Adrenal gland

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Adrenal gland is a little organ that hangs-out above the kidney. Pathologists rarely see it. It uncommonly is affected by tumours.

Anatomy & histology

Adrenal cortical rest redirects here.

Anatomy

  • Cortex.
  • Medulla.

Microscopic

It is composed of a cortex and a medulla.

Cortex

It has three layers - mnemonic: GFR (from superficial to deep):

  1. Zona glomerulosa - salt (e.g. aldosterone).
    • Eosinophilic cytoplasm. (???)
    • Layer normally discontinuous.
  2. Zona fasciculata - sugar (e.g. cortisol).
    • Clear cytoplasm - key feature.
    • Largest part of the cortex ~ 70%.
    • Cells in cords/nests. (???)
  3. Zona reticularis - steroid (e.g. dehydroepiandrosterone).
    • Marked eosinophilia of cytoplasm - key feature.
    • Granular/reticular cytoplasm.

Note:

  • Normal cortex may not be completely encapsulated, i.e. the adrenal capsule may have defects.[1]
    • In other words: the cortex may "spill" into the surrounding fat.

Medulla

It consists of two cell types:[2]

  1. Chromaffin cells.
    • Arise of neural crest.
  2. Sustentacular cells (supporting cells).

Produce NED: norepinephrine, epinephrine, dopamine.

Images

www:

IHC

Adrenal cortex:[3]

  • Chromogranin A -ve.
  • Synaptophysin +ve.
  • Alpha-inhibin +ve.
  • Vimentin +ve.
  • Melan A +ve.
  • AE1/AE3 -ve.

Clinical

Patients getting a bilateral adrenalectomy get pre-treatment with steroids.[4]

Adrenal insufficiency is an immediate danger post-op.[5]

Benign

The section covers non-neoplastic pathologies of the adrenal gland. These uncommonly come to the pathologist.

Stress response

Spironolactone bodies

Hemorrhagic adrenalitis

  • AKA Waterhouse-Friderichsen syndrome.

General

  • Classically thought to be only due to Neisseria meningitidis; however, more recently also associated with Staphylococcus aureus,[7] and Streptococcus pneumoniae.[8]

Gross

Features:

  • Massive haemorrhage within the substance of the adrenal gland.

DDx (autopsy):

  • Post-mortem changes.

Microscopic

Features:

  • Massive haemorrhage within the substance of the adrenal gland.

Image: Haemorrhage in adrenal (nih.gov).

Adrenal cytomegaly

  • AKA adrenocortical cytomegaly.
  • AKA adrenal gland with cytomegaly.

General

May be associated with:[9]

Microscopic

Features:

  • Large cells in the adrenal cortex.[10]

Addison disease

General

  • Chronic adrenocortical insufficiency.

Clinical:

  • Brown skin - due POMC (a precursor of ACTH and melanocyte stimulating hormone (MSH)).[11]
  • Hypotension.
  • Nausea and vomiting.

DDx:[12]

Notes:

  • Secondary adrenocortical insufficiency (due to pituitary pathology):[13]
    • No hyperpigmentation (as no POMC).
    • Aldosterone usu. normal.

Microscopic

Features:[11]

  • Atrophy adrenal cortex - specifically zona fasciculata and zona reticularis.

Notes:

  • There is preservation of zona glomerulosa and medulla.

Benign neoplasms

Adrenal cortical adenoma

General

Epidemiology:

  • Often an incidental finding.

Pathologic/clinical:

  • May be hormonally active.
  • Radiologists are good at identifying adenomas, as they are usually lipid rich and have a characteristic low HU signal.[14]

Indications for excision:[15][16]

  • Lesions >30 mm.
  • Hormonally active.
  • Non-incidental finding. (???)

Notes:

  • Cushing disease is due to the ACTH over-production by the pituitary.
  • In cortisol producing tumours (Cushing syndrome): atrophy of the non-hyperplastic cortex (due to feedback inhibition from the pituitary gland).

Microscopic

Classic features:

  • Well-defined cell borders.
  • Clear cytoplasm.
  • May have foci of necrosis/degeneration and nuclear atypia.

