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Congenital Mesoblastic Nephroma: Report of a Case with Review of the Most Significant Literature
PATHOLOGY RESEARCH AND PRACTICE
e Urban &Fischer Verlag
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Congenital Mesoblastic Nephroma: Report of a Case with Review of the Most Significant Literature Michele Bisceglia 1, IIluminato Carosi 1, Matteo Vairol, Lucia Zaffarano\ Michele Bisceglia 2 and Giuseppe Creti 3 Departments of 'Anatomic Pathology, 'Neonatal Pathology, and 'Urology, IRCCSHospital "C asa Sollievo della Sofferenza", San Giovanni Rotondo (FG ), Italy
Summary Aims and background: Congenital mesoblastic nephroma (CMN) is a rare pediatric tumor of the kidney with the highest peak of incidence during the first 3 postnatal months. It has previously been confused with Wilms' tumor (which, on the contrary, is rare during the first six months of age and is still considered a histogenetic congener). CMN almost always has a favourable prognosis. Therefore, CMN needs to be correctly diagnosed and differentiated from other pediatric renal neoplasms. Two morphological SUbtypes are current ly distinguished histologically: the classical or leiomyomatous type and the atypical or cellular type. Mixed forms with a combination of the two patterns arc also on record. Recurrence and even tumor-related death have been described in the literature and always related to the atypical form or to the mixed form, particularly in patients aged more than 3 months and in those cases in which the surgical removal was not complete. Opinions concerning post-surgical clinical management, especially in regard to adjuvant therapy, are not unanimous. Methods: A case of CMN, predominantly of the classical hi stological subtype diagnosed in a baby with a follow-up of 6 years, is herein presented. The tumor was discovered at birth and surgically removed after one month. Since the tumor showed a high mitotic index (one of the characteristics of the cellular subtypc) and the perirenal fat was focally involved with the tumor, the poss ibility of giving adjuvant chemotherapy was considered. Flow cytometric analysis was also performed which showed a diploid DNA content of neoplastic cells. Results: The tumor was completely removed, surgical margins were free histologically, and no clear-cut hi sto-
Pathol. Res. Pract. 196: 199- 204 (2000)
logical features of the atypical SUbtype were noted. Flow cytomctrically, it showed the euploid DNA content. Consequently no additional therapy was given. Six years after surgery the patient is developing well and is free of disease. He has regular follow-up examinations. Conclusions: CMN almost always pursues a benign clinical coursc if diagnosed under three months of age and if totally surgically excised independent of histological type. Criteria for management of atypical cases are not unanimous in regard to the benefit of additional therapy after surgery.
Key words: Congenital mesoblastic nephroma Wilms' tumor - Kidney - Renal tumor - Pecliatric neoplasm
Introduction "Mesoblastic nephroma" is the most common renal neoplasm in the neonate [43]. One-third to one-half of cases occur in the first week of life and are usually discovered within 6 months of age - the explanation for its designation as "congenital". It is rare in later childhood and exceptional in adulthood . Mesoblastic nephroma is also eponimically called "Bolande's tumor" after the author who in 1967 first coined the most frequently used term "congenital mesoblastic nephroma" (CMN) [10]. He was also the first to di stinguish this neoplasm Address for correspondence: Dr. Michele Bisceglia. Scrvizio di Anatomia Patologica, IRCSS-Ospedale "Casa Soltiev<) delta Sofferenza". I - 7101 3 San Giovanni Rotondo (FG). Italy. Tel.: ++39-0882-4 10366. -410365, -410364, Fax: ++39-0882-411705.
0344 -0338/20001196/3-199 $12.00/0
200 . M. Bisceglia et al.
from congenital Wilms' tumor (WT), with which it was previously confused {II]. CMN usually runs an indolent clinical course following surgical treatment alone (35, 58/. Some appellations commonly used in the old literature, such as "fetal mesenchymal hamartoma" [70a-bl, "Ieiomyomatous hamartoma" [91, and "renal leiomyoma" {73J clearly illustrate this "benign" behaviour. However, a "cellular", or atypical subtype of CMN was subsequently recognized (4, 38, 6lJ, which some authors associate with more aggressive clinical behaviour, in contrast to the "classical" sUbtype (4, 33, 38, 59]. The so-called "malignant mesenchymal nephroma of infancy" {29J has to be regarded nowadays as a variant of the cellular subtype and equated with the malignant form of CMN. This report aims to describe a case of a CMN of the "conventional" type with high mitotic activity in a onemonth old baby.
