Cervical Lymph Node Micrometastases Research Articles

Prophylactic central lymph node dissection in differentiated thyroid cancer - benefits and risk.

Papillary thyroid cancer is the most common thyroid malignancy. Lymph nodes involvement is common in differentiated thyroid cancer, and cervical lymph node micrometastases are observed in up to 85% of patients with papillary thyroid cancer during surgery. While the therapeutic central lymph node dissection has been accepted, the debate on the prophylactic in differentiated thyroid carcinoma (DTC) continues.

Significance of micrometastases in the calculation of the lymph node ratio for papillary thyroid cancer.

PurposeThe lymph node ratio (LNR) is an important prognostic factor in papillary thyroid carcinoma (PTC), but micrometastases in cervical lymph nodes (LNs) are not of great clinical importance. In this study, we analyzed the accuracy of prediction of the prognosis depending on whether micrometastases were included in the number of metastatic LNs when calculating LNR.MethodsThe study included 353 PTC patients who underwent total thyroidectomy with neck LN dissection, and calculated LNR by 2 methods according to whether micrometastases were included in the number of metastatic LNs: Method 1 did not and method 2 did include. To compare the predictive values of LNR by the 2 methods, correlation coefficients and receiver operating characteristic (ROC) curves were analyzed.ResultsPositive correlations were found between LNR and preablation stimulated thyroglobulin (sTg) levels in both methods, but the correlation between method 1 LNR and preablation sTg level was significantly stronger than that for method 2 (Fisher z = 1.7, P = 0.045). The areas under these 2 independent ROC curves were analyzed; the prognostic efficacy of method 1 LNR was more accurate than that of method 2 LNR, and the difference was statistically significant (P = 0.0001).ConclusionRegional recurrence of PTC can be predicted more accurately by not including micrometastases in the number of metastatic LNs when calculating LNR.

Clinical significance of prophylactic central compartment neck dissection in the treatment of clinically node-negative papillary thyroid cancer patients.

BackgroundLymph nodal involvement is very common in differentiated thyroid cancer, and in addition, cervical lymph node micrometastases are observed in up to 80 % of papillary thyroid cancers. During the last decades, the role of routine central lymph node dissection (RCLD) in the treatment of papillary thyroid cancer (PTC) has been an object of research, and it is now still controversial. Nevertheless, many scientific societies and referral authors have definitely stated that even if in expert hands, RCLD is not associated to higher morbidity; it should be indicated only in selected cases.Main bodyIn order to better analyze the current role of prophylactic neck dissection in the surgical treatment of papillary thyroid cancers, an analysis of the most recent literature data was performed. Prophylactic or therapeutic lymph node dissection, selective, lateral or central lymph node dissection, modified radical neck dissection, and papillary thyroid cancer were used by the authors as keywords performing a PubMed database research. Literature reviews, PTCs large clinical series and the most recent guidelines of different referral endocrine societies, inhering neck dissection for papillary thyroid cancers, were also specifically evaluated. A higher PTC incidence was nowadays reported in differentiated thyroid cancer (DTC) clinical series. In addition, ultrasound guided fine-needle aspiration citology allowed a more precocious diagnosis in the early phases of disease. The role of prophylactic neck dissection in papillary thyroid cancer management remains controversial especially regarding indications, approach, and surgical extension. Even if morbidity rates seem to be similar to those reported after total thyroidectomy alone, RCLD impact on local recurrence and long-term survival is still a matter of research. Nevertheless, only a selective use in high-risk cases is supported by more and more scientific data.ConclusionsIn the last years, higher papillary thyroid cancer incidence and more precocious diagnoses were worldwide reported. Among endocrine and neck surgeons, there is agreement about indications to prophylactic treatment of node-negative “high-risk” patients. A recent trend toward RCLD avoiding radioactive treatment is still debated, but nevertheless, prophylactic dissections in low-risk cases should be avoided. Prospective randomized trials are needed to evaluate the benefits of different approaches and allow to drawn definitive conclusions.

Detection of Cervical Lymph Node Micrometastases in Patients with Squamous Cell Carcinoma of the Oral Cavity, Pharynx and Larynx.

The goal of this prospective study was to determine the frequency of micrometastases in patients with squamous cell carcinoma (SCC) of the oral cavity, pharynx and larynx in whom elective neck dissection was indicated (cN0). A total of 12 patients (10 males and 2 females) were enrolled in the study. The age ranged 42-73 years (median 62 years). Elective neck dissection was performed in all patients (8 ipsilateral, 4 bilateral) and a total of 256 lymph nodes were removed and sent for microscopic examination. The presence of tumor cells in cervical lymph nodes was found in 5/12 (42%) patients. Micrometastases of SCC were found in two patients and isolated tumor cells (ITC) in two other patients. In the remaining one patient with oropharyngeal SCC, a micrometastasis of papillary thyroid carcinoma (PTC) was detected. Positive lymph nodes were localized in level II in three patients with SCC of larynx, hypopharynx and tongue base, respectively, in level I in one patient with SCC of oral tongue and in level III in one patient with PTC. Our results indicate that SCC of head and neck has a high potential for creating micrometastases which frequency is higher compared to clinically detected macrometastases. Therefore, elective neck dissection or radiotherapy of the neck should be considered in patients with high risk of occult metastases or micrometastases.

