Neoplasia/Hematology - Mechanisms of Disease - Dermatopathology; Soft Tissue Tumors; Infectious Agents and Cancer Flashcards
(127 cards)
1
Q
Which specific skin layer is most at risk of cancer development?
A
The stratum basale
2
Q
What is seborrheic keratosis?
A
A benign epidermal keratinocytic neoplasm
3
Q
During a routine examination of one of your adult patients, you note the attached skin structure.
What is it?
A
Seborrheic keratosis
4
Q
What findings might indicate that a skin finding is seborrheic keratosis rather than melanoma?
A
Greasy or verrucous consistency
5
Q
Are seborrheic keratoses singular or multiple?
Are they large or small?
A
Large variety
6
Q
Identify the term for the given definition:
‘keratinocytic dysplasia of the lower epidermis overlying solar elastosis’
A
Actinic keratosis
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.
8
Q
What non-malignant lesion is shown here?
A
Actinic keratosis
9
Q
True/False.
Actinic keratoses can be single or multiple.
A
True.
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
11
Q
True/False.
Actinic keratoses can lead to horn-like structures.
A
True.
12
Q
True/False.
Seborrheic keratoses are precancerous lesions.
A
False.
Actinic keratoses are precancerous lesions.
13
Q
What are the two main keratinocytic malignant neoplasms?
A
Basal cell carcinoma;
squamous cell carcinoma
14
Q
What dermatological cancer is often described as a pearly/translucent patch?
A
Basal cell carcinoma
15
Q
Does basal cell carcinoma have a variety of skin presentations?
A
Yes.
16
Q
What color are basal cell carcinoma cells (typically) under the microscope?
A
Blue-ish purple
(basophilic)
17
Q
What malignant lesion is shown here?
A
Squamous cell carcinoma
18
Q
What color are squamous cell carcinoma cells (typically) under the microscope?
A
Pink
(eosinophilic)
19
Q
What is the term for a well-differentiated cystic squamous cell carcinoma?
A
Keratoacanthoma
20
Q
Which keratinocytic malignancy is characterized by immature cells?
A
Basal cell carcinoma
21
Q
Which keratinocytic malignancy is characterized by mature cells?
A
Squamous cell carcinoma
22
Q
True/False.
Nevi can be epidermal, dermal or compound.
A
True.
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.
24
Q
On what part(s) of the body do males most often get melanomas?
A
Back and shoulders
25
On what part(s) of the body do females most often get melanomas?
Legs
26
Merkel cell carcinomas are an example of n\_\_\_\_\_\_\_\_\_\_\_\_\_e tumors.
Merkel cell carcinomas are an example of n**_euroendocrin_**e tumors.
27
Dermatofibromas are factor-\_\_\_\_\_\_ positive.
Dermatofibromas are factor-**VIIIa** positive.
28
A \_\_\_\_\_\_fibroma is a stromal neoplasm of the skin.
A **_dermato_**fibroma is a stromal neoplasm of the skin.
29
What fungus causes mycosis fungoides?
**None**!
It is a historical name --- this is a primary cutaneous T cell lymphoma
30
What is a mycosis fungoides?
A primary cutaneous T cell lymphoma
31
Describe the progression of mycosis fungoides according to cutaneous presentation.
**Patch** --\> **Plaque** --\> **Tumor**
32
What syndrome is characterized by the progression of mycosis fungoides (a T cell lymphoma) to the bloodstream (becoming leukemic)?
**Sézary** syndrome
33
\_\_\_\_\_\_\_ neoplasms of the skin are tumors forming from the extra-cutaneous structures of the skin (e.g. hair follicles, arrector pili, etc.).
**_Adnexal_** neoplasms of the skin are tumors forming from the extra-cutaneous structures of the skin (e.g. hair follicles, arrector pili, etc.).
34
What term refers to a benign neoplasm growing out of a hair follicle?
Pilomatricoma
(pilus + matrix + oma)
35
Describe the 'ghost cells' seen in pilomatricomas (benign neoplasms of the hair follicles).
