Pediatric Hematology and Oncology
ISSN: 0888-0018 (Print) 1521-0669 (Online) Journal homepage: http://www.tandfonline.com/loi/ipho20
Preoperative Chemotherapy of Cellular Congenital Mesoblastic Nephroma in a 5-Month-Old Infant Jean-Philippe Stalens, Serge Gosseye, Philippe Clapuyt & Jacques Ninane To cite this article: Jean-Philippe Stalens, Serge Gosseye, Philippe Clapuyt & Jacques Ninane (1992) Preoperative Chemotherapy of Cellular Congenital Mesoblastic Nephroma in a 5-Month-Old Infant, Pediatric Hematology and Oncology, 9:4, 335-345, DOI: 10.3109/08880019209016605 To link to this article: http://dx.doi.org/10.3109/08880019209016605
Published online: 09 Jul 2009.
Submit your article to this journal
Article views: 7
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipho20 Download by: [RMIT University Library]
Date: 27 April 2016, At: 05:14
Siron! Communication
PREOPERATIVE CHEMOTHERAPY OF CELLULAR CONGENITAL MESOBLASTIC NEPHROMA IN A 5-MONTH-OLD INFANT
Jean-Philippe Stalens, MD
Downloaded by [RMIT University Library] at 05:14 27 April 2016
0 Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium
Serge Cosseye, MD
0 Department of Pathology, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium
Philippe Clapuyt, MD 0 Division of Pediatric Radiology, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium JacquesNinane, MD, PhD
Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium
0 Cellular (or aopical) congenital mesoblastic nephroma (CMN) is a potentially agpessive form of the benign classical congenital mesoblastic nebhroma. WC report here a case of cellular C M N in a 5-monthold boy treated preoperatively with chemotherapy with an excellent response allowing a complete surgical resection.
KEY WORDS: cellular coqenital mesoblastic ncphroma, injants, chemotherapy.
I NTRODUCTlON Congenital mesoblastic nephroma (CMN) is the most common renal neo1-3 plasm in the first few months of life. The classical form has a benign course justifying nephrectomy alone as the treatment of choice with an excellent p r o g n ~ s i sThe . ~ cellular (or atypical) form of CMN is more aggressive, especially when complete resection is not possible and when the infant is older than 3 The authors are very grateful to Dr. J. Bruce Beckwith from the Children’s Hospital, Denver, for his very helpful review of the pathology material and his contribution to the diagnosis.
Pediatric he ma to lo^ and O n c o l o ~ ,9:335-345, I992 Copyright @ 1992 by Hemisphere Publishing Corporation
335
336
L-P.STALENS ET A 1
We report here our experience with a 5-month-old infant with a cellular CMN invading the neighboring organs. He was treated with preoperative chemotherapy resulting in a dramatic response and allowing a complete surgical resection.