The current status of lymph node dissection in the treatment of papillary thyroid cancer. A literature review.

Cervical lymph node micrometastases are observed in up to 90% of papillary thyroid cancers (PTC), showing that lymph nodal involvement is very common. Nevertheless, during the last years, the role of lymph node dissection in the treatment of PTC has been controversial and, at present, the best indications to the routine or therapeutic neck dissection remain subject of research. In order to better analyze the current role of lymph node dissection in the surgical treatment of PTC, an analysis of the most recent literature data was performed. By using as keywords lymph node dissection, selective, lateral or central lymph node dissection, modified radical neck dissection, prophylactic or therapeutic lymph node dissection, papillary thyroid cancer, a Pub Med data base research was carried out. The most recent guidelines of different referral endocrine societies, inhering neck dissection for PTC, were also evaluated. The role of neck dissection in PTC management remains controversial regarding routine or therapeutic indications, surgical extension, and its impact on local recurrence and long term survival. Due to inhomogeneous literature data, the current status of node dissection is still subject of research. There is agreement between endocrine and neck surgeons about the extension of therapeutic lymph node dissection in N+ PTC patients , and also in the prophylactic treatment of N0 "high risk" patients. Considering a recent trend toward routine central lymphadenectomy avoiding radioactive treatment, prospective randomized trials are needed to evaluate the benefits of different approaches.

Immunohistochemistry, A Valuable Tool in Detection of Cervical Lymph Node Micrometastases in Head and Neck Squamous Cell Carcinoma: A Prospective Study

The regional failure after comprehensive clearance of neck metastasis and consequent pathological report of N0 disease has been reported fairly frequently. The role of recurrence of disease in the neck in the cases has been variously reported by different authors. The light microscopy does not detect the micrometastasis and the specimen is reported negative for metastasis. The presence of micrometastasis (the reason for neck failure) has been reported by many studies as 5-58 % (mean 19.6 %). These figures are significantly high. The present study was done to ascertain the micrometastasis after comprehensive neck clearance (pN0 report). Two groups of patients were included in this study. (1) Group I included patients with N0 necks (80 patients). (2) Group II included Patients with N+ necks (107 patients). We found that 20 % case were reported N0 (Group I) in light microscopy but on immunohistochemistry these were positive for disease. 15 % upstaging was reported in N+ cases (Group 2). Immunohistochemistry has been more sensitive for cancer detection and has significantly changed the tumor staging and its consequent management.

Micrometastases in cervical lymph nodes from patients with squamous carcinoma of the head and neck: should they be actively sought? Maybe

Techniques are now being developed, which allow ever smaller metastatic deposits in regional lymph nodes to be detected; the question is, should they be sought, or does their presence convey no additional information for treatment of head and neck carcinoma patients at this time? Preliminary findings have suggested that the presence of micrometastases may carry with it some prognostic information, and as a consequence, the search for micrometastases would, for the foreseeable future, appear to be a fertile ground for investigation. To bring some uniformity to this project, it is suggested that these definitions be adopted: a micrometastasis measures greater than 0.2 mm but less than 2.0 mm in diameter, and smaller deposits should be designated as isolated tumor cells, which, in turn, are subdivided into those isolated tumor cells detected by light microscopy, immunohistochemistry, or molecular methods. At this juncture, the import of such micrometastases remains in the realm of the clinical investigator—it remains an open question whether the identification of micrometastases (however they may ultimately come to be defined) will prove to have an impact on the care of head and neck cancer patients.

Determination of lymph node micrometastases in patients with supraglottic carcinoma

Conclusions. The frequency of loss of heterozygosity (LOH) at D9S 171 microsatellite locus on 9p21 may serve as an available method to evaluate occult micrometastases in laryngeal squamous cell carcinoma. High frequency of LOH was associated with a decreased probability of survival time. Objective. To explore an available and sensitive method to detect cervical lymph node micrometastases in patients with laryngeal squamous cell carcinoma, the frequency of LOH at D9S171 microsatellite locus on 9p21 was studied. Patients and methods. Twenty samples from supraglottic cancer and 182 lymph nodes from neck dissections were examined by LOH comparing immunohistochemical (IHC) staining using cytokeratin 19 (CK19), and hematoxylin and eosin (H&E) staining. The frequency of lymph node metastasis and the clinical relevance were analysed. Results. The frequency of LOH was 37.4% of lymph nodes and all of the primary tumors. Occult micrometastases were present in 9 of 20 cases; 23.6% of lymph nodes were positive for CK19 by IHC; 16.5% of lymph nodes were positive by H&E. There was a highly significant difference among the three methods. The highest rate of positive lymph nodes was at level II of the neck. There was a highly significant difference between overall survival time and lymph node metastasis with LOH and CK19 analysis.

