Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

BACKGROUND: As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. METHODS: A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10 years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. RESULTS: Five hundred and ninety patients were included, with a median follow-up of 28 months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3 years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. CONCLUSION: Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Uracil as a biomarker for spatial pyrimidine metabolism in the development of gingivobuccal oral squamous cell carcinoma.

No biomarker has yet been identified that allows accurate diagnosis and prognosis of oral cancers. In this study, we investigated the presence of key metabolites in oral cancer using proton nuclear magnetic resonance (NMR) spectroscopy to identify metabolic biomarkers of gingivobuccal oral squamous cell carcinoma (GB-OSCC). NMR spectroscopy revealed that uracil was expressed in 83.09% of tumor tissues and pyrimidine metabolism was active in GB-OSCC; these results correlated well with immunohistochemistry (IHC) and RNA sequencing data. Based on further gene and protein analyses, we proposed a pathway for the production of uracil in GB-OSCC tissues. Uridinetriphosphate (UTP) is hydrolyzed to uridine diphosphate (UDP) by CD39 in the tumor microenvironment (TME). We hypothesized that UDP enters the cell with the help of the UDP-specific P2Y6 receptor for further processing by ENTPD4/5 to produce uracil. As the ATP reserves diminish, the weakened immune cells in the TME utilize pyrimidine metabolism as fuel for antitumor activity, and the same mechanism is hijacked by the tumor cells to promote their survival. Correspondingly, the differential expression of ENTPD4 and ENTPD5 in immune and tumor cells, respectively, indicatedtheir involvement in disease progression. Furthermore, higher uracil levels were detected in patients with lymph node metastasis, indicating that metastatic potential is increased in the presence of uracil. The presence of uracil and/or expression patterns of intermediate molecules in purine and pyrimidine pathways, such asCD39, CD73, and P2Y6 receptors together with ENTPD4 and ENTPD5, hold promise as biomarker(s) for oral cancer diagnosis and prognosis.

Impact of spatial metabolomics on immune-microenvironment in oral cancer prognosis: a clinical report.

MALDI imaging for metabolites and immunohistochemistry for 38 immune markers was used to characterize the spatial biology of 2 primary oral tumours, one from a patient with an early recurrence (Tumour R), and the other from a patient with no recurrence 2 years after treatment completion (Tumour NR). Tumour R had an increased purine nucleotide metabolism in different regions of tumour and adenosine-mediated suppression of immune cells compared to Tumour NR. The differentially expressed markers in the different spatial locations in tumour R were CD33, CD163, TGF-ß, COX2, PD-L1, CD8 and CD20. These results suggest that altered tumour metabolomics concomitant with a modified immune microenvironment could be a potential marker of recurrence.

Overexpression of CD73 is associated with recurrence and poor prognosis of gingivobuccal oral cancer as revealed by transcriptome and deep immune profiling of paired tumor and margin tissues.

BACKGROUND: For various cancers, differences in response to treatment and subsequent survival period have been reported to be associated with variation in immune contextures. AIM: We sought to identify whether such association exists in respect of gingivobuccal oral cancer. MATERIALS AND METHODS: We performed deep immune profiling of tumor and margin tissues collected from 46 treatment naïve, Human Papillomavirus (HPV) negative, patients. Each patient was followed for 24 months and prognosis (recurrence/death) noted. Key findings were validated by comparing with TCGA-HNSC cohort data. RESULTS: About 28% of patients showed poor post-treatment prognosis. These patients exhibited a high probability of recurrence even within 1 year and death within 2 years. There was restricted immune cell infiltration in tumor, but not in margin, among these patients. Reduced expression of eight immune-related genes (IRGs) (NT5E, THRA, RBP1, TLR4, ITGA6, BMPR1B, ITGAV, SSTR1) in tumor strongly predicted better quality of prognosis, both in our patient cohort and in TCGA-HNSC cohort. Tumors of patients with better prognosis were associated with (a) lower CD73+ cells with concomitant lower expression level of NT5E/CD73, (b) higher proportions of CD4+ and CD8+ T cells, B cells, NK cells, M1 macrophages, (c) higher %Granzyme+ cells, (d) higher TCR and BCR repertoire diversities. CD73 expression in tumor was associated with low CD8+ and CD4+ T cells, low immune repertoire diversity, and advanced cancer stage. DISCUSSION AND CONCLUSION: High infiltration of anti-tumor immune cells in both tumors and margins results in good prognosis, while in patients with minimal infiltration in tumors in spite of high infiltration in margins results in poor prognosis. Targeted CD73 immune-checkpoint inhibition may improve clinical outcome.

