Non-germ Cell Research Articles

Testicular Germ Cell Tumours - features and prospects of the novel tumour marker microRNA-371a-3p (M371 test): a narrative review

Testicular germ cell tumours (GCTs) represent a paradigm for the usefulness of serum tumour markers in clinical management of diseases. However, the tumour markers currently in use, beta human chorionic gonadotropin (bHCG), alpha fetoprotein (AFP) and lactate dehydrogenase (LDH) are expressed in less than 50% of GCT cases. In 2011, microRNA-371a-3p (currently named M371) was suggested as a novel marker for the first time. Chemically, microRNAS represent small RNA molecules consisting of 18-24 base pairs. Physiologically, these microRNAs play a prominent role in the epigenetic control of protein biosynthesis. M371 can be measured in serum with PCR-techniques.There is high level evidence for a 90% sensitivity and >90% specificity for GCTs of the marker M371. That high diagnostic accuracy is true for both seminoma and nonseminoma but not for the histologic subgroup of teratoma. Testicular tumours of non-germ cell origin and malignant neoplasms of other organs do not express the marker. M371 involves a very short half-life of <24 hours.The test does likely involve the prospects of providing substantial aid in clinical decision-making with respect to instances where improvement of GCT management is still required. In particular, the following clinical scenarios will probably benefit from the employment of the M371 test: (1) diagnostic work-up of incidentally detected small testicular masses with decision-making in regard to testis sparing surgery or full orchiectomy (2) simplifying the follow-up of GCT patients with sparing of imaging procedures in a number of cases; (3) diagnostic evaluation of retroperitoneal lymphadenopathy upon clinical staging; (4) diagnostic evaluation of false-positive elevations of classical tumour markers (AFP, bHCG); (5) rapid appraisal of therapeutic success or failure by means of the very short half-life of M371; (6) diagnostic evaluation of postchemotherapy residual masses particularly those in seminoma patients.The discovery and development of the novel tumour marker M371 probably represents a milestone progress in the history of the clinical management of testicular GCTs.

O-135 The consequences of paternal pre-conceptional health for offspring health and pregnancy outcomes: involvement of the germ-cell epigenome and non-germ cell factors

Abstract Study question Paternal health at conception is important for offspring health. The susceptibility windows within the male reproductive tract and the molecular mechanisms are not completely understood. Summary answer Using mouse genetics, (epi)genomics and in-depth phenotyping, we show that the germ-cell epigenome and components of the seminal fluid are critical for paternal intergenerational effects. What is known already Paternal intergenerational effects are highly conserved across mammals and lower organisms including flies and nematodes. In mammals, the sperm epigenome, as well as the composition of the seminal fluid are sensitive to environmental challenges and influence offspring development and adult phenotypic trajectories. The best known of these mechanisms are DNA methylation and small non-coding RNAs in spermatozoa and the balance between inflammatory and tolerogenic cytokines in the seminal fluid. Small non-coding RNAs are mostly acquired by maturing spermatozoa during the epididymal transit from extracellular vesicle of epididymal epithelial origin, and have the potential to influence embryonic development and offspring health. Study design, size, duration We use two paternal paradigms of pre-conceptional challenge in wild-type C57BL6 mice: high-fat diet feeding for 2 weeks and circadian disruption for 4 weeks before conception. The duration of the environmental challenges has been chosen to meet timing of sperm maturation in the mouse (high-fat diet) or to be the minimum sufficient to induce circadian disruption without overt side effects. Exposed males and their offspring have undergone deep metabolic and molecular phenotyping. Participants/materials, setting, methods We used both bulk and single cell (epi)genomics on exposed males as well as male and female offspring. The molecular phenotyping has been instructed by the results of the metabolic phenotyping performed in collaboration with the German Mouse Clinic, the biggest mouse clinic in Europe, using highly standardized and robust procedures. Importantly, we have used a family-based approach for the data analysis, according to which the experimental n is the exposed father. Main results and the role of chance Paternal circadian disruption achieved by four weeks of day-restricted feeding (food only during the light phase), leads to hyperphagia, hyperglycemia, hypercorticosteronemia and partial circadian disruption in unexposed male offspring. The phenotypes are gender-specific and the females feature partial protection from the paternal effects. Mechanistically, mouse seminal fluid contains corticosterone, whose appearance dynamic follows the organismal circadian rhythm and is blunted upon circadian disruption. Offspring phenotypes are sensitive to the levels of corticosterone in the seminal fluid and consequential to impaired placentation, reduced placental efficiency and fetal growth restriction. Paternal exposure to an acute high-fat diet challenge, instead, leads to a 30% penetrant glucose intolerance phenotype exclusively in male offspring. Mechanistically, this is linked to diet-induced mitochondrial dysfunction in somatic and germ cells and a compensatory burst of mitochondrial DNA transcription in spermatozoa. Mitochondrial DNA encoded small non-coding RNAs accumulate in spermatozoa, are inherited at fertilization, and reprogram early embryo transcription towards premature activation of oxidative metabolism, a predisposing factor to adult-onset glucose intolerance. Importantly, phenotypes and mechanisms are conserved across highly characterized human cohorts. These studies strengthen the importance of paternal health at conception for pregnancy and offspring health and identify germ-cell and non-germ cell factors as potential mechanistic mediators. Limitations, reasons for caution Although we have shown for the first time that stress hormones are present in the seminal fluid and relay paternal stress to the offspring and provided the first example of epigenetic inheritance of sperm small non-coding RNAs, mechanisms are still to be completely uncovered. Complementary mechanisms cannot be excluded. Wider implications of the findings Our findings strengthen the importance of paternal health at conception for pregnancy and offspring health. They also provide potential male tract biomarkers and novel strategies to monitor paternal health at conception and preconception lifestyle interventions aimed at improving pregnancy outcomes and preventing the spread of metabolic disorders through epigenetic inheritance. Trial registration number not applicable

