Sub-centimeter lymphadenopathy in germ cell testicular cancer: An ongoing surveillance challenge.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17011-e17011
Author(s):  
Ruth Kieran ◽  
Iseult Browne ◽  
John McCaffrey
Keyword(s):  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
High Specificity ◽  
Cancer Center ◽  
Correct Identification ◽  
Embryonal Tumors ◽  
Testicular Germ Cell ◽  
Landing Zone ◽  
Mixed Tumors

e17011 Background: Correct identification of retroperitoneal disease is essential for proper staging and management in germ cell tumors. A size threshold of a 10mm diameter has high specificity in assessing nodal metastases, but sensitivity can be poor at this level and many patients have sub-centimeter lymphadenopathy on post-orchidectomy staging. As many staging scans are done soon after surgery, these may represent reactive lymph nodes. We aimed to assess the prevalence of sub-centimeter lymphadenopathy on baseline imaging in our patients, and its association with recurrence. Methods: Records of patients diagnosed with testicular germ cell cancer in a tertiary cancer center (n = 55, 2015-2020) were reviewed (median followup of 26 months, range 1-59). Lymphadenopathy size measurements were taken from the scan report, which had been authorized by a radiology consultant. Results: Patients had a median age of 34 (range 19-63). 37 (67%) had pure seminomas, 2 (4%) pure embryonal tumors, 12 (22%) mixed tumors with a primarily (> 50%) embryonal component, and 4 (7%) other mixed types. 48 (87%) had stage 1 disease, 3 (6%) stage 2 and 4 (7%) stage 3 disease. 26 (47%) had CT staging preoperatively, of the remainder 69% (n = 20) were staged in the first 48 postoperative hours. 28 (51%) had no lymphadenopathy, 15 (27%) had sub-centimeter lymphadenopathy within the landing zone, 8 (15%) had lymphadenopathy measuring > 1 cm within the landing zone, 4 (7%) had lymphadenopathy elsewhere. 7 had immediate chemotherapy, 48 entered surveillance. For the 14 with sub-centimeter lymphadenopathy within the landing zone who did not have immediate chemotherapy, 3 regressed, 8 were stable. 2 underwent a PET for further assessment, 1 a biopsy. 3 increased in size. 6 patients on surveillance had a recurrence – of these 2 had seminomas with no baseline lymphadenopathy, 4 had mixed primarily embryonal tumors (3 with sub-centimeter lymphadenopathy (0.6, 0.7 and 0.9 cm each), one with a 1.3cm para-aortic lymph node). Of those 4, only 1 had significantly elevated HCG pre-operatively, all recurred in the sites of previously noted lymphadenopathy. Those with mixed, primarily embryonal disease with lymphadenopathy (representing 50% of such patients on surveillance) had a higher recurrence risk than other patients on surveillance (OR: 153, 95% CI 6-3709, p= 0.002) Those undergoing preoperative/delayed postoperative imaging (n = 28) were equally likely to have lymphadenopathy to those having imaging in the first 7 postoperative days ( X2 (3, N= 27) = 2.9, p= 0.4). 1 patient had died (unrelated causes), all others were disease-free at most recent followup. Conclusions: Sub-centimeter lymphadenopathy is more likely to be benign in those with seminomas, but even small volume lymphadenopathy in those with mixed tumors with a primarily embryonal component may represent metastatic disease, and should be monitored closely.

Iso-chromosome 12p Analysis by Fluorescent In-Situ Hybridization: An Academic Institutional Experience

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S72-S72
Author(s):  
P P Patwardhan ◽  
S Satturwar ◽  
R Dhir ◽  
G M Quiroga-Garza
Keyword(s):  
In Situ Hybridization ◽  
Germ Cell ◽  
Fluorescent In Situ Hybridization ◽  
Clinical Presentation ◽  
Germ Cell Tumors ◽  
High Specificity ◽  
Testicular Germ Cell ◽  
Chromosome 12P ◽  
Institutional Experience

