Carney-Stratakis syndrome is a rare hereditary tumor-predisposition syndrome defined by the dyad of paraganglioma or pheochromocytoma and gastrointestinal stromal tumor. Classic molecularly confirmed disease is caused by heterozygous germline loss-of-function variants in succinate dehydrogenase complex genes, especially SDHB, SDHC, and SDHD, with incomplete penetrance and variable expression. SDH-deficient tumor cells lose mitochondrial complex II function, accumulate succinate, activate pseudohypoxic transcriptional programs, and develop epigenetic dysregulation that supports multifocal gastric GIST and paraganglioma formation.
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Conditions with similar clinical presentations that must be differentiated from Carney-Stratakis syndrome:
name: Carney-Stratakis syndrome
creation_date: "2026-05-11T17:02:12Z"
updated_date: "2026-05-11T17:02:12Z"
category: Genetic
description: >-
Carney-Stratakis syndrome is a rare hereditary tumor-predisposition syndrome
defined by the dyad of paraganglioma or pheochromocytoma and
gastrointestinal stromal tumor. Classic molecularly confirmed disease is
caused by heterozygous germline loss-of-function variants in succinate
dehydrogenase complex genes, especially SDHB, SDHC, and SDHD, with incomplete
penetrance and variable expression. SDH-deficient tumor cells lose
mitochondrial complex II function, accumulate succinate, activate
pseudohypoxic transcriptional programs, and develop epigenetic dysregulation
that supports multifocal gastric GIST and paraganglioma formation.
parents:
- hereditary neoplastic syndrome
- multiple polyglandular tumor
synonyms:
- Carney dyad
- Carney-Stratakis dyad
- GIST-paraganglioma dyad
- hereditary GIST-paraganglioma syndrome
- paraganglioma and gastrointestinal stromal tumor
disease_term:
preferred_term: Carney-Stratakis syndrome
term:
id: MONDO:0011740
label: Carney-Stratakis syndrome
inheritance:
- name: Autosomal Dominant
description: >-
Carney-Stratakis syndrome is inherited in an autosomal dominant manner with
incomplete penetrance; mutation-positive relatives may be clinically
unaffected.
evidence:
- reference: PMID:31174229
reference_title: "Paragangliomas in Carney-Stratakis Syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CSS has autosomal dominant inheritance, incomplete penetrance, and greater
relative frequency of PGL over GISTs.
explanation: >-
Review abstract explicitly states the inheritance pattern and incomplete
penetrance.
- reference: PMID:34012423
reference_title: "Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CSS is also known as the dyad of GIST and PGL; it affects both genders
equally and is inherited in an autosomal dominant manner with incomplete
penetrance.
explanation: >-
SDH-deficiency review confirms equal sex involvement and autosomal
dominant inheritance with incomplete penetrance.
prevalence:
- population: Worldwide reported literature
percentage: Unknown
notes: >-
Population prevalence has not been established. Published evidence consists
mainly of small family series, case reports, and SDH-deficient GIST/PGL
reviews.
evidence:
- reference: PMID:36387130
reference_title: "Bladder paraganglioma, gastrointestinal stromal tumor, and SDHB germline mutation in a patient with Carney-Stratakis syndrome: A case report and literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
BACKGROUND: Carney-Stratakis syndrome (CSS) is a rare dyad of
paraganglioma (PGL)/pheochromocytoma (PHEO) and gastrointestinal stromal
tumor (GIST).
explanation: >-
Case-report review supports rarity and defines the syndrome by its tumor
dyad.
pathophysiology:
- name: Germline SDH complex loss of function
description: >-
Heterozygous germline pathogenic variants in SDHB, SDHC, or SDHD predispose
to SDH-deficient tumors. Tumor suppressor behavior is supported by loss of
function of the remaining allele in affected GIST tissue.
genes:
- preferred_term: SDHB
term:
id: hgnc:10681
label: SDHB
- preferred_term: SDHC
term:
id: hgnc:10682
label: SDHC
- preferred_term: SDHD
term:
id: hgnc:10683
label: SDHD
biological_processes:
- preferred_term: mitochondrial electron transport, succinate to ubiquinone
modifier: DECREASED
term:
id: GO:0006121
label: mitochondrial electron transport, succinate to ubiquinone
- preferred_term: tricarboxylic acid cycle
modifier: DECREASED
term:
id: GO:0006099
label: tricarboxylic acid cycle
evidence:
- reference: PMID:17667967
reference_title: "Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We investigated 11 patients with the dyad of 'paraganglioma and gastric
stromal sarcoma'; in eight (from seven unrelated families), the GISTs were
caused by germline mutations of the genes encoding subunits B, C, or D
(the SDHB, SDHC and SDHD genes, respectively).
explanation: >-
Landmark molecular series identifies germline SDHB, SDHC, and SDHD
variants as causes of the Carney-Stratakis dyad.
- reference: PMID:34012423
reference_title: "Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CSS is caused by inactivating germline mutations in genes encoding for the
SDH subunits, while CT is mostly caused by a specific pattern of
methylation of the SDHC gene and may be due to germline mosaicism of the
responsible genetic defect.
explanation: >-
Review distinguishes germline SDH-subunit inactivation in
Carney-Stratakis syndrome from Carney triad.
downstream:
- target: Succinate accumulation and pseudohypoxia
description: >-
SDH dysfunction blocks succinate oxidation and promotes succinate-driven
inhibition of oxygen-sensing enzymes.
