Seminomatous Germ Cell Tumors Research Articles

7082 Hypercalcemia Due To Tumoral Production Of Calcitriol By Seminoma In A Patient With Pre-existing Primary Hyperparathyroidism

Abstract Disclosure: E. Naous: None. A. Jain: None. M. ElNajjar: None. A. Sabet: None. Background: Malignant hypercalcemia due to seminoma is extremely rare and has been reported in association with tumoral parathyroid-related protein (PTHrP) and/or calcitriol production. We present a unique case of a patient with seminoma and paraneoplastic calcitriol-induced hypercalcemia with co-existing primary hyperparathyroidism. Case Presentation: A 67-year-old male patient presented in May 2023 with obstructive uropathy and was diagnosed with a metastatic left testicular seminomatous germ-cell tumor with involvement of retroperitoneal soft tissue. At the time of diagnosis, the patient exhibited severe hypercalcemia with an albumin-corrected serum calcium level 14.1 mg/dL [8.6-10.3], phosphorus 3.0 mg/dL [2.5-4.5], intact parathyroid hormone (PTH) 20 pg/ml [15-65], PTHrP <2 pmol/L, 25-hydroxyvitamin-D 32 ng/ml [>30], and normal serum protein electrophoresis. 1,25-hydroxyvitamin-D was elevated at 132 pg/mL [24.8-81.5]. Review of prior records showed that the patient had a history of mild, chronic hypercalcemia (albumin-corrected serum calcium 10.5 mg/dL in August 2021, stable in 2022). His calcium level increased to 11.8 mg/dl in March 2023 and 14.1 mg/dl on presentation in May 2023. Given history of chronic mild hypercalcemia and presentation with severe hypercalcemia and “inappropriately normal” intact PTH, he was initially considered to have hypercalcemia solely due to primary hyperparathyroidism, a condition where elevated calcitriol levels are expected. However, the patient’s hypercalcemia was out of proportion to his intact PTH level, raising concern that tumoral calcitriol was contributory. He underwent left orchiectomy in May 2023 and completed chemotherapy cycles, including bleomycin, etoposide, and cisplatin, in September 2023. For hypercalcemia, he received IV saline, 48 hours of SC calcitonin, and prednisone 20 mg daily for 1 week followed by a rapid taper in addition to cinacalcet 30 mg daily. His serum calcium normalized within 48 hours of prednisone treatment. The patient remained on cinacalcet for a month, and his calcium levels remained normal more than a month after cinacalcet discontinuation. Clinical lesson: Severe hypercalcemia may be multifactorial. Our patient exhibited incompletely suppressed intact PTH and low-normal serum phosphorus, consistent with primary hyperparathyroidism. However, the abrupt onset of severe hypercalcemia, disproportionate to intact PTH, in a patient with seminoma and elevated calcitriol, suggested paraneoplastic hypercalcemia. The rapid response to corticosteroids and cancer chemotherapy, along with sustained normal calcium levels post-cinacalcet discontinuation, supported this diagnosis. Despite primary hyperparathyroidism being common, its presence in patients with severe hypercalcemia and malignancy does not rule out the possibility of co-existing hypercalcemia of malignancy. Presentation: 6/2/2024

Neuroendocrine differentiation in a metachronous metastatic deposit in a case of mature growing ovarian teratoma: A rare occurrence.

Growing teratoma syndrome is a rare condition seen in non seminomatous germ cell tumor after completion of chemotherapy. Ectodermal, mesodermal and endodermal differentiation is commonly seen in mature teratoma. neuroendocrine differentiation in a metastatic deposit of mature teratoma is rarely reported. We are presenting a case of neuroendocrine differentiation in a long standing metastatic deposit of a mature teratoma.

