20 - 110 - EPITHELIAL PRECANCEROUS LESIONS Flashcards
Precursor lesions of cutaneous squamous cell carcinoma (SCC).
ACTINIC KERATOSES
most important etiologic factor in the development of actinic keratoses
Long-term and cumulative ultraviolet (UV) radiation exposure
Risk factors of Actinic keratoses
fair skin, age, cumulative UV radiation exposure, immunosuppression, prior history of non-melanoma skin cancer
Actinic Keratoses
Multiple scaly and erythematous plaques on the dorsal hands of a 71-year-old male patient with a history of significant ultraviolet exposure. The lesions were grade II to grade III actinic keratoses.
They typically develop on sun-exposed areas, such as the balding scalp, head, neck, forearms, dorsal hands, and in women, additionally the dorsal legs (Fig. 110-1).
Mild actinic keratoses on the face of a fairskinned woman (grade I). The lesions appear as erythematous patches with a rough texture on palpation. Note other signs of actinic skin damage such as perioral wrinkling and the presence of solar lentigines.
Field cancerization. There are several ill-defined erythematous and scaly plaques, crusts, and ulcerations affecting a large area (“field”) of the balding scalp. Further alterations, such as mottled hypopigmentation and hyperpigmentation, are present and indicate actinic damage.
Alongside clinically detectable AKs, multiple subclinical lesions may be present (Fig. 110-3). This concept is known as field cancerization and is crucial for the therapeutic approach.
A, Multiple well-defined hypertrophic actinic keratoses on the decollete of a middle-aged female. B, A higher magnification reveals the rough and hyperkeratotic texture of some lesions.
main clues to the transition of AK to SCC
induration, inflammation, pain, and ulceration
type of hypertrophic AK that presents with a conical hypertrophic protuberance emanating from a skin-colored to erythematous papular base
Cutaneous horn, also known as cornu cutaneum, refers to a reaction pattern and not a particular lesion.
A, Cutaneous horn of the ear. Only biopsy will confirm whether this is an actinic keratosis or a squamous cell carcinoma. B, Cutaneous horn of the cheek.
represents confluent AKs on the lips, most often the lower lip
Actinic cheilitis
Persons with this condition have red, scaly, chapped lips, and at times erosions or fissures may be present (Fig. 110-6). The vermilion border of the lip is often indistinct, and focal hyperkeratosis and leukoplakia also may be seen. Individuals with this condition often complain of persistent dryness and cracking of the lips.
Classification of Actinic Keratosis
Olsen classification
Grade 1 includes lesions that are mild, slightly palpable, and are better seen than felt
Grade 2 represents lesions that are moderately thick and easily seen and felt.
Grade 3 lesions are severe, very thick and/or obvious AKs
Roewert-Huber classification (scheme for grading AK severity)
type AK I, atypical keratinocytes are restricted to the lower third of the epidermis and are only found within the basal and suprabasal layers.
type AK II, atypical keratinocytes are found within the lower two-thirds of the epidermis, alternating with zones of normal epidermis. In the upper papillary dermis buds of keratinocytes can be found
type AK III, atypical keratinocytes extend to the lower two-thirds of the full thickness of the epidermis. They can also involve the epithelia of the hair follicle, infundibula, and acrosyringium.
most important contributing factors for the formation of AKs.
Fair skin and exposure to UV radiation
single most effective means of decreasing the risk of AKs
Minimizing UV radiation
squamous cell carcinoma (SCC) in situ
Bowen disease (BD)
Bowenoid papulosis is a precancerous condition of the genitalia caused by infection with high-risk HPV, most commonly with types
16, 18 and 33
Epidermodysplasia verruciformis (EV) is an inherited skin condition with a high local susceptibility to infection with human papillomavirus (HPV), most commonly with HPV types ________
types 5 and 8
Anal intraepithelial neoplasia (AIN) is associated with high-grade human papillomavirus (HPV) types, most commonly with types _________________
types 16, 18, 31, and 33
clinical term that refers to a predominantly white lesion of the oral mucosa that cannot be rubbed off or characterized by any other definable lesion or known disease
LEUKOPLAKIA
most common potential malignant lesion of the oral mucosa, with the potential to become oral SCC
LEUKOPLAKIA
markers for increased risk for additional oral or upper aerodigestive tract malignancies.
