Coexistence of large cell transformed mycosis fungoides and diffuse large B-cell lymphoma in one patient.

Diffuse large B-cell lymphoma (DLBCL) is the most common and aggressive subtype of non-Hodgkin lymphoma. The overall risk of developing DLBCL is increased in patients with other lymphomas, such as mycosis fungoides (MF). In this report, we present an 81-year-old female with early-stage MF who simultaneously progressed to tumor stage, large-cell transformed (LCT) MF and developed a primary DLBCL in a lymph node (LN). She presented with a tumor on her leg and new lymphadenopathy in her right axilla. Skin biopsy of the tumor revealed infiltration of large atypical CD3+, CD4+, and CD30+ cells, and a smaller portion of CD8+ cells in the dermis, consistent with LCT MF. Biopsy of the axillary LN revealed diffuse sheets of CD20+, BCL-2+, c-MYC+, and CD10- cells, highly suggestive of double expressor DLBCL. High-throughput sequencing revealed monoclonal T cells in the skin tumor and a monoclonal B-cell population in the LN. The above findings led to simultaneous diagnoses of LCT MF and nodal double expressor DLBCL. Our case demonstrates the importance of performing a full pathological workup in cutaneous T-cell lymphoma patients presenting with lymphadenopathy.

Skin in the game: a review of single-cell and spatial transcriptomics in dermatological research.

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) are two emerging research technologies that uniquely characterize gene expression microenvironments on a cellular or subcellular level. The skin, a clinically accessible tissue composed of diverse, essential cell populations, serves as an ideal target for these high-resolution investigative approaches. Using these tools, researchers are assembling a compendium of data and discoveries in healthy skin as well as a range of dermatologic pathophysiologies, including atopic dermatitis, psoriasis, and cutaneous malignancies. The ongoing advancement of single-cell approaches, coupled with anticipated decreases in cost with increased adoption, will reshape dermatologic research, profoundly influencing disease characterization, prognosis, and ultimately clinical practice.

Topical Tacrolimus and Alcohol-Induced Facial Flushing: A Case Report and Literature Review.

Flush reactions can be incited by various factors including inherent mutation, drugs, and diseases. A medication that is commonly used in dermatology but less associated with alcohol-induced facial flushing is topical tacrolimus. We present the case of a 44-year-old man experiencing this phenomenon on a distant, non-application site and a review of cases published in the literature.

Recalcitrant Cutaneous Mastocytosis Treated With Genetically Informed Targeted Therapy: A Case Report.

Mastocytosis, a clonal proliferation of mast cells commonly involving the skin and bone marrow, has a varied clinical presentation ranging from cutaneous lesions to systemic disease. Cutaneous mastocytosis is managed symptomatically, but systemic mastocytosis is treated with targeted therapy against the mutated receptor tyrosine kinase c-KIT, the pathogenic driver of mastocytosis. However, there are no guidelines for the treatment of cutaneous mastocytosis refractory to symptomatic management. We herein report a method to select genetically informed therapy for symptomatic and recalcitrant cutaneous mastocytosis. Case presentation: We performed a mutational analysis of dermal mast cells after enrichment by laser capture in a 23-year-old woman with recalcitrant cutaneous mastocytosis. The analysis revealed a aspartic acid to valine substitution at codon 816 (D816V) mutation in the protein c-KIT. Based on these results, we initiated treatment with the multi-kinase/KIT inhibitor midostaurin, a treatment effective against the D816V c-KIT mutation. After 3 months of treatment, the patient exhibited a reduction in the number and size of cutaneous lesions and reported resolution of pruritus and decreased severity of other mast cell-related symptoms. Discussion: The treatment of mastocytosis relies heavily on whether the disease is limited to the skin or systemic. However, there are no guidelines for cutaneous mastocytosis that does not respond to symptomatic management. In the present report describing a patient with recalcitrant cutaneous mastocytosis, we describe a strategy in which skin mutational analysis is used to guide the selection of targeted therapy. Conclusion: Performing mast cell mutational analyses in the skin provides a means to select targeted therapy for symptomatic and refractory cutaneous mastocytosis.

Systemic alterations play a dominant role in epigenetic predisposition to breast cancer in offspring of obese fathers and is transmitted to a second generation.

We previously showed that environmentally-induced epigenetic inheritance of cancer occurs in rodent models. For instance, we reported that paternal consumption of an obesity-inducing diet (OID) increased breast cancer susceptibility in the offspring (F1). Nevertheless, it is still unclear whether programming of breast cancer in daughters is due to systemic alterations or mammary epithelium-specific factors and whether the breast cancer predisposition in F1 progeny can be transmitted to subsequent generations. In this study, we show that mammary glands from F1 control (CO) female offspring exhibit enhanced growth when transplanted into OID females compared to CO mammary glands transplanted into CO females. Similarly, carcinogen-induced mammary tumors from F1 CO female offspring transplanted into OID females has a higher proliferation/apoptosis rate. Further, we show that granddaughters (F2) from the OID grand-paternal germline have accelerated tumor growth compared to CO granddaughters. This between-generation transmission of cancer predisposition is associated with changes in sperm tRNA fragments in OID males. Our findings indicate that systemic and mammary stromal alterations are significant contributors to programming of mammary development and likely cancer predisposition in OID daughters. Our data also show that breast cancer predisposition is transmitted to subsequent generations and may explain some familial cancers, if confirmed in humans.