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Flashcards in SKIN ONCOLOGY Deck (72):
1

Premalignant lesions for squamous cell cancer

Actinic keratoses is a premalignant lesion for squamous cell cancer (actinic is like acral - deadly)

Seborrheic - (water old age lesion) keratosis is a skin lesion that has no malignant potential.

2

A 43-year-old male comes to your office with a suspicious appearing lesion on his back. A full work up is initiated and the patient is found to have an ulcerated melanoma with a thickness of 1.5 mm and two positive lymph nodes. No distant metastases were found.

TNM staging for melanoma is based on depth of tumor and ulceration.
Primary Tumor (T)
T1 lesions are less than 1 mm. -a: without ulceration -b: with ulceration
T2 lesions are between 1.01-2 mm. -a: without ulceration -b: with ulceration
T3 lesions are 2.01-4 mm. -a: without ulceration -b: with ulceration
T4 lesions are greater than 4 mm. -a: without ulceration -b: with ulceration
The absence or presence of ulceration is noted by an “a” or “b” designation, respectively.

Regional lymph nodes (N)
N1 involves one lymph node.
N2 disease includes 2-3 regional lymph nodes.
N3 disease includes four or more regional nodes.

Distant metastasis (M)
M0: No detectable evidence of distant metastases
M1a: Metastases to skin, subcutaneous, or distant lymph node, normal serum LDH
M1b: Lung metastases, normal LDH
M1c: Metastasis to other visceral metastases with a normal LDH, or any distant metastases and an elevated LDH
Bottom Line: TNM staging factors in both depth of tumor and presence of ulceration.

3

MOST common tumors to spread to bone

Breast and prostate cancers are the two most common sources of cancer metastasis to the bone.
Answers C & E: Lung and kidney cancers metastasize frequently to the bone.

4

Hypersensitivity reactions four categories:


Type I, or an immediate hypersensitivity reaction, involves immediate release of IgE and vasoactive substances (choice A). This response is what leads to anaphylaxis.

Type II is an antibody mediated reaction, which involves IgG and IgM binding to target antigens and subsequent compliment activation (choice B).

Type II hypersensitivity is responsible for Goodpasture syndrome and autoimmune hemolytic anemia.

Type III reactions are due to deposition of antibody- antigen complexes and cause serum sickness (choice C).

Type IV are cell mediated reactions. They exhibit a peak response 24-72 hours after exposure and are responsible for contact dermatitis and reaction to PPD testing (choice D).

Bottom Line: PPD tests assess a cell mediated response or a type IV hypersensitivity reaction.

5

Soft tissue sarcomas most important predictors of prognosis are

mitotic index

and

amount of necrosis.

6

Chemotherapy is effective with what type of sarcoma

Ewing's Sarcoma, that show survival benefits with neoadjuvant chemotherapy.

7

staging of sarcoma

High-grade histologic findings, deep location, and tumor > 5 cm are independent prognostic factors for survival.
Staging classifies lesions as:
-T1 - < 5 cm -T2 - > 5 cm
-N1 - regional node involvement
-G1 - well-differentiated -G2 - moderately differentiated -G3 - poorly differentiated -G4 - undifferentiated.
Staging is based on T, N, M and G classification.
Stage IV disease is classified as any G or T with regional nodal involvement (N1) OR evidence of metastatic disease (M1).
Primary therapy includes surgical resection with margin of normal tissue. Limb sparing is often possible. Local control pre-operatively may be achieved with radiation therapy.
Bottom Line: Stage IV soft tissue sarcoma involves regional nodal involvement (N1) or evidence of metastatic disease (M1).

8

Bladder tumors referred to as superficial disease

involve the mucosa (Ta)
and

the lamina propria (T1)

are referred to as superficial disease,

9

Bladder tumors invasive disease

extend beyond the lamina propria and invade muscle (T2a) or greater

Disease that extends through the muscle into the fat (T3), node- positive disease, or metastatic disease requires further treatment with neoadjuvant or adjuvant chemotherapy.
Answer A: Endoscopic resection is optimal treatment for patients with low risk, superficial disease.
Answer B: High-grade T1 lesions recur in more than 80% of cases and progress to muscle-invasive disease in 50% of patients within 3 years. Patients with high- risk superficial disease—defined as carcinoma in situ, stage T1 lesions, or large, high-grade, recurrent, or multifocal Ta lesions—should receive further treatment with intravesical bacillus Calmette-Guérin (BCG).
Answers C & D: Radical cystectomy alone or with lymoh nodes dissection is inadequate treatment for this patient as he has invasive disease that should be treated with either neoadjuvant therapy or radical resection, lymph nodes

10

Bladder tumors that requires further treatment with neoadjuvant or adjuvant chemotherapy.

