Primary Neuroendocrine Carcinoma of the Breast Metastatic to the Bones, Which Chemotherapy?

The primary neuroendocrine carcinoma (NEC) of the breast is defined as immunohistochemical expression of neuroendocrine markers (chromogranin and synoptophysin) in more than 50% of the neoplastic cells according to World Health Organization (WHO) classification of tumors in 2003 (Tumours of the Breast and Female Genital Organs, 2003, Lyon: IARC Press). It accounts for less than 5% of all cancers arising from the breast (Tumours of the Breast and Female Genital Organs, 2003, Lyon, France: IARC Press). However, based on the study conducted by Wang et al., the primary NEC of breast comprises less than 0.1% of all mammary carcinomas (Frankf Z Pathol, 73, 1963, 24). Because of the rarity of the disease and absence of the prospective trials, there is no standard treatment for primary NEC of the breast. Herein, we report the case of a middle age woman with primary NEC with bone metastasis.

Rhabdomyosarcoma masquerading as lymphadenopathy in a patient with newly diagnosed Hodgkin's lymphoma.

BACKGROUND: Hodgkin's lymphoma (HL) is a rare malignancy which often presents with lymphadenopathy and classic "B symptoms" of weight loss, fever, and night sweats. Additional masses or nodes could easily be presumed to be a result of the initial diagnosis. On the other hand, adult rhabdomyosarcoma is a rare malignancy presenting with a new mass in a patient with previous diagnosis of Hodgkin's lymphoma. In both cases, a tissue diagnosis should be obtained to appropriately confirm the diagnosis. CASE PRESENTATION: We present a case of a 64-year-old male who presents with right axillary lymphadenopathy, diagnosed as Hodgkin's lymphoma. He subsequently developed left inguinal lymphadenopathy without the classic B symptoms of HL. Excisional biopsy revealed rhabdomyosarcoma. Stage III Hodgkin's lymphoma (lymph node involvement on both sides of the diaphragm) is not commonly seen without typical B symptoms. Once the diagnosis of two primary malignancies is made, the dilemma becomes determining the treatment course. In the case of Hodgkin's lymphoma and rhabdomyosarcoma, there is some overlap in the chemotherapeutic regimen and use of radiation. CONCLUSIONS: This case illustrates the importance of careful examination of Hodgkin's lymphoma patients and consideration of additional tissue diagnoses in atypical presentations of new masses or lymphadenopathy on the opposite side of the diaphragm.

Food to Overcome Outcomes Disparities: A Randomized Controlled Trial of Food Insecurity Interventions to Improve Cancer Outcomes.

PURPOSE: Food insecurity is prevalent among low-income immigrant and minority patients with cancer. To our knowledge, this randomized controlled trial is the first to prospectively examine the impact on cancer outcomes of food insecurity interventions, with the goal of informing evidence-based interventions to address food insecurity in patients with cancer. METHODS: A three-arm randomized controlled trial was conducted among food-insecure (18-item US Department of Agriculture Household Food Security Survey Module score ≥ 3) patients with cancer (N = 117) at four New York City safety net cancer clinics. Arms included a hospital cancer clinic-based food pantry (arm 1), food voucher plus pantry (arm 2), and home grocery delivery plus pantry (arm 3). Treatment completion (primary outcome) and full appointment attendance were assessed at 6 months. Food security status, depression symptoms (Patient Health Questionnaire-9), and quality-of-life scores (Functional Assessment of Cancer Therapy-General) were assessed at baseline and at 6 months. RESULTS: Voucher plus pantry had the highest treatment completion rate (94.6%), followed by grocery delivery plus pantry (82.5%) and pantry (77.5%; P = .046). Food security scores improved significantly in all arms, and Patient Health Questionnaire-9 and Functional Assessment of Cancer Therapy-General scores improved significantly in the pantry and delivery plus pantry arms. CONCLUSION: Our findings in this preliminary study suggest that voucher plus pantry was the most effective intervention at improving treatment completion, and it met our a priori criterion for a promising intervention (≥ 90%). All interventions demonstrated the potential to improve food security among medically underserved, food-insecure patients with cancer at risk of impaired nutrition status, reduced quality of life, and poorer survival. All patients with cancer should be screened for food insecurity, with evidence-based food insecurity interventions made available.

