Regional Cervical Lymph Nodes Research Articles

Abstract PR004: Differential gene expression analysis comparing Black and White patients with HPV-positive oropharyngeal squamous cell carcinoma reveals suppressed immune response and higher rates P16/HPV DNA discordance in Black patients

Abstract Background-Human papilloma virus (HPV-positive (+)) oropharynx cancer (OPC) are a distinct neoplastic entity associated with a significant survival advantage compared to HPV- OPCs. The survival advantage is so great that the presence of regional cervical lymph node metastasis is no longer considered an advanced stage III/IV cancer. The survival advantage associated with HPV+ OPC is not the same for Black patients compared to all other races and emerging data now suggests Black patients with HPV+ OPC have survival outcomes similar to White patients with HPV- OPC. We conducted a differential gene expression analysis and high-risk HPV serotyping comparing genomic difference between treatment naïve Black and White patients with HPV+ OPC. Methods: Surgical samples were obtained from Duke, the University of Texas Medical Branch, and the University of Mississippi, through an IRB approved protocol. HPV status determined by p16 immunohistochemistry (IHC). We performed digital spatial profiling and conducted a differential gene expression analysis in 14 Black and 13 White patients using the Nanostring™ Whole Transcriptome Atlas. Morphology markers included CD45, PANCK, and alpha SMA to label lymphocytes, epithelium, and stroma, respectively. A component of the bioinformatics pipeline included conducing a KEGG pathway analysis using pre-ranked test statistics from self-reported Black and White patients HPV+ OPC. The presence of high-risk oncogenic HPV was determined in parallel by RT-PCR (Creative Biogene). P16, CD68 and CD3 expression was measured by IHC using standard techniques. Results: There was a significant decrease in antigen processing and presentation and T-cell receptor signaling pathways in CD45+ lymphocytes (p<0.0002) and B-Cell receptor and chemokine signaling pathways in PANCK+ tumor epithelial cells (p<0.03) in Black patients compared to White patients with HPV+ OPC. There was a significant difference in p16 expression and the absence of HPV DNA in Black patients compared to White patients (p<0.017). 32% of Black patients with p16+ OPC were HPV DNA negative. There was no p16/HPV16 DNA discordance observed in the White patient cohort. Three patients were co-infected with other carcinogenic HPV serotypes (45, 51, and 59) in addition to HPV16 (two Black and one White). CD68 expression, associated with M1-like anti-tumor macrophages, was significantly decreased in Black patients with p16+/HPV16+ OPC, compared to White patients (p<0.017), suggesting alterations in tumor immune response may be important in cancer disparities. Conclusion: The favorable prognosis associated with HPV+ OPC, including recruitment in currently ongoing radiation de-escalation clinical trials cannot be widely applied to all patients with HPV+ OPC and studies addressing racial disparities, HPV/p16 discordance, and predictors of poor response represent a significant health equity gap in the field of OPC disparities. Citation Format: Tammara L. Watts, Katerine Gonzalez, Xiangfeng Shen, Layne Rogers, Nosa Osazuwa-Peters, Gina D. Jefferson, Cecilia G. Clement, Danielle Range, Russel R Kahmke, Walter T Lee, Daniel J. Rocke, Trinitia Y Cannon, Yvonne Mowery, Kouros Owzar. Differential gene expression analysis comparing Black and White patients with HPV-positive oropharyngeal squamous cell carcinoma reveals suppressed immune response and higher rates P16/HPV DNA discordance in Black patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr PR004.

Clinicopathological Factors Associated with Lymph Node Metastasis in Oral Cavity Squamous Cell Carcinoma: A Retrospective Analysis

