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

Contrast-enhanced ultrasound (CEUS) is a new form of ultrasound (US) that can dynamically display microvessels in a highly sensitive manner. The purpose of this study was to investigate the efficacy of CEUS for characterizing testicular lesions in comparison with conventional US. Forty-seven patients with testicular lesions were enrolled. The histopathology results revealed that 31 cases were neoplastic (11 cases of seminomas, 8 nonseminomatous germ cell tumors, 8 lymphomas, 2 Leydig cell tumors, and 2 nonspecific tumors), and 16 cases were nonneoplastic (8 cases of infarctions, 3 epidermoid cysts, and 5 inflammation). The indicators of shallow lobulated morphology and cystic-solid echogenicity on conventional US were suggestive of germ cell tumors. More indicators on CEUS were found to be useful for characterizing testicular lesions. All the neoplastic lesions showed hyperenhancement on CEUS. Moreover, germ cell tumors presented with heterogeneous enhancement (73.7%, 14/19), a twisted blood vessel pattern, rapid wash-in and wash-out, and peripheral rim hyperenhancement signs. Lymphoma was characterized by nonbranching linear vessel patterns (87.5%, 7/8), rapid wash-in and slow wash-out. In nonneoplastic lesions, infarction and epidermoid cysts showed no enhancement, and abscesses were observed with marginal irregular enhancement. The sensitivity, specificity, and accuracy of CEUS for differentiating between neoplastic and nonneoplastic lesions were 100%, 93.8%, and 97.9%, respectively, and these values were higher than those for conventional US (90.3%, 62.5%, and 80.9%, respectively). CEUS can sensitively reflect the microvascular perfusion in testicular lesions and offers high accuracy for characterizing them.
Contrast Media ; Diagnosis, Differential ; Epidermal Cyst ; Humans ; Lymphoma ; Male ; Neoplasms, Germ Cell and Embryonal/diagnostic imaging* ; Sensitivity and Specificity ; Testicular Neoplasms/diagnostic imaging* ; Ultrasonography/methods*

Klinefelter syndrome (KS) is characterized by small testes, gynecomastia, tall stature, and hypergonadotropic hypogonadism. This condition is associated with extra X chromosomes. It is well known that these aneuploidies predispose individuals to the development of several cancers. Moreover, there are many case reports that show KS patients to have a higher relative risk for the development of malignancy. However, incracranial germ cell tumor (ICGCT) associated with KS is very uncommon. Herein, we report delayed diagnosis of KS in a 15-year-old boy with ICGCT, embryonal carcinoma of the pineal gland, after multimodality treatment in Korea.
Adolescent ; Aneuploidy ; Carcinoma, Embryonal ; Delayed Diagnosis ; Gynecomastia ; Humans ; Hypogonadism ; Klinefelter Syndrome ; Korea ; Male ; Neoplasms, Germ Cell and Embryonal ; Pineal Gland ; Testis ; X Chromosome

OBJECTIVE: To evaluate the histological and stage characteristics of cervical cancer in women under 25 years old, and to compare them with older women. METHODS: Cross-sectional study of cases from the Hospital Cancer Registry of São Paulo State/Brazil from 2000 to 2015. Variables were age, International Federation of Gynecology and Obstetrics stage and histological type. Prevalence ratio (PR) and its 95% confidence interval (CI) were calculated. RESULTS: Out of 18,423 cervical cancer cases 204 (1.1%) were in women under 25 years old. The most frequent stage was stage I in women under 25 (36.2%) and between 25 and 34 (43.4%), and stage III in older women (31.8%). No statistically significant difference was observed in stages by age group. Squamous carcinomas were the most frequent in 73.5% of women under 25 and 78.5% of older women. In women under 25 the following histological types were more frequent: neuroendocrine carcinomas (PR=6.10, 95% CI=2.03–18.35), malignant germ cell tumors (PR=54.98, 95% CI=26.53–113.95), mesenchymal tumors (sarcomas) (PR=5.67, 95% CI=2.58–12.45) and hematopoietic/lymphoid tumors (PR=0.72, 95% CI=2.90–36.69). CONCLUSION: In women under 25 years old cervical cancer was an uncommon diagnosis and in about one third occurred at early stage. Squamous carcinoma was the most frequent histological type regardless age, but rare histological types were more frequent in young women.
Carcinoma, Neuroendocrine ; Carcinoma, Squamous Cell ; Cross-Sectional Studies ; Diagnosis ; Female ; Gynecology ; Humans ; Neoplasm Staging ; Neoplasms, Germ Cell and Embryonal ; Obstetrics ; Prevalence ; Sarcoma ; Uterine Cervical Neoplasms ; Young Adult

