Mangum, Ross

Malignant transformation of intracranial nongerminomatous germ cell tumors (NGGCTs) is a rare but clinically relevant phenomenon. We present the case of a 13-year-old boy with a localized, pineal NGGCT. After an initial favorable response, tumor growth was noted while still on chemotherapy. Histopathologic characterization revealed that 40% of the tumor was embryonal rhabdomyosarcoma (RMS), consistent with potential malignant transformation. Due to the rare nature of NGGCT malignant transformation, the best clinical approach to these cases remains unclear. We explore existing cases, treatments, and outcomes of malignant transformation in intracranial NGGCTs to help inform future clinical decision-making and the establishment of treatment guidelines.

We present the case of a 12-year-old female who presented with progressive back pain and was found to have a localized mass in the lumbar spine. The resected tissue was characterized by epithelioid cells with a papillary appearance and high mitotic activity. Initial immunohistochemical analysis was consistent with a diagnosis of atypical meningioma. However, comprehensive molecular profiling detected a CRTC1::NCOA2 fusion with a novel NCOA2 gene rearrangement, leading to a revised descriptive diagnosis of epithelioid mesenchymal neoplasm with CRTC1::NCOA2 fusion. This specific fusion has only been reported in 2 other cases involving mesenchymal neoplasms of the palate and urinary bladder. While CRTC1 is frequently associated with MAML2 fusion in mucoepidermoid carcinomas, NCOA2 rearrangements occur in a variety of solid and hematologic malignancies. There is a paucity of information on the prognostic relevance of these fusion partners. This is the first reported case of a CRTC1::NCOA2 fusion in a pediatric patient with a spinal cord malignancy. The mechanistic significance and prognostic implications of this fusion will be discussed.

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive, malignant embryonal tumor with dismal long-term survival despite aggressive multimodal therapy. While this tumor typically presents in infancy or early childhood, there are published case reports of adult-onset ATRT. Making prognostic conclusions or therapeutic decisions for this older patient population remains challenging due to the paucity of these reports. A 25-year-old female with Down syndrome presented with dysphagia and facial droop and was found to have an avidly enhancing, cerebellopontine angle mass. Histology demonstrated sheets of rhabdoid cells with loss of INI1 expression, pathognomonic for ATRT. Further sequencing detected a frameshift SMARCB1 mutation and methylation profiling matched with high confidence to the MYC subclass of ATRT. The patient was treated with subtotal surgical resection and focal proton beam irradiation, followed by chemotherapy on a modified regimen due to concern for heightened risk of treatment-related toxicity. On most recent follow-up 22 months from diagnosis, the patient remains without evidence of disease. This report represents the first known case of ATRT in a young adult patient with Down syndrome, offering unique mechanistic insight into the tumorigenesis of ATRT. Further studies are needed to define an appropriate risk-adapted and standardized therapeutic approach for this patient population.

AbstractBackgroundRenal medullary carcinoma (RMC) is a diagnostically challenging, aggressive primary renal malignancy associated with abysmal survival. Delays in diagnosis contribute to most patients having diffusely metastatic disease at the time of initial presentation.MethodsWe present the case of a 13‐year‐old African American male with sickle cell trait who presented with a renal mass and hematuria. Evaluation included imaging, fluid cultures, and cytologic assessment.ResultsPatient was diagnosed with RMC based on cytologic assessment of sub‐centimeter fluid collections aspirated from the left kidney at the time of cortical biopsy for suspected renal mass. The additional fluid aspiration in conjunction with renal biopsy was an atypical but crucial step in early diagnosis.ConclusionCytomorphologic evaluation of fluid biospecimens is not currently part of the standard work‐up for patients with renal masses but, when available, can provide crucial information that reduces time to diagnosis. Prompt symptom recognition and treatment initiation may improve patient outcomes.

Abstract Background Craniopharyngioma is a histologically benign tumor of the suprasellar region for which survival is excellent but quality of life is often poor secondary to functional deficits from tumor and treatment. Standard therapy consists of maximal safe resection with or without radiation therapy. Few prospective trials have been performed, and response assessment has not been standardized. Methods The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee devised consensus guidelines to assess craniopharyngioma response prospectively. Results Magnetic resonance imaging is the recommended radiologic modality for baseline and follow-up assessments. Radiologic response is defined by 2-dimensional measurements of both solid and cystic tumor components. In certain clinical contexts, response to solid and cystic disease may be differentially considered based on their unique natural histories and responses to treatment. Importantly, the committee incorporated functional endpoints related to neuro-endocrine and visual assessments into craniopharyngioma response definitions. In most circumstances, the cystic disease should be considered progressive only if growth is associated with acute, new-onset or progressive functional impairment. Conclusions Craniopharyngioma is a common pediatric central nervous system tumor for which standardized response parameters have not been defined. A RAPNO committee devised guidelines for craniopharyngioma assessment to uniformly define response in future prospective trials.