Ganglio centinela positivo en melanoma: factores predictivos y resultados del vaciamiento ganglionar / Positive sentinel lymph node in melanoma: predictive factors and results of completion lymph node dissection

RESUMEN Antecedentes: la biopsia del ganglio centinela (GC) es la técnica aceptada para determinar el pronóstico en estadios iniciales de melanoma cutáneo. La ventaja del vaciamiento ganglionar (VG) cuando el GC resulta positivo ha sido recientemente cuestionada. Objetivo: describir los porcentajes y factores asociados a metástasis en el GC, y en los ganglios no centinela (GnC) en los VG de pacientes con GC positivo. Material y métodos: se llevó a cabo un estudio retrospectivo de los registros clínicos y patológicos de 139 pacientes operados por melanoma cutáneo entre enero de 2012 y diciembre de 2019. Resultados: a 96 (69%) pacientes se les realizó biopsia de GC. El promedio de edad fue 61,7 años ± 17,5 (19-93); 53 (55,2%) fueron hombres. La lesión primaria estuvo ubicada en: extremidades 47 (49%), tronco 39 (40,6%), cabeza y cuello 10 (10,4%). El promedio de espesor de Breslow fue 5,01 mm (1,05- 50 mm) y se encontró ulceración en 35 casos (36,4%). El GC fue identificado en todas las oportunidades y en 39 (40,6%) fue positivo. Hubo asociación con el espesor ≥ 3 mm (p = 0,000017) y con la ulceración (p = 0,0011). A los pacientes con GC positivo se les efectuó el VG del territorio afectado: 23 axilar, 10 inguinal y 6 cervical. Veintitrés (59%) presentaron metástasis en GnC. Se asoció con el espesor (p = 0,022) y la ulceración (p = 0,019). Conclusión: existió un alto porcentaje de GnC positivos en la población estudiada, vinculado al espesor y la ulceración. Estas características, así como la dificultad de un estricto seguimiento, inducen a no abandonar el VG en pacientes con GC positivo.

ABSTRACT Background: Sentinel lymph node (SLN) biopsy is the technique accepted to determine the prognosis of early cutaneous melanomas. The advantage of lymph node dissection (LND) when SLN biopsy is positive has recently been questioned. Objective: The aim of this study is to describe the percentages and factors associated with SLN and non-sentinel node (NSN) metastases in LNDs of SLN-positive patients. Material and methods: The clinical records and pathology reports of 139 patients undergoing surgery for cutaneous melanoma between January 2012 and December 2019 were retrospectively reviewed. Results: Ninety-six (69%) patients underwent SLN biopsy. Mean age was 61.7 ± 17.5 years (19-93) and 53 (55.2%) were men. The primary lesion was located in the extremities in 47 (49%) cases, in the trunk in 39 (40.6%), and in the head and neck in 10 (10.4%). Mean Breslow thickness was 5.01 mm (1.05-50 mm) and ulceration was found in 35 cases (36.4%). The SLN was identified in all the cases and was positive in 39 (40.6%). There was an association with thickness ≥ 3 mm (p = 0.000017) and ulceration (p = 0.0011). Those patients with positive SLN biopsy underwent LND of the territory involved: axillary in 23, inguinal in 10 and cervical in 6. Twenty-three (59%) presented NSLN metastases and were associated with thickness (p = 0.022) and ulceration (p = 0.019). Conclusion: There was a high percentage of positive NSLN in the population studied which was associated with thickness and ulceration. These characteristics and the difficulty to achieve strict follow-up are the reasons for completion LND in SLN-positive patients.

Ganglio centinela en el melanoma cutáneo / Sentinel node in cutaneous melanoma

La biopsia selectiva del ganglio centinela (BSGC) se ha desarrollado de tal manera que reemplazó a la linfadenectomía electiva en el tratamiento del melanoma cutáneo (MC). Numerosos estudios demostraron que el estado del ganglio centinela es un factor pronóstico independiente en relación con la supervivencia global y la supervivencia libre de enfermedad de los pacientes con melanoma. El objetivo del presente trabajo fue realizar una revisión bibliográfica para comprender la utilidad y las indicaciones de la BSGC en pacientes con MC a partir de la evidencia actual publicada.

