GYNOR-00161; No. of pages: 3; 4C: 2 Gynecologic Oncology Reports xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Gynecologic Oncology Reports journal homepage: www.elsevier.com/locate/gynor
1
Case Reports
4Q1
Changji Xiao a, Jing Zhao a, Mengtao Li b, Dachun Zhao c, Yang Xiang a,⁎ a
1 0 9
a r t i c l e
11 12 13 14
Article history: Received 3 April 2014 Accepted 20 May 2014 Available online xxxx
15 16 17 18 19
Keywords: Amenorrhoea Lupus nephritis Nephrotic syndrome Placental site trophoblastic tumor
R O
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China Department of Rheumatology & Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
C
T
20 23 22 21
Introduction
25 26
PSTT usually follows a normal pregnancy or an abortion, and can be cured by surgery and chemotherapy (Scully and Young, 1981). The association of PSTT with kidney diseases is very rare. There is a single recorded case of thrombotic microangiopathy (TMA) (Mazzucco et al., 2011) and another of membranous glomerulonephritis (Batra et al., 2007; Bologna et al., 1994). Only 2 other cases of PSTT and kidney lesions have been reported. Both of these were described fully by Young et al. as showing a distinctive glomerular lesion (Young et al., 1985). We describe a case of lupus nephritis (LN) that occurred with PSTT. Kidney biopsy showed diffuse global proliferative LN. This unusual findings must be interpreted appropriately to achieve the correct diagnosis.
33 34 35 36
R
R
31 32
N C O
29 30
E
24
27 28
Case report
38 39
A 31-year-old female presented with amenorrhea lasting since fullterm normal delivery 19 months previously and generalized anasarca for more than 1 month prior to presentation. One month before admission she had developed progressive edema of her face, lower
U
37
40 41
extremities. Upon examination there was mild pallor, facial butterfly erythema, anasarca and ascites. Her blood pressure was 140/90 mmHg. A diagnosis of nephrotic syndrome (proteinuria with 24-h urine specimen, N 7 g/day) with normal kidney function was made (serum creatinine, 50 μmol/L and blood urea nitrogen 7.4 mmol/L). Her hemoglobin concentration was 117 g/L. Blood chemistry tests revealed levels of total serum protein of 42.2 g/L (normal ranges, 60–85 g/L), albumin 26 g/L (normal ranges, 35–51 g/L), triglyceride 1.96 mmol/L (normal ranges, 0.45–1.70 mmol/L), antistreptolysin-O 278 IU/ml, C4 complement 0.0716 g/L (normal ranges, 0.12–0.36 g/L). Tests for IgG type titer of antinuclear antibody were 1:320 (normal ranges, b1:40), but tests for C3 complement, anti-dsDNA antibody, rheumatoid factor, and C-reactive protein were within normal ranges. Because of the persistence of edema, hematuria and nephrotic proteinuria, a kidney biopsy was performed to confirm the diagnosis of glomerulopathy. Light microscopy revealed the renal cortex containing 30 glomeruli. None was sclerotic. There were diffuse and global endothelial and mesangium proliferation, widespread wireloops, thickened basement membranes with focal and segmental subendothelial aggregates and some duplication formation. The tubule epithelial cells were granular and showed vacuolar degeneration. The capillary loops were even and thin. There was no evidence of pathologic changes in the interstitium. Immunofluorescence showed a full-house immunofluorescence pattern, immunoglobulin G (++), IgM (++), IgA (+++), C3 (+++), and C1q (+++) along the glomerular basement membrane. Pathologic findings suggested diffuse global proliferative LN (Class IV-G, active index 11 scores) (Fig. 1). Induction therapy using glucocorticoids and cytotoxic drugs was started and lasted for almost 1 year. However, nephrotic syndrome (NS) didn't improve, as indicated by the persistently elevated levels of the 24-h urine protein, which ranged from 2.76 g to 4.81 g and renal function became poor with the blood urea nitrogen elevation exceeding normal limits. Because the patient's amenorrhea had persisted for more than 19 months with evidence of some uterine enlargement, serum human chorionic gonadotropin (β-hCG) levels were checked, which was elevated at 95.4 mIU/mL. Gynecological examination revealed a uterus of about 14 weeks gestation. An abdominopelvic magnetic resonance imaging (MRI) scan showed uterine expansion with a short T1 and long T2 signal. The uterine junction zone and myometrium were unclear, and the diffuse vascular flow void in myometrium and bilateral parametrium showed significant enhancement (Fig. 2). There was a
P
i n f o
D
c
E
b
O
5 6 7 8
F
3Q2
Lupus nephritis associated with placental site trophoblastic tumor: A case report and review of the literature
2
⁎ Corresponding author at: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu yuan 1#, Dongcheng District, Beijing 100730, China. Fax: +86 10 65124875. E-mail address: [email protected] (Y. Xiang).
