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ROLE OF IMAGING IN ADRENAL GLAND • The adrenal glands are known to be a frequent site of disease and one of the most common pathologic involvement of the adrenal glands is neoplastic in

ROLE OF IMAGING IN ADRENAL

GLAND

• The adrenal glands are known to be a frequent site of disease and one of the most common pathologic involvement of the adrenal glands is

neoplastic in nature A variety of modalities can effectively image the

adrenals, including ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy By far, the

multisequential imaging capabilities of CT supersede the rest in

establishing a definitive diagnosis in adrenal mass, however imaging with MRI and US partaking a complimentary role

• • It is crucial for the radiologist to be able to diagnose and differentiate adrenal masses on imaging Herein, we aim to review the common as

well as the uncommon adrenal masses encountered in one’s practice

Clinical Indications for Adrenal MRI

• As defined by the ACR-SAR-SPR Practice Parameters:

•  Detection of suspected pheochromocytoma and functioning

adrenal adenoma

•  Characterization of indeterminate lesions detected with other

imaging modalities

•  Staging of malignant adrenal neoplasms

•  Detection and characterization of congenital anomalies

Institutional Adrenal MRI

Protocol

• Axial T2-weighted imaging

• Coronal T2-weighted imaging

• Axial pre in and opposed phase imaging

• Coronal in and opposed phase imaging

• Axial DWI sequenceAxial pre fat suppressed

• Axial postcontrast• Arterial – 25 sec• Portal – 60 sec• Venous – 95 sec• Delayed – 3 min

• Axial postcontrast in phase and opposed phase imaging

MR Imaging

• Utility of specific imaging sequences and quantitative variables for

optimal characterization of an adrenal lesion

•  Chemical shift imaging - assessment for fat

•  Calculation of adrenal-to-spleen chemical shift ratio, signal-intensity index

•  Emerging techniques

•  Dynamic contrast enhancement

•  Diffusion

•  MR spectroscopy

Embryologic Development

• Inner portion of adrenal gland = medulla

•  Derived from neural crest

•  Outer portion of adrenal gland = cortex

•  Derived from mesothelium

•  Each adrenal gland composed of body and medial and lateral limbs

•  Glands are located superior, anterior, and medial to the kidneys

•  Right adrenal gland

•  Relatively pyramidal in shape, V or Y shaped

•  Located lateral to right diaphragmatic crus

•  Situated posterior to IVC

•  Left adrenal gland

•  Comparatively crescentic in shape, V or Y shaped

•  Located lateral to left diaphragmatic crus

•  Situated posterior to pancreas & stomach

Normal MRI Appearance

Normal Variants

• Pancake: Flattened appearance, often associated with ectopic kidney

or renal agenesis

• Horseshoe: Congenital fusion of the adrenal glands at the midline,

often associated with other anomalies of the kidney and CNS

• Adrenofusion with liver: Adhered appearance of liver and right

adrenal gland

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COMMON ADRENAL MASSES:A BENIGN

• ADRENAL ADENOMAS

• • ADRENOCORTICAL HYPERPLASIA

• • ADRENAL HEMORRHAGE

• • SIMPLE CYST

Adrenal adenoma

• Adrenal adenomas are benign neoplasms that resemble adrenal cortical cells

histologically They may be lipid-rich (more common, 70%) or lipid-poor, ranging from yellow to red-brown/black in appearance They are typically found to be well-

circumscribed encapsulated solid masses with uniform low CT attenuation values, <10

HU if lipid-rich and >10 HU if lipid-poor Adenomas are typically isointense to mildly

hypointense to liver on T1 and T2-WI While lipid-rich adenomas demonstrate signal drop-out on opposed phase images, lipid-poor adenomas do not In such instances

adrenal washout assessment on CT becomes crucial An absolute washout of >60% and

a relative washout of >40% is diagnostic of adenomas Occasionally, adrenal adenomas and metastases will have nearly identical attenuation values upon immediate

administration of IV contrast (60s) An attenuation cut-off of 24 HU on enhanced CT performed 12 to 18 minutes after contrast administration can differentiate adenomas (24 HU) from metastases (>24 HU) with high sensitivity and specificity

Adrenocortical hyperplasia

• Adrenal hyperplasia is a physiological overgrowth of adrenocortical tissue The adrenal body normally measures 10-12 mm and its limbs measure 5-6 mm On imaging enlargement can either be smooth, characterized by a thickened and elongated gland or nodular,

characterized by a thickened gland with micro or macronodules

However, the overall morphology stays preserved

• Adrenocortical hyperplasia is secondary to long term hormonal

stimulation in patients with Cushing disease, ectopic

adrenocorticotrophic hormone (ACTH) syndrome, or primary

hyperaldosteronism

Adrenal hemorrhage

• Adrenal hemorrhage can be unilateral or bilateral, resulting from a variety of traumatic and non-traumatic causes Non-traumatic causes can be grouped into five categories including: Stress (surgery, burns, sepsis), hemorrhagic diathesis or coagulopathy

