Mixed Cell Tumor Research Articles

BCOR overexpression in pediatric sarcomas- a morphologic continuum of mixed round and spindle cell tumors

Objectives The vast majority of BCOR (BCL6 corepressor) sarcomas occur in the pediatric population and include different clinico-pathologic entities. This study evaluates morphology, immunohistochemistry and clinical outcome in pediatric BCOR sarcomas. Material and Methods Children, aged ≤ 18yrs, diagnosed to have translocation negative Ewing-like sarcoma, clear cell sarcoma of the kidney and primitive myxoid mesenchymal tumor of infancy, over a period of five years were included. Immunohistochemical staining for BCOR antibody was done and the cases with BCOR overexpression were subjected to a further immunopanel comprising of special AT-rich sequence-binding protein 2 (SATB2), Transducin-Like enhancer of split-1 (TLE1), Cyclin D1 and NKX2.2. The clinical outcome of patients with BCOR overexpression was assessed. Results BCOR overexpression was seen in 16/42 cases; Five were primary soft tissue tumors, three were primary bone tumors, seven were clear cell sarcoma of the kidney and one primary renal sarcoma. The median age of this group was 3.5 years (range 2–18 years) with male predominance (75%). All the BCOR positive tumors showed statistically significant morphological and immunohistochemical overlap. 4/16 did not take treatment at our center. Of the 12 who received treatment, 8 are in Complete Remission 1 (CR1). The mean event-free survival (EFS) and overall survival (OS) were 51.89 months (95% CI: 37.36-66.42) and 62.08 months (95% confidence interval (CI): 52.85-71.30) respectively. Conclusion BCOR sarcomas did not show any statistically significant histological and immunohistochemical differences, thus reiterating the morphologic continuum of these clinically distinct tumors.

Diagnostic Value of SALL4 and OCT3/4 in Pediatric Testicular Tumors.

Testicular tumors (TTs) are rare in children, posing diagnostic and therapeutic challenges. This retrospective study evaluates the diagnostic and prognostic utility of SALL4 and OCT3/4 in pediatric TTs. We analyzed 18 cases of different types of TTs using immunohistochemistry (IHC) to assess SALL4 (Spalt-like transcription factor 4) and OCT3/4 (Octamer binding transcription factor 3/4) expression. SALL4 was positive in 83.3% of tumors, while OCT3/4 was positive in 38.9% of tumors, with a significantly higher prevalence in patients aged 12-18 years compared to those aged 0-11 years (p = 0.013). Mixed germinal cell tumors were significantly more frequently associated with OCT3/4 (p = 0.003), and a high immunostaining expression for SALL4 was observed primarily in yolk sac tumors and embryonal carcinoma. Our findings suggest that SALL4 and OCT3/4 immunostaining can aid in accurate diagnosis and treatment planning, and underscores the importance of OCT3/4 as a predictive factor in pediatric testicular tumors, highlighting its substantial correlation with tumor type and its impact on treatment response. These markers may guide personalized therapeutic strategies, potentially improving patient outcomes.

Comprehensive characteristics of pathological subtypes in testicular germ cell tumor: Gene expression, mutation and alternative splicing.

Testicular germ cell tumor (TGCT) is the most common tumor in young men, but molecular signatures, especially the alternative splicing (AS) between its subtypes have not yet been explored. To investigate the differences between TGCT subtypes, we comprehensively analyzed the data of gene expression, alternative splicing (AS), and somatic mutation in TGCT patients from the TCGA database. The gene ontology (GO) enrichment analyses were used to explore the function of differentially expressed genes and spliced genes respectively, and Spearman correlation analysis was performed to explore the correlation between differential genes and AS events. In addition, the possible patterns in which AS regulates gene expression were elaborated by the ensemble database transcript atlas. And, we identified important transcription factors that regulate gene expression and AS and functionally validated them in TGCT cell lines. We found significant differences between expression and AS in embryonal carcinoma and seminoma, while mixed cell tumors were in between. GO enrichment analyses revealed that both differentially expressed and spliced genes were enriched in transcriptional regulatory pathways, and obvious correlation between expression and AS events was determined. By analyzing the transcript map and the sites where splicing occurs, we have demonstrated that AS regulates gene expression in a variety of ways. We further identified two pivot AS-related molecules (SOX2 and HDAC9) involved in AS regulation, which were validated in embryonal carcinoma and seminoma cell lines. Differences in somatic mutations between subtypes are also of concern, with our results suggesting that mutations in some genes (B3GNT8, CAPN7, FAT4, GRK1, TACC2, and TRAM1L1) occur only in embryonal carcinoma, while mutations in KIT, KARS, and NRAS are observed only in seminoma. In conclusion, our analysis revealed the differences in gene expression, AS and somatic mutation among TGCT subtypes, providing a molecular basis for clinical diagnosis and precise therapy of TGCT patients.

