Ovarian tumor and glomerulopathies: case report and review of the literature

We describe a patient who developed nephrotic syndrome in the setting of ovarian tumor. A kidney biopsy showed minimal change nephropathy (MCN). CT scan and MR imaging followed by surgery lead to diagnostic of ovarian dermoid cyst. Surgery combined with corticosteroids resulted in a complete remission of nephrotic syndrome with disappearance of proteinuria after 3 weeks. Ten other cases of ovarian tumor associated with glomerulopathy are reviewed. This is the second case of an ovarian teratoma associated with MCN. Accurate history, physical examination, laboratory data, and kidney biopsy are highlighted in establishing the correct diagnosis in such patients.


Introduction
The relationship between glomerulopathy and malignancy was first described in 1922 by Galloway [1] in a patient with Hodgkin's disease who developed massive proteinuria. This association was confirmed in 1966 by Lee et al. who found 11 patients with cancer in a group of 101 patients with a nephritic syndrome [2]. The most common renal pathology in these patients was membranous nephropathy with deposition of immune complex [3]. Minimal change nephropathy (MCN) is widely known to be associated with lymphoproliferative disorders, especially with Hodgkin's disease [4]. However, few cases of MCN have been reported in patients with solid tumors [5] and only in few previous reports of ovarian neoplasms associated with the nephrotic syndrome. Only one previously case of an ovarian teratoma associated MCN have been reported [6]. We herein describe a second case of such association.

Discussion
In our case, the absence of classic causes of nephrotic syndrome and the briskly response to surgical removal of the tumor, albeit with steroids suggests a relationship between MCN and ovarian teratoma.
Nephrotic syndrome is a rare manifestation of malignancy associated paraneoplastic syndrome. Secondary MCN is defined by the presence of some identifiable extraglomerular disease process occurring concomitantly with the morphologic and functional abnormalities of MCN, irrespective of underlying pathogenetic mechanism [7]. The six categories of secondary MCN (mainly neoplastic) are listed in Table   1 [7]. Remission of paraneoplastic nephrotic syndrome was described at various times after the resection of tumors, which is connected with immunological dysregulation in the course of neoplastic disease [8].
Nephrotic syndrome seems to occur irrespective to the ovarian tumor diagnostic time, either before (n=6, from 1 to 32 months), during a relapse 2 years after the first diagnosis (n=1), or simultaneously  Table   2).
Remission of the NS was seen in 10 cases that achieved successful treatment of ovarian tumor. One patient obtained remission of nephrotic syndrome by excision alone [11], while remission is achieved with chemotherapy alone in another case [16] and by excision with chemotherapy in three other cases [9,14] On the other hand, remission of the NS was not achieved in two patients with ovarian tumor (mixed germ cells and dermoid cyst) treated with prednisone and excision [2,13] .Treatment and outcome could not be analyzed in the other cases due to incomplete information [10]. In our patient, surgical resection of the ovarian tumor, and corticosteroid treatment resulted in briskly and complete remission of the nephrotic syndrome. The possibility of a coincident occurrence of these conditions cannot be completely ruled out. However, considering the patient's age, the lack of other causes of nephrotic syndrome, the temporal relationship between diagnosis of cancer and onset of symptoms and the remission of the nephrotic syndrome following treatment of the ovarian cyst, this association does not seem to be fortuitous. The whole pathogenesis of secondary MCN has not been clearly defined, but a cell-mediated immune response has been postulated [20]; the secretion of a tumoral factor and/or the appropriate production of lymphokines by Tcells to suppress tumor growth could increase glomerular permeability [21]. Despite limitations in identifying a physical, mechanistic link between MCD (Secondary minimal change disease) and ovarian teratoma, future studies may lead to such findings.

Conclusion
We describe the second case of an ovarian teratoma associated with MCN. Accurate history, physical examination, laboratory data, and kidney biopsy are highlighted in establishing the correct diagnosis.
Surgery combined with corticosteroids resulted in a complete remission.

Competing interests
The authors declare no competing interests.

Authors' contributions
All the authors contributed to the care of the patients, the development of the work and read and approved the final version of the manuscript. Table 1: renal histology in nephrotic syndrome associated with ovarian tumors