22. Cancer (L. Crab)
• Any malignant growth of cells (clonal)
• Nearly 7 lakh people die of cancer in
India (2015)
Gross features Microscopic featuresGross features Microscopic features
25. The following figure shows how cancer cases have
been progressively increasing from 2004 to 2010
26. Definition
• “Willis” definition of Neoplasia - (new growth)
abnormal mass of tissue, the growth of which
exceeds and is uncoordinated with the normal
tissues and continues to grow even after the
cessation of the stimulus that evoked the
initial response
• New Definition: (Robbins Path) a neoplasm
can be defined as a disorder of cell growth
that is triggered by a series of acquired
mutations affecting a single cell and its clonal
progeny
28. Neoplasm
The causative mutations give the
neoplastic cells a survival and growth
advantage, resulting in excessive
proliferation that is independent of
physiologic growth signals
(autonomous)
30. Neoplasia
• It is autonomous, purposeless
• Proliferation is uncontrolled
• Competes with normal cells for its needs
• It is a clonal disorder
• It is a genetic disorder
– In 95% of cases acquired genetic disorder
– In 5% of cases inherited
31. Nomenclature
• All tumors have two components
– Parenchyma
• Represents tumor proper; the growth of the tumor
is due to proliferation of these cells
– Stroma
• Provides the framework, blood supply and nutrition
for the parenchymal cells
34. Desmoplasia
• Formation of abundant collagenous stroma
• Stimulated by parenchymal cells
• Ex: Schirrous. ca of breast
Linitus plastica (ca stomach)
Carcinoma prostate
38. Nomenclature
• Tumors are designated by attaching suffix “–oma”
to the cell or tissue of origin
– Fibroma, chondroma, lipoma, osteoma etc
– Benign tumor arising from glandular structure is called
adenoma
– Benign tumor arising from epithelial surface having finger
like projections is called papilloma
– Malignant tumor arising from epithelial tissue is called
Carcinoma
– Malignant tumor arising from mesenchymal tissue is
called Sarcoma
45. Placental epithelium Hydatidiform mole Choriocarcinoma
Testicular epithelium
(germ cells)
Seminoma
Embryonal carcinoma
Melanocytic Tumors Nevus Malignant melanoma
More Than One Neoplastic Cell Type-Mixed Tumors, Usually Derived from
One Germ Cell Layer
Salivary glands Pleomorphic adenoma
(mixed tumor of salivary
origin)
Malignant mixed tumor
of salivary gland origin
Renal anlage Wilms’ tumor
More Than One Neoplastic Cell Type Derived from More Than One Germ
Cell Layer-Teratogenous
Totipotential cells in
gonads or in embryonic
rests
Mature teratoma, dermoid
cyst
Immature teratoma,
teratocarcinoma
46. Tissues with NO benign tumors
• Synovium
• Mesothelium
• Lymphoid tissue
• Hematopoietic cells
• Basal cells of skin or adnexa
47. Nomenclature
• Malignant tumor arising from epithelial
structures is called “Carcinoma”
• Malignant tumor of the mesenchymal
tissues is called “Sarcoma”
• Embryonal tumors usually have the suffix
“Blastoma”
• Malignant lesions of the blood are called
“Leukemia”
• Malignant lesions of the lymphoid tissue is
called “Lymphoma”
50. Neoplasms of Embryonic
Pluripotent Cells
• Pluripotent cells can mature into several
different cell types
• These neoplasms are generally called
Embryomas or Blastomas
51. Blastoma
• All blastomas are childhood tumors
• All blastomas are malignant tumors
Except:
–Chondroblastoma
–Osteoblastoma
–Pulmonary blastoma
54. Exceptions to These Rules
• Neoplasms That Sound Benign But Are
Really Malignant
• Neoplasms That Sound Malignant But Are
Really Benign
• Leukemias
• Mixed Tumors
• Neoplasms Whose Cell of Origin Is
Unknown
Lymphoma
Plasmacytoma
Melanoma
Glioma
Astrocytoma
Osteoblastoma
Chondroblastoma
55. Nomenclature
• Some malignant tumors named like
benign tumors
– Melanoma, Hepatoma, Lymphoma
• Some benign tumors named like
malignant tumors
– Cystosarcoma phylloides, chondroblastoma
• Some unusual tumors
– Mixed tumor of salivary gland (pleomorphic
adenoma)
– Teratoma
56. Mixed tumor
• Tumors with single type of
parenchymal cells that differentiates
into many cell lines
–Eg: Pleomorphic adenoma of salivary
gland.
