Метастазы почечно-клеточного рака без выявленной первичной опухоли являются крайне редкими. Они носят характер спонтанного описания отдельных клинических случаев. Цель. Публикация клинического наблюдения синхронных метастазов почечно-клеточного рака без выявленного первичного очага. Результаты. Больной У., 52 года, на протяжении 5 лет стал отмечать повышение артериального давления до 170/100 мм рт. ст., по поводу чего многократно проходил инструментальные обследования, включая ультразвуковое исследование. В октябре 2017 г. при рентгеновской компьютерной томографии органов брюшной полости в правом надпочечнике выявлена опухоль размером 49×75 мм неоднородной структуры и плотности. По данным совмещенной позитронно-эмиссионной и рентгеновской компьютерной томографии в правом надпочечнике определяется объемное образование размером 79×54×41 мм с повышенной метаболической активностью фтордезоксиглюкозы SUVmax 7.25. В средостении, в бифуркационном пространстве, определяется узловое образование 17×11×24 мм с очаговой фиксацией радиофармпрепарата SUVmax 4.31. В верхнесуставном отростке L3 справа очаг деструкции 10×15 мм. Учитывая олигометастатический характер процесса, в ноябре 2017 г. пациенту выполнили оперативное вмешательство в объеме ретроперитонеоскопической адреналэктомии и торакоскопического удаления опухоли средостения. При гистологическом исследовании в правом надпочечнике светлоклеточная карцинома с участками папиллярного строения. При иммуногистохимическом исследовании опухолевые клетки интенсивно экспрессируют CD10, а часть клеток – RCC. Иммунный фенотип опухоли соответствует светлоклеточной почечной карциноме. В одном лимфоузле из 9 иммуногистологически и иммуногистохимически метастаз аналогичного варианта рака почки. Пациенту назначен пазопаниб. При динамическом наблюдении, включая ежегодную совмещенную позитронно-эмиссионную и рентгеновскую компьютерную томографию, первичную опухоль почки не выявили. Пациент жив на протяжении 32 мес без прогрессирования заболевания. Заключение. Метастазы светлоклеточного рака почки, включая надпочечник, без выявленного первичного очага встречаются крайне редко. Основным методом лечения является хирургический в комбинации с таргетной терапией, которые обеспечивают длительный локальный контроль течения заболевания.
Renal cell cancer metastases without evidence of a primary tumor are extremely rare. These variants are usually showed as a spontaneous description of single clinical cases. Aim. This contribution is a clinical follow-up of synchronous renal cell cancer metastases of unknown primary site. Results. A 52-year-old patient U. with a history of increased blood pressure, up to 170/100 mmHg for the last 5 years, who had undergone many instrumental examinations, including ultrasound examination, because of this disease. The computed tomography of the abdomen showed a 49×75 mm heterogeneous tumor in the right adrenal gland in October 2017. The combined positron emission and X-ray computed tomography showed a 79×54×41 mm mass in the right adrenal gland, associated with elevated fluorodeoxyglucose metabolic activity SUVmax 7.25. Focal accumulation of the radiopharmaceutical SUVmax 4.31 in a 17×11×24 mm mass was detected in the space of bifurcation in the mediastinum. The lytic lesion (10×15 mm) was found in right superior L3 articular process. The patient underwent retroperitoneoscopic adrenalectomy and thoracoscopic removal of mediastinal tumor in November 2017 because of the oligometastatic nature of the process. The histological study identified clear-cell carcinoma with areas of papillary structure in the right adrenal gland. The immunohistochemical study showed carcinoma cells intensively expressing CD10, and some other cells – RCC. The immune phenotype of the tumor was identified as clear-cell renal cell carcinoma. The immunohistological and immunohistochemical analysis reviled the metastases of the same variant of renal cell carcinoma in one of 9 lymph nodes. The patient was treated with pazopanib. The primary renal tumor was not detected during the dynamic observation, including the application of annual combined positron emission and X-ray computed tomography. The patient is alive without disease progression with a follow-up of 32 months. Conclusion. Metastases of clear-cell renal cell carcinoma, including adrenal gland, without evidence of a primary site are extremely rare. The main method of treatment is a combination of surgery and targeted therapy, providing long-term local control of the course of the disease.
Key words: renal cell carcinoma, metastases without evidence of a primary site, surgical treatment, targeted therapy.
