Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r²=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.
Adolescent ; Adult ; Brain Neoplasms/pathology* ; Central Nervous System/pathology* ; Central Nervous System Neoplasms/metabolism* ; Child ; Child, Preschool ; China ; Female ; Germinoma/pathology* ; Histones ; Humans ; Male ; Middle Aged ; Neoplasms, Germ Cell and Embryonal/diagnosis* ; Oncogene Proteins ; Transcription Factors/metabolism* ; Young Adult

OBJECTIVETo investigate the histogenetic origin of primary central nervous system diffuse large B-cell lymphoma (DLBCL) with respect to the stage of B-cell differentiation, and identification of the relevant prognostic markers.

METHODSImmunohistochemical staining (EnVision method) for CD10, bcl-6, MUM-1, CD138 and FOXP1 antigens was performed on 47 paraffin-embedded sections.

RESULTSCD10, bcl-6, MUM-1 and FOXP1 expression in the tumor cells were 6.4%, 53.2%, 91.5% and 93.6% respectively. There was no expression of CD138 in all the cases. Among the 47 patients, 43 cases (91.5%) showed an activated B-cell-like (ABC) phenotype: 21 (44.7%) were bcl-6+ and MUM-1+, suggesting an "activated germinal center (GC) B-cell-like" in origin; 22 (46.8%) were exclusively MUM-1+, suggesting an "activated non-GCB" in origin. No significant correlation of the classification and FOXP1 expression found on the outcome (P=0.279 and P=0.154).

CONCLUSIONSMost primary central nervous system DLBCL are shown belonging to the ABC subgroup, suggesting that primary central nervous system DLBCL is quite similar to a DLBCL subset, which is derived from late GC to early post-GC B cell. The classification and FOXP1 expression do not show prognostic value in primary central nervous system DLBCL.

Adolescent ; Adult ; Aged ; B-Lymphocytes ; pathology ; Biomarkers, Tumor ; analysis ; Central Nervous System ; Central Nervous System Neoplasms ; diagnosis ; Female ; Humans ; Lymphoma, B-Cell ; diagnosis ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; diagnosis ; metabolism ; Male ; Middle Aged ; Prognosis ; Young Adult

One case of primary central nervous system lymphoma was reported. The patient received comprehensive therapy, mainly the surgical treatment, with the survival time 12 months, and local recurrence was considered as the major cause of death. The pathology, imagine examination, diagnosis and treatment of primary central nervous system lymphoma were discussed.
Antigens, CD20 ; analysis ; Central Nervous System Neoplasms ; metabolism ; pathology ; therapy ; Fatal Outcome ; Humans ; Immunohistochemistry ; Lymphoma, B-Cell ; metabolism ; pathology ; therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local

Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Astrocytoma ; metabolism ; pathology ; CD3 Complex ; metabolism ; Central Nervous System ; metabolism ; pathology ; Central Nervous System Neoplasms ; metabolism ; pathology ; Demyelinating Diseases ; diagnosis ; metabolism ; pathology ; Diagnosis, Differential ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Lymphoma ; metabolism ; pathology ; Magnetic Resonance Imaging

This study was aimed to investigate the expression of osteopontin (OPN) in central nervous system leukemia (CNSL) and to understand its clinical significance. The expression level of OPN in serum of 62 pediatric patients (22 cases of CNSL, 20 cases of acute leukemia without extramedullary infiltration and 20 cases of nontumor patients) and 19 cases of CNSL with complete remission (CR)were assayed by ELISA; the expression changes of OPN mRNA in bone marrow of the CNSL patients were detected by RT-PCR. The results indicated that the serum OPN level was significantly higher in CNSL group (25.21 ± 6.87 ng/ml) than that in acute leukemia group (13.24 ± 2.73 ng/ml) (P < 0.001) and nontumorous group (3.14 ± 1.60 ng/ml) (P < 0.001); the serum OPN level (4.35 ± 1.50 ng/ml) in CNSL group with CR decreased obviously (P < 0.001) after therapy; RT-PCR analysis showed that the expression of OPN mRNA was higher in CNSL group as compared with other two groups (P < 0.01). It is concluded that the OPN expression may play a role in central nervous system infiltration of leukemia, the mechanism of which remains to need further clinical exploration.
Bone Marrow Examination ; Case-Control Studies ; Central Nervous System Neoplasms ; blood ; pathology ; Child, Preschool ; Female ; Humans ; Leukemia ; blood ; pathology ; Male ; Osteopontin ; blood ; metabolism

