International collaborative validation of intraneural invasion as a prognostic marker in adenoid cystic carcinoma of the head and neck.
BACKGROUND
The purpose of this study was to characterize the incidence, pattern of spread, and prognostic correlation of nerve invasion in patients with adenoid cystic carcinoma (ACC).


METHODS
Using 3 different pathological categories of perineural invasion, intraneural invasion, and perineural inflammation, we investigated the prognostic value of nerve invasion in a total of 495 ACCs from 9 international patient cohorts with median follow-up 90 months (range, 12-288 months).


RESULTS
Of 239 patients (48%) with nerve invasion, 174 (73%) had perineural invasion, 65 (27%) intraneural invasion, and 37 (15%) perineural inflammation. Multivariate Cox regression analysis identified tumor site (p = .008; hazard ratio [HR] = 1.8; 95% confidence interval [CI] = 0.07-3.7) and intraneural invasion (p < .001; HR = 5.9; 95% CI = 0.8-12.3) as independent prognostic markers for both overall survival (OS) and disease-specific survival (DSS), but not of distant metastases.


CONCLUSIONS
Although perineural invasion has no impact on survival, intraneural invasion is an independent predictor of poor prognosis. Recognition of intraneural invasion may help optimize treatment of patients with head and neck ACC.
The Laboratory for Applied Cancer Research, the Clinical Research Center at Rambam, Rambam Medical Center, Rappaport Medical School, The Technion, Israel Institute of Technology, Haifa, Israel.
Moran
M
Amit
The Laboratory for Applied Cancer Research, the Clinical Research Center at Rambam, Rambam Medical Center, Rappaport Medical School, The Technion, Israel Institute of Technology, Haifa, Israel.
Yoav
Y
Binenbaum
Department of Pathology, Tel Aviv Medical Center, Tel Aviv, Israel.
Leonor
L
Trejo-Leider
Department of Radiotherapy and Oncology, Lok Nayak Hospital, Bahadur Shah Zafar Marg, New Delhi, India.
Kanika
K
Sharma
Department of Pathology, The Mount Sinai School of Medicine, New York, New York.
Naomi
N
Ramer
Department of Pathology, The Mount Sinai School of Medicine, New York, New York.
Ilana
I
Ramer
Department of Otolaryngology, Ichan School of Medicine at Mount Sinai, New York, New York.
Abib
A
Agbetoba
Department of Otolaryngology, Ichan School of Medicine at Mount Sinai, New York, New York.
Brett
B
Miles
Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, People's Republic of China.
Xinjie
X
Yang
Department of Oral and Maxillofacial Surgery, School of Stomatology, the Fourth Military Medical University, People's Republic of China.
Delin
D
Lei
Department of Otolaryngology Head and Neck Surgery, Odense University Hospital Odense, Denmark.
Kristine
K
Bjørndal
Department of Otolaryngology Head and Neck Surgery, Odense University Hospital Odense, Denmark.
Christian
C
Godballe
Department of Oral and Maxillofacial Surgery, Technische Universität München, München, Germany.
Thomas
T
Mücke
Department of Oral and Maxillofacial Surgery, Technische Universität München, München, Germany.
Klaus-Dietrich
KD
Wolff
Department of Cranio-Maxillofacial Surgery, Hannover Medical School, Hannover, Germany.
André M
AM
Eckardt
Maxillo-Facial Surgery, University-Hospital of Parma, Italy.
Chiara
C
Copelli
Maxillo-Facial Surgery, University-Hospital of Parma, Italy.
Enrico
E
Sesenna
Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Frank
F
Palmer
Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Ian
I
Ganly
Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Snehal
S
Patel
The Laboratory for Applied Cancer Research, the Clinical Research Center at Rambam, Rambam Medical Center, Rappaport Medical School, The Technion, Israel Institute of Technology, Haifa, Israel.|Department of Otolaryngology Head and Neck Surgery, Department of Otolaryngology Head and Neck Surgery, Rambam Medical Center, The Technion, Israel Institute of Technology, Haifa, Israel.
Ziv
Z
Gil
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003528:Carcinoma, Adenoid Cystic / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology*; D010524:Peripheral Nervous System Neoplasms / Q000473:pathology*; D011379:Prognosis; D012044:Regression Analysis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
adenoid cystic carcinoma; head and neck cancer; intraneural invasion; perineural invasion; salivary gland; survival