Objectives: Pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), present a challenge for their potential malignancy. Despite promising biomarkers like CEA, amylase, and glucose, our study investigates whether metabolic indices in blood and cystic fluids (CFs), in addition to lymphocyte subsets and hematopoietic stem/progenitor cells (HSPCs), can effectively differentiate between high- and low-risk PCNs. Materials and Methods: A total of 26 patients (11 males, mean age 69.5 ± 9 years) undergoing Endoscopic Ultrasound-guided Fine Needle Aspiration were consecutively enrolled. Analyses included blood, serum, and CF, assessing glucose, CEA, cholesterol (total, HDL, and LDL), and total proteins. Flow cytometry examined immunophenotyping in peripheral blood and cystic fluids. Mass spectrometry was used for the metabolomic analysis of CF. Sensitivity, specificity, and ROC analyses evaluated discriminatory power. Results: A total of 25 out of 26 patients had IPMN. Patients were categorized as low or high risk based on multidisciplinary evaluation of clinical, radiological, and endoscopic data. High-risk patients showed lower CF total proteins and LDL cholesterol (p = 0.005 and p = 0.031), with a marked reduction in CF lymphocytes (p = 0.005). HSCPs were absent in CF. In blood, high-risk patients showed increased non-MHC-restricted cytotoxic T cells (p = 0.019). The metabolomic analysis revealed significantly reduced middle and long-chain acyl carnitines (AcCa) and tryptophan metabolites in high-risk patients. ROC curves indicated comparable discriminant abilities for CF lymphocytes (AUC 0.868), CF total proteins (AUC 0.859), and CF LDL cholesterol (AUC 0.795). The highest performance was achieved by the AcCa 14:2 and 16:0 (AUC: 0.9221 and 0.8857, respectively). Conclusions: CF levels of glucose, CEA, LDL cholesterol, and total proteins together with lymphocyte counts are easy translational biomarkers that may support risk stratification of PCNs in IPMN patients and might be endorsed by metabolomic analysis. Further studies are required for potential clinical integration.

Article Imlifidase: a new interferent on serum protein electrophoresis looking as a rare plasma cell dyscrasia was published on February 24, 2025 in the journal Clinical Chemistry and Laboratory Medicine (CCLM) (volume 0, issue 0).

Breast Implant-Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL) is a rare T-cell non-Hodgkin lymphoma associated with breast prosthetic implants and represents a diagnostic challenge. The National Comprehensive Cancer Network (NCCN) guidelines, updated in 2024, recommend for diagnosis an integrated work-up that should include cell morphology, CD30 immunohistochemistry (IHC), and flow cytometry (FCM). CD30 IHC, although the test of choice for BIA-ALCL diagnosis, is not pathognomonic, and this supports the recommendation to apply a multidisciplinary approach. A close collaboration between pathologists and laboratory professionals allowed the diagnosis of three BIA-ALCLs, presented as case reports, within a series of 35 patients subjected to periprosthetic effusions aspiration from 2018 to 2023. In one case, rare neoplastic cells were identified by FCM, and this result was essential in leading the anatomopathological picture as indicative of this neoplasm. In fact, the distinction between a lymphomatous infiltrate from reactive cells may be very complex in the cytopathology and IHC setting when neoplastic cells are rare. On the other hand, one limitation of FCM analysis is the need for fresh samples. In this study, we provide evidence that a dedicated fixative allows the maintenance of an unaltered CD30 expression on the cell surface for up to 72 h.

Objectives: Ocular lymphomas are rare diseases that occur in ocular adnexa or specific intraocular regions. Although histology remains the gold standard, cytology and flow cytometry (FCM) are fundamental, mainly when a biopsy sampling is technically demanding. This study evaluated the effectiveness of FCM in diagnosing ocular diseases, especially hematologic malignancies, and compared its performance with the other techniques. Methods: In this monocentric study we collected patient characteristics from 165 patients referred to Padua University Hospital. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV), accuracy and concordance rate were evaluated for cytologic, FCM, and/or histologic analyses performed. Results: Patients were classified as having hematologic neoplasms (n=86), non-hematologic neoplasms (n=33) or non-neoplastic diseases (n=46). Hematologic neoplasms comprised 74 cases with ocular adnexal hematologic lesions and 12 cases with intraocular lymphomas and leukemias. FCM analysis of ocular specimens allowed valuable results in 71/86 hematologic cases, failure being mainly due to absence of cellularity (8/15). Histology showed 100 % PPV for both hematologic and non-hematologic neoplasms; FCM reached 97 and 66 %, and cytology 80 and 91 %, respectively. Concordance between FCM and cytology was lower (κ<0.61) than with histology (κ=0.677). FCM phenotype matched ocular lymphoma histotype in 95.8 % of cases. The lymphocytic infiltrate by FCM was 39.5 % in non-neoplastic, 64 % in non-hematologic and 89.5 % in hematologic diseases with B lymphocyte prevalence of 31.3 %, 21.0 % and 93.3 %, respectively. Clonality analysis remains essential regardless of these values. Conclusions: FCM provides rapid results, studies numerous markers simultaneously, and analyzes ocular aspirates from minimally invasive samples. For this reason, it is desirable to permanently integrate this technique into the diagnostic process of ocular disorders, particularly when hematologic malignancies are suspected, as part of an integrated multidisciplinary pathway.