THE PATHOLOGY OF THE ADRENAL GLAND

THE PATHOLOGY OF THE PATHOLOGY OF THE ADRENAL GLANDTHE ADRENAL GLAND

ANATOMYANATOMY The The adrenal glandsadrenal glands are are

endocrine organs consisting of endocrine organs consisting of both cortex and medullaboth cortex and medulla..

ANATOMYANATOMY Adrenal cortex:Adrenal cortex: the narrow layer of zona the narrow layer of zona

glomerulosaglomerulosa

( mineralocorticoids)( mineralocorticoids) Intervening is the broad zona Intervening is the broad zona

fasciculata, which makes up about fasciculata, which makes up about 75% of the total cortex75% of the total cortex

( glucocorticoids) ( glucocorticoids) The narrow layer of The narrow layer of zona reticularis zona reticularis

abuts the medullaabuts the medulla (sex steroids) (sex steroids)

ANATOMYANATOMY The The adrenal medullaadrenal medulla is composed is composed

of chromaffin cells, which of chromaffin cells, which synthesize and secrete synthesize and secrete catecholaminescatecholamines, mainly , mainly epinephrine. epinephrine.

ANATOMYANATOMY The The adrenal cortexadrenal cortex synthesizes three different synthesizes three different

types of steroids:types of steroids: (1) (1) glucocorticoidsglucocorticoids (principally cortisol), which (principally cortisol), which

are synthesized primarily in the zona fasciculata are synthesized primarily in the zona fasciculata and to a lesser degree in the zona reticularis;and to a lesser degree in the zona reticularis;

(2) (2) mineralocorticoidsmineralocorticoids, the most important , the most important being aldosterone, which is generated in the being aldosterone, which is generated in the zona glomerulosa; zona glomerulosa;

(3) (3) sex steroidssex steroids (estrogens and androgens), (estrogens and androgens), which are produced largely in the zona which are produced largely in the zona reticularisreticularis

Developmental Developmental anomaliesanomalies

Adrenal Hypoplasia:Adrenal Hypoplasia:– Anencephalic type: may have adrenal agenesis.Anencephalic type: may have adrenal agenesis.– Cytomegalic type: Large eosinophilic cells, may be Cytomegalic type: Large eosinophilic cells, may be

X-linked.X-linked. Ectopic Adrenal:Ectopic Adrenal:

– Accessory adrenal (cortex) can be found from Accessory adrenal (cortex) can be found from diaphragm to pelvis in the retroperitoneum (Medulla diaphragm to pelvis in the retroperitoneum (Medulla can also be found if near celiac ganglion). can also be found if near celiac ganglion).

– May be seen in hernial sacs (Marchand rests). May be seen in hernial sacs (Marchand rests). – These may give origin to neoplasms or undergo These may give origin to neoplasms or undergo

hyperplasia.hyperplasia. Adrenal myelolipoma: Adrenal myelolipoma:

– a metaplasia-choristoma made of bone marrow. a metaplasia-choristoma made of bone marrow. They can be big but are generally harmless. They can be big but are generally harmless.

ADRENOCORTICAL ADRENOCORTICAL HYPERFUNCTION HYPERFUNCTION (HYPERADRENALISM(HYPERADRENALISM))

TThere are three basic types of here are three basic types of hyperadrenal syndromes:hyperadrenal syndromes:

(1) (1) Cushing syndromeCushing syndrome, characterized , characterized by an excess of cortisol;by an excess of cortisol;

(2) (2) hyperaldosteronismhyperaldosteronism; ; (3) (3) adrenogenitaladrenogenital or virilizing or virilizing

syndromes caused by an excess of syndromes caused by an excess of androgens. androgens.

Hypercortisolism Hypercortisolism (Cushing Syndrome)(Cushing Syndrome) Cushing syndrome can be broadly Cushing syndrome can be broadly

divided into divided into exogenousexogenous and and endogenousendogenous causes. causes.

