Multiple endocrine neoplasia type 2 differential diagnosis: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
[[Image:Home_logo1.png|right|250px|link=https://www.wikidoc.org/index.php/Multiple_endocrine_neoplasia_type_2]] | |||
{{CMG}}; {{AE}} {{Ammu}} | {{CMG}}; {{AE}} {{Ammu}} | ||
==Overview== | ==Overview== | ||
Multiple endocrine neoplasia type 2 must be differentiated from other hereditary tumors such as [[medullary thyroid carcinoma]], [[ | Multiple endocrine neoplasia type 2 must be differentiated from other hereditary tumors such as [[medullary thyroid carcinoma]], C-[[Cell (biology)|cell]] [[hyperplasia]], [[pheochromocytoma]], [[von Hippel Lindau syndrome]], [[Heredity|hereditary]] [[paraganglioma]]-[[pheochromocytoma]], [[polycythemia]] and [[paraganglioma]]/[[pheochromocytoma]] [[syndrome]], [[neurofibromatosis type 1]], and [[multiple endocrine neoplasia type 1]] ([[MEN 1]]). | ||
== | ==Differential Diagnosis== | ||
Multiple endocrine neoplasia type 2 must be differentiated from the following | Multiple endocrine neoplasia type 2 must be [[Differentiate|differentiated]] from the following [[Disease|diseases]].<ref name="ToledoLourenco Jr2013">{{cite journal|last1=Toledo|first1=SP|last2=Lourenco Jr|first2=DM|last3=Toledo|first3=RA|title=A differential diagnosis of inherited endocrine tumors and their tumor counterparts|journal=Clinics|volume=68|issue=7|year=2013|pages=1039–1056|issn=18075932|doi=10.6061/clinics/2013(07)24}}</ref> | ||
{| style="border: 0px; font-size: | {| style="border: 0px; font-size: 85%; margin: 3px; width: 600px" align="center" | ||
|+ | |+ | ||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Disease}} | ! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Disease}} | ||
! style="background: #4479BA; width: | ! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Gene}} | ||
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Chromosome}} | |||
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Differentiating Features}} | |||
! colspan="3" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Components of MEN}} | |||
! rowspan="2" style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Diagnosis}} | |||
|- | |- | ||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Parathyroid}} | |||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pitutary}} | |||
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Pancreas}} | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[von Hippel-Lindau syndrome]] | ||
| style="padding: 5px 5px; background: # | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
* [[Von Hippel-Lindau tumor suppressor|Von Hippel–Lindau tumor suppressor]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |3p25.3 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Angiomatosis]], | |||
* [[Hemangioblastoma|Hemangioblastomas]] | |||
* [[Pheochromocytoma]] | |||
* [[Renal cell carcinoma]] | |||
* [[Pancreatic cyst|Pancreatic cysts]] (pancreatic serous cystadenoma) | |||
* [[Endolymphatic sac tumor]] | |||
*[[Bilateral]] papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women) | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | + | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Clinical diagnosis | |||
* In hereditary VHL, disease techniques such as [[Southern blotting]] and [[gene sequencing]] can be used to analyse [[DNA]] and identify mutations. | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[ | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Carney complex]] | ||
| style="padding: 5px 5px; background: # | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
* [[PRKAR1A]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | 17q23-q24 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Myxomas]] of the [[heart]] | |||
* [[Hyperpigmentation]] of the [[skin]] ([[lentiginosis]]) | |||
* [[Endocrine]] ([[Adrenocorticotropic hormone|ACTH]]-independent [[Cushing's syndrome]] due to primary pigmented nodular adrenocortical disease) | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Clinical diagnosis | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[ | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Neurofibromatosis type 1]] | ||
| style="padding: 5px 5px; background: # | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
* [[RAS]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Scoliosis]] | |||
* [[Learning disabilities]] | |||
* [[Visual disturbance|Vision]] disorders | |||
* [[Cutaneous]] [[lesion]]s | |||
* [[Epilepsy]]. | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |'''<u>Prenatal</u>''' | |||
* [[Chorionic villus sampling]] or [[amniocentesis]] can be used to detect [[Neurofibromatosis type I|NF-1]] in the fetus. | |||
'''<u>Postnatal</u>''' | |||
Cardinal Clinical Features" are required for positive diagnosis. | |||
* Six or more [[Café-au-lait spot|café-au-lait spots]] over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals. | |||
