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we report a 32-year - old female with nephrotic syndrome that was first diagnosed along with invasive thymoma and treated by means of cisplatin - based chemotherapy for the thymoma .
chest radiography and computed tomography scans revealed right pleural effusion and a mass in the right middle lung field , which were confirmed by a percutaneous lung biopsy as metastatic invasive thymoma .
severe hypoalbuminemia , heavy proteinuria , hyponatremia , and hypercholesterolemia were features of the nephrotic syndrome .
all of the symptoms of nephrotic syndrome were resolved simultaneously during the first 2 cycles of chemotherapy .
the patient was on regular follow - up with no specific treatment for nephrotic syndrome and underwent successful resection of the left pleura and anterior thymoma .
we conclude that chemotherapy for invasive thymoma is an effective treatment for nephrotic syndrome accompanying the thymoma .
thymomas are uncommon neoplasms that develop from thymic epithelial cells with an annual incidence of 0.13 per 100,000 individuals in 2003 in the united states of america .
the median 5-year survival rate varies from 45% to 74% , which influenced by histologic staging based on the guidelines of the world health organization .
reports suggest that paraneoplastic syndromes associated with thymoma are diverse , including myasthenia gravis , hashimoto thyroiditis , and pure red cell aplasia .
nephrotic syndrome is characterized by 24-hour proteinuria above 3.5  g , hypoalbuminemia , elevated cholesterol level , and edema , and includes primary nephrotic syndrome without clear cause and secondary nephrotic syndrome with various etiologies such as viral infection , autoimmune disease , and diabetes mellitus .
secondary nephrotic syndrome related to malignant neoplasms has also been reported . in such cases ,
patients with decreased renal function may be unable to tolerate treatment - related toxicities , leading to difficulties in neoplasm management . here
, we report a case of a metastatic thymoma accompanied by nephrotic syndrome that was resolved after 2 cycles of chemotherapy against the malignancy .
a 32-year - old , nonsmoking female came to seoul national university bundang hospital with dyspnea and generalized edema .
prior medical history and family history of hypertension and diabetes were not documented . at admission ,
her vital signs were blood pressure137/84  mm hg , pulse rate89 beats / min , respiration rate18 breaths / min , body temperature36.6  c , height162.8  cm , and body weight73.35  kg . the patient had gained 10  kg in body weight over the preceding 1 month .
auscultatory chest examination revealed fine inspiratory crackles in the bilateral lower lung field with decreased lung sound .
laboratory results included white blood cell count7490/mm , hemoglobin14.2  g / dl , platelet count in peripheral complete blood253,000/mm , blood urea nitrogen13  mg / dl , creatinine0.9  mg / dl , total protein3.1  g / dl , albumin1.1  g / dl , total bilirubin0.2  mg / dl , aspartate transaminase18  iu / l , alanine transaminase6  iu / l , alkaline phosphatase81 
iu / l , total cholesterol480  mg / dl , sodium ( na)132  meq / l , potassium2.7  meq / l , and chloride93  meq / l .
twenty - four - hour urine included 37,731  mg protein , 34,081  mg microalbumin , and 1.0  mg creatinine .
serologic markers were negative for hepatitis b and c. rheumatoid factor , anticytoplasmic antibody , antineutrophil antibody , and anti 
monoclonality ( m - spike ) was not found in serum and urine electrophoresis results .
other laboratory results included immunoglobulin ( ig ) g / a / m144/112/134  mg / dl ( reference range : 7001700/90400/45230  mg / dl ) and complement 3 ( c3)/complement 474.6/20.9  mg / dl ( reference range : 70150/1035  mg / dl ) . a chest x - ray revealed a mass in the right middle lung . computed tomography ( ct )
scans of the chest revealed right pulmonary and pleural metastases with a malignant mass in the anterior mediastinum ( fig .
review at gyeongsang national university hospital of a fine - needle biopsy specimen taken from the kidney suggested that most glomeruli were normal in size and cellularity .
light - microscopic findings of global glomerulosclerosis and interstitial lymphocytic infiltrations were not compatible with minimal change disease ( fig .
electron - microscopic examination showed diffuse effacement of epithelial foot processes compatible with focal segmental glomerulosclerosis ( fig .
immunofluorescent staining of igg , iga , igm , c3 , c1q , and fibrin was negative , which is compatible with focal segmental glomerulosclerosis .
