Neoplasia I-General Principles

Question 1

Uncontrolled cell proliferation due to abnormal regulation of cellular signaling pathways leading to a mass or nodule defines:

1) dysplasia
2) metaplasia
3) neoplasia
4) hyperplasia

Answer 1

Neoplasia.
Dysplasia is the presence of polymorphism (cells of different shape and size), disordered growth of epithelium, it is a precancerous condition.
Metaplasia is the tissue transformation from one type to another (Barret’s esophagus is due to metaplasia of squamous epithelium into columnar epithelium)
Hyperplasia is the increase in tissue size due to an increase in cell numbers

Question 2

Tumour and neoplasia are synonymous. T/F

Answer 2

False.
Tumor = any type of lump or mass from any cause e.g. hematoma, abscess, scar, whereas neoplasm is the Uncontrolled cell proliferation due to abnormal regulation of cellular signaling pathways leading to a mass or nodule

Question 3

what differentiates hyperplasia from neoplasia?

Answer 3

hyperplasia is controlled whereas neoplasia is uncontrolled by the immune system

Question 4

define monoclonal vs polyclonal proliferation

Answer 4

Monoclonal-all cells are derived from one cell line (in leukemias all neoplastic cells are derived from 1 cell), whereas in polyclonal (for example an infection or inflammatory states) all cells are derived from different cells

Question 5

what is autonomous proliferation?

Answer 5

Cells decide whether to grow and divide by integrating internal and external signals. Non-autonomous cell growth and proliferation occur when microenvironmental signals from neighboring cells, both physical and secreted, license this decision. Autonomy means that the cell does not require any external signal or growth factor to grow!!!!!. Autonomous replication of tumor cells seems to be an essential factor in the definition of the malignant tumor itself, although tumor cell proliferation is, in general, controlled by the host response including immunological reactions and microenvironment. The cause of the autonomy can hypothetically be classified into four categories as follow: (a) auto- and paracrine growth stimulation; (b) growth factor receptor abnormalities; (c) abnormal signal transduction; (d) self-incitement of ‘initiator-replicon’ system in DNA replication.

Question 6

list 6 features of neoplastic proliferation.

Answer 6

• Autonomous
• Uncontrolled
• Purposeless
• Progressive
• Parasitic
• Monoclonal (derived from one mother cell)

Question 7

what is the difference between benign and malignant tumors?

Answer 7

1) well-differentiated (resemble original tissue) vs poorly differentiated
2) slow growth vs rapid growth and high rate of cell division
3) no irregularities microscopically vs cellular atypia (polymorphism, polychromasia, mitotic figure)
4) no metastasis vs metastasis

Question 8

what is the most important feature that differentiates benign and malignant tumours?

Answer 8

Ability to metastasize

Question 9

malignant cells that arise from epithelium are termed?

Answer 9

• carcinoma

Question 10

list cancer with the highest mortality in males?

Answer 10

Lung 20%
Colon 15%
Prostate 14%

Question 11

list cancer with the highest mortality in females?

Answer 11

Breast 25%
Lung 20%
Colon 15%

Question 12

what is the most common cancer overall

Answer 12

Basal cells carcnioma, rarly metastasize, low mortality (vs melanoma)

Question 13

do benign neoplasms have the ability of malignization?

Answer 13

Yes

For example adenoma of the colon

Question 14

what are the macroscopic features of benign neoplasms?

Answer 14

– Well circumscribed(malignant have the ragged edge because they infiltrate into surrounding stroma)
– Often encapsulated
– Rarely hemorrhage
– Rarely necrosis

Question 15

benign neoplasms are commonly encapsulated.

True/False

Answer 15

True

Question 16

benign neoplasms commonly undergo necrosis and hemorrhage. True/False

Answer 16

False

Question 17

why malignant neoplasms may show hemorrhage and necrosis?

Answer 17

The malignant cell grows rapidly so they outgrow their own blood supply (necrosis in the center getting least blood) + due to neovascularization— they are small, weak and fragile so easily break causing hemorrhages.

Question 18

what is the key to the microscopic assessment of a neoplasm and malignancy?