- name: Succinate accumulation and pseudohypoxia
description: >-
Loss of SDH activity causes succinate accumulation. Succinate inhibits
alpha-ketoglutarate-dependent prolyl hydroxylases, stabilizing HIF signaling
under normoxic conditions and increasing angiogenic, glycolytic, and
proliferative transcriptional programs.
biological_processes:
- preferred_term: cellular response to hypoxia
modifier: INCREASED
term:
id: GO:0071456
label: cellular response to hypoxia
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:31773431
reference_title: "Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
SDH deficiency leads to accumulation of succinate, an oncometabolite that
promotes tumorigenesis.
explanation: >-
Management review directly links SDH deficiency to succinate accumulation
and tumorigenesis.
- reference: PMID:34012423
reference_title: "Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
This mechanism implies that due to SDH deficiency, succinate is
accumulated; this inhibits propyl hydroxylases (PHDs) resulting in
induction of the hypoxic response despite normoxic conditions
(pseudohypoxia)
explanation: >-
Review explains the succinate-to-pseudohypoxia mechanism underlying
SDH-deficient tumor biology.
downstream:
- target: Epigenetic dysregulation
description: >-
Succinate also inhibits dioxygenases involved in DNA and histone
demethylation.
- target: Multifocal SDH-deficient tumor development
description: >-
Pseudohypoxia supports growth and survival of GIST and paraganglioma
precursor cells.
- name: Epigenetic dysregulation
description: >-
Succinate accumulation inhibits alpha-ketoglutarate-dependent dioxygenases,
including JmjC-domain histone demethylases, producing hypermethylation and
altered differentiation programs in SDH-deficient tumors.
biological_processes:
- preferred_term: chromatin organization
modifier: DYSREGULATED
term:
id: GO:0006325
label: chromatin organization
evidence:
- reference: PMID:34012423
reference_title: "Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
this acts as an alpha-ketoglutarate competitor, inhibiting
a-KG-dependent dioxygenases, JIp1, which is involved in sulfur metabolism
and Jhd1 which belongs to the JmjC-domain-containing histone demethylase
(JHDM) enzymes.
explanation: >-
Review supports the dioxygenase-inhibition branch of SDH-deficient tumor
pathogenesis.
downstream:
- target: Multifocal SDH-deficient tumor development
description: >-
Pseudohypoxic and epigenetic programs converge on tumor predisposition.
- name: Multifocal SDH-deficient tumor development
description: >-
SDH-deficient tumor biology predisposes to multifocal gastric GIST and
multicentric paraganglioma or pheochromocytoma. GISTs are usually
KIT/PDGFRA-wildtype, often gastric, and show loss of SDHB protein by
immunohistochemistry.
cell_types:
- preferred_term: chromaffin cell
term:
id: CL:0000166
label: chromaffin cell
evidence:
- reference: PMID:31174229
reference_title: "Paragangliomas in Carney-Stratakis Syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The PGLs in CSS are multicentric and GISTs are multifocal in all the
patients, suggesting an inherited susceptibility and associating the two
manifestations.
explanation: >-
Review supports multicentric paraganglioma and multifocal GIST as core
Carney-Stratakis tumor behavior.
- reference: PMID:21997692
reference_title: "Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
SDH-deficient GISTs especially include pediatric GISTs and those
associated with Carney triad (CT) or Carney-Stratakis syndromes (CSSs);
the latter 2 also include paraganglioma as a component.
explanation: >-
Clinicopathologic series places Carney-Stratakis GISTs in the broader
SDH-deficient GIST class and notes paraganglioma as the associated tumor
component.
histopathology:
- name: SDHB-negative gastric epithelioid GIST
diagnostic: true
description: >-
Carney-Stratakis-associated GISTs are SDH-deficient gastric tumors with loss
of SDHB immunostaining, epithelioid morphology, and absence of KIT or PDGFRA
driver mutations.
evidence:
- reference: PMID:20890271
reference_title: "SDHB immunohistochemistry: a useful tool in the diagnosis of Carney-Stratakis and Carney triad gastrointestinal stromal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
All SDHB-negative GISTs were located in the stomach, had an epithelioid
morphology, and had no KIT or PDGFRA mutations.
explanation: >-
Pathology study supports gastric location, epithelioid morphology, and
KIT/PDGFRA-wildtype status as diagnostic features of SDHB-negative
Carney-Stratakis/Carney-triad-associated GIST.
- name: Microplexiform muscularis propria involvement
description: >-
SDH-deficient gastric GISTs often grow as multiple separate nodules in the
muscularis propria, producing a microplexiform or multinodular pattern.
evidence:
- reference: PMID:21997692
reference_title: "Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The tumors commonly involved muscularis propria as multiple apparently
separate nodules, creating a "microplexiform" pattern
explanation: >-
Clinicopathologic cohort directly describes the characteristic
microplexiform muscularis propria growth pattern.
- name: Epithelioid hypercellular morphology
description: >-
Epithelioid cytology and epithelioid hypercellular morphology are common
microscopic features of SDH-deficient GISTs.
evidence:
- reference: PMID:21997692
reference_title: "Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Epithelioid cytology dominated in 37 cases, 20 tumors had mixed
epithelioid and spindle cell, 7 spindle cell, and 1 had extensively
pleomorphic cytology.
explanation: >-
Cohort histology supports epithelioid cytology as the dominant morphology
among SDH-deficient GISTs.
