389 lines
23 KiB
Markdown
389 lines
23 KiB
Markdown
---
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title: "Pheochromocytoma"
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docid: "1bfc887d-4686-445b-a0d2-f3b380a0da3a"
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authors:
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- key: "7e25292c-4d6a-4f35-98b2-1877e5989352"
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value: "Ashish P. Wasnik, MD, FSAR"
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breadcrumbs:
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-
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name: "Ultrasound"
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slug: "ultrasound"
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treeNodeId: "e7cdfeb1-bb55-4cca-9854-46cadee515d2"
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-
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name: "Diagnosis"
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slug: "diagnosis"
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treeNodeId: "594506fe-1241-4d01-9b37-a9d64f0c98c4"
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-
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name: "Adrenal Gland"
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slug: "adrenal-gland"
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treeNodeId: "bdbaa036-5505-43ee-94e1-5a2ece43da0f"
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-
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name: "Pheochromocytoma"
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slug: "pheochromocytoma"
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treeNodeId: null
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category: "Ultrasound"
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cmeTopicId: "294ea24b-7fbc-4cf4-89d4-e53caacbe2e6"
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documentVersionId: "84b213c9-8864-4424-b1e5-b6a46d8489bc"
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imageCount: 16
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lastUpdated: "07/01/21"
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pageDescription: "Pheochromocytoma"
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pageKeywords: "Ultrasound, Diagnosis, Adrenal Gland, Pheochromocytoma"
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pageTitle: "Pheochromocytoma | STATdx"
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enhancedTitle: "Pheochromocytoma"
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type: "DX"
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references: true
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breadcrumbs:
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- "Ultrasound"
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- "Diagnosis"
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- "Adrenal Gland"
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- "Pheochromocytoma"
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---
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# KEY FACTS
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- ## Terminology
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- Rare catecholamine-secreting tumor arising from chromaffin cells of adrenal medulla
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- Termed **paraganglioma** if extraadrenal
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- ## Imaging
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- Best diagnostic clue
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- Adrenal mass in setting of clinical symptoms or biochemical abnormality
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- Paroxysmal headache, palpitations, sweating
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- ↑ levels of 24-hour urine-fractionated metanephrines
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- "**Imaging chameleon**": Variable US/CT/MR appearance; mimics other lesions
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- Commonly solid and hypervascular ± cystic change, necrosis, and calcification
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- Can be purely cystic
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- **1st line**: CT or MR
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- **US**: Comparable to CT in detecting adrenal tumors; limited for extraadrenal disease
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- **I-123 MIBG**: For extraadrenal, metastatic, or recurrent disease
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- ## Top Differential Diagnoses
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- Adrenal adenoma
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- Adrenal metastases or lymphoma
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- Adrenocortical carcinoma
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- Adrenal neuroblastoma
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- Adrenal granulomatous infection
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- ## Diagnostic Checklist
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- Remembered as "**r****ule of 10s**"
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- 10% extraadrenal (paraganglioma)
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- 10% bilateral (suggest hereditary disease)
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- 10% pediatric (suggest hereditary disease)
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- 10% contain calcification
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- 10% malignant (↑ extraadrenal cases)
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- 25% familial (previously thought to be 10%)
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# TERMINOLOGY
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- ## Definitions
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- Paraganglioma: Neuroendocrine tumor arising from paraganglia anywhere in sympathetic chain
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- Pheochromocytoma: Adrenal medullary paraganglioma arising from catecholamine-secreting chromaffin cells of adrenal medulla
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# IMAGING
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- ## General Features
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- ### Best diagnostic clue
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- Adrenal mass in setting of clinical symptoms or biochemical abnormality
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- ### Location
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- Paragangliomas can occur along sympathetic chain from neck to urinary bladder
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- Majority are subdiaphragmatic (98%)
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- Adrenal (90%)
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- Extraadrenal (10%)
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- Organ of Zuckerkandl, 2.5% [from superior mesenteric artery (SMA) to aortic bifurcation, mostly around inferior mesenteric artery]
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- Urinary bladder sympathetic chain, 1%
