Solid cancers

Question 1

Breast carcinoma in situ:

• Definition
• DCIS - definition, investigations, management
• LCIS - definition, investigations, management

Answer 1

Breast carcinoma in situ:

• Definition: neoplasms contained within breast ducts and contained within basement membrane. There’s 2 types: ductal DCIS and lobular LCIS. Mostly assymptomatic!!

DCIS:

-Definition: most common type where malig of ductal tissue. 5 types: comedo, cribriform, micropapillary, papillary, solid types

• Investigations: microcalcifications on mammography, biopsy
• Management: wide local excision. If widespread or multifocal then mastectomy

LCIS:

• Definition: of secretory lobules. Greatest risk of developing into invasive. Mostly diagnosed before menopause.
• Investigations: incidental finding on biopsy (as no microcalc)
• Management: low grade = monitor. If BRCA1/2 gene prophylactic mastectomy

Question 2

Invasive breast cancer:

• Definition
• Where does it met to
• Risk factors
• Symptoms
• Investigations
• Management
• Prognosis
• Screening

Answer 2

Invasive breast cancer:

• Definition: most common F cancer in UK. Invasive ductal carcinoma most common (microscopically nests + cords of tumour cells with associated gland formation) or invasive lobular carcinoma which is more common in older women and harder to detect
• Risk factors: F, inc age (doubles every 10 yrs until menopause), BRCA1/2 gene (also inc risk ovarian/prostate/pancreatic), early menarche/late menopause/nulliparity/HRT (exposure to unopposed oestrogens), previous benign breast disease, obesity, alc, smoking, western
• Symptoms: assymp, breast/axillary lumps, assymetry, swelling, abnormal nipple discharge, nipple retraction, mastalgia, peau d’orange, pagets (scaling, ulceration, eczema change to nipple epidermis where 85% have underlying neoplasm and need surgery to remove nipple and perhaps radio/malig treatment)
• Investigations: triple assessment (history/exam, imaging mammography/uss, core needle or fine needle biopsy), check ER/PR/HER2 human epidermal GF expression, sentinel node biopsy, Then MDT of surgeons, oncologists, radiologists, nurses
  Then TNM staging
• Management:
  Surgical: wide local excision or mastectomy with sentinel node biopsy (and if + axillary node clearance). SE: lymphoedema, damage to brachial plexus, infection, pain, anaesthetic risks (stroke, VTE, MI, aspiration)
  Radiotherapy: adjuvant following WLE or if higher stages
  Chemo: for HER2+ patients
  Biological: Herceptin/trastuzumab is monoclonal ab to HER2+
  Hormonal: anastrozole (aromatase inhibitor): if postmenopausal or tamoxifen for premenopausal ER+ patients
• Prognosis: nottingham prognostic index uses nodal status, grade, size, receptor status
• Screening: 50-70 yrs every 3 years mammogram
  Urgent referral if >30 + lump, >50 with any changes

Question 3

Lung cancer:

• Definition
• Classification
• Common mets
• Risk factors
• Symptoms
• Signs
• Paraneoplastic syndromes
• Investigations
• Management

Answer 3

Lung cancer:

• Definition: most common cause of death.
• Classification:

SCLC (from neuroendocrine cells which develop centrally near main bronchus and grow/mets quickly + assoc with smoking)

NSCLC:
1. squamous - strong assoc with smoking, develop centrally
2. Adenocarcinoma - develop peripherally, assoc smoking
3. Large cell
4. Carcinoid

• Risk factors: smoking, asbestos exposure, air pollution, exposure to radon gas, exposure to ionising radiation
• Symptoms: cough, haemoptysis, sob, weight loss, fatigue, night sweats, met symptoms (personality changes, bone pain)
  Local invasion symptoms:
  Upper limb paralysis (pan coast NSCLC compresses brachial plexus)
  Horners syndrome (ptosis, miosis, anhydrosis) (on cervical sympathetic chain)
  Ipsilateral hemidiaphragm (compression on phrenic nerve)
  Hoarse voice (recurrent laryngeal)
  Facial plethora (SVC obstruction)
• Paraneoplastic syndrome:
  1. Squamous cell: Hypercalc due to PTHrp
  2. SCLC: produce ADH leading to SIADH resulting in hyponatraemia
  3. SCLC: produces ACTH resulting in cushings
  4. Adenocarcinoma: hypertrophic osteoarthropathy causes clubbing, joint pain, bone pain
  5. SCLC: produce ab against presynaptic ca channel at NMJ causing Lambert eaton syndrome (proximal muscle weakness) as SCL
• Investigations: bloods (fbc, crp, U+es, bone profile), cxr (nodule mass), contrast CT chest, transbronchial or endoscopic or transthoracic biopsy
• Management:
  Mets: chemo + radio, prophylactic radioth for brain esp if SCLC
  Surgical: only curative treatment. Lobectomy for SCLC. Pneumonectomy, wedge resection, sleeve resection. Do lung function testing before

