Follow-Up of Patients Diagnosed With Germinal Testicular Tumors (Seminomas and Non-seminomatous) Treated With a Bone Marrow Transplant and a High Dose of Chemotherapy.

INTRODUCTION: Germinal testicular tumors are the most common malignant neoplasm in men around 20 to 34 years. Even though they are unusual, they have increased incidence in the last decade; they have an excellent prognosis and overall survival at five years, approximately 95%. Divergent data exists regarding treatment options in patients with first, second, and third relapses with conventional therapy. Some studies describe the possible benefit of using high-dose chemotherapy associated with a bone marrow transplant with variable results. METHODS:  The present study describes clinical outcomes, clinical response, mortality, overall survival, and progression-free survival to two years in a group of patients with germinal malignant tumors, seminoma versus non-seminomatous with evidence of progression of the disease at first, second, or third conventional chemotherapy regimens, and who received high dose chemotherapy and bone marrow transplantation at the National Cancer Institute between 2010 and 2021. RESULTS: A retrospective observational study of case series showed that 57% of patients in third-line therapy received high-dose chemotherapy and bone marrow transplantation, with progression disease median time from diagnosis more than two years. Patients in the post-graft period presented infectious complications (71%). The most common were febrile neutropenia (29%) with a mortality rate of 71% (n=5), progression-free survival of 2.3 months, and overall survival of 7.4 months. CONCLUSIONS:  These results show that in this group of patients, regimens with high-dose chemotherapy associated with bone marrow transplants, have a worse prognosis compared to other cohorts of patients, and may not be the best candidates for this rescue therapy.

Bone Metastases in Non-Seminomatous Germ Cell Tumors: A 20-Year Retrospective Analysis.

Background: Non-seminomatous germ cell tumors (NSGCTs) represent a rare yet the most prevalent malignancy among young men. Bone metastases (BMs) are exceedingly uncommon in this neoplasm, and available data regarding the initial disease presentation, survival outcomes, and prognostic significance of BMs are limited. Methods: We conducted a retrospective analysis of 40 NSGCT patients with BMs treated between 2001 and 2021 in our tertiary care center. The cohort was stratified into synchronous (n = 29) and metachronous (n = 11) groups based on the presence of BM at diagnosis or only at relapse, respectively. We assessed overall survival (OS), progression-free survival (PFS), disease presentation, and treatments. Results: After a median follow-up of 93 months, the 5-year PFS and OS rates were 37.6% and 53.9% in the synchronous group and 18.2% and 36.4% in the metachronous group, respectively. At the initial diagnosis, most patients were classified into the IGCCCG poor prognostic group (n = 34, 85%). BMs were mostly asymptomatic (n = 23, 57.5%), involved the spine (n = 37, 92.5%), and could become visible only after disease response (n = 4, 10%). A pathological examination of resected bone lesions after first-line treatment revealed necrosis (n = 5, 71.4%), teratoma, or seminoma (both n = 1, 14.3%). At first relapse, eight patients in the synchronous group did not experience bone recurrence, while eight patients experienced recurrence at the initial affected bone site. Conclusions: In NSGCT patients, BMs often present asymptomatically and may initially be unnoticed. However, these patients may have a poorer prognosis compared to those in the IGCCCG poor prognostic group. Further studies including control groups are needed to assess the independent prognostic significance of BMs.

Emergent Management of Growing Teratoma Syndrome: A Case Presentation.

Growing teratoma syndrome (GTS) represents a rare yet significant complication following treatment for non-seminomatous germ cell tumors (NSGCT), characterized by the growth of mature teratoma elements despite prior chemotherapy. We present the case of a 30-year-old male who, following orchidectomy for NSGCT and subsequent chemotherapy, developed acute abdominal pain and pulmonary metastasis. Despite normal serum tumor markers, imaging revealed a large retroperitoneal mass encasing significant vessels. Surgical excision led to symptom resolution. This case underscores the diagnostic challenges GTS poses, the importance of imaging in diagnosis, and the efficacy of prompt surgical intervention in achieving favorable outcomes.

