We report a rare case of a woman with bilateral papillary cystadenomata of the broad ligament with von Hippel-Lindau disease (VHL) (other manifestations: capillary hemangioblastomas of the spinal cord). Patient surveillance is important, because in the course of VHL-associated tumors malignant lesions may arise that are relevant for the prognosi

Bruder, Elisabeth

Troeger, Carolyn

Wight, Edward

Zanotelli, Diana

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Arch Gynecol Obstet (2010) 282:343–346DOI 10.1007/s00404-010-1386-4SHORT COMMUNICATIONBilateral papillary cystadenoma of the mesosalpinx: a rare manifestation of Von Hippel–Lindau diseaseDiana Bätschmann Zanotelli · Elisabeth Bruder · Edward Wight · Carolyn Troeger Received: 7 December 2009 / Accepted: 25 January 2010 / Published online: 16 February 2010© Springer-Verlag 2010Abstract We report a rare case of a woman with bilateralpapillary cystadenomata of the broad ligament with vonHippel–Lindau disease (VHL) (other manifestations: capil-lary hemangioblastomas of the spinal cord). Patient surveil-lance is important, because in the course of VHL-associatedtumors malignant lesions may arise that are relevant for theprognosis.Keywords Von Hippel–Lindau disease · Papillary cystadenoma of the mesosalpinxIntroductionVon Hippel–Lindau disease (VHL) was Wrst described in 1926as an inherited disease, characterized by tumors of the retina,brain, kidney, adrenal gland, and pancreas. Recently the VHLgene was identiWed as a tumor suppressor gene on the shortarm of chromosome 3 (3p25-26). VHL disease is an autosomaldominantly inherited multisystemic tumor syndrome due to agene mutation with an incidence of one in 36,000 live births[1]. In 20% of cases de novo mutations occur [2]. The muta-tions cause a situation analogous to hypoxia with an increasein various growth and angiogenic factors [3].AVected individuals are at high risk for developing vari-ous benign and malignant tumors. Lesions in VHL diseasetend to be multiple and bilateral in paired organs (Table 1)[1, 4–6]. Though rarely described in the literature (n = 4),a benign adnexal papillary tumor of probable mesonephricorigin (APMO) is highly signiWcantly associated with VHLdisease. The WHO classiWcation diVerentiates between twomain clinical types, based on the risk for developing apheochromocytoma and/or renal cell carcinoma and isrelated to the type of mutation (Table 2) [1, 7]. Most tumors develop at younger age, i.e. between 20 and40 years. The penetrance of the disease is about 96% by theage of 60 years with renal cell cancer in 69%, retinal tumorin 70% and cerebellar hemangioblastoma in 85% [1, 6].Metastases determine the prognosis and can be found inpatients with renal cell carcinoma, rarely in pheochromocy-tomas or islet cell tumors. Intracerebral hemorrhages due tobleeding from carcinomas or hemangioblastomas of thebrain are the main cause of death [4].Improved surveillance, earlier diagnosis of the lesionswith modern imaging (MRI), improvements in treatmentand increased knowledge of this disease have resulted in animproved prognosis and reduced rates of complications. Aninterdisciplinary team is beneWcial for optimal assessment,treatment, and follow-up. It is also recommended that thefamily of the index patient is examined, because individu-als with a predisposition for an inherited tumor syndrome,such as VHL disease, beneWt from early screening ataround 11 years of age, ophthalmologic examination, cate-cholamine testing, and magnetic resonance imaging [4].Case reportA woman aged 23, nulligravida, underwent a gynecologicalexamination at our institution, because of lower abdominalpain of unclear etiology. Ultrasonographic examinationD. B. Zanotelli · E. Wight · C. Troeger (&)Department of Obstetrics and Gynecology, University