Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive neoplasm with biological heterogeneity. Mutations in multiple genes have been identified in LCNEC. However, associations between gene alterations, histopathological characteristics, and prognosis remain ambiguous. Here, we investigated the clinicopathologic, immunohistochemical, and genomic characteristics of 19 patients with LCNEC and 9 patients with atypical carcinoid (AC). We revealed high mutation frequencies of TP53 (89.5 %), RB1 (42.1 %), APC (31.6 %), and MCL1 (31.6 %) in LCNEC, while genetic alterations were rarely found in AC. APC alterations mainly occurred to the exon 16 and were only identified in LCNEC with wild-type RB1. The 19 LCNEC were further subgrouped into APC wild-type (LCNEC-APCMT, 6/19) and APC-mutated (LCNEC-APCWT, 13/19) subgroups. In comparison with LCNEC-APCWT, LCNEC-APCMT displayed lower TMB (median: 12.64 vs 4.20, P = 0.045), and relatively mild cytologic atypia. In addition, LCNEC-APCMT distinguished itself from AC and LCNEC-APCWT by obviously downregulated expression of neuroendocrine markers (CD56 and Syn, P < 0.01) and significantly altered expression of genes downstream of APC (β-catenin migrating into the cytoplasm and nucleus, P < 0.001; c-Myc upregulating, P = 0.005). The OS of LCNEC-APCMT was numerically intermediate between AC and LCNEC-APCWT. We first proposed that APC alterations were common in LCNEC with wild-type RB1 and that LCNEC-APCMT was associated with lower TMB and better OS in comparison with LCNEC-APCWT.

OBJECTIVE: To report a rare gastroblastoma; discuss its clinical features, histopathological morphology, diagnosis, differential diagnosis, treatment, and prognosis; and so as to improve the understanding on this disease and provide reference for its diagnosis, treatment, and prognosis.
METHODS: The diagnosis and treatment, imaging examination, pathological, and genetic data of a 19-year-old young female patient with gastroblastoma were analyzed retrospectively, and the relevant literature was reviewed and summarized.
RESULTS: The patient was found to have a \"gastrointestinal stromal tumor\" for 3 days by physical examination in another hospital. Abdominal CT and MRI considered \"solid pseudopapilloma of pancreas\" and clinically planned to perform \"radical pancreatoduodenectomy.\" During the operation, the tumor was observed to bulge from the posterior wall of the gastric antrum, and the root was located in the gastric antrum, so it was changed to \"partial gastrectomy + Ronx-y gastrojejunal anastomosis.\" The postoperative pathology showed that the tumor was bi-differentiated between gastric epithelium and mesenchymal. Combined with the results of IHC and the opinions of several consultation units, the diagnosis of gastric blastoma (low-grade malignancy) was supported. However, the fracture rearrangement of GLI1 and EWSR1 genes was not detected by FISH. After 19 months of follow-up, no signs of tumor recurrence and metastasis were found.
CONCLUSIONS: Combined with existing literature reports, gastroblastoma occurs in young people, equally in men and women, and tends to occur in the gastric antrum. The biological behavior of the tumor tends to be inert, and the prognosis of most cases is good. Postoperative pathology and IHC are reliable methods for the diagnosis of gastric blastoma, and surgical resection of the lesion is the preferred treatment.