Abstract Background: Metastasis to regional cervical lymph nodes is an important prognostic factor for oral-cavity squamous cell carcinomas (OSCC). However, it is difficult to predict nodal metastasis in OSCC. The current study was done with an aim to find the association of various clinicopathological factors to the presence of cervical lymph node metastasis in OSCC. Materials and Methods: A retrospective analysis of hospital records from January 2020 to June 2023 was conducted in a tertiary care center. The records of 65 patients were included as per the inclusion criteria. The data were divided into two groups based on the presence or absence of neck nodal metastasis. Various factors such as tumor size, volume, depth of invasion (DOI), lymphovascular invasion, and perineural invasion were statistically compared between the study groups. Results: The oral tongue was the most common subsite (25, 38.5%), followed by buccal mucosa (18, 27.7%). The mean DOI in the group with cervical lymph node metastasis was 9.83 ± 4.83 mm, and it was significantly higher than the group without cervical lymph node metastasis (6.15 ± 4.20 mm, P = 0.004). Conclusion: DOI assessment is one of the most important preoperative assessments in the clinicoradiological assessment of OSCC cases. Further, it is recommended that in cases with DOI >5 mm, the intraoperative frozen section on the nodes dissected in elective neck dissection is done for further determination of the extent of neck dissection.

Papillary thyroid carcinoma: a case of extremely rare sternal metastasis with concurrent lung involvement

Introduction: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer which arises from thyroid follicular cells. PTC is typically characterized by its slow growth and propensity for lymphatic spread to regional cervical lymph nodes. While distant metastasis, particularly to the lungs and bones, is uncommon, rare presentations such as sternal metastasis pose diagnostic and therapeutic challenges. Case description: We are reporting A 49-year-old male with dyspnea and a progressively enlarging mass in the neck and chest. Imaging studies including chest X-ray and CT scan confirmed lung and sternal metastasis along with lymph node enlargement. Fine-needle aspiration biopsy indicated a follicular neoplasm. Following total thyroidectomy with radical neck dissection, sternal and clavicle bone resection with titanium sternum reconstruction, histopathological analysis revealed PTC with lymphovascular invasion. Postoperative recovery was uncomplicated, leading to discharge on day 10, and planned radioiodine therapy. Conclusion: A multidisciplinary approach is crucial for managing sternal metastasis in papillary thyroid carcinoma due to its atypical presentation.

Possibilities of bioregulation therapy in the treatment of patients with chronic tonsillitis

Background. There are numerous diagnostic methods and therapy regimens for chronic tonsillitis (CT). Different methods of treatment in certain conditions do not always show high efficiency, so the search for new ways of conservative management of CT is needed, the main task of which is palatine tonsils preservation.Objective: to evaluate the efficacy and tolerability of a multicomponent preparation with low dosage of active substances Lymphomyosot® in adult patients with CT and cervical lymphadenopathy in real clinical practice.Material and methods. A total of 170 male and female patients aged 18–65 years with CT (simple form and 1st degree toxic-allergic form) and cervical lymphadenopathy were included in an observational, open, prospective study. In the main group (n=85), a combined therapy consisting of standard CT therapy (a course of palatine tonsils lavage with 0.9% NaCl solution) with the addition of Lymphomyosot® was administered. In the control group (n=85), topical non-steroidal anti-inflammatory drugs or phytotherapy were used instead of the studied drug. Ultrasound examination of regional cervical lymph nodes with measuring of their diameter (longitudinal, transverse) was chosen as a parameter of objective assessment of patients' condition dynamics. The results of therapy at Visit 1 and Visit 2 (12±2 days after Visit 1) were compared. The effectiveness of treatment regimens was analyzed according to the following parameters: complaints related to CT; oropharyngoscopic data; evaluation of CT indicators by the doctor and the patients; dynamics of cervical regional lymph nodes size; satisfaction of the doctor and the patients with the clinical effect and tolerability of therapy.Results. The dynamic observation showed a significant decrease in the number of complaints and symptoms according to objective examination, oropharyngoscopy, as well as evaluation of symptoms by the doctor and the patients at Visit 2 in both groups (p<0.001). However, in the main group, where Lymphomyosot® was administered in the complex treatment, there was a more significant decrease in cervical lymph nodes size compared to the control group (p<0.01).Conclusion. The study demonstrated that Lymphomyosot® increased the efficacy of complex therapy, reducing cervical lymphoadenopathy and other manifestations of the disease in patients with CT (simple and 1st degree toxic-allergic forms).

