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As a rare lymphoproliferative disorder, many patients with HHV-8/HIV-negative Castleman disease (CD) have hypoalbuminemia. However, data is limited on whether hypoalbuminemia is an independent predictor of CD. We retrospectively collected data from 230 patients diagnosed at 12 medical centers in China and the U.S. Different classifications included 147 patients with unicentric CD (UCD) and 83 with idiopathic multicentric CD (iMCD). Adjusted smooth curve fitting showed that the relationship between albumin and all-cause death of patients with CD and iMCD was linear. Cox proportional hazards regression modeling showed a negative association between the risk of death and albumin level (hazard ratio [HR]: 0.84; 95% CI, 0.76, 0.93). Using the Kaplan-Meier method, we determined that hypoproteinemia was a risk factor for poorer prognosis in patients with CD, UCD, and iMCD. Albumin was independently and negatively associated with the risk of death in CD patients, especially those with iMCD.

Exuberant large T-cell proliferations in Kikuchi disease can potentially be misdiagnosed as lymphoma. In this study, we explore their clinicopathological features and summarize key points that can be used to distinguish them from T-cell lymphoma. The cohort consisted of 25 cases of Kikuchi disease with an exuberant large T-cell proliferation, which, in part, mimicked lymphoma. The median age was 25 years with a female:male ratio of 4:1. By B-scan ultrasonography, patients presented with either isolated lymphadenopathy (68%) involving the cervical and axillary regions or generalized lymphadenopathy (32%). Histologically, lymph nodes showed paracortical and interfollicular expansion by sheets of large cells associated with karyorrhectic debris. Histiocytes and plasmacytoid dendritic cells were present in the background. No case showed complete effacement of lymph node architecture. The large cells were CD8-positive cytotoxic T-cells with a high proliferation rate. These T-cells showed decreased BCL-2 in 17 (68%) cases. CD5 expression was decreased in 10 (40%) cases. Histiocytes in the background were positive for myeloperoxidase. Clonal TRG and/or TRB rearrangements were detected in 2 of 10 (20%) cases. In conclusion, large T-cell proliferations in Kikuchi disease can be alarming at the morphologic and immunophenotypic levels and need to be distinguished from T-cell lymphoma. Clinical features helpful in the differential diagnosis include young patients and lymphadenopathy involving the cervical and axillary regions. Major pathologic features helpful in this differential diagnosis include partial involvement of the lymph node and the presence of karyorrhectic debris, crescent-shaped histiocytes, and/or loose aggregates of plasmacytoid dendritic cells.

Background Patients with multicentric Castleman disease (MCD) who are negative for human immunodeficiency virus and human herpesvirus 8 are considered to have idiopathic MCD (iMCD). The clinical presentation of iMCD varies from mild constitutional symptoms to life-threatening symptoms or death. The treatment strategy varies from “watchful waiting” to high-dose chemotherapy. This diverse clinical presentation calls for a classification stratification system that takes into account the severity of the disease. Subjects, Materials, and Methods We analyzed the clinical, laboratory, and pathologic abnormalities and treatment outcomes of 176 patients with iMCD (median follow-up duration 12 years) from the U.S. and China to better understand the characteristics and prognostic factors of this disease. This discovery set of iMCD results was confirmed from the validation set composed of additional 197 patients with iMCD organized from The International Castleman Disease Consortium. Results Using these data, we proposed and validated the iMCD international prognostic index (iMCD-IPI), which includes parameters related to patient characteristics (age > 40 years), histopathologic features (plasma cell variant), and inflammatory consequences of iMCD (hepatomegaly and/or splenomegaly, hemoglobin Conclusion This study represents the largest series of studies on patients with iMCD in the field and proposed a novel risk-stratification model for iMCD-IPI that could be used to guide risk-stratified treatment strategies in patients with iMCD. Implications for Practice Patients with idiopathic multicentric Castleman disease (iMCD) can benefit from care based on clinical symptoms and disease severity. This study in 176 patients with iMCD constructed an iMCD-IPI score based on five clinical factors, including age >40 years, plasmacytic variant subtype, hepatomegaly and/or splenomegaly, hemoglobin

