Xuyou Zhu

The expression and clinical relevance of PD-1, PD-L1, and TP63 in patients with diffuse large B-cell lymphoma

Abstract Latest study showed that a novel translocation between programmed cell death ligand 1 (PD-L1) (cluster of differentiation 274) and TP63 (tumor protein 63) can be found in diffuse large B-cell lymphoma (DLBCL), resulting in their conjunct overexpression in tumor cells at RNA level. However, the expressed pattern of these 2 genes at protein level in DLBCL remains largely unknown, and the clinical relevance of PD-L1 and TP63 expression in DLBCL are also unclear. Tumor tissues from 76 Chinese DLBCL patients were immunostained for programmed cell death 1 (PD-1), PD-L1, and TP63 using the EnVision system. Clinical relevance of PD-1, PD-L1, and TP63 in 74 DLBCL were analyzed by chi-square test, the Kaplan–Meier curves with log rank test, and Coxs proportional hazards regression model. PD-1 was mainly expressed in tumor-infiltrating lymphocytes (TILs) of 39.5% patients. PD-L1 was expressed in tumor cells of 26.3% patients, and TP63 was immunostained in nucleoli of tumor cells of 31.6% cases. PD-1 expression was significantly associated with the patients’ gender and B symptoms (P = 0.032, P = 0.026). DLBCL with PD-L1 or TP63 expression in tumor cells showed low International Prognostic Index (IPI) score (P = 0.007, P = 0.009). PD-1+ TILs was related to prolonged overall survival rate (OS) of DLBCL patients (P = 0.02), whereas PD-L1 expression was associated with worse clinical outcome of patients (P = 0.049). Immunoreactivity of TP63 was not correlated with patients’ survival time. Besides, PD-1 expression, patients’ age, Ann Arbor stage, and IPI score were significant prognostic markers for OS, but PD-L1 and TP63 had no prognostic significance. PD-1, PD-L1, and TP63 are frequently expressed in DLBCL. PD-1/PD-L1/TP63 blockade may be a potential therapeutic strategy for some patients.

Transmission electron microscopy of sputum deposition in the diagnosis of pulmonary alveolar proteinosis.

Objective: To clarify the diagnostic value of sputum in pulmonary alveolar proteinosis (PAP) through transmission electron microscopy (TEM) of sputum deposition (SD). Methods: Eleven SD samples and 9 bronchoalveolar lavage (BAL) sediments from a PAP group including 11 patients were observed by TEM and compared with sputum direct smear, BAL cytology, and lung biopsy histopathology. Eleven healthy adults were chosen as controls. Results: The 11 sputum smears from the PAP group showed no diagnostic component, but TEM of SD revealed 7 of 11 samples had many myelin-like lamellar bodies with degeneration in the cytoplasm of macrophages, alveolar epithelial cells, and extracellular spaces, which suggested PAP. Especially, 2 patients on whom lung biopsy could not be performed and who failed to be diagnosed by BAL fluid were finally diagnosed by TEM of SD. TEM of BAL sediments showed 7 of 9 cases had diagnostic myelin-like lamellar bodies. No statistical significance was found between BAL fluid and SD by TEM. The control group didn’t show diagnostic components by cytology or TEM of SD. Conclusion: TEM of SD is an important noninvasive diagnostic method especially for patients against lung biopsy and BAL.

Clinicopathologic and Ultrastructural Study of Non-HIV-related Primary Pulmonary Cryptococcosis in China: Report of 43 Cases

Objective: To clarify the clinicopathologic and ultrastructural features of primary pulmonary cryptococcosis (PC). Methods: 43 cases of PC were observed by light microscopy and histochemical staining, including mucicarmine (MC), Alcian blue (AB), periodic acid–Schiff (PAS), and Grocott methenamine–silver (GMS). Transmission electron microscopy (TEM) was performed on 11 fresh and 8 formalin-fixed specimens. Results: The detective rate of Cryptococcus neoformans (CN) by MC, AB, PAS, GMS staining, and TEM was 61.3% (19/31), 62.2% (23/37), 85.7% (30/35), 79.1% (34/43), and 89.5% (17/19), respectively. All CN detected by TEM had a capsule. Most of them possessed simple structure with undeveloped cellular organelles. Conclusion: Electron microscopy has a high rate of detecting CN. A combination of histochemical staining and electron microscopy can make an accurate diagnosis of PC.