BCOR overexpression in pediatric sarcomas: A morphologic continuum of mixed round and spindle cell tumors

BCOR overexpression in pediatric sarcomas: A morphologic continuum of mixed round and spindle cell tumors

Thrombin‐PAR1 signaling in pancreatic cancer promotes an immunosuppressive microenvironment

Unlabelled Box AbstractBackgroundPancreatic ductal adenocarcinoma (PDAC) is characterized by a prothrombotic state and a lack of host antitumor immune responsiveness. Linking these two key features, we previously demonstrated that tumor‐derived coagulation activity promotes immune evasion. Specifically, thrombin‐protease‐activated receptor‐1 (PAR1) signaling in mouse PDAC cells drives tumor growth by evading cytotoxic CD8a+ cells. MethodsSyngeneic mixed cell tumor growth, transcriptional analyses, and functional tests of immunosuppressive response genes were used to identify cellular and molecular immune evasion mechanisms mediated by thrombin‐PAR‐1 signaling in mouse PDAC tumor cells. ResultsElimination of tumor cell PAR1 in syngeneic graft studies increased cytotoxic T lymphocyte (CTL) infiltration and decreased tumor‐associated macrophages in the tumor microenvironment. Co‐injection of PAR1‐expressing and PAR1‐knockout (PAR‐1KO) tumor cells into immunocompetent mice resulted in preferential elimination of PAR‐1KO cells from developing tumors, suggesting that PAR1‐dependent immune evasion is not reliant on CTL exclusion. Transcriptomics analyses revealed no PAR1‐dependent changes in the expression of immune checkpoint proteins and no difference in major histocompatibility complex‐I cell surface expression. Importantly, thrombin‐PAR1 signaling in PDAC cells upregulated genes linked to immunosuppression, including Csf2 and Ptgs2. Functional analyses confirmed that both Csf2 and Ptgs2 are critical for PDAC syngeneic graft tumor growth and overexpression of each factor partially restored tumor growth of PAR1KO cells in immunocompetent mice. ConclusionsOur results provide novel insight into the mechanisms of a previously unrecognized pathway coupling coagulation to PDAC immune evasion by identifying PAR1‐dependent changes in the tumor microenvironment, a PAR1‐driven immunosuppressive gene signature, and Csf2 and Ptgs2 as critical PAR1 downstream targets.

GCT-22. PROTEIN DEUBIQUITINATION PATHWAY IS A NOVEL THERAPEUTIC TARGET AGAINST MALIGNANT NON-GERMINOMATOUS CNS GERM CELL TUMORS

Central nervous system germ cell tumors (CNSGCTs) are rare intracranial neoplasm usually developed in adolescents and young adults. However, in East Asia including Japan, incidence of CNSGCTs is considerably higher compare with other regions of the world. Whereas germinomas generally respond to chemo-radiotherapy well, malignant subtypes of non-germinomatous germ cell tumors (NGGCT) are refractory, and development of novel therapy against NGGCTs is urgently needed. To develop a new therapeutic strategy against aggressive NGGCTs, we have investigated novel molecular targets for NGGCT treatment. We screened a total of 120 CNSGCT tumor tissues (including 55 NGGCT), which were registered to the Intracranial Germ Cell Tumor Consortium (iGCT), and discovered multiple mutations of a molecule that regulates protein ubiquitination and degradation specifically in NGGCT cases (5 of 55 cases; 1 immature teratoma, 3 mixed gem cell tumors, and 1 embryonal carcinoma). An in vitro ubiquitination assay revealed the mutations of this molecule discovered in NGGCT cases were loss of function mutations. Reduced expression of this molecule by knockdown in an established human seminoma cell line Tcam2 or a human yolk sac tumor cell line YST1, which was recently established in our institute, resulted in enhanced proliferation as well as upregulation of MEK-ERK activation. Importantly, treatment of these two GCT cell lines with reduced expression of this molecule by MEK inhibitor trametinib suppressed augmented proliferation of these cells. Taken together, these results suggest that protein ubiquitination-related pathways as well as MEK-ERK cascade may serve as a novel therapeutic target against NGGCTs.