The vast majority of cases of The vast majority of cases of Cushing syndrome are the result Cushing syndrome are the result of the administration of of the administration of exogenous glucocorticoidsexogenous glucocorticoids ("iatrogenic" Cushing syndrome).("iatrogenic" Cushing syndrome).

Hypercortisolism Hypercortisolism (Cushing Syndrome)(Cushing Syndrome) The endogenous causes can, in The endogenous causes can, in

turn, be divided into those that turn, be divided into those that are are ACTH dependentACTH dependent and those and those that are that are ACTH independentACTH independent

Hypercortisolism Hypercortisolism (Cushing Syndrome)(Cushing Syndrome)

ACTH-DEPENDENTACTH-DEPENDENT Cushing disease (pituitary adenoma; rarely CRH-dependent pituitary Cushing disease (pituitary adenoma; rarely CRH-dependent pituitary

hyperplasia)hyperplasia) Ectopic corticotropin syndrome (ACTH-secreting pulmonary small-cell Ectopic corticotropin syndrome (ACTH-secreting pulmonary small-cell

carcinoma, bronchial carcinoid)carcinoma, bronchial carcinoid) ACTH-INDEPENDENTACTH-INDEPENDENT Adrenal adenomaAdrenal adenoma Adrenal carcinomaAdrenal carcinoma Macronodular hyperplasia (ectopic expression of hormone receptors, Macronodular hyperplasia (ectopic expression of hormone receptors,

including GIPR, LHR, vasopressin and serotonin receptors)including GIPR, LHR, vasopressin and serotonin receptors) Primary pigmented nodular adrenal disease (Primary pigmented nodular adrenal disease (PRKARIAPRKARIA and and PDE11PDE11

mutations)mutations) McCune-Albright syndrome (McCune-Albright syndrome (GNASGNAS mutations) mutations)

Cushing's Syndrome Cushing's Syndrome MMiddle-aged 3F/1M iddle-aged 3F/1M 4 main causes: 4 main causes:

1.1. Pituitary adenoma - secretes ACTHPituitary adenoma - secretes ACTH2.2. Adrenal tumors - secrete cortisol Adrenal tumors - secrete cortisol 3.3. Ectopic production of ACTH Ectopic production of ACTH 4.4. Iatrogenic Cushing's Syndrome Iatrogenic Cushing's Syndrome

1.1. Pituitary adenomaPituitary adenoma

-- secretes ACTH secretes ACTH-- 60-70% of cases of pathologic 60-70% of cases of pathologic causescauses-- adrenal glands are hyperplastic adrenal glands are hyperplastic-- Biochemistry Biochemistry: : Increased ACTH Increased ACTH and cortisoland cortisol

2. 2. Adrenal tumorsAdrenal tumors - secrete cortisolsecrete cortisol- 20-25% of cases of Cushing's20-25% of cases of Cushing's- adrenal adenoma (50%), adrenal adenoma (50%),

carcinoma (50%)carcinoma (50%) atrophy of contralateral gland atrophy of contralateral gland

- BiochemistryBiochemistry: : low ACTH and low ACTH and high cortisolhigh cortisol

3. 3. Ectopic production of ACTH Ectopic production of ACTH - by tumorsby tumors

- lung cancerlung cancer, , - bronchial and thymic carcinoids, bronchial and thymic carcinoids, - medullary thyroid carcinoma, medullary thyroid carcinoma, - islet cell cancerislet cell cancer

- 10-15% of cases10-15% of cases- adrenals are hyperplasticadrenals are hyperplastic- BiochemistryBiochemistry: : Increased ACTH Increased ACTH

and cortisoland cortisol

4. 4. Iatrogenic Cushing's SyndromeIatrogenic Cushing's Syndrome- commonest cause overallcommonest cause overall- ddue to long-term corticosteroid ue to long-term corticosteroid

therapy for treatment of:therapy for treatment of:- connective tissue diseases- connective tissue diseases- - asthmaasthma- rheumatoid arthritis - rheumatoid arthritis - - cancercancer- transplant rejection- transplant rejection- Biochemistry- Biochemistry: : High cortisol and High cortisol and ACTH suppressedACTH suppressed