Intratumoral Heterogeneity, Chemoresistance and Lymph Node Landing Zone Prognosis in Testicular Tumors Based on Histopathological Characteristics.

BACKGROUND: Existing data on the histopathological correlation of testicular tumors with lymph node prognosis have been poorly explored. We aimed to investigate the relationship of the histopathological properties of testicular tumors with lymph nodes and their involvement with chemoresistance and heterogeneity of testicular tumors. METHODS: Patients with non-seminomatous germ cell tumor (NSGCT) were selected for histopathological correlation of testicular tumor with lymph nodes and its relationship with chemoresistance and heterogeneity. Histopathological and radiological parameters associated with the risk of chemoresistance and tumor progression were measured pre- and post-chemotherapy. Binomial logistic regression and Kaplan-Meier analysis were implemented to determine the predictors of progression and adverse overall patient survival. All categorical variables were analyzed using the Chi-square test, while Pearson's R coefficient determined the correlation. RESULTS: Male patients who were diagnosed with NSGCT from March 2017 to December 2018 at Guwahati Medical College, Guwahati, India, were included in this study. Lymph node groups were predominantly incriminated with the EYST or EYS groups and minimally linked with the pure E and YCS groups. Furthermore, the highest number of lymph node stations was associated with pre-chemotherapy. In salvage chemotherapy in the form of VIP, we found exciting outcomes, as approximately 41% of cases responded positively, especially in the EYS group. CONCLUSION: Our study classifies NSGCT according to the most favorable histopathological grouping and explores the tumoral response in different intrinsic and extrinsic variables. Our analysis can serve as a triumphant histopathological nomogram for a sublime management protocol to deal with the onerous histological pairing in NSGCT.

Unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection in Stage II non-seminomatous germ cell tumor: A tertiary care experience.

Objective: Post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) represents an integral component of the management of patients with non-seminomatous germ cell tumor (NSGCT). Modified templates have been proposed to minimize the surgical morbidity of the procedure. Moreover, the implementation of robotic surgery in this setting has been explored. We report our experience with unilateral post-chemotherapy robot-assisted retroperitoneal lymph node dissection (PC-rRPLND) for clinical Stages IIA and IIB NSGCTs. Methods: A retrospective single institution review was performed including 33 patients undergoing PC-rRPLND for Stages IIA and IIB NSGCTs between January 2015 and February 2019. Following orchiectomy, patients were scheduled for chemotherapy with three cycles of bleomycin-etoposide-cisplatin. Patients with a residual tumor of <5 cm and an ipsilateral metastatic disease on pre- and post-chemotherapy CT scans were eligible for a unilateral template in absence of rising tumor markers. Descriptive statistics were provided for demographics, clinical characteristics, intraoperative and postoperative parameters. Perioperative, oncological, and functional outcomes were recorded. Results: Overall, 7 (21.2%) patients exhibited necrosis or fibrosis; 14 (42.4%) had mature teratoma; and 12 (36.4%) had viable tumor at final histology. The median lymph node size at surgery was 25 (interquartile range [IQR] 21-36) mm. Median operative time was 180 (IQR 165-215) min and no major postoperative complications were observed. Anterograde ejaculation was preserved in 75.8% of patients. Median follow-up was 26 (IQR 19-30) months and a total of three recurrences were recorded. Conclusion: PC-rRPLND is a reliable and technically reproducible procedure with safe oncological outcomes and acceptable postoperative ejaculatory function in well selected patients with NSGCTs.

A Challenging Case of Heart Displacement by a Large Mediastinal Germ Cell Tumor.

