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Membranous glomerulonephritis in a patient with choriocarcinoma: case report. (Case Report).



Abstract

A 26-year-old woman presented at our hospital with pretibial edema, swelling, and vaginal bleeding. She had nephroticlevel proteinuria proteinuria /pro·tein·uria/ (-ur´e-ah) an excess of serum proteins in the urine, as in renal disease or after strenuous exercise.proteinu´ric

pro·tein·u·ri·a
n.
1.
 and was diagnosed with choriocarcinoma choriocarcinoma: see neoplasm.  after a histologic examination of her uterine curetting was performed. The renal biopsy specimen was compatible with membranous glomerulonephritis. The renal pathology in this case was thought to be secondary to choriocarcinoma because the nephrotic syndrome regressed after hysterectomy. We briefly present this first case of choriocarcinoma causing membranous glomerulonephritis.

**********

Choriocarcinoma is a malignant tumor derived from trophoblasts that has high metastatic potential. (1) Rapid dissemination by the hematogenous hematogenous /he·ma·tog·e·nous/ (he?mah-toj´e-nus)
1. produced by or derived from the blood.

2. disseminated through the blood stream.


he·ma·tog·e·nous
adj.
1.
 or lymphatic route to the lungs, brain, and, rarely, kidneys is possible. (2) Renal involvement by choriocarcinoma has been reported to have an incidence of 1 3%. (3) Membranous glomerulonephritis (MGN) might be secondary to drug use, systemic lupus erythematosus Systemic Lupus Erythematosus Definition

Systemic lupus erythematosus (also called lupus or SLE) is a disease where a person's immune system attacks and injures the body's own organs and tissues. Almost every system of the body can be affected by SLE.
, tumors, or hepatitis B virus infection. (4) An underlying malignancy may coexist with MGN in 6 to 11% of patients. (5,6) We report the first case described in the literature of a patient who developed MGN at the time of presentation with choriocarcinoma and whose nephrotic syndrome regressed after resection of the tumor.

Discussion

Renal involvement by choriocarcinoma is quite rare. When it does metastasize to the kidneys, it generally presents with a renal mass and hematuria hematuria

Blood in the urine. It usually indicates injury or disease of the kidney or another structure of the urinary system or possibly, in males, the reproductive system. It may result from infection, inflammation, tumours, kidney stones, or other disorders.
. (7-13) Previously, only two cases of trophoblastic tumor manifesting as nephrotic syndrome were reported in literature;14'15 however, neither of those two patients had biopsy-proved glomerulonephritis glomerulonephritis: see nephritis.  (GN). Our patient had the first case of choriocarcinoma with biopsy-proved glomerulopathy.

MGN is the most common cause of nephrotic syndrome in adults. (4) It can be caused by infections (eg, hepatitis B, malaria), tumors, drugs (eg, gold, penicillamine penicillamine /pen·i·cil·la·mine/ (pen?i-sil´ah-men) a degradation product of penicillin that chelates certain heavy metals and also binds cystine and promotes its excretion; used in the treatment of Wilson's disease, cystinuria, ), or systemic disease (eg, systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus). (4) Lee et al (16) found a 10.9% prevalence of malignancy among 101 patients with nephrotic syndrome. In their study, the most common renal lesion was MGN, which was diagnosed in 8 of 11 patients.

In patients with malignancy, glomerular disease might develop as a result of the deposition of tumor-associated, antigen-containing immune complexes or vascular permeability factors (probably cytokines) produced by the tumor. (17) The strongest evidence that malignancy is responsible for GN is their simultaneous appearance and the regression of glomerular disease with radiotherapy, chemotherapy, or resection of the tumor. (18) The treatment of MGN that is secondary to tumors involves the resection of the tumor or the administration of chemotherapy for the malignancy. (4)

In our case, the presentation of the patient with simultaneous choriocarcinoma and nephrotic syndrome makes the possibility that it was mere coincidence less likely. One possible explanation for glomerulopathy might be drugs. Our patient was administered anthracycline and methotrexate, which are known to be nephrotoxic nephrotoxic /neph·ro·tox·ic/ (nef´ro-tok?sik) destructive to kidney cells.
Nephrotoxic
Toxic, or damaging, to the kidney.
 agents. These drugs are not responsible for the nephropathy in our case, however, because the patient had GN before chemotherapy was initiated. Drugs such as cyclophosphamide, however, which is used to treat patients with idiopathic MGN, might also be responsible for the resolution of the proteinuria. This explanation does not seem to be true in our case, however, because the patient's proteinuria persisted after six courses of chemotherapy with cyclophosphamide. After resection of the tumor, hCG levels normalized. When the probable stimulus of the development of MGN was abolished, the nephrotic syndrome disappeared. All of these factors support the hypothesis that MGN was secondary to chorioca rcinoma in this case.