Downloaded by [RMIT University Library] at 05:14 27 April 2016
CASE REPORT This white boy was the product of normal gestation and delivery. At the age of 2 months, he was admitted for a viral meningitis from which he recovered completely. He presented at 5 months of age with a 10-day history of numerous episodes of crying that lasted for 20-30 minutes with pallor, sweating, and nausea, and ending with a loose stool. He was then seen by his pediatrician who noticed an enlarged abdomen and palpated a right flank mass. The child was then referred for further investigations. Upon admission, a very large mass was palpable in the right side of the abdomen which was tense. The rest of the physical examination was normal. Laboratory data were normal including renal function. Ultrasonography and computerized axial tomography (CT) of the abdomen revealed that the right side of the abdomen was filled by an enormous retroperitoneal mass containing many internal septations (Figures 1 and 2). It seemed to be attached to the right kidney, which was displaced toward the midline. Chest and bone X rays were unremarkable. Bone marrow examination was normal. An exploratory laporatomy with biopsy of the mass was then performed. The specimen measured about 9 X 8 X 7 mm. Histological examination showed a homogeneous, dense proliferation of rather small, round to moderately elongated cells with scanty eosinophilic cytoplasm (Figure 3). The nucleus was hyperchromatic, round to ovoid, sometimes with a small nucleolus, and showed some variations in size and some irregularities in shape. Mitoses were numerous. The diagnosis of embryonal rhabdomyosarcoma was then suggested. Since the tumor was unresectable, the child was first treated with chemotherapy. Four courses of the IVA regimen were given at 3-week intervals: vincristine 1.5 mg/m2, actinomycin D 0.5 mg/m2, and ifosfamide 2 g/m2/day for two consecutive days. The tumor shrank dramatically as demonstrated by clinical examination and imaging. Indeed, a repeated C T scan showed only a very small tumor originating from the right kidney (Figure 4). The child then underwent a right radical nephrectomy with extensive lymph node dissection. The tumor was adherent to the colon and a right colectomy with ileotransverse anastomosis had to be performed. The resected specimen included the right kidney, perirenal fat, the right adrenal, a segment of proximal ureter, renal vessels with lymph nodes and,
v
W W
seen in the right hemiabdomen pushing the kidney forward (arrowheads). There is a focal close connection between the tumor and the renal parenchyma (short black arrows).
FIGURE 1. Ultrasound study (US): transverse section of the right flank. A huge multicystic retroperitoneal mass (thin white arrows) is
Downloaded by [RMIT University Library] at 05:14 27 April 2016
FIGURE 2. CT scan with contrast IV injection: same data as US. Note a small solid mass at the site of connection between the tumor and the kidney (star). Hypodensity of the renal parenchyma in front of this abnormality (arrowheads).
Downloaded by [RMIT University Library] at 05:14 27 April 2016
339
Downloaded by [RMIT University Library] at 05:14 27 April 2016
CHEMOTHERAPY OF MESOBLASTIC NEPHROMA
FIGURE 3. Histological appearance of the biopsy specimen. At least four mitoses are seen in this field (H&E, X420).
separately, a segment of terminal ileum with a piece of mesentery, cecum, appendix, and ascending colon. In the perirenal fat, in contact with the surface of the kidney there was an ill-defined mass extending from the middle part of the external border to the lower pole, measuring about 5 X 2 X 2 cm and composed of a tissue of variegated consistency and appearance. Slightly below the middle part of the kidney, there was a horizontal strand of whitish, fibrous tissue across the
w
e 0
between this abnormality and the renal cortex. Note also the defect of renal parenchymography in front of it (arrowheads).
FIGURE 4. CT scan after chemotherapy. Dramatic reduction of tumor size. Persistent infiltration of perirenal fat (star) and connection
Downloaded by [RMIT University Library] at 05:14 27 April 2016
Downloaded by [RMIT University Library] at 05:14 27 April 2016
CHEMOTHERAPY OF MESOBLASTIC NEPHROMA
341