Hospital Basel, Spitalstrasse 21, 4031 Basel, Switzerlande-mail: ctroeger@uhbs.chE. BruderInstitute of Pathology, University Hospital Basel, Basel, Switzerland123344 Arch Gynecol Obstet (2010) 282:343–346revealed a partly solid, partly cystic mass of 3.5 cm diame-ter in the right adnexal region (Fig. 1). Ca-125 was withinnormal limits (15.9 U/ml). Laparoscopy was performed anda cystic tumor was found in the right mesosalpinx (Fig. 2)and removed completely. In the left mesosalpinx a smaller(8 mm diameter) cystic tumor was detected and subse-quently removed. On both sides ovaries and fallopian tubeswere unaVected and could be preserved.Histological examination revealed bilateral clear cell pap-illary cystadenomas of the mesosalpinx. The tumors werecomposed of tightly packed papillae with loose or denseWbrous cores, covered by a monolayered epithelium (Fig. 3).These Wndings prompted genetic testing on the adnexal pap-illary tumor of probable mesonephric origin (APMO) andshowed a point mutation P86L on the exon 1 of the VHLgene. The patient has been counseled accordingly.Five years before, the patient had undergone a laminec-tomy of thoracic vertebrae 2 and 3 for symptomatic capil-lary hemangioma with insertion of syringoperitonealdrainage (Fig. 4). The size of the hemangioblastoma of thethoracic vertebral column at that time was 3 £ 1.5 cm. Dur-ing follow-up, MRI now shows two additional similarlesions at the cervical vertebral body IV (1 £ 1 cm) and thesacral body which until now have been treated conserva-tively and examined every 6–12 months (picture notshown).CommentPapillary cystadenomas of the mesosalpinx are rare benignlesions. Bilaterality can be a diagnostic hint of VHL disease[1]. Surgery is necessary if symptoms occur. The APMO ishistologically identical to the papillary cystadenoma of theepididymis in males, where it is usually diagnosed easier[8, 9]. With regard to long-term consequences proper fol-low-up concerning renal cell carcinoma is mandatory,because the risk of metastatic disease increases with tumorsize [4]. Vice versa proper surveillance of the gonadalregion in VHL patients is necessary, since metastasis ofrenal cell carcinomas to the adnexae and epididymes aredescribed. These metastases might even develop withinexisting VHL lesions, such as in hemangioblastoma of thebrain or in cystadenomas of the epididymis, the adrenalgland, and in the gall bladder [7].The histological similarity between papillary cystade-noma and renal cell carcinoma can be explained by thesimilar phylogenetic origin of renal tubules, ductules eVer-entes, and mesonephric remnants [10]. Thus papillary cys-tadenomas can be found intra- and extraperitoneally inremnant parts of the mesonephric duct including the broadligament, the mesosalpinx, along the lateral wall of theuterus and in the wall of the vagina [11, 12]. There arereports on VHL tumors of both Mullerian and WolYan ori-gin containing numerous glands (characterized by tallcolumnar cells) [9, 13]. Interestingly, these lesions mightbe associated with a histological identical papillary middleear/temporal bone tumor [11].Table 1 Typical VHL lesionsFrequency(%)Onset(years)CNSRetinal hemangioblastoma 10–72 25–33Endolymphatic sac tumorCraniospinal hemangioblastomaVisceralRenal cell carcinoma 25–70 30–39PheochromocytomaPancreatic tumor (cyst, serous cystadenomas, neuroendocrine tumor)Cystadenoma of epididymis or broad ligamentTable 2 WHO classiWcation of VHL diseaseType 1 Low risk for pheochromocytoma, hemangioblastoma, renal cell cancer, pancreatic neoplasms and cystsType 2A Pheochromocytoma, hemangioblastoma, low risk for renal cell carcinoma and pancreatic tumorsType 2B Pheochromocytoma, hemangioblastoma, high risk for renal cell carcinoma and pancreatic tumorsType 2C Predominantly pheochromocytoma, very limited risk of hemangioblastoma and of renal cell cancerFig. 