Neoplasia Flashcards
Neoplasia
abnormal proliferation of cells. These cells are unresponsive to typical mechanisms to regulate cell division.
Oncogenesis
The development of a tumour
Outline the 3 steps in the development of a malignant tumour
- Initiation (mutagenesis) - may be inherited/spontaneous/caused by ROS/pathogen
- Promotion - promoters themselves are not mutagenic but create a promotive environment where initiated cells have an advantage
- Progression - genetic instability increase tumour cell heterogeneity
Mutagenesis
the production of genetic mutations
Anaplasia
poor cellular differentiation; cells lose their morphological characteristics and their orientation with respect to each other and endothelial cells
What are the most important factors for classification of a tumour as benign vs malignant?
- Differentiation
- Growth rate
- Local invasion
- Metastasis
- Host consequences
Describe the differentiation shown by benign tumours
- Well-differentiated
- Similar to tissue of origin
- Little to no anaplasia
Describe the differentiation shown by malignant tumours
- Lack of differentiation
- Atypical structure
- Variable anaplasia
Describe the growth rate of benign tumours
- Slow, progressive growth
- Rare mitotic figures
- Normal mitotic figures
Describe the growth rate of malignant tumours
- Slow to rapid growth
- Many mitotic figures
- Abnormal mitotic figures
Describe the local invasion of benign tumours
- No invasion
- Cohesive growth
- Capsule often present
Describe the local invasion of malignant tumours
- Local infiltration
- Infiltrative growth
- Usually no capsule
Describe the metastasis shown by benign tumours
No metastasis
Describe the metastasis shown by malignant tumours
Frequent metastasis
Describe the host consequences of benign tumours
Space occupying lesion- effect depends on location
Describe the host consequences of malignant tumours
Life-threatening
Describe the nuclear morphology of benign tumours
- Minimal to mild anisokaryosis
Describe the nuclear morphology of malignant tumours
- Marked anisokaryosis with frequent binucleation/multinucleation
Anisokaryosis
Variation in the size of nuclei in the cell
Describe the cellular morphology of benign tumours
- Minimal to mild anisocytosis
Describe the cellular morphology of malignant tumours
- Marked anisocytosis
Anisocytosis
Cells that differ from one another in size
Describe the nuclear:cytoplasmic ratio of benign tumour cells
Normal to reduced
Describe the nuclear:cytoplasmic ratio of malignant tumour cells
Increased
Describe the mitotic count of benign tumour cells
Low
Describe the mitotic count of metastatic tumour cells
High
Describe the presence of necrosis in benign tumours
Minimal or absent
Describe the presence of necrosis in malignant tumours
Frequently present
Where do malignant tumours invade in their surroundings?
Blood and lymphatic vessels
What are the common neoplastic lesions seen in practice?
- Mesenchymal
- connective tissue - fibrosarcoma, fibroma, lipoma
- endothelium - haemangioma, haemangiosarcoma
- haematopoietic - lymphoma, leukaemia, histocytoma, MCT
- muscle - rhabdomyosarcoma
- Epithelial
- lining epithelial - SCC, melanoma
- glandular epithelium - adenocarcinoma
- Nervous
- glial cell - astrocytoma, olidodendroglioma, PNST
- neural cell - ganglioneuroma
Benign - sebaceous adenoma
Pre-malignant - Bowenoid carcinoma
Once there has been invasion of the basement membrane, this is considered malignant
Malignant - squamous cell carcinoma
Describe the process of metastasis
- Metastasis: spread of a tumour
- Cancer cells leave the primary tumour and travel through blood and lymphatic vessels
- 90% of deaths from cancer are due to cancerous growths at body locations distant from the primary tumour
- Invasion and metastasis are the major causes of cancer-related morbidity and mortality
Pathways of metastasis
- Transcoelomic: cancers that arise on the surface of abdominal and thoracic structures
- Lymphatic: lymph node closest to the tumour is colonised earliest, and develop the largest tumour masses
- Haematogenous: tumours generally invade veins rather than arteries as thinner walls. Ultimately enter lungs and liver.
