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Tuberose sclerosis complex: analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minimal-fat-containing angiomyolipoma
Clinical Radiology (2005) 60, 663–664
COMMENTARY
Tuberose sclerosis complex: analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minimal-fat-containing angiomyolipoma M.J. Weston* Ultrasound Department, St James’s University Hospital, Leeds, UK
The paper by Patel et al.1 raises some interesting points. The authors have retrospectively reviewed a cohort of 12 patients with tuberous sclerosis complex and renal lesions, in an attempt to show that renal cell carcinoma may be detected by a growth rate of over 0.5 cm/year. The first point is that no one knows what risk renal cell carcinoma poses for individuals with tuberous sclerosis. Most will die of something else and, even though renal failure is their second commonest cause of death, it is not related to the presence of renal cell carcinoma. Patel et al.1 quote a per capita prevalence of renal cell carcinoma in tuberous sclerosis of 4%, although others would argue that it is nearer 2%.2 Secondly, the assumption that a growth rate of over 0.5 cm/year identifies renal cell carcinoma is unproven. A retrospective review conducted once the first cancer has been identified becomes a selffulfilling prophecy. Patel et al.1 rightly state that they do not know what most of the non-fatcontaining indeterminate masses in their series were. Some may have been as yet undeclared renal cell carcinomas. So perhaps it would be better to consider whether the rate of growth of a lesion does define the likelihood of metastasis. Oda et al.3 compared 16 incidentally found renal cell carcinomas without metastasis, with 16 which had already metastasised. They found that the growth rate of the primary lesions of incidentally found renal cell carcinoma was lower than that of metastatic lesions, but there was considerable overlap. Rendon et al.4 found that it was the fastest * Guarantor and correspondent. E-mail address: [email protected].
growing lesions that caused symptoms, but even so none had metastasized. They postulate that tumours that are destined to grow and possibly metastasise do so early on. This raises a third point. When should screening for renal tumours in tuberous sclerosis start? The tumours found in tuberous sclerosis are likely to be a different subtype to those found incidentally in the elderly general population; they may exhibit different growth and metastatic potential. There are case reports of renal cell carcinoma developing in children with tuberous sclerosis, including one child of 5 years of age.5 Furthermore, the ideal interval between screenings is unknown. Tumours may change their characteristics and metastasize within less than 1 year. Annual renal radiographic screening from the initial diagnosis of tuberous sclerosis has been advised, but I would suggest not using CT for this because of the cumulative radiation dose. Tuberous sclerosis involves defects in two tumour suppressor genes, TSC1 and TSC2; minimizing the radiation dose would seem prudent. US could be used more frequently but suffers from reproducibility errors in the assessment of lesion growth. Lastly, malignant transformation of renal angiomyolipoma may not be as uncommon as Patel et al.1 suggest. Tuberous sclerosis may make transformation more likely.6 In this case, all lesions need to be kept under review and not only the indeterminate ones. In conclusion, tuberous sclerosis is a condition in which the risk of renal cell carcinoma, the risk of metastasis, the time at which to start screening and the optimum interval between screens are all unknown. Patel et al.1 are to be congratulated for
0009-9260/$ - see front matter Q 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2005.01.010
664
trying to study these problems, but I fear their paper does not prove the contention that looking for growth rates of over 0.5 cm/year will identify significant lesions.
References 1. Patel U, Simpson E, Kingswood JC, Saggar-Malik AK. Tuberous sclerosis complex: analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minima-fatcontaining angiomyolipoma. Clin Radiol 2005;60:665—73. 2. Cook JA, Oliver K, Mueller RF, Sampson J. A cross sectional study of renal involvement in tuberous sclerosis. J Med Genet 1996;33:480—4.
M.J. Weston
3. Oda T, Miayo N, Takahashi A, Yanase M, Masumori N, Itoh N, et al. Growth rates of primary and metastatic lesions of renal cell carcinoma. Int J Urol 2001;8:473—7. 4. Rendon RA, Stanietzky N, Panzarella T, Robinette M, Klotz LH, Thurston W, et al. The natural history of small renal masses. J Urol 2000;164:1143—7. 5. Robertson FM, Cendron M, Klauber GT, Harris BH. Renal cell carcinoma in association with tuberous sclerosis in children. J Pediatr Surg 1996;31:729—30. 6. Kawaguchi K, Oda Y, Nakanishi K, Saito T, Tamiya S, Nakahara K, et al. Malignant transformation of renal angiomyolipoma: a case report. Am J Surg Pathol 2002;26: 523—9.
