ABSTRACT Objective: The aim of this study was to evaluate the association between this characteristic and outcomes in patients with lymph node metastasis in a Brazilian cohort. Subjects and methods: This study examined a retrospective cohort of adult patients diagnosed with differentiated thyroid cancer and lymph node metastases from 1998 to 2015 in two referral centers. Number, location, size and extranodal extension (ENE) of metastatic lymph nodes were assessed and correlated with response to initial therapy. Results: A greater number of metastatic nodes, larger size, presence of lateral neck disease and ENE were all associated with a lower probability of achieving an excellent response to initial therapy (p ≤ 0.05 for all these parameters). Local recurrent disease had a significant association with lymph node number (6 in the recurrence/persistence group versus 4 in the non-recurrent group; p = 0.02) and ENE (19.2 versus 75%, p = 0.03). Lateral neck disease was the only characteristic associated with distant metastasis and was present in 52.1% of the group without metastasis and 70.4% of the group with metastasis (p = 0.001). Conclusion: The lymph node characteristics were associated with response to initial therapy and neck recurrence/persistence, confirming the importance of the analysis of these factors in risk stratification in a Brazilian population and its possible use to tailor initial staging and long term follow-up.

RESUMO Objetivo: Avaliar a importância da reatividade linfonodal na recidiva e mortalidade em pacientes com carcinoma epidermoide de laringe estagiados como pT3 ou pT4 pN0 M0. Métodos: Entre 2002 e 2005, foram selecionados 105 pacientes matriculados na Seção de Cirurgia de Cabeça e Pescoço do Instituto Nacional de Câncer (INCA) com o diagnóstico de carcinoma epidermoide de laringe, com estágio III ou IV. A radioterapia foi indicada em 69 casos. Todos os pacientes foram estagiados como pT3 ou pT4 e pN0. Todos os linfonodos ressecados foram analisados e classificados conforme os quatro padrões de reatividade linfonodal: hiperplasia folicular associada à resposta imune humoral, hiperplasia paracortical associada à resposta imune celular, histiocitose sinusal sem relação com resposta imune específica, e linfonodo normal. Os dois primeiros padrões são definidos como linfonodos estimulados e os dois últimos como linfonodos não-estimulados. O padrão linfonodal mais frequente em cada paciente foi considerado para a análise da relação com a recidiva e mortalidade. Resultados: Foi analisado um total de 3.648 linfonodos, com média de 34,7 linfonodos por paciente. O padrão de reatividade mais frequente foi a histiocitose sinusal (50 casos), seguido da hiperplasia paracortical (35 casos) e da hiperplasia folicular (20 casos), sendo esses padrões sem relação com a recidiva (p = 0,98) ou mortalidade (p = 0,49). No entanto, o estímulo da imunidade celular relacionada à hiperplasia paracervical apresentou relação com significância estatística com melhor sobrevida global em cinco anos (76 versus 60%; log-rank = 0,05). Conclusões: houve correlação positiva entre o padrão de estímulo da imunidade celular e o aumento da sobrevida em cinco anos em paciente pN0 com carcinoma epidermoide de laringe sugerindo a indicação de tratamento adjuvante em casos que apresentarem diminuição da imunidade celular mesmo na ausência de metástases patológicas detectadas pelos métodos habituais.

ABSTRACT Objective: To evaluate the influence of lymph node reactivity on recurrence and survival rates in a population of pT3 or pT4 pN0 patients with laryngeal squamous cell carcinoma. Methods: Between 2002 and 2005, 105 patients with LSSC underwent total laryngectomy with bilateral selective neck dissection including levels II, III and IV. Most (69) received PO radiotherapy. All pathological specimens were either pT3 or pT4, and all necks were pN0. All lymph nodes were analyzed and their reactivity status were classified as the following four patterns: follicular hyperplasia associated with humoral response, paracortical hyperplasia associated with cellular response, sinus histiocytosis with no association with specific immune response, or normal lymph node. Only the first two patterns were considered stimulated, whereas the last two were considered non-stimulated. The most prevalent pattern in a particular neck specimen was considered for the analysis of recurrence and survival. Results: The total number of lymph nodes studied was 3,648, with an average of 34.7 lymph nodes/neck specimens. The most frequent lymph node reactivity patterns were sinusal histiocytosis (50 cases), paracortical hyperplasia (35 cases), and follicular hyperplasia (20 cases). There was no statistical association of these individual patterns with recurrence rate (p = 0.98) or mortality (p = 0.49). However, there was a statistically significant association between paracortical hyperplasia pattern (related to cellular lymph node immunity) and improved five-year survival (76 versus 60%; log-rank = 0.05). Conclusions: There was a positive correlation between stimulated cellular lymph node pattern and improved 5-year survival rate in patients with pN0 laryngeal squamous cell carcinoma, suggesting the indication of adjuvant treatment for those individuals with decreased immune response, even in the absence of pathologic metastases detected by the usual methods.

