Cutaneous Neoplasms

Question 1

What are seborrheic keratoses?

Answer 1

• one of the most common cutaneous neoplasms
• develop in middle age or older patients
• brown/tan waxy papules and plaques with a “stuck on” warty appearance most commonly on face/trunk/upper extremities

Question 2

What is the Leser-Trelat sign?

Answer 2

Sudden onset of multiple seborrheic keratoses associated with internal malignancy (most commonly stomach cancer)

Question 3

What do seborrheic keratoses look like on histology?

Answer 3

• Hyperkeratotic, papillomatous and verrucous epidermis
• Horn and pseudo horn cysts (invaginations of keratin)
• Variable melanin pigmentation is present, accounting for the brown coloration seen clinically

Question 4

What is actinic keratosis?

Answer 4

• also known as solar keratosis; common lesions that develop as a result of chronic sun damage
• middle aged to elderly onset (esp with fair complexion)
• red or tan/brown macues with “gritty” sandpaper like scales
  
  • some lesions regress or may remain stable
• 0.1-10% become malignant squamous cell carcinoma

Question 5

What does actinic keratosis look like on histology?

Answer 5

• Atypia of the basal layer of the epidermis
• Corneal layer is thickened with retained nuclei (parakeratosis)
• Loss of granular layer in some places
• Dermis contains thickened, blue-gray elastic fibers (solar elastosis), the result of chronic sun damage

Question 6

Describe the etiology/prevalence of squamous cell carcinoma

Answer 6

• common neoplasm in older individuals (40+); 20% of all skin cancers
• UV radiation is the most common cause (DNA damage)
• Other predisposing factors include;
  
  • chronic ulcers
  • old burn scars
  • HPV (esp in head and neck)
  • toxic exposure (radiation, arsenic)
  • immunosuppression (esp in solid organ transplant)
• 1-5% risk of metastasis in low risk area (~20% in high risk area such as lip/mucosa)

Question 7

What are the clinical symptoms of squamous cell carcinoma?

Answer 7

• red scaly plaque
• risk of metastasis is related to the location and degree of invasion
  
  • ~2-4% higher risk in immunosuppressed patients

Question 8

How does SCC differ when it becomes invasive?

Answer 8

• invasive lesions (5% of SCCs) tend to be nodular and may ulcerate
• roughly 30% of invasive SCCs have metastatic potential
• classified as invasive when the neoplastic cells break through the basement membrane

Question 9

What does SCC look like on histology?

Answer 9

• full-thickness dysplasia (characteristically involves the entire epidermis)
• disorganization of the epidermal architecture
• loss of maturation
• lack of polarity of cells

Question 10

What is keratoacanthoma?

Answer 10

• variant of squamous cell carcinoma
• pink papule/nodule with a central keratin plug that grows rapidly (period of 2-10 weeks)
  
  • can cause extensive local destruction
• occurs mainly on sun damaged skin
• some lesions will resolve spontaneously (or can become very aggressive)
• multiple lesions may be present in immunocompromised patients

Question 11

What do keratoacanthomas look like on histology?

Answer 11

• exophytic lesions with an invaginating mass of keratinizing, well-differentiated squamous epithelium at the sides and bottom
• central keratin-filled crater that enlarges with the maturation and evolution of the lesion
• epidermis on either side of the lesion is thrown up into a well-formed collarette
• epithelium is typically characterized by well-differentiated, often pale-staining, eosinophilic, glassy cytoplasm showing a striking tendency towards keratinization

Question 12

Describe basal cell carcinoma

Answer 12

• most common human cancer
• secondary to chronic sun exposure/UV radiation
• slow growing tumor that rarely metastasizes (unless immunocompromised)
  
  • can be locally destructive
• associated with dysregulation of the sonic hedgehog or PTCH pathway (30-40%)

Question 13

What does basal cell carcinoma look like on histology?

Answer 13

• several histologic variants
  
  • multifocal growths originating from the epidermis (superficial type)
  • nodular lesions growing downward into the dermis (nodular type) of variably basophilic cells with peripheral palisading.
• tumor cells are small and uniform with round, darkly staining nuclei and minimal cytoplasm
• characteristic clefting artifact between the tumor nodules and the stroma

Question 14

What are melanocytic nevi?

Answer 14

• An above normal amount of melanocyte in the epidermis
  
  • acquired from sun exposure
  • congenital at birth (can be severe/widespread and increase risk of melanoma)

Question 15

What are the histological classifications of nevi?

Answer 15

• junctional (epidermis only)
• compound (epidermis and dermis)
• intradermal (dermis only)

Question 16

What are dysplastic nevi?