BACKGROUNDCentral nervous system leukemia (CNSL) is an important relapse in children with acute lymphoblastic leukemia (ALL). We investigated the possible role of endogenous hydrogen sulfide (H(2)S) of cerebrospinal fluid (CSF) in predicting CNSL.

METHODSFrom August 2008 to December 2010, 380 children were enrolled in this study at Shijitan Hospital, China. These children were from 2 to 16 years old, and the median age was 6.5 years. They were divided into a CNSL group (7 cases), a leukemia group (307 cases), a non-leukemia group (26 cases) and a healthy group (40 children). CSF specimens were obtained from conventional lumbar punctured, then centrifuged and supernatants preserved for H(2)S detection. Leukemic cells precipitates from CSF were found in three cases, the hCSE and hCBS mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR), and H(2)S levels in serum were also measured. The receiver operating characteristic (ROC) curve and area under curve (AUC) were used to assess the predictive diagnosis role of CSF H(2)S in children with ALL and CNSL.

RESULTSThe serum H(2)S contents of the CNSL and leukemia groups were (96.98 ± 15.77) µmol/L and (93.35 ± 17.16) µmol/L respectively, much higher than those of healthy, (44.29 ± 2.15) µmol/L, and non-leukemia, (46.32 ± 6.54) µmol/L, groups (P < 0.01). Compared with the leukemia group, CSF H(2)S content of the CNSL group was significantly high (P < 0.01). Meanwhile, in contrast to the non-leukemia group, CSF H(2)S contents of the CNSL and leukemia groups were both significantly increased (P < 0.01). In addition, leukemic cells from CSF precipitations could express CBS and CSE mRNA. Furthermore, the ROC analysis showed the UAC was 0.929 (95%CI: 0.857 - 1.000), and the optimum cut-off value of CSF H(2)S was 12.08 µ mol/L, and the sensitivity and specificity were 83.3% and 97.2% respectively.

CONCLUSIONSCSF H(2)S contents were significantly increased in children with CNSL. After treatment, H(2)S contents were decreased subsequently. Therefore, we speculated that H(2)S levels of CSF would predict CNSL in ALL children.

Adolescent ; Central Nervous System Neoplasms ; cerebrospinal fluid ; metabolism ; pathology ; Child ; Child, Preschool ; Cystathionine beta-Synthase ; genetics ; Female ; Humans ; Hydrogen Sulfide ; cerebrospinal fluid ; Leukemia ; cerebrospinal fluid ; Lyases ; genetics ; Male

Adenocarcinoma ; metabolism ; Adenoma ; metabolism ; Breast Neoplasms ; metabolism ; Carcinoma, Papillary ; metabolism ; Carcinoma, Small Cell ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; Central Nervous System Neoplasms ; metabolism ; Diagnosis, Differential ; Digestive System Neoplasms ; metabolism ; Female ; Genital Neoplasms, Female ; metabolism ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; metabolism ; Liver Neoplasms ; metabolism ; Lung Neoplasms ; metabolism ; Neuroendocrine Tumors ; metabolism ; Nuclear Proteins ; metabolism ; Pituitary Neoplasms ; metabolism ; Small Cell Lung Carcinoma ; metabolism ; Thyroid Neoplasms ; metabolism ; Thyroid Nuclear Factor 1 ; Transcription Factors ; metabolism

OBJECTIVETo evaluate the value of FOXP1 and Cyclin E gene in primary central nervous system lymphoma(PCNSL) of immunocompetent patients on prognostic significance.

