Bone metastatic cancer of unknown primary at initial presentation.

INTRODUCTION: Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. RESULTS: Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2 months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. DISCUSSION: Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results.

SEOM-GECOD clinical guideline for unknown primary cancer (2021).

Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity.

2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary.

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.

SEOM clinical guideline on unknown primary cancer (2017).

Cancer of unknown primary site is a histologically confirmed cancer that manifests in advanced stage, with no identifiable primary site following standard diagnostic procedures. Patients are initially categorized based on the findings of the initial biopsy: adenocarcinoma, squamous-cell carcinoma, neuroendocrine carcinoma, and poorly differentiated carcinoma. Appropriate patient management requires understanding several clinical and pathological features that aid in identifying several subsets of patients with more responsive tumors.

Management of Squamous Cancer Metastatic to Cervical Nodes With an Unknown Primary Site.

Squamous cell carcinoma of an unknown primary (SCCUP) of the head and neck is a rare disease. As a diagnosis of exclusion, the manner in which it is assigned merits consideration. Despite the development and refinement of several techniques designed to locate an occult tumor, including cross-sectional anatomic imaging, functional imaging, and transoral surgical techniques, delineating SCCUP remains an active clinical problem. Its relative rarity has prevented prospective study of the entity. Hence, investigators must rely on retrospective analyses to understand the disease and its appropriate treatment. The current understanding of SCCUP differs substantially from when it was initially described decades ago. The most common site of a small primary tumor initially thought to represent SCCUP is the tonsil or base of the tongue, and an increasing percentage are associated with human papilloma virus. Modern treatment of SCCUP by neck dissection alone, neck dissection followed by radiation with or without concurrent chemotherapy, or primary chemoradiation according to initial nodal disease burden produces extraordinarily low recurrence rates. Whether the potential mucosal primary site and/or the contralateral neck should be electively treated is controversial. Efficacy data seem to be similar; therefore, an evaluation of the toxicity of both treatment paradigms is warranted.

Clinical guideline SEOM: cancer of unknown primary site.

Cancer of unknown primary site is a histologically confirmed cancer which is manifested in advanced stage, with no identifiable primary site after the use of standard diagnostic procedures. Patients are initially placed into one of categories based upon the examination of the initial biopsy: adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma and poorly differentiated carcinoma. Appropriate patient management requires an understanding of several clinicopathologic features that help to identify several subsets of patients with more responsive tumors.

Somatic mosaicism caused by monoallelic reversion of a mutation in T cells of a patient with ADA-SCID and the effects of enzyme replacement therapy on the revertant phenotype.

Patients with adenosine deaminase (ADA) deficiency exhibit spontaneous and partial clinical remission associated with somatic reversion of inherited mutations. We report a child with severe combined immunodeficiency (T-B- SCID) due to ADA deficiency diagnosed at the age of 1 month, whose lymphocyte counts including CD4+ and CD8+ T and NK cells began to improve after several months with normalization of ADA activity in Peripheral blood lymphocytes (PBL), as a result of somatic mosaicism caused by monoallelic reversion of the causative mutation in the ADA gene. He was not eligible for haematopoietic stem cell transplantation (HSCT) or gene therapy (GT); therefore he was placed on enzyme replacement therapy (ERT) with bovine PEG-ADA. The follow-up of metabolic and immunologic responses to ERT included gradual improvement in ADA activity in erythrocytes and transient expansion of most lymphocyte subsets, followed by gradual stabilization of CD4+ and CD8+ T (with naïve phenotype) and NK cells, and sustained expansion of TCRγδ+ T cells. This was accompanied by the disappearance of the revertant T cells as shown by DNA sequencing from PBL. Although the patient's clinical condition improved marginally, he later developed a germinal cell tumour and eventually died at the age of 67 months from sepsis. This case adds to our current knowledge of spontaneous reversion of mutations in ADA deficiency and shows that the effects of the ERT may vary among these patients, suggesting that it could depend on the cell and type in which the somatic mosaicism is established upon reversion.

Unknown primary cancer of the head and neck: a multidisciplinary approach.

The management of patients with cervical lymph node metastases from an unknown primary cancer (CUP) remains a matter of controversy. Although new advanced diagnostic tools, such as positron emission tomography, have recently been introduced in oncology, the frequency of this tumour entity in clinical practice means it is still relevant. Recently introduced molecular profiling platforms may provide biological classification for the primary tissue of origin as well as insights into the pathophysiology of this clinical entity, including the characterisation of the Epstein-Barr virus and human papilloma virus genomas in the metastatic cervical nodes. Due to the lack of randomised trials, a standard therapy has not been identified yet. Although neck dissection followed by post-operative radiotherapy is the most generally accepted approach, there are other curative options that can be used in some patients: neck dissection alone, nodal excision followed by post-operative radiotherapy or radiotherapy alone. A major controversy remains in the target radiation volumes that range from ipsilateral neck irradiation to prophylactic irradiation of all potential mucosal sites and both sides of the neck. Finally, the administration of concurrent chemotherapy is currently being advised for patients with adverse prognostic factors.

