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.
Humans ; Neoplasms, Unknown Primary/genetics* ; Carcinoma/drug therapy* ; Gene Expression Profiling/methods* ; Microarray Analysis ; Prognosis

Objective: To explore the etiologies and clinical characteristics of fever of unknown origin (FUO) and to provide clues for early diagnosis of FUO. Methods: The data about etiology, age, sex, clinical course, length of hospital stays and the expression levels of inflammatory factors in fever phase of 357 pediatric inpatients who were diagnosed with FUO in Children's Hospital of Fudan University from 1 January 2016 to 31 December 2020 were collected and retrospectively analyzed. Participants were grouped into infectious disease, inflammatory disease, malignancy and others and according to the classification of diseases and also grouped into those aged<1 year, 1-<3 years,3-<6 years, 6-<12 years and 12-<18 years. Comparisons between groups were performed using the Mann-Whitney U test, Kruskal-Wallis H test and χ² test. Results: Among the 357 patients (217 males and 140 females). The age of onset was 3.9 (1.3, 9.2) years and visiting age was 5.1 (2.0, 9.3) years. The time-consuming of diagnosis was 94 (66, 213) days. The hospital stay was 8 (6, 14) days. The most frequently identified cause of FUO was infectious diseases (163 cases, 45.7%), followed by non-infectious inflammatory diseases (133 cases, 37.2%), malignancy (21 cases, 5.9%) and others (40 cases, 11.2%). The patients at younger age were more likely to be attacked by malignancy, oncologic diagnoses, and others, nevertheless patients at older age were more likely to be attacked by non-infectious inflammatory diseases oppositely (9.8 (3.6, 11.5) vs. 3.0 (1.2, 7.0), 2.3 (1.0, 5.2), 0.9 (0.5, 1.8) years, U=41.30, 15.94, 37.08, all P<0.01);106 (65%) patients were male, and 57 (35%) patients were female. This result indicated that boys were more susceptible to infectious diseases (χ²=14.73, P<0.01). Analysis of inflammatory factors in serum among 103 patients, interleukin (IL)-6 level in 40 infectious diseases patients (9 (2, 38) ng/L) was significantly lower than those of 6 tumor patients (89 (64, 599) ng/L) and 57 non-infectious inflammatory diseases patients (25 (8, 78) ng/L, U=51.05, 15.70, both P<0.05), no significant difference was observed in IL-2, IL-4, IL-10, tumor necrosis factor α and interferon among the groups (all P>0.05). The patients grouped into those aged 1-<3 years and 3-<6 years were more likely to be attacked by infectious diseases (51.3% (59/115) and 57.1% (40/70)), while patients grouped into those aged 6-<12 years and 12-<18 years were more likely to be attacked by non-infectious inflammatory diseases (55.6% (65/117) and 72.4% (21/29)). Conclusions: Infectious disease is still the main cause of FUO in children and the boys are more susceptible to infectious diseases. However, the morbidity of non-infectious inflammatory diseases increases to number 1 in FUO of children over 6 years of age.
Aged ; Child ; Communicable Diseases/complications* ; Female ; Fever of Unknown Origin/etiology* ; Humans ; Length of Stay ; Male ; Neoplasms/complications* ; Retrospective Studies

We report the first case demonstrating an association between Kawasaki disease (KD) and erythema nodosum (EN). A 3-year-old girl presented with EN as an initial manifestation of KD. At the initial visit, she showed high fever of 40℃, injection of the oropharynx, cervical lymphadenopathy, and red-purple cutaneous nodules, particularly on the lower limbs. She complained of severe pain in the neck and cutaneous lesions. Initially, the development of EN was attributed to Salmonella spp infection, which was detected in stool culture. However, the patient did not respond to high-dose ampicillin/sulbactam to which the Salmonella spp is sensitive. Echocardiography performed as screening for fever of unknown origin revealed medium-sized aneurysms of the left anterior descending artery. EN masked the diagnosis of KD, and the patient developed a coronary artery lesion. KD should be considered in the differential diagnosis of refractory EN in pediatric patients.
Aneurysm ; Arteries ; Bacterial Infections ; Child, Preschool ; Coronary Vessels ; Diagnosis ; Diagnosis, Differential ; Echocardiography ; Erythema Nodosum ; Erythema ; Exanthema ; Female ; Fever ; Fever of Unknown Origin ; Humans ; Lower Extremity ; Lymphatic Diseases ; Masks ; Mass Screening ; Mucocutaneous Lymph Node Syndrome ; Neck ; Oropharynx ; Salmonella ; Skin ; Subcutaneous Tissue

