Malignancy Flashcards
Gorlins
Inheritance
Gene
Age at presentation
Key features
Inheritance: AD
Gene : PTCH1 gene on 9q22-31
Age at presentation : birth (bossing, skeletal), childhood: (BCC, jaw)
Key features:
Skin: BCCs, palmarplantar pits, milium, epidermoid cysts
MSK: jaw cysts (odontogenic keratocytsis)(lining with malignant potential), frontal bossing, bifid ribs, vertebral fusion, kyphoscoliosis
CNS: calcification of falx cerebri, agenesis of corpus callosum, medulloblastoma, mental retardation (less common)
Eyes: hypertelorism, congenital blindness, cataracts, colobomas, strabismus
Genitorurinary: ovarian fibromas, fibrosarcoma.
Gorlins DDx Ix Mx Prognossi
DDx:
Bazex syndrome, Rombo syndrome, Unilateral linear naevoid BCC, Melanocytic naevi, Xeroderma pigmentosa
Investigations: Skin bx, skeletal surveys
Management: referral to dentist/oral surgeon, ophthal, neurologist
Photoprotection, consider oral retinoids, C&C, imiquimod
Avoid radiotherapy/xrays
Prognosis : normal life span if no other malignancies develop
Peutz-jegher
Inheritance
Gene
Age at presentation
Inheritance: AD
Gene : STK11 gene
Spontaneous mutation – approximately 40%
Age at presentation: birth to first few years (pigmented macules), first to 3rd decade of life (polyps)
Peutz jegher
Clinical
Skin: pigmented macules 0.2-7mm: periorificial, lips, buccal mucosa, digits, nails, palms, soles, mucosal. All except mucosal will fade with time.
GIT: hamartomatous polyps: small intestine > large intestine, GIT bleeding, intersussception, obstruction, adenoCA
Neoplasm: increased incidence of ovarian, breast and pancreatic CA
Peutz jegher
DDx
Investigations
Management
Prognosis
DDx: LEOPARD, carney complex, laugier-hunziker, cronkhite-cannida, addisons, gardner
Investigations: scopes, mammography
Management: gastro referral, ob/gyn exam
Prognosis :normal lifespan if malignancy detected early.
Muir-Torre syndrome
Inheritance
Gene
Age at presentation
Key features
Inheritance: AD
Gene : MSH 1 and 2
Age at presentation : 5th-6th decades of life (internal malig usually 1st)
Key features: Skin sebaceous tumors eg: sebaceous adenoma, sebaceous CA, hyperplasias, epitheliomas, BCC with sebaceous differentiation, KA
NEOPLASMS: adenoca of the colon, genitourinary tract, lung, breast, haematological malignancies
Muir tORRE
DDx
Investigations
Management
Prognosis
DDx: Cowden, Gardner
Investigations: Skin bx, endoscopy/colonoscopy, cystoscopy
Management: close f/u malignancy
Gastroenterologist , UROLOGY
Prognosis : malignancies usually low grade with good prognosis
Dyskeratosis congenita
Inheritance
Gene
age at onset
Inheritance: X linked recessive – most common, can be AD
Gene:DKC1 gene (most common)
Age at presentation : 1st decade of life (skin, nail, mucosal)
Dyskeratosis congenita
Key features
Skin: reticulated grey-brown hyperpigmentation on neck, face, trunk, upper thighs, hypopigmentation and telangiectasias. Palmar/plantar hyperkeratosis, hyperhidrosis, friction bullae, acrocyanosis. Hair: thinning
Haem: fanconi’s type pancytopenia with secondary infection, bleeding
Mouth & mucous membranes: premalignant leucoplakia of the tongue, buccal mucosa, pharynx, dental caries, early loss of teeth
Eyes: blepharitis, conjunctivitis, lacrimal duct obstruction with epiphora, ectropion
CNS: mild – mod mental retardation (50%)
Dyskeratosis congenita
DDx
Investigations
Management
Prognosis
DDx: fanconi syndrome, pachyonychia congenital, rothmund-thomson, chronic GVHD
Investigations: Bone marrow, mucosal bx
Management: photoprotect, refer haem, gastro, opthal
Prognosis : death usually 20s-30s from malignancy eg SCC, GIT haemorrhage, opportunistic infection
Gardner
Inheritance
Gene
Age at presentation
Inheritance: AD
Gene : APC gene
Age at presentation: infancy to early childhood (bone, skin), 2nd to 4th decade
Gardner
Key features
Key features:
Skin: epidermoid cyst (head and neck but can occur toe, scalp, shin), fibromas
MSK: osteomas
GIT: polyposis, risk of adenoCA, desmoid tumours (post abdo surgery, uteral or intestinal obstruction)
Eyes: Congenital hypertrophy of retinal pigment epithelium (CHRPE)
Teeth: Odontomaws, supernumerary teeth
Gardner
DDx
Investigations
Management
Prognosis
DDx: Epidermoid cysts, familial polyposis coli, turcot syndrome
Investigations: colonoscopy, endoscopy, skeletal survey, DNA analysis
Management: Referral: gastro, ophthal, dentist
Prognosis : if total colectomy prior to mets, then normal life span
Cowden
Inheritance
Gene
Age at presentation
Inheritance: AD
Gene : PTEN
Age at presentation : 2nd to 3rd decade, range from 4-75
Cowden
Clinical features
Key features:
Skin: facial tricholemmomas, Oral papillomas (cobblestone) appearance on lips, gingival, labial, buccal mucosa, oropharynx
Acral keratotic papules, palmoplantar translucent punctate keratoses, lipomas, angiomas
Breasts: fibrocystic disease, fibroadenomas, adenoCA, gynaecomastia
Thyroid: goiter, adenomas, thyroglossal duct cysts, follicular adenoCA
GIT: hamartomatous polyps
Genitorurinary: ovarian cysts, menstrual irregularities
Craniofacial/skeletal: adenoid facies, high arches palate, craniomegaly, kyphoscoliosis.
