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.

Perfil dos pacientes com diagnóstico de câncer de sítio primário desconhecido em um centro terciário de atenção oncológica / Profile of patients with diagnosis of cancer of unknown primary site in a tertiary cancer center

Introdução: O câncer de sítio primário desconhecido caracteriza-se pela presença de doença metastática ao diagnóstico, sem localização do tumor primário. Objetivo: Conhecer o perfil dos pacientes com diagnóstico de câncer de sítio primário desconhecido em um centro de oncologia terciário. Material e método: Estudo retrospectivo e descritivo no qual foram analisados os prontuários dos pacientes com câncer de sítio primário oculto entre 2002 e 2012. Resultados: Entre os 68 prontuários analisados, observou-se que o adenocarcinoma é o tipo histológico mais frequente (39,71%) seguido pelo carcinoma espinocelular (29,41%). Os sítios de metástases mais recorrentes foram a região cervical (38,23%), fígado (20,58%) e peritônio (16,71%). A imuno-histoquímica foi realizada em 44,12%, os pacientes com acometimento cervical não se beneficiaram da elucidação diagnóstica por este meio, devido à falta de marcadores específi cos para este sítio. Em relação ao tratamento, 60,29% dos pacientes foram submetidos a alguma modalidade terapêutica, sendo a quimioterapia a mais comum, onde a cisplatina foi o antineoplásico mais utilizado de forma isolada (11,76%) e o esquema etoposídeo e cisplatina mais realizado em combinação (7,35%). Conclusão: O estudo está em consonância com os dados da literatura sobre o perfil destes pacientes; entretanto, apesar dos avanços nas técnicas diagnósticas, esta síndrome ainda representa um desafio na prática oncológica.

Introduction: Cancer is characterized by the presence of metastatic disease at diagnosis, without location of the primary tumor. Aim: To know the profile of patients diagnosed with cancer of unknown primary site in a tertiary cancer center. Methods: A retrospective study in which the medical records of patients with cancer of unknown primary site were analyzed between 2002 and 2012. Results: From the 68 charts analyzed adenocarcinoma was found to be the most common histological type (39.71 %), followed by squamous-cell carcinoma (29.41%). The most frequent metastasis sites were the cervical region (38.23%), liver (20.58%) and peritoneum (16.71%). Immunohistochemistry was performed on 44.12%, patients with cervical involvement did not benefi t from such diagnostic clarification due to lack of specific markers for this site. Regarding treatment, 60.29% of patients underwent some form of therapy, the most common being chemotherapy, where cisplatin was the most often antineoplastic used alone (11.76%) and etoposide plus cisplatin the most often used regimen used in combination (7.35%). Conclusion: The study is consistent with published data on the profile of these patients. Despite the advances in diagnostic techniques, however, this syndrome is still a challenge in oncology practice.

Incremental (?) role of positron emission tomography/computed tomography in clinically unknown primary patients with neck metastasis.

OBJECTIVE: To study the incremental role of positron emission tomography (PET)/computed tomography (CT) in the detection of primary site in cases of occult primary with neck metastasis. STUDY DESIGN: A prospective study on 79 consecutive patients. SETTING: A tertiary care otolaryngology and head and neck surgery center. MATERIALS AND METHODS: This prospective study compares the results of PET/CT in 79 patients of occult primary with neck metastasis with that of detailed comprehensive head and neck examination including imaging and panendoscopy. This study also attempts to define the incremental role of PET/CT in patients of occult primary. RESULTS: The sensitivity of PET/CT in identifying the primary tumor was 62.4%, the specificity was 64.7%, the positive predictive value was 69.7% and the negative predictive value was 93%. We had a false positive rate of 33.6% and a false negative rate of 2.6%. CONCLUSION: PET/CT is a sensitive investigation for detection of occult primary. However, it has a low specificity rate and a high false positivity rate. Due to a high false positive rate, multiple biopsies from suspicious sites should be taken rather than solely relying on PET/CT. PET/CT guided fine needle aspiration cytology should be utilized more frequently than we did in this study.

The Appearance of a Candidate Site for a Primary Melanoma: A 5 Year-gap with a Melanoma of an Unknown Site

Although more than 90% of melanomas have cutaneous origins, melanomas sometimes present metastatically with no apparent primary lesion. A 62-year-old female presented with black pigmentation on her left thumbnail that had begun 2 years earlier and after the biopsy, she was diagnosed with malignant melanoma. Interestingly, 7 years earlier, a 4 cm palpable mass on her left axilla had been diagnosed as melanoma from an unknown primary site (MUP) with the involvement of an axillary lymph node. We speculate that the melanoma of the left thumb was the primary site and the melanoma in the axilla was a metastasis from the left thumb, and suggest several hypotheses explaining the appearance of the primary lesion as acral lentiginous melanoma after detecting a metastatic site. We consider this case interesting because it helps us to understand the pathogenesis of MUP and reminds physicians to conduct careful periodical work-ups of melanoma patients, and highlights the importance of continued long-term follow-up, especially for patients with MUP.

