Paraganglioma and gastric stromal sarcoma

Other Names: Carney-Stratakis syndrome; Paraganglioma and gastrointestinal stromal tumor; Paraganglioma and GIST; Carney-Stratakis dyad of paraganglioma and gastric stromal sarcoma; Carney dyad

Carney-Stratakis syndrome is a recently described familial syndrome characterized by gastrointestinal stromal tumors (GIST) and paragangliomas, often at multiple sites.

Patients with Carney-Stratakis syndrome have both GIST and paraganglioma. The gastric stromal sarcomas are multifocal and the paragangliomas are multicentric. The clinical spectrum of Carney-Stratakis syndrome varies widely, depending on the localization and the size of the tumors, and may include a palpable mass, dysphagia, abdominal pain, weight loss, hematemesis, melena, obstruction, perforation, cranial nerve palsies, tinnitus and hearing loss. GIST are intramural mesenchymal tumors of the gastrointestinal tract that originate from stem cells with characteristics of the interstitial cells of Cajal (the pacemaker cells which regulate peristalsis in the digestive tract). Paragangliomas are usually benign tumors that occur without clinical evidence of oversecretion and that arise within the sympathetic nervous system from cells of the paraganglia.

Cause

The vast majority of Carney-Stratakis syndrome cases are due to germline mutations of the mitochondrial tumor suppressor gene pathway succinate dehydrogenase (SDH) subunit genes SDHB, SDHC and SDHD.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

Predisposition to developing these tumors is inherited in an autosomal dominant manner with incomplete penetrance.

Symptoms

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Gastrointestinal stroma tumor
• Paraganglioma

30%-79% of people have these symptoms

• Abdominal pain(Pain in stomach)
• Cranial nerve paralysis
• Dysphagia(Poor swallowing)
• Gastrointestinal hemorrhage(Gastrointestinal bleeding)
• Hearing impairment(Deafness)
• Intestinal obstruction(Bowel obstruction)
• Tinnitus(Ringing in ears)
• Weight loss

Diagnosis

Diagnosis is made by clinical and radiologic examination, and confirmed immunohistochemically. Genetic testing to determine if SDH defects may be contributing to tumor growth or recurrence should be offered to pediatric GIST patients.

Differential diagnosis

The main differential diagnosis includes Carney triad.

Treatment

Treatment modalities are surgery, embolization and radiotherapy. Chemotherapy with imatinib mesylate may be helpful for some patients with advanced-stage GIST. Targeting SDH function may potentially be useful in treating Carney-Stratakis syndrome patients but, at present, there are no drugs that restore SDH function. Life-long follow-up should be offered to patients with Carney-Stratakis syndrome. The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Iobenguane I 131 (Brand name: Azedra)iobenguane I 131 (Azedra) was approved for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.

Epidemiology

It is a very rare syndrome reported in less than 20 unrelated families to date. It presents at a young age (median age: 19 years) with an apparently equal ratio of male and female patients.

NIH genetic and rare disease info

• NIH info on Paraganglioma and gastric stromal sarcoma

Paraganglioma and gastric stromal sarcoma is a rare disease.