Cowden
DDx
Investigations
Management
Prognosis
Cowden
DDx : lipoid proteinosis, muir-torre, MEN2b, TS
Investigations:
Mammography, thyroid scan, TFTs, FBC, urinalysis, stool guiaic
Management
Referral gynae:pelvic exam, breast screen
Endo – thyroid, gastroenterologist
Prognosis: normal if CA detected early
Conditions associated with GI malignancy
Peutz-jegher Gardner Cowden Muir-torre Dyskeratosis congenita : tongue
MENIIb
DDx
Investigations
Management
Prognosis
DDx MENIIA-Sipple NF1 Marfan Investigations: serum/urine calcitonin urine catecholamine thyroid scan/tfts abdominal ct/uss barium enema
Management
Refer to thyroid, gastro, ophthal,
Prognosis : normal if thyroid CA detected early, otherwise 20-30
MEN Type IIB
Inheritance
Gene
Age at presentation
Key features
Inheritance: AD spontaneous in 50%
Gene : RET protooncogene
Age at presentation : birth to few years of life (mucosal lesions may proceed)
Key features:
Mucocutaneous: mucosal neuromas, thickened, blubbery lips
Endocrine: medullary CA of the thyroid, phaeochromocytoma
MSK: marfanoid
Eyes: conjunctival neuromas, upper eyelids thickened everted; thickened white medullated nerve fibres in cornea.
GIT: ganglioneuromatosis with secondary megacolon, diarrhoea constipation
Birt – Hogg Dube
Inheritance
Gene
Age at presentation
Key features
DDx
Investigations
Management
Prognosis
Inheritance: AD
Gene : BHD gene
Age at presentation: >25 often
Key features
Skin:fibrofolliculomas, trichodiscomas, acrochordons
Kidney: renal cell CA
Lung: recurrent spontaneous penumothoraces, lung cysts, bullous emphysema
DDx: Cowden, TS, brooke-spiegler, rombo, basaloid follicular haemartoma`
Investigations: skin Bx, CT/renal USS
Management: referral to renal, resp, screen all 1st year relatives for kidney and lung manifestations
Prognosis : good if renal cell ca detected early
Xeroderma pigmentosum
Inheritance
Pathogenesis
Age at presentation
Key features
DDX
Ix
Mx
Inheritance: AR
Age at presentation : first few years of life
Pathogenesis: mutations in genes encoding DNA repair enzymes leads to defective excision repair upon exposure to UV radiation
DDx: Erythropoeitic protoporphyria, congenital erythropoietic porphyria, blood syndrome, cockayne syndrome, hartnup, rothmund Thomson
Ix: DNA analysis, UDS assay from cultured skin fibroblasts
Mx: Photoprotection, physical blockers, 3 monthly skin checks, window tinting
Referral ophthal, neurologist
Support group
Isotretinoin to prevent new cancers
XP
Key features
Acute sun sensitivity in infancy
Then (in order)
Pigmented macules, achromic macules, telangiectasias
Dry, scaly, atrophic with narrowing of mouth and nares
AKs, KA, 1000x increased risk for BCC, SCC, MM
Eyes: photophob ia, conjunctivitis, telangiectasia, pigmentation of lid, conjunctiva, ectropion, benign lid papillomas
Neuro (20%) – esp A&D: progressive neurologic degeneration, mental retardation, sensorineural deafness, hyporeflexia, spasticity, ataxia, with/without microcephaly
Syndromes associated with BCC
Gorlins, rombo, Basex-dupre-christol
Rombo:
Basex-dupre-christol: X-linked dominant inherited disorder of the hair follicle characterised by:
• Follicular atrophoderma (breakdown of follicles on the skin) of the extremities
• Multiple basal cell carcinomas of the face
• Milia
• Localised or generalised hypohidrosis (diminished sweating)
• Hypotrichosis (reduced body and scalp hair).