Mediastinal germ cell tumors (GCTs) are rare and aggressive cancers originating from the germ cells in the mediastinum. Early detection and treatment are vital due to their high potential for metastasis and recurrence. We present a case of a 28-year-old man who exhibited a cough and shortness of breath. Laboratory tests revealed elevated tumor markers, alpha-fetoprotein, and beta-human chorionic gonadotropin. Imaging studies displayed a large mediastinal mass, causing the right displacement of the mediastinum and cardiac tamponade. The biopsy confirmed a non-seminomatous GCT, specifically a yolk sac tumor. The patient experienced pericardial effusion and cardiac tamponade after receiving two cycles of etoposide and cisplatin chemotherapy. To relieve the tamponade, an emergency pericardiocentesis was performed malignant GCTs necessitate prompt diagnosis and treatment and utilizing multimodal therapy such as chemotherapy to achieve tumor control. Due to the high risk of metastasis, vigilant surveillance for recurrence is essential, emphasizing the need for specific criteria for accurate early detection.

An Aberrant Seminoma as a Complication in an Undescended Testis: A Case Report and Review of Literature.

Testicular germ cell tumors are testicular neoplasms in young and middle-aged men. Undescended testis dramatically increases the risk of testicular germ cell tumors. We report the case of a 33-year-old male who complained of swelling and pain in his lower abdomen. The patient also had an undescended left testis. An intrabdominal mass was detected on ultrasound that was further characterized using contrast-enhanced CT. Imaging findings suggested testicular germ cell tumor, developing as a complication in the undescended testis. The patient was operated and the diagnosis was confirmed on histopathological examination.

Diagnostic Value of the Texture Analysis Parameters of Retroperitoneal Residual Masses on Computed Tomographic Scan after Chemotherapy in Non-Seminomatous Germ Cell Tumors.

After chemotherapy, patients with non-seminomatous germ cell tumors (NSGCTs) with residual masses >1 cm on computed tomography (CT) undergo surgery. However, in approximately 50% of cases, these masses only consist of necrosis/fibrosis. We aimed to develop a radiomics score to predict the malignant character of residual masses to avoid surgical overtreatment. Patients with NSGCTs who underwent surgery for residual masses between September 2007 and July 2020 were retrospectively identified from a unicenter database. Residual masses were delineated on post-chemotherapy contrast-enhanced CT scans. Tumor textures were obtained using the free software LifeX. We constructed a radiomics score using a penalized logistic regression model in a training dataset, and evaluated its performance on a test dataset. We included 76 patients, with 149 residual masses; 97 masses were malignant (65%). In the training dataset (n = 99 residual masses), the best model (ELASTIC-NET) led to a radiomics score based on eight texture features. In the test dataset, the area under the curve (AUC), sensibility, and specificity of this model were respectively estimated at 0.82 (95%CI, 0.69-0.95), 90.6% (75.0-98.0), and 61.1% (35.7-82.7). Our radiomics score may help in the prediction of the malignant nature of residual post-chemotherapy masses in NSGCTs before surgery, and thus limit overtreatment. However, these results are insufficient to simply select patients for surgery.

A rare case of brain metastatic of primary mediastinal yolk sac tumor.

Primary yolk sac tumors are extragonadal germ cell tumors commonly seen in children and young adults. They are more common in men. Germ cells tumor on histopathological characteristics is classified as seminoma and non-seminomatous (NSGC). The rarest form of NSGC is an extragonadal yolk sac tumor of mediastinum. Clinical presentations are not specific and may imitate other chronic disease such as other malignancies or tuberculosis such as chest discomfort, vena cava superior syndrome, fever, weight loss, and chronic cough. Immunohistochemistry showed a positive result in Alpha-fetoprotein and pan-cytokeratin. Due to its rarity, brain metastases' clinical signs and symptoms, anatomical sites, and characteristics are less well documented. However, the metastatic brain process gave similar histological findings to the primary site. Additional radiological and laboratory tests can be carried out to identify other metastatic processes. Standardized treatment of primary mediastinal sac tumors with brain metastasis has not yet been established. Combining chemotherapy, surgery and radiation treatment could improve overall outcomes and prognosis. We present a scarce case of primary mediastinal yolk sac tumor with metastatic brain process in a 32-year-old male with a short survival period.