1. Maldazys JD, deKernion JB. Prognostic factors in metastatic renal carcinoma. J Urol 1986; 136: 376–9. DOI: 10.1016/s0022-5347(17)44873-7
2. Bianchi M, Sun M, Jeldres C et al. Distribution of metastatic sites in renal cell carcinoma: a population based analysis. Ann Oncol 2012; 23 (4): 973–80. DOI: 10.1093/annonc/mdr362
3. Kane CJ, Mallin K, Ritchey J et al. Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer 2008; 113 (1): 78–83. DOI: 10.1002/cncr.23518
4. Handorf CR, Kulkarni A, Grenert JP et al. A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors. Am J Surg Pathol 2013; 37: 1067–75. DOI: 10.1097/PAS.0b013e31828309c4
5. Özturk H. Bilateral synchronous adrenal metastases of renal cell carcinoma: a case report and review of the literature. Oncol Lett 2015; 9: 1897–901. DOI: 10.3892/ol.2015.2915
6. Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history of renal cell carcinoma. J Urol 2001; 166: 1611–23. DOI: 10.1016/S0022-5347(05)65640-6
7. Golimbu M, Joshi P, Sperber A et al. Renal cell carcinoma: survival and prognostic factors. Urology 1986; 27: 291–301. DOI: 10.1016/0090-4295(86)90300-6
8. Bhatia S, Ng S, Hodder SC Metastatic cutaneous head and neck renal cell carcinoma with no known primary: case report. Br J Oral Maxillofac Surg 2010; 48: 214–5. DOI: 10.1016/j.bjoms.2009.11.012
9. Wei EY, Chen YB, Hsieh JJ Genomic characterisation of two cancers of unknown primary cases supports a kidney cancer origin. BMJ Case Rep 2015. DOI: 10.1136/bcr-2015-212685
10. Costantino C, Thomas GV, Ryan C et al. Metastatic renal cell carcinoma without evidence of a renal primary. Int Urol Nephrol 2016; 48 (1): 73–7. DOI: 10.1007/s11255-015-1145-3
11. Fayaz MS, Al-Qaderi AE, El-Sherify MS Metastatic renal cell carcinoma with undetectable renal mass presenting as lymphadenopathy. CEN Case Rep 2017; 6 (1): 36–8. DOI: 10.1007/s13730-016-0239-9
12. Heary RF, Agarwal N, Barrese JC et al. Metastatic renal cell carcinoma, with a radiographically occult primary tumor, presenting in the operative site of a thoracic meningioma: long-term follow-up. Case report. J Neurosurg Spine 2014; 21 (4): 628–33. DOI: 10.3171/2014.6.SPINE13448
13. Woodhouse L, Watkins J, Navalkissoor S, Gillmore R Metastatic bone disease from an occult renal primary. BMJ Case Rep 2019; 12 (4): e227657. DOI: 10.1136/bcr-2018-227657
14. Johnson MT, Bahnson RR Zynger, DL Metastatic clear cell renal cell carcinoma to the adrenal gland without an identifiable primary tumor. Int J Urol 2012; 19: 92–3. DOI: 10.1111/j.1442-2042.2011.02904.x
15. Cancer today. In: GLOBOCAN 2018. https://gco.iarc.fr/today/data/factsheets/cancers/34-Non-hodgkin-lymphoma-fact-sheet.pdf.
16. Kumar RM, Aziz T, Jamshaid H et al. Metastatic renal cell carcinoma without evidence of a primary renal tumour. Curr Oncol 2014; 21 (3): e521–e54. DOI: 10.3747/co.21.1914
17. Choi YR, Han HS, Lee OJ et al. Metastatic Renal Cell Carcinoma in a Supraclavicular Lymph Node with No Known Primary: A Case Report. Cancer Res Treat 2012; 44 (3): 215–8. DOI: 10.4143/crt.2012.44.3.215
18. Walton J, Li J, Clifton MM et al. Metastatic clear cell renal cell carcinoma to the forearm without identifiable primary renal mass. Urol Case Rep 2019; 27: 100989. DOI: 10.1016/j.eucr.2019.100989
19. Kawakita M, Kawamura J, Hida S et al. Renal cell carcinoma, primary lesion which was not easily identified: report of two cases. Hinyokika Kiyo 1985; 31 (3): 463–73. PMID: 4025083
20. Wayne M, Wang W, Bratcher J et al. Renal cell cancer without a renal primary. World J Surg Oncol 2010; 8: 18. DOI: 10.1186/1477-7819-8-18
21. Abdou AG, Kandil M, Elshakhs S et al. Renal Cell Carcinoma With Rhabdoid and Sarcomatoid Features Presented as a Metastatic Thigh Mass With an Unusual Immunohistochemical Profile. Rare Tumors 2014; 6 (1): 5037. DOI: 10.4081/rt.2014.5037
22. Higuchi T, Yamamoto N, Hayashi K Long-term patient survival after the surgical treatment of bone and soft-tissue metastases from renal cell carcinoma. Bone Joint Lett J 2018; 100-B: 1241–8. DOI: 10.1302/0301-620X.100B9.BJJ-2017-1163.R3