kidney, joining the renal sinus to the external border of the kidney where it came in contact with the extrarenal mass. Microscopic examination of the mass along the kidney showed infiltration of adipose tissue by a process similar to that seen on the biopsy, except that the background was often fairly myxoid and numerous collections of foamy and hemosiderin-laden macrophages were seen. In addition, the cellular proliferation contained variably sized cavities lined by a row of tumor cells assuming a vaguely epithelial appearance, and one group of a few small undifferentiated tubules similar to nephroblastoma tubules was observed at a distance from the kidney (Figure 5). Also noticeable were groups of fairly large vessels sometimes with a thick fibromuscular wall. Immunoperoxidase staining for desmin, myoglobin, neuron specific enolase, protein SlOO, cytokeratin, epithelial membrane antigen (EMA), and vimentin were performed on blocks of the mass and on the biopsy. The tumor cells were convincingly positive only for vimentin. The fibrotic band across the kidney had an indistinct border interdigitating with the adjacent renal parenchyma and was made of a moderately cellular connective tissue containing cystically dilated renal glomeruli and tubes and some small undifferentiated tubules. Also present were dysplastic-type tubes with a collarette of stromal cells in the medulla and a small piece of cartilage. From the area where the fibrous strand abutted on the renal surface, one could see fascicles of leiomyoma-like mesenchymal cells irradiating in the perirenal fat and merging into the preponderant, more cellular component of the extrarenal tumor (Figure 6). In the specimen of bowel resection, the intestinal wall was intact but the piece of mesentery was infiltrated by the tumor. The final diagnosis was cellular mesoblastic nephroma growing mostly outside the kidney with an intrarenal lesion having the feature of both medullary renal dysplasia and intralobar nephrogenic rest, and with an small area of more conventional leiomyoma-like mesoblastic nephroma on the surface of the kidney at the junction of the intrarenal lesion with the extrarenal tumor. We elected to give postoperative chemotherapy for four reasons: (1) our patient was older than 3 months at that time and had obviously a cellular invasive mesoblastic nephroma, two features of poor prognosis; (2) he had responded dramatically to chemotherapy; (3) despite the young age, chemotherapy was well tolerated; and (4) although the resection was macroscopically complete, there was some doubt about possible microscopic residues in the mesentery. This postoperative chemotherapy consisted of nine courses of vincristine (1.5 mg/m2), cyclophosphamide (600 mg/m2), and actinomycin D (0.5 mg/kg) every three weeks. No major adverse reaction was noted. The patient is receiving no treatment and there is no evidence of disease 21 months from diagnosis, 18 months after surgery, and 12 months after the end of chemotherapy.
Downloaded by [RMIT University Library] at 05:14 27 April 2016
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J.-R STALENS ET AL
FIGURE 5. Group of tubules among hemosiderin-laden macrophages in the tumor, at a distance from the kidney (H&E, X 420).
DISCUSSION Our patient was 5 months old when he developed a cellular mesoblastic nephroma which became resectable thanks to preoperative chemotherapy. Bolande in 1967 was the first to identify CMN as a distinctive type of neoplasm and to distinguish it clearly from Wilms' tumor.'" This distinction is important since the classical form of CMN has a benign course and only requires nephre~tomy."'~
Downloaded by [RMIT University Library] at 05:14 27 April 2016
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343
CMN is a rare tumor. However, it is the most common renal neoplasm in the first few months of life,Is3justifying the recommendation that nephrectomy be the initial treatment of a renal solid tumor in the first year of life.4 Since 1973, a cellular (also called atypical) variant of CMN has been described. Seven cases of relapse (local recurrence or pulmonary metastasis) have been reported in infants with cellular CMN"" and 3 of them died. Reviewing the prognostic factors of cellular CMN, Beckwith found that adequacy of surgical resection and age at presentation are the determining factors of prognosis in patients with recurrent disease. He notes that cellular CMN in 10 a patient older than 3 months is of concern. Gormley, however, believed that an infiltrated surgical margin is the only statistically significant factor that predicts recurrence in cellular CMN regardless of the age of presentation and suggests initial surgery, early reexploration for gross residual disease, and VAC chemotherapy associating vincristine, actinomycin D, and cyclophosphamide in case of microscopic residual disease or rupture of the tumor.'' Chan's opinion is a little different. He advises adjuvant chemotherapy for older infants with grossly unresected tumors and those patients whose tumors have an unequivocally malignant histological appearance or evidence of aggressive biological behavior. l 3
FIGURE 6. Cellular rnesoblastic nephrorna infiltrating perirenal fat on the let, and classical appearance of rnesoblastic nephrorna on the right (H&E, X 140).
