Expanding the clinicopathological spectrum of succinate dehydrogenase-deficient renal cell carcinoma with a focus on variant morphologies: a study of 62 new tumors in 59 patients
Por:
Fuchs, TL, Maclean, F, Turchini, J, Vargas, AC, Bhattarai, S, Agaimy, A, Hartmann, A, Kao, CS, Ellis, C, Bonert, M, Leroy, X, Kunju, LP, Schwartz, L, Matsika, A, Williamson, SR, Rao, P, Divatia, M, Guarch, R, Algaba, F, Balancin, ML, Zhou, M, Samaratunga, H, da Cunha, IW, Brimo, F, Ryan, A, Clouston, D, Aron, M, O'Donnell, M, Chan, E, Hirsch, MS, Moch, H, Pang, CY, Wah, C, Yin, WH, Perry-Keene, J, Yilmaz, A, Chou, A, Clarkson, A, van der Westhuizen, G, Morrison, E, Zwi, J, Hes, O, Trpkov, K, Gill, AJ
Publicada:
1 jun 2022
Ahead of Print:
1 dic 2021
Resumen:
Most succinate dehydrogenase (SDH)-deficient renal cell carcinomas (RCCs) demonstrate stereotypical morphology characterized by bland eosinophilic cells with frequent intracytoplasmic inclusions. However, variant morphologic features have been increasingly recognized. We therefore sought to investigate the incidence and characteristics of SDH-deficient RCC with variant morphologies. We studied a multi-institutional cohort of 62 new SDH-deficient RCCs from 59 patients. The median age at presentation was 39 years (range 19-80), with a slight male predominance (M:F = 1.6:1). A relevant family history was reported in 9 patients (15%). Multifocal or bilateral tumors were identified radiologically in 5 patients (8%). Typical morphology was present at least focally in 59 tumors (95%). Variant morphologies were seen in 13 (21%) and included high-grade nuclear features and various combinations of papillary, solid, and tubular architecture. Necrosis was present in 13 tumors, 7 of which showed variant morphology. All 62 tumors demonstrated loss of SDHB expression by immunohistochemistry. None showed loss of SDHA expression. Germline SDH mutations were reported in all 18 patients for whom the results of testing were known. Among patients for whom follow-up data was available, metastatic disease was reported in 9 cases, 8 of whom had necrosis and/or variant morphology in their primary tumor. Three patients died of disease. In conclusion, variant morphologies and high-grade nuclear features occur in a subset of SDH-deficient RCCs and are associated with more aggressive behavior. We therefore recommend grading all SDH-deficient RCCs and emphasize the need for a low threshold for performing SDHB immunohistochemistry in any difficult to classify renal tumor, particularly if occurring at a younger age.
Filiaciones:
Fuchs, TL:
Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia
Kolling Inst Med Res, Canc Diag & Pathol Grp, St Leonards, NSW, Australia
Royal North Shore Hosp, Dept Anatomical Pathol, NSW Hlth Pathol, St Leonards, NSW, Australia
Maclean, F:
Kolling Inst Med Res, Canc Diag & Pathol Grp, St Leonards, NSW, Australia
Son Healthcare, Anatomical Pathol, Douglass Hanly Moir Pathol, Macquarie Pk, NSW, Australia
Macquarie Univ, Macquarie Med Sch, Discipline Pathol, Macquarie Pk, NSW, Australia
Turchini, J:
Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia
Kolling Inst Med Res, Canc Diag & Pathol Grp, St Leonards, NSW, Australia
Son Healthcare, Anatomical Pathol, Douglass Hanly Moir Pathol, Macquarie Pk, NSW, Australia
Macquarie Univ, Macquarie Med Sch, Discipline Pathol, Macquarie Pk, NSW, Australia
Vargas, AC:
Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia
Kolling Inst Med Res, Canc Diag & Pathol Grp, St Leonards, NSW, Australia
Son Healthcare, Anatomical Pathol, Douglass Hanly Moir Pathol, Macquarie Pk, NSW, Australia
Macquarie Univ, Macquarie Med Sch, Discipline Pathol, Macquarie Pk, NSW, Australia
Bhattarai, S:
Leeds Teaching Hosp, Leeds, W Yorkshire, England
Agaimy, A:
Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany
Hartmann, A:
Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Pathol, Erlangen, Germany
Kao, CS:
Stanford Univ, Med Ctr, Stanford, CA USA
Ellis, C:
Northwestern Univ, Chicago, IL USA
Bonert, M:
McMaster Univ, Hamilton, ON, Canada
Leroy, X:
CHRU, Inst Pathol, Ctr Biol Pathol, Lille, France
Kunju, LP:
Univ Michigan, Ann Arbor, MI 48109 USA
Schwartz, L:
Univ Penn, Philadelphia, PA USA
Matsika, A:
Mater Hlth, Brisbane, Qld, Australia
Univ Queensland, Brisbane, Qld, Australia
Williamson, SR:
Cleveland Clin, Robert J Tomsich Pathol & Lab Med Inst, Wright Patterson AFB, OH USA
Rao, P:
Univ Texas MD Anderson Canc Ctr Houston, Houston, TX USA
Divatia, M:
Houston Methodist Hosp, Houston, TX USA
Guarch, R:
Complejo Hosp Navarra, Navarra, Spain
Algaba, F:
Univ Autonoma Barcelona, Fundacio Puigvert, Barcelona, Spain
Balancin, ML:
Oncoctr Fdn, Sao Paulo, Brazil
Zhou, M:
Tufts Med Ctr, Boston, MA USA
Samaratunga, H:
Univ Queensland, Brisbane, Qld, Australia
Aquesta Pathol, Toowong, Qld, Australia
da Cunha, IW:
Rede DORSao Luiz & DOr Inst Res & Educ IDOR, Inst Pathol, Sao Paulo, Brazil
Brimo, F:
McGill Univ, Montreal, PQ, Canada
Ryan, A:
TissuPath Pathol, Melbourne, Vic, Australia
Clouston, D:
TissuPath Pathol, Melbourne, Vic, Australia
Aron, M:
Univ Southern Calif, Los Angeles, CA USA
O'Donnell, M:
NHS Lothian, Edinburgh, Scotland, Scotland
Chan, E:
Univ Calif San Francisco, San Francisco, CA USA
Hirsch, MS:
Brigham & Womens Hosp, Boston, MA 02115 USA
Harvard Med Sch, Boston, MA 02115 USA
Moch, H:
Univ Hosp Zurich, Dept Pathol & Mol Pathol, Zurich, Switzerland
Univ Zurich, Zurich, Switzerland
Pang, CY:
St Teresas Hosp, Kowloon, Hong Kong, Peoples R China
Wah, C:
Queen Elizabeth Hosp, Kowloon, Hong Kong, Peoples R China
Yin, WH:
Peking Univ, Shenzhen Hosp, Shenzhen, Peoples R China
Perry-Keene, J:
Aquesta Pathol, Toowong, Qld, Australia
Sunshine Coast Univ Hosp, Pathol Queensland, Birtinya, Qld, Australia
Yilmaz, A:
Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada
Alberta Precis Labs, Calgary, AB, Canada
Chou, A:
Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia
Kolling Inst Med Res, Canc Diag & Pathol Grp, St Leonards, NSW, Australia
Royal North Shore Hosp, Dept Anatomical Pathol, NSW Hlth Pathol, St Leonards, NSW, Australia
Clarkson, A:
Kolling Inst Med Res, Canc Diag & Pathol Grp, St Leonards, NSW, Australia
Royal North Shore Hosp, Dept Anatomical Pathol, NSW Hlth Pathol, St Leonards, NSW, Australia
van der Westhuizen, G:
Mediclin Bloemfontein Hosp, PathCare, Bloemfontein, South Africa
Morrison, E:
NHLS, Bloemfontein Area, Bloemfontein, South Africa
Zwi, J:
Lab Plus, Auckland, New Zealand
Hes, O:
Alberta Precis Labs, Calgary, AB, Canada
Charles Univ Prague, Med Fac, Prague, Czech Republic
Charles Univ Prague, Univ Hosp Plzen, Prague, Czech Republic
Trpkov, K:
Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada
Gill, AJ:
Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia
Kolling Inst Med Res, Canc Diag & Pathol Grp, St Leonards, NSW, Australia
Royal North Shore Hosp, Dept Anatomical Pathol, NSW Hlth Pathol, St Leonards, NSW, Australia
|