The molecular landscape of ETMR at diagnosis and relapse.

Embryonal tumours with multilayered rosettes (ETMRs) are aggressive paediatric embryonal brain tumours with a universally poor prognosis1. Here we collected 193 primary ETMRs and 23 matched relapse samples to investigate the genomic landscape of this distinct tumour type. We found that patients with tumours in which the proposed driver C19MC2-4 was not amplified frequently had germline mutations in DICER1 or other microRNA-related aberrations such as somatic amplification of miR-17-92 (also known as MIR17HG). Whole-genome sequencing revealed that tumours had an overall low recurrence of single-nucleotide variants (SNVs), but showed prevalent genomic instability caused by widespread occurrence of R-loop structures. We show that R-loop-associated chromosomal instability can be induced by the loss of DICER1 function. Comparison of primary tumours and matched relapse samples showed a strong conservation of structural variants, but low conservation of SNVs. Moreover, many newly acquired SNVs are associated with a mutational signature related to cisplatin treatment. Finally, we show that targeting R-loops with topoisomerase and PARP inhibitors might be an effective treatment strategy for this deadly disease.

Current outstanding challenges in germ cell tumors.

PURPOSE OF REVIEW: Despite the remarkable advances in the treatment of germ cell tumors (GCT), several challenges remain. This review aims to highlight some of these challenges and provide guidance on how to navigate through them. RECENT FINDINGS: Patients with International Germ Cell Cancer Collaborative Group poor risk disease have worse prognosis and investigating novel therapeutic interventions are warranted in this population. Patients with brain metastases require a multidisciplinary approach by a group of clinicians experienced in the management of germ cell tumors. Patients with platinum refractory disease have poor prognosis and development of novel treatment options is urgently needed. Conventional tumor markers including alpha fetoprotein and human chorionic gonadotropin remain standard. Development of novel biomarkers to detect minimal residual disease or teratoma is needed. SUMMARY: Management of patients with GCT requires a multidisciplinary approach. Patients should preferably be evaluated at tertiary care centers with expertise in the management of this disease.

Pathogenesis and pathobiology of testicular germ cell tumours: a view from a developmental biological perspective with guidelines for pathological diagnostics.

Testicular germ cell tumours (GCT) are divided into three different subtypes (types I-III) regarding to their developmental origin, histological differences and molecular features. Type I GCT develop from disturbed primordial germ cells and most commonly occur in children and young adolescents, which is why they are referred to as prepubertal GCT. Type II GCT develop from a non-invasive germ cell neoplasia in situ (GCNIS) and show an isochromosome 12p (i12p) or gain of 12p material as a common and characteristic molecular alteration. Type III GCT originate from distorted postpubertal germ cells (e.g. spermatogonia) in adult patients and have changes on chromosome 9 with amplification of the DMRT1 gene. Type I GCT encompass prepubertal-type teratomas and yolk-sac tumours (YST). Type II GCT include seminoma, embryonal carcinoma, choriocarcinoma, postpubertal-type teratoma and postpubertal-type YST. Types I and II GCT both show similar morphology, but are separated from each other by the detection of a GCNIS and an i12p in type II GCT. For type II GCT it is especially important to detect non-seminomatous elements, as these tumours have a worse biological behaviour and need a different treatment to seminomas. In contrast to types I and II GCT, type III tumours are equivalent to spermatocytic tumours and usually occur in elderly men, with few exceptions in young adults. The development of types I and II GCT seems to depend not upon driver mutations, but rather on changes in the epigenetic landscape. Furthermore, different pluripotency associated factors (e.g. OCT3/4, SOX2, SOX17) play a crucial role in GCT development and can be used as immunohistochemical markers allowing to distinguish the different subtypes from each other in morphologically challenging tissue specimens. Especially in metastatic sites, a morphological and immunohistochemical diagnostic algorithm is important to detect small subpopulations of each non-seminomatous GCT subtype, which are associated with a poorer prognosis and need a different treatment. Furthermore, primary extragonadal GCT of the retroperitoneum or mediastinum develop from misguided germ cells during embryonic development, and might be challenging to detect in small tissue biopsies due to their rarity at corresponding sites. This review article summarises the pathobiological and developmental aspects of the three different types of testicular GCT that can be helpful in the histopathological examination of tumour specimens by pathologists.

Primary germ cell tumours of the mediastinum: A review with emphasis on diagnostic challenges.