Retroperitoneal lymph node dissection: the past, present, and future, a review

Testicular cancer is a malignancy that impacts young men worldwide. The modern treatment of testicular cancer has evolved due to innovations in medical approaches and surgical techniques. The retroperitoneal lymph node dissection (RPLND) is an integral component in the treatment of testicular cancer. We aim to highlight the advances in surgical approaches and oncologic considerations noted over the past century. Once recognized as a highly morbid procedure, innovations in the understanding of anatomy and minimally invasive approaches have greatly improved patient outcomes. In addition to surgical approaches, we describe oncologic principles associated with modern dissection templates for both non-seminomatous germ cell tumors as well as more recent indications for surgery in seminomatous germ cell tumors. The overall goal of this review is to provide a summary in the utility and recent advances in RPLND techniques.

Prognostic Factor Risk Groups for Clinical Stage I Seminoma: An Individual Patient Data Analysis by the European Association of Urology Testicular Cancer Guidelines Panel and Guidelines Office

BackgroundThe relapse rate in patients with clinical stage I (CSI) seminomatous germ cell tumor of the testis (SGCTT) who were undergoing surveillance after radical orchidectomy is 4–30%, depending on tumor size and rete testis invasion (RTI). However, the level of evidence supporting the use of both risk factors in clinical decision-making is low. ObjectiveWe aimed to identify the most important prognostic factors for relapse in CSI SGCTT patients. Design, setting, and participantsIndividual patient data for 1016 CSI SGCTT patients diagnosed between 1994 and 2019 with normal postorchidectomy serum tumor marker levels and undergoing surveillance were collected from nine institutions. Outcome measurements and statistical analysisMultivariable Cox proportional hazard regression models were fit to identify the most important prognostic factors. The primary endpoint was the time to first relapse by imaging and/or markers. Relapse probabilities were estimated by the Kaplan-Meier method. Results and limitationsAfter a median follow-up of 7.7 yr, 149 (14.7%) patients had relapsed. Categorical tumor size (≤2, >2–5, and >5 cm), presence of RTI, and lymphovascular invasion were used to form three risk groups: low (56.4%), intermediate (41.3%), and high (2.3%) risks with 5-yr cumulative relapse probabilities of 8%, 20%, and 44%, respectively. The model outperformed the currently used model with tumor size ≤4 versus >4 cm and presence of RTI (Harrell’s C index 0.65 vs 0.61). The low- and intermediate-risk groups were validated successfully in an independent cohort of 285 patients. ConclusionsThe risk of relapse after radical orchidectomy in CSI SGCTT patients under surveillance is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse. Patient summaryThe risk of relapse after radical orchidectomy in patients with clinical stage I seminomatous germ cell tumor of the testis is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse.

Tc-99m MDP Scan with Unusual and Isolated Skeletal Metastasis in Skull Bone in a Case of Testicular Seminoma.

Seminomas are common germ cell tumors (GCT) that may arise in the testes as well as in extra testicular locations such as mediastinum with/without testicular tumor. Testicular tumors are usually detected early due to their location and presentation as testicular mass. The overall prognosis of the seminomatous GCTs is good with surgery as the mainstay of treatment in localized disease. Bone metastases, especially when present in isolation are exceedingly rare in seminoma. Here, we present a rare case of skull bone metastasis in a case of testicular seminoma which was detected on technetium-99m labeled methylene diphosphonate bone scintigraphy with single-photon emission computed tomography with computed tomography.

Onco-TESE (Testicular Sperm Extraction): Insights from a Tertiary Center and Comprehensive Literature Analysis.

