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T1 - Phase 2 - Systems Modules (I) > Neoplasia/Hematology - Mechanisms of Disease - Dermatopathology; Soft Tissue Tumors; Infectious Agents and Cancer > Flashcards

Neoplasia/Hematology - Mechanisms of Disease - Dermatopathology; Soft Tissue Tumors; Infectious Agents and Cancer Flashcards

1
Q

Which specific skin layer is most at risk of cancer development?

A

The stratum basale

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2
Q

What is seborrheic keratosis?

A

A benign epidermal keratinocytic neoplasm

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3
Q

During a routine examination of one of your adult patients, you note the attached skin structure.

What is it?

A

Seborrheic keratosis

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4
Q

What findings might indicate that a skin finding is seborrheic keratosis rather than melanoma?

A

Greasy or verrucous consistency

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5
Q

Are seborrheic keratoses singular or multiple?

Are they large or small?

A

Large variety

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6
Q

Identify the term for the given definition:

‘keratinocytic dysplasia of the lower epidermis overlying solar elastosis’

A

Actinic keratosis

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7
Q

Actinic keratosis is defined as ______cytic dysplasia of the ______ epidermis overlying solar _______.

A

Actinic keratosis is defined as keratinocytic dysplasia of the lower epidermis overlying solar elastosis.

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8
Q

What non-malignant lesion is shown here?

A

Actinic keratosis

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9
Q

True/False.

Actinic keratoses can be single or multiple.

A

True.

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10
Q

What type of keratosis is typically described as scaly?

What type of keratosis is typically described as verrucous or greasy?

A

Actinic keratoses;

seborrheic keratoses

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11
Q

True/False.

Actinic keratoses can lead to horn-like structures.

A

True.

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12
Q

True/False.

Seborrheic keratoses are precancerous lesions.

A

False.

Actinic keratoses are precancerous lesions.

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13
Q

What are the two main keratinocytic malignant neoplasms?

A

Basal cell carcinoma;

squamous cell carcinoma

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14
Q

What dermatological cancer is often described as a pearly/translucent patch?

A

Basal cell carcinoma

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15
Q

Does basal cell carcinoma have a variety of skin presentations?

A

Yes.

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16
Q

What color are basal cell carcinoma cells (typically) under the microscope?

A

Blue-ish purple

(basophilic)

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17
Q

What malignant lesion is shown here?

A

Squamous cell carcinoma

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18
Q

What color are squamous cell carcinoma cells (typically) under the microscope?

A

Pink

(eosinophilic)

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19
Q

What is the term for a well-differentiated cystic squamous cell carcinoma?

A

Keratoacanthoma

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20
Q

Which keratinocytic malignancy is characterized by immature cells?

A

Basal cell carcinoma

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21
Q

Which keratinocytic malignancy is characterized by mature cells?

A

Squamous cell carcinoma

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22
Q

True/False.

Nevi can be epidermal, dermal or compound.

A

True.

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23
Q

True/False.

Melanocytes are of neural crest origin, meaning the cells in melanomas are often very invasive and capable of spread.

A

True.

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24
Q

On what part(s) of the body do males most often get melanomas?

A

Back and shoulders

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25
Q

On what part(s) of the body do females most often get melanomas?

A

Legs

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26
Q

Merkel cell carcinomas are an example of n_____________e tumors.

A

Merkel cell carcinomas are an example of neuroendocrine tumors.

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27
Q

Dermatofibromas are factor-______ positive.

A

Dermatofibromas are factor-VIIIa positive.

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28
Q

A ______fibroma is a stromal neoplasm of the skin.

A

A dermatofibroma is a stromal neoplasm of the skin.

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29
Q

What fungus causes mycosis fungoides?

A

None!

It is a historical name — this is a primary cutaneous T cell lymphoma

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30
Q

What is a mycosis fungoides?

A

A primary cutaneous T cell lymphoma

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31
Q

Describe the progression of mycosis fungoides according to cutaneous presentation.

A

Patch –> Plaque –> Tumor

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32
Q

What syndrome is characterized by the progression of mycosis fungoides (a T cell lymphoma) to the bloodstream (becoming leukemic)?