Downloaded by [RMIT University Library] at 05:14 27 April 2016
344
J.-P. STALENS ET AL
In our case, because of an uncertain initial diagnosis due to the extrarenal localization of the tumor and to a biopsy suggesting an embryonal rhabdomyosarcoma, a preoperative chemotherapy associating ifosfamide, vincristine, and actinomycin D was given. This treatment led to a major decrease in the volume of this cellular CMN and allowed its complete surgical resection. The diagnosis of cellular CMN was given only 3 months after the operation. In the meanwhile we gave a postoperative chemotherapy as for a rhabdomyosarcoma. Since ifosfamide is known to be more toxic in a patient having only one kidney,l4 we replaced ifosfamide with cyclophosphamide and gave nine courses of VAC therapy. The tumor in this case was very peculiar by its almost exclusive extrarenal growth, which is the reason a diagnosis of mesoblastic nephroma was not even contemplated at the beginning. Another interesting feature is the coexistence of an intrarenal lesion from which the tumor seemed to originate. A part of this lesion had obvious features of intralobar nephrogenic rest15 while other parts had features of medullary dysplasia.I6 A piece of cartilage was found in the area resembling a nephrogenic rest but, as no cartilage has been described in typical nephrogenic rests, its presence might be linked to the associated dysplasia. This case shows that preoperative chemotherapy associating ifosfamide (2 g/m‘ for two consecutive days), vincristine (1.5 mg/m2), and actinomycin D (0.5 mg/m2) is effective in cellular CMN. Such a treatment should, however, be restricted to the cellular form of CMN in which the preoperative evaluation identifies an invasive and not a completely resectable neoplasm.
REFERENCES 1. Bolande RP, Brough AJ, Izant RJ. Congenital mesoblastic nephroma of infancy. Pediatrics. 1967;40:272-278. 2. Bolande RP. Congenital mesoblastic nephroma of infancy. Persp Pediutr Padol. 1973;1:227-250. 3. Bolande RP. Congenital and infantile neoplasia of the kidney. Lunccf. 1974;11:1497-1499. 4. Howell CG, Othersen HB, Kiviat NE, Norkool P, Beckwith JB, D’Angio GJ. Therapy and outcome in 51 children with mesoblastic nephroma: a report of the National Wilms’ Tumor Study. J Ptdiutr Surf. 1982; 17:826-831. 5. Joshi VV, Kay S, Milsten R, Koontz WW, McWilliams NB. Congenital mesoblastic nephroma of infancy. Report of a case with unusual clinical behavior. Am J Clin Pufhol. 1973;60:811-816. 6. Joshi W, Kasznica J, Walters TR. Atypical mesoblastic nephroma: pathologic characterization of potentially aggressive variant of conventional congenital mesoblastic nephroma. Arch Pufhol Lob Med. 1986; 110: 100- 106. 7. Stenfeld AD, Growley CA, O’Shea PA, Tefft M. Recurrent and metastatic mesoblastic nephroma in infancy. J Clin Oncol. 1984;2:956-960. 8. Walker D, Richard GA. Fetal mesenchymal hamartoma of the kidney. Recurrence and death of a patient. J Urol. 1973;110:352-353. 9. Gonzales-Crussi F, Sotelo-Avila C, Kidd JM. Malignant mesenchymal nephroma of infancy: report of a case with pulmonary metastases. Am J Sua Puthol. 1980;4:185-190.
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10. Beckwith JB, Weeks DA. Congenital mesoblastic nephroma: when should we worry? Arch Pafhol Lab Med. 1986;110:98. 11. Gormley TS,Skoog SJ, Jones RV, Maybee D. Cellular congenital mesoblastic nephroma: what are the options? J Urol. 1989;142:479-483. 12. Pettinato G,Manivel JC, Wick MR, Dehner LP. Classical and cellular (atypical) congenital mesoblastic nephroma. A clinicopathologic ultrastructural, immunohistochemical and flow cytometric study. Hum Pathol. 1989;20:682-690. 13. Chan HSL, Chen M-Y,Mancer K, Payton D, Weitzman S, Kotechar P, Daneman A. Congenital mesoblastic nephroma: a clinicoradiologic study of 17 cases representing the pathologic spectrum of the disease. J Pediatr. 1987;111:64-70. 14. Skinner R, Pearson ADJ, Price L, Cunningham K, Craft AW. Hypophosphatemic rickets after ifosfamide treatment in children. Br Med J . 1989;298:1560-1561. 15. Beckwith JB, Kiviat NB, Bonadio JF. Nephrogenic rests, nephroblastomatosis and the pathogenesis of Wilms’ tumor. Pediatr Pathol. 199O;lO:l-36. 16. Bemstein J. Developmental abnormalities of the renal parenchyma, renal hypoplasia and dysplasia. Pathol Ann. 1968:3:213-247. Received November 19, 1991 Accepted January 22, 1992
Address correspondence to Jacques Ninane.
