lh CO Canine and Feline Cytology OTe LL A Ld i Maxey L. Wellman, DVM, PhD, DACVP Ralston Purina Company Clinical Handbook SeriesTable of Contents Introduction .. Part I Chapter | Sample Collection and Specimen Preparation Chapter 2 Approach ta a Cytolagie Specimen Part Il Chapter 3 Interpretation of a Cytologic Specimen ....u 3 \ Ly ’ Chapter 4 i ~a ~ Cytologic Appearance of Etiolagie Agents 19 Interpretation of Part Ill Canine and Feline Chapter 5 Body Cavity Bffusions and 83 Cytology Cate Stadler Chapter 6 M. Judith Radin, DVM, PhD, DACVP Skin and Connective Tissue — Case Studies 33 Maxey L. Wellman, DVM, PhD, DACVP Chapter a Lymph Node and Spleen —Cave Studies Chapter 8 tem and Internal C Part iV Guidelines to Distinguishing Transdate and Evaluation of Synovial Fluid Index of Figures ston Purina Company EL ee Clinical Handbook Series Suggested Reading Subject Inde uuuJ7gay Ralston Purina Company Inerreation of Canine and Fline CytologyIntroduction Cytology is tt microscopi cytology can be w evaluation of cells. In many cases eful in establishing a provisional diagnosis, determining a prognosis, and formulating a diagnostic or thera- should be viewed as a screening tool peutic plan. Although cyto most reactions can be classified as inflammatory, hyperplastic, or neoplastic. The type of iuflammation usually can be determined, and etiologic agents sometimes can be identified. For neoplastic process es, an experienced cytologist can definitively diagnose several specif ic neoplasms, make a tentative diagnosis of neoplasia for of tumors, identify sites of tumor metastasis, and monitor tumor recurrence following anticancer therapy. There are several advantages to cytology. Most tissues, organs, and fluids can be sampled; sample collection is relatively noninv and most samples can be collected on an outpatient basis. Sample collection and specimen preparation make use of inexpensive equip- ment that is readily available in most veterinary practices. In-house inte ns can be made the same day, and interpretations from reference laboratories frequently are available within 24 hours. Complications associated with sample collection are uncommon and usually are limited 10 minor hemorthage. Infection, injury to adjacent structures, and dissemination of neoplastic cells are rare. Absence tissue architecture is the most notable disadvantage of cytology. The arrangement of neoplastic cells within tissues is critical in the diggno- sis of many types of tumors, in evaluating surgical margins, and in establishing whether a tumor is benign or malignant. When the cytologic diagnosis of neoplasia is uncertain, the presence of a tumor and the tumor cell type should be confirmed histologically. Some lesions do not shed cells well, and too few cells may be present for the cytologist to evaluate. In those cases, histologic evaluation may Interpretation of Canin Part T covers basic information on sample collection, spec ind Feline Cytology is divided into four paris reparation, and microscopic evaluation. Part II discusses interpreta tion of the microscopic evaluation to cytologic diagnosis of inflammation, hyperplasia, or neoplasia and includes a chapter devot ‘od to identification of organisms. Part III contains case studies orga n Part IV. This nized by systems. Reference material is located handbook provides an introduction to cytology, presents some of the ‘more common abnormalities in which cytology is useful for establish: ing a diagnosis, and points out certain situations in which the eyto- logic interpretation results in a provisional diagnosis that should be Ralston Purina Company Ilerprtation of Canine and Feline CytologyRake Purina Company Inepretation of Canine and Fs ie Cytology 3Chapter 1: Sample Collection and Specimen Preparation Choosin wn area from which to collect a sample for cytology and deciding the method of sample collection depend on what abnormality is detected clinically. Samples collected by fine needle aspira tion, touch impression, or gentle tissue scraping. Ultra sound is useful for guiding fine needle aspiration of internal to decrease the risk of complications, ‘within the lesion may be beneficial to avoid missin g only an area that is not rep tive of the lesion, sampling only’ a necrotie area, or obtain: ing only blood. Preparation of the Collection Site Preparation of the superficial sites to be aspirated is sal preparation similar to preparing for venipuncture. Su of the aspiration site is recommended for collection from internal masses, joint fuid, body cavity fluids, cerebrospinal uid, and bone marrow. Specific aspiration sampling tech niques for a wide variety of tissues are described in numer- Fine needle aspirates from solid tissues “Tlanes cally aopirted inca abincand subertijdaep snd superficial lymph nodes, spleen, liver kidneys, kings, con orga is dened ly palpation; eadiogrnphys oF ultrasonography and manually isolated. Fine needle apirs ge needle of the tion is performed using a 21- to 2 appropriate length for the desired specimen, coupled to a Some clinicians prefer using an aspira. Helmuth industries, Linden, NJ), 6- to 20-mal syring tion device (AspirGun which allows one hand to remain free to immobilize a mass while the other hand is wsed to aspirate the sample. The needle, coupled to a syringe of aspiration device, is intro duced through she skin to penetrate the lesion or tissue and negative pressure is applied several times. Negative pres: sure should be rele ed before removing the needle from the mass to avoid contamination of the sample with blood or cells from surrounding tissue. For some small skin masses, using only a small ge nee dle to “prick and poke” several times seems to work better Ralston Purina Company’ Interpretation of Canine and Faline Cytology than using a syringe to apply negative pressure. After the mass has been sampled, a syringe filled with air is attach, to expel the sample onto a glass slide. This method is simila has been described fo to the nonaspiration technique th ation of internal masses, it which a syringe Filled with Few milliliters of air is attacked to a needle. The mass is iso lated and the needle is introduced into the mass and redirect ced several times, No negative pr ple is collected only by the cutting action of the needle. The needle is removed, and the air in the s nge is used to expel ample onto a glass slide Frequently only a smal volume of aspirated mater present in the needle or hub of the syringe, but this amount usually is adequate to produce several smears, cean be removed from the needle, filled with air, and reat tached to the needle to dispel the sample onto a slide (stationary slide). A second (spreader) slide is used to disperse the sample using a pull (Figure 1.1) or push tech nique (Figure 