58. Teratoma
• Tumor arising from totipotent cells (germ
cells) showing differentiation towards
tissues derived from all the three germ cell
layers
– Seen usually along the midline
– Common sites
• Ovary, testis, sacro-coccygeal region, retro-
peritoneum, mediastinum, base of the brain etc
59. What are the common sites for teratomas ?
• Gonads
• Mid line
• Lines of fusion
69. Hamartomas & Choristomas
• A hamartoma is composed of tissues that are
normally present in the organ in which the tumor
arises
– Eg: a hamartoma of the lung consists of a
disorganized mass of bronchial epithelium and
cartilage that may become so large that it presents as
a lung mass. Its growth is coordinated with that of the
lung itself
• A choristoma resembles a hamartoma but
contains tissues that are not normally present in
its site of origin
– Eg: A orderly mass of pancreatic acini and ducts in
the wall of the stomach is properly called a
choristoma.
71. Hamartoma
• Definition - Jumbled mixture of tissue native to
the site / organ
• Eg: Hamartoma of lung
72. Choristoma
• Definition – Normal organized tissue at an abnormal
site (ectopic rest of normal tissue)
• Eg: adrenal cells under kidney capsule, pancreas in
stomach
74. In 1915 Drs. Koichi Ichikawa
and Katsusaburo Yamagiwa of
the Hokkaido University, Japan
painted coal tar on the ears of
101 rabbits every 2 or 3 days.
75. In 1775, Dr. Percivall Pott, a British surgeon,
reported one of the earliest observations on
environmental / occupational cancer
76. Two common
cancers in
our country
in India, cancers of
lung and mouth in
men and cervix and
breast in women are
the biggest killers
What do you think we are going to discuss in this chapter?
I will give you some clinical examples to grasp the central idea.
What is the common name given for these lesions?
Can you name the etiological agent responsible for this?
Lifted ear lobule is characteristic feature of parotid tumor
Which structure is involved in this abnormality?
What is this common lesion?
Another common problem in our country.
Have seen these types of cases?
What is the diagnosis?
What is this case?
Describe the abnormality.
What is this case?
Can you add something more?
Identify the structure and describe the abnormality?
Identify the structure?
Is it normal or abnormal?
What is the common name for this?
Identify the structure?
Is it normal or abnormal?
What is the common name for this?
This is the sectioned uterus.
Identify the structure?
Is it normal or abnormal?
What is the common name for this?
Laparoscopic view of the same.
Identify the structure?
Is it normal or abnormal?
Describe the abnormality.
What is this skin lesion?
Malignant = evil
Malignant = (of a disease) very virulent or infectious.
Malignancy (from Latin male, meaning "badly", and -gnus, meaning "born")
Malignant = evil
Malignant = (of a disease) very virulent or infectious.
Malignancy (from Latin male, meaning "badly", and -gnus, meaning "born")
Second most common cause of death in US
One in 3 Americans will die of cancer:
According to a World Health Organization report, premature deaths by non-communicable diseases is one of the highest in India. Of all the other non-communicable diseases like cardiovascular ailments, chronic respiratory problems and diabetes, cancer is a major public health concern.
The cancer burden in developing countries is reaching pandemic proportions. Cancer is one of the leading causes of death in India, with about 2.5 million cancer patients, 1 million new cases added every year and with a chance of the disease rising five-fold by 2025. Indian Council of Medical Research (ICMR) has urged the Government of India to make cancer a notifiable disease. There is a high probability of treating cancers if detected early -- in Stage I or Stage II.
As per a Boston Consulting Group study, 70-80% of cancer patients are diagnosed late when treatment is less efficient and 60% of them do not have access to quality cancer treatment. Out of 300+ cancer centres in India, 40% are not adequately equipped with advanced cancer care equipment. This study further suggests India will need at least 600 additional cancer care centres to meet the requirements by 2020.
A report quotes Dr Pankaj Chaturvedi of Tata Memorial Hospital as saying that annually, nearly 5 lakh people die of cancer in India. As per WHO Report 2005, this number is only expected to rise to 7 lakh by 2015.
Tumor parenchyma and stroma
Note the desmoplasia – whitish area with irregular margins.
Fibrosis retracts the tumor from the surrounding tissue.
Note the bulging of surrousnt fat above the grey white retracted tumor.
Siffix –oma indicates tumor.
