Transcriptome analysis reveals upregulation of immune response pathways at the invasive tumour front of metastatic seminoma germ cell tumours

Background Testicular germ cell tumours (TGCTs) have a high metastasis rate. However, the mechanisms related to their invasion, progression and metastasis are unclear. Therefore, we investigated gene expression changes that might be linked to metastasis in seminomatous testicular germ cell tumour (STGCT) patients. Methods Defined areas [invasive tumour front (TF) and tumour centre (TC)] of non-metastatic (with surveillance and recurrence-free follow-up >2 years) and metastatic STGCTs were collected separately using laser capture microdissection. The expression of 760 genes related to tumour progression and metastasis was analysed using nCounter technology and validated with quantitative real-time PCR and enzyme-linked immunosorbent assay. Results Distinct gene expression patterns were observed in metastatic and non-metastatic seminomas with respect to both the TF and TC. Comprehensive pathway analysis showed enrichment of genes related to tumour functions such as inflammation, angiogenesis and metabolism at the TF compared to the TC. Remarkably, prominent inflammatory and cancer-related pathways, such as interleukin-6 (IL-6) signalling, integrin signalling and nuclear factor-κB signalling, were significantly upregulated in the TF of metastatic vs non-metastatic tumours. Conclusions IL-6 signalling was the most significantly upregulated pathway in metastatic vs non-metastatic tumours and therefore could constitute a therapeutic target for future personalised therapy. In addition, this is the first study showing intra- and inter-tumour heterogeneity in STGCT.

Depression, anxiety and health-related quality of life in paediatric intracranial germ cell tumor survivors

Background Little is known about depression and anxiety among paediatric intracranial germ cell tumour (iGCT) survivors. We aimed to evaluate the risk factors associated with depression, anxiety and health-related quality of life (HRQoL) in paediatric iGCT survivors. Methods We recruited 200 iGCT patients (and their parents) from Beijing Tiantan Hospital and assessed their HRQoL using the Paediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales. The Children’s Depression Inventory, Screen for Child Anxiety Related Emotional Disorders, and Symptom Checklist 90 were used to evaluate depression and anxiety. The results were analysed based on disease recurrence, tumour location and treatment strategies. Results Survivors with recurrent tumours had worse HRQoL scores than those with non-recurrent tumours. Patients with tumours involving both the suprasellar and basal ganglia regions had the worst HRQoL scores. A large proportion of survivors had depression or anxiety. Both depression and anxiety scores were highly correlated with the HRQoL emotional functioning scores. The parent proxy-reports (PPR) and child self-reports were highly correlated in all domains. Conclusions This study demonstrated the clinical factors affecting paediatric iGCT survivors’ depression, anxiety, and HRQoL. Therefore, psychological interventions should be implemented. It also suggests that the PedsQL PPR would be helpful for routine screening.

Choriocarcinoma syndrome: a rare presentation of testicular germ cell tumour

Published in August 2021.

Carboplatin-induced Renal Salt Wasting Syndrome in Paediatric Patients with Intracranial Germ Cell Tumours and Concomitant Diabetes Insipidus

We report the first case series of 14 children with intracranial germ cell tumour (iGCT) and concomitant central diabetes insipidus (DI), who developed hyponatremia secondary to renal salt wasting syndrome (RSWS) following the administration of carboplatin. Clinicians prescribing platinum-based chemotherapy for this group of patients should be alert to the risk of RSWS. Regular monitoring should be performed as hyponatraemia can be asymptomatic until it is severe.

Mixed Germ Cell Tumour of Ovary WTH Chemotherapy Side Effect

Introduction: Mixed germ cell tumour is a very rare type of aggressive cancer, consisting of more than one type of germ cell components. The most common component reported was dysgerminoma, followed by endodermal sinus tumour, teratoma, choriocarcinoma and embryonal carcinoma respectively. This study focuses on the combination of dysgerminoma and endodermal sinus tumour (yolk sac tumour) along with the hearing loss as the side effect of chemotherapy. Clinical Findings: Pain in the lower abdomen (lump is visible and has occupied hypogastrium along with bilateral iliac region extending 2-3 cm above the umbilicus), backache, fever (100.6 °F). Later after the third chemo cycle, it was found that the patient has progressive mild hearing loss. Diagnostic Evaluation: HB= 9.7gm%, TLC= 10300/cumm, PLT= 5,49 lakhs/cumm, CA 125= 909 U/ML. Histopathology Report: Ascitic fluid along with thirteen containers containing right ovarian mass, right ovary with mass, right fallopian tube, bowel deposits as well as residual nodules and pelvic deposits were sent of which, the reports indicated mixed germ cell tumour of the ovary. Therapeutic Intervention: Packed red blood cells transfusion, Pre-chemo and post-chemo hydration, Pre-chemo and post-chemo drugs, BEP Chemotherapy (Bleomycin, Etoposide, Cisplatin). Conclusion: My patient aged 11 years old female was admitted to Gynaecology Ward No – 16, AVBRH on 27/12/2020 for the first cycle of chemotherapy with the complaints of lower abdominal pain, backache and fever. The patient was diagnosed as the case of mixed germ cell tumour, further had mild hearing loss as the side effect of chemotherapy The patient is on chemo and is advised for follow up care once a month.

Digital Pathology Transformation in a Supraregional Germ Cell Tumour Network

Background: In this article we share our experience of creating a digital pathology (DP) supraregional germ cell tumour service, including full digitisation of the central laboratory. Methods: DP infrastructure (Philips) was deployed across our hospital network to allow full central digitisation with partial digitisation of two peripheral sites in the supraregional testis germ cell tumour network. We used a survey-based approach to capture the quantitative and qualitative experiences of the multidisciplinary teams involved. Results: The deployment enabled case sharing for the purposes of diagnostic reporting, second opinion, and supraregional review. DP was seen as a positive step forward for the departments involved, and for the wider germ cell tumour network, and was completed without significant issues. Whilst there were challenges, the transition to DP was regarded as worthwhile, and examples of benefits to patients are already recognised. Conclusion: Pathology networks, including highly specialised services, such as in this study, are ideally suited to be digitised. We highlight many of the benefits but also the challenges that must be overcome for such clinical transformation. Overall, from the survey, the change was seen as universally positive for our service and highlights the importance of engagement of the whole team to achieve success.

Synchronous Development of Acute Megakaryoblastic Leukaemia and Disseminated Melanoma following Treatment of a Germ Cell Tumour: A Case Report

Somatic malignant transformation of germ cell tumours is a well-described but poorly understood phenomenon. It is characterized by differentiation of pluripotent teratoma cells into somatic tumour cells. Following malignant transformation, the most common histologies are sarcomas and primitive neuroectodermal tumours; however, other subtypes have been recognized including melanoma, leukaemia, and renal cell carcinoma. We report a case of a 38-year-old male who had recently completed treatment for a mediastinal germ cell tumour with teratomatous components. He presented several months after completion of chemotherapy with metastatic lesions in his spine and liver accompanied with severe pancytopenia. He was subsequently diagnosed with acute megakaryoblastic leukaemia (AMKL), and a biopsy of a liver lesion was consistent with metastatic melanoma. This case illustrates the simultaneous development of 2 rare malignant entities: mediastinal germ cell tumour-associated AMKL and somatic malignant transformation to melanoma. It also highlights the importance of close surveillance to detect these metastatic sequelae and the emerging role of tumour sequencing to establish targetable pathways.