Sentinel lymph biopsy (SLNB) has been developed in such a way that is has replaced elective lymphadenectomy in the treatment of cutaneous melanoma (CM). Numerous studies have shwn that sentinel node status is an independent prognostic factor in relation to overall survival and disease-free survival of patients with CM. The purpose of this article is to carry out a literature review to understand the usefulness and indications of SLNB in patients with CM based on the current evidence.

Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma / Receptores HER2, compromiso ganglionar axilar y sobrevida en mujeres con cáncer de mama ductal invasivo

ABSTRACT Background: Breast cancer (BC) is the most common malignancy in women. Aim: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. Patients and Methods: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. Results: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. Conclusions: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.

Antecedentes: El cáncer de mama es el tumor maligno más común en mujeres. Objetivo: Conocer el impacto del estado HER2 sobre el compromiso ganglionar axilar al momento del diagnóstico y durante los primeros cuatro años después de la cirugía en mujeres con carcinoma ductal invasivo de tipo no especial (IDC-NST). Pacientes y Métodos: Incluimos retrospectivamente a 375 mujeres en etapas clínicas iniciales de IDC-NST que fueron operadas en un hospital clínico. Ellas se dividieron en grupos de acuerdo al fenotipo: HR+HER2-, HR+HER2+, HR-HER2+y HR-HER2-. La disección de ganglios axilares se efectuó solo en las pacientes con macrometástasis en el ganglio centinela. Si había más de tres ganglios comprometidos, se efectuó radioterapia. Todas las pacientes se trataron con quimioterapia. Las pacientes HER2+ recibieron trastuzumab y las pacientes HR+ recibieron hormonoterapia. Resultados: Tumores más grandes, de mayor grado de malignidad, HR+, HER2+ y la invasión linfovascular fueron predictivos de la presencia de metástasis axilares al momento del diagnóstico. La sobrevida más baja se observó en pacientes HR-HER2+. La sobrevida libre de recurrencia locorregional más baja, se observó en pacientes HR-HER2+ y HR-HER2-. HER2 no fue predictor de sobrevida. Conclusiones: En estas mujeres, HER2+fue predictor de la presencia de compromiso ganglionar axilar al momento del diagnóstico pero no de la sobrevida a cuatro años.

Association between tumor-infiltrating lymphocytes and sentinel lymph node positivity in thin melanoma

Abstract: Background: Sentinel lymph node biopsy in thin invasive primary cutaneous melanoma (up to 1mm thick) is a controversial subject. The presence of tumor-infiltrating lymphocytes could be a factor to be considered in the decision to perform this procedure. Objective: To evaluate the association between the presence of tumor-infiltrating lymphocytes and lymph node metastases caused by thin primary cutaneous melanoma. Methods: Cross-sectional study with 137 records of thin invasive primary cutaneous melanoma submitted to sentinel lymph node biopsy from 2003 to 2015. The clinical variables considered were age, sex and topography of the lesion. The histopathological variables assessed were: tumor-infiltrating lymphocytes, melanoma subtype, Breslow thickness, Clark levels, number of mitoses per mm2, ulceration, regression and satellitosis. Univariate analyzes and logistic regression tests were performed as well the odds ratio and statistical relevance was considered when p <0.05. Results: Among the 137 cases of thin primary cutaneous melanoma submitted to sentinel lymph node biopsy, 10 (7.3%) had metastatic involvement. Ulceration on histopathology was positively associated with the presence of metastatic lymph node, with odds ratio =12.8 (2.77-59.4 95% CI, p=0.001). The presence of moderate/marked tumor-infiltrating lymphocytes was shown to be a protective factor for the presence of metastatic lymph node, with OR=0.20 (0.05-0.72 95% CI, p=0.014). The other variables - clinical and histopathological - were not associated with the outcome. Study limitations: The relatively small number of positive sentinel lymph node biopsy may explain such an expressive association of ulceration with metastatization. Conclusions: In patients with thin invasive primary cutaneous melanoma, few or absent tumor-infiltrating lymphocytes, as well as ulceration, represent independent risk factors for lymph node metastasis.