The Correlation Between Depth of Invasion, and Degree of Differentiation with Cervical Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Objective: To study the significance of Depth of invasion (DOI), and the degree of differentiation (DOD) as predictors of cervical nodalmetastasis in oral squamous cell carcinoma. To determine a cut-off depth beyond which there is a high risk of cervical metastasis. Todetermine whether the DOI can be is alone enough as predictor for lymphatic metastasis despite the DOD. Methods: Forty-eight patients with OSCC were included in the study 28 males and 20 females ranging between 25 to 80 years. Alltreated in Ghazi Al-Hariri hospital for surgical specialties in Baghdad Medical city between 2017 to 2019. Slides were examined afterimmunohistochemical staining. Depth of invasion was measured according to the criteria of AJCC, and the WHO system of grading was, all histopathological parameters were recorded after immunohistochemical staining. Results: The depth of invasion ranged between 2 and 13 mm with a mean of 6.58 mm and SD of ± 2.56 mm and it was found to be ahighly significant predictor for lymphatic metastasis (P-value = 0.001), the cut-off point with a significant risk of metastasis was 5 mm. Thedegree of differentiation was also a significant predictor for cervical metastasis (P-value = 0.024) with poorly differentiated SCC carrying the highest risk of cervical metastasis despite the depth of the tumor invasion. Conclusion: DOI and DOD were significant histological parameters that predict the behavior of the well and moderately differentiated oral squamous cell carcinoma and hence the management of the neck in OSCC. However, the depth of invasion was not significance in cases of poorly differentiated OSCC. Therefore, we recommend that elective neck dissection should be done in cases of poorly differentiated OSCC despite the DOI.

Assessment of sentinel lymph node detection by radioisotope scan and methylene blue alone in operable oral cavity cancer to assess its accuracy for metastasis

Background: Squamous cell carcinoma (SCC) is the most common malignancy affecting the oral cavity. It typically metastasizes into the regional cervical lymph nodes before spreading to distant organs.Methods: A prospective study on sentinel lymph node biopsy (SLNB) in early oral cancers using methylene blue dye and sentinel node localisation using pre-operative lymphoscintigraphy and intraoperative gamma probe in early oral cavity cancer.Results: Present study had a male to female ratio of 1.9:1, with (65.5%) male and (34.5%) female patients. Present study had a side distribution of disease more on left side with 138 patients (62.7%) and ratio of left to right was approximately 1.7:1. In present study most predominating gross morphological pattern of growth was ulcerative (35%) followed by ulcero-infilterative (25%). Buccal mucosa was the most common sub-site of origin of carcinoma in oral cavity, followed by tongue, with 83 (37.7%) and 64 (29.1%) patients. Identification rate of methylene blue dye was 91.7% (100 out of 109 patient). Identification rate of radionuclide tracer was 94.6% (105 out of 111 patient). In methylene blue dye group out of 103 metastatic sentinel lymph nodes, 9 metastatic sentinel lymph nodes were detected on IHC.Conclusions: With the above results it can be concluded the SLNB study is liable in detection of actual positive node and can avoid unnecessary neck dissections in patients with SCC with negative sentinel lymph node, as having very low risk of occult lymphatic metastases in the remaining lymphatic drainage.

Clinical Outcomes of Diffuse Sclerosing Variant Papillary Thyroid Carcinoma in Pediatric Patients.

The diffuse sclerosing variant of papillary thyroid carcinoma (DSV) may be more aggressive than conventional well-differentiated non-DSV related papillary thyroid carcinomas (N-PTC). Retrospective chart review. Retrospective review of clinical outcomes for patients 21 years of age or younger who underwent initial surgery for PTC at a single institution from January 1, 2005 to April 1, 2020. Genomic analysis was performed using targeted next-generation sequencing. Data were analyzed using Fischer's exact test and Kaplan-Meier curve log-rank test. Our cohort consisted of 72 patients, nine with DSV and 63 with N-PTC. Age at diagnosis was comparable (15.4 vs. 16.2 years, respectively, P=.46). DSV were more likely to be in the high-risk American Thyroid Academy pediatric risk group (100% vs. 41.3%, P=.004), to present with regional cervical lymph node metastases (100% vs. 60.3%, P=.036), and to present with distant metastases (67% vs. 22%, P=.005). No mortality seen in either group over 27.5 (interquartile range 14.8, 46.00) months average follow-up. Throughout the follow-up period, DSV were more likely to experience progression than N-PTC (hazard ratio=5.7 [95% confidence interval 1.7-20.0; P=.0056]). In a subset of 19 patients with aggressive disease who had molecular testing as part of clinical care we detected RET fusions in nearly all DSV compared to a minority of N-PTC (83% vs. 15.4%, P=.0095). Pediatric patients with DSV have more advanced disease at diagnosis and are more likely to experience progression of disease compared to patients with N-PTC. The prevalence of RET fusions in our cohort recapitulates the frequency of this alteration described in prior studies. 4 Laryngoscope, 132:1132-1138, 2022.