A

Sézary syndrome

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33
Q

_______ neoplasms of the skin are tumors forming from the extra-cutaneous structures of the skin (e.g. hair follicles, arrector pili, etc.).

A

Adnexal neoplasms of the skin are tumors forming from the extra-cutaneous structures of the skin (e.g. hair follicles, arrector pili, etc.).

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34
Q

What term refers to a benign neoplasm growing out of a hair follicle?

A

Pilomatricoma

(pilus + matrix + oma)

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35
Q

Describe the ‘ghost cells’ seen in pilomatricomas (benign neoplasms of the hair follicles).

A
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36
Q

What term refers to a benign neoplasm growing out of a sebaceous gland?

A

Sebaceous adenoma

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37
Q

What term refers to a malignant neoplasm growing out of a sebaceous gland?

A

Sebaceous carcinoma

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38
Q

What term refers to a benign neoplasm growing out of an eccrine sweat gland?

A

Cylindroma

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39
Q

True/False.

UV exposure is strongly implicated in the formation of cutaneous angiosarcomas.

A

True.

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40
Q

What term refers to benign vascular (endothelial) neoplasms?

A

Hemangiomas

(strawberry, cherry, etc.)

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41
Q

While hemangiomas are benign vascular (endothelial) neoplasms, what term refers to malignant vascular neoplasms?

A

Angiosarcomas

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42
Q

Angiosarcomas most typically arise where?

A

Sun-damaged (or irradiated) heads and necks

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43
Q

What is the prognosis for angiosarcomas?

A

Very poor

(extremely rapid metastasis because they are already in the bloodstream)

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44
Q

Define leukoplakia.

A

A firmly attached white patch on a mucous membrane

(associated with an increased risk of cancer)

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45
Q

What is another term for melanoma in situ?

A

Lentigo maligna

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46
Q

Define: Lentigo maligna.

A

Melanoma in situ

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47
Q

How much more common are benign soft tissue tumors than malignant?

A

100:1

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48
Q

3 broad categories of soft tissue tumors:

  • Benign
  • ___________ behaving (locally aggressive and recurring but never metastasize or those with <2% metastasis rate)
  • ___________ (sarcoma)
A

3 broad categories of soft tissue tumors:

  • Benign
  • Intermediate behaving (locally aggressive and recurring but never metastasize or

those with <2% metastasis rate)

• Malignant (sarcoma)

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49
Q

Describe the typical characteristics of most sarcomas in terms of the following:

Location

Relative size

Mortality

A

Extremities / deep below fascia;

large size;

high mortality

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50
Q

Terms used to generally describe the cell shape of sarcoma tumor cells:

______ cell – rod shaped (fibroblast, smooth muscle cell)

Round cell – small, lymphocyte size, little cytoplasm (Ewings,

rhabdomyosarcoma)

Epithelioid – Round, larger, lots of cytoplasm, “epithelial-like”

A

Terms used to generally describe the cell shape of sarcoma tumor cells:

Spindle cell – rod shaped (fibroblast, smooth muscle cell)

Round cell – small, lymphocyte size, little cytoplasm (Ewings,

rhabdomyosarcoma)

Epithelioid – Round, larger, lots of cytoplasm, “epithelial-like”

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51
Q

Terms used to generally describe the cell shape of sarcoma tumor cells:

Spindle cell – rod shaped (fibroblast, smooth muscle cell)

_______ cell – small, lymphocyte size, little cytoplasm (Ewings,

rhabdomyosarcoma)

Epithelioid – Round, larger, lots of cytoplasm, “epithelial-like”

A

Terms used to generally describe the cell shape of sarcoma tumor cells:

Spindle cell – rod shaped (fibroblast, smooth muscle cell)

Round cell – small, lymphocyte size, little cytoplasm (Ewings,

rhabdomyosarcoma)

Epithelioid – Round, larger, lots of cytoplasm, “epithelial-like”

52
Q

Terms used to generally describe the cell shape of sarcoma tumor cells:

Spindle cell – rod shaped (fibroblast, smooth muscle cell)

Round cell – small, lymphocyte size, little cytoplasm (Ewings,

rhabdomyosarcoma)

_________ – Round, larger, lots of cytoplasm, “epithelial-like”

A

Terms used to generally describe the cell shape of sarcoma tumor cells:

Spindle cell – rod shaped (fibroblast, smooth muscle cell)

Round cell – small, lymphocyte size, little cytoplasm (Ewings,

rhabdomyosarcoma)

Epithelioid – Round, larger, lots of cytoplasm, “epithelial-like”

53
Q

‘Spindle cell’ sarcomas typically arise from what cell types?