Case Report A living female baby weighing 3.800 gr was delivered by a Caesarian section at 37 weeks of gestation. The mother suffered from gestosis during the last trimester of pregnancy. At birth an abdominal mass located in the right flank was physically discovered, localized by ultrasound and computed tomography scan in the lower pole of the ipsilateral kidney. No other physical abnormalities were found. All metabolic and electrolytic parameters were within normal range, including serum calcium level and serum renin assay. At one month of age, the baby was
operated on and a total right nephrectomy was performed. Grossly speaking the tumor was 3 cm in size, somewhat circumscribed but unencapsulated, with a smooth external surface, which upon cutting exhibited a fibromyomatous consistency (Fig. I). The microscopical appearance was that of a mesenchymal unencapsulated spindle cell neoplasm infiltrating the parental renal parenchyma with tubules and glomeruli encased in the neoplastic growth. Mitoses were numerous, with a counting of 15 per 10 HPF, whilst necrosis and hemorrhage were not seen (Fig. 2-3). The perirenal fat was also found focally invaded by tumor, but surgical margins were not involved (Fig. 4). Immunohistochemically the neoplasm was immunoreactive throughout for vimentin (monoclonal V9, 1:50, Dakopatts, Glostrup, Denmark), and focally for muscle-specific actin (monoclonal HHF-35, prediluted, Dakopatts), as well as for alpha-smooth muscle actin (monoclonal IA4, I:300, Sigma Chemical , Dorset, UK). Immunostains for desmin (monoclonal DERII , 1:50, Dakopatts), CD34 (monoclonal QBEND I 0, I: 10, Serotec, Oxford, UK), epithelial membrane antigen (monoclonal E29, prediluted, Dakopatts), and cytokeratins (monoclonal MNF1I6, 1:5, Dakopatts) were all negative. An electron microscopical study was also performed, which showed that the neoplastic elements exhibited the fine structure of myofibroblasts. In conclusion a specimen of deparaffinized tumor tissue was analyzed by now cytometry, which showed a euploid DNA content. The tumor was diagnosed as a classical CMN with some features (high mitotic index) of the cellular variant. The patient was discharged with no adjunctive therapy on the 13th postoperative day. Currently, about six years following surgery, the patient is still well, alive and free of disease.
Discussion
Fig. 1. A solid fibromyomatous-like tumor replaces almost entirely the lower pole of the kidney and part of its midportion .
CMN usually presents as an incidentally discovered, asymptomatic abdominal mass in the newborn in the nursery or later by parents. An uncommon presentation around or after birth is an intratumoral hemorrhage or tumor rupture with hemoperitoneum and shock, requiring emergency surgery {28i. Sometimes the diagnosis of tumor is heralded by metabolic disturbances, such as a transient hypercalcemia or nephrocalcinosis, a paraneoplastic phenomenon probably related to a pathogenetic role of prostaglandins (23, 69]. On other occasions, the first presentation of tumor in a newborn is manifested by a syndrome of hyperreninism {lSI which is explained by an increased production of renin by afferent arteriolae supplying normal glomeruli entrapped in the tumor. CMN is the predominant renal neoplasm in the first 3 months of life, but is uncommon after 6 months {43 j.
Congenital Mesoblastic Nephroma . 201 Very rare examples in adulthood have also been observed with around 15 cases on record [7, 13, 14, 16, 19,22,27,3 1, 46. 49,50,55,64,67,68,7 IJ. Tumor weight ranges from ten gr to more than a couple of kg, as recorded in the "giant" case of Ogawa et al. [50J. CMN is usually solid, but cystic variants (mainly pertinent to the atypical subtype) have also been described [16, 26, 41, 53 J. It is usually unilateral, even though exceptional bilateral examples are also on record /63J and even a case occurring in a solitary kidney has been reported [48 /. CMN histologicall y presents in two variants. the "classical", "conventional" , or "Ieiomyomataus" variant and the "atypical" or "cellular" variant. The former is characterized by interlacing bundles of spindle cells lacking a significant mitotic activity (0-8 mitoses per I 0 high power field), while the latter exhibits a densely cellular proliferation, shorter spindle or oval cells, high mitotic index (8- 30 mitoses per I 0 high power field ), cystic degeneration, necrosis and hemorrhage j38j. The incidence of the two variants is estimated at around 50% each [2,9,25,53,63]. Cases of CMN of the "mixed" form, with a combination of the two patterns, are on record as well [20, 38. 53]. ImmunohislOchemically CMN usually shows diffuse immunoreactivity for vimentin and fibro-
Fig. 2. The tumor is comprised of a monotonous population of spindle cells armnged in disorderly orientated fascicles. HE xiIS. Fig. 3. A few tubular structures as well as one glomerulus entrapped in the tumor are shown in this field. HE x270. Inset: Frequent mitotic figures are seen. HE x460. Fig. 4. The perirenal fat is infiltrated by th e tumor. On the lower right corner a m s all focus of renal parenchy-
ma isversible. HE x iI S.