(antiphospholipid syndrome, DIC, anticoagulants), Neonatal stress (asphyxia,

septicemia), underlying adrenal tumors (myelolipoma, hemangioma,

pheochromocytoma, adenoma, carcinoma and metastasis) and idiopathic disease

Trauma typically produces unilateral, right-sided hemorrhage and is frequently

associated with injuries of higher severity

• Unilateral hemorrhage usually goes unnoticed while bilateral hemorrhage can result in catastrophic adrenal insufficiency necessitating prompt steroid replacement therapy

On CT, adrenal hematomas appear round to oval with periadrenal fat stranding and an attenuation value of 40-60 HU Most decrease in size with time and some resolve

completely, while others become organized pseudocysts with or without calcification

Simple adrenal cyst

• Adrenal cysts account for 4-22% of incidentalomas on imaging and are

histologically categorized into four subtypes: endothelial, pseudocyst,

epithelial, and parasitic Endothelial cysts represent the ‘simple adrenal cyst’ and comprise 45% of all adrenal cysts at autopsy These can arise from ectasia

of lymphatic vessels (lymphangiomatous cyst) or blood vessels (angiomatous cyst) in the adrenal gland They are lined with flattened endothelium and are filled with clear/milky fluid

• On imaging they are typically unilateral, variable in size with a thin

non-enhancing smooth wall and pure cystic internal structure Lymphangiomatous cyst variants may show thin internal septa CT attenuation values are generally less that 20 HU Like cysts elsewhere in the body they appear dark on MR T1

WI and bright on T2 WI

COMMON ADRENAL MASSES:A MALIGNANT

• ADRENAL METASTASIS

• • PHEOCHROMOCTOMA

Bilateral adrenal metastasis

• Metastases are the most common malignant lesions to affect the

adrenal gland and are almost always clinically silent The most

common primary tumors to metastasize to the adrenal gland are

lung, breast, colon and melanoma Small adrenal metastases are

typically homogeneous in density, whereas larger lesions tend to

become necrotic Adrenal collision tumors occur when metastases and adenoma are found in same adrenal gland The treatment at this stage is usually chemotherapy and follow up, though isolated adrenal metastasis may be considered for resection or ablation

• Pheochromocytomas are catecholamine secreting tumors arising from

paraganglionic cells of the adrenal medulla Classically, these present with

uncontrolled secondary hypertension They may also present with cardiac

dysfunction or exhibit neurological symptoms 90% of patient have elevated urine vanillylmandelic acid (VMA) levels They are mostly sporadic but 10% are associated with heritable conditions e.g NF-1, Von-Hippel-Lindau, Tuberous sclerosis, Men IIa and IIb When extra-adrenal (10%), they are termed as paragangliomas and are

more likely malignant CT has a high sensitivity in detecting pheochromocytomas Large tumors often display hemorrhage, necrosis, and cyst formation On T1-WI

they are hypo or isointense to liver, kidney or muscle and hyperintense on T2-WI Metaiodobenzylguanidine (MIBG) scan shows accumulation of the norepinephrine analogue at sites of norepinephrine synthesis 10% are malignant and metastasize

to bone, liver and lung

• • Variable appearance (“chameleon tumors”)

• • Can be solid, solid and cystic, or purely cystic

• • Additional work-up

• • Metabolic (elevated serum and urinary metanephrines)

• • 123-I metaiodobenzylguanidine (MIBG)

• Bilateral

• Extra-adrenal

• Occur in children

UNCOMMON ADRENAL MASSES:A BENIGN

• MYELOLIPOMA

• • GANGLIONEUROMA

Adrenal Myelolipoma

• Myelolipoma is an uncommon, benign, metabolically inactive tumor that is typically unilateral, accounting for 7-15% of incidental adrenal masses It is usually seen in the older population with no sex

predilection Histologically, the lesion iscomposed of adipose and

proliferating hematopoietic tissue with foci of hemorrhage and

calcification commonly seen Spontaneous hemorrhage can rarely be significant enough to cause hypovolemic shock

• On MR, fat suppressed images are helpful and demonstrate signal

loss within the mass On the other hand, chemical shift imaging is not useful in diagnosis as the fat in a myelolipoma is extracellular

