Combined translabyrinthine, anterior petrosal approach for resection of collision vestibular schwannoma and petrous apex meningioma in neurofibromatosis type 2, with auditory brainstem implant placement

The natural history of neurofibromatosis type 2 (NF2) is profound bilateral hearing loss. The decision to pursue microsurgery may be more complicated in NF2 than with sporadic tumors. Schwannomas in NF2 often occur with other skull base tumors. Treatment should be tailored to preserve auditory perception for as long as possible. The authors present the case of a man with NF2 and a vestibular schwannoma who has poor hearing on the same side as a large petrous apex meningioma, both opposite to a well-hearing ear. This case highlights surgical decision-making and technical nuances during resection of collision tumors in NF2. The video can be found here: https://stream.cadmore.media/r10.3171/2021.7.FOCVID21130

Mutational signature profiling classifies subtypes of clinically different mismatch repair deficient tumors with a differential immunogenic response potential

ABSTRACTBackgroundMismatch repair (MMR) deficiency is the hallmark of tumors from Lynch syndrome (LS), sporadic MLH1 hypermethylated, and Lynch-like syndrome (LLS), but there is a lack of understanding of the variability in their mutational profiles based on clinical phenotypes. The aim of this study was to perform a molecular characterization to identify novel features that can impact tumor behavior and clinical management.MethodsWe tested 105 MMR-deficient colorectal cancer tumors (25 LS, 35 LLS, and 45 sporadic) for global exome microsatellite instability, cancer mutational signatures, mutational spectrum and neoepitope load.Results78% of tumors showed high contribution of MMR-deficient mutational signatures, high level of global exome microsatellite instability, loss of MLH1/PMS2 protein expression and included sporadic tumors. 22% of tumors showed weaker features of MMR deficiency, 73% lost MSH2/MSH6 expression and included half of LS and LLS tumors. Remarkably, 9% of all tumors lacked global exome microsatellite instability. Lastly, HLA-B07:02 could be triggering the neoantigen presentation in tumors that show the strongest contribution of MMR-deficient tumors.ConclusionsNext-generation sequencing approaches allow for a granular molecular characterization of MMR-deficient tumors, which can be essential to properly diagnose and treat patients with these tumors in the setting of personalized medicine.

Diagnosis of Lynch Syndrome and Strategies to Distinguish Lynch-Related Tumors from Sporadic MSI/dMMR Tumors

Microsatellite instability (MSI) is a hallmark of Lynch syndrome (LS)-related tumors but is not specific to it, as approximately 80% of MSI/mismatch repair-deficient (dMMR) tumors are sporadic. Methods leading to the diagnosis of LS have considerably evolved in recent years and so have tumoral tests for LS screening and for the discrimination of LS-related to MSI-sporadic tumors. In this review, we address the hallmarks of LS, including the clinical, histopathological, and molecular features. We present recent advances in diagnostic and screening strategies to identify LS patients. We also discuss the pitfalls associated with the current strategies, which should be taken into account to improve the diagnosis of LS and avoid inappropriate clinical management.

DISSEMINATED GASTROINTESTINAL STROMAL TUMOR IN PREGNANCY. A CASE REPORT

Background. Gastrointestinal stromal tumor (GIST ) is a rare neoplasm with an incidence of only 10–20 cases per million population. All gastrointestinal neoplasms may have malignant potential and most of them are sporadic tumors. GIST occurring during pregnancy is extremely rare, therefore, surgeons face challenging ethical, surgical and oncological issues. Case. We describe a clinical cause of GIST found at the 16–17-th week of pregnancy in a 31-year-old woman. The patient was under the supervision of obstetricians-gynecologists, radiologists and oncologists, and a weekly ultrasound examination was performed. Caesarean delivery was performed at the 26th week of pregnancy due to disease progression and in order to start anticancer therapy as soon as possible. Conclusion. We described the first reported case of a successful treatment in a 31-yearold pregnant patient with GIST of the small intestine complicated by peritoneal carcinomatosis and ascites. We compared our case with other reported cases of GIST during pregnancy and discussed the problems faced by both patients and surgeons. There are no recommendations on the optimal timing of tumor resection during pregnancy, and therefore key decisions must be made in a multidisciplinary team (MDT ), taking into account the wishes of the patient. Our clinical case demonstrates the feasibility of changing the approaches to the management and treatment of patients with intraperitoneal dissemination, as well as emphasizes the importance of interdisciplinary team including oncologists, obstetricians, gynecologists, neonatologists and other specialists.

