New strategies for the treatment of carcinoma of unknown primary / 中华肿瘤杂志

Carcinoma of unknown primary (CUP) is a kind of metastatic tumor whose primary origin cannot be identified after adequate examination and evaluation. The main treatment modality of CUP is empiric chemotherapy, and the median overall survival time is less than 1 year. Compared with immunohistochemistry, novel method based on gene expression profiling have improved the sensitivity and specificity of CUP detection, but its guiding value for treatment is still controversial. The approval of immune checkpoint inhibitors and pan-cancer antitumor agents has improved the prognosis of patients with CUP, and targeted therapy and immunotherapy based on specific molecular characteristics are the main directions of future research. Given the high heterogeneity and unique clinicopathological characteristics of CUP, "basket trial" is more suitable for clinical trial design in CUP.

Surgery associated with radiotherapy in patients affected by metastatic medular compression: scientific production of the health area / Cirurgia associada à radioterapia em pacientes acometidos por compressão medular metastática: produção científica da área da saúde

INTRODUCTION: The spine is the most frequent area of bone metastasis in patients with systemic neoplastic disease. The goal of its treatment is immediate decompression, in order to prevent deterioration or reverse the deficit in neurological functionOBJECTIVE: To analyze the characteristics of the scientific literature on the effectiveness of surgery associated with radiotherapy to improve the neurological deficit caused by metastatic spinal cord compressionMETHODS: Descriptive study based on bibliometric and scientometric methods. Using both, it is possible to qualify, verify and give meaning to the data and have, as a result, a broad study about the productions of the theme in question. Articles published in the National Library of Medicine (Pubmed), Web of Science and Virtual Health Library (VHL) were used, searched using keywords obtained from the Descriptors in Health Sciences (DeCS), of the VHLRESULTS: The searches resulted in 131 articles. After filtering by reading titles, 100 articles were selected for reading the abstract. At the end of the collection, 15 articles were selected. Of these, the year of publication was distributed every two years for analysis, with a significant growth in 2015 and 2016. As for the origin of the studies, 60% (n = 9) had data collection developed in China, Japan or the United States of America. Regarding the gender of the sample, 57.14% of them contained the predominantly or totally male sample and 42.85% female. Regarding the histological type of tumor, there was a wide variation between studies. In some of them, the sample contained different groups of tumor diagnosisCONCLUSION: The combination of surgery with postoperative radiotherapy proved to be effective and more efficient than these alone for the treatment of patients affected by metastatic neurological compression

INTRODUÇÃO: A coluna vertebral é a área mais frequente de metástase óssea em pacientes com doença neoplásica sistêmica. O objetivo do seu tratamento a descompressão imediata, a fim de evitar deterioração ou reverter o déficit da função neurológicaOBJETIVO: Analisar as características da literatura científica sobre a eficácia da cirurgia associada a radioterapia para melhora do déficit neurológico causado por compressão medular metastáticaMÉTODO: Estudo descritivo, a partir dos métodos da bibliometria e cientometria. Utilizando ambos, pode-se qualificar, constatar e atribuir sentido aos dados e ter, como resultado, um estudo amplo acerca das produções do tema em questão. Foram utilizados artigos publicados no National Library of Medicine (Pubmed), Web of Science e Biblioteca Virtual em Saúde (BVS), pesquisados através de palavras-chave obtidas no Descritores em Ciências da Saúde (DeCS), da BVSRESULTADOS: As buscas resultaram em 131 artigos. Após a filtragem por leitura de títulos, selecionou-se 100 artigos para leitura do resumo. Ao final da coleta foram selecionados 15 artigos. Destes, o ano de publicação foi distribuído bienalmente para análise, com um crescimento significativo no ano de 2015 e 2016. Quanto à procedência dos estudos, 60% (n = 9) tiveram a coleta dados desenvolvida na China, Japão ou Estados Unidos da América. Em relação ao sexo da amostra, 57,14% deles continham a amostra predominante ou totalmente masculina e 42,85% feminina. Em relação ao tipo histológico do tumor, houve uma grande variação entre os estudos. Em alguns deles, a amostra continha grupos diferentes de diagnostico tumoralCONCLUSÃO: A combinação de cirurgia com radioterapia pós-operatória se mostrou eficaz e mais eficiente do que estas isoladas para o tratamento de pacientes acometidos por compressão neurológica metastática

Unknown primary tumor sites in spinal metastasis / Metástase vertebral em tumor primário de localização desconhecida / Metástasis vertebral en tumor primario de localización desconocida

ABSTRACT Objective: The goal of the study was to report the prevalence of spinal metastasis with unknown primary tumor, clinical features, treatment results and patient survival. Methods: A retrospective evaluation of 103 patients with spinal metastasis and epidural compression, who underwent surgical treatment between March 2009 and August 2015. The prevalence of metastatic spinal tumor with unknown primary tumor was evaluated, as well clinical features, survival and treatment results. Results: Of 103 patients with spinal metastasis and epidural compression, seven patients (6.8%) with unknown primary tumor site were identified; five (71.4%) male and two (28.6%) female, with ages ranging from 37 to 67 years (50.7 years). The metastasis was located in the thoracic spine in six of the patients (85.7%) and in the cervical spine in one (14.3%). The mean survival time was 44.8 days. Conclusion: Spinal metastasis with unknown primary tumor was found in 6.8% of patients. The prognosis and outcomes were poor, and patients had poor survival rates. Level of evidence III; Experimental study.