Tumors are named after their tissue of origin. Eg: fibrous tissue - fibroma
Neoplasms of totipotent cells (germ cell neoplasms, bottom), compared with the development of the normal zygote (top). Neoplastic germ cells retain the same potential for differentiation as the zygote and are classified according to the types of differentiation present.
==================
Neoplasms of Totipotent Cells
The prototype of the totipotent cell—ie, a cell that is capable of differentiating (maturing) into any cell type in the body—is the zygote, which gives rise to the embryo, and the eventual fetus. In postnatal life, the only totipotent cells in the body are the germ cells. These are most commonly found in the gonads but also occur in the retroperitoneum, mediastinum, and pineal region.
Germ cell neoplasms (Figure 17-3) may remain with minimal differentiation as a mass of malignant primitive germ cells (seminoma and embryonal carcinoma) or may develop into a variety of tissues, including trophoblast (choriocarcinoma), yolk sac (yolk sac carcinoma), or somatic structures (teratoma) (Table 17-4). Mixtures of different tissues frequently coexist in a single neoplasm.
Teratomas show somatic differentiation and contain elements of all three germ layers: endoderm, ectoderm, and mesoderm. Thus, brain, respiratory and intestinal mucosa, cartilage, bone, skin, teeth, or hair may be seen in the neoplasm. The constituent tissues are not limited to those normally present in the area of origin. One older hypothesis held that teratomas represented a maldeveloped included twin (twin within a twin), but teratomas differ from fetuses in that the various tissues are largely disorganized. Testicular teratomas are diploid or aneuploid, with both X and Y chromosomes; they appear to arise before the first meiotic division and contain the same heterozygous pairs of alleles as are found in the normal host cells. In the ovary, teratomas are usually 46,XX but frequently show homozygous allelic pairs, suggesting an origin after the first meiotic division.
Teratomas are classified as mature (well-differentiated and composed of adult-type tissues) or immature (made up of fetal-type tissues). Immature teratomas are malignant, whereas mature teratomas vary in their biologic potential. Most mature teratomas are benign, eg, mature teratoma of the ovary (dermoid cyst) (Chapter 52: The Ovaries & Uterine Tubes). Mature testicular teratomas are benign when they occur in childhood but are usually malignant in adult testes. In teratomas, the distinction between benign and malignant incorporates unusual criteria such as maturity of constituent tissues, site of occurrence, and age of the patient.
Pluripotent cells can mature into several different cell types, and the corresponding neoplasms have the potential for formation of diverse structural elements; neoplasms of the renal anlage cells (nephroblastoma) commonly differentiate into structures resembling renal tubules and less often into rudiments of muscle, cartilage, and bone
These neoplasms are generally called embryomas or blastomas
Name some childhood tumors:
Name all blastomas except, Chondroblastoma, Osteoblastoma, Pulmonary blastoma.
Pluripotent cells can mature into several different cell types, and the corresponding neoplasms have the potential for formation of diverse structural elements; neoplasms of the renal anlage cells (nephroblastoma) commonly differentiate into structures resembling renal tubules and less often into rudiments of muscle, cartilage, and bone. These neoplasms are generally called embryomas or blastomas
Embryonic pluripotent cells are found only in the fetal period and during the first few years of postnatal life. The corresponding neoplasms usually occur in early childhood and only rarely in adults.
Blastomas may be completely undifferentiated—ie, are composed of small, malignant, primitive-appearing, hyperchromatic cells—or may show evidence of differentiation, eg, the presence of primitive renal tubules in nephroblastoma or of ganglion cells in neuroblastoma. Evidence of differentiation generally signifies less malignant biologic behavior.
Epithelial Neoplasms
A benign epithelial neoplasm is called an adenoma if it arises within a gland (eg, thyroid adenoma, colonic adenoma) or a papilloma (Latin, papilla = nipple) when arising from an epithelial surface. Papillomas may arise from squamous, glandular, or transitional epithelium (eg, squamous papilloma, intraductal papilloma of the breast, and transitional cell papilloma, respectively). Not uncommonly, descriptive adjectives are incorporated in the nomenclature; eg, colonic adenomas may be villous or tubular.
Malignant epithelial neoplasms are called carcinomas (adenocarcinomas if derived from glandular epithelia; squamous carcinoma and transitional cell carcinoma if originating in those kinds of epithelia). Names may also include the organ of origin and often an adjective as well, eg, clear cell adenocarcinoma of the kidney, papillary adenocarcinoma of the thyroid, verrucous squamous carcinoma of the larynx.