This article will review current aspects of the histopathological, immunohistochemical and molecular analysis of primary mediastinal germ cell tumours (PMGCTs) as well as their aetiological, epidemiological, clinical and therapeutic features. PMGCTs represent an important differential diagnosis in the spectrum of mediastinal tumours, and their diagnosis is usually made on small tissue samples from core needle biopsies in combination with diagnostic imaging and serum tumour markers. As in lymphomas, a small biopsy is often the only viable tumour sample available from these patients, as they receive chemotherapy prior to eventual surgical resection. Pathologists therefore need to apply an efficient combination of immunohistochemical markers to confirm the diagnosis of a PMGCT and to exclude morphological mimics.

Clinical characteristics and predictive factors of delayed diagnosis in patients with sellar germ cell tumors.

PURPOSE: To investigate the clinical characteristics and predictive factors associated with delayed diagnosis in patients with sellar germ cell tumors (GCTs), aiming for early diagnosis. METHODS: A total of 345 patients with sellar GCTs were retrospectively collected. Patients were classified into a delayed diagnosis group (> 6 months from onset to diagnosis) and a non-delayed diagnosis group (≤ 6 months). We compared general characteristics, clinical symptoms, diagnostic methods, treatment strategies, tumor prognosis, and pituitary function between the two groups. Predictive factors for delayed diagnosis were explored using multivariate logistic regression analysis. RESULTS: 225 patients (65.2%) experienced delayed diagnosis. Although there was no association between delayed diagnosis and survival rates or tumor recurrence rates, the delayed diagnosis group had a higher incidence of central diabetes insipidus, central adrenal insufficiency, central hypothyroidism, central hypogonadism, and growth hormone deficiency. Moreover, polyuria/polydipsia (OR 5.46; 95% CI 2.33-12.81), slow growth (OR 5.86; 95% CI 2.61-13.14), amenorrhea (OR 6.82; 95% CI 2.68-17.37), and germinoma (OR 4.99; 95% CI 1.08-3.61) were associated with a higher risk of delayed diagnosis, while older age of onset (OR 0.88; 95% CI 0.84-0.94) and nausea/vomiting (OR 0.31; 95% CI 0.15-0.63) contributed to earlier diagnosis. CONCLUSION: In patients with sellar GCTs, delayed diagnosis is common and linked to increased pituitary dysfunction. The initial symptoms of slow growth, polyuria/polydipsia, and amenorrhea, as well as germinoma with negative tumor markers, predict the possibility of a delayed diagnosis. Early diagnosis is crucial to minimize the impact of sellar GCTs on pituitary function.

MicroRNAs for detecting occult genitourinary cancer.

PURPOSE OF REVIEW: Genitourinary (GU) malignancies are a real burden in global health worldwide. Each model has its own clinical challenges, and the early screening and/or detection of occult cancer in follow-up is transversal to all of them. MicroRNAs (miRNAs) have been proposed as minimally invasive liquid biopsy cancer biomarkers, due to their stability and low degradation. RECENT FINDINGS: The different GU tumor models are in different stages concerning miRNAs as biomarkers for cancer detection. Testicular germ cell tumors (TGCTs) already have a specific defined target, miR-371a-3p, that has shown high sensitivity and specificity in different clinical settings, and is now in final stages of preanalytical testing before entering the clinic. The other GU malignancies are in a different stage, with many liquid biopsy studies (both in urine and plasma/serum) being currently performed, but there is not an agreeable miRNA or set of miRNAs that is ready to follow the footsteps of miR-371a-3p in TGCTs. SUMMARY: Further studies with proper molecular characterization of miRNA profiles of GU malignancies and standardization of sampling, biobanking and formal analysis may aid in the advance and choosing of specific target sets to be used for occult cancer detection.

The Effect of Socioeconomic Status and Race/Ethnicity on the Risk of Presenting With Advanced Stage at Diagnosis in Embryonal Tumors.

We evaluated whether socioeconomic status (SES), race/ethnicity, and their interaction were associated with the presentation of advanced stage at diagnosis in embryonal tumors. Children 0 to 19 years of age diagnosed with embryonal tumors between 2006 and 2018 were identified from the US Surveillance, Epidemiology, and End Results program database specialized with Census Tract SES/Rurality. SES quintile was derived from a composite index for census tracts. We performed logistic regression to estimate odds ratios (ORs) and 95% confidence intervals by SES and race/ethnicity, adjusting for sex, age, and diagnosis year. Overall, no significant associations were found between either SES or race/ethnicity and the risk of presenting with advanced stage at diagnosis, although patterns of risk reductions were observed in atypical teratoid/rhabdoid tumors and embryonal rhabdomyosarcoma with increasing SES. In the stratified analysis, decreased odds of presenting with advanced-stage embryonal rhabdomyosarcoma were observed for Hispanics with higher SES (OR: 0.24, 95% Confidence Interval: 0.08-0.75) compared with Hispanics with lower SES. Future studies incorporating individual-level SES, cancer-specific staging information, and potential demographic, clinical, epidemiological, and genetic risk factors are warranted to confirm our findings.