Muscle metastasis of carcinoma.

Metastatic carcinoma of the soft tissue is extremely rare compared with bone metastases. An intramuscular mass is often thought to be a primary soft tissue sarcoma because intramuscular metastases are very uncommon. Any painful soft tissue mass occurring in patients with a known history of carcinoma, particularly with extensive peritumoral enhancement associated with central necrosis, is highly suspicious for skeletal muscle metastasis. A needle biopsy is necessary for proper diagnosis. It is very important to make a differential diagnosis between metastasis and primary cancer in these cases. Here we present a review of known evidence.

Diagnosis of unknown primary cancer based on molecular techniques may influence therapeutic approach and improve survival.

Unknown primary cancer (UPC) is a common clinical syndrome classically associated with a poor prognosis. Pathological examination including immunohistochemistry continues to be essential in tumour origin characterization, although in many cases primary tumour site remains unknown. Gene expression based analysis may offer important diagnostic information that could lead to therapeutic decisions.

Cervical lymph node metastases of squamous cell carcinoma from an unknown primary site: a favourable prognosis subset of patients with CUP.

Squamous cervical cancer of unknown primary site (SQCCUP) presents in patients as neck lymph nodes involved by squamous carcinoma in the absence of identifiable primary in the head, neck or lung. This CUP subset affects male patients previously exposed to alcohol and tobacco, though a proportion of cases may be related to chronic infection of the oropharynx by human papilloma virus. A standardised diagnostic work-up consisting of panendoscopy of the upper aerodigestive tract, CT of the chest/abdomen and histology supplemented by immunohistochemistry is warranted for the diagnosis. The scant available evidence on the molecular biology of the disease is reviewed. The cornerstones of management are excisional biopsy or surgical extirpation of the disease followed by bilateral neck external beam radiotherapy and chemotherapy. The necessity for complete surgical resection of involved neck nodes, irradiation of all head/neck mucosal sites and administration of concurrent chemotherapy is currently being debated. Aggressive multimodal therapy results in longterm disease control in 50-60% of patients, though data are mainly based on retrospective cohorts. Factors predicting for superior patient outcome are radical management with surgery or radiotherapy, low stage and volume of disease, absence of extracapsular spread and good performance status. Recently introduced molecular profiling platforms may provide biological classification to a primary tissue of origin as well as insights into the pathophysiology of this clinical entity.

Diagnóstico e terapêutica do câncer com sítio primário desconhecido / Diagnosis and therapeutical of the cancer with unknow primary site

Apesar de o Câncer de Sítio Primário Desconhecido (CSPD) não ser um dos mais prevalentes na clínica médica, sabe-se que o diagnóstico e o tratamento de pacientes com tal patologia são um dilema. Mesmo com os recentes avanços na imunohistoquímica, na tecnologia de imagens e no surgimento de novas drogas antineoplásicas, a maioria dos pacientes é relativamente resistente ao tratamento sistêmico e apresenta uma pequena sobrevida. Compreender a apresentação clínica, a histopatologia, conhecer as formas de investigação diagnóstica, bem como as possibilidades de tratamento desta patologia tão diferenciada e que mexe com a ansiedade do médico, faz parte da formação de muitas especialidades da medicina.

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.

[Metastatic cutaneous adenocarcinoma of unknown primary site. Case report]. / Adenocarcinoma metastático cutâneo de origem desconhecida. Relato de um caso.

BACKGROUND: Metastases may be the first manifestation of adenocarcinoma. Up to 60% are cutaneous and present in advanced stage neoplasms. Research for the primary site is costly and requires endoscopy, imaging and immunohistochemical exams. The primary site becomes obvious in only 15% to 20% of live patients and is detected mainly at autopsy. AIM: To report a case of metastatic cutaneous moderately differentiated adenocarcinoma of unknown primary site, located in the lower left abdomen. RESULTS: The lesion was surgically resected. Primary site was not found by any imaging or endoscopy exams. The immunohistochemistry was negative for CEA, CK20, PSA and positive for CK7. Based on these exams, prostate and colorectal cancer were excluded. The pancreas and biliary tract were considered as the probable primary site. CONCLUSION: The research for the primary site still is difficult, expensive and is not effective to the treatment of metastatic adenocarcinomas.