RESUMO Objetivo: O objetivo deste estudo foi relatar a prevalência de metástases vertebrais em tumores primários desconhecidos, suas características clínicas, resultados do tratamento e sobrevida dos pacientes. Métodos: Avaliação retrospectiva de 103 pacientes com metástase da coluna vertebral e compressão epidural, submetidos a tratamento cirúrgico entre março de 2009 e agosto de 2015. Avaliou-se a prevalência de tumores metastáticos vertebrais com tumor primário desconhecido, assim como as características clínicas, a sobrevida e os resultados do tratamento. Resultados: Dos 103 pacientes com metástase vertebral e compressão epidural, foram identificados sete pacientes (6,8%) com tumor primário de origem desconhecida; cinco pacientes (71,4%) eram do sexo masculino e dois pacientes (28,6%) do sexo feminino, com idades variando de 37 a 67 anos (50,7 anos). A localização da metástase vertebral era na coluna torácica em seis pacientes (85,7%) e na coluna cervical em um paciente (14,3%). A média de sobrevida dos pacientes foi de 44,8 dias. Conclusões: As metástases vertebrais com tumor primário de origem desconhecida foram observadas em 6,8% dos pacientes. O prognóstico e os resultados foram ruins, e os pacientes tiveram sobrevida bastante baixa. Nível de evidencia III; Estudo Comparativo Retrospectivo.

RESUMEN Objetivo: El objetivo de este estudio fue relatar la prevalencia de metástasis vertebrales en tumores primarios desconocidos, sus características clínicas, resultados del tratamiento y sobrevida de los pacientes. Métodos: Evaluación retrospectiva de 103 pacientes con metástasis de la columna vertebral y compresión epidural, sometidos a tratamiento quirúrgico entre marzo de 2009 y agosto de 2015. Se evaluó la prevalencia de tumores metastásicos con tumor primario desconocido, así como las características clínicas, la sobrevida y los resultados del tratamiento. Resultados: De los 103 pacientes con metástasis vertebral y compresión epidural, fueron identificados siete pacientes (6,8%) con tumor primario de origen desconocido; cinco pacientes (71,4 %%) eran del sexo masculino y dos (28,6%) del sexo femenino, con edades variando de 37 a 67 años (50,7 años). La localización de la metástasis vertebral era en la columna torácica en seis pacientes (85,7%) y en la columna cervical en un paciente (14,3%). El promedio de sobrevida de los pacientes fue de 44,8 días. Conclusiones: Las metástasis vertebrales con tumor primario de origen desconocido fueron observadas en 6,8% de los pacientes. El pronóstico y los resultados fueron malos y los pacientes tuvieron sobrevida bastante baja. Nivel de evidencia III; Estudio Comparativo Retrospectivo.

Metástasis cervical con primario desconocido, cambios en los paradigmas: revisión sobre el enfrentamiento clínico, estudio y tratamiento / Cervical metastases from unknown primary tumor, paradigm changes: review on clinical confrontation, study and treatment

Resumen En adultos, una masa cervical detectada mediante examen físico o un estudio de imagen puede ser la única manifestación de un cáncer proveniente de cabeza y cuello. Un retraso en el diagnóstico repercute en el pronóstico de la enfermedad, por lo que debe haber un alto índice de sospecha. Las metástasis cervicales con primario desconocido (MCCPD) son tumores metastásicos en los que el estudio diagnóstico no logró identificar el sitio primario del cáncer, con una histología predominantemente de tipo escamosa. Según algunos estudios, el origen más frecuente resultó ser la orofaringe, incluyendo amígdala palatina y base de lengua. Factores de riesgo conocidos son edades avanzadas, consumo de tabaco y de alcohol. Actualmente, la infección por el virus del papiloma humano (VPH) está teniendo un rol cada vez más importante como factor de riesgo, formando parte de entre 20%-25% de los cánceres de cabeza y cuello. Al enfrentarse a un paciente con masa cervical es importante realizar una completa anamnesis y examen físico acucioso para detectar cualquier elemento sugerente de malignidad. Se debe complementar con nasofibroscopía para visualizar estructuras que no alcanzan a evaluarse en el examen habitual. También se puede orientar la búsqueda del primario desconocido en base a los patrones de drenaje linfático. Dentro del estudio complementario se puede comenzar con una tomografía computada (TC) y se puede considerar también el ultrasonido o un PET/TC. Si con esto aún no se logra definir el primario, continuar con una punción aspirativa con aguja fina (PAAF), luego biopsia core que consiste en tomar una muestra del centro de la lesión guiada por ecografía, si fuese necesario, incluyendo inmunohistoquímica para VPH; ambos estudios histológicos son preferibles en vez de una biopsia abierta debido al menor riesgo de diseminación y complicaciones. El siguiente paso incluye estudio endoscópico y biopsias bajo anestesia. El tratamiento de los pacientes con MCCPD, va a depender de factores relacionados con el estadio de la enfermedad: desde cirugía o radioterapia (RT) únicas, cirugía más RT, y en algunos casos quimioterapia. Se recomienda seguimiento clínico frecuente durante los primeros años y con imágenes dentro de los 6 primeros meses postratamiento.