Mesenchymal Neoplasms
Benign mesenchymal neoplasms are named after the cell of origin (a Greek or Latin word is used) followed by the suffix -oma (Table 17-4). The names of these tumors may contain the organ of origin and an adjective, eg, cavernous hemangioma of the liver.
Malignant mesenchymal neoplasms are named after the cell of origin, to which is added the suffix -sarcoma. Again, adjectives are commonly used; liposarcomas are classified as sclerosing, myxoid, round cell, or pleomorphic.
Exceptions to These Rules
This simple scheme is complicated by several neoplasms that do not fit in.
Neoplasms That Sound Benign But Are Really Malignant
The names of some malignant neoplasms are formed by adding the suffix -oma to the cell of origin, eg, lymphoma (lymphocyte), plasmacytoma (plasma cell), melanoma (melanocyte), glioma (glial cell), and astrocytoma (astrocyte). The adjective malignant should be used—malignant lymphoma, malignant melanoma—but if it is not, these neoplasms are assumed to be malignant because there is no benign lymphoma, melanoma, glioma, etc.
Neoplasms That Sound Malignant But Are Really Benign
Two rare bone neoplasms, osteoblastoma and chondroblastoma, may sound malignant because of the suffix -blastoma but are in fact benign neoplasms derived from osteoblasts and chondroblasts present in adult bone.
Leukemias
Neoplasms of blood-forming organs are called leukemias. These disorders are all considered malignant, although some exhibit a slower clinical course than others (Chapter 26: Blood: III. the White Blood Cells). Leukemias are classified on the basis of their clinical course (acute or chronic) and cell of origin (lymphocytic, granulocytic [myelocytic], monocytic, etc). Leukemias are characterized by the presence of neoplastic cells in bone marrow and peripheral blood; they rarely produce localized tumors.
Mixed Tumors
Neoplasms composed of more than one neoplastic cell type are called mixed tumors. Malignant mixed tumors may have two epithelial components, as in adenosquamous carcinoma; two mesenchymal components, as in malignant fibrous histiocytoma; or an epithelial and a mesenchymal component, as in carcinosarcoma of the lung and malignant mixed müllerian tumor of the uterus.
The existence of mixed tumors poses certain conceptual problems: Are they neoplasms derived from two separate cell lines that coincidentally became neoplastic at the same time, or are they neoplasms of a single multipotent cell type that then differentiates along more than one pathway? The latter is considered more likely.
In the case of benign mixed tumors such as fibroadenoma of the breast, most investigators believe that only the epithelial (adenoma) component is neoplastic and that fibrous tissue represents some form of reaction to the adenoma cells.
Neoplasms Whose Cell of Origin Is Unknown
When the cell of origin is unknown, the name of the person who first described the neoplasm is commonly used to name the tumor (Table 17-5). As the histogenesis of these neoplasms is clarified, the name is often changed: Wilms' tumor is now called nephroblastoma, and Grawitz's tumor is better known as renal adenocarcinoma. Some neoplasms of uncertain histogenesis are named descriptively, eg, granular cell tumor (from Schwann cells?), alveolar soft part sarcoma (from rhabdomyoblasts?).
Teratoma of trestis and ovary
Neoplasms of totipotent cells (germ cell neoplasms, bottom), compared with the development of the normal zygote (top). Neoplastic germ cells retain the same potential for differentiation as the zygote and are classified according to the types of differentiation present.
==================
Neoplasms of Totipotent Cells
The prototype of the totipotent cell—ie, a cell that is capable of differentiating (maturing) into any cell type in the body—is the zygote, which gives rise to the embryo, and the eventual fetus. In postnatal life, the only totipotent cells in the body are the germ cells. These are most commonly found in the gonads but also occur in the retroperitoneum, mediastinum, and pineal region.
Germ cell neoplasms (Figure 17-3) may remain with minimal differentiation as a mass of malignant primitive germ cells (seminoma and embryonal carcinoma) or may develop into a variety of tissues, including trophoblast (choriocarcinoma), yolk sac (yolk sac carcinoma), or somatic structures (teratoma) (Table 17-4). Mixtures of different tissues frequently coexist in a single neoplasm.