COMMENTARY
Tuberose sclerosis complex: analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minimal-fat-containing angiomyolipoma M.J. Weston* Ultrasound Department, St James’s University Hospital, Leeds, UK
The paper by Patel et al.1 raises some interesting points. The authors have retrospectively reviewed a cohort of 12 patients with tuberous sclerosis complex and renal lesions, in an attempt to show that renal cell carcinoma may be detected by a growth rate of over 0.5 cm/year. The first point is that no one knows what risk renal cell carcinoma poses for individuals with tuberous sclerosis. Most will die of something else and, even though renal failure is their second commonest cause of death, it is not related to the presence of renal cell carcinoma. Patel et al.1 quote a per capita prevalence of renal cell carcinoma in tuberous sclerosis of 4%, although others would argue that it is nearer 2%.2 Secondly, the assumption that a growth rate of over 0.5 cm/year identifies renal cell carcinoma is unproven. A retrospective review conducted once the first cancer has been identified becomes a selffulfilling prophecy. Patel et al.1 rightly state that they do not know what most of the non-fatcontaining indeterminate masses in their series were. Some may have been as yet undeclared renal cell carcinomas. So perhaps it would be better to consider whether the rate of growth of a lesion does define the likelihood of metastasis. Oda et al.3 compared 16 incidentally found renal cell carcinomas without metastasis, with 16 which had already metastasised. They found that the growth rate of the primary lesions of incidentally found renal cell carcinoma was lower than that of metastatic lesions, but there was considerable overlap. Rendon et al.4 found that it was the fastest * Guarantor and correspondent. E-mail address: [email protected].
growing lesions that caused symptoms, but even so none had metastasized. They postulate that tumours that are destined to grow and possibly metastasise do so early on. This raises a third point. When should screening for renal tumours in tuberous sclerosis start? The tumours found in tuberous sclerosis are likely to be a different subtype to those found incidentally in the elderly general population; they may exhibit different growth and metastatic potential. There are case reports of renal cell carcinoma developing in children with tuberous sclerosis, including one child of 5 years of age.5 Furthermore, the ideal interval between screenings is unknown. Tumours may change their characteristics and metastasize within less than 1 year. Annual renal radiographic screening from the initial diagnosis of tuberous sclerosis has been advised, but I would suggest not using CT for this because of the cumulative radiation dose. Tuberous sclerosis involves defects in two tumour suppressor genes, TSC1 and TSC2; minimizing the radiation dose would seem prudent. US could be used more frequently but suffers from reproducibility errors in the assessment of lesion growth. Lastly, malignant transformation of renal angiomyolipoma may not be as uncommon as Patel et al.1 suggest. Tuberous sclerosis may make transformation more likely.6 In this case, all lesions need to be kept under review and not only the indeterminate ones. In conclusion, tuberous sclerosis is a condition in which the risk of renal cell carcinoma, the risk of metastasis, the time at which to start screening and the optimum interval between screens are all unknown. Patel et al.1 are to be congratulated for
0009-9260/$ - see front matter Q 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2005.01.010
664
trying to study these problems, but I fear their paper does not prove the contention that looking for growth rates of over 0.5 cm/year will identify significant lesions.
References 1. Patel U, Simpson E, Kingswood JC, Saggar-Malik AK. Tuberous sclerosis complex: analysis of growth rates aids differentiation of renal cell carcinoma from atypical or minima-fatcontaining angiomyolipoma. Clin Radiol 2005;60:665—73. 2. Cook JA, Oliver K, Mueller RF, Sampson J. A cross sectional study of renal involvement in tuberous sclerosis. J Med Genet 1996;33:480—4.
M.J. Weston
3. Oda T, Miayo N, Takahashi A, Yanase M, Masumori N, Itoh N, et al. Growth rates of primary and metastatic lesions of renal cell carcinoma. Int J Urol 2001;8:473—7. 4. Rendon RA, Stanietzky N, Panzarella T, Robinette M, Klotz LH, Thurston W, et al. The natural history of small renal masses. J Urol 2000;164:1143—7. 5. Robertson FM, Cendron M, Klauber GT, Harris BH. Renal cell carcinoma in association with tuberous sclerosis in children. J Pediatr Surg 1996;31:729—30. 6. Kawaguchi K, Oda Y, Nakanishi K, Saito T, Tamiya S, Nakahara K, et al. Malignant transformation of renal angiomyolipoma: a case report. Am J Surg Pathol 2002;26: 523—9.