ISSN: 0888-0018 (Print) 1521-0669 (Online) Journal homepage: http://www.tandfonline.com/loi/ipho20
Preoperative Chemotherapy of Cellular Congenital Mesoblastic Nephroma in a 5-Month-Old Infant Jean-Philippe Stalens, Serge Gosseye, Philippe Clapuyt & Jacques Ninane To cite this article: Jean-Philippe Stalens, Serge Gosseye, Philippe Clapuyt & Jacques Ninane (1992) Preoperative Chemotherapy of Cellular Congenital Mesoblastic Nephroma in a 5-Month-Old Infant, Pediatric Hematology and Oncology, 9:4, 335-345, DOI: 10.3109/08880019209016605 To link to this article: http://dx.doi.org/10.3109/08880019209016605
Published online: 09 Jul 2009.
Submit your article to this journal
Article views: 7
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipho20 Download by: [RMIT University Library]
Date: 27 April 2016, At: 05:14
Siron! Communication
PREOPERATIVE CHEMOTHERAPY OF CELLULAR CONGENITAL MESOBLASTIC NEPHROMA IN A 5-MONTH-OLD INFANT
Jean-Philippe Stalens, MD
Downloaded by [RMIT University Library] at 05:14 27 April 2016
0 Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium
Serge Cosseye, MD
0 Department of Pathology, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium
Philippe Clapuyt, MD 0 Division of Pediatric Radiology, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium JacquesNinane, MD, PhD
Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium
0 Cellular (or aopical) congenital mesoblastic nephroma (CMN) is a potentially agpessive form of the benign classical congenital mesoblastic nebhroma. WC report here a case of cellular C M N in a 5-monthold boy treated preoperatively with chemotherapy with an excellent response allowing a complete surgical resection.
KEY WORDS: cellular coqenital mesoblastic ncphroma, injants, chemotherapy.
I NTRODUCTlON Congenital mesoblastic nephroma (CMN) is the most common renal neo1-3 plasm in the first few months of life. The classical form has a benign course justifying nephrectomy alone as the treatment of choice with an excellent p r o g n ~ s i sThe . ~ cellular (or atypical) form of CMN is more aggressive, especially when complete resection is not possible and when the infant is older than 3 The authors are very grateful to Dr. J. Bruce Beckwith from the Children’s Hospital, Denver, for his very helpful review of the pathology material and his contribution to the diagnosis.
Pediatric he ma to lo^ and O n c o l o ~ ,9:335-345, I992 Copyright @ 1992 by Hemisphere Publishing Corporation
335
336
L-P.STALENS ET A 1
We report here our experience with a 5-month-old infant with a cellular CMN invading the neighboring organs. He was treated with preoperative chemotherapy resulting in a dramatic response and allowing a complete surgical resection.