The role of total parotidectomy in high-grade parotid malignancy: A multisurgeon retrospective review

Determine rates of intra-parotid and neck nodal metastasis, identify risk factors for recurrence, and report outcomes in patients with primary high-grade parotid malignancy who undergo total parotidectomy and neck dissection. Retrospective review of patients undergoing total parotidectomy and neck dissection for high-grade parotid malignancy between 2005 and 2015. The presence and number of parotid lymph nodes, superficial and deep, as well as cervical lymph nodes involved with metastatic disease were assessed. Risk factors associated with metastatic spread to the parotid deep lobe were identified and recurrence rates reported. 75 patients with median follow-up time of 47months. 35 patients (46.7%) had parotid lymph node metastasis. Seven patients (9.3%) had deep lobe nodal metastasis without metastasis to the superficial lobe nodes. Nine patients (12%) had positive intra-parotid nodes without positive cervical nodes. Cervical nodal disease was identified in 49.3% patients (37/75). Local, parotid-bed recurrence rate was 5.3% (4/75). Regional lymph node recurrence rate was also 5.3% (4/75). Rate of distant metastasis was 30.6% (23/75). The overall disease free survival rate for all patients at 2 and 5years were 71% and 60% respectively. Parotid lymph node metastasis occurred at a similar rate to cervical lymph node metastasis (46.7% and 49.3%, respectively). Deep lobe parotid nodal metastasis occurred in nearly a quarter of patients and can occur without superficial parotid nodal metastasis. Rate of recurrence in the parotid bed, which may represent local or regional recurrence, was similar to regional cervical lymph node recurrence. Total parotidectomy and neck dissection should be considered high-grade parotid malignancy regardless of clinical nodal status.

Role of CXCR4 and MMP-9 Expressions with Regional Cervical Lymph Nodes Metastatic Status in Papillary Thyroid Carcinoma

Background: Papillary thyroid carcinoma (PTC) that has metastasized has a higher risk because of the poor prognosis, ranging from decreased quality of life of the patient to death. There is a need for markers that can understand the image of the tumor so that it can predict earlier the level of aggressiveness and the ability of tumor cells to metastasize. Tumor cells that proliferate excessively will cause CXCR4 expression. Activation of CXCR4 will increase MMP-9 via the MAPK/ ERK line. MMP-9 will degrade the extracellular matrix causing tumor cell metastasis. This study is aimed to analyze the correlation of CXCR4 and MMP-9 expressions with lymph node metastasis (LNM) in PTC.Methods: This cross-sectional analytic observational study was conducted in 43 PTC samples taken from the Anatomical Pathology Laboratory of Dr. Soetomo Hospital from January 2011 to December 2018. The samples were divided into 2 groups based on the regional cervical LNM status. Immunohistochemical staining was used to assess the expression of CXCR4 and MMP-9. Spearman test was used to analyze the correlation of CXCR4 and MMP expression with cervical LNM status.Results: The expression of CXCR4 and MMP-9 was higher in the papillary thyroid carcinoma group with cervical regional LNM (p = 0.007 and p = 0.030). There was a significant positive relationship between CXCR4 and MMP-9 expressions with regional LNM status with rs = 0.468 and p = 0.001 (p < 0.05). Conclusions: Expression of CXCR4 and MMP-9 was proven to correlate with regional cervical LNM status in papillary thyroid carcinoma. Both can be used as predictive markers for metastasis in papillary thyroid carcinoma.