• Ganglioneuroma is a benign neurogenic neoplasm of sympathetic

ganglia that commonly manifests as an asymptomatic mass on

routine imaging It is typically un-encapsulated, sharply marginated, firm and gray-white in appearance The adrenal gland is the third

most common location after posterior mediastinum and the

retroperitoneum Clinically, urinary catecholamines and their

metabolites may be elevated On CT, ganglioneuromas appear

homogeneously hypodense with slight to moderate enhancement On

MR, they demonstrate low signal intensity on T1-WI and high signal intensity on T2-WI Enhancement on MR is variable, ranging from

mild to marked with early enhancement being atypical

UNCOMMON ADRENAL MASSES:A MALIGNANT

• Adrenocortical carcinomas are rare, highly malignant neoplasm of the

adrenal cortex, accounting for 0.05-0.2% of all cancers in USA They are

typically large, solid and unilateral Functioning tumors usually present at 5

cm and non-functioning tumors typically present at 10 cm Clinical

syndromes with functioning tumors include Cushing syndrome (30-40%) and virilization in females (23-30%) amongst others

• On NECT they appear heterogeneous owing to necrosis and enhance

inhomogeneously on contrast administration The most common

metastatic sites are lung, liver, nodes and bone Invasion of renal vein and IVC occurs early on with most patients presenting at stage III or IV

Adrenocortical oncocytic tumor

• Oncocytic tumors of the adrenal gland are rare neoplasms that originate from the adrenal cortex and are histologically, composed of epithelial cells with

abundant mitochondria in their cytoplasm and no lipid deposition These

tumors tend to be female predominant with a wide age range Most are

hormonally inactive and are incidentally discovered on imaging They can range from 3-22 cm in size, with the malignant ones being larger in size at

presentation and causing significant mass effect

• Both benign and malignant tumors tend to have T1 and T2 WI MR intensities similar to the spleen Like adrenocortical carcinomas there is a slight left sided predominance, however, preservation of the capsule and lack of local invasion even in large tumors can be considered features that differentiate adrenal

oncocytic tumor from adrenal cortical carcinoma

Collision Tumor

• Adrenal Collision tumors (ACTs) are tumors with two histologically distinct

pathological entities coexisting in the adrenal gland with no admixture at

interface These could be two benign tumors, two malignant tumors, or a

benign tumor in contiguity with a malignant tumor for example adenoma with myelolipoma, myelolipoma with adrenocortical carcinoma or an adenoma with metastasis The most common ACT reported in literature is an adenoma with a myelolipoma However, the most problematic is an ACT composed of adenoma and metastasis in terms of diagnosis and management

• Cross sectional imaging modalities like CT and MRI can play a paramount role

in reliably depicting the different tumoral component in each entity thereby, guiding the appropriate management

• Neuroblastoma is primarily a childhood malignancy with only 10% of cases occurring after the age of 10 In adults(> 18 years ) they have an incidence of 1 case per

million /year as compared to 1 case per 100,000/ year in children Fundamentally,

these tumors arise from primitive sympathetic neural cells in the adrenal medulla They can however arise from anywhere in the sympathetic nervous system at a

paraspinal location, in the retroperitoneum or chest Metastasis occurs to regional lymph nodes, liver, skin, brain, and bone

• Growing evidence suggests that adult neuroblastoma may have distinct biologic

features, including low incidence of MYCN amplification, urine catecholamine

elevation, and MIBG avidity Adult patients have been reported to have a higher

incidence of unfavorable histologies and up to 1/3 of patients present with metastatic disease with an overall survival of 36% at 5 years as compared to 85% for infants

• Primary adrenal lymphoma (PAL) is very rare, with fewer than 200 cases reported in literature It has a tendency to affect elderly males and presents with local pain or systemic symptoms such as fever, weight loss or adrenal insufficiency In 70% of

cases it is bilateral Tumors generally tend to be large with a median size of 8 cm On

CT, they may appear homogeneous /heterogeneous, hypodense /hyperdense with slight to moderate enhancement On MR, they maybe iso/hypointense on T1-WI and hyperintense on T2-WI Most demonstrate a restricted diffusion pattern with high signal intensity on diffusion weighted images (DWI), owing to their typical high

cellularity

• PAL is generally not a hypervascular tumor but is highly metabolically active showing increased glucose uptake on PET Typical imaging findings can possibly point to the diagnosis, however, definitive diagnosis is only established upon tissue biopsy

Cystic adrenal lymphoma

• In the 1990’s and earlier, case reports of primary adrenal lymphomas with cystic changes were being more frequently reported in the literature This gave rise to the assumption that primary adrenal lymphomas were

complex cystic masses and secondary adrenal involvement by lymphoma presented as a well-defined, relatively homogenous soft tissue mass

However , more recently several studies have shown variable results

Studies have reported an equal incidence of homogeneous and

heterogeneous appearing primary adrenal lymphomas, debunking this

theorem Cystic adrenal lymphomas like their non-cystic counterparts are primarily non-Hodgkins B-cell lymphomas and essentially demonstrate

the same clinical and biochemical characteristics.