Conclusion

Until this article, choriocarcinoma as a cause of MGN was not reported in the literature. Although renal involvement in choriocarcinoma is rare, it must be considered in the diagnosis of patients with urinary abnormalities. Chemotherapy and/or surgery must be performed immediately, because they both cure the malignancy and halt the progression of the glomerular disease.

Accepted February 14, 2002.

References

(1.) Robboy SI, Duggan MA, Kurman RJ. The female reproductive system, in Rubin E, Farber IL (eds): Pathology. Philadelphia, Lippincott williams & Wilkins, 1999, ed 3, pp 962-1026.

(2.) Li MC. Trophoblastic tro·pho·blast  
n.
The outermost layer of cells of the blastocyst that attaches the fertilized ovum to the uterine wall and serves as a nutritive pathway for the embryo. Also called trophoderm.
 disease: Natural history, diagnosis, and treatment. Ann Intern Med 1971;74:102-112.

(3.) Soper JT, Mutch DG, Chin N, Clarke-Pearson DL, Hammond CB. Renal metastases of gestational trophoblastic disease Gestational trophoblastic disease
A rare, aggressive, malignant, often metastatic (spreading to other organs) cancer in women of childbearing age in which cancer cells grow in the tissues that are formed in the uterus after conception
: A report of eight cases. Obstet Gynecol 1988;72:796-798.

(4.) Short CD, Mallick NP. Membranous membranous /mem·bra·nous/ (mem´brah-nus) pertaining to or of the nature of a membrane.

mem·bra·nous
adj.
1. Relating to, made of, or similar to a membrane.

2.
 glomerulopathy, in Heptinstall RH: Pathology of the Kidney. Boston, Little, Brown & Co., 1992, vol 1, ed 4, pp 726-734.

(5.) Hopper J Jr. Tumor-related renal lesions. Ann Intern Med 1974;81:550-551 editorial).

(6.) Row PG, Cameron JS, Turner DR, Evans DJ, white RH, Ogg CS, et al. Membranous nephropathy: Long-term follow-up and association with neoplasia. Q J Med 1975;44:207-239.

(7.) Snoddy WM, Nelson RP, Nyberg LM Jr, Turner WR Jr, Curry N, Betsill W Jr, et al. Symptomatic renal mass in a patient with a positive pregnancy test. J Urol 1985;133:1015-1018.

(8.) Devasia A, Nath V, Abraham B, Gopalkrishnan G, Nair S. Hematuria, renal mass and amenorrhea amenorrhea (āmĕn'ərē`a, əmĕn'–), cessation of menstruation. Primary amenorrhea is a delay in or a failure to start menstruation; secondary amenorrhea is an unexpected stop to the menstrual cycle. : Indicators of a rare diagnosis. J Urol 1994;151:409-410.

(9.) Tai KS, Chan FL, Ngan HY. Renal metastasis from choriocarcinoma: MRI appearance. Abdom Imaging 1998;23:536-538.

(10.) Thanikasalam K. Post-hysterectomy choriocarcinoma with pulmonary and renal metastases. Med J Malaysia 1991;46:187-191.

(11.) Wang YE, Song HZ, Yang XY, Dong SY, Gan N. Renal metastases of choriocarcinoma: A clinicopathological study of 31 cases. Chin Med J (Engl) 1991;104:716-720.

(12.) Huang CH, Chen L, Hsieh HH. Choriocarcinoma presenting as a unilateral renal mass and gross hematuria in a male: report of a case. J Formos Med Assoc 1992;91:922-925.

(13.) Ikeda I, Miura T, Kondo I, Kimura A. Metastatic choriocarcinoma of the kidney discovered by refractory hematuria. Hinyokika Kiyo 1996;42:447-449.