Subcategorization of Perineural Invasion and Its Impact on Survival in Patients with Oral Squamous Cell Carcinoma.

BACKGROUND: Perineural invasion (PNI) is  recognized as a poor prognostic factor in oral squamous cell carcinoma (OSCC). However, the prognostic significance of further histologic  subcategorization of PNI is inconclusive. In this study, we determined the prognostic relevance of histologic subcategories of PNI and their correlation with the presence of other clinical and pathological parameters METHODS: This is a retrospective study of 207 homogeneously treated OSCC patients with histologically documented PNI from a single center. Univariate and multivariate survival outcomes, namely, local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) of patients with various subcategories of PNI,namely- number of foci, size of the involved nerve, extratumoral or intratumoral extent, and intraneural or perineural location-were determined. RESULTS: Within the histologic subcategories of PNI, tongue primary and presence of lymph node metastasis correlated significantly with the number of nerves involved with PNI. Larger size of involved nerve correlated with advanced tumor stage. Number of foci, extent, and location of PNI were not prognostically significant except size of the involved nerve which showed an inverse correlation with disease outcome as involvement of larger nerves displayed better outcomes in terms of DFS and LRFS but not of OS on multivariate analysis. Addition of adjuvant chemotherapy to radiotherapy emerged as a significant predictor of improved LRFS, DFS, and OS. CONCLUSIONS: Histologic subcategorization of PNI did not have prognostic relevance in our study. Involvement of even small nerves was associated with poor prognosis. Addition of chemoradiation was seen to improve prognosis.

Preoperative risk factors associated with peri-operative psychiatric diagnosis in oral cancer patients.

Background: Head and neck cancers (HNCs) are one of the commonest cancers in low- and middle-income countries. There is a paucity of data on comorbid psychiatric problems associated with HNCs. The present study is aimed at reporting the pattern of psychiatric caseness in HNC patients who were referred to specialist psycho-oncology service and also investigate the predictors of psychiatric caseness in oral cancer patients. Methods: Case records of all patients with HNC referred to an integrated psycho-oncology service over 7 years (October 2011-December 2018) from a cancer hospital were analysed. All patients were assessed by a trained consultant psychiatrist and ICD-10 diagnoses were ascertained based on a clinical interview with the patients and family members. Associations of psychiatric caseness for consecutive oral cancer patients assessed by the psycho-oncology services over 2 years (January 2017-December 2018) were calculated by using univariate and multivariate statistical methods. Simple descriptive statistics of the referred patients were conducted, followed by logistic regression to find the associations of psychiatric caseness in oral cancer patients. Results: The psycho-oncology service assessed 771 HNC patients over 7 years. The commonest referrals were patients with oral cancer (75%, 558/771). For the years 2017-2018, 179 consecutive oral cancer patients were evaluated by the psycho-oncology service. Multivariate logistic regression analysis showed that being a woman (OR = 2.33; 95% CI = 1.02-5.32; p = 0.04); having worries about having pain in the post-operative period (OR = 2.55; 95% CI = 1.2-5.38; p = 0.01); worries about implications of the cancer and its treatment on the family (OR = 3.5; 95% CI = 1.19-10.57; p = 0.02); and longer duration of hospital stay period (OR = 1.08; 95% CI = 1.003-1.16; p = 0.04) were independently associated with psychiatric caseness even after controlling for confounders. Discussion: Specialist psycho-oncology services are important in the management of oral cancer patients and in addressing the mental health needs of this very vulnerable group of patients. A combination of psychoeducation, pragmatic psychological interventions and medications were used to treat these patients.

Outcomes of clinico-radiologically advanced cancer (cT4b) of buccal mucosa: a retrospective analysis of 104 patients.

