Exam 3: Neoplasia Diagnostics

Question 1

Name four things a frozen section may be used for?

Answer 1

A. Determine presence or absence of malignancy
B. Determine presence or absence of inflammation/organisms
C. Whether surgical margins are free of neoplasm
D. Whether diagnostic tissue is present
**FIXATION RATE OCCURS AT 1MM/HR

Question 2

What are the five intermediate filaments and their cells of origin?

Answer 2

Tumor cells often contain intermediate filaments characteristic of their cell of origin.

1) Keratin→ Carcinomas, mesotheliomas
2) Desmin→Muscle tumors: smooth, striated
3) Vimentin→ Mesennchymal tumors, some carcinomas
4) Glial filaments→ Gliomatous tumors
5) Neurofilaments→ Neuronal tumor

Question 3

With respect to breast cancer what prognostic information can be obtained from immunohistochemistry, flow cytometry and FISH techniques?

Answer 3

Immunohistochemistry: Used to determine the site of origin of metastatic tumors. Detection of molecules that have prognostic or therapeutic significance (especially true with breast cancers). ER/PR (estrogen/progesterone) positive is favorable

Flow Cytometry: Rapidly and quantitatively measures some cell characteristics such as membrane antigens and DNA content of tumor cells. DNA content (ploidy) is divided into diploid and aneuploid tumors.
Diploid tumors→ have major population mode at the normal diploid DNA value
Aneuploid tumors→ have a cell population with a DNA content other than diploid. (Aneuploidy associated with poorer prognosis)

FISH techniques: (Fluorescence in situ hybridization); Is used for the detection of specific DNA or RNA sequences in tissue sections or cell preps using a labeled complementary nucleic acid sequence or probe. Used for the detection of viral infections (HIV, HPV, EBV). Used to determine the prognosis of malignant neoplasms especially in breast cancer.
HER-2/NEU gene (over expression not favorable)

Question 4

Know the CD groupings for T (2,3,4,5,7,8), B(10,19-23), monocyte/macrophage(13-15,33), NK(16,56), stem(34) and all leukocytes(45) (Portions of table 13-5)

Answer 4

T cells→ 2, 3, 4, 5, 7, 8
B cells→ 10, 19-23
Macrophages→ 13-15, 33
NK cells→ 16, 56
Stem cells→ 34
Leukocytes→ 45; leukocyte common antigen covers all leukocytes

Question 5

Be able to classify a leukemia/lymphoma as B or T cell origin when given CD designations.

Answer 5

If a leukemia/lymphoma is of B cell origin→ designated CD (10, 19-23)

If a leukemia/lymphoma is of T cell origin→ designated CD (2,3,4,5,7,8)

Question 6

What two things can flow cytometry measure?

Answer 6

Flow cytometry rapidly and quantitatively measure some cell characteristics such as membrane antigens and DNA content of tumor cells.
Flow cytometry can measure:
1) Membrane antigens→ cell surface markers present on lymphoid neoplasms (can determine monoclonal versus polyclonal, and can determine cell lineage- B, T, monocyte/macrophage, NK, or stem cell)
2) DNA content of tumor

Question 7

DNA content or ploidy can be divided into what two subsets? Which subset is generally associated with a poor prognosis when identified in a tumor?

Answer 7

DNA content can be divided into: Diploid and aneuploid

Diploid tumors→ have major population mode at the normal diploid DNA value Aneuploid tumors→ have a cell population with a DNA content other than diploid. (Aneuploidy associated with poorer prognosis)

Question 8

What does FISH stand for? What is the advantage it has over standard karyotyping (IHC)?