Molecular Genetics and the Role of Molecularly Targeted Agents in Metastatic Colorectal Carcinoma.

BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is the third most common malignancy and fourth leading cancer-related deaths worldwide. In the USA, CRC is the third most commonly diagnosed cancer in both men and women. It is caused by genetic components and potential environmental factors such as consumption of processed meat, red meat, animal fats, low fiber intake, and obesity. Despite the utilization of effective screening modalities and guidelines in the USA, a significant number of patients are diagnosed with advanced, metastatic disease at the time of presentation to the physician. Recent advances in the understanding of molecular medicine with subsequent development and incorporation of newer therapeutic agents into current chemotherapeutic regimens have improved outcomes; however, the management of metastatic CRC remains challenging, particularly for the treating oncologists. METHODS: We conducted a literature search on CRC mainly related to molecular genetics, targeted biologic agents, and published clinical trials. We also searched and reviewed ongoing clinical trials from Clinicaltrials.gov. RESULTS AND CONCLUSIONS: Alterations in several oncogenes are associated with CRC, among those RAS, BRAF, and HER2 are of current clinical importance. Chemotherapy drugs, along with vascular endothelial growth factor or epidermal growth factor receptor monoclonal antibodies, are proven to be efficient with manageable toxicity profiles in metastatic CRC. Additional researches on Her-2-directed therapy, BRAF-targeted agents, immunotherapeutic, and newer molecularly targeted agents are needed for further improvement in outcome.

Rare Acute Presentation of a Low-Grade Thymic Neuroendocrine Tumor.

Primary neuroendocrine tumor (NET) of the thymus is very rare. Here we report an unusual presentation of grade-I typical thymic NET in a 63-year-old female who presented with signs and symptoms of congestive heart failure (CHF) due to the mass effect from the huge tumor. A computed tomography (CT) scan of the chest revealed a mediastinal mass measuring 16.4 x 12 x 15.3 cm displacing most of the left lung parenchyma, with mass effect on the heart, and encasing the ascending aorta and main pulmonary trunk. Pathology report from the thymic mass biopsy showed tumor cells strongly expressing synaptophysin, chromogranin A, and cluster of differentiation (CD)56 markers. The diagnosis was consistent with grade-I typical thymic NET based on low Ki-67 and morphology. The patient was not in agreement for acute surgery or oncological treatment options. Thus, the plan was made to embolize the arteries from the right coronary artery that were feeding the mass in an effort to shrink the size with goals of future surgical resection. However, given the advanced stage of the diagnosis with mass effect on the heart and the patient's reluctance to consider the main definitive treatment options, the prognosis was extremely poor and the patient eventually passed away.

A case of classic Kaposi sarcoma in an immunocompetent human immunodeficiency virus-negative Dominican man.

Kaposi sarcoma is an uncommon tumor that primarily arises in the skin and mucosal surfaces, but may metastasize to the internal organs. Four main variants of Kaposi sarcoma are recognized as the following: classic Kaposi sarcoma, which occurs in middle-aged or elderly men; epidemic Kaposi sarcoma, associated with human immunodeficiency virus infection; iatrogenic Kaposi sarcoma seen in patients on immunosuppressive drug therapy; and endemic Kaposi sarcoma. This report is of a case of classic Kaposi sarcoma in 55-year-old immunocompetent and human immunodeficiency virus-negative Dominican man who had lived in the United States for 2 years, who presented with a 2-year history of skin lesions on his lower extremities and soft palate. Biopsy of the soft palate was consistent with Kaposi sarcoma. The patient was treated with paclitaxel with a good response. This case report demonstrates the importance of recognizing that classic Kaposi sarcoma, first described almost 150 years ago, can still present in immunocompetent middle-aged men of all ethnicities.

