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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2013  |  Volume : 24  |  Issue : 4  |  Page : 777-782
Profound nephrotic syndrome in a patient with ovarian teratoma

1 Baylor College of Medicine, Houston, TX, USA
2 The Methodist Hospital, Houston, TX, USA

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Date of Web Publication24-Jun-2013


The nephrotic syndrome (NS) has been associated with a variety of malignancies in a number of reports in the literature, but has been reported in only nine cases associated with ovarian neoplasms. Membranous nephropathy is the most common glomerular pathology causing the NS in patients with solid tumors. There has been only one report of an ovarian neoplasm associated with minimal change disease (MCD). We describe the case of a 36-year-old woman who presented with the NS secondary to biopsy-proven MCD, likely secondary to mature ovarian teratoma. Treatment by tumor removal and prednisone led to remission of the NS. To the best of our knowledge, this is the first report of an ovarian teratoma and the second report of an ovarian neoplasm associated with MCD.

How to cite this article:
Jeroudi A, Kadikoy H, Gaber L, Ramanathan V, Frome A, Anwar N, Abdellatif A. Profound nephrotic syndrome in a patient with ovarian teratoma. Saudi J Kidney Dis Transpl 2013;24:777-82

How to cite this URL:
Jeroudi A, Kadikoy H, Gaber L, Ramanathan V, Frome A, Anwar N, Abdellatif A. Profound nephrotic syndrome in a patient with ovarian teratoma. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2022 Jan 27];24:777-82. Available from: https://www.sjkdt.org/text.asp?2013/24/4/777/113883

   Introduction Top

The association between the nephrotic syndrome (NS) and a variety of malignancies has been reported in the literature beginning in 1966. [1] Among the histologic variants, membranous nephropathy (MN) is the most common cause of the NS associated with solid tumors, [2],[3] while minimal change disease (MCD) has been described in patients with Hodgkin's lymphoma (HL). [4],[5] However, the association of the NS with ovarian neoplasms is rare and only nine cases have been reported in the literature. [1],[6],[7],[8],[9],[10],[11],[12] To the best of our knowledge, this is the first report of an ovarian teratoma and the second report of an ovarian neoplasm associated with MCD. [12]

   Case Report Top

A 36-year-old Hispanic-American woman, with past medical history significant for preeclampsia two years prior to presentation, was referred for evaluation of new-onset generalized edema. The patient was previously asymptomatic until one week prior to presentation when she developed fatigue, dyspnea on exertion, foamy urine and generalized edema, with a 7 lbs weight gain. The patient had laboratory evaluation at an outside facility, which showed normal kidney function, proteinuria, hypoalbuminemia and elevated serum cholesterol, which prompted the referral for evaluation and management of the NS.

Her vital signs on initial evaluation were as follows: Blood pressure 122/87 mmHg, heart rate 111 beats/min and temperature 36.39°C. Physical examination was normal except for bilateral lower extremity edema. Cardiopulmonary examination was unremarkable. Abdominal examination did not show masses or hepatosplenomegaly. No generalized lymphadenopathy was noted. Dipstick urinalysis was significant for 4+ proteinuria and urine microscopic examination showed rare red cells. No cellular casts were seen. Repeat laboratory tests showed total cholesterol of 317 mg/dL, total serum protein of 4.2 g/dL, serum albumin of 1.2 g/dL, blood urea nitrogen of 33 mg/dL and creatinine of 1.1 mg/dL. Furthermore, the anti-nuclear antibody, serum protein electrophoresis, hepatitis profile and serum complements were unremarkable.

