Celiac Disease Masquerading as Arthralgia.

Celiac disease is an immune-mediated disorder triggered by dietary gluten. It classically presents with gastrointestinal symptoms. It may also present with atypical manifestations like anemia, arthritis, infertility, or other neurological symptoms. However, arthralgia as a sole manifestation of celiac disease is a rare clinical scenario. Even though the clinical spectrum of celiac disease is broad, prompt diagnosis and management exert a protective effect against complications of celiac disease. We want to highlight and expand on the existing knowledge on atypical presentations about celiac disease.

Adenosquamous Carcinoma of the Breast: Case Report and Literature Review.

Low-grade adenosquamous breast carcinoma (LGASC) is an atypical variant of metaplastic breast cancer. It differs from metaplastic carcinoma and has an indolent behavior. It usually presents as a palpable lump, unlike in our case, which had an incidental presentation. Because of its rarity, it often creates a clinical and diagnostic challenge. With the risk of local recurrence, the current management is aggressive with excision. Chemoradiation has been used in a few cases, but optimal management is unclear. Our manuscript aims to add to the existing knowledge on LGASC.

COVID-19 Presenting With a Challenging Combination of Thrombocytopenia and Thrombosis.

Coronavirus disease 2019 (COVID-19) causes various hematological abnormalities, leading to several complications in the disease course. We report two COVID-19 cases presenting with a combination of thrombocytopenia and coagulopathy complications in late 2020. A 73-year-old male with a history of immune thrombocytopenic purpura (ITP) presented with acute ischemic stroke and acute thrombocytopenia in the setting of COVID-19. He was managed with steroids and intravenous immunoglobulin (IVIG) and had a subsequent acute ischemic stroke with microhemorrhages. Another 72-year-old female with a history of cryptogenic liver cirrhosis and chronic thrombocytopenia presenting with acute thrombocytopenia in the setting of COVID-19 was managed with steroids and IVIG. She had a coagulopathic complication of deep venous thrombosis (DVT) later in her disease course managed with inferior vena cava filter and low-dose enoxaparin, but she subsequently died with a bleeding complication of retroperitoneal hemorrhage. Despite the aggressive ongoing research, the treatment options for severe COVID-19 are limited to date and the mortality remains high. Both these cases are examples of challenging situations that the physicians are currently facing with COVID-19 pandemic.

Hypoglycemia in a Patient with Hypercortisolism and Adrenocortical Carcinoma: A Paradoxical Entity.

Adrenal cortical carcinoma is a rare and aggressive cancer with poor prognosis. Cases usually present with signs and symptoms of excessive hormone production. Hyperglycemia and Cushing syndrome are common, but tumor-associated hypoglycemia due to paraneoplastic secretion of insulin-like growth factor-2 (termed Anderson's syndrome) is uncommon. Given the rarity of adrenal cortical carcinoma, diagnosis and management of associated complications is challenging. In this study, we present a case of metastatic adrenal cortical carcinoma with a myriad of hormonal abnormalities. We will also briefly review literature regarding genetic association, pathophysiology, treatment options, and prognosis.

Hyperprogression: A Unique Phenomenon of Progression of Existing Tumor Secondary to Immunotherapy.

Immunotherapy is a relatively new approach for cancer treatment that has demonstrated prolonged survival by enhancing the body's immunologic response among advanced cancer patients. Although the benefits of immunotherapy have been well documented, potentially detrimental consequences such as pseudoprogression and hyperprogression have been identified. Hyperprogression is a tumor response in which the existing underlying tumor grows rapidly after initiating treatment with an immune checkpoint inhibitor. This report presents a case of hyperprogression of non-small-cell lung cancer in a 71-year-old male who was initially treated with four cycles of chemotherapy (carboplatin and pemetrexed) and later started on maintenance therapy with pembrolizumab and chemotherapy. Two weeks after receiving the first cycle of immunotherapy, he presented with a complaint of shortness of breath. On repeat computed tomography of the chest, he was found to have a two-fold increase in the size of the preexisting tumor with new large multiloculated right pleural effusion and abdominal ascites.

A Case Report on Adenosquamous Carcinoma of Gallbladder: A Very Rare Malignancy.

Gallbladder (GB) carcinoma is a rare carcinoma with a poor prognosis. The prevalence is 0.7-21/100,000 worldwide and 1-2/100,000 in the United States. Adenosquamous cell carcinoma is composed of glandular and squamous components. The overall five-year survival rate is less than 5%, with a median survival of fewer than six months. We are presenting a case of adenosquamous carcinoma of the GB in a 76-year-old female who presented with right upper quadrant abdominal pain and was found to have an enlarged GB, with thickened irregular wall likely inflammatory or malignant and mildly dilated common bile duct on ultrasound imaging of the abdomen. Core needle biopsy of GB showed findings compatible with adenosquamous carcinoma and immunohistochemistry was positive for P40, CK5,6. She was diagnosed with stage T4 N0 M0. She was started on chemotherapy with cisplatin and gemcitabine (25 mg/m2 and 1000 mg/m2), respectively, every three weeks but her condition worsened after the fifth cycle of chemotherapy and she decided to move forward with hospice care given her bad prognosis. Unfortunately, she passed away one week after being discharged home.

