Neoplasms and Cancer Stats

• A neoplasm is an abnormal mass growth that exceeds and is uncoordinated with normal tissues, persisting after the stimuli evoking the change cease
• Neoplasms arise from heritable genetic alterations, excessive and unregulated proliferation, and autonomous proliferation independently of physiologic growth stimuli

Cancer Statistics and Epidemiology:

• Worldwide, in 2000, there were 10 million new cases of malignant tumors
• Worldwide, in 2000, malignancies caused 6 million deaths
• In Europe in 2006, there were 3.2 million new cases of malignant tumours
• In Europe in 2006, malignancies caused 1.7 million deaths
• In Latvia in 2006, there were 9102 new cases of malignant tumours
• In Europe in 2006, the most frequent newly diagnosed cancer types were breast (13.5%), colorectal (12.9%), and lung (12.1%)
• In Europe in 2006, the most common cancer-related death cases were lung (19.7%), colorectal, and breast cancer
• Estimated global cancer statistics indicated 18.1 million new cancer cases in 2018, an increase from 10 million in 2000
• Estimated global cancer statistics indicated 9.6 million cancer deaths in 2018, compared to 6 million in 2000
• By frequency in both sexes: lung cancer (11.6%) iand breast cancer (11.6%) were most common, followed by prostate (7.1%) and colorectal cancer (6.1%)
• By mortality in both sexes: lung cancer (18.4%) was highest, followed by Gastric cancer (8.2%) and Liver cancer each (8.2%), then Colorectal cancer (9.2%)
• In males in 2018, lung, prostate, and colorectal cancers had the highest incidence
• In males in 2018, lung, liver, and gastric cancers had the highest mortality
• In females in 2018, breast, colorectal, and lung cancers had the highest incidence
• In females in 2018, breast, lung, and colorectal cancers had the highest mortality

Tumour Components

• Parenchyma, which is the proliferating neoplastic cells, and Stroma, which provides support and determines consistency

Classification of Tumours

• Classification is done by the clinical course/biological properties of the tumour and by histogenesis

Benign Tumours

• Benign tumours grow locally, remain localized, and do not metastasize
• Benign tumours exhibit expanse growth, usually have a benign clinical course, and can cause health problems through local complications or endocrine disturbances
• Benign tumours usually have clear borders and a capsule

Nomenclature of Benign Tumours

• Benign tumour names often end with the suffix "-oma"
• Mesenchymal benign tumors: named by "cell of origin" + -oma (e.g., chondroma, fibroma, lipoma)
• Epithelial benign tumors: nomenclature describes the cell of origin, microscopic architecture, and gross pattern
• Epithelial benign tumors include papilloma, adenoma, and cystadenoma
• Exceptions to the "-oma" rule include: Basolioma (basal cell cancer), melanoma, and lymphoma

Epithelial Tumour Definitions

• Adenoma: benign epithelial tumour that forms glandular patterns
• Papilloma: benign epithelial tumour with papillary ("finger-like") projections above the surface of cells
• Cystadenoma: benign epithelial tumour that forms cysts

Malignant Tumours

• Malignant tumours can cause death
• Malignant tumours characteristically exhibit invasive growth, the ability to develop and spread metastases, and lead to Anaplasia
• Malignant tumours can influence the whole organism and do not have clear borders

Nomenclature of Mabignant Tumours

• Epithelial malignant tumour = carcinoma
• Carcinomas include adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and undifferentiated carcinoma
• Mesenchymal malignant tumour = sarcoma

Nomenclature of Epithelial-Origin Tumours

• Squamous epithelium benign tumours are papillomas, while the malignant tumors are named squamous cancer
• Basal layer of skin epithelium benign tumours have no specific name provided, while the malignant tumors are named basal cell cancer
• Glandular or ductal epithelium benign tumours are adenomas/papillomas, while the malignant tumors are called adenocarcinoma/papillary cancer

Nomenclature of Mesenchymal-Origin Tumours (I)

• Connective tissue/fibroblasts benign tumours are fibromas, while the malignant tumors are called fibrosarcomas
• Fat cells benign tumours are Lipomas, while the malignant tumors are named liposarcomas
• Cartilage benign tumours are chondromas, while the malignant tumors are called chondrosarcomas

Nomenclature of Mesenchymal-Origin Tumours (II)

