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A retroperitoneal immature teratoma with rhabdomyoblastic and nephroblastic differentiation
364
CORRESPONDENCE
Pathology (2006), 38(4), August
A retroperitoneal immature teratoma with rhabdomyoblastic and nephroblastic differentiation Sir, Wilms’ tumour and immature teratoma are commonly encountered tumours of the paediatric age group. In most cases, these two neoplasms display distinct histological features from which the correct diagnosis can be easily made. However, overlap occasionally exists. In those cases with a very large nephroblastoma-like or small malignant cell component without any differentiation, distinction between these two neoplasms can be very difficult on small biopsies, as the better differentiated diagnostic component may not be sampled. The condition is even more complicated when the tumour is situated at an extra-renal location. We present a retroperitoneal immature teratoma with nephroblastic and rhabdomyoblastic differentiation in a 4year-old Chinese boy. He presented with slight abdominal distension and intermittent generalised abdominal pain for 3 months. Computer tomography scan showed a retroperitoneal soft tissue mass measuring 7 cm across with extension to the aortic bifurcation. The mass compressed the left mid-ureter leading to left hydronephrosis. The paraaortic lymph nodes were enlarged. Both left and right kidneys were normal and did not reveal any connection to the tumour. Laparoscopic biopsy showed typical features of an extra-renal Wilms’ tumour. The patient subsequently underwent a 6-month course of chemotherapy using the National Wilms’ Tumour Proctocol (NWT51 DD4A). In view of the presence of para-aortic lymph node metastasis, irradiation was given. The tumour was excised after 4 months of treatment. Pathological findings revealed an immature teratoma with nephroblastic and rhabdomyoblastic differentiation. The patient then completed the remaining 2 months of chemotherapy. Repeat computed tomography scans showed complete resolution with no evidence of tumour recurrence 2 years after treatment.
CORRESPONDENCE
Fig. 1 First incisional biopsy showed classical triphasic Wilms’ tumour with epithelial, stromal and blastemal components (H&E, 610).
365
The first incisional biopsy sections showed a classical Wilms’ tumour with a triphasic pattern. Epithelial, blastemal and mesenchymal components were present (Fig. 1). The epithelial cells formed tubular and glomeruloid structures while the blastemal element consisted of primitive cells with very scanty cytoplasm and the mesenchymal component consisted of spindled immature cells. No heterogenous elements were seen. The diagnosis of extra-renal Wilms’ tumour was made. Since Wilms’ tumour features can be a component of an immature teratoma, we suggested that the latter could not be completely excluded in this small biopsy. The post-treatment excisional specimen was a dumb-bell shaped tumour measuring 76462 cm. Its cut surface showed a variegated appearance with focal myxoid changes. Histological sections showed a fairly circumscribed lesion with cystic cavities lined by bland mucinous glandular epithelium. Some of the epithelium was surrounded by smooth muscle coat, resembling the architecture of intestinal wall (Fig. 2A). The adjacent tissue was
Fig. 2 The excised post-treatment tumour showed a fairly circumscribed lesion with cystic cavities lined by bland mucinous glandular epithelium. (A) Some of the epithelium was surrounded by a smooth muscle coat, resembling the architecture of intestinal wall (H&E, 64). (B) Aggregates of micropapillary structures and tubules resembling nephrogenic rests were present (H&E, 610). (C) In areas, large numbers of tumour cells showed abundant eosinophilic cytoplasm, eccentric nuclei and prominent nucleoli (H&E, 610). These cells displayed (Di) strong immunohistochemical cytoplasmic positivity for desmin and (Dii) focal nuclear positivity for myogenin, and hence confirmed their rhabdomyoblastic differentiation (610).