Mediastinal Germ-cell Tumors Relapse in a Male With Klinefelter Syndrome. Is Longer Surveillance Needed?

Germ cell tumors (GCTs) are a heterogeneous group of pediatric cancers. In up to one-third of male patients, a primary mediastinal location is associated with the presence of Klinefelter syndrome (KS). We describe a case of mediastinal GCT in a patient, with unacknowledged KS, that presented a relapse 7 years from diagnosis, that is, 2 years after the end of the follow-up program usually recommended for patients with GCT. There are no recommendations for screening for KS in patients with mediastinal GCT and there are no specific guidelines for surveillance of GCT in KS patients. Our experience suggests that KS should be suspected in patients with mediastinal GCT, and a longer follow-up plan should be implemented when GCT occurs in patients with KS.

Clinical characteristics and management of adipsic arginine vasopressin deficiency in children and adolescents with sellar germ cell tumors.

Adipsic arginine vasopressin deficiency(aAVP-D) is a rare, high-risk syndrome, particularly difficult to recognize and manage in children and adolescents. This investigation examined the clinical features and management of aAVP-D in children and adolescents with sellar germ cell tumors (GCTs). A retrospective survey was performed on 260 patients with sellar GCTs, categorized into aAVP-D and non-aAVP-D groups based on thirst presence. General characteristics, hypothalamic syndrome, pituitary function, metabolic indicators, and complications were compared. Biochemical indicator changes in the aAVP-D group were analyzed after systematic management, and receiver operating characteristic (ROC) curve analysis established the optimum serum sodium cut-off for predicting the aAVP-D. 25 patients (9.6%) developed aAVP-D. The aAVP-D group had larger tumors with hypothalamic involvement and more surgical resections. They also demonstrated more hypothalamic syndrome, central adrenal insufficiency, central hypogonadism, and insulin-like growth factor-1 levels below norms. Furthermore, aAVP-D patients exhibited significantly higher rates of hypernatremia (100% vs 20.9%, p < 0.001), hyperuricemia (60.0% vs 23.4%, p < 0.001), renal impairment (32.0% vs 1.7%, p < 0.001), and venous thrombosis (4.0% vs 0%, p = 0.002). Following systematic management, aAVP-D patients experienced significant reductions in serum sodium, uric acid, and creatinine levels, although these remained higher than in the non-aAVP-D group. ROC analysis indicated that a serum sodium level above 149.5 mmol/L predicted aAVP-D. Conclusion Patients with aAVP-D had more tumor involvement in the hypothalamic region, surgical resections, hypothalamic syndrome, hypopituitarism, and complications. Serum sodium levels above 149.5 mmol/L necessitated heightened vigilance for aAVP-D. Early identification and systematic management reduced complications, though clinical management remained challenging. What is Known • Adipsic arginine vasopressin deficiency (aAVP-D) is a rare and high-risk syndrome that is difficult to recognize and manage. • There are few reports on aAVP-D, most of which focus on adult patients. • The characteristics and management of aAVP-D in children and adolescents remain unclear. What is New • Children and adolescents with aAVP-D experienced higher rates of hypothalamic region tumor involvement, surgical resections, hypothalamic syndrome, hypopituitarism, and associated complications. • Serum sodium levels above 149.5 mmol/L necessitated heightened vigilance for aAVP-D. • Early recognition and structured management of ADI lowered the risk of complications.

Undifferentiated embryonal sarcoma of the liver in children: our experience in four difficult cases and three-dimensional practical exploration.

