Do Not Judge a Book by Its Cover! When a B-All Pretended to Be a CLL
A 45-year-old man was admitted with B symptoms and pancytopenia. Peripheral blood smear analysis demonstrated numerous small lymphoid cells with occasional blasts and moderate myelemia. Bone marrow aspiration showed a marked infiltration by lymphoid cells (97%) morphologically consistent with chronic lymphocytic leukaemia. However, flow cytometry ultimately confirmed the diagnosis of B-cell acute lymphoblastic leukaemia. Molecular testing revealed a missense mutation in exon 10 of the ZEB2 gene (p.H1038R). The patient received treatment according to the GRAALL 2024, in combination with rituximab. Chemoresistance was observed at day 8, leading to an allogeneic haematopoietic stem cell transplant. This observation illustrates the diagnostic difficulty raised by unusual morphologic variants of acute lymphoblastic leukaemia.
Comparison of Cytoplasmic and Nuclear MTAP Loss in Pleural Effusion Cytology: Correlation With Homozygous p16/CDKN2A Deletion
Pleural mesothelioma (PM) is an aggressive malignancy in which pleural effusion cytology is often the first diagnostic material. MTAP immunohistochemistry, while not a stand-alone diagnostic tool, may serve as a useful adjunct when combined with other markers in the evaluation of pleural mesothelioma. However, the diagnostic relevance of nuclear versus cytoplasmic MTAP loss in cytology specimens remains unclear.
Ensemble Learning Model: A Novel Technique to Detect Malignancy in Effusion Cytology
This study applied an ensemble learning model combining six transfer learning architectures to detect malignancy in effusion cytology.
Cytological Diagnosis of Primary Effusion Lymphoma in the Uncommon Clinical Setting of an HIV-Negative Patient With End-Stage Renal Disease: A Case Report and Literature Review
Primary effusion lymphoma (PEL) represents a small proportion of non-Hodgkin lymphomas. It typically manifests as a serous effusion in HIV-positive patients and is associated with Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV8). We, herein, describe a case of PEL in an 84-year-old male, with HIV-negative status and on haemodialysis (HD) for end-stage renal disease (ESRD). This report emphasizes the significance of cytological examination of effusions, especially in those with no tumour mass, who present with persistent or recurrent effusions.
A Sneak Peek Into a Rare Case of Metastatic Cervix Adenocarcinoma in Pleural Fluid With an Approach to Diagnosis
Effusion samples are the minimally invasive cytology specimens, harbouring metastases from variable primary sites. Pleural metastasis from cervical carcinoma is quite rare and comprises 2.1%-6.1% of all the tumours. Endocervical adenocarcinoma with pleural metastasis is even rarer. Through this, we try to emphasise the cytomorphological and immunohistochemical approach along with histopathological correlation, all of which were indispensable in such a rare case.
Enigma Portal Case: Exceptional Urinary Crystals
Quiz focusing on the cytological analysis of urine in a case of urinary tract infection caused by E. coli, and its management with ceftriaxone treatment.
Cytological and Immunocytochemistry Findings in Fallopian Tube Brush Specimens and Their Correlation With Histology
High-grade serous carcinoma (HGSC), the most prevalent and lethal form of ovarian cancer, is increasingly recognised to originate in the fimbrial end of the fallopian tube (FT). Timely detection remains a critical unmet clinical need due to ineffective screening methods. This prospective observational study assesses the diagnostic potential of FT brush cytology by correlating cytomorphological and immunocytochemical findings with histologically confirmed HGSC.
PDL1 and IDO-2 Immunohistochemistry in Bronchoalveolar Lavage Versus Bronchoscopic Biopsy of Non-Small Cell Lung Cancer
Cytology specimens are less invasive than tissue biopsies, and in some cases of non-small cell lung cancer (NSCLC), they may be the only available material. The expression of programmed death ligand-1 (PD-L1) and indoleamine 2-3 dioxygenase 2 (IDO-2) predicts the response to new treatment modalities. The aim of the study was to investigate the validity of cell blocks prepared from cytology for evaluation of PD-L1 and IDO-2 expression in NSCLC and to compare the expression of these markers in cell blocks and the corresponding tissue sample.
Subcutaneous Fat Necrosis of the Newborn: An Uncommon Presentation With Typical Complications
Subcutaneous fat necrosis of the newborn (SCFN) is an uncommon skin disorder seen in neonates, typically manifesting as subcutaneous nodules or plaques within the first few weeks after birth, often following a difficult delivery. The condition is associated with hypercalcaemia, which can present with symptoms such as lethargy, irritability, hypotonia and dehydration, sometimes resembling sepsis. Fine-needle aspiration cytology typically reveals adipocytes and needle-shaped crystals while showing little to no fat necrosis, inflammatory infiltrate or multinucleated giant cells. The diagnosis is confirmed by histopathology, which shows distinctive features of lobular panniculitis, mixed inflammatory cell infiltration and crystals arranged in a radial pattern. It is important to distinguish SCFN from other causes of lobular panniculitis, as early diagnosis and intervention are crucial to prevent potential long-term complications.
