Apparent Diffusion Coefficient Histograms of Human Papillomavirus–Positive and Human Papillomavirus–Negative Head and Neck Squamous Cell Carcinoma: Assessment of Tumor Heterogeneity and Comparison with Histopathology

Fellows’ Journal Club

One hundred five consecutive patients with primary oropharyngeal and oral cavity head and neck squamous cell carcinoma underwent MR imaging with anatomic and DWI sequences. The collected tumor voxels from the contoured ROIs provided histograms from which position, dispersion, and form parameters were computed. Histogram data were correlated with histopathology, p16-immunohistochemistry, and polymerase chain reaction for human papillomavirus DNA. Diffusion phenotypes of human papillomavirus–positive and human papillomavirus–negative head and neck squamous cell carcinomas showed significant differences, which reflect their distinct degree of tumor heterogeneity.

Abstract

Figure 2 from paper
A 59-year-old womam with HPV− HNSCC (T2N0M0). A, T2-weighted image reveals a left tonsillar tumor (arrow) with intermediate signal intensity. B, B1000 and C, gray-scale ADC map show restricted tumor diffusion (arrows). The freehand ROI contoured on the ADC map is visible as a blue line. D, On the color-coded ADC map (same level as C), tumor heterogeneity (purple and various shades of blue-green areas within the tumor) is more easily appreciated than in C. E, Histology (hematoxylin-eosin; original magnification, 200X) shows heterogeneous tumor matrix with areas of densely packed and loosely packed squamous cells of variable size. Variable amounts of keratin pearls (asterisk) and necrosis were present in this tumor. F, Immunohistochemistry for p16 (original magnification, 200X) is negative (ie, most cells show no brownish coloration).

BACKGROUND AND PURPOSE

Head and neck squamous cell carcinoma associated with human papillomavirus infection represents a distinct tumor entity. We hypothesized that diffusion phenotypes based on the histogram analysis of ADC values reflect distinct degrees of tumor heterogeneity in human papillomavirus–positive and human papillomavirus–negative head and neck squamous cell carcinomas.

MATERIALS AND METHODS

One hundred five consecutive patients (mean age, 64 years; range, 45–87 years) with primary oropharyngeal (n = 52) and oral cavity (n = 53) head and neck squamous cell carcinoma underwent MR imaging with anatomic and diffusion-weighted sequences (b = 0, b = 1000 s/mm2, monoexponential ADC calculation). The collected tumor voxels from the contoured ROIs provided histograms from which position, dispersion, and form parameters were computed. Histogram data were correlated with histopathology, p16-immunohistochemistry, and polymerase chain reaction for human papillomavirus DNA.

RESULTS

There were 21 human papillomavirus–positive and 84 human papillomavirus–negative head and neck squamous cell carcinomas. At histopathology, human papillomavirus–positive cancers were more often nonkeratinizing (13/21, 62%) than human papillomavirus–negative cancers (19/84, 23%; P = .001), and their mitotic index was higher (71% versus 49%; P = .005). ROI-based mean and median ADCs were significantly lower in human papillomavirus–positive (1014 ± 178 × 10−6 mm2/s and 970 ± 187 × 10−6 mm2/s, respectively) than in human papillomavirus–negative tumors (1184 ± 168 × 10−6 mm2/s and 1161 ± 175 × 10−6 mm2/s, respectively; P < .001), whereas excess kurtosis and skewness were significantly higher in human papillomavirus–positive (1.934 ± 1.386 and 0.923 ± 0.510, respectively) than in human papillomavirus–negative tumors (0.643 ± 0.982 and 0.399 ± 0.516, respectively; P < .001). Human papillomavirus–negative head and neck squamous cell carcinoma had symmetric normally distributed ADC histograms, which corresponded histologically to heterogeneous tumors with variable cellularity, high stromal component, keratin pearls, and necrosis. Human papillomavirus–positive head and neck squamous cell carcinomas had leptokurtic skewed right histograms, which corresponded to homogeneous tumors with back-to-back densely packed cells, scant stromal component, and scattered comedonecrosis.

CONCLUSIONS

Diffusion phenotypes of human papillomavirus–positive and human papillomavirus–negative head and neck squamous cell carcinomas show significant differences, which reflect their distinct degree of tumor heterogeneity.

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Apparent Diffusion Coefficient Histograms of Human Papillomavirus–Positive and Human Papillomavirus–Negative Head and Neck Squamous Cell Carcinoma: Assessment of Tumor Heterogeneity and Comparison with Histopathology
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jross
Jeffrey Ross • Mayo Clinic, Phoenix

Dr. Jeffrey S. Ross is a Professor of Radiology at the Mayo Clinic College of Medicine, and practices neuroradiology at the Mayo Clinic in Phoenix, Arizona. His publications include over 100 peer-reviewed articles, nearly 60 non-refereed articles, 33 book chapters, and 10 books. He was an AJNR Senior Editor from 2006-2015, is a member of the editorial board for 3 other journals, and a manuscript reviewer for 10 journals. He became Editor-in-Chief of the AJNR in July 2015. He received the Gold Medal Award from the ASSR in 2013.