Advanced features:

Disease that extends through the muscle into the fat (T3),

node- positive disease,

or

metastatic disease



** Radical cystectomy alone or with lymoh nodes dissection is inadequate treatment for this patient as he has invasive disease that should be treated with either neoadjuvant therapy or radical resection, lymph nodes

11

Bladder tumors optimal treatment for patients with low risk, superficial disease.

Endoscopic resection


Answer B: High-grade T1 lesions recur in more than 80% of cases and progress to muscle-invasive disease in 50% of patients within 3 years. Patients with high- risk superficial disease—defined as carcinoma in situ, stage T1 lesions, or large, high-grade, recurrent, or multifocal Ta lesions—should receive further treatment with intravesical bacillus Calmette-Guérin (BCG).

12

Myofibroblasts

responsible for wound contraction

13

Most squamous cell carcinomas of the tongue are

T2 or smaller at the time of identification and can be successfully managed by wide local excision with clear margins. Nearly ! of the tongue can be excised with preservation of oral function, although musculocutaneous free flaps are required with larger resections to prevent tongue tethering.

14

A sentinel lymph node biopsy (SLNB) is indicated in the case of invasive malignant melanoma with the following characteristics:

greater than 1 mm
or
tumor less than 1 mm in thickness with either ulceration, regression, Clark levels IV or V,
or
mitotic rate > 1 per 10 high powered fields.

A frozen section is not performed because special stains are needed including : S100, HMB 45, MART 1, Melan A, and Mitf.

15

A positive sentinel lymph node biopsy of melanoma management

mandate a completion lymphadenectomy of the draining basin,
level I, II, and III in the axilla,

16

Advanced stage cervical tumors are defined as what and how are they treated

IIB-IVA

treated aggressively with a multi-modal approach,

Primary radiotherapy (RT) with external beam and brachytherapy is the main stay of treatment for this disease!

including radiation therapy and cisplatin-based chemotherapy.

Clearing the lymph node basin may have some therapeutic advantage.

Presence of para-aortic lymph node spread has significant effect on
prognosis.



Cisplatin-based chemotherapy is also of some value in the treatemt.

NOT primary surgical approach - would not be appropriate in the setting of
advanced disease.

17

Any patient with a solid testicular mass, w

hich has been confirmed on ultrasound, is considered to have testicular cancer until proven otherwise, and should undergo a radical orchiectomy to make a definitive diagnosis.
When performing a radical orchiectomy, the surgery should be performed by an inguinal approach rather than a scrotal approach. If the scrotum is surgically violated by performing a scrotal orchiectomy, metastatic spread to both the retroperitoneal and the inguinal nodes becomes possible.
Bottom Line: Inguinal exploration with early vascular control of the spermatic cord structures is the initial intervention to exclude testicular neoplasm. If cancer cannot be excluded by examination of the testis, then radical orchiectomy is warranted. Scrotal approaches and open testicular biopsies should be avoided.

18

Testicular cancer is the most common cancer in men between the ages of

20 and 35 years

19

Ninety to 95% of all primary testicular tumors are

germ cell tumors

(seminoma and nonseminoma)

while the remainder are nongerminal neoplasms (Leydig cell, Sertoli cell, gonadoblastoma)


20

staging choice for testicular cancer


A CT scan is the study of choice for . CT scan allows you to evaluate retroperitoneal adenopathy and lung metastases.

21

The metastatic spread of testicular cancer is ordered and predictable.

primary metastatic landing site for left and right testicular cancers is the

para-aortic

and

interaortocaval nodes in the retroperitoneum, respectively.