Endobronchial Ultrasound-guided Transbronchial Needle Biopsy for Diagnosis of Mediastinal Lymphadenopathy in Patients with Extrathoracic Malignancy

Mediastinal lymphadenopathy associated with extrathoracic malignancy or a metastasis of unknown origin (MUO) requires pathological verification. Surgical exploration or endoscopic ultrasound-guided fine needle aspiration is limited to application. We investigated the effectiveness of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) for evaluating mediastinal lymphadenopathy in patients with an extrathoracic malignancy. We retrospectively analyzed data from 59 patients who underwent EBUS-TBNA with a core biopsy because of a suspected mediastinal metastasis between September 2008 and August 2010. All patients had previously been diagnosed with an extrathoracic malignancy (n = 39, 66.1%) or a suspected MUO without a thoracic lesion (n = 20, 33.9%). A total of 88 lymph nodes was analyzed. EBUS-TBNA findings indicated malignancies in 34 patients (57.6%). The EBUS-TBNA sensitivity and specificity for the detection of mediastinal malignancy in patients with a previous extrathoracic malignancy were 96.3% and 100%, respectively. For MUO patients without a thoracic lesion, the sensitivity and specificity were 61.5% and 100%, respectively. The overall sensitivity and specificity were 81.0% and 100%, respectively (P = 0.053). EBUS-TBNA is a safe and effective modality for evaluating mediastinal lymphadenopathy in patients with a previous extrathoracic malignancy or a MUO without a thoracic lesion. The application of this diagnostic tool is likely to have significant clinical implications.

Two Cases of Malignant Melanoma with Nodal Metastasis from Unknown Primary Site / 대한이비인후과학회지

About 1% of malignant melanoma is found in the head and neck region and among them, about 2-16% is presented with palpable regional metastatic melanoma with unknown primary lesion (MUP). We have experienced two cases of MUP which were diagnosed after excisional biopsy. MUP has better prognosis than that with known primary lesion. To get good prognosis, the initial treatment of MUP should be regional lymphadenectomy, indicating the importance of an accurate diagnosis. Although the radiologic finding for malignant melanoma may offer no specific findings, physicians should be aware of the possibility of melanoma in neck mass patients. We present two cases of MUP with a literature review.

A case of inguinal lymph node squamous cell carcinoma of unknown origin, accompanied with carcinoma in situ of cervix / 부인종양

Metastatic Cancer of Unknown Primary Site (CUP) accounts for approximately 3-5% of all malignant neoplasms. CUP represents a heterogeneous group of metastatic tumors for which no primary site can be detected following a thorough medical history, careful clinical examination, and extensive diagnostic work-up. Several authors have reported poor prognosis of this malignancy, because there is no consensus on diagnostic guidelines and optimal therapy. Historically, chemotherapy has been the cornerstone of treatment for patients with CUP. We experienced a case of inguinal lymph node squamous cell carcinoma of unknown origin, accompanied with carcinoma in situ of the cervix. We report this case with a brief review of the literatures.

Adenocarcinoma of Unknown Primary Site

BACKGROUND: Metastatic cancer of unknown primary site occupies 0.5~10% of all diagnosed cancer patients and includes various tumors with diverse responses to systemic chemotherapy. Adenocarcinoma of unknown primary site (ACUPS), the most common subtype, has no standard treatment, rarely responds to conventional treatment and has a poor survival rate. METHODS: The retrospective study was performed to investigate the clinical characteristics and the treatment outcomes of ACUPS. RESULTS: Eighty-one patients with ACUPS diagnosed at Samsung Medical Center from May 1995 to July 1999 were included. The median age was 58 years (range, 29~77). The common sites of metastases were the lymph node, liver, lung and bone in order. In 49 of 81 patients (60.5%), the dominant tumor location was below the diaphragm. The majority of patients (76 of 81) were initially treated with systemic chemotherapy including cisplatin. Responses were evaluable in 70 of 76. Eighteen of 70 patients (25.7%) responded to chemotherapy and complete remission was observed in 6 patients. The overall median survival of 81 patients was 5.6 months. The median survival of the responding patients was 18.3 months but the median survival of the nonresponding patients was 4.6 months (p<0.01). In univariate and multivariate analysis, age, performance status and response to initial chemotherapy were significant prognostic factors for overall survival. CONCLUSION: We observed poor response to the treatment and survival rate in ACUPS, but complete remission and long-term survival were observed in a small number of patients.

Adenocarcinoma of unknown primary site / 대한내과학회지

BACKGROUND: To study clinical characteristics and treatment outcomes of adenocarcinoma of unknown primary site (ACUPS). METHODS: A retrospective analysis of 81 patients who were diagnosed as ACUPS, seen at Samsung Medical Center from May, 1995 to July, 1999, was performed. RESULTS: The median age of the patients was 58 years. The common sites of metastases were the lymph node, liver, lung, bone. In 49 of 81 patients (60.5%), the dominant tumor location was below the diaphragm. The majority of patiens (76 of 81) were initially treated with systemic chemotherapy including cisplatin. Responses were evaluable in 70 of 76. Eighteen of 70 patients (25.7%) responded to chemotherapy and complete remission was observed in 6 patients. The overall median survival of 81 patients was 5.6 months. The median survival of the responding patients was 18.3 months but the median survial of the nonresponding patients was 4.6 months (p<0.01). In univariate and multivariate analysis, age, performance status and response to initial chemotherapy were significant prognostic factors for overall survial. CONCLUSION: Poor survival rate and treatment response were observed in ACUPS but complete response and long-term survival were observed in several patients.