HEPATIC RHABDOMYOMATOUS TUMOR: Late Sequel of a Fetal Rhabdomyomatous Nephroblastoma
Theodorus H. van der Kwast, MD, Fiebo J. W. ten Kate, MD, Vojislav D. Vuzevski, MD, and Gerard C. Madern, MD 0 Departments of Pathology and
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of British Columbia on 12/09/14 For personal use only.
Paediatric Surgery, Erasmus University and University Hospital Dijkzigt-Sophia Childrens Hospital, 3000 D R Rotterdam, The Netherlands
Onno T. Terpstra, M D
0 Department of General Surgery, Erasmus University and University Hospital Dijkzigt-Sophia Children’s Hospital, 3000 DR Rotterdam, The Netherlands
A mesenchymal tumor with the macroscopic and microscopic features o f a fetal rhabdomyoma arose in the liver of a 14-year-old boy. Thirteen years previously this boy had been treated for a fetal rhabdomyomatous nephroblastoma with nephrectomy and-for subsequent peritoneal disseminations-with surgical excision, radiotherapy, and chemotherapy. The unusual hepatic location of the rhabdomyomatous tumor in this patient supports the view that this mature tumor developedfrom a metastasis of the original nephroblastoma. As such, this case may represent an example of irreversible chanfe of a malignant process into a benign tumor probably caused by the action of systemic chemotherapy. KEY WORDS: fetal rhabdomyomatous nephroblastoma, hepatic metastasis, fetal rhabdomyoma, chemotherapy.
INTRODUCTION The presence of skeletal muscle fibers is common in nephroblastomas. Predominance of tumor areas with skeletal muscle differentiation has been found in a substantial number of nephroblastomas diagnosed below the age of 1 year (13). The less aggressive clinical behavior of the latter tumors, despite their frequent bilateral occurrence and huge size at diagnosis, justified the assignment of fetal rhabdomyomatous nephroblastoma as a variant of nephroblastoma (1). Fetal rhabdomyomas are rare benign tumors composed of disordered bundles of fetal-type skeletal muscles embedded in a loose myxoid stroma. They chiefly affect male children below the age of 3 years and they are usually located in the subcutaneous tissues of head and neck (4,5 ) . A hepatic tumor with the morphological characteristics of a fetal rhabdomyoma arose in a patient 13 years after treatment of a nephroblastoma that had predominantly rhabdomyomatous differentiation. The relationship between the two tumors is discussed. Address reprint requests to Dr. Th.H. van der Kwast, Department of Pathology, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. Pediatric Pathology, 12:449-456, 1992 Copy%ht 0 1992 by Hemisphere Publishinf Corporation
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REPORT OF A CASE A 10-month-old white boy was admitted for excision of a large retroperitoneal tumor adjacent to the right kidney. Tumor extirpation (1360 g) and right nephrectomy with resection of a double ureter was performed. A diagnosis of Wilms’ tumor (nephroblastoma) was made. The patient had no clinical features to suggest the existence of a Wilms’ tumor-associated syndrome such as Beckwith-Wiedemann syndrome or aniridia-Wilms’ tumor (Miller’s) syndrome. Six weeks after the first operation a local recurrence was demonstrated that could not be resected. The patient was then treated with combined chemotherapy (actinomycin D, 15 pg/day) for 5 days, followed by abdominal irradiation (1 .O Gy) and local irradiation of the kidney area (2.2 Gy). Subsequently, every 6 weeks a course of chemotherapy was given. One and a half years later the patient had surgery for radical removal of residual peritoneal tumor deposits that had invaded the small intestine. Chemotherapy courses (actinomycin D and vincristine) were continued for 2 years thereafter. Abdominal ultrasound analysis of bilateral cryptorchism at the age of 14 years revealed the presence of an intrahepatic tumor in the right liver lobe with a diameter of 4 cm. A needle biopsy of the tumor showed skeletal muscle fibers surrounded by collagen-rich stroma. As no clinical suspicion of malignancy existed, an expectant policy was pursued. After removal of an abdominal testicular remnant the patient was treated with testosterone replacement. Three years later the well-demarcated hepatic tumor had grown to a size of 13 X 15 cm (Fig. 1). Preoperative work-up revealed no metastases. At exploratory laparotomy the tumor in the right liver lobe was found to be encapsulated without evidence of extrahepatic growth. A right hemihepatectomy was performed. Although a growth-promoting influence of the androgen treatment was suspected, expression of androgen receptors could not be demonstrated in the tumor tissue either in a ligand-binding assay or immunohistochemically (data not shown). The patient was discharged 22 days after operation.
