A Machine Learning Model to Predict the Histology of Retroperitoneal Lymph Node Dissection Specimens.

BACKGROUND/AIM: While post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) benefits patients with teratoma or viable germ cell tumors (GCT), it becomes overtreatment if necrosis is detected in PC-RPLND specimens. Serum microRNA-371a-3p correctly predicts residual viable GCT with 100% sensitivity; however, prediction of residual teratoma in PC-RPLND specimens using current modalities remains difficult. Therefore, we developed a machine learning model using CT imaging and clinical variables to predict the presence of residual teratoma in PC-RPLND specimens. PATIENTS AND METHODS: This study included 58 patients who underwent PC-RPLND between 2005 and 2019 at the University of Tsukuba Hospital. On CT imaging, 155 lymph nodes were identified as regions of interest (ROIs). The ResNet50 algorithm and/or Support Vector Machine (SVM) classification were applied and a nested, 3-fold cross-validation protocol was used to determine classifier accuracy. RESULTS: PC-RPLND specimen analysis revealed 35 patients with necrosis and 23 patients with residual teratoma, while histology of 155 total ROIs showed necrosis in 84 ROIs and teratoma in 71 ROIs. The ResNet50 algorithm, using CT imaging, achieved a diagnostic accuracy of 80.0%, corresponding to a sensitivity of 67.3%, a specificity of 90.5%, and an AUC of 0.84, whereas SVM classification using clinical variables achieved a diagnostic accuracy of 74.8%, corresponding to a sensitivity of 59.0%, a specificity of 88.1%, and an AUC of 0.84. CONCLUSION: Our machine learning models reliably distinguish between necrosis and residual teratoma in clinical PC-RPLND specimens.

Initial surveillance in men with marker negative clinical stage IIA non-seminomatous germ cell tumours.

OBJECTIVES: To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. PATIENTS AND METHODS: Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. RESULTS: Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. CONCLUSIONS: Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.

Non-invasive differential diagnosis of teratomas from other intracranial germ cell tumours using MRI-based fractal and radiomic analyses.

OBJECTIVES: The histologic subtype of intracranial germ cell tumours (IGCTs) is an important factor in deciding the treatment strategy, especially for teratomas. In this study, we aimed to non-invasively diagnose teratomas based on fractal and radiomic features. MATERIALS AND METHODS: This retrospective study included 330 IGCT patients, including a discovery set (n = 296) and an independent validation set (n = 34). Fractal and radiomic features were extracted from T1-weighted, T2-weighted, and post-contrast T1-weighted images. Five classifiers, including logistic regression, random forests, support vector machines, K-nearest neighbours, and XGBoost, were compared for our task. Based on the optimal classifier, we compared the performance of clinical, fractal, and radiomic models and the model combining these features in predicting teratomas. RESULTS: Among the diagnostic models, the fractal and radiomic models performed better than the clinical model. The final model that combined all the features showed the best performance, with an area under the curve, precision, sensitivity, and specificity of 0.946 [95% confidence interval (CI): 0.882-0.994], 95.65% (95% CI: 88.64-100%), 88.00% (95% CI: 77.78-96.36%), and 91.67% (95% CI: 78.26-100%), respectively, in the test set of the discovery set, and 0.944 (95% CI: 0.855-1.000), 85.71% (95% CI: 68.18-100%), 94.74% (95% CI: 83.33-100%), and 80.00% (95% CI: 58.33-100%), respectively, in the independent validation set. SHapley Additive exPlanations indicated that two fractal features, two radiomic features, and age were the top five features highly associated with the presence of teratomas. CONCLUSION: The predictive model including image and clinical features could help guide treatment strategies for IGCTs. CLINICAL RELEVANCE STATEMENT: Our machine learning model including image and clinical features can non-invasively predict teratoma components, which could help guide treatment strategies for intracranial germ cell tumours (IGCT). KEY POINTS: • Fractals and radiomics can quantitatively evaluate imaging characteristics of intracranial germ cell tumours. • Model combing imaging and clinical features had the best predictive performance. • The diagnostic model could guide treatment strategies for intracranial germ cell tumours.

