Chapter 111: Cutaneous Neoplasms Lisa Spiguel, MD

True or False: Cutaneous melanomas account for 4 % of skin cancer diagnosis, but 75% of skin cancer deaths

Which of the following below is NOT a risk factor for cutaneous melanoma? UVA exposure UVB exposure Tanning beds Seborrheic Keratosis All of the above

What is the most common site of distant metastasis in melanoma? Liver Small Bowel Brain Lung

What is the most common type of melanoma? Lentigo maligna Superficial spreading Nodular Acral lentiginous

What is the most indolent type of melanoma? Lentigo maligna Superficial spreading Nodular Acral lentiginous

What is the most aggressive type of melanoma? Lentigo maligna Superficial spreading Nodular Acral lentiginous

Which type of melanoma most commonly arises from a pre-existing nevus? Lentigo maligna Superficial spreading Nodular Acral lentiginous

Which of the following is NOT an indication for sentinel lymph node biopsy in a patient with a thin melanoma? Presence of ulceration Presence of regression Invasion into reticular dermis Increased mitotic rate All of the above are indications for sentinel lymph node biopsy

A patient presents to your office with a lesion suspicious for a melanoma. You perform a biopsy that demonstrates a 1.25 mm thick melanoma. What margin is necessary during surgical excision? 0.5 cm 1 cm 2 cm 3 cm

A 55 you right-handed male is diagnosed with a subungual melanoma of his left index finger. The appropriate surgical resection is? Amputation at the DIP joint Amputation at the PIP joint Amputation at the MCP joint Excision with negative microscopic margins

Which of the following below is NOT a immunostain for melanoma? Melan-A HMB-45 Melatonin

Which of the following therapies have been approved by the FDA for the treatment of Stage IV melanoma? IL-2 IFN α IFN δ Traztuzamab

Which of the below adjuvant therapies is used for Stage IIB or Stage III melanoma? IL-2 IFN α IFN δ Traztuzamab

Best treatment of a single in-transit melanoma of the right lower extremity involves which of the following below? Isolated limb perfusion Systemic chemotherapy with Melphalan Surgical excision None of the above

I solated limb perfusion involves hyperthermic administration to the limb involved using which chemotherapeutic agent? IL-2 IFN α Cisplatin Melphalan

Skin Cancer 1.4 million new cases of skin cancer annual in US Nonmelanoma skin cancer types: Basal cell and Squamous cell (4:1) Melanoma accounts for 4%, but up to 75% of skin cancer deaths Incidence of melanoma is on the rise

Melanoma Risk Factors: Genetic Causes: UVA/UVB exposure: sun exposure, occupation, history of sunburns, tanning beds Fair complexion (inversely related to skin pigmentation) Atypical Nevi Dysplastic nevus syndrome: > 100 , one mole > 8 cm, 1 mole w/ atypical histology Genetic Causes: Mutation in CDKN2A (p16) MC1R gene mutation FAMM (Familial Atypical Multiple Mole Melanoma syndrome): AD Xeroderma Pigmentosa: AR Congenital Melanocytic Nevi (CMN)

Congenital Melanocytic Nevi Appear at birth or within 1st 6 months of infancy Incidence is 1-6% Classification/ Risk of Malignancy: Small < 1.5 cm Medium 1.5-19.9 cm Giant > 20 cm/ 5-20% risk, 70% dx prior to age 10 Risk of Neurocutaneous melanocytosis: Occurs with Giant CMN on posterior axis Benign ormalignant leptomeningeal tumors Dx: MRI

Melanoma Characteristics A (Asymmetry) one portion of the mole does not match the other B (Border) edges are irregular, notched, or blurred C (Color) different shades of black or brown, patchy colors D (Diameter) spot is 6 millimeters across, or growing larger

Melanoma Subtypes Lentigo maligna melanoma 10-15% Chronically sun exposed areas Superficial spreading melanoma 70% Typically arises in pre-existing nevus Nodular melanoma 15% Most aggressive form due to rapid growth Acral Lentiginous Melanoma Subungual melanoma 2-8% in Caucasians, 35-60% in African Americans Worse prognosis is related to delayed detection not aggressiveness of tumor Others: Mucosal, Anal, Vulvovaginal

Staging Breslow Staging: Clark level of Invasion: Classifies tumor according to thickness in millimeters Inverse correlation between thickness and survival Clark level of Invasion: Classifies based on level of invasion into the histologic layer of the skin I-V Independent Prognostic Factors: Tumor stage, ulceration, nodal status, distant metastasis

TNM Stage 0: in situ Stage I: Local Disease Stage II: Local Disease Stage III: Regional nodal disease, in-transit, or satellite metastasis Stage IV: Distant Disease

Evaluation Clinical Exam: ABCD Biopsy: Full thickness biopsy to the adipose tissue: Punch biopsy if > 2 cm lesion Excisional biopsy if < 2 cm lesion with 1-2 mm margins Never superficial shave biopsy

