1 Neoplasms introduction 2017 Magdalena Bogdańska Barbara Górnicka Neoplasia - definition Neoplasia – new growth A neoplasm is an abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the changes – Willis Genetic changes allow excessive and unregulated proliferation independent of physiologic growth-regulatory stimuli Certain degree of autonomy – some require endocrine support and depend on the host for their nutrition and blood supply Epidemiology USA: 1.5 million new cancers per year 0.5 million per year will die Incidence: Men: prostate 33%, lung 13%, colorectal 10%, urinary bladder 6% Women: Breast 31%, lung 12%, colorectal 11%, uterine 6% Cancer death: Men: lung 31%, prostate 9%, colon and rectum 10%, pancreas 6% Women: lung 26%, breast 15%, colon and rectum 10%, pancreas 6% Nomenclature Benign tumours: by attaching the suffix –oma to the cell type from which the tumor arises Nonepithelial tumours Fibrous tissue – fibroma Bone – osteoma Vascular tissue – angioma Cartilage – chondroma Epithelial tumours Adenoma: benign epithelial neoplasm producing gland patterns or derived from glands. Cystadenoma: adenoma with cyst formation (ovary) Papilloma: benign epithelial neoplasms growing on any surface and producing finger-like projection Adenoma Nomenclature Non neoplastic instances with suffix – oma Hamartoma: malformation that presents a mass of disorganized tissue indigenous to the particular site Horistoma: congenital anomaly (heterotopic rests) Some malignant neoplasms: lymphoma, seminoma, melanoma, mesothelioma
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Neoplasmsintroduction
2017
Magdalena Bogdańska
Barbara Górnicka
Neoplasia - definition
Neoplasia – new growthA neoplasm is an abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the changes – WillisGenetic changes allow excessive and unregulated proliferation independent of physiologic growth-regulatory stimuli Certain degree of autonomy – some require endocrine support and depend on the host for their nutrition and blood supply
Epidemiology
USA: 1.5 million new cancers per year0.5 million per year will die
Epithelial tumoursAdenoma: benign epithelial neoplasm producing gland patterns or derived from glands. Cystadenoma: adenoma with cyst formation (ovary)Papilloma: benign epithelial neoplasms growing on any surface and producing finger-like projection
AdenomaNomenclature
Non neoplastic instances with suffix –oma
Hamartoma: malformation that presents a mass of disorganized tissue indigenous to the particular site
Horistoma: congenital anomaly (heterotopic rests)
Some malignant neoplasms: lymphoma, seminoma, melanoma, mesothelioma
Mixed tumor of the salivary gland(pleomorphic adenoma); Epithelial component and fibrous stroma with cartilage or bone – myoepithelial cells origin
Fibroadenoma of the breast: epithelial component (adenoma) and mesenchymal component (fibro)
Mixed tumor of the salivary glandBenign v/s malignant neoplasm
Benign Malignant
Local invasion No Yes
Distant metastases No Yes
Angioinvasion No Yes
Growth Slow Rapid
Capsule Almost always yes No
Local recurrences No Yes
Morphology Well different. Anaplastic
Angiogenesis Small Numerous vessels
Heterogeneity Small Very big
Pathways of disseminating
Lymphatic spread
Hematogenous spread
Seeding within body cavities
Perineural spread
Angioinvasion and distant metastases
Lymphatic (cancers) and hematogenous spread (sarcomas)
Numerous interconnection between lymphatic and vascular system so all forms of cancer may disseminate through either or both systems
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Sarcomas – pulmonary metastases
Cancer network.
Osteogenic sarcoma – pulmonary metastasis
Pediatric Oncology Education Materials
Pulmonary metastases – breast carcinomaInd.J of Cancer 2013.50.4 Lymphatic spread
The pattern of lymph node involvement depends principally on the site of the primary neoplasm and natural pathways of lymphatic drainage of the siteLung carcinoma: first regional bronchial, then to tracheobronchial and hilar lymph nodesSometimes: cancer cells seem to traverse the lymphatic channels within the immediately proximate nodes to be trapped in subsequent lymph nodes – skip metastases
Lymph node metastasis of adenocarcinoma
Sentinal lymph node
First lymph node in a regional lymphatic basin that receives lymph flow from a primary tumour
Biopsy of sentinal lymph node allows determination of the extent of spread of tumour and can be used to plan treatment
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The JAMA Network
Spread by seeding
Occurs when neoplasms invade natural body cavities
Cancers of the ovary which often widely covers the peritoneal surface
Neoplasms of central nervous system may penetrate the cerebral ventricles and be carried by the cerebrospinal fluid to reimplant on the meningeal surfaces either within the brain or the spinal cord
Neoplastic cells in cerebrospinal fluid
Slide Player
Patient with peritoneal carcinomatosis
World Journal of Surgical Oncology2009 7:5Gabriel Glockzin et al
Peritoneal tumor dissemination arising from colorectal cancer, appendiceal cancer, gastric cancer, gynecologic malignancies or peritoneal mesothelioma is a common sign of advanced tumor stage or disease recurrence and mostly associated with poor prognosis.