Note:

  • In aldosterone producing tumours:

DDx:

Pheochromocytoma

General

  • Considered to be a paraganglioma.[19]
  • Literally means "dusky" (pheo) "colour" (chromo) - dull appearance on gross.
  • Tumour arises from adrenal medulla - chromaffin cells.[20]

Memory device - the rule of 10s:[20]

Clinical

  • Classic finding: hypertension.
  • Paroxysms (i.e. episodes) of tachycardia, headache, anxiety, hypertension.

Laboratory findings (urine):

  • Vanillylmandelic acid (VMA).
  • Metanephrines.

Microscopic

Features:[21]

  • Chief cells:
    • Usu. polygonal cells, may be spindled.
    • Arranged in cell nests - "Zellballen" (literally cell balls) - key feature.
    • Stippled chromatin (AKA salt and pepper chromatin) - coarsely granular chromatin.
    • Granular cytoplasm, often basophilic - important.
  • Sustentacular cells (structural support cell).
  • Often haemorrhagic - highly vascular.
  • +/-Nuclear pleomorphism.

Notes:

  • The nested architecture (Zellballen) is useful for differentiating from ACC.
  • Metastasis sole criteria of malignancy.[20]
  • Surrounding adrenal cortex is typically compressed.[22]

DDx:

Images

Pheochromocytoma versus adrenal cortical carcinoma
  • Pheochromocytoma and adrenal cortical carcinoma overlap histologically.[23]

Favour pheochromocytoma:

  • Small chickenwire-pattern blood vessels, nests, salt-and-pepper chromatin, red blood cell extravasation.

Favour adrenal cortical carcinoma:

  • Nucleolus, sheeting.

Malignant pheochromoctyoma

  1. Robbins says metastases are the sole criteria of malignancy.[20]
  2. Thompson suggests one can differentiate benign from malignant with the aid of the following:[24]
    • Marked nuclear atypia.
    • Invasion:
      • Capsular.
      • Vascular.
    • Necrosis.
    • Cellular monotony.
    • Mitoses:
      • Rate.
      • Atypical mitosis.

IHC

  • Chief cells:
    • Chromogranin A +ve.
    • Synaptophysin +ve.
  • Sustentacular cells:
    • S100 +ve.

Electron microscopy

  • Membrane-bound secretory granules.

Sign out

ADRENAL MASS, RIGHT, ADRENALECTOMY:
- PHEOCHROMOCYTOMA.
- SURGICAL MARGIN NEGATIVE FOR PHEOCHROMOCYTOMA.

COMMENT:
The tumour cells stains for chromogranin and synaptophysin. S-100 marks the sustentacular cells.
Inhibin is negative in the tumour cells. The immunostaining pattern is consistent with a 
pheochromocytoma.

Micro

The sections shows a partially hemorrhagic lesion in the medulla of the adrenal gland that is arranged in nests (Zellballen). The tumour cells have abundant grey/blue granular cytoplasm, and nuclei with granular chromatin (salt and pepper chromatin). The lesion is surrounded by a compressed rim of adrenal cortex and fibrosis tissue. The core of the lesion is fibrotic and has clusters of hemosiderin-laden macrophages.

There is no capsular invasion. Vascular invasion is not identified. There is no necrosis. Mitotic activity is not appreciated.

The adrenal cortex is unremarkable.

Adrenal ganglioneuroma

General

Gross

  • Solid.
  • White.
  • Firm.
  • Well-circumscribed.
  • May be nodular.

DDx (gross):

Images:

Microscopic

Features:

  • Ganglion cells - key feature.
    • Large cells with large nucleus.
      • Prominent nucleolus.
  • Disordered fibrinous material.

Images:

Adrenal myelolipoma

Myelolipoma redirects here.

General

  • Benign and rare.
  • Typically asymptomatic and hormonally inactive.[25]
    • Symptoms: back or abdominal pain.
  • Diagnosis - usu. by abdominal CT.

Treatment:

  • Watchful waiting if small (<=7 cm) and asymptomatic.[25]

Microscopic

Features:[26]

  • Adipose tissue.
  • Hematopoietic elements from all three lineages:
    1. Erythroid.
    2. Myeloid.
    3. Megakaryocytic.
  • +/-Calcification.[25]

DDx:[27]

Images

www:

Adenomatoid tumour

See: Adenomatoid tumours (uterine tumours).