AIMS: To explore rare and difficult cases of undifferentiated embryonal sarcoma of the liver (UESL) in children in a single centre, summarize the diagnosis and treatment experience and analyse the role of a computer-assisted surgery system (Hisense CAS), thus providing a new global vision and three-dimensional perspective. METHODS: We retrospectively collected the clinical data including the diagnoses and treatment processes, of children with UESL confirmed by histopathological examination in our hospital from January 2009 to December 2020. The relationship between the tumour volume and important blood vessels and between the liver volume and tumour volume, as well as other three-dimensional characteristics in the reconstructed three-dimensional model were analysed using Hisense CAS. The findings from this analysis can be used to aid in surgical decision-making and preoperative planning. RESULTS: Four children-3 girls and 1 boy-with UESL were included in the study. The age at onset ranged from 6 to 8 years. All four children presented with symptoms of abdominal discomfort, and abdominal masses were detected during physical examination. Owing to the wishes of their parents and the possibility that the disease was benign, all four children underwent one-stage radical surgery. For patient 1, a three-dimensional reconstruction was created during the initial diagnosis, which made accurate evaluation and planning of the preoperative procedure challenging. In patient 2, the tumour was located in the middle lobe of the liver and involved the first and second hepatic hilum. For patient 3, the pathological diagnosis of the tumour after surgery was challenging, but eventually, the diagnosis was confirmed through histochemistry and consultation with higher-level hospitals. Patient 4 had a giant tumour, which had a preoperative simulated future liver remnant volume (FLV) that was 21.0% of the total volume of the liver and tumour (TLTV). According to the standard liver volume (SLV) for children, the FLV was 77.0% of the SLV, making surgery feasible. All four children underwent complete resection, and only patient 4 experienced recurrence below the diaphragm 19 months after surgery. Currently, the 3-year overall survival rate is 100%, and the 3-year event-free survival rate is 75%. CONCLUSION: UESL in children is rare, and the key to diagnosis and treatment is complete surgical resection. Through individualized three-dimensional surgical planning, accurate and complete resection of difficult and complex UESL in children can be achieved, leading to a favourable prognosis.

Embryonal and pineal tumours.

Embryonal and pineal tumours represent a diverse group of central nervous system (CNS) neoplasms. While many of the small round blue cell tumours that make up the embryonal neoplasms share similar histologic qualities, there are several morphologic and cytologic characteristics that are useful in distinguishing different tumour types. Similarly, pineal parenchymal tumours represent clinically diverse tumours, ranging from benign to overtly malignant. The most recent iteration of the World Health Organization Classification of CNS Tumours expanded greatly on the significance of molecular alterations in brain tumour diagnostics. In this article, we summarize the salient cytologic and histologic features of CNS embryonal and pineal tumours, and highlight diagnostically relevant molecular alterations within each tumour type.

Application of microRNAs in the diagnosis and monitoring of pediatric germ cell tumors: Kazakh experience.

GCT is characterized by specific biochemical markers expression, such as human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP), which are the main tools in the diagnosis and monitoring of GCT treatment. They are expressed in 15-20% of cases of seminoma and in 60-80% of cases of non-seminoma. MicroRNA profiling allows to identify a number of microRNAs that are superior to classical serum tumor markers in the diagnosis of primary tumors, as well as in subsequent monitoring and prediction of recurrence. We analyzed the expression of 9 microRNAs (microRNA clusters 302/367 and 371-373, microRNA375) in the blood serum of 20 children with extracranial GCT at different stages of therapy and showed their usefulness and informativeness in early detection of events. Taking into consideration the high sensitivity and specificity, serum microRNAs 367,371,372,373,302d are of great interest for clinical use in malignant GCT. Significant expression of miR 375-3p was not detected either in malignant GCT or in teratomas.

MicroRNAs in Testicular Germ Cell Tumors: The Teratoma Challenge.

Testicular germ cell tumors (TGCTs) are relatively common in young men, making accurate diagnosis and prognosis assessment essential. MicroRNAs (miRNAs), including microRNA-371a-3p (miR-371a-3p), have shown promise as biomarkers for TGCTs. This review discusses the recent advancements in the use of miRNA biomarkers in TGCTs, with a focus on the challenges surrounding the noninvasive detection of teratomas. Circulating miR-371a-3p, which is expressed in undifferentiated TGCTs but not in teratomas, is a promising biomarker for TGCTs. Its detection in serum, plasma, and, potentially, cystic fluid could be useful for TGCT diagnosis, surveillance, and monitoring of therapeutic response. Other miRNAs, such as miR-375-3p and miR-375-5p, have been investigated to differentiate between TGCT subtypes (teratoma, necrosis/fibrosis, and viable tumors), which can aid in treatment decisions. However, a reliable marker for teratoma has yet to be identified. The clinical applications of miRNA biomarkers could spare patients from unnecessary surgeries and allow for more personalized therapeutic approaches. Particularly in patients with residual masses larger than 1 cm following chemotherapy, it is critical to differentiate between viable tumors, teratomas, and necrosis/fibrosis. Teratomas, which mimic somatic tissues, present a challenge in differentiation and require a comprehensive diagnostic approach. The combination of miR-371 and miR-375 shows potential in enhancing diagnostic precision, aiding in distinguishing between teratomas, viable tumors, and necrosis. The implementation of miRNA biomarkers in TGCT care could improve patient outcomes, reduce overtreatment, and facilitate personalized therapeutic strategies. However, a reliable marker for teratoma is still lacking. Future research should focus on the clinical validation and standardization of these biomarkers to fully realize their potential.

