Vulvar Cutaneous Myxoma in a Patient With Carney Complex: Avoiding Pitfalls of Myxoid Lesions of the Vulva.

We present the case of a 31-year-old woman who underwent surgical excision for a polypoid, vulvar lesion. Histopathological analysis showed a diffuse myxoid stroma admixed with scant collagen fibrils. Thin-walled and branching blood vessels were prominent, with a mild perivascular lymphocytic infiltrate. Cytologically bland spindle cells with inconspicuous nucleoli were immersed in a loose myxoid stroma. This combination of histopathological features along with multinodularity in the subcutaneous fat raised concern for deep angiomyxoma, a locally destructive neoplasm. Among our differential of myxoid lesions of the vulva, we ultimately favored the diagnosis of vulvar cutaneous myxoma. Upon further investigation, we learned that our patient was indeed known for the Carney complex. We highlight that vulvar cutaneous myxomas arising in the context of the Carney complex pose a significant diagnostic challenge for pathologists and should not be overdiagnosed as aggressive lesions such as deep angiomyxoma or other malignant stromal neoplasms.

Fatal hemorrhagic complication after coil embolization of a petrosal arteriovenous shunt.

BACKGROUND: Cerebello-pontine AVMs (CPAVMs) and petrous apex dural arteriovenous fistulae (DAVFs) are rare and sometimes difficult to distinguish. We report a fatal hemorrhagic complication after coil embolization of the petrosal vein draining a trigeminal AVM misdiagnosed as a DAVF. CASE PRESENTATION: A 73-year-old woman with a petrous apex arteriovenous shunt with dual dural and pial arterial supply presented with posterior fossa hemorrhage. The draining petrosal vein was catheterized and coiled via the superior petrosal sinus. Two episodes of contrast extravasation occurred during coiling, but the lesion was completely occluded at the end of the procedure. The patient developed a fatal posterior fossa hemorrhage in the recovery room. Microscopic pathology revealed numerous dilated vessels within the trigeminal nerve. CONCLUSION: CPAVMs and DAVFs with pial drainage should be distinguished pre-operatively. Occlusion of a pial vein (as opposed to a sinus) in the treatment of an arteriovenous shunt carries hemorrhagic risk if a liquid embolic agent is not used to completely occlude all pathological vessels.

Adult Medulloblastoma Demographic, Tumor and Treatment Impact since 2006: A Canadian University Experience.

Medulloblastoma is an aggressive primary brain tumor that is extremely rare in adults; therefore, prospective studies are limited. We reviewed the information of all MB patients treated at the CHUM between 2006 and 2017. We divided our cohort by age and further divided adult patients (53%) in two groups, those diagnosed between 2006-2012 and 2013-2017. In our adult population, median follow up was 26 months and SHH-activated MB comprised 39% of tumors. Adult 5yOS was 80% and first-line therapy led to a 5yPFS of 77%. The absence of radiosensitizing chemotherapy (100% vs. 50%; p = 0.033) negatively influenced 5yPFS. 96% of adult patients received radiotherapy and 48% of them received concomitant radiosensitizing chemotherapy. Complete surgical resection was performed on 85% of adults, but the extent of resection did not have a discernable impact on survival and did not change with time. Adjuvant chemotherapy did not clearly affect prognosis (5yOS 80% vs. 67%, p = 0.155; 5yPFS 78% vs. 67%, p = 0.114). From 2006-2012, the most common chemotherapy regimen (69%) was Cisplatinum, Lomustine and Vincristine, which was replaced in 2013 by Cisplatinum, Etoposide and Cyclophosphamide (77%) with a trend for worse survival. Nine patients recurred and seven of these (78%) were treated with palliative chemotherapy. In conclusion, we did not identify prognostic demographic or tumor factors in our adult MB population. The presence of radiosensitizing chemotherapy was associated with a more favorable PFS. Cisplatinum, Lomustine and Vincristine regimen might be a better adjuvant chemotherapy regimen.

Repeated Retching and Vomiting in the Pathophysiology of Isolated Spinal Aneurysms.

