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.

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.

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.

Cutaneous metastasis of unknown primary presenting as massive and invasive abdominal lesion: an elective approach

Abstract: We describe herein what is to our knowledge the first reported case of an invasive cutaneous metastasis with unknown primary, electively treated solely with electrochemotherapy. We describe a female patient with a large, invasive and painful lesion in her hypogastric region, extending up to the pubic area. The cutaneous biopsy and instrumental and laboratory analyses, all failed to reveal the primary site. A final diagnosis of cutaneous metastasis with unknown primary was made and treatment was performed with electrochemotherapy. Our case highlights the importance of interdisciplinary choices in clinical practice to cope with the lack of a primary site and to improve quality of life, since no standardized therapy exists for these classes of patients.

Cutaneous metastasis from gastrointestinal adenocarcinoma of unknown primary origin

AbstractCutaneous metastasis is a rare manifestation of visceral malignancies that indicates primarily advanced disease. Due to its low incidence and similarity to other cutaneous lesions, it is not uncommon to have a delayed diagnosis and a shortened prognosis. We describe the case of a patient who presented with a cutaneous nodule in the sternal region as a first sign of malignancy.

Hepatocellular Carcinoma with Cervical Spine and Pelvic Bone Metastases Presenting as Unknown Primary Neoplasm / 대한소화기학회지

The occurrence of hepatocellular carcinoma (HCC) is closely associated with viral hepatitis or alcoholic hepatitis. Although active surveillance is ongoing in Korea, advanced or metastatic HCC is found at initial presentation in many patients. Metastatic HCC presents with a hypervascular intrahepatic tumor and extrahepatic lesions such as lung or lymph node metastases. Cases of HCC presenting as carcinoma of unknown primary have been rarely reported. The authors experienced a case of metastatic HCC in a patient who presented with a metastatic bone lesion but no primary intrahepatic tumor. This case suggests that HCC should be considered as a differential diagnosis when evaluating the primary origin of metastatic carcinoma.

Melanoma metastásico con tumor primario oculto / Metastatic melanoma with occult primary tumor

In 3 percent of melanomas, the primary tumor is occult. We report a 58 years old female presenting with rapidly growing painless left inguinal lymphadenopathies. The patient was reassessed two months later, verifying that the lesions enlarged further. A CAT scan of the left inguinal region showed a solid mass in the subcutaneous of the proximal region of the left thigh. An incisional biopsy of the inguinal mass was performed. The pathological study disclosed malignant melanoma. The patient was subjected to an iliofemoral lymphatic excision and to five sessions of regional radiotherapy. After two years of follow up, the patient is without evidence of tumor recurrence.

En el 3 por ciento de los melanomas, el tumor primario está oculto. Reportamos una mujer de 58 años, que presentaba linfadenopatías inguinales dolorosas. Reevaluada dos meses después, se constató crecimiento de la masa. Una TAC motró una masa sólida subcutánea en zona proximal de muslo izquierdo, la que fue biopsiada, demostrándose un melanoma. Se realizó disección linfática ilofemoral y cinco sesiones de radioterapia. A los dos años, la paciente no evidencia recurrencia tumoral.

Utility of PET in unknown primary with cervical metastasis: A retrospective study.

Background: FDG-PET is recommended as an investigation in unknown primary tumors, but its definitive role and cost effectiveness are yet to be established. Aims: dditional value of FDG-PET over conventional imaging in unknown primary tumors with cervical metastasis. Setting and Design: Retrospective study in a tertiary level oncology centre. Materials and Methods: A total of 112 patients were divided into three groups; 53 with conventional modalities (either computed tomography or magnetic resonance imaging) (group I), 59 with FDG-PET (group II), and group III (subgroup of group II) with both (40 patients). Statistical Analysis: Sensitivity and specificity of both conventional modality and PET were calculated. Association between neck nodes and distant metastasis was analysed using multivariate logistic regression analysis. Results: Sensitivity and specificity for conventional modalities was 92.3% and 50% and sensitivity and specificity of FDG-PET was 92.8% and 71.4%, respectively. FDG-PET detected metastasis in 52.54% of patients. Multivariate logistic regression analysis showed statistically significant association between distant metastasis and multiplicity of nodes (N2b, N2c) (P = 0.007). Among all patients with low neck nodes in group II, FDG-PET detected primaries in 12 patients, 9 of which were infraclavicular (75%). FDG-PET added information to conventional imaging in 32.5% of patients and influenced an overall change in management in 38.9% of patients. Conclusions: FDG-PET is a valuable tool influencing change of management in unknown primary with cervical metastasis. It is recommended especially in the presence of low or multiple neck nodes in view of high incidence of infraclavicular primary and distant metastasis, respectively.