Invasive Aspergillosis in a Patient with Stage III (or 3a or 3b) Non-Small-Cell Lung Cancer Treated with Durvalumab.

Durvalumab is a therapeutic monoclonal antibody that blocks the checkpoint inhibitor, programmed death ligand 1 (PD-L1), resulting in T-cell activation and an antitumor response. Durvalumab is approved for patients with unresectable stage III non-small-cell lung cancer (NSCLC) which has not progressed following platinum-based chemoradiotherapy. A 63-year-old man presented to the emergency department with a 15-day history of increasing shortness of breath. Several months previously, he had been diagnosed with a poorly differentiated stage IIIB NSCLC. He had completed six cycles of chemotherapy with paclitaxel and carboplatin and four cycles of immunotherapy with durvalumab 13 days before his emergency hospital admission. Computed tomography (CT) imaging showed a large left-sided loculated hydropneumothorax suggestive of empyema, patchy opacification of the left lung, and a left upper lobe lung mass. Histology of the cell block from the pleural fluid and decorticated lung tissue showed hyphae suggestive of invasive Aspergillus fumigatus. Treatment with voriconazole resulted in clinical improvement. To our knowledge, this is the first reported case of pleural aspergillosis in a patient treated with durvalumab. However, the increasing use of immune checkpoint inhibitors in oncology requires increased awareness by clinicians of immune-related adverse events (irAEs) due to opportunistic infection.

Splenic infarction in babesiosis: A rare presentation.

Babesiosis is a protozoan parasitic infection transmitted by the Ixodes tick. Splenic infarction is a rare, but potentially life-threatening complication of babesiosis; it is therefore vital that this complication is recognized.

Hypercoagulable workup in a community hospital setting: to test or not to test; that is the question.

Background: Thrombophilia tests are often ordered unnecessarily and/or inappropriately, with significant impact on healthcare costs, hospital resources, time, and potential harm to the patient. Objective: To identify the incidence of unnecessary and inappropriate thrombophilia testing in a community hospital setting. Methods: We retrospectively reviewed electronic medical records for patients who underwent inpatient thrombophilia testing at The Brooklyn Hospital Center from 1/1/2018 to 12/31/2018. The indications, and details of the tests, and associated costs were recorded. Results: A total of 62 patients were included (mean age 45.8, 67.7% female). In 57/62 (91.9%) patients, tests were ordered in the acute phase of thrombosis. At the time the tests were ordered, 29/62 (46.8%) patients were on anticoagulation. Positive results were found in 21/62 (53.2%) patients, but was repeated in only 1/21 (4.7%) patient. Results for 51/62 (82%) patients were obtained after discharge. The hematology-oncology service was consulted in 5/62 (8.1%) cases and recommended testing in only 1 (1.6%) patient. Only 1 (1.6%) patient had both an appropriate indication and appropriate testing. Costs for the 273 total tests were $26,400. Conclusion: Thrombophilia tests were often ordered inappropriately and unnecessarily. We recommend testing only for patients with inpatient status under recommendation from the hematology-oncology service.

Checkpoint inhibitors plus chemotherapy for first-line treatment of advanced non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: We conducted a meta-analysis to evaluate the efficacy and safety of upfront add-on immunotherapy for advanced non-small cell lung cancers (NSCLC). METHODS: We performed a literature search on first-line chemotherapy ± immunotherapy in NSCLC. We utilized Revman version 5.3 to calculate the estimated pooled hazard ratio for overall survival (OS) and progression-free survival (PFS) and pooled risk ratio for objective response rate (ORR), all-grade and high-grade adverse events with 95% CI. RESULTS: We analyzed 4322 patients. The pooled hazard ratios for OS, PFS and ORR were 0.74 (95% CI: 0.62-0.88; p = 0.0007), 0.62 (95% CI: 0.57-0.68; p = 0.00001) and 1.51 (95% CI: 1.3-1.74; p = 0.00001), respectively. The pooled risk ratios for all-grade and high-grade adverse events were 1.01 (95% CI: 0.99-1.03; p = 0.27) and 1.17 (95% CI: 1.07-1.28; p = 0.0006), respectively. CONCLUSION: Add-on immunotherapy significantly improves PFS, OS and ORR for the first-line treatment of advanced NSCLC with a reasonable safety profile.

