Hepatotoxicity After CDK 4/6 Inhibitor Initiation in the Treatment of Hormone-Positive Metastatic Breast Cancer

Cancer cells proliferate using various mechanisms. One mechanism of preventing tumor cell growth is blockade of the cyclin-dependent kinase (CDK) 4/6 axis. Multiple CDK 4/6 inhibitors - ribociclib, palbociclib, and abemaciclib - have significantly improved progression-free survival rates. However, they can cause hepatotoxicity. We present a case of a 67-year-old female who was diagnosed with stage 1C invasive ductal carcinoma. She was treated with letrozole and ribociclib due to recurrence as metastatic disease, but within 10 days, she developed transaminitis. She then started palbociclib but experienced elevated transaminases within two weeks, needing discontinuation of palbociclib. Subsequent positron-emission tomography/computed tomography imaging showed disease progression, and she was started on fulvestrant. We considered adding abemaciclib, but the patient declined and has had stable disease for more than a year on fulvestrant. CDK 4/6 inhibitors are used to treat metastatic breast cancer and are generally well tolerated. The most common side effect is neutropenia; however, our patient developed transaminitis. The novelty of our case is the development of hepatotoxicity even after the introduction of another CDK 4/6 inhibitor, indicating at least some degree of class effect. In summary, CDK 4/6 inhibitors have significantly improved outcomes in hormone-positive metastatic breast cancers. However, a small percentage suffer from hepatic injury enough to warrant discontinuation of the drug, and we must continue to assess the risk versus benefit profile when offering them to our patients

A Rare Presentation of Concomitant Lung Disease and Hepatitis After Rituximab Treatment: A Case Report

Rituximab (RTX) is a chimeric monoclonal antibody that is a standard component of treatment for all B-cell malignancies. The most common adverse events related to RTX are infusion-related reactions, such as fever, chills, urticaria, flushing, and headaches. However, RTX-induced lung disease (RTX-ILD) is a rare but potentially fatal adverse reaction, and diagnosing RTX-ILD is challenging, especially when accompanied by other rare adverse reactions, such as hepatitis. Here, we report a case of RTX-ILD with concomitant RTX-induced hepatitis in a 55-year-old man with follicular B-cell non-Hodgkin lymphoma who was on maintenance RTX therapy. The patient presented with a subacute, persistent dry cough, shortness of breath, fevers, and chills shortly after having traveled. Outpatient antibiotic therapy did not relieve symptoms, and laboratory studies revealed evidence of liver injury. A computed tomography (CT) of the chest showed predominately basilar airspace disease and ground glass opacities suggestive of multifocal pneumonia. Extensive infectious and autoimmune workups were negative. RTX-ILD with concomitant RTX-induced hepatitis was considered because antibiotic therapy did not resolve symptoms or improve signs of liver damage. Prednisone (1 mg/kg) led to symptom resolution and liver enzyme improvement. The patient underwent a 30-day steroid taper and the withholding of RTX infusions. A CT of the chest three months after discharge showed nearly resolved multifocal ground glass opacities. RTX-ILD should be considered after infectious and autoimmune etiologies have been ruled out for all patients on RTX therapy who experience symptoms of lung pathology or infection

Acute Myeloid Leukemia: The Race to Diagnosis and Treatment!