Background and Objectives: The peak of incidence of testicular cancer (TC) occurs among individuals in their reproductive age, emphasizing the importance of fertility preservation as an integral aspect of disease management. Sperm cryopreservation performed before orchiectomy is ineffective in azoospermic men, necessitating alternative approaches such as microdissection testicular sperm extraction (mTESE) at the time of orchiectomy (onco-mTESE) to obtain viable sperm. This study presents the findings from our institution's experience with onco-mTESE and critically discusses our results in light of the existing body of literature. Materials and Methods: This is a tertiary center retrospective analysis of onco-mTESE procedures performed at a single center between December 2011 and July 2022. The included patients were post-puberal men with testicular tumors requiring orchiectomy, along with concomitant severe oligozoospermia or azoospermia. Bilateral mTESE was performed in all cases. Surgical outcomes, sperm retrieval rates, the usage of preserved viable sperm, assistive reproductive techniques' results, and post-operative serum testosterone were recorded. Results: A total of nine patients were included, with a median age of 34 (IQR 29-36) years. All patients had germ cell tumors (GCTs), with seminomatous and non-seminomatous GCTs accounting for 44.4% (n = 4) and 55.6% (n = 5) of patients, respectively. Sperm retrieval occurred in three (33%) patients: one patient in the ipsilateral testis, one in the contralateral testis, and one in both testes. No complications were reported during the procedure, and no post-operative hypogonadism was observed. Among the three patients with successful sperm retrieval, an intracytoplasmic sperm injection (ICSI) was performed in two patients, resulting in two pregnancies, leading to one healthy live birth and one miscarriage. Conclusions: In the context of TC, it is essential to conduct a thorough evaluation of testicular function, including a semen analysis and cryopreservation. Onco-mTESE has proven its safety in preserving fertility in azoospermic cases while ensuring the efficacy of oncological treatment.

The Subtype Identity of Testicular Cancer Cells Determines Their Immunostimulatory Activity in a Coculture Model.

Testicular germ cell cancer (TGCC) is subdivided into several subtypes. While seminomatous germ cell tumors (SGCT) are characterized by an intensive infiltration of immune cells which constitute a pro-inflammatory tumor micromilieu (TME), immune cells in non-seminomatous germ cell tumors (NSGCT) are differently composed and less abundant. Previously, we have shown that the seminomatous cell line TCam-2 promotes T cell and monocyte activation in a coculture model, resulting in mutual interactions between both cell types. Here we set out to compare this feature of TCam-2 cells with the non-seminomatous cell line NTERA-2. Peripheral blood T cells or monocytes cocultured with NTERA-2 cells failed to secrete relevant amounts of pro-inflammatory cytokines, and significantly downregulated the expression of genes encoding activation markers and effector molecules. In contrast, immune cells cocultured with TCam-2 cells produced IL-2, IL-6 and TNFα, and strongly upregulated the expression of multiple pro-inflammatory genes. Furthermore, the expression of genes involved in proliferation, stemness and subtype specification remained unaltered in NTERA-2 cells during coculture with T cells or monocytes, indicating the absence of mutual interactions. Collectively, our findings uncover fundamental differences between SGCT and NSGCT in their capability to generate a pro-inflammatory TME, which possibly impacts the clinical features and prognosis of both TGCC subtypes.

Bilateral germ cell tumor of the testis (TGCT): Implications for a stem cell versus genetic origin of cancers.

428 Background: Bilateral TGCT offers a unique opportunity to elucidate a stem cell versus genetic origin of cancer (Coffey, 2008). Comparison of the epigenetics and genetics of disparate tumors in either synchronous or metachronous bilateral TGCT from the same patients is feasible and may be informative. Methods: We examined the clinical characteristics and natural history of 37 patients with bilateral TGCT. We performed reduced representation bisulfite sequencing (RRBS) of FFPE DNA and whole exon sequencing (WES) of 5 of those patients whose tumor samples were available for the study. Results: We identified 37 patients with bilateral TGCT, who underwent their first orchiectomy between January 1984 and April 2022 and the second between August 1997 and April 2022. Thirty-five (95%) of these patients are still alive. Seven patients had synchronous, while 30 had metachronous bilateral TGCT. There were 13 bilateral seminomas, 14 bilateral nonseminomas, and 10 bilateral seminoma and nonseminoma. For those patients with metachronous bilateral TGCT, the median time between the two TGCT was 59 months (range 6-400). WES revealed a mutation in 189 (<1%) out of about 20,000 genes in the 10 paired samples from 5 patients. A total of 2 genes were mutated in more than 1 sample: KIT (n=4), and KRAS (n=2). Although one patient with synchronous bilateral seminomas shared KIT mutation, another did not with KIT and KRAS mutations (Table). RRBS showed a similar methylation profile in the 2 metachronous nonseminomas, which did not share any genetic mutations in the WES study. Conclusions: The clinical course of our patients with synchronous and metachronous bilateral TGCT and the results of our RRBS and WES reaffirmed that a preponderance of TGCT was curable and alluded to whether its epigenetic vs genetic origins might be causative or contributory to its general curability vs potential lethality. Coffey J et al. Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature. Genes Chromosomes Cancer 2008;47:34-42. [Table: see text]