Ultrasound-guided biopsy of the right kidney was performed. The needle-core biopsy had ample renal cortex with at least 22 glomeruli. The glomeruli were unremarkable by light microscopy evaluation, with the exception of minimal and focal increase in mesangial cellularity seen in a few glomeruli [Figure 1]. Lesions of focal and segmental glomerulosclerosis were not noted in multiple-step sections. Likewise, the tubules exhibited minimal changes, namely vacuolization of the tubular epithelial cells and a single mitosis without any obvious changes suggestive of acute tubular necrosis. There was no interstitial fibrosis. The blood vessels were normal. Evaluation of the frozen tissue for immunoglobulins and complement components was negative and there was no evidence of monoclonal paraprotein deposition in the tissue. Ultrastructural examination revealed diffuse effacement of the foot processes along with features of hypertrophy and reactive changes in the podocytes [Figure 2]. These consisted of hypertrophy of intra-cytoplasmic organelles and prominent intra-cellular filaments toward the epi-membranous portions of the cell body. Electron-dense deposits were not detected. Significant swelling of the endothelial cells in the glomerular capillaries was also noted. Fibrin tactoids was identified in the lumen of rare glomerular capillaries.
Figure 1: Normal glomerulus by light microscopy. A single mitosis in otherwise normalappearing proximal convoluted tubules is seen (PAS-H-stained section; ×20 original magnification).

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Figure 2: Electron micrograph of a portion of a glomerulus showing diffuse effacement of the foot processes and micro-villous hyperplasia. The glomerular endothelial cells appear reactive as they display hypertrophy of the intra-cytoplasmic organelles (uranyl acetate and lead citrate; ×5000).

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After the kidney biopsy, the patient developed borderline low-blood pressure and her hemoglobin had dropped from a baseline value of 14.6 g/dL to 12.9 g/dL, which prompted evaluation to rule out possible post-biopsy bleed. Ultrasound showed a small peri-nephric hematoma and moderate free fluid in the pelvis. Computerized tomography scan of the abdomen and pelvis was performed to further evaluate the pelvic fluid, which revealed a 7 cm left adnexal mass consistent with ovarian teratoma [Figure 3].
Figure 3: Computerized tomography of the abdomen and pelvis without intravenous or oral contrast showing a 7 cm maximal diameter ovarian teratoma involving the left adenxa. In the surrounding mesentery, diffuse infiltrative changes are seen suggesting edema with a small amount of free pelvic fluid.

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The patient underwent laparascopic left salpingo-oophorectomy and surgical pathology confirmed a benign mature cystic teratoma. We contemplated on watchful waiting after tumor removal for resolution of proteinuria. She was managed with diuretics, statin and angiotensin-converting enzyme inhibitor. However, in view of profound anasarca and significant weight gain, she was started on oral prednisone. She had a brisk response with resolution of her symptoms and the NS with less than four weeks of therapy. Her kidney function improved to baseline serum creatinine of 0.7 mg/dL.

   Discussion Top

The NS and its association with malignancy is an uncommon occurrence that was first documented in the literature by Lee et al in 1966, when he described the presence of the NS and glomerular pathology in conjunction with a variety of malignancies. He reported 11 patients without evidence of renal amyloidosis, renal vein thrombosis or renal involvement of cancer. [1] In the absence of an etiology for the NS occurring around the time of diagnosis of cancer, he postulated that the body's response to tumor products and antigens may be responsible for the NS and associated glomerular pathology. In essence, he postulated the occurrence of a para-neoplastic syndrome. [1]

Defined as a clinical disorder that accompanies malignancy, para-neoplastic syndromes are caused by the release of tumor products and are not directly related to mass effects or invasion. [13],[14] Review of the literature by Bacchetta et al [14] documents a large collection of case reports associating the presence of the NS as a possible para-neoplastic phenomenon of a wide array of different neoplasms. To theoretically qualify as a para-neoplastic syndrome, Bachetta et al [14] outlines well the general requirements: (a) Absence of other obvious alternative etiology; (b) temporal relationship between the NS and cancer diagnosis; (c) remission of the syndrome clinically and histologically by either surgery or chemotherapy and (d) worsening of the symptoms with tumor recurrence. Two limitations in the literature concerning this definition involve the ethical implications of verifying histological remission of the NS by kidney biopsy [2] and inability to completely cure many of the cancers reported as associated with this syndrome. [2],[15] Compounding these issues is the lack of identification of the mechanism leading to para-neoplastic NS. [2],[14] Although the mechanism of the para-neoplastic NS is hard to establish, [2],[14] a link is suggested by the time relationship between development of the NS and detection of cancer as well as several examples of resolution of proteinuria after tumor removal [7],[15],[16],[17] and treatment. [3],[5]

Despite limitations in identifying a physical, mechanistic link between the NS and malignancy, the literature does show an association between certain glomerular pathological findings and certain malignancies. [2],[3],[4],[5],[14] To date, the NS, in patients with solid tumors, is commonly caused by MN, [2],[3],[14] while MCD has mainly been described in HL, [4],[5],[14] and other hematological malignancies. [14] While MCD has been observed in cases of the NS associated with solid tumors, the review by Bacchetta et al [14] in 2009 highlights this uncommon finding by reporting only 64 cases in the literature.