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202 . M. Bisceglia et al.
neetin as well as for actins, whilst it exhibits only focal or weak desmin positivity [20, 47]. Ultrastructurally, the feature of myofibroblasts is usually seen [52, 54]. At flow cytometric analysis, a diploid DNA content was consistently found in the classical CMN [3, 19,53, 62}, whereas a variable DNA content - often aneuploid and rarely diploid - was shown in the cellular or mixed sUbtype [3, 53, 62}. Cytogenetic and molecular studies have consistently documented chromosomal changes in most cases of cellular CMN, especially trisomy 11 [42, 45} and translocation t(12;15) (pI3;q25) associated with ETV6NTRK3 gene fusions {42, 57], both of which are also present in congenital fibrosarcoma of soft tissue. This genetic evidence - in addition to the morphological resemblance between these two tumors - strongly support the histo-pathogenetic hypothesis that the two tumors represent a single entity in different locations. Furthermore, the fact that chromosomal polysomy and the ETV6-NTRK3 gene fusions have only been documented in the cellular (or mixed) forms provides insight into potential mechanisms involved in the transformation of one SUbtype into another [42]. Microscopically, CMN needs to be differentiated from some other pediatric and adult tumor entities, although these diagnostic problems are usually solved by means of immunohistochemistry and electron microscopy. Leiomyomatous tumors ("true" leiomyoma' fl2, 18, 40) and leiomyosarcoma [I2} usually display diffuse, strong immunoreactivity for desmin - in addition to reactivity for actins - along with the ultrastructural features of smooth muscle cells. Angiomyolipoma, even considering those variants with scarce or without any adipocytic component [21, 52}, should not represent a diagnostic pitfall, due to its characteristic vascular component of thick-walled blood vessels and its typical immunophenotypic expression of HMB-45 antigen*' related to gplOO-cl gene product, in addition to reactivity for smooth muscle markers.
* The tenn "leiomyoma" was also synonymically used in the old literature to refer to CMN {73]. Currently this old-fashioned use is strongly discouraged and totally abandoned. ** HMB-45 - a melanoma-associated antigen - has also been found positive in smooth muscle tumors of the renal capsule
[12J,
therefore posing the question of the relationship be-
tween these latter tumors and angiomyoLipoma. Outside the
kidney this marker has also been found positive in lymphangioiciomyomatosis, and in the sugar tumors of lung and pancreas: the restricted group of tumors expressing HMB-45 antigen is currently labelled under the acronymic term PEC (Perivascular Epithelioid Cells) - omas [72].