- name: Lymphovascular invasion
description: >-
Lymphovascular invasion can be common in SDH-deficient gastric GIST, although
in the cited cohort it was not independently associated with adverse
outcome.
evidence:
- reference: PMID:21997692
reference_title: "Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Lymph node metastases were detected in 5 patients, but lymphovascular
invasion was present in >50% of cases studied; these 2 were not related to
adverse outcome.
explanation: >-
Cohort evidence supports lymphovascular invasion as a frequent
histopathologic feature in SDH-deficient GIST.
phenotypes:
- category: Neoplastic
name: Paraganglioma or pheochromocytoma
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Paraganglioma, and less often pheochromocytoma, is one of the two defining
tumor classes in the syndrome. Tumors may be multicentric and can occur in
head and neck, retroperitoneal, adrenal, pelvic, or other paraganglionic
sites.
phenotype_term:
preferred_term: Paraganglioma
term:
id: HP:0002668
label: Paraganglioma
evidence:
- reference: PMID:36387130
reference_title: "Bladder paraganglioma, gastrointestinal stromal tumor, and SDHB germline mutation in a patient with Carney-Stratakis syndrome: A case report and literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
BACKGROUND: Carney-Stratakis syndrome (CSS) is a rare dyad of
paraganglioma (PGL)/pheochromocytoma (PHEO) and gastrointestinal stromal
tumor (GIST).
explanation: >-
Case-report review identifies PGL/PHEO as a defining component of the
syndrome.
- reference: PMID:31174229
reference_title: "Paragangliomas in Carney-Stratakis Syndrome."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CSS has autosomal dominant inheritance, incomplete penetrance, and greater
relative frequency of PGL over GISTs.
explanation: >-
Review supports the high relative frequency of paraganglioma within
Carney-Stratakis syndrome.
- category: Neoplastic
name: Gastrointestinal Stromal Tumor
frequency: VERY_FREQUENT
diagnostic: true
description: >-
SDH-deficient GIST is the other defining tumor class. Tumors are generally
gastric, KIT/PDGFRA-wildtype, may be multifocal, and can recur or metastasize
after long intervals.
phenotype_term:
preferred_term: Gastrointestinal stromal tumor
term:
id: HP:0100723
label: Gastrointestinal stroma tumor
evidence:
- reference: PMID:17667967
reference_title: "Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In a subset of patients with GISTs, the lesions are associated with
paragangliomas; the condition is familial and transmitted as an
autosomal-dominant trait.
explanation: >-
Landmark series supports GIST plus paraganglioma as a familial tumor dyad.
- reference: PMID:21997692
reference_title: "Succinate dehydrogenase-deficient GISTs: a clinicopathologic, immunohistochemical, and molecular genetic study of 66 gastric GISTs with predilection to young age."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
SDH-deficient GISTs constitute a small subgroup of gastric GISTs; they
usually occur in children and young adults, often have a chronic course
similar to that of pediatric and CT GISTs, and have potential association
with paraganglioma, necessitating long-term follow-up.
explanation: >-
Clinicopathologic cohort supports gastric location, younger age tendency,
chronic course, and paraganglioma association of SDH-deficient GIST.
- category: Cardiovascular
name: Hypertension from catecholamine-secreting paraganglioma
frequency: OCCASIONAL
description: >-
Catecholamine-secreting paragangliomas or pheochromocytomas may cause
episodic or sustained hypertension, headache, palpitations, and sweating.
phenotype_term:
preferred_term: Hypertension
term:
id: HP:0000822
label: Hypertension
evidence:
- reference: PMID:34012423
reference_title: "Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
A patient with any type of PGL will present in any of the following
contexts: a) because of signs and/or symptoms of excess catecholamine
secretion (e.g. hypertension, headache, palpitations, hyperhidrosis,
tremor);
explanation: >-
Review supports hypertension as a catecholamine-related manifestation of
paraganglioma in the SDH-deficiency spectrum.
- category: Gastrointestinal
name: Abdominal pain or gastrointestinal bleeding
frequency: OCCASIONAL
description: >-
Gastric SDH-deficient GIST may present with abdominal pain, ulcer symptoms,
or gastrointestinal bleeding, but presentation can be nonspecific.
phenotype_term:
preferred_term: Abdominal pain
term:
id: HP:0002027
label: Abdominal pain
evidence:
- reference: PMID:31773431
reference_title: "Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Many patients with GIST are diagnosed after presenting with severe
epigastric pain or gastrointestinal bleeding due to ulceration
explanation: >-
Management review supports abdominal pain and bleeding as common
presentations for GIST.
diagnosis:
- name: SDHB immunohistochemistry
description: >-
Loss of granular SDHB staining in tumor cells, with retained internal
control staining, is a diagnostic hallmark of SDH-deficient GIST and should
prompt consideration of Carney-Stratakis syndrome or Carney triad.
evidence:
- reference: PMID:20890271
reference_title: "SDHB immunohistochemistry: a useful tool in the diagnosis of Carney-Stratakis and Carney triad gastrointestinal stromal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
We show that Carney-Stratakis syndrome- and Carney-triad-associated GISTs
are negative by immunohistochemistry for SDHB in contrast to KIT- or
PDGFRA-mutated GISTs and a majority of sporadic GISTs.
explanation: >-
Pathology study establishes SDHB immunohistochemistry as a practical
discriminator for Carney-Stratakis/Carney-triad-associated GIST.
- reference: PMID:20890271
reference_title: "SDHB immunohistochemistry: a useful tool in the diagnosis of Carney-Stratakis and Carney triad gastrointestinal stromal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
In case of negative SDHB staining in GISTs, Carney-Stratakis syndrome or
Carney triad should be considered and appropriate clinical surveillance
should be instituted.
explanation: >-
Same study provides the diagnostic follow-up implication of negative SDHB
staining.