OBJETIVO: Avaliar o valor prognóstico da invasão de cartilagens (tireóide, cricóide) no câncer de laringe, com relação à sobrevida livre de doença. MÉTODO: Foi realizada uma análise retrospectiva de 102 pacientes com câncer de laringe atendidos no período de 1992 a 1994 no Hospital do Câncer - INCA/MS-RJ, que foram divididos em quatro grupos: pacientes com tumores T3N0M0, estádio III (excluídos os pacientes com tumores T3N1M0); T4N0M0 (com invasão tumoral de cartilagem do laringe sem extravasamento); T4N0M0 (com extravasamento neoplásico pelo compartimento laríngeo); e pacientes com linfadenopatia cervical metastática (T3N2-3/T4N1-2-3). Foram realizadas curvas de sobrevida para cada grupo e comparada a diferença de sobrevida entre estes grupos, utilizando o método de Kaplan-Meier. O valor da significância estatística da diferença de sobrevida dos quatro grupos foi avaliado pelo método de Wilcoxon-Gehan. RESULTADOS: Os pacientes que apresentaram apenas invasão tumoral de cartilagem de laringe, sem extravasá-la (T4N0M0), se comportam como os pacientes com tumores T3N0M0, sem diferença estatística com relação à sobrevida (p=0,36). Os que apresentam apenas invasão neoplásica de cartilagens de laringe (T4N0M0) tiveram melhor prognóstico com relação à sobrevida, do que aqueles com extravasamento neoplásico pelo compartimento laríngeo (T4N0M0) (p=0,02). A presença de linfonodos metastáticos foi o fator que apresentou maior impacto adverso no prognóstico com relação à sobrevida (p=0,002). CONCLUSÃO: Os achados deste estudo questionam a validade da atual classificação TNM em estadiar tumores T4N0M0 de laringe. Novos estudos, com uma casuística maior, são necessários para que os resultados obtidos sejam corroborados.

BACKGROUND: To evaluate the prognostic value of the cartilage invasion (thyroid, cricoid) in laryngeal cancer, in relation to disease free survival period. METHOD: Examination was made of the charts of 102 patients with cancer of the larynx treated at the INCA/MS-RJ Cancer Hospital between 1992 and 1994. These patients were divided into 4 groups: those having T3N0M0 stage III tumors (excluding patients with T3N1M0); those having T4N0M0 (with tumoral invasion of laryngeal cartilage without extralaryngeal spread); those having T4N0M0 (with neoplastic spread through the laryngeal compartment); and those having metastatic cervical lymphadenopathy (T3N2-3/T4N1-2-3). Survival rate curves were drawn for each group and the survival rate differences between the groups were compared using the Kaplan-Meier method. The value of statistical significance were calculated using the Wilcoxon-Gehan method. RESULTS: Those patients who presented with tumoral invasion of laryngeal cartilage without neoplastic spread, behaved like those with T3N0M0 tumors, with no statistical survival rate difference (p=0.36). Patients who had neoplastic invasion of the laryngeal cartilage (T4N0M0) had a better prognostic than those with extra laryngeal neoplastic spread (T4N0M0) (p=0.02). The presence of metastatic lymph nodes was the main adverse factor affecting prognosis (p=0.002). CONCLUSION: The findings of this study call into question the validity of the present TNM classification in the staging of T4N0M0 laryngeal tumors. New studies, based on a larger number of cases, are needed to corroborate our results.

