Download PDF
J Neurol Surg B Skull Base 2016; 77(02): 086-095
DOI: 10.1055/s-0036-1571834
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Perineural Spread in Noncutaneous Head and Neck Cancer: New Insights into an Old Problem

Moran Amit
1   The Laboratory for Applied Cancer Research, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion, Israel Institute of Technology, Haifa, Israel
2   The Head and Neck Center, Department of Otolaryngology-Head and Neck Surgery, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion, Israel Institute of Technology, Haifa, Israel
,
Ayelet Eran
3   Department of Radiology, Rambam Healthcare Campus, Israel Institute of Technology, Haifa, Israel
,
Salem Billan
4   Department of Oncology, Rambam Healthcare Campus, Israel Institute of Technology, Haifa, Israel
,
Eran Fridman
1   The Laboratory for Applied Cancer Research, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion, Israel Institute of Technology, Haifa, Israel
2   The Head and Neck Center, Department of Otolaryngology-Head and Neck Surgery, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion, Israel Institute of Technology, Haifa, Israel
,
Shorook Na'ara
1   The Laboratory for Applied Cancer Research, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion, Israel Institute of Technology, Haifa, Israel
2   The Head and Neck Center, Department of Otolaryngology-Head and Neck Surgery, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion, Israel Institute of Technology, Haifa, Israel
,
Tomer Charas
4   Department of Oncology, Rambam Healthcare Campus, Israel Institute of Technology, Haifa, Israel
,
Ziv Gil
1   The Laboratory for Applied Cancer Research, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion, Israel Institute of Technology, Haifa, Israel
2   The Head and Neck Center, Department of Otolaryngology-Head and Neck Surgery, Rambam Healthcare Campus, Clinical Research Institute at Rambam, Rappaport Institute of Medicine and Research, The Technion, Israel Institute of Technology, Haifa, Israel
› Author Affiliations
Further Information

Publication History

Publication Date:
26 February 2016 (online)

    Permissions and Reprints

Abstract

Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell carcinoma and adenoid cystic carcinoma are the most commonly involved tumors. The most commonly involved nerves are the trigeminal (cranial nerve [CN] V) and facial (CN VII) and their branches. Neural spread away from a tumor is encountered less often and usually causes specific symptoms such as pain, muscle weakness, and atrophy, depending on the involved nerves. While clinical symptoms and physical examination may suggest the presence of neural invasion, specific imaging modalities such as fat-suppressed T1-weighted magnetic resonance images, should be utilized to identify perineural tumor spread in its early phases. Perineural tumor spread should be considered and addressed in the treatment planning of patients with head and neck or skull base cancers as it can influence the extent of surgery, and the dosage and fields of radiation therapy. In the current review, we discuss the clinical course of perineural tumor spread and its therapeutic implications.

Keywords

adenoid cystic carcinoma - squamous cell carcinoma - survival - neural - base of skull - head and neck cancer
 

