DCNP - Cutaneous Malignancies Flashcards
pathogenesis of skin cancer in OTR
Initial antirejection regimen includes prednisone + calcineurin inhibitor + antimetabolite
Prednisone compromises repair and elimination of UV damaged and malignant cells, inhibits macrophage infiltration
Calcineurin inhibitors (cyclosporin, tacrolimus) have direct carcinogenic effect on keratinocytes which promotes skin cancer
Antimetabolite (azathioprine, mycophenolate mofetil) affect T-cells and B-cells allowing proliferation of oncogenic viruses: HPV, HHV-8, Merkel cell polyomavirus Compromised capacity of immune system to repair UV damaged cells and eliminate malignant cells
incidence of skin cancer in OTR
40-70% of OTRs will develop NMSC* 100% of cardiac and 88% of renal OTRs will develop new NMSCs within 5 years* Melanoma rate is 2-3X greater with increasing incidence over time to 5Xo Risk of death from melanoma is 3X higher* Cutaneous SCC rate is 65-250X greater than general population* BCC rate is 6-16X greater than general population
Melanoma 1-4 yrs post-transplant
SCC 2-7 yrs post-transplant
BCC 7-9 yrs post-transplant
AKs
UV radiation induces cellular mutations which result in formation of atypicalkeratinocytes
lead to impaired apoptosis, uncontrolled cell proliferation,progression to SCC
Progression rates from AK to SCC range from 0.03 – 10%
Spontaneous regression rates range between 20%-30% per year and can reappear
Can be hypertrophic, pigmented, or atrophic
May be pink to brown if pigmented
dermoscopy: A strawberry pattern consistent with undulated vessels surrounding hairfollicles filled with yellow keratin plugs on an erythematous backgroundo Pigmented AKs have same features as non-pigmented with addition of graydots/granules
Ablative with YAG (yttrium aluminum garnet) fractional laser, dermabrasion,glycolic acid peels, topical retinoids
SCC
Associated with:* TP53 gene mutation* UVR exposure (often has had actinic keratoses) and light skin types* Hydrocarbons, arsenic, tobacco, osteomyelitis, HPV, burns, chronic trauma* Chronic inflammation (discoid Lupus, oral Lichen planus, Lichen sclerosis)
Lymphoproliferative disease (CLL) is an independent risk factor for SCC
Low risk lesions* Arise from chronic UVB, heavy metals (arsenic) & chemical carcinogens (tar)exposure
High risk lesions* Location: Scalp, eyes, ears, nose, lips, genitalia, digits, and sites of scar tissue,chronic inflammation (Lupus), field of prior radiation, PUVA* Vermillion lip lesions 5x >risk for nodal metastasis than cutaneous lip lesionsindependent of the depth of invasion* Size* Depth* History: older, male, immunocompromised* Histology: Moderately-Poorly differentiated, Peri-neural, Peri-vascular, Single Cell,Recurrent
Verrucous carcinoma – giant condyloma acuminatum of genitalia (Buschke-Lowenstein tumors), epithelioma cuniculatum on plantar foot, oral floridpapillomatosis
Dermoscopyo Linear, dotted, or coiled vessels, sometimes linearo Ovoid structureso Pigmented SCC – gray or brown linear dots or globuleso White circles in irregular clusterso Invasive SCC – white structureless areas (keratinization), perifollicular circlesin irregular groups
Persistent/ recurrent tumors penetrate underlying tissues
“High-stage SCC” defined by presence of 2 or more risk factors:o Diameter ≥2 cmo Tumor invasion beyond subcutaneous fato Poorly differentiated histologic features,o Large-caliber nerve invasion ≥0.1 mmo Confers an elevated risk of nodal metastases and death* 50% of SCC pts will develop another SCC within 3-5 yrs of 1st
metastatic rate of SCC 3-4%
Adjuvant XRTo Invasion into vital organ (eye or ear)o Invasion into nerves or blood vesselso Tumors with regional or distal lymphatic metastasiso Metastatic spread of SCC to lymph nodeso Regional lymph node dissectiono + Irradiation of nodal basin