Testicular Radiomics To Predict Pathology At Time of Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminomatous Germ Cell Tumor.

INTRODUCTION: Testicular germ cell tumors are the most common malignancy in young adult males. Patients with metastatic disease receive standard of care chemotherapy followed by retroperitoneal lymph node dissection for residual masses >1cm. However, there is a need for better preoperative tools to discern which patients will have persistent disease after chemotherapy given low rates of metastatic germ cell tumor after chemotherapy. The purpose of this study was to use radiomics to predict which patients would have viable germ cell tumor or teratoma after chemotherapy at time of retroperitoneal lymph node dissection. PATIENTS AND METHODS: Patients with nonseminomatous germ cell tumor undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) between 2008 and 2019 were queried from our institutional database. Patients were included if prechemotherapy computed tomography (CT) scan and postchemotherapy imaging were available. Semiqualitative and quantitative features of residual masses and nodal regions of interest and radiomic feature extractions were performed by 2 board certified radiologists. Radiomic feature analysis was used to extract first order, shape, and second order statistics from each region of interest. Post-RPLND pathology was compared to the radiomic analysis using multiple t-tests. RESULTS: 45 patients underwent PC-RPLND at our institution, with the majority (28 patients) having stage III disease. 24 (53%) patients had teratoma on RPLND pathology, while 2 (4%) had viable germ cell tumor. After chemotherapy, 78%, 53%, and 33% of patients had cystic regions, fat stranding, and local infiltration present on imaging. After radiomic analysis, first order statistics mean, median, 90th percentile, and root mean squares were significant. Strong correlations were observed between these 4 features;a lower signal was associated with positive pathology at RPND. CONCLUSIONS: Testicular radiomics is an emerging tool that may help predict persistent disease after chemotherapy.

Diffusion-weighted imaging in pediatric extracranial germ cell tumors.

BACKGROUND: Germ cell tumors (GCTs) comprise a rare and heterogeneous group of neoplasms presenting different clinical and histological characteristics, leading to a challenging scenario in clinical practice. Diffusion-weighted imaging (DWI) has been suggested as an indirect marker of tumor density and cellularity and could be used to monitor therapeutic response. However, its role in pediatric GCTs needs to be clarified. PURPOSE: Here, we evaluated the features of DWI in pediatric extracranial GCTs in a reference Brazilian institution. MATERIAL AND METHODS: We included 43 pediatric patients with primary GCTs treated between 2008 and 2022 in Hospital de Amor de Barretos. The patients' MRI images included T1-weighted without contrast, T2-weighted, DWI and apparent diffusion coefficient (ADC) maps. DWI was evaluated in the section that exhibited the greatest restricted diffusion in the largest hypersignal area of the image. The lowest ADC value was determined to define the region of interest (ROI). We used a small ROI, avoiding necrotic, adipose tissue, noisy or nonenhancing lesion voxels as recommended. ROI determination was established by visual inspection by two radiologists in accordance. We used two values of b (b = 50 mm2/s or b = 800) for ADC values. RESULTS: The highest mean ADC (mADC) value was observed in pure teratomas (1,403.50 ± 161.76 x10-3 mm2/s; mean ± SD) compared to other histologies (yolk sac, mixed teratoma, dysgerminoma and mixed GCT) of GCT (p<0.001). Furthermore, ROC analysis determined a cutoff mADC value of 1,179.00 x 10-3 mm2/s that differentiated pure teratomas from the other GCT histologies with a sensitivity of 95.8% and a specificity of 92.9% (AUC = 0.979; p<0.01). A significant increase in mADC was observed for malignant GCTs in treatment (1,197.00 ± 372.00 mm2/s; p<0.001) compared to that exhibited at the time of diagnosis (780.00 ± 168.00 mm2/s; mean ± SD. Our findings suggest that mADC assessment could be used as a tool to distinguish pure teratomas from malignant CGT histologies at diagnosis. Additionally, we demonstrated reasonable evidence that it could be used as a complementary tool to monitor treatment response in patients with malignant GCT.