22

The most common types of small bowel malignancies include

carcinoid,
adenocarcinoma,
and
stromal tumors.

lymphoma is rare

23

Stage ovarian cancer

Stage I ovarian cancer involves one or BILATERAL of the ovaries!
treated with resection alone.

Stage II is extended involvement of tumor, but limited to the pelvis.

Stage III tumor involvement into the abdomen.

Stage IV will have distant metastasis.

24

The most common clinical manifestation of a lip cancer is

an ulcerated lesion along the vermillion border.

25

predominant histologic variant and occurs primarily on the lower lip of Caucasian males between 50 and 70 years of age

Squamous cell!

(CAREFUL - most common skin cancer over all is basal cell - but think head and neck is most associated with squamous)


26

bigest risk factors for dvlp of squamous cell cancer of the lip

Sun exposure and tobacco use are the most significant risk factors.

Caucasian males between 50 and 70 years of age

27

Compare treatment of squamous cell cancer of the lip

Surgery and radiation therapy are equally effective for early stage tumors!

BUT PERFER - SURGERY - wide local excision with histologic confirmation of at least a 3mm margin is the preferred approach.

28

treatment of adjvanced squamous cell cancer of the lip

NO Sentinel lymph node biopsy - thus far not proved as effective in head and neck cancers as it has for melanoma and is therefore NOT considered to be standard of care.

Radiation therapy is a component of the POST operative ADJUVANT management for patients with clinically evident neck disease or advanced-stage primary tumors.

Neck metastases are an infrequent finding occurring in only 10% of cases thereby obviating the need for more extensive procedures including selective, modified, or radical neck dissections for most cases..

29

Hypertrophic scars

develop within six to eight weeks after injury.

They can worsen up to six months but subside with time

The boundaries of the original scar are maintained.

Hypertrophic scar healing is related to closing a wound under tension.


Both hypertrophic and keloid scars are raised, erythematous, and often pruritic

Hypertrophic scars express an increased density of blood vessels, whereas keloid scars show a decreased density of blood vessels.

Myofibroblasts are present in hypertrophic scars but are absent in keloids

30

Keloid scars

may develop months after the injury.

Unlike hypertrophic scars, they do not regress and overgrow the original boundaries of the wound.

Keloid scars are commonly found on the deltoid, upper back, chest, and earlobes.

They have a familial predisposition and are more common in African Americans.

Both hypertrophic and keloid scars are raised, erythematous, and often pruritic


Fibroblasts cultured from keloids have increased proliferation rates and decreased apoptosis when compared with fibroblasts cultured from hypertrophic scars.

Hypertrophic scars express an increased density of blood vessels, whereas keloid scars show a decreased density of blood vessels.

Myofibroblasts are present in hypertrophic scars but are absent in keloids

31

the most significant prognostic factor affect survival in malignant melanoma

lymph node involvement.

tumor thickness,

mitotic rate,

ulceration,

LDH

32

Soft-tissue sarcomas prognostic factores and what is most important


Histologic grade most important prognostic indicator in evaluating soft tissue sarcomas of the extremities.

Other factors that are included in the staging system are the size

depth of the tumor

nodal

metastatic disease.


There is currently no staging system for retroperitoneal sarcomas.

33

One of the more commonly seen risk factors for melanoma is

UV radiation.

UVA

AND

UVB

radiation exposure in fair skinned individuals both elevate the risk of melanoma formation.


Other factors include

previous sunburns,
congenital nevi,
dysplastic nevi,
xeroderma pigmentosa
family history.


34

skin cancer risk from Actinic keratoses

risk factor for SQUAMOUS cell cancer, but not for melanoma.

35

wound healing is divided into four stages:

1.) hemostasis
2.) inflammation
3.) proliferation
4.) remodeling

36

The remodeling phase of wound healing

Final phase:

begins at 3 weeks

lasts for up to one year after the onset of injury

replacing Type III collagen with Type I collagen to increase the tensile strength

37

wound The maximum tensile strength attained is

80% that of normal skin

38

EBV can be associated with

nasopharyngeal cancer,

Hodgkin's disease,

Burkitt’s lymphoma,

lymphoproliferative disease in AIDS patients.

