NDT Advance Access originally published online on October 4, 2005
Nephrology Dialysis Transplantation 2006 21(1):64-69; doi:10.1093/ndt/gfi149
© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Incidental neoplasms in renal biopsies
Tanya Pankhurst1,
Alexander J. Howie2,
Dwomoa Adu1,
D. Michael A. Wallace3 and
Graham W. Lipkin1
1 Department of Nephrology, University Hospital Birmingham, Birmingham B15 2TH, 2 Department of Pathology, University College London, London WC1E 6BT and 3 Department of Urology, University Hospital Birmingham, Birmingham B15 2TH, UK
Correspondence and offprint requests to: Dr G. W. Lipkin, MD, Department of Nephrology, University Hospital Birmingham, Birmingham B15 2TH, UK. Email: Graham.Lipkin{at}uhb.nhs.uk
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Abstract
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Background. Incidental neoplastic lesions are occasionally found
in renal biopsy specimens, but there is no evidence to indicate
how they should be managed.
Methods. A retrospective review was made of the management and clinical course of patients in whom an unsuspected neoplasm had been found in a renal biopsy.
Results. In 11 880 biopsies taken over 22 years, there were incidental neoplasms in 25 (0.2%). Twenty-three of the 25 patients were men, and the median age was 59 years (range, 42–83 years). All had chronic renal damage, with a median index of chronic damage of 37% (range, 10–83%; normal = 0%). Twenty-two neoplasms were papillary, two were clear cell renal carcinomas and one was in situ carcinoma in a collecting duct. The two clear cell carcinomas, three papillary neoplasms with residual masses after biopsy and the two papillary neoplasms in renal allografts were resected by nephrectomy or partial nephrectomy. Seven patients without resection were imaged with computerized tomography, six with magnetic resonance imaging and three with ultrasound scanning. Two were not imaged. None of the 11 patients who died, nor any of the other 14, had evidence of renal cell carcinoma at death or last follow-up respectively, at median 3.6 years after biopsy (range, 1 month–18.2 years).
Conclusions. When an incidental neoplasm is found, the pathological type should be defined, and imaging should be performed. Surgery should be considered in patients in whom there is a neoplasm of any type detectable by imaging, and limited resection may be possible. Neoplasms that are undetectable with imaging cannot be resected as the site of the lesion is unknown. We suggest surveillance of these, but whether this is necessary is undetermined. There is no evidence whether neoplasms undetectable with imaging in renal allografts require aggressive treatment.
Keywords: papillary adenoma; papillary carcinoma; renal allograft; renal biopsy; renal cell carcinoma; renal neoplasm
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Introduction
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Incidental discovery of a neoplasm is rare in a renal biopsy
not performed to investigate a renal mass. There is no published
evidence about the frequency and significance of this finding,
and it is unclear what practical course should be taken in management.
We reviewed all patients in our unit who had such a finding,
to determine its frequency, the clinical management and the
eventual outcome.
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Methods
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During the 22 years from 1982–2003 inclusive, a note was
made of renal biopsy specimens that contained a neoplasm, excluding
(1) biopsies of masses in or near the kidney detected before
the biopsy, (2) biopsies in patients known to have a neoplasm
outside the kidney and in whom the neoplasm in the renal biopsy
was metastatic and (3) biopsies containing a haemangioma or
a renomedullary interstitial cell neoplasm, formerly called
medullary fibroma. Biopsies were reviewed to determine the size
and characteristics of the neoplasm [
1], and to measure the
index of chronic damage [
2]. This is a morphometric method that
uses an interactive image analysis system to express the extent
of global glomerulosclerosis, tubular atrophy and interstitial
fibrosis as a proportion of cortical cross-sectional area. The
index is 0% in a kidney without chronic damage, and can be any
value up to 100%. Nephrectomy specimens of biopsied kidneys
were sectioned at about 3 mm intervals and any lesions were
taken for microscopy. These were also reviewed. A study of clinical
notes was made to find the method of management at the time
of the biopsy, and whether the patient was alive or dead, and
if dead, cause of death. Reports of imaging investigations were
reviewed for the mention of renal masses or metastatic disease.
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Results
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There were 11 880 renal biopsies. These consisted of 10 025
percutaneous needle biopsies, including 3613 of allografts and
1855 wedge biopsies of allografts at implantation. Neoplasms
were found in 25 specimens (0.2%) (
Table 1). The median age
of patients was 59 years (range, 42–83 years). Twenty-three
of the 25 patients were male. All had chronic renal damage in
the renal biopsy (median index of chronic damage, 37%, range,
10–83%). Twenty-one of the 25 neoplasms were under 1 mm
diameter on the sections, although most contacted at least one
aspect of the specimen and so did not appear completely included
in the biopsy. All but three were papillary neoplasms, sometimes
with foamy macrophages and psammoma bodies. The cells were chromophilic
rather than clear, and nearly all were amphiphilic or eosinophilic
rather than basophilic (
Figures 1 and
2). Three neoplasms were
different. In patients 3 and 21, these were solid, with eosinophilic
or clear cells, indicative of renal cell carcinoma, traditionally
called clear cell type [
1] (
Figure 3). In Patient 24, there
was
in situ neoplasia in a collecting duct [
3].