Castleman disease (CD) has been reported as a group of poorly understood lymphoproliferative disorders, including unicentric CD (UCD) and idiopathic multicentric CD (iMCD) which are human immunodeficiency virus (HIV) negative and human herpes virus 8 (HHV-8) negative. The clinical and independent prognostic factors of CD remain poorly elucidated. We retrospectively collected the clinical information of 428 patients with HIV and HHV-8 negative CD from 12 large medical centers with 15-year follow-up. We analyzed the clinicopathologic features of 428 patients (248 with UCD and 180 with iMCD) with a median age of 41 years. The histology subtypes were hyaline-vascular (HV) histopathology for 215 patients (56.58%) and plasmacytic (PC) histopathology for 165 patients (43.42%). Most patients with UCD underwent surgical excision, whereas the treatment strategies of patients with iMCD were heterogeneous. The outcome for patients with UCD was better than that for patients with iMCD, 5-year overall survival (OS) rates were 95% and 74%, respectively. In further analysis, a multivariate analysis using a Cox regression model revealed that PC subtype, hepatomegaly and/or splenomegaly, hemoglobin ≤ 80 g/L, and albumin ≤ 30 g/L were independent prognostic factors of CD for OS. The model of iMCD revealed that age > 60 years, hepatomegaly and/or splenomegaly, and hemoglobin ≤ 80 g/L were independent risk factors. In UCD, single-factor analysis identified two significant risk factors: hemoglobin ≤ 100 g/L and albumin ≤ 30 g/L. Our study emphasizes the distinction of clinical characteristics between UCD and iMCD. The importance of poor risk factors of different clinical classifications may direct more precise and appropriate treatment strategies.

Colorectal cancer (CRC) is a lethal malignant tumor and 25-30% of CRC patients develop liver metastasis (LM) with a worse prognosis, but the metastasis mechanism is yet elucidated. To identify the potential immune regulatory mechanism of CRC liver metastasis, single-cell sequencing and multiplex immunohistochemistry were applied to identify key cell populations of the tumor microenvironment (TME) in the CRC and LM sites. We found memory CD8

Liver cancer is a common malignant disease in China, while the primary hepatic neuroendocrine tumor (PHNET) is extremely rare presented with various manifestations. We herein describe an interesting PHNET case, which was clinically diagnosed as hepatocellular carcinoma (HCC) based on strong clinical evidence and the national guideline, but confirmed to be PHNET by pathology. A42-year-old Chinese male was admitted for persistent upper abdominal pain, and CT scan revealed a huge liver tumor in the left lobe. The tumor presented attributes of tumor rupture, portal vein tumor thrombus, elevated serum AFP level, background hepatitis B virus infection history, and radiological features mimicking typical HCC. After left semi-hepatectomy was performed for curative treatment of the primary "HCC", the pathology demonstrated the correct diagnosis be poorly differentiated neuroendocrine carcinoma (NEC). The immunohistochemistry assays showed positive neuroendocrine markers of CgA and Syn and negative HCC markers of Hep Par 1 and GPC3, ruling out concurrent HCC. This case and literature review suggest that in spite of rare incidence, PHNET should be considered as a possible diagnosis when lacking a confirmative pathology result, even when sufficient evidence of typical presentation exist to establish the clinical diagnosis of HCC.

The infiltration and invasion of nerve trunks, nerve roots, and cranial nerves by lymphomatous malignant cells is defined as "neurolymphomatosis". It is mainly caused by lymphoma cells directly infiltrating the peripheral nerves, with a low incidence. Neurolymphomatosis is a rare condition of neoplastic endoneurial invasion, which is primary or secondary to non-Hodgkin's lymphoma and leukemia. We describe a case of primary peripheral neurolymphomatosis of multifocal involvement in a 77-year-old male patient. He presented with left lower limb pain and was diagnosed with CD20+ diffuse large B cell lymphoma (DLBCL). Magnetic resonance imaging (MRI), fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) computed tomography (CT), and nerve biopsy contributed to the diagnosis. Genomic profiling, programmed death ligand-1 (PD-L1) expression and tumor mutational burden (TMB) were also assessed. CDKN2A/CDKN2B deletions have been identified. PD-L1 expression assessed by 28-8 antibody was 1% positivity, and TMB of the sample was 11.6 muts/Mb. The patient responded well to rituximab combined with chemotherapy, however, he died after 3 cycles of chemotherapy due to severe lung infection and subsequent complication of respiratory failure. Here we report the clinical, radiological, pathological and molecular findings of the patient affected by multifocal neurolymphomatosis without systemic involvement of other organs.

Background：Primary cardiac CD5 positive diffuse large B-cell lymphoma (CD5+ DLBCL) is a rare subtype of DLBCL with many diagnostic challenges. The case is reported, along with a review of several characteristics of the disease. Case presentation：We described a 64-year-old female who presented with a 12-month history of cough, and a mass in the right atrium observed on imaging studies that extended into the right ventricle. Conclusions：CD5+ DLBCL was confirmed finally by pathological examination of the cardiac biopsy. The patient responded well to the modified R-CHOP regime. The poor prognosis factors include CD5 positive, non-GCB immunophenotype, myc, bcl-2 and bcl-6 gene rearrangements etc. Early diagnosis and aggressive treatment play a key role on improving the prognosis of primary cardiac CD5+ DLBCL.

