Prognostic impact of extratumoral perineural invasion in patients with oral cavity squamous cell carcinoma

Background: The objective of surgical management of oral squamous cell carcinoma (OSCC) is adequate resection with a clear margin. However, there is still a debate as to the optimal length for a mandibular resected margin. Objective: To examine the length of peri-neural spreading in T4 mandibular invaded oral cavity squamous cell carcinoma. Materials and Methods: Twenty-eight T4 pathological OSCC specimens that involved mandible and serial slices were studied and the length of tumor spreading along the inferior alveolar nerve (IAN) was determined. Tumor characteristics, risk factors, and survival were analyzed. Results: The incidence of peri-neural invasion was 11.11%, and IAN invasion was found in 14.29% of the tumor-invaded mandibular marrow. The length of tumor spreading along IAN was 3 to 12 mm. Poor prognostic factors of T4 OSCC were it being located on the tongue (HR 14.16), was pathological N2-3 (HR 31.05), and had high-risk features such as peri-neural invasion, lymphovascular invasion, and extra-nodal extension. Conclusion: A mandibular resected margin of at least 18 mm is recommended as a clear surgical margin in cases of T4 mandibular invasion OSCC. Keywords: Oral cancer, Perineural invasion, Inferior alveolar nerve, Squamous cell carcinoma, Mandibulectomy

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Perineural and Vascular Invasion in Oral Cavity Squamous Carcinoma: Increased Incidence on Re-review of Slides and by Using Immunohistochemical Enhancement

Archives of Pathology & Laboratory Medicine ◽

10.5858/2005-129-354-paviio ◽

2005 ◽

Vol 129 (3) ◽

pp. 354-359 ◽

Cited By ~ 12

Author(s):

Kevin A. Kurtz ◽

Henry T. Hoffman ◽

M. Bridget Zimmerman ◽

Robert A. Robinson

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Vascular Invasion ◽

Perineural Invasion ◽

False Negative ◽

Squamous Carcinoma ◽

Pathology Report ◽

Negative Results

Abstract Context.—Perineural invasion and vascular invasion may be adverse prognostic factors in patients with oral cavity squamous cell carcinoma. However, the incidence of perineural and vascular invasion varies in the literature, and the use of immunohistochemistry to enhance their detection has not been evaluated in oral cavity squamous cell carcinomas. Objective.—To determine if the previously assessed incidence of perineural and vascular invasion in cases of oral cavity squamous cell carcinoma would be increased by re-review of the original routinely hematoxylin-eosin–stained sections as well as review of slides stained immunohistochemically with S100 and CD31 to enhance visualization of nerves and vessels. Design.—Forty cases of oral cavity squamous cell carcinoma in which the status of perineural and vascular invasion had been part of the original pathology report were reviewed. All original routinely stained slides were reviewed as well as S100- and CD31-stained sections of each case's tissue blocks that contained tumor. Results.—Perineural invasion was identified in 30% (12/ 40) of tumors in the original reports, 62% (25/40) of the authors' re-review of the same slides, and 82% (33/40) when cases were stained with S100. Vascular invasion was identified in 30% (12/40) of tumors in the original reports, 35% (14/40) of the authors' re-review of the same slides, and 42% (17/40) when cases were stained with CD31. False-positive and false-negative results were common in the original reports. The number of foci of both types of invasion was related to its discovery in the original reports. Vascular invasion, but not perineural invasion, was significantly associated with death at 5-year follow-up. Conclusions.—Although careful re-review of routinely stained slides will detect a significant number of cases of perineural and vascular invasion, immunohistochemical enhancement further improves the accuracy of the determination.

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Prognostic Impact of Perineural Invasion in Cutaneous Squamous Cell Carcinoma: Results of a Prospective Study of 1,399 Tumors

Journal of Investigative Dermatology ◽

10.1016/j.jid.2020.01.035 ◽

2020 ◽

Vol 140 (10) ◽

pp. 1968-1975 ◽

Cited By ~ 3

Author(s):

Konrad Haug ◽

Helmut Breuninger ◽

Gisela Metzler ◽

Thomas Eigentler ◽

Martin Eichner ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Prospective Study ◽

Cell Carcinoma ◽

Squamous Cell ◽

Perineural Invasion ◽

Cutaneous Squamous Cell Carcinoma ◽

Prognostic Impact ◽

A Prospective Study

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Impact of Perineural Invasion in the Pathologically N0 Neck in Oral Cavity Squamous Cell Carcinoma

Otolaryngology ◽

10.1177/0194599813506867 ◽

2013 ◽

Vol 149 (6) ◽

pp. 893-899 ◽

Cited By ~ 54

Author(s):

Steven B. Chinn ◽

Matthew E. Spector ◽

Emily L. Bellile ◽

Jonathan B. McHugh ◽

Thomas J. Gernon ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Perineural Invasion ◽

N0 Neck

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Perineural Invasion in Squamous Cell Carcinoma of the Oral Cavity: Histology, Tumor Stage, and Outcome

Laryngoscope Investigative Otolaryngology ◽

10.1002/lio2.4 ◽

2016 ◽

Vol 1 (1) ◽

pp. 13-18 ◽

Cited By ~ 7

Author(s):

Roman D. Laske ◽

Irene Scholz ◽

Kristian Ikenberg ◽

Christian Meerwein ◽

Domenic G. Vital ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Perineural Invasion ◽

Tumor Stage

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Molecular and Cellular Mechanisms of Perineural Invasion in Oral Squamous Cell Carcinoma: Potential Targets for Therapeutic Intervention

Cancers ◽

10.3390/cancers13236011 ◽

2021 ◽

Vol 13 (23) ◽

pp. 6011

Author(s):

Carly I. Misztal ◽

Carlos Green ◽

Christine Mei ◽

Rita Bhatia ◽

Jaylou M. Velez Torres ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cavity ◽

Cell Carcinoma ◽

Schwann Cells ◽

Squamous Cell ◽

Therapeutic Intervention ◽

Locoregional Recurrence ◽

Perineural Invasion ◽

Cellular Mechanisms ◽

Cancer Migration

The most common oral cavity cancer is squamous cell carcinoma (SCC), of which perineural invasion (PNI) is a significant prognostic factor associated with decreased survival and an increased rate of locoregional recurrence. In the classical theory of PNI, cancer was believed to invade nerves directly through the path of least resistance in the perineural space; however, more recent evidence suggests that PNI requires reciprocal signaling interactions between tumor cells and nerve components, particularly Schwann cells. Specifically, head and neck SCC can express neurotrophins and neurotrophin receptors that may contribute to cancer migration towards nerves, PNI, and neuritogenesis towards cancer. Through reciprocal signaling, recent studies also suggest that Schwann cells may play an important role in promoting PNI by migrating toward cancer cells, intercalating, and dispersing cancer, and facilitating cancer migration toward nerves. The interactions of neurotrophins with their high affinity receptors is a new area of interest in the development of pharmaceutical therapies for many types of cancer. In this comprehensive review, we discuss diagnosis and treatment of oral cavity SCC, how PNI affects locoregional recurrence and survival, and the impact of adjuvant therapies on tumors with PNI. We also describe the molecular and cellular mechanisms associated with PNI, including the expression of neurotrophins and their receptors, and highlight potential targets for therapeutic intervention for PNI in oral SCC.

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