Non-Epithelial Tumors

Question 1

Types of haematopoietic neoplasm

Answer 1

Leukemia

Lymphoma

Myeloma

Question 2

Leukemia

Answer 2

Hematopoietic neoplasms that circulate in the blood

Question 3

Lymphoma

Answer 3

Hematopoietic neoplasms that arise in secondary lymphoid organs (lymph nodes, spleen, and other lymphoid tissues) and do not circulate.

Question 4

There is significant ____ between leukemias and lymphomas

Answer 4

There is significant overlap between leukemias and lymphomas

Most lymphomas can (and often do) circulate in the blood, and many leukemias can form solid masses. The distinction is usually not clinically significant

Question 5

Myeloma

Answer 5

Hematopoietic neoplasm of terminally differentiated, antibody-forming plasma cells.

Question 6

Melanoma

Answer 6

Neoplasm of melanocytes that usually arises in the skin (although it can arise anywhere melanocytes are present), gets its own category. Although it is of non-epithelial origin, it behaves more like carcinoma than the other non-epithelial cancer types.

Question 7

Glioma

Answer 7

Primary neoplasms arising from the glial cells of the central nervous system.

Question 8

Since non-epithelial tissues do not have a ____, invasion cannot be assessed in the same way for a non-epithelial neoplasm as for a carcinoma.

Answer 8

Since non-epithelial tissues do not have a basement membrane, invasion cannot be assessed in the same way for a non-epithelial neoplasm as for a carcinoma.

Question 9

There are unique features of the biology of hematopoietic cells – related to their role in ____ – that create the potential for carcinogenic pathways that are not possible in epithelia.

Answer 9

There are unique features of the biology of hematopoietic cells – related to their role in the immune response – that create the potential for carcinogenic pathways that are not possible in epithelia.

Question 10

When non-epithelial neoplasms cause morbidity and mortality, they are far more likely than epithelial neoplasms to do so by mechanisms other than _____.

Answer 10

When non-epithelial neoplasms cause morbidity and mortality, they are far more likely than epithelial neoplasms to do so by mechanisms other than invasion and metastasis.

Question 11

Mesenchymal neoplasms include tumors that arise from ____.

Answer 11

Mesenchymal neoplasms include tumors that arise from connective tissue, muscle, and bone.

Question 12

leiomyo-

Answer 12

smooth muscle

Question 13

rhabdomyo-

Answer 13

skeletal muscle

Question 14

Malignant sarcomas do not arise from ______.

Answer 14

Malignant sarcomas do not arise from pre-existing, benign mesenchymal neoplasms.

In general, the genetic lesions present in benign mesenchymal neoplasms are distinct from and non-overlapping with those found in their malignant counterparts. Surgical resection of these is done to alleviate symptoms they may be causing, not out of a fear that they will progress to malignancy – they won’t.

Question 15

Two major categories of sarcoma at the molecular level

Answer 15

Group I: Near-euploid karyotype and a single chromosomal translocation, usually involving a transcription factor.

Group II: Complex, highly aneuploid karyotypes involving the “typical” oncogenes and tumor suppressor genes. These tend to have a worse prognosis.

Question 16

Ewing sarcoma

Answer 16

Typical example of a Group I sarcoma. Several associated translocations, all of which in some way activate the EWS transcription factor on chromosome 22.

Question 17

Distinguishing benign from malignant mesenchymal neoplasms relies on . . .

Answer 17

1. Gross features (infiltrative border, necrosis, hemorrhage)
2. Histologic features, such as dysplasia

Question 18

Rather than invasion and metastasis (the way epithelial neoplasms most often cause morbidity and mortality), sarcomas usually kill through ___ and ____.

Answer 18

Rather than invasion and metastasis (the way epithelial neoplasms most often cause morbidity and mortality), sarcomas usually kill through local recurrence and de-differentiation.

Question 19

Encasing

Answer 19

Sarcomas may grow so rampantly that they completely incase other important strucutres. Attached is a liposarcoma with an incased kidney in the upper left corner.

Question 20

___ and ___ don’t form neoplasms.

Answer 20

Mature red cells and platelets don’t form neoplasms – this is one of the fringe benefits of lacking a nucleus!

However, over-production of these cells can occur as a secondary consequence of a neoplastic process.

Question 21

For the most part, haematopoietic neoplasms arise from ___.

Answer 21

For the most part, haematopoietic neoplasms arise from white blood cells.

Question 22

Haematopoietic neoplasm development

Answer 22

Question 23

Approximately ___% of lymphoid neoplasms are of B cell origin, and about ___% of T cell origin.

Answer 23

Approximately 85% of lymphoid neoplasms are of B cell origin, and about 15% of T cell origin.

This is thought to be attributed to the fact that B cells undergo DNA rearrangements more frequently as part of their biology: rearranging different light chains in receptor editing and heavy chain class switching.