Clinical findings inClinical findings in Cushing's SyndromeCushing's Syndrome

  OOccurs as a ccurs as a consequence of consequence of excess plasma excess plasma glucocorticoid levels glucocorticoid levels o truncal obesity, buffalo truncal obesity, buffalo

hump and moon face hump and moon face due to fat deposition due to fat deposition

o hypertension hypertension o hirsutism - due to hirsutism - due to

increased testosterone increased testosterone o muscle weakness and muscle weakness and

breakdown breakdown o menstrual irregularity menstrual irregularity

o osteoporosis - osteoporosis - decreased calcium decreased calcium absorption, increased absorption, increased bone resorption and bone resorption and suppression of bone suppression of bone formation formation

o impaired glucose impaired glucose tolerance or diabetes tolerance or diabetes mellitus - due to mellitus - due to insulin resistance insulin resistance

o abdominal striae - due abdominal striae - due to inhibition of protein to inhibition of protein synthesis and synthesis and abnormal collagen abnormal collagen maturation maturation

o mental symptoms are mental symptoms are common; depression common; depression and psychosis and psychosis

AdenomaAdenoma

Primary adrenal Primary adrenal hyperplasiahyperplasia

a newly discovered disease: a newly discovered disease: "primary pigmented nodular "primary pigmented nodular

adrenocortical hyperplasia", adrenocortical hyperplasia", – which is part of the autosomal dominant which is part of the autosomal dominant

Carney complexCarney complex– ((Carney complex:Carney complex: cardiac myxomas, cardiac myxomas,

cutaneous myxomas, spotty cutaneous myxomas, spotty pigmentation of the skin, and pigmentation of the skin, and hyperendocrine states)hyperendocrine states)

– genetic syndrome with too many cortisol genetic syndrome with too many cortisol receptors, low plasma cortisol receptors, low plasma cortisol

macronodular hyperplasia with marked macronodular hyperplasia with marked adrenal enlargementadrenal enlargement

Primary Primary HyperaldosteronismHyperaldosteronism HyperaldosteronismHyperaldosteronism is the is the

generic term for a group of generic term for a group of closely related conditions closely related conditions characterized by chronic excess characterized by chronic excess aldosterone secretion. aldosterone secretion.

Primary Primary HyperaldosteronismHyperaldosteronism Hyperaldosteronism may be primary, or it Hyperaldosteronism may be primary, or it

may be secondary to an extra-adrenal cause.may be secondary to an extra-adrenal cause. Primary hyperaldosteronismPrimary hyperaldosteronism stems from an stems from an

autonomous overproduction of aldosterone, autonomous overproduction of aldosterone, with resultant suppression of the renin-with resultant suppression of the renin-angiotensin system and angiotensin system and decreased plasma decreased plasma renin activityrenin activity. .

Blood pressure elevation is the most common Blood pressure elevation is the most common manifestation of primary manifestation of primary hyperaldosteronism, which is caused by one hyperaldosteronism, which is caused by one of three mechanismsof three mechanisms::

Primary Primary HyperaldosteronismHyperaldosteronism Bilateral idiopathic Bilateral idiopathic

hyperaldosteronismhyperaldosteronism (IHA), (IHA), Adrenocortical neoplasmAdrenocortical neoplasm,, Glucocorticoid-remediable Glucocorticoid-remediable

hyperaldosteronismhyperaldosteronism

Bilateral idiopathic Bilateral idiopathic hyperaldosteronismhyperaldosteronism (IHA)(IHA) Bilateral idiopathic hyperaldosteronismBilateral idiopathic hyperaldosteronism (IHA), (IHA),

characterized by bilateral nodular characterized by bilateral nodular hyperplasia of the adrenal glands, is the hyperplasia of the adrenal glands, is the most common underlying cause of primary most common underlying cause of primary hyperaldosteronismhyperaldosteronism, accounting for about , accounting for about 60% of cases. 60% of cases.

