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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

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 tumoursFibrous tissue – fibromaBone – osteomaVascular tissue – angiomaCartilage – chondroma

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

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NomenclatureMalignant neoplasms

Mesenchymal origin – sarcomas

Fibrous tissue origin – fibrosarcoma

Chondrocytes origin –chondrosarcoma

Vascular origin – angiosarcoma

Epithelial origin – carcinomas

With glandular pattern –adenocarcinoma

With squamous pattern – squamous cell carcinoma

Nomenclature

Mostly – monoclonal origin

Sometimes: divergent differentiation. Mixed tumours

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)

Coarse and clumped chromatin

Nucleoli

Numerous mitoses

Atypical mitoses

Loss of normal polarity

Atypical mitosesWell differentiated benign neoplasm -

Lipoma

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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

TNM classification -staging

Nature Reviews Disease Primers 3, Article number: 17048 (2017)

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TNM classification (breast cancer) Benign v/s malignant

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

Functional activity (hormone synthesis, paraneoplastic syndromes)

Bleeding or infection (ulceration)

Symptoms that result from rupture or infarction

Cachexia

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Location

Crucial in both benign and malignant tumours

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.

Paraneoplastic syndromesMechanisms

Hypercoagulability

Nonbacterial thrombotic endocarditis –various cancers

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

Immunohistochemical positive reaction (brown): cytokeratins labeling squamous epithelium

Immunohistochemistry

Marker Carcinoma Lymphoma Sarcoma Melanoma

CK + - -/+ -/+

Vimentine -/+ + + +

LCA - + - -

HMB45 -/+ - - +

S100 -/+ - - +

EMA + -/+ -/+ -

Immunohistochemistry

Origin Markers

Epithelial Cytokeratins, EMA, PSA

Lymphoid LCA

Melanocytic HMB45, MelanA, S100

Muscle Desmin, actin

Glial GFAP, S100

Neuroendocrine Chromogranin A, synaptophysin, insulin

Vascular CD34, CD31, FVIII

Histiocytic CD68

Embryonal antigens AFP, CEA

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Vimentin, diffuse strong positivity