BACKGROUND: Rupture of spinal aneurysms is a rare cause of subarachnoid hemorrhage. These aneurysms are often associated with a variety of vascular malformations that increase blood flow in the spinal circulation or with disorders that compromise the vessel wall. However, spinal aneurysms may be isolated, not associated with any known predisposing condition. The objective of this study is to explore the possible mechanisms associated with the formation and rupture of isolated spinal aneurysms (ISAs). METHODS: We conducted a retrospective review of a series of consecutive patients admitted for a ruptured ISA. In all cases, spinal angiography confirmed the presence of a spinal aneurysm responsible for the bleeding. Particular attention was paid to medical history and symptoms before bleeding, for potential factors predisposing to their formation and rupture. RESULTS: Between 2008 and 2020, ten cases of spinal aneurysms were seen at our institution including 4 cases of ISA. All patients with ISA were female, and in 3 cases the aneurysm involved the territory of the posterior spinal artery. In 3 of these 4 (75%) ISA cases, there was a strikingly similar history of retching and vomiting preceding the thunderclap headache. In 1 patient, the aneurysm was surgically resected; pathologic analysis revealed a fusiform dissecting aneurysm. All 4 patients had a favorable outcome. CONCLUSIONS: We suggest that the straining during prolonged retching and vomiting plays a role in the formation and rupture of some ISAs, possibly because of pressure spikes, increased transmural arterial pressure, and increased wall shear stress during straining.

Corticotroph tumor progression during long-term therapy with osilodrostat in a patient with persistent Cushing's disease.

PURPOSE: Corticotroph tumor progression (CTP) or Nelson's syndrome (NS) can occur in patients with Cushing's disease (CD) following bilateral adrenalectomy. It has rarely been observed in patients treated with long-term medical therapy for persistent CD. Osilodrostat (LCI699) is a new steroidogenesis inhibitor of 11ß-hydroxylase (CYP11ß1) that induced remission of hypercortisolism in 86% of patients with refractory CD in the randomized placebo-controlled trial LINC-3 (NCT02180217). METHODS: A 40-year-old woman with persistent CD following transsphenoidal surgery was treated with osilodrostat in the LINC-3 trial and was followed with regular hormonal assessments and imaging of residual corticotroph tumor. RESULTS: Under oral therapy with osilodrostat 10 mg twice daily, urinary free cortisol (UFC) normalized and clinical signs of CD regressed during therapy. However after 4 years of treatment, ACTH levels increased from 73 to 500 pmol/L and corticotroph tumor size increased rapidly from 3 to 14 mm, while UFCs remained well controlled. Surgical resection of an atypical tumor with weak ACTH expression and increased proliferative index (Ki-67 ≥ 8%) resulted in current remission but will require close follow-up. CONCLUSION: This case highlights the importance of monitoring ACTH and corticotroph tumor size in patients with persistent CD, either under effective treatment with steroidogenesis inhibitors or after bilateral adrenalectomy.

Immunohistochemical Markers in the Diagnosis of Calcifying Pseudoneoplasm of the Neuraxis.

BACKGROUND: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unknown pathogenesis. It is likely under-reported due to diagnostic challenges including the nonspecific radiographic features, lack of diagnostic markers, and often asymptomatic nature of the lesions. METHODS: We performed detailed examination of 11 CAPNON specimens diagnosed by histopathology, with the help of electron microscopy and immunohistochemistry. RESULTS: Electron microscopy revealed the presence of fibrillary materials consistent with neurofilaments. In addition to some entrapped axons at the periphery of CAPNONs, we discovered that all specimens stained positive for neurofilament-light (NF-L) within the granular amorphous cores, but not neurofilament-phosphorylated (NF-p). CAPNONs also showed variable infiltration of CD8+ T-cells and a decreased ratio of CD4/CD8+ T-cells, suggesting an immune-mediated process in the pathogenesis of CAPNON. CONCLUSION: NF-L and CD4/CD8 immunostains may serve as diagnostic markers for CAPNON and shed light on its pathogenesis.

Successful Management of Natalizumab-Associated Primary Central Nervous System Lymphoma through Autologous Stem Cell Transplant.

Natalizumab is used as a second-line treatment for multiple sclerosis (MS). Some reports have linked natalizumab to primary central nervous system lymphoma (PCNSL), although few have described its management. A 45-year-old woman with Balo's Concentric Sclerosis presented dizziness, vertigo accompanied by dysarthria, weakness on the left side and blurred vision to the right eye after the fourth dose of natalizumab. Magnetic resonance imaging (MRI) and a brain biopsy confirmed the diagnosis of PCNSL. The patient received modified PCNSL chemotherapy (MATRix protocol) followed by high-dose chemotherapy (HDC) supported by an autologous hematopoietic stem cell transplant (ASCT) as a consolidation therapy. Thirty months later, she is still in complete remission of her PCNSL and MS. In this case, whole brain radiotherapy was excluded because it may be associated with an increased risk of neurotoxicity in MS. ASCT was preferred because it has been shown to prevent disability progression in less advanced MS stages. Our patient is the second to receive an ASCT in this context and this option of treatment should be the preferred if the patient is eligible.