Abstract Introduction/Objective Chromosome 12 abnormalities like iso-chromosome 12p (i12p) and amplification of 12p are seen in majority (89%) of the primary and metastatic testicular germ cell tumors (TGCTs). i12p can be detected by karyotyping, fluorescent in-situ hybridization (FISH) or reverse transcriptase polymerase chain reaction. The aim of this study was to review i12p FISH data at our institution and assess the clinical utility. Methods/Case Report Laboratory information system was queried over a period of 15 years to search for cases where i12p FISH test was requested. FISH test was performed using TelVysion 12p telomeric probe and CEP 12 centromere probe on paraffin-embedded tissue or cell blocks. A ratio of 12ptel/CEP12 signal of 1.4 or greater was considered as positive. Patient demographics, clinical presentation, pathologic findings, and follow-up data were documented and correlated. Results (if a Case Study enter NA) Total 58 cases were identified with an age range of 14 to 76 years. Majority were male (M=52, F=6). Of these cases, 15 were testicular and 43 extra-testicular cases that included resection (n=35), biopsy (n=20) and cell-blocks (n=3). i12p was detected in 8 out of 15 testicular cases while i12p was detected in 16 out of the 43 extra-testicular cases. The extra- testicular cases included 17 retroperitoneal lesions, 8 lesions from the mediastinum, 6 lymph nodes from other sites and 12 miscellaneous lesions. Using pathology diagnosis with immunohistochemistry as gold standard, overall sensitivity was 60% and specificity was 86%. There were 3 false positive cases [Benign testicular parenchyma (n=1), suspicious for germ cell neoplasia in-situ (n=1) and undifferentiated epithelioid neoplasm (n=1)]. Conclusion Our results show that although the sensitivity was limited, FISH test for i12p demonstrated high specificity(86%) for diagnosis of primary or metastatic TGCTs. As an adjunct test, i12p FISH can help identify and further characterize a significant number of GCTs with unusual morphology or clinical presentation.

Frequent expression of PD-L1 in testicular germ cell tumors.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 379-379 ◽  
Author(s):  
Christian Daniel Fankhauser ◽  
Alessandra Curioni Fontecedro ◽  
Joerg Beyer ◽  
Verena Tischler ◽  
Tullio Sulser ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Germ Cell ◽  
Single Case ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Germ Cell Cancer ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Major Interest

379 Background: Testicular germ-cell cancer is curable even in the presence of metastatic disease. Yet, about 10-15% of patients become cisplatin-refractory and will eventually die of their disease. Moreover, short- and long-term side effects of cisplatin make the search for less toxic treatment strategies worthwile. Programmed Death Receptor 1 (PD-1, CD279) is one member of the extended family of T cell regulators expressed on the surface of activated T cells, B cells, and macrophages. Its ligand, PD-L1 (B7-H1, CD274), is expressed on tumor cells, T cells and other tissues. The interaction of these two molecules negatively regulates immune responses. Of major interest is that inhibition of the interaction between PD-1 and PD-L1 can enhance T-cell responses in vitro and mediate clinical antitumor activity . The aim of this study was to analyze the expression of PD-L1 in testicular germ-cell tumors to evaluate its potential as predictive marker for further therapeutic strategies. Methods: Immunohistochemistry was performed in 486 Formalin Fixed Paraffin Embedded (FFPE) specimens using a monoclonal rabbit antibody (E1L3N, Cell Signaling Technology, Inc. (CST) of Danvers, MA, USA). Results: PD-L1 expression was found in 171 out of 248 (69%) seminomas, 19 out of 48 (40%) yolk sac tumors, 7 out of 46 (15%) teratomas, 2 out of 10 (20%) choriocarcinomas and 53 out of 87 (61%) embryonal carcinomas. In 20 out of 20 Intratubular germ-cell neoplasia unclassified (IGCNU) and also in 20 out of 20 normal tissue specimens no single case exhibited PD-L1 expression. Conclusions: Our study describes for the first time the frequent expression of PD-L1 in a large series of human testicular germ-cell tumors, but not on normal testis tissue or IGCNU. Based on our results, checkpoint inhibition with anti-PD1 and anti-PDL1 antibodies might represent an attractive approach in germ-cell cancer, where new active agents are urgently needed.

scholarly journals Pediatrics Germ Cell Tumors: A Ten Year Audit in a Cancer Center of Nepal

2020 ◽  
Vol 4 (1) ◽  
pp. 102-106
Author(s):  
Krishna Sagar Sharma ◽  
S Mehta ◽  
D Misra ◽  
Jitendra Pariyar ◽  
Sabita Panthi
Keyword(s):  
Germ Cell ◽  
Adolescent Girls ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Germ Cell Cancer ◽  
Disease Stage ◽  
Treatment Modalities ◽  
Cancer Center ◽  
Early Presentation ◽  
Fertility Sparing

