Tumor Infiltrating Lymphocytes in Occult Primary HPV+ Oropharyngeal Squamous Cell Carcinoma (OPSCC): Comparison of the Primary Tumor and Regional Lymph Node Metastases

Introduction: Several studies suggest an estrogen receptor alpha (ERα)-mediated influence on the pathogenesis of oral squamous cell carcinoma (OSCC), as described for other malignancies that are not considered to be primarily hormone-dependent. Recently, an association between ERα expression and improved survival in oropharyngeal squamous cell carcinoma (OPSCC) has been found. However, the prognostic relevance of ERα in OSCC has not been proven to date. Therefore, the aim of this study was to evaluate ERα expression in OSCC in a large patient cohort and analyze its influence on survival and recurrence. Material and Methods: A total of 316 patients with primary OSCC who received initial surgical therapy were included in this analysis. The expression of ERα was evaluated on tissue microarrays by immunohistochemistry in the primary tumor and/or primary lymph node metastases. The expression level was quantified by light microscopy using the immunoreactive score (IRS) for estrogen receptor detection. An IRS equal to or greater than 2 was considered positive. The 5-year overall survival (OS) and relapse-free survival (RFS) were examined by the Kaplan–Meier method and log-rank test. Results: A total of 316 patients (111 females; 205 males) with a mean age of 61.3 years (range 27–96 years) were included in this study. In 16 patients (5.1%; 6 females and 10 males), positive ERα expression was found in the primary tumor (n = 11; 11/302) or lymph node metastases (n = 5; 5/52). Patients with positive ERα expression in primary tumors/primary lymph node metastases had a significantly lower OS and RFS (p = 0.012; p = 0.0053) compared to ERα-negative patients. Sub-group analysis in relation to gender revealed a highly significant influence of ERα expression on OS and RFS in males but not in females, both for the ERα-positive primary tumor cohort (males: p = 0.0013; p < 0.0001; females: p = 0.56; p = 0.89) and the ERα-positive primary tumor/primary lymph node metastasis cohort (males: p < 0.0001; p < 0.0001; females: p = 0.95; p = 0.96). In multivariate cox regression analysis, the ERα IRS of primary tumors (dichotomized; ERα+ vs. ERα−) was an independent risk factor for OS (HR = 4.230; 95%CI 1.616–11.076; p = 0.003) and RFS (HR = 12.390; 95%CI 4.073–37.693; p < 0.001) in the male cohort. There was a significant difference (p = 0.006) of ERα positivity with regard to the localization of the primary tumor. ERα positivity in the primary tumor was significantly associated (p = 0.026) with UICC stage, with most of the cases being diagnosed in stage IV. Furthermore, there was a significantly (p = 0.049) higher rate of bone infiltration in ERα-positive patients. Conclusion: Expression of ERα is rare in OSCC; however, it is associated with a dramatic decrease in OS in male patients. Further studies are necessary to confirm our results and to evaluate the exact mechanism underlying this observation. Hence, ERα-positive OSCC patients might benefit from an ER-based therapeutic (adjuvant) approach in the future.

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Correlation between disease progression and histopathologic criterions of the lip squamous cell carcinoma

Vojnosanitetski pregled ◽

10.2298/vsp1001019g ◽

2010 ◽

Vol 67 (1) ◽

pp. 19-24 ◽

Cited By ~ 2

Author(s):