39

Kaposi’s sarcoma is associated with what virus

HHV-8

40

Mech of radiation

Radiation causes oxygen free radicals tdamage to cellular DNA.

tissues with high oxygen levels will have the greatest response

M phase of the cell cycle is most susceptible to radiation.

high dose radiation is that it has a skin preserving effect

Radiation induces apoptosis which is what ultimately leads to cell death if the cell is unable to repair the damage.

If cells successfully repair DNA damage induced by ionizing radiation, they may resume proliferation

Alternatively, radiation may kill cancer cells by three pathways:

1. Inducing apoptosis by the intrinsic (p53-dependent) or the extrinsic pathway

2. Causing permanent cell cycle arrest or terminal differentiation

3. Inducing “mitotic cell death” from aberrant mitosis, resulting in mitotic catastrophe.

41

LDH is used as a tumor marker for

testicular cancer and other germ cell tumors
(It’s not as useful as AFP and HCG )

MELANOMA

neuroblastoma

lymphoma




42

tumor marker for panc cancer

PREDICTIVE OF UNRESECTABLE!

A level above 1000 is diagnostic of pancreatic cancer and has a high risk of being unresectable metastatic disease.

CA 19-9 level HAS been shown to correlate with tumor burden.

For example, higher CA 19-9 levels typically correlate with higher tumor stage, and more than 95% of patients with unresectable disease have levels higher than 1000 U/mL.


Serial measurement of CA 19-9 is used to monitor response to therapy.

A rise in CA 19-9 after curative resection has been shown to precede clinical or computed tomographic evidence of recurrence by 2 to 9 months.

In patients with unresectable/metastatic disease, failure of CA 19-9 levels to fall with chemotherapy reflects poor tumor response.


Bottom Line: CA 19-9 is the most frequently checked tumor marker for pancreatic cancer.

43

Undifferentiated spindle cell tumor

(malignant fibrous histiocytoma of bone)

most common site of occurrence is the proximal tibia and distal metaphyses of the femur. It may also be found in the pelvis, humerus, and scapula.


Radiographic features include loss of normal trabeculation and cortical destruction.

Adjacent soft tissue invasion and mass formation may occur.

high grade lesions (> 90%) and a tumor showing fiboblasts in a whirling pattern with multinucleated giant cells, inflammatory cells, and foamy mononuclear giant cells.

NEOadjuvant CHEMO can be administered in which can relieve pain and decrease local edema, contracture, and the size of the soft tissue tumor.

Urgent surgical resection is indicated if at high risk for pathologic fracture.

Surgical excision with wide margin is advised whether or not the patient receives neoadjuvant therapy.

Amputation can normally be avoided.

Bottom Line: Undifferentiated spindle cell

44

biochem mech of steroid dcr wound strength

glucocorticoids inhibit PROcollagen gene transcription,

thereby leading to decreased collagen synthesis


45

vitamin C (ascorbic acid) deficiency biochem mech of dcr wound strength

proline hydroxylation is prevented,

unstable triple helices secondary to the synthesis of defective pro-a chains

46

Vitamin C deficiency is characterized by clinical features of

gradual loss of preexisting normal collagen,

which leads to fragile blood vessels and loose teeth.


47

collagen,

Type I

most common

principal collagen of

skin

bone

48

inflammatory phase of wound healing is characterized by

increased vascular permeability,

migration of cells into the wound by chemotaxis,

secretion of cytokines and growth factors into the wound,

activation of the migrating cells

49

The proliferative stage of wound healing is characterized by



the formation of granulation tissue.

50

Li-Fraumeni syndrome associated cancer

a cancer predisposition syndrome associated with the development of the following classic tumors:
soft tissue sarcoma,
osteosarcoma,
pre-menopausal breast cancer,
brain tumors,
adrenocortical carcinoma (ACC),
leukemias.

51

Li-Fraumeni syndrome screening recs

(1) children and adults undergo comprehensive annual physical examination;

annual breast MRI and twice annual clinical breast examination beginning at age 20-25 years.