A

Fibroblasts;

smooth muscle;

Schwann cells

54
Q

‘Round cell’ sarcomas typically arise from what cell types?

A

Skeletal muscle

(also seen in Ewing’s sarcoma)

55
Q

Name the benign fibroblastic tumor described by the following:

‘subcutaneous (superficial) rapidly growing “spindle cell” lesion of extremities or trunk.’

A

Nodular fasciitis

56
Q

Name the benign fibroblastic tumor described by the following:

‘Locally aggressive lesion of fibroblasts, benign spindle cells set in collagenous background. Beta-catenin positive by IHC’

A

Fibromatosis

(can be superficial or visceral)

57
Q

A ________ (‘strawberry’) hemangioma (including pyogenic granulomas) is a hypercellular proliferation of small or primitive vascular spaces (often in children, tends to regress with age).

A

A capillary (‘strawberry’) hemangioma (including pyogenic granulomas) is a hypercellular proliferation of small or primitive vascular spaces (often in children, tends to regress with age).

58
Q

What hemangioma type is made of large and mature vascular spaces; does not regress; and may be associated with Maffucci’s syndrome?

A

Cavernous hemangioma

59
Q

Vascular tumors are positive for endothelial markers CD____ and CD____.

A

Vascular tumors are positive for endothelial markers CD31 and CD34.

60
Q

Name two forms of benign tumor that arise from Schwann cells.

A

Granular cell tumor;

Schwannomas

61
Q

Schwann cell tumors are _____ positive on immunochemistry.

A

Schwann cell tumors are S-100 positive on immunochemistry.

62
Q

Benign Schwann cell tumors:

Granular cell tumor - Benign tumor of neural origin, round cells with ______ cytoplasmic _________. Tumors are positive for S-100 protein (schwann cell origin)

Schwannoma – Benign tumor with ‘pallisading” spindle cells. Risk of malignant transformation in NF1, “acoustic neuromas” in NF2, S100 positive by IHC.

A

Benign Schwann cell tumors:

Granular cell tumor - Benign tumor of neural origin, round cells with pink cytoplasmic granules. Tumors are positive for S-100 protein (schwann cell origin)

Schwannoma – Benign tumor with “pallisading” spindle cells. Risk of malignant transformation in NF1, “acoustic neuromas” in NF2, S100 positive by IHC.

63
Q

Benign Schwann cell tumors:

Granular cell tumor - Benign tumor of neural origin, round cells with pink cytoplasmic granules. Tumors are positive for S-100 protein (schwann cell origin)

Schwannoma – Benign tumor with “__________” ________ cells. Risk of malignant transformation in NF1, “acoustic neuromas” in NF2, S100 positive by IHC.

A

Benign Schwann cell tumors:

Granular cell tumor - Benign tumor of neural origin, round cells with pink cytoplasmic granules. Tumors are positive for S-100 protein (schwann cell origin)

Schwannoma – Benign tumor with “pallisading” spindle cells. Risk of malignant transformation in NF1, “acoustic neuromas” in NF2, S100 positive by IHC.

64
Q

What is the most common soft tissue tumor?

In what tissue layer are they found?

A

Lipoma;

subcutaneous

65
Q

Lipomas are benign but can rarely infiltrate what tissue type?

A

Local skeletal muscle

66
Q

What does it mean that most malignant soft tissue tumors are ‘deep-seated’?

A

They are deep to the fascia, well-entrenched within the deeper tissues

67
Q

In general, sarcomas are vimentin ________ and cytokeratin ________.

A

In general, sarcomas are vimentin positive and cytokeratin negative.

