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Visual Abstract, There is ongoing debate as to whether cardiac complications of coronavirus disease 2019 (COVID-19) result from myocardial viral infection or are secondary to systemic inflammation and/or thrombosis. We provide evidence that cardiomyocytes are infected in patients with COVID-19 myocarditis and are susceptible to severe acute respiratory syndrome coronavirus 2. We establish an engineered heart tissue model of COVID-19 myocardial pathology, define mechanisms of viral pathogenesis, and demonstrate that cardiomyocyte severe acute respiratory syndrome coronavirus 2 infection results in contractile deficits, cytokine production, sarcomere disassembly, and cell death. These findings implicate direct infection of cardiomyocytes in the pathogenesis of COVID-19 myocardial pathology and provides a model system to study this emerging disease.

Background: Hypophysitis is primary or idiopathic or secondary to another disease process. The histologic subtypes of hypophysitis are lymphocytic, granulomatous, xanthomatous, xanthogranulomatous, or IgG4-related. Granulomatous hypophysitis is the second most common form and is characterized by multinucleated giant cells with granulomas and histiocytes. It can be idiopathic or secondary to another process such as infection, sarcoidosis, vasculitis, dendritic cell disorders, Crohn's disease (CD) or a reaction to rupture of a Rathke's cyst or pituitary adenoma. We present a case of granulomatous hypophysitis in a patient with CD who had resistance to corticosteroids but a dramatic response to immunosuppressive therapy with anti-tumor necrosis factor (TNF)-α therapy. Case description: A 43-year-old woman with a 9-year history of ileal and colonic CD presented to the Pituitary Center with headaches, visual disturbance, fatigue, nausea, and secondary amenorrhea. She was not on active therapy for her CD at the time of presentation and had no gastrointestinal symptoms. Hormonal evaluation revealed hyperprolactinemia, secondary hypothyroidism and adrenal insufficiency. MRI revealed a 12 × 12 × 19 mm sellar lesion abutting the optic chiasm, reported as a macroadenoma. The patient underwent endoscopic transsphenoidal biopsy of the pituitary mass. Pathology revealed granulomatous hypophysitis. Evaluation for secondary causes of hypophysitis, apart from CD, was negative. Despite a course of high dose prednisone, her symptoms and MRI findings worsened and she developed symptoms consistent with diabetes insipidus. Using a personalized medicine approach, she was started on anti-(TNF)-α therapy with infliximab combined with azathioprine, which are indicated for treatment of CD. Her headaches and polyuria resolved and her menstrual cycles resumed. MRI at 3 months and more than 1.5 years after initiation of anti-TNF-α therapy revealed durable resolution of the pituitary mass. Conclusion: To our knowledge, this is the first report of successful use of anti-TNF-α therapy for a patient with granulomatous hypophysitis, in this case associated with a previous diagnosis of CD. Although glucocorticoids are used frequently as first-line therapy for primary hypophysitis, granulomatous hypophysitis can be corticosteroid resistant and other immunosuppressive approaches may need to be considered within the context of the patient.

Spinal epidermoid tumors are rare, benign tumors that are either acquired from trauma, surgery, or lumbar puncture or arise as congenital lesions, particularly spinal dysraphisms. We report a case of a massive spinal epidermoid tumor and review the literature with a focus on the surgical outcomes. A 71-year-old female patient presented after a fall with subsequent symptoms of severe back and hip pain, as well as loss of motor strength in the left leg. Her magnetic resonance imaging demonstrated a T2/short tau inversion recovery hyperintense mass extending from the level of the T10–11 disc caudally through S2. A biopsy was recommended to determine whether the tumor was radio- or chemo-sensitive. The patient underwent a L4 laminectomy and a pearly-white tumor was encountered, with a subsequent biopsy confirming it to be an epidermoid tumor. The following conclusions can be drawn from a review of the literature. Spinal epidermoid tumors are more common in women and tend to present in younger patients (median age of 23). The majority of patients had acquired lesions (46%). In terms of surgical outcomes for adherent tumors, gross total resection was found to provide optimal outcomes, with 90% of patients improving clinically after surgery.