Complex Treatment of A Rare Non-Germinomatous Germ Cell Optic-Chiasmal Brain Tumor In An Adolescent Child-A Clinical Case With Literature Review

Non-germ cell tumours (NGCTs) are rare intracranial neoplasms occurring in adolescents and young adults. A multidisciplinary team including a neurosurgeon, oncologist, radiologist, pathohistologist, ophthalmologist, pediatric oncohematologist, neurologist and endocrinologist is required for diagnosis and treatment. We present a rarely diagnosed optic-chiasmal non-germinomatous germ cell tumour (NGGCT) in a 16-year-old boy, accompanied by pituitary insufficiency (diabetes insipidus and central hypothyroidism) and severely impaired vision bilaterally. The immunohistochemistry (IHC) of the tumor biopsy, as well as the level of tumor markers (human chorionic gonadotropin and alpha-fetoprotein) in the serum and cerebrospinal fluid are significant factors for determining the diagnosis-cranial GCT or cranial NGCT. Because the tumor was inoperable, we performed 3 courses of neoadjuvant chemotherapy followed by definitive radiotherapy to a total tumor dose of 55 Gy. In such rare childhood brain tumors, complex treatment achieves long-term local tumor control, requiring long-term monitoring by an ophthalmologist and endocrinologist.

Ameliorating Effects of Curcumin on Testicular Cancer

In the young men’s population, testicular cancer (TC) is characterized as one of the main causes of morbidity and mortality around the world. This cancer is mainly divided into germ cell and nongerm cell types and manifests different signs and symptoms, like bone pain, nausea, lower back pain, and anorexia. Also, TC is associated with serious conditions, such as urogenital disorders, infertility, cardiovascular diseases, and solid tumors. Unfortunately, common remedies for TC, including chemotherapy and surgery, have not provided a promising outlook due to their adverse effects on life quality. Ergo, finding a new therapeutic candidate with high effectiveness and low detrimental impacts is indispensable. Newly, herbal remedies have attracted much interest because of their potential to improve diverse diseases, like cancer. In this context, increasing evidence indicated that curcumin, as a polyphenol compound originating from the plant Curcuma longa, has beneficial effects for treating TC. Hence, in this narrative review, we aimed to review documents showing the therapeutic potential of this herbal candidate against TC.