Background: Situs inversus totalis (SIT) is a rare genetic congenital disease, characterized by complete right-left inversion of all the internal organs. We herein describe a meaningful case which was diagnosed as gallbladder adenosquamous carcinoma, a rare histology type of gallbladder cancer, with SIT. Case presrntaton: A 59-year-old Chinese woman was admitted for persistent epigastric distention and intermittent abdominal pain. The abdominal CT scan revealed a huge mass at the gallbladder bottom, involving the adjacent transverse colon and liver. En-bloc radical resection of the gallbladder cancer, including partial colonectomy and hepatectomy with regional node dissection, followed by colocolostomy and Roux-en-Y choledochojejunostomy, was successfully performed Pathology analysis indicated an adenosquamous carcinoma with positive adenocarcinoma marker (CK7, CK19) and squamous carcinoma markers (CK5/6, P63). Conclusion: The SIT anomaly might increase the risk of malignancies by sharing genome mutations, suggesting the importance of surveillance in the SIT settings.

Background The present study constructed and validated the use of contrast‐enhanced computed tomography (CT)‐based radiomics to preoperatively predict microvascular invasion (MVI) status (positive vs negative) and risk (low vs high) in patients with hepatocellular carcinoma (HCC). Methods We enrolled 637 patients from two independent institutions. Patients from Institution I were randomly divided into a training cohort of 451 patients and a test cohort of 111 patients. Patients from Institution II served as an independent validation set. The LASSO algorithm was used for the selection of 798 radiomics features. Two classifiers for predicting MVI status and MVI risk were developed using multivariable logistic regression. We also performed a survival analysis to investigate the potentially prognostic value of the proposed MVI classifiers. Results The developed radiomics signature predicted MVI status with an area under the receiver operating characteristic curve (AUC) of .780, .776, and .743 in the training, test, and independent validation cohorts, respectively. The final MVI status classifier that integrated two clinical factors (age and α‐fetoprotein level) achieved AUC of .806, .803, and .796 in the training, test, and independent validation cohorts, respectively. For MVI risk stratification, the AUCs of the radiomics signature were .746, .664, and .700 in the training, test, and independent validation cohorts, respectively, and the AUCs of the final MVI risk classifier‐integrated clinical stage were .783, .778, and .740, respectively. Survival analysis showed that our MVI status classifier significantly stratified patients for short overall survival or early tumor recurrence. Conclusions Our CT radiomics‐based models were able to predict MVI status and MVI risk of HCC and might serve as a reliable preoperative evaluation tool., (1)Preoperative computed tomography images of hepatocellular carcinoma (HCC) were collected from two institutions for training and independent validation.(2)The least absolute shrinkage and selection operator regression algorithm was used to construct radiomics signatures.(3)Radiomics‐based prediction models predicted the microvascular invasion status (positive vs. negative) and risk (low vs. high) of HCC.

Introduction We evaluated the current status of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detection in invasive breast carcinoma (IBC) in various laboratories across China. Materials and Methods The Breast Pathology Study Group of the Chinese Society of Pathologists collected HR and HER2 data from 12,467 IBC cases from 19 representative clinical centers in China. The data from every center were compared with the pooled data from the other centers. Results The assessment of HR status showed that the overall positive estrogen receptor (ER) and progesterone receptor (PR) rates were 71.7% and 63.7% (range, 60.9%-87.9% and 43.9%-84.8%), respectively. The ER results in 3 centers and the PR results in 6 centers were outside the 99.5% confidence interval and were considered to be outliers (P Conclusions As the largest study of HR and HER2 status in Chinese patients with IBC, the data from the present study have indicated that the overall rates of HR and HER2 were comparable to those reported in previous studies. However, the rates varied among the laboratories. Individual centers had not met the target values, and they need to improve the detection.

Recurrent hydatidiform moles (RHM) are aberrant human pregnancies characterized by absence of, or abnormal, embryonic development, hydropic degeneration of chorionic villi, and hyperproliferation of the trophoblast. Biallelic mutations in two maternal-effect genes, NLRP7 and KHDC3L, underlie the causation of RHM in 60% of patients. We performed exome sequencing on a patient with six pregnancy losses, two miscarriages and four HM, and found no variants that affect the functions of the known genes. We found biallelic missense variants that affect conserved amino acids in PADI6 and segregate with the disease phenotype in the family. PADI6 is another maternal-effect gene and a member of the subcortical maternal complex that has been shown to have recessive variants that affect the gene function in four unrelated women with infertility who also experienced early embryonic arrest during preimplantation development after IVF. We demonstrated that PADI6 co-localizes with NLRP7 in human oocytes and preimplantation embryos and reviewed the morphology and genotypes of four products of conception from our patient. Our data expand the involvement of PADI6 to other forms of reproductive loss and highlight the commonality between infertility, miscarriages, and molar pregnancies, in some cases.