Introduction: Acute myeloid leukemia (AML) is one of the hematologic emergencies that require prompt treatment. Advanced changes in the molecular pathogenesis has been emerging with major impact on prognosis and treatment. FLT3 mutation is associated poor prognosis and early relapse in AML. Midostaurin is a multi-kinase inhibitor, when combined with induction 7+3 chemotherapy, improves the response rate and disease-free survival. Purpose: To evaluate our institution efficiency obtaining the appropriate molecular studies in AML cases at the time of diagnosis. Time is very sensitive in the management of acute myeloid leukemia. Induction chemotherapy should be administered once morphologic diagnosis is made. It requires high collaboration between the hematologist, pathologist and laboratory staff. Once molecular studies are available, the need for targeted therapy will be determined. next generation sequencing (NGS) is fast and comprehensive method in molecular analysis Methods: The electronic medical records were reviewed for all AML cases diagnosed between January 2016 and December 2018. Quality measures were defined by: Average duration between bone marrow biopsy and the morphology results, average duration between bone marrow biopsy and date of molecular order, the type of molecular study ordered, average duration between molecular order and available results. We investigated the delay in administering midostaurin in cases with FLT3 mutation. Results: Between January 2016 and December 2018, there was 86 AML cases diagnosed and treated in our hospital. All patients were admitted to the hospital. The average duration between bone marrow biopsy and morphology results is 3 days. Molecular studies were obtained in 65 cases (75.5%). In 2018, molecular studies were ordered in 91% of new AML cases. Molecular studies were ordered as: (NGS)-54 gene in 18 cases; the rest were ordered as custom panel. The average duration between the molecular order and result dates is 9.3 days. The Average duration between induction date and molecular results is 8.8 days. FLT 3 mutation analysis was included in 51 cases (59%) and was detected in 18 cases (21%). Midostaurin is administered in 13 cases. The average delay in administering midostaurin is 2.75 days. Discussion: Our institution experience has improved in the past 3 years increasing the rate of ordering molecular studies. However, there is an average 2.7-day delay in administering targeted therapy due to the delay ordering and getting the results in appropriate time manner. We suggested the following changes: 1. Standardize the order by obtaining NGS-54 gene panel on all Leukemia cases. 2. Discuss all new leukemia cases in multidisciplinary conference to ensure better communication. 3. Address the efficacy of these measures in new AML cases diagnosed in 2019.https://scholarlycommons.henryford.com/merf2019qi/1007/thumbnail.jp

Carcinoma En Cuirasse: A Rare but Striking Cutaneous Manifestation of Metastatic Breast Cancer

Carcinoma en cuirasse is a rare cutaneous metastatic presentation of breast cancer with a poor prognosis. We report a female in her 70s with a prior history of left breast ductal carcinoma in situ status post-radiation and lumpectomy who presented with skin thickening of the left breast and a few solid masses in bilateral breasts. Biopsy showed invasive ductal carcinoma of the left breast (estrogen receptor [ER]/progesterone receptor positive [PR], human epidermal growth factor receptor-2 [HER2] negative) and ductal carcinoma in situ of the right breast (ER/PR positive). She underwent a right breast lumpectomy; however, the left breast mastectomy was aborted due to the worsening of her skin findings on preoperative examination. A skin biopsy revealed poorly differentiated invasive ductal carcinoma. She was diagnosed with stage 4 breast cancer, specifically carcinoma en cuirasse. Systemic treatment was initiated, followed by a left breast mastectomy. A surgical biopsy was HER2-positive, and therefore anti-HER2 therapy was given. She remains on maintenance therapy with an excellent response at present.Any unexplained skin findings in breast cancer patients should prompt consideration of carcinoma en cuirasse. With ongoing treatment advances, many newer therapy options are available for metastatic breast cancer. Based on our case, we think that patients with this disease can have better outcomes

A rare case of follicular lymphoma transformed to a high-grade B-cell lymphoma in orbit

Transformation of lymphoma is an infrequent phenomenon, and involvement of the eye as such is even uncommon. Histological transformation in patients with follicular lymphoma who were previously treated with immune-chemotherapy carry a poor outcome. Here, we illustrate such a case with aggressive histological transformation from a low-grade lymphoma

ALK-Positive Anaplastic Large Cell Lymphoma Associated With Hemophagocytic Lymphohistiocytosis