Nerve sheath tumors (neurinoma and malignant schwan noma), which are almost always S-IOO protein positive with clear-cut ultrastructural schwannian differentiation, represent an extremely rare occurrence in the renal parenchyma [56, 65]. However it is worth mentioning that a palisading pattern reminiscent of nerve sheath tumors is sometimes seen in another mesenchymal renal neoplasm of infancy, i.e., the clear cell sarcoma of the kidney [5}. Clear cell sarcoma of the kidney ("bone metastasizing renal tumor of childhood") can enter into differential diagnosis with CMN of the cellular subtype [53 , 54}, even though the absence of the arborizing vascularity typical of the former, along with the absence of sclerosis and hyalinization in the latter, help to make the correct diagnosis. WT may sometimes be difficult to differentiate from CMN: in fact, although WT of the "classical" type is usually easily differentiated from CMN by virtue of the identification of the blastoma which is absent in the latter [20}, "WTwith stromal predominance" may be confused with CMN [20}, as is the case also with the "mature (tenminally differentiated) nephroblastoma" [36}, or with the so-called "cystic partially differentiated nephroblastoma" [26, 39}, or even with "multilocular cystic nephroma" a variant of which "with stromal (sarcomatous) overgrowth" has also been reported [2]. "Nephrogenic adenofibroma " , a novel kidney tumor of young people [34], despite being classically comprised of two components with an epithelial nephroblastomatosis-like portion, may easily be misdiagnosed as CMN. From the prognostic point of view, classical CMN runs a favourable outcome following a complete removal of the tumor. Nevertheless, as far as the cellular subtype is concerned, opinions are not unanimous: to somc authors it seems to portend a more aggressive clinical course [24, 29, 30, 32, 33, 37, 38, 58, 65J. especially cases with accompanying hemorrhage and necrosis [32, 59}, while to others the clinical outcome seems an age-related phenomenon, in the sense that this subtype can recur or even metastasize almost exclusively in patients over 3 months of age [6, 8}. However, it must be emphasized that so far the only cases which have proved recurrent or even fatal were of the cellular SUbtype [20, 59} or of the mixed form [33}: in a review on this subject Gormley et aJ. [32} found a 20% recurrence for the cellular variant, often related to a surgically incomplete removal. Distant metastases have been described mainly to the lungs [29, 38, 59, 66} as well as to the brain [1, 33, 59, 60}. Although some authors advocate an additional chemotherapeutical treatment for CMN of the cellular variant {l?, 44}, most authors consider that an adequate surgical resection with free margins is a sufficient therapeutic option for the control of this tumor, regardless of histological type {35, 58}. However, as far as the CMN of the cellular variant is concerned, a strict, careful follow-up is always recom-
Congcnilal Mesoblastic Nephroma mended [6, 32, 59J and additional chemotherapy can be considered for those cases in which surgical margins are histologically in volved . [58]. Acknowledgement. The authors gratefully acknowledge Dr. A. Barletta of the Oncologic Institute "Mater D ei" (Ex perimen tal Oncology Section), Bari. Italy, fo r performing the flo w cytometric analysis of the case herein reported.
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Congenital Mesoblastic Nephroma: Report of a Case with Review of the Most Significant Literature Michele Bisceglia 1, IIluminato Carosi 1, Matteo Vairol, Lucia Zaffarano\ Michele Bisceglia 2 and Giuseppe Creti 3 Departments of 'Anatomic Pathology, 'Neonatal Pathology, and 'Urology, IRCCSHospital "C asa Sollievo della Sofferenza", San Giovanni Rotondo (FG ), Italy
Summary Aims and background: Congenital mesoblastic nephroma (CMN) is a rare pediatric tumor of the kidney with the highest peak of incidence during the first 3 postnatal months. It has previously been confused with Wilms' tumor (which, on the contrary, is rare during the first six months of age and is still considered a histogenetic congener). CMN almost always has a favourable prognosis. Therefore, CMN needs to be correctly diagnosed and differentiated from other pediatric renal neoplasms. Two morphological SUbtypes are current ly distinguished histologically: the classical or leiomyomatous type and the atypical or cellular type. Mixed forms with a combination of the two patterns arc also on record. Recurrence and even tumor-related death have been described in the literature and always related to the atypical form or to the mixed form, particularly in patients aged more than 3 months and in those cases in which the surgical removal was not complete. Opinions concerning post-surgical clinical management, especially in regard to adjuvant therapy, are not unanimous. Methods: A case of CMN, predominantly of the classical hi stological subtype diagnosed in a baby with a follow-up of 6 years, is herein presented. The tumor was discovered at birth and surgically removed after one month. Since the tumor showed a high mitotic index (one of the characteristics of the cellular subtypc) and the perirenal fat was focally involved with the tumor, the poss ibility of giving adjuvant chemotherapy was considered. Flow cytometric analysis was also performed which showed a diploid DNA content of neoplastic cells. Results: The tumor was completely removed, surgical margins were free histologically, and no clear-cut hi sto-
Pathol. Res. Pract. 196: 199- 204 (2000)
logical features of the atypical SUbtype were noted. Flow cytomctrically, it showed the euploid DNA content. Consequently no additional therapy was given. Six years after surgery the patient is developing well and is free of disease. He has regular follow-up examinations. Conclusions: CMN almost always pursues a benign clinical coursc if diagnosed under three months of age and if totally surgically excised independent of histological type. Criteria for management of atypical cases are not unanimous in regard to the benefit of additional therapy after surgery.