Although guidelines recommend non-surgical management for cT4b patients, recent studies have shown that upfront surgery in carefully selected patients can be performed with acceptable long-term survival benefit. In this study, we analysed the survival outcome of curative intent treatment on cT4b patients. Data from 104 patients who were staged cT4b and underwent upfront surgery for squamous cell carcinoma of buccal mucosa were retrospectively analysed. Outcome measures were locoregional recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS). The study cohort comprised 104 patients who had a median age of 52.5 years (range 27-81 years) and included 81 males (77.9%). Thirty-six patients had masticator space involvement on final histopathology, designating them as pT4b. Contrast enhanced computed tomography scan demonstrated 91.67% sensitivity in identifying masticator space involvement, albeit with a lower accuracy of 31.7%. Pathologically, clear margins were achieved in 79 (76%) patients. 62 (59.7%) and 20 (19.2%) patients received adjuvant radiotherapy (RT) and adjuvant chemoradiotherapy respectively. 2-year LRFS, DFS and OS were 61.8%, 60% and 68.1%, respectively. On multivariate analyses, involved margins (hazard ratio (HR) 28.766, p = 0.006), pN2b status (HR 4.68, p = 0.027) and perineural invasion (PNI) (HR 3.001, p = 0.027) showed statistically significant impact on LRFS, involved margins (HR 28.859, p = 0.008) and pN2b status (HR 4.018, p = 0.004) affected DFS. Involved margins (HR 14.139, p = 0.023) and pN2b status (HR 3.166, p = 0.025) showed statistically significant impact on OS. In conclusion, upfront surgery is a feasible option for patients with carcinoma of the buccal mucosa with the involvement of the masticator space. Survival outcomes are better in patients where resection is achieved with clear margins, and regional disease is limited to a single cervical lymph node.

Emergence of hybrid states of stem-like cancer cells correlates with poor prognosis in oral cancer.

Cancer cell state transitions emerged as powerful mechanisms responsible for drug tolerance and overall poor prognosis; however, evidences were largely missing in oral cancer. Here, by multiplexing phenotypic markers of stem-like cancer cells (SLCCs); CD44, CD24 and aldehyde dehydrogenase (ALDH), we characterized diversity among multiple oral tumor tissues and cell lines. Two distinct patterns of spontaneous transitions with stochastic bidirectional interconversions on 'ALDH-axis', and unidirectional non-interconvertible transitions on 'CD24-axis' were observed. Interestingly, plastic 'ALDH-axis' was harnessed by cells to adapt to a Cisplatin tolerant state. Furthermore, phenotype-specific RNA sequencing suggested the possible maintenance of intermediate hybrid cell states maintaining stemness within the differentiating subpopulations. Importantly, survival analysis with subpopulation-specific gene sets strongly suggested that cell-state transitions may drive non-genetic heterogeneity, resulting in poor prognosis. Therefore, we have described the phenotypic-composition of heterogeneous subpopulations critical for global tumor behavior in oral cancer; which may provide prerequisite knowledge for treatment strategies.

Risk of Hypocalcemia and the Need to Augment Calcium Supplementation After Total Thyroidectomy.

Hypocalcemia is the most common complication after total thyroidectomy. The aim of this study was to determine the predictors of postoperative hypocalcemia requiring augmentation of routine calcium supplementation. Prospectively collected data of 61 patients who underwent total thyroidectomy from December 2018 to June 2019 was considered for the study. All patients received calcium and vitamin D supplementation after the surgery. In the postoperative period, serum calcium and parathormone (PTH) levels were monitored. The need of additional oral or intravenous (i.v.) calcium supplementation was evaluated as an outcome measure. This cohort comprised 61 patients with median age of 46 years (range 16-80 years) and 49 (80%) females. Central compartment clearance (CCC) was done in 32 patients. Escalation to increased oral and intravenous calcium was required in 15 patients (24.6%) and 2 patients (3.3%), respectively. Serum parathormone level of 11.5 pg/ml on postoperative day 1 predicted the requirement of additional calcium with a sensitivity of 82.4% and specificity of 77.3%. On univariate analysis, serum PTH (p < 0.001), CCC (p = 0.018), and intraoperative parathyroid gland congestion (p = 0.021) predicted the need for escalation of calcium supplementation. On multivariate analysis, only serum PTH showed a significant impact on the need for augmentation of calcium supplementation (p = 0.003). The need for calcium dose augmentation after total thyroidectomy was significantly associated with CCC, parathyroid gland congestion, and serum PTH levels. Intraoperative identification of parathyroid gland congestion and postoperative serum PTH levels is effective in predicting postoperative hypocalcemia with implications on time and cost.

Factors predicting contralateral nodal spread in papillary carcinoma of thyroid.