Corrigendum: Clinical Utilization Pattern of Liquid Biopsies (LB) to Detect Actionable Driver Mutations, Guide Treatment Decisions and Monitor Disease Burden During Treatment of 33 Metastatic Colorectal Cancer (mCRC) Patients (pts) at a Fox Chase Cancer Center GI Oncology Subspecialty Clinic.

[This corrects the article DOI: 10.3389/fonc.2018.00652.].

Evolving treatment modalities for immune thrombocytopenia in adults.

The management of patients with relapsed or refractory immune thrombocytopenia (ITP) remains challenging for hematologists. While there are a multitude of drugs available, it is largely an individualized management based on patient preferences, side effects, previous treatment received, and responses to them, comorbidities and cost associated with the treatment. We hereby review the newer approaches in the treatment of ITP.

Bilateral Primary Marginal Zone Lymphoma of the Breast - A Rare Breast Malignancy.

Extranodal marginal zone lymphoma (EMZL) presents only rarely within the breast, although the incidence of breast EMZL has increased in the past decade for unclear reasons. Due to its rarity, the etiology, course, and treatment response of this cancer are less studied. Case Report: We present the case of a 64-year-old female who had bilateral diffuse irregularity in a trabecular pattern on screening mammogram. Random ultrasound-guided breast biopsy of the right breast demonstrated an extra-nodal marginal zone B-cell lymphoma. She also had approximately 25% marrow involvement by mucosa-associated lymphoid tissue-type marginal zone lymphoma and splenomegaly. Clinically she remained asymptomatic during a 1-year follow-up. Although she presented with advanced-stage disease involving both breasts, spleen and bone marrow, given her lack of associated symptoms, she was observed with active surveillance. Conclusion: Asymptomatic cases of breast EMZL can be managed with close observation as exemplified by our case.

A Rare Presentation of an Invasive Ductal Carcinoma of Ectopic Axillary Breast Tissue.

Ectopic breast tissue (EBT) is a rare entity and can present anywhere along the milk line, including the axilla, inframammary region, thighs, perineum, groin, and vulva. However, the axilla is the most common area of presentation. EBT can present as supernumerary breasts or aberrant breast tissue. Malignancy arising in EBT is rare, but the most common morphological variant is invasive ductal carcinoma. We report a case of a 43-year-old woman, a smoker with a family history of breast cancer, who presented to our clinic with a small mass in the right axillary area. After monitoring it for one year, the mass increased in size, so she returned to the clinic and decided with her care team to excise the mass. Histopathology showed invasive mammary adenocarcinoma arising in EBT and was diagnosed as right accessory stage I breast cancer. This case illustrates the imperative that any mass in the axillary region should be thoroughly assessed to rule out carcinoma in the accessory axillary tissue for timely management.

Institutional Experience of Using Andexanet Alfa.

Given their ease of use, safety, and efficacy, direct-acting oral anticoagulants (DOACs) are nowadays widely used in patients with atrial fibrillation or venous thromboembolism, with or without an association with malignancy. Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that reverses the inhibition of factor Xa. After Food and Drug Administration (FDA) approval in May 2018, andexanet has been used for life-threatening bleeding in patients treated with apixaban or rivaroxaban. In this article, we present a single institutional retrospective review of patients receiving andexanet alfa at Guthrie Robert Packer Hospital. A total of four patients in a period of 10 months received andexanet for intracranial bleeding, 50% (2) had excellent hemostasis, 30 days mortality was 75% (3), and 25% (1) had a thromboembolic event. Anticoagulation was never started in all patients. This review tends to show the real-world utilization data of andexanet in a community hospital setting.

Dual Checkpoint Inhibition with Ipilimumab plus Nivolumab After Progression on Sequential PD-1/PDL-1 Inhibitors Pembrolizumab and Atezolizumab in a Patient with Lynch Syndrome, Metastatic Colon, and Localized Urothelial Cancer.

Immune checkpoint blockade (ICB) is an approved therapy for advanced metastatic mismatch repair (MMR)-deficient cancer regardless of tissue of origin. Although therapy is effective initially, recurrence rates are significant, and long-term outcomes remain poor for most patients. It is not currently recommended to give sequential ICB for advanced MMR-deficient colorectal cancer (CRC) or for patients with metastatic cancer from Lynch syndrome. The need for subsequent therapy options in advanced MMR-deficient cancer beyond the first ICB regimen arises in clinical practice, and there are often no effective standard chemotherapies or other targeted therapies. We report the case of a Lynch syndrome patient with metastatic CRC and urothelial cancer who was treated sequentially with pembrolizumab (targeting PD1), atezolizumab (targeting PD-L1), brief rechallenge with pembrolizumab, and finally the combination of ipilimumab (targeting CTLA-4) and nivolumab (targeting PD1). Over a 28-month period the patient experienced prolonged disease control with each different regimen the first time it was given, including metabolic response by positron emission tomography and computed tomography scanning and tumor marker reductions. The case suggests that some patients with advanced MMR-deficient CRC may experience meaningful clinical benefit from multiple sequential ICB regimens, a strategy that can be further tested in clinical trials. KEY POINTS: The case exemplifies clinical benefit from sequential immune checkpoint blockade in a patient with Lynch syndrome with advanced metastatic colorectal cancer and urothelial cancer.Metabolic response, with decreased fluorodeoxyglucose avidity on positron emission tomography and computed tomography, and reductions in tumor markers, such as carcinoembryonic antigen, were helpful in this case to monitor disease status over a 28-month period of therapy.The concept of sequential immune checkpoint blockade in patients with advanced mismatch repair-deficient cancer merits further study to determine which patients are most likely to benefit.

