The Role of Regional Disease and Patterns of Treatment Failure in Primary Sinonasal Malignancies.

BACKGROUND: The question how to treat the clinically negative neck in sinonasal malignancies is controversial. OBJECTIVES: To investigate patterns of treatment failure and to assess outcome measures in patients with primary sinonasal malignancies. METHODS: Retrospective cohort study of patients treated for primary malignant sinonasal malignancies. RESULTS: Lymph node (LN) metastases at initial presentation were present in 8 of 152 patients (5.3%). Ipsi- and contralateral LN levels 1 and 2 were identified as nodal basins at risk. We found a 5-year overall survival (OS) of 75.2% and disease free survival of 61.1%. Among patients with cN0 neck, nodal recurrence free survival was not different between patients with and without elective neck treatment (P = .23). On logistic regression analysis, we found initial T classification as an independent factor for achievement of complete remission (CR) and OS. CONCLUSIONS: LN metastases at initial presentation are rare and initial T classification was identified as the most important prognostic factor for OS and CR, emphasizing the need for a thorough initial staging of the primary tumor.

Aggressive Squamous Cell Carcinoma in Organ Transplant Recipients.

Importance: Squamous cell carcinoma (SCC) is the most frequent malignant neoplasm found in solid organ transplant recipients and is associated with a more aggressive disease course and higher risk of metastasis and death than in the general population. Objectives: To report the clinicopathologic features of and identify factors associated with aggressive SCC in solid organ transplant recipients. Methods: This retrospective multicentric case series included 51 patients who underwent solid organ transplantation and were found to have aggressive SCC, defined by nodal or distant metastasis or death by local progression of primary SCC. Standard questionnaires were completed by the researchers between July 18, 2005, and January 1, 2015. Data were analyzed between February 22, 2016, and July 12, 2016. Results: Of the 51 participants, 43 were men and 8 were women, with a median age of 51 years (range, 19-71 years) at time of transplantation and 62 years (range, 36-77 years) at time of diagnosis of aggressive SCC. The distribution of aggressive SCC was preferentially on the face (34 [67%]) and scalp (6 [12%]), followed by the upper extremities (6 [12%]). A total of 21 tumors (41%) were poorly differentiated, with a median tumor diameter of 18.0 mm (range, 4.0-64.0 mm) and median tumor depth of 6.2 mm (range, 1.0-20.0 mm). Perineural invasion was present in 20 patients (39%), while 23 (45%) showed a local recurrence. The 5-year overall survival rate was 23%, while 5-year disease-specific survival was 30.5%. Conclusions and Relevance: Results of this case series suggest that anatomical site, differentiation, tumor diameter, tumor depth, and perineural invasion are important risk factors in aggressive SCC in solid organ transplant recipients.

Preoperative assessment of CD44-mediated depth of invasion as predictor of occult metastases in early oral squamous cell carcinoma.

BACKGROUND: Epithelial-mesenchymal transition and cancer stem-like cells (CSC) have been linked to increased metastatic potential. We evaluated the prognostic impact of CD44, a CSC biomarker, on depth of invasion (DOI) and outcome in oral squamous cell carcinoma (OSCC). METHODS: Using a multivariable logistic regression model, we evaluated in early OSCCs the relationship between CD44 expression at the invasive tumor front, DOI, sentinel lymph node biopsy, extension of nodal involvement, and survival. We also assessed whether CT and/or MRI could predict DOI preoperatively. RESULTS: CD44 expression was associated with increased DOI (P = .018), worse disease-specific survival (P = .041) but not with positive sentinel lymph node biopsy (P > .05). Each millimeter increase in DOI was associated with a 31.1% higher risk for positive sentinel lymph node biopsy (95% CI: 5.8%-62.4%, P = .013) and with higher metastatic ratio (P = .015). Preoperative estimation of DOI by CT and/or MRI and histopathological DOI showed a strong correlation (P < .0001). CONCLUSIONS: CD44 expression correlates with DOI, which predicts occult lymph node metastasis. Preoperative CT and/or MRI provides an accurate estimation of histopathological DOI. Both pieces of information gained preoperatively can help surgeons tailor their operation in regard to the surgical management of the neck.

Maximum Standardized Uptake Value (SUVmax) of Primary Tumor Predicts Occult Neck Metastasis in Oral Cancer.

The aim of this study was to investigate the predictability of occult lymph node metastasis using maximum standardized uptake value (SUVmax) in the primary tumor on pre-treatment 18-fluorodeoxyglucose positron emission tomography FDG-PET in oral squamous cell carcinoma (OSCC) patients who were clinically node negative (cN0) before surgery. A retrospective analysis of all patients treated at the University Hospital Zurich from 2007 to 2016 for OSCC with available pre-therapeutic FDG-PET was performed. We assessed the correlation of SUVmax of the primary tumors with the presence of occult nodal disease in the neck dissection specimen (pN+). The study included a total of 71 patients. In the nodal negative group (cN0/pN0), the median SUVmax of primary tumors was 9.0 (interquartile range (IQR) 7.4-13.9), while it was 11.4 (IQR 9.9-15.7) in the occult metastatic group (cN0/pN+). The difference was statistically significant (independent samples median test, P = 0.037). In a multivariable model, the only independent predictor of occult metastatic disease for cN0 patients was a SUVmax ≥ 9.5 (P = 0.028). Further, primary tumors with SUVmax ≥ 9.5 had a significantly higher risk of local recurrence (Log rank test, P = 0.020). In conclusion, we showed that higher SUVmax (≥9.5) of the primary tumor is associated with higher occurrence of occult metastatic nodal disease and worse local survival. High SUVmax of the primary tumor may encourage clinicians towards more aggressive treatment.

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

OBJECTIVES/HYPOTHESIS: To analyze the impact of different types of perineural invasion (PNI) in squamous cell carcinoma (SCC) of the oral cavity on overall survival and recurrence rate, with a special focus on histologic subtypes and tumor stage. STUDY DESIGN: Retrospective case-control study with clinicopathological analysis. METHODS: Seventeen patients who received primary surgical treatment for SCC of the oral cavity with PNI were matched to a control group. In a histologic review, PNI was classified into subtypes according to an adapted Liebig classification. The term type A was used to describe tumor invasion into the nerve, whereas type B was used to describe circumferential growth around the nerve. Clinical charts were reviewed, and a Kaplan-Meier survival analysis was performed. RESULTS: The recurrence-free survival rates were 47.1% versus 80.4% (PNI vs. matched control group, P < 0.05), 60.0% versus 94.1% (PNI in stage I and II disease vs. matched control group, P < 0.05) and 41.7% versus 73.5% (PNI in stage III and IV disease vs. matched control group, P < 0.05). In most cases (n = 9) of PNI, both histologic subtypes (type A and type B) were present. Five cases exclusively showed type A, and three cases exclusively showed type B. CONCLUSIONS: Perineural invasion in early disease oral carcinoma has a particularly high impact on survival. Both histologic subtypes showed a significantly worse recurrence-free survival rate when compared to the control group. LEVEL OF EVIDENCE: 3.