- name: Germline SDHx testing
description: >-
Germline testing for SDHB, SDHC, and SDHD, with deletion/duplication testing
when sequencing is negative and clinical suspicion remains high, is used to
confirm the inherited syndrome and guide family surveillance.
evidence:
- reference: PMID:34012423
reference_title: "Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Genetic testing for SDHx mutations in any of the above patients,
particularly if there are other family members with any of those tumors
(do not only include first-degree relatives) should be performed.
explanation: >-
SDH-deficiency review recommends SDHx genetic testing in relevant tumor
contexts and family settings.
genetic:
- name: SDHB
association: Germline Loss-of-Function Variants
inheritance:
- name: Autosomal Dominant
notes: >-
SDHB pathogenic variants are an established cause of Carney-Stratakis
syndrome and are particularly important because SDHB-related paraganglioma
syndromes have higher metastatic risk in the broader SDHx literature.
evidence:
- reference: PMID:17667967
reference_title: "Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the GISTs were caused by germline mutations of the genes encoding subunits
B, C, or D (the SDHB, SDHC and SDHD genes, respectively).
explanation: >-
Landmark CSS series includes SDHB among causal germline genes.
- name: SDHC
association: Germline Loss-of-Function Variants
inheritance:
- name: Autosomal Dominant
notes: >-
SDHC pathogenic variants are an established cause of Carney-Stratakis
syndrome; this differs from Carney triad, where SDHC promoter methylation is
more typical.
evidence:
- reference: PMID:17667967
reference_title: "Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the GISTs were caused by germline mutations of the genes encoding subunits
B, C, or D (the SDHB, SDHC and SDHD genes, respectively).
explanation: >-
Landmark CSS series includes SDHC among causal germline genes.
- name: SDHD
association: Germline Loss-of-Function Variants
inheritance:
- name: Autosomal Dominant
notes: >-
SDHD pathogenic variants are an established cause of Carney-Stratakis
syndrome and should be evaluated as part of SDHx testing.
evidence:
- reference: PMID:17667967
reference_title: "Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
the GISTs were caused by germline mutations of the genes encoding subunits
B, C, or D (the SDHB, SDHC and SDHD genes, respectively).
explanation: >-
Landmark CSS series includes SDHD among causal germline genes.
treatments:
- name: Complete surgical resection
description: >-
Complete resection is the main treatment for localized SDH-deficient GIST or
paraganglioma when feasible, with attention to multifocal, nodal, and
recurrent disease.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:36387130
reference_title: "Bladder paraganglioma, gastrointestinal stromal tumor, and SDHB germline mutation in a patient with Carney-Stratakis syndrome: A case report and literature review."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The unique mechanism of tumorigenesis including hypoxia and
hypermethylation caused by SDH deficiency renders target therapy with
tyrosine kinase inhibitors ineffective, therefore complete surgical
resection is the optimal treatment in the absence of tumor metastases.
explanation: >-
Case-report review supports surgery as the preferred local treatment and
notes limited TKI effectiveness.
- reference: PMID:31773431
reference_title: "Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Thus, surgical resection is the mainstay of treatment for localized
disease, but recurrence is common.
explanation: >-
Management review supports surgical resection for localized SDH-deficient
GIST and cautions that recurrence remains common.
- name: KIT-directed tyrosine kinase inhibitors
description: >-
Standard KIT/PDGFRA-directed therapies such as imatinib are often ineffective
in SDH-deficient, KIT/PDGFRA-wildtype GIST. Anti-angiogenic TKIs may have
limited activity in selected advanced SDH-deficient GIST cases, but evidence
remains incomplete.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
evidence:
- reference: PMID:31773431
reference_title: "Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: >-
SDH-deficient GISTs are generally resistant to tyrosine-kinase inhibitors,
the standard treatment for advanced or metastatic GIST.
explanation: >-
Supports avoiding over-reliance on standard GIST TKIs in SDH-deficient
disease; marked as partial because some non-imatinib TKIs can have limited
activity in selected advanced cases.
- name: Genetic counseling and surveillance
description: >-
Genetic counseling, cascade testing, and long-term surveillance for
paraganglioma, pheochromocytoma, gastric GIST recurrence, and related
SDH-deficient tumors are central management components for affected
individuals and at-risk relatives.
treatment_term:
preferred_term: genetic counseling
term:
id: MAXO:0000079
label: genetic counseling
evidence:
- reference: PMID:34012423
reference_title: "Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
Patients and family members should be referred for genetic counseling.
explanation: >-
Review explicitly recommends genetic counseling for patients and family
members in SDH-deficient tumor predisposition contexts.
- reference: PMID:31773431
reference_title: "Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
For all GIST patients with completely resected disease, follow-up with
physical exams and cross sectional imaging (i.e., CT or MRI) of the
abdomen/pelvis is recommended every 3-6 months for the first 5 years and
then annually.
explanation: >-
Management review provides an imaging follow-up framework after resection
of GIST, relevant to SDH-deficient GIST surveillance.
differential_diagnoses:
- name: Carney triad
description: >-
Carney triad overlaps by including GIST and paraganglioma, but also includes
pulmonary chondroma, has a strong female predominance, and is usually linked
to SDHC promoter hypermethylation rather than inherited germline SDHB, SDHC,
or SDHD variants.
evidence:
- reference: PMID:34012423
reference_title: "Carney Triad, Carney-Stratakis Syndrome, 3PAS and Other Tumors Due to SDH Deficiency."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
CT is a very rare disease; PGL, GIST and pulmonary chondromas constitute
CT which shows female predilection and may be a mosaic disorder.
explanation: >-
Review defines the triad and differentiates it from the inherited dyad.
