Cellular Mesoblastic Nephromain an Infant:Report of the Cytologic Diagnosis of a RarePaediatric Renal TumorRuchika Gupta, M.D.,1 Sandeep R. Mathur, M.D.,1* Priti Singh, M.B.B.S.,1

Sandeep Agarwala, M.S., M.Ch.,2 and S. Datta Gupta, M.D.1

Congenital mesoblastic nephroma is a rare pediatric tumor witha favorable clinical outcome. Cytological features of this uncom-mon tumor and diagnostic difficulties with other commoner pedi-atric renal neoplasms have been inadequately discussed in theavailable literature. We describe the case of a 1-year-old girlwho presented with a right renal mass. Fine-needle aspirationsmears consisted of a few cellular clusters of spindle cells withmitotic activity and mild nuclear pleomorphism. No blastemawas identified. A cytologic impression of mesoblastic nephromawas rendered, which was confirmed on histopathological exami-nation of the right nephrectomy specimen as a cellular meso-blastic nephroma.

Cytologic diagnosis of mesoblastic nephroma has importantprognostic and therapeutic implications. The cytopathologistshould carefully evaluate smears from such patients andattempt to differentiate mesoblastic nephroma from Wilms’ tu-mor and clear cell sarcoma. Diagn. Cytopathol. 2009;37:377–380. ' 2009 Wiley-Liss, Inc.

Key Words: mesoblastic nephroma; cellular variant; aspirationcytology

Congenital mesoblastic nephroma (CMN) is a rare pediat-

ric renal tumor with clinical presentation similar to other

commoner neoplasms in this age group.1 Cytologic diag-

nosis of this rare lesion is difficult and has been discussed

in few case reports,2–4 where the majority of cases of

CMN were diagnosed cytologically as Wilms’ tumor

(WT) or clear cell sarcoma. Differentiation of these vari-

ous pediatric neoplasms in aspiration smears has not been

adequately discussed in the available literature.

We report the cytologic features of a CMN, diagnosed

accurately in cytology, along with a detailed discussion of

the various differential diagnoses.

Case Reports

A 1-year-old female child presented with a history of

right-sided abdominal swelling for the past 2 weeks along

with loss of appetite and weight. On examination, the

child was emaciated and pale. There was a large firm mass

palpated in the right hypochondrium extending to right

iliac and umbilical regions. Routine investigations revealed

anemia (hemoglobin 9 g/dl). Biochemical parameters,

including renal function and liver function tests were

within normal range. Ultrasonography (USG) of the abdo-

men showed a large, 130 3 90 mm tumor in the upper

pole of right kidney. Bilateral ureters and left kidney ap-

peared normal. Contrast-enhanced computed tomography

(CECT) scan confirmed a right renal tumor (Fig. 1). The

clinicoradiological impression was WT and USG-guided

fine-needle aspiration (FNA) was performed on two sepa-

rate occasions.

FNA smears were stained by the Papanicolaou and

May–Grunwald–Giemsa methods. After the cytological

report, the patient underwent right nephrectomy under

general anesthesia. She is on close follow-up and is doing

well 8 months after surgery.

Cytologic Findings

Aspirate smears were paucicellular and showed a few cell

clusters in a hemorrhagic background. The clusters were

cellular and were composed of spindle cells with elon-

1Department of Pathology, All India Institute of Medical Sciences,New Delhi, India

2Department of Pediatric Surgery, All India Institute of Medical Scien-ces, New Delhi, India

*Correspondence to: Sandeep R. Mathur, M.D., Department of Pathol-ogy, All India Institute of Medical Sciences, Ansari Nagar, New Delhi110029, India. E-mail: drsunnymathur@yahoo.com

Received 4 October 2008; Accepted 24 November 2008DOI 10.1002/dc.21028Published online 13 February 2009 in Wiley InterScience (www.

interscience.wiley.com).

