Sarcomatoid urothelial carcinoma accompanied by elevated serum beta-HCG: Two case reports

Sarcomatoid urothelial carcinoma is a rare and aggressive variant. Serum beta-hCG levels are used as a tumor marker in gestational trophoblastic diseases and germ cell tumors, but may also be elevated in high-grade bladder cancers. Here, we report two urothelial carcinoma cases with sarcomatoid differentiation that relapsed early after surgery with elevated serum beta-hCG levels. The first case was a 65-year-old female and the second case was a 67-year-old man with sarcomatoid urothelial carcinoma located in the ureter and renal pelvicalyceal system, both of them relapsed with elevated beta-hCG serum level to 146.8 mIU/ mL and 242 mIU/mL, respectively. They died a few months after initial diagnosis;4.9 and 2.5 months respectively. Both sarcomatoid variant and beta-hCG expression were associated with poor prognosis and advanced stage. However, beta-hCG is not used as a tumor marker in urinary tract cancers yet, and its relationship with variant pathologies has not been clarified. We need multi-centered studies to reveal this relationship.Copyright © 2023, Derman Medical Publishing. All rights reserved.

A retrospective review of primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) for patients with genitourinary malignancies receiving chemotherapy during the COVID-19 pandemic and implications for the future

Background: To mitigate the risks of chemotherapy associated neutropenia, during the COVID-19 pandemic, all genitourinary (GU) cancer patients treated with chemotherapy at the Princess Margaret Cancer Centre (PMCC) were offered primary prophylaxis with GCSF. We hypothesize that this reduced rates of febrile neutropenia, hospitalizations, healthcare costs and improved overall outcomes, compared to GU cancer patients treated with chemotherapy without GCSF in the 2 years prior to the pandemic. Method(s): We performed a retrospective review of GU cancer patients, receiving curative or palliative intent chemotherapy, with or without primary GCSF prophylaxis between January 2018 and June 2022. GCSF was given either as a single dose or as consecutive doses post chemotherapy. Main outcomes were incidence of febrile neutropenia, hospitalization, health care expenditures as well as disease specific outcomes. Result(s): Overall, 248 patients with prostate cancer (44%), urothelial cancers (33%) germ cell (21%), and rare GU cancers (4%) were identified. Median age was 70 (range 19-91), 92% were male, 65% were ECOG 0/1. Treatment intent was neoadjuvant (13%), adjuvant (20%), or palliative (67%). Main regimens used were docetaxel, cabazitaxel, carboplatin, cisplatin/ etoposide, gemcitabine/cisplatin and BEP. Median follow-up was 10.5 months (0.23-52.3 months). A total of 206/248 received primary GCSF prophylaxis. During chemotherapy, the median white blood cell levels were higher in the GCSF group compared to the non-GCSF group (14.1+/-10+/-9/L vs 2.90+/-10+/-9/L, p<0.0001);and neutropenia rates were markedly lower (2% vs. 93%, P=,0.0001). Hospital admission rates were significantly lower in G-CSF users compared to nonusers (19% vs. 69%, P,0.0001). Symptomatic disease progression 13% was the leading cause of admission in the G-CSF group. Infectious causes such as UTI, pneumonia, COVID-19, and sepsis were seen in only 12% of the G-CSF group compared to 31% in the non-users. G-CSF was generally well tolerated with just 0.97% discontinuing G-CSF. Conclusion(s): During the COVID-19 pandemic, primary prophylactic G-CSF use in GU cancer patients, undergoing chemotherapy significantly lowered rates of both febrile neutropenia and hospitalizations and could be a cost-effective strategy in this patient population that warrants further study.

Comprehensive analysis of the novel omicron receptor AXL in cancers.

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.

Successful surgical management of massive hemoretroperitoneum caused by spontaneous rupture of retroperitoneal lymph node metastases in a patient with advanced mixed germ cell tumor: a COVID-19 pandemic-related surgical challenge.

