Mesoblastic Nephroma

Background

This is a rare, usually congenital, neoplasm of the kidney. It was first identified in the kidneys sent in for Wilm's tumors and indeed the chief differential diagnosis is with this latter malignant tumor of the kidney.

OUTLINE

Epidemiology

Disease Associations

Pathogenesis

Laboratory/Radiologic/Other Diagnostic Testing

Gross Appearance and Clinical Variants

Histopathological Features and Variants

Special Stains/Immunohistochemistry/Electron Microscopy

Differential Diagnosis

Prognosis

Treatment

Commonly Used Terms

Internet Links

EPIDEMIOLOGY CHARACTERIZATION

INCIDENCE Rare

AGE RANGE-MEDIAN Usually congenital

DISEASE ASSOCIATIONS CHARACTERIZATION

HYPERCALCEMIA

Hypercalcemia in association with mesoblastic nephroma: report of a case and review of the literature.

Ferraro EM, Klein SA, Fakhry J, Weingarten MJ, Rose JS.
Pediatr Radiol 1986;16(6):516-7 Abstract quote
Hypercalcemia, often associated with certain types of adult tumors, has also been described in pediatric neoplasms.

In childhood, the more common associations include lymphoma, leukemia, rhabdomyosarcoma and rarely neuroblastoma. However, recently, several infants with hypercalcemia were described having renal tumors without bone metastases.

The following is a case report of a 2-month-old infant who presented with severe hypercalcemia and a large right-sided abdominal mass, which at surgery was diagnosed as a cellular mesoblastic nephroma.

PATHOGENESIS CHARACTERIZATION

CHROMOSOMAL ABNORMALITIES

Cytogenetic abnormalities in mesoblastic nephroma: a link to Wilms' tumour?

Roberts P, Lockwood LR, Lewis IJ, Bailey CC, Batcup G, Williams J.

Regional Cytogenetics Unit, St. James's University Hospital, Leeds, England.
Med Pediatr Oncol 1993;21(6):416-20 Abstract quote
Cytogenetic analysis of tumour material from a congenital mesoblastic nephroma is reported. Two cell lines were found, one with a normal 46,XY karyotype and the other with a hyperdiploid 51,XY karyotype, including a rearrangement of chromosome 11 at 11p15.

This finding is of interest since loss of allelic heterozygosity at polymorphic 11p15 loci has been described in sporadic Wilms' tumour [1], and both cytogenetic [2] and molecular [3] changes of 11p15 are found in the Wiedemann-Beckwith syndrome, a condition with a predisposition to embryonal tumours, particularly Wilms' tumour.

Our results lead us to speculate on the implications relating to the pathogenesis of this relatively benign tumour variant with respect to the current understanding of the genetics of Wilms' tumour.

ETV6

ETV6 Rearrangements in Patients with Infantile Fibrosarcomas and Congenital Mesoblastic Nephromas by Fluorescence In Situ Hybridization

Camilo Adem, M.D., David Gisselsson, Ph.D., Paola Dal Cin, Ph.D. and Antonio G. Nascimento, M.D.

Department of Laboratory Medicine and Pathology (CA, AGN), Mayo Clinic, Rochester, Minnesota; and Department of Pathology (DG, PDC), Brigham and Women�s Hospital and Harvard Medical School, Boston, Massachusetts

Mod Pathol 2001;14:1246-1251 Abstract quote

Congenital mesoblastic nephroma (CMN) and infantile fibrosarcoma (IFS) are two pediatric tumors arising in the kidneys and soft tissues of infants, respectively. Recently, a t(12;15)(p13;q25) resulting in ETV6-NTRK3 gene fusion was detected in patients with IFS and in patients with the cellular type of CMN, suggesting a common pathogenetic pathway.

We investigated the presence or absence of ETV6 rearrangements and numerical abnormalities of chromosome 11 by using fluorescence in situ hybridization on paraffin-embedded material from five cases of IFS, two of CMN, and one of mixed type (CMN and IFS) found in our files. In three cases of IFS, we found ETV6 gene rearrangement but a normal copy number of chromosome 11. One case each of IFS, the cellular type of CMN, and the mixed type (CMN and IFS) had both abnormalities. In a case of classic CMN, neither trisomy 11 nor gene rearrangement was found. It is possible that trisomy 11 is a later, nonessential event in the pathogenetic process or that this secondary aberration is associated with still-unrecognized clinical or biological characteristics.

We confirmed that IFS and the cellular type of CMN are cytogenetically related and can occur synchronously in the same organ.

TRISOMY 11

Presence or absence of trisomy 11 is correlated with histologic subtype in congenital mesoblastic nephroma.

Mascarello JT, Cajulis TR, Krous HF, Carpenter PM.

Genetic Services, Children's Hospital-San Diego, CA 92123.
Cancer Genet Cytogenet 1994 Oct;77(1):50-4 Abstract quote
Fluorescence in situ hybridization utilizing a probe for the alpha satellite repeat sequence on chromosome 11 was used to detect variations in the number of chromosomes 11 in 24 formalin-fixed, paraffin-embedded congenital mesoblastic nephromas.

Evidence of trisomy 11 was found in nearly half of the tumors. More importantly, the presence of trisomy 11 was associated with the cellular histologic variant of this tumor.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

FLOW CYTOMETRY

Atypical congenital mesoblastic nephroma. Report of a case with karyotypic and flow cytometric analysis.

Varsa EW, McConnell TS, Dressler LG, Duncan M.

Department of Pathology, University of New Mexico School of Medicine, Albuquerque 87131.

Arch Pathol Lab Med 1989 Sep;113(9):1078-80 Abstract quote

Atypical congenital mesoblastic nephroma is a rare infantile renal tumor that may behave aggressively in older infants. A case of atypical congenital mesoblastic nephroma occurring in an 8-month-old hispanic male was analyzed by routine histopathologic, cytogenetic, and retrospective flow cytometric analysis for DNA ploidy. Light microscopy revealed marked hypercellularity.

The karyotype was abnormal, with the following configuration: 45,XY,-1,-3,-9,-9,-15,-17,-21,+del(1)(q21q25),+der(3), t(3;9;15)(q23;p22;q11),+der(9),t(3;9;15) (q23;p22;q11),+der(9),t(9;?) (p?22;?),+r21, + mar. Retrospective DNA ploidy analysis revealed a DNA index of 1.0. The significance of karyotypic changes occurring in mesenchymal renal tumors of this type is currently unknown.