Downloaded by [RMIT University Library] at 05:14 27 April 2016
CASE REPORT This white boy was the product of normal gestation and delivery. At the age of 2 months, he was admitted for a viral meningitis from which he recovered completely. He presented at 5 months of age with a 10-day history of numerous episodes of crying that lasted for 20-30 minutes with pallor, sweating, and nausea, and ending with a loose stool. He was then seen by his pediatrician who noticed an enlarged abdomen and palpated a right flank mass. The child was then referred for further investigations. Upon admission, a very large mass was palpable in the right side of the abdomen which was tense. The rest of the physical examination was normal. Laboratory data were normal including renal function. Ultrasonography and computerized axial tomography (CT) of the abdomen revealed that the right side of the abdomen was filled by an enormous retroperitoneal mass containing many internal septations (Figures 1 and 2). It seemed to be attached to the right kidney, which was displaced toward the midline. Chest and bone X rays were unremarkable. Bone marrow examination was normal. An exploratory laporatomy with biopsy of the mass was then performed. The specimen measured about 9 X 8 X 7 mm. Histological examination showed a homogeneous, dense proliferation of rather small, round to moderately elongated cells with scanty eosinophilic cytoplasm (Figure 3). The nucleus was hyperchromatic, round to ovoid, sometimes with a small nucleolus, and showed some variations in size and some irregularities in shape. Mitoses were numerous. The diagnosis of embryonal rhabdomyosarcoma was then suggested. Since the tumor was unresectable, the child was first treated with chemotherapy. Four courses of the IVA regimen were given at 3-week intervals: vincristine 1.5 mg/m2, actinomycin D 0.5 mg/m2, and ifosfamide 2 g/m2/day for two consecutive days. The tumor shrank dramatically as demonstrated by clinical examination and imaging. Indeed, a repeated C T scan showed only a very small tumor originating from the right kidney (Figure 4). The child then underwent a right radical nephrectomy with extensive lymph node dissection. The tumor was adherent to the colon and a right colectomy with ileotransverse anastomosis had to be performed. The resected specimen included the right kidney, perirenal fat, the right adrenal, a segment of proximal ureter, renal vessels with lymph nodes and,
v
W W
seen in the right hemiabdomen pushing the kidney forward (arrowheads). There is a focal close connection between the tumor and the renal parenchyma (short black arrows).
FIGURE 1. Ultrasound study (US): transverse section of the right flank. A huge multicystic retroperitoneal mass (thin white arrows) is
Downloaded by [RMIT University Library] at 05:14 27 April 2016
FIGURE 2. CT scan with contrast IV injection: same data as US. Note a small solid mass at the site of connection between the tumor and the kidney (star). Hypodensity of the renal parenchyma in front of this abnormality (arrowheads).
Downloaded by [RMIT University Library] at 05:14 27 April 2016
339
Downloaded by [RMIT University Library] at 05:14 27 April 2016
CHEMOTHERAPY OF MESOBLASTIC NEPHROMA
FIGURE 3. Histological appearance of the biopsy specimen. At least four mitoses are seen in this field (H&E, X420).
separately, a segment of terminal ileum with a piece of mesentery, cecum, appendix, and ascending colon. In the perirenal fat, in contact with the surface of the kidney there was an ill-defined mass extending from the middle part of the external border to the lower pole, measuring about 5 X 2 X 2 cm and composed of a tissue of variegated consistency and appearance. Slightly below the middle part of the kidney, there was a horizontal strand of whitish, fibrous tissue across the
w
e 0
between this abnormality and the renal cortex. Note also the defect of renal parenchymography in front of it (arrowheads).