' 2009 WILEY-LISS, INC. Diagnostic Cytopathology, Vol 37, No 5 377

gated homogeneously-staining cytoplasm and oval to elon-

gated nuclei having fine chromatin and indistinct nucleoli

(Figs. 2a,b). Mild nuclear pleomorphism and occasional

mitotic figures were identified. No foci of necrosis were

seen. Extensive search failed to detect any round cell com-

ponent (blastema) of WT in the smears. No nuclear

grooves or mucoid intercellular material, as seen in clear

cell sarcoma of kidney (CCSK), were noted in the cell

clusters. Considering the cytomorphological features, a

presumptive cytologic diagnosis of mesoblastic nephroma

was rendered along with a differential diagnosis of

stroma-predominant WT and metanephric stromal tumor.

Histopathologic Findings

The child underwent right nephrectomy and the resected

kidney contained a 14.5 3 10.5 3 8.5 cm solid tumor,

which was gray-white on cut-section with a firm consis-

tency and few cystic areas (Fig. 2c). Multiple sections

from solid areas showed an ill-circumscribed spindle cell

tumor with focal hemangiopericytoma-like pattern. The tu-

mor was infiltrating the renal parenchyma and perinephric

fat. The spindle cells contained pink elongated cytoplasm,

oval to elongated nuclei with finely dispersed chromatin,

occasional mitotic figures (3–6/10 high power fields) and

mild nuclear pleomorphism (Fig. 2d). Few foci of cystic

degeneration were noted. There was neither blastemal

component, as seen in WT nor the characteristic vascular

pattern, clear cells or nuclear grooves characteristic of

CCSK in the numerous sections examined. One differen-

tial diagnosis considered was a renal monophasic synovial

sarcoma. Immunohistochemistry showed the spindle cells

to be positive for vimentin (diffuse) and smooth muscle

actin (focal) while being negative for desmin,

S-100 protein, cytokeratin, epithelial membrane antigen,

bcl-2, and CD99. Thus, the morphological features and

immunohistochemical profile helped to confirm the cyto-

logic impression of mesoblastic nephroma, cellular variant.

Discussion

CMN was recognized as an uncommon renal tumor of

infancy in 1967.1 CMN is usually diagnosed at birth or

within the first 3 months of life with an equal gender inci-

dence.1 Rare cases of CMN reported in adults are now

considered to represent mixed epithelial and stromal

tumors.5,6 The clinical presentation of CMN is similar to

other pediatric renal neoplasms. Hence, with the advent

of successful preoperative chemotherapy in WT, an accu-

rate diagnosis of a pediatric renal neoplasm is essential.7

FNA description of CMN has been reported in only

rare case reports in the available literature (Table I).2–4,8,9

In addition to these cases, Sharifah10 in a report of the

cytologic characteristics of renal tumors in children,

described six cases of mesoblastic nephroma. Of the

reported cases, the majority were diagnosed as WT or

clear cell sarcoma of kidney (CCSK) on aspiration cytol-

ogy. In our case, the cytomorphological features were dis-

tinctive enough to warrant a presumptive cytologic diag-

nosis of CMN. This case underscores the importance of

considering CMN while examining cytology smears of a

pediatric renal neoplasm with spindle cell morphology.