- name: Sporadic KIT/PDGFRA-mutant gastrointestinal stromal tumor
description: >-
Sporadic KIT/PDGFRA-mutant GIST is usually SDHB-positive by
immunohistochemistry and lacks the inherited PGL/GIST dyad.
evidence:
- reference: PMID:20890271
reference_title: "SDHB immunohistochemistry: a useful tool in the diagnosis of Carney-Stratakis and Carney triad gastrointestinal stromal tumors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
The five GISTs with a KIT or PDGFRA gene mutation were all
immunohistochemically positive for SDHB.
explanation: >-
Pathology study supports SDHB staining as a distinction between
KIT/PDGFRA-mutant sporadic GIST and SDH-deficient syndromic GIST.
Carney–Stratakis syndrome (CSS) is a rare hereditary tumor-predisposition syndrome defined by the dyad of paraganglioma (PGL) and/or pheochromocytoma (PCC) together with gastrointestinal stromal tumor (GIST), typically a KIT/PDGFRA-wildtype, succinate dehydrogenase (SDH)-deficient GIST. (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2)
Synonyms / alternative names include “Carney–Stratakis dyad,” “dyad of paraganglioma and GIST,” and “hereditary GIST–paraganglioma syndrome.” (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 1-2)
Evidence type: The syndrome definition and genotype–phenotype associations are derived from aggregated disease-level resources (reviews, guidelines) and from small family series/case reports due to rarity. (pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2)
Using the available tools in this run, I was not able to directly retrieve authoritative database identifiers (OMIM, Orphanet, MeSH, ICD-10/11, MONDO) for CSS; therefore these identifiers are not reported here to avoid uncited or incorrect mapping.
Genetic (germline) SDH complex loss-of-function is the established cause of classic CSS. Multiple sources describe CSS as autosomal dominant with incomplete penetrance and as being caused by germline heterozygous loss-of-function pathogenic variants in SDH subunit genes, especially SDHB, SDHC, SDHD. (pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2, pasini2008clinicalandmolecular pages 4-6)
Abstract-supported definition (example quote): Lobato et al. state, “Carney-Stratakis syndrome (CSS) is an autosomal dominant rare syndrome, with incomplete penetrance, characterized by the association of paragangliomas and/or pheochromocytomas and gastrointestinal stromal tumors (GISTs).” (lobato2023threecasesof pages 1-2)
No protective factors or gene–environment interactions specific to CSS were identified in the retrieved sources.
CSS manifests as combinations of: 1) Paragangliomas (PGLs) and/or pheochromocytomas (PCCs), often multicentric/multifocal. (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 1-2) 2) Gastrointestinal stromal tumors (GISTs) that are SDH-deficient and usually KIT/PDGFRA-wildtype; in CSS, GISTs are frequently multifocal and preferentially gastric. (khurana2019paragangliomasincarney–stratakis pages 3-4, pasini2008clinicalandmolecular pages 1-2, khurana2019paragangliomasincarney–stratakis pages 2-3)
Khurana et al. emphasize that CSS has “greater relative frequency of PGL over GISTs,” and that “PGLs in CSS are multicentric and GISTs are multifocal.” (khurana2019paragangliomasincarney–stratakis pages 1-2)
Note: Exact HPO IDs for “GIST” should be verified against the current HPO release when implementing.
Classic CSS is most consistently linked to germline loss-of-function variants in: - SDHB (HGNC:10681) - SDHC (HGNC:10682) - SDHD (HGNC:10683)
These genes encode subunits of mitochondrial complex II (SDH), and germline disruption predisposes to the CSS dyad. (pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2, pasini2008clinicalandmolecular pages 4-6)
SDHA is frequently mutated in SDH-deficient GIST overall, but recent review synthesis indicates SDHA germline cases more often present as isolated SDH-deficient GIST rather than classic CSS; co-occurrence with PGL is described as rare. (schipani2023sdhagermlinemutations pages 8-9)
In the landmark CSS series, Pasini et al. studied 11 patients and reported that in eight (from seven unrelated families) GISTs were caused by germline mutations in SDHB, SDHC, or SDHD, with autosomal-dominant inheritance and incomplete penetrance. (pasini2008clinicalandmolecular pages 1-2)
Reported variants from the Pasini cohort include (examples; not exhaustive): - SDHB: c.72+1G>T, c.423+1G>C, c.45_46insCC, large deletions. (pasini2008clinicalandmolecular pages 4-6, pasini2008clinicalandmolecular pages 1-2) - SDHC: c.43C>T (p.Arg15X), c.405+1G>A (splice), and later a germline SDHC exon 3 deletion reported in a 2023 case series. (pasini2008clinicalandmolecular pages 4-6, lobato2023threecasesof pages 1-2) - SDHD: c.57delG. (pasini2008clinicalandmolecular pages 1-2)
CSS is described as autosomal dominant with incomplete penetrance, supported by unaffected mutation carriers in pedigrees (e.g., SDHB/SDHC splice variants inherited from clinically unaffected mothers). (pasini2008clinicalandmolecular pages 4-6, pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2)
Quantitative penetrance estimates are more available for SDHx carrier cohorts broadly (PPGL predisposition) than for CSS specifically. For example, SDH-related syndromes have subunit-specific penetrance features; one synthesis notes SDHB has lower penetrance but higher metastatic risk, while SDHD often has higher penetrance and head/neck predominance. (pitsava2021carneytriadcarneystratakis pages 3-4)