Treatment Course and Outcomes of Intracranial Teratomas in Pediatric Patients: A Retrospective 15-Year Case Series Study.

INTRODUCTION: There is no standard treatment paradigm for intracranial teratomas, a rare subset of primary intracranial non-germinomatous germ cell tumors (NGGCT), which comprise less than 1% of pediatric brain tumors. This case series retrospectively analyzes treatment and outcomes of pediatric intracranial teratomas from a single institution. METHODS: Authors reviewed a comprehensive pathology database at Stanford's Lucile Packard Children's Hospital for intracranial teratomas in pediatric patients treated from 2006 to 2021; their demographics, treatment, and clinical course were analyzed. RESULTS: Among 14 patients, median follow-up time was 4.6 years and mean age at diagnosis was 10.5 years. Ten had elevated tumor markers and underwent chemotherapy as initial treatment for NGGCT. Ultimately, these patients all required surgery for progressive or residual disease. Two patients did not undergo radiation. After biopsy or resection, 8 patients had pure mature teratoma, five had mixed germ cell tumor with teratoma component, and one had immature teratoma. The patient with immature teratoma died during chemotherapy from septic shock. No patients experienced recurrence. Common sequelae were endocrine (42.8%) and eye movement (50.0%) abnormalities. DISCUSSION/CONCLUSION: We highlight the variable treatment course and outcome for pediatric patients with intracranial teratomas. Elevated tumor markers at presentation, along with imaging findings, favor chemotherapy initiation for presumed NGGCT. Resection of residual tumor is recommended even if tumor markers return to normal. Prognosis remains excellent; no patients had recurrence with a median follow-up of 4.6 years.

​Occult extracranial malignancy after complete remission of pineal mixed germ cell tumors: a rare case report and literature review.

BACKGROUND: ​Extracranial metastasis can occur in intracranial germ cell tumors (GCTs), but it is very rare. Recurrence or metastasis of non-germinomatous germ cell tumors (NGGCTs) is often accompanied by elevated tumor markers. ​Occult extracranial metastases or recurrences with negative markers are often difficult to detect in time, resulting in a very poor prognosis. CASE PRESENTATION: A 12-year-old boy was admitted to our institution with dizziness, headache, vomiting, and sleepiness. Magnetic resonance imaging (MRI) showed a pineal mass, accompanied by a significant increase in serum alpha-fetoprotein (AFP). The patient subsequently underwent total removal of the tumor. Pathology revealed that the tumor was a mixed GCT, consisting of mature teratoma, germinoma, and yolk sac tumor. Intracranial GCT achieved complete remission after intensive adjuvant chemotherapy and radiotherapy. Regular follow-up MRI revealed no recurrence of the intracranial tumor and continued monitoring of tumor markers revealed no abnormalities. ​Eight months later, the patient was readmitted due to progressive abdominal pain. Imaging and physical examination revealed abdominal occupation and lymphatic mass in the neck. He received salvage chemotherapy, anti-PD-1 immunotherapy, and palliative chemotherapy, but still developed multiple organ dysfunction syndromes (MODS) due to tumor progression and eventually died after one month. CONCLUSIONS: ​This profound case suggests that intracranial NGGCTs may develop occult extracranial malignancy, which can be very severe at the time of clinical symptoms and has an extremely poor prognosis. Therefore, in addition to tumor marker monitoring, regular follow-up with extracranial imaging may be warranted to detect extracranial tumors as early as possible, although perhaps not as frequently as with neuroimaging.

Imaging Techniques to Differentiate Benign Testicular Masses from Germ Cell Tumors.

