Paraganglioma of the Vagina Associated With Germline SDHB Mutation: Report of a Case With Review of the Literature

Abstract

Paragangliomas are rare neuroendocrine neoplasms in the vagina, and their molecular pathogenesis has not been documented. We report a case of vaginal paraganglioma in a 15-yr-old adolescent girl who presented with irregular heavy menses and anemic symptoms. Examination under anesthesia revealed a polypoid mass of 3 cm size in the left anterior vaginal wall, which was resected piecemeal. Histology showed a circumscribed nodular tumor with typical nested morphology of paraganglioma and no significant nuclear atypia. Immunohistochemically the tumor cells were diffusely positive for synaptophysin and chromogranin while being negative for cytokeratin, accompanied by S100-positive sustentacular cells. SDHB immunohistochemistry demonstrated the absence of cytoplasmic staining in the tumor cells with preserved staining in sustentacular cells, raising the possibility of a germline mutation in the genes encoding subunits of succinate dehydrogenase. Sanger sequencing for all the exons and exon-flanking intronic regions of the SDHB gene revealed no mutation, but further investigation with multiplex ligation-dependent probe amplification identified a heterozygous deletion of exon 1 of the SDHB gene in the patient and her mother, confirming the diagnosis of SDHB-related hereditary paraganglioma-pheochromocytoma syndrome. The patient had no evidence of disease upon imaging surveillance and follow-up for 56 mo. A review of the published cases of vaginal paraganglioma seems to suggest a relatively young age of presentation, commonly encountered as incidental findings in asymptomatic patients or presenting with abnormal vaginal bleeding. The association between vaginal paraganglioma and germline SDHB mutation has not been reported. We believe this case illustrates the clinical significance of SDHB immunohistochemistry and genetic testing for this rare vaginal neoplasm.

Recurrent paraganglioma of the vulva: A rare case report and review of the literature

“…PPGLs are rarely reported along the genital tract and are even rarer in juveniles. Only three cases of juvenile vaginal PGLs have been reported, with the patients' aged 11, 17 and 15 years (8,13,15). The latter involved functional tumours (13).…”

“…The largest diameter of any previously reported PGL of the vagina or vulva was 5 cm, making the current case the largest functional PGL of the vulva ever reported by diameter (8). Only 2 genetic investigations were documented in the reported cases (15,16).…”

Solitary vaginal paraganglioma with mature sacrococcygeal teratoma: a rare case report

“…Primary vaginal paraganglioma are extremely rare with only 10 previous cases reported [ 1 , 5 – 13 ]. We have provided details extracted from the previous reports.…”

“…Vaginal paraganglioma appear to have quite favorable prognosis, and there is no report of tumor recurrence. However, we must note that this finding may be due to the limited cases and short follow-up periods, with the longest being 56 months [ 5 ]. In our case, the tumor volume was relatively large, which compressed the bladder vertically.…”

“…The mechanisms of tumorigenesis of vaginal PG are still poorly understood due to the limited number of cases. In 2019, Wong et al identified the deletion of heterozygosity in exon 1 of SDHB gene as the etiology of a young girl’s vaginal PG [ 5 ]. However, in this case, we investigated 36 high-risk PG related genes including the SDH series but found no mutations.…”