MOD 2 more lectures (dermatopathology and cancer genetics) Flashcards
Risk factors for skin cancer
solar dmg (melanoma, basal, squam, and merkel cell carcinoma, angiosarcoma)
viral infection (squam cell)
chemical (squam cell)
genetic (melanoma, basal cell nevus)
Melanocytic nevi and types
morphology?
(mole)
junctional: dermo-epidermal junction
compound nevus: dermo-epiderm jxn and dermis
intradermal: melanocyte aggregates in dermis
-morph: spitz (spindle/epith melanocytes), and halo nevi (w chronic inflam)
-blue nevi: dnedritic melanocytic nevi assoc with pigmentation and dermal fibrosis
Lentigo maligna?
Invasive melanoma?
Lentigo: melanoma in situ on sun dmgd skin
Invasive: breslows thickness , clarks level, ulceration and invasion in dermis or beyond
- seborrheic keratosis
- actinic keratosis
- basal cell carcinoma
- squmaous cell carcinoma
- keratoacanthoma
- merkel cell carcinoma
SK: benign, looks like moles. epid
AK: dysplasia of lower epid above solar, forearms/scalp, precancerous, plaques (UV causes basal layer to disorg), can excise it easily
MALIG:
BCC: malig immature basal cell keratinocytic neoplasm (most common human cancer), flesh or red papules, bluish cells on biopsy bc large nucl, can lose eyes/nose but wont metas, basal cell prolif caused by UV (low grade cancer that rarely metast)
SCC: malig mature keratinocytic neoplasm (scaly ulcerated plaque on head/neck/genitals, irreg dermis nodules (pink keratin pearls), UV light or HPV (genitals)
KA: well diff SCC with crater formation
MCC: primary cutaneous neuroendocrine carcinoma (older person, head and neck, sun dmg)
Fibriohistiocytic neoplasia
benign factor XIIIa expressing dermal dendrocytic neoplasm
Mycosis fungoides
chronic cutaneous CD4 T-cell lymphoma
- patch, laque, lympo infiltrate of epid and dermis
- pautrier mciroabcess, abnormal CD markers, clonal prolif
- Sezarys syndrome: cut T-cell lymphoma with tumor cell sin blod with erythema and other sys issues
Adnexal neoplasia
ben/mal
pilomatricoma: diff of hair follics, sebaceous hyperplasia and tumors etc
- eccrine (hidrademona aka sweat gland tumor) etc
Vascular neoplasia
- hemangioma
- angiosarcoma
- kaposi’s sarcoma
- hemang: benign
- angiosarc: malig, high grade neoplasms with diff in sun dmg skin, head and neck, older ppl
- kaposi: low grade malig vasc spindle cell neoplasm (herpes virus 8 transformation aka HHV8)
Skin layers
Epidermis (5 layers CLGSB)
Dermis
Subcutaneous tissue (mostly fat)
4 main keratinocytic neoplasms?
SK
AK
BCC
SCC
congenital vs acquired nevus
congenital usu benign
How to estimate melanoma vol? rank
Breslows thickness for vol
Clarks levels
What does merkel cell carcinoma look like on slides and what is it assoc with
dense core neuroendocrine granules on EM
assoc with sun dmged skin and polyomavirus
Adenxal neoplasms (3)
tumors of skin appendages
Cylindroma
Pilomatricoma
Sebaceous adenoma
Hematopoeitic neoplasms (2)
- Mycosis fungoides: hemo neoplasm, older patients, clocnal prolif, of lymphocytes in upper epidermis, forms patch then plaque then tumor
- Sezary’s syndrome: cut t cell lympoma, erythrema can evolve into leukemia
Dermatofibroma
A type of stromal neoplasm, fibrous histiocytoma–benign dermal dnedrocyte neoplasm (firm solitary nodules, squeezing forms dimple, firbroblast prolif, common in legs of females eg induced by razor)
3 vascular neoplasms
Hemangioma (benign, bv’s dilate)
Angiosarcoma (UV dmg, blood vessel prolif in head and neck of elderly)
Kaposi sarcoma (vasc spindle neoplasm from HHSV-8) dont know if ben/mal (common if low CD4 count), small red purple lesions
TABLE:
Actinic keratosis
- from UV, epidermis basal layer, keratinocytes partially transformed
- scaly lesion, may be red, common on forearms and scalp
- histo: dysplasia of lower epidermis
Basal cell carcinoma
- mal immature basla keratin neoplasm, most common, cuased by UV
- red papule, pearl like, may be pigmented, assoc with upper lip, stem cell like prolif nests
- rarely metast, destruction to surr tissue
- slides: blueish, bc high nucl:cyto ratio
Squamous cell carcinoma
malig mature keratin neo, tumor modules in derms, lower lip, invasive, irreg cells, prom nuclei, irreg mitosis
- aggro, lethal, not just in skin
- slides: cells look like upper layers of epidermis
Keratoacanthoma
- skin tumor, unlikely to metas, caused by uv
- dome shaped symm, surr by inflamed skin, keratin scales
- fast growing, necrosis and healing w scarring
Seborrheic keratosis
- benign epid neoplasm >30, may be pigmented, inflam, thickening of epid, senile warts
- slides: porlif of keratinocytes with cystic formation
Melanoma types (3) And clinical course/px?
