In the realm of veterinary medicine, accurate diagnosis is paramount. For English speakers seeking to understand medical terminology, especially when encountering terms in different languages, it’s helpful to start with the basics. If you’re wondering “Diagnosis Means In Hindi,” the Hindi word for diagnosis is निदान (nidaan). Essentially, whether in English, Hindi, or any language, diagnosis refers to the process of identifying the nature of a disease or condition by careful examination of the symptoms and signs.
In veterinary practice, particularly in fields like cytology, diagnosis becomes incredibly detailed and nuanced. Cytology, the study of cells, plays a crucial role in identifying various conditions, including inflammations and tumors, in animals. This article, drawing upon expert insights in veterinary diagnostics, delves into the cytological aspects of diagnosis, focusing on inflammations and tumor classifications, while keeping the concept of “diagnosis means in hindi” in mind as the fundamental goal of this detailed analysis.
Understanding Inflammation Through Cytology
Inflammation, a common condition encountered in veterinary medicine, is often categorized based on the predominant cell type present at the site of inflammation. Cytological examination of samples from inflamed areas allows for this categorization, helping to pinpoint the underlying cause and guide treatment strategies.
Types of Inflammation Based on Cell Population
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Neutrophilic Inflammation: Characterized by a high proportion (at least 80%) of neutrophils, a type of white blood cell. This type of inflammation is frequently observed in acute conditions and bacterial infections. The severity of cellular degeneration within neutrophilic inflammation often depends on the toxicity of the inflammatory process. Notably, in purely pneumonic inflammations, degeneration may be less pronounced. Neutrophils are attracted to the site of inflammation in the pleural cavity even without the presence of microorganisms.
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Macrophagocytic Inflammation: Defined by a dominance of macrophages (at least 50%). Macrophages, another type of immune cell, are typically associated with chronic and less toxic inflammations. Their presence is a hallmark of areas with cellular necrosis or persistent microbial infections. Conditions like mycoses, mycobacterioses, and feline infectious peritonitis (FIP) are often characterized by macrophagocytic inflammation.
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Neutrophilic-Macrophagocytic Inflammation: This category represents a mixed inflammatory response, falling between purely neutrophilic and macrophagocytic types.
Interestingly, even relatively non-toxic agents like fats in chylothorax (a condition where lymphatic fluid leaks into the chest cavity) can trigger an inflammatory response, attracting both macrophages and neutrophils. These cells can then engulf chylomicrons, the fat globules present in chyle.
In the context of Feline Infectious Peritonitis, cytological examination typically reveals a picture of macrophagocytic or neutrophilic-macrophagocytic inflammation. Samples obtained through puncture often show a mixture of macrophages, neutrophils, lymphocytes, and plasma cells. The overall cellularity can vary considerably, ranging from 300 to 1200 nucleated cells per microliter [19].
Preparing Cytology Smears for Diagnosis
To prepare samples for cytological examination, smears are made by applying the sample directly onto slides or using a brush moistened with physiological serum. These smears must then be fixed to preserve cell structure. Fixation can be achieved through air-drying or by immersing wet slides in fixative fluids. A common fixative is 95% ethyl alcohol, or a mixture of polyethylene glycol and ethyl alcohol, particularly when Papanicolaou staining is intended. However, other fixatives can be used depending on the specific staining techniques or histochemical reactions required for research or diagnostic purposes.
Common staining methods include May-Grünwald-Giemsa and Papanicolaou stains, as well as Romanowsky and Wright stains. Polychrome blue is also a rapid staining method that has proven effective. In specific cases, the Periodic acid–Schiff (PAS) reaction and alcian blue staining may be recommended to highlight particular cellular components.
Ultimately, cytological and histopathological examinations are crucial diagnostic tools. While a definitive diagnosis (निदान – nidaan) isn’t always attainable in every case, these examinations provide vital information for prognosis and developing appropriate therapeutic strategies for individual patients.
Cytological Criteria for Neoplasia Diagnosis
The initial step in any diagnostic procedure is to identify a pathological condition. Once a condition is established, the next step is to determine its nature – whether it’s cancerous, inflammatory, or another type of pathology. Finally, the goal is to arrive at a definitive diagnosis (निदान – nidaan). Achieving a positive diagnosis often requires correlating cytological findings with clinical observations and other laboratory investigations.