Introduction: Pediatric Germ cell tumors are rare disease in pediatric and adolescent age group. Germ cell tumors are the most frequently found malignancies which are highly chemo sensitive. GCTs are curable if diagnosed and treated adequately even in resources poor setting in resource constraints countries like Nepal. Objective: To study the clinic pathological profile and treatment outcome of Pediatrics Germ cell tumors (GCTs) among children and adolescent group seeking treatment at B.P. Koirala Memorial Cancer Hospital (BPKMCH), Nepal. Methodology: Descriptive study was done at BPKMCH Nepal. All available case records of pediatric and adolescent girls diagnosed to have GCTs from 2002 to 2011 were collected and analyzed in terms of age, clinical features, malignancy types, treatment modalities and outcome.  Results: Total 70 girls were with female gynecological malignancy. There are 46 (76.66%) with ovarian malignancies. Among the ovarian cancers, 42 had malignant germ cell cancer (91.3%) among all ovarian malignancies which are enrolled in the study. The commonest presentation was abdominal distension and pain in70%. Onset of symptoms ranged from three days to 730 days (mean 95 days). Disease stage at presentation was early stage 18 (30%) and advanced disseminated disease 42 (70%). In treatment modality, 8 (13.33%) underwent fertility sparing surgery only, 21(35%) underwent chemotherapy only and 31(51.66%) underwent multimodality treatment. 82.5% patients who were completed recommended treatment were cured. Conclusion: Malignant germ cell cancer is the commonest ovarian malignancies among pediatric and adolescent girls. Early presentation and prompt appropriate treatment would offer chances of cure even with preservation of fertility.

Long-term sexual impairment in relationship with metabolic health in testicular germ-cell tumor survivors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16060-e16060
Author(s):  
Michal Chovanec ◽  
Lucia Vasilkova ◽  
Lucia Petrikova ◽  
Jana Obertova ◽  
Patrik Palacka ◽  
...  
Keyword(s):  
Sexual Function ◽  
Germ Cell ◽  
Molecular Mechanisms ◽  
Germ Cell Tumors ◽  
Thyroid Stimulating Hormone ◽  
Metabolic Health ◽  
Cancer Center ◽  
Testicular Germ Cell ◽  
Severe Difficulty

e16060 Background: Treatment for germ-cell tumors (GCT) results in long-term sexual difficulties in GCT survivors, as we have shown previously. This study aimed to correlate the long-term sexual difficulties with serum parameters of metabolic functioning. Methods: GCT survivors (N = 155) from a national cancer center completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire at a median 10 years of follow up (range 5-32). Twenty-nine (18%), 30 (19%) and 20 (13%) survivors have suffered from severe difficulty to achieve erection, maintain erection and achieve orgasm, respectively. Severe difficulty was characterized as a score of 0-2 (scale 0-5) in respective questions from the questionnaire. Sexual impairment was then correlated with parameters of metabolic functioning assessed from peripheral blood of all survivors drawn at the day of the clinical visit. Results: Survivors with difficulty to achieve erection had significantly higher levels of alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) and lactate-dehydrogenase (all P < 0.05). Impaired ability to achieve an orgasm also correlated with significantly higher levels of ALT, AST and LDH (all P < 0.05). Survivors with difficulty to maintain erection had higher levels of LDH (P = 0.02) and AST (trend for P = 0.06), but not ALT ( P = 0.5) and their cholesterol levels were significantly higher ( P = 0.04). Furthermore, survivors with higher levels of glucose ( P = 0.04), thyroid stimulating hormone ( P = 0.04), but not of free-thyroxin ( P = 0.3) suffered from difficulty to achieve orgasm. Conclusions: Our prospective study shows that an impairment in sexual function resulting from curative treatment of GCTs may be related to metabolic health. Higher liver enzymes may be indicative of endothelial dysfunction and cardiovascular disorder. Long-term sexual impairment in GCT survivors should be a subject of further translational research to uncover the underlying molecular mechanisms.