The use of mammograms has been controversial because of radiation exposure and limited sensitivity. When included, annual mammograms should alternate with breast MRI, with one modality every six months;

colonoscopy every 2-3 years beginning no later than age 25 years;

52

malignant melanomas dictates the treatment plan and margins of resection and SLNB recs

Current guidelines recommend:
-5 mm margin for melanoma in situ
-1 cm margin for lesions less than 1 mm in thickness
-2 cm margin for 1 mm or greater


Sentinel lymph node biopsy for 1 mm or greater

Positive biopsies warrant complete lymphadenectomy.


53

Neutrophils peak in a wound at

24 – 48 hrs after injury occurrence

54

fxn of Neutrophils in the wound

Neutrophils are attracted by local prostaglandin release, chemotatic substances, and increased vascular permeability.

Neutrophils are responsible for the phagocytosis of bacteria and wound debris and are a major source of cytokine secretion in early wound healing.

55

Macrophages peak in a wound at

48 to 96 hours after injury occurs.

They remain in the wound until healing is completed.

Macrophages are derived from monocytes

56

The series of events a skin graft progresses through when placed on a well vascularized wound are:

imbibition,
inosculation,
then revascularization.

57

Imbibition

diffusion of nutrients into the graft without a direct blood supply.

This is easily disrupted with seroma or hematoma formation and shear stress.

58

Inosculation

donor and recipient capillary beds come into alignment with each other.

(CAREFUL, this sound like revasc - but it is the step before revasc)

59

Revascularization after graft

happens after about 5 days,

when arterial inflow and venous outflow can be detected.

60

Sarcoma staging is based on

tumor grade (G), size (T), Lymph node involvement (N) and distant metastasis (M).


(CAREFUL, this includes nodes even though rare to go to nodes!)

" SLN biopsy is not indicated because sarcomas usually do not metastasize to LN" but included in staging

61

most common site of metastasis of sarcomas.

The lung is the most common

hematogenous metastasis

62

Staging of sarcoma should include

CHEST CT - rule out lung metastasis, especially for high grade, large (> 5 cm) sarcomas.


NOT mandatory to do CT of the abdomen and pelvis with extremity sarcoma,

MAY consider CT abd/pelv if:
myxoid liposarcoma,
epitheliod,
angiosarcoma
synovial sarcoma,
which commonly metastasize to the abdomen...

63

lymphangiosarcoma treatment

wide local excision

with or without chemo or radiation therapy

64

Sarcoma staging is based on

tumor grade (G),
size (T),
Lymph node involvement (N)
distant metastasis (M).

65

most common site metastasis of sarcomas.

The lung of hematogenous

66

best test to rule out sarcoma mets

Chest CT is indicated to rule out lung metastasis,

especially for high grade,

large (> 5 cm) sarcomas.




67

when would you consider CT chest AND ABDOMEN for sarcoma

Sarcomas that commonly metastasize to the abdomen:

myxoid liposarcoma,
epitheliod, angiosarcoma
synovial sarcoma,

and POSSIBLE for:

high grade

> 5cm

68

what sarcoma may not need adjuvant

may not need radiation therapy, provided that they can be reliably followed:

small (1 cm)

of nonneoplastic tissue or biologic barrier (fascia)

69

extemity sarcoma Staging evaluation is completed with

a chest x-ray (for low-grade malignancies)

or

chest CT scan (for intermediate-grade or high-grade malignancies).

NOT Routine PET

ONLY head CT scan if alveolar soft part sarcoma)

70

when would Imaging alone be considered diagnostic (without bx)

well-differentiated liposarcoma

(also known as atypical lipomatous tumors).

71

breast sarcoma

Primary angiosarcoma

breast parenchyma young women.

The only potentially curative therapy is surgery.

patients should be offered a simple mastectomy instead of lumpectomy.

Partial resection of pectoralis major may be necessary to achieve negative margins!

The skin may be closed primarily.

staging with:
CT chest, abdomen, and pelvic

MRI of the breast!

contralateral breast may be a site for metastatic disease, but to date, a contralateral prophylactic mastectomy has no proven benefit.

in general responsive to systemic chemotherapy.

However, once chemotherapy is stopped, the disease tends to regrow.

AND NO proven survival benefit from systemic therapy.



72

non-op tx of desmodis

first choice

NSAIDS

Tomxafen


maybe: cytotoxic intravenous chemotherapy with different agents and schedules, oral tyrosine kinase inhibitors, GLEVAC?