UNASSIGNED: Granulomatous lobular mastitis (GLM) is a rare, benign, and complex breast disease that can be easily misdiagnosed as breast cancer. The etiology of GLM is unclear, and optimal treatment has not been established.
UNASSIGNED: Medical records for 333 patients with GLM in recent 5 years at Longhua Hospital, Shanghai, China, were analyzed. Potential pathogens in 33 fresh tissue specimens were also analyzed using 16S rDNA sequencing technology, matrix-assisted laser desorption ionization time of flight mass spectrometry, and bacterial cultures.
UNASSIGNED: The median age of patients was 32 years (range 22-47 years). Among 333 patients, 38.7% displayed elevated prolactin, while 23.7% displayed high interleukin-2. In the granulomatous lesion, CD3-positive T lymphocytes were significantly more than CD20-positive B lymphocytes around the vacuoles or microabscesses. Gram-positive organisms were observed in 82 cases, including in 22 cases from fresh tissue specimens. Thirty-three cases yielded associated pathogens and all displayed multiple pathogenic infections, as identified using 16S rDNA sequencing technology. Pathogenic infections were further identified as belonging to 16 main genera and 8 main pathogenic species.
UNASSIGNED: GLM displays distinct histological and clinical features similar to those that have been previously reported in the literature. Using 16S rDNA sequencing technology, all of our cases demonstrated multiple pathogenic infections, which provided more useful information for clinical treatment.

PD-L1+ exosome have been reported to be a promising prognostic biomarker in various cancers. However, its clinical value in diffuse large B cell lymphoma (DLBCL) has not been defined yet. In this study, a total of 165 plasma samples from 78 patients with DLBCL undergoing standard first-line R-CHOP regimens were collected at three different time points (pretreatment, and after 3 and 6 cycles of R-CHOP) to determine the proportions of PD-L1+ exosomes by flow cytometry. We found that high pretreatment plasma PD-L1+ exosome correlated with indicators of poor clinical outcome that included high Ki-67 expression (P = 0.02), double expressor lymphoma (P = 0.005), immunohistochemical PD-L1+ tumor tissue (P = 0.006), and the baseline maximal standardized uptake values (P = 0.0003). Pretreatment plasma PD-L1+ exosome was an independent factor by multivariate analysis with logistic regression (P = 0.0301). Moreover, the pretreatment PD-L1+ exosome was a strong predictor of final treatment responses of either CR or non-CR by ROC analysis (P < 0.001). PD-L1+ exosome level declined significantly in patients who experienced CR (pretreatment vs. after 3 cycles/after 6 cycles, P < 0.05), but not in the non-CR group. Intriguingly, plasma PD-L1+ exosome after 3 cycles (AUC = 0.857; 95%CI: 0.728-0.939) might represent a more sensitive indicator than radiographic assessment after 3 cycles (AUC = 0.626; 95%CI: 0.477-0.758) for evaluating the therapeutic response of DLBCL patients (P = 0.0136). Our results suggest that plasma PD-L1+ exosomes may represent a new biomarker for the dynamic monitoring of treatment response.

BACKGROUND: Ovarian cancer (OC) is the second most common gynecological tumor with the highest mortality rate worldwide. High FAM111B expression has been reported as a predictor of poor prognosis in other cancers, but its correlation with OC has not been reported.
METHODS: Immunohistochemistry of tissue microarrays was performed to detect FAM111B expression levels in 141 OC patient tissues. The prognostic value of FAM111B was determined by Kaplan-Meier survival analysis, and correlations between FAM111B expression and clinicopathologic features were investigated by the Clu-square test. The significance of FAM111B expression was verified bioinformatically using the Gene Expression Omnibus database. Protein-protein interaction were performed to explore downstream mechanisms of FAM111B in OC.
RESULTS: Among 141 OC patients, FAM111B was positively expressed in 87.23%, 58.16%, and 87.94%; and highly expressed in 8.51%, 17.02%, and 19.86%, as evaluated by cytoplasmic, nuclear, and combined cytoplasmic/nuclear staining. FAM111B expression was positively correlated with the expression of tumor protein markers KI67, EGFR, and PDL-1. Patients with high FAM111B expression had aggressive clinicopathologic features and shorter overall survival (P value 0.0428, 0.0050, 0.0029) and progression-free survival (P value 0.0251, 0.012, 0.0596) compared to the low FAM111B expression group for cytoplasmic, nuclear, and combined cytoplasmic/nuclear groups, respectively. These results were verified using patient data from the Gene Expression Omnibus. Seventeen genes co-expressed with FAM111B were primarily involved in \"negative regulation of histone modification\", \"hippo signaling\" and \"inner ear receptor cell differentiation\".
CONCLUSIONS: High FAM111B expression may serve as a novel prognostic predictor and molecular therapeutic target for OC.