A case of gastric small cell carcinoma with metastases to bone and liver.

Gastric small cell carcinoma (GSCC) is a rare entity in the western hemisphere. GSCC's typically arise in the upper one-third of the stomach and have histologic features similar to those of small-cell lung carcinoma (SCLC). They have an aggressive natural history that is characterized by early and widespread metastases. Prognosis is dismal with an overall survival of less than 12 months. We present the case of a 79-year-old African-American woman who presented with two weeks of progressive dysphagia associated with nausea, vomiting and a foreign body sensation in the throat. Computed tomography (CT) imaging showed multiple hepatic and lymph node lesions but revealed no gastric thickening. Endoscopy revealed a large ulcer on the lesser curvature of the stomach. Biopsy proved the diagnosis of pure-type GSCC. Bone scan identified multiple focal bony lesions at the thoracolumbar vertebrae, ribcage, bilateral scapulae, pelvic bones and right proximal femur. Treatment was started with cisplatin and etoposide. To our knowledge, this is the one of the first reported cases of gastric small cell cancer with bone metastases in the western hemisphere. Our report shows the importance of doing a full metastatic workup in these patients to identify sites of metastases.

Myelophthisic Anemia in a Patient with Lobular Breast Carcinoma Metastasized to the Bone Marrow.

Breast tumors have a predilection for metastasizing to the bone leading to cells being displaced by the cancer cells subsequently producing immature leukocytes and erythrocytes in the peripheral blood. We present a case of a 57-year-old female who was found to have myelophthisic anemia secondary to stage four lobular breast carcinoma metastasized to the bone marrow after being misdiagnosed as having thrombotic thrombocytopenia purpura. Diagnosis of myelophthisic anemia requires a thorough workup and treatment is based upon secondary management of the malignancy.

Myelodysplastic Syndrome Clinically Presenting with the "Classic TTP Pentad".

The clinical presentation of myelodysplastic syndrome (MDS) is not specific. Many patients can be asymptomatic and can be detected only due to an abnormal complete blood cell count (CBC) on routine exam or for other reasons while others can be symptomatic as a consequence of underlying cytopenias. Thrombotic thrombocytopenic purpura (TTP) usually is suspected under the evidence of microangiopathic hemolytic anemia (MAHA) and thrombocytopenia and because it is a life-threatening condition (medical emergency) immediate initiation of plasmapheresis could be life-saving. The following case illustrates an unusual presentation of MDS in a patient who came in to the emergency room with the classic TTP "pentad" of fever, renal involvement, MAHA, mental status changes, and thrombocytopenia. We will focus our discussion in the clinical presentation of this case.

Benefit and risk of primary thromboprophylaxis in ambulatory patients with advanced pancreatic cancer receiving chemotherapy: a systematic review and meta-analysis of randomized controlled trials.

As vascular thromboembolism (VTE) is a leading cause of death in cancer patients, it has been postulated that primary thromboprophylaxis (PTP) in cancer patients might improve survival by reducing VTE occurrence. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) to investigate the benefit and risk of PTP with low-molecular-weight heparins (LMWHs) in ambulatory advanced pancreatic cancer (APC) patients receiving chemotherapy. We undertook a literature search using MEDLINE and EMBASE databases through May 2015. RCTs with reduction in symptomatic VTE as a primary or secondary endpoints were included. Mantel-Haenszel method was used to estimate the pooled event-based risk ratio as well as the pooled absolute risk difference with 95% confidence interval (CI). Seven hundred and thirty-eight APC patients were eligible for analysis. PTP lasted 3-6 months. The crude VTE incidence was 2.1 and 11.2% in LMWH and in control groups, respectively (risk ratio, 0.18; 95% CI, 0.083-0.39; P < 0.0001). The absolute risk difference in VTE was -0.092 (95% CI, -0.127 to -0.057; P < 0.0001), with an estimated number needed to treat of 11 patients to prevent one symptomatic VTE event. The pooled risk ratio for major bleeding was 1.25 (95% CI, 0.48-3.3, P = 0.65). Although these findings are encouraging to deploy PTP in APC patients receiving chemotherapy, uncertainties remain as to its survival benefit, optimal PTP duration, type and dose of LMWH, and costs of care. Therefore, adequately powered randomized phase III studies are warranted to address these questions.