Answer 18

nuclear features

Question 19

list nuclear features of a malignant neoplasm.

Answer 19

• pleomorphism (variability in size, shape, and staining of cells)
• hyperchromasia (deep, dark staining chromatin)
• increased mitotic activity
• High Nuclear/Cytoplasmic ratio= 1:1 (nucleus is larger than normal, occupying more space in the cytoplasm) normal ratio is 1:4 or 1:6

Question 20

what is the nuclear/cytoplasmic ration of malignant cells?

Answer 20

1:1, normally 1:4 or 1:6

Question 21

loss of maturation is seen with benign neoplasms. True/False

Answer 21

False. They are well differentiated and resemble the original tissue

Question 22

cytological features of the nuclei are used for?

Answer 22

to distinguish between:
–Normal cells/benign neoplasms
–Benign neoplasms and malignant neoplasms
– Grade malignant neoplasms

Question 23

what feature is used to grade malignant neoplasms?

Answer 23

cytological features of nuclei

vs stage in which tumor metastasis are used, more clinically useful

Question 24

what is a secondary tumor?

Answer 24

tumor due to metastasis

Question 25

example of borderline neoplasia?

Answer 25

``` ovarian. General classification: • Benign • Borderline – very rare (mainly ovary) • Malignant: - Primary - Secondary (Metastasis) ```

Question 26

what is the most common primary malignancy?

Answer 26

Carcinoma - 90% Lymphoma - 3% Sarcoma - 1%

Question 27

papilloma is derived from? 1) Squamous epithelium 2) glandular epithelium 3) transitional epithelium

Answer 27

Squamous epithelium--papilloma glandular epithelium--adenoma transitional epithelium--transitional/urothelial papilloma

Question 28

transitional papilloma arises where??

Answer 28

commonly bladder, urinary tract

Question 29

sarcomas arise from what cells?

Answer 29

mesenchymal origin (cartilage, fat, muscle, bone). Is malignant. Chondrosarcoma, liposarcoma, osteosarcoma, fibrosarcoma

Question 30

list benign tumors arising from mesenchymal tissue (connective tissue)

Answer 30

Lipoma (Fat) Neuroma (Nerve) Angioma (Vessel) Chondroma (Cartilage

Question 31

list few benign tumors arising from lymphoid tissue

Answer 31

Doesn'texist, always malignant-lymphoma (although end with 'oma' but are malignant). ? Lymph tissue already has access to the lymphatics-metastasize

Question 32

uterine fibromas are benign or malignant?

Answer 32

Benign, leiomyoma is the correct name, exceptionally low rate of malignization (<1%)

Question 33

a common benign neoplasm arising inside the skull?

Answer 33

meningioma, female>male, commonly estrogen receptor-positive, dural tale radiographically, commonly calcify

Question 34

An ovarian cyst is benign or malignant?

Answer 34

benign (cystadenoma), malignant one is called cystadenocarcinoma

Question 35

what are the main clinical features of benign tumors?

Answer 35

Due to mass effect pressure surrounding tissues leading to: •Lump •Bleeding, eg Hematemesis (Vomiting blood), Hemoptysis (Coughing of blood), Maelena (Black Stools)(bleeding through G.I. tract but by the time it reaches stool- it’s altered- black, can result in Fe Deficiency Anaemia •Mass (Effect of)-Cerebral Stroke, GIT Obstruction, Prostatic Outflow Obstruction • Pain

Question 36

benign neoplasms can spread locally to adjacent tissues.T/F

Answer 36

True | but do not metastasize

Question 37

what is the best treatment option for benign neoplasm?

Answer 37

surgery

Question 38

how adenoma of the colon become malignant?

Answer 38

Due to additional genetic alterations which facilitate invasion

Question 39

APC gene mutations lead to increased risk of | colon adenoma or colon adenocarcinoma

Answer 39

colon adenoma, as well as β-catenin gene and KRAS gene

Question 40

what is the Knudson's hypothesis

Answer 40

also known as the two-hit hypothesis, is the hypothesis that most genes require two mutations to cause a phenotypic change. Knudson suggested that two "hits" to DNA were necessary to cause cancer. In the children with inherited retinoblastoma, the first mutation in what later came to be identified as the RB1 gene was inherited, the second one acquired.