23. Marcus PB, Kemp CB Ectopic renal cell carcinoma: pathologist’s problem. Urology 1978; 1978 (12): 453–7. DOI: 10.1016/0090-4295(78)90303-5
24. Terada T Extra-renal clear cell renal cell carcinoma probably arising from mesodermal embryonic remnants. Pathol Int 2012; 62: 291–3. DOI: 10.1111/j.1440-1827.2011.02780.x
25. Sorscher SM, Greco FA Papillary Renal Carcinoma Presenting as a Cancer of Unknown Primary (CUP) and Diagnosed through Gene Expression Profiling. Case Rep Oncol 2012; 5 (2): 229–32. DOI: 10.1159/000339130
26. Overby A, Duval L, Ladekarl M et al. Carcinoma of Unknown Primary Site (CUP) With Metastatic Renal-Cell Carcinoma (mRCC) Histologic and Immunohistochemical Characteristics (CUP-mRCC): Results From Consecutive Patients Treated With Targeted Therapy and Review of Literature. Clin Genitourin Cancer 2019; 17 (1): e32–e37. DOI: 10.1016/j.clgc.2018.08.005
27. Lombardo R, Tosi F, Nocerino A et al. The Quest for Improving Treatment of Cancer of Unknown Primary (CUP) Through Molecularly-Driven Treatments: A Systematic Review. Front Oncol 2020; 10: 533. DOI: 10.3389/fonc.2020.00533
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1. Maldazys JD, deKernion JB. Prognostic factors in metastatic renal carcinoma. J Urol 1986; 136: 376–9. DOI: 10.1016/s0022-5347(17)44873-7
2. Bianchi M, Sun M, Jeldres C et al. Distribution of metastatic sites in renal cell carcinoma: a population based analysis. Ann Oncol 2012; 23 (4): 973–80. DOI: 10.1093/annonc/mdr362
3. Kane CJ, Mallin K, Ritchey J et al. Renal cell cancer stage migration: analysis of the National Cancer Data Base. Cancer 2008; 113 (1): 78–83. DOI: 10.1002/cncr.23518
4. Handorf CR, Kulkarni A, Grenert JP et al. A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors. Am J Surg Pathol 2013; 37: 1067–75. DOI: 10.1097/PAS.0b013e31828309c4
5. Özturk H. Bilateral synchronous adrenal metastases of renal cell carcinoma: a case report and review of the literature. Oncol Lett 2015; 9: 1897–901. DOI: 10.3892/ol.2015.2915
6. Pantuck AJ, Zisman A, Belldegrun AS. The changing natural history of renal cell carcinoma. J Urol 2001; 166: 1611–23. DOI: 10.1016/S0022-5347(05)65640-6
7. Golimbu M, Joshi P, Sperber A et al. Renal cell carcinoma: survival and prognostic factors. Urology 1986; 27: 291–301. DOI: 10.1016/0090-4295(86)90300-6
8. Bhatia S, Ng S, Hodder SC Metastatic cutaneous head and neck renal cell carcinoma with no known primary: case report. Br J Oral Maxillofac Surg 2010; 48: 214–5. DOI: 10.1016/j.bjoms.2009.11.012
9. Wei EY, Chen YB, Hsieh JJ Genomic characterisation of two cancers of unknown primary cases supports a kidney cancer origin. BMJ Case Rep 2015. DOI: 10.1136/bcr-2015-212685
10. Costantino C, Thomas GV, Ryan C et al. Metastatic renal cell carcinoma without evidence of a renal primary. Int Urol Nephrol 2016; 48 (1): 73–7. DOI: 10.1007/s11255-015-1145-3
11. Fayaz MS, Al-Qaderi AE, El-Sherify MS Metastatic renal cell carcinoma with undetectable renal mass presenting as lymphadenopathy. CEN Case Rep 2017; 6 (1): 36–8. DOI: 10.1007/s13730-016-0239-9
12. Heary RF, Agarwal N, Barrese JC et al. Metastatic renal cell carcinoma, with a radiographically occult primary tumor, presenting in the operative site of a thoracic meningioma: long-term follow-up. Case report. J Neurosurg Spine 2014; 21 (4): 628–33. DOI: 10.3171/2014.6.SPINE13448
13. Woodhouse L, Watkins J, Navalkissoor S, Gillmore R Metastatic bone disease from an occult renal primary. BMJ Case Rep 2019; 12 (4): e227657. DOI: 10.1136/bcr-2018-227657
14. Johnson MT, Bahnson RR Zynger, DL Metastatic clear cell renal cell carcinoma to the adrenal gland without an identifiable primary tumor. Int J Urol 2012; 19: 92–3. DOI: 10.1111/j.1442-2042.2011.02904.x
15. Cancer today. In: GLOBOCAN 2018. https://gco.iarc.fr/today/data/factsheets/cancers/34-Non-hodgkin-lymphoma-fact-sheet.pdf.