Most CSS variants are consistent with loss of function (splice-site, nonsense, frameshift, or large deletion), consistent with tumor-suppressor biology and frequent “second-hit” loss of the wild-type allele (LOH) in tumors. (pasini2008clinicalandmolecular pages 4-6)
No consistent non-genetic environmental triggers, lifestyle determinants, or infectious agents specific to CSS were identified in the retrieved literature. CSS is primarily genetic. (pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2)
1) Germline SDHx loss-of-function → reduced SDH (mitochondrial complex II) activity in susceptible tissues. (pasini2008clinicalandmolecular pages 1-2, khurana2019paragangliomasincarney–stratakis pages 2-3) 2) Succinate accumulation (oncometabolite) due to impaired conversion of succinate to fumarate. (pitsava2021carneytriadcarneystratakis pages 3-4, khurana2019paragangliomasincarney–stratakis pages 2-3) 3) Pseudohypoxia: succinate inhibits prolyl hydroxylases, stabilizing HIF-1α, driving hypoxia-like transcriptional programs. (khurana2019paragangliomasincarney–stratakis pages 2-3) 4) Epigenetic reprogramming: succinate inhibits TET/JmjC demethylases, promoting DNA/histone hypermethylation and altered differentiation programs. (pitsava2021carneytriadcarneystratakis pages 3-4, khurana2019paragangliomasincarney–stratakis pages 2-3) 5) Downstream signaling changes in SDH-deficient GIST can include VEGF/IGF2 upregulation and activation of PI3K/AKT and MAPK signaling as summarized in a 2024 mini-review. (kim2024pathologicdiagnosisand pages 3-4)
SDH is localized to the mitochondrial inner membrane (complex II); dysfunction is therefore a mitochondrial metabolic defect. (khurana2019paragangliomasincarney–stratakis pages 2-3)
CSS often presents in childhood/adolescence/young adulthood, particularly for SDH-deficient GIST, and can show multifocal tumors and metastatic potential but with variable/indolent clinical courses in some cases. (khurana2019paragangliomasincarney–stratakis pages 3-4, pasini2008clinicalandmolecular pages 1-2)
CSS is rare; no robust prevalence/incidence estimates were retrieved in the available texts for this run.
Reviews describe CSS as affecting both genders (in contrast to Carney triad, which has female predilection). (pitsava2021carneytriadcarneystratakis pages 3-4)
A surveillance series summarized in a 2019 SDH-deficient GIST management review reported that among 65 asymptomatic SDHB mutation carriers undergoing annual abdominal MRI-based surveillance, 25% developed SDHB-related cancers within 6 years, and 16.6% had an asymptomatic tumor detected on the first surveillance scan. (neppala2019currentmanagementof pages 6-7)
Loss of SDHB immunohistochemical staining is a validated surrogate marker of SDH deficiency and helps distinguish SDH-deficient GIST (including CSS-associated tumors) from KIT/PDGFRA-mutant GIST. (gaal2011sdhbimmunohistochemistrya pages 6-8)
A representative example of this real-world diagnostic pattern is shown in Gaal et al. Figure 1 panel (a): a CSS-associated GIST demonstrates negative SDHB staining in tumor cells, with endothelial cells serving as internal positive control. (gaal2011sdhbimmunohistochemistrya media 9958076a)
Biochemical evaluation for catecholamine excess (e.g., plasma metanephrines/normetanephrines) is used in real-world CSS/PCC evaluation and perioperative planning (α-blockade). (lobato2023threecasesof pages 1-2)
Cross-sectional imaging (CT/MRI) and functional imaging (e.g., PET/CT) are used for tumor localization and staging in CSS cases and broader SDHx syndromes. (lobato2023threecasesof pages 1-2, khurana2019paragangliomasincarney–stratakis pages 2-3)
Key distinctions include: - Carney triad (PGL + GIST + pulmonary chondroma), often associated with SDHC promoter hypermethylation and female predominance, and frequently non-hereditary/mosaic rather than classic autosomal dominant inheritance. (pitsava2021carneytriadcarneystratakis pages 3-4) - Sporadic KIT/PDGFRA-mutant GIST (typically SDHB-positive by IHC). (gaal2011sdhbimmunohistochemistrya pages 6-8)
No CSS-specific survival rates were identified in retrieved sources. SDH-deficient GIST can metastasize (including nodal metastasis) yet may have relatively indolent behavior compared with other GIST subsets, with clinical course varying substantially. (khurana2019paragangliomasincarney–stratakis pages 3-4, kim2024pathologicdiagnosisand pages 3-4)
For localized CSS-associated tumors, complete surgical resection is a primary approach, particularly because SDH-deficient GIST is often not responsive to standard KIT-directed tyrosine kinase inhibitors. (shi2022bladderparagangliomagastrointestinal pages 1-2, neppala2019currentmanagementof pages 1-2)
For completely resected SDH-deficient GIST, a commonly cited follow-up framework includes physical exams and cross-sectional abdominal/pelvic imaging every 3–6 months for 5 years, then annually, as summarized in a management review discussing guideline-consistent practices. (neppala2019currentmanagementof pages 6-7)
Primary prevention is not established for CSS because it is an inherited tumor predisposition syndrome. Secondary/tertiary prevention relies on genetic counseling, cascade testing, and surveillance imaging/biochemical monitoring for early tumor detection and management in SDHx variant carriers. (neppala2019currentmanagementof pages 6-7, lobato2023threecasesof pages 1-2)
No naturally occurring CSS analog in non-human species was identified in retrieved sources.