Answer 16

• clinically and histologically distinctive
  
  • clincially larger than acquired nevi (>0.5 cm), irregular shape and uneven color
• may occur sporadically or in a familial form
• patients with multiple dysplastic nevi have increased risk of melanoma

Question 17

What is dysplastic nevus syndrome?

Answer 17

• familial or sporadic
  
  • familial variant is autosomal dominant (mutations in CDKN2A gene in 40% of cases)
• large number of dysplastic nevi (80+)
• increased incidence of melanoma
  
  • patients can also develop other malignancies (e.g. pancreatic carcinoma)

Question 18

Contrast familial and sporadic dysplastic nevus syndrome

Answer 18

• sporadic
  
  • lower number of nevi (2-10)
  • lifetime risk of melanoma ~10%
• familial
  
  • hundreds of nevi
  • lifetime risk of melanoma approaches 100%

**both show identical histological features (may be junctional of compound)

Question 19

What is the prevalence of melanoma?

Answer 19

• represents 3% of all cutaneous malignancies
  
  • 6th most common cancer in the US
• more common in white population… affects men and women equally
  
  • most common on back in men
  • most common on legs in women
• typically a disease of adulthood

Question 20

What are the risk factors for melanoma?

Answer 20

• UV exposure at early age (most important risk factor)
• fair complexion and older age
• dysplastic nevus syndrome
• xeroderma pigmentosum (autosomal recessive disease)
• history of melanoma in the family
• tanning bed use

Question 21

What are the clinical features of melanoma? (ABCDE)

Answer 21

• Asymmetry
• Borders (notched, uneven, or blurred)
• Color (uneven; shades of brown, tan, red, and black may be present… 3+ is concerning)
• Diameter (>6 mm)
• Evolving (change in color/size of the lesion)

Question 22

What are the growth phases of melanoma?

Answer 22

• Radial growth phase
  
  • melanocytes will proliferate within the epidermis (in situ… NO metastatic potential at this stage)
• Vertical growth phase
  
  • dermal invasion and potential for metastasis
  • extent of this phase determines the biological behavior (Breslow thickness/depth of invasion is the most important prognostic indicator)
  • lesions >1.7 mm have greater potential for metastasis, <1 mm rarely metastasize

Question 23

What factors determine a melanoma’s metastatic potential?

Answer 23

• Breslow thickness/depth of invasion is the most important prognostic indicator
• ulceration
• mitotic rate
• angioinvasion

**sentinel lymph node biopsy is considered if a lesion is deep

Question 24

What are some types of melanoma?

Answer 24

• superficial spreading type (most common, 70%, located on back and extremities)
• nodular type (NO radial growth phase, poor prognosis)
• lentigo maligna type (most commonly located on the head and neck in sun exposed areas)
• acral lentignous type (located on the palm, sole, or beneath nail… most common in african americans)

Question 25

What does a melanoma look like on histology?

Answer 25

* radial growth phase= asymmetric population of melanocytes within the epidermis (located along the dermal epidermal junction) * melanoma cells are large with abundant cytoplasm, often showing dusty melanin pigmentation... often show pleomorphic vesicular nuclei with prominent eosinophilic nucleoli * vertical growth phase= cells in dermis that grow in poorly formed _nests_ or individual cells as an expansile nodules. There is lack of melanocytic maturation at the base of the lesion

Question 26

What is mycosis fungoides?

Answer 26

* most common cutaneous lymphoma * occurs in late adulthood with a male predominance * usually presents as red or pink scaly patches * stages of patch, plaque, and nodules * usually chronic course although may become aggressive

Question 27

What are the stages of mycosis fungoides?

Answer 27

* _Patch stage_: nonspecific dermatitis (patches often found on the lower trunk and buttocks... ill-defined patches of varying hue, often with a fine scale, irregular in size and shape) This stage may persist for many years before progression occurs * _Plaque stage_: well-demarcated lesions which are often annular in shape, violaceous in appearance and occasionally scaly (may develop de novo or from patches) * _Tumor stage_: usually develops in association with pre-existing lesions. The tumors are red in color, with a tense shiny surface. Ulceration may occur. The lesions usually measure 1 cm in diameter or more.

Question 28

What is sezary syndrome?

Answer 28

* blood involvement of T cell lymphoma * erythroderma (skin is diffusely red and scaly; sometimes misdiagnosed as chronic eczema) * poor prognosis (survival 1-3 years)

Question 29

What does mycosis fungoides look like on histology?

Answer 29

* mature T-cells show a tendency to colonize the epidermis (_epidermotropism_), although this is more evident in the patch and plaque forms than in tumor-stage disease. * infiltrate contains large cells with highly irregular, convoluted or cerebriform nuclei, known as _Sézary or mycosis cells_. * presence of atypical lymphoid cells in an intraepidermal vesicle (the _Pautrier microabscess_) is typical