* Two or more [[Neurofibroma|neurofibromas]] of any type or 1 [[plexiform neurofibroma]] | |||
* Freckling in the [[axillary]] ([[Crowe sign]]) or [[Inguinal region|inguinal]] regions | |||
* [[Optic glioma]] | |||
* Two or more [[Lisch nodules]] (pigmented iris [[hamartomas]]) | |||
* A distinctive [[osseous]] lesion such as [[Sphenoid bone|sphenoid]] [[dysplasia]], or thinning of the long bone cortex with or without [[pseudarthrosis]]. | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Li-Fraumeni syndrome]] | ||
| style="padding: 5px 5px; background: # | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
* [[TP53 (gene)|TP53]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Early onset of diverse amount of [[cancer]]s such as | |||
* [[Sarcoma]] | |||
* [[Cancer]]s of | |||
** [[Breast]] | |||
** [[Brain]] | |||
** [[Adrenal gland]]s | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
'''<u>Criteria</u>''' | |||
* [[Sarcoma]] at a young age (below 45) | |||
* A first-degree relative diagnosed with any [[cancer]] at a young age (below 45) | |||
* A first or second degree relative with any [[cancer]] diagnosed before age 60. | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Gardner's syndrome]] | ||
| style="padding: 5px 5px; background: # | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
* [[APC]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | 5q21 | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Multiple [[polyps]] in the [[colon]] | |||
* [[Osteomas]] of the [[skull]] | |||
* [[Thyroid cancer]] | |||
* [[Epidermoid cyst|Epidermoid cysts]] | |||
* [[Fibroma|Fibromas]] | |||
* [[Desmoid tumor|Desmoid tumors]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Clinical diagnosis | |||
* [[Colonoscopy]] | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[ | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Multiple endocrine neoplasia type 2]] | ||
| style="padding: 5px 5px; background: # | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
* ''[[RET gene|RET]]'' | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Medullary thyroid carcinoma]] (MTC) | |||
* [[Pheochromocytoma]] | |||
* [[Primary hyperparathyroidism]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | + | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Hypercalcemia]] | |||
* [[Hypophosphatemia]], | |||
* Elevated [[parathyroid hormone]], | |||
* Elevated [[norepinephrine]] | |||
'''<u>Criteria</u>''' | |||
Two or more specific endocrine tumors | |||
* [[Medullary thyroid carcinoma]] | |||
* [[Pheochromocytoma]] | |||
* [[Parathyroid]] hyperplasia | |||
|- | |- | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[ | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Cowden syndrome]] | ||
| style="padding: 5px 5px; background: # | | style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | ||
* [[PTEN]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Hamartomas]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* ''[[PTEN]]'' mutation probability risk calculator | |||
|- | |- | ||
| style="padding: 5px 5px; background: # | | style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Acromegaly]]/[[gigantism]] | ||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Enlargement of the [[hand]]s, [[feet]], [[nose]], [[lip]]s and [[ear]]s, and a general thickening of the [[skin]] | |||
}}</ref> | * [[Hypertrichosis]] | ||
* [[Hyperpigmentation]] | |||
* [[Hyperhidrosis]] | |||
* [[Carpal tunnel syndrome]]. | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* An elevated concentration of serum [[Growth hormone|growth hormone (GH)]] and [[Insulin-like growth factor|insulin-like growth factor 1(IGF-1)]] levels is diagnostic of [[acromegaly]]. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Pituitary adenoma]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Visual field defect]]s classically [[bitemporal hemianopsia]] | |||
* [[Increased intracranial pressure]] | |||
* [[Migraine]] | |||
* [[Lateral rectus]] palsy | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
*Elevated serum level of [[prolactin]] | |||
*Elevated or decreased serum level of [[adrenocorticotropic hormone]] (ACTH) | |||
*Elevated or decreased serum level of [[growth hormone]] (GH) | |||
*Elevated or decreased serum level of [[thyroid-stimulating hormone]] (TSH) | |||
*Elevated or decreased serum level of [[follicle-stimulating hormone]] (FSH) | |||
*Elevated or decreased serum level of [[luteinizing hormone]] (LH) | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Hyperparathyroidism]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Kidney stone]]s | |||
* [[Hypercalcemia]] | |||
* [[Constipation]] | |||
* [[Peptic ulcer]]s | |||
