Neoplastic Skin Disorders Flashcards
Solar Lentigo
- Definition: Hyperpigmented, brown macules caused by an increase in number of melanocytes within sun-exposed areas
- Common finding in older adults•In contradistinction, freckles have a normal number of melanocytes but an increase in melanosomes.•Not precancerous
Melanocytic Nevi AKA ‘Moles’
•Definition: Benign neoplastic melanocytic disorder of neural crest–derived nevus cells (modified melanocytes)•Epidemiology/clinical–Whites have an average of 15 to 40 nevi on their skin.–Frequently contain hair–Nevus cells are modified melanocytes–Begins in early childhood as junctional nevus
Juctional nevus
–usually occurs in children and adolescents–Nevus cells extend along the basal cell layer–Pigmented lesion with papillomatous surface
compound nevus
•develops when a junctional nevus cells extend into the superficial dermis
intradermal nevus
develops wen a compound nevus loses its junctional component
Dysplastic nevus
•> 5 mm in diameter•Flat or containing a flat component•Variable, irregular pigmentation•Irregular or asymmetric outline•Indistinct borders•May arises sporadically•May be part of dysplastic nevus syndrome–Autosomal dominant syn with > nevi on skin–May develop into melanoma–Family members with this syndrome will develop melanoma
Melanoma
•Most deadly of all skin cancers•Estimated 100,350 new cases in US in 2020 (96,480 in 2019)–60,190 in males, 40,160 in females•Estimated 6,850 deaths in US in 2020–7,230 deaths in 2019 which was 19% fewer than in 2018)•Exposure to UVB radiation in sunlight plays a role in many new cases•Most common locations:–Upper back in males, back and legs in females•Lighter skinned at greater risk–2.5% Whites, 0.1% Blacks, 0.5% Hispanics
Melanoma cont
•Relatively common neoplasm–Increasing incidence over past 30 years especially in >50 years–Potentially curable if detected and treated early–Salvage even Stage IV with targeted +/- immunotherapy (durable response)•Most arise on skin but also nail bed•Other sites–Oral and anogenital mucosal surfaces–Oropharynx, gastrointestinal (stomach, duodenum, rectum)–Esophagus, meninges, uvea of eye
- *Melanoma Clinical Features**
- *‘Warning Signs’**
•A = Asymmetry•
B = Border irregular•
C = Color variegated•
D = Diameter _>_6 mm•
E = Evolving (Enlarging/Elevation)
(••Radial: growth along dermal epidermal junction
•Vertical: downward growth BAD–DEEPER POORER PROGNOSIS–See with nodular melanoma
Sun Exposure
- Excessive exposure to Ultraviolet (UV) radiation injures skin–Sunburn–Photoaging (Solar elastosis)–Skin cancer risk (Basal Cell Carcinoma BCC, Squamous CC, Melanoma)
- Most common form of UV radiation is sunlight, which produces three main types of UV rays:–UVA (95%)•Long wavelength (320-400 nm) reaches dermis•Responsible for tanning, photoaging, wrinkling, and some effect on development of skin cancers
UVB
–UVB (5%) some absorbed by Earth’s ozone layer•Medium wavelength (290-320 nm) reaches epidermis•Responsible for burning, photoaging, and development of skin cancers–UVC all absorbed by Earth’s ozone layer: shortest wavelength•“Broad spectrum” sunscreen provide UVA and UVB protection•SPF_>15 (FDA, USPTF); SPF>_30 American Academy of Dermatology•2-8 minutes unprotected sun during summer for adequate synthesis of Vitamin D3
Melanoma Risk Factors
•Ultraviolet (UV) radiation (UVA more deleterious than UVB)–Severe blistering sunburns during childhood–Regular use of tanning booths, especially if start during adolescence•100s of dysplastic nevi (increased risk with increased number) in FAMMM•Giant ‘bathing trunk’ congenital melanocytic nevus (5-10%)•Fair skin, freckling, light hair•Family history of melanoma•Personal history of melanoma•Personal history of other skin cancers•Weakened immune system•Being older•Being male•Xeroderma pigmentosum (highest risk of SCC)
Melanoma Pathogenesis
- 85-90% sporadic•Most frequent “driver” mutations in melanoma affect cell cycle regulators (p16/INK4a, CDK4), pro-growth signaling factors (growth factor receptors [e.g., KIT], RAS, BRAF), and telomerase•>50% associated with BRAF mutation
- Dysplastic nevus syndrome:–Dysplastic nevus syndrome (also known as familial atypical multiple mole melanoma syndrome, or FAMMM)–100s of dysplastic nevi–100% lifetime risk of melanoma–Increased risk pancreatic carcinoma
Asymmetric growth pattern
No maturation (smaller cells) at base
Mitoses
Cytologic atypia
Nested collections (‘theques’)
Upward Pagetoid spread with single cells or clusters in upper epidermis
Large cell size, dusty cytoplasmic pigment, epithelioid appearance, pleomorphic nuclei, large prominent cherry red nucleoli, nested growth pattern
Positive IHC: S100, HMB-45, SOX10, vimentin; negative IHC: pancytokeratin
Melanoma Prognosis
•Tumor depth (the Breslow thickness)–SINGLE MOST IMPORTANT thinner better, deeper vertical growth worse–Measured from stratum granulosum (granular cell layer) to deepest tumor cell•Number of mitoses (any number unfavorable)–None best, but good if <1 mitosis per mm2•Tumor regression bad•Ulceration of overlying skin unfavorable at all pathologic T stages•Location–upper back, posterior arm, posterior neck, posterior scalp worse than on limbs•Tumor satellites unfavorable•Vascular invasion unfavorable