Efficiency of Crizotinib on an ALK-Positive Inflammatory Myofibroblastic Tumor of the Central Nervous System: A Case Report.

Inflammatory myofibroblastic tumors (IMT) of the central nervous system (CNS) are rare entities that have a predilection for local recurrences. Approximately half of the inflammatory myofibroblastic tumors contain translocations that result in the over-expression of the anaplastic lymphoma kinase (ALK) gene. We hereby present the case of a patient diagnosed with a left parieto-occipital IMT that recurred after multiple surgeries and radiotherapy. Immuno-histochemical examination of the tumor demonstrated ALK overexpression and the presence of an ALK rearrangement observed in lung cancers. The patient was subsequently started on an ALK inhibitor. A response evaluation criteria in solid tumors (RECIST) partial response was observed by the seventh month of ALK inhibition and the tumor remained in control for 14 months. The current case reiterates the activity of ALK inhibitors within the CNS and suggests that radiotherapy may potentiate the permeability of ALK inhibitors in CNS tumors addicted to ALK signalling.

Fatal avulsion of choroidal or perforating arteries by guidewires. Case reports, ex vivo experiments, potential mechanisms and prevention.

Innovations in endovascular tools have permitted an increasingly broad range of neurovascular lesions to be treated via minimally invasive methods. However, some device modifications may carry additional risks, not immediately apparent to operators. A patient with a symptomatic, partially thrombosed basilar apex aneurysm was allocated balloon-assisted coiling. Attempts were made to place a microwire across the basilar apex through the posterior communicating artery. Overlapping courses of the posterior cerebral and posterior choroidal arteries on the roadmap images were not recognized and a flanged-tip microwire was inadvertently advanced deep into the choroidal artery. Following the wire with a microcatheter led to binding of arterial tissue within the microcatheter. Removing the wire led to an avulsion of the choroidal artery and a severe hemorrhagic complication which proved fatal. Tissue was identified on the tip of the guidewire. Pathology showed layers of vascular tissue within the laser-cut flanges of the distal wire tip. A similar complication, also fatal, occurred during balloon angioplasty of a distal vertebral artery, when an exchange wire was accidently introduced into a perforator from a posterior cerebral artery. Ex vivo catheterization of distal mesenteric arterial branches showed that the wall of small arteries can be entrapped by laser-cut, flanged, but not by smooth guidewire tips. Microwires with a flanged instead of smooth distal tip, when placed into small caliber vessels, may cause hemorrhagic complications from avulsions*.

Inflammatory myofibroblastic tumors of the central nervous system that express anaplastic lymphoma kinase have a high recurrence rate.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) of the central nervous system (CNS) are rare entities with diverse histopathological features and varying propensities to recur. CASE DESCRIPTION: A 26 year-old male with an IMT of the CNS of the left tentorium had tumor progression 2 months after partial surgical resection. Histopathological studies confirmed expression of ALK. Macroscopic total resection was performed followed by radiotherapy. A recurrence occurred 20 months after the second surgery that necessitate reoperation. Including the present case, we identified 30 cases of IMT of the CNS corresponding to our search criteria in the literature. The extent of resection was reported in 26 of these cases. Gross total resection was done in 75% of ALK-positive and in 61% of ALK-negative cases. Recurrence rate after gross total resection for ALK-positive and ALK-negative cases was 33% and 9%, respectively. Every recurrence in ALK-positive patients occurred within 2 years after surgery. CONCLUSION: IMT of the CNS are a heterogeneous group of tumors and the treatment of choice is complete surgical resection. Because of the high recurrence rate reported for IMT of the CNS expressing ALK, a closed follow-up is recommended. When faced with an early recurrence, a surgical resection followed by radiotherapy may be advised.

A 30 year old man with an acute presentation of a cerebellopontine angle lesion.