BACKGROUND: Spontaneous rapture of a germ cell tumor (GCT) metastases causing massive hemoretroperitoneum in a patient without choriocarcinoma component who has not received previous systemic chemotherapy is an exceedingly rare event. In such a devastating case scenario, a high index of clinical suspicion for early diagnosis and appropriate management is crucial. CASE PRESENTATION: We report on a 25-year-old male patient with a 4-month history of orchiectomy for testicular GCT (tGCT), who presented in the emergency department with acute abdomen and hemodynamic instability. Urgent computed tomography scan depicted a retroperitoneal mass measuring approximately 13 × 11.4 × 15 cm and massive intraperitoneal hemorrhage. Hemoperitoneum caused by spontaneous rapture of the metastatic retroperitoneal mass was suspected. COVID-19 pandemic-related deviation from the oncologic surveillance standards combined with COVID-19-related patient's emotional distress and self-neglect had led to loss of opportunity for appropriate adjuvant chemotherapy, obviously leading to the development of this devastating complication. An emergency, surgical exploration was decided. The bleeding mass was adequately exposed following a Cattell-Braasch maneuver and active bleeding was controlled by a challenging resection of approximately 80% of the lymph node mass volume. Pathological evaluation of the specimen revealed teratoma with low volume of yolk sac tumor component and extensive necrosis, findings compatible with the patient's history. Postoperative recovery was uneventful, followed by early start of adjuvant chemotherapy. Two years after the operation the patient is doing well with no evidence of recurrent disease. CONCLUSIONS: Massive hemoperitoneum is a devastating event that exceedingly rarely can complicate the clinical course of patients with advanced tGCT. Emergency surgical intervention is usually necessary however, sound judgement and careful surgical techniques are required for a positive and uneventful outcome. During COVID-19 pandemic, first-line medical personnel push their limits further not only to ensure health care services standards but also, to manage unpredictable, life-threatening cancer-related complications, associated with COVID-19-related deviation from appropriate oncologic surveillance and care.

Surprisingly high frequency of pituitary stalk thickening in pediatric patients during COVID-19 pandemic in Chile

Introduction: Pituitary stalk thickening (PST) is a rare condition in pediatric patients. As there are few studies published in pediatric population, the definition has been difficult to establish. The etiologies involved in PST can be divided in neoplastic, congenital, inflammatory/infectious or autoimmune diseases. In children the most frequent causes are neoplastic, followed by congenital lesions. The inflammatory/infectious and autoimmune diseases are rare. Method(s): During the pandemic of COVID-19, we observed an increased incidence in the diagnosis of pediatric patients with PST in Chile, compared with previous years. A multicentric retrospective chart review of clinical, radiological and histological data was conducted on patients with confirmation of PST that presented during COVID-19 pandemic in Chile. The diagnosis of PST was made in patients with neuro-ophthalmic symptoms or pituitary dysfunction, who had a cerebral MRI with a pituitary stalk 3 mm or more at pituitary insertion or 4 mm or more at the optic chiasm, based on consensus guidelines. Result(s): A total of 11 patients were diagnosed with PST during the pandemic period, most of them were girls (82%). The mean age at the onset of symptoms was 10.1 years (range 1.1-18). The most common causes were neoplasms. Germinal cell tumors (GCT) were diagnosed in 10 patients and Langerhans cell histiocytosis in 1 patient. Tumor markers for GCT were negative in serum and cerebrospinal fluid in all patients (alpha-fetoprotein and chorionic gonadotropin). All patients presented with central diabetes insipidus and at least one anterior pituitary hormonal deficit. Thirty six percent had an abnormal campimetry. The diagnoses were confirmed by biopsy in all the patients and four patients required a second biopsy to confirm the diagnosis. Discussion(s): A surprisingly high frequency of PST presented during the COVID-19 pandemic among Chilean pediatric patients. The most frequent diagnosis was GCT. All had negative tumor markers, with a greater incidence in girls, opposed to data previously reported. The etiological diagnosis still remains challenging, and 36% of the patients required a second biopsy. It is important to establish new markers to assess patients with PST in order to make a prompt diagnosis.