Hemophagocytic lymphohistiocytosis (HLH) has been rarely reported as a complication of anaplastic large cell lymphoma (ALCL), especially in the adult population. We herein present a case of a young woman who presented with multiorgan failure and disseminated intravascular hemolysis and was later found to have ALCL-associated HLH. We also review the current literature on ALCL-associated HLH in adult patients, with their respective treatments and outcomes. We discuss the challenges associated with the diagnosis of lymphoma in the setting of HLH and multiorgan failure. Further, given its high mortality rates, we highlight the importance of promptly identifying and treating the underlying etiology of HLH

Impact of COVID-19 Infection on 24 Patients with Sickle Cell Disease One Center Urban Experience, Detroit, MI, USA

The city of Detroit has a large population of individuals with sickle cell disease, and hospitals in Detroit have seen some of the highest numbers of cases of coronavirus disease-19 (COVID-19) in 2020. The purpose of this study was to examine the pathophysiological characteristics of COVID-19 in patients with sickle cell disease or trait to determine whether these patients have unique manifestations that might require special consideration. This retrospective analysis included 24 patients with confirmed COVID-19 and sickle cell disease or trait who were seen at the Henry Ford Hospital, Detroit, MI, USA, between March 1 and April 15 2020. Of the 24 patients, 18 (75.0%) had heterozygous sickle cell trait, one (4.0%) was a double heterozygote for Hb S (HBB: c.20A\u3eT)/β(+)-thalassemia (β(+)-thal), four had sickle cell anemia (β(S)/β(S)) and one (4.0%) had Hb S/Hb C (HBB: c.19G\u3eA) disease. A total of 13 (54.0%) patients required hospitalization. All four patients with sickle cell anemia, developed acute pain crisis. We observed one patient who developed acute pulmonary embolism and no patients developed other sickle cell associated complications. Additionally, three (13.0%) patients required packed red blood cell transfusion without the need of exchange transfusion, and one patient required admission to the intensive care unit (ICU), mechanical ventilation and subsequently died. Patients with sickle cell disease or trait and laboratory-confirmed COVID-19 had a generally mild, or unremarkable, course of disease, with lower chances of intubation, ICU admission and death, but with a slightly longer hospitalization

A mysterious cause of chest pain.

LEARNING OBJECTIVE #1: Recognize the clinical features of primary cardiac tumors LEARNING OBJECTIVE #2: Manage chest pain by ruling out the most serious and fatal etiologies first CASE: A 42-year-old African American male with a past medical history significant for previously treated non-medullary thyroid carcinoma presented to our hospital with acute onset pleuritic chest pain and dyspnea on exertion. Initial workup revealed a slightly elevated Troponin-I along with a diffuse ST-segment elevation on electrocardiogram. Left sided heart catheterization with coronary angiogram did not show any obstructive lesions. No evidence of pulmonary embolism was seen on computed tomography (CT) angiogram. A transthoracic echocardiogram showed a large right atrial mass, which was further evaluated by a cardiac magnetic resonance imaging (MRI) and found to be involving the right atrial wall and pericardium with evidence of central necrosis on T2 signal. Patient underwent gross total resection of the mass, pathology showed areas of spindle cells and vascular spaces which stained positive for CD31 and CD34 indicating vascular differentiation consistent with angiosarcoma. Staging CT scan of the chest, abdomen and pelvis did not show evidence of distant metastasis. Patient received adjuvant chemotherapy with adriamycin and ifosfamide, postchemotherapy cardiac MRI showed a possible evidence of persistent disease for which he received external beam radiation therapy (EBRT) to the remnant mass. Patient has been stable since then with no evidence of active disease for 2 years. IMPACT: Chest pain is a common presenting complaint in many patients, while the etiology is benign in several occasions, the clinical approach would differ for each particular case depending on several factors which should be incorporated to formulate a specific diagnostic approach and subsequent therapy plan. Younger patients with chest pain should be investigated thoroughly after ruling out deadly cardiac, pulmonary or vascular conditions. DISCUSSION: Primary cardiac tumors are very rare; based upon data from22 large autopsy series the approximate frequency is 0.02%, corresponding to 200 tumors in 1 million autopsies. Malignant tumors constitute around one quarter of these with the majority being sarcomas. Cardiac angiosarcoma typically affects middle aged males and it usually involves the right atrium with pericardial, caval and tricuspid-valve invasion. Metastases are usually found at time of presentation in up to 89% of cases with lungs being the most common site. Presentation is variable depending on the site of involvement. It can be incidentally discovered or might cause symptoms secondary to embolization, direct invasion of adjacent structures or hemodynamic instability due to obstructing cardiac flow. The mainstay of treatment for cardiac tumors remains surgical resection, however chemotherapy and in some occasions radiation therapy are essential adjuvant modalities to achieve cure