The primary function of intraoperative frozen consultation is to provide an as accurate and prompt diagnosis as possible during surgery and to guide the surgeon in further management. However, the evaluation of frozen section (FS) is sometimes difficult because of suboptimal tissue quality and frozen artifacts compared with routinely processed tissue section. The pathologist responsible for the FS diagnosis requires experience and good judgment. Ovarian tumors are a heterogeneous group of tumors including primary surface epithelial tumors, germ cell tumors and sex cord-stromal tumors, secondary tumors, and other groups of tumors of uncertain histogenesis or nonspecific stroma. Intraoperative FS is a very important and reliable tool that guides the surgical management of ovarian tumors. In this review, the diagnostic key points for the pathologist and the implication of the FS diagnosis on the operator’s decisions are discussed.
Artifacts ; Diagnosis ; Frozen Sections ; Judgment ; Neoplasms, Germ Cell and Embryonal ; Sex Cord-Gonadal Stromal Tumors

ObjectiveTo identify genetic susceptibility genes and the loci of their single nucleotide polymorphisms (SNPs) in patients with testicular germ cell tumor (TGCT) and provide some new ideas for the prediction, diagnosis and treatment of TGCT.

METHODSWe identified 41 SNP loci of TGCT-related genetic susceptibility genes from the literature published abroad. Using the iMLDRTM genotyping technique, we examined the SNP loci of the genetic susceptibility genes in the blood samples from 76 TGCT patients (aged 16－68 years) and 148 healthy men (aged 22－61 years) in China and analyzed their correlation with TGCT.

RESULTSIn China, TGCT was found to be correlated with the SNP loci rs2978381, rs10146204, rs12435857 and rs1256063 of the ESR2 gene, rs9397080 of the ESR1 gene, rs11202586 of the PTEN gene, rs2606345 and rs4646903 of the CYP1A1 gene, and rs1456432 of the CYP19A1 gene.

CONCLUSIONSThe results of our study indicated some difference in the positive SNP loci of the TGCT patients between Chinese and foreign cohorts as well as in different groups in China.

Adolescent ; Adult ; Aged ; Case-Control Studies ; China ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Neoplasms, Germ Cell and Embryonal ; diagnosis ; genetics ; therapy ; Polymorphism, Single Nucleotide ; genetics ; Testicular Neoplasms ; diagnosis ; genetics ; therapy ; Young Adult

Mature cystic teratoma (MCT) is the most common ovarian tumor. Secondary malignant tumors rarely arise in MCTs, and squamous cell carcinoma (SCC) is the most common form of such tumors. MCT-derived SCC in situ (CIS) is mostly found together with invasive SCC; it is seldom detected alone. A 44-year-old woman with breast cancer was found to have a left ovarian cyst (size > 8 cm) before treatment. She underwent bilateral salpingo-oophorectomy, and frozen biopsy showed MCT with focal proliferation of squamous epithelium and mild atypism. However, definitive pathologic diagnosis confirmed CIS arising in MCT. In addition, germline BRCA 1/2 test and human papillomavirus test of tumor tissue yielded negative results. This report is the first case of its kind in Korea. Our report can aid in clinical decision making and serve as a basis for follow-up studies on this rare type of CIS arising in MCT.
Adult ; Biopsy ; Breast Neoplasms ; Carcinoma in Situ ; Carcinoma, Squamous Cell* ; Clinical Decision-Making ; Diagnosis ; Epithelial Cells* ; Epithelium ; Female ; Follow-Up Studies ; Humans ; Korea ; Neoplasms, Germ Cell and Embryonal ; Ovarian Cysts ; Teratoma*