68
Q

Name the sarcoma:

“Intermediate behaving, rarely metastasizing nodular lesion infiltrating subcutis (superficial tissue); prominent spindle cell storiform patterns, CD34 positive spindle cells.”

A

Dermatofibrosarcoma protuberans (DFSP)

69
Q

Name the sarcoma:

“Adults 40 – 55 years — Deep soft tissue; especially lower extremities and trunk; Grossly has classic “fish-flesh” appearance in high grade lesions; Hypercellular spindle cell “herringbone” pattern. No consistent IHC expression.”

A

Fibrosarcoma

70
Q

Name the sarcoma:

“(Undifferentiated pleomorphic sarcoma) - Sarcoma of late adult life (over 50); Deep soft tissue of extremities and trunk; composed of fibroblastic, myofibroblastic, and pleomorphic histiocytic-like cells. No consistent IHC expression.”

A

Malignant fibrous histiocytoma

71
Q

Name the sarcoma:

Most common sarcoma of middle adult life; deep tumor especially retroperitoneum. Adult lipocytes with variable numbers of cells with hyperchromatic enlarged nuclei (lipoblasts). Supernummerary ring chromosomes and MDM2 gene amplification. Typically well-differentiated; myxoid variant with t(12;16) chromosome translocation.

A

Liposarcoma

72
Q

Name the sarcoma:

“A sarcoma of young adult life; knee, thigh, and foot; often a biphasic (epithelial and spindled) pattern; Expresses epithelial markers by IHC (cytokeratin, epithelial membrane antigen); characteristic chromosomal translocation t(x;18).”

A

Synovial sarcoma

73
Q

Name the sarcoma:

“Malignant tumor of smooth muscle; spindle cells in fascicles and eosinophilic cytoplasm, smooth muscle actin and desmin IHC.”

A

Leiomyosarcoma

74
Q

Name the sarcoma:

“Malignant sarcoma of blood vessels; can be post radiation; CD31 and CD34 IHC”

A

Angiosarcoma

75
Q

Name the sarcoma:

“Malignant childhood sarcoma of skeletal muscle; can be spindle or round cell; desmin and myogenin IHC.”

A

Rhabdomyosarcoma

76
Q

Describe the two subtypes of rhabdomyosarcoma.

A
  1. Embryonal (including botryoides variant) — grape like mass seen in GU tract
  2. Alveolar — t(1;13) and t(2;13) chromosome translocations
77
Q

Dermatofibrosarcoma protuberans is characterized by ____+ ________ cells.

A

Dermatofibrosarcoma protuberans is characterized by CD34+ spindle cells.

78
Q

What is another term for a malignant fibrous histiocytoma?

A

Undifferentiated pleomorphic sarcoma

79
Q

Synovial sarcomas express what markers on immunohistochemistry?

A

Epithelial (cytokeratin, epithelial membrane antigen);

80
Q

Angiosarcomas express what markers on immunohistochemistry?

A

CD31 and CD34

81
Q

Leiomyosarcomas express what markers on immunohistochemistry?

A

Smooth muscle actin and desmin

82
Q

Rhabdomyosarcomas express what markers on immunohistochemistry?

A

Desmin and myogenin

83
Q

Which tumor presents as grape-like masses in the genitourinary tracts of children?

A

Embryonal rhabdomyosarcoma

84
Q

Alveolar rhabdomyosarcomas are associated with the following translocations:

t(1,__)

t(2,__)

A

Alveolar rhabdomyosarcomas are associated with the following translocations:

t(1,13)

t(2,13)

85
Q

Was this slide taken from a capillary hemangioma or a cavernous hemangioma?

A

Capillary

(image of cavernous hemangioma attached below)

86
Q

Glomus tumor is a benign neoplasm composed of glomus cells, which are thought to be modified ______ ______ cells based on their ultrastructural appearance. These tumors mostly occur in the distal extremities in young or middle-aged adults.

A

Glomus tumor is a benign neoplasm composed of glomus cells, which are thought to be modified smooth muscle cells based on their ultrastructural appearance. These tumors mostly occur in the distal extremities in young or middle-aged adults.

87
Q

True/False.

Angiosarcoma, rhabdomyosarcoma, and epithelioid sarcoma are some examples of sarcomas that tend to metastasize lymphatically as well as hematogenously.