366
CORRESPONDENCE
Fig. 3 Immunohistochemical studies with desmin and myogenin showed a portion of the small round cells were reactive for (A) desmin and (B) myogenin (610).
composed of loose fibrous stroma, glial tissue and nerve bundles. Aggregates of micropapillary structures and tubules resembling nephrogenic rests were present (Fig. 2B). In areas, large numbers of cells with abundant eosinophilic cytoplasm, eccentric nuclei and prominent nucleoli, consistent with rhabdomyoblasts, were seen (Fig. 2C). These cells were immunohistochemically reactive for desmin and myogenin (Fig. 2Di,ii). The blastemal elements identified in the previous biopsy were not seen. Primitive neural elements and necrosis were absent. In view of the abundant rhabdomyoblasts identified in the post-treatment tumour, immunohistochemical studies with myogenic markers desmin and myogenin were conducted in the previous biopsy. A considerable proportion of the blastemal cells were positive for both skeletal muscle markers desmin and myogenin (Fig. 3). The final diagnosis of the tumour was a retroperiteoneal immature teratoma with nephroblastic and rhabdomyoblastic differentiation. Teratoid Wilms’ tumor is a rare histological variant of the classical Wilms’ tumor. The term was introduced by Variend et al.1 to define a subtype of nephroblastoma in which over 50% of the tumour mass was composed of heterologous elements, e.g., adipose tissue, muscle, cartilage, or bone. The behaviour of this kind of tumour is usually described as less aggressive than the conventional Wilms’ tumour. Surgery should be the treatment of choice because the efficacy of chemotherapy and radiotherapy is probably reduced by the high amount of differentiated and mature tissue.2 Successful demonstration of myogenic expression in the ‘blastema’-like component in the initial biopsy confirmed its rhabdomyoblastic differentiation at the initial presentation. As a result of chemo-irradiation, these primitive small round cells were transformed into more differentiated, morphologically recognisable rhabdomyoblasts. The presence of rhabdomyoblastic component in Wilms’ tumour is not uncommon, especially in post-treatment specimens. Histologically, primitive rhabdomyoblasts display similar morphology as the blastemal element of a conventional
Pathology (2006), 38(4), August
Wilms’ tumour. In these conditions, myogenin may be used as an immunohistochemical marker in distinguishing Wilms’ tumour with rhabdomyoblastic differentiation from conventional Wilms’ tumour. According to Folpe, none of the nine studied Wilms’ tumours showed a significant positive staining pattern (more than 5% positive cells) with myogenin.3 On the other hand, a positive signal is found by Kumar in two Wilms’ tumours with rhabdomyoblastic differentiation.4 According to a review of 14 cases of rhabdomyoblastic nephroblastoma by Pollono et al. in 2003,5 in which one extra-renal case was included, chemotherapy proved not as effective as in other variants of nephroblastoma. In addition, the prognosis depends highly on tumour staging at presentation. Therefore, for an extra-renal teratoid Wilms’ tumour with rhabdomyoblastic differentiation, a surgical approach rather than chemo-irradiation therapy would appear to be the more appropriate treatment. In the current case, there are several conflicting features that are not supportive of the diagnosis of an extra-renal teratoid Wilms’ tumour. The arrangement of cysts lined by mucinous gland and smooth muscle coat, resembling the architecture of intestinal tract, are described as organoid arrangement. In teratoid Wilms’ tumour, although these components can be identified, they are usually disposed in a haphazard fashion rather than in an organised manner. Moreover, nerve bundles and glial tissue are more commonly seen in immature teratoma than teratoid Wilms’ tumour. As a result, we considered the current case as a retroperitoneal immature teratoma with nephroblastic and rhabdomyoblastic differentiation. To date, there have been five reported cases of retroperitoneal/sacral-coccygeal immature teratoma with nephroblastic differentiation. Most were treated with chemo-irradiation and surgical excision despite the presence of metastasis at presentation.6–10 The origin and proper treatment of this neoplasm is not settled