EDEN (Etude Désescalade sEmiNome): Prospective therapeutic de-escalation and miRNA-M371 biomarker evaluation phase II study for stage IIa/IIb < 3 cm seminomas.

TPS434 Background: At diagnosis, 10 to 15% of testicular pure seminomas have a stage II defined by the presence of retroperitoneal lymph node metastases. The optimal choice of treatment modalities are associated with excellent efficacy but also acute and late toxicities. De-escalating treatment for seminoma patients with stage IIb, IIc and III and good prognosis according to IGCCCG (International Germ Cell Cancer Collaborative Group) based on negative FDG-PET (Fluorodeoxyglucose Positron Emission Tomography) after 2 cycles of EP (etoposide, cisplatine) chemotherapy seems feasible and safe according to SEMITEP cohort 2 results (Loriot Y, and al GETUG SEMITEP Trial: Eur Urol. 2022 Aug;82(2):172-179). Serum levels of microRNA (miR)-371a-3p (miRNA-M371) have been significantly associated with clinical stage and response to treatment in testicular germ cell tumors, with sensitivity and specificity higher than those of classic markers. The aim of the study NCT05529251 is to propose a new therapeutic approach for the stages IIa/IIb. Methods: This phase II, multicenter, prospective, randomized, non-comparative, de-escalation study will include patient with primary testicular seminomatous germ cell tumor with stage IIa/IIb < 3 cm in largest diameter seminoma, histologically proved after orchiectomy and good prognosis according to IGCCCG and LDH (Lactate DesHydogenase) < 2.5 x Upper Limit of Normal (ULN). They must have progressive disease and no prior treatment with radiotherapy or chemotherapy. In case of negative week-3 (after 1 EP cycle) PET-scan, patients will be randomized according to 2 arms ARM A: Boost of radiotherapy 20 to 30 Gray (Gy); ARM B Carboplatin AUC7 chemotherapy. In case of positive week-3 PET-scan: 3 courses of EP chemotherapy (ARM C). Primary outcome will include progression-free rate at 36 months. Secondary Outcome Measures will be serum level of miRNA M371, correlation with response to treatments and PET scan results, overall survival (OS), quality of life and tolerance to treatment. Blood samples (miRNA-M371) will be collected at screening, at the time of randomization before second cycle of chemotherapy or radiotherapy, at the end of treatment and at relapse. Enrollment has started in October 2022. A total of 90 patients will be included in the interventional study, leading to approximately 60 patients with negative FDG-PET randomized. Clinical trial information: NCT05529251 .

Fertility preservation in growing Teratoma syndrome: Case report

Background: Teratomas are the most common ovarian germ cell tumors. Growing teratoma syndrome is a rare condition that entails the appearance of extragonadal teratomas during or after chemotherapy treatment of non seminomatous germ cell tumors.

End-of-Treatment FDG PET-CT (EOT-PET) in Patients with Post-Chemotherapy Masses for Seminoma: Can We Avoid Further Intervention?