Question 41

what gene mutation leads to colon adenoma malignization.

Answer 41

P53 which is the most important tumor suppressor gene

Question 42

why NSAIDs decrease the risk of colon adenoma malignization.

Answer 42

because Adenomas overexpress COX-2 which are inhibited by NSAIDs

Question 43

define borderline neoplasms

Answer 43

These are neoplasms that show some nuclear features that suggest malignancy but not enough to be certain that the neoplasm will behave like a malignant neoplasm. Most commonly are ovarian neoplasms

Question 44

what are the steps for malignant cell metastasization?

Answer 44

1. dissociate from one another and 2. break down basement membrane and 3. release enzymes to access capillaries and 4. Attach to endothelial cells 4. Become a clump of cells and then embolism

Question 45

why surgery is not always curative and chemotherapy may be required in malignant neoplasms?

Answer 45

because of the feature of metastasization

Question 46

how malignant neoplasm is differentiated from a benign one?

Answer 46

by evidence of invasion and/or microscopic nuclear features

Question 47

germ cell neoplasms commonly arise in?

Answer 47

Testis and Ovary

Question 48

neoplasms arising from non-neuronal cells in the brain are termed?

Answer 48

glial neoplasms (glioblastoma multiforme-very malignant)

Question 49

what defines carcinoma in situ?

Answer 49

No invasion beyond the basement membrane (the basement membrane separates the mucosa from the submucosa)

Question 50

do carcinoma in situ are capable to metastasize?

Answer 50

in situ carcinomas are not capable of metastases as they have no access to lymphatics or blood vessels when they are still in situ

Question 51

list the types of carcinoma

Answer 51

1) squamous cell carcinoma (SCC) 2) adenocarcinoma (glandular epithelium) 3) small cell carcinoma (in lung) 4) transitional/urothelial carcinoma-bladder, urinary tract 5) neuroendocrine carcinoma 6) Basal cell carcinoma (skin) 7) anaplastic carcinoma (not differentiated so does not resemlbe epitheium, very malignant) 8) mixed carcinoma

Question 52

classification of malignant neoplasms

Answer 52

1) carcinoma 2) lymphoma 3) leukemia 4) sarcoma 5) melanoma 6) carcinosarcoma 7) embryonic neoplasms 8) germ cell neoplasms 9) glial neoplasms

Question 53

classification of lymphomas

Answer 53

• Nodal • Extranodal Extranodal involves sites other than LN, spleen, thymus and pharyngeal lymphatic ring. Extranodal lymphoma, by definition, involves sites other than lymph nodes, spleen, thymus, and the pharyngeal lymphatic ring. The involvement of the spleen in HD is considered as a nodal disease but in the case of non-Hodgkin lymphoma (NHL), the spleen is regarded as an extranodal site.

Question 54

example of extranodal lymphoma?

Answer 54

is gastric lymphoma – aggregates of lymphoid cells - MALT (if undergo a malignant transformation -MALToma)

Question 55

what is the difference between nodal vs extranodal lymphoma?

Answer 55

Extranodal involves sites other than LN, spleen, thymus and pharyngeal lymphatic ring

Question 56

lymphomas generally are classified as (except nodal vs extranodal)

Answer 56

Hodgkin’s lymphoma vs. Non-Hodgkin’s lymphoma | Hodgkin’s lymphoma has very specific factors and criteria (anything else-- NHL)

Question 57

list a few important sarcomas?

Answer 57

* Osteosarcoma (bone) * Chondrosarcoma (cartilage) * Angiosarcoma (vessel) * Neurofibrosarcoma (nerve) * Leiomyosarcoma (smooth muscle)

Question 58

what are the clinical effects of primary malignant neoplasm?

Answer 58

``` •Mass e.g. Cancer of the breast •Obstruction e.g. |Colon •Bleeding - -Hemoptysis -Hematemesis -Malaena - p.v. Bleeding -p.r. Bleeding -Fe deficiency anemia •Loss of function e.g. fracture of a bone ```

Question 59

what are the clinical effects of metastasized neoplasm?