Abstract In adults, a cervical mass detected by physical examination or an imaging study may be the only manifestation of cancer from the head and neck. A delay in the diagnosis affects the prognosis of the disease, so there must be a high index of suspicion. Cervical metastases from unknown primary tumor (CUP) are metastatic tumors in which the diagnostic study failed to identify the primary site of cancer, with predominantly squamous histology. According to some studies, the most frequent origin was the oropharynx, including palatine tonsil and tongue base. Known risk factors are advanced ages, tobacco and alcohol consumption. Currently, human papilloma virus (HPV) infection is playing an increasingly important role as a risk factor, being the cause of between 20-25% of cancers of the head and neck. When confronting a patient with cervical mass it is important to carry out a complete anamnesis and a thorough physical examination to detect any element suggestive of malignancy. Physical examination could be complemented with a flexible nasal endoscopic to evaluate structures that can not be evaluated in the habitual examination. The search for the unknown primary can also be oriented based on lymphatic drainage patterns. Within the complementary evaluations, one can start with a study of images such as computed tomography (CT) or magnetic resonance imaging (MRI) with contrast, and also could consider ultrasound or PET/CT. If the primary can not be defined yet, fine needle aspiration (FNAP) can be the next choice and then a core biopsy that consisting of taking a sample from the center of the ultrasound-guided lesion, if necessary, including immunohistochemistry for HPV; both histological studies are preferable to an open biopsy because of the lower risk of complications. The next step searching for the primary includes endoscopic study and biopsies under anesthesia. Regarding to the management of patients with CUP, it will depend on factors related to the stage of the disease: from surgery or radiotherapy (RT) only, surgery and RT, and in some cases chemotherapy. Frequent clinical follow-up is recommended during the first years and images within the first 6 months after treatment.

Cáncer de mama ectópica axilar: caso clínico / Ectopic axillary breast cancer: case report

Resumen Introducción El tejido mamario ectópico es consecuencia de la involución incompleta de la cresta mamaria. Su localización más frecuente es axilar siendo más común en el sexo femenino. Nuestro objetivo fue presentar el caso de una patología infrecuente en su localización. Materiales y Método Se presenta el caso de una paciente de 39 años, con diagnóstico de cáncer de mama ectópica en la región axilar izquierda. Resultados Presentamos el estudio y la resolución quirúrgica de una paciente con cáncer de mama ectópica. Discusión La presencia de tejido mamario ectópico ocurre en el 2%-6% de la población general. Este tejido sufre cambios fisiopatológicos similares a los de la mama normal, entre los cuales se encuentra la malignización. El carcinoma primario de este tejido es infrecuente y su manifestación más común es el tumor palpable. Conclusiones La incidencia de carcinoma en tejido ectópico es de 0,3% de todos los cánceres de mama. El tratamiento debe seguir las mismas recomendaciones que el cáncer de mama normotópico, con igual estadio TNM.

Introduction Ectopic mammary tissue is consecuence of the incomplete involution of the mammary crest. The most frequent location is the axillary region and more common in women. Our gol was present the case of an infrequent pathology in its location. Materials and Method A case of a 39-year-old patient with a diagnosis of ectopic breast cancer in the left axillary region. Results We present the study and surgical resolution of a patient with ectopic breast cancer. Discussion Ectopic breast tissue occurs in 2-6% of the general population. This tissue undergoes pathophysiological changes similar to those of the normal breast, among which malignancy is found. The primary carcinoma of this tissue is infrequent and its most common manifestation is the palpable tumor. Conclussion The incidence of carcinoma in ectopic tissue is approximately 0.3% of all breast cancers. Treatment should follow the same recommendations as those for breast tumors with the same TNM stage.

Tomografía por emisión de positrones con 18F-fluordeoxiglucosa-tomografía computarizada en el diagnóstico del tumor primario de origen desconocido / Value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography ın the diagnosis of carcinoma of unknown primary origin

Introducción: La incidencia de tumores primarios de origen desconocido en pacientes oncológicos es del 0,5 al 7 por ciento en el momento del diagnóstico con una supervivencia a los 3 y 5 años de 11 y 6 por ciento, respectivamente. Objetivo: valorar la utilidad de la técnica PET/CT-FDG (Tomografía por emisión de positrones con 18F-Fluordeoxiglucosa) en el diagnóstico de tumor primario de origen desconocido (TOD). Material y método: Se analizaron retrospectivamente los estudios PET/CT-FDG realizados en pacientes con el diagnóstico de TOD para la búsqueda de tumor primario, con estudios convencionales previos negativos, entre noviembre de 2017 y junio de 2018. El diagnóstico final se estableció mediante confirmación histológica y/o seguimiento clínico/radiológico por 8 meses. Resultados: 42 pacientes fueron estudiados, en 19 estudios PET/CT se evidenciaron focos de captación sugestivos de tumor primario, de los cuales 9 se confirmaron histológicamente como verdaderos positivos y sólo 1 correspondió a un falso positivo. De los 23 pacientes con PET/CT negativos para tumor primario, todos continuaron con diagnóstico de TOD a pesar de las múltiples pruebas diagnósticas. Conclusiones: La técnica PET/CT permitió identificar el 45,2 por ciento de los tumores primarios en la muestra de pacientes, lo que la convierte en una herramienta útil para el diagnóstico en pacientes con metástasis de origen desconocido. Se considera que el PET/CT-FDG debe ser incluido de manera precoz en los algoritmos diagnósticos en Cuba, permitiendo orientar la realización de pruebas complementarias subsiguientes(AU)

Introduction: The incidence of carcinoma of unknown primary origin in oncologic patients is from 0,5 percent to 7 percent at the time of diagnosis with an overall 3-year and 5-year survival of 11 percent and 6 percent, respectively. Objective: To assess the effectiveness of 18 F-FDG-PET/CT (18F-fluorodeoxyglucose posıtron emıssıon tomography) in the diagnosis of carcinoma of unknown primary origin (CUP). Material and Methods: F-FDG-PET/CT studies were conducted in patients with CUP in the search for primary tumor with negative previous conventional studies carried out from November, 2017 to June 2018. The final diagnosis was established by histological confirmation and/or clinical/radiological follow-up during 8 months. Results: A total of 44 patients were studied. There were evidences of suggestive CUP in 19 patients; 9 of them were histologically confirmed as true-positive and only 1 was a false-positive. Of the 23 patients with negative F-FDG-PET/CT studies for primary tumor, all of them continued with the diagnosis of CUP in spite of multiples diagnostic tests. Conclusions: The FDG-PET/CT technique allowed to identify 45,2 percent of the primary tumors in this study, which demonstrates that it is very useful tool for the diagnosis of metastases of unknown origin. It is considered that F-FDG-PET/CT studies should be included earlier in the diagnostic algorithms in Cuba, which will allow to indicate subsequent complementary tests(AU)