Accuracy of sentinel lymph node mapping in detecting occult neck metastasis in papillary thyroid carcinoma

ABSTRACT Objectives: The objectives of this study were to evaluate the following: 1) the accuracy of sentinel lymph node mapping (SLNM) in detecting metastasis in papillary thyroid carcinoma (PTC), and 2) if SLNM could modify the American Joint Committee on Cancer (AJCC) staging of previous cN0 PTC patients. Subjects and methods: Forty SLNM were performed prospectively in 38 consecutive cN0 PTC patients, with total thyroidectomy and elective compartment neck dissection (CND). The results of SLNM were compared with CND pathological findings to verify the accuracy of sentinel SLNM. Results: The mean patients' follow-up was 36 months. A total of 133 SLN were found at levels VI, II, III and IV. The SLN was identified in 95% of the patients with one false negative, 95% sensitivity, a 94% negative predictive value and 97% accuracy. The SLNM upstaging from cN0 to pN+ was 49%, and to stages III and IVa, it was 21%. Conclusions: For this series of cN0 PTC patients: 1) SLNM accuracy was 97%, and 2) SLNM upstaging from cN0 to pN+ was 49%, whereas to stages III and IVa, it was 21%.

Intraoperative imprint cytology versus histological diagnosis for the detection of sentinel lymph nodes in breast cancer treated with neoadjuvant chemotherapy

OBJECTIVES: To compare imprint cytology and paraffin section histology for sentinel lymph node detection in women with breast cancer treated with neoadjuvant chemotherapy. METHOD: A cross-sectional study and report of the sentinel lymph node statuses of 64 patients with breast cancer who underwent intraoperative imprint cytology and neoadjuvant chemotherapy in a referral cancer institute in Rio de Janeiro, Brazil, between 2014 and 2016. RESULTS: The mean age was 51 years. The most common histological type was invasive ductal carcinoma (93.75%), and the most common differentiation grade was 2 (62.5%). Overall, 153 lymph nodes were identified, with a mean of 2.39/case. Thirty-four lymph nodes tested positive for malignancy by imprint cytology, and 55 tested positive by histology. Of the 55 positive lymph nodes, 41 (74.5%) involved macrometastases, and 14 (25.5%) involved micrometastases. There were 21 false negatives with imprint cytology, namely, 7 for macrometastases and 14 for micrometastases, resulting in a rate of 17.6%. The sensitivity of imprint cytology was 61.8%, with a specificity and positive predictive value of 100%, a negative predictive value of 82.4% and an accuracy of 86.3%. The method presented null sensitivity for the identification of micrometastases. CONCLUSIONS: The false-negative rate with imprint cytology was associated with the number of sentinel lymph nodes obtained. The rate found for complete response to neoadjuvant chemotherapy was comparable to the rates reported in the literature. The accuracy of imprint cytology was good, and its specificity was excellent for sentinel lymph node detection; however, the method was unable to detect lymph node micrometastases.