Background Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms “‘gastrointestinal stromal tumor’ AND brain AND metastasis”” was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included. Case presentation A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day). Conclusions Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.

Background: Intramedullary melanocytomas are exceedingly rare and their management is largely based on case reports and small clinical series. They have characteristic imaging and histologic findings that can aid in their diagnosis. Genetic testing may be required for definitive diagnosis and management guidance in ambiguous cases. Case Description: We present the case of a thoracic intramedullary meningeal melanocytoma in a patient unable to undergo an MRI. Conclusion: This is the first reported S-100-negative case with genetic testing to support the diagnosis of a rare intramedullary melanocytoma.

Introduction Glioblastoma rarely coincides with multiple sclerosis. Although registries have reported a higher proportion of brain tumors—most of which are glial—these events appear to be underreported. The relative contribution of JC virus (an oncogenic virus) and disease modifying therapies that may facilitate JC virus neurotropism and tumor-specific immune evasion remain unknown. Case report We present the case of a 64-year-old woman who developed a primary glioblastoma eight years after diagnosis of multiple sclerosis while on dimethyl fumarate. Conclusion Systematic reporting may help answer whether JC virus seropositivity and certain disease modifying therapies confer higher risk for glioblastoma in patients with multiple sclerosis.

Background. Meningiomas constitute one-third of all primary brain tumors. Although typically benign, about 20% of these tumors recur despite surgery and radiation, and may ultimately prove fatal. There are currently no effective chemotherapies for meningioma. We, therefore, set out to develop patient-derived orthotopic xenograft (PDOX) mouse models of human meningioma using tumor. Method. Of nine patients, four had World Health Organization (WHO) grade I tumors, five had WHO grade II tumors, and in this second group two patients also had recurrent (WHO grade III) meningioma. We also classified the tumors according to our recently developed molecular classification system (Types A, B, and C, with C being the most aggressive). We transplanted all 11 surgical samples into the skull base of immunodeficient (SCID) mice. Only the primary and recurrent tumor cells from one patient&mdash, both molecular Type C, despite being WHO grades II and III, respectively&mdash, led to the formation of meningioma in the resulting mouse models. We characterized the xenografts by histopathology and RNA-seq and compared them with the original tumors. We performed an in vitro drug screen using 60 anti-cancer drugs followed by in vivo validation. Results. The PDOX models established from the primary and recurrent tumors from patient K29 (K29P-PDOX and K29R-PDOX, respectively) replicated the histopathology and key gene expression profiles of the original samples. Although these xenografts could not be subtransplanted, the cryopreserved primary tumor cells were able to reliably generate PDOX tumors. Drug screening in K29P and K29R tumor cell lines revealed eight compounds that were active on both tumors, including three histone deacetylase (HDAC) inhibitors. We tested the HDAC inhibitor Panobinostat in K29R-PDOX mice, and it significantly prolonged mouse survival (p &lt, 0.05) by inducing histone H3 acetylation and apoptosis. Conclusion. Meningiomas are not very amenable to PDOX modeling, for reasons that remain unclear. Yet at least some of the most malignant tumors can be modeled, and cryopreserved primary tumor cells can create large panels of tumors that can be used for preclinical drug testing.

Idiopathic hypereosinophilic syndrome is a condition of unknown etiology characterized by proliferation of eosinophils and their infiltration into tissues. Although cardiac involvement is rare, eosinophilic myocarditis can lead to life-threating fulminant congestive heart failure. Treatment of patients with eosinophilic myocarditis is challenging as heart failure can be caused by biventricular dysfunction. To our knowledge, this is the first case reported in the literature describing a patient with acute severe biventricular heart failure caused by eosinophilic myocarditis with mural left ventricular apical thrombus who was successfully treated with implantation of a total artificial heart as a bridge to heart transplant.

• Gangliogliomas are rare neuroepithelial tumors composed of neoplastic mature ganglion cells in combination with glial cells.