PURPOSE OF REVIEW: To discuss role of different diagnostic imaging modalities in differentiation of benign testicular masses from seminomatous germ cell tumors (SGCTs) and non-seminomatous GCTs (NSGCTs). RECENT FINDINGS: New modalities of ultrasonography, including contrast enhancement and shear wave elastography, may help differentiate between benign and malignant intratesticular lesions. Ultrasonography remains the recommended imaging modality for initial evaluation of testicular masses. However, MRI can be used to better define equivocal testicular lesions on US.

Malignant Germ Cell Tumors of the Ovary: Clinical and Imaging Features.

Ovarian malignant germ cell tumors are a diverse set of masses originating from the primitive gonadal germ cells, often in young females. They have useful imaging and clinical features, including serum tumor marker elevation, that may aid the radiologist at the time of diagnosis, and also during follow-up. Accurate and timely diagnosis is essential, as standard-of-care therapies lead to a high rate of cancer remission.

[A Case of Hepatic Undifferentiated Embryonal Sarcoma in an Adult].

A 20-year-old woman was admitted with abdominal pain and a cystic liver tumor. A hemorrhagic cyst was suspected. Contrast-enhanced computed tomography(CT)and magnetic resonance imaging(MRI)revealed a space-occupying solid mass in the right lobule. Positron emission tomography(PET)-CT revealed 18F-fluorodeoxyglucose uptake in the tumor. We performed a right hepatic lobectomy. Histopathological evaluation of the resected tumor revealed an undifferentiated embryonal sarcoma of the liver(UESL). The patient refused adjuvant chemotherapy but showed no recurrence 30 months postoperatively. UESL is a rare malignant mesenchymal tumor that occurs in infants and children. It is extremely rare and is associated with poor prognosis in adults. In this report, we described a case of adult UESL.

German specialists treating testicular cancer follow different guidelines with resulting inconsistency in assessment of retroperitoneal lymph-node metastasis: clinical implications and possible corrective measures.

BACKGROUND: Testicular germ cell tumors (GCTs) are aggressive but highly curable tumors. To avoid over/undertreatment, reliable clinical staging of retroperitoneal lymph-node metastasis is necessary. Current clinical guidelines, in their different versions, lack specific recommendations on how to measure lymph-node metastasis. OBJECTIVE: We aimed to assess the practice patterns of German institutions frequently treating testicular cancer for measuring retroperitoneal lymph-node size. METHODS: An 8-item survey was distributed among German university hospitals and members of the German Testicular Cancer Study Group. RESULTS: In the group of urologists, 54.7% assessed retroperitoneal lymph nodes depending on their short-axis diameter (SAD) (33.3% in any plane, 21.4% in the axial plane), while 45.3% used long-axis diameter (LAD) for the assessment (42.9% in any plane, 2.4% in the axial plane). Moreover, the oncologists mainly assessed lymph-node size based on the SAD (71.4%). Specifically, 42.9% of oncologists assessed the SAD in any plane, while 28.5% measured this dimension in the axial plane. Only 28.6% of oncologists considered the LAD (14.3% in any plane, 14.3% in the axial plane). None of the oncologists and 11.9% of the urologists (n = 5) always performed an MRI for the initial assessment, while for follow-up imaging, the use increased to 36.5% of oncologists and 31% of urologists. Furthermore, only 17% of the urologists, and no oncologists, calculated lymph-node volume in their assessment (p = 0.224). CONCLUSION: Clear and consistent measurement instructions are urgently needed to be present in all guidelines across different specialistic fields involved in testicular cancer management.

Mimicker of Osteoblastic Skeletal Metastasis on 18 F-FDG PET/CT Scan in a Case of Primary Mediastinal Germ Cell Tumor.