because of the small number of cases reported. According to Emerson et al., loss of heterozygosity was observed at locus 11p13 (WT1) in the nephroblastic component of a testicular immature teratoma. This locus is usually inactivated in patients who are genetically predisposed to nephroblastoma. The demonstrated loss of heterozygosity at this focus may suggest an important genetic mechanism in the nephroblastic differentiation of an immature teratoma. Moreover, using tissue microdissection and loss of heterozygosity analysis, a common clonal origin for nephroblastoma and the immature teratoma has been demonstrated. Despite the presence of supraclavicular and retroperitoneal lymph node metastasis in that reported case, no recurrence was noted with 21 months of additional follow-up after chemotherapy.11 Literature search did not reveal a single reported case of retroperitoneal immature teratoma with rhabdomyoblastic differentiation. However, in the few case reports of gonadal immature teratoma with rhabdomyoblastic differentiation, the tumour appears to be much more aggressive.12–14 Despite surgical excision, aggressive chemotherapy and irradiation, patients suffered from repeated recurrences and finally died of the disease. Although the primary tumour contained only a few rhabdomyoblasts, rhabomyosarcoma appeared to be the predominant component in the recurrent tumours. The findings in this small number of cases suggest that the rhabdomyoblastic component arising
CORRESPONDENCE
from an immature teratoma should be treated with great caution. In conclusion, we consider the current case as an immature teratoma with nephroblastic and rhabdomyoblastic differentiation. It appears from literature review that the teratomatous and nephroblastomatous components are more amenable to surgical excision. The rhabdomyoblastic component should be treated aggressively as it may relapse as a pure sarcoma. Yuen-Shan Fan* Ui-Soon Khoo{ Gavin Shueng-Wai Chan* Departments of Pathology, *Queen Mary Hospital, and {University of Hong Kong, Hong Kong SAR, China Contact Dr Y. S. Fan. E-mail: [email protected] ACKNOWLEDGEMENT We would like to thank Dr G. M. Vujanic for her expert opinion on this case.
1. Variend S, Spicer RD, Mckinnon AE. Teratoid Wilms’ tumour. Cancer 1984; 53: 1936–42. 2. Cecchetto G, Alaggio R, Scarzello G, et al. Teratoid Wilms’ tumor: report of a unilateral case. J Pediatr Surg 2003; 38: 259–61. 3. Folpe AL, Patterson K, Gown AM. Antibodies to desmin identify the blastemal component of nephroblastoma. Mod Pathol 1997; 10: 895–900. 4. Kumar S, Perlman E, Harris CA, et al. An immunohistochemical study in paraffin-embedded tissue. Mod Pathol 2000; 13: 988–33. 5. Pollono D, Drut R, Tomarchio S, et al. Fetal rhabdomyomatous nephroblastoma: report of 14 cases confirming chemotherapy resistance. J Pediatr Hematol Oncol 2003; 25: 640–3. 6. Kim YW, Park YK, Oh SM, et al. Retroperitoneal teratoma with predominance of nephroblastic elements–a case report. J Korean Med Sci 1990; 5: 237–42. 7. Tebbi K, Ragab AH, Ternberg JL, et al. An extrarenal Wilms’ tumor arising from a sacrococcygeal teratoma. Clin Pediatr (Phila) 1974; 13: 1019–21. 8. Malik TK, Malik GB, Diesh G. Retroperitoneal teratoma with nephroblastic tissue as the main component. Int Surg 1967; 47: 246– 9. 9. Ward SP, Dehner LP. Saccroccygeal teratoma with neprhoblastoma (Wilms’ tumour): A variant of extragonadal teratoma in childhood. Cancer 1974; 33: 1355–63. 10. Park HR, Park CY, Choi NK, et al. A case of retroperitoneal teratoma with nephroblastoma. J Korean Med Sci 1991; 6: 95–102.
367
11. Emerson RE, Ulbright TM, Zhang S, et al. Nephroblastoma arising in a germ cell tumor of testicular origin. Am J Surg Pathol 2004; 28: 687–92. 12. Yanai H, Matsuura H, Kawasaki M, et al. Immature teratoma of the ovary with a minor rhabdomyosarcomatous component and fatal rhabdomyosarcomatous metastases: the first case in a child. Int J Gynecol Pathol 2002; 21: 82–5. 13. Terrier-Lacombe MJ, Martinez-Madrigal F, Porta W, et al. Embryonal rhabdomyosarcoma arising in a mature teratoma of the testis: a case report. J Urol 1990; 143: 1232–4. 14. Haines IE, Schwarz MA, Westmore DD, et al. Rhabdomyosarcoma in a patient treated for metastatic germ cell tumour of the testis containing teratoma–a case report. Aust N Z J Surg 1985; 55: 141–3.