Leukaemic Effusion or Extramedullary Haematopoiesis?
We describe a case of leukaemic pleural effusion in a patient with acute myeloid leukaemia and marked marrow fibrosis. Cytologic evaluation of the pleural fluid revealed numerous large atypical cells, morphologically consistent with dysplastic megakaryocytes. This case underscores an important diagnostic pitfall, as such findings may be misinterpreted if the possibility of leukaemic infiltration is not considered. It highlights the critical importance of recognising key cytomorphologic features and integrating immunophenotyping, clinical history and radiologic findings to arrive at an accurate diagnosis. Awareness of this potential presentation is essential to avoid misclassification and ensure appropriate clinical management.
Distinguishing the Tall Cell From Classic Subtypes of Papillary Thyroid Carcinoma on FNA: A Cytological and Morphometric Study
Tall cell subtypes of papillary carcinoma thyroid (T-PTC) are defined as tumour cells with a height: breadth ratio of > 3. The tall cell subtype of papillary thyroid carcinoma is known for its poor outcomes and aggressive nature. Its definitive preoperative recognition would be advantageous and would help the surgeon to plan a more effective treatment regimen. We aim to determine if the cytomorphological features are sufficiently characteristic to enable their distinction from classic subtypes of PTC on FNAC.
A Case of Mistaken Identity: When All Mimics AML
A 39-year-old man was diagnosed with acute lymphoblastic leukaemia (B-ALL) with SYNRG::ZNF384 and P2RY8::CRLF2 gene fusions. He was treated according to the GRAALL 2014 and underwent an allogeneic transplantation, achieving complete remission. Twenty-five months later, he developed pancytopenia. The bone marrow examination showed blasts with an immunophenotype consistent with minimally differentiated acute myeloid leukaemia (AML M0). Although the P2RY8::CRLF2 fusion persisted, no molecular evidence of a lineage switch was detected. This rare presentation underlines the diagnostic challenges of acute leukaemias. The patient was finally treated with azacitidine and venetoclax.
Pleural Fluid Homing by Anaplastic Large Cell Lymphoma-Cytopathologic Diagnosis of a Rare Presentation
Anaplastic large cell lymphoma (ALCL) is a rare and aggressive subtype of non-Hodgkin lymphoma characterised by large, anaplastic lymphoid cells with strong CD30 expression. Although ALCL commonly presents with nodal and extranodal involvement, pleural effusion as an initial manifestation is exceedingly uncommon. Pleural fluid involvement generally indicates advanced disease, often resulting from direct pleural infiltration or systemic dissemination, and is associated with a poor prognosis.
Beyond Tissue in the Era of Liquid Biopsy: Pathologists' Perspectives and Insights
Liquid biopsy is transforming cancer diagnostics and management by enabling minimally invasive molecular profiling through blood. Beyond plasma, cytology specimens such as pleural effusions, cerebrospinal fluid and urine offer valuable sources for molecular testing. In this narrative review, we highlight the central role of cytopathology in integrating liquid biopsy into clinical practice, discussing pre-analytical and analytical challenges across different samples and exploring the contribution of artificial intelligence in improving both morphological and molecular interpretation.
Optimisation of a Standardised Automated Bleaching and Staining Protocol for Melanin-Rich Cytology Specimens
Melanin-rich cytologic specimens, particularly those from melanocytic lesions, present diagnostic challenges due to pigment-induced obscuration of cellular details and interference with immunocytochemistry (ICC) interpretation. These limitations are especially pronounced in cell transfer preparations, which differ significantly from tissue sections in cellular distribution and density. Existing bleaching protocols are inconsistent, often incomplete in pigment removal and can compromise cellular morphology. This study aimed to develop and evaluate an automated platform incorporating optimised melanin bleaching, ICC and cytomorphologic staining to enhance diagnostic accuracy in heavily pigmented cytologic samples.
The Unexpected Abdominal Mass in a 3-Year-Old
Paediatric abdominal masses encompass a wide range of differential diagnoses including various inflammatory, benign and malignant aetiologies. A thorough clinical examination and imaging are the preliminary investigations of choice to ascertain the nature and extent of the abdominal mass. Fine needle aspiration biopsy cytology (FNABC) is a rapid, reliable and cost-effective tool for the definitive diagnosis. In the present case, a 3-year-old child presenting with a gradually increasing large abdominal mass was subjected to FNABC.