CBMS-11 PROTEIN DEUBIQUITINATION PATHWAY IS A NOVEL THERAPEUTIC TARGET AGAINST MALIGNANT CNS NON-GERMINOMATOUS GERM CELL TUMORS

Central nervous system germ cell tumors (CNSGCTs) are rare intracranial neoplasm usually developed in adolescents and young adults. However, in East Asia including Japan, incidence of CNSGCTs is considerably higher compare with other regions of the world. Whereas germinomas generally respond to chemo-radiotherapy well, malignant subtypes of non-germinomatous germ cell tumors (NGGCT) are refractory, and development of novel therapy against NGGCTs is urgently needed. To develop a new therapeutic strategy against aggressive NGGCTs, we have investigated novel molecular targets for NGGCT treatment. We screened a total of 120 CNSGCT tumor tissues (including 55 NGGCT), which were registered to the Intracranial Germ Cell Tumor Consortium (iGCT), and discovered multiple mutations of a molecule that regulates protein ubiquitination and degradation specifically in NGGCT cases (5 of 55 cases; 1 immature teratoma, 3 mixed gem cell tumors, and 1 embryonal carcinoma). An in vitro ubiquitination assay revealed the mutations of this molecule discovered in NGGCT cases were loss of function mutations. Reduced expression of this molecule by knockdown in an established human seminoma cell line Tcam2 or a human yolk sac tumor cell line YST1, which was recently established in our institute, resulted in enhanced proliferation as well as upregulation of MEK-ERK activation. Importantly, treatment of these two GCT cell lines with reduced expression of this molecule by MEK inhibitor trametinib suppressed augmented proliferation of these cells. Taken together, these results suggest that protein ubiquitination-related pathways as well as MEK-ERK cascade may serve as a novel therapeutic target against NGGCTs.

SPDR-06 PROTEIN DEUBIQUITINATION PATHWAY IS A NOVEL THERAPEUTIC TARGET AGAINST MALIGNANT CNS NON-GERMINOMATOUS GERM CELL TUMORS

Central nervous system germ cell tumors (CNSGCTs) are rare intracranial neoplasm usually developed in adolescents and young adults. However, in East Asia including Japan, incidence of CNSGCTs is considerably higher compare with other regions of the world. Whereas germinomas generally respond to chemo-radiotherapy well, malignant subtypes of non-germinomatous germ cell tumors (NGGCT) are refractory, and development of novel therapy against NGGCTs is urgently needed. To develop a new therapeutic strategy against aggressive NGGCTs, we have investigated novel molecular targets for NGGCT treatment. We screened a total of 120 CNSGCT tumor tissues (including 55 NGGCT), which were registered to the Intracranial Germ Cell Tumor Consortium (iGCT), and discovered multiple mutations of a molecule that regulates protein ubiquitination and degradation specifically in NGGCT cases (5 of 55 cases; 1 immature teratoma, 3 mixed gem cell tumors, and 1 embryonal carcinoma). An in vitro ubiquitination assay revealed the mutations of this molecule discovered in NGGCT cases were loss of function mutations. Reduced expression of this molecule by knockdown in an established human seminoma cell line Tcam2 or a human yolk sac tumor cell line YST1, which was recently established in our institute, resulted in enhanced proliferation as well as upregulation of MEK-ERK activation. Importantly, treatment of these two GCT cell lines with reduced expression of this molecule by MEK inhibitor trametinib suppressed augmented proliferation of these cells. Taken together, these results suggest that protein ubiquitination-related pathways as well as MEK-ERK cascade may serve as a novel therapeutic target against NGGCTs.

Development of a Novel AOP for Cyp2F2-Mediated Lung Cancer in Mice.