http://dx.doi.org/10.1016/j.gynor.2014.05.003 2211-338X/© 2014 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Please cite this article as: Xiao, C., et al., Lupus nephritis associated with placental site trophoblastic tumor: A case report and review of the literature, Gynecol Oncol Rep (2014), http://dx.doi.org/10.1016/j.gynor.2014.05.003
42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82
C. Xiao et al. / Gynecologic Oncology Reports xxx (2014) xxx–xxx
E
D
P
R O
O
F
2
E
R
R
91
O
89 90
C
87 88
showed strong cytoplasmic positivity for HPL and negative for β-hCG. Because of the patient's poor kidney function, she was not given chemotherapy. Two weeks later, a post-operative β-hCG reduced to 0.5 mIU/ml, which is just within normal limits (WNL, b5 mIU/ml). The quantity of the 24-h urine protein decreased to 0.40 g/L (normal ranges from 0 to 0.20 g/L). One month after operation the β-hCG level of this patient was WNL with no proteinuria. Additional follow-up visits for the subsequent 15 months showed no evidence of recurrence or metastasis of
N
85 86 Q3
little fluid in the pelvic cavity. Given the slightly elevated β-hCG level, enlarged uterus of about 14 weeks gestational size and diffuse lesions of the uterus by MRI scan, PSTT was highly suspected. But she was not suitable for chemotherapy with poor kidney function. A total abdominal hysterectomy with a bilateral salpingo-oophorectomy was performed. Pathologic investigation showed typical features of PSTT deeply infiltrating the whole layer of uterine corpus wall to the serosa (Young et al., 1985). Sections were immunohistochemically evaluated for β-hCG and human placental lactogen (HPL). These tumor cells
U
83 84
C
T
Fig. 1. (A) H&E staining shows increases in the number of glomerular cells, and visible thrombosis (arrow) (200×). (B) Periodic acid-Schiff staining shows a glomerulus with diffuse endothelial and mesangium proliferation (arrow) (400×). (C) Masson staining shows thickened basement membranes with focal and segmental subendothelial aggregates (400×). (D) Immunofluorescence photomicrograph displaying diffuse deposition of C1q along basement membranes (200×).
Fig. 2. Pelvic MRI scan showing uterine cavity expansion. (A) Scan showing diffuse vascular flow void in myometrium and (B) bilateral parametrium with a significant enhancement.
Please cite this article as: Xiao, C., et al., Lupus nephritis associated with placental site trophoblastic tumor: A case report and review of the literature, Gynecol Oncol Rep (2014), http://dx.doi.org/10.1016/j.gynor.2014.05.003
92 93 94 95 96 97 98 99 100
C. Xiao et al. / Gynecologic Oncology Reports xxx (2014) xxx–xxx t1:1 t1:2
3
Table 1 Review of literature of cases of renal lesions associated with GTD.
t1:3
Diagnosis of renal lesion
GTD
Author
Renal biopsy performed
No.
