A Rare Case of Aggressive Systemic Mastocytosis With Skeletal Osteosclerotic Lesions on Presentation: A Diagnostic Conundrum.

Systemic mastocytosis (SM) is a heterogeneous group of disorders caused by mast cell proliferation. SM often presents with non-specific symptoms making it a diagnostic challenge. Moreover, presentation with bone involvement is highly uncommon. Here, we report a rare case of SM in a 68-year-old female who initially presented with gastrointestinal symptoms and was later found to have sclerotic bone lesions on imaging. This case highlights an unusual presentation of SM, informing clinicians of the importance of keeping this disease process on the differential list of diagnostic conundrums.

Vulvar Cancer with Cutaneous and Breast Metastases.

Vulvar cancer accounts for about 5% of cancer of female genitalia. It may initially present as benign symptoms resulting in potential delay in diagnosis. Few cases of distant metastases to skin or breast have been reported. We present the case of a 76-year-old female with possible delay in diagnosis of her squamous cell carcinoma of vulva. After 4 months of the diagnosis, she presented with concurrent cutaneous and breast metastases.

Synchronous Presence of EGFR, ALK Driver Mutations Along With PD L1 Overexpression in a Resected Early Stage Non-Small Cell Lung Cancer: A Case Report and Review of Literature.

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.

Correction: Rapidly Progressing Myelodysplastic Syndrome Initially Presenting as Acute Leukemia.

[This corrects the article DOI: 10.7759/cureus.1096.].

Anti-PD-1/PD-L1 antibodies in non-small cell lung cancer: the era of immunotherapy.

INTRODUCTION: Advanced non-small cell lung cancer (NSCLC) has been conventionally treated with cytotoxic chemotherapy with short-lived responses and significant toxicities. Monoclonal antibodies to programmed death-1 receptor (PD-1) and programmed death ligand 1 (PD-L1) have shown tremendous promise in the treatment of advanced NSCLC in various clinical trials. Areas covered: In this article, we will review the outcomes of various trials of anti-PD-1/anti-PD-L1 antibodies in the treatment of NSCLC. We will also discuss their mechanism of action and toxicities. Expert commentary: Anti-PD-1/PD-L1 antibodies offer several advantages including significant antitumor activity, induction of long lasting responses, and favorable safety profile. Several trials are now being conducted to evaluate their efficacy as first line agents as well as in combination with other agents. More research is also needed to identify other biomarkers, in addition to PD-L1 expression, that could more reliably predict response to these drugs, and aid in better patient selection.

Salvage therapies in relapsed and/or refractory myeloma: what is current and what is the future?

The treatment landscape for multiple myeloma (MM) is evolving with our understanding of its pathophysiology. However, given the inevitable cohort heterogeneity in salvage therapy, response to treatment and overall prognoses tend to vary widely, making meaningful conclusions about treatment efficacy difficult to derive. Despite the hurdles in current research, progress is underway toward more targeted therapeutic approaches. Several new drugs with novel mechanism of action and less toxic profile have been developed in the past decade, with the potential for use as single agents or in synergy with other treatment modalities in MM therapy. As our discovery of these emerging therapies progresses, so too does our need to reshape our knowledge on knowing how to apply them. This review highlights some of the recent landmark changes in MM management with specific emphasis on salvage drugs available for relapsed and refractory MM and also discusses some of the upcoming cutting-edge therapies that are currently in various stages of clinical development.

Novel Drugs and Combination Therapies for the Treatment of Metastatic Melanoma.

Metastatic melanoma (MM) still remains as one of the most worrisome cancer known to mankind. In last two decades, treatment of melanoma took a dramatic turn with the discovery of targeted therapy which targets the mutations in mitogen-activated protein kinase (MAPK) pathway and immune checkpoint inhibitors. These new findings have led to emergence of many novel drugs that have been approved by FDA. Targeted therapy drugs such as vemurafenib, trametinib and dabrafenib target the MAPK pathway whereas immunotherapies such as ipilimumab, nivolumab and pembrolizumab block immune checkpoint receptors on T lymphocytes. All these drugs have shown to improve the overall survival in MM. Despite these recent discoveries, treatment of MM remains challenging because of rapid development of resistance to targeted therapy. This review will discuss recently approved drugs and their adverse effects and also shed light on combination therapy in treatment of melanoma.

Bronchial myeloid sarcoma with concurrent Aspergillus fumigatus infection in a patient presenting with hemoptysis.

Myeloid sarcoma (MS) is an extramedullary myeloid neoplasm characterized by proliferation of myeloblasts which can occur in any organ or site. Bronchial and pulmonary involvement, however, is uncommon. We describe a case of bronchial MS in an 81-year-old female with a history of high-grade myelodysplastic syndrome; she was started on treatment few months before, and she presented with fever, cough and profuse hemoptysis. She was found to be pancytopenic with bilateral airspace consolidations, most notably in the right upper and lower lobes, on imaging studies. She was treated with broad-spectrum antibiotics and antifungals without much improvement in her clinical or radiological status. Ultimately, biopsy of the lung lesions showed myeloid sarcoma with concurrent Aspergillus fumigatus infection. Bronchial/pulmonary MS should be considered in the list of differential diagnoses in a patient with a history of myeloid neoplasm and presenting with respiratory related symptoms, as early administration of chemotherapy may help to improve survival rates.

Role of Topotecan in Non-Small Cell Lung Cancer: A Review of Literature.

Topotecan (TPT), a chemotherapeutic agent, is a topoisomerase-I inhibitor. Topoisomerase-I is a nuclear enzyme that relieves torsion strain in DNA by opening single strand breaks which helps in DNA replication. TPT inhibits this enzyme, thus preventing DNA replication and causes cell death. TPT has demonstrated to have broad spectrum of antitumor activity in tumors like cervical, ovarian, endometrial and small cell lung cancers (SCLCs). The intravenous (IV) formulation of the drug is currently approved by the US Food and Drug Administration for the treatment of patients with SCLC and ovarian cancer at a dose of 1.5 mg/m2 administered daily for five consecutive days, with treatment cycles repeated every 3 weeks. TPT has shown some promising activity in the treatment of non-small cell lung cancer (NSCLC) with favorable side effect profile. Several clinical trials have been conducted with TPT in either IV or oral formulation for the treatment of NSCLC as a first or second-line treatment. Here we reviewed all the clinical trials done with TPT to date in the treatment of NSCLC both as a single-agent and combination therapy.

An Exceptionally Favorable Response to Etoposide and Cisplatin.

A 66-year-old female with multiple medical co-morbidities was diagnosed with limited-stage small cell lung carcinoma (SCLC) about 11 years ago, back in 2004. The patient was treated with concomitant chemotherapy and radiotherapy, along with prophylactic whole brain radiation. She received a total of four cycles of etoposide and cisplatin. The patient showed a complete response to the above-mentioned treatment and had no evidence of tumor recurrence on any of the scans until 2015. Her last computed tomography (CT) scan of the chest in October 2015 showed bilateral hilar and mediastinal lymphadenopathy. Fine needle aspiration (FNA) of the left hilar node revealed the presence of malignant cells consistent with SCLC. Median survival for limited stage SCLC ranges from 16-24 months, and the reported five-year survival is 14%. In this report, we present the case of a 66-year-old female who showed an exceptionally favorable response to cisplatin and etoposide chemotherapy characterized by a disease-free survival of 11 years.