Cytogenetic analysis might be of prognostic value in these potentially aggressive tumors.

Congenital mesoblastic nephroma: possible prognostic and management value of assessing DNA content.

Barrantes JC, Toyn C, Muir KR, Parkes SE, Raafat F, Cameron AH, Marsden HB, Mann JR.

Department of Oncology, Children's Hospital, Ladywood, Birmingham.
J Clin Pathol 1991 Apr;44(4):317-20 Abstract quote
The case records and pathology of all children with kidney tumours treated in the West Midlands Health Authority Region (WMHAR) from 1957 to 1986 were reviewed. The histology was reviewed by a panel of three paediatric pathologists. Thirteen (6%) out of 211 cases were considered to have congenital mesoblastic nephroma (CMN). Nine were of the conventional type, three of the atypical cellular type, and one mixed. DNA ploidy was investigated and showed two of the tumours to be aneuploid and nine diploid (tissue was not available in the two other cases).

The two aneuploid tumours were of atypical cellular and mixed histology, respectively; the diploid tumours were of the conventional type in eight cases and atypical cellular in one. The atypical cellular type has been reported to behave more aggressively, but the benefit of additional treatment after surgery to prevent recurrence remains unclear.

Measurement of DNA content by flow cytometry, together with histological subclassification, may be useful in selecting patients who will benefit from further treatment after surgery.

RENIN

Renin production in congenital mesoblastic nephroma in comparison with that in Wilms' tumor.

Tsuchida Y, Shimizu K, Hata J, Honna T, Nishiura M.

Department of Surgery, National Children's Hospital, Tokyo, Japan.
Pediatr Pathol 1993 Mar-Apr;13(2):155-64 Abstract quote
The case of an infant with congenital mesoblastic nephroma and associated reninism is presented. The patient was a 39-day-old boy who presented with a left abdominal mass and mild hypertension (112/70 mm Hg).

Both plasma renin activity (PRA) and plasma total renin concentration (PTRC) were elevated; the PTRC value of 1458 pg/mL of this case was the highest we had seen in patients with childhood renal tumors. The tumor was successfully removed and histologically confirmed as a congenital mesoblastic nephroma (cellular variant). The patient's PRA and PTRC returned to normal after nephrectomy. Indirect immunoperoxidase staining showed renin localized predominantly in the juxtaglomerular apparatuses adjacent to the glomeruli entrapped by the tumor. No positive staining was seen in the tumor cells.

These findings indicate that the entrapped glomeruli may play a significant role in producing renin. More important, PTRC was extremely high compared to the moderate increase of PRA and to the mild elevation of blood pressure. The mechanism of renin production by childhood renal tumors is discussed, and the importance of studying inactive renin and total renin is emphasized.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

ADULT

Mesoblastic nephroma of adulthood. Report of three cases.

Durham JR, Bostwick DG, Farrow GM, Ohorodnik JM.

Department of Pathology, Henry Ford Hospital, Detroit, Michigan 48202.
Am J Surg Pathol 1993 Oct;17(10):1029-38 Abstract quote
Mesoblastic nephroma is an uncommon congenital tumor of infancy that rarely occurs in adults.

We report three patients (two were female, one was male) who had mesoblastic nephroma of adulthood and who presented at 45, 64, and 66 years of age with hematuria, flank mass, and pain. All underwent nephrectomy without postoperative adjuvant therapy.

The tumors were solitary yellow-tan masses with solid and cystic areas involving the renal cortex (three cases) with extension into the renal pelvis and calyces (two) and ureter (one). Microscopically, all consisted of uniform spindle cell proliferations with entrapped dilated renal tubules. Focal necrosis was present in two, but no atypia or mitoses were identified in any case.

The spindle cells displayed cytoplasmic immunoreactivity for vimentin, desmin, panmuscle actin (HHF-35), and alpha-smooth-muscle actin, but were nonreactive for keratin (AE1/AE3), epithelial membrane antigen, and S-100 protein. Electron microscopy revealed the presence of smooth-muscle differentiation in two cases and undifferentiated mesenchyme in one. All tumors were DNA diploid by flow cytometry. The patients were free of recurrence 8 months-2 years postoperatively.

Because surgical excision may be curative, mesoblastic nephroma in adult patients must be differentiated from spindle cell neoplasms of the kidney that require additional therapy.

Mesoblastic nephroma in adulthood: a case report.

Shiraishi K, Yamamoto M, Gondo T, Shirataki S, Naito K.

Department of Urology, Yamaguchi University School of Medicine, Ube, Japan.
Int J Urol 1999 Aug;6(8):414-8 Abstract quote
BACKGROUND: Mesoblastic nephroma is an uncommon renal tumor of infancy and rarely occurs in adults. We report an adult case of mesoblastic nephroma.

METHODS: A 50-year-old woman was found incidentally to have a right renal mass by abdominal ultrasonography. Computed tomography and magnetic resonance imaging revealed a heterogeneous tumor and angiography showed a mixture of hypervascularity and hypovascularity. Right radical nephrectomy was performed.

RESULTS: The tumor was an encapsulated yellowish solid mass. Microscopically, the tumor was composed of spindle cell proliferation. Atypia and mitoses were not identified. Among the tumor cells, there were tubular arranged epithelial elements.

CONCLUSION: The patient was free of recurrence 14 months postoperatively. Mesoblastic nephroma is classified as a benign tumor but recurrence and malignant formation of this tumor have been reported so regular postoperative follow up is required.

CYSTIC

Multicystic congenital mesoblastic nephroma.

Drut R.

Servicio de Patologia, Hospital de Ninos "Superiora Sor Maria Ludovica", La Plata, Argentina.
Int J Surg Pathol 2002 Jan;10(1):59-63 Abstract quote
This report describes an unusual example of congenital mesoblastic nephroma cellular variant that presented in a 1-week-old neonate as a multicystic tumor of the kidney. Extensive pseudocystic cavitation resulted from progressive accumulation of ground substance in a loosely myxoid tissue composed of stellate- and spindle-shaped cells that compressed and infiltrated renal tissue. The cells of the tumor were positive for vimentin and smooth muscle actin.

The patient is alive and well 16 years after surgery. Differential diagnosis from segmental cystic dysplasia, cystic intralobar nephrogenic rest, cystic nephroma, cystic partially differentiated nephroblastoma, cystic nephroblastoma, and cystic clear cell sarcoma of the kidney, all of which may present at this age, is discussed.

