Clinicopathologic Characteristics and Mutational Status of Succinate Dehydrogenase Genes in Paraganglioma of the Urinary Bladder: A Multi-Institutional Korean Study.
BACKGROUND
- Because of the limited number of available primary bladder paraganglioma (PBPG) cases, the rates of succinate dehydrogenase (SDH) mutations and the clinicopathologic characteristics of SDH-deficient tumors have not been fully studied.


OBJECTIVE
- To define the clinicopathologic and molecular characteristics of PBPGs.


METHODS
- A total of 52 PBPGs were collected retrospectively. SDHA and SDHB immunohistochemical stains were performed. In cases of SDHB expression loss, mutation analyses of SDHB, SDHC, and SDHD were performed.


RESULTS
- The clinicopathologic features were analyzed for 52 cases (M:F = 27:25), with a mean age of 56 years (range, 22-79 years). Tumor sizes were 0.5 to 8 cm (mean, 2.4 cm). Tumor necrosis was present in 5 of 52 cases (10%), involvement of muscularis propria in 41 (79%), and lymphovascular tumor invasion in 6 (12%). During a mean follow-up period of 41 months (range, 1-161 months), 3 of 52 patients (6%) developed metastases, but no one died from the disease. Immunohistochemistry for SDHA and SDHB showed that all cases were SDHA intact. Among them, 43 cases had intact SDHB, whereas 9 cases were SDHB deficient. Compared with the SDHB-intact cases, the SDHB-deficient cases were characterized by large tumor sizes (4.5 versus 1.9 cm; P < .001), a higher number of mitoses per 10 high-powered fields (2.6 versus 0.1; P = .002), and frequent lymphovascular tumor invasion (33% versus 7%; P = .02) and metastases (22% versus 2%; P = .02). Mutational analyses for SDHB, SDHC, and SDHD were performed in 9 SDHB-deficient cases. Among them, 6 cases were successfully sequenced and revealed SDHB mutations only.


CONCLUSIONS
- Large tumor size, a higher number of mitoses, and the presence of lymphovascular tumor invasion and SDHB mutations suggest malignant paraganglioma.
Sanghui
S
Park
So Young
SY
Kang
Ghee Young
GY
Kwon
Ji Eun
JE
Kwon
Sang Kyum
SK
Kim
Ji Yeon
JY
Kim
Chul Hwan
CH
Kim
Hyun-Jung
HJ
Kim
Kyung Chul
KC
Moon
Ju Yeon
JY
Pyo
Won Young
WY
Park
Eun Su
ES
Park
Ji-Youn
JY
Sung
Sun Hee
SH
Sung
Young-Ha
YH
Oh
Seung Eun
SE
Lee
Wonae
W
Lee
Jong Im
JI
Lee
Nam Hoon
NH
Cho
Soo Jin
SJ
Jung
Min-Sun
MS
Cho
Yong Mee
YM
Cho
Hyun Yee
HY
Cho
Eun Jung
EJ
Cha
Yang-Seok
YS
Chae
Gheeyoung
G
Choe
Yeong Jin
YJ
Choi
Jooryung
J
Huh
From the Department of Pathology, Ewha Womans University School of Medicine, Seoul, Korea (Drs S. Park, S.H. Sung, and M.S. Cho); the Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea (Drs Kang and G.Y. Kwon); the Department of Pathology, Ajou University School of Medicine, Suwon, Korea (Dr J.E. Kwon); the Department of Pathology, Yonsei University College of Medicine, Seoul, Korea (Dr S.K. Kim and N.H. Cho); the Department of Pathology, Inje University Haeundae Paik Hospital, Pusan, Korea (Dr J.Y. Kim); the Department of Pathology, Korea University School of Medicine, Seoul, Korea (Drs C.H. Kim and Chae); the Department of Pathology, Inje University Sanggye Paik Hospital, Seoul, Korea (Dr H.J. Kim); the Department of Pathology and Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea (Dr Moon); the Department of Pathology, College of Medicine, Hanyang University Guri Hospital, Guri, Korea (Drs Pyo and Oh); the Department of Pathology, Pusan National University Hospital College of Medicine, Pusan, Korea (Dr W.Y. Park); the Department of Hospital Pathology, Incheon St Mary's Hospital, College of Medicine, Catholic University of Korea, Incheon, Korea (Dr E.S. Park); the Department of Pathology, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea (Dr J.Y. Sung); the Department of Pathology, Konkuk University School of Medicine, Seoul, Korea (Dr S.E. Lee); the Department of Pathology, Dankook University College of Medicine, Cheonan, Korea (Dr W. Lee); the Department of Pathology, Dongguk University College of Medicine, Gyeonju, Korea (Dr J.I. Lee); the Department of Pathology, Inje University Busan Paik Hospital, Pusan, Korea (Dr Jung); the Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (Drs Y.M. Cho and Huh); the Department of Pathology, Gachon University Gil Medical Center, Incheon, Korea (Dr H.Y. Cho); the Department of Pathology, Konyang University School of Medicine, Daejeon, Korea (Dr Cha); the Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea (Dr Choe); the Department of Hospital Pathology, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea (Dr Choi); and the Department of Pathology and Genomic Medicine, The Methodist Hospital and Weill Medical College of Cornell University, Houston, Texas (Dr Ro).
Jae Y
JY
Ro
D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010235:Paraganglioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D001743:Urinary Bladder / Q000201:enzymology / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D055815:Young Adult
C491545:SDHD protein, human; D013385:Succinate Dehydrogenase