MATERIALS AND METHODS Sections of paraffin-embedded formalin-fixed tissues of the nephroblastoma, of the residual tumor at first and second reoperation, and of the hepatic tumor at first diagnosis and the hemihepatectomy were investigated after staining with hemtoxylin and azophloxin or phosphotungstic acid-hematoxylin. Immunohistochemistry was performed on sections of paraffin-embedded material with the indirect conjugated peroxidase method (6) using antibodies to keratin (DAKO, Denmark), vimentin (DPC), desmin (Sanbio, The Netherlands), muscle-specific actin (Enzo, United States), and myoglobin (DAKO, Denmark). On frozen material of the hepatic tumor the presence of proliferating
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451
FIGURE 1. Computed tomographic scan of the upper abdomen revealing a large well-demarcated tumor in the right liver lobe.
cells was assessed with the monoclonal antibody Ki-67 (DAKO, Denmark). This antibody detects a proliferation-associated nuclear antigen (7). Routine transmission electron microscopy was done on glutaraldehyde and osmium tetroxide-fixed tissue of the liver tumor.
PATHOLOGY Histopathology and lmmunohistochemistry of the Primary Kidney Tumor and Recurrences The kidney tumor was largely composed of cells with skeletal muscle differentiation closely resembling a fetal rhabdomyoma (Fig. 2) In various sections blastema with multilayered tubules was present; here mitotic figures were frequent. The tumor masses were largely surrounded by a fibrous capsule. The residual tumors removed 4 and 7 months later also contained extensive areas with skeletal muscle differentiation as judged from cross-striation in muscle fibers and reactivity with desmin, muscle-specific actin and antimyoglobin antibodies. Areas with necrosis and hemorrhages were also present in several specimens.
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FIGURE 2. Rhabdomyomatous tissue adjacent to blastema tissue from kidney tumor. The rhabdomyomatous component contains several spindle-shaped cells with a mature appearance (hematoxylinazophloxin staining, X 325).
Histopathology of the Hepatic Tumor The hepatic tumor was composed of bundles of elongated cells with eosinophilic cytoplasm that often showed cross-striations. These bundles of skeletal muscle fibers were embedded in loose, more immature-appearing stroma. The tumor was surrounded by a thick fibrous capsule separating it from liver parenchyma. No infiltration of the tumor into the capsule was detected. Mitoses were extremely rare and anisonucleosis was not noted. Light microscopy of the tumor showed a striking similarity to the areas with skeletal muscle differentiation in the nephroblastoma (Fig. 3). Skeletal muscle differentiation was confirmed by the reactivity with antibodies specific for actin, desmin (Fig. 4), and myoglobin. Immunostaining with monoclonal antibody Ki-67 revealed occasional immunoreactive nuclei exclusively within the loose stroma between the muscle fibers. Transmission electron microscopy showed an abundance of longitudinal myofibrils with characteristic spindle-shaped densities (Z-bands) in the cytoplasm of the elongated cells (Fig. 5). The cytoplasm of surrounding spindled mesenchymal cells did not contain organelles specific for skeletal muscle differentiation; only small arrays of filaments without cross-striation were present in addition to ribosomes, rare mitochondria, and some endoplasmic reticulum cisternae.
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FIGURE 3. Rhabdornyomatous tissue of the hepatic tumor containing many spindle-shaped cells ernbedded in loose matrix (haematoxylin-azophloxin staining, X 325).