Answer 8

FISH: Fluorescence In Situ Hybridization. FISH demonstrates complex translocations that are not detected by routine karyotyping!
Process: Detection of specific DNA or RNA sequences via labeled complementary nucleic acid probe
Advantage over IHC:
1) Detects productive and latent infections (cells don’t need to be dividing), and can segregate subtypes.
2) Very sensitivity and rapid
3) Five fluorochromes and computer generated signals can visualize whole genome
4) Can detect numerical chromosomal abnormalities as well as translocations
⇒ Detects subtle micro-deletions
⇒ Analysis of gene amplification
⇒ Maps newly isolated genes to chromosomes
⇒ Whole chromosome can be labeled with a series of fluorescent probes

Question 9

Define PCR. How is the technology used in molecular diagnosis?

Answer 9

PCR→ polymerase chain reaction (nucleic acid amplification) Cannot detect NOT fragile X!
Uses:
1) Detection of circulating tumor cells in peripheral blood
2) Detection of relapse of CML (chronic myelogenous leukemia) after bone marrow transplant
3) Identification of RNA viruses (HIV)
4) Detection of Ig or TCR gene rearrangements to determine clonality of B or T cell proliferations
5) Detection of chromosomal translocations in hematologic malignancies
6) Detection of point mutations
7) Detection of abnormalities in tumor suppressor genes
8) Detection of gene amplification
9) Detection of tumor related viruses
10) Detection of microsatellite instability
11) Rapid detection and identification of microorganisms

Question 10

What does DNA microarray analysis provide for molecular profiling? What does proteomics provide for molecular profiling?

Answer 10

DNA microarray: One of the most useful analyses for cancer research is hierarchial clustering. You can compare profiles of different individual tumors with different outcomes. Other benefits:
⇒ Can measure expression of essentially all genes in the genome simultaneously
⇒ Large scale analysis of gene expression
⇒ Profile ability to stratify patient’s risk and guide treatment beyond limits of histology and pathologic staging

Proteomics:
⇒ Large scale characterization of the entire protein complement of a cell type, tissue or organism
⇒ Identifs a serum proteomic pattern that will help in early detection of cancer

Question 11

What are the two features are helpful to divide blood vessel tumors into benign and malignant categories? (Table 11-5)

Answer 11

1) Degree of well formed vascular channels present

2) Extent and regularity of the endothelial cell proliferation

Question 12

What are the three categories of hemangiomas?

Answer 12

A Hemangioma is an increased number of normal or abnormal vessels; very common especially in children and usually benign

1) Capillary Hemangioma (mm to several cm)
2) Juvenile Hemangioma (strawberry type)
3) Cavernous Hemangioma (1-2 cm)

Question 13

Capillary hemangiomas are found predominantly in what locations? What is the natural course of the strawberry or juvenile type of capillary hemangioma?

Answer 13

Capillary hemangiomas are predominantly found:
Normally in a children→  Seen visually on the skin, subcutaneous tissue, mucous membranes
Juvenile hemangiomas (Strawberry type)→ Found in newborn; grows rapidly for a few months then fades at 1-3 years

Question 14

What are the three main differences between a cavernous and a capillary hemangioma? (Low yield “FYI” per McCarver)

Answer 14

Cavernous: Larger, less circumscribed (borders less defined), more frequently involves deep structures

Capillary: Smaller, found level with skin surface or slightly elevated, un-encapsulated aggregates of closely packed thin wall capillaries, little stroma

Question 15

What are the gross and microscopic characteristics of a pyogenic granuloma? 1/3 develop after what?

Answer 15

Morphological features: Peduncular red nodules on skin, oral mucosa; rapidly growing, bleeds easily, often ulcerated
Proliferating capillaries with edema and acute / chronic inflammation

1/3 develop after trauma

Question 16

Where do glomus tumors occur? What distinctive clinical symptom do they have?

Answer 16

Occurrence: Distal portions of digits under fingernails (subungal)
Clinical symptom: Distinctive clinical symptom is pain

Question 17

What are three types of vascular ectasias? How does an ectasia differ from a telangiectasia? What is the common name for nevus flammeus? What is a port-wine-stain and what is the clinical significance?

Answer 17

A vascular ectasia→ is a dilation, expansion or distention of a blood vessel.
A telangiectasia→ is a congenital anomaly or acquired exaggeration of preformed vessels.