Unusual presentation of pulmonary tumor thrombotic microangiopathy with no detectable primary tumor.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare condition characterized by the presence of diffuse thrombotic microthrombi and fibrocellular intimal proliferation in the pulmonary vasculature. Its development is linked to the presence of pulmonary tumor microemboli (PTM) and should be suspected in patients with unexplained dyspnea, especially in the presence of adenocarcinoma. PTTM presents in a similar fashion to respiratory disease such as pulmonary embolism, pulmonary hypertension or pneumonia and is usually only diagnosed post-mortem. We report a case of PTTM identified ante-mortem by bronchial biopsy in an 82-year-old woman presenting with a clinical picture of atypical pneumonia. Autopsy confirmed PTTM, from an unknown primary neoplasm.

Cancer de mama oculto: dos casos clínicos analizados según el concepto actual / Occult breast cancer: Report of two cases

Occult breast cancer is expressed as a metastatic axillary lymph node without clinical or imaging evidence of a primary tumor in the breast. The old concept involved non palpable tumors. Its incidence is low, representing only 0.3 to 1 percent of all breast cancer cases. The search for the primary tumors is performed with mammography, whose sensitivity is low, ranging from 0 to 56 percent. Several studies have shown a higher sensitivity of magnetic resonance imaging, ranging from 85 to 100 percent, to detect occult lesions. The treatment of isolated axillary metastases of breast cancer is controversial. An axillary dissection is recommended. If there is a suspicious image, a radiosurgical or stereotaxic biopsy should be done. However, in patients without radiological lesions in the breast, the tendency is not to perform a radical mastectomy as previously recommended, since the primary tumor will not be found in the surgical specimen in two thirds of cases. A superior and external quadrantectomy or exclusive radiotherapy should suffice. An expecting behavior is not recommended as a therapeutic alternative. Treatment should be complemented with hormonal therapy or chemotherapy. The literature suggests that prognosis is better than stage II, with a ten years survival ranging from 50 to 71 percent. We report two patients with a well defined occult breast cancer and based on them, a review of the subject is attempted. Considering its prognosis, physicians should be aware of this uncommon and difficult to diagnose disease.

Manifestações oftalmológicas de carcinoma neuroendócrino: relato de caso / Ophthalmic manifestations of neuroendocrine carcinoma: case report

Relatar o caso de um paciente de 43 anos com metástase de carcinoma neuroendócrino intracraniana e intra-orbitária, cujas primeiras manifestações foram oftalmológicas. Relato de caso. Remissão temporária do quadro clínico após um ciclo de quimioterapia. A análise histopatológica e a imuno-histoquímica foram sugestivas de carcinoma neuroendócrino. A regressão das manifestações clínicas após quimioterapia e o óbito posterior aos ciclos de quimioterapia nos faz pensar na necessidade da criação de protocolos de tratamento para essa forma de neoplasia, levando em consideração, fatores locais e/ou sistêmicos.

Chest wall metastases from unknown primary hepatocellular carcinoma.

Metastases of hepatocellular carcinoma (HCC) to the bones are common but bone metastases of hepatocellular carcinoma in the presence of a normal liver are an uncommon entity. A 50-year-old male patient presented with a rapidly growing tumour on the sternum. Biopsy of the lesion showed metastatic sternal tumour from a primary hepatocellular carcinoma. Radiological evaluation however, failed to detect a primary lesion in the liver. Bone metastases of hepatocellular carcinoma localized to the chest wall in the presence of a normal liver are scarcely reported as anecdotal case reports in the literature.

Metástasis de primario desconocido / Metastasis of unknown primary

El cáncer metastásico de primario desconocido corresponde a un grupo heterogéneo de neoplasias que comparten algunas características clínicas y biológicas similares. Para realizar el diagnóstico se debe contar con la confirmación histológica de la metástasis y después de un estudio estándar no haber identificado un tumor primario. Existen varias teorías en relación al comportamiento biológico de esta entidad. Constituyen entre el 2,3 a 4,2 por ciento de todos los canceres diagnosticados, con una edad media de 60 años. Clínicamente se caracterizan por presentar una evolución breve, síntomas inespecíficos y un patrón metastásico inusual, existiendo en algunas oportunidades tres o más órganos comprometidos. Los órganos más frecuentemente involucrados son los linfonodos, hígado, hueso y pulmón. Histológicamente se dividen en cuatro grupos, siendo el adenocarcinoma bien o moderadamente diferenciado el más frecuente. En general, el pronóstico es ominoso con una sobrevida media de 10 a 12 meses en las mejores series, no obstante existen algunos grupos de buen pronóstico. El objetivo principal del estudio de estos tumores es definir los grupos de buen y mal pronóstico, evitando estudios exhaustivos para localizar el primario, puesto que ello no produce un impacto en la sobrevida. Un porcentaje pequeño de pacientes puede ser incluidos en un grupo favorable, los cuales manejados apropiadamente pueden tener un pronóstico alentador.

