Clinicopathologic Predictive Factors of Cervical Lymph Node Metastasis in Differentiated Thyroid Cancer

Background

Cervical lymph node metastasis (LNM) has been proven to be a predictor for locoregional recurrence in differentiated thyroid carcinoma (DTC). Clinicopathological features could be effective predictive factors for central and lateral LNM of DTC, and provide references to surgeons for cervical neck dissection.

Gene Therapy for Head and Neck Cancer

Objectives/Hypothesis New treatment methods are needed for head and neck cancer to improve survival without increasing morbidity. Gene therapy is a potential method of improving patient outcome. Progress in gene therapy for cancer is reviewed with emphasis on the limitations of vector technology and treatment strategies. Given the current technological vector limitations in transmitting the therapeutic genes, treatments that require the fewest number of cells to be altered by the new gene are optimal. Therefore an immune‐based gene therapy strategy was selected in which the tumors were transfected with the gene for an alloantigen, human leukocyte antigen (HLA)–B7, a class I major histocompatibility complex (MHC). This would restore an antigen presentation mechanism in the tumor to induce an antitumor response. This gene therapy strategy was tested in patients with advanced, unresectable head and neck cancer. Study Design Prospective trial. Methods Twenty patients with advanced head and neck cancer who had failed conventional therapy and did not e‐press HLA‐B7 were treated with gene therapy using a lipid vector by direct intratumoral injection. The gene therapy product contained the HLA‐B7 gene and the β2‐microglobulin gene, which permits complete e‐pression of the class I MHC at the cell surface. Patients were assessed for any adverse effects, for changes in tumor size, for time to disease progression, and for survival. Biopsy specimens were assessed for pathological response, HLA‐B7 e‐pression, apoptosis, cellular proliferation, CD‐8 cells, granzyme, and p53 status. Results There were no adverse effects from the gene therapy. At 16 weeks after beginning gene therapy, four patients had a partial response and two patients had stable disease. Two of the tumors completely responded clinically, but tumor was still seen on pathological examination. The time to disease progression in the responding patients was 20 to 80 weeks. The median survival in patients who completed gene therapy was 54 weeks, compared with 21 weeks in patients whose tumors progressed after the first cycle of treatment. One patient survived for 106 weeks without any additional therapy. HLA‐B7 was demonstrated in the treated tumors, and increased apoptosis was seen in the responding tumors. Conclusion Significant advances have been made in the field of gene therapy for cancer. Alloantigen gene therapy has had efficacy in the treatment of cancer and can induce tumor responses in head and neck tumors. Alloantigen gene therapy has significant potential as an adjunctive treatment of head and neck cancer.     

Electroporation Therapy in Head and Neck Cancer

Objective—To prove the efficacy of electroporation therapy (EPT) in T1 and T2 squamous cell cancers of the oral cavity and oropharynx. Material and Methods—Twelve patients were treated with EPT within the framework of a European trial. Tumors were infiltrated with a bleomycin solution and subsequently treated with EPT. Four weeks after treatment the necrotic mass at the site of the former tumor was resected with save margins and accurately examined histologically. Results—Whereas 10 specimens were completely free of cancer cells, 2 cases showed viable tumor cells. Conclusion—EPT has the potential to serve as an interesting alternative in the treatment of head and neck cancer.     

Papillary Thyroid Cancer: Controversies in the Management of Neck Metastasis

Objective/Hypothesis: To describe our institution's experience with the management of cervical metastasis in papillary thyroid carcinoma (PTC) and suggest a treatment strategy based on the incidence of pathologic nodes and cervical recurrence in patients undergoing varied surgical approaches to address lymphadenopathy over the study dates. Materials and Methods: Between December 1, 1972 and September 1, 2007, 183 total patients diagnosed with PTC at the University of Pittsburgh Medical Center were treated with lymphadenectomy. Pathologic parameters, including number of pathologic nodes and extent of lymphadenectomy were correlated to disease recurrence. Study Design: Retrospective chart review. Results: The incidence of pathologic nodes in lymphadenectomy specimens (57.9%) and the recurrence rate (33.7%) were high, in our study population. In comparing techniques with address lymphadenopathy, the highest recurrence rate was observed in patients with pathologic nodes treated with “lymph node plucking” procedures at the time of thyroidectomy and those patients with multiple nodes involved. Few patients with no pathologic nodes, regardless of lymphadenectomy extent recurred. Conclusions: Our data show that limited neck dissection and disease burden are associated with the highest rates of cervical recurrence in regional metastatic PTC. Comprehensive functional neck dissection would seem to offer the patient the best opportunity for control of cervical metastasis. The American Thyroid Association recommends thyroglobulin monitoring and ultrasound evaluation of the neck in all postoperative patients. Therefore patients with the diagnosis of papillary thyroid cancer need preoperative ultrasound of the lateral neck and fine needle aspiration of suspicious nodes to avoid undertreating patients scheduled for total thyroidectomy. Neck dissection of the compartments in which pathologic nodes were detected (central, lateral, or both) should then be undertaken at the time of initial thyroidectomy. Eliminating all disease remains elusive and the prognosticsignificance of cervical disease persistence and recurrence is still unknown. Patients with cervical metastasis are at substantial risk of regional recurrence, necessitating repeat surgery. Parathyroid implantation should be considered at the time of the initial surgery to reduce the risk of hypoparathyroidism should subsequent procedures be required. More information will be necessary to better understand the prognostic significance of these regional metastases. In the interim, many patients may be overtreated, whereas some remain at risk of death because of disease.     