Answer 59

•Lump/Mass (in a distal site) e.g. Axillary nodal mass(metastasized lymph nodes from the breast) •Obstruction e.g. of bronchus due to a metastasis •Bleeding e.g. -hemoptysis due to lung metastasis •Loss of function e.g. Stroke due to metastasis in the brain

Question 60

what other clinical effects can have malignant tumors on the body?

Answer 60

1)Effects of hormone secretion •ACTH from small cell carcinoma of the lung causing Cushing’s syndrome (when there is excess cortisol, regardless of cause) Cushing disease is a condition in which the pituitary gland releases too much ACTH (due to pituitary tumor) leading to osteoporosis, moon facies, purple striae, hyperglycemia, depression/psychosis, gynecomastia. •Estrogen from a testicular tumor causing gynaecomastia 2)constitutional signs •Weight Loss •Fatigue •Anorexia •Lassitude

Question 61

what are the features of Cushing syndrome?

Answer 61

osteoporosis, moon facies, purple striae, hyperglycemia, depression/psychosis, gynecomastia

Question 62

what is the paraneoplastic effect of the tumor?

Answer 62

Tumour-associated syndromes in which the symptoms are not directly related to the spread of tumour or to hormone effect indigenous to tumour tissue. Maybe due to immune reactions/certain cytokines. •Peripheral neuropathy •Dermatomyositis

Question 63

what are the ways to diagnose malignancy?

Answer 63

``` •History •Clinical examination •Special tests -Radiology: CT, MRI, PET -Pathology: FNA, Bx, Aspirate, Resection ```

Question 64

Why is it important for the Pathologist to give the precise type of carcinoma in the Pathology Report?

Answer 64

1) To determine whether a primary Cancer or a metastasis | 2) Different treatments may be available depending on the type of carcinoma

Question 65

in what areas of body squamous cell carcinomas occur?

Answer 65

Any area lined by squamous epithelium e.g. skin, mouth, esophagus, cervix.

Question 66

keratin production is the feature of what type of malignant neoplasm?

Answer 66

carcinoma, eg keratin pearl which is a concentric layer of epithelial cells, common in skin and lung SCC, helps pathologist to diagnose carcinoma

Question 67

in which organ adenocarcinomas occur?

Answer 67

``` in the area lined with columnar/glandular epithelium GIT BREAST THYROID UTERUS ```

Question 68

mucin production is characterisitc to squamous cell carcinoma.T/F

Answer 68

False | It is a feature of adenocarcinoma which arise from glandular epithelium

Question 69

in what organ transitional cell carcinoma arise?

Answer 69

in organs lined with transitional/urothelial epithelium: pelvis of kidney, bladder, urethra, umbrella cells on histology

Question 70

which is the most aggressive carcinoma?

Answer 70

small cell (oat cell) carcinoma

Question 71

small cell carcinoma in lung is central or peripheral?

Answer 71

central

Question 72

what hormones can be secreted by small cell carcinoma?

Answer 72

secrete ADH or ACTH resulting in SIADH or Cushing syndrome respectively

Question 73

small cell carcinomas are neuroendocrine tumors. True/False

Answer 73

True. | Small/round, blue cells

Question 74

what mutations are commonly associated with small cell carcinoma?

Answer 74

p53, Rb or p16 mutations

Question 75

describe small cell carcinoma

Answer 75

- Usually in the lung (but can be anywhere; if lung- centrally located) - High-grade neuroendocrine carcinoma (arise from neuroendocrine cells called Kulchitsky cells) - May be associated with hormonal effects(may secrete ADH or ACTH) - May be associated with paraneoplastic effects(peripheral neuropathy) - High frequency of p53, Rb or p16 mutations

Question 76

what does it mean anaplastic carcinoma?

Answer 76

No differentiating feature @ L.M. or E.M. So identified by immunohistochemistry-process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues.