Decision-Making in Clival Mass Lesions: Risk Factors for Malignant Disease and an Illustrative Case Example.

Introduction Clival tumors are rare and heterogeneous. Although some benign prototypical sellar lesions may present as clival tumors, the likelihood of malignant disease is higher. Here we define a novel algorithm for the workup and management of clival masses through an illustrative case of colorectal adenocarcinoma metastasis to the clivus. Methods In this case report, the best practice guidelines for managing clival masses are described through a literature review and refined by senior author consensus. We conducted a focused systematic review to characterize the present case in the context of clival metastasis from gastrointestinal malignancy. Results An 83-year-old woman presented with 4 weeks of headaches and blurry vision. Examination revealed partial right abducens and left oculomotor palsies. Magnetic resonance imaging (MRI) identified a large, weakly enhancing sellar and clival mass with sphenoid sinus extension. An aggressive subtotal endoscopic endonasal resection was performed with removal of all sphenoid, clival, and sellar disease without cavernous sinus wall resection. Pathology confirmed colorectal adenocarcinoma; computed tomography (CT) imaging identified an ascending colon mass with metastases to the liver and mesenteric nodes. Palliative oncologic therapies were recommended, but she elected hospice, and died 3 months after initial presentation. Gastrointestinal clival metastases are exceedingly rare among sellar and clival pathologies, with eight prior cases reported, most of which presented with diplopia from abducens nerve involvement. Conclusion Clival masses are uncommon skull base lesions that are associated with more aggressive diseases. We present a consolidated framework for decision-making in these challenging patients, alongside an unusual case example that illustrates the importance of increased suspicion for malignant clinical entities in this setting.

Primary squamous cell carcinoma of the thyroid treated with concurrent chemoradiation and palliative immunotherapy: a case report.

BACKGROUND: Primary squamous cell carcinoma of the thyroid is a very rare malignancy with aggressive growth and poor prognosis. There is currently no consensus for treatment modality, however, most patients with primary squamous cell carcinoma of the thyroid are treated with surgery and adjuvant chemoradiation. CASE PRESENTATION: We report a rare case of primary squamous cell carcinoma of the thyroid in a 68-year-old White male who underwent chemoradiation and palliative immunotherapy after declining surgery. He was treated with intensity-modulated radiation therapy to 70 Gy in 35 fractions, with concurrent carboplatin-paclitaxel and palliative pembrolizumab. Local thyroid disease recurrence occurred at 6 months post-chemoradiation, and the patient died at 16 months post-chemoradiation. CONCLUSIONS: This is the first case report demonstrating the use of pembrolizumab as palliative therapy for primary squamous cell carcinoma of the thyroid. Our study also highlights the importance of chemoradiation in decreasing primary mass size and immunotherapy in preventing metastatic disease progression.

Thoracic endometriosis presenting as hemopneumothorax.

Thoracic endometriosis is very rare. Usually, the thorax is the most frequent affected site outside the pelvis. Common symptoms include chest pain, dyspnea, and hemoptysis. Common manifestations include pneumothorax, hemothorax, and pulmonary or pleural nodules. In addition, symptoms and manifestations can be "catamenial" happening a few days after menstruation onset. This disease can be debilitating, causing a significant impact on the quality of life of young women. We present a case of a young female who was referred to our hospital with recurrent right-sided pleural effusions and pneumothoraces. Pleural fluid drainage was consistent with hemothorax. Transvaginal ultrasound showed mild intraperitoneal fluid in the Cul-de-Sac. Due to concerns for thoracic endometriosis, video-assisted thoracoscopic surgery was performed confirming the diagnosis by pathology. Therapeutic pleurectomy with diaphragmatic repair and pleurodesis was performed. The patient was started on medroxyprogesterone acetate injections two weeks after with great clinical response.

Polymorphous low-grade neuroepithelial tumor of the young: Rare tumor and review of the literature.

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described low-grade neuroepithelial tumor with an infiltrative growth pattern and oligodendrocyte-like cells that are CD34 immunopositive. Correlating histology and results from molecular testing is critical to correctly diagnosing PLNTY, as its histologic appearance is similar to oligodendrogliomas and shares genetic abnormalities common to other low-grade epilepsy associated tumors (LEATs). In this case report, we describe a 31-year-old female with intractable epilepsy found to have a temporal mass and diagnosed with PLNTY after histopathologic and molecular testing. We describe the radiographic, histologic, and genetic features in relation to the epileptic and oncologic outcomes for this patient. Then, we compare these features and outcomes to other cases of PLNTY described in the literature.

The Discrepancy Between Standard Histologic WHO Grading of Meningioma and Molecular Profile: A Single Institution Series.

Introduction: Meningiomas are the most common primary central nervous system (CNS) tumor. They are most often benign, but a subset of these can behave aggressively. Current World Health Organization (WHO) guidelines classify meningiomas into three grades based on the histologic findings and presence or absence of brain invasion. These grades are intended to guide treatment, but meningiomas can behave inconsistently with regard to their assigned histopathological grade, influencing patient expectations and management. Advanced molecular profiling of meningiomas has led to the proposal of alternative molecular grading schemes that have shown superior predictive power. These include methylation patterns, copy number alterations, and mutually exclusive driver mutations affecting oncogenes, including BAP1, CDKN2A/B, and the TERT promoter, which are associated with particularly aggressive tumor biology. Despite the evident clinical value, advanced molecular profiling methods are not widely incorporated in routine clinical practice for meningiomas. Objective: To assess the degree of concordance between the molecular profile of meningiomas and the histopathologic WHO classification, the current method of predicting meningioma behavior. Methods: In a two-year single-institution experience, we used commercially available resources to determine molecular profiles of all resected meningiomas. Copy number aberrations and oncogenic driver mutations were identified and compared with the histopathologic grade. Results: One hundred fifty-one total meningioma cases were included for analysis (85.4% WHO grade 1, 13.3% WHO grade 2, and 1.3% grade 3). Chromosomal analysis of 124 of these samples showed that 29% of WHO grade 1 tumor featured copy number profiles consistent with higher grade meningioma, and 25% of WHO grade 2 meningiomas had copy number profiles consistent with less aggressive tumors. Furthermore, 8% harbored mutations in TERT, CDKN2A/B, or BAP1 of which 6% occurred in grade 1 meningiomas. Conclusions: Routine advanced molecular profiling of all resected meningiomas using commercially available resources allowed for identification of a significant number of meningiomas whose molecular profiles were inconsistent with WHO grade. Our work shows the clinical value of integrating routine molecular profiling with histopathologic grading to guide clinical decision making.

Advancing Fellowship Training in Selective Pathology.

CONTEXT.­: Program requirements for Selective Pathology fellowships in the United States were established by the Accreditation Council for Graduate Medical Education (ACGME) in 2011 to govern fellowships providing advanced training in surgical pathology, focused anatomic pathology, or focused clinical pathology. Selective Pathology entered the ACGME's Next Accreditation System in 2015 with the introduction of the Selective Pathology Milestones 1.0, a set of benchmarks for evaluating fellow progress in each of the 6 ACGME core competencies. In 2019, the ACGME convened a work group for a planned periodic update to these milestones. OBJECTIVE.­: To summarize changes to the Selective Pathology milestones. DESIGN.­: The study design featured expert opinion and survey. RESULTS.­: The Patient Care milestones for anatomic pathology-focused fellowships contain a renewed emphasis on both gross and microscopic examination, whereas for clinical pathology-focused fellowships, the emphasis is on interpretation of laboratory assays. The milestones for the non-Patient Care, non-Medical Knowledge competencies have been updated to a harmonized set of milestones designed to extend across all specialties and subspecialties. New to the milestones program is a supplemental guide that provides examples, suggested assessment tools, and references to aid in implementation. Public comments were supportive of the changes. CONCLUSIONS.­: The Milestones 2.0 are set for implementation in July 2021. Updates in the new milestones are aimed at facilitating training and harmonizing evaluation across subspecialties.

Rosette-forming glioneuronal tumor: an illustrative case and a systematic review.

BACKGROUND: Rosette-forming glioneuronal tumors (RGNTs) are rare, low-grade, primary CNS tumors first described in 2002 by Komori et al. RGNTs were initially characterized as a World Health Organization (WHO) grade I tumors typically localized to the fourth ventricle. Although commonly associated with an indolent course, RGNTs have the potential for aggressive behavior. METHODS: A comprehensive search of PubMed and Web of Science was performed through November 2019 using the search term "rosette-forming glioneuronal tumor." Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. English, full-text case reports and series with histopathological confirmation were included. Patient demographics, presentations, MRI features, tumor location, treatment, and follow-up of all 130 cases were extracted. RESULTS: A 19-year-old man with a history of epilepsy and autism presented with acute hydrocephalus. MRI scans from 2013 to 2016 demonstrated unchanged abnormal areas of cortex in the left temporal lobe with extension into the deep gray-white matter. On presentation to our clinic in 2019, the lesion demonstrated significant progression. The patient's tumor was identified as RGNT, WHO grade I. One hundred thirty patients were identified across 80 studies. CONCLUSION: RGNT has potential to transform from an indolent tumor to a tumor with more aggressive behavior. The results of our systematic review provide insight into the natural history and treatment outcomes of these rare tumors.

