Reactive nodular fibrous pseudotumor (RNFP) is a rare benign fibrocollagenous lesion that often poses diagnostic challenges because of its nonspecific clinical and radiological features, particularly at unusual sites such as the lung. This study aimed to characterize the clinicopathological, immunohistochemical, and prognostic features of RNFP and summarize the literature. We retrospectively analyzed four pathologically confirmed RNFP cases, including a rare pulmonary case, and combined them with 40 reported cases (n = 44). RNFP occurred at multiple anatomical sites, most commonly in the abdomen, followed by the extremities and chest. The pulmonary lesion presented as a solitary nodule mimicking malignancy. Histologically, all lesions showed low cellularity, abundant hyalinized collagen, and scattered bland spindle cells without cytologic atypia or mitoses. Immunohistochemically, all cases were positive for vimentin; 50% expressed SMA and 25% showed focal CD34 expression, whereas STAT6, β-catenin, S-100, and desmin were consistently negative. All molecular detection results were uniformly negative. During follow-up (6-60 months), no recurrence or progression was observed. RNFP is a benign reactive lesion with characteristic histological and immunophenotypic features. Diagnosis relies on morphological assessment and immunohistochemical exclusion of mimics. Awareness of its anatomical distribution, including rare pulmonary involvement, is essential to avoid misdiagnosis and overtreatment.

BACKGROUND Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a rare and recently described histiocytic neoplasm characterized by ALK gene rearrangements. Several ALK fusion partners have been reported, particularly in patients with multisystem disease. We report the first case of single-site ALK-positive histiocytosis involving a TFG-ALK fusion, a rearrangement previously linked to disseminated disease. CASE REPORT A man in his 50s with obesity, obstructive sleep apnea, diabetes mellitus, hypertension, coronary artery disease, and a 40-pack-year smoking history underwent computed tomography for lung cancer screening; the results showed a solitary 1.6-cm left lower lobe pulmonary nodule. Positron emission tomography demonstrated hypermetabolic activity confined to the lesion. He subsequently underwent video-assisted thoracoscopic wedge resection with mediastinal lymphadenectomy. Histopathologic evaluation revealed a well-circumscribed spindle cell neoplasm expressing histiocytic markers CD4, CD68, and CD163, with cytoplasmic ALK positivity. A TFG-ALK gene fusion was detected using Archer FusionPlex Pan Solid Tumor panel testing with anchored multiplex polymerase chain reaction via Illumina NextSeq 500. Immunohistochemical and flow cytometric studies excluded alternative ALK-rearranged neoplasms, including inflammatory myofibroblastic tumor, anaplastic large cell lymphoma, and ALK-positive diffuse large B-cell lymphoma. The patient received no systemic therapy and remains disease-free on radiographic surveillance. CONCLUSIONS To our knowledge, this case represents the first reported instance of single-site ALK-positive histiocytosis with a TFG-ALK fusion. It expands the molecular and clinical spectrum of this rare entity, suggesting that certain ALK fusion partners are associated with localized disease and an indolent clinical course. Recognition of such presentations is essential to avoid unnecessary systemic therapy.

A 69-year-old male patient developed a painless, gradually increasing mass in the upper part of his right thigh, with no pulmonary symptoms. Magnetic resonance imaging revealed a nodular lesion in the lateral femoral muscle, which was initially suspected to be a primary soft tissue tumour. After the mass was surgically removed, the histopathological examination confirmed squamous cell carcinoma (SCC), and the immunohistochemical staining of P63 and CK5/6 was positive. Subsequent FDG PET/CT examination revealed a hypermetabolic nodule in the upper lobe of the right lung. Endobronchial ultrasound-guided biopsy confirmed it as primary lung SCC. This case indicates that isolated skeletal muscle metastasis can be the initial manifestation of occult lung cancer. The research results suggest that seemingly isolated soft tissue masses may be the first sign of latent malignant tumours.

Liquid biopsy demonstrates clinical utility as a non-invasive tool for discriminating malignant tumours from benign pulmonary nodules, as evidenced by recent research. This systematic review compared the diagnostic performance of current clinical modalities for pulmonary nodules, aiming to generate evidence-based solutions to address the underdiagnosis of malignant nodules and the overdiagnosis of benign lesions. A Bayesian bivariate random-effects model was employed to perform meta-analysis across diagnostic categories, followed by meta-regression and subgroup analyses. Results were visualised using summary receiver operating characteristic curves. Subgroup analysis revealed that liquid biopsy-derived multimodal diagnostic models achieved superior performance (sensitivity: 90.2%; specificity: 83.6%) compared to CT-based evaluation (81.5%, 67.9%) and risk prediction models (68.7%, 70.6%). These findings indicate that multimodal models integrating liquid biopsy, radiological features, and risk prediction significantly outperform single-modality approaches, thereby potentially addressing diagnostic imbalances in pulmonary nodule assessment. Key Words: Liquid biopsy, Pulmonary nodules, Multimodal diagnostic model, Comparative diagnostic test accuracy studies.

A 66-year-old man with a history of 50 pack-years of cigarette use, hypertension, type 2 diabetes mellitus, OSA, and a left upper lobe lung nodule that had been stable on imaging for nearly 2 years presented with dizziness. His vital signs were within normal limits; the rest of the examination was notable for a bony protuberance from the vertex of the calvarium to the right side of the skull.

Pulmonary nodules are often encountered in primary care during radiographic evaluation of respiratory symptoms, incidental imaging, and lung cancer screening. While most nodules are low risk, accurately identifying nodules that require surveillance, determining appropriate follow-up intervals, and deciding when specialist evaluation and intervention is indicated are challenging.