First-Line Therapies for Metastatic Lung Adenocarcinoma Without a Driver Mutation.

Lung cancer is the leading cause of cancer-related death worldwide. The majority of these cancers are non-small-cell lung cancer, of which adenocarcinoma is the most common histologic subtype. Most patients are diagnosed at advanced stages when systemic treatment is needed. Whereas prognosis has improved for patients with targetable driver mutations, the majority of patients do not possess tumors with such molecular mutations. Platinum-based chemotherapy has traditionally been the mainstay of treatment, although in recent years immunotherapy has emerged as a treatment option and can result in robust and durable treatment responses in a subset of patients. Recent clinical trials on novel immunotherapy combinations and immunochemotherapy combinations may broaden the number of patients that may benefit from checkpoint inhibitors and elicit responses in those who otherwise may not have experienced a response to monotherapy with an immunotherapy drug. This review will outline the currently available therapies for the first-line treatment of metastatic adenocarcinoma that do not possess a driver mutation and provide a recommended approach and algorithm by which to select the best first-line therapy.

Clinical Utilization Pattern of Liquid Biopsies (LB) to Detect Actionable Driver Mutations, Guide Treatment Decisions and Monitor Disease Burden During Treatment of 33 Metastatic Colorectal Cancer (mCRC) Patients (pts) at a Fox Chase Cancer Center GI Oncology Subspecialty Clinic.

Background: Liquid biopsy (LB) captures dynamic genomic alterations (alts) across metastatic colorectal cancer (mCRC) therapy and may complement tissue biopsy (TB). We sought to describe the utility of LB and better understand mCRC biology during therapy. Methods: Thirty-three patients (pts) with mCRC underwent LB. We used permutation-based t-tests to assess associations between alts, and clinical variables and used Kendall's tau to measure correlations. Results: Of 33 pts, 15 were women; 22 had colon, and the rest rectal cancer. Pts received a median of two lines of therapy before LB. Nineteen pts had limited testing on TB (RAS/RAF/TP53/APC), 11 extended NGS, and 3 no TB. Maxpct and alts correlated with CEA (p < 0.001, respectively). In 3/5 pts with serial LB, CEA correlated with maxpct trend, and CT tumor burden. In 6 pts, mutant RAS was seen in LB and not TB; 5/6 had received anti-EGFR therapy prior to LB, suggesting RAS alts developed post-therapy. In two pts RAS-mutated by TB, no RAS alts were detected on LB; these pts had low disease burden on CT at time of LB that also did not reveal APC or TP53 alts. In six patients who were KRAS wt based on TB, post anti-EGFR LB revealed subclonal KRAS mutations, likely a treatment effect. The median number of alts was higher post anti-EGFR LB (n = 12) vs. anti-EGFR naïve LB (n = 22) (9.5 vs. 5.5, p = 0.059) but not statistically significant. More alts were also noted in post anti-EGFR therapy LB vs. KRAS wt anti-EGFR-naïve LB (n = 6) (9.5 vs. 5) among patients with KRAS wild-type tumors, although the difference was not significant (p = 0.182). Conclusions: LB across mCRC therapy detects driver mutations, monitors disease burden, and identifies sub-clonal alts that reflect drug resistance, tumor evolution, and heterogeneity. Interpretation of LB results is impacted by clinical context.

Emerging drugs for the treatment of gastrointestinal stromal tumour.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have transformed the treatment landscape for patients with gastrointestinal stromal tumors (GIST). Unfortunately, resistance to the currently approved TKIs poses a huge challenge, and patients are in need of additional therapeutic options. Fortunately, many novel therapeutic approaches are being tested in treatment of GIST to overcome resistance to the approved TKIs Areas covered: We performed an extensive literature (PUBMED) search to identify emerging drugs being tested in treatment of GIST in early phase clinical trials. We discuss recent ongoing research and emerging novel inhibitors of KIT and PDGFRA receptors, inhibitors in downstream signaling pathways (mTOR and PIK3 inhibitors), inhibitors of other potential targets including ETV1/MEK, MET, FGFR, IGF1R, histone deacetylase inhibitors, heat shock protein 90 inhibitors, cyclin-dependent kinase inhibitors and immune checkpoint inhibitors in treatment of GIST Expert opinion: Multiple agents are under evaluation; those that benefit GIST patients with imatinib resistant mutations, or those with benefit in patients refractory to approved agents are most likely to be developed in this disease. The role of immunotherapy for GIST is still investigational.