(14.) Timoshenko NI, Kaliuzhina MI, Afonin VI, Shcherbakov VI. Kidney involvement in trophoblastic disease (chorionepithelioma) [in Russian]. Ter Arkh 1995;67:59-61.

(15.) Eckstein RP, Paradinas FJ, Bagahawe KD. Placental site trophoblastic tumour (trophoblastic pseudotumour): A study of four cases requiring hysterectomy including one fatal case. Histopathalogy 1982;6:211-226.

(16.) Lee JC, Yamauchi H, Hopper I Jr. The association of cancer and the nephrotic syndrome. Ann Intern Med 1966;64:41-51.

(17.) Glassock RJ, Massry SG. Neoplasia, in Massry SG, Glassock RJ (eds): Textbook of Nephrology. Baltimore, Williams & Wilkins, 1995, vol 2, pp 1117-1123.

(18.) Martinez-Maldonado M, Benabe JE. Nonrenal neoplasms and the kidney, in Schrier RW, Gottschalk CW (eds): Diseases of the Kidney. Boston, Little, Brown & Co., 1993, vol III, pp 2265-2285.

RELATED ARTICLE: Key Points

* Although choriocarcinoma does rarely affect the kidneys, producing hernaturia or renal mass effect, biopsyproved glomerulonephritis has not been reported previously.

* Physicians should look for an underlying malignancy in patients with membranous glomerulonephritis, because it is present in 6 to 11% of cases.

* The simultaneous appearance of malignancy and glomerulonephritis, along with the regression of renal disease with treatment of the tumor, suggests that the glomerulonephritis in our case was secondary to malignancy.

Case Report

A 26-year-old married woman presented at our hospital with complaints of fatigue, pretibial edema, and swelling. She described severe vaginal bleeding after 3 months of secondary amenorrhea. The physical examination performed at admission revealed the patient's blood pressure to be 140/95 mm Hg and her heart rate to be 96 beats/min. The laboratory values were hemoglobin, 7.1 g/dl; white blood cell count white blood cell count,
n a diagnostic clinical laboratory test to determine the number and types of leukocytes present in a measured sample of blood. Overall the normal number of leukocytes ranges from 5000 to 10,000/mm3.
, 9,300/[mm.sup.3] platelets, 215,000/[mm.sup.3] erythrocyte sedimentation rate Erythrocyte Sedimentation Rate Definition

The erythrocyte sedimentation rate (ESR), or sedimentation rate (sed rate), is a measure of the settling of red blood cells in a tube of blood during one hour.
, 117 mm/h; blood urea nitrogen blood urea nitrogen
n. Abbr. BUN
Nitrogen in the form of urea in the blood or serum, used as a indicator of kidney function.


Blood urea nitrogen (BUN) 
, 11 mg/dl; creatinine, 0.6 mg/dl; total protein, 6.67 g/dl; albumin, 1.64 g/dl; total cholesterol, 123 mg/dl; and triglycerides, 186 mg/dl. The other biochemical values were within normal limits. Urinalysis showed proteinuria (3+) with oval fat bodies in the sediment. Urine total protein was 5.2 g/d, and creatinine clearance was 81 ml/min. The tests for hepatitis B surface antigen hepatitis B surface antigen
n. Abbr. HBsAg
An antigen derived from the surface of the hepatitis B virus that is present in the blood in active hepatitis B infection. Also called Australia antigen.
, anti-hepatitis C virus antigen, and anti-human immunodeficiency virus antigen, as well as the Venereal Disease Research La boratory test, were negative. The tests for fluorescent antinuclear antibody, rheumatoid factor, anti-double-stranded DNA, and cryoglobulin cryoglobulin /cryo·glob·u·lin/ (-glob´u-lin) an abnormal globulin that precipitates at low temperatures and redissolves at 37° C.

cry·o·glob·u·lin
n.
 also were negative. The third and fourth components of complement (C3 and C4) levels and the triiodothyronine triiodothyronine /tri·io·do·thy·ro·nine/ (tri?i-o?do-thi´ro-nen) one of the thyroid hormones, an organic iodine-containing compound liberated from thyroglobulin by hydrolysis. It has several times the biological activity of thyroxine. , thyroxine, and thyroid-stimulating hormone levels were normal. Immunoglobulin quantitation was within normal range. Serum electrophoresis revealed polyclonal gammopathy, and urine immunoelectrophoresis Immunoelectrophoresis

A combination of the techniques of electrophoresis and immunodiffusion used to separate the components of a mixture of antigens and make them visible by reaction with specific antibodies.
 was normal. The chest x-ray film and electrocardiogram revealed no pathology. On renal ultrasonograms, the kidneys were observed to be of normal size with mildly increased echogenicity.