Phase II study of avelumab in multiple relapsed/refractory testicular germ cell cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16045-e16045 ◽  
Author(s):  
Michal Mego ◽  
Daniela Svetlovska ◽  
Michal Chovanec ◽  
Katarina Rejlekova ◽  
Jana Obertova ◽  
...  
Keyword(s):  
Germ Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Cancer ◽  
Objective Response ◽  
Germ Cell Tumors ◽  
Progression Free Survival ◽  
Testicular Tissue ◽  
Testicular Germ Cell ◽  
End Point

e16045 Background: Testicular germ cell tumors (TGCTs) represent a highly curable disease; however, a small proportion of patients develop disease recurrence. PD-L1 expression is significantly higher in germ cell tumors (GCTs) in comparison to normal testicular tissue and high PD-L1 expression is associated with inferior progression-free and overall survival compared to patients with low PD-L1 expression. This study aimed to determine the efficacy and toxicity of PD-L1 antagonist, Avelumab, in patients with refractory GCTs. Methods: From November 2017 to January 2018, 8 patients with refractory GCTs were enrolled in the phase II study. All patients were pretreated with at least 2 cisplatin-based therapies (median 5, range 2 – 6); 5 tumors (62.5%) were absolutely refractory to cisplatin and 5 patients (62.5%) had visceral non-pulmonary metastases. Avelumab was administered at a dose of 10mg/kg biweekly until progression or unacceptable toxicity. The primary end point was 12-weeks progression-free survival (PFS). If < 8 responses to study therapy will be observed among the first 15 patients, the study will be terminated. Results: Median age was 29 years (range: 22 – 52 years). During a median follow-up period of 2.6 months (range: 0.3 - 14.4), 7 (87.5%) patients experienced disease progression and 6 patients (80.0%) died. Twelve-week PFS was 0%, median PFS was 1.4 months, 95%CI (0.9 – 1.4) and median OS was 2.7 months, 95% CI (1.0 – 3.3). No objective response was observed. Avelumab was well tolerated, no severe adverse event was observed. Conclusions: This study failed to achieve its primary end point and our data suggest lack of Avelumab efficacy in unselected multiple relapsed/refractory TGCTs. Clinical trial information: NCT03403777.

Comparing diagnosis, management, and outcomes of synchronous versus metacrhonus brain metastases from testicular germ cell tumors (TGCT): Multinstitutional experience from the Spanish Germ Cell Cancer Group (SGCCG).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4560-4560
Author(s):  
Jorge Aparicio ◽  
Regina Girones ◽  
Pere Roure ◽  
Jose R. Germa-Lluch ◽  
Sergio Vazquez-Estevez ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Germ Cell ◽  
Cell Cancer ◽  
Germ Cell Tumors ◽  
Testicular Germ Cell Tumors ◽  
Testicular Germ Cell ◽  
Term Survival ◽  
Cancer Group ◽  
Group 2 ◽  
Group 1

4560 Background: Metastases of testicular germ cell tumors (TGCT) to brain are a rare event. Prognostic is poor and there is little evidence on optimal management of these patients. Methods: A retrospective review of case records of germ cell tumor patients within the Spanish Germ Cell Cancer Group from 1994 to 2012 was conducted. Results: Thirty-tree cases of testicular germ cell tumors from 17 institutions were reported. Nineteen patients (57%) presented with brain metastases at primary diagnosis (group 1: synchronous), thirteen (40%) developed brain metastases at relapse (group 2: metachronous) and only one patient developed brain metastasis during cisplatin based-chemotherapy (3%) (excluded from the analysis). Main demographics and comparison between series are shown on table. Median serum BHCG levels at initial diagnosis were higher in group 1(279.083 versus 175.873), whereas those of AFP were higher in group 2(1320 versus 4181). The most common histology in the primary tumor was choriocarcinoma for group; versus embryonal carcinoma for group 2. Patients had neurological symptoms at diagnosis of brain metastases (63% synchronic/93% metachronus). Performance status was also poor (PS 2-3: 52,6%group 1-62,2% group 2). Four patients (21%) in group 1 had a solitary brain lesion vs seven (54%) on group 2. Median time since last dose of cisplatin to development of brain metastases on group 2 was 6 months (3-22).Median overall survival was 16 months (95% CI 5,3-26,6): group 1: 16 (95% CI 13,9-18);23 group 2 (95% CI 0-165). We have not found significant differences in survival between both groups. Overall 37,5% of patients achieved long-term survival (38,9% in group 1 versus 38,5% in group 2). Patients achieving complete response of brain metastases had a better survival (log rank p:0,003). Conclusions: Long term survival can be achieved in approximately 1/3 of patients with brain metastases. Chemotherapy remains the cornerstone of treatment. Selection bias because of the retrospective nature of review should make us be careful with the conclusions.

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