Background: Lymph node metastasis (LNM) is evident in about 20-50% of cases at presentation in papillary carcinoma thyroid (PTC). There are no clear recommendations for the need and extent of lateral and central compartment dissection in PTC. Methods: A total of 83 patients who underwent total thyroidectomy and bilateral selective neck dissection for diagnosed PTC from September 2011 to October 2017 were retrospectively analyzed. Results: Tumor site was bilobar or involving isthmus in 40 patients. Contralateral LNM was seen in 42 patients. Both radiological (median size 2.6 cm, P = 0.051) and pathological (median size 3.65 cm, P = 0.015) size of tumor, tumor involving isthmus or bilateral lobes (P = 0.006), and lymphovascular invasion (LVI) (P = 0.026) had significant correlation with contralateral LNM. Conclusion: Size and site of tumor, ipsilateral lateral compartment nodes involvement, and LVI status of tumor significantly increases the probability of contralateral LNM in patients of PTC.

Radiation-induced hypothyroidism in patients of oral squamous cell carcinoma: A retrospective analysis of 195 patients.

Background: Radiation-induced hypothyroidism (RIH) is common after neck irradiation, and biochemical evaluation of thyroid function is recommended periodically for early diagnosis and treatment. This study aimed to evaluate the predictors of RIH after completion of adjuvant radiotherapy (RT) for primary oral squamous cell carcinoma (OSCC). Methods: This is a retrospective study involving 195 patients who received RT after surgery for OSCC between August 2011 and December 2016. Thyroid function tests were obtained every 6 months and patients were considered to be hypothyroid if thyroid-stimulating hormone level was >5 mIU/mL. Results: The study cohort comprised 130 men with a median age of 52 years (range 21-77 years). About 107 (54.87%) patients developed hypothyroidism, with a median of 21 months (range 2-67 months) for the development of RIH. Women [41 (63.1%) versus 66 (50.8%), p=0.035], addition of chemotherapy [36 (63.2%) versus 71 (51.4%), p= 0.019], and higher cumulative dose to the thyroid gland (median dose 4690 cGy versus 2981 cGy, P < 0.001) resulted in higher incidence of RIH on univariate analysis. On multivariate Cox regression analysis, female sex (P = 0.042), bilateral irradiation (P = 0.046), and cumulative dose to the thyroid (P = 0.001) were factors associated with increased risk of developing RIH. Conclusion: The addition of chemotherapy, high dose of radiation to the thyroid gland, bilateral irradiation, and female sex were at higher risk of developing RIH. However, more studies are required to identify the dose-volume constraints of the thyroid gland.

Determinants of prognosis in patients with oral squamous cell carcinoma metastasizing to a single cervical lymph node.

OBJECTIVES: Metastasis in a single lymph node without adverse tumour factors and perineural invasion has been assigned to a lower risk category by the ASCO recommendations of 2019. We analyzed patients with a single positive node with a view to identifying high risk features and their impact on prognosis within this subgroup. MATERIALS AND METHODS: The study retrospectively analyzed 707 patients with OSCC. Descriptive statistics were used to compare distribution of clinicopathologic risk features between 323 N0 and 121 single node positive (Ns) patients. The Ns group was further analyzed for the impact of clinicopathologic factors on disease free (DFS) and overall survival (OS) using univariate and multivariate models. RESULTS: The Ns group exhibited greater depth of invasion compared to the N0 group and significantly higher proportion of lymphovascular invasion (LVI), perineural invasion (PNI) and poorly differentiated tumors. Within the Ns group, primary tumor localised to the gingivobuccal subsite (HR 2.55, 1.18-5.52 95%CI, p = 0.02) and PNI (HR 2.55, 1.14-5.62, 95%CI p = 0.02) exhibited poor DFS. PNI also contributed to poor OS (HR 2.86, 1.27-6.47 95%CI, p = 0.01). Uninvolved margins (HR 0.46, 0.22-0.96 95%CI, p = 0.04) and chemoradiation (HR 0.18,0.05-0.68 95% CI, p = 0.01) improved OS. CONCLUSION: Significant differences are noted in the prevalence of pathologic risk factors between the single node positive and node negative groups. Within the single node positive group, tumour factors like the gingivobuccal subsite, PNI and margin positivity impacted survival. Among nodal factors, deposit size of 12 mm or more and presence of ENE are pointers to poor prognosis. These patients would benefit from adjuvant treatment.

Fabricating Flaps in the Forearm Prior to Tracheal Reconstruction.

