Neoplasia (I, V): Intro and Epidemiology Flashcards
Definitions and Classification
Neoplasm: Suffix -oma
_Uncontrolled, *Autonomous *Overgrowth of Cells without protective purpose for the host
_Progressive and Persistent
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Benign Tumors: _Suffix: -oma _Prefix: Cell/Tissue of Origin Example: Adenoma = Benign Epithelial Neoplasm producing glands or derived from glands
Malignant Tumors:
_Suffix: Carcinoma or Sarcoma
_Prefix: Cell/Tissue of Origin
Carcinoma (karkinos, crab): = *Epithelial Malignant Neoplasm Examples: _Squamous cell or epidermoid carcinoma _Basal cell carcinoma _Adenocarcinoma (adenos = gland)
Sarcoma (sarkos, flesh): = *Connective Tissue Malignant Neoplasms (stroma) Examples: _Liposarcoma _Fibrosarcoma _Osteosarcoma
Mixed Tumors
Mixed Tumors: = Neoplasms Composed of More Than One Cell Type Derived from One Germ Cell Layer Examples: _Mixed Tumor of Salivary Gland _Pleomorphic Adenoma _Fibroadenoma of the Breast
Teratomas:
= Neoplasms composed of More Than One Cell Type Derived from More Than One Germ Cell Layer:
_Typically Arise from Totipotential Cells in Gonads
_Can be Benign (Mature) or Malignant (Immature).
Exceptions: Malignant -Omas
Exceptions: Malignant -Omas
1) Lymphoma, Mesothelioma, Melanoma, Seminoma:
= MALIGNANT
_Lymphomas are ALWAYS Malignant.
_Mesotheliomas are most often Malignant. Frequently occur in Pleura.
_Melanomas are the Most Malignant Tumors that exist.
_Seminomas are Malignant.
2) Blastoma: MALIGNANT = Primitive or Embryonal Malignant Tumors. _Occur in Children. _Highly Malignant _Childhood cancers have better prognosis, though, and respond well to chemotherapy. Examples: _Neuroblastoma _Retinoblastoma _Hepatoblastoma
3) Endocrine Tumors: Named by Secretory Product => Some behave Benign; Some behave Malignant. Difficult to Predict. Examples: _Insulinoma _Glucagonoma _Prolactinoma 4) Hamartoma: NOT CANCER = NOT A NEOPLASM = IS A Congenital Malformation
Eponyms
Eponyms:
1) Hodgkin’s Disease:
= MALIGNANT Lymphoma with
Diagnostic Reed-Sternberg Cells
2) Burkitt’s Lymphoma:
= MALIGNANT Lymphoma of Small Non-cleaved Lymphocytes,
usually involving Extranodal sites.
3) Kaposi’s Sarcoma:
= Single or Disseminated Vascular-Like Proliferation that Develops Spontaneously or Complicates AIDS.
4) Wilms’ Tumor or Nephroblastoma:
= Embryonal Carcinosarcoma of Kidney
5) Ewing’s Sarcoma:
= Primitive Neuroectodermal Tumor of Bone and Paraskeletal Soft Tissue
Secondary Descriptors
Secondary Descriptors:
1) Cystadenoma:
= Hollow Cystic Masses typically seen in Ovaries
_The Malignant form
= Cystadenocarcinoma
2) Polyp:
= Neoplasm that projects above the Mucosal surface, producing an Exophytic Mass:
_Fibroepitihelial Polyps of Skin
_Adenomatous Polyps of colon, aka Tubular Adenoma
Polyps can be Benign or Malignant.
3) Papilloma (papilla, nipple):
= Benign Epithelial Neoplasm that grows exophytically in Finger-like Fronds like a Cauliflower
_Benign or Malignant.
4) Papillary Adenocarcinoma:
= Adenocarcinomas in which Neoplastic Cells grow upon Stromal Finger-like projections.
Benign vs. Malignant
Benign Neoplasm:
1) Composed of Well-Differentiated Cells
2) Well Circumscribed
3) Remains Localized
4) Lacks Capacity to Invade or Spread Distantly (Metastasis)
Malignant Neoplasm:
1) Characterized by a Wide Range of Cell Differentiation, from Well-Differentiated to Completely Undifferentiated (Anaplastic) Cells.
2) Poorly Circumscribed
3) Invades Surrounding Tissues
4) Capable of Spreading Distantly or Metastasizing
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Differentiation:
= Resemblance to Parental Mature Cell and Tissue of Origin
_Morphologically, Phenotypically, Functionally
Dedifferentiation: = Process of Progressive Loss of Resemblance => Dedifferentiated Cells Display: (1) Marked Nuclear Pleomorphism (2) Hyperchromatic Nuclei (Dark) (3) Enlarged Nuclei (Increased N/C Ratio) (4) Increased Mitosis (5) Loss of Polarity
Anaplasia:
= Complete LOSS of Resemblance to Parental Mature Cell and Tissue of Origin
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1) Differentiation:
Benign: Very Well Differentiated;
_Closely Resemble Cell of Origin.