melanoma in situ
invasive
nodular
-biopsy the lesion, use melan-a stain to det if cause of lesion is melanoma, deeper ulcer means worse px, measure depth from gran layer ot base ot det invasion and px
melanoma in situ
confined to epid, no metas, no lymph
invasive melanoma appearance
dermis or beyond, melanocytes with prom mitoses, necrosis, shotgun pattern, cells have diff shapes
nodular melanoma appearance
cells create nodule in dermis, usus invasive, rec when it becomes a bump, varies in color
Merkel cell carcinoma
- cut neuroendo carcionma, dnese granules, older ppl head and neck, sun dmg, blue cell tumor, hard to treat
- slides: stem cell prolif, primitive blue cells with high N;C ratio
Acanthosis nigricans
- velvety hyperppigmentation in skin in body folds, ben or mal, assoc with obesity or endocrine issues
- slides: hyperkeratosis church spire appearance
Fibrous histiocytoma
dermatofibroma, benign factor XIIIa expressing dermal dendrocytic neoplasm, legs of females due to razor, dense fibrous tissues
epidermal cysts
benign cyst on skin, result of implantation of epid into dermis
-slides: thin layer of squamous epith
Junctional nevus
Compound nevus
Intradermal nevus
- jxnl: melanocyte agg at dermo-epid jxn, flat w smooth border, nest, no mitoses/necroses
- cpd: melan agg mix of jxnl and intraderm porlif, raised, brown/black beauty mark
- intraderm: mel agg in dermis, raised, flesh colored
Pilomatricoma (follicular)
Sebaceous adenoma
Cylindroma (eccrine)
Pilo: benign neo with pilomatrix diff in hair follic, firm irreg nodules, scalp or anywhere
- seb ad: benign with seb diff, large nodules in dermis, smooth borders, non aggro, monotonous cells, not many mitoses, yellow-orange, slides have vacuoles with sebum
- cyclindroma: benign wtih islands of cuboidal cells with thick BM material, histo: nest like cylinders with thick fibrous band around nodules
Cancer genetics
ALL are genetic, but only small portion are inherited
Characteristics of hereditary cancer
early onset, relatives with the same cancer, bilateral tumors, multiple primary tumors of same cancer type, AD inheritance
Retinoblastoma (Rb)
most common eye tumor in children
herit and non herit
Rb is a TSG, RB1 gene on chrom 13
Knudson’s two hit model, and tumor’s involved
can have predisposition, but need second mutation to develop cancer (dominant inheritance, but need recessive gentoype)
Rb, wilm’s, p53, APC
Why cant you give ionized radiation therapy to patient with de novo heritable form of Rb?
bc mutation is de novo so patient may be prone to other types of cancers and radiation could cause their onset (eg sarcomas)
genes involved in BC/ovarian cancer
usu sporadic, but can inv BRCA1 mostly (also BRCA2, and a lil bit p53/ PTEN)
BRCA1 assoc cancers
BC, some ovarian, a lil bit of others (pancreatic, prostate)
BRCA2 assoc cancers
BC, OC, others (prev, and melanoma, laryng), and male breast cancer
Sx that may indicate BRCA mutation
multiple early onset cases, ovarian cancer with fam history of either, BC and OC in same person, bilateral, ashkenazi jew, male BC
TABLE:
Cancer, inheritance, clinical findings, genes, tx
BC
BCRA 1 (and 2??) tx: mamo, mastectomy, prostate screening in men with mutation
Wilm’s tumor
WAGR, 11p13 deletion
tx: serum tumor marker for AFP and ultrasounds of abd as kid
Hereditary melanoma
relatives affected, seen w pancreatic cancer, CDKN2A, CDK4, screen by age 10
Ataxia Telengiectasia
AR, clumsy gait, weird eye vessels, genes ATM 7:24 transloc, screen both carrier women and partners, preven BC/pancr cancer
Li Fraumeni syndrome
Diff cancers, TP53, same prevention methods as prevs
Cowden syndrome
Thyroid tumors, mucocutaneous stimata, cobblestone appearance around lips and nose, PTEN, same methods (with endometr biopsies)
Multiple endocrine neoplasia type 2
Tall, medullary thyroid carcinoma, neuromas of tongue and eyelids, RET, tx by removing thyroid gland
Von Hippel-Lindau syndrome
AD, hemangioblastomas, pancreatic cysts, neuroendocirne tumors, renal carcinoma, bilateral
VHL gene
Peutz-Jeghers
AD, intestinal polyps and hyperpigmented macules, STK11 mutation
Basal cell nevus syndrome
AD, jaw cysts, basal cell carcinomas thru skin, kids, calcification of falx cerebri (PTCH, SUFU)
Which involves thryoid tumors?
cowden syndrome
Which involves intestinal polyps and hyperpig macules
Peutz-jeghers sydnrome
Which involves calicfication of falx cerebri?
Basal cell nevus syndrome
Tx or preventative methods for ovarian cancer
salpingo-oophorectomy to elim (can still cause peritoneal)
PARP (poly ALD ribose polymerase) last resort if chemo isnt working
lifestyle
prophylatic surgery (remove all breast tissue eg mastectomy), mammo/MRI
FAP
what cancer risk
genes
tx
Familial Adenomatous Polyposis
risk for colorectal cancers, colonic polyps in teens (min 100), prophylatic colectomy (found on APC gene chrom 5, de novo, AD)
Lynch syndrome or HNPCC
hereditary non-polyposis colorectal cancer
AD
-microsatellite instability: HNPCC related genes are in DNA mismatch repair, instability,
-IHC: look for MMR genes to see which gene is mtuated
(use tests together)
-colorectal cancer (do colonoscopy), endometrial cancer (do transvag ultrasound)
