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Neoplasms with plasma cell differentiation may occasionally involve the skin. Cutaneous lesions may represent the first sign of an underlying systemic plasma cell malignancy, such as multiple myeloma, or the skin itself may be the primary site of occurrence of a hematological tumor with plasma cell differentiation. Starting from examples encountered in our daily practice, we discussed the diagnostic approach pathologists and clinicians should use when faced with cutaneous lesions with plasma cell differentiation. Cases of primary cutaneous marginal zone lymphoma, localized primary amyloidosis/amyloidoma, and cutaneous manifestations (secondary either to multiple myeloma or to plasmablastic lymphoma) are discussed, focusing on the importance of the adequate patient’s work-up and precise clinicopathological correlation to get to the correct diagnosis and appropriate treatment. The pertinent literature has been reviewed, and the clinical presentation, pathological findings, main differential diagnoses, treatment, and outcome of neoplasms with plasma cell differentiation involving the skin are discussed.

The Alcohol Use Disorders Identification Test (AUDIT) and its short form, the AUDIT-C, the main clinical instruments used to identify unhealthy drinking behaviors, are influenced by memory bias and under-reporting. In recent years, phosphatidylethanol (PEth) in blood has emerged as a marker of unhealthy alcohol use. This systematic review aims to investigate the molecular characteristics of PEth and summarize the last ten years of published literature and its use compared to structured questionnaires. A systematic search was performed, adhering to PRISMA guidelines, through “MeSH” and “free-text” protocols in the databases PubMed, SCOPUS, and Web of Science. The inclusion criteria were as follows: PEth was used for detecting unhealthy alcohol consumption in the general population and quantified in blood through liquid chromatography coupled to mass spectrometry, with full texts in the English language. Quality assessment was performed using the JBI critical appraisal checklist. Twelve papers were included (0.79% of total retrieved records), comprising nine cross-sectional studies and three cohort studies. All studies stratified alcohol exposure and quantified PEth 16:0/18:1 through liquid chromatography coupled to mass spectrometry (LC-MS) in liquid blood or dried blood spots (DBS) with lower limits of quantitation (LLOQ) ranging from 1.7 ng/mL to 20 ng/mL. A correlation between blood PEth level and the amount of alcohol ingested in the previous two weeks was generally observed. PEth interpretative cut-offs varied greatly among the included records, ranging from 4.2 ng/mL to 250 ng/mL, with sensitivity and specificity in the ranges of 58–100% and 64–100%, respectively. Although the biomarker seems promising, further research elucidating the variability in PEth formation and degradation, as well as the molecular mechanisms behind that variability, are necessary.

In an immune-competent context nivolumab showed long-term benefit in overall survival in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC); however, in special cancer population such as these patients with immunodeficiency and viral infections, data on checkpoint inhibitors (ICI) activity are scant. Herein, we report a patient with a Human papilloma virus (HPV)-related oropharyngeal cancer (OPC) and CD4 lymphocytopenia. After a first-line treatment complete remission, the patient experienced Human Polyomavirus (JCV) infection in the brain. Consequently, to the recovery from progressive multifocal leukoencephalopathy (PML) the patient metastasized and was enrolled in a single-arm trial with nivolumab (EudraCT number: 2017-000562-30). A complete and durable response (more 3 years) was observed after 10 nivolumab injections Q2wks, interrupted for persistent drug related G2 diarrhea and a syndrome of inappropriate antidiuretic hormone secretion. We describe the circulating immune profile (before-, during-, and after nivolumab), consistent with the clinical history. Moreover, during nivolumab treatment, brain MRI evidenced the presence of small punctuate areas of contrast enhancement, reflecting a mild immune response in perivascular spaces. By cytofluorimetry, we observed that during JCV infection the CD4/CD8 ratio of the patient was under the normal values. After JCV infection recovery and before nivolumab treatment, CD4/CD8 ratio reached the normality threshold, even if the CD4+ T cell count remained largely under the normal values. During ICI, gene expression xCell analyses of circulating immune cells of the patient, showed a progressive normalization of the total immune profile, with significant boost in CD4+ and CD8+ T cells and a reduction in NK T, comparable to the circulating immune profile of reference tumor-free HNSCC patients. The present case supports the activity of ICI in a population of special cancer patients; whether JCV and HPV infections (alone or together) might have a possible role as immune booster(s), require further investigations.

Background: Alcohol consumption during pregnancy, even at low doses, may damage the fetus. Pregnant women tend to underreport their alcohol consumption generating the need for sensitive and specific biomarkers, among which PEth has emerged due to its high specificity and possibility to be measured in both maternal and neonatal blood. The aim of this study is to systematically review the latest 20 years of literature for depicting the state of the art, the limitations, and the prospects of PEth for estimating alcohol consumption during pregnancy. Materials and methods: A systematic search, adhering to PRISMA guidelines, of the latest 20 years of literature through “MeSH” and “free-text” protocols in the databases PubMed, SCOPUS, and Web of Science, with time limits 1 January 2002–1 March 2022, was performed. The inclusion criteria were as follows: PEth used for detecting alcohol consumption during pregnancy, quantified in blood through liquid chromatography coupled to mass spectrometry, and full texts in the English language. Opinion papers, editorials, and narrative reviews were excluded. Results: Sixteen (16) papers were included in the present review (0.81% of total retrieved records). All the included records were original articles, of which there were seven prospective cohort/longitudinal studies, six cross-sectional studies, two observational-descriptive studies, and one retrospective study. All studies assayed PEth in at least one biological matrix; seven (7) studies quantified PEth in maternal blood, seven studies in newborn blood, and only two studies in both maternal and neonatal blood. In several included papers, PEth proved more sensitive than self-reports for identifying pregnant women with an active alcohol intake with the diagnostic efficiency improving with the increase of the maternal alcohol intake. Conclusions: Further studies, performed on wider and well-stratified populations, are needed to drive any definitive conclusion. PEth is a promising marker for monitoring alcohol use in pregnancy; however, at the present time, its use is still limited mainly by the absence of a globally agreed interpretative cut-off, the paucity of data regarding its specificity/sensitivity, and the lack of standardization on the diagnostic efficiency of the different isoforms.