MKP-1 is required to limit myeloid-cell mediated oral squamous cell carcinoma progression and regional extension

To determine the significance of myeloid-based expression of MKP-1 in oral cancer. The Cancer Genome Atlas (TCGA) was used to address DUSP1 expression in oral squamous cell carcinoma (OSCC). Syngeneic and carcinogen-induced mouse models using global and myeloid-specific Dusp-1 deficient mice with immunophenotypic, histologic, and transcriptomic analyses and in vitro migration assays. Data from TCGA indicates the DUSP1 expression is inversely related to oral cancer burden and nodal involvement. Using murine models of OSCC, the role of MKP-1 signaling in tumor associated macrophages (TAMs) was assessed. Dusp1-deficient mice had increased tumor burden and TAM infiltrate with increased M2 macrophage polarization. Transcriptomic signatures of TAMs from Dusp1-deficent mice indicated a pro-metastatic phenotype as well as concomitant differences in myeloid-associated genes, cytokine/chemokine signaling, and Notch signaling consistent with tumor progression. In vitro and in vivo assays revealed mouse OSCC cells had a higher migration rate using TAM cell-free supernatant from Dusp1 deficiency mice compared to controls with enhanced regional cervical lymph node metastasis, respectively. To validate TAM studies using implantable mouse models, an OSCC progression model with conditional myeloid-specific Dusp-1 deficient mice demonstrated enhanced OSCC disease progression, characterized by advanced onset, histological stage, and tumor burden. Myeloid-based Dusp1-deficiency increases OSCC burden and metastasis through alteration in TAM recruitment, gene profile, and polarity suggesting that MKP-1 could be a viable target to reprogram TAM to limit local/regional OSCC extension.

Preliminary study of superselective lymph node dissection in regional lateral cervical lymph node metastasis of papillary thyroid carcinoma

Objective: To explore the applied value of super-selective cervical lymph node dissection in papillary thyroid carcinoma (PTC) patients with clinically suspicious lateral lymph node metastasis (LNM). Methods: We retrospectively analyzed the clinical data of 232 cN1b PTC patients who underwent surgery from September 2013 to May 2018 in the Department of Head and Neck Surgical Oncology, National Cancer Center. Among them, 90 cases received super-selective neck dissection (level Ⅲ and IV) and 142 cases underwent selective neck dissection (level Ⅱ-Ⅳ). The LNM of two groups were analyzed. Results: Postoperative pathological results showed that 173 cases had LNM in the central compartment. The LNM cases of level Ⅱ-Ⅳ were 47, 147 and 130, respectively. Eight patients of super-selective neck dissection and 6 of selective neck dissection had postoperative lymphatic fistulas (P=0.146). No patients in super-selective neck dissection group while 9 patients in the selective lymph node dissection group had postoperatively permanent impairment of shoulder mobility, the difference was statistically significant (P=0.015). In the super-selective neck dissection group, 2 patients had long-term postoperative incision discomfort, and 5 cases had obvious cicatrix after surgery. In the patients with selective neck dissection, 27 cases experienced long-term incision discomfort after surgery, and 26 patients had apparent scar tissue, the differences were statistically significant (P<0.005). There was no recurrence during the follow-up. Conclusions: Super-selective neck dissection is a feasible, safe and effective treatment for cN1b PTC patients. It can improve the quality of postoperative life and avoid the over treatment for patients.

A rare presentation recurrent nasopharyngeal carcinoma with axillary lymph node metastasis

Introduction: Nasopharyngeal carcinoma (NPC) has the highest rate of local and regional cervical lymph node re-currence amongst other head and neck epithelial malignant tumour. Distant recurrence is less common and usually occurs in bone, liver and lung. Recurrent NPC to axillary lymph node is rare.Case report: A 44-year-old male presented with two-month history of painless right axillary swelling. He was di-agnosed with nasopharyngeal carcinoma (NPC) stage IVA (T2N3M0) two years prior to presentation and had underwent neoadjuvant chemotherapy with 5-Fluorouracil and Cisplatin, and concurrent chemo-radiotherapy (CCRT) of total 70 Gy over 35 sessions with Cisplatin. He was on regular monthly surveillance reviews, with no signs of recurrence. Fine Needle Aspiration Cytology (FNAC) of the axillary swelling was reported as metastatic NPC and Positron Emission Tomography/ Com-puted tomography (PET-CT) scan showed foci of high FDG hypermetabolism at right axillary lymph node confirming the diagnosis of recurrent NPC.Conclusion: Recurrence usually occurs in the first two years after completion of treatment. Patients with an overall TNM stage IV or N3, high pre-treatment or persistently detectable post-treatment plasma EBV DNA (pEBV DNA) load are at greatest risk. Management of recurrent NPC depends on local, regional or distant recurrence. Both PET scan and pEBV DNA load can be used for relapse detection. The man-agement for each recurrent NPC case is unique and should be determined by a multidisciplinary team, local expertise and facilities. Knowledge of potential sites of recurrence is essential to both physicians and patients for early detection.