Impact of Colchicine on Histology of Testis in Rats

Colchicine is a drug widely used for the management of many disorders, such as acute gout and Behçet’s disease. It is also prescribed for the treatment of pericarditis, atrial fibrillation coronary artery diseases, and secondary amyloidosis. In case this drug is used at the early stages of coronavirus infection, its anti-inflammatory properties may reduce the severe inflammatory reactions related to a cytokine storm by affecting the inflammasome. The purpose of the present study was to determine the toxicity of Colchicine on testis in rats from different age groups for 10 days. A total of 27 male Wistar rats were divided into three groups. The rats in group I (control group) were administered distilled water by oral gavage. Group II consisted of young rats (5-6 months old) who orally received Colchicine 3 mg/kg body weight. Group III entailed rats of 14-16 months who were orally administered colchicine 3 mg/kg body weight. The testis of the treated groups was dissected and examined for histological changes and morphometrical analysis. The obtained results indicated that high doses of Colchicine (3 mg/kg body weight) could induce tissue damage to the testis, including degeneration and necrosis of both Sertoli and Leydig cells with irregular divisions of germinal epithelium, even when it was used for short periods (10 days). In the elderly treated rats, there were severe tissue damages, including degeneration and necrosis of germinal epithelium with irregular divisions of germ cells, necrosis of Sertoli and Leydig cells with sloughing of germinal epithelium toward the lumen of the tubule. Therefore, there is a need to conduct more studies to investigate the side effect of Colchicine as it is excessively used in the management of coronavirus.

FOOL'S MOLD: UNUSUAL SEQUELAE OF COVID-19 INFECTION IN A YOUNG PATIENT

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: COVID-19 Associated Pulmonary Aspergillosis (CAPA) is a subset of invasive pulmonary aspergillosis occurring in patients actively infected with or recovering from COVID-19. It has mostly been described in immunocompromised or severely ill patients requiring invasive mechanical ventilation[1-6]. The authors report a case of CAPA infection in an ambulatory and immunocompetent patient with prior lung resection. CASE PRESENTATION: A 20-year-old male presented to a Comprehensive Cancer Center for fever and hemoptysis. He carried a diagnosis of metastatic germ cell tumor to his lungs, status post left upper-lobe wedge resection. He had completed bleomycin, etoposide, and cisplatin (BEP) chemotherapy one year earlier. He was recently diagnosed with COVID-19 one month prior to admission and treated as an outpatient with monoclonal antibodies. He reported ongoing cough productive of clear sputum since his diagnosis, which had worsened over the previous two days and was now blood-tinged. He had been afebrile for weeks before noting new fevers over the same period. Physical examination was notable for fever to 38.6°C and lungs clear to auscultation. His labs were significant for a WBC of 14.5 K/mcl (82.5% neutrophils), Cr 2.1 mg/dL (baseline 1.5 mg/dL), and normal platelets and coagulation studies. Serum Aspergillus galactomannan was normal. Repeat SARS-CoV-2 PCR was negative. Chest x-ray was unchanged. V/Q scan showed no evidence of pulmonary embolism. Non-contrast CT chest performed on hospital day #4 revealed a partial opacification and increased wall thickness of patient's largest left upper lobe surgical cavitation (see Image 1). A bronchoscopy was performed day #6, with bronchoalveolar lavage (BAL) galactomannan >5.56 (normal <0.5)7;fungal culture was significant for septate hyphae. He was started on voriconazole with improvement in his symptoms and discharged day #9. DISCUSSION: Immunocompromised patients with prolonged neutropenia, solid-organ or stem cell transplants, and patients with advanced AIDS are at highest risk of contracting PA[8-9]. ARDS secondary to viral pneumonia is also a common precipitant in immunocompetent patients[1-6,10,11]. The exact mechanism of this association remains unknown, but it is postulated to occur due to multiple factors, including host immune dysregulation[1,2], widespread exposure to corticosteroids[1,2], concomitant lung disease[1], and viral-induced lymphopenia[2]. We report a case of an immunocompetent patient with prior lung resection recovering from COVID-19 who experienced a secondary worsening of symptoms ultimately found to have CAPA to further highlight the link between these conditions. CONCLUSIONS: While many of CAPA case reports describe patients with typical risk profiles for CAPA, this case suggests that clinicians should consider structural lung disease alone in an otherwise immunocompetent, ambulatory individual to be a potential risk factor. Reference #1: See Image 2 for full list of references. DISCLOSURES: No relevant relationships by Raphael Rabinowitz No relevant relationships by Matthew Velez