In the specific context of neoplasia (tumor formation), cytological examination focuses on specific cellular criteria to identify a neoplastic process [15]. These criteria involve assessing various aspects of the cells:
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Cytoplasm: Features such as basophilia (degree of blue staining), presence of vacuoles (empty spaces) or a foamy appearance, density, irregular shape, and size are evaluated.
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Nucleus: Nuclear characteristics examined include size, and whether its appearance is homogeneous (uniform) or reticular (net-like).
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Mitoses: The presence and frequency of mitoses (cell division) are noted, categorized as absent, rare, moderate, or numerous.
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Nucleoli: The size, prominence, number (single or multiple), and shape (regular or irregular) of nucleoli (structures within the nucleus) are assessed.
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Nucleocytoplasmic Ratio: The ratio of the nucleus size to the cytoplasm size is considered, which is typically high in neoplastic cells.
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Cell Size: Neoplastic cells are often larger than normal cells.
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Cell Number: The number of cells present in the sample can be indicative. High cell numbers are frequently seen in carcinomas and tumors with distinct cells, and sometimes in sarcomas.
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Intercellular Relationships: How cells relate to each other is observed, looking for indistinct borders (common in carcinomas), nuclear disaggregate agglomerates (clumps of nuclei), and subaggregates or acini-like structures (gland-like arrangements).
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Cell Activity: Evidence of cellular product elaboration (secretion) is noted.
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Cell Position: Aberrant (abnormal) cell positioning can be a clue.
Cytological examination also aims to determine if cells are actively proliferating and if undifferentiated or poorly differentiated cells are present. These undifferentiated cells, such as hematopoietic tissue blastocytes, share certain characteristics: basophilic cytoplasm, large nuclei with smooth or finely reticular chromatin, a high nucleocytoplasmic ratio favoring the nucleus, and distinct nucleoli. However, it’s crucial to recognize that these features alone are not definitive for neoplasia, as they can also be seen in normal proliferating tissues [14].
Differentiating Neoplastic from Non-Neoplastic Changes
The key distinction between non-neoplastic and neoplastic changes lies in the nature of cell proliferation. Normal proliferation follows a continuous differentiation pathway, dependent on the tissue type. In contrast, neoplastic proliferation exhibits minimal differentiation, and neoplastic cells are almost always pleomorphic, meaning they show variability in size and staining. Their nuclei are also polymorphic in size, shape, and staining. Neoplastic cells may have multiple nuclei, very large nucleoli, and irregular shapes.
Carcinomas and discrete tumors often yield numerous cells in smears, while sarcomas, obtained by aspiration, may produce inconsistent and sometimes insufficient cell numbers for diagnosis (निदान – nidaan). However, if a sarcoma scrape is available, the resulting smear can be diagnostic.
A significant indicator of malignancy is the presence of immature, pleomorphic cells in an abnormal location or tissue, which can also signal metastasis (spread of cancer).
Cytologically, malignant tumors can be broadly classified into three types based on tissue origin: discrete cell tumors, carcinomas, and sarcomas.
Types of Malignant Tumors Identified Cytologically
1. Discrete Cell Tumors
Discrete (hidden) cell tumors are characterized by cells that function relatively independently and can be found as individual cells within foreign tissues. This category includes:
- Malignant Leukocytes: Leukemias involving malignant white blood cells.
- Mastocytomas: Tumors of mast cells, a type of immune cell found in tissues.
- Melanomas: Tumors of melanocytes, pigment-producing cells.
- Venereal Round Cell Sarcomas in Dogs (Transmissible Venereal Tumor – TVT): Sexually transmitted tumors in dogs.
These tumor types are typically easy to identify in smears from aspirated material or impression smears. Each type has distinct cellular characteristics that allow for a positive diagnosis (निदान – nidaan).
2. Carcinomas
Carcinomas are characterized by a high number of poorly delimited cells grouped in large clusters. In adenocarcinomas (carcinomas of glandular origin), intercellular connections may be visible as ductal or acinar arrangements in smears. Adenocarcinoma cells may sometimes contain large vacuoles or clear granular structures indicative of secretory products.