Clinical outcomes of oral cancer patients who survive for more than 5 years in Taiwan

Oral cancer patients who survive for more than 5 years are supposed to have a reduced local cancer recurrence rate and survive longer. This study evaluated whether oral cancer patients who survived for more than 5 years might have reduced rates of local cancer recurrence, development of the second or third primary oral cancer, or the late regional cervical lymph node metastasis. This study analyzed the clinical outcomes of 127 oral cancer patients (101 men and 26 women; mean age, 50.8±12.1 years) who survived for more than 5 years after proper treatments of the initial primary oral cancers. The 127 primary oral cancers included 117 squamous cell carcinomas (SCCs), 7 mucoepidermoid carcinomas, and 3 others. Of the 127 oral cancer patients who survived for more than 5 years, 47 survived for 5-9 years, 45 for 10-14 years, 22 for 15-19 years, 10 for 20-24 years, two for 25-29 years, and one for 30 years. Ten patients had local cancer recurrence 5.4 years-13.7 years, 12 patients had a second or a third primary oral cancer 3.6 years-17.2 years, and one mucoepidermoid carcinoma patient had a late regional cervical lymph node metastasis 11.9 years after total excision of the initial primary oral cancers. Oral cancer patients who survive for more than 5 years may still have local cancer recurrence, the second or third primary oral cancer, or the late regional cervical lymph node metastasis but with a reduced rate.

Lymphotoxin‐β receptor‐NIK signaling induces alternative RELB/NF‐κB2 activation to promote metastatic gene expression and cell migration in head and neck cancer

Head and neck squamous cell carcinomas (HNSCC) preferentially spread to regional cervical tissues and lymph nodes. Here, we hypothesized that lymphotoxin-β (LTβ), receptor LTβR, and NF-κB-inducing kinase (NIK), promote the aberrant activation of alternative NF-κB2/RELB pathway and genes, that enhance migration and invasion of HNSCC. Genomic and expression alterations of the alternative NF-kB pathway were examined in 279 HNSCC tumors from The Cancer Genome Atlas (TCGA) and a panel of HNSCC lines. LTβR is amplified or overexpressed in HNSCC of the larynx or oral cavity, while LTβ, NIK, and RELB are overexpressed in cancers arising within lymphoid oropharyngeal and tonsillar sites. Similarly, subsets of HNSCC lines displayed overexpression of LTβR, NIK, and RELB proteins. Recombinant LTβ, and siRNA depletion of endogenous LTβR and NIK, modulated expression of LTβR, NIK, and nuclear translocation of NF-κB2(p52)/RELB as well as functional NF-κB promoter reporter activity. Treatment with a NIK inhibitor (1,3[2H,4H]-Iso-Quinoline Dione) reduced the protein expression of NIK and NF-κB2(p52)/RELB, and blocked LTβ induced nuclear translocation of RELB. NIK and RELB siRNA knockdown or NIK inhibitor slowed HNSCC migration or invation in vitro. LTβ-induces expression of migration and metastasis related genes, including hepatocyte growth/scatter factor receptor MET. Knockdown of NIK or MET similarly inhibited the migration of HNSCC cell lines. This may help explain why HNSCC preferentially migrate to local lymph nodes, where LTβ is expressed. Our findings show that LTβ/LTβR promotes activation of the alternative NIK-NF-κB2/RELB pathway to enhance MET-mediated cell migration in HNSCC, which could be potential therapeutic targets in HNSCC.

