NOR-1 distinguishes acinic cell carcinoma from its mimics on fine-needle aspiration biopsy specimens.

Acinic cell carcinoma of the salivary gland (ACC-SG) is characterized by a recurrent chromosomal rearrangement (t(4; 9)(q13; q31)) that upregulates the transcription factor NR4A3. Studies conducted on formalin-fixed paraffin-embedded (FFPE) tissue have found that nuclear expression of a monoclonal antibody NR4A3 (NOR-1) is a sensitive and specific diagnostic marker for ACC-SG. The aims of this study were to evaluate the performance of the NOR-1 antibody and to compare its utility in separating ACC-SG from its mimics on cytology cell block specimens. Cell blocks were obtained from 70 fine-needle aspiration specimens from multiple institutional archives over a 7-year period (2013-2019). These included 10 cases of conventional low-grade ACC-SG, 1 case of dedifferentiated high-grade ACC-SG, and 59 cases of non-ACC-SG. An automated immunohistochemistry system (Bond-III, Leica) was used for the detection of NR4A3, using the commercially available antibody NOR-1 (sc-393902 [H-7], Santa Cruz Biotechnology Inc.). Optimization of the antibody on the cell blocks was successfully completed by increasing the titer from 1:100 (suggested titer for FFPE specimens) to 1:30. Distinct nuclear reactivity was observed in all 11 cases of ACC-SG (10 of 11 with 3+ diffuse nuclear positivity and 1 case with 2+ focal reactivity). Expression of NR4A3 was absent in all non-ACC-SG cases in the cell blocks. Application of the NOR-1 immunohistochemical staining in fine-needle aspirates of salivary gland tumors for which ACC-SG is a diagnostic consideration successfully distinguishes ACC-SG from its cytologic mimics and provides an early opportunity for oncologic intervention.

Myxedema Coma Complicated by Pancytopenia.

Hypothyroidism is common, with an extreme manifestation of myxedema coma if untreated. Hematologic consequences of myxedema coma include mild leukopenia and anemia, rarely pancytopenia. We present a patient with typical symptoms of myxedema coma, but found to be pancytopenic, with sustained response to levothyroxine and blood transfusion for anemia.

Case Report: Monoclonal Gammopathy of Undetermined Significance is Associated with Loa loa Infection.

A 63-year-old woman who migrated from Nigeria to the United States was found to have an elevated total serum protein, anemia, and eosinophilia. Serum protein electrophoresis (SPEP) and serum protein immunofixation electrophoresis (SPIFE) demonstrated monoclonal immunoglobulin G (IgG) κ restricted bands (IgG 3,820 mg/dL; κ/λ ratio 4.47), indicative of monoclonal gammopathy of unknown significance (MGUS). A rapid diagnostic test (RDT) for malaria was positive for Plasmodium falciparum (BinaxNOW®; Alere Scarborough Inc., Scarborough, ME). Giemsa-stained blood smears were negative for malarial parasites, however, Loa loa microfilariae were identified. Reverse transcription polymerase chain reaction for P. falciparum, Plasmodium ovale, Plasmodium malariae, and Plasmodium vivax yielded a negative result. She was treated for loiasis with diethylcarbamazine and received no malaria medication. Treatment resulted in a resolution of the microfilaremia and eosinophilia, a negative RDT for malaria, and marked reduction in the monoclonal gammopathy. This is the first reported human case of MGUS associated with loiasis and its resolution after antiparasitic treatment.

Cardiac Involvement by HIV-Associated DLBCL.

Non-Hodgkin's lymphoma (NHL) is a common AIDS-defining malignancy among people living with HIV. Of the different types of NHLs, diffuse large B-cell lymphoma (DLBCL) is the most common. Prognosis of DLBCL has improved over the years in the general population but remains relatively poor in HIV-positive individuals. Almost any organ system can be affected by DLBCL; however, cardiac involvement remains rare and suggests aggressive disease. We present a case of DLBCL in an HIV-positive patient, who had cardiac involvement, with the only clue to cardiac involvement being symptom being tachycardia and dysphagia.

