BACKGROUND: Claudin-4 has been described as a highly sensitive immunocytochemical marker for detection of metastatic carcinoma cells in effusion cytology specimens. This study aims to challenge the performance of claudin-4 in different types of malignancies and low cellularity specimens, by comparison with other markers in a large cohort of carcinomatous effusion specimens.
METHODS: Cell block preparations from peritoneal and pleural fluid specimens were retrieved, with malignant (carcinoma) diagnoses confirmed by review of hospital diagnosis code and pathology reports. Claudin-4, BerEP4, CEA, and MOC31 immunocytochemistry were performed and scored by expression proportion and intensity. Tumor cellularity was assessed for subgroup analysis of low cellularity specimens.
RESULTS: Totally 147 specimens (70 pleural, 77 peritoneal) of 68 lung, 62 breast, 9 gynecological, and 7 gastrointestinal carcinomas were retrieved. The average proportion expression of claudin-4 was highest (89.6%, vs. CEA 40.5%, BerEp4 18.6%, MOC31 16.8%) and the percentage of strong expression was highest for claudin-4 (72.1%). Expression levels of claudin-4 were consistently higher than other markers in subgroups of all primary sites. The difference was more significant for low cellularity specimens. High (≥50%) proportion expression was seen for 96.61% of cases for claudin-4 (vs. BerEp4 8.77%, CEA 46.55%, MOC31 8.77%, p < 0.001). These factors contributed to a low concordance between claudin-4 and BerEp4, CEA and MOC31 (K = 0.010-0.043).
CONCLUSIONS: Claudin-4 is more sensitive than CEA, BerEp4 and MOC31, suitable for low cellularity specimens of most types of metastatic carcinoma and is a robust immunocytochemical marker for carcinoma that can be used solitarily.

The recent introduction of the WHO cytology classification of pancreatobiliary tumours aimed to improve the diagnosis and management of these tumours. The present paper briefly describes the methods of diagnosis. Emphasis is then put on a detailed comparison of the previous Papanicolaou classification and the new WHO classification and description of the changes brought about by the introduction of the WHO classification. In the last part of the paper, we present interesting cases from our practice illustrating possible diagnostic pitfalls of cytological evaluation.

Preoperative cytopathology of pancreatobiliary neoplastic lesions is a sensitive and specific method and is irreplaceable in the diagnosis and clinical management of these diseases. Pathologists should make every attempt to provide diagnosis as precise as possible and minimize the rate of \"atypical\" results, which create management dilemmas. The diagnostic accuracy of cytopathology can be significantly improved by judicious use of ancillary studies, including immunohistochemistry and molecular genetics. Next generation sequencing (NGS) is the latest addition to pancreatobiliary cytopathology diagnostic arsenal. NGS is not only a very robust diagnostic tool, but also carries significant prognostic and therapeutic information.

UNASSIGNED: A 2-year-old domestic longhair crossbred female cat was referred for a second opinion on a non-healing surgical wound after left eye enucleation. In addition to the left orbital lesion, ulcerative granular masses protruding from the left nostril and on the base of the left ear were noted. A diagnosis of cryptococcosis was established using histopathological examination and a latex cryptococcal antigen agglutination test. The cat was successfully treated with itraconazole.
UNASSIGNED: Cryptococcosis, commonly reported in Australia, western Canada and the western USA, is rarely reported in companion animals in Europe. This marks the first report of cryptococcosis in cats in Bosnia and Herzegovina, emphasising the need to raise awareness within the veterinary community, both local and regional, about this disease.

The practice of cytopathology has been significantly refined in recent years, largely through the creation of consensus rule sets for the diagnosis of particular specimens (Bethesda, Milan, Paris, and so forth). In general, these diagnostic systems have focused on reducing intraobserver variance, removing nebulous/redundant categories, reducing the use of \"atypical\" diagnoses, and promoting the use of quantitative scoring systems while providing a uniform language to communicate these results. Computational pathology is a natural offshoot of this process in that it promises 100% reproducible diagnoses rendered by quantitative processes that are free from many of the biases of human practitioners.

Precision medicine translates through molecular assays and in minimally invasive diagnosis, evident in analyses of effusions that serve therapeutic and diagnostic purposes. This cost-effective and low-risk approach provides advantages, playing a pivotal role in late-stage oncology and frequently standing as the primary resource for cancer diagnosis and treatment pathways. This article outlines the workflow for managing serous fluid and explores how cytology effusion analysis extends beyond immunocytological diagnosis. Combined with current molecular tests it showcases the potential to be a skillful tool in precision cytopathology.

Pancreatic lesions can be solid or cystic and comprise a wide range of benign, premalignant, and malignant entities. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the current primary sampling method for the preoperative diagnosis of pancreatic lesions. Optimal handling of cytology/small tissue specimens is critical to ensure that the often-scant diagnostic material is appropriately utilized for ancillary and/or molecular studies when appropriate. Ultimately, evaluation of EUS-FNA cytology and small biopsy material can provide accurate and timely diagnoses to guide patient management and triage them to surveillance or surgical intervention.

With the advancement of tissue procurement techniques, in-depth knowledge of morphology is crucial for cytopathologists to diagnose neoplastic and nonneoplastic lung diseases optimally. Cytopathologists must also be well versed in immunohistochemistry/immunocytochemistry markers and their interpretation for an accurate diagnosis.

Small biopsies of lung are routinely obtained by many methods, including several that result in cytologic specimens. Because lung cancer is often diagnosed at a stage for which primary resection is not an option, it is critical that all diagnostic, predictive, and prognostic information be derived from such small biopsy specimens. As the number of available diagnostic and predictive markers expands, cytopathologists must familiarize themselves with current requirements for specimen acquisition, handling, results reporting, and molecular and other ancillary testing, all of which are reviewed here.

BACKGROUND: Severe Eosinophilic Asthma (SEA) may be the prodromal phase of Eosinophilic Granulomatosis with Polyangiitis (EGPA). Nevertheless, few studies have tried to recognize EGPA in the early stages of the disease.
OBJECTIVE: To identify a panel of clinical and biological markers to detect which severe asthmatic patient might be considered in a prodromal phase of EGPA and crafting a strategy for diagnostic decision-making.
METHODS: 30 patients with EGPA and 49 with SEA were enrolled. A complete pulmonary, ear, nose and Throat (ENT) and rheumatologic assessment were made. Blood (eosinophil count, eosinophilic cationic protein-ECP, IL5, IL4, total-IgE, IgG4, anti-neutrophil cytoplasmic antibody (ANCA), sputum (eosinophils count, periostin, IL8 and GMCSF) and nasal smear (eosinophilia) biomarkers were assessed. Asthma Control Test, Short Form-36, SinoNasalOutcome Test-22, and Asthma Quality of Life Questionnaire were also used.
RESULTS: SEA patients had poorer asthma control (p<0.001) and higher level of sputum eosinophils (p<0.002) while EGPA patients reported higher levels of blood eosinophils in the past. Sputum GMCSF was the only biomarker significantly increased in EGPA patients compared with SEA (p<0.0001). Among SEA patients, those with some suggestive but not diagnostic criteria of EGPA, particularly tissue eosinophilic infiltrates, presented higher levels of sputum GMCSF (p<0.0005), blood and sputum eosinophils (p<0.0006, p<0.011) in comparison with the other patients.
CONCLUSIONS: Sputum GMCSF and eosinophils might be useful biomarkers to support early diagnosis and treatment choices in SEA patients, suspected of having EGPA.