Morphometric analysis of tumor stromal lymphatic vessels and lymphangiogenesis in oral squamous cell carcinoma

Abstract Oral squamous cell carcinoma (OSCC) often causes lymphatic metastasis, particularly to the regional cervical lymph nodes. Although lymphatic metastasis is closely associated with lymphangiogenesis in the tumor tissues, the detailed mechanisms are not yet fully understood. The purpose of this study was to examine the morphological association of lymphangiogenesis in the tumor stromal tissue with cervical lymph node metastases in OSCC. The medical records of 13 patients treated for OSCC affecting the tongue at the Department of Oral Surgery of Nihon University School of Dentistry at Matsudo Hospital between November 2003 and March 2011 were reviewed. The 13 cases were divided into two groups, with 7 cases in the metastasis group and 6 cases in the non-metastasis group. Histopathological (hematoxylin-eosin stain) and immunohistochemical (D2-40 antibody) examinations were performed. Lymphatic vascular density and lymphatic vascular area, lymphatic vascular morphology, and the number of lymph vessels were quantified using ImageJ software. The lymphatic vessels in the metastasis group were distributed with higher density and ran irregularly, with more remarkable deformation than those in the non-metastasis group. Cervical lymph node metastasis is one of the factors affecting progression and the prognosis of OSCC patients. In the present study, lymphatic vessels were found in the OSCC stroma, which also suggests that an increased density of lymphatic vessels leads to cervical lymph node metastases.

Surgery for Advanced Nodal Metastasis in Thyroid Cancer

Metastases to regional cervical lymph nodes occur frequently in patients with thyroid cancer. The appropriate management of regional lymph node is important to achieve good disease control and to classify risk stratification for adjuvant radioactive iodine. However, there are some occasions that neck dissection is difficult and embarrassing in thyroid cancer. Especially, extensive or unusual nodal metastases bring challenges and makes neck dissection more difficult. Carotid artery management is one of the most difficult procedure in neck dissection. The management of patients who have persistent or recurrent cervical metastasis involving the carotid artery has been controversial and treatment dilemma to the surgeon. Metastasis of well differentiated thyroid cancer to the retropharyngeal lymph nodes is rare but occasionally encountered. The complete surgical excision is usually recommended for retropharyngeal lymph node metastasis of well differentiated thyroid cancer. An extensive mediastinal dissection in advanced differentiated thyroid carcinoma is occasionally required. This paper will review recent reports of management of advanced nodal metastasis of thyroid cancer and share the author's personal experience.

Prognostic values of the integrated model incorporating the volume of metastatic regional cervical lymph node and pretreatment serum Epstein\u2013Barr virus DNA copy number in predicting distant metastasis in patients with N1 nasopharyngeal carcinoma

BackgroundAccording to the 7th edition of the American Joint Committee on Cancer (AJCC) staging system, over 50% of patients with nasopharyngeal carcinoma (NPC) have N1 disease at initial diagnosis. However, patients with N1 NPC are relatively under-researched, and the metastasis risk of this group is not well-stratified. This study aimed to evaluate the prognostic values of gross tumor volume of metastatic regional lymph node (GTVnd) and pretreatment serum copy number of Epstein–Barr virus (EBV) DNA in predicting distant metastasis of patients with N1 NPC, and to develop an integrated prognostic model that incorporates GTVnd and EBV DNA copy number for this group of patients.MethodsThe medical records of 787 newly diagnosed patients with nonmetastatic, histologically proven N1 NPC who were treated at Sun Yat-sen University Cancer Center between November 2009 and February 2012 were analyzed. Computed tomography-derived GTVnd was measured using the summation-of-area technique. Blood samples were collected before treatment to quantify plasma EBV DNA. The receiver operating characteristic (ROC) curve analysis was used to evaluate the cut-off point for GTVnd, and the area under the ROC curve was used to assess the predicted validity of GTVnd. The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model.ResultsThe 5-year distant metastasis-free survival (DMFS) rates for patients with GTVnd > 18.9 vs. ≤ 18.9 mL were 82.2% vs. 93.2% (P < 0.001), and for patients with EBV DNA copy number > 4000 vs. ≤ 4000 copies/mL were 83.5% vs. 93.9% (P < 0.001). After adjusting for GTVnd, EBV DNA copy number, and T category in the Cox regression model, both GTVnd > 18.9 mL and EBV DNA copy number > 4000 copies/mL were significantly associated with poor prognosis (both P < 0.05). According to combination of GTVnd and EBV DNA copy number, all patients were divided into low-, moderate-, and high-risk groups, with the 5-year DMFS rates of 96.1, 87.4, and 73.8%, respectively (P < 0.001). Multivariate analysis confirmed the prognostic value of this model for distant metastatic risk stratification (hazard ratio [HR], 4.17; 95% confidence interval [CI] 2.34–7.59; P < 0.001).ConclusionsGTVnd and serum EBV DNA copy number are independent prognostic factors for predicting distant metastasis in NPC patients with N1 disease. The prognostic model incorporating GTVnd and EBV DNA copy number may improve metastatic risk stratification for this group of patients.