Background The process of reconstruction of tracheal defects is complex and still not optimum. Options range from using staged reconstructions, combining flaps with autologous or alloplastic implants, as well as use of tissue-engineered constructs combined with vascularized tissues which are lined with cell cultures. Staged reconstructions using prelaminated epithelium, and prefabricated flaps, help in reconstruction of this complex structure. Prefabricating the flap at a different site allows for integration of the tissues prior to its transfer. Method This article reports two patients planned for tracheal reconstruction for the purpose of advanced papillary carcinoma of the thyroid invading the trachea. Staged reconstruction using a prefabricated radial artery forearm flap (RAFF) and split rib cartilage was performed. In the second patient, a young girl, a similar construct of the RAFF, prelaminated with buccal mucosa, was performed. However, in the latter case, an intraoperative decision by the head and neck team to limit excision of the trachea sparing the mucosa was taken; the reconstruct in the forearm was redundant and needed to be discarded, replacing the defect with a free superficial circumflex iliac artery perforator (SCIP) flap. Result At 3 years follow-up, both the patients are free of disease, with the construct serving its purpose in the older female.

Two novel cell culture models of buccal mucosal oral cancer from patients with no risk-habits of tobacco smoking or chewing.

OBJECTIVE: Tobacco consumption is one of the major etiological factors for oral cancer, but it also develops in non-tobacco users, with unknown etiologies. Cellular models for tobacco associated oral cancer are available, however; reports of cellular models for studying non-tobacco associated oral cancer are limiting. We report here the establishment and characterization of two novel buccal mucosal cancer cell lines 'GBC02' and 'GBC035' derived from non-tobacco users. MATERIALS AND METHODS: Short tandem repeats (STR) profiling, Next-generation sequencing for whole-genome, exome and copy number alterations, immunofluorescence, flow-cytometry, proliferation, live-cell chemotaxis, 3D-spheroid formation, chemotherapy response, gene-expression microarray, gene-set enrichment analysis and xenograft development were performed. RESULTS: Sources of the established cultures were matched to their donors through STR profiling. Genome sequence analysis revealed somatic mutations in TP53, CASP8, CDKN2A for GBC02 with deletions and amplifications encompassing CDKN2A, FAT1 and CCND1, PIK3CA, SOX2, EGFR, MYC genes, respectively. GBC035 harbored mutations in FAT1, NOTCH1, HRAS, CDKN2A, HLA-B, HLA-A genes. While GBC035 cells showed higher E-Cadherin positive cell-cell junctions and collective cell migration in chemotaxis; GBC02 cells were vimentin-positive and demonstrated individual cell migration. Further, exhibiting their relevance to preclinical research, GBC02 3D-spheroids demonstrated enrichment of development-related gene-signatures in microarray transcriptome analysis and were resistant to Cisplatin, but showed sensitivity to cancer stem cells-targeting drug, Salinomycin. Additionally, tumorigenic ability of GBC02 was demonstrated. CONCLUSIONS: Altogether, we present here comprehensively characterized unique cell lines established from non-tobacco associated tumors, which may serve as models for preclinical investigations of oral cancers caused independent of tobacco usage.

Feasibility, Safety, Nodal yields and Learning curves in Retroauricular Robot/Endoscope Assisted Neck Dissection in the Management of Head and Neck Cancer.

Head and neck cancer is one of the most common in India. There is an increasing incidence of oral cancer in young patients. Where the primary lesion is amenable to transoral resection for early cancer, young patients are concerned about cosmesis and would prefer a surgical approach that would avoid a visible scar in the neck. Robot/endoscope-assisted neck dissection by retroauricular approach was performed in a total of 28 patients of cN0 patients between June 2016 and December 2019. The duration of surgery, perioperative complications, number of lymph nodes retrieved, and cosmetic outcomes were analyzed. Robot- and endoscope-assisted neck dissections were done in 15 and 13 cases, respectively. The mean age of the cohort was 46.18 ± 9.68 years. Twenty-four patients had tongue cancer. Mean time for skin flap raising, docking, and robotic console use was 48.21 ± 7.48 min, 10 ± 3.16 min, and 176.67 ± 47.27 min, respectively. Mean neck dissection time from skin incision to skin closure was 231.79 ± 54.94 min for completing level I to IV neck dissection. The mean number of retrieved nodes was 33.69 ± 12.81. Majority of the patients were highly satisfied with their cosmetic outcomes. During a median follow-up of 19.5 months, 3 patients developed recurrence. Robot/ endoscope-assisted neck dissection was feasible and safe but took a longer time to perform. Nodal yields were adequate and better cosmetic outcomes were achieved.

Contribution of Weight and Volume of the Extirpated Thyroid Gland on Voice Alterations After Total Thyroidectomy in Patients With Papillary Carcinoma of the Thyroid.