Socio-economic Barriers to Care and Medical Complexity Leading to a 5-year Diagnostic Delay of Untreated Chronic Diabetes Insipidus and Rapidly Progressive Puberty in a 10-year-old Venezuelan Immigrant

Introduction: Germ cell tumors, including germinomas, account for 10% of pediatric chronic Diabetes Insipidus (DI) cases. Delays in diagnosis of germinomas are generally longer than six months, however, no reported cases of suprasellar germinomas causing chronic DI and precocious puberty have been known to exceed a 5-year delay in both treatment of DI symptoms and a definitive diagnosis. Case Description: A 10-year-old Hispanic male presented with a 5-year history of polydipsia and polyuria. He underwent evaluation in Venezuela, where DI was reportedly 'ruled out';however, no head MRI was performed. After two years in the US struggling to acquire insurance, he presented to his pediatrician with worsening symptoms. A head MRI, ordered to evaluate dilute high-volume urine output, revealed a suprasellar mass. He was admitted for diagnostic evaluation and met the criteria for DI. Notably, he had an elevated Beta-Human Chorionic Gonadotropin (B-HCG) level. Biopsy confirmed the diagnosis of a Central Nervous System (CNS) germinoma. He was treated with DDAVP and proton therapy with subsequent remission of his tumor. Discussion: Throughout the patient's disease course, there were multiple delays in seeking and receiving care. These include a 5-year delay in seeking care despite worsening symptoms, a one-month delay in completing a 24-hour urine collection, a one-month delay in consulting pediatric nephrology, and another month delay before completing a retroperitoneal ultrasound. Multiple medical and socio-economic factors led to these delays. The patient did not present with symptoms more typical of CNS Germinomas like headaches, nausea, and vomiting. He had no visual disturbances despite mass effect on his optic chiasm. His increased stretched penis length and Tanner staging, which were identified later in his disease course, were contradicted by his pre-pubertal testicular volume and bone age. The patient is from a Spanishspeaking/Limited English Proficiency (SSLEP) household. While Spanish interpreters were present at each appointment, the language barrier proved to be a consistent issue. Initially, the child's mother indicated that the diagnosis of DI was 'ruled out' in Venezuela. In reality, the recommended imaging was never performed. Mychart messages left by his father further highlighted communication difficulties. Without access to an interpreter, he was forced to use broken English to relay his concerns. These frantic messages indicated misunderstandings regarding scheduling with various services and completing vital labs. Care only proceeded after significant physician intervention. Poverty in Venezuela, lack of insurance, and anxiety regarding COVID-19 also contributed to these delays. Conclusion: To our knowledge, this is the first case report of a pediatric patient presenting with a 5-year history of untreated polyuria and polydipsia due to undiagnosed DI with a B-HCG secreting CNS germinoma, without spinal metastasis. This study also illustrates the importance of supporting SSLEP families as they grapple with the complicated process of navigating our healthcare system. Sagittal T1 post gadolinium contrast image (A) and axial T2 FLAIR image (B) show an enigmatic, homogeneous, briskly enhancing mass in the suprasellar cistern (red arrow) with mass effect on the optic chiasm which is displaced upward and anteriorly (green arrow).

The effect of the COVID-19 pandemic on patients with testicular germ cell tumor.