Traditional methods for carcinogenicity testing rely heavily on the rodent bioassay as the standard for identification of tumorigenic risk. As such, identification of species-specific outcomes and/or metabolism are a frequent argument for regulatory exemption. One example is the association of tumor formation in the mouse lung after exposure to Cyp2F2 ligands. The adverse outcome pathway (AOP) framework offers a theoretical platform to address issues of species specificity that is consistent, transparent, and capable of integrating data from new approach methodologies as well as traditional data streams. A central premise of the AOP concept is that pathway progression from the molecular initiating event (MIE) implies a definable "response-response" (R-R) relationship between each key event (KE) that drives the pathway towards a specific adverse outcome (AO). This article describes an AOP for lung cancer in the mouse from an MIE of Cyp2F2-specific reactive metabolite formation, advancing through KE that include protein and/or nucleic acid adducts, diminished Club Cell 10 kDa (CC10) protein expression, hyperplasia of CC10 deficient Club cells, and culminating in the AO of mixed-cell tumor formation in the distal airways. This tumor formation is independent of route of exposure and our AOP construct is based on overlapping mechanistic events for naphthalene, styrene, ethyl benzene, isoniazid, and fluensulfone in the mouse. This AOP is intended to accelerate the explication of an apparent mouse-specific outcome and serve as a starting point for a quantitative analysis of mouse-human differences in susceptibility to the tumorigenic effects of Cyp2F2 ligands.

Abstract 4252: Detecting microsatellite instability in ffpe tissue from crc subjects using next generation sequencing

Abstract Background Microsatellite instability (MSI) is a hypermutable phenotype resulting from DNA mismatch repair deficiency and is observed in up to 10-15% of early-stage colorectal cancers (CRC). It manifests as abnormal lengthening or shortening of DNA repeats at specific genomic loci. MSI-High (MSI-H) CRC patients have been shown to respond favorably towards both chemotherapy and immunotherapy and have different prognosis than MSS patients and the FDA has approved Pembrolizumab as the first cancer therapy based on a class of biomarkers rather than a cancer type. With increasing options for targeted therapy in solid tumors, being able to combine MSI testing with other cancer biomarkers for approved therapies is beneficial. We show proof of concept of a pan-cancer gene panel using an NGS-based assay and bioinformatics workflow that enables classification of MSI status along with detection of SNVs, fusions, indels and CNVs from tumor tissue samples. Unlike the gold standard PCR-based test, our method does not require a matched normal sample, thus enabling MSI detection based on tumor tissue alone. Methods Our workflow combines whole genome library preparation, hybrid capture target enrichment, high-throughput sequencing and a proprietary analysis algorithm. We expanded the number of genomic loci to improve the sensitivity of MSI detection. The analysis algorithm was trained using DNA from pure and mixed cell lines, tumor tissue and normal samples with known MSI status to classify the molecular alterations between MSI-H and MSS genotypes from sequencing reads. The algorithm leverages repeat lengths in homopolymeric MSI loci in order to predict instability of individual loci followed by aggregation using a statistical framework to make the final call on MSI status. Results The above algorithm was evaluated on a cohort of 134 stage II and stage III CRC subjects who underwent curative intent surgery. MSI status for these samples was orthogonally tested using a PCR-based MSI Analysis System (31 positives, 103 negatives) and a dMMR system. Using a pre-determined threshold, the algorithm yielded 100% sensitivity and 100% specificity on the above cohort without using matched normal tissue. A second cohort evaluated includes 47 CRC patients that are enriched for MSI positive status by virtue of their selection criteria (BRAF positive). Very high concordance on MSI status with an orthogonal method was observed. Data demonstrating high concordance with a PCR_based MSI system will be available at the presentation. Conclusions Here we present an NGS-based assay and bioinformatics workflow with robust analytical performance for MSI detection in FFPE tissue samples without a paired normal. Citation Format: Amrita Pati, Hao Wang, Hamid Mirebrahim, Seng Saelee, Joshua Lefkowitz, Sean Chien, Ashla Singh, Fergal Casey, Vera Rapoport, Xiaoju Max Ma, John Lee, Alex Lovejoy, Daniel Klass, Hans-Peter Adams. Detecting microsatellite instability in ffpe tissue from crc subjects using next generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4252.