HISTOLOGICAL TYPES CHARACTERIZATION

GENERAL Deeply infiltrative border
Lacks prominent vasculature
Desmin+

Congenital mesoblastic nephroma.

Gerber A, Gold JH, Bustamante S, Lorch V, Mirza M.
J Pediatr Surg 1981 Oct;16(5):758-9 Abstract quote
Neonatal renal neoplasms are rare: most are congenital mesoblastic nephroma. In the past this neoplasm has been confused with Wilms' tumor, which in part may account for some of the more favorable prognosis ascribed to Wilms' tumor in children less than 1 yr of age.

Congenital mesoblastic nephroma is usually a benign tumor. The recommended treatment is surgical excision. This is a report of two cases of congenital mesoblastic nephroma in infants who were treated successfully by nephrectomy.

Classical and cellular (atypical) congenital mesoblastic nephroma: a clinicopathologic, ultrastructural, immunohistochemical, and flow cytometric study.

Pettinato G, Manivel JC, Wick MR, Dehner LP.

Department of Pathology, Second Medical School, University of Naples, Italy.

Hum Pathol 1989 Jul;20(7):682-90 Abstract quote
Sixteen cases of congenital mesoblastic nephroma (CMN) were studied. The tumors showed variable patterns of growth, degrees of cellularity, and mitotic activity.

Six tumors had the classical pattern of CMN, seven were of the cellular or atypical variant and three showed combined features. The mean ages at presentation were 16 days, 5.3 months, and 2.3 months, respectively. Average size and weight were 5.1 cm and 94 g for classical CMN, 9.1 cm and 620 g for cellular CMN and 10.5 cm and 150 g for combined tumors. Cyst formation, hemorrhage and necrosis were confined to cellular CMNs and to cellular areas of combined CMNs. Mitotic activity ranged from 0 to 1/10 high-power fields (HPFs) in classical tumors to 25 to 30/10 HPFs in cellular tumors. Clear cell sarcoma-like areas were observed in three neoplasms. In ten cases there was invasion of perirenal fat; in one case each, invasion of the psoas muscle, renal vein wall, and renal vein lumen was observed.

Ultrastructural and immunohistochemical studies showed features consistent with myofibroblastic differentiation. Flow cytometric analysis revealed euploidy in one classic CMN, one cellular CMN and in classic areas of a combined CMN; cellular areas of the latter tumor were aneuploid.

All patients with follow-up were alive without evidence of disease after a mean period of 5 years following nephrectomy alone. No correlation was observed between the pathologic features assessed and the biologic behavior of these neoplasms.

VARIANTS

ATYPICAL

Atypical mesoblastic nephroma. Pathologic characterization of a potentially aggressive variant of conventional congenital mesoblastic nephroma.

Joshi VV, Kasznica J, Walters TR.

Arch Pathol Lab Med 1986 Feb;110(2):100-6 Abstract quote
A case of an aggressive variant of conventional congenital mesoblastic nephroma (CMN) occurred in a 10-month-old male infant. The tumor proved to be fatal, with two abdominal recurrences, but no metastases were found. Of the various terms used to designate the tumor, atypical mesoblastic nephroma (AMN) is preferred.

We reviewed 17 previously reported cases to attempt pathologic characterization of AMN. The features that distinguish AMN from CMN are as follows: (1) atypical gross features consisting of one or more of the following: fleshy areas, foci of hemorrhage, necrosis, involvement of adjacent structures other than connective tissue; and (2) high cellularity and mitotic index. Aggressive behavior was noted at surgery or on follow-up in seven of the 18 cases.

It was characterized by one or more of the following: (1) invasion of adjacent structures, such as adrenal gland, spleen, colon, and diaphragm (three cases); (2) one or more recurrences (four cases); and (3) metastasis (two cases). Atypical mesoblastic nephroma should be recognized as a potentially aggressive lesion separate from CMN.

CELLULAR

Cellular congenital mesoblastic nephroma in a newborn.

Schmidt D, Harms D, Lehner-Geisser M.
Pathol Res Pract 1984 Nov;179(2):242-9 Abstract quote
Typical nephroblastoma (Wilms'tumor) is uncommon within the first 6 months of life. Renal tumors most commonly found in this age constitute of two groups which have a better and worse prognosis, respectively, than typical nephroblastomas.

The group of tumors with a better prognosis encompasses congenital mesoblastic nephroma (CMN), fetal rhabdomyomatous nephroblastoma and cystic, partially differentiated nephroblastoma. The group of tumors with a worse prognosis consists of rhabdoid tumor of the kidney and bone metastasizing renal tumor (clear cell sarcoma) of childhood. Adequate therapy for these two neoplasms has as yet to be developed. Among the low-grade malignant tumors congenital mesoblastic nephroma can be successfully treated with simple nephrectomy.

There, are however, variants of CMN which may differ in clinical behavior from the typical form of CMN. These variants include the cellular CMN2 and, possibly, the malignant mesenchymal nephroma of infancy. A case of cellular congenital mesoblastic nephroma is presented here. Its clinical and pathologic features are discussed.

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

SPECIAL STAINS

IMMUNOPEROXIDASE

Congenital mesoblastic nephroma: an immunohistochemical and lectin study.

Nadasdy T, Roth J, Johnson DL, Bane BL, Weinberg A, Verani R, Silva FG.

Department of Pathology, University of Oklahoma, Oklahoma City.
Hum Pathol 1993 Apr;24(4):413-9 Abstract quote
Eight cases of congenital mesoblastic nephroma (CMN) were examined. Three CMNs were of the classical (typical) variant, two were cellular (atypical), and three showed a mixed pattern.

A panel of nephron segment-specific tubular epithelial markers (the lectins Tetragonolobus purpureas, Phaseolus vulgaris erythroagglutinin, and Arachis hypogaea and antibodies to epithelial membrane antigen, cytokeratin, and Tamm-Horsfall protein) were used to differentiate epithelial structures within the tumor. Antibodies against vimentin, desmin, and muscle-specific actin were used as mesenchymal markers. A monoclonal antibody to the long (embryonic) form of polysialic acid (PSA) on the neural cell adhesion molecule was used as a putative renal oncodevelopmental marker. An antibody to proliferating cell nuclear antigen also was applied, which revealed increased proliferative rate in cellular CMNs.