Leukoplakia and erythroplakia
strongest risk factor for the development of leukoplakia
Tobacco
In leukoplakia, if causative agents, such as tobacco or mechanical irritation, are detected, it is recommended to eliminate these factors for a period of
2 to 6 weeks
clinical term used to describe a red macule or patch on a mucosal surface that cannot be categorized as any other known disease entity caused by inflammatory, vascular, or traumatic factors
Erythroplakia (or erythroplasia)
Of all potentially malignant lesions in the oral cavity, _______ is considered to be the most dangerous and carries the greatest risk of progressing to or harboring invasive carcinoma.
erythroplakia
Precancerous lesions that result from long-term exposure to infrared radiation; can progress to squamous cell carcinoma (SCC).
THERMAL KERATOSES
Precursor lesion of thermal keratoses
Erythema ab igne
Precancerous lesions resulting from prolonged exposure to tar.
HYDROCARBON KERATOSES
precancerous lesions that may arise at irradiated sites years after such exposure and may progress to squamous cell carcinoma.
CHRONIC RADIATION KERATOSES
All are true in describing AK, except:
a. The overall risk of progression to invasive SCC is 1-5%
b. Risk factors include fair skin, age, cumulative UV radiation exposure, immunosuppression, prior history of non-melanoma skin cancer.
c. Workers with a long history of outdoor occupation, such as farmers, construction workers, or fishermen, have an up to 2.5-fold increased risk compared to indoor workers.
d. The prevalence increases with age in both sexes.However, men are more likely to develop AK than women.
ANSWER: A. Page. 1857. The overall risk of progression to invasive SCC is estimated as 5% to 10%.
A. Erythematous AK
B. Hypertrophic AK
- has a propensity for dorsal hands, arms, and scalp.
- It is usually more easily felt than seen
- most often found against a background of photodamaged skin
ANSWER: B,A,A
P.1858 The typical AK lesion presents most commonly as a 2to 6-mm, erythematous, flat, rough, gritty or scaly papule (Fig. 110-2). It is usually more easily felt than seen. They are most often found against a background of photodamaged skin
p. 1859. A hypertrophic AK presents as a thicker, scaly, rough papule or plaque that is skin- colored, gray-white, or erythematous (Fig. 110-4). It can be found on any chronically sun-exposed body site, but has a propensity for dorsal hands, arms, and scalp
LL are main clues to the transition of AK to SCC, except:
a. Induration
b. Inflammation
c. Telangiectasia
d. Pain
ANSWER: C; P.1859. Induration, inflammation, pain, and ulceration are the main clues to the transition of AK to SCC.
A pyrimidine analog and acts as an antimetabolite and via inhibition of the thymidylate synthetase as a cytostatic drug
a. Imiquimod
b. 5-FU
c. Diclofenac
d. Ingenol mebutate
ANSWER: B; p.1866 5-FU is a pyrimidine analog and acts as an antimetabolite and via inhibition of the thymidylate synthetase as a cytostatic drug.
EV is a rare inherited skin condition that is characterized by a high susceptibility to infection with some types of HPV, in particular types _ and _
a. 6, 11
b. 16,18
c. 5,8
d. 2,3
ANSWER: C; p. 1872 EV is a rare inherited skin condition that is character- ized by a high susceptibility to infection with some types of HPV, in particular types 5 and 8
All statements are correct, except
a. treatment is optional for LSIL (AIN 1)
b. AIN is usually asymptomatic
c. Major risk factors for AIN are UV exposure, HPV infection, smoking and immunosuppression
d. AIN is commonly localized within the transitional zone of squamous epithelium of the anus.
ANSWER: C.UV EXPOSURE NOT INCLUDED.. p.1874 at a glance. Major risk factors for AIN are HPV infection, high-risk sexual behavior (anal intercourse), HIV infection with low levels of CD4+ T cells, smoking, immunosuppression, a history of genital warts, and a history of cervical cancer in females.
a. Genital bowen disease
b. Erythroplasia of queyrat
c. Both
d. None
9. common type of PIN usually associated with HPV 8 and HPV 16 infection.
10. has a higher risk of progression to invasive SCC
ANSWER: B, B. p.1875 EQ is a common type of PIN usually associated with HPV 8 and HPV 16 infection; The EQ variant of PIN has a higher risk of progression to invasive SCC (∼30%) than the GBD variant (3% to 6%).
Fill in the blanks.
Field cancerization definition.
(a) more than ______ AKs within ___skin area with signs of solar damage,
(b) at least ____ AKs within ____ cm2 of skin, or
(c) more than ____ AKs in ____ body region or field and contiguous areas of chronic actinic sun damage and hyperkeratosis
(a) more than** 2 AKs **within **1 skin area **with signs of solar damage,
(b) at least 3 AKs within 25 cm2 of skin, or
(c) more than 5 AKs in 1 body region or field and contiguous areas of chronic actinic sun damage and hyperkeratosis
Identify the clinical classification of actinic keratosis (Olsen et al)
Choices:
* Grade 1 (Mild)
* Grade 2 (Moderate)
* Grade 3 (Severe)
Slight palpability
Grade 1 (Mild)
Identify the clinical classification of actinic keratosis (Olsen et al)
Choices:
* Grade 1 (Mild)
* Grade 2 (Moderate)
* Grade 3 (Severe)
Very thick or obvious AK
Grade 3 (Severe)
Identify the clinical classification of actinic keratosis (Olsen et al)
Choices:
* Grade 1 (Mild)
* Grade 2 (Moderate)
* Grade 3 (Severe)
Moderately thick AK
Grade 2 (Moderate)
Identify the clinical classification of actinic keratosis (Olsen et al)
Choices:
* Grade 1 (Mild)
* Grade 2 (Moderate)
* Grade 3 (Severe)
Easily seen and felt
Grade 2 (Moderate)
Identify the clinical classification of actinic keratosis (Olsen et al)
Choices:
* Grade 1 (Mild)
* Grade 2 (Moderate)
* Grade 3 (Severe)
AK better felt than seen
Grade 1 (Mild)
Identify the Histologic Classification of Actinic Keratosis (Roewert-Huber et al.)
Choices:
* Early in situ SCC (type AK I)
* Early in situ SCC (type AK II)
* In situ SCC (type AK III)
Involvement of the lower two-thirds of the epidermis
Early in situ SCC (type AK II)
Identify the Histologic Classification of Actinic Keratosis (Roewert-Huber et al.)
Choices:
* Early in situ SCC (type AK I)
* Early in situ SCC (type AK II)
* In situ SCC (type AK III)
Involvement of basal and suprabasal layers of the epidermis
Early in situ SCC (type AK I)
Identify the Histologic Classification of Actinic Keratosis (Roewert-Huber et al.)
Choices:
* Early in situ SCC (type AK I)
* Early in situ SCC (type AK II)
* In situ SCC (type AK III)
Alternation with zones of normal epidermis
Early in situ SCC (type AK II)
Identify the Histologic Classification of Actinic Keratosis (Roewert-Huber et al.)
Choices:
* Early in situ SCC (type AK I)
* Early in situ SCC (type AK II)
* In situ SCC (type AK III)
Nuclei hyperchromatic and variable in size
Loss of nuclear polarity
Early in situ SCC (type AK I)
Identify the Histologic Classification of Actinic Keratosis (Roewert-Huber et al.)
Choices:
* Early in situ SCC (type AK I)
* Early in situ SCC (type AK II)
* In situ SCC (type AK III)
Buds of keratinocytes in the upper papillary dermis
BOTH Early in situ SCC (type AK II)
and In situ SCC (type AK III)
Identify the Histologic Classification of Actinic Keratosis (Roewert-Huber et al.)
Choices:
* Early in situ SCC (type AK I)
* Early in situ SCC (type AK II)
* In situ SCC (type AK III)
Involvement of more than two-thirds of the full epidermal thickness
In situ SCC (type AK III)
Identify the Histologic Classification of Actinic Keratosis (Roewert-Huber et al.)
Choices:
* Early in situ SCC (type AK I)
* Early in situ SCC (type AK II)
* In situ SCC (type AK III)
**
Involvement of hair follicle, infundibula, and acrosyringium**
In situ SCC (type AK III)
indications for biopsy for AK lesions
- rapidly enlarging lesions,
- bleeding or ulceration,
- evidence of inflammation,
- strong induration,
- lesions extending beyond 1 cm of size, or
- resistance to treatment
The alternation of hyperorthokeratosis and hyperparakeratosis is common in later stages, a feature that is referred to as “flag sign” or “pink and blue.”