In terms of ovarian malignancies associated with the NS, case reports are rare, with only nine other cases reported in the literature. [1],[6],[7],[8],[9],[10],[11],[12] In all but two of these cases, the glomerular pathology was known [Table 1]. Pathological diagnoses reveal that five of the seven biopsy-proven cases were associated with MN, [1],[6],[8],[11] which is in line with the concept that solid tumors associated with the NS tend to display MN on pathological examination. [2],[3],[14] One of the seven biopsy-proven cases showed membranoproliferative glomerulonephritis on histology. [10] To the best of our knowledge, this is the first report of ovarian teratoma associated with MCD and the second case of ovarian neoplasm to be associated with MCD. [12]
Table 1: Pathological findings and outcomes of cases with ovarian tumor associated with the nephrotic syndrome reported in the literature.

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Remission of the NS should theoretically accompany tumor removal and treatment of the culprit disease process, but that is not always the case in the literature. [14] Cases detailing the resolution of the NS rapidly after tumor removal without adjunct treatments are extremely rare, [8],[16],[17] but theoretically provide the strongest link between the NS and cancer. [14] Other cases involving the use of steroids and immuno-suppressants for cancer treatment may pose a dilemma as these compounds are also used to treat MCD and MN. [18] Conversely, it can be argued that successful treatment of the cancer causes remission of the NS. In the retrospective study of 21 patients with MCD-related NS and HL by Audard et al, [5] patients in a sub-group of the NS, poorly responsive to steroids, achieved remission of the NS with successful treatment of HL by chemotherapy.

In the case reports of ovarian malignancies associated with the NS, the results are mixed concerning remission of the NS and ovarian cancer [Table 1]. Remission of the NS was seen in five cases that achieved successful treatment of ovarian cancer: One by excision alone; [8] one by chemotherapy alone; [11] and three by excision with chemotherapy. [6],[9],[12] On the other hand, remission of the NS was not achieved in a patient with mixed-germ cell ovarian tumor treated with prednisone and excision; [10] yet, this could have been secondary to the development of chronic kidney disease. In the two cases reported by Lee et al, [1] remission of the NS was not seen in the patient who died without receiving treatment as well as the patient who had received prednisone and excision of the ovarian dermoid cyst. Treatment and outcome could not be analyzed in one of the cases due to incomplete information. [7]

Several factors in this case strengthen the association of MCD and the ovarian teratoma. First, MCD NS is classically a childhood condition, [18] and accounts for only 10-15% of adult cases, [18],[19] with an average age at onset of 45.1 years and a standard deviation of 1.6 years. [20] Second, there is an excellent temporal relationship between diagnosis of cancer and onset of symptoms. The patient lacked any significant medical history considered to be associated with secondary MCD picture such as drugs, infection, atopy and certain chronic medical conditions. [21] Third, even though the remission rate is excellent in adult patients with MCD, the time to response is prolonged. Our patient responded very briskly to surgical removal of tumor and short-term prednisone therapy. Despite limitations in identifying a physical, mechanistic link between MCD and ovarian teratoma, future reports and studies may lead to such findings.