Genomics and Epigenomics in Parathyroid Neoplasia: from Bench to Surgical Pathology Practice

The majority of parathyroid disease encountered in routine practice is due to single parathyroid adenoma, of which the majority arise as sporadic tumors. This is usually a straightforward diagnosis in endocrine pathology when in the appropriate clinical setting, although subsets of cases will exhibit atypical histological features that may warrant additional immunohistochemical and genetic analyses to estimate the malignant potential. Parathyroid carcinomas on the other hand, are bona fide malignant tumors characterized by their unequivocal invasion demonstrated through routine histology or metastasis. The ultimate endpoint for any molecular marker discovered through laboratory investigations is to be introduced in clinical routine practice and guide the surgical pathologist in terms of diagnostics and prognostication. For parathyroid tumors, the two main diagnostic challenges include the distinction between parathyroid adenoma and parathyroid carcinoma, as well as the pinpointing of hereditable disease for familial screening purposes. While numerous markers on genetic, epigenetic, and protein levels have been proposed as discriminative in these aspects, this review aims to condense the scientific coverage of these enigmatic topics and to propose a focused surgical pathology approach to the subject.

Anesthetic Management of a Large Retroperitoneal Paraganglioma: A Rare Case Report

Paragangliomas are rare tumors derived from the neural crest cells. Most of the paragangliomas occur as sporadic tumors. The commonest incidence occurs in the second and third decade of life with a slight male preponderance. Clinically patients with a retroperitoneal paraganglioma often present with back pain or a palpable mass. There is a 5% incidence of turning into malignancy and these tumors are associated with a high risk of morbidity and mortality from cardiovascular complications. Management for paragangliomas typically involves complete surgical excision. A multi-disciplinary approach is suggested for a better outcome of the procedure

Clinical Outcomes in Patients With Colon Cancer With Microsatellite Instability of Sporadic or Familial Origin Treated With Adjuvant FOLFOX With or Without Cetuximab: A Pooled Analysis of the PETACC8 and N0147 Trials

PURPOSE The microsatellite instability (MSI) or deficient mismatch repair (dMMR) phenotype is usually regarded as a single biologic entity, given the absence of comparative analyses regarding prognosis and response to chemotherapy between sporadic and familial dMMR cancers. PATIENTS AND METHODS Patients with stage III colon cancers were randomly assigned to FOLFOX (leucovorin, fluorouracil, and oxaliplatin) with or without cetuximab in 2 large adjuvant phase III trials (N = 5,577). Among patients with MSI and KRAS exon 2 wild-type (WT) tumors, the prognostic and predictive impacts of sporadic versus familial dMMR cancers and BRAF V600E mutational status were determined. Multivariable Cox proportional hazards models were used to assess disease-free survival (DFS) by treatment arm, adjusting for age, sex, tumor grade, Eastern Cooperative Oncology Group performance status, pT/pN stage, and primary tumor location. RESULTS Among patients with MSI status with complete data for dMMR mechanism analysis (n = 354), 255 (72%) had sporadic ( BRAF mutation and/or MLH1 methylation) and 99 (28%) had familial tumors ( BRAF WT and unmethylated MLH1 or loss of MSH2/MSH6/PMS2 protein expression). A large proportion of dMMR sporadic tumors were mutated for BRAF (n = 200). In patients treated with FOLFOX, DFS did not differ statistically by dMMR mechanism, whereas in patients treated with FOLFOX plus cetuximab, those with sporadic tumors had worse DFS than those with familial cancers (multivariable hazard ratio, 2.69; 95% CI, 1.02 to 7.08; P = .04). Considering the predictive utility, the interaction between treatment and dMMR mechanism was significant ( P = .03). Furthermore, a nonsignificant trend toward a deleterious effect of adding cetuximab to FOLFOX was observed in patients with BRAF-mutant but not BRAF WT tumors. CONCLUSION The addition of cetuximab to adjuvant FOLFOX was associated with shorter DFS in patients with sporadic dMMR colon cancer. Additional studies are needed to validate these results in metastatic disease.