ABSTRACT: Primary mediastinal germ cell tumors are uncommon tumors, of which the nonseminomatous type is more likely to metastasize than the seminomatous type. Primary mediastinal germ cell tumors may also present with superior vena cava obstruction. Here, we present this case of primary mediastinal germ cell tumor with superior vena cava obstruction causing dilatation of collaterals in dorsal intravertebral venous plexus, which strongly mimics sclerotic skeletal lesions/metastasis on a Contrast-enhanced CT scan and also appears FDG avid on PET scan. Herein, we can differentiate the two by just a simple review of plain CT scan image.

Recurrence of primitive germ cell tumour 20 years on.

We present a case of a woman in her 20s, with a prior history of paediatric sacrococcygeal germ cell tumour, presenting with a 6-month history of perianal pain. An MRI pelvis revealed a heterogeneous soft tissue mass causing destruction of the sacrococcygeal bone. A staging CT demonstrated metastatic deposits in the lungs and hypodense foci in the liver suspicious of metastatic disease. Her alpha-fetoprotein levels were raised and a CT-guided biopsy was in keeping with recurrent germ cell tumour. She was referred to a national centre for the treatment of germ cell tumours in adults and was rechallenged with cisplatin-based multiagent chemotherapy with a curative intent. This case raises the important question of how long we should follow-up these patients and whether they can ever be safely discharged from oncology surveillance.

The Importance of Repeat Imaging Prior to Treatment Decision-making in Testicular Cancer: Commentary From the Inaugural Global Society of Rare Genitourinary Tumors Summit.

Testicular cancer is a rare cancer that often affects young and otherwise healthy patients. Imaging plays a critical role in the staging and surveillance of patients with testicular cancer. Indeterminate findings on staging or surveillance imaging, can lead to challenging management decisions for clinicians and patients. In this article, we review the importance of short-interval, repeat imaging for several scenarios faced by patients with testicular cancer and their clinicians. The challenging scenarios and recommendations provided in this article summarize the discussion from the inaugural Global Society of Rare Genitourinary Tumors (GSRGT) Summit held on December 11-12, 2020.

Should we reduce routine surveillance imaging in pediatric germ cell tumors?

This paper retrospectively investigated the site and the detection method of relapses in children and adolescents with malignant germ cell tumors enrolled in the TCGM-AIEOP-2004 Study and subsequently developed a relapse, in order to evaluate a possible reduction in radiological exposure during follow-up. Including all malignant cases, serum tumor markers identified a relapse in more than 70% and, according to the selection criteria published by Children Oncology Group in 2018, in more than 90% of cases. These results confirm the importance of serum tumor markers as a relapse detection method, with possible reduction of radiology exams in specific subgroups.

Expanded Endoscopic Endonasal Transtuberculum Approach for Resection of Germ Cell Tumor.

We present the case of a 16-year-old with short stature, fatigue, memory impairment, and pituitary gland failure. Imaging and cerebrospinal fluid (CSF) studies supported the diagnosis of a suprasellar nongerminomatous germ cell tumor with no clear radiologic disease in the spine; however, a single atypical cell was present in the CSF. After a period of external drainage via an Ommaya device, he was treated with chemotherapy, followed by craniospinal radiation. Three months post completion of chemoradiotherapy, he had ongoing residual macroscopic enhancing disease anatomically located in the basal third ventricle and intimately related to pituitary stalk and basal thalamoperforators. In order to maximize his chance of progression-free survival, a decision was made to surgically resect the lesion via an expanded endoscopic endonasal approach with planned stalk sacrifice because of the known pituitary gland failure. In Video 1, the technical nuances underpinning the use of an expanded endoscopic endonasal transtuberculum transchiasmatic sulcus approach to resect the adherent lesion in a postradiated field in its entirety are presented. We emphasize the strategies for perforator preservation including thalamoperforators and superior hypophyseal arteries to avoid ischemic injury and visual dysfunction, respectively. Postoperative scans demonstrated gross total resection without any ischemic injury. The patient was discharged without any neurologic deficit, visual dysfunction, or CSF leak.