FIGURE 4. Hepatic tumor stained with antidesrnin revealing cross-striation of spindle-shaped tumor cells (nuclear counterstain with hernatoxylin, X 325).
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FIGURE 5. Transmission electron micrograph of hepatic rhabdomyomatous tumor cell ( X 4000). The cytoplasm is filled with fibrils composed of thick and thin filaments as well as Z-lines (arrows).
DISCUSSION Fetal rhabdomyomatous nephroblastomas should be distinguished from other malignant kidney tumors of childhood with a predominance of striated muscle such as rhabdomyosarcomas and from rhabdoid tumors (8, 9). The well-differentiated appearance of the muscle cells in association with (metanephric) blastema and tubular formations, as well as the absence of significant numbers of small-sized rhabdomyosarcoma tumor cells, excludes the diagnosis of rhabdomyosarcoma or rhabdoid tumor of the kidney. The age below 1 year at diagnosis and the large size of the tumor without accompanying metastases conform with earlier clinical features of fetal rhabdomyomatous nephroblastoma (1-3). Metastases of fetal rhabdomyomatous nephroblastoma were reported in 4 of the 20 cases reviewed by Wigger (1) but unfortunately, no description of the light microscopy of the metastases of fetal rhabdomyomatous nephroblastoma was given. Interestingly, the only metastasis of a fetal rhabdomyomatous nephroblastoma with available microscopy showed resemblance to a pleomorphic type of rhabdomyosarcoma (2). Metastases of nephroblastomas usually become manifest within 2 years after therapy, but achievement of long-term survival due to improvement of therapy has led to the occurrence of pulmonary metastases after a 5-year diseaseinterval in a small number of patients (10). Strikingly, in all these patients, the
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age at diagnosis of the primary nephroblastoma was above 1 year and no rhabdomyomatous variants of nephroblastoma were included. The hepatic tumor was resected 16 years after diagnosis of the fetal rhabdomyomatous nephroblastoma and had the histopathological characteristics of a fetal rhabdomyoma (4). The unusually large number of fibers with crossstriation suggests a high differentiation level of this tumor. The tumor was considered a benign neoplasm, both clinically and histopathologically, on the following grounds: 1) its expansive instead of infiltrating growth pattern, 2) the rarity of mitotic figures, 3) absence of metastases elsewhere even after the long interval of 3 years between diagnosis of the hepatic tumor process and its resection, and 4) lack of systemic symptoms despite the large size of the tumor at the time of removal. The occurrence of a tumor with the features of fetal rhabdomyoma in a patient 13 years after treatment of unilateral fetal rhabdomyomatous nephroblastoma raises the question of whether this tumor arose independently of the former process, as a metastasis, or as a hamartoma associated with nephroblastoma. Although a genetic predisposition for the development of neoplasia may underlie the development of the hepatic rhabdomyoma in our patient, the rare occurrence of fetal rhabdomyomas above the age of 3 years and the unusual localization of the tumor process virtually rule out the possibility that this tumor is a primary fetal rhabdomyoma. Furthermore, this patient did not suffer from Wilms’ tumor-associated syndromes such as BeckwithWiedemann syndrome or Miller syndrome, which are known to increase the risk for development of neoplasias (11). The strong morphological resemblance of the liver tumor and the nephroblastoma is strong argument for a link between these two tumors. Probably, the manipulations and spill during the multiple operations to remove residual tumor may have led to metastases. Subsequent chemotherapy may have destroyed the immature compartments of the metastases, leaving unaffected the more mature skeletal muscle fiber components, as described previously for a rhabdomyomatous nephroblastoma after chemotherapy (12). The more mature components of the metastasized nephroblastoma apparently retained their proliferative activity, losing their potential for infiltrative growth and metastasis.