BCC
UVR exposure or exposure to heavy metals lead toDNA mutations inactivating the patched (PTCH) tumor suppressor gene, part of hedgehogsignaling pathway
Micronodular BCC* Microscopic islands of tumor cells beyond the clinical margins* Morpheaform / Sclerosing BCCo Pale white - yellow, waxy plaques with indistinct marginso Tumor cells can extend far beyond the clinical margins
Dermoscopyo Arborizing blood vesselso Leaf-like structureso Concentric spoke wheel–like structureso Large blue-gray ovoid nestso Multiple blue-gray non-aggregated globules
C&E is not recommended for BCCs located on terminal hair-bearing skin,due to the risk of follicular extension of the tumor
radiation: To treat primary BCCs or as adjunctive treatment for positive margins* Mainly used if pt is not a suitable surgical candidate* Avoid in young patients and in genetic conditions predisposing to skin cancer* Generally good cosmetic results* Risk of radio dermatitis, late recurrence, and new tumors
Targeted therapy refers to the hedgehog signalling pathwayinhibitors, vismodegib and sonidegib;
MCC
cutaneous neuroendocrine cancer* Rare, but increasing incidence
Associated with Merkel cell polyomavirus (MPV)
UVR-induced DNA damage implicated in MCV-negative tumors
Fast growing, aggressive, high rates of recurrence* High rates of regional, nodal & distant metastasis* 25-40% local recurrence s/p local wide excision* 80-90% recurrences occur within first 2 yrs* 5 yr survival: 60-80% if SLNB (-), 50-62% if SLNB (+)
Due to the high incidence of spread at the time of diagnosis:* MRI, CT or PET/CT may be indicated* SLNB should be considered for all pts (imaging does not replace SLNB)
Surgical Ablation: SLNB + excision with 1-3 cm margins or MMS* Radiation monotherapy is an alternative for non-surgical caseso Adjunctive radiotherapy may improve overall survival* Pharmacologic therapy for metastatic MCC
cutaneous b-cell lymphoma
Hyper-reactive inflammatory response related to immunodeficiency disorder, viralor bacterial infection
most often indolent (slow-growing)* Solitary/multiple red nodules/plaques; slightly raised and smooth* Commonly at the face, trunk, extremities
Tends to recur in new places on the skin, but it rarely affects other areas* Nearly 50% experience a recurrence after an initial complete response to treatment.Prognosis is usually very good
CBC & Bone marrow biopsy (to look for lymphoma cells)* Due to the high incidence of spread at the time of diagnosis:* CT or PET/CT
Primary cutaneous follicle center lymphoma and cutaneous marginal zone B-celllymphoma may be observed or treated locally with either radiation therapy orsurgery* Active treatment is started if the pt begins to develop symptoms or there are signsthat the disease is progressing based: surgery, topicals, intralesional steroids, XRT* Systemic disease: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,and prednisone) with or without XRT, relapse is common
cutaneous t-cell lymphoma
Malignant helper T-cells migrate to the skin* Not a skin cancer; but presents on the skin* Class of non-Hodgkin’s lymphoma* Most often evolves through several stages: mycosis fungoides, patch, plaque, tumor
Patients may have only 1 stage or a combination of all lesions at any time
Sub-types* Mycosis Fungoides (MF)* Sezary Syndrome (SS)
Topical steroids, topical retinoids, topical chemotherapy (nitrogen mustard,carmustine)* Interferon, denileukin, systemic retinoids* Methotrexate, prednisone, cyclophosphamide
mycosis fungoides
more common > 50 years, males, Blacks* Increased incidence of 2nd cancers, especially lymphoma* May invade lymph nodes, blood, internal organs