1.2). Failure to disperse the cells on the slide creates smears that are too thick for interpretation (Figure 1.3). Too much pressure during slide preparation results in broken cells. Preparation of high-quality smears is critical for optimal microscopic evaluation and interpretation. Gentle handling of samples and application of minimal pressure during slide preparation usually result in slides of acceptable qua (Figure 14), After smear slides are made, they should be air-dried and labeled. They should not be fixed with heat or ace tone or exposed to formalin fumes, as subsequent staining may be inadequate. After the slides have been air-dried they can be sent to a reference laboratory or stained for Fine needle aspirates of fluid samples Fluid from body and fluid-filled mass Collected es can be collected using fine needle aspiration fluid should be placed in a tube containing ethylenedi aminetetraacetic acid (EDTA) to prevent clotting. J counts will be inaccurate because most sample clots, cell of the cells will be retained in the clots. A portion fluid can be placed in a sterile tube for culture and sensi1. Place a drop of cytologi specimen toward the end of two slides. Invert one Slide, 10uch the slides together, and alow the material to bogin spreading 2, Gently pull the slides apart using @ parallel mation, — ee 3, This wll reeultin two pull smears of similar appearance. 1. Place a drop of eytologe spacimen, cra stationary slide. Move the spreader slide backward into the drop of specimen {and allow the material to spread along the base ofthe spreader slide i 2. Push the spreader away from the drop to spread the material onthe stationary slide. _ ay 3. This will result in one smear ‘on the stationary side, __ A Figure 1.1 The pl technique tr makin Figure 1.2. The push tech (austetion by Tim Vo.) ue for making a smear fr cytology. Sey @ ie Figure 1.3 This spetiman-wes not gaperané on the ele, seutng ina ‘moar tha s 100 thee for eolgle evaluation riviny testing. Analysis of eell count, protein concentra: tion, and specific gravity will determine if the fluid is a transudate, a modified transudate, or an exudate (oe the table" Guidelines to Distinguishing Transudates and Eudes,” Fart IV), Cells should be enumerated manually or by elec- tronie particle counters, or should be estimated from a igure 44. This specimen was genty disperse wing the pus echniqu. The smear ga monolayer of nat cls that is agequate fr ctoaac va dicect sinear. Total protein concentration, specific gravie ty, or both should be determined by refractometry. Direct smears should be made if the cll count is 10,000) or if the fui is turbid or bloody: The pull oF push technique van be use. ithe Ghd is relatively clear, then the call count will belo and cytologic interpretation is more Ralston Purina Company’ Interpretation of Canine and Feline Cytology AAA RRRKRAARARKRRAHRAARHRARARA FLFigure 1.5, This ui specimen was prepared using a cylocentrituge. The calls are concentrated nw smal cirelar area onthe slide. readily accomplished ifthe cells are concentrated. Cells can be concentrated using a cytoventrifuge (Figure 1.5) or using techniques similar to preparing urine sediment. The slides are then air-dried and sent to a reference laboratory or stained for in-house interpretation. Ifa fluid sample isto be sent toa reference laboratory, airried direct and sediment smears should be made and submitted with the fluid. Many changes can occur during transport of fluid specimens, including cell degeneration and bacterial overgrowth, Slides made at the time the sample was collected are useful to the clinical pathol ‘gist in assessing cell morphology and determining whether clinically significant bacteria are present Impression smears with an ulcerated surface or from excised tissue, Imprints wastes may reveal only secondary inf from uleerated sm ‘mation o dysplasia, whereas an aspirate of the underlying tissue might be more diagnostic. Impression smears of ulcerated masses should be made before and afier ger cleansing with 0.9% sterile saline. The ulcerated surface is gently imprinted on a clean glass slide, and the slides are air-dried. For impression smears of tissue biopsies, a scalpel is used to make a freshly cut surface from an area represen- tative of the lesion. The tissue should be gently blotted to remove blood and tissue fluid, then lightly touched to the surface of a clean glass slide. Several impressions can be made from the same tissue on one glass slide (Figure 1.6). sue scrapings Tissue scrapings can be used for superficial lesions or for cexcised tissue. Cells are collected by gently scraping the sur- Ralston Purina Compacy’ Interpretation of Canine and Feline Cytology rs wore made of an excised piece of Uissu. Each impression is adequate fo eytlopic evaluation face ofthe lesion with the dull side of a scalpel blade or the edge of microscope slide. The cells are then gently smeared across the surface of a clean microscope slide and allowed to airdry. This method of sample collection is especially useful neoplasms, which may not release many cells when fine needle aspirates or impression smears are attempted. Disadvantages of using this method include sampling ouly superficial areas of the lesion and breakage of many of the cells Mailing Slides to a Reference Laboratory Slides thar are to be sent to a reference laboratory should be air-dried and placed in appropriate slide mailers which often are provided by the laboratory. The slide should be transported at room temperature 10 prevent water from condensing on the surface and causing cell Iysia Ideally, cytology samples should be mailed to the ref erence luboratory separately from formalin avoid contact with formalin fumes, which may inkibit opti mal staining of air-dried smears. Cytology specimens should be submitted to the refer ‘ence laboratory with all of the following information signalment a brief history relevant physical examination findings, a summary of results of pertinent diagnostic tests, the tentative diagnosis, and the site from which the sample was collected. (Often the sit animal inchided on the sabmission form from the reference tan be indieated on a line drawing of thehelpful to the pat! making an interpretation, Stains Wright’ stain, Wright-Giemsa stain, and new methylene blue stain are most commonly used for cytologic prepara tions. Most commercially available stains, such a Diff Quik (Harleco, Gibbstown, NJ) and Dip-Stat (Medi Chem Corp, Santa Monica, CA), are modifications of Wright’s or Wright Giemsa stain and are inexpensive and easy to use. Wri nd Wright-Gieme ins provide good color contrast, cyto plasmic detail is ery good, maclear detail ie acceptable, and most infectious agents are stained. These stains also ace per (0 practitioners who