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CASE REPORT

METANEPHRIC ADENOMA: CASE REPORT AND REVIEW OF LITERATURE

SHAHIDA NIAZI, MADIHA ARSHAD, NASIR KARIM AND M. H. BUKHARI

Department of Pathology, King Edward Medical University, Lahore – Pakistan

ABSTRACT

Metanephric Adenoma (MA) is a histologically and clinically unique and rare benign renal epithe-lial tumour. Only a few reports are found in literature regarding this novel tumour entity. We re-port this neoplasm in a 40 – year old male who presented with flank pain and microscopic haema-turia. USG and operative findings were suggestive of Renal Cell Carcinoma. Microscopic examina-tion showed a tumour composed of small bland cells forming small tubular structures in an acellu-lar stroma. Occasional papillary formations were also seen but no blastema was identified. The case was finally diagnosed as Metanephric Adenoma. It has a histological similarity to developing metanephric tubular epithelium and is considered to represent the benign counterpart of Wilms’ Tumour. The unique pathological features of Metanephric Adenoma should be recognised because of its invariable indolent clinicobiological behaviour.

INTRODUCTION

Metanephric Adenoma (MA) also designated “Ne-phrogenic adenoma” or “Embryonal adenoma” is a rare benign renal tumour which is histologically, immunohistochemically and clinically unique, with an indolent clinicobiological behaviour.1,2 It accou-nts for only about 0.2% of adult renal epithelial neo-plasms with only 130 well documented cases repor-ted in world literature.3 Origin of this renal mass from persistent primitive metanephric epithelium of the proximal nephron is postulated and partly subs-tantiated.1,2 Histologically this tumour seems to be related to epithelial Wilms’ Tumour and Nephroge-nic Rests and in fact these lesions may coexist.4,5

MA occurs predominantly in middle aged fema-les but well documented cases have been reported in children.5--9 Usually these tumours are asymptoma-tic and discovered incidentally on investigation for other problems.5,6,9-11 Symptoms when present in-clude an abdominal mass, flank pain, microscopic haematuria, hypertension and fever.5,12 About 12% cases of MA are responsible for producing the para-neoplastic syndromes like polycythaemia and hy-percalcaemia.5,7 Radiologically and morphologically these tumours are frequently solid, well circumscri-bed, calcified and hypovascular.3,12 From the clinical and diagnostic viewpoint the importance of this tu-mour depends on differentiating it from nephroge-nic rests (nodular renal blastema), epithelial Wilms’ tumour, solid papillary renal cell carcinoma and metastatic cancers.5,7,13 Recognition of this tumour as benign is of utmost importance as conservative tumour resection with organ sparing surgery is suf-

ficient in almost all cases.9,12

CASE REPORT

A left nephrectomy specimen of a 40 year old male was referred from the Urology Ward of Mayo Hos-pital, Lahore to the Department of Pathology, King Edward Medical University, Lahore. The patient had a history of pain left lumbar region and micro-scopic haematuria for the last 6 months. Abdominal USG findings reported a solid, well circumscribed renal tumour occupying the mid region of the left kidney measuring 5 x 4 x 4.5 cm with the provision-al diagnosis of renal cell carcinoma. The right kid-ney was completely normal. A left radical nephrec-tomy with removal of the perinephric fat was per-formed.

Gross examination and sectioning of the renal specimen revealed a well circumscribed white, solid, encapsulated tumour measuring 4 × 4 × 3 cm occu-pying the central portion of the left kidney. There was no extension of the tumour into the renal vein, Gerota’s fascia or surrounding renal parenchyma. On histological examination post-graduate residents diagnosed the tumour as a round blue cell tumour consistent with the diagnosis of Wilms’ Tumour. The tumour comprised of small, round, uniform dark staining cells forming small acinar and tubular structures with focal areas showing papillary forma-tions. Individual tumour cells had no pleomorphism and no mitosis. blastema component was not seen. Tumour was surrounded by a distinct well defined fibrous capsule. The case was diagnosed and confir-med as metanephric adenoma.

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Fig. 1: Low power microscopic image showing the sharp demarcation of the tumour from the surrounding renal parenchyma. The tumour cells are small, hyperchromatic forming small acinar / tubular structures.

Fig. 2: Higher magnification showing the tumour com-posed of small, round to oval acinar structures separated by scant stroma. Individual tumour cells are bland with hyperchromatic nuclei and scant cytoplasm.

DISCUSSION

In embryonic life the kidney develops from the me-tanephric blastema. If remnants of this tissue re-main within the renal parenchyma in post natal life, they often develop into Wilms’ tumour or rarely into metanephric adenoma.6 Thus Wilms’ tumour and metanephric adenoma are histogenetically related and MA is considered to be the benign counterpart of Wilms’ tumour in adults.4,6,14 Since they arise from the same precursor tissue, metanephric adeno-ma and Wilms’ tumour may sometimes co-exist and adequate histological sampling is essential to diffe-rentiate between the two tumours.4,5 Histologically metanephric adenoma is also very similar to the

