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Neoplasia introduction
This document provides information on neoplasia (new growth) and tumor nomenclature. It defines neoplasia as abnormal and uncontrolled cell growth that exceeds normal tissues. Tumors are named based on their cell or tissue of origin, with benign tumors ending in "-oma" and malignant tumors called carcinomas for epithelial cells and sarcomas for mesenchymal cells. Common sites for teratomas are the gonads and along midline fusion lines. Hamartomas contain normal tissues for the organ, while choristomas contain ectopic tissues. Environmental exposures like coal tar were found to induce skin cancer in rabbits.
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Neoplasia introduction
- 1.
- 2. • Metaplasia • Dysplasia •Anaplasia • Complication of chronic inflammation / irritation
- 3. Clinical examples ofNeoplasia
- 19. Nomenclature • Neoplasia • Neoplasm •Tumor • Oncology • Clonal / Clonality • Benign • Malignant (Latin) • Cancer
- 20. Neoplasia - Definition •Neo = New • Plasia = Growth Neoplasia = New growth • Tumor = Swelling • Cancer = Crab (L) • Oncology = Study of tumor / Neoplasm (Oncos = Tumor)
- 21. Nomenclature • Normal • Abnormal –Non neoplastic • Hyperplasia • Metaplasia – Precancerous (dysplasia / in situ carcinomas) – Neoplastic • Benign – Epithelial – Mesenchymal • Malignant – Epithelial – Mesenchymal
- 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
- 23.
- 24.
- 25. The following figureshows how cancer cases have been progressively increasing from 2004 to 2010
- 26. Definition • “Willis” definitionof 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
- 27. Normal – Hyperplasia– Dysplasia – Carcinoma
- 28. Neoplasm The causative mutationsgive the neoplastic cells a survival and growth advantage, resulting in excessive proliferation that is independent of physiologic growth signals (autonomous)
- 29. Makes an interestingreading…
- 30. Neoplasia • It isautonomous, 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 tumorshave 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
- 32.
- 34. Desmoplasia • Formation ofabundant collagenous stroma • Stimulated by parenchymal cells • Ex: Schirrous. ca of breast Linitus plastica (ca stomach) Carcinoma prostate
- 35. Scirrhous carcinoma ofbreast
- 36. Scirrhous carcinoma ofbreast
- 37.
- 38. Nomenclature • Tumors aredesignated 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
- 39. Papilloma / Polyp/ Adenoma
- 40. Papilloma / Polyp/ Adenoma Pedunculated polyp Sessile polyp
- 41. Papilloma / Polyp/ Adenoma
- 42. Tissue of OriginBenign Malignant Composed of One Parenchymal Cell Type Tumors of mesenchymal origin Connective tissue and derivatives Fibroma Fibrosarcoma Lipoma Liposarcoma Chondroma Chondrosarcoma Osteoma Osteogenic sarcoma Endothelial and related tissues Blood vessels Hemangioma Angiosarcoma Lymph vessels Lymphangioma Lymphangiosarcoma Synovium Synovial sarcoma Mesothelium Mesothelioma Brain Coverings Meningioma Invasive meningioma
- 43. Tissue of OriginBenign Malignant Blood cells and related cells Hematopoietic cells Leukemias Lymphoid tissue Lymphomas Muscle Smooth Leiomyoma Leiomyosarcoma Striated Rhabdomyoma Rhabdomyosarcoma
- 44. Tumors of epithelialorigin Stratified squamous Squamous cell papilloma Squamous cell carcinoma Basal cells of skin or adnexa Basal cell carcinoma Epithelial lining of glands or ducts Adenoma Adenocarcinoma Papilloma Papillary carcinomas Cystadenoma Cystadenocarcinoma Respiratory passages Bronchial adenoma Bronchogenic carcinoma Renal epithelium Renal tubular adenoma Renal cell carcinoma Liver Cell Adenoma Hepatocellular carcinoma Urothelial cell Papilloma Urothelial carcinoma
- 45. Placental epithelium Hydatidiformmole 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 NObenign tumors • Synovium • Mesothelium • Lymphoid tissue • Hematopoietic cells • Basal cells of skin or adnexa
- 47. Nomenclature • Malignant tumorarising 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”
- 49.