interpret cytology in-house and want a second opinion from a clinical st. Wright's s purpl able quick stains do not consistently stain mast cell path 1 Wright-Giemsa stains will stain mast cell granv whereas some commercially avail: + occur relatively commonly in dog may be misdiagnosed by cytology if enly commercial quick tains are used Now methylene blue stain results in better nuclear detail than does Wright's stain, but color contrast is poor and itis not a permanent stain. Nucleoli are very prominently stained with new methylene blue, which may lead the novice cytologist to incorrectly interp ‘a malignant one. New methylene blue also does not stain Because the gran: ules are such a characteristic fearure of mast cell tumors wained with new methylene blue may be incor rectly interpreted as macrophages, Special stains may sometimes be used to determine cell lineage or to identify etiologic agents, These stains usually are available at commercial reference laboratories or acade- sic institutions. Identification of intermediate filaments, mmunophenotyping, determination of immunop i surface antigens, and polymerase chain tion technology are newer tech niques that have been used to increase the sensitivity of cytologic evaluation: ‘SAMPLE COLLECTION AND SPECIMEN PREPARATION TIPS Use clean glass slides. Avoid formalin Fumes. Disperse cells on the slide. Avoid blood contamination. ‘Be gentle in preparing smears ‘Sample several representative areas. le slides from each lesion. Airdry specimens quickly (do not use heat or hairspray), ‘Work quickly s0 sample does not clot or dry Evaluate mul before smears are prepared. Ralston Purina Company Merpreation of Canine and Feline Cytology HARA ARARA AMR ARAARAAARARAARAChapter 2: Approach to a Cytologic Specimen Microscopic Evaluation The eytologist should use a high quality mien equipped with 10x and 100x (oil immersion) abject adjusted for optimal Koehler illumination (Figere 2. q and laboratory information to avoid misinterpretation, ologic Findings should be correlated with other clinical Primary differentials may vary with species, breed, and age of che patient, and geographic area. Knowledge about tumor incidence, site predilection, and gross morphology is useful nosis of neoplasia. The cytologist should recognize that histologic evaluation of excised tissue might be necessary to distinguish hyperplasia from neoplasia and to make the definitive diagnosis for y neoplasms. A cytologic smear or imprint should be observed grossly INSTRUCTIONS FOR KOEHLER ILLUMINATION OF A MICROSCOPE Place a glass slide with a stained smear on the stage, turn on the light source, swing the 10x objective in place, and use the coarse focus knob to adjust the image to slightly out of focus. Close the field diaphragm to its smallest size using the field diaphragm control ring. The field diaphragm control ring usually is located con the base of the microscope. Visualize closing the field diaphragm as a circle of light that decreases in size (B) ‘Move the condenser vertically by rotating the condenser focus knob until a sharp image of the leaves of the field diaphragm forms on the specimen. The condenser focus knob usually is located on the side of the microscope, just below the stage. As the knob is moved, the leaves or edges of the field diaphragm come into focus. When the edges are in sharp focus, they typically appear slightly green or light orange. Use the condenser centering screws to boring the image ofthe field diaphragm to the center ofthe field of view. The con- denser centering screws are located on the front or sides of the condenser, which is the apparatus under the stage of the mir scope. When this adjustment is made, a cir cle of light moves toward the center of the Field of view (B). Use the field diaphragm control ring to open the field diaphragm so that the diaphragm’s image is about the same size Ralston Parina Company Ilepretation st Caine and Feline Cytology 10x objective Condenser Condenser centering serous Condenser_— as that of the field of view. The circle of light becomes larger as this adjustment is made. Check frequently to ensure that the condenser is prope erly positioned for optimal illumination, especialy if the microscope has multiple users. Image of tld daphragm Stage Coarse focus knob Fine focus kr Fs cashragm conto ng 04 with 0X objective, B, Representation of the field diaphragm. (station by Tim Volt.)to evaluate the quality of the preparation and to locate cellular areas on the slide to examine microscopically. The slide ie then scanned with the 10% objective to estimate cellularity of the sample; observe cell-to-cell associations identify large etiologic agents, such as parasites and fun. gal hyphae; and locate areas to be examined with higher magnification, Scanning the entire slide with the 10x objective is important because cells nay be distributed on only a small pact of the slide, or a single etiologic agent may be present that would be missed if only portions of the slide were examined. 10 The 100x (oil immersion) objective is used to deter mine what kinds of cells are present, examine cellular detail, and identify etiologic agents. Changes in nuclear and cytoplasmic morphology charset stic of neoplastic cells are best evaluated at this higher magnification. Only ntact cells that are adequately dispersed should be exam. ined and interpreted. Disrupted cells reveal arifactually enlarged auclei, pale-staining diffuse chromatin, and nucleolar prominence, all of which may be misinterpreted as cytologic characteristics of neoplastic cells. Nuclear and cytoplasmic detail cannot be adequately evaluated in cells are inadequately dispersed. Ralston Purina Company Interpretation of Canin 34 Feline Cytology AAARARARANRAANAAANRANRAAANRN |Ralston Purina Company Interpretation of Canine and Feline Cyialogy n — —— — — — = = a — =UUUUUUUveUuUuUuUuUUuUUuUUeUuETds Chapter 3: Interpretation of a Cytologic Specimen Interpreting eytoloy specimens requires knowledge of normal cellular and tissue morphology: recognition of the limitations of cytology, and experience. Correlation of cytologic findings with clinical and laboratory inforraation as well as knowledge of location, gross appearance, and behavior of the lesion allow maximum useful information to be obtained from a sample and help avoid overinterpi ion. It is helpful to try to catego Fize a cytologic specimen as inflammatory or noninflammatory, to distinguish between hyper- plasia and neoplasia, to differentiate between ative changes in neutrophils usually is suggestive of a bacterial etiology. The specimen should be carefully examined for bacteria (Figure 32) and a culture should be performed As an inflammatory response becomes more chronic, nereasing sumbers of lymphocytes, plasma