Consensus guidelines for the management of pineal region tumours for low- and middle-income countries.

Pineal region tumours are rare and mainly arise at a younger age. They can be categorized into various types: germ cell tumours (GCT), pineal parenchymal tumours (PPT), meningiomas, gliomas, pineoblastoma, pineal parenchymal tumours of intermediate differentiation, papillary tumours of the pineal region, and SMARCB1- mutant desmoplastic myxoid tumour. Within GCT, germinomas are the most prevalent, comprising the majority of tumours in this region, while nongerminomatous GCTs are also present. In rare instances, metastases from other sites may manifest. These tumours often lead to obstructive hydrocephalus and commonly exhibit symptoms related to mass effect, including headache, nausea, vomiting, and impaired gait stability. Different subtypes of pineal region tumours exhibit distinct radiological characteristics, thus imaging remains the primary diagnostic tool. Histologic diagnosis necessitates biopsy, unless in cases of germ cell tumours, particularly germinomas, which can be identified through elevated levels of tumour markers like alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in both cerebrospinal fluid (CSF) and serum. While benign tumours might be effectively treated with radical resection alone, malignant tumours demand additional chemotherapy and radiotherapy following surgical removal.

Intracranial Germ Cell Tumors.

Intracranial germ cell tumors are rare tumors occurring in adolescents and young adults, which include germinomas and non-germinomatous type germ cell tumors (NGGCT). In the past few decades, cooperative trial groups in Europe and North America have developed successful strategies to improve survival outcomes and decrease treatment-related toxicities. New approaches to establishing diagnosis have deferred the need for radical surgery. The 5-year event-free survival (EFS) is above 90% and even patients who present with metastatic germinoma can still be cured with chemotherapy and craniospinal irradiation. The combination of surgery, chemotherapy, and radiation therapy is tailored to patients based on grouping and staging. For NGGCT, neoadjuvant chemotherapy followed by delayed surgery for residual disease and radiotherapy can yield a 5-year EFS of 70%. Further strategies should focus on reducing long-term complications while preserving high cure rates.

Implications of deferred diagnosis of paediatric intracranial germ cell tumours.

AIMS: This study analysed the clinical features of a cohort of children with intracranial germ cell tumours (IC-GCTs). We retrospectively reviewed timelag between symptoms onset, clinic-radiological findings, diagnosis and outcomes. METHODS: Symptoms at diagnosis were divided into four groups: (1) raised intracranial pressure (RICP); (2) visual impairment; (3) endocrinopathies; (4) other. Total diagnostic interval (TDI), defined as the interval between symptom onset (including retrospective recall of symptoms) and definitive diagnosis of IC-GCT, was calculated and compared to survival rates. RESULTS: Our cohort included 55 children with median follow-up of 78.9 months (0.5-249.9). The majority (63.6%) had germinomas and 10.9% were metastatic at diagnosis. IC-GCTs were suprasellar (41.8%), pineal (36.4%), bifocal (12.7%) or in atypical sites (9.1%). The most common presenting symptoms were related to RICP (43.6%); however, by the time of tumour diagnosis, 50.9% of patients had developed endocrine dysfunctions. All pineal GCTs manifested with RICP or visual impairment. All suprasellar GCTs presented with endocrinopathies. TDI ranged between 0.25 and 58.5 months (median 4 months). Pineal GCTs had the shortest TDI (median TDI 1 month versus 24 months in suprasellar GCTs, p < .001). TDI > 6 months was observed in 47.3% of patients and was significantly associated with endocrine presenting symptoms. No statistically significant difference was found in progression-free survival and overall survival between patients with TDI > 6 months and with TDI ≤ 6 months. CONCLUSION: Approximately half of the IC-GCT patients in this cohort had TDI > 6 months. These presented mostly with endocrine deficits. TDI > 6 months was not associated with increased relapse or mortality rates.

Ovarian Malignant Mixed Germ Cell Tumor With Prominent Embryoid Bodies (Polyembryoma Background): A Case Report and Literature Review.