Cryptococcal Choroid Plexitis and Non-Communicating Hydrocephalus.

Cryptococcus neoformans is a fungus that commonly invades the central nervous system. While the choroid plexus, the site of the blood-cerebrospinal fluid barrier, serves as one potential entry point for the pathogen, disease involvement of the choroid plexus itself remains a very rare manifestation of Cryptococcus infection. In cases in which choroid plexus involvement blocks cerebrospinal fluid flow, obstructive hydrocephalus may occur. Here we report the case of a 63-year-old woman who presented with choroid plexitis causing obstructive hydrocephalus at the foramen of Monro. Endoscopic biopsy confirmed Cryptococcus neoformans, and the patient was successfully treated with amphotericin, flucytosine, and fluconazole. With proper recognition and treatment of this pathology, patients can fully recover from this condition.

Exosomes as drug delivery vehicle and contributor of resistance to anticancer drugs.

Exosomes are small membranous vesicles implicated in intercellular signalling. Through their uncanny ability to carry and deliver donor cellular cargo (biomolecules) to target cells, they exert a profound effect on the regular functioning of healthy cells and play a significant role in pathogenesis and progression of several diseases, including cancer. The composition and number of endogenously circulating exosomes frequently vary, which is often reflective of the pathophysiological status of the cell. Applicability of exosomes derived from normal cells as a drug carrier with or without modifying their intraluminal and surface components are generally tested. Conversely, exosomes also are reported to contribute to resistance towards several anti-cancer therapies. Therefore, it is necessary to carefully evaluate the role of exosomes in cancer progression, resistance and the potential use of exosomes as a delivery vehicle of cancer therapeutics. In this review, we summarize the recent advancements in the exploitation of exosomes as a drug delivery vehicle. We also discuss the role of exosomes in conferring resistance to anti-cancer therapeutics. While this review is focused on cancer, the exosome-based drug delivery and resistance is also applicable to other human diseases.

Spontaneous Regression of Atypical Teratoid Rhabdoid Tumor Without Therapy in a Patient With Uncommon Regional Inactivation of SMARCB1 ( hSNF5/INI1).

Atypical teratoid/rhabdoid tumor (ATRT) is a high-grade central nervous system tumor, with poor prognosis despite intensive multimodal therapy. Loss of nuclear immunostaining for INI1 due to inactivation of the hSNF5/INI1 tumor suppressor gene is pathognomonic of ATRT. We present a patient with congenital ATRT, who had spontaneous tumor regression without therapy, and is disease-free 4 years later. Tumor histopathology showed rhabdoid cells characteristic of ATRT, but immunohistochemistry revealed heterogeneous loss of nuclear INI1 staining. The populations of INI1-intact and INI1-deficient cells were separated by laser microdissection, for molecular analysis with DNA sequencing and fluorescence in situ hybridization. The INI1-negative cells were found to harbor a heterozygous deletion and truncating mutation of the hSNF5/INI1 locus, while the INI1-intact cells had 2 copies of the wild-type INI1 gene. To our knowledge, this is the first report of spontaneous regression of ATRT, with molecular heterogeneity for SMARCB1 inactivation, with no radiographic signs of recurrence at 4 years after diagnosis.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on Pathological Methods and Prognostic Factors in Vestibular Schwannomas.

TARGET POPULATION: Adults diagnosed with vestibular schwannomas. QUESTION 1: What is the prognostic significance of Antoni A vs B histologic patterns in vestibular schwannomas? RECOMMENDATION: No recommendations can be made due to a lack of adequate data. QUESTION 2: What is the prognostic significance of mitotic figures seen in vestibular schwannoma specimens? RECOMMENDATION: No recommendations can be made due to a lack of adequate data. QUESTION 3: Are there other light microscopic features that predict clinical behavior of vestibular schwannomas? RECOMMENDATION: No recommendations can be made due to a lack of adequate data. QUESTION 4: Does the KI-67 labeling index predict clinical behavior of vestibular schwannomas? RECOMMENDATION: No recommendations can be made due to a lack of adequate data. QUESTION 5: Does the proliferating cell nuclear antigen labeling index predict clinical behavior of vestibular schwannomas? RECOMMENDATION: No recommendations can be made due to a lack of adequate data. QUESTION 6: Does degree of vascular endothelial growth factor expression predict clinical behavior of vestibular schwannomas? RECOMMENDATION: No recommendations can be made due to a lack of adequate data. The full guideline can be found at: https://www.cns.org/guidelines/guidelines-management-patients-vestibular-schwannoma/chapter_6.