MON-LB068 Incidental Finding of a Functioning Corticomedullary Mixed Adrenal Tumor

Background: Incidental adrenal adenoma prevalence ranges from 0.4-4% and reaches up to 10% in older patients, but only 10-15% secrete excess amounts of hormones. Functioning adrenal tumors composed of corticomedullary mixed cells are very rare. Clinical Case: A 78-year-old female patient with a 2-year history of slowly progressive involuntary weight-loss (20kg), recent diagnosis of type 2 diabetes, and incidental finding upon abdominal ultrasound of a right adrenal mass, is admitted to our hospital due to a left hip fracture. She denied hypertension. Physical examination revealed no signs of hypercortisolism and/or catecholamine excess other than tachycardia (120bpm). Abdominal CT Scan showed an enlarged right adrenal mass, 2.7x3.3cm, 40UH. Institutional laboratory results were consistent with a pheochromocytoma: Metanephrines: 180pg/mL (n<65 pg/mL), Normetanephrines: 356 pg/mL (n<196 pg/mL), and an ACTH-independent Cushing Syndrome: elevated 24-hour urinary cortisol: 628.3nmol/L (n<110nmol/L), abnormal 1mg overnight Dexamethasone test: Cortisol 8am: 14.4mcg/dL (positive >1.8mcg/dL), normal ACTH: 19.97pg/mL (n:7-62pg/mL) and DHEASO4: 161.21mcg/dL (n:25-460mcg/dL). Fasting glycemia: 142mg/dL. Laparoscopic right adrenalectomy is performed. Postoperative results: normal Cortisol 8am: 18.6mcg/dL (n:4.46-22.1mcg/dL), fasting glycemia: 94mg/dL. Histological and immunohistochemistry results showed a mixed corticomedullary adrenal tumor with pheochromocytoma (chromogranin A+++, synaptophysin+++), ganglioneuroma (S100+++, synaptophysin ++) and cortical adenoma ((inhibin +++, Melan A +++) components, capsular invasion but no evident angioinvasion. Conclusion: This case is one of the very few reports of a functioning mixed cell tumor with adrenal cortical, medullary and neural lineage in a single gland confirmed by immunohistochemistry. Key words: corticomedullary tumor, mixed adrenal tumor, pheochromocytoma, Cushing’s syndrome

46, XY pure gonadal dysgenesis with malignant mixed germ cell tumor: a case report and literature review

46, XY pure gonadal dysgenesis with malignant mixed germ cell tumor: a case report and literature review

Evaluation of lysophosphatidic acid in vaginal fluid as a biomarker for ovarian cancer: A pilot study

There remains a need to differentiate between women with a benign or a malignant adnexal mass prior to surgery. As part of an ongoing evaluation of vaginal fluid compounds as potential tumor biomarkers we evaluated whether vaginal lysophosphatidic acid (LPA) predicted the subsequent diagnosis of a malignant adnexal mass. In this prospective pilot study vaginal fluid was obtained from 100 post-menopausal women referred for evaluation of a suspicious adnexal mass and tested for LPA by ELISA. Clinical data and serum CA125 results were obtained only after completion of all laboratory testing. Twenty eight of the women were subsequently diagnosed with an ovarian malignancy, four had a borderline tumor and 68 had a benign diagnosis. Among women with a malignant ovarian mass, 11 (39.3%) had an endometrioid adenocarcinoma +/− Clear cell tumor components, 6 (21.4%) had a high grade serous carcinoma, 3 (10.7%) had a mucinous tumor, 2 each (7.1%) had a malignant mixed mesodermal or a granulosa tumor and 1 each (3.6%) had a Clear cell tumor, a mixed cell tumor, leimyosarcoma or metastatic adrenal tumor. Compared to the median vaginal LPA level in women with benign lesions (1.5 μM), LPA was significantly elevated only in women with endometrioid ovarian cancer (7.9 μM) (p = 0.0137). Of the 6 endometrioid tumors in which values for both plasma CA125 and vaginal LPA were available 5 were positive only for LPA while one was only CA125 positive. Detection of LPA in vaginal secretions may be of value for the noninvasive diagnosis of endometrioid ovarian malignancies in post-menopausal women.