Ovarian malignant mixed germ cell tumors are rare tumors occurring in young women. The presence of prominent embryoid bodies in these tumors is extremely uncommon. Herein, we report such a case, with a histomorphologic description and immunohistochemical and fluorescence in situ hybridization analyses.

Molecular Evidence for Epithelial Origin of Mixed Ovarian Epithelial-Germ Cell Neoplasms: Report of 2 Cases and Review of Literature.

Ovarian germ cell tumors (GCT) account for 2% to 3% of malignant ovarian neoplasms in Western countries and typically occur within the first 2 decades. When presenting later in life, GCTs may be associated with epithelial malignancies. In these circumstances, it has been theorized that these tumors may originate from a somatic, rather than germ cell origin, especially in the postmenopausal setting; however, the true derivation is not fully understood. Our database was searched for primary ovarian GCTs associated with a malignant epithelial component in patients above 35 yr of age, from 2006 to 2021. Two cases were identified and in each case, slides were reviewed and targeted next-generation sequencing was utilized to identify and compare gene mutation variants in morphologically distinct components. Patient A is a 58-yr-old, with choriocarcinoma and minor component of mucinous adenocarcinoma, and patient B is a 43-yr-old, with yolk sac tumor and minor component of endometrioid adenocarcinoma. The morphologically distinct areas in each case showed disparate staining patterns; however, next-generation sequencing demonstrated identical mutation variants within both the germ cell and epithelial components. Variants in CDKN2A , PIK3CA , PIK3R1 , and TP53 were present in patient A's tumor, while patient B's tumor showed CTNNB1 , PIK3R1 , and 2 PTEN variants. These mutational patterns are similar to those seen in pure epithelial counterparts, suggesting somatic derivation of the germ cell component. These rare tumors portend a poor prognosis and understanding their origin has clinical and therapeutic implications.

Comparison between free ß subunit of human chorionic gonadotropin (hCG) and total hCG assays in adults with testicular cancer.

OBJECTIVES: We tested the hypothesis that the free-ß subunit (ßhCG) is diagnostically more sensitive with total hCG assays (hCGt) not detecting all tumours secreting ßhCG. The effects of sex, age, and renal failure were investigated as secondary objectives. METHODS: We compared ßhCG with hCGt in 204 testicular cancer patients (99 seminomas, 105 non-seminonatous germ cell tumours). The effects of sex and age were determined in 125 male and 138 female controls and that of renal failure was investigated in 119 haemodialysis patients. Biochemical assessment of gonadal status was performed with LH, FSH, oestradiol and testosterone. RESULTS: Discordant results were common with isolated increases of hCGt observed in 32 (15.7 %) and ßhCG in 14 (6.9 %) patients. Primary hypogonadism was the most common cause of isolated hCGt increases. After therapeutic interventions ßhCG decreased below its upper reference more rapidly than hCGt. We observed unequivocal false negative results in two patients with non-seminomatous germ cell tumours. Both occurred in patients with clinical tumour recurrences; in one instance we observed a false negative hCGt while in the second false negative ßhCG's were documented in serial samples. CONCLUSIONS: The similar false negative rates did not support the hypothesis that ßhCG will detect more patients with testicular cancer than hCGt. In contrast to hCGt, ßhCG was unaffected by primary hypogonadism which is a predictably frequent complication in testicular cancer patients. We therefore recommend ßhCG as the preferred biomarker in testicular cancer.

Germ cell tumors of the central nervous system: A brief review and site-specific considerations.

Germ cell tumors of the central nervous system (GCT-CNS) arise predominantly in midline locations of the CNS and affect young patients in their first to third decades of life. Involvement of the CNS is thought to be a sequelae of residual primordial germ cells with incomplete embryologic migration. Clinically, GCT-CNS present with symptoms of ventricular obstruction or compression of affected brain structures. Histologically, these tumors are analogous to their gonadal and extra-gonadal counterparts. Diagnosis relies heavily on morphology and immunohistochemical findings, and can be complicated by limited tumor sampling. There is currently only a limited role for molecular studies. Treatment of these lesions is made difficult by their involvement of deep and vital brain structures and accurate pathologic diagnosis is essential for appropriate therapy. Diagnosis should involve review of the clinical history, imaging studies, and assessment of serum and cerebrospinal fluid tumor markers. Current therapeutic strategies involving radiation therapy with or without chemotherapy are quite effective, in spite of the locational difficulties that often prevent gross total resection.