PURPOSE: Voice change after thyroid surgery is common despite preservation of laryngeal nerves. In this study, we sought to find if the change in voice after total thyroidectomy is related to the weight and volume of the removed thyroid gland. METHODS: This is a prospective cohort study of 50 patients of papillary carcinoma of the thyroid treated with total thyroidectomy from December 2016 through May 2018. Both objective and subjective voice parameters were analyzed preoperatively and at 1 and 3 months following surgery. RESULTS: A cohort of 29 patients, with a median age of 31 years (18-64 years), comprising 22 women were eligible for final analysis. Speaking fundamental frequency showed a mean change of 17.21 Hz (SD 34.49) while the mean intensity change was 5.54 dB (SD 18.21). The mean weight and volume of thyroid gland was 18.99 g (SD 8.93) and 15.67 ml (SD 8.70), respectively. On multivariate analysis, both weight and volume affected the range of frequency (P = 0.002 and 0.035, respectively) and range of intensity (P = 0.014 and 0.008, respectively). CONCLUSION: Larger thyroid tumors are more likely to be associated with transient change in voice quality following their surgical removal despite physical preservation of external and recurrent laryngeal nerves, which may persist up to 3 months. This study affirms that perturbations in voice after thyroidectomy can still exist in spite of clinical demonstration of integrity of neuromuscular function.

Lymph node characteristics and their prognostic significance in oral squamous cell carcinoma.

BACKGROUND: The prognostic significance of various histopathologic lymph node-based biomarkers in oral squamous cell carcinoma (OSCC) needs further evaluation. METHODS: Retrospective analysis of 212 OSCC patients with regional metastasis to determine the association of extranodal extension (ENE), extent of ENE, size of metastatic deposit, lymph node yield (LNY), lymph node ratio (LNR), and topography of involvement with survival outcomes. RESULTS: The presence of ENE, larger nodal deposit, higher pN stage, lymph nodes in the lower levels, and patients who did not receive adjuvant treatment had poor disease-free survival (DFS). In addition, more positive nodes and high LNR showed worse overall survival (OS). ENE beyond 5 mm resulted in poorer outcomes. Larger sizes of metastatic deposit predisposed to ENE. Multivariate analyses showed only lower level of neck involvement to affect both DFS and OS. CONCLUSIONS: Lymph node metastasis to lower levels and other lymph node characteristics affect prognosis and must be considered in the evolution of staging systems for OSCC.

Redefining adequate margins in oral squamous cell carcinoma: outcomes from close and positive margins.

PURPOSE: Adequacy of surgical margins impacts outcomes in oral cancer. We sought to determine whether close and positive margins have different outcomes in patients with oral cancer. METHODS: Retrospective data from 612 patients with oral carcinoma were analyzed for the effect of margin status on locoregional recurrence-free survival (LRFS), disease-free survival (DFS) and overall survival (OS). RESULTS: A total of 90 cases (14.7%) had close margins and 26 patients (4.2%) had positive margins. Recurrences were documented in 173 patients (28%), of which 137 (22% of the study sample) were locoregional, and 164 patients (27%) had died. Among patients with close or positive margins, a cutoff of 1 mm optimally separated LRFS (adjusted p = 0.0190) and OS curves (adjusted p = 0.0168) whereas a cutoff of 2 mm was sufficient to significantly separate DFS curves (adjusted p = 0.0281). CONCLUSIONS: Patients with oral carcinoma with positive margins (< 1 mm) had poorer outcomes compared to those with close margins (1-5 mm) in terms of LRFS, DFS and OS. There is a suggestion that a cutoff of < 2 mm might provide slightly more separation for DFS.

Adenoid Cystic Carcinoma with Transformation to High Grade Carcinomatous and Sarcomatoid Components: A Rare Case Report with Review of Literature.

Adenoid cystic carcinoma (AdCC) comprises of less than 1% of all head and neck cancers and less than 10% of all salivary gland neoplasms. Dedifferentiation/high-grade transformation (HGT) in AdCC is a rare but well known phenomenon which is associated with aggressive clinical behaviour and poor prognosis. We herein report the clinical, cytologic, histologic and immunohistochemical findings of a left submandibular gland AdCC with transformation to high grade carcinomatous and probable dedifferentiation to sarcomatoid component, occurring in a 64 year old male patient. To the author's best knowledge, this is the first case report of such dual transformation occurring in adenoid cystic carcinoma.