36
What term refers to a benign neoplasm growing out of a sebaceous gland?
Sebaceous adenoma
37
What term refers to a malignant neoplasm growing out of a sebaceous gland?
Sebaceous carcinoma
38
What term refers to a benign neoplasm growing out of an eccrine sweat gland?
Cylindroma
39
**True/False**.
UV exposure is strongly implicated in the formation of cutaneous angiosarcomas.
True.
40
What term refers to benign vascular (endothelial) neoplasms?
**Hemangiomas**
| (strawberry, cherry, etc.)
41
While hemangiomas are benign vascular (endothelial) neoplasms, what term refers to malignant vascular neoplasms?
Angiosarcomas
42
Angiosarcomas most typically arise where?
Sun-damaged (or irradiated) heads and necks
43
What is the prognosis for angiosarcomas?
Very poor
(extremely rapid metastasis because they are already in the bloodstream)
44
Define leukoplakia.
A firmly attached **white** **patch** on a **mucous** **membrane**
(associated with an increased risk of cancer)
45
What is another term for melanoma in situ?
Lentigo maligna
46
Define: Lentigo maligna.
Melanoma in situ
47
How much more common are benign soft tissue tumors than malignant?
100:1
48
_3 broad categories of soft tissue tumors:_
* **Benign**
* ___________ behaving (locally aggressive and recurring but never metastasize or those with \<2% metastasis rate)
* ___________ (sarcoma)
_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)
49
Describe the _typical_ characteristics of most sarcomas in terms of the following:
## Footnote
**Location**
**Relative size**
**Mortality**
**Extremities** / **deep** **below fascia;**
**large** size;
**high** mortality
50
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”
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”
51
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”
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
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”
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
'Spindle cell' sarcomas typically arise from what cell types?
Fibroblasts;
smooth muscle;
Schwann cells
54
'Round cell' sarcomas typically arise from what cell types?
Skeletal muscle
| (also seen in Ewing's sarcoma)
55
Name the benign fibroblastic tumor described by the following:
*'subcutaneous (superficial) rapidly growing "spindle cell” lesion of extremities or trunk.'*
Nodular fasciitis
56
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'*
Fibromatosis
| (can be superficial or visceral)
57
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 **_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
What hemangioma type is made of large and mature vascular spaces; does not regress; and may be associated with Maffucci's syndrome?
**Cavernous** hemangioma
59
Vascular tumors are positive for endothelial markers CD\_\_\_\_ and CD\_\_\_\_.
Vascular tumors are positive for endothelial markers CD**_31_** and CD**_34_**.
60
Name two forms of benign tumor that arise from Schwann cells.
Granular cell tumor;
Schwannomas
61
Schwann cell tumors are _____ positive on immunochemistry.
Schwann cell tumors are **_S-100_** positive on immunochemistry.
62
_Benign Schwann cell tumors:_
## Footnote
**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.
_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
Benign Schwann cell tumors:
## Footnote
**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.
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
What is the most common soft tissue tumor?
In what tissue layer are they found?
Lipoma;
subcutaneous
65
Lipomas are benign but can rarely infiltrate what tissue type?
Local **skeletal** **muscle**
66
What does it mean that most malignant soft tissue tumors are 'deep-seated'?
They are **deep to the fascia**, well-entrenched within the deeper tissues
67
In general, sarcomas are vimentin ________ and cytokeratin \_\_\_\_\_\_\_\_.
In general, sarcomas are vimentin **_positive_** and cytokeratin **_negative_**.
68
Name the **sarcoma**:
"Intermediate behaving, rarely metastasizing nodular lesion infiltrating subcutis (superficial tissue); prominent spindle cell storiform patterns, CD34 positive spindle cells."
Dermatofibrosarcoma protuberans (DFSP)
69
Name the **sarcoma**:
## Footnote
"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."
Fibrosarcoma
70
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."
Malignant fibrous histiocytoma
71
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.
Liposarcoma
72
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)."