Background Multiple myeloma (MM) is a type of hematological malignancy with significant heterogeneity in clinical features and prognosis. Cytogenetic abnormalities are the major factors affecting patient outcomes. Studies have shown that immunohistochemistry (IHC)-based detection of cancer-related genes expression could be alternative indicators for the prognosis of MM. Methods Nuclear expression of c-maf protein in the bone marrow plasma cells of 128 multiple myeloma patients were examined by IHC, and its association with the clinicopathological features of MM patients was analyzed as well. Results Among the 128 patients, the positive rate of c-maf protein expression was up to 30.5%, which had no correlation with patient age, M protein type, Durie-Salmon staging system, the International Staging System, abnormal plasma cell ratio in the bone marrow, or the level of peripheral blood hemoglobin, serum calcium or lactate dehydrogenase. However, the c-maf-positive patients had a significantly higher rate of hypoproteinemia (p = 0.026) and higher serum β2-microglobulin levels (>2500 μg/L) (p = 0.007). Patients with negative c-maf expression had higher remission rates upon the treatment of non-bortezomib-based regimens although no effect of c-maf expression on progression-free survival or overall survival was observed. Conclusion Patients with negative c-maf expression had higher remission rates upon the treatment of non-bortezomib-based regimens although no effect of c-maf expression on survival was observed. A further large-scale prospective study is required to verify these findings.

Esophageal chondromatous hamartomas are very rare tumors, characterized by proliferating hyaline cartilage cells. We described the case of a 64-year-old woman, with a progressive foreign body sensation in the laryngopharynx caused by an intraluminal pedicled mass. Transcervical esophagectomy was performed and intraoperative biopsy revealed the mass was a cervical esophageal chondromatous hamartoma. The patient’s postoperative course was uneventful and she recovered well. A review of the literature was conducted, and the symptoms, locations, histopathology findings, treatment methods and follow up results of esophageal hamartoma cases were summarized. We found that pre-operative endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) can aid in diagnosis and that aggressive surgical treatment should be recommended for cervical esophageal hamartomas.

Renal angiomyolipoma (AML) is the most common type of benign mesenchymal tumor of the kidney. AMLs typically present as benign lesions without local invasion. However, the tumor may exhibit aggressive behavior. Intravascular extension into the inferior vena cava (IVC) and hemorrhagic aneurysm formation associated with AML has rarely been reported in the past. In the current study, the novel case of a 77-year-old female is described who presented with a tumor thrombus extending to the IVC. The patient subsequently underwent a radical nephrectomy and an IVC tumor thrombectomy. In addition, the available literature regarding this unusual complication of a common renal neoplasm has been reviewed. It is essential for radiologists and clinicians to be aware that AMLs may exhibit these types of aggressive behaviors.

Objective: To evaluate the correlation of EGFR mutation and histological subtypes of lung adenocarcinoma based on the IASLC/ATS/ERS classification. Methods: EGFR exons 18-21 of 206 resected lung adenocarcinoma specimens were analyzed with pyrosequecing, then the differences between histological subtypes and EGFR mutation were compared. Results: EGFR mutation was detected in 123 specmens, most of which were papillary and acinar predominant adenocarcinoma. EGFR mutation rate of the specimens with papillary, acinar or lepidic component was higher than without these components (P < 0.05), and with solid or mucinous component was lower than that without the component (P < 0.05). EGFR mutation in solid predominant mixed other subtypes was more commonly found than that of pure solid component (P=0.018). Conclusions: The presence of well-differentiated components in lung adenocarcinoma, such as lepidic, papillary and acinar, indicates a higher EGFR mutation rate, while the solid and mucinous component indicate a lower EGFR mutation rate. There is heterogeneity of EGFR mutation in lung adenocarcinoma.

We aimed to explore the association of blood Zn, Fe, and Cu concentrations and changes in the pediatric risk of mortality (PRISM) score in critically ill children, to predict prognosis. We included 31 children (22 boys and 9 girls, 1 month to 5 years old), who had been admitted to the intensive care unit of our hospital and who were critically ill according to PRISM score of III. Another 20 children (12 boys, 8 girls, 3 months to 5 years old) who were brought to the hospital for a health checkup were included as controls. We recorded clinical data, time in the intensive care unit, prognosis, and PRISM III score for critically ill children. Blood Cu, Zn, and Fe values were measured by inductively coupled plasma atomic emission spectrophotometry. Zn and Fe levels were significantly lower in patients than in controls (all p 0.05). Cu levels differed between patients and controls, but not significantly (p 0.05). In ill children, blood Zn and Fe concentrations were inversely correlated with PRISM III score (Zn: r = -0.36; Fe: r = -0.50, both p 0.05), with no significant correlation of blood Cu level and PRISM III score (r = -0.13, p 0.05). Serious illness in children may lead to decreased Zn and Fe blood concentrations. Zn and Fe supplements may be beneficial for critically ill children.