Purpose: The aim of this study was to investigate the effects of the COVID-19 pandemic on the referral, diagnosis, treatment, and follow-up of germ cell tumor (GCT). Methods: A retrospective single-center analysis of all patients who underwent diagnostic and surgical procedures due to GCT was performed from September 2018 to September 2021. Results: 65 patients were enrolled into the study by dividing them into two groups as before pandemic (Pre-CovGCT) and during the pandemic (CovGCT). 33 patients in the Pre-CovGCT group and 32 patients in the CovGCT group were evaluated and compared. A significant increase was observed for symptom duration (p = 0.018), the duration between diagnosis and surgical procedure (p = 0.028), and occult metastasis risk of stage 1 tumors (p = 0.05) during the pandemic period. Conclusions: The duration of symptoms and the duration between the diagnosis and surgical procedure were prolonged in GCT patients diagnosed during the pandemic. Furthermore, an increased risk of occult metastasis has been observed in stage 1 GCT patients. We underline the importance of raising the awareness of patients about admission to the hospital without delay in the presence of testicular cancer symptoms and recommend to be careful not to delay the treatment process.

Successful restart of chemotherapy in a patient with primary mediastinal nonseminomatous germ cell tumor after COVID-19 infection.

Cancer patients are considered highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, it is not well known when chemotherapy can be safely restarted in cancer patients after coronavirus disease 2019 (COVID-19). Here, we describe the case of an 18-year-old man diagnosed with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) in which chemotherapy could be safely restarted after COVID-19. On day 11 of the third cycle of bleomycin, etoposide, plus cisplatin (BEP), he was diagnosed with mild COVID-19. On day 16 after the onset of COVID-19 (day 26 of third cycle of BEP), chemotherapy for his PMNSGCT was restarted. He received surgery after the fourth cycle of BEP without recurrence of COVID-19. Chemotherapy could be restarted and followed by surgery in this post-COVID-19 patient who had experienced mild illness after the discharge criteria were met and all symptoms had disappeared. We report this case with a review of the literature on restarting chemotherapy after SARS-CoV2 infection.

An Unexpected Occurrence of Malignancy in a Patient After a Fontan Operation.

An 18-year-old male with complex single ventricle physiology status post Fontan and Kawashima procedures who presented with progressive dyspnea was found to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rhinovirus, and a new retroperitoneal mass. Biopsy of the retroperitoneal mass revealed a mixed germ cell tumor with areas consistent with choriocarcinoma. Imaging showed metastatic disease, including to the lungs which ultimately led to worsening respiratory failure that required intubation and ultimately, death.

BIOINFORMATIC ANALYSIS OF RNA SEQUENCING DATA OF TESTIS FROM SARS-COV-2 INFECTED MEN REVEALS MOLECULAR ALTERATION OF GERM CELL-SERTOLI CELL JUNCTION SIGNALING PATHWAY

INTRODUCTION AND OBJECTIVE: Angiotensin-converting enzyme II (ACE2) is the main receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) to enter the host cells. The higher expression of ACE2 receptor in the testis makes it more susceptible to SARS-COV-2 infection. Recent studies have reported orchitis, impaired spermatogenesis, and presence of viruses in semen of affected men. The main objective of this study is to understand the molecular alterations induced by SARS-CoV-2 and signaling pathways dysregulated in testis. METHODS: A data mining approach was employed to identify the RNA sequencing data of human testis infected with SARS-CoV-2. The FASTQ files (PRJNA661970) were retrieved from European Nucleotide Archive (ENA) for both the infected and control groups (noninfected). RNA seq data were further processed and analyzed, using BioJupies to generate a list of differentially expressed genes (DEGs). In addition, downstream analysis was carried out, using ingenuity pathway analysis software (Qiagen, USA) to identify the differentially regulated pathways and unique non-directional gene networks. RESULTS: A total of 17,824 genes were identified in the testis of both SARS CoV-2 infected and control groups, of which 4,131 genes were differentially expressed (2,492 downregulated and 1,639 upregulated) with a fold change cut-off of±2 and P <0.05. Bioinformatic analysis revealed that molecular pathways, such as inflammatory response, reproductive system development and function, and cell-to-cell signaling and interaction, were dysregulated in testes of men infected with SARSCoV- 2. Furthermore, we have also identified enrichment of 37 DEGs in the germ cell-Sertoli cell junction signaling pathway (Table 1). CONCLUSIONS: Our bioinformatic results clearly indicate that homeostasis of germ cell-Sertoli cell junction is disturbed during SARSCoV- 2 infection, which could be a predisposing cause for impaired spermatogenesis. Future studies are warranted to understand the impact of mild, moderate, and severe SARS-CoV-2 infections on germ cell-Sertoli cell junction in both vaccinated and unvaccinated populations that may affect their reproductive performance and fertility.

