Superior mesenteric arteriovenous fistula as a rare manifestation of Cowden syndrome: A case report and review of literature

Table 1 Summary of clinical characteristics of patients with Cowden syndrome associated with gastrointestinal and hepatic vascular malformations, mean ± SD

Variable category	Specific item	By patients, n = 14	By lesion, n = 23	Percentage
Demographics	Sex-male	7	NA	50.0
	Sex-female	7	NA	50.0
	Age at diagnosis in years	48.1 ± 18.0	NA	NA
	Age at diagnosis in years, median	Stillbirth-65	NA	NA
Genetics	PTEN mutation-positive	11	NA	78.6
	PTEN mutation-negative/not tested	3	NA	21.4
Lesion type	Hemangioma	NA	3	13.0
	AVM	NA	8	34.8
	VM	NA	5	21.7
	Varices	NA	1	4.3
	Vein dilatation	NA	1	4.3
	Others	NA	2	8.7
Lesion location	Esophagus	NA	2	8.7
	Jejunum/ileum (small intestine)	NA	10	43.5
	Colorectum	NA	1	4.3
	Liver	NA	6	26.1
	Others	NA	2	8.7
Extent of involvement	Single lesion	NA	7	30.4
	Multiple lesions: ≥ 2 sites	NA	13	56.5
Clinical presentation	Asymptomatic	1	NA	7.1
	Chronic hemorrhage	5	NA	35.7
	Acute hemorrhage	2	NA	14.3
	Abdominal pain/obstruction	2	NA	14.3
	Others	5	NA	35.7
Treatment	Conservative management	2	NA	14.3
	Endoscopic therapy	1	NA	7.1
	Interventional radiology (embolization)	3	NA	21.4
	Surgery	3	NA	21.4
Follow-up and outcome	Improved/stable	6	NA	42.9
	Death	2	NA	14.3

AVM: Arteriovenous malformation; NA: Not applicable; VM: Venous malformation.

Table 2 Clinical data of patients with Cowden syndrome associated with gastrointestinal and hepatic vascular malformations

Ref.	Sex	Age	PTEN mutation status	Lesion site 1	Lesion type 1	Lesion site 2	Lesion type 2	Multifocal	Extraintestinal vascular lesions	Main symptom	Treatment	Follow-up (months) and outcome	Notes
Takaya et al[18], 1999	Male	22	PTEN 10q22–23	Liver	AVMs	Liver	Hemangiomas	Yes	Pelvis AVMs, the fifth cervical vertebra AVMs, right supraclavicular area AVMs, right hip and leg hemangiomas, right chest subcutaneous hemangiomas	High output heart failure; pain and weakness in the right upper extremity	Not mentioned	Death	NA
Suphapeetiporn et al[19], 2006	Male	48	PTEN c.511C>T/p.Gln171Ter	Liver	Large AVM	Esophagus	Varices	Yes	Centrifugal superficial vein dilatation	Chronic blood loss, Acute painless hematochezia	Performed embolization three times	Improved	NA
Pan et al[20], 2011	Female	45	PTEN exon 8 c.1003C>T/p.Arg335Ter	Liver	Hemangioma	NA	NA	No	Not mentioned	Epigastric distension and pain	Not mentioned	Not mentioned	NA
Nakayama et al[21], 2013	Male	54	Not mentioned	Jejunum	AVMs	Ileum	AVMs	Yes	Not mentioned	Chronic blood loss	Partial resection of the small intestine	Improved	NA
Toya et al[22], 2016	Female	65	Not mentioned	Jejunum	VMs	Ileum	VMs	Yes	Not mentioned	Chronic blood loss	Conservative	Improved	NA
Harada et al[23], 2018	Female	65	PTEN c.1003C>T/p.Arg335Ter	Jejunum	VMs	Ileum	VMs	Yes	Skin of the trunk and the limbs; several small hemangiomas	Not mentioned	Not mentioned	Not mentioned	Small varices-like lesions in the esophagus
Inukai et al[24], 2018	Male	48	Not mentioned	Sigmoid colon	AVM	NA	NA	No	Not mentioned	Chronic blood loss, shortness of breath	Sigmoidectomy	Improved, no recurrence was observed 1 year post-surgery	NA
Duhaut et al[25], 2021	Female	56	PTEN c.71A>G/p.Asp24Gly	Liver	AVM	NA	NA	No	Not mentioned	Refractory ascites, Portal hypertension, Esophageal varices	TIPS, LT	Not mentioned	NA
Zhang et al[26], 2022	Male	44	PTEN	Small intestine	Possible vascular malformation	NA	NA	No	Intermuscular space of the left chest wall; vascular malformation; A1 segment of the right anterior cerebral artery; aneurysm	Increased frequency of defecation, unformed stool, occasional fresh blood in stool	Not mentioned	Not mentioned	NA
Piazzolla et al[27], 2022	Female	62	PTEN c.1003C>T/p.Arg335Ter	Jejunum	VMs	NA	NA	No	Shoulder-upper arm region AVM	Chronic blood loss	Conservative	Improved	NA
Saiki et al[28], 2024	Male	66	PTEN c.1003C>T/p.Arg335Ter	Small intestine	VMs	NA	NA	No	Trunk (ventral and dorsal); multiple hemangiomas	Asymptomatic (only positive fecal occult blood test, no subjective symptoms)	Not mentioned	Not mentioned	NA
Zhu et al[29], 2024	Male	Stillbirth	PTEN c.193T>G/p.Tyr65Asp	Subcapsular of the liver	Hemangioma (giant, 96 mm × 64 mm)	Intra-abdominal umbilical vein	vein dilatation	Yes	Striped blood flow signals were seen in the mass below the liver	Congestive cardiac insufficiency	Not mentioned	Termination of pregnancy by induced labor	NA
Woller et al[30], 2025	Female	48	PTEN	Jejunum	AVM	NA	NA	No	Not mentioned	Acute bleeding	Conservative + endoscopic therapy + embolization + surgery	Improved,	NA
Present study	Female	50	PTEN c.80A>G/p.Tyr27Cys	Superior mesenteric artery	AVM	Liver	Hemangiomas	Yes	Not mentioned	Progressive abdominal distension	TIPS (lesion 1)	Death	Esophageal and gastric varices