REFERENCES variant of Wilms’ tumor. Hum Pathol 1976;7:613-23. 2. Ugarte N, Gonzalez-Crussi F, Wsueh W. Wilms’ tumor: Its morphology in patients under one year of age. Cancer 1981 ;48:346-53. 3 . Marsden HB, Lawler W. Primary renal turnours in the first year of life. A population based review. Virchows Arch [A] 1983;399:1-9. I . Wigger HJ. Fetal rhabdomyomatous nephroblastoma-a
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of British Columbia on 12/09/14 For personal use only.
456
T. H. VAN DER KWAST ET AL.
4. Enzinger FM, Weiss SW. Soft Tissue Tumors. St. Louis: C. V. Mosby, 1983;325-37. 5. Di Sant’Agnese PA, Knowles DM 2d. Extracardiac rhabdomyoma: A clinicopathologic study and review of the literature. Cancer 1980;46:780-9. 6. Lansdorp PM, Van der Kwast T H , De Boer M, Zijlemaker WP. Stepwise amplified immunoperoxidase (PAP) staining. I. Cellular morphology in relation to membrane markers. J Histochem Cytochem 1984;32:172-8. 7. Gerdes J , Lemke H, Baisch H , Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67, J Immunol 1984;133:1710-5. 8. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms’ tumors. Results from the first National Wilms’ Tumor Study. Cancer 1978;41:1937-48. 9. Lawler W, Marsden HB, Palmer MK. Wilms’ tumor-histologic variation and prognosis. Cancer 1975;36:1122-6. 10. Kim TH, Zaatari GS, Baum ES, et al. Recurrence of Wilms’ tumor after apparent cure. J Pediatr 1985;107:44-9. 11. Sotelo-Avila C , Gonzalez-Crussi F, Fowler JW. Complete and incomplete forms of BeckwithWiedemann syndrome: Their oncogenic potential. J Pediatr 1980;96:47-50. 12. Guarda LA, Ayala AG, Jaffe N, Sutow WW, Brosken RB. Chemotherapy-induced histologic changes in Wilms’ tumors. Pediatr Pathol 1984;2:197-206. Receiued May 29, 1991 Accepted August 20, 1991
Theodorus H. van der Kwast, MD, Fiebo J. W. ten Kate, MD, Vojislav D. Vuzevski, MD, and Gerard C. Madern, MD 0 Departments of Pathology and
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of British Columbia on 12/09/14 For personal use only.
Paediatric Surgery, Erasmus University and University Hospital Dijkzigt-Sophia Childrens Hospital, 3000 D R Rotterdam, The Netherlands
Onno T. Terpstra, M D
0 Department of General Surgery, Erasmus University and University Hospital Dijkzigt-Sophia Children’s Hospital, 3000 DR Rotterdam, The Netherlands
A mesenchymal tumor with the macroscopic and microscopic features o f a fetal rhabdomyoma arose in the liver of a 14-year-old boy. Thirteen years previously this boy had been treated for a fetal rhabdomyomatous nephroblastoma with nephrectomy and-for subsequent peritoneal disseminations-with surgical excision, radiotherapy, and chemotherapy. The unusual hepatic location of the rhabdomyomatous tumor in this patient supports the view that this mature tumor developedfrom a metastasis of the original nephroblastoma. As such, this case may represent an example of irreversible chanfe of a malignant process into a benign tumor probably caused by the action of systemic chemotherapy. KEY WORDS: fetal rhabdomyomatous nephroblastoma, hepatic metastasis, fetal rhabdomyoma, chemotherapy.
INTRODUCTION The presence of skeletal muscle fibers is common in nephroblastomas. Predominance of tumor areas with skeletal muscle differentiation has been found in a substantial number of nephroblastomas diagnosed below the age of 1 year (13). The less aggressive clinical behavior of the latter tumors, despite their frequent bilateral occurrence and huge size at diagnosis, justified the assignment of fetal rhabdomyomatous nephroblastoma as a variant of nephroblastoma (1). Fetal rhabdomyomas are rare benign tumors composed of disordered bundles of fetal-type skeletal muscles embedded in a loose myxoid stroma. They chiefly affect male children below the age of 3 years and they are usually located in the subcutaneous tissues of head and neck (4,5 ) . A hepatic tumor with the morphological characteristics of a fetal rhabdomyoma arose in a patient 13 years after treatment of a nephroblastoma that had predominantly rhabdomyomatous differentiation. The relationship between the two tumors is discussed. Address reprint requests to Dr. Th.H. van der Kwast, Department of Pathology, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. Pediatric Pathology, 12:449-456, 1992 Copy%ht 0 1992 by Hemisphere Publishinf Corporation
449
450
T. H. VAN DER KWAST ET AL.
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of British Columbia on 12/09/14 For personal use only.