Analysis of Microarray-Identified Genes and MicroRNAs Associated with Idiopathic Pulmonary Fibrosis

The aim of this study was to identify potential microRNAs and genes associated with idiopathic pulmonary fibrosis (IPF) through web-available microarrays. The microRNA microarray dataset GSE32538 and the mRNA datasets GSE32537, GSE53845, and GSE10667 were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DE-miRNAs)/genes (DEGs) were screened with GEO2R, and their associations with IPF were analyzed by comprehensive bioinformatic analyses. A total of 45 DE-microRNAs were identified between IPF and control tissues, whereas 67 common DEGs were determined to exhibit the same expression trends in all three microarrays. Furthermore, functional analysis indicated that microRNAs in cancer and ECM-receptor interaction were the most significant pathways and were enriched by the 45 DE-miRNAs and 67 common DEGs. Finally, we predicted potential microRNA-target interactions between 17 DE-miRNAs and 17 DEGs by using at least three online programs. A microRNA-mediated regulatory network among the DE-miRNAs and DEGs was constructed that might shed new light on potential biomarkers for the prediction of IPF progression.

Usual interstitial pneumonia coexisted with nonspecific interstitial pneumonia, What's the diagnosis?

The differential diagnosis between idiopathic nonspecific interstitial pneumonia(INSIP) and idiopathic pulmonary fibrosis(IPF)/usual interstitial pneumonia(UIP)is tough in both clinicians and pathologists. In this study, we analyzed the lesions of right lung removed from a 58-year-old patient by gross and microscopy. The results showed that the pathological appearance of nonspecific interstitial pneumonia (NSIP) and UIP coexisted in his upper lobe. Besides, because of severe fibrosis in middle and lower lobes, it was hard to distinguish the lesions of NSIP fibrotic pattern (NSIP-F) or UIP. Based on clinic-radiologic-pathological data, the diagnosis of INSIP-F was made for this patient finally. Our study suggests that UIP is not always an accurate diagnosis when the NSIP and UIP coexist, and NSIP can have regions of UIP.Virtual slideThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2573531681608730

Reduced expression of BMP3 contributes to the development of pulmonary fibrosis and predicts the unfavorable prognosis in IIP patients

Idiopathic pulmonary fibrosis (IPF) and idiopathic nonspecific interstitial pneumonia (INSIP) are two related diseases involving varying degrees of pulmonary fibrosis with no effective cure. Bone morphogenetic protein 3 (BMP3) is a member of the transforming growth factor-β (TGF-β) super-family, which has not been implicated in pulmonary fibrosis previously. In this study, we aimed to investigate the potential role of BMP3 playing in pulmonary fibrosis from clinical diagnosis to molecular signaling regulation. RNA sequencing was performed to explore the potential biomarker of IIP patients. The expression of BMP3 was evaluated in 83 cases of IPF and INSIP by immunohistochemistry. The function of BMP3 was investigated in both fibroblast cells and a bleomycin-induced murine pulmonary fibrosis model. The clinical relevance of BMP3 expression were analyzed in 47 IIP patients, which were included in 83 cases and possess more than five-year follow-up data. Both RNA-sequencing and immunohistochemistry staining revealed that BMP3 was significantly down-regulated in lung tissues of patients with IPF and INSIP. Consistently, lower expression of BMP3 also was found in pulmonary fibrotic tissues of bleomycin-induced mice model. Up-regulation of BMP3 prevented pulmonary fibrosis processing through inhibiting cellular proliferation of fibroblasts as well as TGF-β1 signal transduction. Finally, the relatively higher expression of BMP3 in IPF patients was associated with less/worse mortality. Intravenous injection of recombinant BMP3. Taken together, our results suggested that the low expression level of BMP3 may indicate the unfavorable prognosis of IPF patients, targeting BMP3 may represent a novel potential therapeutic method for pulmonary fibrosis management.