In addition to clearly entrapped native renal tubules, CMNs contain tubular structures with immature, dysplastic epithelium and occasional epithelial cell clusters embedded deep within the tumor. These immature tubules and clusters express distal nephron, including collecting duct markers and, occasionally, vimentin and PSA.

We propose that these primitive tubules and epithelial structures may originate from the ureteric bud. An epithelial differentiation of the tumor cells also is possible. In one pure cellular CMN and two mixed CMNs the cellular component showed diffuse staining for PSA. The PSA (neural cell adhesion molecule) expression of the cellular component suggests that CMN may originate from the uninduced nephrogenic mesenchyme.

RENIN

Renin in mesoblastic nephroma: an immunohistochemical study.

Cook HT, Taylor GM, Malone P, Risdon RA.

Department of Experimental Pathology, St. Mary's Hospital Medical School, Paddington, London, England.
Hum Pathol 1988 Nov;19(11):1347-51 Abstract quote
Congenital mesoblastic nephroma (CMN) is the most common renal tumor of early infancy. It is usually evident at birth as an abdominal mass and is composed of spindle-shaped cells resembling smooth muscle cells and fibroblasts.

There is macroscopic and microscopic infiltration of the surrounding kidney and entrapped tubules and glomeruli are common at the edge of the tumor. In this report, we describe a case of CMN associated with hyperreninaemia and hypertension. We examined the tumor from this case and 11 other cases for the presence of renin using a polyclonal antibody to human kidney renin. Hypertension was present in three of four additional cases for which records were available.

Immunoreactive renin was present in ten of the 12 cases studied. In all of these cases, intense staining was present in vessels within the areas of the trapped cortex. In seven cases, renin was identified in the walls of vessels within the tumor itself without identifiable adjacent cortical structures. These findings indicate that CMN may often be associated with primary reninism in early infancy.

ELECTRON MICROSCOPY

A study of the cellularity and ultrastructure of congenital mesoblastic nephroma.

Shen SC, Yunis EJ.
Cancer 1980 Jan 15;45(2):306-14 Abstract quote
This study reported 10 cases of congenital mesoblastic nephroma (CMN) from Children's Hospital of Pittsburgh: five were the typical fibromatous lesion, two were the cellular variant, and three had both components. Six cases occurred in infants less than one week of age.

The degree of cellularity had no correlation with patient or tumor size. Three- to 10-year follow-ups of nine patients showed neither local recurrence nor metastasis. One infant died of generalized bleeding post nephrectomy. Ultrastructural study of seven cases showed mesenchymal cells with varying degrees of fibroblastic and/or myofibroblastic differentiation.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

WILM'S TUMOR

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

Congenital mesoblastic nephroma: relationship to other renal tumors of infancy.

Snyder HM 3rd, Lack EE, Chetty-Baktavizian A, Bauer SB, Colodny AH, Retik AB.
J Urol 1981 Oct;126(4):513-6 Abstract quote
Although nephroblastomas (Wilms tumor) do occur in the newborn most of the solid renal tumors in this age group constitute a distinctly different pathologic entity, congenital mesoblastic nephroma. While a more cellular histologic variant of congenital mesoblastic nephroma has been recognized recently, which occasionally may follow a malignant course, the tumor with conventional histology has never been reported to metastasize and follows a benign course when treated by adequate local excision alone.

We report our 50-year experience with 11 cases of this tumor (9 cases with conventional histology and 2 with cellular variant histology). Typically, the tumor presented in the newborn as a large asymptomatic mass. Local invasion was never seen and the tumors were resected without difficulty. Grossly, the tumors usually resembled a uterine "fibroid" and, unlike nephroblastomas, rarely exhibited hemorrhage or necrosis.

Microscopically, the conventional histologic congenital mesoblastic nephroma was composed of sheets of spindle-shaped cells. The cellular variant of congenital mesoblastic nephroma exhibited increased cellularity and a higher mitotic index. The relationship of congenital mesoblastic nephromas to other neonatal renal tumors is discussed and a unifying schema of neoplasia in infantile renal tumors is proposed

Congenital mesoblastic nephroma: report of a Case with review of the most significant literature.

Bisceglia M, Carosi I, Vairo M, Zaffarano L, Bisceglia M, Creti G.

Department of Anatomic Pathology, IRCCS-Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.

Pathol Res Pract 2000;196(3):199-204 Abstract quote
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 currently distinguished histologically: the classical or leiomyomatous type and the atypical or cellular type. Mixed forms with a combination of the two patterns are 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 histological 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 subtype) and the perirenal fat was focally involved with the tumor, the possibility 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 histological features of the atypical subtype were noted. Flow cytometrically, 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 course 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.

METASTASIS

Congenital mesoblastic nephroma metastatic to the brain.

Heidelberger KP, Ritchey ML, Dauser RC, McKeever PE, Beckwith JB.

Department of Pathology, University of Michigan Hospital, Ann Arbor.
Cancer 1993 Oct 15;72(8):2499-502 Abstract quote
BACKGROUND. Congenital mesoblastic nephroma (CMN) is generally considered to be a benign neoplasm requiring only total excision. Rare local recurrences have usually been related to incomplete removal, and distant metastases to the lung have been reported three times.

METHODS. The authors reported the first case of CMN metastatic to the brain, illustrating a comparison of the histopathology of the primary and secondary lesions.

RESULTS. The gross appearance of the renal tumor was that of a benign CMN. On histopathologic examination, there was a single nodule of more cellular tissue with focal necrosis. This area was diagnosed as within the designation "cellular" mesoblastic nephroma. The appearance of the brain metastasis corresponded to that of the cellular nodule.

CONCLUSIONS. This report expands the spectrum of metastatic potential of CMN. Though a rare event, this case underscores the need for close follow-up of infants with CMN.

TREATMENT

Congenital mesoblastic nephroma: a clinicoradiologic study of 17 cases representing the pathologic spectrum of the disease.

Chan HS, Cheng MY, Mancer K, Payton D, Weitzman SS, Kotecha P, Daneman A.
J Pediatr 1987 Jul;111(1):64-70 Abstract quote
Congenital mesoblastic nephroma (CMN) is a rare infantile renal tumor with a generally excellent prognosis.