REPORT OF A CASE A 10-month-old white boy was admitted for excision of a large retroperitoneal tumor adjacent to the right kidney. Tumor extirpation (1360 g) and right nephrectomy with resection of a double ureter was performed. A diagnosis of Wilms’ tumor (nephroblastoma) was made. The patient had no clinical features to suggest the existence of a Wilms’ tumor-associated syndrome such as Beckwith-Wiedemann syndrome or aniridia-Wilms’ tumor (Miller’s) syndrome. Six weeks after the first operation a local recurrence was demonstrated that could not be resected. The patient was then treated with combined chemotherapy (actinomycin D, 15 pg/day) for 5 days, followed by abdominal irradiation (1 .O Gy) and local irradiation of the kidney area (2.2 Gy). Subsequently, every 6 weeks a course of chemotherapy was given. One and a half years later the patient had surgery for radical removal of residual peritoneal tumor deposits that had invaded the small intestine. Chemotherapy courses (actinomycin D and vincristine) were continued for 2 years thereafter. Abdominal ultrasound analysis of bilateral cryptorchism at the age of 14 years revealed the presence of an intrahepatic tumor in the right liver lobe with a diameter of 4 cm. A needle biopsy of the tumor showed skeletal muscle fibers surrounded by collagen-rich stroma. As no clinical suspicion of malignancy existed, an expectant policy was pursued. After removal of an abdominal testicular remnant the patient was treated with testosterone replacement. Three years later the well-demarcated hepatic tumor had grown to a size of 13 X 15 cm (Fig. 1). Preoperative work-up revealed no metastases. At exploratory laparotomy the tumor in the right liver lobe was found to be encapsulated without evidence of extrahepatic growth. A right hemihepatectomy was performed. Although a growth-promoting influence of the androgen treatment was suspected, expression of androgen receptors could not be demonstrated in the tumor tissue either in a ligand-binding assay or immunohistochemically (data not shown). The patient was discharged 22 days after operation.
MATERIALS AND METHODS Sections of paraffin-embedded formalin-fixed tissues of the nephroblastoma, of the residual tumor at first and second reoperation, and of the hepatic tumor at first diagnosis and the hemihepatectomy were investigated after staining with hemtoxylin and azophloxin or phosphotungstic acid-hematoxylin. Immunohistochemistry was performed on sections of paraffin-embedded material with the indirect conjugated peroxidase method (6) using antibodies to keratin (DAKO, Denmark), vimentin (DPC), desmin (Sanbio, The Netherlands), muscle-specific actin (Enzo, United States), and myoglobin (DAKO, Denmark). On frozen material of the hepatic tumor the presence of proliferating
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of British Columbia on 12/09/14 For personal use only.
HEPATIC RHABDOMYOMATOUS TUMOR
451
FIGURE 1. Computed tomographic scan of the upper abdomen revealing a large well-demarcated tumor in the right liver lobe.
cells was assessed with the monoclonal antibody Ki-67 (DAKO, Denmark). This antibody detects a proliferation-associated nuclear antigen (7). Routine transmission electron microscopy was done on glutaraldehyde and osmium tetroxide-fixed tissue of the liver tumor.