  • References

  • 1 Ginsberg LE. Imaging of perineural tumor spread in head and neck cancer. Semin Ultrasound CT MR 1999; 20 (3) 175-186
    CrossrefPubMedGoogle Scholar
  • 2 Nemec SF, Herneth AM, Czerny C. Perineural tumor spread in malignant head and neck tumors. Top Magn Reson Imaging 2007; 18 (6) 467-471
    CrossrefPubMedGoogle Scholar
  • 3 Barrett AW, Speight PM. Perineural invasion in adenoid cystic carcinoma of the salivary glands: a valid prognostic indicator?. Oral Oncol 2009; 45 (11) 936-940
    CrossrefPubMedGoogle Scholar
  • 4 Liebig C, Ayala G, Wilks JA, Berger DH, Albo D. Perineural invasion in cancer: a review of the literature. Cancer 2009; 115 (15) 3379-3391
    CrossrefPubMedGoogle Scholar
  • 5 Soo KC, Carter RL, O'Brien CJ, Barr L, Bliss JM, Shaw HJ. Prognostic implications of perineural spread in squamous carcinomas of the head and neck. Laryngoscope 1986; 96 (10) 1145-1148
    PubMedGoogle Scholar
  • 6 Brandwein-Gensler M, Teixeira MS, Lewis CM , et al. Oral squamous cell carcinoma: histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol 2005; 29 (2) 167-178
    CrossrefPubMedGoogle Scholar
  • 7 Carter RL, Foster CS, Dinsdale EA, Pittam MR. Perineural spread by squamous carcinomas of the head and neck: a morphological study using antiaxonal and antimyelin monoclonal antibodies. J Clin Pathol 1983; 36 (3) 269-275
    CrossrefPubMedGoogle Scholar
  • 8 Nabili V, Tan JW, Bhuta S, Sercarz JA, Head CS. Salivary duct carcinoma: a clinical and histologic review with implications for trastuzumab therapy. Head Neck 2007; 29 (10) 907-912
    CrossrefPubMedGoogle Scholar
  • 9 Chong VF, Fan YF, Khoo JB. Nasopharyngeal carcinoma with intracranial spread: CT and MR characteristics. J Comput Assist Tomogr 1996; 20 (4) 563-569
    CrossrefPubMedGoogle Scholar
  • 10 Chong VF, Fan YF. Hypoglossal nerve palsy in nasopharyngeal carcinoma. Eur Radiol 1998; 8 (6) 939-945
    CrossrefPubMedGoogle Scholar
  • 11 Schmalfuss IM, Tart RP, Mukherji S, Mancuso AA. Perineural tumor spread along the auriculotemporal nerve. AJNR Am J Neuroradiol 2002; 23 (2) 303-311
    PubMedGoogle Scholar
  • 12 Kang HP, Devine LJ, Piccoli AL, Seethala RR, Amin W, Parwani AV. Usefulness of a synoptic data tool for reporting of head and neck neoplasms based on the College of American Pathologists cancer checklists. Am J Clin Pathol 2009; 132 (4) 521-530
    CrossrefPubMedGoogle Scholar
  • 13 Caldemeyer KS, Mathews VP, Righi PD, Smith RR. Imaging features and clinical significance of perineural spread or extension of head and neck tumors. Radiographics 1998; 18 (1) 97-110 , quiz 147
    CrossrefPubMedGoogle Scholar
  • 14 Parker GD, Harnsberger HR. Clinical-radiologic issues in perineural tumor spread of malignant diseases of the extracranial head and neck. Radiographics 1991; 11 (3) 383-399
    CrossrefPubMedGoogle Scholar
  • 15 Nemzek WR, Hecht S, Gandour-Edwards R, Donald P, McKennan K. Perineural spread of head and neck tumors: how accurate is MR imaging?. AJNR Am J Neuroradiol 1998; 19 (4) 701-706
    PubMedGoogle Scholar
  • 16 Garden AS, Weber RS, Morrison WH, Ang KK, Peters LJ. The influence of positive margins and nerve invasion in adenoid cystic carcinoma of the head and neck treated with surgery and radiation. Int J Radiat Oncol Biol Phys 1995; 32 (3) 619-626
    CrossrefPubMedGoogle Scholar
  • 17 Gil Z, Carlson DL, Gupta A , et al. Patterns and incidence of neural invasion in patients with cancers of the paranasal sinuses. Arch Otolaryngol Head Neck Surg 2009; 135 (2) 173-179
    CrossrefPubMedGoogle Scholar
  • 18 Mitsunaga S, Hasebe T, Kinoshita T , et al. Detail histologic analysis of nerve plexus invasion in invasive ductal carcinoma of the pancreas and its prognostic impact. Am J Surg Pathol 2007; 31 (11) 1636-1644
    CrossrefPubMedGoogle Scholar