FIGURE 4. CT scan after chemotherapy. Dramatic reduction of tumor size. Persistent infiltration of perirenal fat (star) and connection
Downloaded by [RMIT University Library] at 05:14 27 April 2016
Downloaded by [RMIT University Library] at 05:14 27 April 2016
CHEMOTHERAPY OF MESOBLASTIC NEPHROMA
341
kidney, joining the renal sinus to the external border of the kidney where it came in contact with the extrarenal mass. Microscopic examination of the mass along the kidney showed infiltration of adipose tissue by a process similar to that seen on the biopsy, except that the background was often fairly myxoid and numerous collections of foamy and hemosiderin-laden macrophages were seen. In addition, the cellular proliferation contained variably sized cavities lined by a row of tumor cells assuming a vaguely epithelial appearance, and one group of a few small undifferentiated tubules similar to nephroblastoma tubules was observed at a distance from the kidney (Figure 5). Also noticeable were groups of fairly large vessels sometimes with a thick fibromuscular wall. Immunoperoxidase staining for desmin, myoglobin, neuron specific enolase, protein SlOO, cytokeratin, epithelial membrane antigen (EMA), and vimentin were performed on blocks of the mass and on the biopsy. The tumor cells were convincingly positive only for vimentin. The fibrotic band across the kidney had an indistinct border interdigitating with the adjacent renal parenchyma and was made of a moderately cellular connective tissue containing cystically dilated renal glomeruli and tubes and some small undifferentiated tubules. Also present were dysplastic-type tubes with a collarette of stromal cells in the medulla and a small piece of cartilage. From the area where the fibrous strand abutted on the renal surface, one could see fascicles of leiomyoma-like mesenchymal cells irradiating in the perirenal fat and merging into the preponderant, more cellular component of the extrarenal tumor (Figure 6). In the specimen of bowel resection, the intestinal wall was intact but the piece of mesentery was infiltrated by the tumor. The final diagnosis was cellular mesoblastic nephroma growing mostly outside the kidney with an intrarenal lesion having the feature of both medullary renal dysplasia and intralobar nephrogenic rest, and with an small area of more conventional leiomyoma-like mesoblastic nephroma on the surface of the kidney at the junction of the intrarenal lesion with the extrarenal tumor. We elected to give postoperative chemotherapy for four reasons: (1) our patient was older than 3 months at that time and had obviously a cellular invasive mesoblastic nephroma, two features of poor prognosis; (2) he had responded dramatically to chemotherapy; (3) despite the young age, chemotherapy was well tolerated; and (4) although the resection was macroscopically complete, there was some doubt about possible microscopic residues in the mesentery. This postoperative chemotherapy consisted of nine courses of vincristine (1.5 mg/m2), cyclophosphamide (600 mg/m2), and actinomycin D (0.5 mg/kg) every three weeks. No major adverse reaction was noted. The patient is receiving no treatment and there is no evidence of disease 21 months from diagnosis, 18 months after surgery, and 12 months after the end of chemotherapy.
Downloaded by [RMIT University Library] at 05:14 27 April 2016
342
J.-R STALENS ET AL
FIGURE 5. Group of tubules among hemosiderin-laden macrophages in the tumor, at a distance from the kidney (H&E, X 420).
DISCUSSION Our patient was 5 months old when he developed a cellular mesoblastic nephroma which became resectable thanks to preoperative chemotherapy. Bolande in 1967 was the first to identify CMN as a distinctive type of neoplasm and to distinguish it clearly from Wilms' tumor.'" This distinction is important since the classical form of CMN has a benign course and only requires nephre~tomy."'~
Downloaded by [RMIT University Library] at 05:14 27 April 2016
CHEMOTHERAPY OF MESOBIASTIC NEPHROMA
343
CMN is a rare tumor. However, it is the most common renal neoplasm in the first few months of life,Is3justifying the recommendation that nephrectomy be the initial treatment of a renal solid tumor in the first year of life.4 Since 1973, a cellular (also called atypical) variant of CMN has been described. Seven cases of relapse (local recurrence or pulmonary metastasis) have been reported in infants with cellular CMN"" and 3 of them died. Reviewing the prognostic factors of cellular CMN, Beckwith found that adequacy of surgical resection and age at presentation are the determining factors of prognosis in patients with recurrent disease. He notes that cellular CMN in 10 a patient older than 3 months is of concern. Gormley, however, believed that an infiltrated surgical margin is the only statistically significant factor that predicts recurrence in cellular CMN regardless of the age of presentation and suggests initial surgery, early reexploration for gross residual disease, and VAC chemotherapy associating vincristine, actinomycin D, and cyclophosphamide in case of microscopic residual disease or rupture of the tumor.'' Chan's opinion is a little different. He advises adjuvant chemotherapy for older infants with grossly unresected tumors and those patients whose tumors have an unequivocally malignant histological appearance or evidence of aggressive biological behavior. l 3
FIGURE 6. Cellular rnesoblastic nephrorna infiltrating perirenal fat on the let, and classical appearance of rnesoblastic nephrorna on the right (H&E, X 140).