OBJECTIVE: To examine survival of teenage women with pregnancies complicated by primary ovarian cancer. METHODS: This is a secondary analysis of a previously organized systematic literature review of primary ovarian cancer diagnosed during pregnancy. Cases eligible for analysis were patients whose age at cancer diagnosis and survival outcome were known (n=201). Pregnancy and oncologic outcome were then examined based on patient age. RESULTS: These were comprised of 95 (47.3%) epithelial ovarian cancers (EOCs), 82 (40.8%) malignant germ cell tumors (MGCTs), and 24 (11.9%) sex-cord stromal tumors (SCSTs). Teenage pregnancy was seen in 21 (10%) cases, and was highest among the SCST group compared to the other cancer types (EOC, 1.1%; MGCT, 14.6%; and SCST, 29.2%, p < 0.001). Live birth rates, neonatal weight, full term delivery rates, and Cesarean section rates were similar between the teenage group and the non-teenage group (all, p > 0.05); however, teenage pregnancy was significantly associated with an increased risk of serious maternal/neonatal adverse events (50% vs. 22.7%, p = 0.013). On univariable analysis, teenage pregnancy was significantly associated with decreased ovarian cancer-specific survival (5-year rate: age ≥ 30, 79.6%; age 20–29, 87.2%; and age < 20, 41.6%; p < 0.001). On multivariable analysis controlling for calendar year, cancer type, cancer stage, and gestational age at ovarian cancer diagnosis, teenage pregnancy remained an independent prognostic factor for decreased ovarian cancer-specific survival compared to women aged ≥ 30 (adjusted-hazard ratio=4.71; 95% confidence interval=1.17–18.9; p = 0.029). CONCLUSION: Teenage women with pregnancies complicated by primary ovarian cancer may be at increased risk of poor survival from ovarian cancer.
Cesarean Section ; Diagnosis ; Female ; Gestational Age ; Humans ; Live Birth ; Neoplasms, Germ Cell and Embryonal ; Ovarian Neoplasms* ; Pregnancy ; Pregnancy in Adolescence*

Germinoma is the most common type of intracranial germ cell tumors (GCTs). Pineal gland and suprasellar region are the most frequent sites of central nervous system (CNS) involvement. Intracranial masses caused by Langerhans cell histiocytosis (LCH) mimics features of CNS GCTs. LCH frequently involve spine and is the most common cause of vertebra plana in children. A 15-year-old boy presented with progressing symptoms of polydipsia, polyuria, general headache, nausea and severe back pain. Brain MRI showed brain tumor with simultaneous involvement of suprasellar region and pineal gland. An excisional biopsy of suprasellar mass was done. The pathologic assessment confirmed the diagnosis of germinoma. Patient's treatment continued accordingly. A spine MRI, done due to persistent backache, showed a vertebra plana. We reevaluated the primary diagnosis suspecting LCH. Germinoma of CNS was confirmed and a biopsy of vertebral lesion resulted in hemangioma. Thus we report a case of CNS germinoma with co-occurrence of vertebra plana. We emphasized the importance of histopathologic diagnosis of pineal/suprasellar masses and primary investigation of other CNS regions including spine for possible metastasis or comorbidities.
Adolescent ; Back Pain ; Biopsy ; Brain ; Brain Neoplasms ; Central Nervous System ; Child ; Comorbidity ; Diagnosis ; Germinoma* ; Headache ; Hemangioma ; Histiocytosis, Langerhans-Cell ; Humans ; Magnetic Resonance Imaging ; Male ; Nausea ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal ; Pineal Gland ; Polydipsia ; Polyuria ; Spine*

PURPOSE: This study was conducted to investigate the neurocognitive functioning of children with intracranial germ cell tumor (IGCT) prior to receiving proton beam therapy (PBT), and to identify differential characteristics of their neurocognitive functioning depending on tumor location. As a secondary object of this study, neurocognitive functions were followed up at 1-2 years after PBT to examine early post-treatment changes. MATERIALS AND METHODS: Between 2008 and 2014, 34 childrenwith IGCT treatedwho received PBT atNational Cancer Center, Korea were enrolled in this study. Standardized neurocognitive tests of intelligence, memory, and executive functioning were performed with baseline psychological assessments using the Child Behavior Checklist (CBCL). Follow-up assessments after PBT were conducted in 20 patients (T2). The results were analyzed based on the locations of tumors, which included the suprasellar, pineal gland, basal ganglia, and bifocal regions. RESULTS: The neurocognitive function of IGCT patients was significantly lower than that of the normal population in performance intelligence quotient (p=0.041), processing speed (p=0.007), memory (p < 0.001), and executive functioning (p=0.010). Patients with basal ganglia tumors had significantly lower scores for most domains of neurocognitive functioning and higher scores for CBCL than both the normal population and patients with IGCT in other locations. There was no significant change in neurocognitive function between T1 and T2 for all types of IGCT patients in first 1-2 years after PBT. CONCLUSION: Tumor location significantly affects the neuropsychological functioning in patients with IGCT. Neuropsychological functioning should be closely monitored from the time of diagnosis in IGCT patients.
Basal Ganglia ; Brain Neoplasms ; Checklist ; Child Behavior ; Child* ; Cognition ; Diagnosis ; Follow-Up Studies ; Germ Cells* ; Humans ; Intelligence ; Korea ; Memory ; Neoplasms, Germ Cell and Embryonal* ; Pineal Gland ; Proton Therapy