Individuals with IHA tend to be older and to Individuals with IHA tend to be older and to have less severe hypertension than those have less severe hypertension than those presenting with adrenal neoplasms. presenting with adrenal neoplasms.

Adrenocortical Adrenocortical neoplasmneoplasm EEither an aldosterone-producing adenoma (the ither an aldosterone-producing adenoma (the

most common cause) or, rarely, an adrenocortical most common cause) or, rarely, an adrenocortical carcinoma. carcinoma.

In approximately 35% of cases, primary In approximately 35% of cases, primary hyperaldosteronism is caused by a solitary hyperaldosteronism is caused by a solitary aldosterone-secreting adenoma, a condition aldosterone-secreting adenoma, a condition referred to as referred to as Conn syndromeConn syndrome..

This syndrome occurs most frequently in adult This syndrome occurs most frequently in adult middle life and is more common in women than in middle life and is more common in women than in men (2 : 1).men (2 : 1).

Multiple adenomas may be present in an Multiple adenomas may be present in an occasional patient.occasional patient.

Glucocorticoid-Glucocorticoid-remediable remediable hyperaldosteronismhyperaldosteronism

Glucocorticoid-remediable hyperaldosteronismGlucocorticoid-remediable hyperaldosteronism is an is an uncommon cause of primary familial uncommon cause of primary familial hyperaldosteronism.hyperaldosteronism.

In some families, it is caused by a chimeric gene In some families, it is caused by a chimeric gene resulting from fusion between resulting from fusion between CYP11B1CYP11B1 (the (the 11β-11β-hydroxylasehydroxylase gene) and gene) and CYP11B2CYP11B2 (the (the aldosterone aldosterone synthasesynthase gene). gene).

This leads to a sustained production of hybrid This leads to a sustained production of hybrid steroids in addition to both cortisol and aldosterone. steroids in addition to both cortisol and aldosterone.

The activation of aldosterone secretion is under the The activation of aldosterone secretion is under the influence of ACTH and hence is suppressible by influence of ACTH and hence is suppressible by exogenous administration of dexamethasone.exogenous administration of dexamethasone.

Primary Primary hyperaldosteronismhyperaldosteronism

low-renin hyperaldosteronismlow-renin hyperaldosteronism too much mineralocorticoidtoo much mineralocorticoid not due to excess ACTHnot due to excess ACTH 0.5% of hypertensives have primary 0.5% of hypertensives have primary

hyperaldosteronism hyperaldosteronism Patients exhibit hypokalemia, alkalosis, Patients exhibit hypokalemia, alkalosis,

and low renin, and low renin, Low potassium is likely to cause muscle Low potassium is likely to cause muscle

weakness, and even paralysis. weakness, and even paralysis. – these patients can die from hypokalemia if these patients can die from hypokalemia if

you give them thiazide diuretics to treat you give them thiazide diuretics to treat their high blood pressure. their high blood pressure.

Secondary Secondary aldosteronismaldosteronism In In secondary hyperaldosteronismsecondary hyperaldosteronism, in contrast, , in contrast,

aldosterone release occurs in response to activation of aldosterone release occurs in response to activation of the renin-angiotensin system.the renin-angiotensin system.

It is characterized by It is characterized by increased levels of plasma reninincreased levels of plasma renin and is encountered in conditions such as the following: and is encountered in conditions such as the following:

Decreased renal perfusion (arteriolar nephrosclerosis, Decreased renal perfusion (arteriolar nephrosclerosis, renal artery stenosis)renal artery stenosis)

Arterial hypovolemia and edema (congestive heart Arterial hypovolemia and edema (congestive heart failure, cirrhosis, nephrotic syndrome)failure, cirrhosis, nephrotic syndrome)

Pregnancy (due to estrogen-induced increases in Pregnancy (due to estrogen-induced increases in plasma renin substrate)plasma renin substrate)

Hypofunction of Hypofunction of adrenaladrenal cortex cortex

PrimaryPrimary causes causes Loss of Cortex:Loss of Cortex:

– aautoimmuneutoimmune– bacterialbacterial– hhemorrhageemorrhage – amyloidosisamyloidosis– sarcoidosissarcoidosis– hhemochromatosisemochromatosis– metastatic diseasemetastatic disease– surgical ablation.surgical ablation.

