GP 22 - Pathology of Neoplasia 3

Question 1

List the major types of effects tumors often have on their hosts.

Answer 1

• Local Effects (e.g. - location/infringement).
• Functional Effects (e.g. - hormone production).
• Acute Symptoms (e.g. - infarctions, rupture).
• Wasting, fever.
• Paraneoplastic Syndrome.
• Metastasis

Question 2

What types of local effects are often caused by the following:

• submucosal leiomyoma
• GIT tumors (benign and malignant)
• pituitary adenoma
• urogenital tumors
• ovarian tumors.

Answer 2

• Submucosal leiomyoma - bleeding
• GIT tumors (both benign and malignant) - bowel obstruction and bleeding
• Pituitary adenoma - destruction of the remaining gland
• Urogenital tumors - bleeding
• Ovarian tumors - torsion (rotation of the ovary at its pedicle to such a degree as to occlude the ovarian artery and/or vein.)

Question 3

What are the hormonal effects caused by the following:

• β cell adenoma in pancreas
• adrenal cortex adenoma
• carcinoid tumor.

Answer 3

• β cell adenoma in pancreas - increased insulin production leading to hypoglycemia.
• Adrenal cortex adenoma - increased steroid production leading to various secondary effects.
• Carcinoid (neuroendocrine tumors) - production of various hormones leading to carcinoid syndrome

Question 4

What is Cachexia and what causes it?

Answer 4

Often in cancer patients there is a progressive loss of fat and lean body mass with weakness, anorexia, and anemia. Causal mechanisms are poorly understood but the following factors are present:

• reduced food intake
• reduced synthesis and storage of fat
• increased mobilization of fatty acids from adipocytes.
• tumor necrosis factor α (TNFα)

Question 5

How does fever correlate with cancer and what usually causes the fever?

Answer 5

Fever generally increases with tumor growth, disappers following treatment, and will reappear with recurrence. The fever is caused by the release of pyrogens, most notably IL-1 and TNFα

Question 6

What is paraneoplastic syndrome (PNS) and what causes it?

Answer 6

PNS is a complex of endocrine, neurological, mucocutaneous, and hematological symptoms that are often seen in cancer patients. The cause of PNS is idiopathic

Question 7

What is the clinical significance of PNS?

Answer 7

• The symptoms may be the earliest sign of an occult neoplasm (a cancer of unknown primary origin)
• May cause significant or even lethal clinical problems
• May mimic metastatic disease
• May lead to the wrong diagnosis

Question 8

List the PNS symptoms often seen in patients with small cell bronchogenic carcinomas.

Answer 8

• Cushing’s Syndrome
• Syndrome of Inappropriate Antidiuretic Hormons Secretion (SIADH)
• Hypercalcemia
• Myasthenia (also commonly associated with thymomas)
• Acanthosis Nigricans (hyperpigmentation of the skin)
• Hypertrophic osteoarthropathy (clubbing and periostitis of the small hand joints)
• Venous thrombosis

Question 9

What is the gold standard test for cancer?

Answer 9

Microscopic tissue examination

Question 10

What MUST accompany every possible tumor sample before being sent to the lab?

Answer 10

A properly completed surgical pathology requisition form (either electronic or hard copy)

Question 11

What are the methods of sampling and fixing cancer samples?

Answer 11

Sampling Methods - biopsy, excision, fine needle aspiration biopsy, smear, body fluid.

Tissue Fixation Methods - fresh, formalin, gluteraldehyde, fine needle aspiration, cytology smear

Question 12

What are the steps to routine tissue processing?

Answer 12

1. Fixation
2. Dehydration in alcohol
3. Xylene (clearing agent)
4. Paraffin embedding
5. Sectioning and staining

Question 13

When is fine needle aspiration biopsy used to collect a cancer sample?

Answer 13

Useful for palpable or radiologically accessible lesions. Can be performed in the office for thyroid, breast, and salivary gland cancers. And for surface lumps and bumps. Deeper tissues like liver and lung require imaging guidance.

Question 14

How is immunocytochemistry useful in diagnosing cancers?

Answer 14

With the help of specific antibodies, it can detect nuclear or cytoplasmic proteins which is useful in detecting the cell origin. However, there can be false positives and false negatives

Question 15

List the common immunohistochemical stains we need to know.

Answer 15

• Epithelium (except prostate and melanomas) - Keratin
• Mesenchyme - Vimentin
• Muscle - Desmin
• Prostatic Epithelium - PSA
• Thyroid Follicular Cells - thyroglobulin
• Neuroendocrine Cells - Chromogranin
• Melanoma - S100/HMB45/Melan A

Question 16

How is flow cytometry used in diagnosing cancer? What cancers in particular are it used for?

Answer 16

A single cell suspension is stained with various fluorescence labeled surface markers which are detected using specific antibodies and sorted out based on size and quantity (fluorescence intensity). Useful for characterizing lymphomas and leukemias

Question 17

List the most commonly checked for tumor markers and the cancers they correlate with.

Answer 17

• PSA (prostate specific antigen) - prostatic adenocarcinoma
• CEA (carcino embryonic antigen) - colonic, pancreatic, breast, and gastric adenocarcinomas
• AFP (α feto protein) - hepatocellular carcinoma

Question 18

How useful are tumor markers in diagnosing cancers?

Answer 18

They aren’t because these markers are often eleveated in inflammatory conditions. They’re usually used to monitor how cancers are responding to therapy.

Question 19

Where is colorectal cancer incidence very high? Why is this thought to be?

Answer 19

Canada/US. Believed to be due to the high fat content of the diet

Question 20

What is the primary cause of Burkitt’s Lymphoma?

Answer 20

EBV infection

Question 21

What are the two major factors believed to cause higher cancer incidence in the elderly?

Answer 21

Accumulation of somatic mutations and a decline in immune competence

Question 22

What types of cancers are more common in children?

Answer 22

• Neuroblastomas.
• Wilms Tumor (kidney)
• Retinoblastoma
• Some sarcomas

Question 23

List the inherited cancer syndromes we need to know. What genes are mutated in these syndromes? What is the pattern of inheritance of these diseases?

Answer 23

All are autosomal dominant

• Multiple Endocrine Neoplasia (MEN1, RET)
• Li-Fraumenii Syndrome (P53)
• Familial Adenomatous Polyposis (APC)

Question 24

Whats the difference between a familial cancer and a cancer with hereditary predisposition. Give examples of familial cancers.

Answer 24

Familial cancers run in families but the hereditary predispostion is not clear. Examples - breast, colon, gastric, and ovarian cancers

Question 25

List the syndromes of defective DNA repair we need to know, which genes they affect, and their patterns of inheritance.

Answer 25

Autosomal Dominant Mutations in MLH1, MSH2, MSH6, and/or PMS2 cause hereditary non-polyposis colon cancer

Autosomal Recessive Syndromes - Xeroderma Pigmentosa (squamous cell cancer), Ataxia Telengiectesia (lymphoma), Fanconi’s Anemia (AML)