Significance of Worst Pattern of Invasion-5 in Early-Stage Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: There is an ongoing need to identify pathologic prognosticators in early-stage oral cavity squamous cell carcinoma (OCSCC) to aid selection of patients who may benefit from adjuvant treatment. The objective of this study was to evaluate the prognostic ability of worst pattern of invasion-5 (WPOI-5) defined by the presence of satellite nodules, extratumoural perineural invasion (PNI) and/or extratumoural lymphovascular space invasion (LVI) in low-stage, node negative OCSCC. METHODS: This was a retrospective study of 160 patients with T1/T2N0 tumours staged using TNM7 treated surgically. Histology of the primary tumour was re-reviewed as appropriate to assess for the presence of WPOI-5 parameters. Univariate and multivariate analysis assessing impact of pathological features on survival outcomes was performed. RESULTS: On univariate analysis, WPOI-5 and its 3 constituent components of satellite nodules, extratumoural PNI and extratumoural LVI were all significantly associated with disease-specific survival (DSS) and overall survival (OS). On multivariate analysis, satellite nodules (odds ratio 6.61, 95% CI 2.83-15.44, p < 0.0001) and extratumoural LVI (odds ratio 9.97, 95% CI 2.19-45.35, p = 0.003) were independently associated with OS. Postoperative radiotherapy (odds ratio 0.40, 95% CI 0.19-0.87, p = 0.02) and non-tongue subsite (odds ratio 3.03, 95% CI 1.70-5.39, p = 0.0002) were also significantly associated with OS on multivariate analysis. CONCLUSION: Satellite nodules and extratumoural LVI correlated significantly with survival outcomes in our early-stage OSCC cohort. Further study is required to investigate the benefit of adjuvant treatment in these cases and to ascertain if WPOI-5 parameters including satellite nodules should be mandatory reporting data elements.

Comparison of royal college of pathologists and college of american pathologists definition for positive margins in oral cavity squamous cell carcinoma.

BACKGROUND: Pathological margin assessment is an essential component of surgical management of oral cavity squamous cell carcinoma (OCSCC), however, in many studies, variable definitions of involved margins have been used. The purpose of the present study was to compare the prognostic ability of involved margins according to Royal College of Pathologists (RCPath) and College of American Pathologists (CAP) guidance. METHODS: Retrospective study of 300 patients with previously untreated OCSCC undergoing definitive surgical management. Main specimen margin status was defined according to RCPath guidance and CAP guidance. "Final margin status", incorporated the results of frozen sections and extra tumour bed resections. The prognostic impact of each margin definition was studied using univariate analysis, and in multivariate models including T-stage (AJCC 8th edition), nodal status (pN+), extranodal extension (ENE), and use of adjuvant radiotherapy. RESULTS: Both RCPath and CAP positive margins were associated with local recurrence (LR), disease-specific survival (DSS), and overall survival (OS) on univariate analysis, while final margin status was associated with LR and DSS, but not OS. On multivariate analysis, only CAP positive main specimen margin status was independently associated with LR (odds ratio 2.44, 95% CI 1.37, 4.34), DSS (odds ratio 2.28, 95% CI 1.31, 3.82), and OS (odds ratio 1.59, 95% CI 1.04, 2.42). CONCLUSIONS: Involved main specimen margin as defined by CAP guidance has the advantage of being an independent prognosticator of LR and survival in our cohort.

Cytokeratin 7 and 19 expression in oropharyngeal and oral squamous cell carcinoma.

PURPOSE: The precise etiopathogenesis of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC), and reasons for predilection for crypt epithelium, remain uncertain. The purpose of this study is to investigate the interaction between HPV and specific cytokeratins 7 (CK7) and 19 (CK19) in crypt epithelium. METHODS: This is a retrospective cohort study of patients presenting between 1999 and 2015 at a tertiary referral center. CK7 and CK19 positivity and H Scores were determined by immunohistochemistry. Disease-specific and overall survival rates were analyzed. RESULTS: There were 253 patients presenting with OPSCC (134), squamous cell carcinoma (SCC) of unknown primary site (22), and oral tongue SCC (97). Primary tumor CK7 and CK19 positivity and H Scores were significantly higher in HPV-positive OPSCC than HPV-negative OPSCC and oral tongue SCC. Higher CK19 Scores, but not CK7 Scores, were also seen in regional metastases from HPV-positive OPSCC than other sites. No impact on disease-specific or overall survival was identified on multivariate analysis. CONCLUSION: The increased expression of CK7 and CK19 in HPV-positive OPSCC compared to HPV-negative disease supports the theory for a role for these cytokeratins in the etiopathogenesis of HPV-related OPSCC.

Prognostic performance of TNM8 staging rules in oral cavity squamous cell carcinoma.