   References Top

1.Lee JC, Yamauchi H, Hopper J Jr. The association of cancer and the nephrotic syndrome. Ann Intern Med 1966;64:41-51.  Back to cited text no. 1
2.Ronco PM. Paraneoplastic glomerulopathies: New insights into an old entity. Kidney Int 1999;56:355-77.  Back to cited text no. 2
3.Lefaucheur C, Stengel B, Nochy D, et al. Membranous nephropathy and cancer: Epidemiologic evidence and determinants of high-risk cancer association. Kidney Int 2006;70:1510-7.  Back to cited text no. 3
4.Mallouk A, Pham PT, Pham PC. Concurrent FSGS and Hodgkin's lymphoma: Case report and literature review on the link between nephrotic glomerulopathies and hematological malignancies. Clin Exp Nephrol 2006;10:284-9.  Back to cited text no. 4
5.Audard V, Larousserie F, Grimbert P, et al. Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: Report of 21 cases and review of the literature. Kidney Int 2006;69:2251-60.  Back to cited text no. 5
6.Hoyt RE, Hamilton JF. Ovarian cancer associated with the nephrotic syndrome. Obstet Gynecol 1987;70:513-4.  Back to cited text no. 6
7.Torres VE, Donadio JV Jr. Clinical aspects of the nephrotic syndrome in systemic diseases. In: Cameron SJ, Glassock RJ, eds. Nephrotic Syndrome, ed 1. New York. Dekker; 1988. p. 555-651.  Back to cited text no. 7
8.Beauvais P, Vaudour G, Boccon Gibod L, Levy M. Membranous nephropathy associated with ovarian tumour in a young girl: Recovery after removal. Eur J Pediatr 1989;148:624-5.  Back to cited text no. 8
9.Forgy A, Ewing T, Flaningam J. Two para-neoplastic syndromes in a patient with ovarian cancer: Nephrotic syndrome and paraneoplastic cerebellar degeneration. Gynecol Oncol 2001;80:96-8.  Back to cited text no. 9
10.Salazar-Exaire D, Rodríguez A, Galindo-Rujana ME, et al. Membranoproliferative glomerulonephritis associated with a mixed-cell germinal ovary tumor. Am J Nephrol 2001;21:51-4.  Back to cited text no. 10
11.Kim YT, Rha SY, Shim CY, et al. A case of paraneoplastic nephrotic syndrome in a patient with ovarian carcinoma. Yonsei Med J 2003; 44:539-43.  Back to cited text no. 11
12.Ryu DR, Yoo TH, Kim YT, et al. Minimal change disease in a patient with ovarian papillary serous carcinoma. Gynecol Oncol 2004;93:554-6.  Back to cited text no. 12
13.Jameson JL, Johnson Bruce E, "Chapter 96. Paraneoplastic Syndromes: Endocrinologic/ Hematologic (Chapter): Harrison's Principles of Internal Medicine, 17e. Available from: http://www.Accessmedicine.com/content. aspx?aID=2868813. [Last accessed on 02/10/2010  Back to cited text no. 13
14.Bacchetta J, Juillard L, Cochat P, Droz J. Paraneoplastic glomerular diseases and malignancies. Crit Rev Oncol Hematol 2009;70:39-58.  Back to cited text no. 14
15.Pai P, Bone JM, McDicken I, Bell GM. Solid tumor and glomerulopathy. Q J Med 1996;89: 361-7.  Back to cited text no. 15
16.Lumeng J, Moran JF. Carotid body tumor associated with mild membranous glomerulonephritis. Ann Int Med 1966;65:1266-70.  Back to cited text no. 16
17.Cantrell E. Nephrotic syndrome cured by removal of gastric carcinoma. Br Med J 1969; 2:739-40.  Back to cited text no. 17
18.Lewis Julia B, Neilson Eric G, "Chapter 277. Glomerular Diseases" (Chapter): Harrison's Principles of Internal Medicine, 17e. Available from: http://www.accessmedicine.com/content.aspx? aID=2897259. [Last accessed on 02/10/2010  Back to cited text no. 18
19.Hass M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: A comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kid Dis 1997;30:621-31.  Back to cited text no. 19
20.Waldman M, Crew RJ, Valeri A, et al. Adult minimal-change disease: Clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol 2007;2:445-53.  Back to cited text no. 20
21.Glassock, RJ. Secondary minimal change disease. Nephrol Dial Transplant 2003;18 (Suppl 6):vi52-8  Back to cited text no. 21

Correspondence Address:
Abdul Abdellatif
Assistant Professor of Medicine, Baylor College of Medicine, 1709 Dryden Suite 900, Houston, TX 77030
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DOI: 10.4103/1319-2442.113883

PMID: 23816730

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  [Figure 1], [Figure 2], [Figure 3]

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