Mixed reproductive cell tumor of the pancrea: report of a case

Mixed reproductive cell tumor of the pancrea: report of a case

Treatment of 21 cases of chronic radiation intestinal injury by staging ileostomy and closure operation

To summarize the application of staged ileostomy and closure operation combined with nutritional support therapy in the treatment of chronic radiation intestinal injury(CRII). Clinical data of patients with definite radiation history and pathological diagnosis of CRII receiving treatment at Department of General Surgery, Jinling Hospital from January 2012 to December 2016 were retrospectively analyzed. Patients who were diagnosed with tumor recurrence during operation or by postoperative pathology were excluded. Patients undergoing stageI( ileostomy and stageII( closure operation combined with nutrition support therapy were enrolled to the cohort. Detailed scheme of stage I( ileostomy and therapeutic time were determined by clinical symptoms and nutritional status. While performing ileostomy, the removal of intestinal lesions depended on range and degree of intestinal injury. Nutritional support therapy and other symptom-relieving therapy were offered after surgery. Timing for stageII( closure operation was decided according to nutritional status of patients. Lesions of remaining intestine were determined during operation, then necessary intestinal resection and closure operation were performed. Adhesion classification of radiation intestinal injury (total five levels) proposed by our center was adopted to evaluate the level and range of intestinal lesions. Level 0 indicated no adhesion between injured intestinal loop and surrounding organs; level 1 indicated that the adhesion and fibrosis were limited to right pelvis; level 2 indicated that the adhesion included all pelvis and the adhesion was severe and difficult to divide; level 3 was the forward extension of level 2 adhesion, which was between injured intestinal loop and anterior pelvic wall; level 4 was the upward extension of level 3 adhesion, which was between injured intestinal loop and anterior abdominal wall. Clavien-Dindo classification (lower level means milder symptom) and complication comprehensive index(CCI, lower CCI means milder symptom) calculated by on-line program (http:∕∕www.assessurgery. com) were applied to estimate postoperative complications. Resected intestinal length, adhesion classification of radiation intestinal injury, postoperative complications and time to total enteral nutritional (TEN) of both surgeries and nutritional status (body mass index and serum albumin) were compared between stageI( ileostomy and stageII( closure operation. Twenty-one patients were enrolled in the research with 2 males and 19 females. Primary tumor included 14 cervical cancers, 3 rectal cancers, 1 endometrial cancer, 1 ovarian carcinoma, 1 seminoma and 1 mixed germ cell tumor. Median interval between the end of radiation and radiation intestinal injury was 7(2 to 91) months and median interval between the incidence of radiation intestinal injury and ileostomy was 5(<1 to 75) months. Operative indications for ileostomy were obstruction in 14 cases (66.7%), intestinal internal fistula in 1 case (4.8%), intestinal outer fistula in 2 cases (9.5%), radiation proctitis in 3 cases (14.3%) and acute intestinal perforation in 1 case (4.8%). Average age of patients undergoing stageI( ileostomy was 48 (18 to 60) years with BMI (17.0±2.7) kg/m2 and serum albumin (36.8±5.2) g/L. Patients undergoing stageII( closure operation had significantly higher BMI [(18.4±2.0) kg/m2, t=-2.747, P=0.013] and higher serum albumin [(40.8±3.6) g/L, t=-3.505, P=0.002]. Average interval between stageI( ileostomy and stageII( closure surgery was (197±77) days. Resected intestinal length of stageI( ileostomy was which was significantly longer than that of stageII( closure surgery [(74.0±56.1) cm vs. (15.5±10.4) cm, t=4.547, P= 0.000]. Abdominal adhesion classification of stageII( ileostomy plus closure operation was significantly better as compared to stage I( ileostomy(Z=-3.347, P=0.001). Morbidity of postoperative complications in stageI( ileostomy was 52.4% (11/21), which decreased to 19.0% (4/21) in stageII( operation with significant difference (χ²=5.081, P=0.024). Postoperative complication Clavien-Dindo classification and CCI scores in stageII( operation were significantly lower than those in stageI( operation (P=0.006 and P=0.002). Till June 2017, 17 of 21 patients(81.0%) were followed-up for (28±18) months. Except for 2 cases of relapse, 15 patients recovered to normal diet. Application of staged ileostomy and closure operation combined with nutritional support therapy to CRII is in accordance with the principle of injury control surgery. Furthermore, this staged approach is safe and effective, can reduce the morbidity and the severity of complications, and can also be helpful to decide the margin for intestinal resection.