Distribution of Lymph Nodes in the Neck in Cases of Tuberculous Cervical Lymphadenitis

Objective —To investigate the distribution of lymph nodes in the neck during the process of development of tuberculous cervical lymphadenitis (TCL) in patients attending an outpatient clinic over a 1-year period.

Material and Methods —This was a prospective, cross-sectional, observational study which included 100 cases of histopathologically confirmed TCL of >6 weeks duration.

Results —Lymph nodes in the posterior triangle (PT) were found to be commonest (51%), followed by those in the upper deep cervical (UDC; 48%) and submandibular (SM; 36%) regions. The supra-clavicular (SC; 3%), submental (Sment; 4%) and lower deep cervical (LDC; 9%) regions were found to be the least frequently affected. Uni- and bilateral disease were observed in 83% and 17% of patients, respectively. A single group of lymph nodes was involved in 68% of patients, 2 groups in 29% and >2 groups in 13% of patients.

Conclusions —These results indicate that if unilateral, painless, enlarged and mated lymph nodes are found in either the PT or the UDC or SM areas, lymphadenitis of tuberculous origin should be suspected rather than lymphadenitis of any other etiology.     

Animal Models of Cancer in the Head and Neck Region

Animal models that resemble the cancers of the head and neck region are of paramount importance in studying the carcinogenesis of these diseases. Although several methods for modeling cancer in the head and neck are available, none are fully satisfactory. Subcutaneous xenograft models of cancer in nude mice are often used in preclinical studies. However, these models are problematic in several aspects as they lack the specific interactions that exist between the tumor cells and their native environment. Establishment of tumors at the orthotopic sites restore these distinct patterns of interactions between the tumor and the host organs that are lost or altered when the tumors are established in ectopic sites. With regard to the transgenic model of cancer in the head and neck region, it should be kept in mind that the transgene used to drive the malignant transformation may not be representative of the carcinogenic process found in human tumors. Low penetrance of tumor formation also translates into high cost and time commitment in performing studies with transgenic models. In this review, we will discuss some of the commonly used methods for modeling cancer in the head and neck region including squamous cell carcinoma of the head and neck as well as thyroid carcinoma.     

Screening for Distant Metastases in Patients With Head and Neck Cancer

Objectives The detection of distant metastases at initial evaluation may alter the selection of therapy in patients with head and neck squamous cell carcinoma (HNSCC). In this study the value of screening for distant metastases is evaluated. Study Design Retrospective analysis. Methods The results of screening for distant metastases were retrospectively analyzed in 101 consecutive HNSCC patients with high‐risk factors who were scheduled for major surgery. All patients had computed tomography (CT) scan of the thorax, bone scintigraphy, examination of the liver by ultrasound and/or CT scan, and blood tests. Results Distant metastases were found in 17% of the patients. Patients with four or more clinical lymph node metastases or low jugular lymph node metastases had the highest incidence of distant metastases (33%). CT scan of the thorax detected in 12 patients, lung metastases; in 4, mediastinal lymph node metastases; and in 2, primary lung tumors. Bone scintigraphy detected in four patients bone metastases; in all four patients lung or mediastinal lymph node metastases were also found. Ultrasound and/or CT scan of the liver revealed one patient with metastases. Blood tests did not show any significant difference between patients with or without bone or liver metastases. Conclusions Screening in patients with three or more lymph node metastases, bilateral lymph node metastases, lymph nodes of 6 cm or larger, low jugular lymph node metastases, locoregional tumor recurrence, and second primary tumors revealed distant metastases in 10% or more. CT scan of the thorax is currently the single most important diagnostic technique for screening of distant metastases.     

Pathologic Detection of Occult Metastases in Regional Lymph Nodes in Patients with Head and Neck Cancer

Squamous carcinomas of the head and neck region are exceedingly common problems in the routine practice of head and neck tumour surgery. Well-defined treatment protocols have evolved to manage patients afflicted with such tumours. This article explores the role of the hospital pathologist in the detection of occult metastases. The conventional approach to evaluation of cervical nodes from a neck dissection is reviewed, and then the potential utility of more recently developed diagnostic approaches (such as immunohistochemistry and polymerase chain reaction) is explored.