OBJECTIVE: To investigate the clinical significance of bone marrow unclassifiable cells in diagnosis of fever of unknown origin(FUO). METHODS: The clinical data of 60 patients with FUO admitted in the first affiliated hospital of Xi'an Jiaotong university from June 2014 to May 2016 were collected, and 60 patients with FUO were divided into 2 group: group A(30 cases) in which the unclassifiable cells in bone marrow were observed by bone marrow examination, and group B(30 cases) in which the unclassifiable cells in bone marrow not were found by bone marrow examination. The clinical characteristics, bone marrow features, immunophenotypes of bone marrow cells and prognosis of patients in 2 groups were analyzed retrospectively. RESULTS: Out of 30 patients in group A, 18 were diagnosed as malignant tumors including 12 cases of lymphoma, while out of 30 patients in group B, 5 cases were diagnosed as malignant tumor, including 3 cases of lymphoma. For the patients with non-tumor diseases, the bone marrow unclassifiable cells disappeared after the patients condition was improved. CONCLUSION The bone marrow examination including the smear and biopsy shonld be performed routinely for the patients with FUO. If the unclassifiable cells are observed morphologically in bone marrow of patients with FUO, the disease of patients should be considered as malignant tumor, especially, lymphoma.
Bone Marrow ; Bone Marrow Cells ; Bone Marrow Examination ; Fever of Unknown Origin ; Humans ; Retrospective Studies

Adult-onset Still's disease (AOSD) is a rare systemic febrile disorder of unknown etiology. AOSD is characterized by spiking fever, arthralgia, sore throat, skin rash, and multi-organ involvement but is difficult to diagnose due to the lack of specific clinical features. AOSD is most frequently observed among young adults. We describe the case of an 18-year-old male patient with multiple cerebral infarction who was diagnosed with AOSD based on the clinical features observed during rehabilitation treatment after the diagnosis of ischemic stroke. Clinical symptoms of the patient was controlled with steroid therapy. If cerebral infarction is accompanied by unusual clinical features as non-infectious fever, rash, and arthralgia, AOSD should be considered in young stroke patient.
Adolescent ; Arthralgia ; Cerebral Infarction* ; Diagnosis ; Exanthema ; Fever ; Fever of Unknown Origin ; Humans ; Male ; Pharyngitis ; Rehabilitation ; Still's Disease, Adult-Onset* ; Stroke ; Young Adult

Prognosis has not been known for patients with fever of unknown origin (FUO) whose ¹⁸fluoro-deoxyglucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO that underwent ¹⁸F-FDG PET/CT were retrospectively identified January 2016 - June 2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with microscopic polyangitis and Kikuchi's disease and one patient was transferred to another hospital. Of five patients whose diagnoses were not confirmed, four patients received non-steroidal anti-inflammatory drug and/or low dose steroid and symptoms disappeared. Our study suggests that outcome of patients with FUO whose ¹⁸F-FDG PET/CT finding is non-diagnostic would be favorable.
Diagnosis ; Electrons* ; Fever of Unknown Origin* ; Fever* ; Histiocytic Necrotizing Lymphadenitis ; Humans ; Korea ; Positron-Emission Tomography and Computed Tomography ; Prognosis ; Retrospective Studies ; Tertiary Care Centers