Metabolic Metabolic Failure:Failure:– Primary failure of Primary failure of

adrenal glandsadrenal glands, , – DDrug induced rug induced

inhibition of inhibition of adrenocortical adrenocortical function.function.

SecondSecondaryary causes causes

hhypothalamic / pituitary ypothalamic / pituitary disease disease

nneoplasm eoplasm infection infection hhypothalamic / pituitary ypothalamic / pituitary

suppression: suppression: – long term steroid long term steroid

administration. administration.

AAdrenocorticaldrenocortical InsufficiencyInsufficiency((Hypoadrenocorticism)Hypoadrenocorticism)

Primary Acute Adrenal Primary Acute Adrenal Insufficiency:Insufficiency:

Precipitated by stress Precipitated by stress in a patient with in a patient with Addison's. Addison's.

Precipitated by Precipitated by withdrawal of withdrawal of steroids in an steroids in an adrenalectomized adrenalectomized patient. patient.

In patients with acute In patients with acute bilateral hemorrhagic bilateral hemorrhagic necrosis of adrenals. necrosis of adrenals.

Chronic insufficiencyChronic insufficiency:: Addison's Addison's

diseasedisease

Acute InsufficiencyAcute InsufficiencyAcute Hemorrhagic Necrosis of Acute Hemorrhagic Necrosis of

AdrenalsAdrenals Waterhouse-Friedricksen SyndromeWaterhouse-Friedricksen Syndrome

– DDue particularly to meningococcal septicemia,ue particularly to meningococcal septicemia, less commonly Staph, pneumococcus, or less commonly Staph, pneumococcus, or

Haemophilus Haemophilus

– Newborns due to perinatal trauma.Newborns due to perinatal trauma.

DICDIC adrenal glands are hemorrhagic with cortical adrenal glands are hemorrhagic with cortical

necrosisnecrosis purpuric rashpurpuric rash vascular collapse vascular collapse shock: shock: due to endotoxin due to endotoxin

and vomiting, decreased and vomiting, decreased steroids and steroids and NaNa++ , , increased Kincreased K++ in blood and dehydration in blood and dehydration..

Waterhouse-Friedricksen Waterhouse-Friedricksen SyndromeSyndrome

Primary cPrimary chronic hronic adrenal adrenal insufficiencyinsufficiency Addison's diseaseAddison's disease

– 60-60-75% due to 75% due to auto-immune destructionauto-immune destruction of of adrenal cortex with lymphocytic and plasma cell adrenal cortex with lymphocytic and plasma cell infiltrateinfiltrate

– normal medullanormal medulla– TuberculosisTuberculosis ( (2nd commonest cause2nd commonest cause))– more than 90% of cortex needs to be destroyedmore than 90% of cortex needs to be destroyed– ClinicallyClinically

Lethargy, muscle weakness, anorexia, nausea & Lethargy, muscle weakness, anorexia, nausea & vomiting, wt loss, hypotension, vomiting, wt loss, hypotension, hyperpigmentation of skin and mucous hyperpigmentation of skin and mucous membranes.membranes.

Addison’s disease:Addison’s disease: HHyperpigmentation of mucous yperpigmentation of mucous

membranesmembranes

Primary:Primary: – due to adrenal insufficiencydue to adrenal insufficiency– sshould be suspected when there is hould be suspected when there is

marked skin pigmentation due to high marked skin pigmentation due to high ACTH levels.ACTH levels.

Secondary:Secondary: – ppituitary or hypothalamic ituitary or hypothalamic iinsufficiency nsufficiency

(no skin pigmentation).(no skin pigmentation).– Addison's disease is rare.Addison's disease is rare.