3 Types of vascular ectasias:

1) Nevus Flammeus: (Ordinary Birthmark)
⇒ Port Wine Stain with Sturge Webber (lesion in trigeminal nerve can be seen in the syndrome)
⇒ Port wine stain-dilation and proliferation, grows with child, thickens surface, no tendency to fade

2) Spider Talengiectasis: (looks like a spider)
⇒ Hyperestrogenic State (pregnant woman and liver disease)

3) Hereditary Hemorrhagic Telangiectasis
⇒ Osler-Weber-Rendu disease – autosomal dominant
⇒ Present from birth

Question 18

What causes bacillary angiomatosis? What group of patients get bacillary angiomatosis? Is bacillary angiomatosis a true tumor? How do you treat it?

Answer 18

Causes:
1) Infectious disease, treated with antibiotics

At risk populations: Immunocompromised / HIV patients get bacillary angiomatosis

A bacillary angiomatosis is characterised by the proliferation of blood vessels, resulting in them forming tumour-like masses in the skin and other organs. Not a true tumor.

Treatment: macrolide antibiotics (erythromycin)

Question 19

What are the two intermediate grade blood vessel tumors?

Answer 19

Per McCarver’s review she said to be able to just name them (info provided just in case she forgets)

1) Epitheliod Hemangioendothelioma:
o Occurs around veins in soft tissue of adults
o Well defined vascular channels hard to find, tumor cells plump, cuboidal=epithelial like
2) Kaposi’s Sarcoma:
o Four variants based on population demographic and risks
• Chronic – classic, European form
• Lymphadenopathic – African Kaposi’s
• Transplant associated
AIDS Associated

Question 20

What are the four types of Kaposi sarcoma? What is considered the underlying infectious cause?

Answer 20

1) Chronic (or classic) KS
o Older men, eastern Europe, Mediterranean
o Not associated with HIV, usually asymptomatic, remain localized

2) Lymphadenopathic KS (African)
o Not associated with HIV
o Very aggressive
o Most common tumor in Central Africa

3) Transplant Associated KS
o Seen with solid-organ transplant seeking long term immunosupression
o Aggressive
o Lesions may regress when immune therapy lessened at the expense of increased risk of organ rejection

4) AIDS Associated (epidemic) KS
o Originally found in 1/3 of HIV patients, male homosexuals
o Most patients die of infection, not KS
o Can involve lymph nodes and viscera, wide dissemination early, SKIN (mentioned by McCarver)
o

*95% of KS lesions have HUMAN HERPESVIRUS 8 (KS associated herpes virus [KSHV]

Question 21

What are the three KS stages? What are the microscopic hallmarks? (Fig. 11-32)

Answer 21

Stages:

1) Spectrum of lesions: red purple coalescent patch, plaques and nodules
2) Early: jagged thin walled, dilated vascular spaces in epidermis with interstitial inflammatory cells and extravagated red cells
3) Later: Plump, spindle shaped stromal cells with irregular, angulated, slit like spaces filled with red cells

Microscopic features: slit like spaces filled with red cells

Question 22

What are the two malignant blood vessel tumors? What three carcinogens are hepatic angiosarcomas associated with? What does the term lymphangiosarcoma refer to?

Answer 22

1) Angiosarcoma→ induced by radiation, foreign material introduced into body
Associated Carcinogens
• Arsenic, Thorotrast, Polyvinyl chloride (PVC)
• Long latencies
2) Hemangiopericytoma (FYI’ed in class)
3) Lymphangiosarcoma

Question 23

What are the two types of lymphangiomas? What is the other term for cavernous lymphangioma ? Where and in whom do they occur? What syndrome are they associated with?

Answer 23

1) Simple Lymphangioma→ Masses of small lymphatic channels, subcutaneous head/neck
2) Cavernous Lymphangioma→ (Cystic Hygoma)
o Cavernous lymphatic spaces
o Occurs in children, neck (cystic hygroma), associated with Turner’s Syndrome