Myeloid sarcoma of the skull base: A case report and systematic literature review.

Background: Myeloid sarcoma (MS), or chloroma, is a rare extramedullary malignant tumor that consists of undifferentiated granulocytic cells, and it is most commonly associated with acute myeloid leukemia (AML). Intracranial MS accounts for 0.4% of MS cases, and involvement of the skull base and visual dysfunction is rarely reported. However, the optimal treatment and response to treatment of skull base MS in the presence of visual symptoms is unknown. Case Description: A 30-year-old male with a history of AML presented with rapidly progressive vision loss and a sellar and parasellar mass with bilateral cavernous sinus and optic nerve encasement. The patient underwent endoscopic endonasal transsphenoidal biopsy revealing intracranial MS. He was treated postoperatively with high-dose intravenous and intrathecal cytarabine and had complete restoration of his vision by postoperative day 11. A systematic review of the literature identified six cases of skull base MS, five of whom presenting with visual symptoms. All patients underwent systemic chemotherapy with cytarabine and/or cyclophosphamide, with infrequent use of intrathecal chemotherapy or radiation. Those with reported visual outcomes were diagnosed 4 months or longer after symptom onset and demonstrated no visual improvement with treatment. Conclusion: Skull base MS is a rare disease entity with a high prevalence of visual dysfunction. Our patient's complete disappearance of intracranial disease and resolution of visual symptoms with systemic and intrathecal chemotherapy highlight the importance of timely diagnosis and appropriate treatment without a need for direct surgical decompression.

An Unusual Case of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Introduction: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare disease entity associated with textured breast implants. Though the clinical course is typically indolent, BIA-ALCL can occasionally invade through the capsule into the breast parenchyma with spread to the regional lymph nodes and beyond including chest wall invasive disease. Case: We present the case of a 51-year-old female with a history of bilateral silicone breast implants placed approximately twenty years ago who presented with two months of progressively enlarging right breast mass. Ultrasound-guided biopsy of right breast mass and right axillary lymph node showed CD 30-positive ALK-negative anaplastic large cell lymphoma, and staging work up showed extension of the tumor to chest wall and ribs consistent with advanced disease. She received CHP-BV (cyclophosphamide, doxorubicin, prednisone, and brentuximab vedotin) for six cycles with complete metabolic response. This was followed by extensive surgical extirpation and reconstruction, radiation for residual disease and consolidation with autologous stem cell transplant. She is currently on maintenance brentuximab vedotin with no evidence of active disease post autologous stem cell transplant. Conclusion: Treatment guidelines for advanced chest wall invasive BIA-ALCL are not well defined. Lack of predictive factors warrants mutation analysis and genetic sequencing to identify those at highest risk of progression to chest wall invasive disease. This rare case highlights the need for definitive consensus on the optimal management of chest wall invasive BIA-ALCL.

Pathology Trainee Redeployment and Education During the COVID-19 Pandemic: An Institutional Experience.

Pathology training programs throughout the United States have endured unprecedented challenges dealing with the ongoing coronavirus disease 2019 pandemic. At Houston Methodist Hospital, the Department of Pathology and Genomic Medicine planned and executed a trainee-oriented, stepwise emergency response. The focus was on optimizing workflows among areas of both clinical and anatomic pathology, maintaining an excellent educational experience, and minimizing trainee exposure to coronavirus disease 2019. During the first phase of the response, trainees were divided into 2 groups: one working on-site and the other working remotely. With the progression of the pandemic, all trainees were called back on-site and further redeployed within our department to meet the significantly increased workload demands of our clinical laboratory services. Adjustments to trainee educational activities included, among others, the organization of a daily coronavirus disease 2019 virtual seminar series. This series served to facilitate communication between faculty, laboratory managers, and trainees. Moreover, it became a forum for trainees to provide updates on individual service workflows and volumes, ongoing projects and research, as well as literature reviews on coronavirus disease 2019-related topics. From our program's experience, redeploying pathology trainees within our department during the coronavirus disease 2019 pandemic resulted in optimization of patient care while ensuring trainee safety, and importantly, helped to maintain continuous high-quality education through active involvement in unique learning opportunities.

Use of PEG-asparaginase in monomorphic epitheliotropic intestinal T-cell lymphoma, a disease with diagnostic and therapeutic challenges.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), previously known as enteropathy associated T-cell lymphoma (EATL) type II, is a rare haematological malignancy with a difficult and delayed diagnosis. Symptoms can include abdominal pain, weight loss, and chronic diarrhoea. However, most patients are only diagnosed after complications, such as perforation or obstruction, have developed. There is no standard treatment for MEITL; most accepted regimens consist of surgical resection and anthracycline-based chemotherapy. Prognosis is poor with an approximate survival of less than a year. Even though other therapies, such as autologous stem cell transplant, has shown promising results, not all patients can tolerate this course of treatment especially if they are elderly, have several comorbidities or are malnourished. Innovative therapies that improve survival and can be used as an alternative for more intensive treatment are needed. We report the use of PEG-asparaginase along with conventional anthracycline therapy in a 70-year-old woman diagnosed with MEITL, who went into remission and survived for more than one year before succumbing to relapsed disease.

SIRT1 positively regulates breast cancer associated human aromatase (CYP19A1) expression.

Breast cancer remains one of the leading causes of death in women diagnosed with cancer. In breast cancer, aberrant expression of the CYP19A1 gene, which encodes the aromatase enzyme, contributes to increased intratumoral levels of estradiol. Regardless of whether this estrogen is produced by peripheral tissues or within specific subpopulations of cells within the breast tumor, it is clear that the aromatase enzymatic activity is critical for the growth of estrogen-dependent tumors. Currently, aromatase inhibitors have proven to be highly effective in blocking the growth of estrogen-dependent forms of breast cancer. CYP19A1 transcription is tightly controlled by 10 tissue-specific promoters. In breast cancer, however, aromatase transcription is driven by multiple promoters that somehow override the tissue-specific regulation of normal tissue. Here, we explore the role that the deacetylase, sirtuin-1 (SIRT1), plays in positively regulating aromatase in breast cancer. We demonstrate that the use of cambinol and the SIRT1/2 inhibitor VII, 2 small molecule inhibitors of SIRT1 and SIRT2, as well as small molecule inhibitors and small interfering RNA specific to SIRT1, all reduce the levels of aromatase mRNA. We further demonstrate that pharmacologic inhibition causes a marked reduction in aromatase protein levels. Additionally, by chromatin immunoprecipitation, we demonstrate that SIRT1 occupies the promoter regions PI.3/PII and PI.4, and its inhibition leads to increased acetylation of estrogen-related receptorα, a transcription factor that positively regulates CYP19A1 transcription in epithelial cells. Finally, we demonstrate by immunohistochemistry that SIRT1 is significantly up-regulated in invasive ductal carcinoma relative to normal tissue adjacent to tumor, further suggesting a role of SIRT1 in breast cancer. This work uncovers a new mechanism for the regulation of aromatase and provides rationale for further investigation of how the inhibition of specific sirtuins may provide a unique strategy for inhibiting aromatase that may complement or synergize with existing therapies.