UNASSIGNED: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are a rare, highly malignant subset of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, how to predict the prognosis of GEP-NECs by clinical features is still under study. This study aims to establish and validate a nomogram model of overall survival (OS) in patients with GEP-NECs for predicting their prognosis.
UNASSIGNED: We selected patients diagnosed with GEP-NECs from the Surveillance, Epidemiology, and End Results (SEER) database and two Chinese hospitals. After randomization, we divided the data in the SEER database into the train cohort and the test cohort at a ratio of 7:3 and used the Chinese cohort as the validation cohort. The Cox univariate and multivariate analyses were performed to incorporate statistically significant variables into the nomogram model. We then established a nomogram and validated it by concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, the area under the curve (AUC), and the decision curve analysis (DCA) curve.
UNASSIGNED: We calculated the nomogram C-index as 0.797 with a 95% confidence interval (95% CI) of 0.783-0.815 in the train cohort, 0.816 (95% CI: 0.794-0.833) in the test cohort and 0.801 (95% CI: 0.784-0.827) in the validation cohort. Then, we plotted the calibration curves and ROC curves, and AUCs were obtained to verify the specificity and sensitivity of the model, with 1-, 3- and 5-year AUCs of 0.776, 0.768, and 0.770, respectively, in the train cohort; 0.794, 0.808, and 0.799 in the test cohort; 0.922, 0.925, and 0.947 in the validation cohort. The calibration curve and DCA curves also indicated that this nomogram model had good clinical benefits.
UNASSIGNED: We established the OS nomogram model of GEP-NEC patients, including variables of age, race, sex, tumor site, tumor grade, and TNM stage. This model has good fitting, high sensitivity and specificity, and good clinical benefits.

Primary lymphoma in soft tissue is very rare. In order to understand the clinicopathological features of primary lymphoma in soft tissue, we found 13 cases (0.3%) of primary lymphoma in soft tissue by reviewing 4303 lymphomas diagnosed in our institution from 2010 to 2019. Tumors were found in the following sites: 8 in lower extremity (2 in leg, 1 in calf, 1 in knee and 4 in buttock), 1 in upper extremity (left shoulder) and 4 in the trunk (3 in waist and 1 in thoracolumbar). The most common histologic type was DLBCL (7/13, 54.8%). 6 cases of which had follow-up information. 25 patients were also selected by screening the English literature search (from Jan 2010 to December 2019) including 1102 studies. Compared to the results of literature review, our results are similar with them. The tumor sites were as follows: 10 in lower extremity, 4 in upper extremity, 9 in the trunk and 2 in masticatory muscle. The most common histological type was also DLBCL (n=11/25, 44%). Overall survival analysis of all 31 patients including our 6 cases with primary lymphoma in soft tissue showed no significant difference between different histological type (Log Rank P=0.120, Breslow P=0.157). The differential diagnosis includes malignant melanoma, rhabdomyosarcoma and metastatic carcinoma in soft tissue.

Intravascular large B-cell lymphoma (IVLBCL) is a rare and highly malignant non-Hodgkin B-cell lymphoma with uncommon clinical presentation and poor prognosis. The diagnostic pitfall of IVLBCL is mainly due to the fact that subtle histological changes could be easily overlooked, in addition to its rare occurrence, non-specific and variable clinical presentations, and the absence of significant mass lesions. The purpose of this study is to further explore the clinicopathologic and molecular features of IVLBCL to ensure an accurate diagnosis of this entity. Here, we retrospectively present the data of the four new cases and the literature cases. The age ranged from 23 to 92, with a medium age of 67 and a male-to-female ratio of 1:1. The clinical manifestations are extremely variable, including fever, night sweats, weight loss, anemia, thrombocytopenia, unexplained hypoxemia, impaired consciousness, and skin lesions, as well as the extremely low levels of serum albumin, high levels of serum lactate dehydrogenase (LDH), soluble interleukin-2 receptor (sIL2R), and ferritin. Morphologically, 99.9% of cases showed a selective growth pattern with large, atypical lymphocytes within the lumen of small blood vessels. In addition, vast majority of cases were positive for CD20, CD79a, PAX5, MUM1, and BCL6, and a subset of cases expressed BCL2 and CD5, whereas CD3 and CD10 were typically negative. Ki-67 proliferative index ranged from 20% to 100%. To sum up, we have conducted comprehensive case reports, to the best of our knowledge, this is the largest reported cohort of IVLBCL cases. Comprehensive assessments and more IVLBCL cases are required for early diagnosis and prompt treatment.