A liver with metastatic cancer Macroscopic type of growth
*Exophytic
*Mesophytic
*Endophytic
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Benign v/s malignant neoplasm
Benign Malignant
Local invasion No Yes
Distant metastases No Yes
Angioinvasion No Yes
Growth Slow Rapid
Capsula Almost always yes No
Local recurrences No Yes
Morphology Well differentiated Anaplastic
Angiogenesis Small Numerous vessels
Heterogenity Small Very big
Differentiation and anaplasiaBenign: well differentiated cells that closely resemble their normal counterparts. Mitoses are normal and are extremely scant
Lipoma – mature fat cells
Chondroma – mature cartilage
Differentiation and anaplasia
Malignant: wide range of parenchymal cell differentiation, from surprisingly well differentiated to completely undifferentiated (anaplastic).
Between these two extremes: moderately differentiated
Atlas of Genetics and Cytogenetics in Oncology
THYROID anaplastic (undifferentiated carcinoma)
Atypia and anaplasia
Pleomorphic cells
Extremely hyperchromatic (darkly stained) nuclei
Nuclear-cytoplasmatic ratio 4:1 (normally 1:1)
Giant cells
Bizarre nuclei (large and various in size and in shape)
Well differentiated malignant neoplasm (fibrosarcoma)
Anaplastic cancer
Grading GHistological differentiation
First described by Broders in 1926Establish histological aggressiveness and level of malignancyIs based on the cytological differentiation and the number of mitosesThe cancers may be classified as grade I, II, III and IVGrade I – well differentiated tumour, grade IV anaplasticGrading not always correlate with biologic behavior
Grading
Is determined by cytologic appearance
Is based on the idea, that behavior and differentiation are related
Poorly differentiated tumours are more aggressive and have a worse prognosis (usually)
Staging
Staging is based on the size of the primarytumour (T), its extent of spread to regionallymph nodes (N) and presence or absence of metastases (M).T1, T2, T3, T4 describe the increasing size of the primary lesionN0, N1, N2, N3 indicate progressivelyadvancing node involvementM0 and M1 absence or presence of distantmetastasesStaging has greater clinical value thangrading
Benign resemble the tissue of origin and are well differentiated; malignant are poorly or completely undifferentiatedBenign are slow growing; malignant tumours generally grow fasterBenign are well circumscribed and have the capsule; malignant are poorly circumscribed and invade the surrounding normal tissueBenign tumours are localized to the site of origin; malignant are locally invasive and they metastasize to distant sites
Benign v/s malignant neoplasm Neoplasms with local malignancy
Def: Tumour with invasive local growth (destruction and penetration of the surrounding tissues) but without metastases
Basal cell carcinoma of the skin, pleomorphic adenoma of the salivary gland.
Often with local recurrences
Basal cell carcinomaPreneoplastic disorders
Def: Clinical condition with well-recognized predispositions to the development of malignant neoplasia
Persistent regenerative cell replication: squamous cell ca in the margin of the skin wound, liver cell ca in cirrhosis
Hyperplastic and dysplastic proliferations: endometrial ca in atypical endometrial hyperplasia
Chronic atrophy gastritis: in pernicious anemia or following long standing H. pylori infection
Chronic ulcerative colitis
Leukoplakia of the oral cavity, vulva or penis
Villous adenoma of the colon
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Are benign tumours precancerous?
What is the risk of malignant transformation in benign neoplasm?