Mediastinal teratoma with double malignant transformation

We report a case of a 65-year-old woman with retrosternal discomfort, dyspnea, and weight loss in whom the computed tomography showed a multicystic mass with fat content and calcified wall in the anterior mediastinum. After surgical resection, pathological examination revealed synchronous primary colorectal adenocarcinoma and primary carcinoid tumor arising in a mediastinal mature cystic teratoma. Treatment with oxaliplatin and capecitabine was instituted, and subsequent checkups showed no evidence of recurrence. Malignant transformation of mature cystic teratoma is a rare complication that occurs in 1–3% of these tumors and consists of a nongerm cell malignant tumor arising from a preexisting mature teratoma. Any of the constituent tissues of a teratoma has the potential to undergo malignant transformation. In case of limited disease, treatment should be surgical. There is no consensus regarding adjuvant treatment, and the existence of a double neoplastic lineage may complicate the choice of chemotherapy treatment.

The value of contrast-enhanced ultrasonography in differential diagnosis of primary testicular germ cell tumors and non-germ cell tumors over 50 years old.

Unlike young and middle-aged patients, seminoma is not common in patients with primary testicular tumors over the age of 50, so it cannot follow the general ideas and norms for diagnosing and treating testicular tumors, and its characteristics need to be considered separately. The conventional ultrasonography and contrast-enhanced ultrasonography (CEUS) findings of primary testicular tumors in patients over 50 years old were retrospectively analyzed and compared with the pathological results to compare the diagnostic value of these two methods. Of the 13 primary testicular tumors, 8 were primary lymphomas. Conventional ultrasound of 13 cases of testicular tumors showed hypoechoic with rich blood flow, and it was difficult to identify the type accurately. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of conventional ultrasonography in diagnosing non-germ cell tumors (lymphoma and Leydig cell tumor) were 40.0%, 33.3%, 66.7%, 14.3%, and 38.5%, respectively. CEUS findings: 7 of 8 lymphomas showed uniform hyperenhancement. 2 cases of Leydig cell tumors showed uniform high enhancement. 2 cases of seminoma and 1 case of spermatocytic tumor showed heterogeneous enhancement, with necrosis in the interior. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy rate of non-germ cell tumor diagnosis according to the non-necrotic area of CEUS were 90.0%, 100.0%, 100.0%, 75.0% and 92.3%, respectively. Compared with conventional ultrasound, the difference was statistically significant (P=0.039). Primary testicular tumors in patients over 50 years old are mainly lymphoma, and CEUS is significantly different between germ cell tumors and non-germ cell tumors. Compared with conventional ultrasound, CEUS can distinguish testicular germ cell tumors from non-germ cell tumors more accurately. Preoperative ultrasonography is significant for accurate diagnosis and can guide clinical treatment.

Malignant testicular tumors in children: A single institution's 12-year experience.

Testicular neoplasms are not commonly found in children and are a formidable threat if treated inappropriately. However, there is no consensus regarding its management. This study aimed to create a holistic picture of the interprofessional team in the management of malignant testicular tumors.Seventeen patients had mixed germ cell tumors, 15 had pure yolk sac tumors, 2 had immature teratomas, 2 had teratocarcinomas, and 1 had a sex cord stromal tumor. Five lesions were diagnosed as nongerm cell tumors: 2 embryonal rhabdomyosarcomas, 2 lymphomas, and 1 acute myeloid leukemia. At initial presentation, retroperitoneal (n = 2), bone marrow (n =1), and mediastinal (n = 1) metastases were identified in 4 (10%) patients. The operative interventions performed included radical inguinal orchiectomy (n = 5), scrotal orchiectomy (n = 31), and testicular biopsy or testis-sparing enucleation of the tumor (n = 6). Postoperatively, 18 patients received either adjuvant chemotherapy (n = 14) or chemoradiation (n = 5). Five patients with mixed germ cell tumors (n = 2), group IV paratesticular rhabdomyosarcoma (n = 2), and acute myeloid leukemia with myeloid sarcoma (n =1) died of disease progression. Thirty-six patients remained alive and disease-free at the last visit.Malignant testicular tumors in children deserve proper diagnostic support from a therapeutic perspective. Any concern or suspicion of a testicular tumor warrants an inguinal approach to avoid scrotal violation.

