Mucoepidermoid carcinoma (MEC) is a relatively common salivary tumor with varying potential for aggressive behavior. Mucoepidermoid carcinoma grading has evolved from descriptive two-tiered schemata ...to more objective three-tiered systems. In 2001, we published a grading system Brandwein et al. in Am J Surg Pathol 25:835–845, (
2001
) which modified the prevailing criteria of Auclair et al. in Cancer 69:2021–2030 (
1992
), and included additional features of aggressive MEC. Here we seek to validate our modified grading system in a new multicenter cohort. The retrospective cohort consisted of 76 patients with confirmed MEC and known outcome data. The resection specimens were reviewed and uniformly graded according to our modified criteria Brandwein et al. in Am J Surg Pathol 25:835–845 (
2001
), and the Auclair criteria Auclair et al. in Cancer 69:2021–2030, (
1992
), Goode et al. in Cancer 82:1217–1224, (
1998
). Case distribution was as follows: Montefiore Medical Center: 41 (1977–2009), University of Alabama at Birmingham: 21 (1999–2010), and Rhode Island Hospital: 14, (1995–2011). Patient age ranged from 7 to 81 years (mean 51 years). The female to male ratio was 3:1. The most commonly involved sites were: parotid: n = 39 (
51
%), palate: n = 10 (
13
%), retromolar trigone: n = 6 (
8
%), buccal: n = 5 (
7
%), and submandibular gland: n = 5 (
7
%). The modified criteria upgraded 41 % MEC; 20/25 MEC from AFIP Grade 1 to Grade 2 and 5/25 from AFIP Grade 1 to Grade 3. Eleven patients had positive lymph nodes; the AFIP MEC grade for cases were: Grade 1–3/11, Grade 2–1/11, and Grade 3–7/11; the modified grading criteria distribution for these cases were Grade 1: 0/11, Grade 2: 1/11, and Grade 3: 10/11. Nine patients developed disease progression after definitive treatment. High-stage and positive lymph node status were significantly associated with disease progression (
p
= 0.0003 and
p
< 0.0001, respectively). For the nine patients with disease progression, the modified grading schema classified eight MEC as Grade 3 and one as Grade 2. By comparison, the AFIP grading schema classified three of these MEC as Grade 1, and the remaining six as Grade 3. Despite the fact that this multicenter retrospective study accrued 76 patients with outcome, the predictive performance of the two grading schema could not be compared due to the few patients who experienced disease progression and were also reclassified with respect to grade (n = 3).
Identification of epigenetically affected genes has become an important tool for understanding both normal and aberrant gene expression in cancer. Here we report a whole-genome analysis of DNA ...methylation profiles in fresh-frozen oropharyngeal squamous cell carcinoma (OPSCC) tissues and normal mucosa samples using microarray technology with patient genomic DNA. We initially compared whole-genome patterns of DNA methylation among 24 OPSCC primary tumors and 24 matched normal mucosal samples. From a survey of 27,578 CpG dinucleotide loci spanning more than 14,000 genes, we identified 958 CpG loci in which measurements of DNA methylation were altered in the primary tumors relative to the normal mucosal samples. These alterations were validated in an independent set of 21 OPSCC patients. A survey of these loci by chromosomal location revealed an abnormally high number of differentially methylated loci on chromosome 19. Many of the loci on chromosome 19 are associated with genes belonging to the Krüppel-type zinc finger protein genes. Hypermethylation was accompanied by a significant decrease in expression of these genes in OPSCC primary tumors relative to adjacent mucosa. This study reports the epigenetic silencing of Krüppel-type zinc finger protein genes on chromosome 19q13 in oropharyngeal cancer. The aberrant methylation of these genes represents a new avenue of exploration for pathways affected in this disease.
Half of the patients with head and neck squamous cell carcinoma (HNSCC) can be expected to fail therapy, indicating that more aggressive treatment is warranted for this group. We have developed a ...novel risk model that can become a basis for developing new treatment paradigms. Here we report on the performance of our model in a new multicenter cohort.
Eligible patients from 3 institutions (Montefiore Medical Center, University of Manitoba, and New York University Medical Center) were identified and pathology slides from their resection specimens were reviewed by Margaret Brandwein-Gensler; risk category was assigned as previously published. Kaplan-Meier analysis was performed for disease progression and survival. Cox proportional hazards regression was performed, adjusted for potential confounders. A teaching module was also developed; attending pathologists were asked to score coded slides after a lecture and multiheaded microscope teaching session. Agreement was assessed by calculating Cohen unweighted kappa coefficients.
The validation cohort consisted of 305 patients, from the above institutions, with 311 primary HNSCC of the oral cavity, oropharynx, and larynx. The median follow-up period for all patients was 27 months. Risk category predicts time to disease progression (P=0.0005), locoregional recurrence (P=0.013), and overall survival (P=0.0000) by Kaplan-Meier analysis. High-risk status is significantly associated with decreased time to disease progression, adjusted for clinical confounders (P=0.015, hazard ratio 2.32, 95% confidence interval 1.18-4.58) compared with collapsed intermediate and low-risk groups. We also demonstrate substantial interrater agreement (kappa=0.64), and very good rater agreement when compared with the standard (kappa=0.87).
We demonstrate significant predictive performance of the risk model in a new cohort of patients with primary HNSCC, adjusted for confounders. Our training experience also supports the feasibility of adapting the risk model in clinical practice.
•Occult contralateral nodal disease rate in surgically-managed HPV+ OPSCC is not definitively known.•Multi-institutional population of resectable oropharyngeal cancers.•Occult contralateral nodal ...metastases rate was low (7.4% in the entire cohort; 5% in the p16+ cohort).
Knowledge of the rate of occult contralateral nodal disease for oropharynx cancers (OPSCC) in the era of Human Papillomavirus-dominated disease would inform practitioners as to who may be a candidate for unilateral neck management. The objective of this study was to determine the rate of pathologic contralateral positive nodes in patients in OPSCC patients with pT1 and pT2 disease treated with TORS and bilateral neck dissections (BND).
Retrospective review of medical records was performed at Princess Margaret Cancer Center, Toronto; Icahn School of Medicine at Mount Sinai, New York City; and Montefiore Medical Center, New York City. Patients with pT1-2 N0-3 (AJCC 8th Edition) OPSCC disease treated with TORS and BND were included.
Thirty-two patients met inclusion criteria. Twelve patients (37.5%) had a tonsil primary site, 19 (59.4%) patients had a base of tongue primary site, and 1 (3.1%) patient had a pharyngeal wall primary. Twenty-four (75%) patients were known to be p16+. Twenty-seven patients (84.4%) were radiographically negative in the contralateral neck preoperatively, and two of these patients had pathologic contralateral positive nodes. The occult pathologic contralateral nodal metastasis rate was 7.4% (2/27). The sensitivity, specificity, positive predictive value, and negative predictive value of suspicious contralateral nodes on preoperative imaging for pathologically positive nodes were 33.3%, 86.2%, 20% and 93% respectively. In the p16+ subgroup, the occult nodal positive rate in the contralateral neck was 5%.
pT1-2 OPSCC patients undergoing TORS and elective contralateral neck dissection have a low rate of pathologic contralateral nodal positivity.
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