Melanoma Depth of Invasion
Primary (Breslow) thickness
•Maximum tumor thickness measured with a calibrated ocular micrometer at right angle to adjacent normal skin•Measured from granular cell layer of epidermis•If ulcerated melanoma, measured from base of ulcer•Lower reference point deepest tumor invasion•>1.5 mm unfavorable prognosis
Clark levels
- I (intraepidermal or melanoma in situ)
- II (melanoma present in but does not fill and expand papillary dermis)
- III (melanoma fills and expands papillary and reticular dermis)
- IV (melanoma invades reticular dermis)•V (melanoma invades subcutaneous fat)
superficial spreading of melanoma
70%. Peak 4th-5th decade. Most common type in Caucasians. Slowly changing pre-existing nevus. Intermittent intensive sun-exposure. Severe sunburns in childhood. Upper backs in males & females and lower legs of females
Nodular melanoma
•15-20%. Median age 53 years.•Most often on trunk, head, and neck•No radial growth phase•Only vertical growth•More common to begin in normal skin rather than in a preexisting lesion.•Rapid growth characteristic•Poor prognosis
Acral Lentiginous Melanoma
•10%. Most common types among African Americans, Latin Americans, Japanese, Native Americans.•Median age 65 years.•Equal gender distribution•Most common site in African Americans is the feet, with 60% of patients having subungual or plantar lesions.•Can occur on palms or soles or beneath the nail plate.•Sole most common site for ALM in all races.•Average size at diagnosis 3 cm often due to delayed diagnosis•Poor prognosis•Not related to sun exposure
Subungual melanoma (left) is a rare variant of acral lentiginous melanoma. Most subungual melanomas involve the great toe or thumb and generally arise from the nail matrix.
Hutchinson’s sign is the finding of pigmentation on the posterior nail fold and is associated with advanced subungual melanoma.
tonsillar melanoma
Other more uncommon variants of melanoma include melanoma of the mucosa and desmoplastic melanoma.
When melanoma occurs on the mucosa, it usually develops on the mucosal surfaces of the head and neck (nasal and oral cavities), genital, or anorectal mucosa. Patients can present with bleeding or a mass lesion.
Lentigo Maligna Melanoma
•4-15%.•Occurs in parts of the body most exposed to the sun•Sun-damaged atrophic skin in elderly persons.•Equally in men and women•Usually in 7th & 8th decades of life.•Head & neck, nose and cheeks•Least likely to have a vertical phase
Key prognostic factors for primary tumor
seborrheic keratosis
•Most common benign tumor in elder people•Occurs in individuals > 50 years of age•Commonly occurs on the face of elderly people•Arise spontaneously, most numerous on the trunk, although the extremities, head, and neck may also be involved•Multiple small SKs on faces of African Americans: dermatosis papulosa nigra•Round, greasy/waxy, granular, stuck on, exophytic, sharply demarcated•Acanthosis•Proliferation of basal keratinocytes•Invagination of surface keratin forming horn cysts•No risk of transformation to a malignant skin tumor•Leser-Trelat sign: rapid appearance of these lesions on the body over short period of time–May be a sign of visceral malignancy: stomach adenocarcinoma
•Fibroepithelial polyp usually sporadic•AKA acrochordon, skin tag•Acanthosis, loose fibroconnective stroma•One of the most common cutaneous lesions•Middle-aged and older on neck, trunk, face, and intertriginous areas•More numerous and prominent during pregnancy
Epithelial cyst/Epidermal inclusion cyst/Cyst of follicular infundibulum
•Very common lesions on face, base of ears and trunk•Formed by invagination and cystic expansion of epidermis or hair follicle as a result of trauma at times•Prominent granular layer, intraluminal keratin flakes (grossly appears cheese-like, foul-smelling)•When large may be subject to traumatic rupture, acute and chronic inflammation, histiocytic reaction to keratin flakes, and secondary infection•Spontaneous inflammation and rupture may occur•The cyst lining is by normal epidermis that produces keratin•Lumen is filled with keratin•Differs from dermoid cyst in that, the dermoid cyst has adnexal tissues in the wall
identify each
Other benign cysts
Trichilemmal or pilar cyst no granular layer, dense eosinophilic luminal content with keratin and lipids
Steatocystoma multiplex crenated eosinophilic cuticle, sebaceous glands, pilosebaceous unit
Dermoid cyst has sebaceous glands in the cyst wall
Solar Elastosis
•Accumulation of abnormal elastin (elastic tissue) in dermis of the skin•Result of the cumulative effects of prolonged and excessive sun exposure, a process of photoaging•Loss of eosin staining on H&E sections resulting in a bluish color of the upper dermis with accumulation of irregularly thickened elastic fibers
SOLAR ELASTOSIS can be found in the dermis in association with ALL SKIN CANCERS including basal cell carcinoma, squamous cell carcinoma, melanoma as well as actinic keratosis.