A

True.

88
Q

What are some factors that might increase an individual’s risk of sarcoma development?

A
  1. External stressors:

E.g. Toxins (phenoxyacetic herbicides, chlorophenols, dioxin); radiation

  1. Germline mutations / cancer syndromes:

E.g. RB, Gardner’s syndrome (mesenteric fibromatosis, osteomas, colon polyps); NF1 (MPNST); Li-Fraumeni syndrome (p53) (soft tissue and bone sarcoma).

89
Q

____% of soft tissue sarcomas are located on the extremities (thigh is most common site).

A

75% of soft tissue sarcomas are located on the extremities (thigh is most common site).

90
Q

3/4 of sarcomas are histologically _____ grade.

A

3/4 of sarcomas are histologically high grade.

91
Q

What sarcoma is associated with a ‘Herringbone’ fasciculated pattern on histology?

A

Fibrosarcoma

92
Q

Where do half of all cases of dermatofibrosarcoma protuberans (a low grade sarcoma) appear on the body?

A

The trunk

93
Q

True/False.

Most cases of alveolar rhabdomyosarcomas occur in the lung base.

A

False.

Most common in extremities within skeletal muscle.

94
Q

Decide if each of the following oncoviruses is an RNA or DNA virus:

HPV

EBV

HBV

HTLV-1

A

DNA

DNA

DNA

RNA

95
Q

True/False.

In an infection with DNA oncoviruses, the viral genome inserts into the host genome and forms a stable association

A

True.

96
Q

When an oncogenic virus integrates its DNA into the host DNA, it often disrupts genes essential for viral replication.

What is the result?

A

The virus remains in a latent state indefinitely

97
Q

What is the scientific term for genital warts?

A

Condyloma acuminatum

98
Q

Condyloma acuminatum (genital warts) is associated with what low-risk strains of HPV?

A

6, 11

99
Q

Squamous cell carcinoma of the cervix, anogenital region, and upper respiratory tract are associated with what high risk strains of HPV?

A

16, 18, 31, 33, 35, 51

100
Q

What cancers are associated with the high-risk strains of HPV (16, 18, 31, 33)?

A

Squamous cell carcinoma of the cervix, anogenital region, and upper respiratory tract

101
Q

True/False.

In benign lesions, the HPV genome is not integrated into the host DNA (It is maintained in an episomal/extrachromosomal form);

in malignant lesions, it is integrated.

A

True.

102
Q

Where do oncogenic viruses integrate their DNA into the host DNA?

A

It is a random event

(different cancers have different integration sites)

(however, once the DNA has been integrated, all cells of a given cancer will have the same integration pattern — clonality)

103
Q

When HPV is inserted into the host genome, the _____ and _____ viral genes are disrupted, leading to over expression of E6 and E7, which bind host P53 and RB/P21, respectively.

(Thus, E6 and E7 are oncogenes leading to uninhibited cell progression.)

A

When HPV is inserted into the host genome, the E1 and E2 viral genes are disrupted, leading to over expression of E6 and E7, which bind host P53 and RB/P21, respectively.

(Thus, E6 and E7 are oncogenes leading to uninhibited cell progression.)

104
Q

When HPV is inserted into the host genome, the E1 and E2 viral genes are disrupted, leading to over expression of ____ and ____, which bind host P53 and RB/P21, respectively.

(Thus, E6 and E7 are oncogenes leading to uninhibited cell progression.)

A

When HPV is inserted into the host genome, the E1 and E2 viral genes are disrupted, leading to over expression of E6 and E7, which bind host P53 and RB/P21, respectively.

(Thus, E6 and E7 are oncogenes leading to uninhibited cell progression.)

105
Q

When HPV is inserted into the host genome, the E1 and E2 viral genes are disrupted, leading to over expression of E6 and E7, which bind host ______ and ______, respectively.

(Thus, E6 and E7 are oncogenes leading to uninhibited cell progression.)

A

When HPV is inserted into the host genome, the E1 and E2 viral genes are disrupted, leading to over expression of E6 and E7, which bind host P53 and RB/P21, respectively.