Immunohistochemical detection of cervical lymph node micrometastases from T2N0 tongue cancer

ConclusionsThese results indicate that extensive, multiple cervical micrometastases occurred from an early stage in patients with T2N0 tongue cancer. The presence of micrometastases suggests the necessity of preventive neck dissection for Level I–IV nodes as a radical treatment.ObjectiveCervical lymph node metastases occur with a relatively high frequency in patients with T2N0 squamous cell carcinoma of the tongue, and control of the metastases greatly influences the prognosis of patients. In this study, micrometastases in the cervical lymph nodes were investigated to clarify the necessity and required extent of preventive neck dissection.Material and methodsWe investigated micrometastases in 24 subjects who had previously been diagnosed with T2N0 tongue cancer. We performed immunostaining with anti-cytokeratin antibody cocktail AE1/AE3 of sections of 401 paraffin-embedded lymph nodes obtained from these patients.ResultsMicrometastases were observed in 14 patients (58%) and were most abundant in Level II nodes (n=11; 46%). Micrometastases were observed in the Level IV nodes of 3 patients (13%), and upstaging to pN2b occurred in 7 patients (29%).

Detection of cervical lymph node micrometastases in oral squamous cell carcinoma by cytokeratin 8 mRNA with reverse transcription-polymerase chain reaction

Detection of cervical lymph node micrometastases in oral squamous cell carcinoma by cytokeratin 8 mRNA with reverse transcription-polymerase chain reaction

Keratin mRNA for detecting micrometastasis in cervical lymph nodes of oral cancer

We studied three keratin (K) gene candidates, K13, K19, and K20 mRNAs, for detecting micrometastases in cervical lymph nodes (LNs) by reverse transcriptase-polymerase chain reaction (RT-PCR). Of 166 histologically metastasis-negative nodes, 24 micrometastatic LNs (14.4%) were detected based on K13 gene expression. Keratin 19 mRNA is an inadequate marker for the genetic diagnosis due to not only illegitimate gene expression from lymphatic tissue but also gene expression from the ectopic salivary gland. Keratin 20 mRNA showed low sensitivity. It is suggested that K13 mRNA may be a promising tumor marker among these keratin genes for detecting the micrometastases in cervical LNs of oral cancer.

Genetic diagnosis of micrometastasis based on SCC antigen mRNA in cervical lymph nodes of head and neck cancer.

This study is designed to assess gene expression of squamous cell carcinoma antigen (SCCA) mRNA to detect micrometastases in cervical lymph nodes (LNs) of head and neck cancer. We examined the expression of SCCA mRNA in 12 primary tumors and 212 cervical LNs (101 LNs taken from 8 patients with tongue cancer, 71 from 7 patients with gingival cancer, 19 from 2 patients with laryngeal cancer, 9 from 2 patients with pharyngeal cancer, 7 from 1 patient with cancer of the buccal mucosa, and 5 from 1 patient with cancer of floor of the mouth). Detectability of metastatic LNs by nested and single reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with semiserial sections (hematoxylin-eosin staining and keratin immunostaining). All primary tumors expressed SCCA mRNA. Of 198 histologically metastasis-negative nodes, SCCA mRNA was detected in 37 (18.7%) by nested PCR. Eleven micrometastatic foci in 9 LNs (4.6%) were discovered by semiserial sectioning. This suggests that SCCA mRNA is a promising tumor marker for detecting the micrometastases in cervical LNs of head and neck cancer.

Micrometastases from squamous cell carcinoma in neck dissection specimens

The incidence of micrometastases in cervical lymph nodes from squamous cell carcinomas of the head and neck was studied using routine histopathological examination. Micrometastases were found in 66 lymph nodes in 41 of the 92 tumor-positive neck dissection specimens. The detection of these micrometastases influenced postoperative treatment in 3 of the 77 patients with neck node metastases. The value of additional sectioning for detecting micrometastases was thus assessed. Sectioning at a deeper level in 600 originally histopathologically negative lymph nodes from 64 patients revealed 7 additional micrometastases in 5 patients. Antikeratin staining with a mixture of two monoclonal antibodies (AE1 and AE3) revealed 4 micrometastases in 739 originally histopathologically negative lymph nodes in 3 of 13 patients studied. Because of the unknown prognostic significance of micrometastases and the consequent arbitrary consequences for postoperative treatment, present findings show that the extra workload of immunostaining and deeper sectioning does not warrant their routine use in clinical practise.