Schwannomas are slow-growing tumors with symptoms manifesting progressively. We report the case of a patient who manifested a sudden loss of consciousness as clinical presentation of an intracranial schwannoma with no acute hemorrhage or hydrocephalus. A 30-year-old male presented comatose and posturing. Cerebral CT revealed an extra-axial lesion with a heterogeneous enhancement and a cystic component located on the right cerebellopontine angle (CPA), displacing the brain stem. No acute hemorrhage or hydrocephalus was documented. Through a retrosigmoid suboccipital craniotomy, an extended subtotal tumor resection was performed. The patient experienced no functional hearing impairment and resumed his daily-life activities 3 months after surgery. Histopathological examination was compatible with a benign schwannoma. An exuberant lymphoplasmacytic infiltrate was found in many areas, signing the presence of an unusual inflammatory reaction with adjacent important intratumoral edema. We propose that the exuberant inflammatory infiltrate and the associated intratumoral edema acted as determining elements in the increase of mass effect and sudden clinical deterioration.

Failure of temozolomide and conventional doses of pegvisomant to attain biochemical control in a severe case of acromegaly.

It has been suggested that treatment with adequate dose titration of pegvisomant, a GH antagonist, up to a maximum of 40 mg daily, can achieve IGF-1 normalisation in virtually all patients with acromegaly. On the other hand, temozolomide (TMZ), an alkylating cytostatic agent, has been reported to reduce pituitary tumour size and hormone hypersecretion in a small number of aggressive pituitary macroadenomas. In this paper we report the case of a patient resistant to very high doses of pegvisomant used in combination with somatostatin analogs (SSA) and to TMZ therapy. The patient, initially a 22 year-old man with an invasive GH-secreting pituitary macroadenoma (IGF-1, 371% upper limit of normal), had active acromegaly despite a repeat transsphenoidal surgery followed by radiotherapy and SSA (octreotide 800 µg sc daily) (IGF-1, 262% ULN). In combination with SSA, pegvisomant was started at 20 mg daily and doses were titrated up to 60 mg daily. IGF-1 was moderately reduced and stabilized at 200% ULN after 1 year of treatment. Serum pegvisomant level was 30,500 ng/l, the denaturalized GHBP concentration 1,120 pM and the endogenous GH level was 220 µg/l. Pegvisomant was stopped and TMZ therapy was given for 5 cycles. However, the patient reported an increase of acromegaly symptoms and the serum IGF-1 was raised to the same level prior to pegvisomant therapy. Consequently, pegvisomant was tried again with doses up to 100 mg daily finally resulting in normalisation of serum IGF-1 level and improvement of acromegaly symptoms and patient well-being. We conclude that in some patients with severe acromegaly refractory to multimodal therapy, biochemical control may be difficult to attain with conventional doses of pegvisomant or TMZ therapy.

Cooperation between cyclin E and p27(Kip1) in pituitary tumorigenesis.

Cushing's disease is caused by glucocorticoid-resistant pituitary corticotroph adenomas. We have previously identified the loss of nuclear Brg1 as one mechanism that may lead to partial glucocorticoid resistance: this loss is observed in about 33% of human corticotroph adenomas. We now show that Brg1 loss of function correlates with cyclin E expression in corticotroph adenomas and with loss of the cell cycle inhibitor p27(Kip1) expression. Because Brg1 is thought to have tumor suppressor activity, the present study was undertaken to understand the putative contribution of cyclin E derepression produced by loss of Brg1 expression on adenoma development. Overexpression of cyclin E in pituitary proopiomelanocortin cells leads to abnormal reentry into cell cycle of differentiated proopiomelanocortin cells and to centrosome instability. These alterations are consistent with the intermediate lobe hyperplasia and anterior lobe adenomas that were observed in these pituitaries. When combined with the p27(Kip1) knockout, overexpression of cyclin E increased the incidence of pituitary tumors, their size, and their proliferation index. These results suggest that cyclin E up-regulation and p27(Kip1) loss-of-function act cooperatively on pituitary adenoma development.

An unusual association of a sellar gangliocytoma with a prolactinoma.

The simultaneous occurrence of a hypothalamic and sellar gangliocytoma with a pituitary prolactinoma is very rare. The explanation for such an association is not known. We describe the case of a woman who had a coexisting adjacent pituitary prolactinoma and gangliocytoma within the same sellar mass. The tumor cells of the gangliocytoma demonstrated expression of enkephalin, a product of proopiomelanocortin known to be a prolactin secretagogue. We postulate that in this patient there may be a link between gangliocytoma enkephalin and prolactin hypersecretion.