Lymphangiomatosis involving the pulmonary and extrapulmonary lymph nodes and surrounding soft tissue: A rare case report

Background: Diffuse pulmonary lymphangiomatosis (DPL) mainly affects the lung and pleura. There are very few pathological reports of lung damage accompanied by diffuse involvement of the extrapulmonary lymph nodes and surrounding soft tissue. The clinicopathological significance of coexistence of pulmonary and extrapulmonary lesions is unknown. Methods: Here, we report a 16-year-old male patient. The pathological specimens of the supraclavicular lymph node and soft tissue together with the lung biopsy were analyzed by pathological observation and immunohistochemical staining. Literatures were reviewed and clinical and imaging findings were discussed. Results: The patient presented with coughing and expectoration for 1 year and intermittent hemoptysis for 4 months. Ultrasound revealed swollen lymph nodes in bilateral neck, left armpit, and pubic symphysis. Chest CT scan showed diffuse grid and linear shadows, bilateral pleural thickening, and nodule formation. Multiple enlarged lymph nodes were mainly investigated in bilateral hilar, mediastinal, para-aortic, lesser curvature, and retroperitoneal. Supraclavicular lymph node biopsy confirmed the lymphatic hyperplasia and expansion in the capsule and surrounding soft tissue. The thoracoscopic examination found bloody chylothorax on the left chest. And lung biopsy showed the lymphatic vessel hyperplasia and expansion on the pleura and adjacent lung tissue. Immunohistochemical stains showed that the lymphatic endothelial cells were positive for D2–40 and CD31. Lymphangiomatosis involving the pulmonary and extrapulmonary lymph nodes and surrounding soft tissue was diagnosed based on the aforementioned histological findings. Conclusion: Lymphangiomatosis of superficial lymph node mainly involves the capsule of lymph nodes and its surrounding soft tissue. The information obtained from the lymph node biopsy can prompt and assist the diagnosis of DPL.

Lower expression of platelet derived growth factor is associated with better overall survival rate of patients with idiopathic nonspecific interstitial pneumonia

BACKGROUND Idiopathic nonspecific interstitial pneumonia (INSIP) presents with varying degrees of interstitial inflammation and fibrosis exhibiting a uniform appearance. Lack of knowledge on the underlying mechanisms of INSIP has contributed to few effective treatment strategies. Our study is designed to explore aberrantly expressed cytokines involvement in INSIP development. METHODS Oligo GEArray was employed to detect the expression of cytokines in INSIP patients, and idiopathic pulmonary fibrosis (IPF) was setup as isotype control. Real-time PCR and immunohistochemistry analysis were used to further confirm the expression of abnormally expressed cytokines. The correlationship between cytokines expression and overall survival rate of patients with IPF and INSIP were analyzed. RESULTS From microarray detection, transforming growth factor-beta-1 (TGF-β1), fibroblast growth factor 10 (FGF10), and platelet derived growth factor (PDGF) were predominantly up-regulated in patients with INSIP. Real-time PCR and immunohistochemistry also showed these cytokines was abnormally expressed in INSIP. In addition to, the clinical relevance analysis demonstrated relatively lower expression of PDGF patients had longer overall survival rate than those with higher expression of PDGF. CONCLUSIONS Our study suggests that TGF-β1, FGF10, and PDGF are required for the pathogenesis of INSIP, and may therefore be ideal targets in INSIP treatment. Moreover, INSIP patients with lower expression of PDGF had better survival rate.