Atypical cell cycle regulation promotes mammary stem cell expansion during mammary development and tumourigenesis.

BACKGROUND: The cell cycle of mammary stem cells must be tightly regulated to ensure normal homeostasis of the mammary gland to prevent abnormal proliferation and susceptibility to tumorigenesis. The atypical cell cycle regulator, Spy1 can override cell cycle checkpoints, including those activated by the tumour suppressor p53 which mediates mammary stem cell homeostasis. Spy1 has also been shown to promote expansion of select stem cell populations in other developmental systems. Spy1 protein is elevated during proliferative stages of mammary gland development, is found at higher levels in human breast cancers, and promotes susceptibility to mammary tumourigenesis when combined with loss of p53. We hypothesized that Spy1 cooperates with loss of p53 to increase susceptibility to tumour initiation due to changes in susceptible mammary stem cell populations during development and drives the formation of more aggressive stem like tumours. METHODS: Using a transgenic mouse model driving expression of Spy1 within the mammary gland, mammary development and stemness were assessed. These mice were intercrossed with p53 null mice to study the tumourigenic properties of Spy1 driven p53 null tumours, as well as global changes in signaling via RNA sequencing analysis. RESULTS: We show that elevated levels of Spy1 leads to expansion of mammary stem cells, even in the presence of p53, and an increase in mammary tumour formation. Spy1-driven tumours have an increased cancer stem cell population, decreased checkpoint signaling, and demonstrate an increase in therapy resistance. Loss of Spy1 decreases tumor onset and reduces the cancer stem cell population. CONCLUSIONS: This data demonstrates the potential of Spy1 to expand mammary stem cell populations and contribute to the initiation and progression of aggressive, breast cancers with increased cancer stem cell populations.

Primary Spinal Melanoma: Case Report and Systematic Review.

INTRODUCTION: Primary malignant melanoma of the spinal cord (PSM) is a rare condition with limited evidence regarding its diagnosis (clinical and radiographic), management, and prognosis. Our aim was to report an extremely rare two cases of primary malignant melanoma of the spine one of them is sacral melanoma which represents the second reported case in the literature and to conduct a systematic review of the relevant literature. METHODS: The diagnosis and management of these cases were retrospectively reviewed. Using the PRISMA guideline, we conducted a systematic review of the literature to analyze different management strategies and the prognosis of such pathology. RESULTS: All two patients were operated on, and received gross total removal of their tumors, with extended follow up for tumor recurrences. One of the cases involved a sacral tumor, which was resected without adjuvant therapy. The other one was seen by oncology and received post-operative chemo- and radio- therapy. In addition to the aforementioned cases, we present a comprehensive review of the literature on PSM from 1950 to the present, demonstrating that PSM is a very rare tumor, with a limited counted number of cases reported worldwide. CONCLUSION: In conclusion, we report an exceedingly rare two cases of primary malignant melanoma of the spine. Early surgical intervention is key to the management of these rare and aggressive tumors. GTR should be attempted if possible.

Surgical intervention for spontaneous intracranial hypotension Type 4 CSF leak: A case report.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a rare condition that can be very debilitating. SIH is well understood to be due to a CSF leak, however, identifying the source of the leak is still a challenge. We are presenting a case of Type 4 CSF leak and reviewing the related literature. CASE DESCRIPTION: A 46-year-old female presenting with intractable orthostatic headaches was diagnosed with SIH. She was unable to mobilize due to the severity of her symptoms. MRI scans of the brain and spine did not identify a source of the leak. After failing conservative therapy and multiple epidural blood patches, the patient underwent surgery which resulted in significant improvement in symptoms. CONCLUSION: This study has shown that surgical intervention improves symptoms in patients who do not have an identifiable source of CSF leak. Further studies need to be done to fully understand the role of surgery in Type 4 CSF leaks.

Cervical Spine Chondrosarcoma in an Adult with a History of Wilms Tumor.

INTRODUCTION: We report the first case of cervical spine chondrosarcoma in a Wilms tumor survivor. CASE DESCRIPTION: A 52-year-old female patient presented with myelopathic symptoms including poor balance, difficulty walking, and numbness of both feet. A magnetic resonance imaging of the spine showed a mass at the right C7-T1 foramen causing significant cord compression. The patient's symptoms improved after posterior decompression and fusion with excision of the tumor. CONCLUSION: Through our experience with this case, we would like to suggest a possible unknown genetic syndrome predisposing patients with Wilms tumor to chondrosarcoma as secondary neoplasms. We would also like to re-emphasize the need for vigilance when assessing patients with a history of Wilms tumor.

Challenges, Learning Curve, and Safety of Endoscopic Endonasal Surgery of Sellar-Suprasellar Lesions in a Community Hospital.

BACKGROUND AND OBJECTIVE: Endoscopic endonasal surgery (EES) for the management of sellar, suprasellar, and anterior skull base lesions is gaining popularity. Our aim was to analyze and present the clinical outcomes of EES for the management of these lesions in a community hospital setting. METHODS: We retrospectively reviewed the charts of 56 patients with sellar, suprasellar, and anterior skull base lesions who underwent EES between 2010 and 2018. RESULTS: There was male predominance (53.6%) with a mean age of 54.9 ± 13.7 years. Lesions were 45 pituitary adenomas, 5 meningiomas, 3 metastatic, 1 craniopharyngioma, 1 Rathke cyst, and 1 mucocele. Gross total excision was achieved in 57.1%, subtotal excision occurred in 37.5%, and decompression and biopsy were achieved in 5.4% patients. Postoperative vision normalized or improved in 27 patients (86.1%) and was stable in 4 patients (13.9%). Recovery of a preexisting hormonal deficit occurred in 13 (23.2%) patients, and a new hormonal deficit occurred in 9 patients (16.1%). The mean hospital stay was 6.1 ± 4.9 days. Postoperative complications included cerebrospinal fluid leak in 8 patients (14.3%). Four patients (7.1%) had meningitis. Diabetes insipidus was present in 19 patients (33.9%), and postoperative intracranial hematoma requiring evacuation was necessary in 2 patients (3.6%). The mean follow-up duration was 47.5 ± 25.8 months. Lesion progression or recurrence requiring redo surgery occurred in 5 patients (8.9%). Regarding the learning curve, the postoperative cerebrospinal fluid leak, meningitis, new hormonal deficits, and diabetes insipidus decreased in the second half of the patients. CONCLUSIONS: EES provides an effective and safe surgical option with low morbidity and mortality for the treatment of sellar, suprasellar, and anterior skull base lesions in a community hospital setting.