Synovial sarcoma
73
Name the **sarcoma**:
"Malignant tumor of smooth muscle; spindle cells in fascicles and eosinophilic cytoplasm, smooth muscle actin and desmin IHC."
Leiomyosarcoma
74
Name the **sarcoma**:
"Malignant sarcoma of blood vessels; can be post radiation; CD31 and CD34 IHC"
Angiosarcoma
75
Name the **sarcoma**:
"Malignant childhood sarcoma of skeletal muscle; can be spindle or round cell; desmin and myogenin IHC."
Rhabdomyosarcoma
76
Describe the two subtypes of rhabdomyosarcoma.
1. **Embryonal** (including botryoides variant) --- grape like mass seen in GU tract
2. **Alveolar** --- t(1;13) and t(2;13) chromosome translocations
77
Dermatofibrosarcoma protuberans is characterized by \_\_\_\_+ ________ cells.
Dermatofibrosarcoma protuberans is characterized by **_CD34_**+ **_spindle_** cells.
78
What is another term for a malignant fibrous histiocytoma?
Undifferentiated pleomorphic sarcoma
79
Synovial sarcomas express what markers on immunohistochemistry?
Epithelial (**cytokeratin**, **epithelial** **membrane** **antigen**);
80
Angiosarcomas express what markers on immunohistochemistry?
**CD31** and **CD34**
81
Leiomyosarcomas express what markers on immunohistochemistry?
Smooth muscle **actin** and **desmin**
82
Rhabdomyosarcomas express what markers on immunohistochemistry?
**Desmin** and **myogenin**
83
Which tumor presents as grape-like masses in the genitourinary tracts of children?
Embryonal rhabdomyosarcoma
84
Alveolar rhabdomyosarcomas are associated with the following translocations:
t(1,\_\_)
t(2,\_\_)
Alveolar rhabdomyosarcomas are associated with the following translocations:
t(1,**_13_**)
t(2,**_13_**)
85
Was this slide taken from a capillary hemangioma or a cavernous hemangioma?
Capillary
(image of cavernous hemangioma attached below)
86
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.
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
**True/False**.
_Angiosarcoma_, _rhabdomyosarcoma_, and _epithelioid_ _sarcoma_ are some examples of sarcomas that tend to metastasize lymphatically as well as hematogenously.
True.
88
What are some factors that might increase an individual's risk of sarcoma development?
1. **_External stressors_**:
E.g. **Toxins** (phenoxyacetic herbicides, chlorophenols, dioxin); **radiation**
2. **_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
\_\_\_\_**%** of soft tissue sarcomas are located on the extremities (thigh is most common site).
**_75_****%** of soft tissue sarcomas are located on the extremities (thigh is most common site).
90
3/4 of sarcomas are histologically _____ grade.
3/4 of sarcomas are histologically **_high_** grade.
91
What sarcoma is associated with a 'Herringbone' fasciculated pattern on histology?
Fibrosarcoma
92
Where do **half** of all cases of dermatofibrosarcoma protuberans (a low grade sarcoma) appear on the body?
The trunk
93
**True/False**.
Most cases of alveolar rhabdomyosarcomas occur in the lung base.
**False**.
Most common in extremities within skeletal muscle.
94
Decide if each of the following oncoviruses is an RNA or DNA virus:
HPV
EBV
HBV
HTLV-1
## Footnote
**DNA**
**DNA**
**DNA**
**RNA**
95
**True/False**.
In an infection with DNA oncoviruses, the viral genome inserts into the host genome and forms a stable association
True.
96
When an oncogenic virus integrates its DNA into the host DNA, it often disrupts genes essential for viral replication.
What is the result?
The virus remains in a **latent** **state** indefinitely
97
What is the scientific term for genital warts?
Condyloma acuminatum
98
Condyloma acuminatum (genital warts) is associated with what **low-risk** strains of HPV?
6, 11
99
Squamous cell carcinoma of the cervix, anogenital region, and upper respiratory tract are associated with what high risk strains of HPV?