Key words: Congenital mesoblastic nephroma Wilms' tumor - Kidney - Renal tumor - Pecliatric neoplasm
Introduction "Mesoblastic nephroma" is the most common renal neoplasm in the neonate [43]. One-third to one-half of cases occur in the first week of life and are usually discovered within 6 months of age - the explanation for its designation as "congenital". It is rare in later childhood and exceptional in adulthood . Mesoblastic nephroma is also eponimically called "Bolande's tumor" after the author who in 1967 first coined the most frequently used term "congenital mesoblastic nephroma" (CMN) [10]. He was also the first to di stinguish this neoplasm Address for correspondence: Dr. Michele Bisceglia. Scrvizio di Anatomia Patologica, IRCSS-Ospedale "Casa Soltiev<) delta Sofferenza". I - 7101 3 San Giovanni Rotondo (FG). Italy. Tel.: ++39-0882-4 10366. -410365, -410364, Fax: ++39-0882-411705.
0344 -0338/20001196/3-199 $12.00/0
200 . M. Bisceglia et al.
from congenital Wilms' tumor (WT), with which it was previously confused {II]. CMN usually runs an indolent clinical course following surgical treatment alone (35, 58/. Some appellations commonly used in the old literature, such as "fetal mesenchymal hamartoma" [70a-bl, "Ieiomyomatous hamartoma" [91, and "renal leiomyoma" {73J clearly illustrate this "benign" behaviour. However, a "cellular", or atypical subtype of CMN was subsequently recognized (4, 38, 6lJ, which some authors associate with more aggressive clinical behaviour, in contrast to the "classical" sUbtype (4, 33, 38, 59]. The so-called "malignant mesenchymal nephroma of infancy" {29J has to be regarded nowadays as a variant of the cellular subtype and equated with the malignant form of CMN. This report aims to describe a case of a CMN of the "conventional" type with high mitotic activity in a onemonth old baby.
Case Report A living female baby weighing 3.800 gr was delivered by a Caesarian section at 37 weeks of gestation. The mother suffered from gestosis during the last trimester of pregnancy. At birth an abdominal mass located in the right flank was physically discovered, localized by ultrasound and computed tomography scan in the lower pole of the ipsilateral kidney. No other physical abnormalities were found. All metabolic and electrolytic parameters were within normal range, including serum calcium level and serum renin assay. At one month of age, the baby was
operated on and a total right nephrectomy was performed. Grossly speaking the tumor was 3 cm in size, somewhat circumscribed but unencapsulated, with a smooth external surface, which upon cutting exhibited a fibromyomatous consistency (Fig. I). The microscopical appearance was that of a mesenchymal unencapsulated spindle cell neoplasm infiltrating the parental renal parenchyma with tubules and glomeruli encased in the neoplastic growth. Mitoses were numerous, with a counting of 15 per 10 HPF, whilst necrosis and hemorrhage were not seen (Fig. 2-3). The perirenal fat was also found focally invaded by tumor, but surgical margins were not involved (Fig. 4). Immunohistochemically the neoplasm was immunoreactive throughout for vimentin (monoclonal V9, 1:50, Dakopatts, Glostrup, Denmark), and focally for muscle-specific actin (monoclonal HHF-35, prediluted, Dakopatts), as well as for alpha-smooth muscle actin (monoclonal IA4, I:300, Sigma Chemical , Dorset, UK). Immunostains for desmin (monoclonal DERII , 1:50, Dakopatts), CD34 (monoclonal QBEND I 0, I: 10, Serotec, Oxford, UK), epithelial membrane antigen (monoclonal E29, prediluted, Dakopatts), and cytokeratins (monoclonal MNF1I6, 1:5, Dakopatts) were all negative. An electron microscopical study was also performed, which showed that the neoplastic elements exhibited the fine structure of myofibroblasts. In conclusion a specimen of deparaffinized tumor tissue was analyzed by now cytometry, which showed a euploid DNA content. The tumor was diagnosed as a classical CMN with some features (high mitotic index) of the cellular variant. The patient was discharged with no adjunctive therapy on the 13th postoperative day. Currently, about six years following surgery, the patient is still well, alive and free of disease.