This is seen in what condition?
Actinic Keratosis
Initially, a compact packing of basal and suprabasal atypic keratinocytes with hyperchromatic and pleomorphic nuclei can be seen.
Atypic mitotic figures, apoptotic cells and dyskeratosis may be present.
The architecture is increasingly lost in the basal layers, but not the full thickness of the epidermis.
Per definition, the lesion is confined to the epidermis. The underlying dermis often shows solar elastosis and a superficial inflammatory infiltrate.
Dermoscopy findings of AK
**Nonpigmented lesions **
- scales that appear as whitish or yellowish crystalline structures and a reddish pseudonetwork with erythema and wavy configuration of telangiectasias between enlarged hair follicles.
- The follicles may show a perifollicular halo, resulting in a “strawberry pattern.”
- Hyperkeratotic AK lesions on the face may have prominent keratotic plugs within the hair follicles (targetoid-like pattern).
- The **rosette sign **consists of white dots localized inside the follicular openings, which may reflect alternating orthokeratosis and parakeratosis.
**Pigmented lesions **
- brown dots and globules surrounding the follicular openings
Inactivating mutations of the _____________ occur as early and common events in AK
tumor-suppressor gene p53
- p53 has a critical role in cell-cycle progression and DNA damage repair.
- If the gene is inactivated, p53mutant keratinocytes show unrestricted cell growth and acquire cellular and morphologic atypia.
are adnexal epithelium involved in actinic keratosis?
NO
there is sparing of adnexal epithelium
Dermoscopic findings of intense pigmentation and gray rhomboidal lines are diagnostic clues for what condition?
Lentigo Maligna
Lesion tartgeted therapies for AK
Topical treatment options for AK
this vitamin was reported safe and effective in reducing the rates of new nonmelanoma skin cancer and AK in high-risk patients
nicotinamide (vitamin B3 )
How many percent of bowen disease can progress to Bowen carcinoma (invasive SCC)?
5%
Men are more likely to have bowen disease on what areaS?
balding scalp, ear, and anterior trunk
Women commonly have bowen disease on what areas?
cheeks and lower legs
Sites of predilection of bowen disease
sun-exposed areas such as the** head and neck and lower legs, **although any site of the body may be affected.
Clinical variants of bowen disease
pigmented, intertriginous, periungual, and subungual BD.
The most important etiologic factors for the development of BD
long history of significant UV exposure and infection with HPV
histologic findings of bowen disease
- full-thickness epidermal atypia with loss of the stratified epidermal architecture that is clearly demarcated from the surrounding physiologic structures
- Abnormal mitoses, acanthosis, and hyperkeratosis
- parakeratosis is usually present.
- The degree of cytologic atypia may be variable.
- Typical are hyperchromatic, pleomorphic, and enlarged nuclei
Most common associated HPV types with Bowenoid papulosis (BP)
HPV 16,18
Most common associated HPV types with Epidermodysplasia verruciformis (EV)
HPV 5, 8
Most common associated HPV type with Digital/periungual Bowen disease
HPV 16
Most common associated HPV types with Penile intraepithelial lesions (PIN)
HPV 16
Most common associated HPV types with Vulvar intraepithelial lesions (VIN)
HPV 16
Most common associated HPV types with Anal and perianal intraepithelial lesions (AIN, PaIN)
HPV 16
Most common associated HPV types with Epidermodysplasia verruciformis (EV)
HPV 5 & 8
precancerous condition of the genitalia caused by infection with high-risk HPV, most commonly with types 16, 18, and 33.
BOWENOID PAPULOSIS
Bowenoid papulosis is a precancerous condition of the genitalia caused by infection with high-risk HPV, most commonly with types
HPV 16, 18, 33
age group and gender most commonly affected with bowenoid papulosis
young to middle-aged sexually active individuals with a male predominance
T/F. Bowenoid papulosis is highly contagious
True
BP is highly contagious and patients with BP and their sexual partners should be followed and examined periodically, because of the increased risk of developing SCC or cervical or vulvar neoplasia.