We describe 17 tumors that fit into the pathologic spectrum of CMN proposed by Beckwith, which ranges from benign renal tumors, through atypical "gray zone" lesions of more aggressive potential, to "crossover" tumors akin to clear cell sarcoma of kidney. Nine patients with histologically typical CMN were significantly younger and had smaller tumors than did eight patients with atypical CMN. Clinical features did not differ in the two groups of patients.

A distinctive "ring sign" on renal sonography was commonly seen in patients with typical intrarenal CMN. All 17 patients were alive with no evidence of disease at a mean follow-up of 10 years. Nephrectomy was adequate therapy for younger infants and for those with typical CMN. Nephrectomy was probably also adequate therapy for infants 3 months of age or younger with atypical CMN, even if the tumor extended to the surgical resection margins and into the perinephric connective tissues.

Adjuvant chemotherapy or radiation or both should be reserved for patients older than 3 months who have grossly unresected tumors and for those patients whose tumors have an unequivocally malignant histologic appearance or evidence of aggressive biologic behavior.

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Pathologists Who Make A Difference
Search for a Physician Specialist

Last Updated 9/18/2003

PATHOGENESIS	CHARACTERIZATION
CHROMOSOMAL ABNORMALITIES
Cytogenetic abnormalities in mesoblastic nephroma: a link to Wilms' tumour? Roberts P, Lockwood LR, Lewis IJ, Bailey CC, Batcup G, Williams J. Regional Cytogenetics Unit, St. James's University Hospital, Leeds, England.	Med Pediatr Oncol 1993;21(6):416-20 Abstract quote Cytogenetic analysis of tumour material from a congenital mesoblastic nephroma is reported. Two cell lines were found, one with a normal 46,XY karyotype and the other with a hyperdiploid 51,XY karyotype, including a rearrangement of chromosome 11 at 11p15. This finding is of interest since loss of allelic heterozygosity at polymorphic 11p15 loci has been described in sporadic Wilms' tumour [1], and both cytogenetic [2] and molecular [3] changes of 11p15 are found in the Wiedemann-Beckwith syndrome, a condition with a predisposition to embryonal tumours, particularly Wilms' tumour. Our results lead us to speculate on the implications relating to the pathogenesis of this relatively benign tumour variant with respect to the current understanding of the genetics of Wilms' tumour.
ETV6
ETV6 Rearrangements in Patients with Infantile Fibrosarcomas and Congenital Mesoblastic Nephromas by Fluorescence In Situ Hybridization Camilo Adem, M.D., David Gisselsson, Ph.D., Paola Dal Cin, Ph.D. and Antonio G. Nascimento, M.D. Department of Laboratory Medicine and Pathology (CA, AGN), Mayo Clinic, Rochester, Minnesota; and Department of Pathology (DG, PDC), Brigham and Women�s Hospital and Harvard Medical School, Boston, Massachusetts	Mod Pathol 2001;14:1246-1251 Abstract quote Congenital mesoblastic nephroma (CMN) and infantile fibrosarcoma (IFS) are two pediatric tumors arising in the kidneys and soft tissues of infants, respectively. Recently, a t(12;15)(p13;q25) resulting in ETV6-NTRK3 gene fusion was detected in patients with IFS and in patients with the cellular type of CMN, suggesting a common pathogenetic pathway. We investigated the presence or absence of ETV6 rearrangements and numerical abnormalities of chromosome 11 by using fluorescence in situ hybridization on paraffin-embedded material from five cases of IFS, two of CMN, and one of mixed type (CMN and IFS) found in our files. In three cases of IFS, we found ETV6 gene rearrangement but a normal copy number of chromosome 11. One case each of IFS, the cellular type of CMN, and the mixed type (CMN and IFS) had both abnormalities. In a case of classic CMN, neither trisomy 11 nor gene rearrangement was found. It is possible that trisomy 11 is a later, nonessential event in the pathogenetic process or that this secondary aberration is associated with still-unrecognized clinical or biological characteristics. We confirmed that IFS and the cellular type of CMN are cytogenetically related and can occur synchronously in the same organ.
TRISOMY 11
Presence or absence of trisomy 11 is correlated with histologic subtype in congenital mesoblastic nephroma. Mascarello JT, Cajulis TR, Krous HF, Carpenter PM. Genetic Services, Children's Hospital-San Diego, CA 92123.	Cancer Genet Cytogenet 1994 Oct;77(1):50-4 Abstract quote Fluorescence in situ hybridization utilizing a probe for the alpha satellite repeat sequence on chromosome 11 was used to detect variations in the number of chromosomes 11 in 24 formalin-fixed, paraffin-embedded congenital mesoblastic nephromas. Evidence of trisomy 11 was found in nearly half of the tumors. More importantly, the presence of trisomy 11 was associated with the cellular histologic variant of this tumor.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
FLOW CYTOMETRY
Atypical congenital mesoblastic nephroma. Report of a case with karyotypic and flow cytometric analysis. Varsa EW, McConnell TS, Dressler LG, Duncan M. Department of Pathology, University of New Mexico School of Medicine, Albuquerque 87131.	Arch Pathol Lab Med 1989 Sep;113(9):1078-80 Abstract quote Atypical congenital mesoblastic nephroma is a rare infantile renal tumor that may behave aggressively in older infants. A case of atypical congenital mesoblastic nephroma occurring in an 8-month-old hispanic male was analyzed by routine histopathologic, cytogenetic, and retrospective flow cytometric analysis for DNA ploidy. Light microscopy revealed marked hypercellularity. The karyotype was abnormal, with the following configuration: 45,XY,-1,-3,-9,-9,-15,-17,-21,+del(1)(q21q25),+der(3), t(3;9;15)(q23;p22;q11),+der(9),t(3;9;15) (q23;p22;q11),+der(9),t(9;?) (p?22;?),+r21, + mar. Retrospective DNA ploidy analysis revealed a DNA index of 1.0. The significance of karyotypic changes occurring in mesenchymal renal tumors of this type is currently unknown. Cytogenetic analysis might be of prognostic value in these potentially aggressive tumors.