Entrustable Professional Activities for Pathology: Recommendations From the College of American Pathologists Graduate Medical Education Committee.

Competency-based medical education has evolved over the past decades to include the Accreditation Council for Graduate Medical Education Accreditation System of resident evaluation based on the Milestones project. Entrustable professional activities represent another means to determine learner proficiency and evaluate educational outcomes in the workplace and training environment. The objective of this project was to develop entrustable professional activities for pathology graduate medical education encompassing primary anatomic and clinical pathology residency training. The Graduate Medical Education Committee of the College of American Pathologists met over the course of 2 years to identify and define entrustable professional activities for pathology graduate medical education. Nineteen entrustable professional activities were developed, including 7 for anatomic pathology, 4 for clinical pathology, and 8 that apply to both disciplines with 5 of these concerning laboratory management. The content defined for each entrustable professional activity includes the entrustable professional activity title, a description of the knowledge and skills required for competent performance, mapping to relevant Accreditation Council for Graduate Medical Education Milestone subcompetencies, and general assessment methods. Many critical activities that define the practice of pathology fit well within the entrustable professional activity model. The entrustable professional activities outlined by the Graduate Medical Education Committee are meant to provide an initial framework for the development of entrustable professional activity-related assessment and curricular tools for pathology residency training.

14-Year-Old Boy With Mild Antecedent Neck Pain in Setting of Acute Trauma: A Rare Case of Benign Fibrous Histiocytoma of the Spine.

A 14-year-old boy presented to the emergency department with neck pain after a football accident. Imaging revealed a discrete, expansile, lytic, radiolucent mass extending anterior from the left C2 vertebral body. The differential diagnosis for this mass is broad and includes both benign and malignant lesions. A thorough history and physical examination, along with selective imaging and a tissue sample, are essential in making the correct diagnosis. We report a case of benign fibrous histiocytoma (BFH) in the cervical spine of a pediatric patient, present the diagnostic dilemma involved in diagnosing BFH, and review the literature to compare the characteristics of BFH with those of other benign bone lesions. To our knowledge, this is only the second reported case of BFH in the cervical spine of a pediatric patient.

Ectopic ganglion in cauda equina: case report.

Macroscopic ectopic or heterotopic ganglionic tissue within the cauda equina is a very rare pathological finding and is usually associated with spinal dysraphism. However, it may mimic genuine neoplasms of the cauda equina. The authors describe a 29-year-old woman with a history of back pain, right leg pain, and urinary incontinence in whom imaging demonstrated an enhancing mass located in the cauda equina at the L1-2 interspace. The patient subsequently underwent biopsy and was found to have a focus of ectopic ganglionic tissue that was 1.3 cm in greatest dimension. To the authors' knowledge, ectopic or heterotopic ganglionic tissue within the cauda equina in a patient without evidence of spinal dysraphism has never been reported. This patient presented with imaging and clinical findings suggestive of a neoplasm, and an open biopsy proved the lesion to be ectopic ganglionic tissue. The authors suggest that ectopic ganglionic tissue be added to the list of differential diagnoses of a space-occupying lesion arising from the cauda equina.

A Novel Method for Removing a Spinal Cord with Attached Cervical Ganglia from a Pediatric Decedent.

A diagnosis of child abuse is dependent on a comprehensive and accurate assessment of injury in the context of a thorough investigation. However, signatures of trauma are often subtle and interpretation can be very difficult. Recently, researchers have refocused their attention from the head to the neck in search of traumatic signatures of abusive head trauma. HCIFS has developed a technique to remove the cervical spinal cord with the ganglia attached that is less destructive and more time and cost efficient than alternative methods previously published. Once removed, the dorsal nerve roots and ganglia are evaluated for the presence of hemorrhage. The authors performed a small pilot study using the novel method to evaluate 20 decedents with a history of blunt force trauma and eight without a traumatic history. Fifteen of the traumatic deaths and two of the nontraumatic deaths were found to have dorsal nerve root and/or ganglia hemorrhage.