Discussion
Fig. 1. A solid fibromyomatous-like tumor replaces almost entirely the lower pole of the kidney and part of its midportion .
CMN usually presents as an incidentally discovered, asymptomatic abdominal mass in the newborn in the nursery or later by parents. An uncommon presentation around or after birth is an intratumoral hemorrhage or tumor rupture with hemoperitoneum and shock, requiring emergency surgery {28i. Sometimes the diagnosis of tumor is heralded by metabolic disturbances, such as a transient hypercalcemia or nephrocalcinosis, a paraneoplastic phenomenon probably related to a pathogenetic role of prostaglandins (23, 69]. On other occasions, the first presentation of tumor in a newborn is manifested by a syndrome of hyperreninism {lSI which is explained by an increased production of renin by afferent arteriolae supplying normal glomeruli entrapped in the tumor. CMN is the predominant renal neoplasm in the first 3 months of life, but is uncommon after 6 months {43 j.
Congenital Mesoblastic Nephroma . 201 Very rare examples in adulthood have also been observed with around 15 cases on record [7, 13, 14, 16, 19,22,27,3 1, 46. 49,50,55,64,67,68,7 IJ. Tumor weight ranges from ten gr to more than a couple of kg, as recorded in the "giant" case of Ogawa et al. [50J. CMN is usually solid, but cystic variants (mainly pertinent to the atypical subtype) have also been described [16, 26, 41, 53 J. It is usually unilateral, even though exceptional bilateral examples are also on record /63J and even a case occurring in a solitary kidney has been reported [48 /. CMN histologicall y presents in two variants. the "classical", "conventional" , or "Ieiomyomataus" variant and the "atypical" or "cellular" variant. The former is characterized by interlacing bundles of spindle cells lacking a significant mitotic activity (0-8 mitoses per I 0 high power field), while the latter exhibits a densely cellular proliferation, shorter spindle or oval cells, high mitotic index (8- 30 mitoses per I 0 high power field ), cystic degeneration, necrosis and hemorrhage j38j. The incidence of the two variants is estimated at around 50% each [2,9,25,53,63]. Cases of CMN of the "mixed" form, with a combination of the two patterns, are on record as well [20, 38. 53]. ImmunohislOchemically CMN usually shows diffuse immunoreactivity for vimentin and fibro-
Fig. 2. The tumor is comprised of a monotonous population of spindle cells armnged in disorderly orientated fascicles. HE xiIS. Fig. 3. A few tubular structures as well as one glomerulus entrapped in the tumor are shown in this field. HE x270. Inset: Frequent mitotic figures are seen. HE x460. Fig. 4. The perirenal fat is infiltrated by th e tumor. On the lower right corner a m s all focus of renal parenchy-
ma isversible. HE x iI S.
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202 . M. Bisceglia et al.
neetin as well as for actins, whilst it exhibits only focal or weak desmin positivity [20, 47]. Ultrastructurally, the feature of myofibroblasts is usually seen [52, 54]. At flow cytometric analysis, a diploid DNA content was consistently found in the classical CMN [3, 19,53, 62}, whereas a variable DNA content - often aneuploid and rarely diploid - was shown in the cellular or mixed sUbtype [3, 53, 62}. Cytogenetic and molecular studies have consistently documented chromosomal changes in most cases of cellular CMN, especially trisomy 11 [42, 45} and translocation t(12;15) (pI3;q25) associated with ETV6NTRK3 gene fusions {42, 57], both of which are also present in congenital fibrosarcoma of soft tissue. This genetic evidence - in addition to the morphological resemblance between these two tumors - strongly support the histo-pathogenetic hypothesis that the two tumors represent a single entity in different locations. Furthermore, the fact that chromosomal polysomy and the ETV6-NTRK3 gene fusions have only been documented in the cellular (or mixed) forms provides insight into potential mechanisms involved in the transformation of one SUbtype into another [42]. Microscopically, CMN needs to be differentiated from some other pediatric and adult tumor entities, although these diagnostic problems are usually solved by means of immunohistochemistry and electron microscopy. Leiomyomatous tumors ("true" leiomyoma' fl2, 18, 40) and leiomyosarcoma [I2} usually display diffuse, strong immunoreactivity for desmin - in addition to reactivity for actins - along with the ultrastructural features of smooth muscle cells. Angiomyolipoma, even considering those variants with scarce or without any adipocytic component [21, 52}, should not represent a diagnostic pitfall, due to its characteristic vascular component of thick-walled blood vessels and its typical immunophenotypic expression of HMB-45 antigen*' related to gplOO-cl gene product, in addition to reactivity for smooth muscle markers.