Congenital mesoblastic nephroma: possible prognostic and management value of assessing DNA content. Barrantes JC, Toyn C, Muir KR, Parkes SE, Raafat F, Cameron AH, Marsden HB, Mann JR. Department of Oncology, Children's Hospital, Ladywood, Birmingham.	J Clin Pathol 1991 Apr;44(4):317-20 Abstract quote The case records and pathology of all children with kidney tumours treated in the West Midlands Health Authority Region (WMHAR) from 1957 to 1986 were reviewed. The histology was reviewed by a panel of three paediatric pathologists. Thirteen (6%) out of 211 cases were considered to have congenital mesoblastic nephroma (CMN). Nine were of the conventional type, three of the atypical cellular type, and one mixed. DNA ploidy was investigated and showed two of the tumours to be aneuploid and nine diploid (tissue was not available in the two other cases). The two aneuploid tumours were of atypical cellular and mixed histology, respectively; the diploid tumours were of the conventional type in eight cases and atypical cellular in one. The atypical cellular type has been reported to behave more aggressively, but the benefit of additional treatment after surgery to prevent recurrence remains unclear. Measurement of DNA content by flow cytometry, together with histological subclassification, may be useful in selecting patients who will benefit from further treatment after surgery.
RENIN
Renin production in congenital mesoblastic nephroma in comparison with that in Wilms' tumor. Tsuchida Y, Shimizu K, Hata J, Honna T, Nishiura M. Department of Surgery, National Children's Hospital, Tokyo, Japan.	Pediatr Pathol 1993 Mar-Apr;13(2):155-64 Abstract quote The case of an infant with congenital mesoblastic nephroma and associated reninism is presented. The patient was a 39-day-old boy who presented with a left abdominal mass and mild hypertension (112/70 mm Hg). Both plasma renin activity (PRA) and plasma total renin concentration (PTRC) were elevated; the PTRC value of 1458 pg/mL of this case was the highest we had seen in patients with childhood renal tumors. The tumor was successfully removed and histologically confirmed as a congenital mesoblastic nephroma (cellular variant). The patient's PRA and PTRC returned to normal after nephrectomy. Indirect immunoperoxidase staining showed renin localized predominantly in the juxtaglomerular apparatuses adjacent to the glomeruli entrapped by the tumor. No positive staining was seen in the tumor cells. These findings indicate that the entrapped glomeruli may play a significant role in producing renin. More important, PTRC was extremely high compared to the moderate increase of PRA and to the mild elevation of blood pressure. The mechanism of renin production by childhood renal tumors is discussed, and the importance of studying inactive renin and total renin is emphasized.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
ADULT
Mesoblastic nephroma of adulthood. Report of three cases. Durham JR, Bostwick DG, Farrow GM, Ohorodnik JM. Department of Pathology, Henry Ford Hospital, Detroit, Michigan 48202.	Am J Surg Pathol 1993 Oct;17(10):1029-38 Abstract quote Mesoblastic nephroma is an uncommon congenital tumor of infancy that rarely occurs in adults. We report three patients (two were female, one was male) who had mesoblastic nephroma of adulthood and who presented at 45, 64, and 66 years of age with hematuria, flank mass, and pain. All underwent nephrectomy without postoperative adjuvant therapy. The tumors were solitary yellow-tan masses with solid and cystic areas involving the renal cortex (three cases) with extension into the renal pelvis and calyces (two) and ureter (one). Microscopically, all consisted of uniform spindle cell proliferations with entrapped dilated renal tubules. Focal necrosis was present in two, but no atypia or mitoses were identified in any case. The spindle cells displayed cytoplasmic immunoreactivity for vimentin, desmin, panmuscle actin (HHF-35), and alpha-smooth-muscle actin, but were nonreactive for keratin (AE1/AE3), epithelial membrane antigen, and S-100 protein. Electron microscopy revealed the presence of smooth-muscle differentiation in two cases and undifferentiated mesenchyme in one. All tumors were DNA diploid by flow cytometry. The patients were free of recurrence 8 months-2 years postoperatively. Because surgical excision may be curative, mesoblastic nephroma in adult patients must be differentiated from spindle cell neoplasms of the kidney that require additional therapy.
Mesoblastic nephroma in adulthood: a case report. Shiraishi K, Yamamoto M, Gondo T, Shirataki S, Naito K. Department of Urology, Yamaguchi University School of Medicine, Ube, Japan.	Int J Urol 1999 Aug;6(8):414-8 Abstract quote BACKGROUND: Mesoblastic nephroma is an uncommon renal tumor of infancy and rarely occurs in adults. We report an adult case of mesoblastic nephroma. METHODS: A 50-year-old woman was found incidentally to have a right renal mass by abdominal ultrasonography. Computed tomography and magnetic resonance imaging revealed a heterogeneous tumor and angiography showed a mixture of hypervascularity and hypovascularity. Right radical nephrectomy was performed. RESULTS: The tumor was an encapsulated yellowish solid mass. Microscopically, the tumor was composed of spindle cell proliferation. Atypia and mitoses were not identified. Among the tumor cells, there were tubular arranged epithelial elements. CONCLUSION: The patient was free of recurrence 14 months postoperatively. Mesoblastic nephroma is classified as a benign tumor but recurrence and malignant formation of this tumor have been reported so regular postoperative follow up is required.
CYSTIC
Multicystic congenital mesoblastic nephroma. Drut R. Servicio de Patologia, Hospital de Ninos "Superiora Sor Maria Ludovica", La Plata, Argentina.	Int J Surg Pathol 2002 Jan;10(1):59-63 Abstract quote This report describes an unusual example of congenital mesoblastic nephroma cellular variant that presented in a 1-week-old neonate as a multicystic tumor of the kidney. Extensive pseudocystic cavitation resulted from progressive accumulation of ground substance in a loosely myxoid tissue composed of stellate- and spindle-shaped cells that compressed and infiltrated renal tissue. The cells of the tumor were positive for vimentin and smooth muscle actin. The patient is alive and well 16 years after surgery. Differential diagnosis from segmental cystic dysplasia, cystic intralobar nephrogenic rest, cystic nephroma, cystic partially differentiated nephroblastoma, cystic nephroblastoma, and cystic clear cell sarcoma of the kidney, all of which may present at this age, is discussed.