Improved survival of poor-risk non-seminomatous germ cell tumor patients: real-world data from a single institute in Japan.

OBJECTIVES: The International Germ Cell Cancer Collaborative Group Update Consortium showed the improved survival of patients with a non-seminomatous germ cell tumor. We updated the survival data of the non-seminomatous germ cell tumor patients treated at our hospital. PATIENTS AND METHODS: We analyzed the outcomes of 138 patients treated in 1981-2018. We compared the survival of the patients treated in the early (1981-99) and later (2000-18) periods and determined the groups' progression-free survival and overall survival using the Kaplan-Meier method. We used a web-based application of the International Germ Cell Cancer Collaborative Group Update model to calculate each patient's predicted 3-year progression-free survival. RESULTS: The 5-year progression-free survival rates of the good, intermediate and poor prognosis groups were 91, 83 and 64%, and their 5-year overall survival rates were 97, 89 and 82%, respectively. There were no significant differences in the progression-free survival or overall survival of the good and intermediate prognosis groups by treatment year. The 5-year progression-free survival of the poor prognosis group was almost identical in both treatment year (60 and 65%, respectively). By contrast, the 5-year overall survival in the later period (85%) was higher than that in the early period (70%). The median-predicted 3-year progression-free survival rates of the good, intermediate and poor prognosis groups were 92, 83 and 51% (P < 0.01), respectively. The concordance index for the good, intermediate and poor prognosis groups were 0.56, 0.79 and 0.67, respectively. CONCLUSION: The survival of our poor prognosis non-seminomatous germ cell tumor patients improved over time. The 5-year overall survival of patients treated in 2000-18 reached 85%.

Carinal Compression from Primary Mediastinal Germ Cell Tumor.

Mediastinal masses can present as a medical emergency when there is central airway obstruction, superior vena cava (SVC) syndrome, direct mediastinal extension of tumor, or obstruction of the central pulmonary vasculature. Diagnostic evaluation may include the need for invasive tissue biopsy under anesthesia, which can pose several distinct risks for patients. Among the many etiologies of mediastinal tumors, primary mediastinal germ cell tumors are a rare form with a favorable prognosis.

Case of testicular nonseminomatous germ cell tumor cancer soft tissue seeding after inguinal orchiectomy.

A 29-year-old patient presented to his primary care provider complaining of a painful right inguinal swelling. He was referred for inguinal hernia repair, but during surgery, an enlarged necrotic-appearing testicle was observed and removed. Pathology demonstrated a mixed non-seminomatous germ cell tumor (NSGCT) with evidence of tumor violation. After receiving BEPx3 for elevated post-operative AFP his tumor markers normalized. On surveillance, he was found to have several palpable masses around his inguinal incision. On soft tissue excision he was found to have residual teratoma within his soft tissues. We review the literature on germ cell tumor seeding and atypical recurrences.

A massive retroperitoneal mature teratoma from a "burned-out" testicular teratoma and seminoma.

Germ cell tumors are the most common nonhematologic malignancy of young men which often present with metastasis to the retroperitoneum, however a primary retroperitoneal mass should also be considered. The case presented herein reports a 42-year-old male presenting with a massive heterogenous retroperitoneal mass determined to be a mature cystic teratoma. Further investigation revealed a multifocal right testicular mass containing both a viable pure seminoma and a fibrous scar demonstrating germ cell neoplasia in situ thus representing the rare phenomenon of a "burned-out" mixed germ cell testicular tumor. When the radiologist is faced with a large retroperitoneal fat-containing mass, the differential includes a renal angiomyolipoma, liposarcoma, or germ cell tumor (whether primary or secondary). If pathology reveals a germ cell tumor, it is imperative to perform a thorough evaluation of the gonads, as it is much more common for a retroperitoneal germ cell tumor to be a metastasis from the gonads, rather than primary in origin.