Year
t1:4 t1:5 t1:6 t1:7 t1:8 t1:9
Thrombotic microangiopathy Membranous glomerulonephritis Membranous glomerulopathy Membranous glomerulonephritis Membranoproliferative glomerulonephritis Occlusive eosinophilic deposit in capillary lumen
PSTT Invasive mole PSTT Choriocarcinoma Hydatiform mole PSTT
Mazzucco Mazzucco et al. (2011) Yang Yang et al. (2010) Batra Batra et al. (2007) Altiparmak Altiparmak et al. (2003) Komatsuda Komatsuda et al. (1992) Young Young et al. (1985)
Yes Yes Yes Yes Yes Yes
1 1 1 1 1 2
2011 2010 2007 2003 1992 1985
Gestational trophoblastic disease (GTD) is used to refer to a variety of gynecological tumors arising from the trophoblastic cells, including hydatidiform mole (complete or partial), choriocarcinoma, PSTT, and ETT. The malignant transformation of trophoblastic tissue can cause a paraneoplastic syndrome (Yang et al., 2010), which were thought to be mediated by an immune response to malignant cells. Sometimes, the clinical manifestations from the paraneoplastic syndrome are noted prior to the diagnosis of malignancy. A number of different types of glomerular disease, nephrotic or nephritic, may be associated with malignancy (Jhaveri et al., 2013). Effective treatment of the tumor generally leads to remission of the glomerular injury in these situations (Lefaucheur et al., 2006). The association of renal lesions and GTD is very rare. Only a few case reports have reported the association of NS with GTD (Altiparmak et al., 2003; Batra et al., 2007; Komatsuda et al., 1992; Mazzucco et al., 2011; Yang et al., 2010; Young et al., 1985), which were summarized in Table 1. In these cases, membranoproliferative glomerulonephritis (Komatsuda et al., 1992) has been found to be associated with hydatidiform mole, and membranous glomerulonephritis has been observed with invasive mole and choriocarcinoma (Altiparmak et al., 2003; Yang et al., 2010). For PSTT, there has been one reported case of TMA and another of membranous glomerulonephritis (Batra et al., 2007; Mazzucco et al., 2011). Only 2 other cases of PSTT and kidney lesions have been reported (Young et al., 1985). These glomerular lesions have also been observed in the present patient, although similar features may be observed under different circumstances. The present case suggests a diagnosis of a variant of LN. This conclusion is supported not only by light microscopy but also by immunohistochemistry findings. Conclusive evidence of LN comes from clinical and laboratory evidence. According to diagnostic criteria for SLE by the American College of Rheumatology in 1997, LN must be considered first. The mechanism may involve an immunologic process associated with LN, specifically the presence of complement and immunoglobulin on immunofluorescence and large subendothelial and smaller subepithelial and mesangial deposits, as indicated by light microscopy. Because there are several types of glomerulonephritis reported in association with epithelial and hematologic neoplasia, a relationship with the PSTT may exist (Jhaveri et al., 2013). In the present case, LN was considered secondary to PSTT, because this patient had presented with NS having amenorrhea for 19 months
119 120 121 122 123 124 125 126 127 128 129 Q4 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144
C
117 118
E
115 116
R
113 114
R
111 112
N C O
109 110
U
107 108
F
105 106
O
Discussion
R O
104
without a clear etiology. She had no previous history of systemic lupus erythematosus. She had received induction therapy with glucocorticoids and cytotoxic drugs for almost 1 year until PSTT was discovered when the clinical symptoms of LN didn't resolve with medical therapy. The fact that the clinical and biochemical features of nephrotic syndrome disappeared completely after the hysterectomy provides strong evidence that LN was secondary to PSTT, although the pathogenesis of this disease process is still unclear at this point. In conclusion, this case provides a highlight of the correlation between LN and PSTT and also highlights the nephritic complications of GTD. Written informed consent was obtained from the patient for the publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
P
103
PSTT. The patient currently remains free of clinical symptoms of LN. Tests for C3, C4, anti-dsDNA antibody, antinuclear antibody, rheumatoid factor, and C-reactive protein were all within normal ranges.
D
101 102
Conflict of interest statement We declare that we have no conflict of interest.
E
GTD: Gestational trophoblastic disease, PSTT: Placental site trophoblastic tumor.
T
t1:10
145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161
Acknowledgments
162
The authors thank all personnel of the medical record library of Peking Union Medical College Hospital for their data collection. This work was supported by a grant from the National Nature and Science Foundation of China (grant no. 81272890).