DOI: 10.1080/00313020600820765
CORRESPONDENCE
Pathology (2006), 38(4), August
A retroperitoneal immature teratoma with rhabdomyoblastic and nephroblastic differentiation Sir, Wilms’ tumour and immature teratoma are commonly encountered tumours of the paediatric age group. In most cases, these two neoplasms display distinct histological features from which the correct diagnosis can be easily made. However, overlap occasionally exists. In those cases with a very large nephroblastoma-like or small malignant cell component without any differentiation, distinction between these two neoplasms can be very difficult on small biopsies, as the better differentiated diagnostic component may not be sampled. The condition is even more complicated when the tumour is situated at an extra-renal location. We present a retroperitoneal immature teratoma with nephroblastic and rhabdomyoblastic differentiation in a 4year-old Chinese boy. He presented with slight abdominal distension and intermittent generalised abdominal pain for 3 months. Computer tomography scan showed a retroperitoneal soft tissue mass measuring 7 cm across with extension to the aortic bifurcation. The mass compressed the left mid-ureter leading to left hydronephrosis. The paraaortic lymph nodes were enlarged. Both left and right kidneys were normal and did not reveal any connection to the tumour. Laparoscopic biopsy showed typical features of an extra-renal Wilms’ tumour. The patient subsequently underwent a 6-month course of chemotherapy using the National Wilms’ Tumour Proctocol (NWT51 DD4A). In view of the presence of para-aortic lymph node metastasis, irradiation was given. The tumour was excised after 4 months of treatment. Pathological findings revealed an immature teratoma with nephroblastic and rhabdomyoblastic differentiation. The patient then completed the remaining 2 months of chemotherapy. Repeat computed tomography scans showed complete resolution with no evidence of tumour recurrence 2 years after treatment.
CORRESPONDENCE
Fig. 1 First incisional biopsy showed classical triphasic Wilms’ tumour with epithelial, stromal and blastemal components (H&E, 610).
365
The first incisional biopsy sections showed a classical Wilms’ tumour with a triphasic pattern. Epithelial, blastemal and mesenchymal components were present (Fig. 1). The epithelial cells formed tubular and glomeruloid structures while the blastemal element consisted of primitive cells with very scanty cytoplasm and the mesenchymal component consisted of spindled immature cells. No heterogenous elements were seen. The diagnosis of extra-renal Wilms’ tumour was made. Since Wilms’ tumour features can be a component of an immature teratoma, we suggested that the latter could not be completely excluded in this small biopsy. The post-treatment excisional specimen was a dumb-bell shaped tumour measuring 76462 cm. Its cut surface showed a variegated appearance with focal myxoid changes. Histological sections showed a fairly circumscribed lesion with cystic cavities lined by bland mucinous glandular epithelium. Some of the epithelium was surrounded by smooth muscle coat, resembling the architecture of intestinal wall (Fig. 2A). The adjacent tissue was
Fig. 2 The excised post-treatment tumour showed a fairly circumscribed lesion with cystic cavities lined by bland mucinous glandular epithelium. (A) Some of the epithelium was surrounded by a smooth muscle coat, resembling the architecture of intestinal wall (H&E, 64). (B) Aggregates of micropapillary structures and tubules resembling nephrogenic rests were present (H&E, 610). (C) In areas, large numbers of tumour cells showed abundant eosinophilic cytoplasm, eccentric nuclei and prominent nucleoli (H&E, 610). These cells displayed (Di) strong immunohistochemical cytoplasmic positivity for desmin and (Dii) focal nuclear positivity for myogenin, and hence confirmed their rhabdomyoblastic differentiation (610).