The retrieved sources for this run did not provide explicit descriptions of CSS-specific model organisms (e.g., SDHx mouse models reproducing the dyad phenotype). Mechanistic descriptions strongly implicate mitochondrial metabolism and epigenetic dysregulation in SDH-deficient tumors, but dedicated model-system evidence should be curated from additional experimental literature beyond the documents retrieved here. (pitsava2021carneytriadcarneystratakis pages 3-4, khurana2019paragangliomasincarney–stratakis pages 2-3)
Recent case-based and pathology-focused literature reinforces that CSS should be considered when encountering SDH-deficient, KIT/PDGFRA-wildtype gastric GIST and/or PGL/PCC, and that SDHx testing should include deletion/duplication analysis when sequencing is negative. (lobato2023threecasesof pages 1-2, kim2024pathologicdiagnosisand pages 3-4)
A 2024 mini-review summarizes modern diagnostic practice for molecularly diverse GIST, emphasizing that ancillary testing (IHC, NGS) is essential because some epithelioid/mixed tumors may lose canonical KIT/DOG1 signals, and that SDH-deficient GIST (including CSS-associated) behaves as a distinct subgroup with TKI resistance. (kim2024pathologicdiagnosisand pages 3-4)
| Domain | Core fact | Recent source(s) with DOI/URL and publication date | Key evidence source (author-year) |
|---|---|---|---|
| Definition / synonyms | Carney–Stratakis syndrome (CSS) is a rare hereditary tumor-predisposition syndrome defined by the dyad of paraganglioma/pheochromocytoma and gastrointestinal stromal tumor (GIST); synonyms include Carney–Stratakis dyad, dyad of paraganglioma and GIST, and hereditary GIST-paraganglioma syndrome. It is distinct from Carney triad. (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2) | Lobato et al., JCEM Case Reports (Nov 2023), DOI: 10.1210/jcemcr/luad139, https://doi.org/10.1210/jcemcr/luad139; Kim & Lee, Front Oncol (Nov 2024), DOI: 10.3389/fonc.2024.1487467, https://doi.org/10.3389/fonc.2024.1487467 | Pasini-2008; Lobato-2023 |
| Causal genes | Canonical causal genes are germline loss-of-function variants in SDHB, SDHC, and SDHD; these explain most molecularly confirmed CSS families. SDHA is part of the SDH-deficient GIST spectrum, but recent reviews emphasize SDHA more often causes isolated SDH-deficient GIST rather than classic CSS. (pasini2008clinicalandmolecular pages 1-2, schipani2023sdhagermlinemutations pages 8-9, lobato2023threecasesof pages 1-2, pasini2008clinicalandmolecular pages 4-6) | Schipani et al., Genes (Mar 2023), DOI: 10.3390/genes14030646, https://doi.org/10.3390/genes14030646; Lobato et al., JCEM Case Reports (Nov 2023), DOI: 10.1210/jcemcr/luad139, https://doi.org/10.1210/jcemcr/luad139 | Pasini-2008; Schipani-2023 |
| Representative reported variants | Reported CSS-associated variants include SDHB c.72+1G>T, c.423+1G>C, c.45_46insCC, large deletions; SDHC c.43C>T, c.405+1G>A, exon 3 deletion; SDHD c.57delG. Variable family expression and unaffected carriers have been documented. (pasini2008clinicalandmolecular pages 4-6, pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2) | Lobato et al., JCEM Case Reports (Nov 2023), DOI: 10.1210/jcemcr/luad139, https://doi.org/10.1210/jcemcr/luad139 | Pasini-2008; Lobato-2023 |
| Inheritance / penetrance | CSS is generally described as autosomal dominant with incomplete penetrance and variable expressivity. Family studies show mutation-positive but clinically unaffected relatives, supporting reduced penetrance. (khurana2019paragangliomasincarney–stratakis pages 1-2, pasini2008clinicalandmolecular pages 1-2, lobato2023threecasesof pages 1-2) | Lobato et al., JCEM Case Reports (Nov 2023), DOI: 10.1210/jcemcr/luad139, https://doi.org/10.1210/jcemcr/luad139 | Pasini-2008; Khurana-2019; Lobato-2023 |
| Key tumor types | Hallmark tumors are paragangliomas/pheochromocytomas (often multicentric/multifocal) and SDH-deficient wild-type GISTs (often multifocal, usually gastric). PGL may be more frequent than GIST in CSS cohorts/reviews. (shi2022bladderparagangliomagastrointestinal pages 1-2, khurana2019paragangliomasincarney–stratakis pages 1-2, khurana2019paragangliomasincarney–stratakis pages 3-4, lobato2023threecasesof pages 1-2, schipani2023sdhagermlinemutations pages 1-2) | Kim & Lee, Front Oncol (Nov 2024), DOI: 10.3389/fonc.2024.1487467, https://doi.org/10.3389/fonc.2024.1487467; Lobato et al., JCEM Case Reports (Nov 2023), DOI: 10.1210/jcemcr/luad139, https://doi.org/10.1210/jcemcr/luad139 | Khurana-2019; Shi-2022; Kim-2024 |