Anjana JoelContext Patients with seminoma present with advanced disease. End-of-treatment (EOT) positron emission tomography-computed tomography (PET-CT) is done to assess response and direct management of post-chemotherapy residual masses. Purpose This article assesses the utility of EOT PET-CT in the management of post-chemotherapy residual lymph nodal masses seminoma. Materials and Methods We analyzed all patients with seminoma who underwent an EOT PET-CT from January 2015 to January 2020 at our center and calculated the positive predictive value (PPV) and negative predictive value (NPV) of EOT PET-CT in the entire cohort of patients and among subgroups. Results A total of 34 male patients underwent EOT PET-CT. Fourteen (41.2%) were stratified as good risk and 20 (58.8%) as intermediate risk. The median follow-up was 23 months (interquartile range: 9.75-53 months). In 23 patients there were residual masses of size more than 3 cm at the EOT PET scan. EOT PET was positive as per the SEMPET criteria in 18 (78%) out of 23 patients. None underwent retroperitoneal lymph node dissection. All four who underwent image-guided biopsy, showed only necrosis on pathology. One patient with positive mediastinal node (standardized uptake value 13.6) had granulomatous inflammation. There was no relapse or progression during this period of follow-up. The NPV for EOT PET-CT for the entire cohort, > 3 cm, and > 6 weeks cutoff were 100%, respectively. The PPV for EOT PET-CT for the entire cohort, > 3 cm residual mass, and > 6 weeks cutoff were 8.7, 11.11, and 6.67%, respectively. Conclusion EOT PET-CT has a low PPV and high NPV in predicting viable tumor in post-chemotherapy residual masses among patients with seminomatous germ cell tumors. If required, EOT PET positivity can be confirmed by a biopsy or reassessed with a repeat PET-CT imaging to document persistent disease prior to further intervention.

Testicular cancer among Saudi adults: Hands on a nationwide Cancer Registry over 10 years

ABSTRACT Background/objective Testicular cancer (TC) is one of the most curable solid malignancies affecting young adults. The objective of this study was to identify factors affecting survival of Saudi adults who were diagnosed with testicular cancer over 10 years. Methods This was a retrospective study with data extracted from the Saudi Cancer Registry for Saudi Adults diagnosed with TC from 2008 to 2017. We collected demographic information, including age, marital status, region of residency, year of diagnosis, and the survival status. In addition, the tumor factors included the basis of diagnosis, the origin of the tumor, histopathological group and subtype, and tumor behavior, stage, and laterality were collected. Results A total of 869 patients were included, with a median age of 30 (IQR: 25–38). The highest percentage of the cases was 37.5% (326) in the Central region, followed by the Western region 24.6% (214). The primary site of the tumor was the testis 96.9% (842), 3.1% (27) in the undescended testis. The histopathological examination revealed seminoma in 44.8% (389), 33.5% (291) mixed germ cell tumor, 8.4% (73) embryonal carcinoma, 6.1% (53) teratoma, 2.6% (23) yolk sac tumor, 1.6% (14) choriocarcinoma, 0.3% (3) Leydig cell tumor, and 2.6% (23) sarcomas. Kaplan-Meier analysis revealed significant association between survival and the age groups (p = 0.001), histopathology group (p 0.04), histopathology subtypes (p = 0.01), and the stage of the tumor (p < 0.001). Conclusions A notable increase in the incidence of TC among Saudi adults was seen, with a mortality rate of 5.4% over a period of 10 years. Longer survival was associated with age groups, seminomatous germ cell tumor, and lower tumor stage.

Evaluating the discriminatory capacity of miR-371A-3P in the context of pure seminomatous testicular cancer metastases.