In general minimal but with exceptions
Better to say: each type of benign tumour is associated with particular level of risk ranging from high to virtually nonexistent
Villous adenoma of the colon may undergo malignant transformation in 50% of cases
Malignant change in leiomyoma are extremely rare
Dysplasia= Intraepithelial neoplasia
Principally in the epithelia
Architectural disarrangment
Loss of the uniformity of the individual cells
Dysplastic cells are abnormally large, pleomorphic with hyperchromatic nuclei
More abundant mitotic figures, frequently in abnormal location
Dysplasia
Dysplasias do not necessarily progress to cancer
Low grade
High grade
Carcinoma in situ: when dysplastic changes are marked and involve the entire thickness of the epithelium
High-grade dysplasia= carcinoma in situ (preinvasive carcinoma)
Pathology Outlines
Dysplasia in the colonic epitheliumClinical aspects
All neoplasms may cause problems due to:
Location and impingement of the adjacent tissues and structures
Small benign tumour: pituitary adenoma can compress the surrounding gland and lead to hypopituitarism; Small leiomyoma in renal arteries – renal ischemia and hypertension
Small malignant tumours: small bile duct carcinoma may lead to jaundice
Hormone production
In both benign and malignant neoplasms
More likely connected with a well differentiated benign tumour than with a corresponding carcinoma
Most frequently in endocrine organs tumours (adrenal cortex, pancreatic islet)
Cancer cachexia
Def: Progressive loss of body fat and lean body mass, accompanied by profound weakness, anorexia and anemia
Not caused by reduced food intake but by cytokines released by the tumour or host
TNF: suppresses appetite, inhibits the action of lipoprotein lipase
Protein-mobilizing factor (proteolysis-inducing factor): break down of skeletal muscle proteins by the ubiquitin-proteosome pathway
Other cytokines with lypolytic action
No satisfactory treatment
Paraneoplastic syndromes
Def: Symptoms complexes that occur in patients with cancer and cannot be readily explained by local or distant spread of the tumour nor by the elaboration of hormones indigenous to the tissue of origin of the tumour
10 – 15% of patients with cancer
Paraneoplastic syndromes
May represent early manifestation of occult neoplasm
May represent significant clinical problem and may even be lethal
May mimic metastatic disease and confound treatment
Paraneoplastic syndromesMechanisms
Abnormal hormones production
Immunologic response
Hypercoagulability
Unknown
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Abnormal hormone production
Cushing syndrome (ACTH, ACTH-like substance) –small cell ca of the lung, pancreatic ca, neural tumoursHypoglycemia (insulin, insulin-like substance) -hepatocellular ca, mesenchymal sarcomas, fibrosarcomasHypercalcemia (parathyroid hormone-related protein, TNF alfa factor which activates osteoclasts, IL-1, TGF alfa) – squamous cell ca of the lung, breast ca, renal ca, ovarian ca, adult T-cell leukemia/lymphomaPolycythemia (erythropoietin) – renal ca, hepatocellular ca, cerebellar haemangiomaCarcinoid syndrome (serotonin, bradykinin) –bronchial adenoma, pancreatic ca, gastric ca
Immunologic mechanism
Nephrotic syndrome – various cancers
Dermatomyositis – bronchogenic ca, breast ca
Acanthosis nigricans – gastric ca, lung ca, uterin ca
Myasthenia – bronchogenic ca
Disorders in the peripheral and central nervous system – breast ca
Acanthosis nigricans
Acanthosis nigricans is a skin condition characterized by areas of dark, velvety discoloration in body folds and creases. The affected skin can become thickened. Most often, acanthosis nigricans affects armpits, groin and neck.
The skin changes of acanthosis nigricans occur as a paraneoplastic syndrome or in people who are obese or have diabetes.
Venous thrombosis (Trousseau phenomenon) – pancreatic ca, lung ca, others
Unknown mechanism
Anemia – thymic neoplasms
Hypertrophic osteoarthropathy and clubbing of the fingers – bronchogenic ca
Tumour markers
Biochemical assays for tumour-associated enzymes, hormones and other markers in the blood
They cannot be utilized for definitive diagnosis, as they can be elevated in benign disorders and non-neoplastic conditions and can be low in cancers. They have low sensitivity and specificity
To screen some neoplasms, for detection of recurrences, for predicting their behavior
Tumour markers
CEA – carcinomas of the colon, pancreas, stomach, breastAFP – Yolk sac tumor, hepatocellular caBeta hCG – chorioncarcinomaNSE – small cell ca of the lungPSA – prostatic adenocarcinomaCalcitonin – medullary carcinoma of the thyroid glandCatecholamines – pheochromocytomaImmunoglobulins – multiplex myelomaCA15-3 – breast caCA19-9 – ductal adenocarcinomasCA125 – ovarian cancersTdT – leukemias
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Immunohistochemistry
In 1941 Albert Coons first described this method
Powerful adjunct to routine histology
Detection of typical cells substances (proteins) by monoclonal antibodies
The possibility to define the neoplasms origin
Cytokeratis (keratins)
Are intermediate filament proteins and are found within the cytoplasm of allepithelial cells (both: normal and neoplastic)
They form the cytosceleton of all the epithelial cells, along with microfilaments
Are numbered in a sequence contrary to their molecular weight (e.g. lower molecular weight keratins such as CK 19