heart failure

1. NEOPLASIA
Dr Ayana (MD, asst professor of pathology)

2. NEOPLASIA
DEFINITION:
Literally ( Neoplasia-‘new growth’)
• 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 cessation of the stimulus, evoking the
change.
• So the growth is irreversible
• Autonomous (independent of the physiologic hormonal stimulation)
2

3. • a neoplasm is often referred to as a tumor
• the study of tumors is called oncology.
• based on their clinical behaviour there are two categories of
neoplasm.
1. benign
2.malignant ( ?????????? collectively referred to as cancers)

5. Nomenclature
a)Naming of Benign tumors
• In general, benign tumors are designated by attaching the suffix -
oma to the cell type from which the tumor arises.
Examples
• Fibroma-A benign tumor arising in fibrous tissue.
• Adenoma- A benign epithelial neoplasms producing gland
patterns
• Benign tumors sometimes named on the basis of their
microscopic or macroscopic pattern
• Papillomas – those which produce finger-like projections
• A polyp - is a mass that projects above a mucosal surface, as in the gut, to
form a macroscopically visible structure.

6. 6
Colonic
polyp/adenoma

8. b)Naming of Malignant tumors
mesenchymal
• sarcomas (sar = "flesh") : liposarcoma, fibrosarcoma,
osteosarcoma,chondrosarcoma, etc.
epithelial:
carcinoma (karkinos = "crab") : squamous cell carcinoma (pituitary
carcinoma
hepatocellular carcinoma
renal tubular carcinoma
adrenal cortical carcinoma
adeno carcinomas: bronchoalveolar adenocarcinoma
(if glandular patterns) mammary adenocarcinoma

9. c) Mixed Tumors
• the majority of neoplasms are composed of cells representative of a
single germ layer, and the neoplastic cells closely resemble each
other.
• mixed tumors contain more than one cell type, but these are all
derived from one germ layer.
• Eg. nephroblastoma = Wilm’s tumor,a common tumor in children <10
years this tumor may contain multiple tissues (eg epithelium, fibrous
tissue, smooth or striated muscle, cartilage, bone), but all these
tissues are derived from the metanephric mesoderm;

10. d) Teratomas
• are composed of a variety of neoplastic cell types representative of more
than one germ layer, usually all three (ie ectoderm, mesoderm,
endoderm).
• teratomas arise from totipotential embryonic cells (likely primordial germ
cells) and so are primarily found in the gonads, but also rarely in ectopic
primitive cell rests elsewhere.
• these totipotential germ cells can readily express various portions of their
genome and therefore can differentiate into various types of tissues (eg
skin, muscle, fat, gut, tooth structures, brain, eye, etc).
• eg- ovarian teratoma

11. Mature cystic teratoma
• Tangles of hairs & sebum

12. Mature cystic teratoma

13. Misnomers: -granuloma,hematoma
-Hamartoma: tumor-like mass composed of an overgrowth of mature
cells and tissues normally present in the affected part, but often with
one element predominating.
They are present at birth and probably result from an overgrowth of
progenitor cells in the fetus
eg.a hamartoma in the lung may contain islands of cartilage, blood
vessels, bronchial-type structures, and lymphoid tissue.

14. Choristoma
• a mass of histologically normal tissue in an abnormal location (ie an
ectopic rest of normal tissue
• For instance, benign-sounding designations such as lymphoma,
melanoma, mesothelioma, and seminoma are used for certain
malignant neoplasms

15. CHARACTERISTICS OF BENIGN AND
MALIGNANT NEOPLASMS
• The four fundamental features by which benign and malignant
tumors can be distinguished are:
1. Differentiation and anaplasia,
2. Rate of growth
3. Local invasion and
4. Metastasis.

16. Differentiation and Anaplasia
• The differentiation of neoplastic cells refers to the
degree of morphological and functional resemblance
to their cell of their origin
• Benign neoplasms are composed of well-
differentiated cells
• Malignant neoplasms consist parenchymal cell which
can be well differentiated, moderately
differentiated or undifferentiated.

17. • The better the differentiation of the cell, the more
completely it retains the functional capabilities found
in its normal counterparts.
• Malignant neoplasms that are composed of
undifferentiated cells are said to be anaplastic.
• Lack of differentiation, or anaplasia, is considered a
hallmark of malignancy.