Mature teratoma with somatic-type solid malignancy in the mediastinum: A case report of rare and poor prognosis tumour

Background: Germ cell tumor with somatic-type solid malignancy is a germ cell tumor accompanied by a non-germ cell, the somatic-type malignant component in the form of sarcomas or carcinomas. These germ cell tumors are rare, accounting for only about 2% of all germ cell tumors in men. About 25-30% of these tumors occur in the mediastinum. These tumors are often located in the anterior mediastinum and occur in adult males with a peak incidence between 20-40 years. Case description: A 19-year-old female patient came with chief complaints of chest pain and shortness of breath about three months ago. Chest CT scan images showed a right lung reactive pneumonia with suspicious atelectasis at the second and third segments of the right lung. The image also showed a tumor mass with heterogeneous density at the mediastinum. Then thoracotomy surgery and tumor resection were performed. Macroscopically, there was a multicystic tumor mass measuring 14.0x11.0x6.5 cm, partly solid with 7.0x5.0x5.0 cm. Microscopic examination of the tumor mass showed three components of the germ layer, namely ectodermal, mesodermal and endodermal. No immature component appears. The tumor also contains neoplastic epithelial cells that form a solid, cribriform, acinic and papillary structure in the extracellular mucinous pool. Conclusion: Based on the clinical finding, radiologic, and routine histopathological examination, this case was concluded as mature teratoma with somatic-type solid malignancy in the form of mucinous adenocarcinoma.

Intratesticular Rhabdomyosarcoma- A Rare Childhood Tumour

Primary malignant of tumours of the testis are rare in children. Tumours of germ cell origin account for 60-77% of primary testicular tumors. Intrascrotal tumours of nongerm cell origin are rare. Rhabdomyosarcomas (RMS) are the commonest tumours among nongerm cell tumours. RMS are more commonly seen in paratesticular region. Pure testicular RMS are rare. A 16 yr boy was evaluated right sided testicular mass. Histopathology and immunohistochemistry confirmed it to be an anaplastic embryonal rhabdomyosarcoma. Here we report this case with a brief review of literature.

Rare intrascrotal tumors in a tertiary cancer center: A retrospective case series.

415 Background: Given their rarity, the literature on non-germ cell testicular tumors and paratesticular malignancies is still scarce. The objective of this study is to describe clinical and pathological features, as well as treatment patterns and outcomes, of patients with non-germ cell intrascrotal malignancies. Methods: Patients (pts) with benign or malignant non-germ cell intrascrotal tumors who were older than 18 years-old were deemed eligible. Electronic health records (EHR) were reviewed to assess pts clinical features, and disease characteristics and outcomes. Descriptive statistics was used to report data. RECIST 1.1 was used to determine radiological response to treatment. Time-to-event variables were estimated by the Kaplan-Meier method. Results: EHR of 885 pts with a primary diagnosis of ICD-10 C62 treated in a tertiary cancer center from January 2009 to June 2020 were reviewed for eligibility. 29 pts fulfilled eligibility criteria (Sertoli cell tumors, N = 3; Leydig cell tumors, N = 6; granulosa cell tumor, N = 1; testicular tumor of the androgenital syndrome, N = 1; mesotheliomas, N = 3; liposarcomas, N = 3; leiomyosarcomas N = 2; rhabdomyosarcomas, N = 3; spindle cell sarcomas, N = 3; lymphomas, N = 2; carcinoma of the rete testis, N = 1; primary neuroendocrine tumor of the testis, N = 1). The majority of pts (N = 25) had non-metastatic disease at diagnosis, and underwent upfront orchiectomy. The remaining four patients had metastatic disease at diagnosis (lymphoma, N = 1; sarcomas, N = 3), all positive for lymph node (LN) involvement; one with concurrent visceral metastasis. Six other pts posteriorly developed metastatic disease after a median follow-up of 13 months (IQR: 5.8–33.1 months) (Leydig tumor, N = 1; mesothelioma, N = 2; sarcomas, N = 3). The most common metastatic sites were LN (N = 8, 80%), lung (N = 4, 40%), bone (N = 3, 30%), adrenal gland (N = 2, 20%), peritoneum (N = 1, 10%), and skin (N = 1, 10%). Nine pts (90%) received systemic treatment: vincristine, doxorubicin and cyclophosphamide for rhabdomyosarcomas (N = 3), cisplatin plus pemetrexed for mesotheliomas (N = 2), doxorubicin for liposarcomas (N = 2), doxorubicin plus ifosfamide for liposarcoma (N = 1) and doxorubicin, vincristine, cyclophosphamide, and prednisone plus rituximab for lymphoma (N = 1). Of those, 2 pts achieved partial response and 2 had stable disease. Metastasectomy of a single lung metastasis was performed in a patient with metastatic Leydig cell tumor. Median overall survival was 51.2 and 24.5 months for patients with localized and metastatic disease, respectively. Conclusions: Paratesticular and non-germ cell testicular tumors are extremely rare entities with relatively good prognosis if treated at early stages depending on the underlying histology. Most metastatic disease cases were due to paratesticular sarcomas.