metanephric hamartomatous element of nephro-blastomatosis.5 MA was first described in 1979 by Bove et al,2 in a 7 - year old boy and he proposed an origin of this tumour from the persistent primitive epithelium of the proximal tubule of the nephron which had failed to mature adequately. Pages and Granier15 proposed the name “Nephronogenic nephroma” for this tum-our in 1980. Since that time about 130 cases have been reported in world literature.3 The largest series of this rare tumour was published by Davis and col-leagues5 in 1995 who reported on 50 Metanephric Adenomas during a 22 – year period from the retri-eved files of the Armed Forces Institute of Patho-logy, Washington DC. This study included 36 fema-les and 14 males (F:M ratio = 2.6:1) with the histolo-gical diagnosis of MA. Patients ranged in age from 5 to 83 years. MA was detected incidentally in 20 patients (40%) and 6 patients (12%) had polycytha-emia. Presenting complaints included abdominal / flank pain in 11 patients (22%), haematuria in 5 patients (10%) and a palpable mass in 5 patients (10%). Preoperative radiological examination of the-se tumours demonstrated calcifications of 44% ca-ses. Regarding age and sex distribution, metane-phric adenomas occur mostly in young and middle aged females but cases have also been reported in children and adolescents.8,9,14 Liniger16 reported this tumour in a 15-month old boy, the youngest patient yet to be reported with MA. Loeser and friends8 re-ported MA in the left kidney of a 2 – year old girl. In both cases, successful tumour resection with neph-ron sparing surgery was performed. A close associ-ation between polycythaemia and hypercalcaemia has been reported in adults and children with MA.5,7,17 A recent cell culture study by Yoshioka and co-workers18 in Japan proved that MA cells produce erythropoietin and other cytokines which may be responsible for the high incidence of erythrocytosis in these patients. Most imaging studies describe MA as a solid, well circumscribed, hypovascular tumour with fre-quent calcifications as a rather characteristic diag-nostic feature.3,12,19 A study by Bastide and cowor-kers3 analysed and reviewed the clinical and radio-logical features of 9 patients with MA. Six patients were discovered incidentally, 2 had microscopic he-maturia and 1 had polycythemia. Preoperative ima-ging showed all MA’s to be well circumscribed, solid with no vascular flow within the tumours on colour Doppler USG, and frequent calcifications were seen in 6 tumours. However, Patankar20 reported a cystic MA measuring 12 × 5 cm surrounded by a fibrous cyst wall. Morphologically MA is a solid, well circumscri-bed, tan pink to gray cortical tumour surrounded by

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178 Biomedica Vol. 27 (Jul. – Dec. 2011)

a fibrous capsule with no extrarenal extension.1,3,6,7 Unlike renal papillary adenomas which are by defi-nition less than 5 mm in diameter MA can grow to a large size.12 Bouzourene et al21 reported the largest MA measuring 20 × 19 × 15 cm. Other studies repo-rt variable size dimensions of this tumour. In the largest study on 50 MA’s reported by Davis5 the tumours measured from 0.3 cm to 15 cm (mean 5.5 cm) in size. In Jones study6 on 7 patients, size of MA’s ranged from 0.6 to 8 cm and in a case report by Yaqoob19 at Aga Khan University, Karachi the tu-mour measured 10 × 8 cm and was largely haemor-rhagic and necrotic. Many MA’s are mistakenly dia-gnosed as renal cell carcinoma on gross morphology and imaging studies and total nephrectomies are performed.5,10,11 Histopathological examination of MA, often prompts an initial diagnosis of Wilms’ tumour (as was experienced in our case as well) as both lesions show cellular areas composed of small uniform, round blue epithelial cells forming small acinar and tubular formations in an acellular stro-ma.5,7 Glomeruloid bodies composed of lobulated papillary projections are seen focally and blastema is consistently absent in MA.6,13,14 Individual tumour cells are bland, with rounded to ovoid nuclei having delicate chromatin, absolutely no pleomorphism or mitosis and scanty cytoplasm.6,11 Frequent calcifica-tions in the form of psammoma bodies or dystro-phic calcification may be present.5,13,19 Distinction from epithelial Wilms’ tumour, nephrogenic rests, the solid variant of papillary renal cell carcinoma and metastatic thyroid carcinoma can be difficu-lt.3,4,7,9,13 Both nephrogenic rests and Wilms’ tumour on microscopy contain a blastema component whe-reas MA has no primitive blastema.6,4,14 On immu-nohistochemistry (IHC), MA’s are focally positive for CK7 and strongly and diffusely positive with antibodies to WT1 and CD57 as are maturing Wilms tumours and nephrogenic rests.1,4 Papillary renal cell carcinoma has fibrovascular cores containing foamy macrophages and lined by larger cells with pleomorphic nuclei, whereas MA lacks true fibro-vascular cores and has bland uniform cells.13 In the distinction from metastatic thyroid cancer clinical information and immunohistochemical study of TTF-1 may provide assistance.13

Almost all MA’s follow a favourable, benign cli-nical course with no metastasis and recurrences.1,5,6 However Renshaw22 presented the only reported case of metastatic MA to the regional lymph nodes in a 7 – year old child but no deaths related to the tumour have been reported so far. The unique featu-res of metanephric adenoma should be clinically and pathologically recognised because of its invari-ably benign course and treatment with conservative local resection.

ACKNOWLEDGEMENTS

The authors acknowledge the V.C of KEMU for pro-viding the facilities to do this work and the Profes-sor of Pathology for encouraging us.

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