* [[Depression]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>+</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* An elevated concentration of serum [[calcium]] with elevated [[parathyroid hormone]] level is diagnostic of primary hyperparathyroidism. | |||
* Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum [[parathyroid hormone]] level and low to normal serum [[calcium]]. | |||
* An elevated concentration of serum [[calcium]] with elevated [[parathyroid hormone]] level in post [[Kidney transplantation|renal transplant]] patients is diagnostic of tertiary hyperparathyoidism. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Pheochromocytoma]]/[[paraganglioma]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* ''[[VHL]]'' | |||
* ''[[RET gene|RET]]'' | |||
* ''[[NF1]]'' | |||
* ''[[SDHB]]'' | |||
* ''[[SDHD]]'' | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | - | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |Characterized by | |||
* Episodic [[hypertension]] | |||
* [[Palpitation]]s | |||
* [[Anxiety]] | |||
* [[Diaphoresis]] | |||
* [[Weight loss]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* Increased [[Catecholamine|catecholamines]] and [[Metanephrine|metanephrines]] in [[plasma]] ([[blood]]) or through a 24-hour [[urine]] collection. | |||
|- | |||
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |[[Adrenocortical carcinoma]] | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
*[[p53]] | |||
*[[Retinoblastoma]] h19 | |||
*Insulin-like growth factor II (IGF-II) | |||
*[[P57 (gene)|p57]]<sup>kip2</sup> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |17p, 13q | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Cushing syndrome]] ([[cortisol]] hypersecretion) | |||
* [[Conn syndrome]] ([[aldosterone]] hypersecretion) | |||
* [[virilization]] ([[testosterone]] hypersecretion) | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |<nowiki>-</nowiki> | |||
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" | | |||
* [[Hyperglycemia|Increased serum glucose]] | |||
* Increased [[urine]] [[cortisol]] | |||
* Serum [[androstenedione]] and [[dehydroepiandrosterone]] | |||
* [[Hypokalemia|Low serum potassium]] | |||
* Low plasma [[renin]] activity | |||
* High serum [[aldosterone]] | |||
* Excess serum [[estrogen]] | |||
|- | |||
| colspan="8" style="padding: 5px 5px; background: #F5F5F5;" |<small>Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013<ref name="pmid23917672">{{cite journal| author=Toledo SP, Lourenço DM, Toledo RA| title=A differential diagnosis of inherited endocrine tumors and their tumor counterparts. | journal=Clinics (Sao Paulo) | year= 2013 | volume= 68 | issue= 7 | pages= 1039-56 | pmid=23917672 | doi=10.6061/clinics/2013(07)24 | pmc=PMC3715026 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23917672 }} </ref> </small> | |||
|} | |} | ||
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Latest revision as of 14:37, 26 June 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ammu Susheela, M.D. [2]
Overview
Multiple endocrine neoplasia type 2 must be differentiated from other hereditary tumors such as medullary thyroid carcinoma, C-cell hyperplasia, pheochromocytoma, von Hippel Lindau syndrome, hereditary paraganglioma-pheochromocytoma, polycythemia and paraganglioma/pheochromocytoma syndrome, neurofibromatosis type 1, and multiple endocrine neoplasia type 1 (MEN 1).
Differential Diagnosis
Multiple endocrine neoplasia type 2 must be differentiated from the following diseases.[1]
Disease | Gene | Chromosome | Differentiating Features | Components of MEN | Diagnosis | ||
---|---|---|---|---|---|---|---|
Parathyroid | Pitutary | Pancreas | |||||
von Hippel-Lindau syndrome | 3p25.3 |
|
- | - | + |
| |
Carney complex | 17q23-q24 |
|
- | - | - |
| |
Neurofibromatosis type 1 | 17 | - | - | - | Prenatal
Postnatal Cardinal Clinical Features" are required for positive diagnosis.
| ||
Li-Fraumeni syndrome | 17 | Early onset of diverse amount of cancers such as | - | - | - |
Criteria | |
Gardner's syndrome | 5q21 |
|
- | - | - |
| |
Multiple endocrine neoplasia type 2 | - | + | - | - |
Criteria Two or more specific endocrine tumors
| ||
Cowden syndrome | - | - | - | - |
| ||
Acromegaly/gigantism | - | - |
|
- | + | - |
|
Pituitary adenoma | - | - | - | + | - |
| |
Hyperparathyroidism | - | - | + | - | - |
| |
Pheochromocytoma/paraganglioma | - | Characterized by | - | - | - |
| |
Adrenocortical carcinoma |
|
17p, 13q |
|
- | - | - |
|
Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013[2] |
References
- ↑ Toledo, SP; Lourenco Jr, DM; Toledo, RA (2013). "A differential diagnosis of inherited endocrine tumors and their tumor counterparts". Clinics. 68 (7): 1039–1056. doi:10.6061/clinics/2013(07)24. ISSN 1807-5932.
- ↑ Toledo SP, Lourenço DM, Toledo RA (2013). "A differential diagnosis of inherited endocrine tumors and their tumor counterparts". Clinics (Sao Paulo). 68 (7): 1039–56. doi:10.6061/clinics/2013(07)24. PMC 3715026. PMID 23917672.