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL	Deeply infiltrative border Lacks prominent vasculature Desmin+
Congenital mesoblastic nephroma. Gerber A, Gold JH, Bustamante S, Lorch V, Mirza M.	J Pediatr Surg 1981 Oct;16(5):758-9 Abstract quote Neonatal renal neoplasms are rare: most are congenital mesoblastic nephroma. In the past this neoplasm has been confused with Wilms' tumor, which in part may account for some of the more favorable prognosis ascribed to Wilms' tumor in children less than 1 yr of age. Congenital mesoblastic nephroma is usually a benign tumor. The recommended treatment is surgical excision. This is a report of two cases of congenital mesoblastic nephroma in infants who were treated successfully by nephrectomy.
Classical and cellular (atypical) congenital mesoblastic nephroma: a clinicopathologic, ultrastructural, immunohistochemical, and flow cytometric study. Pettinato G, Manivel JC, Wick MR, Dehner LP. Department of Pathology, Second Medical School, University of Naples, Italy.	Hum Pathol 1989 Jul;20(7):682-90 Abstract quote Sixteen cases of congenital mesoblastic nephroma (CMN) were studied. The tumors showed variable patterns of growth, degrees of cellularity, and mitotic activity. Six tumors had the classical pattern of CMN, seven were of the cellular or atypical variant and three showed combined features. The mean ages at presentation were 16 days, 5.3 months, and 2.3 months, respectively. Average size and weight were 5.1 cm and 94 g for classical CMN, 9.1 cm and 620 g for cellular CMN and 10.5 cm and 150 g for combined tumors. Cyst formation, hemorrhage and necrosis were confined to cellular CMNs and to cellular areas of combined CMNs. Mitotic activity ranged from 0 to 1/10 high-power fields (HPFs) in classical tumors to 25 to 30/10 HPFs in cellular tumors. Clear cell sarcoma-like areas were observed in three neoplasms. In ten cases there was invasion of perirenal fat; in one case each, invasion of the psoas muscle, renal vein wall, and renal vein lumen was observed. Ultrastructural and immunohistochemical studies showed features consistent with myofibroblastic differentiation. Flow cytometric analysis revealed euploidy in one classic CMN, one cellular CMN and in classic areas of a combined CMN; cellular areas of the latter tumor were aneuploid. All patients with follow-up were alive without evidence of disease after a mean period of 5 years following nephrectomy alone. No correlation was observed between the pathologic features assessed and the biologic behavior of these neoplasms.
VARIANTS
ATYPICAL
Atypical mesoblastic nephroma. Pathologic characterization of a potentially aggressive variant of conventional congenital mesoblastic nephroma. Joshi VV, Kasznica J, Walters TR.	Arch Pathol Lab Med 1986 Feb;110(2):100-6 Abstract quote A case of an aggressive variant of conventional congenital mesoblastic nephroma (CMN) occurred in a 10-month-old male infant. The tumor proved to be fatal, with two abdominal recurrences, but no metastases were found. Of the various terms used to designate the tumor, atypical mesoblastic nephroma (AMN) is preferred. We reviewed 17 previously reported cases to attempt pathologic characterization of AMN. The features that distinguish AMN from CMN are as follows: (1) atypical gross features consisting of one or more of the following: fleshy areas, foci of hemorrhage, necrosis, involvement of adjacent structures other than connective tissue; and (2) high cellularity and mitotic index. Aggressive behavior was noted at surgery or on follow-up in seven of the 18 cases. It was characterized by one or more of the following: (1) invasion of adjacent structures, such as adrenal gland, spleen, colon, and diaphragm (three cases); (2) one or more recurrences (four cases); and (3) metastasis (two cases). Atypical mesoblastic nephroma should be recognized as a potentially aggressive lesion separate from CMN.
CELLULAR
Cellular congenital mesoblastic nephroma in a newborn. Schmidt D, Harms D, Lehner-Geisser M.	Pathol Res Pract 1984 Nov;179(2):242-9 Abstract quote Typical nephroblastoma (Wilms'tumor) is uncommon within the first 6 months of life. Renal tumors most commonly found in this age constitute of two groups which have a better and worse prognosis, respectively, than typical nephroblastomas. The group of tumors with a better prognosis encompasses congenital mesoblastic nephroma (CMN), fetal rhabdomyomatous nephroblastoma and cystic, partially differentiated nephroblastoma. The group of tumors with a worse prognosis consists of rhabdoid tumor of the kidney and bone metastasizing renal tumor (clear cell sarcoma) of childhood. Adequate therapy for these two neoplasms has as yet to be developed. Among the low-grade malignant tumors congenital mesoblastic nephroma can be successfully treated with simple nephrectomy. There, are however, variants of CMN which may differ in clinical behavior from the typical form of CMN. These variants include the cellular CMN2 and, possibly, the malignant mesenchymal nephroma of infancy. A case of cellular congenital mesoblastic nephroma is presented here. Its clinical and pathologic features are discussed.

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
IMMUNOPEROXIDASE
Congenital mesoblastic nephroma: an immunohistochemical and lectin study. Nadasdy T, Roth J, Johnson DL, Bane BL, Weinberg A, Verani R, Silva FG. Department of Pathology, University of Oklahoma, Oklahoma City.	Hum Pathol 1993 Apr;24(4):413-9 Abstract quote Eight cases of congenital mesoblastic nephroma (CMN) were examined. Three CMNs were of the classical (typical) variant, two were cellular (atypical), and three showed a mixed pattern. A panel of nephron segment-specific tubular epithelial markers (the lectins Tetragonolobus purpureas, Phaseolus vulgaris erythroagglutinin, and Arachis hypogaea and antibodies to epithelial membrane antigen, cytokeratin, and Tamm-Horsfall protein) were used to differentiate epithelial structures within the tumor. Antibodies against vimentin, desmin, and muscle-specific actin were used as mesenchymal markers. A monoclonal antibody to the long (embryonic) form of polysialic acid (PSA) on the neural cell adhesion molecule was used as a putative renal oncodevelopmental marker. An antibody to proliferating cell nuclear antigen also was applied, which revealed increased proliferative rate in cellular CMNs. In addition to clearly entrapped native renal tubules, CMNs contain tubular structures with immature, dysplastic epithelium and occasional epithelial cell clusters embedded deep within the tumor. These immature tubules and clusters express distal nephron, including collecting duct markers and, occasionally, vimentin and PSA. We propose that these primitive tubules and epithelial structures may originate from the ureteric bud. An epithelial differentiation of the tumor cells also is possible. In one pure cellular CMN and two mixed CMNs the cellular component showed diffuse staining for PSA. The PSA (neural cell adhesion molecule) expression of the cellular component suggests that CMN may originate from the uninduced nephrogenic mesenchyme.
RENIN
Renin in mesoblastic nephroma: an immunohistochemical study. Cook HT, Taylor GM, Malone P, Risdon RA. Department of Experimental Pathology, St. Mary's Hospital Medical School, Paddington, London, England.	Hum Pathol 1988 Nov;19(11):1347-51 Abstract quote Congenital mesoblastic nephroma (CMN) is the most common renal tumor of early infancy. It is usually evident at birth as an abdominal mass and is composed of spindle-shaped cells resembling smooth muscle cells and fibroblasts. There is macroscopic and microscopic infiltration of the surrounding kidney and entrapped tubules and glomeruli are common at the edge of the tumor. In this report, we describe a case of CMN associated with hyperreninaemia and hypertension. We examined the tumor from this case and 11 other cases for the presence of renin using a polyclonal antibody to human kidney renin. Hypertension was present in three of four additional cases for which records were available. Immunoreactive renin was present in ten of the 12 cases studied. In all of these cases, intense staining was present in vessels within the areas of the trapped cortex. In seven cases, renin was identified in the walls of vessels within the tumor itself without identifiable adjacent cortical structures. These findings indicate that CMN may often be associated with primary reninism in early infancy.
ELECTRON MICROSCOPY
A study of the cellularity and ultrastructure of congenital mesoblastic nephroma. Shen SC, Yunis EJ.	Cancer 1980 Jan 15;45(2):306-14 Abstract quote This study reported 10 cases of congenital mesoblastic nephroma (CMN) from Children's Hospital of Pittsburgh: five were the typical fibromatous lesion, two were the cellular variant, and three had both components. Six cases occurred in infants less than one week of age. The degree of cellularity had no correlation with patient or tumor size. Three- to 10-year follow-ups of nine patients showed neither local recurrence nor metastasis. One infant died of generalized bleeding post nephrectomy. Ultrastructural study of seven cases showed mesenchymal cells with varying degrees of fibroblastic and/or myofibroblastic differentiation.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE	Rare
AGE RANGE-MEDIAN	Usually congenital