366
CORRESPONDENCE
Fig. 3 Immunohistochemical studies with desmin and myogenin showed a portion of the small round cells were reactive for (A) desmin and (B) myogenin (610).
composed of loose fibrous stroma, glial tissue and nerve bundles. Aggregates of micropapillary structures and tubules resembling nephrogenic rests were present (Fig. 2B). In areas, large numbers of cells with abundant eosinophilic cytoplasm, eccentric nuclei and prominent nucleoli, consistent with rhabdomyoblasts, were seen (Fig. 2C). These cells were immunohistochemically reactive for desmin and myogenin (Fig. 2Di,ii). The blastemal elements identified in the previous biopsy were not seen. Primitive neural elements and necrosis were absent. In view of the abundant rhabdomyoblasts identified in the post-treatment tumour, immunohistochemical studies with myogenic markers desmin and myogenin were conducted in the previous biopsy. A considerable proportion of the blastemal cells were positive for both skeletal muscle markers desmin and myogenin (Fig. 3). The final diagnosis of the tumour was a retroperiteoneal immature teratoma with nephroblastic and rhabdomyoblastic differentiation. Teratoid Wilms’ tumor is a rare histological variant of the classical Wilms’ tumor. The term was introduced by Variend et al.1 to define a subtype of nephroblastoma in which over 50% of the tumour mass was composed of heterologous elements, e.g., adipose tissue, muscle, cartilage, or bone. The behaviour of this kind of tumour is usually described as less aggressive than the conventional Wilms’ tumour. Surgery should be the treatment of choice because the efficacy of chemotherapy and radiotherapy is probably reduced by the high amount of differentiated and mature tissue.2 Successful demonstration of myogenic expression in the ‘blastema’-like component in the initial biopsy confirmed its rhabdomyoblastic differentiation at the initial presentation. As a result of chemo-irradiation, these primitive small round cells were transformed into more differentiated, morphologically recognisable rhabdomyoblasts. The presence of rhabdomyoblastic component in Wilms’ tumour is not uncommon, especially in post-treatment specimens. Histologically, primitive rhabdomyoblasts display similar morphology as the blastemal element of a conventional
Pathology (2006), 38(4), August
Wilms’ tumour. In these conditions, myogenin may be used as an immunohistochemical marker in distinguishing Wilms’ tumour with rhabdomyoblastic differentiation from conventional Wilms’ tumour. According to Folpe, none of the nine studied Wilms’ tumours showed a significant positive staining pattern (more than 5% positive cells) with myogenin.3 On the other hand, a positive signal is found by Kumar in two Wilms’ tumours with rhabdomyoblastic differentiation.4 According to a review of 14 cases of rhabdomyoblastic nephroblastoma by Pollono et al. in 2003,5 in which one extra-renal case was included, chemotherapy proved not as effective as in other variants of nephroblastoma. In addition, the prognosis depends highly on tumour staging at presentation. Therefore, for an extra-renal teratoid Wilms’ tumour with rhabdomyoblastic differentiation, a surgical approach rather than chemo-irradiation therapy would appear to be the more appropriate treatment. In the current case, there are several conflicting features that are not supportive of the diagnosis of an extra-renal teratoid Wilms’ tumour. The arrangement of cysts lined by mucinous gland and smooth muscle coat, resembling the architecture of intestinal tract, are described as organoid arrangement. In teratoid Wilms’ tumour, although these components can be identified, they are usually disposed in a haphazard fashion rather than in an organised manner. Moreover, nerve bundles and glial tissue are more commonly seen in immature teratoma than teratoid Wilms’ tumour. As a result, we considered the current case as a retroperitoneal immature teratoma with nephroblastic and rhabdomyoblastic differentiation. To date, there have been five reported cases of retroperitoneal/sacral-coccygeal immature teratoma with nephroblastic differentiation. Most were treated with chemo-irradiation and surgical excision despite the presence of metastasis at presentation.6–10 The origin and proper treatment of this neoplasm is not settled because of the