Treatment Surgical Excision: (Margins) - Fascia Melanoma in situ: 0.5 cm Thin Melanoma (≤1 mm): 1 cm Intermediate Melanoma (1-4mm): 2 cm Thick Melanoma (>4mm): 2 cm Treatment of In-transit disease: Surgical excision when the feasible and number of lesions is small Ablative therapes Isolated limb perfusion Delivery of 15-25times higher than systemic doses Melphalan chemotherapy delivered at hyperthermic temperatures 38 degree C 80-90 % response rates with complete response rates 40-60% Indications for Sentinel Lymph Node Biopsy: All melanomas > 1 mm (Intermediate and Thick) Thin Melanomas/ or 0.75-1mm, if: Ulceration Regression Into reticular dermis Increased Mitotic Rate: > 1mitosis/mm2 Indications for Axillary Node dissection Clinically positive nodes + Sentinel Lymph Node MSLT II: + SLN  ALND vs Serial US

Treatment Role for Adjuvant Therapy: IFN-α2b RCT: Thick melanomas or + Nodal disease: Increased median overall survival by 1 year 24% improvement in 5 yr survival Indications for Systemic Staging: (Serum LDH, MRI Head, CT C/A/P or PET/CT) Clinically positive nodes (FNA +) Pathologically positive nodes Systemic Therapy in Stage IV disease: IL-2 Cytokine secreted by Thelper cells

True or False: The most common non-melanoma skin cancer is squamous cell carcinoma.

A 75 yo old man presents with the lesion imaged below A 75 yo old man presents with the lesion imaged below. What is the margin need during excision? 0.5 cm 2 cm 4 cm 6 cm

Immunohistochemical staining is positive for which of the below for merkel cell tumors? Melanin cKit CK-20

Which of the following below spreads via lymphatic flow? Merkel cell carcinoma Squamous cell carcinoma Basal cell carcinoma 1 & 2 All of the above

Which of the follow below does NOT require a 2 cm margin for the treatment of squamous cell carcinomas? Squamous cell carcinoma of the neck Squamous cell associated with Marjolin’s ulcer Penile squamous cell carcinoma Vulvar squamous cell carcinoma

A 68 yo male presents to your clinic with the lesion below on his right upper arm. What margin of excision is needed for treatment of this lesion? 0.5 cm 1 cm 2 cm 4 cm

A 38 yo male is diagnosed with 8 mm penile squamous cancer at the tip of his penis. What is the treatment of choice? Total penectomy Partial penectomy Exicsion with negative microscopic margins None of the above

Ture or False: Moh’s surgery can be used for both basal cell and squamous cell carcinomas.

A 75 yo man presents to your office with a new lesion on his face A 75 yo man presents to your office with a new lesion on his face. Your exam demonstrates the lesion below. What is your diagnosis? Squamous cell cardcinoma Merkel cell carcinoma Basal cell carcinoma Melanoma

True or False: Morpheaform basal cell carcinoma has the worst prognosis.

A 75 yo man is diagnosed with a basal cell carcinoma of the right neck A 75 yo man is diagnosed with a basal cell carcinoma of the right neck. What margin of excision is needed for treatment? 0.5 cm 1.0 cm 1.5 cm 2.0 cm

NonMelanoma Skin Cancers Basal Cell Four times more common than squamous cell Risk Factors Same as melanoma UVA/UVB exposure, higher risk in fair individuals Radiation Gorlin Syndrome: AD, multiple BCC, palmoplantar pits, jaw cysts, frontal bossing, hypertelorism Squamous Cell Risk Factors: Sun exposure, Chemicals : Arsenic, hydrocarbons (coal tars, soot, asphalt), Tobacco, HPV, Radiation

Basal Cell Carcinoma Exam: Pathology: Surgical Excision: Pearly papules Nodules with telangiectases Central ulceration with “rolled” borders Pathology: Isolated areas of basaloid tumor islands arising from epidermis with peripheral palisading nuclei and stromal retraction Surgical Excision: 0.3-0.5 mm margin Worst Diagnosis: Morpheaform, sclerosing, or fibrosing

Squamous Cell 2nd most common form of skin cancer Derived from epithelial keratinocyte Most common skin cancer in immunocompromised patients/transplant patients Precursor lesions: Actinic keratoses Bowen disease (in situ SCC) Exam: Nonhealing sore with ulceration and inflammatory pink borders Erythematous papulonodule with overlying keratotic crust or ulceration Pathology: Malignant degeneration of epithelial cells with differentiation toward keratin formation Surgical Excision: 1 cm margin 2 cm margin for Marjolin’s ulcer, penile and vulvar squamous cell carcinomas Prognosis: Metastasis to regoinal LN Poor prognosis with 10 year survival < 20% Distant disease 10 year survival < 10%

Merkel Cell Carcinoma Primary cutaneous neuroendocrine cancer Highly aggressive with high mortality Risk Factors: UVA/UVB, immunosuppression, Merkel cell polyovirus Exam: New-onset growing red or purple dome-shaped subcutaenous nodule Pathology: Blue cell tumor with positive immunohistochemical staining for CK-20 Absent staining of thyroid transcription factor-1 TTF-1 Treatment: Wide local excision with 1-2 cm margins Adjuvant XRT for Stage II disease SLNB and staining for CK-20 ALND or regional radiation therapy if SLNB + Adjuvant chemotherapy for Stage IV disease