Prognostic factors associated with malignant somatic transformation (MST) of germ cell tumors (GCT) in a Mexican cohort: The experience of the Instituto Nacional de Cancerología, Mexico (NCIM).

427 Background: MST is a rare entity defined as the development of somatic non-germ cell malignancies within GCT, its incidence varies between 2.7% and 8.6% of GCT’s. Previously reported favorable prognostic factors include synchronous diagnosis of MST and GCT, absence of non-pulmonary visceral metastases (NPVM) and presence of rhabdomyosarcoma. Methods: Retrospective study to describe prognostic factors of MST in GCT in a Hispanic population. Patients (pts) with diagnosis of MST from 2006 to 2019 were identified from the GCT database of the NCIM. Pts’ characteristics and outcomes were collected from clinical charts and recorded. Overall survival (OS) was performed with the Kaplan Meier (KM) method in the whole cohort and in patients with advanced disease (AD) (stage II and III). Comparisons were calculated with the log-rank test for KM and Chi squared test for categorical factors. Results: Seventy-one pts with MST were included in the overall population (OP). Non-seminoma 95.8%; testicular primary 97.2%; clinical stage (CS) I 32.4%, II 16.3%, III 49.3%; S2-S3 42.3%, 39.6% poor IGCCCG prognosis, 11.3% NPVM. Type of MST: 56.3% rhabdomyosarcoma (RMS), 21.1% spindle cell sarcoma, 12.7% PNET, 9.9% adenocarcinoma. 18.3% more than 1 MST histology. Median follow-up: 43.8 months (m). For the OP, mOS 71.1m (95% CI 80.0 – 119.2). OS for CS I have not been reached (NR). Forty-seven pts with AD were included, mOS 37m (95% CI 9.69 – 64.36). Characteristics associated with prognosis for OS for the OP and the AD cohorts are summarized in table. Pts with AD and RMS had more frequently a synchronous tumor (87.5% vs 58.3%, p=0.02) and absence of surgery for MST (70.8% vs 37.5%, p=.02). Conclusions: As far as we know, this is the largest cohort of hispanic pts with MST. Prognostic factors differed between OP and AD cohorts. Pts with MST and AD have a poor prognosis. Synchronous diagnosis of MST and presence of rhabdomyosarcoma are adverse prognostic factors for AD pts. Further study with a larger population is needed to verify these findings. Univariate analysis for OS.[Table: see text]

Rare tumors in pediatrics. First report in Argentina.

Collaborative clinical trials have enlarged the knowledge base about pediatric tumors; however, this is not the case for rare tumors (RT). To describe the prevalence, clinical characteristics, and course of RT in pediatric patients diagnosed at Hospital Garrahan. Descriptive, retrospective study of patients aged 0-18 years diagnosed with a RT and admitted between January 2007 and December 2017. Out of 1657 patients diagnosed with solid tumors, 164 (9.9 %) were RT; 71.95 % (118) of patients were younger than 14 years and 81.7 % (130) were males. In order of frequency, RT were thyroid carcinoma (60), adrenal carcinoma (14), lung tumors (14), melanoma (13), salivary gland cancer (11), gastrointestinal tumors (8), non-germ cell gonadal tumors (7), pancreatic tumors (7), renal carcinomas (6), nasopharyngeal carcinomas (5), pheochromocytoma and paraganglioma (5), and thymic carcinoma in 1 patient. Treatment depended on tumor type and stage. The median follow-up was 34.9 months (range: 1-128.5 months); 133 patients (78.7 %) are alive and only 10 patients (6 %) were lost-to-follow-up. The prevalence of RT was 9.9 %. Twenty-seven percent occurred in adolescents. The most frequent tumors included thyroid carcinoma, adrenal carcinoma, and melanoma. Treatment and course varied based on tumor histology. Predisposing molecular alterations were found in 5.3 % of patients; 3.5 % had a history of cancer.