Teratomas show somatic differentiation and contain elements of all three germ layers: endoderm, ectoderm, and mesoderm. Thus, brain, respiratory and intestinal mucosa, cartilage, bone, skin, teeth, or hair may be seen in the neoplasm. The constituent tissues are not limited to those normally present in the area of origin. One older hypothesis held that teratomas represented a maldeveloped included twin (twin within a twin), but teratomas differ from fetuses in that the various tissues are largely disorganized. Testicular teratomas are diploid or aneuploid, with both X and Y chromosomes; they appear to arise before the first meiotic division and contain the same heterozygous pairs of alleles as are found in the normal host cells. In the ovary, teratomas are usually 46,XX but frequently show homozygous allelic pairs, suggesting an origin after the first meiotic division.
Teratomas are classified as mature (well-differentiated and composed of adult-type tissues) or immature (made up of fetal-type tissues). Immature teratomas are malignant, whereas mature teratomas vary in their biologic potential. Most mature teratomas are benign, eg, mature teratoma of the ovary (dermoid cyst) (Chapter 52: The Ovaries & Uterine Tubes). Mature testicular teratomas are benign when they occur in childhood but are usually malignant in adult testes. In teratomas, the distinction between benign and malignant incorporates unusual criteria such as maturity of constituent tissues, site of occurrence, and age of the patient.
1Although the histogenesis is known, the eponyms are retained because they denote a specific type of neoplasm that differs from others with a similar histogenesis.
An eponym is a person or thing, whether real or fictional, after which a particular place, tribe, era, discovery, or other item is named or thought to be named.
Hamartomas & Choristomas
Hamartomas and choristomas are tumor-like growths thought to be the result of developmental anomalies. They are not true neoplasms (ie, they do not show continuous excessive growth). The tumors are abnormal, disorganized, proliferating masses of several different adult cell types.
A hamartoma is composed of tissues that are normally present in the organ in which the tumor arises; a hamartoma of the lung consists of a disorganized mass of bronchial epithelium and cartilage that may become so large that it presents as a lung mass. Its growth is coordinated with that of the lung itself.
A choristoma resembles a hamartoma but contains tissues that are not normally present in its site of origin. A disorderly mass of smooth muscle and pancreatic acini and ducts in the wall of the stomach is properly called a choristoma. A gastric choristoma such as this may present as an intramural mass that is clinically indistinguishable from a benign neoplasm.
Increased vascularity of sarcoma results in local raise of temperature and may clinically resemble an inflammatory lesion.
In 1915 Drs. Koichi Ichikawa and Katsusaburo Yamagiwa of the Hokkaido University, Japan painted coal tar on the ears of 101 rabbits every 2 or 3 days.
Rabbit ear experiment to prove chemical carcinogenesis.
Drs. Koichi Ichikawa and Katsusaburo Yamagiwa of the Hokkaido University, Japan painted coal tar on the ears of 101 rabbits every 2 or 3 days. They designed their experiment because of the common knowledge that boys who were chimney sweeps developed cancers from exposure to tar build-up on the inside of chimneys. Abnormal growths were seen on the rabbit ears in just 30 to 100 days. After 150 days, 100% of the rabbits developed cancer.For this discovery, the first of its kind, Ichikawa and Katsusaburo were nominated for a Nobel Prize, which would have been Japan's first. Ironically they lost out to a Danish researcher who had compelling evidence that stomach cancers were caused by parasites, which was later proven to be false.
How does this relate to coal tar sealants? While coal tar sealants have some rather inert substances added to them, research has shown the following:
coal tar sealants, like coal tar, are potent mutagens (Just How Toxic are Coal Tar Sealants?")
coal tar sealants, like coal tar, contain human carcinogens. (National Institutes of Health says: "Coal tars and coal-tar pitches are known to be human carcinogens based on sufficient evidence of carcinogenicity from studies in humans.http://ntp.niehs.nih.gov/ntp/roc/twelfth/profiles/CoalTars.pdf
Cancer Risks Shown "Significant" For Children Near Coal Tar Sealant Dust/Dirt
the toxic portion of coal tar, PAHs (polycyclic aromatic hydrocarbons) are about 25% less in coal tar sealants than in a standard coal tar solution. Purity of Refined Coal Tar
Now if only we all had a briar patch to keep coal tar sealants from affecting us as well or maybe we should just stop using them altogether.
In 1775, Dr. Percivall Pott, a British surgeon, reported one of the earliest observations on environmental cancer. SOURCE: U.S. Government.
in India, cancers of lung and mouth in men and cervix and breast in women are the biggest killers