Diagnostic Cytology of Cancer Cases Somporn Techangamsuwan Companion Animal Cancer Research Unit (CAC-RU) Department of Pathology, Faculty of Veterinary Science, Chulalongkorn University 1
Tumor or Non-tumor 1 2 3 2
Tumor cells? Inflammatory cells? Infectious agents? Fluid? 3
Cytology >>> Fastest! Some tumors are diagnosed by cytology better than biopsy, eg.; round cell tumor. Is that final conclusion? 4
Tumor cell interpretation Step-by-Step 5
At First Glance on Slide 1. Significant tumor cells: presence or absence (fluid, blood) >> DIY: Prepare 2-3 slides 2. Size and shape of tumor cell >> Easy way to compare tumor size 3. Cellular arrangement >> clump, sheet, glandular, individual 4. Nuclei and cytoplasm of tumor cell >> criteria of malignancy >> intracytoplasmic granules (black, metachromatic) 5. Extracellular matrix (keratin, mucin, osteoid), Foreign bodies, Pathogen 6
Interpretation: First Step Approach Which cell type?? Inflammatory cells Differentiate cell type Inflammatory cells + Tissue cells - Differentiate cell type - History taking Tissue cells Differentiate cell type and origin Neutrophils>85% = suppurative (pus) Neutrophils, Macrophages, pus cells = pyogranulomatous Macropahges, Lymphocytes, fibroblasts, plasma cells, low neutrophils = granulomatous Many Eosinophils >10% = eosinophilic plaques (granuloma) or allergic reaction Epithelium Mesenchymal Round cell Mixed, pleomorphic >> difficult for diagnosis Most malignant tumor 7
3 basic tumor cell types Epithelial Size Shape Cellularity Cluster Large Round to Usually high Yes caudate Mesenchymal Small to Spindle to Usually low No medium stellate Discrete round cell Mast cell Lymphoma Small to Round Usually high No medium TVT Histocytoma 8
General criteria Criteria of Malignancy Pleomorphism Multinucleation Anisocytosis Normal Abnormal Abnormal mitosis Macrocytosis Coarse chromatin Increase cell no. Hypercellularity Nuclear molding Nuclear criteria Anisokaryosis RBC Anisonucleosis Macrokaryosis & Increased N:C ratio Angular nucleoli 9
Cell Arrangement Cellular Arrangement VG Single,solitary Basal cell Chain, row Hepatoid cell Sheet Mesothelial cell Cluster Fibrosarcoma MG adenocarcinoma Glandular Clump Mal. histiocytosis 10
Anisocytosis Cellular morphology VG Pleomorphism 11
Cytoplasm Cell Arrangement VG Abundant pale, Multiple vacuoles Basal cell Scant cytoplasm, basophilic Hepatoid cell Abundant pale blue cyto. Mesothelial cell Abundant pale cyto., eccentric vacuole Fibrosarcoma MG adenocarcinoma Mal. histiocytosis 12 Abundant basophilic cytoplasm Low to moderate pale blue cytoplasm Abundant pale blue cyto. with multiple vacuoles
Nuclear pattern Cell Arrangement VG Heterochromatin, non-prominent nucleoli Basal cell Homogeneous, non-obvious nucleoli Hepatoid cell Vesicular-prominent large nucleoli Mesothelial cell Heterochromatin Prominent large nucleoli Fibrosarcoma MG adenocarcinoma Mal. histiocytosis Homogeneous, prominent large nucleoli Heterochromatin, non-obvious small nucleoli 13
Abnormal mitosis Abnormal Nuclei Multinucleation 14
Intracytoplasmic Granules Extracellular Matrix 15
Epithelial Cell Tumor Cluster/single + scant cytoplasm Basal cell tumor group Cluster/single+ abundant cytoplasm vacuoles vacuoles glands Cluster/sheet/row Squamous cell tumor group Glandular cell tumor group Sebaceous cell tumor group Epidermal inclusion cyst Squamous papilloma Squamous cell carcinoma Carcinoma Adenoma Adenocarcinoma Site of mass Sebaceous adenoma Sebaceous epithelioma 16
Epithelial Cell Tumor Cluster/single + scant cytoplasm Basal cell tumor group = Epidermal basal cells (eg ; basal cell tumor, trichoblastoma, basal cell carcinoma) = Benign hair follicular cells (eg; trichoepithelioma, pilomatricoma) Trichoblastoma 17
Cluster/single+ abundant cytoplasm Epithelial Cell Tumor vacuoles Squamous cell tumor group Epidermal inclusion cyst Squamous papilloma Squamous cell carcinoma Carcinoma Epidermal inclusion cyst 18
Cluster/single+ abundant cytoplasm Epithelial Cell Tumor vacuoles Squamous cell tumor group Epidermal inclusion cyst Squamous papilloma Squamous cell carcinoma Carcinoma SCC 19