**16**, **18**, **31**, **33**, 35, 51
100
What cancers are associated with the high-risk strains of HPV (16, 18, 31, 33)?
_Squamous cell carcinoma_ of the **cervix**, **anogenital** region, and **upper** **respiratory** tract
101
**True/False**.
## Footnote
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.
True.
102
Where do oncogenic viruses integrate their DNA into the host DNA?
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
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.)
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
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.)
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
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.)
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
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.)
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
(Hyper-/Hypo-) \_\_\_\_\_\_\_-phosphorylated RB proteins are activated, thus inhibiting cell cycle progression by binding E2F transcription factor.
**_Hypo_**-phosphorylated RB proteins are activated, thus inhibiting cell cycle progression by binding E2F transcription factor.
108
**Hypo**-phosphorylated RB proteins are activated, thus inhibiting cell cycle progression by binding _____________ factor.
**Hypo**-phosphorylated RB proteins are activated, thus inhibiting cell cycle progression by binding **_E2F transcription_** factor.
109
What happens when cyclin-dependent kinases phosphorylate RB?
It becomes **inactivated**, leading to **release** **of E2F transcription factor**
110
P53 genes are typically activated by cell \_\_\_\_\_\_\_\_\_, leading to **DNA** __________ (or \_\_\_\_\_\_\_\_sis).
P53 genes are typically activated by cell **_damage_**, leading to **DNA _repair_** (or **_apopto_**sis).
111
Are oncogenic infections typically enough to cause malignancy on their own?
No, they are inciting events
| (usually, other stressors needed)
112
Which EBV gene acts as a B cell oncogene?
*LMP-1*
| (mimics CD40's effects)
113
Upon infectinig B cells, the EBV oncogene *LMP-1* mimics ______ activity, leading to up-regulation of \_\_\_-\_\_\_ and \_\_\_\_\_\_-\_\_\_\_\_\_ pathways.
Upon infectinig B cells, the EBV oncogene *LMP-1* mimics **_CD40_** activity, leading to up-regulation of **_NF_**-**_kB_** and **_JAK_**-**_STAT_** pathways.
114
Besides *LMP-1*, what other gene is involved in the B cell proliferation seen in infection with EBV?
***EBNA-2***
| (activates cyclin D1)
115
What oncogene is amplified in Burkitt lymphoma?
Via what translocation?
*C-Myc*
t(8;14)
116
What percentage of nasopharyngeal carcinomas contain EBV?
100%
117
HBV is associated with development of what malignancy?
Hepatocellular carcinoma
118
How does HBV cause hepatocellular carcinoma.
Via chronic hepatocellular inflammation
(and resultant hyperplasia / increased mitotic rate --\> increased risk of cancer development)
119
Name the P53-binding (growth promoting) protein synthesized by the HBV genome.
HBx
120
Where is Human T-Cell Leukemia Virus (HTLV)-1 endemic?
Japan;
the caribbean
121
What malignancy is characterized by flower-like lymphocytes?
Adult T-cell leukemia/lymphoma (ATLL)
(caused by HTLV-1)
122
What malignancy is associated with HTLV-1 infection?
Adult T-cell leukemia/lymphoma (ATLL)
123
**True/False**.
HTLV-1 causes leukemia in 50% of infected individuals (although decades after intial infection). It infects CD4+ T cells, similarly to HIV.
**False**.
HTLV-1 causes leukemia in **_3 - 5_**% of infected individuals (decades after intial infection). It infects CD4+ T cells, similarly to HIV.
124
What gene is necessary for HTLV-1 to cause leukemia?
*tax*
125
**True/False**.
The mechanism by which *H. pylori* causes gastric adenocarcinomas and MALT lymphomas to arise is via chronic inflammation.
True.
126
**True/False**.
Latent DNA viruses are the most potent (e.g. EBV, HPV).
True.
127
**True/False**.
The expression of oncofetal proteins (e.g. AFP, CEA) in adults is exclusively seen in malignancy.
**False**.
Increased expression is sometimes seen in inflammatory and/or some normal tissues.