  • 19 de Matos FR, Lima Ed, Queiroz LM, da Silveira EJ. Analysis of inflammatory infiltrate, perineural invasion, and risk score can indicate concurrent metastasis in squamous cell carcinoma of the tongue. J Oral Maxillofac Surg 2012; 70 (7) 1703-1710
    CrossrefPubMedGoogle Scholar
  • 20 Yildiz O, Buyuktas D, Ekiz E, Selcukbiricik F, Papila I, Papila C. Facial nerve palsy: an unusual presenting feature of small cell lung cancer. Case Rep Oncol 2011; 4 (1) 35-38
    CrossrefPubMedGoogle Scholar
  • 21 Tsutsumi T, Nakajima N, Hirose T, Watanabe K. Total-length invasion of the facial nerve by parotid carcinoma ex pleomorphic adenoma. Auris Nasus Larynx 2009; 36 (5) 618-622
    CrossrefPubMedGoogle Scholar
  • 22 Ojiri H. Perineural spread in head and neck malignancies. Radiat Med 2006; 24 (1) 1-8
    CrossrefPubMedGoogle Scholar
  • 23 Yu E, O'Sullivan B, Kim J, Siu L, Bartlett E. Magnetic resonance imaging of nasopharyngeal carcinoma. Expert Rev Anticancer Ther 2010; 10 (3) 365-375
    CrossrefPubMedGoogle Scholar
  • 24 Catalano PJ, Sen C, Biller HF. Cranial neuropathy secondary to perineural spread of cutaneous malignancies. Am J Otol 1995; 16 (6) 772-777
    PubMedGoogle Scholar
  • 25 Gandhi D, Gujar S, Mukherji SK. Magnetic resonance imaging of perineural spread of head and neck malignancies. Top Magn Reson Imaging 2004; 15 (2) 79-85
    CrossrefPubMedGoogle Scholar
  • 26 Gandhi MR, Panizza B, Kennedy D. Detecting and defining the anatomic extent of large nerve perineural spread of malignancy: comparing “targeted” MRI with the histologic findings following surgery. Head Neck 2011; 33 (4) 469-475
    CrossrefPubMedGoogle Scholar
  • 27 Baulch J, Gandhi M, Sommerville J, Panizza B. 3T MRI evaluation of large nerve perineural spread of head and neck cancers. J Med Imaging Radiat Oncol 2015; 59 (5) 578-585
    CrossrefPubMedGoogle Scholar
  • 28 Nguyen BD, Roarke MC. Salivary duct carcinoma with perineural spread to facial canal: F-18 FDG PET/CT detection. Clin Nucl Med 2008; 33 (12) 925-928
    CrossrefPubMedGoogle Scholar
  • 29 Curtin HD. Detection of perineural spread: fat suppression versus no fat suppression. AJNR Am J Neuroradiol 2004; 25 (1) 1-3
    PubMedGoogle Scholar
  • 30 Binmadi NO, Basile JR. Perineural invasion in oral squamous cell carcinoma: a discussion of significance and review of the literature. Oral Oncol 2011; 47 (11) 1005-1010
    CrossrefPubMedGoogle Scholar
  • 31 Woolgar JA. Histopathological prognosticators in oral and oropharyngeal squamous cell carcinoma. Oral Oncol 2006; 42 (3) 229-239
    CrossrefPubMedGoogle Scholar
  • 32 O'Brien CJ, Lahr CJ, Soong SJ , et al. Surgical treatment of early-stage carcinoma of the oral tongue—wound adjuvant treatment be beneficial?. Head Neck Surg 1986; 8 (6) 401-408
    CrossrefPubMedGoogle Scholar
  • 33 Fagan JJ, Collins B, Barnes L, D'Amico F, Myers EN, Johnson JT. Perineural invasion in squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 1998; 124 (6) 637-640
    CrossrefPubMedGoogle Scholar
  • 34 Sutton DN, Brown JS, Rogers SN, Vaughan ED, Woolgar JA. The prognostic implications of the surgical margin in oral squamous cell carcinoma. Int J Oral Maxillofac Surg 2003; 32 (1) 30-34
    CrossrefPubMedGoogle Scholar
  • 35 Rahima B, Shingaki S, Nagata M, Saito C. Prognostic significance of perineural invasion in oral and oropharyngeal carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004; 97 (4) 423-431
    CrossrefPubMedGoogle Scholar
  • 36 Kurtz KA, Hoffman HT, Zimmerman MB, Robinson RA. Perineural and vascular invasion in oral cavity squamous carcinoma: increased incidence on re-review of slides and by using immunohistochemical enhancement. Arch Pathol Lab Med 2005; 129 (3) 354-359
    PubMedGoogle Scholar
