Metabolic syndrome (MS) is a cluster of conditions including central obesity, hypertriglyceridemia, low HDL cholesterol, hyperglycaemia, and hypertension with a prevalence rate of 20–25% of the world’s adult population. Metabolic syndrome is often characterized by insulin resistance, which some have suggested is a major supportive connection between physical inactivity and MS. Various studies suggest that moderately elevated iron and ferritin levels are associated with an increased prevalence of metabolic syndrome and are markers of insulin resistance. Increased body iron stores are associated with the development of glucose intolerance, type 2 diabetes mellitus, and insulin resistance syndrome (IRS). This is a hospital-based cross-sectional observational study, which was conducted in the department of internal medicine of a tertiary care hospital in northern India. The study was conducted from 1 January 2019 to 30 June 2020 and included 100 patients and 100 controls. All subjects in the age group of 35–65 years were enrolled and investigated as per the study design. Metabolic syndrome patients were diagnosed according to the modified National Cholesterol Education Program Adult Treatment Panel-III (NCEP ATP-III) with BMI > 23 kg/m². All baseline investigations were undertaken, including serum ferritin levels. Insulin resistance (IR) was calculated using the homeostasis model assessment IR (HOMA-IR) formula. We found a positive association between an increase in serum ferritin with the prevalence of metabolic syndrome and its clinical parameter. The serum ferritin level was positively correlated with the level of insulin resistance and inversely correlated with the insulin level of the patients.

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology with heterogeneous clinical manifestations and significant diagnostic challenges, particularly when extrapulmonary involvement predominates. Although splenic, hematologic, metabolic, and lymphatic manifestations are individually recognized, their simultaneous occurrence is exceptionally rare. We report a diagnostically complex case of sarcoidosis presenting with massive splenomegaly, pancytopenia, parathyroid hormone-independent hypercalcemia with renal dysfunction, and bone marrow findings suggestive of myelodysplastic syndrome. A 53-year-old man was incidentally found to have pancytopenia during routine evaluation and was asymptomatic at presentation, without constitutional symptoms. Abdominal imaging revealed massive splenomegaly with preserved hepatic morphology. Bone marrow aspiration and biopsy demonstrated multilineage dysplasia with low blast percentage, favoring myelodysplastic neoplasia; however, this diagnosis was discordant with the presence of massive splenomegaly. Subsequent biochemical evaluation revealed hypercalcemia with suppressed parathyroid hormone levels and associated renal dysfunction, prompting further investigation. 18F-fluorodeoxyglucose positron emission tomography-computed tomography demonstrated extensive FDG-avid mediastinal, hilar, cervical, and abdominal lymphadenopathy with gross splenomegaly, a pattern suggestive of granulomatous disease. Elevated serum angiotensin-converting enzyme levels supported this impression. Definitive diagnosis was established by excisional cervical lymph node biopsy, which revealed non-caseating granulomatous lymphadenitis consistent with sarcoidosis. This case illustrates a rare and misleading presentation of sarcoidosis that closely mimicked a primary hematologic disorder. It underscores the importance of maintaining a broad differential diagnosis and emphasizes the critical role of integrated clinicopathologic correlation and tissue confirmation in patients presenting with unexplained cytopenias and massive splenomegaly.

Mutation-based liquid biopsy supports diagnosis and disease monitoring in hematologic malignancies, but interpretation of plasma variants may be complicated by clonal hematopoiesis, treatment-related changes, and nonmalignant blood-cell turnover. This structured narrative review evaluates whether cell-free DNA (cfDNA) fragmentomics, DNA methylation, and 5-hydroxymethylcytosine (5hmC) provide complementary information beyond mutation detection. Direct plasma evidence is most developed for selected fragmentomic and 5hmC applications, although most studies remain retrospective, internally validated, or proof of concept. Fragmentomic studies have reported associations with lymphoma classification, outcome assessment, and longitudinal tumor-effector profiling during chimeric antigen receptor T-cell therapy, but routine clinical utility and decision thresholds are not established. Plasma 5hmC studies have reported associations with lymphoma classification, treatment response, prognosis, and measurable residual disease in acute myeloid leukemia, whereas pharmacodynamic monitoring during Bruton's tyrosine kinase inhibition remains hypothesis-generating. DNA methylation may support source-cell or lineage inference, but lineage assignment does not establish malignant fraction, and key disease-assessment studies remain largely tissue-based, cellular-DNA-based, cross-cancer, or methodological. The novelty of this review is a structured evidence map that distinguishes direct plasma evidence from indirect support and compares the three modalities by biological information, assay compatibility, and validation maturity. We also propose a hypothesis-generating framework for sample-level integration using separate assay-specific aliquots and computational combination of outputs. No universal analytical order or clinically validated integrated workflow has been established. Fragmentomic and epigenomic profiling should therefore be regarded as investigational complements to mutation-based testing, requiring independent prospective validation against established genomic, cellular, imaging, and tissue-based methods.