16. Kumar RM, Aziz T, Jamshaid H et al. Metastatic renal cell carcinoma without evidence of a primary renal tumour. Curr Oncol 2014; 21 (3): e521–e54. DOI: 10.3747/co.21.1914
17. Choi YR, Han HS, Lee OJ et al. Metastatic Renal Cell Carcinoma in a Supraclavicular Lymph Node with No Known Primary: A Case Report. Cancer Res Treat 2012; 44 (3): 215–8. DOI: 10.4143/crt.2012.44.3.215
18. Walton J, Li J, Clifton MM et al. Metastatic clear cell renal cell carcinoma to the forearm without identifiable primary renal mass. Urol Case Rep 2019; 27: 100989. DOI: 10.1016/j.eucr.2019.100989
19. Kawakita M, Kawamura J, Hida S et al. Renal cell carcinoma, primary lesion which was not easily identified: report of two cases. Hinyokika Kiyo 1985; 31 (3): 463–73. PMID: 4025083
20. Wayne M, Wang W, Bratcher J et al. Renal cell cancer without a renal primary. World J Surg Oncol 2010; 8: 18. DOI: 10.1186/1477-7819-8-18
21. Abdou AG, Kandil M, Elshakhs S et al. Renal Cell Carcinoma With Rhabdoid and Sarcomatoid Features Presented as a Metastatic Thigh Mass With an Unusual Immunohistochemical Profile. Rare Tumors 2014; 6 (1): 5037. DOI: 10.4081/rt.2014.5037
22. Higuchi T, Yamamoto N, Hayashi K Long-term patient survival after the surgical treatment of bone and soft-tissue metastases from renal cell carcinoma. Bone Joint Lett J 2018; 100-B: 1241–8. DOI: 10.1302/0301-620X.100B9.BJJ-2017-1163.R3
23. Marcus PB, Kemp CB Ectopic renal cell carcinoma: pathologist’s problem. Urology 1978; 1978 (12): 453–7. DOI: 10.1016/0090-4295(78)90303-5
24. Terada T Extra-renal clear cell renal cell carcinoma probably arising from mesodermal embryonic remnants. Pathol Int 2012; 62: 291–3. DOI: 10.1111/j.1440-1827.2011.02780.x
25. Sorscher SM, Greco FA Papillary Renal Carcinoma Presenting as a Cancer of Unknown Primary (CUP) and Diagnosed through Gene Expression Profiling. Case Rep Oncol 2012; 5 (2): 229–32. DOI: 10.1159/000339130
26. Overby A, Duval L, Ladekarl M et al. Carcinoma of Unknown Primary Site (CUP) With Metastatic Renal-Cell Carcinoma (mRCC) Histologic and Immunohistochemical Characteristics (CUP-mRCC): Results From Consecutive Patients Treated With Targeted Therapy and Review of Literature. Clin Genitourin Cancer 2019; 17 (1): e32–e37. DOI: 10.1016/j.clgc.2018.08.005
27. Lombardo R, Tosi F, Nocerino A et al. The Quest for Improving Treatment of Cancer of Unknown Primary (CUP) Through Molecularly-Driven Treatments: A Systematic Review. Front Oncol 2020; 10: 533. DOI: 10.3389/fonc.2020.00533
1 ФГБОУ ВО «Тамбовский государственный университет им. Г.Р. Державина», Тамбов, Россия;
2 ГБУЗ «Тамбовский областной онкологический клинический диспансер», Тамбов, Россия;
3 ООО «ПЭТ-Технолоджи», Центр ядерной медицины, Тамбов, Россия;
4 ТОГБУЗ «Патологоанатомическое бюро», Тамбов, Россия
*ognerubov_n.a@mail.ru
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Nikolai A. Ognerubov*1,2, Tatyana S. Antipova3, Galina E. Gumareva4