Multifocality in Sporadic Medullary Thyroid Carcinoma: An International Multicenter Study.
Current surgical standard of care in sporadic medullary thyroid carcinoma (sMTC) consists of a minimum of total thyroidectomy with central neck dissection. Some have suggested thyroid lobectomy with isthmusectomy and central neck dissection for patients with sMTC, given their lower frequency of bilateral disease, although this topic has not been thoroughly studied. This study assessed the prevalence of multifocality in sMTC via a large international multi-institutional retrospective review to quantify this prevalence, including the impact of geography, to assess more accurately the risks associated with alternative surgical approaches.



A retrospective chart review of sMTC patients from 11 institutions over 29 years (1983-2011) was undertaken. Data regarding focality, extent of disease, RET germline analysis plus family and clinical history for multiple endocrine neoplasia type 2 (MEN2), and demographic data were collected and analyzed.



Patients from four continents and seven countries were included in the sample. Data for 313 patients with documented sMTC were collected. Of these, 81.2% were confirmed with negative RET germline testing, while the remaining 18.8% demonstrated a negative family history and no manifestations of MEN2 syndromes other than MTC. Bilateral disease was identified in 17/306 (5.6%) patients, while multifocal disease was noted in 50/312 (16.0%) sMTC patients. When only accounting for germline negative patients, these rates were not significantly different (5.6% and 17%, respectively). Among them, when disease was unifocal in the ipsilateral lobe and isthmus, bilateral disease was present in 6/212 (2.8%) cases. When disease was multifocal in the ipsilateral lobe or isthmus, then bilateral disease was present in 8/37 (21.6%) cases (p < 0.001). No geographic differences in focality were identified.



The 5.6% prevalence of bilateral foci in sMTC suggests that total thyroidectomy should remain the standard of care for initial surgery, as less complete thyroid surgery may fail to address fully the primary site of disease. Whether ipsilateral tumor focality should be an independent factor determining the need for completion thyroidectomy when sMTC is diagnosed after hemithyroidectomy remains to be determined.
1 Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center , Columbus, Ohio.
Garth F
GF
Essig
2 Center for Biostatistics, The Ohio State University Wexner Medical Center , Columbus, Ohio.
Kyle
K
Porter
3 Section of Endocrine Surgery, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin.
David
D
Schneider
4 Department of Clinical Medicine and Surgery, University of Naples Federico II , Naples, Italy .
Debora
D
Arpaia
5 Division of Endocrinology, Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of Sao Paulo , São Paulo, Brazil .
Susan C
SC
Lindsey
6 Section of Endocrinology and Metabolism, Department of Medical, Surgical, and Neurological Sciences, University of Siena , Siena, Italy .
Giulia
G
Busonero
7 Department of Endocrinology and Diabetes, Alfred Health, Monash University , Melbourne, Australia .
Daniel
D
Fineberg
8 Département of Endocrinology and Nephrology, Pierre Oudot Hospital , Bourgoin-Jallieu, France .
Barbara
B
Fruci
9 School of Clinical and Experimental Medicine, Centre for Endocrinology, Diabetes, and Metabolism, Institute of Biomedical Research, University of Birmingham , Birmingham, United Kingdom .
Kristien
K
Boelaert
10 Department of Internal Medicine, Radboud University Medical Centre , Nijmegen, The Netherlands .
Johannes W
JW
Smit
11 Department of Internal Medicine, Albert Schweitzer Hospital , Dordrecht, The Netherlands .
Johannes Arnoldus Anthonius
JA
Meijer
12 Evgenidion Hospital, Unit of Endocrinology, Diabetes and Metabolism, Thyroid Section, University of Athens , Athens, Greece .
Leonidas H
LH
Duntas
13 Institute of Head and Neck Studies and Education, University of Birmingham , Birmingham, United Kingdom .
Neil
N
Sharma
14 Department of Medicine, Institut Jules Bordet , Brussels, Belgium .
Giuseppe
G
Costante
15 Dipartimento Di Medicina Interna, University of Roma La Sapienza , Rome, Italy .
Sebastiano
S
Filetti
3 Section of Endocrine Surgery, University of Wisconsin School of Medicine and Public Health , Madison, Wisconsin.
Rebecca S
RS
Sippel
4 Department of Clinical Medicine and Surgery, University of Naples Federico II , Naples, Italy .
Bernadette
B
Biondi
7 Department of Endocrinology and Diabetes, Alfred Health, Monash University , Melbourne, Australia .
Duncan J
DJ
Topliss
6 Section of Endocrinology and Metabolism, Department of Medical, Surgical, and Neurological Sciences, University of Siena , Siena, Italy .
Furio
F
Pacini
5 Division of Endocrinology, Laboratory of Molecular and Translational Endocrinology, Department of Medicine, Federal University of Sao Paulo , São Paulo, Brazil .
Rui M B
RM
Maciel
1 Department of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center , Columbus, Ohio.
Patrick C
PC
Walz
16 Veracyte, Inc. , South San Francisco, California.
Richard T
RT
Kloos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D018276:Carcinoma, Medullary / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control / Q000601:surgery; D018278:Carcinoma, Neuroendocrine / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control / Q000601:surgery; D015331:Cohort Studies; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D009367:Neoplasm Staging; D017410:Practice Guidelines as Topic; D015995:Prevalence; D012189:Retrospective Studies; D013961:Thyroid Gland / Q000473:pathology* / Q000601:surgery; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000517:prevention & control / Q000601:surgery; D013965:Thyroidectomy / Q000009:adverse effects; D047368:Tumor Burden; D055815:Young Adult
humans; medullary thyroid carcinoma; multifocality; surgery; thyroid neoplasm