Pheochromocytoma and Paraganglioma


Syndrome

Gene (chromosome)a,b

Clinical manifestations

% With PHEO

% Bilateral

von Hippel-Lindauc

VHL (3p25-p26)

PHEO, cerebellar hemangioblastoma, retinal angiomas, renal cell carcinoma, pancreatic cysts, pancreatic NETs in 5–10 %

10–20 %

40–80

Multiple endocrine neoplasia type 2Ad

RET (10q11.2)

PHEO, MTC, hyperparathyroidism

50 %

50–80

Multiple endocrine neoplasia type 2B

PHEO, MTC, mucosal neuromas, colonic ganglioneuromatosis, marfanoid facies, skeletal abnormalities

von Recklinghausen’s disease

NF1 (17q11.2)

Neurofibromata, >6 café au lait spots, axillary freckling, skeletal abnormalities, and PHEO

5–10 %

10

PGL-1

SDHD (11q23)

Parasympathetic head and neck PGL +/− PHEO

Uncommon

–

PGL-2

SDHAF2 (11q13.1)

Parasympathetic head and neck PGL (nonfunctioning)

Not described

–

PGL-3

SDHC (1q21)

Parasympathetic head and neck PGL, PHEO rare

Rare

–

PGL-4

SDHB (1p35-p36)

Sympathetic abdominal PGL and PHEO – 50 % malignant

PGL or PHEO in 70 %
 
Familial pheochromocytoma

TMEM127 (2q11)

PHEO

?

43

Familial neural crest-derived tumors

KIF1B (1p36.2)

PHEO or neuroblastoma

?

?


a RET rearranged during transfection, SDH succinate dehydrogenase, SDHAF2 succinate dehydrogenase complex assembly factor 2, TMEM127 transmembrane 127, NF1 neurofibromatosis type 1, KIF1B kinesin family member 1B (microtubule motor)

bHomozygous mutations of SDHA cause Leigh syndrome which is not associated with PHEO or PGL

cFour types of VHL disease are recognized (1, 2A, 2B, and 2C) – type 1 is not associated with PHEO

dMedullary thyroid cancer (MTC) is usually the initial presentation. MEN2A is associated with Hirschsprung’s disease in 5%

? not currently known




  • PHEO/PGL of genetic origin is more likely to be bilateral, extra-adrenal, multifocal and associated with an increased risk of malignancy.


  • Macroscopically, PHEO and PGL are soft vascular tumors with a pink-tan color on slicing. Microscopically, they exhibit a regular nested “Zellballen” pattern of polyhedral cells that are chromaffin positive on staining.


  • The definitive markers for malignancy are local invasion and distant metastasis. However size >5 cm, presence of lymphovascular or capsular invasion, and increased Ki-67 proliferation index are associated with increased risk.






      Presentation






      • May be symptomatic or asymptomatic.


      • Symptomatic tumors present with typical triad of paroxysmal headache (90 %), sweating (92 %), and palpitations (72 %).


      • 0.2 % of patients investigated for hypertension will have a PHEO, and 70 % of those with PHEO will have sustained hypertension.


      • About 10 % of PHEO are discovered incidentally on CT/MRI for unrelated symptoms (adrenal “incidentaloma”).


      • Asymptomatic tumors may be diagnosed during screening for genetic disorders in which PHEO or PGL is part of the disease phenotype (in order of commonality, VHL, MEN2A or B, NF1, SDHB/C/D).


      • Clinical signs are usually absent.


      Investigations (See Chap.​ 1)




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      Feb 26, 2017 | Posted by in ENDOCRINOLOGY | Comments Off on Pheochromocytoma and Paraganglioma

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