Epidermodysplasia verruciformis (EV) is associated with loss of function mutations of what genes?
Loss-of-function mutations of the genes** EVER1 and EVER2**
2 different morphologies of Epidermodysplasia verruciformis (EV)
- EV-plane warts - numerous thin, pink, flat-topped papules and plaques that resemble flat warts (verrucae planae)
- widespread scaly, erythematous, or hypopigmented macules and flat papules that appear similar to **tinea versicolor **
erythroplasia of Queyrat (EQ) is a common type of Penile intraepithelial neoplasia (PIN) is usually associated with what HPV subtypes?
HPV 8 and HPV 16 infection
2 Clinical presentations of leukoplakia
- Homogeneous leukoplakia has been defined as a mostly white, flat, uniform lesion. It may have shallow cracks and a smooth, wrinkled, or corrugated surface (Fig. 110-13).
- Nonhomogeneous leukoplakia is defined as a mostly white or white-reddish lesion (“erythroleukoplakia”) that may be irregular and flat, nodular, ulcerative, or verrucous.
T or F. Nonhomogeneous leukoplakia has a significant higher risk of malignancy than does homogeneous leukoplakia.
True
This represents a rare form of leukoplakia, which is most often found in patients who do not use tobacco products. It has a high rate of malignant transformation and recurrence after treatment.
Proliferative verrucous leukoplakia
the most important indicators for malignant transformation of leukoplakia
epithelial dysplasia and nonhomogeneous clinical subtype
This has been well described in the chutta smokers (reverse cigar smokers) of India.
Erythroplakia
In erythroleukoplakia, the red ______ are most prone for malignant transformation.
patches
After excision of erythroplakia, lesions that exceed ___ mm2 have a significant higher risk of recurrence.
80mm2
Arsenic keratosis are commonly localized where?
Palms and soles
appear as gray-to-yellow keratotic papules
- Clinically, they appear as gray-to-yellow keratotic papules.
- Further signs of a chronic exposure to arsenic are diffuse hyperpigmentation and the presence of superficial basal cell carcinoma or BD.
umbrella term covering malignant changes within a scar from any cause.
Marjolin ulcer
Acute Marjolin ulcer develops within 1 year of the time of injury; chronic Marjolin ulcer develops more than 1 year after an injury.
Clinical course and prognosis of AK
- Established AKs usually take a chronic course and lesions may persist, spontaneously regress, or progress to invasive SCCs.
- Overall, it is estimated that only 5% to 10% of all AKs progress to invasive SCC
- Spontaneous resolution without treatment may occur.
- The annual regression rates for single AK lesions identified in cohort studies generally range from 20% to 30% with a large variation, depending on the presence and maintenance of risk factors.
differentiate bowen and paget’s disease histopathologically
- Both: atypical cells with pleomorphic, hyperchromatic nucleus, clear cytoplasm, and mitotic figures.
- BD affects the full-thickness of the epidermis
- Paget cells typically form nest-like or glandular-like patterns with a central lumen that are most abundant in the basal layers
- (+) CEA, mucin, Alcian blue, aldehyde fuchsin, and periodic acid-Schiff and are diastase resistant; (+) cytokeratin 7, and gross cystic disease fluid protein 15 (GCDFP-15)
differentiate AK type III and bowen disease
- AK type III (bowenoid AK) displays cell atypia throughout the entire thickness of the epidermis but they do not have a clear border and show a diffuse transition into the surrounding epidermis
what do you call the transitional zone of squamous epithelium of the anus and columnar epithelium of the rectum, which is highly susceptible to HPV infection?
dentate line
Anal intraepithelial neoplasia (AIN) is commonly localized within this area
this type of vulvar intraepithelial neoplasia (VIN) affects postmenopausal females with a unifocal presentation and has a significant association with lichen sclerosus
VIN differentiated type
this type of vulvar intraepithelial neoplasia (VIN) is associated with** high-risk human papillomavirus (HPV) (types 16, 18, 31),** occurs in younger premenopausal females, and presents with multifocal and multicentric lesions
VIN usual type
- Clinical appearance comprises punctuate, keratotic, yellow papules overlying pressure points on palms and soles.
- they result from chronic exposure to arsenic
Arsenical keratoses (ArKs)