Prospective two-arm study of fertility in men with COVID-19

Introduction & Objectives: COVID-19 infection is hypothesized to have a potentially negative effect on male fertility through direct damage to the testes. The current trial is aimed at investigating the effect of SARS-CoV-2 on fertility and determining if viral bodies directly damage testicularfunction.Materials & Methods: This prospective study included controls comprising healthy participants and cases of patients suffering from pneumoniabased on chest CT and a positive of SARS-CoV-2 throat swab exhibited only moderate symptoms in accordance with the WHO classification.Extensive epidemiological, clinical, laboratory (hormonal levels, etc.) and ultrasound data (color doppler ultrasound of the scrotum) were collected. Asperm examination was performed in cases during their COVID-19 related hospital stay and 3 months after the discharge home. We also assessedthe testicles of COVID-19 patients who died of their disease (n=20) obtained during autopsies.Results: A total of 88 participants were included (44 controls and 44 cases). Blood testosterone levels were below normal (local reference values,5-50 nmol/ml) in 27.3% of the cases (12/44). The mean level (7.3±2.7 nmol/ml) was lower than that in the healthy controls (13.5±5.2 nmol/ml,p<0.001). At 3 months after discharge, the level returned to normal (13.7±4.5 nmol/ml) and was no different from that of the controls. An increase inLH and FSH was also detected compared to the healthy controls (p=0.047 and p=0.002). The spermogram revealed decreased motility in COVID-19patients (p=0.001), and higher number of immobile sperm (during COVID-19 – 58.8% and at 3 months 47.4%, p=0.005). All these parametersreturned to normal at 3 months after discharge. As for pathology findings, in the majority of autopsies (18/20) structural disorders of the testiculartissue, with signs of damage to germ cells were observed.Conclusions: COVID-19 and its treatment significantly affect hormone levels and sperm quality during the disease. Postmortem examinationconfirms inflammation and viral infiltration of the testicles. However, in those who had moderate to severe disease, decline in hormone levels andsperm quality was transient with values returning to baseline at 3 months

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.

Identification of Novel Malaria Transmission-Blocking Vaccine Candidates.

Control measures have significantly reduced malaria morbidity and mortality in the last two decades; however, the downward trends have stalled and have become complicated by the emergence of COVID-19. Significant efforts have been made to develop malaria vaccines, but currently only the RTS,S/AS01 vaccine against Plasmodium falciparum has been recommended by the WHO, for widespread use among children in sub-Saharan Africa. The efficacy of RTS,S/AS01 is modest, and therefore the development of more efficacious vaccines is still needed. In addition, the development of transmission-blocking vaccines (TBVs) to reduce the parasite transmission from humans to mosquitoes is required toward the goal of malaria elimination. Few TBVs have reached clinical development, and challenges include low immunogenicity or high reactogenicity in humans. Therefore, novel approaches to accelerate TBV research and development are urgently needed, especially novel TBV candidate discovery. In this mini review we summarize the progress in TBV research and development, novel TBV candidate discovery, and discuss how to accelerate novel TBV candidate discovery.

Testicular seminoma with pagetoid spread into the vas deferens: A rare histopathological presentation.

Testicular cancer, in particular testicular germ cell tumours, is the most common malignancy in young adult men. Defining prognosis and the best therapeutic strategy is challenging since accurate staging could be controversial. We report an unusual case of seminoma with pagetoid spread into the rete testis and, unexpectedly, also within the epithelium of the vas deferens, up to the margin of excision of the spermatic cord. Focussing on the extremely rare pathological finding and the challenge in defining the stage and the best post-surgical management, we would like to raise some issues about the knowledge gap on this topic.