Testicular Tumors: A 15-Year Archive Review and Histopathological Evaluation

Aim: Testicular tumors are one of the most common malignancies in men in the age group of 15-40 years, although they are rarely observed. In our study, it was aimed to evaluate their histopathological features by retrospectively examining of the cases diagnosed as testicular tumor in our department. Materials and Methods: Age, tumor localization, tumor size, pathological stage, tumor type and frozen information of 65 cases diagnosed as testicular tumor in the Department of Medical Pathology at Tokat Gaziosmanpasa University Faculty of Medicine between 2006-2020 were examined. Results: The mean age of 65 cases diagnosed as tumor was 37.9±17.73 years. Their ages ranged from 1 to 78 years. Macroscopic tumor diameter was an average of 4.6 ± 2.36 cm, 36 (55.4%) of them were located in the right and 29 (44.6%) of them were located in the left testis. Histopathological diagnosis was germ cell tumor in 53 (81.7%) cases and non-germ cell tumor in 12 (18.3%) cases. The most common tumor was seminoma with 22 (33.9%) cases and the second was mixed germ cell tumor with 19 (29.3%) cases. In components forming mixed germ cell tumors, embryonal carcinoma was the most commonly seen. Intraoperative frozen section examination was performed in 17 cases, it was determined that 10 cases were malignant and 7 cases were benign. Conclusion: The histopathological and general features of our series of testicular tumor was determined to be compatible with the literature to a great extent. Intraoperative frozen section examination is an important auxiliary diagnostic method in terms of organ preserving surgery.

Incidence, Prognostic Factors, and Survival Trend in Pineal Gland Tumors: A Population-Based Analysis.

IntroductionPineal gland tumors are exceedingly rare and account for 0.4-1.0% of brain neoplasms. Their rarity has confounded a clear understanding of the prognostic factors and standards of care for these neoplasms. In this study, we aimed to investigate the incidence, prognostic indicators, and survival trend of tumors emanating from the pineal gland.MethodsWe accessed the Surveillance, Epidemiology, End Results (SEER) Program for pineal gland tumors from 1975-2016. A multivariate Cox regression model was used to investigate the impact of clinicopathological parameters on all-cause mortality. For survival trend analysis, we employed the Kaplan Meier curve and pairwise comparisons to examine the trend.ResultsWe found 1,792 and 310,003 pineal gland and brain neoplasms during 1975-2016 resulting in an incidence of 0.6%. In the multivariate Cox proportional hazards model, older age, male gender, non-germ cell tumor, and receipt of chemotherapy were significantly associated with poor survival (p < 0.001). The extent of resection and radiotherapy administration did not produce survival advantages. Our result also highlighted an increased survival of pineal gland tumors over the years.ConclusionOur study investigated the prognostic factors that influenced survival in patients with pineal gland tumors. Chemotherapy use adversely affected patient outcomes and should be considered carefully in specific circumstances to avoid its harmful effects. These findings provide important evidence to improve current standards of care for this rare group of tumors. The survival of pineal tumors has improved over time reflecting improvements in current practice.

An annotated T2-weighted magnetic resonance image collection of testicular germ and non-germ cell tumors

Testicular cancer is a rare tumor with a worldwide incidence that has increased over the last few decades. The majority of these tumors are testicular non-germ (TNGCTs) and germ cell tumors (TGCTs); the latter divided into two broad classes - seminomatous (SGCTs) and non-seminomatous germ cell tumors (NSGCTs). Although ultrasonography (US) maintains a primary role in the diagnostic workup of scrotal pathology, magnetic resonance imaging (MRI) has emerged as the imaging modality recommended for challenging cases, providing additional information to clarify inconclusive/equivocal US. In this work we describe and publicly share a collection of 44 images of annotated T2-weighted MRI lesions from 42 patients. Given that testicular cancer is a rare tumor, we are confident that this collection can be used to validate statistical models and to further investigate TNGCT and TGCT peculiarities using medical imaging features.

Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors.

Circadian rhythm synchronizes each body function with the environment and regulates physiology. Disruption of normal circadian rhythm alters organismal physiology and increases disease risk. Recent epidemiological data and studies in model organisms have shown that maternal circadian disruption is important for offspring health and adult phenotypes. Less is known about the role of paternal circadian rhythm for offspring health. Here, we disrupted circadian rhythm in male mice by night-restricted feeding and showed that paternal circadian disruption at conception is important for offspring feeding behavior, metabolic health, and oscillatory transcription. Mechanistically, our data suggest that the effect of paternal circadian disruption is not transferred to the offspring via the germ cells but initiated by corticosterone-based parental communication at conception and programmed during in utero development through a state of fetal growth restriction. These findings indicate paternal circadian health at conception as a newly identified determinant of offspring phenotypes.

Clinical and morphological characteristics or immunohostochemical factors determine the results of treatment for diffuse large B-cell lymphoma?

e19539 Background: Diffuse large B-cell lymphoma (DLBCL) is and aggressive heterogeneous tumor. The treatment is ineffective in more than 30% cases: primary resistance is observed in 20%, and relapses in 10%. Clinical prognostic indices do not allow assessing the DLBCL course and treatment outcomes. The purpose of the study was to evaluate the results of treatment of DLBCL patients depending on clinical and immunohistochemical factors of the disease prognosis. Methods: Patients with DLBCL (n = 48): men – 25 (52.1%, mean age 52±3.8 years), women – 23 (47.9%, mean age 60±4.3 years) received standard treatment R-CHOP, R-CHOEP, R-EPOCH. Results: After the treatment, 27 (56.2%) patients were in remission for 3 years, 10 (20.8%) patients developed relapses, and 11 (23%) patients were refractory to the therapy. All groups demonstrated Ki-67 &gt; 80%, overexpression of Bcl2, Bcl6, CD10, MUM-1 on tumor cells, C-MYC gene rearrangements. Patients with stage I and II nodal spread were more likely to be in remission; refractory patients and those with early relapses had stages III and IV. Relapses were detected at different periods after treatment: early relapses (n = 5) within 6 months and late relapses (n = 5) after 12 months or later. Among patients with early relapses, 2 (40%) had extranodal disease and 3 (60%) nodal disease; high/medium IPI was noted in 3 patients, low/medium and low IPI – 1 patient each. Among patients with late relapses, 3 patients had nodal disease and 2 – primary extranodal disease; high/medium IPI was noted in 2 patients, low/medium – in 3 patients. Among recurrent patients, 9 had non-germ cell DLBCL and 1 - germ cell DLBCL. Among refractory patients, 8 (73%) had nodal disease and 3 (27%) - extranodal disease; low/medium IPI was registered in 4 patients, high/medium IPI in 2, low IPI in 5 patients; germ cell tumors in 2 patients, non-germ cell tumors in 9 patients. Conclusions: 33% of DLBCL patients did not benefit from the treatment. Molecular markers such as Ki-67, Bcl2, Bcl6 and CD10 were not prognostically significant. The tumor type had a prognostic value only in the group of patients with relapses - non-germ cell tumors were found in 90% of cases.

AB145. SOH21AS087. Preservation of fertility potential in a solitary testis with germ cell tumour and prior azoospermia by utilising on table sperm extraction

Background: Currently, cryopreservation of semen prior to commencement of anti-cancer therapy is the method of choice for preserving male fertility. Success of this technique depends on the presence of sperm/spermatozoa in semen, and so is not suitable in azospermic patients. In non-germ cell tumour (GCT) patients, specialised facilities and time to treatment permits the use of testicular sperm extraction (TESE) to collect appropriate sperm/spermatozoa prior to definitive management. It becomes a significant challenge, where patients have tumour in solitary testis, bilateral testicular tumours, or significantly atrophic contralateral testis. In such situations, there is risk that fertility preservation can be overshadowed by the urgent treatment of GCT. We share our experience of Onco-TESE to preserve fertility in an azospermic patient with GCT in solitary testis.