163
References
167
Altiparmak, M.R., Pamuk, O.N., Pamuk, G.E., et al., 2003. Membranous glomerulonephritis in a patient with choriocarcinoma: case report. South. Med. J. 96, 198–200. Batra, V., Kalra, O.P., Mathur, P., et al., 2007. Membranous glomerulopathy associated with placental site trophoblastic tumour: a case report. Nephrol. Dial. Transplant. 22, 1766–1768. Bologna, C., Jorgensen, C., Anaya, J.M., et al., 1994. Association of systemic lupus erythematosus and choriocarcinoma: a role of hormonal immunomodulation? Clin. Exp. Rheumatol. 12, 59–61. Jhaveri, K.D., Shah, H.H., Calderon, K., et al., 2013. Glomerular diseases seen with cancer and chemotherapy: a narrative review. Kidney Int. 84, 34–44. Komatsuda, A., Nakamoto, Y., K A, et al., 1992. Case report: nephrotic syndrome associated with a total hydatidiform mole. Am. J. Med. Sci. 303, 309–312. Lefaucheur, C., Stengel, B., Nochy, D., et al., 2006. Membranous nephropathy and cancer: epidemiologic evidence and determinants of high-risk cancer association. Kidney Int. 70, 1510–1517. Mazzucco, G., Colla, L., Monga, G., 2011. Kidney involvement in a patient affected by placental site trophoblastic tumor. Am. J. Kidney Dis. 57, 516–520. Scully, R.E., Young, R.H., 1981. Trophoblastic pseudotumor: a reappraisal. Am. J. Surg. Pathol. 5, 75–76. Yang, J.W., Choi, S.O., Kim, B.R., et al., 2010. Nephrotic syndrome associated with invasive mole: a case report. Nephrol. Dial. Transplant. 25, 2023–2026. Young, R.H., Scully, R.E., McCluskey, R.T., 1985. A distinctive glomerular lesion complicating placental site trophoblastic tumor: report of two cases. Hum. Pathol. 16, 35–42.
168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190
Please cite this article as: Xiao, C., et al., Lupus nephritis associated with placental site trophoblastic tumor: A case report and review of the literature, Gynecol Oncol Rep (2014), http://dx.doi.org/10.1016/j.gynor.2014.05.003
164 165 166
Contents lists available at ScienceDirect
Gynecologic Oncology Reports journal homepage: www.elsevier.com/locate/gynor
1
Case Reports
4Q1
Changji Xiao a, Jing Zhao a, Mengtao Li b, Dachun Zhao c, Yang Xiang a,⁎ a
1 0 9
a r t i c l e
11 12 13 14
Article history: Received 3 April 2014 Accepted 20 May 2014 Available online xxxx
15 16 17 18 19
Keywords: Amenorrhoea Lupus nephritis Nephrotic syndrome Placental site trophoblastic tumor
R O
Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China Department of Rheumatology & Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
C
T
20 23 22 21
Introduction
25 26
PSTT usually follows a normal pregnancy or an abortion, and can be cured by surgery and chemotherapy (Scully and Young, 1981). The association of PSTT with kidney diseases is very rare. There is a single recorded case of thrombotic microangiopathy (TMA) (Mazzucco et al., 2011) and another of membranous glomerulonephritis (Batra et al., 2007; Bologna et al., 1994). Only 2 other cases of PSTT and kidney lesions have been reported. Both of these were described fully by Young et al. as showing a distinctive glomerular lesion (Young et al., 1985). We describe a case of lupus nephritis (LN) that occurred with PSTT. Kidney biopsy showed diffuse global proliferative LN. This unusual findings must be interpreted appropriately to achieve the correct diagnosis.