Aspirate smears from CMN, as in the present case,

show few cohesive cellular and fibroblastic tissue frag-

ments. The cells are bland, spindle or tadpole-shaped, and

embedded in a fibrillary background with a few stripped

nuclei. The nuclei are oval to elongated, smooth in con-

tour with evenly dispersed chromatin and indistinct nucle-

oli. Frequent mitotic figures and necrosis may rarely be

seen.2–4,8,9 These features may also be seen in spindle

cell type of CCSK, which is a close differential diagnosis

of CMN. CCSK, unlike CMN, shows the presence of

abundant magenta-colored matrix material extracellularly,

nuclear grooves, nuclear pleomorphism and prominent

perivascular arrangement of the cells.11 Metanephric stro-

mal tumor (MST) also needs to be considered in the dif-

ferential of renal spindle cell tumors in paediatric popula-

tion. MST, unlike mesoblastic nephroma, occurs in older

children and shows variable cellularity composed of spin-

dle to stellate-cells with infiltration into the adjacent renal

parenchyma. A characteristic concentric arrangement of

cells around blood vessels and tubules is noted.12

The cellular variant of CMN yields cellular smears com-

posed of round to oval cells, which may resemble blastemal

component of WT.3 A thorough search for the classic blas-

temal cells (small cells with scant cytoplasm, round nuclei,

fine granular chromatin) along with epithelial and/or mes-

enchymal (especially rhabdomyoblastic) components helps

to make an accurate diagnosis in difficult cases.11,12 Rhab-

doid tumor shows intermediate-sized cells with moderate

Fig. 1. CECT scan showing a large heterogeneous soft tissue mass(arrows) in the right renal fossa.

GUPTA ET AL.

378 Diagnostic Cytopathology, Vol 37, No 5

Diagnostic Cytopathology DOI 10.1002/dc

amount of cytoplasm containing paranuclear eosinophilic

inclusion and vesicular nuclei with prominent nucleoli, and

hence can be easily recognized in aspirate smears.3,13 Other

round cell tumors, including primitive neuroectodermal tu-

mor (PNET) of kidney, also need to be considered. PNET

demonstrates aggregates of small round cells with occa-

sional rosettes containing central fibrillary material.

Immunocytochemistry can also help in the differential

diagnosis. CMN shows immunohistochemical features of

myofibroblasts, i.e. positivity for vimentin, actin, and des-

min. Tumor cells in CCSK are negative for all markers

except vimentin. WT shows positivity for vimentin and

nuclear reactivity for WT1 in the blastemal component

whereas mesenchymal foci show immunohistochemical

staining according to the type of differentiation. PNET,

on the other hand, demonstrates membranous staining for

CD99 along with positive staining for one or more of the

neural markers.11 In the present case, immunocytochemis-

Table I. Summary of Cytologically Reported Cases of Congenital Mesoblastic Nephroma

Authors Age/sex Size of tumor Cytologic diagnosis Histologic diagnosis

Dey et al.2 4 months/NA NA CMN Atypical CMNDrut3 1 year/F 10 3 8 3 5 cm Tumor ?nature CMNKaw4 NB/M 6 3 4 3 2 cm CMN CMNRavindra and Kini9 3 days/M NA Wilms tumor Cellular CMNPortugal and Barroca8 NB/F 11 3 9 3 8 cm Mesenchymal neoplastic tumor Cellular CMN

NA, not available; M, male; F, female; NB, newborn; CMN, congenital mesoblastic nephroma.

Fig. 2. Photomicrographs of aspirate smears showing cellular clusters of spindle cells with elongated nuclei and mild pleomorphism (a, Papanicolaoustain; b, May-Grunwald-Giemsa stain). Resected specimen shows a large gray-white tumor with areas of cystic degeneration (c). Histopathologic photo-micrograph demonstrating a cellular spindle cell tumor with few mitotic figures (d, H&E). [Color figure can be viewed in the online issue, which isavailable at www.interscience.wiley.com.]

CYTOLOGY OF CELLULAR MESOBLASTIC NEPHROMA

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try could not be performed due to the scant material,

inspite of repeated aspirations.

In recent times, molecular diagnostics have become in-

dispensable diagnostic tools. Among pediatric renal tumors,

WTs are associated with deletions of mutations of WT1 or

p53, especially in those associated with genetic syndromes.

CMN has shown to harbor t(12;15) resulting in fusion tran-

script ETV6-NTRK3, which is also seen in infantile fibro-

sarcoma. CCSK does not have a characteristic cytogenetic

abnormality, although a study showed one recurrent finding

of t(10;17) and del(14q) in these tumors.14

Surgical resection is usually the only therapy required

in cases of CMN because it has an excellent prognosis,

as compared to WT.11 The cytopathologists should be

aware of the features of this uncommon neoplasm to be

able to suggest this diagnosis, which may be confirmed

on histology.

References

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11. Radhika S, Bakshi A, Rajwanshi A, et al. Cytopathology of uncom-mon malignant renal neoplasms in the pediatric age group. DiagnCytopathol 2005;32:281–286.

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