UNASSIGNED: The clinicopathologic characteristics of nephropathy associated with mitochondrial disease (MD) remain unknown. We retrospectively analyzed a cohort of patients with proteinuria, decreased glomerular filtration rate, or Fanconi syndrome who had a genetic mutation confirmed as the cause of MD, defined as mitochondrial nephropathy.
UNASSIGNED: This nationwide survey included 757 nephrology sections throughout Japan, and consequently, data on 81 cases of mitochondrial nephropathy were collected.
UNASSIGNED: The most common renal manifestation observed during the disease course was proteinuria. Hearing loss was the most common comorbidity; a renal-limited phenotype was observed only in mitochondrial DNA (mtDNA) point mutation and COQ8B mutation cases. We found a median time delay of 6.0 years from onset of renal manifestations to diagnosis. Focal segmental glomerular sclerosis (FSGS) was the most common pathologic diagnosis. We then focused on 63 cases with the m.3243A>G mutation. The rate of cases with diabetes was significantly higher among adult-onset cases than among childhood-onset cases. Pathologic diagnoses were more variable in adult-onset cases, including diabetic nephropathy, nephrosclerosis, tubulointerstitial nephropathy, and minor glomerular abnormalities. During the median observation period of 11.0 years from the first onset of renal manifestations in patients with m.3243A>G, renal replacement therapy (RRT) was initiated in 50.8% of patients. Death occurred in 25.4% of the patients during the median observation period of 12.0 years. The median estimated glomerular filtration rate (eGFR) decline was 5.4 ml/min per 1.73 m2/yr in the cases, especially 8.3 ml/min per 1.73 m2/yr in FSGS cases, with m.3243A>G.
UNASSIGNED: Here, we described the clinicopathologic features and prognosis of mitochondrial nephropathy using large-scale data.

OBJECTIVE: The aim of this study was to evaluate the expression of MALAT1 and the relationship between its expression with clinical characteristics in an Iranian gastric cancer patient.
BACKGROUND: Long non-coding RNAs (LncRNAs) play critical roles in the initiation and development of gastric cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a highly conserved lncRNA and plays key roles in various types of human cancer. However, our understanding of the role of lncRNAs in the occurrence and development of gastric cancer is not fully clear.
METHODS: This cross-sectional study was performed on 41 gastric tumor tissue samples with matched normal adjacent tumor tissues. The RNA level of lncRNA MALAT1 gene was assessed using quantitative Real-time polymerase chain reaction. B2M was used as an internal control. The 2 -ΔΔCq method was adopted to determine expression fold changes.
RESULTS: A significant association was observed between the levels of MALAT1 in gastric tumor tissues compared with normal adjacent tissues (mean= 1.558, p= 0.014). In addition, clinicopathologic data on MALAT1 RNA expression levels in gastric cancer tissues was evaluated. No significant association was observed between the relative expression of MALAT1 and the stage, grade, H. pylori infection, and tumor size groups among gastric cancer patients (p= 0.82, p= 0.904, p= 0.407, and p= 0.701, respectively).
CONCLUSIONS: The current results showed that MALAT1 has a significant association in gastric cancer. The expression of MALAT1 may be used as a diagnostic biomarker for monitoring gastric cancer patients.