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Fig. 3. Clear cell renal carcinoma in the renal biopsy from Patient 21, at the top, with chronic damage to adjacent renal cortex at the bottom.
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Fifteen of the 25 patients had ultrasonography (US) of the kidneys
before biopsy, and 22 had renal imaging immediately after the
biopsy (
Table 2). Imaging included computed tomography (CT)
with contrast (11 patients), or in patients who were considered
high risk for contrast study, magnetic resonance imaging (MRI)
(7 patients). Four had US alone.
Renal masses were reported in six patients, bilaterally in one.
Five of these, Patients 3, 12, 13, 16 and 21, had nephrectomy
or partial nephrectomy shortly after the biopsy. In the other,
Patient 20, an ill-defined mass was reported, possibly a haematoma,
and surveillance by US at 6-monthly intervals showed that this
was unchanged in size at the last examination. Patients 10 and
17, both with renal allografts, had nephrectomy, although there
was no detectable mass. The other one with a renal allograft,
Patient 4, and the other 16 patients did not have nephrectomy.
These included Patient 24, who was followed with renal imaging,
cystoscopy and ureteroscopy, which showed no abnormality, and
regular urine cytopathological examination, which showed malignant
transitional cells in the urine in the first 5 months following
biopsy, but not at any time after that. Because the site of
origin of the malignant cells could not be identified initially
and they were later undetectable, no resection was performed.
In six of the seven nephrectomy or partial nephrectomy specimens, there were multiple neoplasms. In the other one, Patient 21, there was a clear cell carcinoma, as seen in the biopsy. The multiple neoplasms were papillary neoplasms in five patients, all under 5 mm diameter, and in the other one (Patient 3), renal cell carcinomas, with a mixture of clear, eosinophilic and spindle cells. No patient had evidence of invasion through the renal capsule or spread to lymph nodes. There was no family history of renal cancer in patients with multiple neoplasms, nor any other features to suggest inherited syndromes.
At the time of review, 11 patients were dead. The causes of death were myocardial infarction in three patients, respiratory failure in two, and in one each, stroke, adenocarcinoma of stomach, adenocarcinoma of prostate, sepsis, liver failure and renal failure. In none of the patients was the cause of death related to renal cell carcinoma, although two died of histologically proven disseminated adenocarcinomas of other organs, Patients 5 and 19, and two had paraproteins with systemic effects, Patients 23 and 25.
Nine patients were under surveillance by imaging. Those who had not had CT or MRI for 5 years had further US of the kidneys. Apart from Patient 20, these patients showed no evidence of a renal mass or metastatic carcinoma. The remaining five were Patients 12 and 21, who had had nephrectomy, Patients 10 and 17, who had had allograft nephrectomy and Patient 2, who had moved elsewhere. They were examined regularly and there was no clinical evidence of malignancy. The duration of follow-up to the time of review, or to death, ranged from 1 month to 18.2 years, with a mean of 4.8 years and a median of 3.6 years.
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Discussion
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No similar series has been published reporting the incidental
finding of neoplasms in renal biopsies. We show that this finding
is rare (0.2%, or one in 500 biopsies), and occurs most commonly
in men aged over 50 years with renal impairment and a marked
amount of chronic renal damage. Most neoplasms appeared tiny
and of the papillary pattern [
1]. Assigning these neoplasms
to two different types of papillary neoplasms, as suggested
by Delahunt and Eble [
4,
5], was not straightforward, and because
many experts do not carry out subtyping [
3,
6], this was not
done. The distinction between papillary adenomas and papillary
carcinomas of the kidney is, to some extent, arbitrary and based
on size, in the absence of evidence of malignancy, such as capsular
invasion. Lesions no more than 5 mm in diameter are considered
adenomas, but they are otherwise similar to carcinomas [
1].
Papillary adenomas are the commonest neoplasms found in the
kidney, and are often bilateral and multiple, as we found in
several of the nephrectomy specimens. They occur more commonly
with increasing age, and are found at autopsy in 10% of people
under 40 years and in 40% of those over 70 years [
1].
In contrast, all non-papillary neoplasms are considered malignant, whatever their size, if they consist of clear or eosinophilic or chromophobe cells [1]. The lesions in Patients 3 and 21 were not papillary and were considered malignant. Residual masses were detected by imaging after biopsy, and their nephrectomy specimens confirmed renal cell carcinomas, multiple and bilateral in one patient. The management of patients with similar findings appears straightforward. The finding of in situ carcinoma in a collecting duct in Patient 24 was followed by investigations to detect transitional neoplasia in the urinary tract [3], and there was cytopathological evidence of this for some time after the biopsy. Management of similar patients with suspected transitional malignancy requires investigations different from those with suspected renal cell neoplasia.