* The tenn "leiomyoma" was also synonymically used in the old literature to refer to CMN {73]. Currently this old-fashioned use is strongly discouraged and totally abandoned. ** HMB-45 - a melanoma-associated antigen - has also been found positive in smooth muscle tumors of the renal capsule
[12J,
therefore posing the question of the relationship be-
tween these latter tumors and angiomyoLipoma. Outside the
kidney this marker has also been found positive in lymphangioiciomyomatosis, and in the sugar tumors of lung and pancreas: the restricted group of tumors expressing HMB-45 antigen is currently labelled under the acronymic term PEC (Perivascular Epithelioid Cells) - omas [72].
Nerve sheath tumors (neurinoma and malignant schwan noma), which are almost always S-IOO protein positive with clear-cut ultrastructural schwannian differentiation, represent an extremely rare occurrence in the renal parenchyma [56, 65]. However it is worth mentioning that a palisading pattern reminiscent of nerve sheath tumors is sometimes seen in another mesenchymal renal neoplasm of infancy, i.e., the clear cell sarcoma of the kidney [5}. Clear cell sarcoma of the kidney ("bone metastasizing renal tumor of childhood") can enter into differential diagnosis with CMN of the cellular subtype [53 , 54}, even though the absence of the arborizing vascularity typical of the former, along with the absence of sclerosis and hyalinization in the latter, help to make the correct diagnosis. WT may sometimes be difficult to differentiate from CMN: in fact, although WT of the "classical" type is usually easily differentiated from CMN by virtue of the identification of the blastoma which is absent in the latter [20}, "WTwith stromal predominance" may be confused with CMN [20}, as is the case also with the "mature (tenminally differentiated) nephroblastoma" [36}, or with the so-called "cystic partially differentiated nephroblastoma" [26, 39}, or even with "multilocular cystic nephroma" a variant of which "with stromal (sarcomatous) overgrowth" has also been reported [2]. "Nephrogenic adenofibroma " , a novel kidney tumor of young people [34], despite being classically comprised of two components with an epithelial nephroblastomatosis-like portion, may easily be misdiagnosed as CMN. From the prognostic point of view, classical CMN runs a favourable outcome following a complete removal of the tumor. Nevertheless, as far as the cellular subtype is concerned, opinions are not unanimous: to somc authors it seems to portend a more aggressive clinical course [24, 29, 30, 32, 33, 37, 38, 58, 65J. especially cases with accompanying hemorrhage and necrosis [32, 59}, while to others the clinical outcome seems an age-related phenomenon, in the sense that this subtype can recur or even metastasize almost exclusively in patients over 3 months of age [6, 8}. However, it must be emphasized that so far the only cases which have proved recurrent or even fatal were of the cellular SUbtype [20, 59} or of the mixed form [33}: in a review on this subject Gormley et aJ. [32} found a 20% recurrence for the cellular variant, often related to a surgically incomplete removal. Distant metastases have been described mainly to the lungs [29, 38, 59, 66} as well as to the brain [1, 33, 59, 60}. Although some authors advocate an additional chemotherapeutical treatment for CMN of the cellular variant {l?, 44}, most authors consider that an adequate surgical resection with free margins is a sufficient therapeutic option for the control of this tumor, regardless of histological type {35, 58}. However, as far as the CMN of the cellular variant is concerned, a strict, careful follow-up is always recom-
Congcnilal Mesoblastic Nephroma mended [6, 32, 59J and additional chemotherapy can be considered for those cases in which surgical margins are histologically in volved . [58]. Acknowledgement. The authors gratefully acknowledge Dr. A. Barletta of the Oncologic Institute "Mater D ei" (Ex perimen tal Oncology Section), Bari. Italy, fo r performing the flo w cytometric analysis of the case herein reported.
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