424 Background: Conventional serum tumor markers (STMs) are noted to have poor specificity in detecting seminomatous germ cell tumors (SGCTs). Recent publications have suggested that miR-371a-3p may offer improved performance for these cases. However, miR-371a-3p’s performance in detecting pure seminoma at retroperitoneal lymph node dissection (RPLND) has yet to be elucidated in any publicly available study. This lack of data is in part due to the rare occurrence of such cases, and it represents a distinct path for exploring miR-371a-3p’s clinical utility. Methods: Pre-surgical serum samples were collected prospectively from patients prior to RPLND. Within the 15-patient cohort, 6 were assigned as ‘Control’ and 9 were assigned as ‘Seminoma’ based on pathological confirmation of viable GCT. Out of all 15 patients, 10 were chemotherapy naïve prior to RPLND. Post-chemotherapy patients made up 5/6 ‘Control’ patients. MiR-371a-3p levels were quantified by RT-qPCR. Using 2−∆∆Cq method, miR-371a-3p expression was first normalized to the miR-30b-5p reference gene and then calculated relative to the mean target expression across a collection of RNA extracts from healthy male donors’ serum. The Cq values were statistically evaluated to obtain performance characteristics (sensitivity and specificity). Results: Although assay results revealed no significant difference in miR-371a-3p expression between groups, median relative expression in the seminoma group trended higher than the control group (Rq = 3705 and 241 respectively, p = 0.2844). Out of all chemotherapy naïve patients, 9/10 had viable GCT at RPLND whereas 7/10 showed elevated miR-371a-3p. Among the five post-chemotherapy patients, 0/5 had viable GCT at RPLND and 2/5 had elevated miR-371a-3p. The assay provided 7/9 true positive designations in the seminoma group and 4/6 true negatives in the control group. The two false positive results were from post-chemotherapy patients. Of the two optimal thresholds calculated by Youden’s J statistic, the lower threshold of 28.62 (78% sensitivity ad 67% specificity) was selected because it was more in line with previously published data. ROC analysis provided an AUC of 0.704 (95% confidence interval: 0.43-0.98, p = 0.1949). STMs performance was poorer at 67% sensitivity and 17% specificity. Conclusions: Performance metrics for miR-371a-3p exceed those of STMs but were substantially lower than previous reports that evaluated performance in pre-orchiectomy and primary RPLND settings. A possible explanation for this disparity is that miR-371a-3p’s performance is hindered in the post-chemotherapy RPLND setting. However, any strong conclusions from these results are limited by the small sample size which is partly due to the rarity of this clinical scenario. These results suggest that pure seminoma at RPLND may be a key clinical context wherein the miRNA assay may require further refinement.

A0562 - Surgical and oncological outcomes of post chemotherapy laparoscopic retroperitoneal lymph node dissection in stage IIA-III non seminomatous germ-cell tumors

A0562 - Surgical and oncological outcomes of post chemotherapy laparoscopic retroperitoneal lymph node dissection in stage IIA-III non seminomatous germ-cell tumors

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

BackgroundTesticular 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.MethodsDefined 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.ResultsDistinct 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.ConclusionsIL-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.

Survival Outcomes of Patients With Mediastinal Germ Cell Tumors: Experience of a Cancer Center in South America.

PurposeMediastinal germ cell tumors (GCT) are rare neoplasms associated with poor survival prognosis. Due to their low incidence, limited information is available about this disease in South America. The objective of this study is to report the clinical characteristics and outcomes of patients with mediastinal GCT in a cancer center in Colombia.Materials and MethodsWe conducted a retrospective analysis of patients with mediastinal GCT treated at the National Cancer Institute at Bogota (Colombia) between 2008 and 2020. Survival curves were presented using the Kaplan–Meier method. Chi-square and Cox proportional hazard model tests were used for data analysis.ResultsSixty-one patients were included in the study. Of them, 60 were male and 51 (83.6%) of whom had non-seminomatous germ cell tumors (NSGCT). Twenty-nine patients (47.5%) presented with superior vena cava syndrome, and 18 (29.5%) patients had extrapulmonary metastatic involvement. The three-year overall survival (OS) of NSGCT patients was 26%. The 3-year OS of NSGCT patients who underwent surgical resection of residual mediastinal mass after chemotherapy was 59%. Non-surgical management after first-line chemotherapy was associated with a worse survival prognosis in NSGCT patients (p = 0.002). Ten patients with mediastinal seminomatous germ cell tumors (SCGT) achieved a 3-year OS of 100%.ConclusionMediastinal NSGCT had poor outcomes. Surgery of the residual mass after first-line chemotherapy seems to improve the outcome of NSGCT patients. Advanced disease at presentation may reflect inadequate access to reference cancer centers in Colombia and potentially explain poor survival outcomes in this cohort. On the other hand, mediastinal SCGT is a biologically different disease; most patients will achieve disease remission and long-term survival with first-line chemotherapy.