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- Typically unilateral
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- Bilateral: Commonly with hereditary conditions
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- ### Size
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- Variable: Typically 3-5 cm (can be up to 15 cm)
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- ### Morphology
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- Well-circumscribed, encapsulated tumor
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- Variable size and appearance on morphology and imaging renders name "chameleon tumors"
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- Commonly solid and hypervascular ± cystic change, necrosis, and calcification
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- Can be purely cystic
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- Pheochromocytomas and paragangliomas demonstrate similar imaging features but vary in location
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- ## Ultrasonographic Findings
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- ### Grayscale ultrasound
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- Variable appearance: Solid (75%) > solid/cystic or cystic
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- Iso-/hypoechoic (75%) or hyperechoic (25%) to renal cortex
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- Small tumors: Solid, well-circumscribed; uniform echoes → can be poorly delineated due to obscuration from overlying bowel gas
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- Large tumors: Solid, heterogeneous, or homogeneous echotexture
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- Heterogeneity due to necrosis (hypoechoic) and hemorrhage (hyperechoic)
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- Can be predominantly cystic due to chronic hemorrhage and necrotic debris (fluid-fluid level)
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- Always evaluate bladder wall, renal hilum, and organ of Zuckerkandl at origin of inferior mesenteric artery (CT more sensitive)
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- ### Color Doppler
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- Hypervascular ± heterogeneous
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- Compression/invasion of inferior vena cava (IVC)/renal vein
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- Seen with both benign and malignant tumors
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- ## CT Findings
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- **NECT**: Well-defined mass with low soft tissue attenuation
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- Generally attenuation > 10 HU; however, rarely intracellular fat may result in lower attenuation → posing challenge to differentiate from adenoma
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- ± ↑ density (hemorrhage), ↓ density (cystic degeneration; necrosis), calcification (rare; 10%)
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- **CECT**: Marked enhancement; may be heterogeneous due to hemorrhage/necrosis
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- Variable washout characteristics: Can show rapid washout that mimics adenoma
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- No convincing evidence that IV injection of iodinated contrast precipitates hypertensive crisis
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- ## MR Findings
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- **T1WI**: **Isointense** to muscle and hypointense to liver
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- Variable signal intensity if necrosis/hemorrhage present
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- Rarely, contain microscopic fat on chemical shift imaging, mimicking adenoma
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- **T2WI**: T2 hyperintense due to ↑ water content (cystic/liquefactive necrosis)
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- Classic light bulb appearance of marked T2-bright signal intensity (SI), variably (present in up to 2/3)
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- 35% have low T2 SI (isointense to spleen)
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- Most common: Heterogeneously enhancing lesion with multiple high-SI pockets
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- **T1WI C+**: Characteristic **salt and pepper** pattern
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- **Salt** (enhancing parenchyma); **pepper** (↑ vascular flow voids due to hypervascular tumor)
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- ## Nuclear Medicine Findings
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- **1st line**: I-123 metaiodobenzylguanidine (**MIBG**)
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- Norepinephrine analog
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- After 24-72 hours: ↑ uptake of I-123 MIBG in tumor
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- Useful for extraadrenal, metastatic, recurrent disease
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- Sensitivity (77-90%); specificity (95-100%)
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- 2nd line: 111In-pentetreotide FDG PET
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- F-18 fluorodopamine, F-18 dihydroxyphenylalanine (DOPA) analogs
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- ## Imaging Recommendations
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- ### Best imaging tool
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- **NE + CECT**: Overall 93-100% sensitive; however, up to 40% of extraadrenal lesions may be missed on CT
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- **I-123 MIBG**: Superior detection of extraadrenal, metastatic, &/or recurrent disease
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- US limited for smaller adrenal tumors; poor sensitivity for extraadrenal lesions
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- ### Protocol advice
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- Include aortic bifurcation in CT/MR FOV to evaluate for paragangliomas (along sympathetic chain)
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# DIFFERENTIAL DIAGNOSIS
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- [Adrenal Adenoma](/document/adrenal-adenoma/25bd0538-d37f-4bd1-9eb3-094d625723a5)
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- Most common benign adrenal lesion
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- Pheochromocytomas tend to be larger than adenomas
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- Cystic and rare microscopic fat-containing pheochromocytomas may also be hypodense on NECT
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- Adenoma: Characteristic CT washout and MR signal dropout (majority)
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- ## Adrenal Metastases
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- Most common malignant adrenal neoplasm (up to 25%)
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- Typically bilateral; delayed contrast washout
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- [Adrenal Lymphoma](/document/adrenal-lymphoma/44639c90-bd04-4e2a-a470-2c28a0e2ff78)