PATHOLOGY Histopathology and lmmunohistochemistry of the Primary Kidney Tumor and Recurrences The kidney tumor was largely composed of cells with skeletal muscle differentiation closely resembling a fetal rhabdomyoma (Fig. 2) In various sections blastema with multilayered tubules was present; here mitotic figures were frequent. The tumor masses were largely surrounded by a fibrous capsule. The residual tumors removed 4 and 7 months later also contained extensive areas with skeletal muscle differentiation as judged from cross-striation in muscle fibers and reactivity with desmin, muscle-specific actin and antimyoglobin antibodies. Areas with necrosis and hemorrhages were also present in several specimens.
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FIGURE 2. Rhabdomyomatous tissue adjacent to blastema tissue from kidney tumor. The rhabdomyomatous component contains several spindle-shaped cells with a mature appearance (hematoxylinazophloxin staining, X 325).
Histopathology of the Hepatic Tumor The hepatic tumor was composed of bundles of elongated cells with eosinophilic cytoplasm that often showed cross-striations. These bundles of skeletal muscle fibers were embedded in loose, more immature-appearing stroma. The tumor was surrounded by a thick fibrous capsule separating it from liver parenchyma. No infiltration of the tumor into the capsule was detected. Mitoses were extremely rare and anisonucleosis was not noted. Light microscopy of the tumor showed a striking similarity to the areas with skeletal muscle differentiation in the nephroblastoma (Fig. 3). Skeletal muscle differentiation was confirmed by the reactivity with antibodies specific for actin, desmin (Fig. 4), and myoglobin. Immunostaining with monoclonal antibody Ki-67 revealed occasional immunoreactive nuclei exclusively within the loose stroma between the muscle fibers. Transmission electron microscopy showed an abundance of longitudinal myofibrils with characteristic spindle-shaped densities (Z-bands) in the cytoplasm of the elongated cells (Fig. 5). The cytoplasm of surrounding spindled mesenchymal cells did not contain organelles specific for skeletal muscle differentiation; only small arrays of filaments without cross-striation were present in addition to ribosomes, rare mitochondria, and some endoplasmic reticulum cisternae.
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FIGURE 3. Rhabdornyomatous tissue of the hepatic tumor containing many spindle-shaped cells ernbedded in loose matrix (haematoxylin-azophloxin staining, X 325).
FIGURE 4. Hepatic tumor stained with antidesrnin revealing cross-striation of spindle-shaped tumor cells (nuclear counterstain with hernatoxylin, X 325).
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FIGURE 5. Transmission electron micrograph of hepatic rhabdomyomatous tumor cell ( X 4000). The cytoplasm is filled with fibrils composed of thick and thin filaments as well as Z-lines (arrows).
DISCUSSION Fetal rhabdomyomatous nephroblastomas should be distinguished from other malignant kidney tumors of childhood with a predominance of striated muscle such as rhabdomyosarcomas and from rhabdoid tumors (8, 9). The well-differentiated appearance of the muscle cells in association with (metanephric) blastema and tubular formations, as well as the absence of significant numbers of small-sized rhabdomyosarcoma tumor cells, excludes the diagnosis of rhabdomyosarcoma or rhabdoid tumor of the kidney. The age below 1 year at diagnosis and the large size of the tumor without accompanying metastases conform with earlier clinical features of fetal rhabdomyomatous nephroblastoma (1-3). Metastases of fetal rhabdomyomatous nephroblastoma were reported in 4 of the 20 cases reviewed by Wigger (1) but unfortunately, no description of the light microscopy of the metastases of fetal rhabdomyomatous nephroblastoma was given. Interestingly, the only metastasis of a fetal rhabdomyomatous nephroblastoma with available microscopy showed resemblance to a pleomorphic type of rhabdomyosarcoma (2). Metastases of nephroblastomas usually become manifest within 2 years after therapy, but achievement of long-term survival due to improvement of therapy has led to the occurrence of pulmonary metastases after a 5-year diseaseinterval in a small number of patients (10). Strikingly, in all these patients, the