Síndrome de teratoma creciente. Reporte de caso / Growing Teratoma Syndrome. A Case Report

Resumen El síndrome de teratoma creciente es una entidad en la cual existen modificaciones histológicas de un teratoma maligno inmaduro tratado con quimioterapia y con marcadores tumorales negativos a un teratoma maduro. Dada la baja incidencia de la patología, se presenta el caso de una paciente con antecedente de tumoración ovárica con reporte de teratoma inmaduro la cual fue extraída. Recibió quimioterapia y normalización de marcadores séricos. Posteriormente presentó la aparición de una tumoración pélvica, retroperitoneal y hepática que nuevamente requirió intervención quirúrgica, con reporte patológico de teratoma quístico maduro.

Abstract Growing teratoma syndrome is an entity in which there are histological modifications of an immature malignant teratoma treated with chemotherapy and with negative tumor markers to a mature teratoma. Given the low incidence of the pathology, a case of a patient with a history of ovarian tumors with report of immature teratoma which was extracted is reported. The patient received chemotherapy with normalization of serum markers. Subsequently she presented a pelvic, retroperitoneal and hepatic tumor that again required surgical intervention with pathological report of mature cystic teratoma.

Diagnostic and Imaging Features of a Non-seminomatous Germ Cell Tumor of the Testis: A Case Report and Review of the Literature.

Neoplasms involving the testes are uncommon. They account for up to 10% of all malignant diseases affecting the male genitourinary system and for around 2% of all malignant neoplasms in males. Testicular tumors are the third highest cause of mortality in males between the age of 20 and 40 years. We present a case of a young patient with right-sided scrotal swelling associated with pain. Ultrasonography, elastography, computed tomography, and magnetic resonance imaging features revealed non-seminomatous germ cell tumors of the testis. The patient underwent inguinal orchidectomy for the same and was sent for histopathological evaluation. The imaging diagnosis was consistent with the histopathological diagnosis. This case report adds to the knowledge of imaging features of testicular tumors and their identification based on imaging.

Metastatic Mature Teratoma and Growing Teratoma Syndrome in Patients with Testicular Non-Seminomatous Germ Cell Tumors.

Metastatic mature teratoma is a common radiologic and histopathologic finding after chemotherapy for metastatic non-seminomatous germ cell tumors. The leading theory for these residual tumors is the selective chemotherapy resistance of teratomas versus the high chemotherapy sensitivity of the embryonal components. Growing teratoma syndrome is a relatively rare phenomenon defined as an enlarging residual mass histologically proven to be a mature teratoma in the setting of normal serum tumor markers. Metastatic mature teratomas should be resected because of their malignant potential and occasional progression to growing teratoma syndrome with the invasion of the surrounding structures. CT is the preferred imaging modality for post-chemotherapy surveillance and should cover all sites of potential metastatic disease. This article reviews the clinical, pathologic, and multimodality imaging features of metastatic mature teratomas in patients with primary testicular non-seminomatous germ cell tumors.

Histiocytic sarcoma following combination chemotherapy for primary mediastinal germ cell tumor: a diagnostic dilemma.