Gastrointestinal Manifestations of Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibroproliferative alterations of the microvasculature leading to fibrosis and loss of function of the skin and internal organs. Gastrointestinal manifestations of SSc are the most commonly encountered complications of the disease affecting nearly 90% of the SSc population. Among these complications, the esophagus and the anorectum are the most commonly affected. However, this devastating disorder does not spare any part of the gastrointestinal tract (GIT), and includes the oral cavity, esophagus, stomach, small and large bowels as well as the liver and pancreas. In this review, we present the current understanding of the pathophysiologic mechanisms of SSc including vasculopathy, endothelial to mesenchymal transformation as well as the autoimmune pathogenetic pathways. We also discuss the clinical presentation and diagnosis of each part of the GIT affected by SSc. Finally, we highlight the latest developments in the management of this disease, addressing the severe malnutrition that affects this vulnerable patient population and ways to assess and improve the nutritional status of the patients.

A case of hypertrophic herpes simplex virus affecting the eyelid and cornea masquerading as IgG4-related disease.

PURPOSE: To report a case of hypertrophic herpes simplex virus (HSV) of the eyelid and cornea masquerading as IgG4-related disease. OBSERVATIONS: A 37-year old African American female with a past medical history of human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART) and a recent history of treated genital herpes, presented with an ulcerative lesion of the left upper and lower eyelids, and severe ocular inflammation with symblepharon. Initially, eyelid biopsy revealed findings consistent with IgG4-related disease, and the patient was treated with high dose oral prednisone. After one week of therapy, there was no improvement in the patient's symptoms, and she subsequently developed a corneal epithelial defect which progressed to chronic ulceration. Repeat biopsy and corneal cultures revealed herpes simplex virus type 2. The patient was treated with high dose acyclovir, and the lid lesion improved. The conjunctival inflammation and corneal epithelial defect resolved but symblepharon restricting her eye movement remained. She also developed corneal vascularization and opacification causing severe vision loss. CONCLUSIONS AND IMPORTANCE: Chronic hypertrophic herpes simplex virus infection is a rare condition reported in patients with HIV. While there have been few reports of hypertrophic HSV affecting the eyelid, this is the first reported case of hypertrophic HSV affecting the eye, resulting in severe vision loss.

Parallel SFC/MS-MUX screening to assess enantiomeric purity.

Enantiomeric excess (ee) was evaluated for two internally synthesized compound libraries using a high-throughput automated, intelligent four-channel parallel supercritical fluid chromatography/mass spectrometry system equipped with a multiplexed ion source interface (SFC/MS-MUX). The two libraries contained compounds spanning a wide range of enantiomeric ratios with structurally diverse chemical scaffolds and stereogenic centers. The system analyzed each sample simultaneously against four chiral columns using up to six organic modifiers. Enhancements to our previously published parallel supercritical fluid chromatography/mass spectrometry system were implemented to address the challenges associated with automated trace enantiomer identification and quantitation. A reversal of enantiomer elution order was observed for several samples across multiple CSPs and modifiers. The relationship between elution order and % ee accuracy is presented for compounds exhibiting high, middle and low % ee values. Despite incidences in which the minor enantiomer eluted prior to the major enantiomer with less than baseline resolution, the overall % ee was in agreement with separations in which full baseline resolution was achieved. The methods presented here demonstrate the value and utility of high-throughput ee determinations to support drug discovery and development programs.

Parallel supercritical fluid chromatography/mass spectrometry system for high-throughput enantioselective optimization and separation.

An automated parallel four-column supercritical fluid chromatography (SFC)/MS system to perform high-throughput enantioselective chromatographic method development and optimization is described in this paper. The initial screening was performed in parallel on four chiral SFC columns over several buffer conditions. Optimization of the separation of enantiomers was achieved on a single chiral column. The screening and optimization were accomplished in a fully automated, user-independent manner. Incorporation of column control valves in front of each chiral column allowed the system to switch from parallel four-column screening mode to single-column optimization mode. To facilitate the process, a custom software program, we termed, intelligent parallel optimization for chiral SFC separation (IPOCSS), was developed in-house. The custom software monitored each of the runs in real-time, processed each data set, and by incorporating user-defined criteria (e.g., resolution of the two enantiomer chromatographic peaks), selected the next set of experiments and automatically optimized the enantioseparation. This new approach, combining parallel SFC/MS screening and intelligent software-controlled method optimization, has resulted in a streamlined, high-throughput tool for enantioselective method development, which has been applied successfully to enantioseparations in support of drug discovery.