18. • Characteristics of Anaplastic cells
• Do not retain specialized functional activity
• Display marked pleomorphism (i.e., marked variation in size and shape)
• Has a very large nuclei , The nuclear-to-cytoplasmic ratio may approach 1 : 1
instead of the normal 1 : 4
• Has hyperchromatic (darkly stained) nuclei

19. Rate of Growth
• Most benign tumors grow slowly
• exceptions .e.g leiomyoma
• Most cancers grow much faster
• the growth rate of tumors depend on
• adequacy of blood supply
• pressure constraints
 The rate of growth of malignant tumors correlates
with their level of differentiation.
• rapidly growing tumors tend to be poorly differentiated.

20. Local Invasion
• local invasiveness is important to differentiate benign
from malignant tumors
• A benign neoplasm
• remains localized at its site of origin.
• It does not have the capacity to infiltrate, invade, or
metastasize to distant sites.
• Develop capsule that separates them from host tissue
• Exceptions, leiomyoma is not encapsulated
• Cancers
• grow by progressive infiltration, invasion, destruction, and
penetration of the surrounding tissue
• They do not develop well-defined capsules.

21. Metastasis
• It is a transfer of malignant cells from one site to another not directly
connected with it.
• the most reliable feature that distinguishes malignant from benign
tumors
• Not all cancers have equivalent ability to metastasize, e.g BCC
• In general, the more anaplastic and the larger the primary neoplasm,
the more likely is metastatic spread

22. Pathways of spread
• Dissemination of malignant neoplasm occur through the following
three pathways:
• (1) seeding within body cavities
• (2) lymphatic spread or
• (3) hematogenous spread.

23. 1. seeding of body cavities &surfaces (transcoelomic
spread)
Transfer of neoplastic cells from one location to
another within a body cavity,
as organs rub against each other or
via the small amount of fluid normally present within
body cavities; also,
 via transplantation of neoplastic cells on surgical
instruments
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24.  May occur whenever a malignant neoplasm penetrates into a
natural “open field”.
 Most involved-peritoneal cavity, others pleura, subarachnoid spaces
& joint spaces
 Characteristics 0f carcinoma arising from ovaries
 Mucus secreting ovarian & appendicial carcinomas fill peritoneal
cavity with a gelatinous neoplastic mass pseudomyxoma
peritonei

25. 2. Lymphatic spread
• Most common pathway for initial dissemination of carcinomas, but
sarcoma may also use this route.
a. Lymphatic embolism: malignant cells invade the wall of a lymph
vessel, detach as small groups and carried by the current of lymph as
tumor emboli
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26. b. Lymphatic permeation:
Tumor cells grow with in the lumen of the lymphatic vessels as solid
cords which extend to a variable distance from the primary tumor,
causes edema in the area
Usually Occurs in breast, prostate, and bronchial carcinoma as these
organs rich in lymphatics

27. The pattern of LN involvement follows the natural routes of drainage.
E.g –Breast Ca in UOQ Axillary LNs
Enlargement of LNs may be caused by:
-spread &growth of cancer cells or
-reactive hyperplasia
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28. 3. Hematogenous spread
 Typical for all sarcomas &certain carcinomas can use it
 liver &lung –frequently involved –because systemic
&venous blood supply (out flow)
 Others include Brain & Bones
 Bone metastasis are common in carcinoma of the
thyroid, breast, lung, kidney, prostate
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29. 29
A liver studded with metastatic cancer

30. 30
Comparison between a benign tumor of the myometrium (leiomyoma) and a

31. Cancer Epidemiology
 The only certain way to avoid cancer is not to be born, to live is to incur
the risk
 due to the typically long delay between exposure to carcinogens and the
development of tumors, specific causes of neoplasms can be determined
accurately only through carefully designed epidemiological studies.
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32. CARCINOGENESIS
• One of the fundamental principles of carcinogenesis is Nonlethal genetic
damage .
• Such genetic damage (or mutation) may be acquired by the action of
environmental agents, such as chemicals, radiation, or viruses, or it may be
inherited in the germ line.
• The principal targets of genetic damage are the normal regulatory genes
• there are four classes of these regulatory genes.
1.growth-promoting proto-oncogenes
2. growth-inhibiting tumor suppressor genes,
3. genes that regulate programmed cell death (i.e., apoptosis),
4. genes involved in DNA repair

33. ETIOLOGY OF CANCER: CARCINOGENIC
AGENTS
• A large number of agents cause genetic damages and induce
neoplastic transformation of cells.
• There are three categories:
• (1) chemicals carcinogen
• (2) radiant energy, and
• (3) microbial agents.
• These agents may act alone , together or sequentially to produce the
multiple genetic abnormalities characteristic of neoplastic cells.