cells, mono. TABLE 1. INFLAMMATORY CELLS AND ASSOCIATED ' a a 1, Prominant Cl ype Differential Diagnosis between hemorrhage and blood contamination. | Neutrophils Bastar anfoction Fungal infection USEFUL DISTINCTIONS FOR A Protozoal infection CYTOLOGIC SPECIMEN Immune-mediated disease Trauma 1 Inflammatory vs noniaflammatory Chemical injury O Hyperplasia vs neoplasia Inflammation secondary O Benign vs malignant tumor to neoplasia O Hemorrhage vs bloed contamination Neutrophils and macrophages Bacterial infection (Nocardia spp. Inflammation Inflammation is characterized by a mixed population of cells that may include neutrophils, lymphocytes, plasma cells, monocytes macrophages, eosinophils. and mast cells, These calls appear in varying proportions, depending fon the cause and chronicity of the inflammatory process (Table 1). Inflarmmati may be presen tious agent, foreign material, tissue necrosis, or allergen. In addition, some benign and malignant neoplasms may induce an inflammatory response In general, an acute inflammatory response is characterized by a pr jominance of neutrophils, Neutrophils can be described as nondegenerate (morphologically normal, Figure 3.2) or degen: erate (Figure 5.2), Characteristics of degenerate karyor rhexis, karyolysis, cytoplasmic basophilia, and neutrophils include nuclear swellin cytoplasmic vacuolization. Presence of degener Ralston Purina Company’ Interpolation of Canine and Flin Cytlogy Macrophages Eosinophils ‘Aetinomees spp) Fungal infection Protozoal infection Foreign body or injection site reaction Trauma Chemical injury Inflammation secondary 10 neopla Fungal infection Protozoal infection Foreign body reaction Lick granuloma Inflammation secondary to neoplasia Neopl macrophages involving Hypersensitivity Parasitic ‘afection Fungal infection Eosinophilic granuloma ‘Mast cell tumor 13igure 3.1. Peuraletasion from aca. The neutrophils have normal ‘morphology (i, are nondegenerate). (Wright stan; 1000%) Figre 3.2. Degenerative changes in neutrophils frequently occur as 3 result of bacterial infection. Note the many 04-shaped bacteria inthis etsion. (Wright's sai: 000%) Figere 3.3. Lymphoplasmacytc inflammation is character population of mature lymphocytes, plasma cells, anda few large Iymphocytes. (Wright's stain; 1000X) 4 phagocyte cellutar stain 10004) is. The arrow inde cytes, and macrophages appear (Figures 3.3 and 5.4). Macrophages may be assessed for level of activity, imclud= ing vacuolization of their cytoplasm and phagocytosis: In chronic responses, epithelioid macrophages or multinucle- ated giant cells (Figure 5.5) may be seen. Mixed or pyo- granulomatous inflammation may result from chromic bac- terial infections, mycotic infections, protozoal infections, oF reactions to Foreign material Eosinophils and mast cells may be part of an jnflamma- tory response. These cells are more likely to be encountered with chroaie inflammation. Allergic reactions, presence of a parasite, and response 10 foreign material are more likely to have an eosinophilic component in the inflammatory response, High numbers of eosinophils are seen in lesions From cats with indoleat ulcers or eosinophilic granulomas. Eosinophils may be associated with some neoplasms, such ‘as mast cell wmors or, occasionally, lymphoma, Hyperplasia, Metaplasia, Dysplasia Hyperplasia, metaplasia, and dysplasia can occur in response to irritation, inflammation, altered cellular signal iog (eg, hormone imbalances) or subsequent 10 tissue destruction and regeneration. Because of the association with inflammatioa. inflammatory cells are often preven in the specimens. Cells from hyperplastic tissues usually appear more immature but otherwise resemble normal cells Figure 3.6). Cytologic characteristics of hyperplastic cells include large oul with poorly condensed chromatin and prominent nucleoli. Cytoplasm is often basophilic Hyperplastic cells have a relatively constant nuclear to sytoplasmic (N:C) ratio (nuclear sie compared to amount Ralston Purina Company Interpretation of Canine and Feline Cytlogy ARANRKRKRTHRANTNATRANARUANAANDADAARASBA= = of cytoplasm present). This is an important feature in dis: tinguishing hyperplasia from neoplasia In metaplasia, cellular characteristics are altered to resemble a different type of tissue and must be distin- guished from the presence of neoplastic cells. This change is most commonly seen when glandular epithelium has areas that take on the appearance of squamous epithelium, for example, in squamous metaplasia of the prostate (igure 5.7). Dysplasia can also occur and is characterized by abnormal development of the cells of the involved tissue. Dysplastic cells may exhibit many of the criteria of malig nancy and be misinterpreted as neoplastic cells. Distinguishing between neoplasia and a hyperplastic, meta plastic, or dysplastic tissue response can be difficult. If there is concern that an inflammatory or other process is associated with a neoplasm, biopsy and histologic evalua- tion may be indicated for a definitive diagnosis Neoplasia In cytologic preparations, neoplasia may be recognized when there are cells present that do not have normal char acteristics expected for the tissue or are clearly out of place (eg, metastatic toa locaton, such as lymph node, liver, or spleen). Because neoplasins are clonal expansions of asin ele cll type, cells from a tumor appear similar and are often described as a uniform or monomorphic population, even though they may show marked morphologic atypia. atures of neoplastic cells vary with the cell of Cyrologi origin. In general, neoplastic cells are larger, more pleomor- riable N:C ratio when phic, and have a higher and wore ‘compared to normal cells from the same tisaue. Some neo: plasms may be associated with an inflammatory response complicating interpretation of the cytologic specimen. Benign neoplasms tend to yield cells that are uniform in size and appearance, and cells appear to be at the sam: stage of differentiation. Nuclei have a similar chromatin pattern, and nucleoli usually are small and regular in out- line and number. Frequently, the variation in N:C ratio is minimal, It is often necessary to use histology to distinguish between a benign tumor and hyperplasia. In malignant neoplasms, cells appear more pleomorphic and less well differentiated (Figure 5.8). There is moderate to marked variation in cell size (anisocytosis) and in nuclear size (anisokaryosis). While the N:C ratio tends to increase with malignancy, marked variability in NiC ratio from cell to cell may occur in a given specimen. In some ceases malignant cells may appear to be at different stages of Balaton Purina Company Interpretation of nd Feline Colony Inthe center isa Figure 3.5. Tachoal wash ram a dog. The large multinucleated