An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract.

Small cell neuroendocrine carcinoma (SNEC) is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck.

A predictable but life-threatening complication of hydroxyurea in a patient with sickle cell anaemia: an experience learned from a Jehovah's Witness.

It is well known that hydroxyurea can cause pancytopaenia secondary to bone marrow suppression, which is reversible with short-term discontinuation of the therapy. However, it is important to note that bone marrow suppressive effects caused by hydroxyurea could be easily potentiated in patients with sickle cell anaemia complicated by chronic kidney disease (CKD). We present a case of a Jehovah's Witness with sickle cell anaemia, who developed severe bone marrow suppression due to the combined effects of hydroxyurea and CKD, resulting in a prolonged recovery period after discontinuation of hydroxyurea.

Spinal cord infarct as a presentation of cholangiocarcinoma with metastases.

It is well-known that malignancies, particularly pancreatic and brain cancers, often present as venous thromboembolism. However, stroke and angina attributable to arterial occlusion are relatively common presentations as well. We are reporting a patient, with treatment-naïve hepatitis C and multiple liver nodules, was admitted for deep vein thrombosis (DVT) and pulmonary embolism (PE). Subsequently, she developed an ascending paralysis due to spinal cord infarct (SCI) despite adequate anticoagulation. She also had an enlargement of left supraclavicular lymph node, which was confirmed histologically metastatic cholangiocarcinoma. To our best knowledge, this is the first literature report showing the association linking SCI to metastatic cholangiocarcinoma as a consequence of hypercoagulable state of malignancy.

Retinal vessel extraction using Lattice Neural Networks with Dendritic Processing.

Retinal images can be used to detect and follow up several important chronic diseases. The classification of retinal images requires an experienced ophthalmologist. This has been a bottleneck to implement routine screenings performed by general physicians. It has been proposed to create automated systems that can perform such task with little intervention from humans, with partial success. In this work, we report advances in such endeavor, by using a Lattice Neural Network with Dendritic Processing (LNNDP). We report results using several metrics, and compare against well known methods such as Support Vector Machines (SVM) and Multilayer Perceptrons (MLP). Our proposal shows better performance than other approaches reported in the literature. An additional advantage is that unlike those other tools, LNNDP requires no parameters, and it automatically constructs its structure to solve a particular problem. The proposed methodology requires four steps: (1) Pre-processing, (2) Feature computation, (3) Classification and (4) Post-processing. The Hotelling T(2) control chart was used to reduce the dimensionality of the feature vector, from 7 that were used before to 5 in this work. The experiments were run on images of DRIVE and STARE databases. The results show that on average, F1-Score is better in LNNDP, compared with SVM and MLP implementations. Same improvement is observed for MCC and the accuracy.

Leptomeningeal involvement in a patient with splenic lymphoma with villous lymphocytes.

Splenic lymphoma with villous lymphocytes (SLVL) is an indolent hematological malignancy. Persistent lymphocytosis and splenomegaly usually last for years before patients develop infectious complications. Organ involvement other than spleen and bone marrow is rare in SLVL. We report a case of SLVL-related meningitis occurring in a patient presenting with altered mental status and seizures. CNS involvement was documented by an MRI of the head and by the presence of atypical lymphocytes in the cerebrospinal fluid (CSF). Morphologic examination and immunophenotypic analyses were conducted to determine the nature of atypical lymphocytes in the peripheral blood, spleen, bone marrow and CSF. The patient improved after treatment with a combination of radiation and chemotherapy.