Melanoma maligno gastrointestinal de origen primario desconocido: reporte de caso / A case report of malignant gastrointestinal melanoma of unknown primary origin

Resumen Una de las características inusuales del melanoma cutáneo es la capacidad de metastatizar en el intestino delgado. A menudo se diagnostica durante la autopsia, en la cual se ha encontrado depósitos metastásicos en el 50%-60% de los casos, pero menos del 2% al 4% de los pacientes con diagnóstico de melanoma tiene metástasis gastrointestinal (GI) durante el curso de la enfermedad y entre el 4%-9% de casos de melanoma GI tiene un primario desconocido. La rápida identificación y resección del melanoma en el tracto digestivo podría mejorar la tasa de supervivencia en aquellos pacientes en los que se presentan complicaciones, como obstrucción intestinal. Se presenta un caso clínico de melanoma gastrointestinal de origen primario desconocido. El porcentaje de este tipo de casos es poco frecuente. La paciente presentó cuadro clínico de náuseas, hiporexia, epigastralgia, fatiga, parestesias en región dorsal derecha y disminución de 9 kilogramos en 3 semanas. Le realizaron tomografía computarizada (TAC) de abdomen contrastado, que reportó 3 lesiones en hígado de predominio isodenso en el parénquima, con algunas áreas de menor densidad al interior, localizadas en los segmentos 2, 5, 7 y 8 del hígado al que se le realizó la biopsia. Se llevó a cabo endoscopia de vías digestivas altas con biopsia de 2 lesiones hiperpigmentadas en la segunda porción de duodeno. El examen histopatológico de las biopsias evidenció melanoma maligno. Se excluyeron todas las localizaciones típicas de melanoma primario durante el procedimiento diagnóstico.

Abstract One of the unusual characteristics of cutaneous melanoma is its ability to metastasize in the small intestine. It is often diagnosed during autopsies of cutaneous melanoma patients. Metastatic deposits have been found in 50% to 60% of these autopsies, but less than 2% to 4% of patients diagnosed with melanoma have gastrointestinal metastasis during the course of the disease. Between 4% and 9% of gastrointestinal melanoma cases have unknown primary tumors. Rapid identification and resection of melanoma in the digestive tract could improve the patient survival rate and prevent complications such as intestinal obstructions from occurring. We present a rare clinical case of gastrointestinal melanoma of unknown primary origin. The patient had a clinical picture of nausea, hyporexia, epigastralgia, fatigue, paresthesias in the right dorsal region and had lost nine kilograms in three weeks. An abdominal CT scan showed three predominantly isodense liver lesions in the parenchyma, with some areas of lower density located in segments 2,5,7 and 8 of the liver. These were biopsied. Upper digestive tract endoscopy took biopsy samples of two hyperpigmented lesions in the second portion of the duodenum. Histopathological examination showed malignant melanoma. All typical locations of primary melanoma were excluded during the diagnostic procedure.

Distribución Topográfica de las Metástasis de Origen Desconocido / Topographic Distribution of Metastases of Unknown Origin

Introducción: La metástasis de origen desconocido es una entidad clínica relativamente común, que representa del 5% de todos los cánceres invasivos. La búsqueda del origen primario puede resultar desafiante por un patrón atípico metastásico, no obstante el adenocarcinoma y carcinomas indiferenciados representan un 75% siendo el adenocarcinoma el más complicado de determinar su sitio primario ya que sus características citológicas/histológicas generalmente no son específicas. Por esta razón surge la necesidad identificar el origen primario de las lesiones metastásica de origen desconocido en pacientes con y sin antecedentes oncológicos personales, el sexo y edad de mayor prevalencia. Métodos: Investigación observacional descriptiva, retrospectiva tomándose como universo de 100 pacientes con diagnóstico histopatológico de Carcinoma/Adenocarcinoma metastásico en el departamento de Anatomía patológica del Instituto Oncológico Nacional "Dr. Juan Tanca Marengo"­ Solca-Guayaquil en el periodo 2013-2015, con y sin antecedentes oncológicos personales. Resultados: Se obtuvo una muestra de 91 pacientes, donde la localización metastásica más frecuente fue en los ganglios cervicales (27%), seguida del hígado (13%), hueso y epiplón (9%). Además, en 69 de ellos pudo ser posible la identificación del origen primario de la lesión metastásica. Conclusión: La topografía metastásica de neoplasia primaria desconocida tales como los ganglios cervicales y el hígado son los lugares de notable predominio, siendo el ganglio cervical el lugar de biopsia por excelencia debido a su mayor accesibilidad. La metástasis de origen desconocido a pesar de ser más frecuente en el sexo femenino, tiene una gran incidencia en el grupo etario entre 61-70 años.