giant cel. (Weights sain; 1000X) Figure 3.6, Sheet of hyprplatc prosaic epltalial cls trom 2 dog with benign prostatic hyperplasia, The Nato uniform, albeit somewhat eater than normal n ad laste base eticolaed chromatin, but ote resemt aie hyperplasia typically ‘occurs secondary to inflammation or 2 hormonal imbalance in oder dogs. Figure 8.7. Squamous metaplasia of pr have an enlrged,lttaned appearance instead ofthe normal tl tahoidl appearance. Tis change may occas ' response to hormonal stimulation, such as estrogen secretion from a Sertoli cel tumor, o in response to inflammation (Wrights stain; 400K) 18carcinoma from 3 dog. These cells display cluding ine chromatin, different jon, and there may be asynchrony in nuclear and eytoplasmie maturation Naclear features are of primary importance in assessing malignancy. Those suggestive of malignancy include anisokaryosis; macromuclei; mulrinucleation with abnormal nucle; nuclear molding: finely dispersed or coarsely clumped chromatin; «thickened, angular, or indented tauclear membrane; nucleoli that are large, multiple in num ber, or irregularly shaped: and abnormal mitotic figures. Cytoplasmic fearsres suggestive of malignancy include increased basophilia, abnormal vacuoles of granules, and Phagocytosis of other cells CRITERIA FOR ASSESSING MALIGNANCY Nuclear features Anisokaryosis “Macromuclei Muhinncleation Nuclear molding Finely dispersed or coarsely clumped chromatin ‘Vhickened, angular or indented nuclear membrane Large, multiple, or ieegularly shaped nucleoh Abnormal mitotic figures Cytoplasmic features Increased basophilia Abnormal vacuoles or granules Cyrophagia Epithelial neoplasms Neoplastic epithelial cells tend to exfoliate readily in clusters and sheets of round to polygonal cells. The cell borders usually are well defined, although some types of neoplastic epithelium tend to lose their cytoplasm as an artifact of preparation. This loss results in clusters of bare nuclei stripped of their eytoplasm (eg, basal cell tumors oF thyroid rumors). Cells from benign epithelial tumors oF adenomas are uniform in appearance and may appear rela rast, cell from malignant epithelial neoplasms or carcinomas can be cly well differentiated (Figure 5.9). in eos snarkedly pleomorphic Adenocarcinomas, originating from glandular epithelial cells, may form patterns reminiscent of ascinar or ductular structures, Their eytoplasm often is deeply basophilic and may be vacuolated or distended, suggesting production of a secretory product (Figure 5.10), In contrast cells obtained from a squamous cell carcinoma are more individualized (Gee Figure 6.16), nave deeply basophilic cytoplasm, and may show varying degrees of keratinization. Cells derived from carcinomas of the urcendothelium (transitional cell ¢ mas) usually are very pleomorphic and may exfoliate as clusters of as individual cells (Figure 3.11). Multinucleation and nuclear molding are common. Cytoplasmic basophilia 4s variable. Often, individual large cells with abundant cytoplasm are interspersed within clusters of cells with higher N:C ratios. neoplasm, have sma nutes wth condensed chromatin and abundant, foamy cytoplasm, Cytoplasmic bord form clstes. These celts are wet diferent etoloicaly to eistngush dit snot possible c90us gland hyperplasia trom HARA A HRAAARANRANRANRANANAAAAN A= a Mesenchymal neoplasms Neoplastic mesenchymal cells generally do not exfoliate well when sampled by aspiration or impression. It may be necessary to scrape the sample to obtain cells For evalua- tion. Mesenchymal cells usually are individualized and may be clongated to spindle-shaped (Figure 5.12). Nuclei are ‘oval to iegular in shape, and the eytoplasm may vary in degree of basophilia. Depending on cell lineage, extracellue lar matrix may be observed (eg, osteoid with osteosarco- ‘as). Malignant mesenchymal neoplasms are called sarco- ‘mas and can be very pleomorphic in appearance. Ralston Purina Company’ Interpretation of Cann Feline Cytology Round cell tumors Several neoplasms involving skin and subcutaneous tissue can be definitively diagnosed with confidence tsing cytology. These neoplasms are referred to as round cell tumors or discrete cell tumors because of their char- acteristic appearance both cytologically and histological- ly. Round cell tumors inchide mast cell tumor, lyme phoma, plasmacytoma, histiocytoma, and transmissible venereal tumor. Microscopically, cells from these tumors are round and have well defined cytoplasmic margins (Figure 3.13). These cells do not have cell-to-cell attach ments and, therefore, appear as separate or discrete cells pale but to moderately basophil (Wrights stain; 1000) 7Most round cell ROUND CELL TUMORS: ‘Mast cell tumor tumors exfoliate welll -when sampled by fine needle aspiration or tenn impression, and many Feemeeces have characteristic Histiocytoma cytologic Teatures that Reaersielple wcncweal are useful in making a Siac definitive diagnosis. Hemorrhage Versus Biood Contamination Ieis important t0 recognize when hemorshage h occurred into body cavities, joint spaces, or other tissues, ‘Many tissues (eg, liver and spleen), as well as many neo- plasms, are highly vascular. As a result, samples from these sites may have significant blood contamination, where ‘ood is introduced during the collection process. Ia these cases, blood in the sample is an artifac of obtaining the sample and does not reflect a pathologic process. Therefore itis important to try to distinguish cytologically between hemorrhage and blood contamination With fresh blood contamin ion, platelets ean be seen However, absence of platelets does not rule out blood cont amination because platelets may be lost prior to slide preparation as a result of clotting. With blood contamina: tion, the distribution of erythrocytes and leukocytes resem: bles that observed in peripheral blood Phagocytosis of erythrocytes by macrophages along with formation of hemosiderin (Figure 3.14) and/or hematoidin crystals (Pigare 5.15) secondary to erythro- eyte breakdown, indicates that hemorrhage has occurred within at least the past 24 hours. Fluids way take on an orange to yellow color (xanthochromia) as erythrocytes are metabolized and bilirubin is released. Interpret of erythrophagocytasis in Muids without evidence of ery- throcyte metabolism may be more problematic if slides are not prepared immediately following sampling, Macrophi phagocytize erythrocytes ex vivo, This is sometimes es may remain active within sample tubes and observed in fluid samples that have been shipped overnight to a reference lab. B Figure 3.14. Eryhvophagocytsis and homosierin within macrophages Indicate that hemorthage has ocurred. The macrophage othe let ‘ontains several erthroytes. The ble-black plgment In the cytoplasm of Figure 