Diagnosis of acinic cell carcinoma of the salivary gland on cytology specimens: Role of NOR-1 (NR4A3) immunohistochemistry.

OBJECTIVES: Acinic cell carcinoma (AcCC) is often a challenging diagnosis on cytology. Recently, NOR-1 (NR4A3) has been demonstrated as a sensitive and specific marker for AcCC. Therefore, we conducted this study to evaluate NOR-1 expression in AcCC cytology specimens and to compare its reactivity in other salivary gland tumours (non-AcCC). METHODS: We retrospectively reviewed our database and selected cytology cases with available cell blocks, including 10 AcCC and 24 non-AcCC tumours (12 benign tumours and 12 malignant tumours). NOR-1 (1:50 dilution; SC393902 [H-7]; Santa Cruz Biotech) immunohistochemistry (IHC) was performed on all cases. RESULTS: All AcCC cases except two (2/10, 80%) showed positive nuclear staining of variable intensity for NOR-1, with the majority of cases (75%) demonstrating at least moderately intense nuclear expression. All non-AcCC cases were negative for NOR-1, demonstrating a specificity of 100%. CONCLUSION: We conclude that NOR-1 IHC is sensitive and very specific on cytology specimens and is able to distinguish AcCC from its mimickers reliably and classify them appropriately for further management.

Uncovering Primary Extranodal Diffuse Large B Cell Lymphoma in the Adrenal and Thyroid Glands.

BACKGROUND Primary extranodal diffuse large B-cell lymphoma (DLBCL) is a rare, yet highly aggressive and invasive malignancy that can masquerade as a solid organ tumor. Timely diagnosis is critical for improving prognosis; however, it is challenging to achieve. CASE REPORT We report 2 cases treated at Yale New Haven Hospital (New Haven, CT, USA) and the West Haven Veteran's Affairs Medical Center (West Haven, CT, USA) in 2023. Case 1 describes a 69-year-old woman who presented with a large left adrenal mass that was suspicious for adrenocortical carcinoma and was found to have primary adrenal DLBCL following surgical resection. Case 2 describes a 59-year-old woman with Hashimoto's thyroiditis and goiter who was found to have primary thyroid DLBCL following partial thyroidectomy. CONCLUSIONS Primary extranodal DLBCL should be included in the differential diagnosis of solid adrenal and thyroid tumors. The risks of biopsy, given currently available techniques, should be weighed against the benefits of achieving a definite diagnosis, allowing for timely initiation of systemic immunochemotherapy. When biopsy can be safely performed, techniques designed to evaluate for DLBCL should be incorporated.

Breast implant-associated anaplastic large-cell lymphoma: A series of two case reports diagnosed by cytopathology.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare T-cell lymphoma with a good prognosis. It occurs in association with textured breast implants. Its most common presentation is a late-onset peri-implant effusion. We present two cases of BIA-ALCL diagnosed by cytopathological examination of the fluid collection and describe the cytopathologic findings. Both patients were disease free after implant removal. This report highlights the contribution of the cytopathologic analysis to early diagnosis and definite treatment of BIA-ALCL.

High-Throughput Screening Uncovers Novel Botulinum Neurotoxin Inhibitor Chemotypes.

Botulism is caused by potent and specific bacterial neurotoxins that infect host neurons and block neurotransmitter release. Treatment for botulism is limited to administration of an antitoxin within a short time window, before the toxin enters neurons. Alternatively, current botulism drug development targets the toxin light chain, which is a zinc-dependent metalloprotease that is delivered into neurons and mediates long-term pathology. Several groups have identified inhibitory small molecules, peptides, or aptamers, although no molecule has advanced to the clinic due to a lack of efficacy in advanced models. Here we used a homogeneous high-throughput enzyme assay to screen three libraries of drug-like small molecules for new chemotypes that modulate recombinant botulinum neurotoxin light chain activity. High-throughput screening of 97088 compounds identified numerous small molecules that activate or inhibit metalloprotease activity. We describe four major classes of inhibitory compounds identified, detail their structure-activity relationships, and assess their relative inhibitory potency. A previously unreported chemotype in any context of enzyme inhibition is described with potent submicromolar inhibition (Ki = 200-300 nM). Additional detailed kinetic analyses and cellular cytotoxicity assays indicate the best compound from this series is a competitive inhibitor with cytotoxicity values around 4-5 µM. Given the potency and drug-like character of these lead compounds, further studies, including cellular activity assays and DMPK analysis, are justified.