Cluster/single+ abundant cytoplasm Epithelial Cell Tumor vacuoles Cluster/sheet/row Sebaceous cell tumor group Sebaceous adenoma Sebaceous epithelioma 20
Cluster/single+ abundant cytoplasm vacuoles glands Glandular cell tumor group Epithelial Cell Tumor Adenoma Adenocarcinoma Site of mass: mammary gland 21
Cluster/single+ abundant cytoplasm vacuoles glands Glandular cell tumor group Epithelial Cell Tumor Adenoma Adenocarcinoma Site of mass: Perianal gland 22
Conclusion: Epithelial Cell Tumor Sheet/ Solitary /Cluster Tumor involving superficial squamous epithelial cells = Benign - squamous epithelium (eg; papilloma) = Squamous cell carcinoma = Basal cells group = Epidermal basal cells (eg ; basal cell tumor, trichoblastoma, basal cell carcinoma) = benign hair follicular cells (eg; trichoepithelioma, pilomatricoma) Sebaceous cell group: -adenoma,-epithelioma,-carcinoma Glandular Pattern Perianal gland adenoma/adenocarcinoma Apocrine gland adenoma/adenocarcinoma Tumor of the subcutaneous glandular tissues (salivary, mammary, thyroid etc) Tumor of internal organs; pancreas, adrenal gl., lung etc. Un-differentiated carcinoma 23
Spindle Cell Tumor (Mesenchymal Origin) + Melanoma - Vacuoles Lipoma/-sarcoma Granules (brown, black, green) - - Secretion (Mucin) Extracellular matrix Myxoma/-sarcoma Chondrosarcoma, Osteosarcoma Fibroma/-sarcoma Hemangioma/-sarcoma Hemangiopericytoma + Giant cells + Whorls Neurofibrosarcoma Malignant Fibrous Histiocytoma + Giant cells 24
Spindle Cell Tumor (Mesenchymal Origin) Granules (brown, black, green) + Melanoma 25
Spindle Cell Tumor (Mesenchymal Origin) Granules (brown, black, green) - Vacuoles Lipoma/-sarcoma 26
Spindle Cell Tumor (Mesenchymal Origin) Granules (brown, black, green) - Extracellular matrix Chondrosarcoma, Osteosarcoma + Giant cells Osteosarcoma Chondrosarcoma 27
Spindle Cell Tumor (Mesenchymal Origin) Granules (brown, black, green) - Extracellular matrix Fibroma/-sarcoma Hemangioma/-sarcoma Hemangiopericytoma + Whorls Fibrosarcoma 28
Spindle Cell Tumor (Mesenchymal Origin) Granules (brown, black, green) - Extracellular matrix Fibroma/-sarcoma Hemangioma/-sarcoma Hemangiopericytoma + Whorls Hemangiosarcoma 29
Spindle Cell Tumor (Mesenchymal Origin) Granules (brown, black, green) - Extracellular matrix Fibroma/-sarcoma Hemangioma/-sarcoma Hemangiopericytoma + Whorls Hemangiopericytoma 30
Conclusion: Spindle Cell Tumor Granulation tissue? Malignant melanoma Lipoma/Liposarcoma Osteoma/osteosarcoma Chondrosarcoma Myxoma & myxosarcoma Fibroma/Fibrosarcoma Hemangiopericytoma Hemangioma/Hemangiosarcoma melanin fat bone matrix, giant cells chondroid matrix mucin production spindle cell whorl endothelial, RBC Neurofibroma/neurofibrosarcoma Malignant fibrous histiocytoma giant cells, macrophage Undifferentiated sarcoma = Malignant mesenchymal cell tumor 31
Round Cell Tumor Granules (+) Granules (-) Red / purple Black Mastocytoma Melanocytoma 32 DIP QUIK Toluidine blue
Round Cell Tumor Granules (+) Granules (-) Red / purple Black Mastocytoma Melanocytoma Melanocytoma 33
Round Cell Tumor < 50 % with plasma cells, neutrophils Granules (+) Dense nuclear chromatin Scant cytoplasm Lymphoid cell = Hyperplasia / Reactive Lymph node >50%, blast cells, multiple nucleoli = lymphoma Granule (-) Large size Histiocytic lymphoma Coarse nuclear chromatin Deep blue cytoplasm Vacuole(+/-) + - TVT Histiocyte, Basal cell Abundant cytoplasm With giant cells Medium size Moderate amount of cytoplasm Malignant histiocytosis Histiocytoma Eccentric nuclei (young dog) Cell-rich FNA Small size Scant cytoplasm Ribbon arrangement Basal cell tumor (middle-aged dog) 34
Mixed breed dog, 12 Y Lymphoma 35
Lymphoma Lymphoglandular bodies Abnormal mitosis Ruptured cells Reactive lymph node Clinical signs gross lymphadenopathy (swollen LN) Cytology Lymphocytes (main) Plasma cells (found) Low lymphoblasts (normal) Low neutrophils Lymphoglandular bodies +/- 36
TVT (VG) / ETVT 37
38 TVT (VG) / ETVT 38
Histiocytoma 39
Histiocytoma 40 40 Histiocytoma
Malignant Histiocytosis 41
Malignant Histiocytosis 42
43