1 Doppler ultrasonographic scan of the papillary cystadenoma ofthe right adnex region (arrow indicates the papillary part of the tumor)123Arch Gynecol Obstet (2010) 282:343–346 345Our patient presented with VHL manifestations in theadnexae and in the spinal column. We report this casebecause only the gynecological Wndings prompted thedeWnitive genetic tests. Our case report intends to makegynecologists aware that APMO could be a Wrst manifesta-tion of VHL disease. Since early diagnosis is relevant forlong-term prognosis of the patient and its family, the gyne-cologist should trigger genetic tests and imaging studies toprove or rule out VHL disease.ConXict of interest statement None.References1. Lonser RR, Glenn GM, Walther M et al (2003) von Hippel–Lindau disease. Lancet 361:2059–20672. Joerger M, Koeberle D, Neumann HP, Gillessen S (2005) VonHippel–Lindau disease: a rare disease important to recognize.Onkologie 28:159–1633. de Paulsen N, Brychzy A, Fournier MC et al (2001) Role of trans-forming growth factor-alpha in von Hippel–Lindau (VHL) (¡/¡)clear cell renal carcinoma cell proliferation: a possible mechanismcoupling VHL tumor suppressor inactivation and tumorigenesis.Proc Natl Acad Sci USA 98:1387–13924. Hes FJ, van der Luijt RB, Lips CJ (2001) Clinical management ofvon Hippel–Lindau (VHL) disease. Neth J Med 59:225–2345. Jarrell ST, Vortmeyer AO, Linehan WM, OldWeld EH, Lonser RR(2006) Metastases to hemangioblastomas in von Hippel–Lindaudisease. J Neurosurg 105:256–2636. Neumann HP (1987) Prognosis of von Hippel–Lindau syndrome.Vasa 16:309–3117. Mehta GU, Shively SB, Gläsker S et al (2007) Von Hippel–Lindaudisease: epididymal cystadenoma targeted by metastatic events.Urology 69:1209.e9–e12Fig. 2 Intraabdominal inspec-tion of the tumors (arrow) (organs as indicated: a uterus, b right fallopian tube, c right ovary)Fig. 3 Histopathology (HE staining) revealed a cystic tumor with papillary excrescences. Tumor papillae are lined by a monolayer of cuboid to columnar epithelial cells with monomorphic oval nuclei and a rim clear cytoplasmFig. 4 Magnetic resonance imaging of a symptomatic hemangioblas-toma of the thoracic spine before tumor resection years earlier (thecurrent lesions were not visible at that time; arrow indicates the lesion)123346 Arch Gynecol Obstet (2010) 282:343–3468. Funk KC, Heiken JP (1989) Papillary cystadenoma of the broadligament in a patient with von Hippel–Lindau disease. Am JRoentgenol 153:527–5289. Gersell DJ, King TC (1988) Papillary cystadenoma of the mesosal-pinx in von Hippel–Lindau disease. Am J Surg Pathol 12:145–14910. Aydin H, Young RH, Ronnett BM, Epstein JI (2005) Clear cellpapillary cystadenoma of the epididymis and mesosalpinx: immu-nohistochemical diVerentiation from metastatic clear cell renal cellcarcinoma. Am J Surg Pathol 29:520–52311. GaVey MJ, Mills SE, Boyd JC (1994) Aggressive papillary tumorof middle ear/temporal bone and adnexal papillary cystadenoma.Manifestations of von Hippel–Lindau disease. Am J Surg Pathol18:1254–126012. Shen T, Zhuang Z, Gersell DJ, Tavassoli FA (2000) Allelicdeletion of VHL gene detected in papillary tumors of the broadligament, epididymis, and retroperitoneum in von Hippel–Lindaudisease patients. Int J Surg Pathol 8:207–21213. Werness BA, Guccion JG (1997) Tumor of the broad ligamentin von Hippel–Lindau disease of probable mullerian origin. IntJ Gynecol Pathol 16:282–285123

Bilateral papillary cystadenoma of the mesosalpinx: a rare manifestation of Von Hippel-Lindau disease

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Bilateral papillary cystadenoma of the mesosalpinx: a rare manifestation of Von Hippel-Lindau disease

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