Adenocarcinoma metastático cutâneo de origem desconhecida: relato de um caso / Metastatic cutaneous adenocarcinoma of unknown primary site: case report

RACIONAL: Metástases podem ser a primeira manifestação de adenocarcinoma. Cerca de 60 por cento destas podem ser cutâneas e correspondem a casos de neoplasia em estágio avançado. A procura pelo sítio primário é onerosa, sendo necessário o emprego de diversos exames de imagem, endoscópicos e imunoistoquímicos. Apesar disto, o sítio primário é descoberto somente em 15 por cento a 20 por cento dos pacientes, sendo os demais casos reconhecidos nas autopsias. OBJETIVO: Relatar um caso de adenocarcinoma, moderadamente diferenciado metastático cutâneo, de sítio primário desconhecido. A região acometida foi a pele da fossa ilíaca esquerda. RESULTADOS: A lesão foi ressecada cirurgicamente. O sítio primário não foi identificado por nenhum exame de imagem ou endoscópico. O estudo imunoistoquímico revelou o seguinte padrão de imunoperoxidase: CEA negativo, CK7 positivo, CK20 negativo e PSA negativo. Com base nestes achados, foram afastados tumores primários do intestino grosso e da próstata (PSA, CK20 e CEA negativos). Os principais sítios primários aventados foram pâncreas e vias biliares. CONCLUSAO: A procura pelo sítio primário de adenocarcinoma metastático continua sendo tarefa difícil, onerosa e com pouco impacto no tratamento dos pacientes acometidos.

Tumor primario desconocido: experiencia del Instituto Nacional de Cancerología de México, periodo de 1981 a 1985 / Unknown primary tumor: experience at the Instituto Nacional de Cancerologia of Mexico, 1981 to 1985 period

Se analiza la experiencia en el Instituto Nacional de Cancerología en 93 casos de tumor primario desconocido vistos entre los años 1981 a 1985. De ellos, 43 correpondieron al sexo masculino (46 por ciento) y 50 al femenino (54 por ciento), no representando mayor diferencia estadística. El promedio de edad a la presentación fue de 56 años y el tiempo de evolución tuvo un rango de 1 a 36 meses con media de seis. El sitio inicial de mayor a menor afección fue el ganglio linfático en 30 por ciento de los casos, seguido de Higado, hueso y pulmón. La estripe tumoral que con mayor frecuencia fue responsable de esta entidad fue el adenocarcinoma (57 por ciento), seguido de Ca epidermoide (13 por ciento) y carcinoma indiferenciado (12 por ciento). El método de estudio de estos pacientes no fue único ni sistematizado. Se realizaron un total de 1,283 estudios de laboratorio con un promedio de 13.7 exámenes por paciente, 434 estudios raqdiológicos simples y contrastados para un promedio de 4.6 estudios por paciente, 81 tomografías computadas, 38 estudios endoscópicos dando un costo aproximado y actualizado por paciente de 2'000,000 (dos millones) de pesos para un total aproximado de 200'000,000 (docientos millones) de pesos. El consumo de tiempo en los estudios tomó un promedio de dos semanas por paciente antes de decidir un manejo terapéutico. En ningún caso se identificó el sitio primario de origen de la metástasis. Desde el punto de vista terapéutico, 30 casos no recibieron nungún manejo (32 por ciento) por lo avanzado de la enfermedad y las malas condiciones generales del enfermo. Seis casos recibieron manejo quirúrgico, 14 tratamiento con radioterapia y 43 quimioterapia sistémica. De todos ellos, solamente tres correspondieron a tumores epidermoides del área de cabeza y cuello, siendo manejados con cirugía y radioterapia y hallándose vivos y en control hasta el momento actual. Los restantes fallecieron en un lapso menor a un año, con progresión generalmente visceral. Se concluye que se sebe identificar a un subgrupo de pacientes que probablemente se beneficiarán del estudio exhaustivo y del tratamiento dirigido (tumores potencialmente curables como germinales, linfoproliferativos, etc.) y que el uso indiscriminado de estudios que intenta identificar el sitio primario no conlleva a mejoría en la sobrevida ni respuesta al tratamiento de los pacientes, debiendo de protocolizarse su estudio y manejo que redituará en un menor costo y mayor calidad de vida para los pro

Câncer oculto como forma especial dos carcinomas mamários / Occult cancer as a special type of breast neoplasms

O câncer oculto de mama, caracterizado como um quadro no qual o diagnóstico da metástase axilar precede a identificaçäo da lesäo primária, deve ser distinguido do câncer subclínico, quando um exame radiológico indica a existência de uma lesäo neoplásica mamária, näo perceptível no exame clínico. Dois casos säo relatados. O primeiro em 1975, com a execuçäo de mastectomia radical após rápida identificaçäo da neoplasia primária, e o segundo em 1985, com o diagnóstico de tumor metastático axilar e localizaçäo tardia da lesäo primitiva após 40 meses de controles periódicos, quando foi executada uma quadrantectomia mamária. Ambas as pacientes encontram-se assintomáticas. Tais casos, assim como outros citados na literatura internacional, permitem encarar o câncer oculto de mama como um tipo especial dentro do grupo genérico de tumores primários desconhecidos, com condiçöes biológicas e prognósticas que permitem um tratamento menos agressivo que o usualmente preconizado para estes tipos de lesäo