Prognosis has not been known for patients with fever of unknown origin (FUO) whose ¹⁸fluoro-deoxyglucose (¹⁸F-FDG) positron emission tomography/computerized tomography (PET/CT) finding is non-diagnostic. A total of eight patients with FUO that underwent ¹⁸F-FDG PET/CT were retrospectively identified January 2016 - June 2017 in a tertiary hospital in Korea. Of these, two patients were diagnosed with microscopic polyangitis and Kikuchi's disease and one patient was transferred to another hospital. Of five patients whose diagnoses were not confirmed, four patients received non-steroidal anti-inflammatory drug and/or low dose steroid and symptoms disappeared. Our study suggests that outcome of patients with FUO whose ¹⁸F-FDG PET/CT finding is non-diagnostic would be favorable.
Diagnosis ; Electrons* ; Fever of Unknown Origin* ; Fever* ; Histiocytic Necrotizing Lymphadenitis ; Humans ; Korea ; Positron-Emission Tomography and Computed Tomography ; Prognosis ; Retrospective Studies ; Tertiary Care Centers

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.
Adenocarcinoma ; Biopsy ; Collagen ; Diagnosis ; Neoplasm Metastasis ; Neoplasms, Unknown Primary ; Prognosis ; Rare Diseases ; Retroperitoneal Fibrosis* ; Tomography, X-Ray Computed

Respiratory-gated ¹⁸F-fluorodeoxygluocse (¹⁸F-FDG) PET/CT has been successfully used to better localize malignancies in the lung or upper abdominal organs. However, clinical usefulness of respiratory-gated ¹⁸F-FDG PET/CT in detection of fever focus has not been reported yet. A 68-year-old male patient with a history of living donor liver transplantation and biliary stenting was referred for ¹⁸F-FDG PET/CT due to fever of unknown origin (FUO). To find the accurate fever focus, respiratory-gated and non-gated ¹⁸F-FDG PET/CT was performed. Respiratory-gated PET/CT readily revealed prominent hypermetabolic lesion in the distal common bile duct (CBD) area where previous surgical graft was in situ. Maximum standardized uptake value (SUVmax) and SUVratio (SUR) were greater in the gated PET/CT (SUVmax 5.4 and SUR 3.5) than in the non-gated PET/CT (SUVmax 4.6 and SUR 3.0). Fever dramatically subsided after removal of the graft in the CBD. This case report implies that respiratory-gated ¹⁸F-FDG PET/CT can visualize upper abdominal fever focus with better contrast than the conventional non-gated method.
Aged ; Common Bile Duct ; Fever of Unknown Origin ; Fever ; Humans ; Liver Transplantation ; Living Donors ; Lung ; Male ; Methods ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Respiratory-Gated Imaging Techniques ; Stents ; Transplants

PURPOSE: Fever is one of the most common symptoms in children. In previous studies, infectious disease was the most common cause of pediatric fever of unknown origin (FUO). The aim of this study is to investigate the etiology, clinical characteristics and prognosis of pediatric FUO in 21 century with more diagnostics available and to analyze the factors for certain disease categories. METHODS: Among the children under 18 years old who were hospitalized at Samsung Medical Center from January 2000 to December 2014, the patients who met the criteria including fever of ≥38.0℃ for longer than ≥14 days and failure to reach a diagnosis after one week of investigations were included. RESULTS: Total 100 patients were identified. Confirmed diagnosis was achieved in 57 patients (57%). Among them, infectious diseases (n=19, 19%) were most common, followed by connective tissue diseases (n=15, 15%), necrotizing lymphadenitis (n=8, 8%), and malignancies (n=7, 7%). Children with fever duration over 28 days had a trend for higher frequency of connective tissue diseases (28.3%) except undiagnosed etiology. The symptoms such as arthritis, lymph node enlargement and only fever without other symptoms were significantly related with connective tissue diseases, necrotizing lymphadenitis and undiagnosed respectively (P<0.001). Ninety-two patients have become afebrile at discharge and 1 patient died (1%). CONCLUSION: Almost half of our patients were left without diagnosis. Although it has been known that infectious disease was most common cause of pediatric FUO in the past, undiagnosed portion of FUO have now increased due to development of diagnostic techniques for infectious diseases.
Arthritis ; Child* ; Communicable Diseases ; Connective Tissue Diseases ; Diagnosis ; Fever of Unknown Origin* ; Fever* ; Humans ; Lymph Nodes ; Lymphadenitis ; Prognosis