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Mixed Epithelial and Stromal Tumor of the Kidney With Elevated Serum Level of Cancer Antigen 125
J Formos Med Assoc 2011;110(2):125–128
Contents lists available at ScienceDirect
Volume 110 Number 2 February 2011
Journal of the Formosan Medical Association
ISSN 0929 6646
Journal of the
Formosan Medical Association Will conjugated pneumococcal vaccines with more serotypes and fewer doses work better? Asymmetric dimethylarginine: clinical applications in pediatric medicine Physician supply and demand in anatomical pathology in Taiwan Outcome of severe obsessive–compulsive disorder
Journal homepage: http://www.jfma-online.com
Formosan Medical Association Taipei, Taiwan
Case Report
Mixed Epithelial and Stromal Tumor of the Kidney With Elevated Serum Level of Cancer Antigen 125 Chih-Hsin Liu,1 Chia-Cheng Yu,2* Chao-Ren Chang,2 Tony T. Wu,2 Jong-Khing Huang2 Mixed epithelial and stromal tumor of the kidney is a newly categorized lesion, with few reported cases. We report a rare case of a 45-year-old woman with a palpable abdominal mass and elevated serum level of serum cancer antigen 125, who was not receiving hormones or contraceptive agents. Abdominal magnetic resonance imaging revealed a large multilocular cystic tumor that arose in the left central kidney. Nephrectomy was performed under the initial impression of cystic renal cell carcinoma; however, a diagnosis of mixed epithelial and stromal tumor was confirmed according to pathological and immunohistochemical findings. Serum level of cancer antigen 125 returned to normal after 1 month postoperatively, and no recurrence was found in the following 18 months. Key Words: CA-125, kidney tumor, mixed epithelial and stromal tumor, ovarian-type stroma
Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare and complex tumor that occurs mostly in middle-aged women. To date, there have only been about 70 cases reported worldwide. In this article, we present a 45-year-old woman with MESTK, who had no history of iatrogenic hormone use. We suggest that serum cancer antigen (CA)-125 plays an important role in the diagnosis and postoperative follow-up.
from the pancreatic tail or the left kidney, which was found by abdominal computed tomography at a local hospital. Abdominal fullness was intermittently observed for about 1 year and a palpable abdominal mass was noted more recently. Tracing back her history, she underwent uterine myomectomy 6 years ago, besides which, she had received no exogenous hormonal treatment for any other reason at any other time. Preoperative biochemical and hematological surveys, including renal function tests, were all within normal ranges (blood urea nitrogen/ creatinine: 15/0.8 mg/dL), except for elevated serum level of CA-125 (63.76 U/mL; normal: < 35.0 U/mL). Otherwise, we noted no flank
Case Report A 45-year-old perimenopausal woman was referred because of a large cystic tumor that originated
©2011 Elsevier & Formosan Medical Association .