  • 37 González-García R, Naval-Gías L, Román-Romero L, Sastre-Pérez J, Rodríguez-Campo FJ. Local recurrences and second primary tumors from squamous cell carcinoma of the oral cavity: a retrospective analytic study of 500 patients. Head Neck 2009; 31 (9) 1168-1180
    CrossrefPubMedGoogle Scholar
  • 38 Tai SK, Li WY, Chu PY , et al. Risks and clinical implications of perineural invasion in T1-2 oral tongue squamous cell carcinoma. Head Neck 2012; 34 (7) 994-1001
    CrossrefPubMedGoogle Scholar
  • 39 Hinerman RW, Mendenhall WM, Morris CG, Amdur RJ, Werning JW, Villaret DB. Postoperative irradiation for squamous cell carcinoma of the oral cavity: 35-year experience. Head Neck 2004; 26 (11) 984-994
    CrossrefPubMedGoogle Scholar
  • 40 Parsons JT, Mendenhall WM, Stringer SP, Cassisi NJ, Million RR. An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity. Int J Radiat Oncol Biol Phys 1997; 39 (1) 137-148
    PubMedGoogle Scholar
  • 41 Liao CT, Chang JT, Wang HM , et al. Does adjuvant radiation therapy improve outcomes in pT1-3N0 oral cavity cancer with tumor-free margins and perineural invasion?. Int J Radiat Oncol Biol Phys 2008; 71 (2) 371-376
    CrossrefPubMedGoogle Scholar
  • 42 Pfister DG, Ang KK, Brizel DM , et al; National Comprehensive Cancer Network. Head and neck cancers, version 2.2013. Featured updates to the NCCN guidelines. J Natl Compr Canc Netw 2013; 11 (8) 917-923
    PubMedGoogle Scholar
  • 43 Pfister DG, Ang K, Brockstein B , et al; National Comprehensive Cancer Network. NCCN practice guidelines for head and neck cancers. Oncology (Williston Park) 2000; 14 (11A): 163-194
    PubMedGoogle Scholar
  • 44 Langendijk JA, Slotman BJ, van der Waal I, Doornaert P, Berkof J, Leemans CR. Risk-group definition by recursive partitioning analysis of patients with squamous cell head and neck carcinoma treated with surgery and postoperative radiotherapy. Cancer 2005; 104 (7) 1408-1417
    CrossrefPubMedGoogle Scholar
  • 45 Bernier J, Cooper JS, Pajak TF , et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck 2005; 27 (10) 843-850
    CrossrefPubMedGoogle Scholar
  • 46 Cooper JS, Pajak TF, Forastiere AA , et al; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004; 350 (19) 1937-1944
    CrossrefPubMedGoogle Scholar
  • 47 Ang KK, Trotti A, Brown BW , et al. Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001; 51 (3) 571-578
    CrossrefPubMedGoogle Scholar
  • 48 Rosenthal DI, Liu L, Lee JH , et al. Importance of the treatment package time in surgery and postoperative radiation therapy for squamous carcinoma of the head and neck. Head Neck 2002; 24 (2) 115-126
    CrossrefPubMedGoogle Scholar
  • 49 Gomez DR, Katabi N, Zhung J , et al. Clinical and pathologic prognostic features in acinic cell carcinoma of the parotid gland. Cancer 2009; 115 (10) 2128-2137
    CrossrefPubMedGoogle Scholar
  • 50 Huang M, Ma D, Sun K, Yu G, Guo C, Gao F. Factors influencing survival rate in adenoid cystic carcinoma of the salivary glands. Int J Oral Maxillofac Surg 1997; 26 (6) 435-439
    CrossrefPubMedGoogle Scholar
  • 51 Fordice J, Kershaw C, El-Naggar A, Goepfert H. Adenoid cystic carcinoma of the head and neck: predictors of morbidity and mortality. Arch Otolaryngol Head Neck Surg 1999; 125 (2) 149-152
    CrossrefPubMedGoogle Scholar
  • 52 Kim GE, Park HC, Keum KC , et al. Adenoid cystic carcinoma of the maxillary antrum. Am J Otolaryngol 1999; 20 (2) 77-84
    CrossrefPubMedGoogle Scholar
  • 53 Chummun S, McLean NR, Kelly CG , et al. Adenoid cystic carcinoma of the head and neck. Br J Plast Surg 2001; 54 (6) 476-480
    CrossrefPubMedGoogle Scholar
  • 54 Khan AJ, DiGiovanna MP, Ross DA , et al. Adenoid cystic carcinoma: a retrospective clinical review. Int J Cancer 2001; 96 (3) 149-158
    CrossrefPubMedGoogle Scholar
  • 55 Kokemueller H, Eckardt A, Brachvogel P, Hausamen JE. Adenoid cystic carcinoma of the head and neck—a 20 years experience. Int J Oral Maxillofac Surg 2004; 33 (1) 25-31