3.15. Hematoldin enstas are yellow-orange, hori shapes rystals tat result from the breakdown of hemoglobin. They may be seen in aspirate of tissues or lids in which hemorrhage has occured, (Wright's stain; 1000%) Its also necessary to determine whether leukocytes pre- sent in a cytology sample are derived from blood contami- nation or are part of an inflammatory response. The best approach is to compare cytologic observations of leukocyte umber and differential with the Findings obtained from « complete blood count (CBO). Ralston Purina Company’ IntrpuuUuUUUUUUS Chapter 4: Cytologic Appearance of Etiologic Agents Infectious agents that can be recognized by cytology Selected organisms in these categories are illustrated in include bacterial, fangal, and parasit BACTERIA ASSOCIATED WITH SKIN LESIONS Organiam Cytologic Appearance Schematic Actinomyess, Nocardia, Branching, filamentous “beaded” rods Fusobacterium spp (anaerobic) 0.2-1.0 jm x 2-6 jm; filaments 10-50 jim long aro (ensersbi) / ~ Dermatiphilus congolensis Branching filaments of paired rows of cocci st Resembles “stackedlcains” (aerable, stem facultative anaerobe) Ei “ Clastridia spp. Large rods; 0.3-2.0 im x. Mycobacterium spp Clear rods stain red with acid- fast stains Usually intracellular (aerobic) 0.2.07 pm x 1-10 pm Simonsielta organises Large rods positioned side by side \ Dark blue ot purple t vf ae e Often adhere to squamous epithelial cells 0.6-1.0 pm x 0.5-3 pm rods, occurring in stack 10-50 jm long xs mn wa Staphylococcus spp Clusters of 4-12 purple cocci (aerobic) 0.51.5 pm Siapleeatas wp ‘Chains of purple cocei (aerobic) ot Oisu crt Figure 4.1, Selected bacteria that canbe esociated with skin lesions. (Holt J, Krieg NR, Sneath PHA, Staley JT, wiiams ST. Bergey's Manva of ‘Determinative Bacteriology, Mint Eston. Baltimore, Md: Willams & Wikies, 1984. station by Tim VoL.) Ralston Purina Company’ Inorretation of Canto 20 Feline Cytlogy 19= FUNG! ASSOCIATED WITH SKIN LESIONS Organiom Cytologic Appearance Schematic ‘Blatomyoni deraiide Rov hive rot ling 20m in diameter e beeen Coes Bas Round spherules that may contain endospores 10-100 jm (epherules) 2-5 ym (endospores) Blue or clea, double-contoured spherules Crypto neoformans Round (ypical) to fusiform yeasts 4-40 pm in diameter depending on capsule Pinle to bluish-purple with thick nonstaining capsule (oocasionally e nonencapeslated) Hatoplasna capoatatum Round to oval yeasts 24 ym in diameter « Pale to medium blue with halo around yeast 20 Eccentric pink or purple nucleus ‘alawcezia organisms Oval or club-shaped yeasts 2.4 ym in diameter Deeply basophilic “Mieowporam, ‘Miycelia and arthrospores within hair shais Trichophyton sp ‘Medium to dark blue with thin, clear halo ‘Spool scent Round, oval, or fusiform (Gigarshaped) yeasts S 3-10 yma long, 1-5 pin wide S Pale to medium blue, pink, or purple nucleus Figure 4.2. Fungl that canbe assoc ated wit skin lesions, Ilusration by Tim Voj.) SELECTED PARASITES ASSOCIATED WITH RESPIRATORY DISEASE Organism Speeiea Cytologic Appearance ‘Aleurasirngyis abana Cota Tir-tage larvae Sabapel tal 560 ym long Capillara seropilia Cats acl dogs ‘Double-operculated, oval eggs Asymmetrical terminal plugs 70 jm long, $5 pm wide Crean valpr Filo bith Dogs Biuntly conieal anterior end Finely tapered posterior end with slight bend 246-508 pm long Doss Tarvae with kinked al 240-390 ym long Found in lang ‘Oolerasalert Peres ole’ Doge Tarvae with Kinked tal 240-390 jm long Found in trachea ‘Paragon Belt Cats and dogs Operculated, ovoid eggs Appear golden 75-120 ym long, 45.65 pm wide Figure 43. Selected parasites that an be associated with respiratory disease, (Iustation by Tim Vol.) 20 Purina Company Interpretation of Canine and Feline CytologyFite 44. Aspirate of a lung mass from aca. The large, hickwale ely basophil yeast Inthe centr af Blatomyces cormatiis. Br base budding typical of this organism is evident. The organism has elicited ulomatous inflammatory response (Wright's stain; 1000X) Figure 45, The spherule af Coccdfoldes imi arge and may ain sy basophil I fs necessary to focus up and dawn to observ the ndospores, a5 lustated. (Wright's stain; 8, Asprate ofa perorital mass rom a dog The extraelular, fungal organisms witha large, clear, prominent capsule are ‘Cyptococcus neoformans. Variation of the yeast and eapsule size results in a gleomarphie appearance. Narrow-based buds are ‘organisms, Nthough neoformans elisa pyogranulomatous Inflammatory response, aspirates the exians often resi in numerous (Weighs tan, 100K) Figure 4.7. Tracheal wash rom a cat. Many Histoplasma capsutatum rganisms are sen within a macrophage. This yeast body witha basophilic contr ang lighter halo, While usually ar within macrophages, iis also commen to see hem tree in the ckground asa resul of break (Wright's stain; 1000) cals ducing smear preparation, Figure 4,8. Ear swab fram 2 dog. The oval to lub-shaped(lootprit- shaped) yeasts onthe surtace ofthe Keratinize epthlil cells are ‘Malasseza spp. A neurotic inflammatory response i (Weights stain; 1000%) ‘Flgure 4.9, aspirate ofa draining skin lesion trom a dog. The ma ‘nthe centr contains thee oval to cigar shaped yeass, compatible with Sporairx schenchi These organisms induce a pyogranulomatous Tymphoeytes, and plasma cells ar seen in his photograph (Wright's stan; 1000%)Figure 4.10, Tracheal wash rom a cat with many first-stage larvae of Figure 4.11. The bronchoalveolar lavage from this dog contain a ‘Alearostrongylus sp. (wright stain; 40x) Paragonius sp 09g. (Wright's sain 400%) 2 Ralston Purine Company Interpretation of Canine and Fete ontologyRalston Purina Company’ Interpretation of Caine and Feline Cytology 23Chapter 5: Body Cavity Effusions and Synovial Fluid— CASE1 SIGNALMENT. Six-year-old male Doberman pinscher dog. CLINICAL FINDINGS: Progressive exercise intolerance and dyspnea. A thoracic effusion ‘was found on radiographs. CYTOLOGIC DESCRIPTION: Pleural Hid ‘Appearance Tighe na ber Specific gravity 1.020 Protein (e/dl) 3.0 Nucleated cells (cells) 4,800 ‘The majority of the cells are large mononuclear cells. ‘There are occasional reactive mesothelial cells (Figure 5.1), Occasional nondegenerate neutrophils and small, lymphocytes are also present. There a (Wright's ta three reactive mesothe 10008) Figure 5.1. Pleura ui trom a haracariste pink tplasm ytlony Case Studies Interpretation: Modified transudate Body cavity Mluids may be classified as transudates, transudates, or exudates, depending on the cellu- eth Part IV). These larity and protein content of the fluid ( le “Guideline to Distinguishing Transdates and Brudates classifications are usefiel when trying to understand how the Hluids are formed. Transudates are noninflammatory fluids that form when there is decreased fluid reabsorption or increased