Introduction: The metastasis of unknown origin is clinical entity relatively common, which represents 5% of all invasive cancer. The research of the primary origin could be difficult because of its atypical pattern, instead that, the undifferentiated adenocarcinoma and carcinoma represents 75% , being adenocarcinoma the most complicated to diagnoses the primary origin because of their unspecific characteristic cytological/histological. For this reason is necessary to identify the primary origin of the metastatic lesion with unknown origin in patients with or without personal oncological background, sex and age with higher prevalence. Methods: Observational, descriptive- retrospective investigation that used the collection 100 patients with histopathologic diagnoses carcinoma/adenocarcinoma metastatic in the Anatomy Pathologic Department of ION-SOLCA period 2013-2015, with and without personal oncological background. Results: Sample of 91 patients, in 69 of them were the most frequently metastatic location was superior cervical ganglion (27%), liver (13%), bone and omentum (9%). Furthermore, 69 patients were possible to identify the primary origin of the metastatic lesion. Conclusion: The metastatic location of the neoplasm unknown primary such as superior cervical ganglion and liver are the places more common, being superior cervical ganglion with most accessibility for biopsies. The neoplasm unknown primary is more frequently in female sex and has a high incidence at the ages of 61-70 years.

Adenopatía axilar metastásica a causa de cáncer primario oculto de mama / Axillary metastatic adenopathy due to hidden breast primary cancer

Se describe el caso clínico de una paciente de 56 años que acudió a la consulta de Oncología del Hospital Gubernamental de Mbabane, en Swazilandia, por padecer una adenopatía en la axila izquierda de varios meses de evolución, confirmada por ecografía. Se realizó una biopsia por aspiración con aguja fina, cuyo resultado reveló la metástasis de un carcinoma ductal. Se completaron los estudios preoperatorios, se determinó el estadio de la entidad clínica (IIA) y se remitió a la paciente a la consulta de Cirugía para realizar una disección axilar y luego aplicar radioterapia en la axila y la mama

The clinical report of a 56 year-old patient who went to the Oncology Service of the Government Hospital from Mbabane, in Swaziland, for suffering an adenopathy in the left armpit with a clinical course of several months, confirmed by echography is described. An aspiration biopsy with fine needle was carried out whose result revealed the metastasis of a ductal carcinoma. The preoperative studies were completed, the stage of the clinical entity was determined (IIA) and the patient was referred to the Surgery service to carry out an axillary dissection and then to apply radiotherapy in the armpit and breast

Estado del Arte Manejo Quirúrgico del Carcinoma Metastásico de Primario Desconocido de Cabeza y Cuello / State of the Art Surgical Management of Metastatic Carcinoma of Unknown Primary of Head and Neck

Propósito de la revisión: el objetivo de la revisión es delinear el rol del Manejo Quirúrgico del carcinoma metastásico primario de cabeza y cuello. Buscamos reportes en indicaciones, posibles hallazgos y subsecuentes tratamientos. Recientes hallazgos: La punción aspirativa con aguja fina, permite diferenciar la etiología de los nódulos del cuello: melanoma, carcinoma tiroideo, linfoma y otros tumores indiferenciados. La medición de tiroglobulina ayuda a diferenciar una neoplasia de tiroides. El nivel ganglionar afectado I al III incluye el protocolo de paratiroidectomia, amigadalectomía. El nivel ganglionar IV y V el primario es infraclavicular. Extracto: El cáncer metastásico de primario oculto es una neoplasia con confirmación histológica pero con lesión primaria desconocida. Su manejo es controversial y en la mayoría de los casos insuficiente para llegar al diagnóstico, incluso con la autopsia. La aproximación inicial comprende una serie de exámenes de laboratorio e imágenes de alta complejidad que incluyen la tomografía por emisión de positrones con el test de la Flúor 2-Deoxi Glucosa (FDG-PET/CT), los estudios de anatomía patológica son el segundo paso dentro del manejo estándar e incluyen la Punción y Aspiración con Aguja fina (PAAF). La microscopia tradicional no es suficiente para identificar el tumor primario, las tinciones inmunohistoquímicas aunque no son especificas ni sensibles ayudan con ese propósito y aún más la microscopia electrónica. La biopsia o procedimientos más agresivos como la amigdalectomía son conductas a seguir si aún no se ha logrado el diagnóstico. Se presenta una revisión del estado del arte del manejo del Carcinoma Metastásico de Primario Desconocido de Cabeza y Cuello.

Purpose of the review: the objective of the review is to delineate the role of Surgical Management of primary metastatic carcinoma of the head and neck. We look for reports on indications, possible findings and subsequent treatments. Recent findings: Fine-needle aspiration can differentiate the etiology of neck nodules: melanoma, thyroid carcinoma, lymphoma and other undifferentiated tumors. The measurement of thyroglobulin helps to differentiate a thyroid neoplasm. The affected lymph node level I to III includes the protocol of parathyroidectomy, amigdalectomy. The nodal level IV and V the primary is infraclavicular. Excerpt: Metastatic cancer of the occult primary is a neoplasm with histological confirmation but with an unknown primary lesion. Its management is controversial and in most cases insufficient to reach the diagnosis, even with autopsy. The initial approach involves a series of laboratory tests and highly complex images that include positron emission tomography with the Flucor 2-Deoxy Glucose test (FDG-PET / CT), pathology studies are the second step within standard handling and include Puncture and Fine Needle Aspiration (FNAP). Traditional microscopy is not enough to identify the primary tumor, immunohistochemical stains although they are not specific or sensitive help with this purpose and even more so electron microscopy. Biopsy or more aggressive procedures such as tonsillectomy are behaviors to follow if the diagnosis has not yet been achieved. A review of the state of the art of metastatic carcinoma of Unknown Head and Neck Primary is presented.