    CrossrefPubMedGoogle Scholar
  • 56 Mendenhall WM, Morris CG, Amdur RJ, Werning JW, Hinerman RW, Villaret DB. Radiotherapy alone or combined with surgery for adenoid cystic carcinoma of the head and neck. Head Neck 2004; 26 (2) 154-162
    CrossrefPubMedGoogle Scholar
  • 57 Rapidis AD, Givalos N, Gakiopoulou H , et al. Adenoid cystic carcinoma of the head and neck. Clinicopathological analysis of 23 patients and review of the literature. Oral Oncol 2005; 41 (3) 328-335
    CrossrefPubMedGoogle Scholar
  • 58 Chen AM, Bucci MK, Weinberg V , et al. Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys 2006; 66 (1) 152-159
    CrossrefPubMedGoogle Scholar
  • 59 Agarwal JP, Jain S, Gupta T , et al. Intraoral adenoid cystic carcinoma: prognostic factors and outcome. Oral Oncol 2008; 44 (10) 986-993
    CrossrefPubMedGoogle Scholar
  • 60 Gomez DR, Hoppe BS, Wolden SL , et al. Outcomes and prognostic variables in adenoid cystic carcinoma of the head and neck: a recent experience. Int J Radiat Oncol Biol Phys 2008; 70 (5) 1365-1372
    CrossrefPubMedGoogle Scholar
  • 61 Amit M, Binenbaum Y, Trejo-Leider L , et al. International collaborative validation of intraneural invasion as a prognostic marker in adenoid cystic carcinoma of the head and neck. Head Neck 2015; 37 (7) 1038-1045
    CrossrefPubMedGoogle Scholar
  • 62 Spiro RH. Distant metastasis in adenoid cystic carcinoma of salivary origin. Am J Surg 1997; 174 (5) 495-498
    CrossrefPubMedGoogle Scholar
  • 63 Vrielinck LJG, Ostyn F, Van Damme B , et al. The significance of perineural spread in adenoid cystic carcinoma of the major and minor salivary glands. Int J Oral Maxillofac Surg 1988; 17: 190-193
    CrossrefPubMedGoogle Scholar
  • 64 Pogodzinski MS, Sabri AN, Lewis JE, Olsen KD. Retrospective study and review of polymorphous low-grade adenocarcinoma. Laryngoscope 2006; 116 (12) 2145-2149
    CrossrefPubMedGoogle Scholar
  • 65 Schwarz S, Müller M, Ettl T, Stockmann P, Zenk J, Agaimy A. Morphological heterogeneity of oral salivary gland carcinomas: a clinicopathologic study of 41 cases with long term follow-up emphasizing the overlapping spectrum of adenoid cystic carcinoma and polymorphous low-grade adenocarcinoma. Int J Clin Exp Pathol 2011; 4 (4) 336-348
    PubMedGoogle Scholar
  • 66 Seethala RR, Johnson JT, Barnes EL, Myers EN. Polymorphous low-grade adenocarcinoma: the University of Pittsburgh experience. Arch Otolaryngol Head Neck Surg 2010; 136 (4) 385-392
    CrossrefPubMedGoogle Scholar
  • 67 Johnston ML, Huang SH, Waldron JN , et al. Salivary duct carcinoma: Treatment, outcomes, and patterns of failure. Head Neck 2015; (e-pub ahead of print). doi: 10.1002/hed.24107
    PubMedGoogle Scholar
  • 68 Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010; 17 (6) 1471-1474 PubMed
    CrossrefPubMedGoogle Scholar
  • 69 Dean NR, White HN, Carter DS , et al. Outcomes following temporal bone resection. Laryngoscope 2010; 120 (8) 1516-1522
    CrossrefPubMedGoogle Scholar
  • 70 Mohan R, Wu Q, Wang X, Stein J. Intensity modulation optimization, lateral transport of radiation, and margins. Med Phys 1996; 23 (12) 2011-2021
    CrossrefPubMedGoogle Scholar
  • 71 Chen AM, Garcia J, Granchi P, Bucci MK, Lee NY. Base of skull recurrences after treatment of salivary gland cancer with perineural invasion reduced by postoperative radiotherapy. Clin Otolaryngol 2009; 34 (6) 539-545
    CrossrefPubMedGoogle Scholar
  • 72 Schoenfeld JD, Sher DJ, Norris Jr CM , et al. Salivary gland tumors treated with adjuvant intensity-modulated radiotherapy with or without concurrent chemotherapy. Int J Radiat Oncol Biol Phys 2012; 82 (1) 308-314
    CrossrefPubMedGoogle Scholar
  • 73 Münter MW, Schulz-Ertner D, Hof H , et al. Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment. Radiat Oncol 2006; 1: 17
    CrossrefPubMedGoogle Scholar