(Thus, E6 and E7 are oncogenes leading to uninhibited cell progression.)

106
Q

When HPV is inserted into the host genome, the E1 and E2 viral genes are disrupted, leading to over expression of E6 and E7, which bind host P53 and RB/P21, respectively.

(Thus, E6 and E7 are ___________, leading to uninhibited cell progression.)

A

When HPV is inserted into the host genome, the E1 and E2 viral genes are disrupted, leading to over expression of E6 and E7, which bind host P53 and RB/P21, respectively.

(Thus, E6 and E7 are oncogenes, leading to uninhibited cell progression.)

107
Q

(Hyper-/Hypo-) _______-phosphorylated RB proteins are activated, thus inhibiting cell cycle progression by binding E2F transcription factor.

A

Hypo-phosphorylated RB proteins are activated, thus inhibiting cell cycle progression by binding E2F transcription factor.

108
Q

Hypo-phosphorylated RB proteins are activated, thus inhibiting cell cycle progression by binding _____________ factor.

A

Hypo-phosphorylated RB proteins are activated, thus inhibiting cell cycle progression by binding E2F transcription factor.

109
Q

What happens when cyclin-dependent kinases phosphorylate RB?

A

It becomes inactivated, leading to release of E2F transcription factor

110
Q

P53 genes are typically activated by cell _________, leading to DNA __________ (or ________sis).

A

P53 genes are typically activated by cell damage, leading to DNA repair (or apoptosis).

111
Q

Are oncogenic infections typically enough to cause malignancy on their own?

A

No, they are inciting events

(usually, other stressors needed)

112
Q

Which EBV gene acts as a B cell oncogene?

A

LMP-1

(mimics CD40’s effects)

113
Q

Upon infectinig B cells, the EBV oncogene LMP-1 mimics ______ activity, leading to up-regulation of ___-___ and ______-______ pathways.

A

Upon infectinig B cells, the EBV oncogene LMP-1 mimics CD40 activity, leading to up-regulation of NF-kB and JAK-STAT pathways.

114
Q

Besides LMP-1, what other gene is involved in the B cell proliferation seen in infection with EBV?

A

EBNA-2

(activates cyclin D1)

115
Q

What oncogene is amplified in Burkitt lymphoma?

Via what translocation?

A

C-Myc

t(8;14)

116
Q

What percentage of nasopharyngeal carcinomas contain EBV?

A

100%

117
Q

HBV is associated with development of what malignancy?

A

Hepatocellular carcinoma

118
Q

How does HBV cause hepatocellular carcinoma.

A

Via chronic hepatocellular inflammation

(and resultant hyperplasia / increased mitotic rate –> increased risk of cancer development)

119
Q

Name the P53-binding (growth promoting) protein synthesized by the HBV genome.

A

HBx

120
Q

Where is Human T-Cell Leukemia Virus (HTLV)-1 endemic?

A

Japan;

the caribbean

121
Q

What malignancy is characterized by flower-like lymphocytes?

A

Adult T-cell leukemia/lymphoma (ATLL)

(caused by HTLV-1)

122
Q

What malignancy is associated with HTLV-1 infection?

A

Adult T-cell leukemia/lymphoma (ATLL)

123
Q

True/False.

HTLV-1 causes leukemia in 50% of infected individuals (although decades after intial infection). It infects CD4+ T cells, similarly to HIV.

A

False.

HTLV-1 causes leukemia in 3 - 5% of infected individuals (decades after intial infection). It infects CD4+ T cells, similarly to HIV.

124
Q

What gene is necessary for HTLV-1 to cause leukemia?

A

tax

125
Q

True/False.

The mechanism by which H. pylori causes gastric adenocarcinomas and MALT lymphomas to arise is via chronic inflammation.

A

True.

126
Q

True/False.

Latent DNA viruses are the most potent (e.g. EBV, HPV).

A

True.

127
Q

True/False.

The expression of oncofetal proteins (e.g. AFP, CEA) in adults is exclusively seen in malignancy.

A

False.

Increased expression is sometimes seen in inflammatory and/or some normal tissues.

T1 - Phase 2 - Systems Modules (I) (27 decks)

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