• Endothelium of blood vessels benign tumours are hemangiomas, while the malignant tumors are called angiosarcomas
• Endothelium of lymph vessels benign tumours are lymphangiomas, while the malignant tumors are called lymphangiosarcomas
• Smooth muscle benign tumours are leiomyomas, while the malignant tumors are called leiomyosarcomas

Nomenclature of Haematologic-Origin Tumours

• Haematopoietic cells (in bone marrow) exhibit leukemia as malignant tumors
• Lymphoid tissue cells exhibit lymphoma as malignant tumors

Nomenclature of Melanocytes and Germ Cell Tumours

• Tumours of melanocytes benign tumors are naevus, malignant lesions are called melanomas
• Germ cell tumours (of the testis) are malignant: seminoma, embryonal carcinoma, yolk sac tumour

Characteristics of the Neoplastic Process

• Relevant charcteristics include differentiation and anaplasia, rate of growth, local growth pattern and Metastasis

Anaplasia

• Anaplasia is a lack of differentiation
• Tissue atypia occurs, where cells look like normal cells, but tissue is arranged abnormally
• Cell atypia refers to cells not resembling their origin cells

Morphologic signs of Anaplasia

• Pleomorphism, hyperchromatism, increased nuclear-cytoplasmic ratio, mitoses, atypical mitoses, loss of cell polarity, tumour giant cells, and tumour necrosis

Dysplasia

• Dysplasia is disordered growth
• Dysplasia is a constellation of changes with loss of cellular uniformity and loss of architectural orientation
• Dysplasia in oncology = Intraepithelial neoplasia This neoplasia is defined as neoplastic epithelium contained within the basement membrane that can progress to invasive cancer

Morphology of Intraepithelial Neoplasia

• Lack of maturation, cellular anaplasia within the epithelial layer, increased mitotic activity & Dypslacement of mitoses

Growth Rate

• Tumour growth rate depends on speed of cellular proliferation / length of mitosis
• Tumour growth is usually not associated with faster mitosis or shortening of cell cycle time
• The proliferative fraction, combined with the rate of tumor cell death, such that more cells are produced Than die, contributes to the tumour growth rate

Cell Proliferation

• Higher growth fraction correlates to faster tumour development and greater effect of cancer chemotherapy
• Fast-growing tumours may have higher cell turnover
• High-grade tumours often grow faster, but some benign tumours grow fast

Cancer Stem Cells and Cell Lineages

• Short-living functional cells and resident tissue stem cells capable of self-renewal appear in normal tissues
• Stem cells rare and depend on paracrine factors for support
• Tissue stem cells divide & produce 2 types of daughter cells with limited proliferative potential
• The cancer stem cells are the essence of cancer "immortality", they confer tumour immortality, they have low proliferative rates resist treatment, and display multiple drug resistance - these cancer stem cells must be treated

Local Growth Pattern Types

• Expansive growth
• Invasive growth
• Intraepithelial growth, Ca in situ, intraepithelial carcinoma, preinvasive malignancy & high-grade dysplasia all considered

Expansive Growth

• In expansive growth, the tumour expands and compresses the surrounding tissue and a capsule may form
• Tumours exhibiting expansive growth are easily moved by Palpation and have Characteristic of benign tumours

Invasive Growth

• In invasive growth, the tumour infiltrates, and its growth is not limited within an anatomical structure
• Pseudocapsules may develop

Metastasis

• Metastasis occurs as tumour implants discontinuous with the primary tumour
• Metastasis represents an unequivocal sign of malignancy and all cancers can develop Metastasis
• Some malignanttumours develop metastasis rarely and late in the course of disease

Pathways of Metastatic Spread

• Lymphatic spread
• Haematogenous spread
• Implantation metastasis

Pattern of Lymphatic Spread

• Sentinel node
• Regional lymph nodes
• Distant lymph nodes
• Skip Metastasis

Features of Haematogenous Metastatic Spread:

• This spread depends on vascular invasion through veins, arteries, and small blood vessels
• This spread depends on on blood flow in both the tumour and the affected organ

Collectors of Metastasis:

• Liver by portal blood flow, lung by caval blood flow, kidneys, bones, and brain by vessels and the vertebral column by paravertebral venous plexus

Implantation Metastases

• Serosal seeding occurs in Ovarian/Colorectal/Other cancers
• latrogenic routes provide another potential mechanism

Benign vs. Malignant Tumours - Summary of Characteristics

• Benign tumours involve local growth and absence of metastases
• Benign tumours exhibit expansive growth and usually have benign course
• Malignant tumours cause death (although can be treated/prevented); are invasive with Anaplasia and metastasis
• Malignant tumours can affect several organs and influence the whole organism

Biological Potential of Tumours

• Benign
• Malignant
• Indeterminate

General Risk Factors for Cancer

• Environmental factors (smoking, obesity, alcohol)
• Infections (HBV, HPV & UV)
• Age
• Certain pathological processes (organ-dependant): Dysplasia, Hyperplasia, Chronic inflammation and benign tumors
• Genetic factors and Inherited cancer syndromes (FAP, HNPCC, HBOC, MEN, familial predisposition)

Carcinogenic Factors

• Chemical factors (carcinogens in tobacco smoke, aflatoxins, initiators/promoters)
• Physical factors (UV and irradiation)
• Infectious factors (HPV, HBV, Epstein-Barr virus, & Helicobacter pylori)

Genetic Principles of Cancer

• Non-lethal genetic damage to growth-promoting proto-oncogenes, growth inhibiting tumour suppressor genes and, genes involved in the apoptosis/DNA repair
• Clonal expansion of single precursor cell that has incurred genetic damage

Tumour Staging:

• Classified by Essential tumor characteristics (related to tumour progression and heterogeneity)
• Staged via Multistep process involving accumulation of multiple mutations

Essential Alterations for Malignant Transformation

• To have cancer involves Self-sufficiency of growth signals, Insensitivity to growth-inhibitory signals Evasion of apoptosis, Limitless replicative potential, Sustained angiogenesis, Ability to invade/metastasize and Defects in DNA repair and Warburg effect (aerobic glycolysis)

Effects of Tumours on the Host

• Physical affects in situ which include MASS
• Functional, bleeding , secondary infections, cancer cachexia & paraneoplastic syndromes are all effects of tumours

Cancer Cachexia

• Cancer cachexia involves Progressive loss of weight and body fat
• Other affects include weakness, anorexia, anemia, reduced food intake, and high caloric expenditure with basal metabolism
• Characterized by equal loss of fat and muscle mass
• Cytokines are: TNF, IL-1, IFN gamma

Paraneoplastic Syndromes

• Symptom complexes related to the cancer presence in the organism
• Cannot be explained by mass effects or elaboration of indigenous “normal” hormones
• Examples include endocrinopathies with ectopic hormone production, neuromuscular syndromes, and dermatologic manifestations

Laboratory Investigations in Oncology

• Tumor Markers are tested, including Cytology (Fine needle aspiration), Histology, Immunohistochemistry and Molecular tests but, currently Histology is the gold standard
• Flow cytometry is also used

Aim of Laboratory Investigations in Oncology

• To analyse presence, determine origin and stage tumours, determine grade and prognosis and pharmacodiagnostics

Tumor Markers

• The cell surface antigens, cytoplasmic proteins, enzymes, and hormones
• Examples are: PSA, CA19-9, CEA
• Are used to see if there are specific test substances occurring, these are tested for, primarily Mainl in blood, and sometimes in other biological substances

Laboratory Tumour Diagnostics

• Gold standard includes the biopsy, and several exceptions include: brain tumours and hepatocellular carcinoma,

Immunohistochemistry

• IHC's indications are for tumour diagnostics that including identification of histogenesis, diagnosis of leukemias/lymphomas, the estimate of spread and evaluation of prognostic and predictive factors, and in pharmacodiagnostics

IHC Markers of Histogenesis:

• Cytokeratin A1/AE3 epithelium markers
• Vimentin marks mesenchymal cells tumours
• LCA – leukocytes haematological Tumours
• HMB-45 melanoma

IHC Examples of Organospecific Markers:

• Mammoglobin - breast epithelium + breast cancer marker
• CDX2 colorectal markers
• TTF1 thyroid and lung parenchyma + tumours
• PSA prostatic tissue+ cancer

The use of Molecular Tests in Oncology

• To study monocolonality, prognostic factors, minimal residual disease and hereditary predisposition Gene expression

Tumour Classification for Diagnosis

• Classified via WHO ,with TNM, via stage and the (TNM scale stands for Tumour, Node, Metastasis), and with WHO

TNM and Grade Classification

• TNM, the spread of the tumour
• T1-T4 describes in tumour
• NO/N3 describes absence/presence of tumour in the node
• MO-1 describes the absence/presence of meta-stasis
• The grading and staging of tumours requires TNM classification which is based on location