Mediastinal Teratoma With Somatic-Type Adenocarcinoma: An Enigmatic Discovery by Fine Needle Aspiration Cytology
Mediastinal masses often present acutely as medical emergencies, necessitating prompt and accurate diagnosis. Imaging-guided fine needle aspiration cytology (FNAC) plays a pivotal role in rapidly identifying rare mediastinal tumours and differentiating them from other potential aetiologies, enabling timely intervention. Primary mediastinal germ cell tumours (PMGCTs) constitute approximately 15% of adult mediastinal neoplasms. The development of somatic-type malignancies, particularly colonic-type adenocarcinoma, in PMGCTs is rare and typically associated with a poor prognosis. Combining cytological findings with imaging, serum tumour marker analysis and immunohistochemistry can facilitate the detection of various germ cell components and aid in diagnosing GCTs. We report the case of a 35-year-old male presenting with symptoms of mediastinal compression. Contrast-enhanced computed tomography (CECT) revealed an ill-defined anterior mediastinal lesion measuring 9.2 cm in maximum dimension with a heterogeneous appearance. Emergency ultrasound-guided FNAC was performed, yielding highly cellular smears that showed malignant epithelial cell clusters with intracytoplasmic and extracellular mucin, as well as strips and clusters of benign intestinal epithelial cells. Based on the cytomorphological features, the patient's age and imaging findings, a diagnosis of somatic-type adenocarcinoma arising in a background of teratoma was suggested. Histopathological examination of the excised mass confirmed the cytological diagnosis. Adenocarcinoma in the mediastinum may arise from primary sites such as the aerodigestive tract or represent metastatic disease. However, in this case, the presence of a benign intestinal epithelial component strongly indicated a teratomatous origin. This report underscores the utility of imaging-guided FNAC as a minimally invasive and effective diagnostic tool, enabling early diagnosis and timely treatment initiation in patients presenting with acute mediastinal obstruction.
Intercenter Study of Interobserver Variability With Optical and Digital Imaging in Cervicovaginal Cytology. Simulation of a Quality Control Program
Participation in diagnostic intercomparison programs is a mandatory requirement for accreditation of cytology laboratories. Results described by these programs in cervico vaginal cytology (CVC) show a significant number of discrepancies. We hypothesised whether the use of IA systems, such as the ThinPrep Genius system, would improve diagnostic concordance.
Evidence-Based Cytopathology: A Call for Implementation
Evidence-based medicine (EBM) emerged in the mid-1990s as a systematic and data-driven approach to clinical practice. It plays a crucial role in cytopathology, which focuses on identifying both neoplastic and non-neoplastic disorders. Despite its importance, cytopathology faces significant challenges in implementing EBM principles. These include diagnostic variability, interobserver discrepancies, and subjective interpretations, which can impact diagnostic consistency and patient outcomes. These issues often lead to inconsistencies in diagnosis, underdiagnosis, or overdiagnosis, ultimately compromising patient outcomes. To address these challenges, evidence-based cytopathology (EBC) emphasises the critical evaluation of diagnostic tests and the utilisation of well-designed and high-quality data to establish robust guidelines. EBC promotes the adoption of standardised diagnostic criteria, integrates robust study designs with the implementation of advanced technologies like artificial intelligence (AI), and leverages clinical decision support systems (CDSS) to enhance diagnostic accuracy and consistency. However, realising the full benefits of EBC requires collaborative research, multicenter trials, and continuous updates to guidelines. In this paper, we discuss the future efforts in improving EBC outcomes, with a focus on developing precise diagnostic instruments, refining methodologies, and exploring machine learning applications to improve diagnostic reliability, enhance patient care, and support informed clinical decision-making.
Performance of MammaTyper in Fine Needle Aspiration Cytology, Core Needle Biopsy and Surgical Breast Cancer Samples
To evaluate the performance and concordance of the MammaTyper molecular test across cytological, biopsy and surgical samples from breast carcinomas, emphasising the applicability of cytology in molecular subtyping.
Commercially Available Artificial Intelligence Solutions for Gynaecologic Cytology Screening and Their Integration Into Clinical Workflow
Historically, gynaecologic cytology, particularly cervical screening through Pap smear tests, has been instrumental in early cancer detection, but not without its challenges. These include variability in interpretation and the labour-intensive nature of manual screening processes. The advent of artificial intelligence (AI) technologies, especially machine learning and deep learning, heralds a new era in cytology, offering enhanced accuracy, consistency, and efficiency. These advancements promise to mitigate traditional limitations by automating routine analyses, aiding early cancer detection, and reducing the workload of laboratory personnel. This review thoroughly examines the current status of commercial AI software in gynaecologic cytology screening. We critically assess the capabilities, performance, and impact of these AI tools in a clinical context. Additionally, the review addresses the integration challenges and potential of AI in clinical practice, including workflow integration, regulatory compliance, and ethical considerations. Through this comprehensive analysis, we aim to provide insights into how AI is reshaping gynaecologic cytology, paving the way for more effective disease management and enhanced patient care in women's health.