- 50. Neoplasms of Embryonic PluripotentCells • Pluripotent cells can mature into several different cell types • These neoplasms are generally called Embryomas or Blastomas
- 51. Blastoma • All blastomasare childhood tumors • All blastomas are malignant tumors Except: –Chondroblastoma –Osteoblastoma –Pulmonary blastoma
- 52. Neoplasms of pluripotentembryonic-type cells (BLASTOMAs)
- 53. Nomenclature of Neoplasmsof Differentiated Cells
- 54. Exceptions to TheseRules • 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 malignanttumors 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 • Tumorswith single type of parenchymal cells that differentiates into many cell lines –Eg: Pleomorphic adenoma of salivary gland.
- 57. Pleomorphic adenoma -Parotid
- 58. Teratoma • Tumor arisingfrom 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 thecommon sites for teratomas ? • Gonads • Mid line • Lines of fusion
- 62. Along the linesof fusion
- 63.
- 65.
- 66.
- 67.
- 68.
- 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.
- 70. Sarcomas are veryvascular -local rise of temperature
- 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
- 73. A wrong decision JohannesFibiger Nobel prize winner in 1926 Katsusaburo Yamagiwa
- 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 ourcountry in India, cancers of lung and mouth in men and cervix and breast in women are the biggest killers
- 77.
Editor's Notes
- #2 What do you think we are going to discuss in this chapter? I will give you some clinical examples to grasp the central idea.
- #5 What is the common name given for these lesions? Can you name the etiological agent responsible for this?
- #6 Lifted ear lobule is characteristic feature of parotid tumor
- #7 Which structure is involved in this abnormality?
- #8 What is this common lesion?
- #9 Another common problem in our country.
- #10 Have seen these types of cases? What is the diagnosis?
- #11 What is this case? Describe the abnormality.
- #12 What is this case? Can you add something more?
- #13 Identify the structure and describe the abnormality?
- #14 Identify the structure? Is it normal or abnormal? What is the common name for this?
- #15 Identify the structure? Is it normal or abnormal? What is the common name for this? This is the sectioned uterus.
- #16 Identify the structure? Is it normal or abnormal? What is the common name for this? Laparoscopic view of the same.
- #17 Identify the structure? Is it normal or abnormal? Describe the abnormality.
- #18 What is this skin lesion?
- #20 Malignant = evil Malignant = (of a disease) very virulent or infectious. Malignancy (from Latin male, meaning "badly", and -gnus, meaning "born")
- #21 Malignant = evil Malignant = (of a disease) very virulent or infectious. Malignancy (from Latin male, meaning "badly", and -gnus, meaning "born")
- #23 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.
- #34 Tumor parenchyma and stroma
- #36 Note the desmoplasia – whitish area with irregular margins.
- #37 Fibrosis retracts the tumor from the surrounding tissue. Note the bulging of surrousnt fat above the grey white retracted tumor.
- #39 Siffix –oma indicates tumor. Tumors are named after their tissue of origin. Eg: fibrous tissue - fibroma
- #50 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.
- #51 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
- #52 Name some childhood tumors: Name all blastomas except, Chondroblastoma, Osteoblastoma, Pulmonary blastoma.
- #53 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.
- #54 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.
- #55 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?).
- #62 Teratoma of trestis and ovary
- #64 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.
- #69 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.
- #70 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.
- #71 Increased vascularity of sarcoma results in local raise of temperature and may clinically resemble an inflammatory lesion.
- #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 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.
- #76 In 1775, Dr. Percivall Pott, a British surgeon, reported one of the earliest observations on environmental cancer. SOURCE: U.S. Government.
- #77 in India, cancers of lung and mouth in men and cervix and breast in women are the biggest killers