_Closely Express Function and Phenotypic Markers of Cell of Origin.
Malignant:
_Differentiation Varies by GRADE.
2) Rate of Growth:
Benign: Slow;
_May Plateau or Regress.
Malignant: Varies; Slow to Rapid; _Usually Progressive;
_Rarely Regress.
3) Mitosis:
Benign:
_Few Mitosis;
_Usually Normal or Bipolar.
Malignant: _Frequent Mitosis, especially in Grade IV; _Often Abnormal: Tripolar, Quadripolar.
4) Karyotype:
Benign: Usually Diploid.
Malignant: Near Diploid;
_Often Aneuploid and Polyploid
5) Local Growth:
Benign: Expansive (Centrifugal)
Malignant: Infiltrative (Crab-Like)
6) Capsule:
Benign: Often Encapsulated
Malignant: Seldom Encapsulated
7) Metastasis:
Benign: Absent
Malignant:
_Potential for Metastasis in Early Stages;
_Often Present in Late Stage
8) Mortality:
Benign: Low Mortality
Malignant: High Mortality
Nuclear Characteristics of Malignant Cells
The Most Significant Microscopic Features of Malignancy Occur
@ Cell Nuclei:
1) Nuclear Enlargement with Increased Nuclear/Cytoplasmic Ratio.
2) Nuclear Hyperchromasia
3) Irregular Nuclear Contour
4) Prominent Nucleoli
5) Abnormal Mitosis
Premalignant / Precancerous Lesions
= Lesions that have a Statistically Significant Potential to Transform or Evolve into a Malignant Neoplasm:
1) Tubular/Villous *Adenomas of Colon
2) *Dysplastic Nevi
(Atypical Melanocytic Hyperplasia)
(Atypical Mole)
3) *Epithelial Dysplasia
4) Actinic Keratosis of Sun-Damaged Skin
Dysplasia
= Disordered Cell Proliferation:
_Loss of Uniformity
_Loss of Architectural Orientation
Dysplastic Cells Have
_Hyperchromatic Nuclei
_Nuclear Pleomorphism
_Increased Mitosis
Dysplasias May Regress, Remain, or Progress into Carcinoma In Situ, which May Remain Localized or Become Invasive.
_Thus, this is a Continuum of Cytological Changes.
Dysplasia applies to squamous epithelia but can also be extended to glandular epithelia.
Carcinoma In Situ and
Intraepithelial Neoplasia
Carcinoma In Situ (CIS):
= Marked Dysplastic Changes involving the Entire Thickness of the Epithelium,
But still Confined Within the Epithelium
= Is a Preinvasive Neoplasm.
Intraepithelial Neoplasia:
= Includes Various grades of Dysplasia and Carcinoma In Situ (Full Thickness Dysplasia)
_Once the Neoplasm spreads beyond the epithelium, it is no longer intraepithelial.
Poor Morphological Correlation
Histologically MALIGNANT,
BUT Rarely Metastasize:
1) **Basal Cell Carcinoma
2) Fibrosarcoma protuberans
Histologically BENIGN or BORDERLINE,
BUT Sometimes MALIGNANT:
1) **Smooth Muscle Tumors
2) Carcinoid Tumors
Grade of Malignancy
= Degree of Cell Differentiation of a Neoplasm.
The Less Differentiation
=> The More Aggressive
=> More Likely to Metastasize
Grade I: Well Differentiated
Grade II: Moderately Differentiated
Grade III: Poorly Differentiated
Grade IV: Anaplastic (Undifferentiated)
Determination of Cell of Origin in Undifferentiated Neoplasms
(Nuclear Cell Morphology provides the diagnosis of Malignancy.)
*Characteristics of the *Cytoplasm Determines the Cell of Origin:
1) **Immunohistochemistry
2) Electron Microscopy
Invasion and Metastasis
Invasiveness and Metastasis are the 2 Most Reliable Features of Malignancy.
_Nearly All Benign Tumors grow cohesively as expandable masses that Remain Localized.
_Malignant Tumors First Invade Locally, then Spread Distantly (Metastasis).
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Growth of Cancer is Accompanied by *Progressive Invasion and *Destruction of Surrounding Tissues
Metastasis is the Single Most Important Criterion of Malignancy.
_Benign tumors do not metastasize.
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Metastasis Occurs 3 Ways:
1) Seeding of Body Cavity Surfaces:
_Examples: Peritoneal, Pleural, or Pericardial Cavities
_Characteristic of Ovarian Cancer
2) Lymphatic Spread:
= The Initial Way of Dissemination for CARCINOMAS
=> The pattern that follows the routes of lymphatic drainage.