Estudio de asociación entre la estirpe histológica y el estadio clínico de los tumores testiculares con los marcadores tumorales

Antecedentes: El tumor testicular es el tumor sólido más frecuente en hombres entre 20 y 34 años. Los tumores testiculares pueden dividirse histológicamente en células germinales que se presentan en 90–95% y no germinales en alrededor del 5%. Los marcadores tumorales son cruciales en el diagnóstico, clasificación, pronóstico y vigilancia posterior al tratamiento de los tumores testiculares.&#x0D; Objetivo: Conocer la prevalencia puntual de cáncer de testículo en nuestro servicio. Determinar las características clínico-patológicas del cáncer de testículo. Correlacionar los niveles de marcadores tumorales con la estirpe histológica y el estadio clínico del cáncer testicular&#x0D; Metodología: Es un estudio transversal en el que se analizó el total de expedientes de pacientes atendidos en el servicio Urología con diagnóstico de cáncer de testículo, durante el período entre el 1° de enero de 2014 al 31° de diciembre de 2018.&#x0D; Resultados: Se incluyeron 99 pacientes, la media de edad fue de 29±8.5 años. Los tumores que con mayor frecuencia se registraron fueron: tumor de células germinales en el 99%: germinal mixto 50 (50.51%), seguido del seminoma con 42 (42.42%), teratoma 5 (5.05%). La combinación TNM mas comúnmente encontrada fue T1 N0 M0. El estadio clínico mas frecuente fue estadio I, seguido del II y finalmente el III. La alfafetoproteína es el único marcador tumoral que se asocia a extirpe histológica y podría estar asociado a enfermedad diseminada.&#x0D; Limitaciones: Las limitaciones de nuestro estudio es un tamaño de muestra pequeño con una incidencia de algunas variedades de tumores también muy baja.&#x0D; Originalidad: El valor de nuestro estudio es que aporta información sobre la materia en población latinoamericana que es escasamente reportada. &#x0D; Conclusiones: La estirpe histológica que se encontró mayor frecuencia fueron los tumores germinales mixtos y la clasificación TNM más comúnmente encontrada en nuestros pacientes fue T1a, N0, M0 y estadio clínico I. La AFP es el único marcador predictor de la estirpe histológica y de una posible enfermedad diseminada.

Ubiquitin proteasome system and autophagy associated proteins in human testicular tumors

Ubiquitin proteasome sytem (UPS) and autophagy govern protein quality control by degradation and clearance of damaged proteins. Many proteins working in these pathways such as p97/VCP, Ubiquitin (Ub), Jab1/CSN5, p62, LC3B and Beclin 1 are known to be essential for different pathological conditions, especially in cancer, but their expression in human testicular tumors has not been characterized yet. In the present study, we aimed to investigate the expression of UPS (p97/VCP, Ubiquitin, Jab1/CSN5) and autophagic (p62, LC3B, Beclin 1) proteins in human testicular tumors and cancer adjacent normal testicular tissues. We used an immunohistochemical staining technique. 120 cases of testicular germ and non-germ cell tumors, which are 42 seminomas, 31 embryonal carcinomas, 11 yolk sac tumors, 25 intratubular germ cell neoplasms, 6 Leydig cell tumors, 5 Sertoli cell tumors, were collected and evaluated on tissue microarray. For the first time, the expression of p97/VCP, Ub, Jab1/CSN5, p62, LC3B and Beclin 1 in different type of human testicular tumors has been confirmed. We found that p97/VCP, Ub and Jab1/CSN5 were frequently expressed at higher levels in testicular tumours. In contrast to UPS markers, p62, LC3B and Beclin 1 showed significantly diminished expressions in testicular tumors. Accordingly, a negative correlation between p97/VCP and autophagic markers (p62 and LC3B) was found, suggesting a relationship between UPS and autophagy in different type of testicular tumors. The current results displayed elevated level of p97/VCP, Ub and Jab1/CSN5 expressions in contrast to the diminished expression of p62, LC3B and Beclin 1 in human testicular tumors, thereby supporting a correlation between p97/VCP and autophagic markers in testicular tumors.