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- Large infiltrative, bilateral masses; maintain adrenal contour
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- 25% secondary to non-Hodgkin lymphoma; primary is rare
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- ## Adrenocortical Carcinoma
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- Rare; aggressive; large, unilateral, heterogeneous solid mass with necrosis; hemorrhage ± calcification
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- T2 hyperintense and T1 hypointense to liver (as with "classic" pheochromocytomas)
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- Aggressive, often with IVC extension
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- ## Adrenal Neuroblastoma
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- Large pediatric adrenal mass; calcification (80-90%)
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- ## Adrenal Granulomatous Infection
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- TB, histoplasmosis, other fungal diseases; usually bilateral
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- Acute (hypoechoic masses) or chronic (small and calcified)
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# PATHOLOGY
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- ## General Features
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- ### Associated abnormalities
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- Majority are sporadic
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- 25% have autosomal dominant gene mutation
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- **Multiple endocrine neoplasia type 2 (MEN2)**
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- *MEN2*mutation; 50% have pheochromocytoma
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- Medullary thyroid carcinoma, hyperparathyroidism, neuromas, and marfanoid habitus
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- **von Hippel-Lindau (VHL) disease**
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- *VHL*tumor suppressor gene; 10-25% risk
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- Multiple benign and malignant tumors
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- **Neurofibromatosis type 1**
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- Rare cause of pheochromocytomas; 1% risk
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- Cutaneous/plexiform neurofibromas, optic nerve gliomas, peripheral nerve sheath tumors, gastrointestinal stromal tumors
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- **Pheochromocytoma-paraganglioma syndromes**
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- Mutations of succinate dehydrogenase gene family; 50% risk
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- ↑ incidence of extraadrenal tumors and head/neck paragangliomas
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- Most are benign; 10% are malignant
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- Diagnosis of malignancy is based solely on presence of direct local tumor invasion or metastatic disease
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- Extraadrenal paragangliomas are more likely to be malignant
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- ## Gross Pathologic & Surgical Features
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- Small tumor: Well-circumscribed, yellow-tan lesion confined to adrenals
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- Large tumor: Hemorrhagic, cystic/necrotic masses
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- ## Microscopic Features
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- Predominantly chromaffin cells; occasionally spindle cells are dominant feature
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- Term pheochromocytoma refers to dusky color of cells stained with chromium salts
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- No single histologic feature of pheochromocytoma consistently predicts malignancy
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- Definitive pathologic diagnosis of malignancy is based on presence of metastatic disease
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# CLINICAL ISSUES
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- ## Presentation
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- ### Most common signs/symptoms
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- Majority are asymptomatic; symptoms may be episodic or paroxysmal
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- Classic triad (arises from adrenergic excess)
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- Paroxysmal headache, palpitations, sweating
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- 90% specific but uncommon (only present in 10.0-36.5% of patients)
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- ### Other signs/symptoms
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- Hypertensive crisis: Palpitations, tremors, arrhythmias, pain, myocardial infarction
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- Laboratory data
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- Tumors typically secrete norepinephrine > epinephrine
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- **↑**levels of 24-hour urine-fractionated metanephrines
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- 90-97% sensitivity; 69-98% specificity
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- ## Demographics
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- ### Age
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- Sporadic cases, 3rd and 4th decades
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- Hereditary cases, 3rd decade
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- 10% are found in children
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- ### Sex
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- Slight female predilection (M:F = 1:1.4)
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- ### Epidemiology
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- Exact incidence: Unknown
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- Prevalence in hypertensive adults 0.1-0.6%
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- Majority of pheochromocytomas are likely asymptomatic (incidentalomas)
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- ## Natural History & Prognosis
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- Hypertensive crises and cardiovascular complications ↑ morbidity/mortality
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- Prognosis: Noninvasive and nonmetastatic: Typically favorable
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- ## Treatment
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- Symptomatic therapy: α-adrenergic blockade and calcium channel antagonists
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- Laparoscopic resection/debulking for both benign and malignant tumors
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- Adjuvant therapy (malignant tumors): I-131 MIBG therapy ± chemotherapy (cyclophosphamide, vincristine, dacarbazine)
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# DIAGNOSTIC CHECKLIST
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- ## Consider