| Typical clinicopathologic pattern | CSS-associated GISTs are usually KIT/PDGFRA-wildtype, gastric, often epithelioid or mixed, multinodular/plexiform, with lymphovascular invasion and occasional nodal/liver metastases; despite metastatic potential, some cases behave relatively indolently. (khurana2019paragangliomasincarney–stratakis pages 4-4, khurana2019paragangliomasincarney–stratakis pages 3-4, kim2024pathologicdiagnosisand pages 3-4, schipani2023sdhagermlinemutations pages 1-2, kim2024pathologicdiagnosisand pages 1-3) | Kim & Lee, Front Oncol (Nov 2024), DOI: 10.3389/fonc.2024.1487467, https://doi.org/10.3389/fonc.2024.1487467; Schipani et al., Genes (Mar 2023), DOI: 10.3390/genes14030646, https://doi.org/10.3390/genes14030646 | Khurana-2019; Kim-2024; Schipani-2023 |
| Diagnostic hallmarks | Key hallmarks are loss of SDHB expression by immunohistochemistry (marker of SDH deficiency) and absence of KIT/PDGFRA driver mutations. SDHA IHC loss can point to SDHA-mutant GIST, while retained SDHB is typical of KIT/PDGFRA-mutant GIST. (khurana2019paragangliomasincarney–stratakis pages 2-3, gaal2011sdhbimmunohistochemistrya pages 6-8, kim2024pathologicdiagnosisand pages 3-4, schipani2023sdhagermlinemutations pages 1-2, gaal2011sdhbimmunohistochemistrya media 9958076a) | Kim & Lee, Front Oncol (Nov 2024), DOI: 10.3389/fonc.2024.1487467, https://doi.org/10.3389/fonc.2024.1487467; Schipani et al., Genes (Mar 2023), DOI: 10.3390/genes14030646, https://doi.org/10.3390/genes14030646 | Gaal-2011; Kim-2024; Schipani-2023 |
| Mechanistic concepts | SDH loss causes succinate accumulation, which inhibits prolyl hydroxylases and stabilizes HIF-1α (pseudohypoxia), and inhibits TET/JmjC demethylases, promoting global DNA/histone hypermethylation. These mechanisms help explain CSS tumorigenesis and reduced sensitivity of SDH-deficient GIST to standard KIT-directed therapy. (shi2022bladderparagangliomagastrointestinal pages 1-2, pitsava2021carneytriadcarneystratakis pages 3-4, khurana2019paragangliomasincarney–stratakis pages 2-3, kim2024pathologicdiagnosisand pages 3-4) | Schipani et al., Genes (Mar 2023), DOI: 10.3390/genes14030646, https://doi.org/10.3390/genes14030646; Kim & Lee, Front Oncol (Nov 2024), DOI: 10.3389/fonc.2024.1487467, https://doi.org/10.3389/fonc.2024.1487467 | Pitsava-2021; Khurana-2019; Kim-2024 |
| Molecular testing / workup | Current practice-oriented reviews and guidelines support SDHB IHC in wild-type GIST, followed by germline SDHx testing and consideration of copy-number analysis (e.g., MLPA) when NGS is negative but clinical suspicion remains high. Ancillary tests may include CT/MRI, PET/CT, catecholamine/metanephrine testing, and pathology review. (neppala2019currentmanagementof pages 6-7, florou2025areviewof pages 4-4, lobato2023threecasesof pages 1-2) | Lobato et al., JCEM Case Reports (Nov 2023), DOI: 10.1210/jcemcr/luad139, https://doi.org/10.1210/jcemcr/luad139; Kim & Lee, Front Oncol (Nov 2024), DOI: 10.3389/fonc.2024.1487467, https://doi.org/10.3389/fonc.2024.1487467 | Lobato-2023; Kim-2024 |
| Recent clinical relevance (2023–2024) | 2023–2024 literature reinforces that CSS belongs within the SDH-deficient GIST / PPGL spectrum, that imatinib is generally ineffective in SDH-deficient GIST, and that genetic counseling/surveillance are important because syndromic disease may be missed if only tumor sequencing is performed. (schipani2023sdhagermlinemutations pages 8-9, kim2024pathologicdiagnosisand pages 3-4, neppala2019currentmanagementof pages 6-7, lobato2023threecasesof pages 1-2) | Schipani et al., Genes (Mar 2023), DOI: 10.3390/genes14030646, https://doi.org/10.3390/genes14030646; Lobato et al., JCEM Case Reports (Nov 2023), DOI: 10.1210/jcemcr/luad139, https://doi.org/10.1210/jcemcr/luad139; Kim & Lee, Front Oncol (Nov 2024), DOI: 10.3389/fonc.2024.1487467, https://doi.org/10.3389/fonc.2024.1487467 | Schipani-2023; Lobato-2023; Kim-2024 |
Table: This table condenses the key definitional, genetic, mechanistic, and diagnostic facts about Carney–Stratakis syndrome for rapid knowledge-base entry. It highlights the SDHx basis of the syndrome, classic tumor dyad, hallmark pathology, and the most relevant 2023–2024 sources.
References
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(shi2022bladderparagangliomagastrointestinal pages 1-2): Yihang Shi, Li Ding, Chengqiang Mo, Yanji Luo, Shaoqing Huang, Shirong Cai, Yanzhe Xia, and Xinhua Zhang. Bladder paraganglioma, gastrointestinal stromal tumor, and sdhb germline mutation in a patient with carney-stratakis syndrome: a case report and literature review. Frontiers in Oncology, Oct 2022. URL: https://doi.org/10.3389/fonc.2022.1030092, doi:10.3389/fonc.2022.1030092. This article has 6 citations.
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(neppala2019currentmanagementof pages 1-2): Pushpa Neppala, Sudeep Banerjee, Paul T. Fanta, Mayra Yerba, Kevin A. Porras, Adam M. Burgoyne, and Jason K. Sicklick. Current management of succinate dehydrogenase–deficient gastrointestinal stromal tumors. Cancer and Metastasis Reviews, 38:525-535, Sep 2019. URL: https://doi.org/10.1007/s10555-019-09818-0, doi:10.1007/s10555-019-09818-0. This article has 62 citations and is from a peer-reviewed journal.
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