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1
Division of Plastic and Reconstructive Surgery, School of Medicine, National Yang-Ming University, Taipei, 2Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. Received: June 2, 2009 Revised: July 6, 2009 Accepted: September 17, 2009
*Correspondence to: Dr Chia-Cheng Yu, Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, 813 Taiwan. E-mail: [email protected]
J Formos Med Assoc | 2011 • Vol 110 • No 2
125
C.H. Liu, et al
pain, gross hematuria, or other endometriosisassociated symptoms, including dysmenorrhea and dyspareunia. Abdominal magnetic resonance imaging revealed a large multilocular cystic tumor that was derived from the ventral cortex of the left central kidney (Figure 1), which was initially considered to be cystic nephroma (CN) or cystic renal cell carcinoma (RCC). This large, centrally located renal tumor was poorly demarcated from its neighboring parenchyma, and the possibility of a malignant renal tumor could not be excluded; therefore, we performed a left radical nephrectomy to completely remove the tumor. The excised specimen was 16 × 13 × 9.5 cm and consisted of an ivory-white, mixed multicystic and solid tumor without necrosis (Figure 2). Microscopic assessment revealed a multilocular cystic lesion that was lined by a columnar or cuboidal epithelium (Figure 3A), and occasionally, this epithelial layer appeared as small papillary tufts that were called “hobnail cells” (Figure 3B). Among the cysts, ovarian-type stroma was composed of mixed solid parts. Meanswhile, in most fields under the microscope, the paucicellular part and the cellular part formed by spindle cells were presented simultaneously in one picture. Some complex branching channels in the stroma containing focal cellular parts (formed majorly spindle cells) were also found. Furthermore, immunohistochemical staining showed that
Michal and Syrucek1 initially defined the term MESTK to demonstrate the biphasic morphology of this tumor, which comprises both cystic and solid components. In 2000, Adsay et al2 described the immunohistochemical characteristics of this newly categorized neoplasm and suggested the possible hormonal role in tumor formation. Recently, Turbiner et al3 compared MESTK with cystic nephroma and coined a new term, renal epithelial and stromal tumor, to encompass both MESTK and CN according to their similarities, although there are still some differences between them. MESTK, as in our case, is basically benign and frequently occurs in perimenopausal women (mean age: 52 years).3 To date, there have been only three male cases of MESTK.2,4–6 The clinical
Figure 1. T2-weighted coronal magnetic resonance imaging showed a well-circumscribed and multicystic tumor that originated from the left kidney.
Figure 2. The excised specimen consisted of an ivory-white, mixed multicystic and solid tumor without necrosis.
126
the stromal cells were positive for estrogen receptor, progesterone receptor, and smooth muscle markers (HHF-35 and desmin) (Figures 3C–F). Therefore, a diagnosis of MESTK was confirmed. The postoperative course was uneventful and the patient was discharged on postoperative day 5. During postoperative follow-up, serum CA-125 returned to normal after 1 month, and there was no tumor recurrence or metastasis during 18 months postoperative follow-up.
Discussion
J Formos Med Assoc | 2011 • Vol 110 • No 2
Kidney mixed epithelial and stromal tumor
A
B
C
D
E
F
Figure 3. (A) MESTK was composed of complex multilocular cysts and gland-enriched stromal areas (hematoxylin & eosin, original magnification 40×). (B) At high power, the cyst was lined by columnar, cuboidal, or flattened epithelium, which partially formed small papillary tufts (hobnail cells) (hematoxylin & eosin, original magnification 400×). (C) Estrogen receptors and (D) progesterone receptors were seen in the nuclei of the stromal cells of MESTK (original magnification 100×). Smooth muscle markers such as (E) HHF-35 and (F) desmin were also seen in the stromal area of MESTK (original magnification 100×). MESTK = Mixed epithelial and stromal tumor of the kidney.
presentation of MESTK includes abdominal mass, flank pain, hematuria, and urinary tract infection.7 Based on the 2004 World Health Organization classification of adult renal tumors,8 MESTK is defined as a complex tumor composed of multilocular cysts lined by columnar or cuboidal J Formos Med Assoc | 2011 • Vol 110 • No 2
epithelium, thicker cystic septa (≥ 5 mm microscopically; the major difference from CN), and ovarian-type stroma which is formed of variable spindle cells. Most reported cases of MESTK show benign histological features and clinical course; however, there have been reports of nine cases of 127