BACKGROUND: Two major changes to the staging of oral cavity squamous cell carcinoma (OCSCC) were adopted in TNM8: (1) depth of invasion is now used for T staging and (2) extranodal extension for N staging. The aim of this study was to evaluate if TNM8 stratifies OCSCC patients more accurately than TNM7 based on overall survival (OS) statistics and hazard discrimination. METHODS: Retrospective study of 297 patients with OCSCC who underwent surgery at our institution. Clinical and pathological data were previously populated from review of medical charts and histological reports. Slides were re-reviewed for depth of invasion measurements. Patients were staged using both TNM7 and TNM8 with overall survival statistics analysed. RESULTS: Overall 118 patients (39.7%) were upstaged using TNM8. Both TNM7 and TNM8 stage categories were highly significant for OS (all p values < 0.0001). Hazard discrimination analysis showed that TNM7 could only differentiate stage III from stage IV disease with significance (OS p = 0.01). In comparison TNM8 could distinguish between stage II and III disease (OS p = 0.047) and between stage III and IV disease (OS p = 0.004). Subsite analysis suggested that both editions of the staging system perform best for tongue primaries. CONCLUSIONS: Although TNM8 showed improved hazard discrimination in comparison to TNM7, problems with discriminative ability persisted with 8th edition staging criteria. Large scale validation studies will be required to direct future refinement of the staging rules and to establish if the continued use of a single staging system for all oral cavity subsites is appropriate.

Impact of 3 mm margin on risk of recurrence and survival in oral cancer.

INTRODUCTION: While positive surgical margins in oral squamous cell carcinoma (OSCC) is generally considered an adverse prognosticator, the significance of close (≤5 mm) margins is more debatable, and has not been widely adopted as an indicator for radiotherapy. MATERIALS AND METHODS: Retrospective study of 244 patients undergoing primary surgical resection of OSCC. The impact on local control (LC), disease-specific survival (DSS) and overall survival (OS) of margins at 1 mm intervals was studied. RESULTS: 65 patients had involved (<1 mm), 119 close (1-5 mm), and 60 clear (>5 mm) main specimen margins. Involved margins was predictive of DSS (p = 0.04), but not LC (p = 0.20) or OS (p = 0.09). Both the 2 mm and 3 mm margin cut-offs were significantly associated with LC (p = 0.02, and p = 0.01), DSS (p = 0.02, and p = 0.007), and OS (p = 0.03. and p = 0.005). In a 3-tier model, use of 3 mm for demarcation between close and clear yielded good separation between survival curves of clear (≥3 mm), and close (1-<3 mm) or involved (<1 mm). Final margins, determined after incorporation of frozen sections and extra margins taken separately, was significant for LC (p = 0.04), but not for DSS (p = 0.05) or OS (p = 0.17). On multivariate analysis, <3 mm margin, T-classification, nodal status, extranodal spread, and postoperative radiotherapy, were independent predictors of DSS and OS. For LC, only T-classification was significant. CONCLUSION: A 3 mm main specimen margin is significantly associated with survival in OSCC and may be useful for demarcation between close and clear. Further study is required to determine any impact on survival of radiotherapy for patients with <3 mm margins as sole indicator for radiotherapy.

High-resolution melting of multiple barcode amplicons for plant species authentication.

In recent years, species identification in herbs has attracted considerable attention due to several cases of fraud; hence inexpensive high-throughput authentication methods are highly welcomed. Species authentication is often performed through DNA analysis and several specific regions (barcodes) are considered suitable. Each barcode (Bar) possesses different qualities in terms of universality and discrimination power. A multiplexed format where information can be extracted simultaneously from several barcode regions is seemingly appropriate to ensure the power of both universality and discrimination. In this approach, we amplified DNA from five different barcode regions in a multiplexed PCR format followed by high-resolution melting (HRM). This multiplexed Bar-HRM approach was first applied to plants spanning the plant kingdom and then gradually narrowing down the genetic variability within the Lamiaceae and the Solanaceae families to finally reach closely related cultivars. Universality was demonstrated through distinct melting profiles obtained for species originating from 29 different families spanning the angiosperms, gymnosperm, mosses, and liverwort (Marchantiophyta). Discrimination power was retained for species, sub-species, and a few cultivars through the application of multivariate statistics to the high-resolution melting profiles. This preliminary investigation has shown the potential to discriminate a vast amount of species within the whole plant kingdom. It requires no a priori knowledge of the species' DNA sequence and occurs in a closed system within 2.5 h at a reduced cost per sample compared to other DNA based approaches.

Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in a Warthin Tumor: Case Report and Literature Review.

Warthin tumor is the second most common salivary gland neoplasm. It occurs more commonly in males than in females. Malignant transformation in Warthin tumor is a rare but well-recognized phenomenon; however, the development or presentation of lymphoma in a Warthin tumor is rare. An 80-year-old man presented with painless mass of the right parotid gland of 2 years duration with recent ulceration of the overlying skin and right cervical lymphadenopathy underwent a surgical resection of parotid mass and biopsy of the periglandular lymph nodes. The histological diagnosis was malignant lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, present within the stroma of a Warthin tumor, and also present within the adjacent lymph node. This case is the third reported case describing a collision of Warthin tumor and chronic lymphocytic leukemia/small lymphocytic lymphoma. It also emphasizes the importance of careful examination of the lymphoid stroma of these tumors.