34. Chemical Carcinogens
• hundreds of chemicals have been shown to be carcinogenic.
Steps in chemical carcinogenesis:
• Cells exposed to chemical carcinogen formation of initiation –promotion
sequence cancer
• Initiation –
• causes permanent DNA damage (mutation) which, is rapid and irreversible
• Need promoters to cause tumor

35. • Promoters
• The transformed (initiated) cell can remain harmless, unless and until
it is stimulated to
undergo further proliferation, upsetting the cellular balance.
• induce rapid proliferation in initiated cells
• non-tumourogenic (do not affect cellular DNA) by themselves
• e.g., phorbol esters, hormones, phenols, and drugs

36. • Chemical carcinogenic agents fall into two categories:
• 1. Direct-Acting Agents
• 2. Indirect-Acting Agents
Direct-acting agents
• They require no metabolic conversion to become carcinogenic.
• few alkylating and acylating agents are directly acting carcinogens
• They are in general weak carcinogens and some of them are cancer
chemotherapeutic drugs.

37. Indirect-Acting Agents
• require metabolic conversion to be an ultimate carcinogen
• Most known carcinogens are metabolized by cytochrome p-450 dependent
mono-oxygenase.
• Examples:
• polycyclic hydrocarbons , aromatic amines, amides, azo dyes
• Natural Plant and Microbial Products
• aflatoxin
• Vinyl chloride, nickel, chromium
• Insecticides, fungicides

38. Radiation Carcinogenesis
Radiation can transform and induce neoplasm
• Two types of radiation injuries are recognized
• I. non-ionizing radiation –
• cause vibration and rotation of atoms in biologic
molecules
• Cause damage and impaired DNA repair
• Example UV radiation from the sun cause skin cancers

39. • II. Ionizing radiation
• can ionize biologic target molecules and eject electrons
• Examples –
• Therapeutic irradiations --Thyroid cancer
• Radioactive elements -- lung cancer
• Atomic bombs -- leukaemia's and later solid
tumours

40. Viral and Microbial Oncogenesis
• Many DNA and RNA viruses have proved to be oncogenic
• Oncogenic RNA Viruses
• HTLV-1
• T-cell leukemia
• Oncogenic DNA Viruses
• human papillomavirus (HPV)
• warts) and SCC of the cervix.
• Epstein-Barr virus (EBV)
• Burkitt lymphoma,Hodgkin lymphoma, NK-cell lymphomas

41. • human herpes virus 8 Kaposi sarcoma
• hepatitis B and C viruses (HBV and C
• hepatocellular carcinoma
Oncogenic bacteria
• Helicobacter pylori
• implicated in the genesis of both gastric adenocarcinomas and gastric
lymphomas.

42. Clinical Effects of tumours
• Although malignant tumors are more threatening than benign
tumors, any tumor, may cause morbidity and mortality.
• tumors may cause problems because of :
1. location and impingement on adjacent structures
2. functional activity such as hormone synthesis or the development
of paraneoplastic syndromes,
3. bleeding and infections when the tumor ulcerates through
adjacent surfaces
4. symptoms that result from rupture or infarction

43. Location is crucial in both benign and malignant tumors.
• A small (1-cm) pituitary adenoma can compress surrounding
gland tissue leading to hypopituitarism.
• A 0.5-cm leiomyoma in the wall of the renal artery may be
enough to cause renal ischemia
• small carcinoma within the common bile duct may induce
fatal biliary tract obstruction.

44. • Hormone production
• seen with neoplasms arising in endocrine glands.
• hormonal activity is a character of well-differentiated benign tumor than a
corresponding carcinoma
• Eg. Neoplasms arising in the β-cells of the islets of the pancreas can produce
hyper insulinism

45. Paraneoplastic Syndromes
• Symptom complexes that cannot be explained
i. By local or distant spread of the tumor and
ii. By the elaboration of hormones indigenous to the tissue of origin of the
tumor.
• They appear in 10% to 15% of patients with cancer.

46. Mechanism of Hypercalcemia in cancer patients:
• synthesis of a parathyroid hormone-related protein (PTHrP) by tumor cells
• Tumor produces TGF-α, a polypeptide factor that activates osteoclasts
• NB. Hypercalcemia following a widespread osteolytic metastatic
disease of bone is not a paraneoplastic syndrome
Mechanism for Cushing syndrome:
• Ectopic production of ACTH or ACTH-like polypeptides by cancer cells.

47. Cancer Cachexia
• It is a progressive loss of body fat and lean body mass
accompanied by profound weakness, anorexia and anemia.
• Its severity correlates with the size and extent of spread of the
cancer
• Causes of cancer cachexia
• the action of cytokines such as TNFα (cachectin) produced by the
tumor – principal cause
• reduced food intake by the patients
• Increased calorie expenditure and basal metabolic rate

48. THANKS