Faculty Bibliography

Paraneoplastic neurological syndromes (PNS) are a group of rare immune-mediated disorders with neurological sequela in cancer patients. It usually occurs when an immune response against a systemic tumor is incorrectly directed to the nervous system. Compared to other reported manifestations of PNS in breast cancer, Guillain Barre syndrome (GBS) is exceedingly rare. There is only one other reported case in the literature of GBS that was diagnosed in a breast cancer patient. We report the second recorded case of a 61-year-old female with a history of early-stage breast cancer, who presented with symptoms of lower extremity weakness initially suspected to be GBS but later found to have been recurrent breast cancer. No specific guidelines are available for the treatment of PNS. Treatment of underlying malignancy with chemotherapy and immunotherapies are usually recommended.

Vancomycin-induced immune thrombocytopenia (ITP) is a rare, potentially life-threatening complication from an antibiotic frequently used in medical practice. We report a case of an 81-year-old male with recent removal of an infected right knee prosthesis and insertion of an articulating antibiotic spacer, presenting from rehabilitation for severe thrombocytopenia (1 X 10³/µL). The patient's thrombocytopenia was initially falsely attributed to rifampin-induced ITP, a much more common cause of drug-induced thrombocytopenia. Only later, after a second precipitous drop in platelet count, vancomycin was correctly identified as the culprit. The patient's serum was tested for drug-dependent platelet antibodies with and without vancomycin. A positive reaction for IgG was detected by flow cytometry in the absence of vancomycin, which was potentiated in the presence of vancomycin. The result indicated the presence of vancomycin-dependent and nondrug-dependent platelet reactive antibodies and confirmed the diagnosis of vancomycin-induced ITP. In this case, the correct diagnosis was masked by the simultaneous administration of two drugs that cause drug-induced ITP and highlights the importance of early recognition of rare, vancomycin-induced ITP.

Primary signet ring cell carcinoma of the lung is a rare non-small cell carcinoma of the lung with extremely aggressive features and poor prognosis. The diagnosis mainly required tissue biopsy with immunohistochemical analysis and gene mutation studies. We describe a unique case of primary signet ring cell carcinoma of the lung presenting with life threatening haemoptysis along with literature review of prognosis and management of this rare clinical entity.

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a unique variant of hepatocellular carcinoma. The majority of cases present with nonspecific symptoms like vague abdominal pain, weight loss and fatigue. Ruptured FL-HCC occurs rarely and mortality in the acute phase is very high. We report a rare case of a ruptured FL-HCC successfully managed with transarterial embolization for hemostasis. A 37-year-old male previously in good health presented with a severe, sharp epigastric pain that started 1 h prior to the presentation. He denied trauma, fever, nausea, vomiting, or diarrhea. Tenderness in the epigastrium was noted, with no palpable masses, guarding or rigidity. His blood pressure and pulse were 159/105 mm Hg and 105 beats/min. Platelets and coagulation parameters were within normal limits; transaminases were elevated. Abdominal computed tomography (CT) scan with contrast revealed an 8 cm lobulated mass with central hypodensity in the left hepatic lobe with perilesional blood and free pelvic fluid, indicating tumor rupture. CT angiography showed tumor neovascularization from a branch of the left hepatic artery which was embolized using transarterial gelfoam. Liver magnetic resonance imaging (MRI) and biopsy were consistent with fibrolamellar variant hepatocellular carcinoma. After 4 days, as the symptoms resolved, and the lab results were stable, patient was discharged and underwent a left hepatectomy 3 weeks later. FL-HCC occurs commonly in the left lobe of a young and non-cirrhotic liver. Typically, cross sectional imaging reveals a lobulated mass with well-defined margins, areas of hypervascularity and a central calcified scar. Histologic appearance is characterized by eosinophilic polygonal shaped cells separated by lamellar fibrosis. Surgical resection is the treatment of choice with better outcome when compared to conventional HCC. Disease recurrence after complete surgical resection is however high in the first 5 years. Tumors > 5 cm in size are at high risk for rupture with high mortality and recurrence rates secondary to significant spillage of tumor. While an emergency hepatectomy is preferred in unstable patients, those that are hemodynamically stable can undergo radiologic transarterial embolization for hemostasis followed by staged hepatectomy.

Cyclin-dependent kinase 4/6 inhibitors, which act by inhibiting progression from the G1 to S phases of the cell cycle, include palbociclib, ribociclib, abemaciclib, and trilaciclib. Palbociclib and ribociclib are currently food and drug administration-approved for use in combination with aromatase inhibitors in postmenopausal women with metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. Palbociclib is also food and drug administration-approved for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Abemaciclib is the newest cyclin-dependent kinase 4/6 inhibitor to gain Food and Drug Administration (FDA) approval, specifically as monotherapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer previously treated with chemotherapy and endocrine therapy. Abemaciclib also shares a similar indication with palbociclib for use in combination with fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer progressing after endocrine therapy. Trilaciclib use remains largely investigational at this time. However, despite FDA-approval for only metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, all four cyclin-dependent kinase 4/6 inhibitors have shown promise in hematologic malignancies and non-breast solid tumors. Although further research is needed, cyclin-dependent kinase 4/6 inhibitors represent intriguing developments in the treatment of various malignancies, including those with such poor prognoses as glioblastoma multiforme, mantle cell lymphoma, and metastatic melanoma. We discuss the approved indications, current research, and areas of future exploration for palbociclib, ribociclib, abemaciclib, and trilaciclib.

Treatment of lung cancer has been revolutionized with development of drugs that target key driver mutations and immune checkpoints. Until recently, it was believed that these driver mutations are mutually exclusive. However, few reports have emerged citing the presence of both mutations either synchronously or metachronously. We describe a case report of lung adenocarcinoma harboring two driver mutations in the same tumor cells as well as exhibiting high PDL1 expression. We further discuss the possible association of these driver mutations with PDL1 expression.

Suppression of gonadal testosterone synthesis represents the standard first line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer (CRPC), it is possible to detect persistent activation of the androgen receptor (AR) through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17α-hydroxylase and 17,20-lyase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a significant improvement in overall survival (OS) with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone (ACTH), providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-lyase (orteronel, galeterone and VT-464) that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors; recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents; and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone benefit or restore abiraterone activity.