( a ) upon light - microscopic examination , most glomeruli were normal in size and cellularity , but there were global glomerulosclerosis and interstitial lymphocytic infiltrations , which are not compatible with minimal change disease ( hematoxylin and eosin stain , 200 ) .
( b ) electron microscopic examination showed diffuse effacement of epithelial foot processes , which is compatible with focal segmental glomerulosclerosis .
lymphocytes and epithelial cells from the thymus were confirmed in a right pleural biopsy specimen ( fig .
testing for c - kit mutation was performed to exclude thymic carcinoma and to consider a targeted agent ; exons 9 , 11 , 13 , and 17 were unidentified .
pathology of the right pleural biopsy ( hematoxylin and eosin stain seen under light microscopy , 200 ) .
the patient was admitted to the hospital for the first cycle of adoc ( adriamycin ( ildong pharmaceutical , seoul , korea ) 40  mg / m , cisplatin ( ildong pharmaceutical , seoul , korea ) 50  mg / m , vincristine ( hospira korea , seoul , korea ) 0.6  mg / m , and cyclophosphamide ( baxter korea , seoul , korea ) 700  mg / m every 3 weeks , full dose ) . at that time , the patient 's body weight was 69.8  kg , compared with 63  kg in her healthy state . pitting edema on both legs was severely palpated .
the patient 's serum na level had decreased to 127  meq / l . for differential diagnosis ,
the results of a rapid adrenocorticotropic hormone stimulation test were within the normal range , and the results of a thyroid function test were thyroid - stimulating hormone4.5  iu / ml ( reference range : 0.34.0  iu / ml ) , free t40.85  ng / dl ( reference range : 0.891.79  ng / dl ) , and t351  ng / dl ( reference range : 79200  ng / dl ) .
the patient 's urine output decreased to < 1  l / d , but recovered after 2 days with a dose of aldosterone receptor antagonist added to loop diuretics . because the recovery appeared to be reliant on the steroid included in the chemotherapy regimen , diuretics were stopped . with no water restriction ,
the overall trends of proteinuria , hypercholesterolemia , and hyponatremia improved throughout the 2 cycles of chemotherapy ( fig .
4b ) , suggesting that the nephrotic syndrome was paraneoplastic and was associated with the malignant thymoma .
( a ) trend of serum sodium level , daily urine output , and body weight .
( b ) trend of proteinuria ( spot urine protein / creatinine ratio and spot urine microalbumin / creatinine ratio ) and serum albumin levels .
after partial remission was achieved following the completion of 6 cycles of adoc regimen , the left diaphragm , left pleura , and anterior thymomectomy were removed , and the disease was confirmed as malignant thymoma ( surgical staging : masaoka stage iva , world health organization type b3 ) .
paraneoplastic nephropathy is a rare disease category with different clinical presentations , pathophysiologic mechanisms , management , and prognoses , depending on the type of associating malignancies .
paraneoplastic glomerulonephritis associated with solid tumors commonly occurs when the materials induced by the cancer form immune complexes that damage the endothelial cells of the glomerulus .
membranous nephropathy is the most common pathologic type of paraneoplastic glomerulonephritis associated with solid tumors , which is followed by minimal change disease .
cytokines , such as interleukin ( il)-12 and interferon , that are related to t - helper 1 cells , may play a role in the development of membranous nephropathy associated with solid tumors .
however , minimal change disease is the most common pathologic type of paraneoplastic glomerulonephritis associated with hematologic malignancies and thymic neoplasms . vascular endothelial growth factor and cytokines such as il-2 , il-4 , and il-13 induced by t - helper 2 cells and macrophages affect the pathogenesis of minimal change disease , resulting in increased permeability of the glomerular basement membrane .
t - cell dysregulation is the key point of the pathogenesis because thymoma is a disorder of the thymus that functions in t - lymphocyte maturation .
cases of nephrotic syndrome associated with malignant thymoma have been reported in korea and in western countries . in early reports ,
nephrotic syndrome developed several years after thymectomy or other treatments in a majority of cases .