Relación entre ganglio centinela positivo y el espesor de Breslow en pacientes con melanoma cutáneo primario / Relationship between positive sentinel lymph node and Breslow's depth in patients with primary cutaneous melanoma

Introducción: es sabido que el pronóstico del melanoma cutáneo depende, entre otros factores, de la existencia de diseminación linfática a ganglios. La biopsia del ganglio centinela busca identificar metástasis ganglionares subclínicas. Objetivo: el presente estudio tuvo por objetivo analizar la asociación entre la presencia de ganglio centinela positivo, identificado mediante rastreo con radioisótopo 99mTc-coloide de Renio, y el espesor de Breslow hallado en la lesión primaria a nivel cutáneo. Metodología: se analizaron 52 pacientes. Se realizó la búsqueda del ganglio centinela por el método de rastreo con radioisótopo 99mTc-coloide de Renio y posterior biopsia del mismo, en pacientes tratados en el Instituto Nacional de Cancerología de México, entre enero de 2015 a agosto de 2016, con diagnóstico de melanoma cutáneo y espesor de Breslow mayor o igual a 1mm o con menor a 1mm y otros criterios de riesgo como la ulceración. Aquellos con biopsia positiva fueron sometidos a linfadenectomía. Además, se recogieron las siguientes variables: sexo, edad, localización, tipo de melanoma, espesor de Breslow y ulceración. Resultados: la edad media de la muestra fue 57 ± 15 años. El 63,5% de los pacientes fue del sexo masculino. El tipo histológico más frecuente fue el melanoma de extensión superficial (69,2%). Se detectó positividad del ganglio centinela en 46,2% y 28,8% presentó Breslow >4,0 mm. Se encontró relación entre la presencia de ganglio centinela positivo y espesor de Breslow (p=0,007). Conclusiones: a medida que aumenta el espesor de Breslow, lo hace también el encuentro de metástasis en ganglio centinela. Se recomienda realizar estudios de casos y controles para evaluar el factor predictivo que puede llegar a tener el encontrar ganglio centinela positivo.

Introduction: It is known that the prognosis of cutaneous melanoma depends, among other factors, on the existence of lymphatic spread to lymph nodes. Sentinel node biopsy seeks to identify subclinical lymph node metastases. Objective: The present study aimed to analyze the association between the presence of positive sentinel lymph node, identified by Rhenium 99mTc-colloid radioisotope tracing, and the Breslow´s depth found in the primary lesion at the cutaneous level. Methodology: 52 patients were analyzed. The sentinel lymph node was searched by the rhenium 99mTc-colloid radioisotope and subsequent biopsy of it in patients treated at the Instituto Nacional de Cancerología of Mexico, between January 2015 and August 2016, with a diagnosis of cutaneous melanoma and Breslow's depth greater-than or equal to 1mm or less-than 1mm and other risk criteria such as ulceration. Those patients with positive biopsy underwent lymphadenectomy. In addition, the following variables were collected: sex, age, location of the lesion, type of melanoma, Breslow's depth, and ulceration. Results: Mean age of the sample was 57±15 years. 63.5% of the patients were male. The most frequent histological type was superficial spreading melanoma (69.2%). 46.2% had positive sentinel lymph node. 28.8% presented Breslow >4.0 mm. A relationship was found between the presence of positive sentinel lymph node and Breslow's depth (p=0.007). Conclusions: As Breslow's depths increases, so does the metastasis encounter in sentinel lymphs nodes. It is recommended to carry out case-control studies to evaluate the predictive factor that may result in finding a positive sentinel lymph node.

Linfonodo centinela en cáncer de mama: correlación entre detección isotópica y quirúrgica / Pre and intraoperative scintigraphic detection of sentinel nodes in breast cancer

Background: Sentinel node detection localizes the first node that drains a malignant lesion aiming to detect tumor dissemination. Aim: To assess the yield of sentinel node detection in breast cancer, using pre or intraoperative scintigraphy. Material and Methods: Review of medical records of patients with breast cancer who had a scintigraphic detection of sentinel nodes. Lymph node scintigraphy and surgery were performed in the same day. Results: We studied 174 women aged 53 ± 13 years, operated with a diagnosis of breast cancer, including six highly suspicious lesions in the contralateral breast (totaling 180 studied breasts). Preoperative scintigraphy showed a sentinel node in 174 of 180 breasts (97%). Intraoperative gamma probe confirmed the presence of the sentinel node in the same 174 breasts and detected an additional one reaching a detection yield of 97%. Four patients in whom a sentinel node was not detected in the preoperative scintigraphy, had macrometastases. Frozen section biopsies were available in 177 of 180 breasts. Metastases were informed in 45 patients who underwent axillary lymph node dissection, plus one additional patient with a suspicious lesion. Conclusions: A high rate of sentinel node detection in the preoperative scintigraphy was observed. Most sentinel nodes not detected with nuclear medicine had macrometastases. In 71% of patients, the detection of sentinel node avoided axillary lymph node dissection.