Downloaded by [RMIT University Library] at 05:14 27 April 2016
344
J.-P. STALENS ET AL
In our case, because of an uncertain initial diagnosis due to the extrarenal localization of the tumor and to a biopsy suggesting an embryonal rhabdomyosarcoma, a preoperative chemotherapy associating ifosfamide, vincristine, and actinomycin D was given. This treatment led to a major decrease in the volume of this cellular CMN and allowed its complete surgical resection. The diagnosis of cellular CMN was given only 3 months after the operation. In the meanwhile we gave a postoperative chemotherapy as for a rhabdomyosarcoma. Since ifosfamide is known to be more toxic in a patient having only one kidney,l4 we replaced ifosfamide with cyclophosphamide and gave nine courses of VAC therapy. The tumor in this case was very peculiar by its almost exclusive extrarenal growth, which is the reason a diagnosis of mesoblastic nephroma was not even contemplated at the beginning. Another interesting feature is the coexistence of an intrarenal lesion from which the tumor seemed to originate. A part of this lesion had obvious features of intralobar nephrogenic rest15 while other parts had features of medullary dysplasia.I6 A piece of cartilage was found in the area resembling a nephrogenic rest but, as no cartilage has been described in typical nephrogenic rests, its presence might be linked to the associated dysplasia. This case shows that preoperative chemotherapy associating ifosfamide (2 g/m‘ for two consecutive days), vincristine (1.5 mg/m2), and actinomycin D (0.5 mg/m2) is effective in cellular CMN. Such a treatment should, however, be restricted to the cellular form of CMN in which the preoperative evaluation identifies an invasive and not a completely resectable neoplasm.
REFERENCES 1. Bolande RP, Brough AJ, Izant RJ. Congenital mesoblastic nephroma of infancy. Pediatrics. 1967;40:272-278. 2. Bolande RP. Congenital mesoblastic nephroma of infancy. Persp Pediutr Padol. 1973;1:227-250. 3. Bolande RP. Congenital and infantile neoplasia of the kidney. Lunccf. 1974;11:1497-1499. 4. Howell CG, Othersen HB, Kiviat NE, Norkool P, Beckwith JB, D’Angio GJ. Therapy and outcome in 51 children with mesoblastic nephroma: a report of the National Wilms’ Tumor Study. J Ptdiutr Surf. 1982; 17:826-831. 5. Joshi VV, Kay S, Milsten R, Koontz WW, McWilliams NB. Congenital mesoblastic nephroma of infancy. Report of a case with unusual clinical behavior. Am J Clin Pufhol. 1973;60:811-816. 6. Joshi W, Kasznica J, Walters TR. Atypical mesoblastic nephroma: pathologic characterization of potentially aggressive variant of conventional congenital mesoblastic nephroma. Arch Pufhol Lob Med. 1986; 110: 100- 106. 7. Stenfeld AD, Growley CA, O’Shea PA, Tefft M. Recurrent and metastatic mesoblastic nephroma in infancy. J Clin Oncol. 1984;2:956-960. 8. Walker D, Richard GA. Fetal mesenchymal hamartoma of the kidney. Recurrence and death of a patient. J Urol. 1973;110:352-353. 9. Gonzales-Crussi F, Sotelo-Avila C, Kidd JM. Malignant mesenchymal nephroma of infancy: report of a case with pulmonary metastases. Am J Sua Puthol. 1980;4:185-190.
Downloaded by [RMIT University Library] at 05:14 27 April 2016
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Address correspondence to Jacques Ninane.
