrenal insufficiency Adrenal glands are frequently involved d/t cancer of the lung, breast, and kidney

Answer 36

Metastatic carcinoma

Question 37

Histologically identical to pheochromocytomas Secrete catechomaines at other sites - sympathetic ganglia

Answer 37

Paragangliomas