Detection of recurrences using serum miR-371a-3p during active surveillance in men with stage I testicular germ cell tumours.

MiR-371a-3p predicts the presence of a macroscopic non-teratomatous germ cell tumour (GCT). We hypothesised that miR-371a-3p can also detect recurrence during active surveillance (AS) of stage I GCT. We prospectively collected serum samples of 33 men. Relative expression of serum miR-371a-3p levels was determined at each follow-up visit using real-time quantitative reverse transcription-polymerase chain reaction. Recurrence was detected using standard follow-up investigations in 10/33 patients (30%) after a median of 7 months. Directly after orchiectomy, miR-371a-3p levels were not elevated in any of the 15 patients with available post-orchiectomy samples. However, all ten recurring patients exhibited increasing miR-371a-3p levels during follow-up, while miR-371a-3p levels remained non-elevated in all but one patient without recurrence. MiR-371a-3p detected recurrences at a median of 2 months (range 0-5) earlier than standard follow-up investigations. MiR-371a-3p levels immediately post orchiectomy are not predictive for recurrences and unfortunately cannot support decision-making for AS vs. adjuvant treatment. However, miR-371a-3p detects recurrences reliably and earlier than standard follow-up investigations. If this can be confirmed in larger cohorts, monitoring miR-371a-3p could replace surveillance imaging in seminomatous GCT and reduce the amount of imaging in non-seminomatous GCT. Earlier detection of disease recurrence may also reduce the overall treatment burden.

The absence of spermatogenesis in radical orchiectomy specimen is associated with advanced-stage nonseminomatous testicular cancer.

To assess if clinical, pathological, and spermatogenesis factors are associated with clinical staging in patients with testicular germ cell tumors. We retrospectively reviewed the pathology reports and slides from 267 men who underwent radical orchiectomy for testicular cancer at our institution during 1998-2019. Histologic slides were reviewed and the presence of mature spermatozoa was documented. Clinical, laboratory and radiographic characteristics were recorded. Logistic regression analyses were used to identify factors associated with advanced disease stage at diagnosis. Of 267 male patients, 115 (43%) patients had testicular non-seminomatous germ cell tumors (NSGCT) and 152 (57%) seminomatous germ cell tumors (SGCT). Among NSGCT patients, those presenting with metastatic disease had a higher proportion of predominant (>50%) embryonal carcinoma (64% vs. 43%, respectively, P = 0.03), and lymphovascular invasion (45.8% vs. 26.6%, respectively, P = 0.03) than non-metastatic patients. Spermatogenesis was observed in 56/65 (86.2%) and 36/49 (73.5%) of non-metastatic and metastatic NSGCT patients, respectively (P = 0.09). On semen analysis, severe oligospermia (<5 million/ml) was more common in metastatic than in non-metastatic NSGCT (26.5% vs. 8.3%, respectively, P = 0.04). On multivariate analysis, predominant embryonal carcinoma and lack of spermatogenesis in pathological specimens were associated with metastatic disease. The absence of spermatogenesis and a high proportion of embryonal carcinoma was associated with advanced disease in patients with NSGCT. Whether it may also translate as a predictor of oncologic outcome needs further evaluation.

ACUTE RESPIRATORY FAILURE WITH FATAL OUTCOME DUE TO PENICILLIUM CHRYSOGENUM IN A MAN FROM GUATEMALA WITH A SEMINOMA (GERM CELL TUMOR )