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Squamous Cell Carcinoma: Commonly found in the skin, conjunctiva (in cattle), ear (in cats), and mucous membranes. Squamous tumor cells are large with a low nucleoplasmic ratio. In smears, cells are usually isolated or in small clusters. They are recognizable by their large size, intensely chromatic nuclei (some pyknotic – shrunken and dense), and moderately basophilic cytoplasm. It’s important to differentiate these from hyperplastic squamous cells in ulcerative lesions, which can appear similar. The presence of squamous cells in unusual locations, like lymph nodes or peritoneal fluid (e.g., in stomach squamous cell carcinoma in horses), strongly suggests a carcinoma diagnosis (निदान – nidaan).
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Uroepithelial Neoplasms: Can occur anywhere in the urinary tract, frequently in the urinary bladder. In smears of urinary sediment, exfoliated cells appear singly or in pleomorphic cell clumps. Cells exhibit significant size variation with well-defined nuclei and distinct, irregular nucleoli. The cytoplasm is moderate to abundant and moderately basophilic. While urinary epithelium can undergo squamous metaplasia (transformation into squamous cells), diagnosing a neoplasm is usually not difficult, though pinpointing the exact location might be challenging.
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Adenocarcinomas: Can arise from various glands, including mammary, pancreatic, gastric, salivary, and prostatic glands. Smears from aspirated material are typically cell-rich. Cells often appear in large clusters, sometimes with ductal or acinar arrangements, with nuclei at the periphery and cytoplasm oriented towards the center of the cluster. Cells are poorly delimited, highly pleomorphic, and intensely basophilic. Cytoplasmic vacuoles are common in gastric and pancreatic adenocarcinomas, and foamy cells may be seen. Signet ring cells, characterized by a large vacuole pushing the nucleus to the periphery, may also be present. Adenocarcinoma nuclei are generally polymorphic with considerable variation in size and staining, and they may have homogeneous or reticular karyoplasm. Single or multiple prominent nucleoli and mitoses may be observed. Thyroid and perianal gland carcinomas can be more challenging to diagnose cytologically from aspiration smears.
3. Sarcomas
Sarcomas, originating from mesenchymal cells (connective tissue cells), often yield few individual, fusiform (spindle-shaped) cells in smears. Therefore, tumor scraping is often preferred to obtain cell-rich smears. Free nuclei and multinucleated cells with prominent, large nucleoli are frequently observed. The cytoplasm is moderately basophilic and may be vacuolated. Diagnosing sarcomas can be difficult due to similarities with granulation tissue, which contains non-pleomorphic hyperplastic fibroblasts and inflammatory cells like neutrophils, macrophages, and mast cells.
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Hemangiopericytoma: Cytologically similar to fibrosarcoma but cells are smaller, conical, and often grouped in small clusters (5–10 cells) with individual cells predominating.
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Leiomyosarcoma and Rhabdomyosarcoma: Cytologically resemble fibrosarcomas, with individual, fusiform cells, moderately basophilic cytoplasm, and a moderate to high nucleocytoplasmic ratio. Multinucleated cells and large nucleoli may occasionally be present.
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Chondrosarcoma and Osteosarcoma: Cytologically, these tumors have round to slightly fusiform cells, most showing a slightly conical cytoplasm. Amorphous azurophilic material (staining blue with azure dyes) is often found intercellularly. The cytoplasm is moderately basophilic, and the nucleoplasmic ratio ranges from moderate to high. Nuclei are eccentric, and cells with 2–4 nuclei are less common.
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Hemangiosarcomas: Cytologically, these tumors are intensely hemorrhagic, containing fusiform cells with basophilic, foamy, or vacuolated cytoplasm. The nucleoplasmic ratio is moderate, nuclei are vesicular with prominent nucleoli, and the cytoplasm is basophilic, moderate to rich, and foamy or vacuolated.
Cytology of Cancer Effusions
Cytological examination of cancer effusions (fluid accumulations in body cavities) serves as a complementary diagnostic tool. It is particularly valuable when there’s suspicion of:
- Mediastinal lymphoma in felines.
- Effusion in patients with mammary or ovarian neoplasms, known for their high metastatic potential.
- Unexplained cavitary effusions, such as asymptomatic pleural effusions.
- Routine examination of any effusions [6].
Fluid sampling for cytology requires strict adherence to protocols, including sterile conditions, avoiding anesthesia if possible, and using appropriate needles and collection tubes (EDTA and dry tubes).
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Pericardial Effusions (fluid around the heart): Harvested with the animal in left lateral recumbitus or standing, via right-side puncture in the 3rd-5th intercostal space, lower to middle third. Ultrasonographic guidance and sometimes anesthesia may be necessary [9,13].