C.H. Liu, et al
MESTK with malignant transformation.9–11 Eight of these were found to contain sarcomatous components in the stroma, and the other had rhabdoid features.11 To date, opinions about the pathogenesis of MESTK are controversial. Through a study of the ovarian-type stroma in pancreatic mucinous cystic tumors, Izumo et al12 have found that the similarity between the ovarian-type and true ovarian stroma included inhibin-positive luteinized cells and stromal positivity for estrogen and progesterone receptors. These similarities could also provide embryological clues to the origin of tumors with ovarian-type stroma, such as MESTK, hepatobiliary cystadenoma, pancreatic mucinous cystic tumor, and primary retroperitoneal mucinous cystadenocarcinoma. The formation of MESTK has two possible hypotheses. One is the fetal primitive mesenchyme in the kidney, which could be hyperstimulated by hormonal imbalance. The other is that the ovarian stromal cells migrate to the ureteric bud and metanephric mesoderm during embryogenesis. In our study, abnormal elevation of CA-125 provided evidence to support both these hypotheses. It is difficult to distinguish MESTK from CN and cystic RCC preoperatively by radiographic assessment because of their gross morphological similarities. Also, percutaneous renal biopsy gives a limited sample and increases the possible risk of extension of malignant cells, especially if the cystic RCC is pathologically confirmed later from the surgical specimen. Hence, a definite diagnosis ought to be based on the pathological results. In the present case, radical nephrectomy was carried out because it is technically difficult to remove completely the poorly demarcated tumor and preserve the function of the remnant kidney simultaneously. However, based on the relatively benign nature of MESTK and recent changes in surgical intervention for small RCC, we suggest that nephron-sparing surgery can still be regarded as the first-choice treatment of MESTK. In conclusion, MESTK is a rare, femalepredominant neoplasm with complex cystic and solid components. Only a few malignant cases 128
have been reported. In our case, serum CA-125 level played an important role in diagnosis and postoperative follow-up. Moreover, the abnormal elevation of CA-125 also supports the current hypotheses about the pathogenesis of MESTK. Due to the relatively low possibility of malignancy, nephron-sparing surgery can be considered as the treatment of choice, if technically feasible.
References 1. Michal M, Syrucek M. Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract 1998;194:445–8. 2. Adsay NV, Eble JN, Srigley JR, et al. Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 2000;24: 958–70. 3. Turbiner J, Amin MB, Humphrey PA, et al. Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term. Am J Surg Pathol 2007;31:489–500. 4. Colombo P, Naspro R, Vallieri L, et al. Non-hormone-induced mixed epithelial and stromal tumor of kidney in a man: description of a rare case. Urology 2008;71:168, e7–9. 5. Yang Y, Nie X, Lu J, et al. Mixed epithelial and stromal tumor of kidney. Zhonghua Bing Li Xue Za Zhi 2006;35:29–31. 6. Michal M, Hes O, Bisceglia M, et al. Mixed epithelial and stromal tumors of the kidney. A report of 22 cases. Virchows Arch 2004;445:359–67. 7. Montironi R, Mazzucchelli R, Lopez-Beltran A, et al. Cystic nephroma and mixed epithelial and stromal tumour of the kidney: opposite ends of the spectrum of the same entity? Eur Urol 2008;54:1237–46. 8. Lopez-Beltran A, Scarpelli M, Montironi R, et al. 2004 WHO classification of the renal tumors of the adults. Eur Urol 2006;49:798–805. 9. Lane BR, Campbell SC, Remer EM, et al. Adult cystic nephroma and mixed epithelial and stromal tumor of the kidney: clinical, radiographic, and pathologic characteristics. Urology 2008;71:1142–8. 10. Jung SJ, Shen SS, Tran T, et al. Mixed epithelial and stromal tumor of kidney with malignant transformation: report of two cases and review of literature. Hum Pathol 2008;39: 463–8. 11. Sukov WR, Cheville JC, Lager DJ, et al. Malignant mixed epithelial and stromal tumor of the kidney with rhabdoid features: report of a case including immunohistochemical, molecular genetic studies and comparison to morphologically similar renal tumors. Hum Pathol 2007;38:1432–7. 12. Izumo A, Yamaguchi K, Eguchi T, et al. Mucinous cystic tumor of the pancreas: immunohistochemical assessment of “ovarian-type stroma”. Oncol Rep 2003;10:515–25.