METHODSClinical data of 71 patients with newly diagnosed PCNSL from 2002 to 2007 was analyzed retrospectively. Immunohistochemistry method (HRP-EnVision(TM)) was performed to observe the expression of FOXP1 and Cyclin E gene in tumor tissue samples. The survival was analyzed by Kaplan-Meier survival curve, survival factors analysis by the Log-rank test and COX proportional hazards regression model.

RESULTSFOXP1 positive was observed in 35 of 51 patients (68.63%) and Cyclin E staining was present in 29 of 50 cases (58.00%). FOXP1(+) patients had a shorter overall survival (OS) than FOXP1(-) ones. 2-year OS rate in FOXP1(+) and FOXP1(-) patients were 23.33% and 73.56%, respectively(P = 0.0015). Cyclin E(+) patients had a shorter overall survival(OS) than cyclinE(-) ones. 2-year OS rate in Cyclin E(+) and Cyclin E(-) patients were 17.56% and 69.76%, respectively (P = 0.0017). Multivariate analysis showed that Cyclin E expression was an independent prognostic factor for shorter OS (P = 0.048). FOXP1 expression might be an important prognostic factor for shorter OS (P = 0.065).

CONCLUSIONCyclin E expression is an independent prognostic factor and FOXP1 expression is a possible prognostic factor for poor clinical outcome in patients with PCNSL.

Aged ; Aged, 80 and over ; Central Nervous System Neoplasms ; genetics ; metabolism ; Cyclin E ; genetics ; metabolism ; Female ; Forkhead Transcription Factors ; genetics ; metabolism ; Humans ; Lymphoma, Non-Hodgkin ; genetics ; metabolism ; Male ; Middle Aged ; Prognosis ; Repressor Proteins ; genetics ; metabolism ; Retrospective Studies ; Survival Rate

Antigens, CD34 ; metabolism ; Astrocytoma ; metabolism ; pathology ; Carcinoma ; metabolism ; pathology ; Central Nervous System Neoplasms ; metabolism ; pathology ; Ependymoma ; metabolism ; pathology ; Fibroma ; metabolism ; pathology ; Ganglioglioma ; metabolism ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Glioma ; metabolism ; pathology ; Gliosarcoma ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Neoplasms, Neuroepithelial ; metabolism ; pathology ; Solitary Fibrous Tumors ; metabolism ; pathology

Pituitary adenoma (PA) is a common benign neuroendocrine tumor; however, the incidence and proportion of hormone-producing PAs in Korean patients remain unknown. Authors analyzed 506 surgically resected and pathologically proven pituitary lesions of the Seoul National University Hospital from 2006 to 2011. The lesions were categorized as: PAs (n = 422, 83.4%), Rathke's cleft cysts (RCCs) (n = 54, 10.6%), inflammatory lesions (n = 8, 1.6%), meningiomas (n = 4), craniopharyngiomas (n = 4), granular cell tumors (n = 1), metastatic renal cell carcinomas (n = 2), germinomas (n = 1), ependymomas (n = 1), and unsatisfactory specimens (n = 9, 1.8%). PAs were slightly more prevalent in women (M: F = 1:1.17) with a mean age of 48.8 yr (9-80 yr). Immunohistochemical analysis revealed that prolactin-producing PAs (16.6%) and growth hormone-producing adenomas (9.2%) were the most common functional PAs. Plurihormonal PAs and nonfunctioning (null cell) adenomas were found in 14.9% and 42.4% of patients with PAs, respectively. The recurrence rate of PAs was 11.1%, but nearly 0% for the remaining benign lesions such as RCCs. 25.4% of patients with PAs were treated by gamma-knife after surgery due to residual tumors or regrowth of residual tumor. In conclusion, the pituitary lesions and the proportions of hormone-producing PAs in Korean patients are similar to those of previous reports except nonfunctioning (null cell) PAs, which are unusually frequent.
Adenoma/*pathology ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Central Nervous System Cysts/pathology ; Child ; Female ; Growth Hormone/metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Pituitary Neoplasms/*pathology ; Prolactin/metabolism ; Recurrence ; Sex Factors ; Young Adult