The management of papillary neoplasms is still a problem. Renal imaging is necessary to determine their size, because those over 5 mm diameter are considered malignant. The limit of size of lesions detectable by US is often considered about 5 mm, but there is no definite evidence for this, and the limit of detection may vary between centres. CT and MRI may be more sensitive, but again this may vary. In most patients in the current series, no mass was detected after biopsy, and in nearly all, no surgery was considered. The two exceptions were Patients 10 and 17, whose renal allografts contained papillary neoplasms. There is no published guidance on management of such patients, and surveillance, rather than immediate nephrectomy, was chosen in Patient 4, who also had a neoplasm in a graft. Because papillary neoplasms are so common [1], there is a likelihood that many have been transplanted unwittingly. Definite renal cell carcinomas are occasionally noted in kidneys that are potential grafts, and the kidneys are then discarded [7]. Tiny neoplasms are not likely to be seen in potential grafts, especially if they are away from the capsular surface, as many were in kidneys in our series (Table 1). Papillary carcinomas probably arise from adenomas [3]. There is accordingly a theoretical risk of progression of small papillary neoplasms in renal allografts into papillary carcinomas, but there is no evidence about how commonly this occurs. There is undoubtedly an increased incidence of neoplasms in immunosuppressed patients, including renal carcinomas and papillary neoplasms, although these are particularly in the patients’ own kidneys, rather than in grafts [8–11]. This suggests that the risk of progression of neoplasms in grafts may not be especially high.
In future, cytogenetic analysis may help to determine the nature of some renal neoplasms detected incidentally [1], but this was not available to us. In any event, this is likely to be difficult on the extremely small amounts of tissue available, and cannot distinguish papillary adenomas from papillary carcinomas [1]. We suggest that when an incidental neoplasm is found in a renal biopsy, the pathological type is defined, and detailed imaging undertaken. Surgery should be considered in patients in whom there is a neoplasm of any histological type detectable by imaging, because it is likely to be over 5 mm in diameter. Limited resection may be possible, rather than nephrectomy. This decision must take into account co-existing disease and whether the patient is fit for surgery. Neoplasms that are not detected with imaging cannot be resected by limited nephrectomy as the site of the lesion is unknown. We suggest surveillance of these, but whether this is necessary is undetermined. There is no evidence whether neoplasms that are undetectable by imaging in renal allografts require aggressive treatment.
Conflict of interest statement. None declared.
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References
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- Eble JN, Sauter G, Epstein JI, Sesterhenn IA (eds). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press, Lyon, 2004; 23–43
- Howie AJ, Ferreira MAS, Adu D. Prognostic value of simple measurement of chronic damage in renal biopsy specimens. Nephrol Dial Transplant 2001; 16: 1163–1169[Abstract/Free Full Text]
- Van Poppel H, Nilsson S, Algaba F et al. Precancerous lesions in the kidney. Scand J Urol Nephrol 2000; [Suppl 205]: 136–165
- Delahunt B, Eble JN. Papillary renal cell carcinoma: a clinicopathologic and immunohistochemical study of 105 tumors. Mod Pathol 1997; 10: 537–544[Web of Science][Medline]
- Grignon DJ, Eble JN. Papillary and metanephric adenomas of the kidney. Semin Diag Pathol 1998; 15: 41–53
- Murphy WM, Grignon DJ, Perlman EJ. Tumors of the Kidney, Bladder, and Related Urinary Structures. Armed Forces Institute of Pathology, Washington, DC, 2004; 160–163
- Carver BS, Zibari GB, McBride V, Venable DD, Eastham JA. The incidence and implications of renal cell carcinoma in cadaveric renal transplants at the time of organ recovery. Transplantation 1999; 67: 1438–1440[Medline]
- Torbenson M, Wang J, Nichols L, Randhawa P, Nalesnik MA. Renal cortical neoplasms in long term survivors of solid organ transplantation. Transplantation 2000; 69: 864–869[Medline]
- Agraharkar ML, Cinclair RD, Kuo Y, Daller JA, Shahinian VB. Risk of malignancy with long-term immunosuppression in renal transplant recipients. Kidney Int 2004; 66: 383–389[Medline]
- Morath C, Mueller M, Goldschmidt H, Schwenger V, Opelz G, Zeier M. Malignancy in renal transplantation. J Am Soc Nephrol 2004; 15: 1582–1588[Free Full Text]
- Roupret M, Peraldi M, Thaunat O et al. Renal cell carcinoma of the grafted kidney: how to improve screeing and graft tracking. Transplantation 2004; 77: 146–148[Medline]
Received for publication: 17. 5.05
Accepted in revised form: 26. 8.05
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Abstract
Introduction