33 34 35 36
R
R
31 32
N C O
29 30
E
24
27 28
Case report
38 39
A 31-year-old female presented with amenorrhea lasting since fullterm normal delivery 19 months previously and generalized anasarca for more than 1 month prior to presentation. One month before admission she had developed progressive edema of her face, lower
U
37
40 41
extremities. Upon examination there was mild pallor, facial butterfly erythema, anasarca and ascites. Her blood pressure was 140/90 mmHg. A diagnosis of nephrotic syndrome (proteinuria with 24-h urine specimen, N 7 g/day) with normal kidney function was made (serum creatinine, 50 μmol/L and blood urea nitrogen 7.4 mmol/L). Her hemoglobin concentration was 117 g/L. Blood chemistry tests revealed levels of total serum protein of 42.2 g/L (normal ranges, 60–85 g/L), albumin 26 g/L (normal ranges, 35–51 g/L), triglyceride 1.96 mmol/L (normal ranges, 0.45–1.70 mmol/L), antistreptolysin-O 278 IU/ml, C4 complement 0.0716 g/L (normal ranges, 0.12–0.36 g/L). Tests for IgG type titer of antinuclear antibody were 1:320 (normal ranges, b1:40), but tests for C3 complement, anti-dsDNA antibody, rheumatoid factor, and C-reactive protein were within normal ranges. Because of the persistence of edema, hematuria and nephrotic proteinuria, a kidney biopsy was performed to confirm the diagnosis of glomerulopathy. Light microscopy revealed the renal cortex containing 30 glomeruli. None was sclerotic. There were diffuse and global endothelial and mesangium proliferation, widespread wireloops, thickened basement membranes with focal and segmental subendothelial aggregates and some duplication formation. The tubule epithelial cells were granular and showed vacuolar degeneration. The capillary loops were even and thin. There was no evidence of pathologic changes in the interstitium. Immunofluorescence showed a full-house immunofluorescence pattern, immunoglobulin G (++), IgM (++), IgA (+++), C3 (+++), and C1q (+++) along the glomerular basement membrane. Pathologic findings suggested diffuse global proliferative LN (Class IV-G, active index 11 scores) (Fig. 1). Induction therapy using glucocorticoids and cytotoxic drugs was started and lasted for almost 1 year. However, nephrotic syndrome (NS) didn't improve, as indicated by the persistently elevated levels of the 24-h urine protein, which ranged from 2.76 g to 4.81 g and renal function became poor with the blood urea nitrogen elevation exceeding normal limits. Because the patient's amenorrhea had persisted for more than 19 months with evidence of some uterine enlargement, serum human chorionic gonadotropin (β-hCG) levels were checked, which was elevated at 95.4 mIU/mL. Gynecological examination revealed a uterus of about 14 weeks gestation. An abdominopelvic magnetic resonance imaging (MRI) scan showed uterine expansion with a short T1 and long T2 signal. The uterine junction zone and myometrium were unclear, and the diffuse vascular flow void in myometrium and bilateral parametrium showed significant enhancement (Fig. 2). There was a
P
i n f o
D
c
E
b
O
5 6 7 8
F
3Q2
Lupus nephritis associated with placental site trophoblastic tumor: A case report and review of the literature
2
⁎ Corresponding author at: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuai fu yuan 1#, Dongcheng District, Beijing 100730, China. Fax: +86 10 65124875. E-mail address: [email protected] (Y. Xiang).
http://dx.doi.org/10.1016/j.gynor.2014.05.003 2211-338X/© 2014 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Please cite this article as: Xiao, C., et al., Lupus nephritis associated with placental site trophoblastic tumor: A case report and review of the literature, Gynecol Oncol Rep (2014), http://dx.doi.org/10.1016/j.gynor.2014.05.003
42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82
C. Xiao et al. / Gynecologic Oncology Reports xxx (2014) xxx–xxx
E
D
P
R O
O
F
2
E
R
R
91
O
89 90
C
87 88
showed strong cytoplasmic positivity for HPL and negative for β-hCG. Because of the patient's poor kidney function, she was not given chemotherapy. Two weeks later, a post-operative β-hCG reduced to 0.5 mIU/ml, which is just within normal limits (WNL, b5 mIU/ml). The quantity of the 24-h urine protein decreased to 0.40 g/L (normal ranges from 0 to 0.20 g/L). One month after operation the β-hCG level of this patient was WNL with no proteinuria. Additional follow-up visits for the subsequent 15 months showed no evidence of recurrence or metastasis of
N
85 86 Q3
little fluid in the pelvic cavity. Given the slightly elevated β-hCG level, enlarged uterus of about 14 weeks gestational size and diffuse lesions of the uterus by MRI scan, PSTT was highly suspected. But she was not suitable for chemotherapy with poor kidney function. A total abdominal hysterectomy with a bilateral salpingo-oophorectomy was performed. Pathologic investigation showed typical features of PSTT deeply infiltrating the whole layer of uterine corpus wall to the serosa (Young et al., 1985). Sections were immunohistochemically evaluated for β-hCG and human placental lactogen (HPL). These tumor cells
U
83 84
C
T
Fig. 1. (A) H&E staining shows increases in the number of glomerular cells, and visible thrombosis (arrow) (200×). (B) Periodic acid-Schiff staining shows a glomerulus with diffuse endothelial and mesangium proliferation (arrow) (400×). (C) Masson staining shows thickened basement membranes with focal and segmental subendothelial aggregates (400×). (D) Immunofluorescence photomicrograph displaying diffuse deposition of C1q along basement membranes (200×).