Analysis of survival in patients with brain metastases treated surgically: Impact of age, gender, oncologic status, chemotherapy, radiotherapy, number and localization of lesions, and primary cancer site

SUMMARY OBJECTIVE To evaluate the survival of patients with brain metastases treated surgically according to the potentially involved factors. METHODS 71 patients treated surgically were analyzed with the diagnosis of brain metastases during the period from January 2011 to November 2014, totaling 47 months of follow-up. The Kaplan-Meier curve method was used for survival analysis. Results We evaluated 71 patients with brain metastases treated surgically, 44 female and 27 male, mean age of 60.1 years. According to the Karnofsky scale, 44 patients were classified with Karnofsky greater than or equal to 70 and 27 patients with Karnofsky inferior to 70. Lung was the primary site most commonly found. Death occurred in twenty patients (28%), and lung tumors were responsible for the most deaths. Twelve patients had supra and infratentorial metastases, fifty-nine only had supratentorial lesions, and lesions were multiple in twenty-eight patients and single in forty-three. Thirty patients were also treated with chemotherapy, eighteen with chemotherapy and radiation therapy, while only three received just radiotherapy. Survival analysis by Kaplan-Meier curve showed no statistical significance regarding age, histological type, location, Karnofsky, chemotherapy, and radiotherapy. There was statistical significance regarding gender. CONCLUSION The factors analyzed did not change survival rates, except for gender. This fact may probably be explained due to the systemic and diffuse behavior of cancer.

RESUMO OBJETIVO Avaliar a sobrevivência de pacientes com metástases cerebrais tratados cirurgicamente de acordo com os fatores potencialmente envolvidos. Métodos 71 pacientes tratados cirurgicamente foram analisados com o diagnóstico de metástases cerebrais durante o período de janeiro de 2011 a novembro de 2014, totalizando 47 meses de seguimento. A curva de Kaplan-Meier foi utilizada para análise de sobrevivência. Resultados Avaliamos 71 pacientes com metástases cerebrais atendidas cirurgicamente, 44 do sexo feminino e 27 do sexo masculino, idade média de 60,1 anos. De acordo com a escala de Karnofsky, 44 pacientes foram classificados com Karnofsky maior ou igual a 70 e 27 pacientes com Karnofsky com menos de 70. O pulmão era o local mais comum. A morte ocorreu em 20 pacientes (28%) e os tumores pulmonares são responsáveis pela maioria das mortes. Doze pacientes apresentavam metástases supra e infratentoriais, 59 apresentavam apenas lesões supratentoriais, e as lesões eram múltiplas em 28 pacientes e isoladas em 43. Trinta pacientes também foram tratados com quimioterapia, 18 foram tratados com quimioterapia e radioterapia, enquanto que apenas três receberam apenas radioterapia. A análise de sobrevivência pela curva de Kaplan-Meier não mostrou significância estatística de acordo com a idade, tipo histológico, localização, Karnofsky, quimioterapia e radioterapia. Houve significância estatística em relação ao gênero. Conclusão Os fatores analisados não alteraram a sobrevivência, exceto o gênero. Este fato provavelmente pode ser explicado devido ao comportamento sistêmico e difuso do câncer.

Unknown primary large-cell neuroendocrine tumor

Large-cell neuroendocrine tumors (NETs) are poorly differentiated malignancies of rare incidence and aggressive nature. NETs mostly arise in the lung followed by the gastrointestinal tract, although they are potentially ubiquitous throughout the body. Primary unknown NET has a worse prognosis and shorter survival comparing with other NETs, with limited available data in the literature concerning this subgroup. The authors report the case of large-cell NET with supraclavicular lymph node presentation. Total excisional biopsy revealed an enlarged adenopathy 18 × 15 × 10 mm, which was extensively infiltrated by a solid malignant neoplasm composed of large cells with granular chromatin, nuclear pseudo-inclusions, high mitotic index, and focal necrosis, with a Ki 67 index 25-30% and positive immunohistochemical study for the expression of cytokeratin 8/18, chromogranin, synaptophysin, and thyroid transcriptional factor-1 (TTF-1). There was no evidence of primary location apart from two infracentimetric lung lesions that could not be accessed for biopsy and were negative at both somatostatin receptor scintigraphy and positron emission tomography. The NET relapsed with three mediastinal masses, so the patient was started on chemotherapy with carboplatin and etoposide with initial total response. Early progression showed no response to further chemotherapy regimens (temozolomide, oral etoposide); therefore, the patient was treated with local radiotherapy. This patient has an atypical long survival (54 months) compared to the literature data. In fact, there are few long-term survivors of large-cell NET and they are all related to complete surgical resection.

Cancer of Unknown Primary Site Mimicking Retroperitoneal Fibrosis / 대한내과학회지

Retroperitoneal fibrosis (RPF) is a rare disease characterized by marked fibro-inflammatory tissue in the retroperitoneum. Approximately 70% of cases of RPF are idiopathic, while the rest can be secondary to several other causes. The diagnosis is mainly obtained by imaging modalities such as computed tomography (CT). However, histological examination should be considered when the clinical manifestations and imaging studies suggest malignancy. In particular, in malignant diseases with retroperitoneal metastases, abnormal collagen plaques are formed from an exuberant desmoplastic response, which may not be distinguishable from RPF on CT scans. Therefore, even if CT suggests RPF, biopsy is essential to identify malignant disease because it typically results in a fatal prognosis. Here, we report a case of metastatic adenocarcinoma of unknown primary site that developed only in the retroperitoneum and was initially diagnosed as RPF based on CT findings.