Histiocytic sarcoma is considered an extremely rare condition. We herein report on a case of histiocytic sarcoma following combination chemotherapy for a primary mediastinal germ cell tumor in a 26-year-old Asian man who visited the General Medicine Department of a hospital with complaints of cough and high fever. Chest computed tomography (CT) imaging revealed a tumor (diameter 10.5 cm) in the anterior mediastinum, with no signs of metastasis, and CT-guided biopsy of the mediastinal tumor revealed the presence of some necrotic cartilages. The patient's serum α-fetoprotein (AFP) level was determined to be high at 160.4 ng/mL and a primary mediastinal non-seminomatous germ cell tumor was suspected, so the patient was referred to the Department of Urology. Despite the presence of severe thrombocytopenia, the patient was treated using a combination of chemotherapy and intermittent transfusion, which was able to normalize his serum AFP level. However, resection of the mediastinal tumor was unsuccessful due to persistent thrombocytopenia and the patient was subsequently transferred to our hospital for further examination and treatment. Despite management by hematologists, the condition of the patient did not improve; although his AFP level remained normal, the tumor increased in size and then metastasized to the liver and spleen. The general condition of the patient deteriorated and he died 9 months after his first visit. The patient was diagnosed with histiocytic sarcoma following a pathological autopsy. Due to the extremely rare incidence of histiocytic sarcoma, this condition should be a differential diagnosis and the appropriate tests must be conducted to give an exact treatment.

Surgical Management of Cervical Non-seminomatous Germ Cell Tumor Metastases.

OBJECTIVE/HYPOTHESIS: Testicular cancer is the most common malignancy of young males. Limited reports describe perioperative and long-term outcomes after surgical resection of metastatic, cervical, non-seminomatous germ cell tumors (NSGCT). The objective of this study was to investigate the effectiveness and safety of cervical lymphadenectomy in the management of metastatic NSGCT. STUDY DESIGN: Retrospective case series. METHODS: A single institution, retrospective review from 1998 to 2020 of patients with metastatic NSGCT who underwent cervical lymphadenectomy was conducted. Clinicopathological, surgical, and postoperative data were collected and analyzed. RESULTS: Sixty-eight predominantly white (91.0%) male patients with mean age 33.0 ± 11.3 years were included. Most (82.2%) presented with stage III disease at initial diagnosis. All patients had undergone primary platinum-based chemotherapy 1.0 to 22.7 months prior to selective ND. Surgery mainly involved nodal levels III (67.6%), IV (92.6%) and/or Vb (77.9%) and was frequently performed with concomitant thoracoabdominal NSGCT resections (63.2%). Cervical specimens predominantly revealed mature teratoma (83.8%) as solitary (69.1%) or component of mixed (14.7%) NSGCT. Ten (14.7%) perioperative complications occurred as vocal cord paresis (n = 6) from thoracic surgery and chyle leakage (n = 4). All resolved conservatively except two vocal cord paralyzes that required surgical repair due to tumor involvement of vagus nerve. Six instances of cervical recurrence occurred at median 12.5 (range, 5.8-38.6) months from ND, all re-demonstrating purely mature teratoma. The two-year cervical, non-cervical, and overall recurrence-free survivals were 83%, 55%, and 55%, respectively. Two-year disease-free and overall survivals were both 93%. CONCLUSIONS: Selective neck dissection is a safe, effective method for managing cervical NSGCT metastases. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1528-1534, 2021.

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

PURPOSE: Mediastinal 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 METHODS: We 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. RESULTS: Sixty-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%. CONCLUSION: Mediastinal 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.

Three distinct hematological malignancies from a single germ cell tumor: a case report.

BACKGROUND: The association between non seminomatous germ cell tumors (GCTs) and hematological malignancies of rare lineage has been described in the literature. In some of these cases there is evidence that the leukemia derives from a pluripotent primitive clone present in the original germ cell tumor. CASE PRESENTATION: We present a highly unusual case of a 23-year-old man of South Asian origin with a history of Klinefelter's syndrome who initially developed mediastinal non seminomatous GCT. Following treatment with surgery and standard chemotherapy he went on to develop three different hematological malignancies of distinct lineages in sequential fashion over a short time period. Despite treatment with multiple intensive chemotherapy regimens and a matched unrelated donor allogeneic stem cell transplant, he died 41 months after initial diagnosis of his GCT and 10 months after the first diagnosis of hematological malignancy. CONCLUSIONS: This is an extreme case that highlights the pluripotency and aggressiveness of these GCT-derived hematological malignancies, and the need for novel therapeutic approaches.