Mileta Golubovic ◽

Bogdan Asanin ◽

Drago Jelovac ◽

Milan Petrovic ◽

Marija Antunovic

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lymph Node Metastases ◽

Tumor Size ◽

Regional Lymph Node ◽

Disease Relapse ◽

Upper Lip ◽

Node Metastases

Background/Aim.The most common malignancy of the lip is squamous cell carcinoma (SCC). In our population, according to epidemiological data, almost a half of all (45%) SCC of oral mucous tissue spreads over the lower and upper lip. The aim of this study was to estimate prognostic importance of histopathologic characteristics - histologic grade, nuclear grade and tumor size in relation to the appearance of lymph node metastases and relapse in SCC of the lip. Methods. In the retrospective- prospective study 70 cases of lower and upper lip SCC were analyzed. They were diagnosed from 2002 to 2006 in the Clinic of Maxillofacial Surgery, Clinical Center of Montenegro. The data about localization of the carcinomas, histopathologic characteristics and lymph node status were taken from medical files of the patients. The patients were followed up in a 3-year period and the disease relapse or/and metastatic disease appearance were registereds. Results. There was statistically significant difference in tumor size among the patients with and without disease relapse (p = 0.027). Logistic regression analysis showed that the tumor size is a statistically significant factor (R = 0.186; p = 0.011) for the appearance of regional lymph node metastases. Relative risk [exp (B)] for the appearance of regional lymph node metastases in relation to tumor size was 2.807. Conclusion. Histologic and nuclear grade of lip SCC are not prognostic factors for the appearance of the disease relapse and regional lymph node metastases. Tumor size is a predictive factor of the relapse appearance, as well as for lymph node metastases appearance. In clinical practice, tumor size is a factor that classifies patients with lip SCC into the groups of higher and smaller risk of relapse appearance and for lymph node metastases appearance. Our results suggest that, risk for lymph node metastases appearance increases 2.8 times with increasing of the tumor size over 2 cm in diameter.

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Distribution of Lymph Node Metastases in Esophageal Carcinoma Patients Undergoing Upfront Surgery: A Systematic Review

Cancers ◽

10.3390/cancers12061592 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1592

Author(s):

Eliza R. C. Hagens ◽

Mark I. van Berge Henegouwen ◽

Suzanne S. Gisbertz

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Cancer ◽

Lymph Node ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lymph Node Metastases ◽

Primary Tumor ◽

Tumor Location ◽

Primary Tumor Location ◽

Node Metastases

Metastatic lymphatic mapping in esophageal cancer is important to determine the optimal extent of the radiation field in case of neoadjuvant chemoradiotherapy and lymphadenectomy when esophagectomy is indicated. The objective of this review is to identify the distribution pattern of metastatic lymphatic spread in relation to histology, tumor location, and T-stage in patients with esophageal cancer. Embase and Medline databases were searched by two independent researchers. Studies were included if published before July 2019 and if a transthoracic esophagectomy with a complete 2- or 3-field lymphadenectomy was performed without neoadjuvant therapy. The prevalence of lymph node metastases was described per histologic subtype and primary tumor location. Fourteen studies were included in this review with a total of 8952 patients. We found that both squamous cell carcinoma and adenocarcinoma metastasize to cervical, thoracic, and abdominal lymph node stations, regardless of the primary tumor location. In patients with an upper, middle, and lower thoracic squamous cell carcinoma, the lymph nodes along the right recurrent nerve are often affected (34%, 24% and 10%, respectively). Few studies describe the metastatic pattern of adenocarcinoma. The current literature is heterogeneous in the classification and reporting of lymph node metastases. This complicates evidence-based strategies in neoadjuvant and surgical treatment.

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Clinicopathological Risk Factors for Contralateral Lymph Node Metastases in Intraoral Squamous Cell Carcinoma: A Study of 331 Cases

Current Oncology ◽

10.3390/curroncol28030175 ◽

2021 ◽

Vol 28 (3) ◽

pp. 1886-1898

Author(s):

Christian Flörke ◽

Aydin Gülses ◽

Christina-Randi Altmann ◽

Jörg Wiltfang ◽

Henning Wieker ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Cell Carcinoma ◽

Squamous Cell ◽

Lymph Node Metastases ◽

Squamous Cell Carcinomas ◽

Patient Specific ◽

Infiltration Depth ◽

Tumor Grading ◽

Node Metastases

The current study aimed to examine the effects of clinicopathological factors, including the region, midline involvement, T classification, histological grade, and differentiation of the tumor on the rate of contralateral lymph node metastasis for oral squamous cell carcinoma and to assess their effects on survival rates. A total of 331 patients with intraoral squamous cell carcinomas were included. The influence of tumor location, T status, midline involvement, tumor grading, and the infiltration depth of the tumor on the pattern of metastasis was evaluated. Additionally, the effect of contralateral metastases on the prognosis was examined. Metastases of the contralateral side occurred most frequently in squamous cell carcinomas of the palate and floor of the mouth. Furthermore, tumors with a high T status resulted in significantly higher rates of contralateral metastases. Similarly, the midline involvement, tumor grading, existing ipsilateral metastases, and the infiltration depth of the tumor had a highly significant influence on the development of lymph node metastases on the opposite side. Oral squamous cell carcinomas require a patient-specific decision. There is an ongoing need for further prospective studies to confirm the validity of the prognostic factors described herein.

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