Groin lymph node detection and sentinel lymph node biopsy in vulvar cancer / 부인종양

OBJECTIVE: To identify suitable diagnostic tools and evaluate the efficacy of sentinel lymph node (SLN) biopsy for inguinal lymph node metastasis in vulvar cancer. METHODS: Data from 41 patients with vulvar cancer were evaluated retrospectively, including magnetic resonance imaging (MRI) measurements, SLN biopsy status, groin lymph node metastasis, and prognosis. RESULTS: SLN biopsy was conducted in 12 patients who had stage I to III disease. Groin lymphadenectomy was omitted in five of the nine patients with negative SLNs. All SLN-negative patients who did not undergo groin lymphadenectomy showed no evidence of disease after treatment. On MRI, the long and short diameters of the inguinal node were significantly longer in metastasis-positive cases, compared with negative cases, in 25 patients whose nodes were evaluated pathologically (long diameter, 12.8 mm vs. 8.8 mm, p=0.025; short diameter, 9.2 mm vs. 6.7 mm, p=0.041). The threshold of >10.0 mm for the long axis gave a sensitivity, specificity, positive predictive value, and negative predictive value of 87.5%, 70.6%, 58.3%, and 92.3%, respectively, using a binary classification test. Decision tree analysis revealed a sensitivity, specificity, and accuracy of 87.5%, 70.6%, and 76.0%, respectively, with the threshold of >10.0 mm for the long axis on MRI. The criteria of >10.0 mm for the long axis on MRI predicted an advanced stage and poorer prognosis using a validation set of 15 cases (p=0.028). CONCLUSION: Minimally invasive surgery after preoperative evaluation on MRI and SLN biopsy is a feasible strategy for patients with vulvar cancer.

Melanoma cutâneo: doença curável? Revisão de literatura e apresentação de um organograma de investigação e tratamento / Cutaneous melanoma: curable disease? Literature review and presentation of an organogram of investigation and treatment

O melanoma cutâneo é hoje o tumor que mais cresce em incidência no mundo. Representa cerca de 4% dos tumores cutâneos. Apresenta prognóstico bem mais reservado em relação ao carcinoma basocelular e epidermóides. Tem fatores de risco bem estudados, como, por exemplo, a história familiar e a exposição solar demasiada. Apresenta como fator prognóstico principal a presença de linfonodos comprometidos nas respectivas cadeias de drenagem. A primeira linha de tratamento é a cirúrgica, destacando-se na área de tratamento medicamentoso o uso de drogas biológicas, como interferon e a interleucina. Seu prognóstico geral de sobrevida em 10 anos varia entre 85% em países desenvolvidos, até 56% em países em desenvolvimento. Os autores realizam uma revisão bibliográfica criteriosa, além de proporem um organograma de investigação e tratamento baseado em dados de literatura internacional (AU)

At the present time the incidence of cutaneous melanoma is growing very fast and it has the highest rising rates in the world. It is responsible for approximately 4% of the cutaneous tumors, and has a worse prognosis when compared to basocelular or epidermoidis. Some risk factors are well studied, like the family history and excess of sun exposure. The most important prognostic factor is the lymph nodes involvement. The gold standard treatment, when possible, is surgery. The pharmacologic treatment is based on the use of biologic drugs like interferon and interleukins. The general prognosis varies from a survival of 56% in 10 years in underdeveloped countries to 85% in developed ones. The authors perform a careful review of the literature and propose a diagnosis and treatment protocol for these patients (AU)