Question 4

Colorectal cancer:

• Definition
• Pathophysiology
• Risk factors
• Symptoms
• Signs
• Investigations
• Management
• Extra facts
  1. Screening
  2. Dukes staging
  3. Familial adenomatous polyposis

Answer 4

Colorectal cancer:

• Definition: adenocarcinoma mostly in rectal + sigmoid. 70% sporadic
• Pathophysiology: progression of normal mucosa –> polyps (colonic adenoma) –> invasive adenocarcinoma. Genetic mutations are APC adenomatous polyposis coli which results in growth of adenomatous tissue, HNPCC a DNA mismatch repair gene causing defects in DNA damage
• Risk factors: AGE, male, fam hx, IBD, decrease fibre, high processed meat, smoking, alcohol, FAP
• Symptoms: palp mass, change in bowel habits, haematochezia, abdominal pain, large bowel obstruction signs
  Right side= fungating, iron deficiency anaemia, palp RIF mass, presents late
  Left = stenosing, tenesmus, palp LIF mass
• Investigations: bloods (fbc (microcytic anaemia), lfts, clotting, CEA carcinoembryonic ag), colonscopy + biopsy (to find out histological subtype, tnm stage, grade, and assessment of lympathic, perineurial and venous invasion) (CT colonography if too fragile), ct chest abdominal pelvis
• Management:

If presents with bowel obstruction = decompressing colostomy or endoscopic stenting

Curative surgery: colectomy removing tumour, margins, lymphatic drainage followed by anastomosis or stoma formation.
1. Right hemicolectomy = caecal/ascending tumours
2. Left = descending
3. Sigmoidcolectomy = sigmoid
4 Anterior resection = high rectal tumours. High removes sigmoid. Low removes upper rectum also
5. Abdominoperineal AP resection (anus + rectum)= low rectal tumours
6. Hartmanns (recto-sigmoid + end colostomy) = emergency

Chemo = if advanced disease
Radio = in rectal cancer (rarely in others as damages small bowel)

• Extra facts:

1. Screening: 60-75 every 2 years faecal immunochemistry test which uses ab against human hb to detect blood
   Refer if >40 with unexplained weight loss + abdominal pain, >50 unexplained bleeding, >60 anaemia/change bowels, + FIT
2. Dukes staging:
   A: confined beneath muscularis propria
   B: extension through propria
   C: Involvement of regional lymph nodes
   D: Distant mets
3. FAP: autosomal Dom where TSG APC doesn’t work leading to development of polyps (adenomas) in colon by 30-40yrs old so they need panprotocolectomy to reduce risk

Question 5

Prostate cancer:

• Definition
• Common mets
• Risk factors
• Symptoms
• Investigations
• Grading
• Management
• Extra facts - screening controversy

Answer 5

Prostate cancer:

• Definition: adenocarcinoma from mostly peripheral zone. Can be acinar where originates in glandular cells or ductal (which grows/mets faster)
• Risk factors: age, black afric/carrib, BRCA1/2, diabetes/metformin, obese, tall, anabolic steroids
• Symptoms: normally incidental screening, obstructive LUTs, UTIs, haematuria, loin pain, bone pain (osteolytic lesion), weight loss
• Investigations: DRE (hard, assymp, irreg, nodular), PSA (serum protease made to break down seminal coagulation so semen more aqeous. 40 yrs >2.5ng/ml, 70yrs >6.5ng/ml, but also inc if inflammation, infection, BPH), urine dip, multiparametric MRI prostate, TRUS transperineal/rectal USS prostate biopsy for diagnosis, CT + PET-CT for staging
• Grading: gleason grading based on differentiation from histology. Small uniform glands to few glands + poorly differentiated and irreg neoplastic cells graded 1-5. Higher score = poorer prognosis. This is used with PSA levels and TNM staging to determine prognosis + risk
• Management:

Local disease: depends on risk stratification. Low risk is active surveillance. Intermed risk active surveillance or radical treatment. Radial prostatectomy (stress, incont, bladder neck stenosis), or ext beam radiotherapy or brachytherapy (transperineal implantation of radioactive seeds) all curative

Mets: chemo + antihormonal agents. Prostate cancer cells are androgen dependant to grow and undergo apoptosis when deprived of testosterone therefore androgen deprivation therapy ADT (hot flushes, sexual dysfunct, gynaecomastia, fatigue, osteoporosis) + radiotherapy. This includes anti androgens (bicalutamide), GnRH agonists/antag or orchiectomy (castration)

1. Watchful waiting in older + unfit where conservative symptom management
2. Active surveillance in high risk with inc survival expectancy and start treatment when disease progression is noted (PSA 3 monthly, DRE 6 monthly, Biopsy 1-3 years)

• Extra facts: screening for assymp controversial because ERSPC showed signif reduction in mortality at 11 years but PLCO showed none at 10 years however it was limited by contamination

Question 6

Head and neck cancer:

• Definition
• Locations
• Risk factors
• Red flags
• Symptoms
• Investigations
• Management
• Complications of treatment
• Extra facts - referral

Answer 6

Head and neck cancer:

• Definition: usually squamous cell carcinomas of mucosa
• Locations: nasal cavity, paranasal sinuses, mouth, salivary glands, pharynx (throat), larynx (epiglottis, supraglottis, vc, glottis, subglottis)
  They usually spread to lymph nodes first so can be found here and the original tumour site unknown
• Risk factors: smoking, chewing tobacco, chewing beta quid (oral), alc, HPV 16, EBV (nasopharyngeal), male
• Red flags: lump in mouth/lip, unexplained mouth ulceration >3 weeks, erythroplakia, erythroleukoplakia (red + white patches are premalig), persistent neck lump, voice hoarseness, unexplained thyroid lump
• Symptoms: cervical lymphadenopathy, weight loss etc
  1. Oral = painless mass, bleeding, localised pain, jaw swelling
  2. Pharyngeal = odynophagia, dysphagia, stertor, referred otalgia, neck lump, trotters syndrome (unilat conductive deafness, trigeminal neuralgia, defective mobility soft palate)
  3. Laryngeal = hoarse voice, stridor, dysphagia, persistent cough, referred otalgia (glottic = better prognosis)
• Investigations: flexible nasal endoscopy to visualise and if seen then EUA + biopsy. If solely lymphadenopathy then USS fine needle aspiration. CT neck + chest to see tumour extension, local invasion, cervical lymphadenopathy, MRI if oropharyngeal lesions
• Management: surgical resection with adjuvant chemo, radio, or primary radio with chemo
  1. Oral: if small wide local excision. If large surgical resection / reconstruction / radio + chemo
  2. Oropharynx: small tonsil tumours surgical resection or radio, large radio +/- chemo. If small at tongue surgical resection, if larger then radio
  3. Larynx: supraglottis - if small surgical resection or radio, if large laryngectomy with radio
  4. Hypopharynx: if small surgical resection or radio, if large laryngopharyngectomy or radio

Also now using monoclonal ab cetuximab

• Complications of treatment: dysphagia, pharyngocutaenous fistula (after laryngectomy), injury to accessory/ vagus / hypoglossal / marginal mandibular nerves, mucositis, xerostomia, hearing loss, persistent hoarse voice
• Extra facts: referrals
  Laryngeal: persistent hoarseness, unexplained neck lump
  Oral: lump, erythroleukoplakia, ulceration >3 weeks, persistent neck lump

Question 7

Malignant melanoma:

• Definition
• Risk factors
• Symptoms
• Signs
• Investigations
• Prognosis
• Management

Question 8

SCC:

• Definition
• Risk factors
• Symptoms
• Management

Question 9

BCC:

• Definition
• Risk factors
• Symptoms
• Management