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- Imaging can mimic other diagnoses; labs essential for diagnosis
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- ## Image Interpretation Pearls
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- Extraadrenal tumors arise anywhere along sympathetic ganglia (neck to bladder), attention to these locations
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c0256142-d2c8-452c-ad4f-032d36d44ba0
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## References
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# Selected References
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1. [Nandra G et al: Technical and interpretive pitfalls in adrenal imaging. Radiographics. 40(4):1041-60, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32609593%5Bpmid%5D)
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1. [Chang CA et al: (68)Ga-DOTATATE and (18)F-FDG PET/CT in paraganglioma and pheochromocytoma: utility, patterns and heterogeneity. Cancer Imaging. 16(1):22, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=27535829%5Bpmid%5D)
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1. [Lattin GE Jr et al: From the radiologic pathology archives: adrenal tumors and tumor-like conditions in the adult: radiologic-pathologic correlation. Radiographics. 34(3):805-29, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24819798%5Bpmid%5D)
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1. [Leung K et al: Pheochromocytoma: the range of appearances on ultrasound, CT, MRI, and functional imaging. AJR Am J Roentgenol. 200(2):370-8, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23345359%5Bpmid%5D)
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1. [Raja A et al: Multimodality imaging findings of pheochromocytoma with associated clinical and biochemical features in 53 patients with histologically confirmed tumors. AJR Am J Roentgenol. 201(4):825-33, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=24059371%5Bpmid%5D)
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1. [Parenti G et al: Updated and new perspectives on diagnosis, prognosis, and therapy of malignant pheochromocytoma/paraganglioma. J Oncol. 2012:872713, 2012](http://www.ncbi.nlm.nih.gov/pubmed/?term=22851969%5Bpmid%5D)
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1. [Blake MA et al: Pheochromocytoma: an imaging chameleon. Radiographics. 24 Suppl 1:S87-99, 2004](http://www.ncbi.nlm.nih.gov/pubmed/?term=15486252%5Bpmid%5D)
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## Images
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### Selected Images
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*Graphic shows a typical pheochromocytoma <img src='img/arrows/WO.png'/>, moderate in size with a well-circumscribed margin and solid appearance. Note hypervascularity <img src='img/arrows/WS.png'/> of the mass, which commonly results in necrosis and cystic change.*
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*Graphic shows a typical pheochromocytoma <img src='img/arrows/WO.png'/>, moderate in size with a well-circumscribed margin and solid appearance. Note hypervascularity <img src='img/arrows/WS.png'/> of the mass, which commonly results in necrosis and cystic change.*
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*Transverse (left) and longitudinal (right) transabdominal ultrasound show a well-demarcated, heterogenous, solid right adrenal mass <img src='img/arrows/WS.png'/> hyperechoic to the renal cortex <img src='img/arrows/CC.png'/>, proven to be a pheochromocytoma.*
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*Longitudinal transabdominal ultrasound demonstrates well-circumscribed, round, heterogeneous, hypoechoic mass <img src='img/arrows/CO.png'/> in the right suprarenal region medially, proven to be a paraganglioma.*
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*Axial CECT in the previous patient shows a well-circumscribed, round, heterogeneous, hypodense mass <img src='img/arrows/CO.png'/>, anteromedial to the upper pole right kidney <img src='img/arrows/CS.png'/>, proven to be a paraganglioma.*
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*Longitudinal transabdominal ultrasound shows a large left adrenal mass <img src='img/arrows/CO.png'/>, slightly heterogeneous and hypoechoic to the renal cortex <img src='img/arrows/WC.png'/>.*
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*Axial CECT in the same patient confirms the left adrenal mass <img src='img/arrows/CO.png'/>, along with right adrenal mass <img src='img/arrows/CS.png'/> and a liver lesion <img src='img/arrows/CC.png'/>, confirmed lung cancer metastases.*
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*Axial T2WI MR shows 2 well-circumscribed, paraaortic paragangliomas <img src='img/arrows/WS.png'/>.*
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*Corresponding axial T1WI C+ FS MR demonstrates the same paragangliomas <img src='img/arrows/WS.png'/>. Notice the salt and pepper appearance of the right-most paragangliomas, consisting of enhancing parenchyma and internal flow void (hypervascularity).*
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*Transverse transabdominal color Doppler ultrasound shows heterogenous, hypervascular mass <img src='img/arrows/CO.png'/> anteromedial to the left kidney, confirmed paraganglioma.*
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*Axial arterial-phase CECT in the same patient confirms a large heterogeneously enhancing mass in the left retroperitoneum <img src='img/arrows/CO.png'/>, confirmed paraganglioma.*
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### Additional Images
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*Transverse transabdominal color Doppler ultrasound of a right adrenal pheochromocytoma shows a well-defined, heterogenous mass <img src='img/arrows/CC.png'/>.*
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*Coronal CECT shows a large, well-defined mass with avidly enhancing solid portions <img src='img/arrows/CS.png'/> and large, hypodense areas of necrosis <img src='img/arrows/CC.png'/>, confirmed paraganglioma.*
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*Axial fused PET/CT demonstrates ↑ radiotracer uptake <img src='img/arrows/WO.png'/> within the solid portions of the paraganglioma, whereas the necrotic areas appear photopenic <img src='img/arrows/WC.png'/>. The mass is distinct from the left kidney <img src='img/arrows/CC.png'/>, but notice abutment/narrowing of the main left renal vein <img src='img/arrows/CS.png'/>.*
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*Transverse color Doppler ultrasound shows a right adrenal pheochromocytoma <img src='img/arrows/WS.png'/> displacing and compressing the inferior vena cava <img src='img/arrows/WO.png'/>.*
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*Axial CECT shows a large, well-circumscribed, moderately enhancing right adrenal pheochromocytoma <img src='img/arrows/CS.png'/> with hypodense area of necrosis <img src='img/arrows/CC.png'/>.*
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*DTPA-MIBG scan of the same patient shows uptake within the pheochromocytoma <img src='img/arrows/WS.png'/>. Note DTPA uptake in kidneys <img src='img/arrows/WO.png'/>. MIBG is useful to detect extraadrenal tumors.*
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