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Pleural Effusions (fluid in the chest cavity): Harvested with the animal standing, on either side, in the 6th-7th intercostal space, lower to middle third.
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Abdominal Effusions (fluid in the abdominal cavity): Harvested with the animal in lateral recumbitus, on the midline, 2 cm behind the umbilicus.
Fluid samples should be processed for smears as soon as possible without preservatives, though they can be stored at 4°C for up to 24 hours without significant cellular changes. Centrifugation can concentrate cells but may disrupt their natural connections. Fixatives like 50° ethyl alcohol or polyethylene glycol fixatives can be added to preserve cell relationships.
Smears should be air-dried immediately to prevent cellular artifacts. For Papanicolaou staining, wet fixation in 95% ethyl alcohol or polyethylene glycol-ethyl alcohol fixatives is recommended. Diagnostic labs commonly use May-Grünwald-Giemsa as a basic stain and Papanicolaou staining for preserved fluids. Polychrome blue and tannic acid staining are also effective routine methods, supplemented by PAS reaction and alcian blue staining when needed.
For accurate diagnosis (निदान – nidaan), cytologists need clinical history, paraclinical investigation results, and the suspected clinical diagnosis. Macroscopic fluid appearance (e.g., serohemorrhagic, hemorrhagic, clear, unclear) is also evaluated.
Fluid smears may contain three main cell categories:
- Cells derived from serous membranes (mesothelium), i.e., mesothelial cells.
- Normal local cells or blood-derived cells (polynucleated cells, lymphocytes, monocytes, histiocytes, mast cells, plasmacytes).
- Malignant cells, most significant for metastasis and rarely for primary tumors, except for mesothelioma [3].
Effusions associated with malignant tumors arise primarily through two mechanisms:
- Serosal Invasion:
- Implantation metastasis (e.g., ovarian or mammary carcinoma) leading to massive shedding of malignant cells into the effusion fluid.
- Contiguous growth of serous tumors, with variable numbers of tumor cells in body cavities.
- Secondary Circulatory or Inflammatory Disorders: Transudates (fluid leakage) related to bleeding, mesothelial hyperplasia, or submesothelial lymphangitis may occur without malignant cells in the effusion, resulting in a negative cytological diagnosis (निदान – nidaan) [5].
A positive cytological result confirms cancer, but a negative result does not rule it out.
Smear examination focuses on: differentiating cell types (requiring detailed morphological knowledge); assessing cell populations in the context of lesion development; and analyzing suspected malignant elements. Interpretation integrates these observations with clinical data.
Mesothelioma and Mesothelial Cells in Effusions
Mesothelioma, a malignant tumor of mesothelial cells, forms a single-layered pavement-like structure on a basement membrane, overlying a connective-elastic and vascular layer. In hyperplastic mesothelioma, mesoepithelial cells proliferate, becoming globular and shedding as isolated cells or cell islands. In cavity fluid, mesothelial cells may become macerated and can proliferate, showing mitoses.
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Basophilic Mesothelial Cells: Early, slightly altered desquamated mesothelial cells, common in effusions, occurring singly or in islands. They are round to oval, with clear outlines, central or slightly eccentric nuclei (15–40 μm diameter), highly basophilic cytoplasm with fine granules and peripheral microvilli, and indistinct cell borders with an acidophilic halo. Nuclei are dense, and nucleoli are hard to see. Mitoses, binucleated cells, and rare syncytial-appearing polynuclear cells may be present.
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Degenerated Mesothelial Cells: Result from basophilic mesothelial cell transformation during inflammatory processes, leading to polymorphic morphology. Nuclei may be folded or indented, chromatin dispersed, and cytoplasm contains granules and vacuoles (phagosomes). These macrophagic cells are categorized into:
- Basophilic macrophagic mesothelial cells: round or kidney-shaped nuclei, poorly vacuolated bluish cytoplasm.
- Vacuolized (microvacuolar) macrophagic mesothelial cells: large, irregular outline, bluish or gray cytoplasm with many vacuoles, resembling histiocytes.
- Macrovacuolar signet ring cells: large, cytoplasm contains large, optically clear vacuoles pushing the nucleus to the periphery [1, 7, 8].
Other Cells in Inflammatory Effusions
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Polynuclear Cells (Neutrophils): Abundant in inflammatory effusions. Degenerative changes indicate purulent effusions.