Fig. 2. Pelvic MRI scan showing uterine cavity expansion. (A) Scan showing diffuse vascular flow void in myometrium and (B) bilateral parametrium with a significant enhancement.
Please cite this article as: Xiao, C., et al., Lupus nephritis associated with placental site trophoblastic tumor: A case report and review of the literature, Gynecol Oncol Rep (2014), http://dx.doi.org/10.1016/j.gynor.2014.05.003
92 93 94 95 96 97 98 99 100
C. Xiao et al. / Gynecologic Oncology Reports xxx (2014) xxx–xxx t1:1 t1:2
3
Table 1 Review of literature of cases of renal lesions associated with GTD.
t1:3
Diagnosis of renal lesion
GTD
Author
Renal biopsy performed
No.
Year
t1:4 t1:5 t1:6 t1:7 t1:8 t1:9
Thrombotic microangiopathy Membranous glomerulonephritis Membranous glomerulopathy Membranous glomerulonephritis Membranoproliferative glomerulonephritis Occlusive eosinophilic deposit in capillary lumen
PSTT Invasive mole PSTT Choriocarcinoma Hydatiform mole PSTT
Mazzucco Mazzucco et al. (2011) Yang Yang et al. (2010) Batra Batra et al. (2007) Altiparmak Altiparmak et al. (2003) Komatsuda Komatsuda et al. (1992) Young Young et al. (1985)
Yes Yes Yes Yes Yes Yes
1 1 1 1 1 2
2011 2010 2007 2003 1992 1985
Gestational trophoblastic disease (GTD) is used to refer to a variety of gynecological tumors arising from the trophoblastic cells, including hydatidiform mole (complete or partial), choriocarcinoma, PSTT, and ETT. The malignant transformation of trophoblastic tissue can cause a paraneoplastic syndrome (Yang et al., 2010), which were thought to be mediated by an immune response to malignant cells. Sometimes, the clinical manifestations from the paraneoplastic syndrome are noted prior to the diagnosis of malignancy. A number of different types of glomerular disease, nephrotic or nephritic, may be associated with malignancy (Jhaveri et al., 2013). Effective treatment of the tumor generally leads to remission of the glomerular injury in these situations (Lefaucheur et al., 2006). The association of renal lesions and GTD is very rare. Only a few case reports have reported the association of NS with GTD (Altiparmak et al., 2003; Batra et al., 2007; Komatsuda et al., 1992; Mazzucco et al., 2011; Yang et al., 2010; Young et al., 1985), which were summarized in Table 1. In these cases, membranoproliferative glomerulonephritis (Komatsuda et al., 1992) has been found to be associated with hydatidiform mole, and membranous glomerulonephritis has been observed with invasive mole and choriocarcinoma (Altiparmak et al., 2003; Yang et al., 2010). For PSTT, there has been one reported case of TMA and another of membranous glomerulonephritis (Batra et al., 2007; Mazzucco et al., 2011). Only 2 other cases of PSTT and kidney lesions have been reported (Young et al., 1985). These glomerular lesions have also been observed in the present patient, although similar features may be observed under different circumstances. The present case suggests a diagnosis of a variant of LN. This conclusion is supported not only by light microscopy but also by immunohistochemistry findings. Conclusive evidence of LN comes from clinical and laboratory evidence. According to diagnostic criteria for SLE by the American College of Rheumatology in 1997, LN must be considered first. The mechanism may involve an immunologic process associated with LN, specifically the presence of complement and immunoglobulin on immunofluorescence and large subendothelial and smaller subepithelial and mesangial deposits, as indicated by light microscopy. Because there are several types of glomerulonephritis reported in association with epithelial and hematologic neoplasia, a relationship with the PSTT may exist (Jhaveri et al., 2013). In the present case, LN was considered secondary to PSTT, because this patient had presented with NS having amenorrhea for 19 months
