ROS1 rearrangements are driver events in a subset of nonsmall cell lung carcinomas and may qualify patients for ROS1-directed treatment. ROS1 immunohistochemistry (IHC) is often used for screening of lung carcinomas for ROS1 gene rearrangement and has a cytoplasmic and/or membranous staining pattern. Here, we report an unusual case of a lung adenocarcinoma displaying a strong nuclear staining pattern on ROS1 IHC. ROS1 fluorescence in situ hybridization (FISH) reflex testing was ordered. ROS1 FISH testing showed an isolated 3 ' signal pattern, indicating a potential rearrangement or deletion in the ROS1 gene. Next-generation sequencing (NGS) analysis revealed a NMP1::ROS1 rearrangement. The tumor was from a 74-year-old male with a previous history of lung squamous cell carcinoma. This new occurrence was determined to be a lung adenocarcinoma and displayed papillary features, whereas concurrent lymphadenopathy was also present. Immunostaining for ALK was negative, and there was no expression of PD-L1 22C3 IHC. This case report highlights an unexpected ROS1 IHC staining associated with a rare ROS1 gene rearrangement.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially life-threatening drug-induced hypersensitivity reaction characterized by delayed onset and variable multi-organ involvement, which can complicate timely diagnosis. We report the case of a 75-year-old female who developed fever, generalized pruritic maculopapular rash, facial edema, lymphadenopathy, and acute kidney injury 10 days after completing a one-week course of amoxicillin-clavulanate for a respiratory infection. Laboratory evaluation revealed leukocytosis with neutrophilia, mild eosinophilia not meeting diagnostic threshold criteria, acute kidney injury with proteinuria and hematuria, and isolated cholestatic liver injury without significant ALT or AST elevation; atypical lymphocytosis was absent. Autoimmune serology and viral hepatitis screening were negative. Based on the RegiSCAR scoring system, the patient achieved a score of 7, consistent with a definite diagnosis of DRESS. Systemic corticosteroid therapy, alongside adjunctive topical treatment and antihistamines, led to progressive clinical and laboratory improvement. This case represents an atypical presentation of DRESS with predominantly renal involvement and isolated cholestatic liver injury, where the absence of typical hematologic manifestations posed a diagnostic challenge. Although viral reactivation, particularly HHV-6, is often implicated in DRESS pathogenesis, its role here remains unconfirmed due to the lack of virological testing. The case highlights the importance of considering DRESS in patients with delayed-onset cutaneous eruptions and unexplained acute kidney injury after drug exposure, even in the absence of classic hematologic features, as early recognition and appropriate management are crucial for favorable outcomes.

Diagnosing lymphoma traditionally relies on invasive tissue biopsies, which can yield insufficient material for histopathological evaluation and carry a risk of complications. Minimally invasive assessment of cell-free DNA (cfDNA) in plasma offers a promising alternative for lymphoma detection that could aid the rapid evaluation of malignant vs. benign lymphadenopathy. Here, we examine the methylome of plasma samples from 165 lymphoma patients and 47 controls using cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq). Differential methylation analysis of a discovery cohort (142 out of 212 samples) revealed 13,897 hypermethylated genomic regions in lymphoma cases, which were subsequently used for classification using regularized binomial generalized linear models. In a validation cohort (70 samples), we identified lymphomas with an accuracy of 0.89, positive predictive value (PPV) of 0.90 and negative predictive value (NPV) of 0.87. cfDNA methylation scores were significantly associated with orthogonal measures of cfDNA tumor burden, stage, and clinical outcomes. Our results highlight the feasibility of cfDNA methylation profiling as a sensitive and minimally invasive method for detecting lymphoma.

Epstein-Barr virus infection usually presents as infectious mononucleosis with fever, pharyngitis, and lymphadenopathy, while cholestatic jaundice is a rare manifestation. We report a 36-year-old man who presented with progressive jaundice, pruritus, and dark-coloured urine with deranged liver function tests showing a cholestatic pattern. Evaluation revealed atypical lymphocytosis and positive EBV IgM serology after exclusion of biliary obstruction and other common causes of hepatitis. The patient improved with supportive treatment alone. This case highlights the importance of considering EBV infection in the differential diagnosis of cholestatic jaundice.

Oral mucosal melanoma is a rare malignancy of the oral cavity and a small subset of melanomas overall, characterized by an aggressive clinical course and diagnostic challenges. These challenges are particularly pronounced in amelanotic variants due to the lack of pigmentation and their histological resemblance to other spindle cell and epithelial tumors. This report describes a 47-year-old man who presented with a progressively enlarging ulcero-exophytic lesion involving the maxilla and hard palate over nine months, accompanied by cervical lymphadenopathy and rapid development of brain metastasis. Initial histopathological evaluation suggested a spindle cell malignancy; however, immunohistochemical analysis demonstrated positivity for S-100, SOX10, and Melan-A, confirming malignant melanoma. This diagnosis was further supported by repeat biopsy and histopathological findings. Despite treatment with pembrolizumab, the disease progressed rapidly both locally and distantly, necessitating palliative care. This case highlights the persistent challenges in diagnosing oral mucosal melanoma due to its atypical clinical and pathological features, emphasizes the critical role of immunohistochemistry in achieving an accurate diagnosis, and underscores the generally poor prognosis despite current therapeutic options. It also reinforces the importance of early detection and timely multidisciplinary management.