Revisamos nossa experiência com carcinoma epidermóide metastático (CEM) para o pescoço com tumor primário desconhecido com a intenção de evidenciar quando o tratamento radioterápico exclusivo ou o tratamento cirúrgico seguido de radioterapia teriam impacto positivo sobre a sobrevida. Este é um estudo retrospectivo de 54 pacientes com CEM tratados na Seção de Cirurgia de Cabeça e Pescoço do Hospital do Câncer/INCa entre 1986 e 1992. Quarenta e oito pacientes (89%) eram do sexo masculino, a idade média foi de 54 anos. Quarenta pacientes tinham metástase para linfonodos cervicais da cadeia jugular interna alta (nível 2). Utilizamos a classificação TNM da UICC de 1992 para estagiar os pacientes, onde oito pacientes foram classificados como N1, vinte como N2, 22 como N3, sendo que quatro pacientes permaneceram não classificados. Todos foram submetidos a endoscopia do trato aerodigestivo superior e raio X de tórax. Trinta e cinco pacientes foram submetidos a biópsia de aspiração com agulha fina. Trinta e oito pacientes tiveram tratamento com intenção curativa e 1.6 tiveram tratamento paliativo com radioterapia. Dos pacientes tratados com intenção curativa, dez foram submetidos a esvaziamento cervical e 28 tiveram tratamento exclusivo com radioterapia. Os 16 pacientes tratados com intenção paliativa foram excluídos dos cálculos de sobrevida e análise das recidivas. As recidivas cervicais foram analisadas usando o método do qui-quadrado, e as curvas de sobrevida foram comparadas usando-se o teste de Wilcoxon. A biópsia aspirativa com agulha fina alcançou o diagnóstico em 85% dos casos. Oito pacientes (15%) apresentaram metástase à distância. O tumor primário foi identificado subseqüentemente em 9% dos pacientes. Dezoito pacientes (64%) tratados com radioterapia exclusiva tiveram recidivas no pescoço, e três pacientes (33%) tratados com cirurgia + radioterapia tiveram recidivas no pescoço. (p=0,05) Os pacientes classificados como N2/N3 tratados com cirurgia + radioterapia tiveram melhores resultados do que os tratados com radioterapia exclusiva (respectivamente p=0,05 e p=0,09). Os pacientes Nl tiveram melhor sobrevida livre de doença do que os pacientes N2/N3 (respectivamente p=0,007 e p=0,OO7). A sobrevida livre de doença em cinco anos foi de 69% para os pacientes Nl, 11 % para os pacientes N2 e 15% para os pacientes N3. A sobrevida livre de doença para todos os estágios foi de 28%. A biópsia aspirativa com agulha fina é um bom meio para diagnóstico e deve ser usada rotineiramente.

We reviewed our experience with metastatic squamous cell carcinoma (MSCC) to the neck from an occult origin in order to assess whether radiotherapy alone or radiotherapy plus surgery improved the local control of disease. This retrospective study reviewed 54 patients with MSCC treated in our service between 1986 and 1992. Six patients (11%) were female and 48 patients (89%) male. The mean age were 54 years old. Forty patients (74%) had metastasis to level 2. Using the TNM classification of UICC 1992, 8 patients were classified as N1, 20 patients as N2, 22 patients as N3, and 4 patients were unclassified. All patients underwent upper aero-digestive endoscopy and chest X-ray. Thirty-five patients (85%) had fine- needle aspiration biopsy, 11 patients had excisional biopsy and 15 underwent incisional biopsy elsewhere. Thirty-eight patients were treated for cure and 16 patients had palliative treatment with radiotherapy. Ten patients were underwent neck dissection and 28 patients radiotherapy alone. Sixteen patients were treated with radiotherapy and palliative intention and were excluded from the survival and local failure analysis. Neck failure was analyzed using thec² methods, comparing the modalities of treatment (surgery plus rxt, rxt alone), and the differences on diseases free survival were analyzed using the Wilcoxon signed rank test Fine-needle biopsy made the diagnosis in 85.3% of the patients. Eight patients (15%) had distant metastasis. Primary carcinomas were identified subsequently in 5 patients (9.4%) Eighteen patients (64%) treated with radiotherapy alone had neck recurrences, 3 patients (33%) treated with surgery + radiotherapy had neck failures, (P=0.05). Control of the neck was better in patients N2 and N3 treated with surgery plus radiotherapy respectively p=0.05 and p=0.09. Comparing the diseases free survival of N 1/N2 patients and N I/N3 patients, the patients staged as N 1 had significant better survival (respectively p=0.007 and p=0.007). The five-year disease free survival was 69%, 11%, 15% for N1/N2/N3 patients, respectively. Disease free survival was 28%forall stages. The fine-needle biopsy was a good method for diagnosis. Control of the neck was better in patients classified as N2 and N3 treated with surgery plus radiotherapy.