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age at diagnosis of the primary nephroblastoma was above 1 year and no rhabdomyomatous variants of nephroblastoma were included. The hepatic tumor was resected 16 years after diagnosis of the fetal rhabdomyomatous nephroblastoma and had the histopathological characteristics of a fetal rhabdomyoma (4). The unusually large number of fibers with crossstriation suggests a high differentiation level of this tumor. The tumor was considered a benign neoplasm, both clinically and histopathologically, on the following grounds: 1) its expansive instead of infiltrating growth pattern, 2) the rarity of mitotic figures, 3) absence of metastases elsewhere even after the long interval of 3 years between diagnosis of the hepatic tumor process and its resection, and 4) lack of systemic symptoms despite the large size of the tumor at the time of removal. The occurrence of a tumor with the features of fetal rhabdomyoma in a patient 13 years after treatment of unilateral fetal rhabdomyomatous nephroblastoma raises the question of whether this tumor arose independently of the former process, as a metastasis, or as a hamartoma associated with nephroblastoma. Although a genetic predisposition for the development of neoplasia may underlie the development of the hepatic rhabdomyoma in our patient, the rare occurrence of fetal rhabdomyomas above the age of 3 years and the unusual localization of the tumor process virtually rule out the possibility that this tumor is a primary fetal rhabdomyoma. Furthermore, this patient did not suffer from Wilms’ tumor-associated syndromes such as BeckwithWiedemann syndrome or Miller syndrome, which are known to increase the risk for development of neoplasias (11). The strong morphological resemblance of the liver tumor and the nephroblastoma is strong argument for a link between these two tumors. Probably, the manipulations and spill during the multiple operations to remove residual tumor may have led to metastases. Subsequent chemotherapy may have destroyed the immature compartments of the metastases, leaving unaffected the more mature skeletal muscle fiber components, as described previously for a rhabdomyomatous nephroblastoma after chemotherapy (12). The more mature components of the metastasized nephroblastoma apparently retained their proliferative activity, losing their potential for infiltrative growth and metastasis.
REFERENCES variant of Wilms’ tumor. Hum Pathol 1976;7:613-23. 2. Ugarte N, Gonzalez-Crussi F, Wsueh W. Wilms’ tumor: Its morphology in patients under one year of age. Cancer 1981 ;48:346-53. 3 . Marsden HB, Lawler W. Primary renal turnours in the first year of life. A population based review. Virchows Arch [A] 1983;399:1-9. I . Wigger HJ. Fetal rhabdomyomatous nephroblastoma-a
Fetal Pediatr Pathol Downloaded from informahealthcare.com by University of British Columbia on 12/09/14 For personal use only.
456
T. H. VAN DER KWAST ET AL.
4. Enzinger FM, Weiss SW. Soft Tissue Tumors. St. Louis: C. V. Mosby, 1983;325-37. 5. Di Sant’Agnese PA, Knowles DM 2d. Extracardiac rhabdomyoma: A clinicopathologic study and review of the literature. Cancer 1980;46:780-9. 6. Lansdorp PM, Van der Kwast T H , De Boer M, Zijlemaker WP. Stepwise amplified immunoperoxidase (PAP) staining. I. Cellular morphology in relation to membrane markers. J Histochem Cytochem 1984;32:172-8. 7. Gerdes J , Lemke H, Baisch H , Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67, J Immunol 1984;133:1710-5. 8. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilms’ tumors. Results from the first National Wilms’ Tumor Study. Cancer 1978;41:1937-48. 9. Lawler W, Marsden HB, Palmer MK. Wilms’ tumor-histologic variation and prognosis. Cancer 1975;36:1122-6. 10. Kim TH, Zaatari GS, Baum ES, et al. Recurrence of Wilms’ tumor after apparent cure. J Pediatr 1985;107:44-9. 11. Sotelo-Avila C , Gonzalez-Crussi F, Fowler JW. Complete and incomplete forms of BeckwithWiedemann syndrome: Their oncogenic potential. J Pediatr 1980;96:47-50. 12. Guarda LA, Ayala AG, Jaffe N, Sutow WW, Brosken RB. Chemotherapy-induced histologic changes in Wilms’ tumors. Pediatr Pathol 1984;2:197-206. Receiued May 29, 1991 Accepted August 20, 1991