EGF induces epithelial-mesenchymal transition and cancer stem-like cell properties in human oral cancer cells via promoting Warburg effect.

“Warburg effect”, the enhanced glycolysis or aerobic glycolysis, confers cancer cells the ability to survive and proliferate even under stressed conditions. In this study, we explored the role of epidermal growth factor (EGF) in orchestrating Warburg effect, the epithelial-mesenchymal transition (EMT) process, and the acquisition of cancer stem-like cell properties in human oral squamous cell carcinoma (OSCC) cells. Our results showed that EGF induces EMT process in OSCC cells, which correlates with the acquisition of cancer stem-like properties, including the enrichment of CD44+/CD24− population of cancer cells and an increased expression of CSC-related genes, aldehyde dehydrogenase-1 (ALDH1) and Bmi-1. We also showed that EGF concomitantly enhanced L-lactate production, while blocking glycolysis by 2-deoxy-D-glucose (2-DG) robustly reversed EGF-induced EMT process and CSC-like properties in OSCC cells. Mechanistically, we demonstrated that EGF promoted EMT process and CSC generation through EGFR/PI3K/HIF-1α axis-orchestrated glycolysis. Using an orthotopic tumor model of human OSCC (UM-SCC1) injected in the tongue of BALB/c nude mice, we showed that treatment with 2-DG in vivo significantly inhibited the metastasis of tumor cells to the regional cervical lymph nodes and reduced the expression of ALDH1 and vimentin in both in situ tumors and tumor cell-invaded regional lymph nodes. Taken together, these findings have unveiled a new mechanism that EGF drives OSCC metastasis through induction of EMT process and CSC generation, which is driven by an enhanced glycolytic metabolic program in OSCC cells.

Kikuchi Disease with Generalized Lymph Node, Spleen and Subcutaneous Involvement Detected by Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Kikuchi-Fujimoto disease, known as Kikuchi disease, is a rare benign and self-limiting disorder that typically affects the regional cervical lymph nodes. Generalized lymphadenopathy and extranodal involvement are rare. We report a rare case of a 19-year-old female with a history of persistent fever, nausea, and debilitating malaise. Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed multiple hypermetabolic generalized lymph nodes in the cervical, mediastinum, axillary, abdomen and pelvic regions with diffuse spleen, diffuse thyroid gland, and focal parotid involvement, bilaterally. In addition, subcutaneous lesions were noted in the left upper paraspinal and occipital regions. An excisional lymph node biopsy guided by 18F-FDG PET/CT revealed the patient’s diagnosis as Kikuchi syndrome.

The presentation of lymph nodes in Hashimoto's thyroiditis on ultrasound.

Comprehensive neck ultrasound (US) examination has become an essential component of preoperative workup for patients with thyroid cancer. Regional cervical lymph nodes may be involved in cases of Hashimoto's thyroiditis (HT). This study seeks to examine the sonographic pattern of lymph nodes in patients with HT. This is a retrospective study looking at patients with confirmed diagnoses of HT on final surgical pathology who underwent preoperative comprehensive neck US. We compared preoperative ultrasound for patients with HT to euthyroid patients with goiter. Data collected included number, size and ultrasonographic features of cervical lymph nodes. We included a total of 417 patients: 202 patients with HT in the study group, and 215 patients with goiter and euthyroid status in the control group. Patients with HT had a higher number of total cervical lymph nodes than the control group (2.00±2.35 vs. 0.76±1.36 mm; P<0.0001), most notably in cervical levels III and IV (P<0.05 for both). HT seems to be associated with an ultrasonographic pattern of increased number of enlarged cervical lymph nodes, particularly in levels III, and IV.