Background Intraventricular cavernous malformations are relatively rare benign vascular malformations. Patients may be asymptomatic or present with headache, seizure, hemorrhage, or neurologic deficits. We report 2 cases of patients with cavernomas in the third ventricle and at the foramen of Monro. We also performed a systematic review of the literature to examine the clinical features and efficacy of the current standard of care for these lesions. Methods We performed the systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Multiple databases were queried; the title/abstract and MeSH keywords used included “cavernous malformation,” “cavernoma,” “cavernous hemangioma,” “cavernous angioma,” “foramen of Monro,” “third ventricle,” and “intraventricular,” along with “AND” and “OR” operators. Patient demographic and clinical data were collected for qualitative synthesis. Results Patients presented at a median age of 38 years; the most common symptom was headaches. Gross total resection was performed in 84.6% of patients, and 81.8% had clinical improvement with intervention. The incidence of intraventricular hemorrhage and hydrocephalus was 15.4% and 59%, respectively. Conclusions The specific location of the cavernoma determines clinical features seen and approach used in surgical resection. Ventriculoperitoneal shunting was not required in most cases, as hydrocephalus improved with removal of the obstruction at the foramen of Monro. Gross total resection appears to be the optimal management strategy in symptomatic patients and leads to a good outcome in most cases.

A previously healthy 50-year-old Chinese woman presented with a low-grade fever, a generalized headache, and chest pain of 2 to 3 weeks’ duration. She described intermittent sharp chest pain over the precordium that intensified when she lay down and shortness of breath after minimal exertion. Despite having lost her appetite, she had gained ≈10 pounds during the past month and had noticed ankle swelling. She denied having had arthralgia or skin rash and had not experienced any nocturnal dyspnea, wheezing, cough, expectoration, or hemoptysis. She had visited her relatives in the Middle East 6 months earlier, but her past medical history was uneventful. She had taken acetaminophen (Tylenol) tablets and a Chinese herbal preparation, but her symptoms continued. On physical examination, she appeared weak and ill. Her temperature was 36.7°C (98.0°F), and her pulse was 110 beats per minute, regular, and had normal volume and character. Her blood pressure was 115/70 mm Hg, which decreased to 90/70 mm Hg on inspiration; her respiratory rate was 22 breaths per minute. Carotid pulsations were normal. Jugular veins were distended to the angle of the mandible when the patient sat upright, but no further venous engorgement was noted on inspiration. There was mild mucosal pallor, but the oropharynx was otherwise normal. The first and second heart sounds were normal, and there were no clicks or gallops. A superficial scratchy systolic sound was heard intermittently over the left lower sternal region. Dullness to percussion, scattered inspiratory crackles, and diminished air entry were evident over both lung bases. Abdominal examination demonstrated a soft, tender liver palpable 2 cm below the right costal margin. Her pelvis and rectum showed no abnormality. A stool guaiac test was negative. Neurological examination was normal. There was moderate pitting edema below the level of the knees. Results of the initial …

A 37-year-old woman was referred to Hermann Hospital from a local health maintenance organization clinic for the evaluation of fatigue, chest pain, and syncope. The patient was in her normal state of health until approximately 6 months before admission, when she began suffering mild fatigue. Her fatigue initially consisted of effort intolerance. She reported having an increased amount of breathlessness when climbing the flight of stairs to her second-floor apartment. Approximately 4 months before her hospital admission, she had the first of four syncopal episodes. The first episode occurred as she proceeded to walk after a long period of standing. At that time, she sensed the onset of chest tightness and dizziness before losing consciousness. She did not initially seek medical attention for her fatigue and syncope. She reported having dizzy spells that were initially associated with chest tightness and mild breathlessness. Her dizzy spells, which initially occurred weekly, became more frequent such that they occurred daily during the month before her hospital admission. Her chest discomfort was described as a squeezing sensation that was substernal in location without radiation to any other position. It was usually associated with dizziness and breathlessness but never with nausea, vomiting, or diaphoresis. Her chest discomfort occurred at rest and with exertion. The three syncopal episodes that followed the first occurred approximately 1 month apart. Each of these episodes occurred as she proceeded to stand and walk from a sitting or lying position. Her syncope was always preceded by substernal chest pressure, dizziness, and breathlessness. The patient is employed as a school bus driver. She reported having symptoms of dizziness and near syncope frequently while driving the bus. There was a history of smoking for approximately 10 years, averaging a …