Von Hippel-Lindau (VHL) syndrome is an autosomal dominant genetic disorder caused by germline mutation of the VHL gene. It is associated with multiple neoplasias including hemangioblastoma, clear cell renal cell carcinoma, pheochromocytoma, and neuroendocrine tumors. Ovarian tumors are extremely rare in this syndrome. We describe the case of a 16-yr-old girl with a previous diagnosis of bilateral pheochromocytoma and several pancreatic neuroendocrine tumors in VHL syndrome context. Follow-up abdominal-pelvic magnetic resonance imaging revealed a 33 mm, well-circumscribed nodule in the right ovary. The patient was submitted to laparoscopic right salpingo-oophorectomy. Microscopically, the tumor consisted of polygonal cells with abundant microvacuolized clear cytoplasm arranged in a solid pattern. The neoplastic cells were immunohistochemically positive for inhibin and calretinin. A diagnosis of ovarian steroid cell tumor was made. Only 4 cases with this association have been reported to date. Of the previously described cases, only one concerns a child; the others were all adult women. All of them had a previous diagnosis of VHL syndrome and presented with secondary amenorrhea and/or hirsutism due to testosterone-secreting ovarian steroid cell tumors. Although extremely rare, the association between VHL syndrome and ovarian steroid cell tumor has been reported, and our case suggests there is a link between the 2 entities.
PatientID: 1
KindredID: 1
Case: F, 17Y0M, Ethnicity Unknown
DiseaseAssertion: assumed VHL
FamilyInfo: N/A - no family history of VHL disease. Authors indicate probably a de novo mutation, however no testing on family members was completed.
CasePresentingHPOs: HP:0006748; HP:0030405; HP:0100615 (pheochromocytoma, pancreatic endocrine tumor, ovarian neoplasm)
CaseHPOFreeText: hospitalized in 2011 (11Y old) due to a hypertensive crisis with end-organ damage (bilateral papilledema and left ventricular hypertrophy). MRI showed 2 heterogenous nodular lesions where the largest was in the right adrenal gland (65x51x39mm) and the other in the left adrenal gland (36x28x25mm). A bilateral adrenalectomy diagnosed both tumors as pheochromocytomas of the adrenal gland. Lymph node metastasis was detected in the adipose tissue surrounding the left adrenal gland. 2 years later (at age 13Y) a PET/CT scan showed a nodular lesion in the tail of the pancreas (11mm) and a nodule in between the inferior vena cava and the portal vein (13mm) and both were later diagnosed as neuroendocrine tumors the former in the pancreas and the latter in the perihaptic ectopic pancreatic tissue. At 14Y, more pancreatic lesions were found. At 16Y, an MRI found a nodule int he right ovary (33mm) which was later diagnosed as a benign ovarian steroid cell tumor
CaseNotHPOs: HP:0010797; HP:0006770 (hemangioblastoma, clear cell renal cell carcinoma)
CaseNotHPOFreeText: Table 1 indicates this was did not have the above manifestations
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: p.R161Q (c.482G>A)
LegacyVariant: p.R161Q (c.695G>A)
CaseProblemVariantFreeText: N/A
ClinVarID: 182983, https://www.ncbi.nlm.nih.gov/clinvar/variation/182983/
CAID: N/A
gnomAD: N/A
VariantEvidence: N/A
MutationType: missense_variant;transition
CivicName: R161Q (c.482G>A)
MultipleGeneVariants: N/A