small number of cases reported. According to Emerson et al., loss of heterozygosity was observed at locus 11p13 (WT1) in the nephroblastic component of a testicular immature teratoma. This locus is usually inactivated in patients who are genetically predisposed to nephroblastoma. The demonstrated loss of heterozygosity at this focus may suggest an important genetic mechanism in the nephroblastic differentiation of an immature teratoma. Moreover, using tissue microdissection and loss of heterozygosity analysis, a common clonal origin for nephroblastoma and the immature teratoma has been demonstrated. Despite the presence of supraclavicular and retroperitoneal lymph node metastasis in that reported case, no recurrence was noted with 21 months of additional follow-up after chemotherapy.11 Literature search did not reveal a single reported case of retroperitoneal immature teratoma with rhabdomyoblastic differentiation. However, in the few case reports of gonadal immature teratoma with rhabdomyoblastic differentiation, the tumour appears to be much more aggressive.12–14 Despite surgical excision, aggressive chemotherapy and irradiation, patients suffered from repeated recurrences and finally died of the disease. Although the primary tumour contained only a few rhabdomyoblasts, rhabomyosarcoma appeared to be the predominant component in the recurrent tumours. The findings in this small number of cases suggest that the rhabdomyoblastic component arising
CORRESPONDENCE
from an immature teratoma should be treated with great caution. In conclusion, we consider the current case as an immature teratoma with nephroblastic and rhabdomyoblastic differentiation. It appears from literature review that the teratomatous and nephroblastomatous components are more amenable to surgical excision. The rhabdomyoblastic component should be treated aggressively as it may relapse as a pure sarcoma. Yuen-Shan Fan* Ui-Soon Khoo{ Gavin Shueng-Wai Chan* Departments of Pathology, *Queen Mary Hospital, and {University of Hong Kong, Hong Kong SAR, China Contact Dr Y. S. Fan. E-mail: [email protected] ACKNOWLEDGEMENT We would like to thank Dr G. M. Vujanic for her expert opinion on this case.
1. Variend S, Spicer RD, Mckinnon AE. Teratoid Wilms’ tumour. Cancer 1984; 53: 1936–42. 2. Cecchetto G, Alaggio R, Scarzello G, et al. Teratoid Wilms’ tumor: report of a unilateral case. J Pediatr Surg 2003; 38: 259–61. 3. Folpe AL, Patterson K, Gown AM. Antibodies to desmin identify the blastemal component of nephroblastoma. Mod Pathol 1997; 10: 895–900. 4. Kumar S, Perlman E, Harris CA, et al. An immunohistochemical study in paraffin-embedded tissue. Mod Pathol 2000; 13: 988–33. 5. Pollono D, Drut R, Tomarchio S, et al. Fetal rhabdomyomatous nephroblastoma: report of 14 cases confirming chemotherapy resistance. J Pediatr Hematol Oncol 2003; 25: 640–3. 6. Kim YW, Park YK, Oh SM, et al. Retroperitoneal teratoma with predominance of nephroblastic elements–a case report. J Korean Med Sci 1990; 5: 237–42. 7. Tebbi K, Ragab AH, Ternberg JL, et al. An extrarenal Wilms’ tumor arising from a sacrococcygeal teratoma. Clin Pediatr (Phila) 1974; 13: 1019–21. 8. Malik TK, Malik GB, Diesh G. Retroperitoneal teratoma with nephroblastic tissue as the main component. Int Surg 1967; 47: 246– 9. 9. Ward SP, Dehner LP. Saccroccygeal teratoma with neprhoblastoma (Wilms’ tumour): A variant of extragonadal teratoma in childhood. Cancer 1974; 33: 1355–63. 10. Park HR, Park CY, Choi NK, et al. A case of retroperitoneal teratoma with nephroblastoma. J Korean Med Sci 1991; 6: 95–102.
367
11. Emerson RE, Ulbright TM, Zhang S, et al. Nephroblastoma arising in a germ cell tumor of testicular origin. Am J Surg Pathol 2004; 28: 687–92. 12. Yanai H, Matsuura H, Kawasaki M, et al. Immature teratoma of the ovary with a minor rhabdomyosarcomatous component and fatal rhabdomyosarcomatous metastases: the first case in a child. Int J Gynecol Pathol 2002; 21: 82–5. 13. Terrier-Lacombe MJ, Martinez-Madrigal F, Porta W, et al. Embryonal rhabdomyosarcoma arising in a mature teratoma of the testis: a case report. J Urol 1990; 143: 1232–4. 14. Haines IE, Schwarz MA, Westmore DD, et al. Rhabdomyosarcoma in a patient treated for metastatic germ cell tumour of the testis containing teratoma–a case report. Aust N Z J Surg 1985; 55: 141–3.
DOI: 10.1080/00313020600820765