TOPIC: Chest Infections TYPE: Global Case Reports INTRODUCTION: This type of mycosis has a rare presentation and even as an oportunistig pathogen is not common. The diagnosis is difficult because there is not a specific clinical finding, and carries a high-mortality risk despite an aggressive therapy. We presented a case of a patient with acute hypoxic respiratory failure with lung involvement, and pericardial tamponade in a patient without past medical history. This was a challenging diagnosis and required a multidisciplinary approach CASE PRESENTATION: 29-year-old man farmer, without past medical history presents with dyspnea on exertion associated with non-specific symptoms for the last two-months. The dyspnea on exertion has progressed to the extent to be present at rest. On the physical exam there are distant heart sounds, and diffuse lung crackles. CT-non contrast of chest showed disseminated miliary nodes with ground glass opacities at the bilateral bases and a large pericardial effusion. There was presence of a large pericardial effusion with right ventricular and atrial collapse in the trans-thoracic echocardiogram. Conidia in chains were found with KOH in the pericardial drainage. A bronchoscopy with bronchoalveolar lavage, brushing and transbronchial biopsy was performed and fungal structures were observed. Later, a lung biopsy was performed and Penicillium chrysogenum grew and was observed with lactophenol blue and confirmed by mass spectrometry (MALDI-TOF). Aggressive treatment with liposomal amphotericin-B plus voriconazol was started. Despite treatment the patient expired and seminomatous germ cell tumor was given, which supported the immunosuppression state of the patient DISCUSSION: The infections caused by the Penicillium species are rare, and can presented as cutaneous, pulmonary or disseminated infections due to the fact that it is a ubiquitous fungus and the spores are easily disseminated. The diagnosis of P.chrysogenum was challenging due low suspicious, lack of knowledge of the immunosuppressive state of the patient, and low prevalence in an immunocompetent patient. The microbiological growth was achieved in lung tissue with the addition of the finding of the seminomatous germ cell neoplasia. We did not consider P.chrysogenum as a contaminating due to the presence of conidia and hyphae in the pericardial fluid and bronchial tissue. Treatment usually includes liposomal Amphotherecin-b, Itraconazole, Voriconazole, and the addition to removal of the source of infection. However, despite prompt interventions the prognosis is poor. CONCLUSIONS: P.chrysogenum is a rare, ubiquitous, oportunistic fungus that was unsuspected due to the lack of knowledge of the immunosuppression status of the patient and despite of the aggressive treatment, the outcome was fatal REFERENCE #1: Barcus AL, Burdette SD, Herchline TE. Intestinal invasion and disseminated disease associated with Penicillium chrysogenum. Ann Clin Microbiol Antimicrob [Internet]. 2005 Dec 21 [cited 2021 Apr 22];4:21. Available from: /pmc/articles/PMC1343575/ REFERENCE #2: Avilés-Robles M, Gómez-Ponce C, Reséndiz-Sánchez J, Rodríguez-Tovar AV, Ceballos-Bocanegra A, Martínez-Rivera Á. Disseminated penicilliosis due to Penicillium chrysogenum in a pediatric patient with Henoch–Schönlein syndrome. Int J Infect Dis. 2016 Oct 1;51:78–80. REFERENCE #3: Ramírez I, Hidrón A, Cardona R. Successful treatment of pulmonary invasive fungal infection by Penicillium non-marneffei in lymphoblastic lymphoma: case report and literature review. Clin Case Reports [Internet]. 2018 Jun 1 [cited 2021 Apr 22];6(6):1153–7. Available from: /pmc/articles/PMC5986030/ DISCLOSURES: No relevant relationships by Jose Aguilar, source=Web Response No relevant relationships by Jorge Luis Aguilar Castellanos, source=Web Response No relevant relationships by SARA BARILLAS, source=Web Response no disclosure on file for jose castillo; No relevant relationships by MARIA EUGENIA CHOC DE AJANEL, source=Web Response No relevant relationships by Jose Cifuentes, source=Web Response No relevant relationships by Cesar Conde-Pereira, source=Web Response No relevant relationships by Gabriel Rios, source=Web Response no disclosure on file for angel soto

SC235 - Perioperative outcomes of post chemotherapy laparoscopic retroperitoneal lymph node dissection in stage IIA-III non seminomatous germ-cell tumors

SC235 - Perioperative outcomes of post chemotherapy laparoscopic retroperitoneal lymph node dissection in stage IIA-III non seminomatous germ-cell tumors