however , additional reports have indicated that treatment for nephrotic syndrome preceded the diagnosis of thymoma . in a systematic review of reported cases of minimal change disease and solid malignant tumors , including thymoma ,
nephrotic syndrome and malignant thymoma were simultaneously diagnosed in only 20% of the cases , whereas nephrotic syndrome was diagnosed after the diagnosis of thymoma in 65% of the cases . besides minimal change disease , which is the most common pathologic type of nephrotic syndrome associated with thymoma , focal segmental sclerosis , membranous nephropathy , and membranoproliferative glomerulonephritis
only a few cases of focal segmental glomerulosclerosis associated with thymoma , such as the case presented here , were reported previously .
most of the previously reported cases showed malignant thymic pathology , except for 1 case that presented with grade - a benign thymoma . among the reported cases of minimal change disease accompanied by thymoma
, 43% responded completely to corticosteroid and/or immunosuppressive agents , and 22% responded partially to treatments .
overall patient survival appears to be better in paraneoplastic minimal change disease accompanied by malignant thymoma than in that accompanied by solid tumors ( 53% and 30% , respectively ) .
there is little prognostic data from cases of focal segmental glomerulosclerosis , because such cases are scarce .
one patient who received steroid treatment achieved a complete response , whereas another patient did not respond to steroid therapy and required maintenance hemodialysis .
renal function in the latter patient improved after thymectomy , and she stopped hemodialysis eventually .
another patient had a good response to steroid treatment , but died of severe neutropenia followed by neutropenic sepsis and multiorgan failure .
first , we should be particularly cautious of infection after chemotherapy or steroid treatment for thymoma , because nephrotic syndrome usually increases the risk of infection .
we should also consider prophylactic administration of granulocyte - colony stimulating factor if possible , although there was no sign of infection in the case reported here .
next , we should consider limiting the use of cisplatin - based chemotherapeutic agents because of patients decreased renal function . in the case
presented here , we applied cisplatin because the patient 's renal function was in the normal range ; however , some physicians have substituted carboplatin or paclitaxel - based regimens for cisplatin . finally , for secondary nephrotic syndrome , the management plan should be tailored by considering that secondary nephrotic syndrome has a chance to get better after management of the primary tumor with chemotherapy or surgical resection .
octreotide treatment has been utilized in certain cases of thymoma , as have targeted agents such as c - kit inhibitors or epidermal growth factor  receptor inhibitors . in such situations , dose adjustment or careful selection of the medication
in particular , patients who underwent resection after shrinking of the tumor with preoperative agents showed good prognosis ; however , approximately 15% of those patients did not remain in a disease - free state .
it is important to trace the symptoms and signs of paraneoplastic syndrome , because they may hint at recurrence during the follow - up period . in summary ,
a case of nephrotic syndrome , which presented initially as a paraneoplastic syndrome with metastatic thymoma , resolved after chemotherapy for the thymoma .
abstractrationale : nephropathy with concurrent invasive thymoma is a type of paraneoplastic syndrome.patient concerns and diagnoses : we report a 32-year - old female with nephrotic syndrome that was first diagnosed along with invasive thymoma and treated by means of cisplatin - based chemotherapy for the thymoma . 
 the patient initially presented with dyspnea and generalized edema . 
 chest radiography and computed tomography scans revealed right pleural effusion and a mass in the right middle lung field , which were confirmed by a percutaneous lung biopsy as metastatic invasive thymoma . 
 severe hypoalbuminemia , heavy proteinuria , hyponatremia , and hypercholesterolemia were features of the nephrotic syndrome . 
 a kidney needle biopsy suggested focal segmental glomerulosclerosis.interventions and outcomes : all of the symptoms of nephrotic syndrome were resolved simultaneously during the first 2 cycles of chemotherapy . 
 the patient was on regular follow - up with no specific treatment for nephrotic syndrome and underwent successful resection of the left pleura and anterior thymoma . 
 the patient has shown no evidence of recurrence for 2 years.lessons:we conclude that chemotherapy for invasive thymoma is an effective treatment for nephrotic syndrome accompanying the thymoma .