J Formos Med Assoc | 2011 • Vol 110 • No 2
Contents lists available at ScienceDirect
Volume 110 Number 2 February 2011
Journal of the Formosan Medical Association
ISSN 0929 6646
Journal of the
Formosan Medical Association Will conjugated pneumococcal vaccines with more serotypes and fewer doses work better? Asymmetric dimethylarginine: clinical applications in pediatric medicine Physician supply and demand in anatomical pathology in Taiwan Outcome of severe obsessive–compulsive disorder
Journal homepage: http://www.jfma-online.com
Formosan Medical Association Taipei, Taiwan
Case Report
Mixed Epithelial and Stromal Tumor of the Kidney With Elevated Serum Level of Cancer Antigen 125 Chih-Hsin Liu,1 Chia-Cheng Yu,2* Chao-Ren Chang,2 Tony T. Wu,2 Jong-Khing Huang2 Mixed epithelial and stromal tumor of the kidney is a newly categorized lesion, with few reported cases. We report a rare case of a 45-year-old woman with a palpable abdominal mass and elevated serum level of serum cancer antigen 125, who was not receiving hormones or contraceptive agents. Abdominal magnetic resonance imaging revealed a large multilocular cystic tumor that arose in the left central kidney. Nephrectomy was performed under the initial impression of cystic renal cell carcinoma; however, a diagnosis of mixed epithelial and stromal tumor was confirmed according to pathological and immunohistochemical findings. Serum level of cancer antigen 125 returned to normal after 1 month postoperatively, and no recurrence was found in the following 18 months. Key Words: CA-125, kidney tumor, mixed epithelial and stromal tumor, ovarian-type stroma
Mixed epithelial and stromal tumor of the kidney (MESTK) is a rare and complex tumor that occurs mostly in middle-aged women. To date, there have only been about 70 cases reported worldwide. In this article, we present a 45-year-old woman with MESTK, who had no history of iatrogenic hormone use. We suggest that serum cancer antigen (CA)-125 plays an important role in the diagnosis and postoperative follow-up.
from the pancreatic tail or the left kidney, which was found by abdominal computed tomography at a local hospital. Abdominal fullness was intermittently observed for about 1 year and a palpable abdominal mass was noted more recently. Tracing back her history, she underwent uterine myomectomy 6 years ago, besides which, she had received no exogenous hormonal treatment for any other reason at any other time. Preoperative biochemical and hematological surveys, including renal function tests, were all within normal ranges (blood urea nitrogen/ creatinine: 15/0.8 mg/dL), except for elevated serum level of CA-125 (63.76 U/mL; normal: < 35.0 U/mL). Otherwise, we noted no flank
Case Report A 45-year-old perimenopausal woman was referred because of a large cystic tumor that originated
©2011 Elsevier & Formosan Medical Association .
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1
Division of Plastic and Reconstructive Surgery, School of Medicine, National Yang-Ming University, Taipei, 2Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. Received: June 2, 2009 Revised: July 6, 2009 Accepted: September 17, 2009
*Correspondence to: Dr Chia-Cheng Yu, Division of Urology, Department of Surgery, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, Kaohsiung, 813 Taiwan. E-mail: [email protected]
J Formos Med Assoc | 2011 • Vol 110 • No 2
125
C.H. Liu, et al
pain, gross hematuria, or other endometriosisassociated symptoms, including dysmenorrhea and dyspareunia. Abdominal magnetic resonance imaging revealed a large multilocular cystic tumor that was derived from the ventral cortex of the left central kidney (Figure 1), which was initially considered to be cystic nephroma (CN) or cystic renal cell carcinoma (RCC). This large, centrally located renal tumor was poorly demarcated from its neighboring parenchyma, and the possibility of a malignant renal tumor could not be excluded; therefore, we performed a left radical nephrectomy to completely remove the tumor. The excised specimen was 16 × 13 × 9.5 cm and consisted of an ivory-white, mixed multicystic and solid tumor without necrosis (Figure 2). Microscopic assessment revealed a multilocular cystic lesion that was lined by a columnar or cuboidal epithelium (Figure 3A), and occasionally, this epithelial layer appeared as small papillary tufts that were called “hobnail cells” (Figure 3B). Among the cysts, ovarian-type stroma was composed of mixed solid parts. Meanswhile, in most fields under the microscope, the paucicellular part and the cellular part formed by spindle cells were presented simultaneously in one picture. Some complex branching channels in the stroma containing focal cellular parts (formed majorly spindle cells) were also found. Furthermore, immunohistochemical staining showed that
Michal and Syrucek1 initially defined the term MESTK to demonstrate the biphasic morphology of this tumor, which comprises both cystic and solid components. In 2000, Adsay et al2 described the immunohistochemical characteristics of this newly categorized neoplasm and suggested the possible hormonal role in tumor formation. Recently, Turbiner et al3 compared MESTK with cystic nephroma and coined a new term, renal epithelial and stromal tumor, to encompass both MESTK and CN according to their similarities, although there are still some differences between them. MESTK, as in our case, is basically benign and frequently occurs in perimenopausal women (mean age: 52 years).3 To date, there have been only three male cases of MESTK.2,4–6 The clinical
Figure 1. T2-weighted coronal magnetic resonance imaging showed a well-circumscribed and multicystic tumor that originated from the left kidney.
