THE BASICS OF TUMOUR IMMUNOLOGY/IMMUNOTHERAPIES

risk factors: paget's disease, prior irradiation, bone infarction

metaphyseal region of the distal femur, upper humerus, tibia and fibula

endochromatosis = the presence of multiple enchondromas e.g. with Ollier's disease or Maffucci syndrome

occurs in the epiphyses of long bones of skeletally immature patients

seen in the pelvis, proximal femur, proximal humerus, distal femur and the ribs in people over 50

often associated with mutations of the IDH1 and/or the IDH2 genes

associated with a recurrent chromosomal translocation t(11;22), fusion of the EWS gene on chr 22 to the FLI-1 gene on chr 11, and this results in the formation of a potent transcription factor

epiphyseal and intramedullary giant cell rich tumours

locally aggressive neoplasms with some metastasising to the lungs

primary ABC associated with an alteration in the USP6 gene

commonly found in the jaw, ribs, skull and long bones

most cases are associated with an alteration involving the GNAS gene

features epitheliod cells with vacuoles containg red blood cells/blister cells

associated with alteration that results in the fusion of the CAMTA1 and the WWTR1 genes

occurs in adults, is aggressive and often multi-focal

elderly patients, superficial aspects of limb girdles nd extremeties

associated with a recurrent translocation involving the ss18 gene t(X;18)

mainly sporadic but some associated with beta-catenin mutation (CTNNB1), or less commonly an APC gene mutation (Gardner syndrome)

the condition should be an important health problem

there should be an available treatment for the disease

facilities for diagnosis and treatment should be available

there should be a latent stage of the disease

there should be a suitable test or examination

the test chould be acceptable to the population

the natural history of the disease should be adequately understood

there should be an agreed policy on whom to treat

the cost of case finding should be acceptable

case finding should be a continuous process

positive predictive value = the proportion of true positivies among all those testing positive

negative predicting value = proportion of true negatives among all those testing negative

lead time bias = apparent improvement in survival that is seen when screening advances the time of diagnosis without any change in the actual time of death

length-time bias = tendency of screening to detect a disproportionate number of cases of slowly progressing cancer compared with more aggressive cases, and aggressive cases may progress during the screening interval

Colorectal cancer screening - free faecal immunochemical testing

measured using the Breslow thickness scale and the Clark level

BRAF inhibitor therapy if BRAF V600 gene mutation present

allows for the avoidance of attack from our own T lymphocytes

malignant melanocytes invading into the dermis

usually congenital but can occur after this, pay attention to those occuring in the middle/older age groups

affects the epithelium of the hair follicle rather than squamous cells in the epidermis

can be associated with Nevoid basal cell carcinoma (Gorlin) syndrome

sharply demarcated and pigmented lesions that protude above the skin surface

benign proliferation of keratinocytes with horn cysts

firm outgrowth of keratinocytes with horn cysts

UV light exposure is a risk factor but can occur in both sun exposed and non-sun exposed areas

germline mutation in the cylindromatosis gene on chromosome 16

autosomal sominant mutation in the MLH1 and MSH2 mismatch repair genes

patients at risk for: colorectal and endometrial adenocarcinoma, and cutaneous sebaceous tumours

autosomal dominant mutation in the PTEN tumour suppressor gene

increased life time risk of thyroid, breast, endometrial, colorectal cancer and melanoma

autosomal dominant mutation in the BDH or FLCN gene on chromosome 17 coding for the folliculin protein

patients are also at risk fro developing lung cysts with pneumothorax and renal cell carcinoma, in particular bilateral chromophobe renal cell carcinoma and oncocytoma

reproductive profile - uninterrupted oestrogen stimulation e.g. with nuns, abstinence

triple negative = HER2 negative, ER/PR negative

surveillance of tumour or excision, depending on the grade of the tumour

treatment with subareolar exploration and removal of tissue

most commonly associated with translocation t(11;22)

if BRAF mutation present, then it can be treated with vemurafenib (a BRAF inhibitor)

CD1a cell surface marker can be identified on IHC

commonly seen in premature babies and very low birth weight infants

mutation in the betacatennin pathway and APC gene inactivation

soft tissue tumour that usually appears in the first decade of life

genetic imprinting disorders e.g. Beckwith Wiedmann syndrome

loss of heterozygosity on chromosome 1p and 16q

extra-cranial tumour of the autonomic nervous system

25% of cases are congenital, but otherwise they occur before the age of 5

other neuroblastic tumours include ganglioneuroblastoma and ganglioneuroma, which are more benign than neuroblastoma

intensive chemotherapy in tandem with a bone marrow transplant

if ALK mutation present, crizotinib (an ALK kinase inhibitor) can be used

bilateral proximal muscular weakness but no rash

poor prognosis if there is interstitial lung disease

20% present with anti-Jo1 antibodies (common to all inflammatory myopathies)

shawl sign - erythermatous rash on shoulders, back and trunk

mechanic's hand - rough surface with lots of cracks

progressive and symmetric proximal muscle weakness

fine motor movements affected as the disease progresses

pharyngeal muscles and neck flexors are commonly involved, resulting in dysphagia and head drop

normal sensation and tendon reflexes maintained

affects extra cranial branches of the carotid arteries mainly

features: multinucleated giant cells in the elastic lamina and the presence of mononuclear infiltrate, scarring with intimal thickening, residual elastic fragmentation and adventitial fibrosis

affects renal and visceral vessels but not pulmonary vessels