Actinic Keratoses = Premalignancy, TP53 mutations
Sun-damage, thick stratum corneum, cytologic atypia in lower epidermis
High incidence with pale skin
Risk: UV radiation, ionizing radiation, industrial hydrocarbons, arsenicals
Progressively worsening dysplasia progressing to squamous cell carcinoma
<1 cm in diameter tan-brown, rough, sandpaper-like consistency
“cutaneous horn” or crust hyperkeratosis
CHRONIC sun exposure face, neck, backs of hands, lips (actinic cheilitis)
Associated solar elastosis
Invasive Squamous cell carcinoma (SCC)
Large polygonal cells, growing in sheets, eosinophilic cytoplasm some with keratinization Classic keratin ‘pearls’ bright red-orange swirls of keratin
Squamous cell carcinoma (SCC) 2nd most common malignant skin tumor
<5% metastases to regional nodes higher risk if SCC LIP or SCC EXTERNAL EAR
DNA damage induced by CHRONIC exposure to UV light (farmer)
Chronic immunosuppression chemotherapy or organ transplantation susceptibility of keratinocytes to infection and oncogenic viruses human papilloma virus (HPV) 5 & 8
Also epidermodysplasia verruciformis
Keratoacanthoma
WHO Classification 2018 Skin Tumors: Well differentiated Squamous Cell Carcinoma
Rapidly growing but can involute
Flask-shaped lesion with central keratin plug
Grows within 4-6 weeks
Male predominance
Cup-shaped collarette of squamous epithelium
No deep infiltration
Central keratin-filled epithelial invagination
Nose, cheeks, dorsa of hands, forearms
Chronic solar overexposure, older age, white
Xeroderma Pigmentosum
•Autosomal recessive•Very high risk of multiple SCC with minimal exposure to sunlight, also BCC, melanoma•Cancers most often on face, lips, eyelids>on the scalp, in the eyes, and on the tip of the tongue.•Dry skin, freckling, premature skin aging•Photophobia, cloudy cornea•Inherited mutations in XPA genes in the nucleotide excision repair pathway required for accurate repair of pyrimidine dimers so DEFECTIVE DNA REPAIR•In sporadic SCC and XP pyrimidine dimers accumulate
Classic Basal Cell Carcinoma (BCC)
•Pearly pink papule with telangiectasias on chronically sun exposed skin•Islands of small basophilic basaloid cells +/- connected to basal layer epidermis•Cells at periphery long axes in parallel (palisading) perpendicular to stroma•Stroma retracts away from invasive islands creating clefts, may contain mucin•Most common invasive malignancy in US almost 1 million cases annually•Locally aggressive VIRTUALLY NEVER METASTASIZES <0.01% metastasis•Risk: CHRONIC SUN EXPOSURE e.g., FARMER, Xeroderma pigmentosum
Superficial BCC
•Usually solitary lesions caused by UV light•‘Superficial’ because of budding of basal cells into superficial dermis with continued attachment to epidermis•Frequently misdiagnosed since plaque on trunk or limbs•Presents as slightly raised, red plaque with adherent scale very well-defined margin•Differential diagnosis: fungal infection (dermatophytosis), melanoma, seborrheic keratosis
Nevoid basal cell carcinoma syndrome (NBCCS)
AKA basal cell nevus or Gorlin syndrome)
Autosomal dominant disorder
Multiple BCCs <20 years
Plus other tumors (especially medulloblastomas and ovarian fibromas)
Odontogenic keratocyte jaw, pits of the palms and soles
Rib anomalies (missing or bifid)
PTCH1 mutation in Gorlin syndrome and in 70% of sporadic BCC
Juvenile hemangioma
•‘Strawberry Type’ capillary hemangioma of skin of newborn•Extremely common (1 in 200 births) and can be multiple•Benign vascular neoplasm, not a malformation•Skin, subcutaneous tissues, mucous membranes of oral cavity and lips•Grows rapidly for a few months and fades by 1 to 3 years of age•Completely regress by age 7 in the vast majority of cases•Lobular proliferation of small vascular channels lined by plump endothelial cells, lobules separated by normal stroma•IHC: +GLUT1: a marker for juvenile hemangiomas
Kaposi sarcoma