Figure 2. The excised specimen consisted of an ivory-white, mixed multicystic and solid tumor without necrosis.
126
the stromal cells were positive for estrogen receptor, progesterone receptor, and smooth muscle markers (HHF-35 and desmin) (Figures 3C–F). Therefore, a diagnosis of MESTK was confirmed. The postoperative course was uneventful and the patient was discharged on postoperative day 5. During postoperative follow-up, serum CA-125 returned to normal after 1 month, and there was no tumor recurrence or metastasis during 18 months postoperative follow-up.
Discussion
J Formos Med Assoc | 2011 • Vol 110 • No 2
Kidney mixed epithelial and stromal tumor
A
B
C
D
E
F
Figure 3. (A) MESTK was composed of complex multilocular cysts and gland-enriched stromal areas (hematoxylin & eosin, original magnification 40×). (B) At high power, the cyst was lined by columnar, cuboidal, or flattened epithelium, which partially formed small papillary tufts (hobnail cells) (hematoxylin & eosin, original magnification 400×). (C) Estrogen receptors and (D) progesterone receptors were seen in the nuclei of the stromal cells of MESTK (original magnification 100×). Smooth muscle markers such as (E) HHF-35 and (F) desmin were also seen in the stromal area of MESTK (original magnification 100×). MESTK = Mixed epithelial and stromal tumor of the kidney.
presentation of MESTK includes abdominal mass, flank pain, hematuria, and urinary tract infection.7 Based on the 2004 World Health Organization classification of adult renal tumors,8 MESTK is defined as a complex tumor composed of multilocular cysts lined by columnar or cuboidal J Formos Med Assoc | 2011 • Vol 110 • No 2
epithelium, thicker cystic septa (≥ 5 mm microscopically; the major difference from CN), and ovarian-type stroma which is formed of variable spindle cells. Most reported cases of MESTK show benign histological features and clinical course; however, there have been reports of nine cases of 127
C.H. Liu, et al
MESTK with malignant transformation.9–11 Eight of these were found to contain sarcomatous components in the stroma, and the other had rhabdoid features.11 To date, opinions about the pathogenesis of MESTK are controversial. Through a study of the ovarian-type stroma in pancreatic mucinous cystic tumors, Izumo et al12 have found that the similarity between the ovarian-type and true ovarian stroma included inhibin-positive luteinized cells and stromal positivity for estrogen and progesterone receptors. These similarities could also provide embryological clues to the origin of tumors with ovarian-type stroma, such as MESTK, hepatobiliary cystadenoma, pancreatic mucinous cystic tumor, and primary retroperitoneal mucinous cystadenocarcinoma. The formation of MESTK has two possible hypotheses. One is the fetal primitive mesenchyme in the kidney, which could be hyperstimulated by hormonal imbalance. The other is that the ovarian stromal cells migrate to the ureteric bud and metanephric mesoderm during embryogenesis. In our study, abnormal elevation of CA-125 provided evidence to support both these hypotheses. It is difficult to distinguish MESTK from CN and cystic RCC preoperatively by radiographic assessment because of their gross morphological similarities. Also, percutaneous renal biopsy gives a limited sample and increases