(Will eventually reach blood b/c lymph returns to bloodstream)
3) Hematogenous Spread:
=> Typical of SARCOMAS
_Can also be seen in Carcinomas.
Stage of Malignancy
= Refers to
1) *Size,
2) *Local Invasiveness,
3) *Distant Spread (Metastasis)
T: Local topography and Size of Primary Lesion; T1-T4
N: # Lymph Node Involvement;
N0-N4
M: Metastasis to Distant Tissues/Organs; M0-M1
Clinically and Therapy-wise, Stage is often More Important than Grade.
Note: Stage and Grade apply only to Malignant cancers.
Cancer Epidemiology: Gender
** 1/5 Chancer of Dying from Cancer in U.S.
- *More than 50% of USA Cancers:
1) **Lung
2) **Breast
3) **Prostate
4) **Colorectal
Most Common:
- *Men:
1) **Prostate
2) **Lung
3) **Colorectal - *Women:
1) **Breast
2) **Lung
3) **Colorectal
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Death Rate has Increased over Last 50 Years (males and females).
Alarming Increase in Death Rates of Lung Cancer (males and females).
Most Recently, Overall Adjusted Cancer Death Rates have Decreased (males and females).
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Cancer Epidemiology: Disparities
Disparities:
1) Higher Mortality:
==> African Americans
2) Latinos: _Lower Frequency of Most Common Cancers _Higher Incidence of Other Cancers: => Stomach (estómago) => Liver (hídago) => Cervix (cuello uterino) => Gallbladder (vesícula)
Cancer Epidemiology: Age
Age has a Profound Effect on Cancer Incidence.
**Most Carciniomas: Over Age 55
**Cancer is FIRST Cause of Death:
=> **Women: Ages 40 - 79
=> **Men: Ages 60 - 79
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Children:
Death Rate 10% Under Age 15
**Acute Leukemias and **CNS Tumors = ** 60% of Deaths
Most Common Cancers of
Infancy and Childhood:
1) Neuroblastoma,
Wilms Tumor / Nephroblastoma,
Retinoblastoma
2) Acute Leukemia
3) Rhabdomyosarcoma
Occupational Cancers
- Asbestos => *Mesothelioma
* Benzene => *Leukemia
Genetic Predisposition to Cancer
*Environmental and *Hereditary Factors Predispose to Most Cancers
**Lung Cancer: Clearly Associated with **Tobacco Smoking
- *Mortality from Lung Cancer is
- 4x Higher Among *Non-Smoking Relatives of Lung Cancer Patients.
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*Genes Associated with *Familial Forms of Cancer are very *Often Also Involved in *Sporadic Cancers.
3 Types of Genetic Predisposition:
1) Autosomal Dominant:
=> Inherited Cancer Syndromes
2) Autosomal Recessive:
=> Defective DNA Repair Syndromes
3) Familial Cancers
Autosomal Dominant Cancer Syndromes
Autosomal Dominant Cancer Syndromes:
=> Inherited Cancer Syndromes
1) *Rb => Retinoblastoma
2) *p53 => Li Fraumeni Syndrome
3) *APC => Familial Adenomatous Polyposis / Colon Cancer
4) *BRCA1, *BRCA2
=> Breast and Ovarian Tumors
5) *MSH2, *MLH1, *MSH6
=> Hereditary Non-Poliposis Colon Cancer
Autosomal Recessive Cancer Syndromes
Autosomal Recessive Cancer Syndromes:
=> Defective DNA Repair Syndromes
(none are in red)
1) Xeroderma Pigmentosum
2) Ataxia-Telangiectasia
3) Bloom Syndrome
4) Fanconi Anemia
Familial Cancer Syndromes
Familial Clustering; Role of Inherited Predisposition is not always clear.
**Onset @ Early Age in 2 or More Close Relatives.
**Multiple or Bilateral Tumors.
Examples: Colon, Breast, Ovary, Brain, Melanoma.
Non-Hereditary Predisposing Conditions
**Regenerative, **Hyperplastic, and **Dysplastic Cell Proliferations
=> Are high risk for malignant transformation.
Examples: endometrial hyperplasia, bronchial metaplasia, cervical dysplasia, etc.
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**Chronic Inflammation:
=> Ulcerative Colitis, Crohn’s Disease, Helicobacter Pylori Gastritis, Viral Hepatitis, Chronic Pancreatitis, etc.
=> **ROS
=> Cytokines
=> COX-2 is overexpressed in colon cancer.
**Precancerous Conditions:
=> Chronic Atrophic Gastritis, Solar Keratosis, Leukoplakia, etc.
Clinical Features
All tumors, including Benign, may cause morbidity and mortality.