•Epidemic form in HIV+•AIDS defining condition•Widespread violaceous plaques/nodules on skin and mucosa•Atypical spindle cell vascular proliferation, slit like spaces, extravasated RBCs, hyaline globules•Vascular malignancyIHC: CD31+, confirm HHV8+
Cutaneous Angiosarcoma
•Face or scalp elderly; M > F; ulcerate/bleed•Single or multifocal, bluish or violaceous nodules, plaques or flat infiltrating•Thrombocytopenia•Common: extensive local growth•Mets to regional lymph nodes and lungs•Poor prognosis, 15% 5-year survival•Poorly circumscribed dermal tumors infiltrating subQ, multifocal•Anastomosing channels between dermal collagen•Lined by hyperchromatic atypical cells•Papillary processes•IHC: +CD31, +ERG
Xanthomatoses
•Lipid deposits in skin and elsewhere resulting from primary hyperlipidemia or secondary to defective metabolism•Flat yellow plaques around eyes – xanthelasmas; common in hyperlipidemia, do occur in normolipemic•Xanthomas – histiocytes with foamy cytoplasm AKA foam cells•Tuberous xanthomas Achilles tendons cLDL (FH)•Foam cells are tissue macrophages which have ingested lipid part of lipoproteins deposited in certain tissues
•Primary hyperlipidemias uncommon: classified according to pattern of lipoprotein electrophoresis•Secondary causes of hyperlipidemia–Hepatic disorders: primary biliary cirrhosis, hemochromatosis–Renal disease: nephrotic syndrome–Pancreatic disorders: chronic pancreatitis–Diabetes mellitus, myxedema (hypothyroidism)–Drugs: estrogens, alcohol
Keloid
•Hyperproliferation to trauma, infection, surgery, burns•Ear lobe, neck, upper trunk•Keloid with acne on sternum, back, shoulders•Inherited tendency esp. in African Americans•Hypertrophic scars: dense fibroblastic proliferation•Broad bundles of bright pink to red hyalinized collagen•Hard to treat
Benign Fibrous Histiocytoma (AKA Dermatofibroma)
A Firm, tan papule on the leg
B Circumscribed dermal proliferation of benign-appearing spindle cells
C Fibroblasts surrounding individual collagen bundles (‘collagen trapping’)
Very common skin tumor lower legs
May be reaction to a long-forgotten insect bite
Raised papule or nodule measuring 0.5-3.0 cm in diameter with a smooth surface
Dermatofibrosarcoma Protuberans (DFSP)
A. The tumor consists of a flesh-colored fibrotic nodule on sectioning.
B. The lesion often infiltrates the subcutis in a manner reminiscent of “Swiss cheese.”
C. Characteristic storiform (swirling) pattern with uniform monomorphous spindled cells
Low grade malignant fibroblastic dermal tumor, very rare mets unless fibrosarcomatous
Early middle age plaques/nodules on back or front of trunk displaying slow growth
Pigmented variant due to melanin called Bednar tumor
IHC: strong diffuse +CD34
Translocation involving the genes encoding collagen 1A1 (COL1A1) and platelet-derived growth factor-β (PDGFB) t(17;22)(q22;q13)
Mycosis fungoides
Lymphoma of skin-homing CD4+ T helper cells
•AKA Cutaneous T-cell lymphoma spectrum lymphoproliferative disorders•In most localized to skin for many years, may evolve into systemic lymphoma•Any age, but most >age 40•Truncal areas scaly, red-brown patches next raised, scaling plaquesadvanced fungatingnodules•Prognosis related to % body surface involved and progression•Development of multiple, large red-brown nodules/plaques correlates with systemic spread
Mycosis fungoides
•Histologic hallmark: Pautrier ‘microabscesses’•Intraepidermal small clusters of Sézary cells •Markedly infolded nuclear membranes, hyperconvoluted or cerebriform contour•If Sezary cells circulating in peripheral blood ( > 1000/mm3: Sezary syndrome)
Epidermotropism: patches/plaques with pronounced epidermal infiltration by SL cells
Advanced stage: nodules tumors in dermis, metastatic capability
Sezary Syndrome
•Subtype of cutaneous T-cell lymphoma•Characterized by generalized erythroderma (pruritic), leukemic involvement, and lymphadenopathy•SS and MF constitute about 60% of CTCLs (Cutaneous T Cell Lymphoma)•Malignant T cell originate from mature skin-homing central memory T cells reason for epidermotropism