The lung is a common site for metastasis of which tumour types
- Osteosarcoma
- Haemangiosarcoma
- Melanoma
- Mammary tumours
- Others: thyroid, tonsillar, pancreatic
The liver, spleen and kidney are common metastatic site for which tumour types?
- Mast cell tumours
- Haemangiosarcomas
Bone is a common metastatic site for which types of tumours?
- Mammary gland tumours
- Prostatic carcinomas
- Urinary bladder turnouts
Describe the range of effects that may arise from a neoplasia
- Direct effects - space-occupying lesion
- Indirect effects - paraneoplastic syndrome; these complications might be the main sign
Paraneoplastic syndromes
Collection of haematological, endocrinological and metabolic complications caused by cancer
Describe cancer cachexia
- Wasting syndrome resulting from altered carbohydrate, protein and lipid metabolism
- Complex pathogenesis due to IL-1, Il-6, TNF-alpha and prostaglandins
Describe endocrinopathies as a result of neoplasia
- Endocrine neoplasm: functioning endocrine tumour e.g. insulinoma (beta islet cell carcinoma or adenoma)
- Non-endocrine neoplasm: hormonally active substance not normally found in the tissue of tumour origin e.g. many tumour cells produce PTH-related protein → causes bone resorption and renal calcium resorption
Describe skeletal syndrome associated with cancer
- Hypertrophic pulmonary osteopathy: rapid periostea new bone growth affecting distal limbs; common with lung tumours (primary or metastatic)
- Myelofibrosis: overgrowth of non-neoplastic fibroblasts in bone marrow, impairing normal haematopoiesis and resulting in cytopenia
Describe some common paraneoplastic syndromes
- Cancer cachexia - most common
- Endocrinopathies
- Skeletal syndromes
- Vascular and haematological disorders
- Epidermal necrosis (Seen with pancreatic and hepatic tumours)
- Nodular dermatofibrosis (renal adenocarcinoma)
- Alopecia (pancreatic carcinoma)
- Exfoliative dermatitis (thymoma)
- Myasthenia gravis (thymoma, hepatic carcinoma, osteogenic sarcoma)
Complete carcinogen
an agent that causes both initiation and promotion.
e.g. ionising radiation → direct DNA damage and ROS generation
Differentiate between direct-acting and indirect-acting chemical carcinogens
- Direct - effective in the form in which they enter the body
- Indirect - pro carcinogens that require metabolic activation by enzymes in order to be effective
Briefly describe the main mechanisms by which viruses may cause neoplastic transformation
- Direct mechanism
- dominant oncogene mechanisms - virus contains a mutated gene that drives tumour development
- Insertional mechanism - virus does not possess its own oncogene, but inserts viral DNA that in turn activates the target cell’s oncogene
- Hit and run mechanism - viral genome causes neoplasm by transient residence in the target cells (virus causes tumour but isn’t detectable in the tumour afterwards)
- Indirect mechanism
- Suppression of immune system
- Stimulation of target cell proliferation
Viral example of hit and run mechanism
Bovine papillomavirus
Viral example of insertional mechanism
Avian leukosis virus
Viral example of dominant oncogene mechanism
Feline leukaemia retrovirus
Canine papillomavirus
How can you diagnose a neoplasm?
- Physical exam and diagnostic imaging → starting point but not enough on its own
- Cytological exam - examination of cells
- Histopathological exam - examination of tissue
True/false: cytology alone (i.e. from an FNA) is adequate to assess a neoplasm.
False
Histopathology is needed - important for diagnosis, but also informs prognosis and treatment plan
Describe the information histopathology of a neoplasm can provide
- Tissue architecture
- Invasion of adjacent issue/vasculature
- Necrosis
- Mitotic count
- Tumour grade
- Predicts biological behaviour
- Based on published grading criteria