the possible risk of extension of malignant cells, especially if the cystic RCC is pathologically confirmed later from the surgical specimen. Hence, a definite diagnosis ought to be based on the pathological results. In the present case, radical nephrectomy was carried out because it is technically difficult to remove completely the poorly demarcated tumor and preserve the function of the remnant kidney simultaneously. However, based on the relatively benign nature of MESTK and recent changes in surgical intervention for small RCC, we suggest that nephron-sparing surgery can still be regarded as the first-choice treatment of MESTK. In conclusion, MESTK is a rare, femalepredominant neoplasm with complex cystic and solid components. Only a few malignant cases 128
have been reported. In our case, serum CA-125 level played an important role in diagnosis and postoperative follow-up. Moreover, the abnormal elevation of CA-125 also supports the current hypotheses about the pathogenesis of MESTK. Due to the relatively low possibility of malignancy, nephron-sparing surgery can be considered as the treatment of choice, if technically feasible.
References 1. Michal M, Syrucek M. Benign mixed epithelial and stromal tumor of the kidney. Pathol Res Pract 1998;194:445–8. 2. Adsay NV, Eble JN, Srigley JR, et al. Mixed epithelial and stromal tumor of the kidney. Am J Surg Pathol 2000;24: 958–70. 3. Turbiner J, Amin MB, Humphrey PA, et al. Cystic nephroma and mixed epithelial and stromal tumor of kidney: a detailed clinicopathologic analysis of 34 cases and proposal for renal epithelial and stromal tumor (REST) as a unifying term. Am J Surg Pathol 2007;31:489–500. 4. Colombo P, Naspro R, Vallieri L, et al. Non-hormone-induced mixed epithelial and stromal tumor of kidney in a man: description of a rare case. Urology 2008;71:168, e7–9. 5. Yang Y, Nie X, Lu J, et al. Mixed epithelial and stromal tumor of kidney. Zhonghua Bing Li Xue Za Zhi 2006;35:29–31. 6. Michal M, Hes O, Bisceglia M, et al. Mixed epithelial and stromal tumors of the kidney. A report of 22 cases. Virchows Arch 2004;445:359–67. 7. Montironi R, Mazzucchelli R, Lopez-Beltran A, et al. Cystic nephroma and mixed epithelial and stromal tumour of the kidney: opposite ends of the spectrum of the same entity? Eur Urol 2008;54:1237–46. 8. Lopez-Beltran A, Scarpelli M, Montironi R, et al. 2004 WHO classification of the renal tumors of the adults. Eur Urol 2006;49:798–805. 9. Lane BR, Campbell SC, Remer EM, et al. Adult cystic nephroma and mixed epithelial and stromal tumor of the kidney: clinical, radiographic, and pathologic characteristics. Urology 2008;71:1142–8. 10. Jung SJ, Shen SS, Tran T, et al. Mixed epithelial and stromal tumor of kidney with malignant transformation: report of two cases and review of literature. Hum Pathol 2008;39: 463–8. 11. Sukov WR, Cheville JC, Lager DJ, et al. Malignant mixed epithelial and stromal tumor of the kidney with rhabdoid features: report of a case including immunohistochemical, molecular genetic studies and comparison to morphologically similar renal tumors. Hum Pathol 2007;38:1432–7. 12. Izumo A, Yamaguchi K, Eguchi T, et al. Mucinous cystic tumor of the pancreas: immunohistochemical assessment of “ovarian-type stroma”. Oncol Rep 2003;10:515–25.
J Formos Med Assoc | 2011 • Vol 110 • No 2