Umbilical mass as the sole presenting symptom of pancreatic cancer: a case report

Nódulos umbilicais são raros. Desde 1846, o comprometimento metastático da região vem sendo descrito. A Irmã Mary Joseph foi a primeira a relacionar o aparecimento de nódulos umbilicais com carcinomas. Esses nódulos podem ser a única manifestação de câncer, normalmente associada a estadios avançados e pior prognóstico. Uma senhora de 64 anos, previamente hígida, apresentava desconforto abdominal inespecífico e aparecimento de nódulo umbilical endurecido há uma semana. O diagnóstico inicial foi hérnia umbilical encarcerada. Após reavaliação, o nódulo foi biopsiado, cujo exame anátomo-patológico demonstrou carcinoma com sítio primário desconhecido. A análise imuno-histoquímica e tomografia, o diagnóstico foi carcinoma de pâncreas. O estadiamento demonstrou doença avançada, com metastáses à distância. A paciente foi submetida a quimioterapia paliativa. Após 8 meses, encontrava-se em mau estado geral. A suspeita clínica deve originar avaliação clínica cuidadosa, auxiliada por exames subsidiários, sempre que um nódulo umbilical apresentar sinais de malignidade.

Ileal Malignant Melanoma Presenting as a Mass with Aneurysmal Dilatation: A Case Report

Malignant melanoma is the most common metastatic tumor of the gastrointestinal tract and can present with fairly common constitutional symptoms. A 36-yr-old woman was found to have a secondary malignant melanoma in the terminal ileum with profuse aneurysmal dilatation, which is not the typical presentation of the malignant melanoma in the small intestine. Radiologic studies revealed a large tumor involving the distal ileum with aneurysmal dilatations having afferent and efferent loops, which needed to be differentiated from malignant lymphoma and other gastrointestinal tumors. Exploratory laparotomy was done, and we found a huge mass with plentiful aneurysmal dilatations; much the same of the findings from the previous studies. Segmental resection with the surrounding omentum was done followed by end-to-end anastomosis between both ends of the remaining ileum. She had been free from any evidence of the local or systemic recurrence for one year after the completion of eighteen months of the subcutaneous interferon treatment; postoperatively however, the occurrence of metastatic mass at the right axilla rendered us from complete resection due to severe penetration into the vital nerves and vessels in the axilla.

What is the Clinical Significance of Transudative Malignant Pleural Effusion?

BACKGROUND: A few reports of transudative malignant effusion on a small number of patients have suggested the need to perform routine cytologic examination in all cases of transudative pleural effusion, whether encountered for malignancy or not. The purpose of this study was to investigate whether cytologic examination should be performed in all cases of transudative pleural effusion for the diagnosis of malignancy. METHODS: We performed a retrospective study of 229 consecutive patients with malignant pleural effusion, proven either cytologically or with biopsy. In patients with transudative pleural effusion, we reviewed medical records, results of transthoracic echocardiography, fiberoptic bronchoscopy, chest X-ray, chest CT scan, and ultrasonogram of the abdomen. These data were examined with particular attention to identifying whether or not the malignancy was suggested on chest X-ray, examining the involvement of the superior vena cava, great vessels, and lymph nodes, determining the presence of pericardial effusion, and observing the endobronchial obstruction. RESULTS: Transudative malignant pleural effusion was observed in seven (3.1%) of the 229 patients, and was caused either by the malignancy itself (6 patients) or by coexisting cardiac diseases (1 patient). All the patients showed evidence suggesting the presence of malignancy at the time of initial thoracentesis, which facilitated the decision of most clinicians on whether to perform cytologic examination for the diagnosis of malignancy. CONCLUSION: Therefore, in all cases of transudative pleaural effusion, no clinical implications indicating malignancy were found on cytologic examination.

CT features of intracranial metastases of unknown primaries.

Intracranial metastases of central nervous system are relatively common in patients with systemic cancer. Computed tomography (CT) scans of 60 patients of intracranial metastatic disease of unknown primaries, at the time of surgery, were retrospectively analyzed. These patients primarily presented with neurological dysfunction. They were operated upon for various reasons and histopathological diagnosis was obtained. There were 39 male and 21 female patients, with age range of 18 to 74 years. The common clinical symptoms were raised intracranial pressure without lateralization, acute onset hemiplegia and seizures. Multiple cranial nerve palsies were observed in 4 patients. Histopathologically the intracranial lesions consisted of metastatic adenocarcinoma (32 cases) or metastatic squamous cell carcinoma (28 cases). Among cases of adenocarcinoma, CT revealed solitary lesions in 17 and multiple lesions in 13 cases. Two had extraaxial deposition in the region of petrous apex. Out of squamous cell carcinomas, 17 lesions were solitary, while 10 were multiple and one had extraaxial deposition in the region of petrous apex. This study is unique as it consisted of CT features of intracranial metastases of unknown primary malignant disease elsewhere in the body.