119 120 121 122 123 124 125 126 127 128 129 Q4 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144
C
117 118
E
115 116
R
113 114
R
111 112
N C O
109 110
U
107 108
F
105 106
O
Discussion
R O
104
without a clear etiology. She had no previous history of systemic lupus erythematosus. She had received induction therapy with glucocorticoids and cytotoxic drugs for almost 1 year until PSTT was discovered when the clinical symptoms of LN didn't resolve with medical therapy. The fact that the clinical and biochemical features of nephrotic syndrome disappeared completely after the hysterectomy provides strong evidence that LN was secondary to PSTT, although the pathogenesis of this disease process is still unclear at this point. In conclusion, this case provides a highlight of the correlation between LN and PSTT and also highlights the nephritic complications of GTD. Written informed consent was obtained from the patient for the publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request.
P
103
PSTT. The patient currently remains free of clinical symptoms of LN. Tests for C3, C4, anti-dsDNA antibody, antinuclear antibody, rheumatoid factor, and C-reactive protein were all within normal ranges.
D
101 102
Conflict of interest statement We declare that we have no conflict of interest.
E
GTD: Gestational trophoblastic disease, PSTT: Placental site trophoblastic tumor.
T
t1:10
145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161
Acknowledgments
162
The authors thank all personnel of the medical record library of Peking Union Medical College Hospital for their data collection. This work was supported by a grant from the National Nature and Science Foundation of China (grant no. 81272890).
163
References
167
Altiparmak, M.R., Pamuk, O.N., Pamuk, G.E., et al., 2003. Membranous glomerulonephritis in a patient with choriocarcinoma: case report. South. Med. J. 96, 198–200. Batra, V., Kalra, O.P., Mathur, P., et al., 2007. Membranous glomerulopathy associated with placental site trophoblastic tumour: a case report. Nephrol. Dial. Transplant. 22, 1766–1768. Bologna, C., Jorgensen, C., Anaya, J.M., et al., 1994. Association of systemic lupus erythematosus and choriocarcinoma: a role of hormonal immunomodulation? Clin. Exp. Rheumatol. 12, 59–61. Jhaveri, K.D., Shah, H.H., Calderon, K., et al., 2013. Glomerular diseases seen with cancer and chemotherapy: a narrative review. Kidney Int. 84, 34–44. Komatsuda, A., Nakamoto, Y., K A, et al., 1992. Case report: nephrotic syndrome associated with a total hydatidiform mole. Am. J. Med. Sci. 303, 309–312. Lefaucheur, C., Stengel, B., Nochy, D., et al., 2006. Membranous nephropathy and cancer: epidemiologic evidence and determinants of high-risk cancer association. Kidney Int. 70, 1510–1517. Mazzucco, G., Colla, L., Monga, G., 2011. Kidney involvement in a patient affected by placental site trophoblastic tumor. Am. J. Kidney Dis. 57, 516–520. Scully, R.E., Young, R.H., 1981. Trophoblastic pseudotumor: a reappraisal. Am. J. Surg. Pathol. 5, 75–76. Yang, J.W., Choi, S.O., Kim, B.R., et al., 2010. Nephrotic syndrome associated with invasive mole: a case report. Nephrol. Dial. Transplant. 25, 2023–2026. Young, R.H., Scully, R.E., McCluskey, R.T., 1985. A distinctive glomerular lesion complicating placental site trophoblastic tumor: report of two cases. Hum. Pathol. 16, 35–42.
168 169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190
Please cite this article as: Xiao, C., et al., Lupus nephritis associated with placental site trophoblastic tumor: A case report and review of the literature, Gynecol Oncol Rep (2014), http://dx.doi.org/10.1016/j.gynor.2014.05.003
164 165 166