hydrosta tic pressure in capillaries or lymphatics. Transudates are low cellularity and may hharacterized by low p ‘occur with congestive heart failure, liver failure, oF any ei ology resulting in hypoproteinemia. In contrast, exudates are the result of inflammation and have high nucleated cell, counts and protein concentration A modified transudate is highly variable in cell count and protein concentration, It is a relatively nonspecific type of effusion that maybe associated with any condition cor event that increases vascular permeability, increases mphatic sys hydrostatic pressure of the vascular ot tems, or both. Examples include liver disease, heart failure, neoplasia, diaphragmatic hernia, and lung lobe torsion. A modified transudate may be a transition stage in the development of an exudate. In this case, the dog had congestive heart failure CLASSIFICATION OF BODY CAVITY FLUID Transudate Modified transudate Exudate witha 25Body Cavity Effusion Cases CASE 2 ‘SIGNALMENT: Two-year-old castrated male domestic longhair cat CLINICAL FINDINGS: Acute onset of dyspnea, lethargy, and fever CYTOLOGIC DESCRIPTION: Pleural fuid Appearance ‘Tan, cloudy. Specific gravity 1.050 Protein (g/l) 48 Nucleated cells (celisfply $5,000 Cellulavty is very high, and the predominant cell ype is a degenerate neutrophil. Many intracelfular and extracellular bacteria are present. These bacteria con- sist of a mixed population with an overabundance of filamentous forms (Figure 3.2). There are large, extra~ cellular clusters of filamentous bacteria (which grossly appear as “sulfa granules"), Figure 5.2. Peural lid from a ea with pytharex. The neutrophils appear de compatible with Actinomyces, Hacardia, 2 large clump o lamentous bacteria. These bacer ox Fusabacerim spp. (Wright stain; 10008) 26 INTERPRETATION: Septic suppurative exudate The high cell count and protein concentration are com- patible with an exudate, Presence of degenerate neutrophils typically accompanies bacterial infection: however, a culture is warranted for any neutrophilic exudate, even if the nev trophils do not show degenerative changes. The filamentous bbacteria observed in this ease likely are Actinomyces or Nocardia species. Both species are grant-positive organisms that require special culture conditions. Nocardia tend to be acid-fast. Fusobacterium are gram-negative bacteria that may’ have & similar filamentous appearance. This cat's pyothorax was probably the result of a bite or puncture wend. Ralston Purina Company’ Interpretation ot CanBody Cavity Effusion Cases INTERPRETATION: Chylous effusion (chylothorax) CASE 3 SIGNALMENT Tea-yearold re aa i sem th ie cv th ‘Siamese cat iymphatic obstruction or, rarely « rupture of the thoracie CLINICAL FINDINGS: Lethargy and dyspnea duct. This results in a fluid that may be milly white to pink CYTOLOGIC DESCRIPTION: Pleural fluid in color. Conditions associated with chylothorax inchide heart disease, neoplasia, trauma, lung lobe torsion, hear. proses iene worm disease, diaphragmatic hernia, and fungal granulo. a tt tration of chylomicrons, Specie grt Nie mas, Because of the high concentration of chy Protein (Al) 55 the triglyceride content of a chylous effusion is greater than Nucleated cells (cells/p!) 9,100 that observed in the serum, and the ratio of cholesterol to : des in the effusion is <1. Early on, the predomi ‘There are 70% lymphocytes, 24% neutrophils, and 6% nant cell type is the small lymphocyte, as seen in this case. large mononuclear cells (igure 5.4). Neutrophils appear nondegenerate. Lymphocytes are stall and ‘well differentiated. No etiologic agents were seen. However, with prolonged duration, the cytologic character: istics often become more in‘lammatory, with increased numbers of neutrophils and macrophages Figure 5.3. Pleural ud frm aca witk Figure 6.4. Pleural tu from a eat with ehylothora. The marty ofthe cal thylotora. This uid has the typical miky pink _Iymphocyes with occasional nondegenerate neutrophils. (Wright stan; 1000X), appearance of a ehylous Ralston Purina Company’ Interpretation of Canine and Feline Cytology a EUTVUuUICvIeIvvvuvuecvugcvwdd dsBody Cavity Effusion Cases CASE 4 SIGNALMENT: Two-year-old neutered male shorthair cat CLINICAL FINDINGS: Progressive abdominal distention CYTOLOGIC DESCRIPTION: Abdominal fluid Appearance Yellow, cloudy Specific gravity 1.045; Protein (g/dl) 68 Nacleated cells (cells!) 5,600 ‘There isa mixture of nondegenerate neutrophils and large mononuclear cells (Figure 5.3). The mononuclear cells have foamy cytoplasm and appear activated. Cytophagia can be seen. There is a pink granular background, which is compatible with the high protein concentration of the fluid. No etiologic agents were seen, Results of a protein electrophoresis of the abdominal fluid were compatible with increased globu- tins anc a polyclonal gammopathy (Figure 5.6). Figure 55. Abdominal ld rom a cat wit FIP. Neuropits appear rondepenerate, and tere are two large mononuclear cls. The hazy background i caused by the presence o precipitated protein. (Wrights ston; 1000X) 28 INTERPRETATION: Proteinaceous effusion, compatible with feline infectious peritonitis (FIP) FIP is caused by a coronavirus and is ofien difficult to diagnose. Typically, the Nid Trom a cat with FIP is yel low and may have fibrin strands. Criteria supporting a diagnosis of FIP include a rotal protein concentration soma globulin in abdominal or thoracic luid. The cellular pattern is nom trophils, large mononuclear cells, and lymphocytes, with (POR) tests for the FIP virus can be performed on the effusion to vccasional plasma cells, Polymerase chain react aid in diagnosis. Albumin Figure 5.6 Protein electrophoresis of abdominal tu frm the eat with FiP. The fobalins toll 72% ofthe protein and consist o 6% alpha, 13% a bata, 5% bea, The high concentration of globulins (>80% a the ttl) bulins (232%) Is compatible with x thagnasis of FP Ralston Purina Company’ Intrprettion o Canine and Feline CytologyUUTETUEUUEUe uuu 8 CASES SIGNALMENT: Foursyear-old spayed female mixed breed dog CLINICAL FINDINGS: Painful and swollen. abdomen after being hit by a ear CYTOLOGIC DESCRIPTION: Abdominal fluid erases core leh Specific gravity 1051 Protein (g/dl) 5.0 Nucleated cells (cells/al) 34,500 ‘There are 80% nondegenerate neutrophils, 18% large mononuclear cells, 1% lymphocytes, and 1% cosinophils. Macrophages contain variable amounts of golden-yellow to blue-green pigment. Yellow pigment aho is fre in the background (Figure 5.7). There are ‘moderate numbers of red blood cells present. Figure 5.7. Abdominal ul rom 2 dg wi mat 3, compatible with bile plymet. Yellow ble pg INTERPRETATION: Suppurative exudate with bile pigment, compatible with bile peritor A tear in the gallbladder or bile duct results in lesa