Neoplasia de sítio primário desconhecido: abordagem diagnóstica e terapêutica / Cancer of onknown primary site: diagnostic and therapeutic approach

Introdução: As neoplasias de sítio primário desconhecido (NSPD) são responsáveis por 3-5% de todas as neoplasias malignas, definidas pela falha de identificação do sítio primário após a investigação diagnóstica. Métodos: Revisão bibliográfica da literatura entre abril e maio de 2018, em artigos de revisão, seminários e artigos originais, em inglês, dos últimos 20 anos. Resultados: A investigação diagnóstica das NSPD envolve uma extensa anamnese, exame físico, exames laboratoriais, exames de imagem, análise anatomopatológica e imuno-histoquímica da lesão metastática. Com base nessa investigação, são classificadas de acordo com critérios clínico-patológicos para melhor conduta terapêutica. Conclusão: As NSPD são um grande desafio para o clínico e oncologista, é imprescindível a investigação adequada dessas neoplasias para o melhor tratamento da doença.

Introduction: Cancer of unknown primary site (CUP) accounts for 3-5% of all malignant neoplasms, which is defined when the anatomical site of origin remains occult after detailed investigations. Methods: Review articles, seminars, and original articles in English for the last 20 years. Results: The diagnostic investigation of CUP involves an extensive anamnesis, physical examination, laboratory exams, imaging, anatomopathological and immunohistochemical analysis of the metastatic lesion. Based on this investigation, the neoplasms are classified according to clinical pathological criteria. Conclusion: CUP can be a challenge for the clinician and medical oncologist, it is essential to adequately investigate these neoplasms in order to define the best treatment approach.

Metástasis musculares no sospechadas detectadas con 18F-FDG PET/TC / Unsuspected muscle metastases detected with 18F-FDG PET/CT Abstract

Objetivo: Evaluar la prevalencia de metástasis musculares (MM) no sospechadas en pacientes con enfermedad maligna conocida, estudiados con tomografía por emisión de positrones integrada con tomografía computada con flúor-18 deoxiglucosa (18F-FDG PET/TC). Materiales y métodos: Se analizaron retrospectivamente 2953 18F-FDG PET/TC, identificando las MM. Se registraron los tumores primarios, el número y localización de las MM y el SUV máximo en cada caso. Fueron incluidos pacientes oncológicos con histología conocida y múltiples lesiones secundarias. Se utilizó el examen 18F-FDG PET/TC como método de referencia para detectar metástasis. Resultados: Se identificaron MM en 33 pacientes (prevalencia: 1,12%) entre los 18 y 88 años de edad. Los tumores primarios incluyeron: riñón en 7 casos, mama en 5, melanoma en 4, pulmón en 3, ovario en 3, tiroides en 3, sarcomas en 3, región colorrectal en 2, vejiga en 2 y endometrio en 1. Se encontraron 96 MM en 33 pacientes: 24 en muslo, 15 en glúteo, 13 en pared torácica, 10 en psoasilíaco,10 en músculos paravertebrales, 7 en pared abdominal, 7 en pierna, 4 en brazo y 6 en otras localizaciones (pelvis, cuello, etc.). Las MM afectaban un solo músculo en 22/33 pacientes y varios en 11/33. El patrón de captación más frecuente fue el foco hipermetabólico, con SUV máximo entre 1,5 y 34. Discusión: Nuestra muestra incluye un número importante de casos comparada con la literatura y coincide con los hallazgos de otros autores en la incidencia y localización de las MM. Conclusión: Las MM son infrecuentes y pueden pasar inadvertidas. Es posible detectarlas con 18F-FDG PET/TC como focos hipercaptantes únicos o múltiples.

Objective: To assess the prevalence of unsuspected muscle metastases (MM) in patients with known malignant disease, examined with 18F-fuorodeoxyglucose positron emission tomography integrated with computed tomography (18F-FDG PET/CT). Materials and methods: A total of 2,953 18F-FDG PET/CT examinations were retrospectively analysed, looking for cases with MM. Primary neoplasm, number and location of MM and SUV max were recorded on each patient. Oncology patients with known histology and multiple secondary lesions were included. The 18F-FDG PET/CT was the reference method for detection of metastases. Results: MM were observed in 33 patients (prevalence: 1.12%) aged between 18 and 88 years. The primary tumours included: kidney in 7 cases, breast in 5, melanoma in 4, lung in 3, ovary in 3, thyroid in 3, sarcomas in 3, colorectal in 2, bladder in 2, and endometrial in 1. A total of 96 MM were observed in 33 patients, and located in: thigh muscles 24, gluteal 15, chest wall 13, iliopsoas 10, paravertebral muscles 10, abdominal wall 7, leg 7, arm 4, and other locations 6 (pelvis, neck, etc.). MM affected only one muscle in 22/33 patients and several muscles in 11/33. Hypermetabolic focus was the most frequent uptake pattern, with SUV max between 1.5 and 34. Discussion: Our series has a significant number of cases, and is consistent with other authors on the incidence and location of MM. Conclusion: MM are uncommon and may be overlooked. MM may be detected with 18F-FDG PET/CT as single or multiple hypermetabolic foci.