A mysterious cause of chest pain.

LEARNING OBJECTIVE #1: Recognize the clinical features of primary cardiac tumors LEARNING OBJECTIVE #2: Manage chest pain by ruling out the most serious and fatal etiologies first CASE: A 42-year-old African American male with a past medical history significant for previously treated non-medullary thyroid carcinoma presented to our hospital with acute onset pleuritic chest pain and dyspnea on exertion. Initial workup revealed a slightly elevated Troponin-I along with a diffuse ST-segment elevation on electrocardiogram. Left sided heart catheterization with coronary angiogram did not show any obstructive lesions. No evidence of pulmonary embolism was seen on computed tomography (CT) angiogram. A transthoracic echocardiogram showed a large right atrial mass, which was further evaluated by a cardiac magnetic resonance imaging (MRI) and found to be involving the right atrial wall and pericardium with evidence of central necrosis on T2 signal. Patient underwent gross total resection of the mass, pathology showed areas of spindle cells and vascular spaces which stained positive for CD31 and CD34 indicating vascular differentiation consistent with angiosarcoma. Staging CT scan of the chest, abdomen and pelvis did not show evidence of distant metastasis. Patient received adjuvant chemotherapy with adriamycin and ifosfamide, postchemotherapy cardiac MRI showed a possible evidence of persistent disease for which he received external beam radiation therapy (EBRT) to the remnant mass. Patient has been stable since then with no evidence of active disease for 2 years. IMPACT: Chest pain is a common presenting complaint in many patients, while the etiology is benign in several occasions, the clinical approach would differ for each particular case depending on several factors which should be incorporated to formulate a specific diagnostic approach and subsequent therapy plan. Younger patients with chest pain should be investigated thoroughly after ruling out deadly cardiac, pulmonary or vascular conditions. DISCUSSION: Primary cardiac tumors are very rare; based upon data from22 large autopsy series the approximate frequency is 0.02%, corresponding to 200 tumors in 1 million autopsies. Malignant tumors constitute around one quarter of these with the majority being sarcomas. Cardiac angiosarcoma typically affects middle aged males and it usually involves the right atrium with pericardial, caval and tricuspid-valve invasion. Metastases are usually found at time of presentation in up to 89% of cases with lungs being the most common site. Presentation is variable depending on the site of involvement. It can be incidentally discovered or might cause symptoms secondary to embolization, direct invasion of adjacent structures or hemodynamic instability due to obstructing cardiac flow. The mainstay of treatment for cardiac tumors remains surgical resection, however chemotherapy and in some occasions radiation therapy are essential adjuvant modalities to achieve cure

Primary Pleural Extranodal Marginal Zone Lymphoma Presenting as Bilateral Chylothorax

Here we describe a case of pleural extranodal marginal zone lymphoma presenting as bilateral chylothorax which has not been reported in the literature prior to this. Primary pleural lymphomas are a rare entity most commonly associated with chronic infections, autoimmune conditions or long-standing pyothorax which were not seen in this case. Chylous pleural effusions in this patient were successfully managed with chemotherapy for the underlying lymphoma