AVM: Arteriovenous malformation; LT: Liver transplantation; NA: Not applicable; PTEN: Phosphatase and tensin homolog; TIPS: Transjugular intrahepatic portosystemic shunt; VM: Venous malformation.

Table 3 Timeline of clinical presentation, diagnosis, and management

Time point	Clinical presentation and diagnostic/therapeutic interventions	Key findings and clinical decisions
Day 0	A 50-year-old woman presented with progressive abdominal distension for more than 6 months	Physical examination revealed a markedly protuberant abdomen, with positive shifting dullness, consistent with massive ascites
Day 1	Laboratory testing for liver function, hepatotropic viruses, autoantibodies, and ascitic fluid analysis	All markers (viral, autoimmune, and biochemical) were within normal limits. Ascites was confirmed as transudate; alcoholic and viral hepatitis were excluded
Day 2	Initial physical examination and contrast-enhanced abdominal MRI	Findings suggested possible early-stage liver cirrhosis, splenomegaly, ascites, and portal vein dilatation (18 mm)
Day 4	DSA with superior mesenteric artery angiography combined with indirect portography	Thickened and tortuous superior mesenteric artery with a distinct arteriovenous malformation; rapid flow with early visualization of mesenteric and portal veins
Day 10	TIPS and transjugular liver biopsy	Liver biopsy showed fibrous hyperplasia but no definitive evidence of cirrhosis
Day 21	Acute hematemesis followed by emergency gastroscopy	Esophagogastric varices and multiple gastric polyps identified; biopsy confirmed fundic gland polyps
Day 22	WES	PTEN mutation identified (c.80A>G/p.Tyr27Cys)
Retrospective review	Detailed retrospective analysis of past medical history	History of multiple neoplasms (endometroid adenocarcinoma, thyroid cancer, uterine leiomyoma, bilateral breast tumors) and vascular malformations (lower-extremity hemangiomas)
Final diagnosis	Integration of clinical, imaging, pathological, and genetic data	Diagnosis of CS established

DSA: Digital subtraction angiography; MRI: Magnetic resonance imaging; TIPS: Transjugular intrahepatic portosystemic shunt; WES: Whole-exome sequencing.