Depth of Invasion and the Correlation with Lymph Node Density in Oral and Maxillofacial Squamous Cell Carcinoma

Lymph node density is defined as the number of positive lymph nodes per total number of excised lymph nodes. In the treatment of oral and maxillofacial cancer, there are recent data showing that increased lymph node density leads to worse outcomes for patients¹, thus advocating the use of lymph node density as an independent prognosticating factor². However, there is paucity of data regarding the correlation of lymph node density with other evidence-based parameters for assessment of prognosis and treatment decision-making, such as the depth of tumor invasion. Our study specifically sought to identify if a correlation exists between depth of invasion and cervical lymph node density.

A retrospective review was completed to include 303 patients treated between 2009 through July 2014, who underwent neck dissection with a resection of oral and maxillofacial squamous cell carcinoma. Four surgeons were involved. Depth of invasion and lymph node status from the final histopathology review was collected. 

Pathology reports with missing depth of invasion or with the diagnosis of carcinoma in situ were excluded from the study. Neck dissections for malignancies other than squamous cell carcinoma were also excluded. Pearson correlation was obtained between the depth of invasion and lymph node density to correlate the strength of linear relationship between the two variables. Statistical significance for the study was set at (p<0.05).  

Mean age at the time of surgery was 63.9 ± 12.5 years. The final study included 169 males and 117 females (N=286). The majority of the procedures (> 97%) were performed by two senior surgeons. The mean depth of invasion was 1.23 ± 1.1 cm, and ranged from 0.1 cm to 6.9 cm.  Mean lymph node density was 0.04 ± 0.1, and ranged from 0 to 0.81. 

For all 286 patients treated, the Pearson correlation between the depth of invasion and the lymph node density showed R=0.21 (P=.0003). Unilateral and bilateral neck dissections were also reviewed independently. For unilateral neck dissections, the Pearson correlation showed R=0.23 (P=0.002, N=181). For bilateral neck dissection, R=0.28 (P=0.004, N=105)

Our review highlights the statistically significant, positively linear, relationship between the lymph node density and depth of invasion for both unilateral and bilateral neck dissection. This provides additional evidence as to the importance of depth of invasion as a predictive feature in lymph node status. However, further studies will be needed to clarify the utility of lymph node density. Our data suggests, and given the recent literature supporting lymph node density as a predictor of outcome, perhaps lymph node density could evolve into a reliable adjunctive or independent parameter. This would ultimately allow more customized treatments and improved outcome for patients with oral and maxillofacial squamous cell carcinoma.

1. Gil, Z., Carlson, D. L., Boyle, J. O., Kraus, D. H., Shah, J. P., Shaha, A. R., Singh, B., Wong, R. J. and Patel, S. G. (2009), Lymph node density is a significant predictor of outcome in patients with oral cancer. Cancer, 115: 5700–5710. doi: 10.1002/cncr.24631

2. Kim KY, Cha IH (2012) Risk stratification of oral cancer patients using a combined prognostic factor including lymph node density and biomarker. J Cancer Res Clin Oncol 138(3): 483–490