of bile into the peritoneal cavity. Because bile is irrtatin it initiates an inflammatory response that may be new trophilic acutely, eventually becoming predominantly mononuclear. Bile pigment is ty ically yellow to green in color and amorphous. Bilirubin erystals may be seen in chronic cases. A chemically determined bilirubin concen. tration for the abdominal fluid will be in comparison to serum bilirubin, tones. The majority ofthe ells are neutrophils, The large mononuciar call (upper le) has phagocyized green t's als ree inthe Deckard. (Wright's stain; 1000) Ralston Purina Company’ Interpretation of Canine and Feline Cytology 29Body Cavity Effusion Cases SIGNALMENT. Ten-year-old female beagle dog CLINICAL FINDINGS: Progressive weight loss and lethargy. The dog has several mammary tumors. CYTOLOGIC DESCRIPTION: Pleural Hluid Appearance Orange, hazy Specific gravity 1.025 Protein (g/l) 35 Nucleated cells (eells/pl) 4,200 ‘The majority of the cells are large mononuclear cel swith moderate numbers of nondegenerate neutrophils ‘There are large clusters of pleomorphic cells that con- tain one to several nuclei with fine chromatin and mul- tiple nucleoli (Figure 5.8). There is marked anisokaryosis, and nuclear molding is observed. The NC ratio is variable. Cytoplasm is basophilic and appears distended with secretory product, These cells are compatible with an adenocarcinoma, INTERPRETATION: Neoplastic effusion, compatible with metastatic mammary adenocarcinoma Wentfication of neoplastic cells in an effusion depends con recognizing the presence of an abnormal cell type and the criteria for malignancy (vce Chapter 3). Neoplastic eff sions can be highly variable in appearance, ranging from a modified transudate to an exudate with marked inflamma- tion, In general, carcinomas and lymphomas are more likely foliate into cavity fluids. The absence of than sarcomas 1 neoplastic ces in an effusion does not rule out the possibil- ity of a tumor Ie is very important to recognize and not overinterpret reactive mesothelial cells (Figure 5. ‘malignancy, including va ‘multinucleasion, pronounced cytoplasmic basophilia, and frequent mitoses. In fact, there are no morphologic criteria that clearly distinguish between reactive mesothelial cells and cells derived from a malignant neoplasm. If a malig. nant neoplasm is suspected following cytology, its presence should be confirmed by histology. 30 Ralston Purina Company’ Interpretation of Canine and Feline CytlogySynoviat Fluid Cases CASE 7 SIGNALMENT Five-year-old spayed female golden retriever dog CLINICAL FINDINGS: Acute onset of polyarthritis CYTOLOGIC DESCRIPTION: Synovial fluid from the left stifle Appearance Red-orange, cloudy Specific gravity 1.052 Protein (wil) 53 Nucleated cells (cells) 15,200 Viscosity Watery -Mucin clot test Poor There are 90% nondegenerate neutrophils, 9% large ‘mononuclear cells, anit 1% Iymphoeytes (Figure 5.10) Arare LE. lupus erythematosus) cell is seen (Figure 5.11), The granular background appears decreased. No etiologic agents are apparent. When other joints are sampled, a similar cytologic pattern is observed. Ralston Purina Company Interpretation of Canine and Normal synovial fluid is clear and colorless, has high vis- cosity, low cell counts (<3,000/p), a protein concentration of about 3.0 g/dl, and does not clot (ce the table Guideline for Evaluation of Synovial Fluid, Part IV). The majority of cells are mononuclear cells with very few neutrophils. Hyaluronic acid content of the )ovial fluid is assessed by the mucin clot test. When synovial fluid from a normal joint is added 10 2.5% acetic acid at a ratio of 1:4, a solid clot forms (rated ‘good. When inlammation results ia degradation of the hyaluronic acid, the elot becomes more friable (rated “fae") or fails to form (rated “poor’). In general, as severity of inflammation ina joint increases, results ofthe mucin clot test are more likely to be fair to poor Neutrophilic iflamaation ia synovial uid usually ind cates infection or immune-mediated disease. The presence of nondegenerate neutrophils in synovial fluid does not pre clude the possibilty of bacterial infection, and a culture is recommended any time suppurative inflammation is observed. In this case, the presence of multiple affected joints and rare LE cells is compatible with an immane- mediated arthropathy. Further evaluation of this dog for systemic lupus erythematosus (SLE) is warranted, In coo: trast to immune-mediated polyarthritides, bacterial arthritis usually involves a single joint. Exceptions are cases of by tion, or polyarthritis secondary to septicemi disease (Borrelia burgdorferi infection), ehrlichial infec Figure 5.11, Synovial fd from a dog with SLE-asociated polarthis The cell in the center is nevtrophi that has phagocylzed the nucleus trom another cel. This isan LE (lupus erythematosus cell and, although mon evolegie finding, supports a dlagnosis ot immune-mediated Aisease, (Wright's stain; 1000X) FTnovial Fluid Cases CASE 8 SIGNALMENT. Ten-year-old male German pherd dog, CLINICAL FENDINGS: Chronic, progressive lameness involving the shoulder joints CYTOLOGIC DESCRIPTION: Synovial uid from the right shoulder joine Appearance Colorless, hazy Specific gravity 3.929 Protein (g/dl) 45 Nacleated cells (cellsl) 5,700 Viscosity Stringy Mucin clot test Good. Caellularity is moderately increased, and the cells line up in rows (windrowing), suggesting thar the Si has relatively high viscosity. The majority of the cells are large mononuclear cells (Fignre 5.12). A few lympho- ‘ytes and rare nondegenerate neutrophils are seen There are scattered red blood cells. No etiologic agents were seen. There is a dense granular background. Figure 6.12. Synovial Mula by the presence of predominanty mononuclear eels. Woe the INTERPRETATION: Nonsuppurative inflammation, compatible with degenerative joint disease Inflammation characterized by predominantly large mononuclear cells may aecur with degenerative joint dis. ease oF trauma. The cellularity and relative proportion of cell types (neutrophils versus mononuclear cells) depends oon the stage of the disease. Recent trauma results in more ‘neutrophils and red blood cells, and erythrophagocytosis may be observed. As the injury resolves, the relative pro- portion of large mononuclear cells increases and the overall number of cells decreases. With degenerative joint disease, acute flare-ups may be associated with higher cell counts and an increased perc ntage of neutrophils With degenerative arthropathy, the synovial fluid is usu- ally colorless, Viscosity is normal to mildly decreased. The results of the mucin clot test are often normal, but way vary to fair of poor in some cases. Ralston Purina Company Intrpratatian of Canin a AARHARAHKRANATAHRNHAADANRADRARAB A