Early: localized or widespread, ill defined, scaly, pink-red plaques resemblingeczema or psoriasiso Patch Stage: sharply demarcated, red-pink, scaly atrophic, mottles,telangiectatic eruptiono Plaque Stage: dusky red-brown, slightly elevated patches & plaques often atthe buttocks, hips, thighs, flexural extremitieso Tumor Stage: red-brown expanding nodules which may ulcerate
sezary syndrome
Leukemic form of CTCLo 10% atypical serum lymphocytes (Sezary cells)Clinical Presentation* Extensive erythroderma (80% BSA)* Exfoliative dermatitis* Hot, tender, extremely pruritic* Alopecia, ectropion, onychodystrophy* Palmar/ plantar hyperkeratosis* Prone to 2nd colonization & infection
Assess for peripheral lymphadenopathy, hepatosplenomegaly* Laboratory and imagingo CBC, peripheral smear for atypical serum lymphocytes (Sezary cells)o LFTs, BUN-creatinine, LDH, CD4/CD8 count & ratioo CXR
Patch / Plaque Stageo Topicals: corticosteroids, bexarotene (Targretin®), nitrogen mustard(Valchor®), carmustine.o PUVA, UVB, total body electron beam therapyo Interferon, denileukin, systemic retinoids* Tumor Stageo Spot radiationo Combinations of Interferon, denileukin, systemic retinoids* Sézary Syndromeo Extracorporal Photophoresis (ECT)o interferon, oral retinoids, methotrexate, prednisone, cyclophosphamide
Patch & Plaque Stage disease can last for many years without progression to tumorstage, adenopathy, or internal organ development* Ulceration and necrosis are common in progressive cases* CTCL may eventually infiltrate lymph nodes/ internal organs, can be fatal
Imiquimod
Immune response modifier* Stimulates cytotoxic T-lymphocytes to produce interferon
Caution with underlying autoimmune condition* Topical therapy on the dorsal hands is more resistant, therefore, combination ofcryotherapy and then chemotherapeutics* Imiquimod 5% (Aldara®) (Zyclara® 5%) - 2 days per week at bedtime for 6 wks
Avoid use near the lips, nostrils and eyes* SEs: flu-like symptoms, hypopigmentation
5-fluorouracil
Antineoplastic, antimetabolite* Interferes with DNA synthesis
Skin should be gently cleansed and dried before application* Photosensitivity, inflammation, erosions
Vismodegib (Erivedge™)
150 mg capsule daily approved for or locally advanced BCC or metastaticBCC* “Locally advanced BCC”o >10mm, locally invasive into underlying tissue, cartilage, bone, nerveo Surgery or XRT would result in disfigurement, deformity or loss of functiono Contraindication to surgery; 2 or more recurrences after surgery* “Metastatic”o Spread to regional lymph nodes, lung, liver, bone, other* Blocks the PTCH hedgehog pathway inhibitor Smoothened (SMO), a transmembraneprotein involved in Hh signal transduction* Indicated for the treatment of adults witho Locally advanced BCC that has recurred following surgeryo Metastatic BCCo Pts who are not candidates for surgery or for radiation* AEs: teratogenic, muscle spasms, myalgia, dysgeusia, fatigue, nausea, diarrhea,↓weight, ↓appetite, constipation, arthralgias, vomiting, amenorrhea, pruritus,alopecia, headache, ↑CK, decreased sense of taste
Sonidegib (Odomzo®)
AEs: Muscle spasms, myalgia, dysgeusia, nausea, diarrhea, ↓weight, ↓appetite,pruritus, alopecia, headache, ↑CK* 2nd oral hedgehog inhibitor drug, was approved by the FDA in 2015 for patients withlocally advanced BCCs* Specifically, pts whose tumors have recurred following surgery or radiation therapy,or who are not candidates for surgery or radiation therapy* Not FDA approved for metastatic disease* 200 mg daily* Complete response 5-20%, partial response 53%* Adverse effects: teratogenic, serious musculoskeletal problems, increased serumcreatine kinase levels, muscle pain, spasms
Acitretin (Soriatane®)
Lowest dose to minimize desquamation of the palms and soles,musculoskeletal symptoms headache, epistaxis, cheilitiso Rebound phenomenon: increasingly aggressive SCCs will recur upondiscontinuation