Malignant neoplasms

Adrenocortical carcinoma

  • AKA adrenal cortical carcinoma.
  • Abbreviated ACC.

General

  • Prognosis sucks, esp. in adults.

Epidemiology:

Gross

  • +/-Encapsulated.
  • Necrotic-appearing.

Image:

Microscopic

Various criteria exist for this diagnosis. The most widely used is the Weiss criteria, which is a big long clunker.

Notes:

  • Tumour may contain fat.[28]

Images

www:

Adult

Weiss criteria

Three of the following:[29]

  1. High nuclear grade.
  2. High mitotic rate; >5/50 HPF (@ 40X obj.) - definition suffers from HPFitis.
  3. Atypical mitoses.
  4. Cleared cytoplasm in >= 25% of tumour cells.
  5. Sheeting (diffuse architecture) in >= 1/3 of tumour cells.
  6. Necrosis in nests.
  7. Venous invasion.
  8. Adrenal sinusoid invasion; lymphovascular space invasion within the adrenal gland.
  9. Capsular invasion.
Volante criteria

There is a simplified set of criteria by Volante et al. - that is not widely used:[30]

  • Reticular network disruption (with reticulin staining).
  • One of the three following:
    1. Abundant mitoses >5/50 high-power fields - definition suffers from HPFitis.
    2. Necrosis.
    3. Vascular invasion.

Pediatric

The criteria in the pediatric setting are somewhat different. This is discussed by Wieneke et al.[31] and Dehner and Hill.[32]

Dehner and Hill propose a very simple system:[32]

  • "Low risk" < 200 g & confined to the adrenal.
  • "Intermediate risk" 200-400 g, no mets, +/-microscopic disease outside adrenal.
  • "High risk" >400 g, or mets, or gross invasion of adjacent structures.

IHC

  • Vimentin +ve.
  • Melan A +ve.
  • Inhibin-alpha +ve.
  • Cytokeratins +ve/-ve.

Others:

Neuroblastoma

See also: olfactory neuroblastoma.

General

Epidemiology:

  • Usually paediatric population.

Laboratory findings:

  • Increased urine homovanillic acid.

Predictors of a poor prognosis:[36]

  • High mitotic-karyorrhectic index.
  • Lack of schwannian stroma.
  • >18 months.
  • Near ploidy.
  • N-MYC amplification.
  • Lymph node spread.
  • Distant spread.

Classification:

Gross

Microscopic

Features:[39]

  • Small round blue cells separated by thin (pink) fibrous septa.
  • Homer-Wright rosettes.
    • Rosette with a small (~100 micrometers - diameter) meshwork of fibers (neuropil) at the centre.[40]
  • Neuropil-like stroma = paucicellular stroma with a cotton candy-like appearance; see comparison below.
    • >50% neuropil-like stroma -- otherwise it's a ganglioneurona or ganglioblastoma.

Notes:

  • The fibrous septa are especially useful for differentiation from lymphoma.

DDx:

Images:

Schwannian vs. neuropil

Feature Schwannian Neuropil
Cellularity high ~ spacing of cells < 30 µm low ~ spacing of cells > 100 µm
Fibrillary yes, long fine strands no
Associations ganglion cells neuroblasts
Cytoplasmic vacuolation yes ?

Classification/grading

Commonly grouped by the Shimada classification, which depends on the presence a number of things including:

  • Mitoses/karyorrhectic cells.
  • Molecular abnormalities.

IHC

  • PGP 9.5 +ve.[42]
    • PGP = protein gene product.
  • NB-84 +ve.[43]
    • More sensitive that synaptophysin.
  • Synaptophysin +ve.
  • CD99 -ve.

EM

Distinctive EM appearance:[44]

  • Dendritic processes with longitudinally oriented microtubules.
  • Membrane bound electron-dense granules (contain catecholamines).
  • Desmosomes
    • Not seen in EWS, RMS, lymphomas.
  • Membrane densities.

Pertinent negative:[44]

  • No glycogen.

See also

References

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