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Monocytes and Macrophages (Histiomonocytes): Arise from blood monocytes or submesothelial connective tissue histiocytes. They are large with irregular nuclei compared to mesothelial cells, bluish-pale or gray, vacuolated cytoplasm with irregular outlines. They may contain phagocytosed particles (erythrocytes, degenerated leukocytes, bacteria, pigments).
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Lymphocytes and Plasmacytes: Present with polynuclear cells and macrophages in inflammatory and tubercular effusions, and lymphomas, showing malignant transformation-related nucleo-cytoplasmic anomalies.
General Cytological Criteria of Malignancy in Effusions
Accurate cytological diagnosis (निदान – nidaan) can be challenging due to overlapping features between irritant reactions and malignant lesions, and the lack of consistently reliable criteria. However, key features can aid in identification:
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Abnormal Monomorphism: Cancerous cell populations often show an abnormal uniformity against the smear’s polymorphic background, with anisocytosis (variation in cell size) and anisokaryosis (variation in nuclear size), suggesting a single, anarchically evolving cell line.
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Tendency to Form Large Cell Plaques and 3D “Bullas” (Clusters): Malignant cells often clump together in large groups.
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Numerous, Often Aberrant Mitoses: Increased and abnormal cell division figures are common.
Progressive cellular characteristics include nuclear abnormalities and cell/cytoplasmic changes.
Nuclear Characteristics:
- High nucleoplasmic ratio.
- Variable shape.
- Aberrant configuration.
- Massive peripheral chromatin distribution.
- Prominent nucleoli of variable sizes, sometimes “nuclei within nuclei”.
Cell and Cytoplasmic Changes:
- Global increase in cell size, sometimes giant cells.
- Less specific cytoplasmic changes: exaggerated basophilia, vacuolization (signet ring cells), atypical granules.
Distinguishing malignant cells from transformed mesothelial cells is a major challenge.
Diagnostic Challenges and Tumor-Specific Effusions
Cytological diagnosis (निदान – nidaan) in effusions presents varying degrees of difficulty: some cases are straightforward, some effusion-causing cancers are often negative in smears, and borderline cases are most challenging.
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Lymphoma with Mediastinal Location: Most common and well-recognized, characterized by large cells, nuclei with sparse chromatin, and basophilic cytoplasm. Lymphoid cells in effusions degrade rapidly, complicating diagnosis.
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Myeloid Leukemias: Rarely present as localized myelomas, but effusions may occur, containing granulocytic cells with malignant elements and numerous eosinophilic polynuclear cells.
Common Effusion-Generating Tumors in Carnivores:
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Ovarian and Mammary Carcinomas: Cause abdominal and thoracic effusions characterized by massive desquamation, large cell plaques or ballooning cells, vacuolated cytoplasm with ring cell formation, and PAS or alcian blue positive intracytoplasmic secretion.
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Digestive Tract and Adnexal Gland Carcinomas: Cause abdominal effusions, often with few diagnostic cells, making positive diagnosis challenging.
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Primitive Lung Adenocarcinomas: Rarer in carnivores, but a major cause of pleural effusions with significant, cytologically positive desquamation.
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Hemangiosarcomas: Frequently cause hemorrhagic effusions with cavitary bleeding. Desquamated tumor cells may be found in the blood mass, but cytological diagnosis (निदान – nidaan) is less frequently used.
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Mesotheliomas: Under-reported and less understood in carnivores, but diagnostically challenging. Mesothelioma and its shed cells lie in a gray area between atypical hyperplasia and malignancy, making definitive cytological diagnosis difficult.
Other tumors that can cause effusions with variable cell content include seminomas, osteosarcomas, thymomas, and malignant fibrous histiocytomas.
Cytological examination of cavitary effusions can yield results categorized as:
- Negative: No abnormal cells detected.
- Suspect: Cells with poorly defined characteristics among normal cells.
- Positive: Presence of cells with malignant characteristics [6].
In conclusion, cytological examination of cavitary effusions is a rapid and readily available tool that provides valuable information to clinicians, aiding in the diagnosis (निदान – nidaan) and management of various conditions in veterinary patients. Understanding “diagnosis means in hindi” as निदान (nidaan) reinforces the universal importance of accurate disease identification in healthcare, regardless of the language used to describe the process.
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