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
WILM'S TUMOR

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
Congenital mesoblastic nephroma: relationship to other renal tumors of infancy. Snyder HM 3rd, Lack EE, Chetty-Baktavizian A, Bauer SB, Colodny AH, Retik AB.	J Urol 1981 Oct;126(4):513-6 Abstract quote Although nephroblastomas (Wilms tumor) do occur in the newborn most of the solid renal tumors in this age group constitute a distinctly different pathologic entity, congenital mesoblastic nephroma. While a more cellular histologic variant of congenital mesoblastic nephroma has been recognized recently, which occasionally may follow a malignant course, the tumor with conventional histology has never been reported to metastasize and follows a benign course when treated by adequate local excision alone. We report our 50-year experience with 11 cases of this tumor (9 cases with conventional histology and 2 with cellular variant histology). Typically, the tumor presented in the newborn as a large asymptomatic mass. Local invasion was never seen and the tumors were resected without difficulty. Grossly, the tumors usually resembled a uterine "fibroid" and, unlike nephroblastomas, rarely exhibited hemorrhage or necrosis. Microscopically, the conventional histologic congenital mesoblastic nephroma was composed of sheets of spindle-shaped cells. The cellular variant of congenital mesoblastic nephroma exhibited increased cellularity and a higher mitotic index. The relationship of congenital mesoblastic nephromas to other neonatal renal tumors is discussed and a unifying schema of neoplasia in infantile renal tumors is proposed
Congenital mesoblastic nephroma: report of a Case with review of the most significant literature. Bisceglia M, Carosi I, Vairo M, Zaffarano L, Bisceglia M, Creti G. Department of Anatomic Pathology, IRCCS-Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.	Pathol Res Pract 2000;196(3):199-204 Abstract quote 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 currently distinguished histologically: the classical or leiomyomatous type and the atypical or cellular type. Mixed forms with a combination of the two patterns are 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 histological 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 subtype) and the perirenal fat was focally involved with the tumor, the possibility 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 histological features of the atypical subtype were noted. Flow cytometrically, 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 course 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.
METASTASIS
Congenital mesoblastic nephroma metastatic to the brain. Heidelberger KP, Ritchey ML, Dauser RC, McKeever PE, Beckwith JB. Department of Pathology, University of Michigan Hospital, Ann Arbor.	Cancer 1993 Oct 15;72(8):2499-502 Abstract quote BACKGROUND. Congenital mesoblastic nephroma (CMN) is generally considered to be a benign neoplasm requiring only total excision. Rare local recurrences have usually been related to incomplete removal, and distant metastases to the lung have been reported three times. METHODS. The authors reported the first case of CMN metastatic to the brain, illustrating a comparison of the histopathology of the primary and secondary lesions. RESULTS. The gross appearance of the renal tumor was that of a benign CMN. On histopathologic examination, there was a single nodule of more cellular tissue with focal necrosis. This area was diagnosed as within the designation "cellular" mesoblastic nephroma. The appearance of the brain metastasis corresponded to that of the cellular nodule. CONCLUSIONS. This report expands the spectrum of metastatic potential of CMN. Though a rare event, this case underscores the need for close follow-up of infants with CMN.
TREATMENT
Congenital mesoblastic nephroma: a clinicoradiologic study of 17 cases representing the pathologic spectrum of the disease. Chan HS, Cheng MY, Mancer K, Payton D, Weitzman SS, Kotecha P, Daneman A.	J Pediatr 1987 Jul;111(1):64-70 Abstract quote Congenital mesoblastic nephroma (CMN) is a rare infantile renal tumor with a generally excellent prognosis. We describe 17 tumors that fit into the pathologic spectrum of CMN proposed by Beckwith, which ranges from benign renal tumors, through atypical "gray zone" lesions of more aggressive potential, to "crossover" tumors akin to clear cell sarcoma of kidney. Nine patients with histologically typical CMN were significantly younger and had smaller tumors than did eight patients with atypical CMN. Clinical features did not differ in the two groups of patients. A distinctive "ring sign" on renal sonography was commonly seen in patients with typical intrarenal CMN. All 17 patients were alive with no evidence of disease at a mean follow-up of 10 years. Nephrectomy was adequate therapy for younger infants and for those with typical CMN. Nephrectomy was probably also adequate therapy for infants 3 months of age or younger with atypical CMN, even if the tumor extended to the surgical resection margins and into the perinephric connective tissues. Adjuvant chemotherapy or radiation or both should be reserved for patients older than 3 months who have grossly unresected tumors and for those patients whose tumors have an unequivocally malignant histologic appearance or evidence of aggressive biologic behavior.