Causes of Addison'sCauses of Addison's DiseaseDisease

1. 1. Autoimmune Autoimmune most cases of Additions show anti-most cases of Additions show anti-

adrenal Antibodies adrenal Antibodies ((60-75%60-75%) ) Two Two types exist. types exist.

Type IType I

-- Addison's + hypoparathyroidismAddison's + hypoparathyroidism + + mucocutaneous candidiasis.mucocutaneous candidiasis.

-- Defect in suppressor cells.Defect in suppressor cells.

Type IIType II ((Schmidt's syndromeSchmidt's syndrome)) - Addison's + autoimmune thyroid disease + Addison's + autoimmune thyroid disease +

insulin dependent diabetes.insulin dependent diabetes.- NNo Candidiasis or PTH deficiencyo Candidiasis or PTH deficiency- AAssociated with HLA-A1 and HLA-B8 ssociated with HLA-A1 and HLA-B8

haplotype. haplotype.

2. 2. TTuberculosisuberculosis ( (~~25% of cases). 25% of cases). 3. 3. Other causes:Other causes:

– hhistoplasmosisistoplasmosis

– amyloidamyloid

– sarcoidsarcoidosisosis

– mmetetastasesastases

- congenital hypoplasia- hemochromatosis- CMV infection (in AIDS)- adrenal leukodystrophy

Addison'sAddison's Disease Disease

PathologyPathology There may be a lymphocytic There may be a lymphocytic

infiltrate or a "burned out" fibrotic infiltrate or a "burned out" fibrotic appearance. Medulla is untouched.appearance. Medulla is untouched.

In TB and other diseases, evidence In TB and other diseases, evidence for these is usually apparent. for these is usually apparent.

Adrenal Medulla Adrenal Medulla PathologyPathology

Adrenal MedullaAdrenal Medulla Synthesizes and secretes Synthesizes and secretes "adrenalin" "adrenalin"

(epinephrine, norepinephrine)(epinephrine, norepinephrine) The only diseases are two tumors which The only diseases are two tumors which

may arise here or at the other chromaffin may arise here or at the other chromaffin tissue massestissue masses– pheochromocytomapheochromocytoma (well-differentiated, (well-differentiated,

adults) adults) – neuroblastomaneuroblastoma (poorly-differentiated, (poorly-differentiated,

children). children).

PheochromocytomaPheochromocytoma (paraganglioma)(paraganglioma) – secrete norepinephrine (most common) secrete norepinephrine (most common)

and/or epinephrine and/or epinephrine Rarely: dopamine, serotonin, ACTH, Rarely: dopamine, serotonin, ACTH,

somatostatin, neuropeptides. somatostatin, neuropeptides.

– The paroxysms of extreme hypertension, The paroxysms of extreme hypertension, accompanied by sweating, headache, accompanied by sweating, headache, and other autonomic disturbances, and other autonomic disturbances, probably result from physical probably result from physical compression and/or ischemia of the compression and/or ischemia of the "pheo". "pheo".

Can present as Can present as Paroxysmal Paroxysmal attacksattacks which may precipitate which may precipitate – congestive cardiac failure, congestive cardiac failure, – coronary thrombosis, coronary thrombosis, – cerebral hemorrhagecerebral hemorrhage– may be brought on by stress, may be brought on by stress,

pressure, exercise pressure, exercise acute release of acute release of catecholamine catecholamine

– Biochemistry:Biochemistry: increased urinary VMA increased urinary VMA (vanillylmandelic acid) excretion (vanillylmandelic acid) excretion

Most (90%) occur in the adrenal Most (90%) occur in the adrenal medullamedulla

Other sites (10%)Other sites (10%)– the organs of Zuckerkandl: chromaffin the organs of Zuckerkandl: chromaffin

tissue at the origin of the tissue at the origin of the inferior mesenteric artery and/or aortic inferior mesenteric artery and/or aortic

bifurcationbifurcation paravertebral sympathetic chainparavertebral sympathetic chain urinary bladder. urinary bladder.