Pelvic ultrasonography revealed that the patient's uterus measured 13.4 X 9.0 X 8.8 cm and contained a dead fetus. Dilation and curettage dilation and curettage
n.
Abbr. D & C A surgical procedure in which the cervix is expanded using a dilator and the uterine lining scraped with a curette, performed for the diagnosis and treatment of various uterine conditions.
 were performed on August 30, 1996. The vaginal bleeding continued for another 2 weeks, so curettage curettage /cu·ret·tage/ (ku?re-tahzh´) [Fr.] the cleansing of a diseased surface, as with a curet.

medical curettage
 was performed again on September 18, 1996. The histopathologic examination of the uterine curetting revealed cytotrophoblastic and syncytial syncytial /syn·cy·tial/ (sin-sish´al) of or pertaining to a syncytium.

syncytial

pertaining to or producing a syncytium.


bovine syncytial virus
see retroviridae.
 trophoblastic cells. Immunocytochemical staining for human chorionic gonadotropin human chorionic gonadotropin (HCG): see gonadotropic hormone.  (hCG) confirmed the diagnosis of choriocarcinoma. Serum hCG level was 402,854 mIU/ml.

A kidney biopsy was performed to discover the cause of the nephrotic nephrotic /ne·phrot·ic/ (ne-frot´ik) pertaining to, resembling, or caused by nephrosis.  level of proteinuria. No amyloid deposition was seen. Light microscopic examination of the glomeruli Glomeruli (singular, glomerulus)
Tiny tufts of capillaries which carry blood within the kidneys. The blood is filtered by the glomeruli. The blood then continues through the circulatory system, but a certain amount of fluid and specific waste products are filtered
 showed diffuse thickening of the capillary basement membrane with mild cellularity in the interstitium (Fig. 1). The immunofluorescent examination revealed the granular appearance of immunoglobulin G along the glomerular basement membrane. An electron microscopic examination could not be performed. The renal biopsy findings provided the basis for the diagnosis of MGN.

The patient was treated with nine courses of methotrexate therapy, at the end of which her serum hCG level was 308,465 mIU/ml with the tumor still present in the uterus. Etoposide, methotrexate, actinomycin actinomycin (ăk'tənōmī`sən), any one of a group of antibiotics produced by bacteria of the genus Streptomyces. Actinomycin was the first antibiotic reported to be able to halt cancer; however, it is not widely used to , cyclophosphamide, and vincristine vincristine /vin·cris·tine/ (vin-kris´ten) an antineoplastic vinca alkaloid; used as the sulfate salt in the treatment of various neoplasms, including Hodgkin's disease, acute lymphocytic leukemia, non-Hodgkin's lymphoma, Kaposi's  therapy was started on July 22, 1997, because the patient was not responsive to treatment with methotrexate. High hCG levels, the tumor in the uterus, and the nephrotic level of proteinuria persisted after six courses of this treatment had been administered. Because the patient had nonmetastatic choriocarcinoma refractory to chemotherapy and MGN secondary to choriocarcinoma, hysterectomy was performed on December 2,1997. Four weeks after surgery, her hCG level was 10.8 mIU/ml and her urine total protein level was in 0.5 g/d. The patient subsequently was seen in June 2001 at her regular follow-up visit. Her physical examination was completely normal, with the hCG level and all other biochemical values within normal ranges, and there was no proteinuria.

From the Departments of Nephrology, Internal Medicine, and Pathology, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, Turkey.

Reprint requests to Mebmet Riza Altiparmak, MD, Rasimpasa Mab, Tashbayir Sok, No. 14, Daire: 10, Kadikoy, Istanbul, Turkey. Email: onpamuk80@hotmail.com

Copyright [c] 2003 by The Southern Medical Association 0038-4348/03/9602-0198
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Author:Ozbay, Gulsen
Publication:Southern Medical Journal
Geographic Code:1USA
Date:Feb 1, 2003
Words:1760
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