Accuracy of Diagnostic Methods for Detection of Head and Neck Primary Origin in Metastatic Neck Mass / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: It is important to localize the primary site when cervical lymph node metastasis is detected. The purpose of this study was to evaluate the accuracy of diagnostic methods to detect the head and neck primary site in patients with metastatic neck mass. SUBJECTS AND METHOD: Sixty-six patients who had presented with neck mass and were confirmed to have metastatic carcinoma by fine needle aspiration cytology from January 1998 to June 2016 were enrolled. We analyzed the accuracy of diagnostic modalities that inluded physical and endoscopic examination, CT, MRI, PET/CT, and guided biopsy. RESULTS: The mean age of patients was 58.7±12.6 years with the male to female ratio of 55:11. The metastatic lymph nodes were most common at level II (60/66, 90.9%) followed by levels III, IV, I and V. The most common primary site was tonsil (45.5%), followed by the nasopharynx, base of tongue and hypopharynx, and eight patients (12.1%) were diagnosed as metastatic carcinoma of unknown origin. The primary sites were detected by: physical and endoscopic examination in 36/66 (54.5%), CT in 41/66 (62.1%), MRI in 39/52 (75%) and PET/CT in 46/63 (73.1%). The primary sites were additionally detected using PET/CT for nine cases of the 20 cases, where primary sites were not found using physical and endoscopic examination, CT or MRI. Guided biopsy was done in 11 cases, where primary sites were not detected by all of the methods; hence, primary sites for 3 cases were additionally revealed. CONCLUSION: PET/CT is a useful method when physical examination, CT and MRI cannot reveal the primary site of metastatic neck mass. Guided biopsy can be performed when primary site is not founded by any of the physical and imaging examinations.

Cutaneous metastasis as the first manifestation of occult malignant breast neoplasia

Abstract Cutaneous metastases from primary internal malignancies represent 0.7-9% of patients with cancer. We report a 65-year-old female patient referred for evaluation of normochromic papules on the trunk and upper limbs that had been present for three months. A skin biopsy revealed diffuse cutaneous infiltration by small round cell tumors. Immunohistochemistry was positive for AE1/AE3, CK7, estrogen receptor and mammaglobin. The final diagnosis was cutaneous metastasis of occult breast cancer, since the solid primary tumor was not identified. The location of the primary tumor can not be determined in 5-10% of cases. In these cases, 27% are identified before the patient’s death, 57% at autopsy, and the remaining 16% can not be located.

Small clonal B-cell population in the bone marrow as a possible tool in the diagnosis of occult primary parotid lymphoma / Pequeña población de células B monoclonales en medula ósea como posible herramienta diagnóstica en el linfoma oculto primario de parótida

Case Description: An 82-years old Hispanic woman with a past medical history significant for pulmonary thromboembolism on oral anticoagulation, rheumatoid arthritis, and hypertension developed a new onset thrombocytopenia. Clinical Findings: Small clonal B-cells populations (SCBP) also known as monoclonal B-cell lymphocytosis was found as part of the workup for an idiopathic thrombocytopenia and lead ultimately to the diagnosis of parotid primary follicular lymphoma coexisting with Warthin tumor involving the bone marrow in a small extent and oncocytic papilloma located in the maxillary sinus. Treatment and Outcome: Patient was treated with Rituximab monotherapy with improvement on her platelet count. Clinical relevance: Although it is unclear the role of this clonal cells, they may work as a possible diagnostic tool for occult lymphomas. Further prospective studies are needed to confirm this possible association.

Descripción de caso: Mujer hispana de 82 años con una historia médica significativa de tromboembolismo pulmonar en anticoagulación, artritis reumatoide e hipertensión, la cual desarrolló recientemente una trombocitopenia. Hallazgos clínicos: Una pequeña población de células B monoclonales también conocida como linfocitosis monoclonal de células B fue encontrado dentro del estudio de una trombocitopenia idiopática que conllevó al diagnóstico de un linfoma folicular primario de parótida coexistiendo con un tumor de Warthin y un papiloma oncocítico localizado en el seno maxilar. Tratamiento y resultado: La paciente fue tratada con monoterapia de Rituximab con una mejoría en su conteo de plaquetas. Relevancia clínica: Aunque el rol de las pequeñas poblaciones B monoclonales no está completamente dilucidado, podrían tener una aplicación como herramienta diagnóstica. Futuros estudios prospectivos son necesarios para confirmar esta posible asociación.

Diagnostic performance of F-18 FDG PET/CT in patients with cancer of unknown primary: additional benefit over CT-based conventional work up

Background: In the era of well-developed site-specific treatment strategies in cancer, identification of occult primary is of paramount importance in CUP patients. Furthermore, exact determination of the extent of the disease may help in optimizing treatment planning. The aim of the present study was to investigate additional value of F-18 FDG PET/CT in patients with cancer of unknown primary [CUP] as an appropriate imaging tool in early phase of initial standard work up

Materials and Methods: Sixty-two newly diagnosed CUP patients with inconclusive diagnostic CT scan of chest, abdomen and pelvis referring for F-18 FDG PET/CT were enrolled in this study. Standard of reference was defined as histopathology, other diagnostic procedures and a 3-month formal clinical follow up. The results of PET/CT were categorized as suggestion for primary site and additional metastasis and classified as true positive, false positive, false negative and true negative. The impact of additional metastasis revealed by F-18 FDG PET/CT on treatment planning and the time contribution of F-18 FDG PET/CT in diagnostic pathway was investigated

Results: Sixty-two patients with mean age of 62 [30 men, 32 women], PET/CT correctly identified primary origin in 32% with false positive rate of 14.8%. No primary lesion was detected after negative PET/CT according to standard of reference. Sensitivity, Specificity and accuracy were 100%, 78% and 85%, respectively. Additional metastatic site was found in 56% with 22% impact on treatment planning. Time contribution for PET/CT was 10% of total diagnostic pathway

Conclusion: Providing higher detection rate of primary origin with excellent diagnostic performance, shortening the diagnostic pathway and improving treatment planning, F-18 FDG PET/CT may play a major role in diagnostic work up of CUP patients and may be recommended as an alternative imaging tool in early phase of investigation