Mikst Germ Hücreli Testis Tümörüne İkincil Gelişen Paraneoplastik Polisitemi

Mikst Germ Hücreli Testis Tümörüne İkincil Gelişen Paraneoplastik Polisitemi

Comparative observational study of serum neoplastic biomarker and immunohistochemistry in 28 cases of intracranial germ cell tumors

Objective To conduct the comparative observational study of serum neoplastic biomarker and immunohistochemistry in intracranial germ cell tumors (GCTs). Methods A retrospective study was conducted on clinical data of 28 cases of germ cell tumors undergoing surgery from March 2013 to July 2016 at Tsinghua University Yuquan Hospital. Presurgical serum neoplastic biomarkers including α-fetoprotein (AFP), β-human chorionic gonadotropin (β-HCG) and alkaline phosphatase (ALP) were measured and compared with postsurgical immunohistochemistry results of tumor specimens. Results Among the 28 cases of GCTs, germinoma was identified in 5 cases, teratoma in 2 cases, immature teratoma in 5 cases, choriocarcinoma in 1 case and mixed germ cell tumor in 15 cases. AFP was inconsisent in 8/28 cases, being positive in serum biomarker and negative in immunohistochemistry, and included 4 cases of immature teratoma and 4 mixed GCTs. β-HCG was incongruent in 5 cases (positive in serum and negative in immunohistochemistry). Among the 18 cases with pure germinoma component, placenta ALP (PLAP) immunohistochemistry revealed positive results in 15 cases, while serum ALP was significantly increased in only 4 cases and not detected in the remaining 14 cases. Conclusions The treatment and prognosis of intracranial GCTs might be correlated with different neoplastic components. Immunohistochemistry combined with serum biomarker could help demonstrate those neoplastic components more accurately and completely. Key words: Central nervous system; Neoplasms, germ cell and embryonal; Neoplastic biomarker; Immunohistochemistry

PET/CT diagnostic procedure from a rare case of ovarian mixed germ cell tumor

PET/CT diagnostic procedure from a rare case of ovarian mixed germ cell tumor

Endoscopic resection of pineal region tumors using infratentorial supracerebellar approach

Objective To investigate the feasibility and efficacy of purely endoscopic resection of pineal region tumors using infratentorial supracerebellar approach. Methods A retrospective study of general clinical data and treatment effect was performed for 4 cases of pineal region tumors who underwent pure endoscopic resection using infratentorial supracerebellar approach in Neurosurgery Department at Zhongshan Hospital of Fudan University from August 2014 to December 2015. Results Gross total resection was achieved in all 4 cases. Except 1 case of transient diplopia, no surgical complications were observed. The pathological diagnoses included germinoma, anaplastic astrocytoma, pilocytic astrocytoma and mixed germ cell tumor. Postoperative radiotherapy was administered in 2 patients and chemotherapy plus radiotherapy was performed in 1 patient. During the follow-up period (0.5 to 2.0 years), all patients had a normal life without tumor recurrence. Conclusions Purely endoscopic resection of pineal region tumors using infratentorial supracerebellar approach seems feasible. It may be considered as an alternative approach for certain pineal region tumors. Key words: Neuroendoscopy; Pinealoma; Approach

A novel mutation in the SRY gene of a Chinese 46, XY female patient with unilateral mixed germ cell tumor

Objective To determine the nosogenetic factors of a 46,XY female with primary amenorrhea and unilateral mixed germ cell tumor. Methods Eight genes associated with 46,XY gonadal dysgenesis were detected in the patient and her parents by target region captured-next generation sequencing. Results An insertion of a single nucleotide (adenine) at the coding site 230 (c.230_231insA) located in the high mobility group (HMG) domain of SRY was revealed, which led to a truncated protein (p.Lys77fsX27). This mutation was at position 2655414 of the Y chromosome, supported with 127 unique mapped reads, however, this mutation was not found in the in-house dataset of 1 092 controls. Additionally, none of the candidate gene was detected in the patient’s parents, which indicated that it is a de novo mutation. Conclusion A novel SRY sporadic mutation due to a single nucleotide insertion at position 230 (c.230_231insA) was identified as the cause of the disease in this patient. Target region captured-next generation sequencing was found to be an effective method for the molecular genetic testing of 46,XY complete gonadal dysgenesis (46,XY CGD).