**Each Tumor Requires careful evaluation to rule out malignancy.
**Mass or **Lump:
=> Most Common Presenting Symptom of Benign or Malignant Tumors.
**All Masses Require Cytological or Histopathological Evaluation
(with some exceptions).
_
**Local Effects due to Impingement on Adjacent Structures
- *Tumor Functional Activity,
e. g. hormone production
**Paraneoplastic Syndromes
**Bleeding or Secondary *Infection, which may result in **Acute Symptoms.
*Symptoms from Metastasis
**Cachexia
Clinical Features:
Local Effect
Pituitary Adenoma:
= Benign Tumor that can Destroy the Pituitary, Leading to Endocrinopathy that can be Lethal.
Meningioma:
= Benign Tumor that can Lead to Intracranial Hypertension and Death.
Gut Tumors:
=> Can Cause Intestinal Obstruction, whether benign or malignant.
Clinical Features:
Hormonal Effect
Tumors @ Endocrine Glands:
=> May Overproduce Hormones, resulting in Endocrinopathy.
Non-Endocrine Tumors:
=> May produce Hormones and Hormone-Like Products,
=> Leading to
**Paraneoplastic Syndromes
Clinical Features:
Paraneoplastic Syndromes
Complex symptoms associated with cancer that
**Cannot be Explained by Local or Distant Spread.
Seen in **10% of Cancer Patients.
May represent the earliest manifestation of an occult tumor.
Symptoms may be a significant clinical problem or even lethal.
May mimic Metastatic Disease.
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Endocrinopathies:
1) *Cushing Syndrome:
_Small Cell Lung Cancer
_Pancreatic Cancer
_ACTH, ACTH-like peptides
2) *Hypercalcemia:
_SCLC, Breast, Renal, Adult T cell Leukemia
_PTH related peptide, TGF-alpha
3) *Hypoglycemia:
_Fibrosarcoma, HCC
_Insulin, Insulin-like hormones
4) *Polycythemia:
_RCC, HCC, Cerebellar Hemangioma
_Erythropoietin
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Nerve and Muscle Syndromes:
1) *Myasthenia:
_Bronchogenic Carcinoma
_Immunologic
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Dermatologic Disorders:
1) *Acanthosis Nigricans:
_Gastric, Lung, Uterine Cancers
_Immunologic, EGF
2) *Dermatomyositis:
_Bronchogenic, Breast
_Immunologic
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Vascular and Hematologic Changes:
1) *Venous Thrombosis
(Trousseau Phenomenon)
_Pancreatic, Bronchogenic
_Tumor products (Mucins)
2) *Anemia:
_Thymic Tumors
_Unknown
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Others:
1) *Nephrotic Syndrome:
_Various cancers
_Tumor Antigens, Immune Complexes
Cachexia
= Wasting Syndrome Associated with Cancer
Characterized By:
1) *Progressive LOSS of Body FAT and MUSCLE Mass
2) *Weakness
3) *Anorexia
4) *Anemia
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*NOT Caused by increased tumor nutritional demands.
Factors released by tumor or the immune response, such as **Cytokines, may be related to the cause.
*Abnormalities in *Taste an *Appetite are often seen in Cancer patients;
_However, reduced food intake is not enough to explain cancer cachexia.
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**Basal Metabolism is Increased,
Despite *Reduced Food Intake.
There is **Equal Loss of Muscle and Fat.
Whereas in Starvation, muscle mass is better preserved.
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Many of these changes, including loss of Appetite and changes in Fat Metabolism,
=> Mimic the Effects of Exogenous **TNF-Alpha Administration.
Releas of TNF-alpha by Macrophages or even Tumor cells may play a major role in cancer cachexia.
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IL-1 and IFN-gamma synergize TNF-alpha and may play a role.
Other soluble factors, such as the
**Proteolysis Inducing Factor (PIF), may play a role.
Administration of PIF causes Rapid Weight Loss in healthy mice without reduction in food intake, increasing Catabolism of muscle and adipose tissue.
Neutralization of Non-cytokine factors, such as PIF, may help to ameliorate cancer cachexia.
Cancer Lab Diagnosis
Histologic Diagnosis Cytologic Diagnosis Immunohistochemistry Flow Cytometry Molecular Pathology
Cancer Biomarkers:
_Hormones:
1) *HCG: Trophoblastic and Germ Cell Tumors
_Oncofetal Antigens:
2) *AFP: Germ Cell Tumors
3) *CEA: Colonic, Pancreatic, Gastric
_Isoenzymes:
4)*NSE: Small Cell Lung Cancer
_Specific Proteins:
5) *PSA: Prostate
6) *Ig: Multiple Myeloma
_Mucins/Glycoproteins:
7) *CA-125: Ovarian
8) *CA-19-9: Colonic, Pancreatic