Question 24

Lymphoid neoplasms

Answer 24

Question 25

B cells are uniquely prone to translocations involving chromosome ___.

Answer 25

B cells are uniquely prone to translocations involving chromosome 14.

That is because chromosome 14 contains the IGH (immunoglobulin heavy chain) locus!

Most B cell lymphomas harbor translocations in which the IGH locus is fused to an oncogene as their oncogenic driver.

Question 26

In B cell lymphomas, you will typically find. . .

Answer 26

. . . a single chromosome 14 IGH locus translocation, and few or no additional mutations.

Question 27

“Weighing” the relative importance of B cell immunity and B cell lymphoma

Answer 27

Question 28

Burkitt’s lymphoma translocation

Answer 28

Question 29

Answer 29

“Starry sky” figure in Burkitt’s lymphoma

Question 30

Despite its aggressive looking appearance, ___ responds very well to chemotherapy.

Answer 30

Despite its aggressive looking appearance, Burkitt’s lymphoma responds very well to chemotherapy.

Question 31

Mantle Cell Lymphoma

Answer 31

Chromosomal translocation of the IGH promoter on chromosome 14 and Cyclin D1 on chromosome 11.

Question 32

CLL vs SLL

Answer 32

Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) is a B cell neoplasm that illustrates the overlap between leukemias and lymphomas.

It is called CLL when it only involves the blood and SLL when there is tissue involvement, but the disease is the same at the molecular level, and the distinction is not important to treatment or prognosis.

Question 33

Diffuse large B cell lymphoma

Answer 33

Can arise de novo as a result of translocations involving the IGH locus and the Bcl-6 gene on chromosome 3.

Bcl-6 is a transcription factor that regulates germinal center differentiation. DLBCL can also arise through transformation of a pre-existing, lowergrade lymphoma.

Question 34

Acute leukemias result from. . .

Answer 34

Acute leukemias result from transformation of early bone marrow precursors, or “blasts”

Question 35

Myeloid neoplasms are frequently driven by molecular lesions that interfere with ___.

Answer 35

Myeloid neoplasms are frequently driven by molecular lesions that interfere with normal pathways of differentiation.

Question 36

Acute promyelocytic leukemia

Answer 36

Myeolma associated with translocations involving the retinoic acid receptor (RARα) on chromosome 17.

Retinoids binding to RARα normally drive myeloid differentiation., but the translocation creates a chimeric receptor with reduced affinity that no longer is activated by physiologic retinoid concentrations, leaving the cells “stuck” in an undifferentiated state. This can be overcome therapeutically by giving high doses of all-trans retinoic acid (ATRA), which overcome the block and drive differentiation.

Question 37

Answer 37

Myeloma cells.

Plasma cells have strikingly and characteristically blue cytoplasm due to the high amount of ribosomal RNA they produce. This is accompanied by a slightly lighter staining perinuclear region which is occupied by the Golgi complex.

In myeloma, they retain these features, but they will be present in the bone marrow in much larger numbers than usual, and also show dysplastic features (binucleation, prominent nucleoli)

Question 38

Answer 38

Lesions in the skull caused by myeloma

Question 39

Answer 39

Myeloma patient antibody test

Demonstrates “immunofixation,” the single clear banding caused by the staggering numbers of monoclonal antibodies produced by myelomas.

Question 40

Paraneoplastic phenomena

Answer 40

Effects of a neoplasm that are the result of mechanisms other than direct growth of the tumor cells themselves

Question 41

Paraneoplasms of myeloma

Answer 41

Excess antibody light chain can form insoluble aggregates that become trapped in the kidney (amyloid), causing renal failure. If the antibody produced is functional, autoimmune disease can result.

Question 42

“Malignancy is a ____ state”

Answer 42

“Malignancy is a hypercoagulable state”

Question 43

In general, like sarcomas (but unlike epithelial neoplasms), most hematopoietic malignancies do not have well-defined _____.

The exception to this is ___.

Answer 43

In general, like sarcomas (but unlike epithelial neoplasms), most hematopoietic malignancies do not have well-defined precursor lesions.

The exception to this is myelodysplastic syndrome, a precursor to acute myeloid leukemia. Unfortunately, this knowledge does little good as there are no treatments that may prevent this progression and the tumor is soluble and therefore cannot be removed.

Question 44

Both low- and high-grade neoplasms ____.

Answer 44

Both low- and high-grade neoplasms take over the bone marrow and “crowd out” normal hematopoiesis, resulting in inability of the bone marrow to maintain adequate numbers of erythrocytes, leukocytes, and/or platelets.

This causes symptoms attributable to lack of the mature cells (anemia, susceptibility to infection, inability to clot properly).

Question 45

A single activating mutation in ___, ____, is present in up to 66% of melanomas

Answer 45

A single activating mutation in BRAF, V600E, is present in up to 66% of melanomas

Question 46

Melanoma development

Answer 46

Question 47

Precursor legion to melanoma

Answer 47

dysplasatic nevi