171. Adrenal Pathology Cortex-Medulla Flashcards
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
Zona reticularis
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
Pheochromocytoma
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
Pheochromocytoma
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
Adrenal cortical adenoma
Gross:
- brown to gray color
- very thin
- 2 mm thick
Microscopically composed of:
- pheochromocytes
- sustentacular cells
- nerves and ganglion cells
Adrenal medulla
Tumor of the adrenal medulla pheochromocytes that has metastasized 10% of pheochromocytomas
malignant pheochromocytoma
Benign tumor of adults
Two components:
- myelo: bone marrow elements
- lipoma: mature adipose
Grossly:
- red (marrow)
- yellow (fat)
Adrenal myelolipoma
Can be epithelial, endothelial, or parasitic
Involve the cortex and/or medulla
Cystic lesions
> 100 g and > 6.5 cm
Adrenal cortical carcinoma in adult
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
Waterhouse-Friderichsen Syndrome
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
Neuroblastoma
> 400 g and > 10.5 cm
Adrenal cortical carcinoma in child
Normal adrenal cortical tissue in an abnormal location
Adrenal cortical heterotopia
Most ___ are sporadic and are not associated with inherited syndromes
Adrenal cortical neoplasms
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
Pheochromocytoma
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
Neuroblastoma
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
Zona glomerulosa
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
Neuropil
Is it possible to tell whether a tumor is functional or nonfunctional from microscopic morphology?
No
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
Adrenal cortical carcinoma
Cell types are prominent in the adrenal medulla
Presence is critical in the process of stimulating release of catecholamines by the pheochromocytes
Nerves and ganglion cells
Spindle shaped support cells
Use immunoperoxidase staining with Abs to S100 to highlight these cells
Exact function unknown
Sustentacular cells
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
Pheochromocytes
Gross:
- solitary, unilateral mass
- May be calcified, well-circumscribed, firm, tan-yellow, often large
Microscopically:
- Mixture of mature schwannian stroma with interspersed ganglion cells
Ganglioneuroma
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
Micronodular pattern of hyperplasia
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
Addison Disease (autoimmune adrenalitis)
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
Adrenal cortical adenoma
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
Macronodular pattern of hyperplasia
Histopathologic criteria to determine if an adrenal cortical neoplasm is benign or malignant
- Pink cytoplasm
- Difference pattern
- Necrosis
- High nuclear grade
- >5 mitoses/50 HPF
- Atypical mitosis
- Venous invasion
- Capsular invasion
- Extraadrenal invasion
>3 criteria –> malignancy
Weiss Criteria
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
Ganglioneuroma
Pattern of hyperplasia
Glands appear symmetrically enlarged grossly
Most common pattern seen in congenital adrenal hyperplasia and Cushing Syndrome
Diffuse pattern of hyperplasia
Li Fraumeni Syndrome
Carney complex
MEN1 (Wermer Syndrome)
Beckwith-Wiedemann
Inherited syndromes that predispose patients to adrenal cortical neoplasms
Middle zone
Cells produce glucocorticoids (70% of cortical volume)
Cells are arranged in columns that are perpendicular to the capsule
Zona fasciculata
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
Adrenal cortical hyperplasia
Renal cell carcinoma, lung carcinoma
- most common
- renal: CA9
- lung: TTF1 HCC, colon, breast cancer
Common primary sites of metastasis
Important cause of secondary adrenal insufficiency
Adrenal glands are frequently involved d/t cancer of the lung, breast, and kidney
Metastatic carcinoma
Histologically identical to pheochromocytomas
Secrete catechomaines at other sites
- sympathetic ganglia
Paragangliomas