Ten percent of pheo cases involve Ten percent of pheo cases involve both adrenals, and many of these both adrenals, and many of these are also among the 10% that are are also among the 10% that are familial. Syndromes include: familial. Syndromes include:

MEN IIa or IIb MEN IIa or IIb von Recklinghausen's neurofibromatosis von Recklinghausen's neurofibromatosis

(NF-I) (NF-I) von Hippel-Lindau von Hippel-Lindau succinic dehydrogenase mutation succinic dehydrogenase mutation

Pheos are still often missed clinically Pheos are still often missed clinically surprises at autopsy surprises at autopsy the patients typically had been told the patients typically had been told

they had "benign essential they had "benign essential hypertension" and "emotional hypertension" and "emotional problems“problems“

high levels of circulating high levels of circulating catecholaminescatecholamines– can damage the myocardium can cause can damage the myocardium can cause

coronary spasm, coronary spasm, – disorders in renal, bowel, brain arteriesdisorders in renal, bowel, brain arteries

Grossly, Grossly, – very bloody (vascular), very bloody (vascular), – often show fibrosis, calcification, often show fibrosis, calcification,

cystic change, or even fatty change cystic change, or even fatty change Microscopically, Microscopically,

– pheos resemble adrenal medullapheos resemble adrenal medulla– special stains are available that show special stains are available that show

norepinephrine and/or epinephrine in norepinephrine and/or epinephrine in granulesgranules

PheochromocytomaPheochromocytoma

Neuroblastoma Neuroblastoma The second commonest solid The second commonest solid

pediatric cancer (after Wilms pediatric cancer (after Wilms tumor).tumor).

It is derived from primitive nerve It is derived from primitive nerve elements, discovered by Virchow. elements, discovered by Virchow.

A majority of neuroblastomas arise A majority of neuroblastomas arise in or near the adrenals. in or near the adrenals.

Grossly, neuroblastomas are soft, Grossly, neuroblastomas are soft, white tumors. white tumors.

Most neuroblastomas produce Most neuroblastomas produce catecholamines, resulting in catecholamines, resulting in elevated urinary metabolites. elevated urinary metabolites.

Portions often undergo dystrophic Portions often undergo dystrophic calcification (radiological diagnosis) calcification (radiological diagnosis)

The tumor eventually metastasizes The tumor eventually metastasizes widely. widely.

"Blueberry muffin baby" is a classic "Blueberry muffin baby" is a classic description for a neuroblastoma description for a neuroblastoma patient with multiple skin patient with multiple skin metastases.metastases.

Neuroblastoma: radiologyNeuroblastoma: radiology

Histologically, neuroblastoma is a Histologically, neuroblastoma is a tumor of "small blue cells", with tumor of "small blue cells", with scanty cytoplasm. scanty cytoplasm.

Often (but not always) the cells are Often (but not always) the cells are arranged in "rosettes" (recalling arranged in "rosettes" (recalling neural tubes) around a tangle of neural tubes) around a tangle of neurites ("Homer Wright rosettes", neurites ("Homer Wright rosettes", pretty-much diagnostic).pretty-much diagnostic).

EM shows neurosecretory granules EM shows neurosecretory granules and  sometimes neurites too. and  sometimes neurites too.

MicroscopyMicroscopy

GanglioneuroblastomaGanglioneuroblastoma benign ganglioneuromabenign ganglioneuroma in 2% of autopsies on infants dying of in 2% of autopsies on infants dying of

unrelated causes, there is a unrelated causes, there is a neuroblastoma-like "incidentaloma".neuroblastoma-like "incidentaloma".

Obviously most of these cure Obviously most of these cure themselves.themselves.

  The process begins with the appearance The process begins with the appearance of S100-positive Schwann cells, which of S100-positive Schwann cells, which are from outside the tumor. If the tumor are from outside the tumor. If the tumor is to self-cure, it must be near-triploid is to self-cure, it must be near-triploid and have intact chromosome 1.and have intact chromosome 1.

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