Introduction. 23 rd Annual Seminar in Pathology. FLUIDS, Part 1. Pittsburgh, PA Gladwyn Leiman UVMMC, VT

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23 rd Annual Seminar in Pathology Pittsburgh, PA Gladwyn Leiman UVMMC, VT FLUIDS, Part 1 "Blue walls", Claudia Hansen, 2009 Introduction o Challenging to everyone o Almost any benign or malignant process may involve serous cavities o Most cells round up in fluid, altering morphology considerably o Classic stains used are Papanicolaou and Giemsa o Immunocytochemistry has become a frequent standby on fluids & cell blocks o All adjunctive tests can be performed on fluids 1

The Body Cavities o Dynamic space o 5-10L of fluid is filtered and reabsorbed each day o Any significant accumulation is abnormal o Maximum accumulation: o 20L in peritoneal cavity o 3L in each pleural cavity and o 600cc in pericardial cavity Neoplastic Exudates Metastasis: most frequent direct involvement or extension Primary tumors: Mesotheliomas Serous tumors Advantages of fluid examination o Easily accessible o Repeated access for monitoring o Provide useful clinical information: o Diagnosis, adjunctive tests o Staging and prognosis o Follow up and disease monitoring o Frequent site of recurrence, metastasis 2

o Thoracentesis o Paracentesis o Culdocentesis o Peritoneal washing o Pelvic washing o During surgery o During endoscopy Fluid collection SEND THE FULL VOLUME 70 100ml lower limit Cells in Benign Fluids Mesothelial cells Macrophages Leukocytes Normal mesothelial cells o Single-layered, flat lining cells of serous membranes. o 10-20 microns in diameter o Appear singly or in small aggregates when naturally shed o Appear in sheets if actively washed o Round, regular nuclei with small nucleoli. May have grooves. 3

Normal mesothelial cells Basophilic, sharply demarcated cytoplasm Two-tone cytoplasm with brush borders. Perinuclear dense zone (due to organelles) Peripheral clear zone with lacy edge Intercellular windows between cells EM: regular, LONG microvilli on cell surface Benign mesothelial cells (Pap) 4

Normal mesothelial cells Pap and Giemsa 5

Reactive mesothelial cells Cellular, with 3D clusters, mimic epithelial cells Nuclear enlargement, binucleation and multinucleation, can appear atypical Can have hyperchromasia with mostly regular nuclear membranes Cytoplasmic vacuolization resemble signet-ring cells (never mucin positive). Often with inflammatory background. Reactive mesothelial cells Reactive mesothelial cells 6

Reactive mesothelial cells (MGG) Other cells Histiocytes - ubiquitous (likely transformed mesos) Similar in size to mesothelials Lightly stained cytoplasm Irregular nuclei with low N/C ratio Some kidney-bean shaped, Multinucleated Phagocytized debris Foamy cytoplasm Cytoplasmic vacuolation (MGG) Other Cells Lymphocytes: Chronic and chylous effusions, TB, (CLL/SLL) Neutrophils: Infection, infarction, rupture Eosinophils: designated eosinophilic if >10% Trauma Hypersensitivity/allergy ~ 5% associated with malignancy. Hydatid disease 7

Congestive Heart Failure Most common cause of benign effusion Pleural, pericardial effusion and ascites Usually transudates except when associated with inflammation Rarely blood-stained CYTOLOGY: Reactive mesos and lymphs if chronic Cirrhosis o Usually transudates: o Low protein synthesis o Portal hypertension o CYTOLOGY: o Reactive mesothelial cells o Atypical mesothelial cells: o papillary clusters o acini, rosettes o Signet ring forms Acute inflammatory processes o Composed of purulent exudate o Bacterial pneumonia o Lung abscess o Pleurisy, pericarditis, peritonitis o CYTOLOGY: Neutrophils ++ Few mesothelials 8

Systemic Lupus Erythematosus o Exudates due to collagen vascular disease o Normal to high glucose o LE cells: Fairly specific feature when present o Neutrophils with phagocytized cytoplasmic homogeneous degenerated material o Tart cells: o Histiocytes with phagocytized degenerated nuclear debris. Lupus Erythematosus LE cell (MGG) LE cell (Pap) Rheumatoid Arthritis o Female > Male o Chronic active disease o Effusion male > female o Green, turbid, pseudochylous o Decreased glucose o Cytology: o Background of granular amorphous debris (may be eosinophilic, cyanophilic, or green) o Elongated fibroblast-like cells and multinucleated giant cells; degenerated leukocytes (from rheumatoid nodule) 9

Rheumatoid Pleurisy Multinucleated giant cells Fibrinoid debris Tuberculosis o Pseudochylous o When TB doesn t directly involve pleura: o Lymphocytosis - mostly T cells o Plasma cells o Rare Langerhans cells o Decreased/absent mesothelial cells TB pleurisy 10

Pulmonary infarction Highly atypical mesothelial cells can be present Eosinophils, neutrophils, siderophages and lymphocytes Can be blood-stained Radiation changes Radiation pleuritis and pericarditis Immediate or delayed - months/years Differential is recurrent malignancy Mesothelial changes: Nuclear enlargement with hyperchromasia Cytoplasmic and intranuclear vacuolation and blebs Multinucleation Radiation changes 11

Miscellaneous cells Hepatocytes May be seen in right-sided pleural effusion Ciliated bronchial cells - trauma, broncho-pulmonary fistula Squamous cells - dermoid cyst Megakaryocytes/hematopoiesis in EMH Detached ciliary tufts Normal, physiologic phenomenon. Anucleated fragments of ciliated columnar epithelial cells from the fallopian tube Seen in peritoneal fluids Do not confuse with organism 12

Peritoneal Washings Obtained intraoperatively during laparotomy for gynecologic surgery Mesothelium characterized by large, flat, monolayer sheets of cells fitting together in orderly mosaic pattern Nuclei are round, oval, regular, grooved (sometimes kidney-bean and convoluted) Mesothelial cells in washings Mesothelial cells in washing specimen 13

DAISY CELLS Source: Diagnostic Cytopathology 43:8:629. 2015 Mesothelial cells in washings Collagen ball With thanks to Jess Crothers for great photo! 14

Pericardial fluids Very large mesothelial cells in aggregates. May have prominent nucleoli Mechanical, d/t rhythmic heartbeat Half Time 15