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Yau Jun Wern (Year 3)

Guillain-Barré Syndrome
 Definition (1)
o Post-infectious, immune-mediated disease targeting peripheral nerves
o A.K.A. acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
 Aetiology (1,2)
o Respiratory and gastrointestinal infections
 Campylobacter jejuni
 Cytomegalovirus (CMV) most common and severe
 Epstein-Barr virus (EBV)
 Mycoplasma pneumoniae
 varicella-zoster virus
 human immunodeficiency virus (HIV)
 Clinical features (1,2,3)
o Presents 1-3 weeks following a relatively benign respiratory or gastrointestinal
o Signs & symptoms:
 Low back pain is a frequent early feature
 Classically presents with symmetrical ascending weakness and/or distal
numbness (predominantly motor) accompanied by absent or depressed
deep tendon reflexes
 Weakness and sensory loss progresses proximally, over several days to 6
 Cranial nerve involvement is observed in 45-75%, most common in cranial
nerve VII (mimicking Bell’s palsy)
 In 20%, weakness in respiratory muscles occurs, sometimes progressing to
complete paralysis
 Pain is present in 89% of patients and dysaesthetic symptoms (burning,
tingling, or shock-like sensations) are observed in approximately 50% of
 Investigations to differentiate from other conditions (1,2)
 established on clinical grounds
 confirmed by nerve conduction studies
 increased latency
 decreased conduction velocity
 normal amplitude
 CSF protein is often raised to 1–3 g/L
 Ddx:
 CIDP: duration of symptoms greater than 8 weeks
 Acute myelopathy (e.g. from compression, transverse myelitis,
vascular injury): MRI of spine, myelography
 Myopathy: Asymmetrical, decreased amplitude on nerve conduction
studies with normal latency and conduction velocity
 Botulism: nausea and vomiting, dry mouth and throat, followed by
CN paralysis
 Metabolic neuropathies
o DM: predominantly sensory neuropathy
Yau Jun Wern (Year 3)

o Alcohol toxicity & beriberi (thiamine deficiency): cardiac

failure, cerebellar signs
o Vitamin B12 deficiency (SACD): megaloblastic anaemia
 Charcot-Marie-Tooth disease: foot drop, pes cavus, toe clawing;
genetic testing


1. Kumar and Clark’s Clinical Medicine (8th edition): Immune-mediated neuropathies, page

PATHOLOGY: Malignant Breast Disease

 Risk factors
o Female
o Age above 40 (peak incidence between 75-79)
o Oestrogen exposure
 Early menarche
 Late menopause
 Nulliparity
 Late age at birth of first child
 Obesity in postmenopausal women
o Family history
 5-10% due to inherited gene
 4% due to BRCA1 and BRCA2
 6% due to combination of genes of lower penetrance
 Significant when
 2 or more individuals on same side of family with related cancers
 More than 1 primary cancer in an individual
 History of medical conditions associated with cancer risk
o Radiation exposure (during puberty)
o Ethnicity (white > African-American)
o Pathologic lesions:
 Proliferative disease without atypia – 1.5-2x relative risk
 Columnar cell lesion (flat epithelial atypia) – Rosen Triad (tubular carcinoma,
columnar cell lesion, and LCIS)
 Proliferative disease with atypia – 4.5-5x
 DCIS and LCIS – 10x relative risk
 Non-invasive
o Ductal carcinoma-in-situ (DCIS)
Yau Jun Wern (Year 3)

 A.K.A. intraductal carcinoma

 30% of breast carcinomas
 Clinical presentation:
 Mammographic calcifications (85%)
 Mass / radiologic density (10%)
 Nipple discharge (5%)
 1% of untreated patients per year develop invasive carcinoma at the site
 Morphology:
 Clonal proliferation of ductal cells that fills the ducts but does not
invade adjacent stroma
 Encompassed by myoepithelial cells
 Cannot metastasise
 Classification for risk of progression to invasive carcinoma:
 Nuclear grade (low, intermediate, high)
 Presence of necrosis/calcification
 ER/PR/HER2 status
 In cases where invasion in uncertain, immunostains (p63) are used to
demonstrate absence/presence of myoepithelial layer
 Treatment: Excision, local radiotherapy, tamoxifen (if ER+)
 Paget disease of the nipple
 Caused by extension of DCIS up the lactiferous ducts and into the
contiguous skin of the nipple
 Produces a unilateral crusting exudate over the nipple and areolar
 Presents with a chronic eczematous disease on the skin of the nipple
and the areola
 An underlying carcinoma is present, and 50% is invasive
o Lobular carcinoma-in-situ (LCIS)
 A.K.A. lobular intraepithelial neoplasia
 Clinical presentation:
 Rarely calcifies and almost never forms a mass
 Usually an incidental finding in biopsy
 Increased long term risk of invasive carcinoma in both breasts (RR x7)
 Morphology:
 Expansion of lobular unit by discohesive monomorphic malignant
 To differentiate pleomorphic LCIS from DCIS, use IHC E-cadherin
 LCIS lack cell adhesion, hence E-cadherin negative
 DCIS is E-cadherin positive
 Invasive
o 70% of breast carcinomas
o Invades beyond basement membrane, through the breast and into skin, nipple and
chest wall
o Metastasise to:
 Lymph nodes (usually axillary)
 Brain, bone, lungs
o Invasive carcinoma, no special type
Yau Jun Wern (Year 3)

 A.K.A. invasive ductal carcinoma

 75% of invasive carcinomas
 Clinical presentation:
 50% in upper outer quadrant
 Hard mass
 May be fixed to chest wall and cause skin dimpling or nipple
 Morphology:
 Gross:
o Hard, gritty, stellate mass with poorly circumscribed lesion
o Large tumours have haemorrhage, necrosis and cystic
 Microscopy:
o Irregular infiltrating cords and nests of malignant cells, often
adjacent to DCIS
o Loss of myoepithelial cell layer
o Grade 1 to 3 assigned to combination of 3 features:
 Tubule formation
 Mitoses
 Nuclear pleomorphism
o May see invasion into lymphatics, blood vessels, nerves
o Invasive lobular carcinoma
 10% of invasive carcinomas
 Often multifocal and bilateral
 Morphology:
 Single file of cells
 Monotonous cells
 Prognosis similar to IDC, later recurrence
o Inflammatory carcinoma
 Clinical presentation: enlarged, swollen, erythematous breast usually
without a palpable mass
 Morphology:
 Generally poorly differentiated and diffusely infiltrative
 Involves dermal lymphatic spaces, causing blockage, oedema, and
characteristic “inflamed” clinical appearance
 True inflammation is minimal to absent
o Medullary carcinoma
 Rare (<1%)
 Morphology:
 Sheets of large anaplastic cells with well-circumscribed ‘pushing’
 Pronounced lymphoplasmacytic infiltrate
 DCIS usually absent or minimal
 Can be mistaken for fibroadenomas
 Usually triple-negative
o Colloid (mucinous) carcinoma
 Rare
Yau Jun Wern (Year 3)

 Morphology:
 Tumour cells produce abundant quantities of extracellular mucin,
which dissects into the surrounding stroma
 Present as well-circumscribe masses and can be mistaken for
 Tumous are usually soft and gelatinous
 Most are ER+/PR+/HER2-
o Tubular carcinoma
 Rarely present as palpable masses
 Usually detected as irregular mammographic densities
 Morphology :
 Well-formed tubules with low-grade nuclei
 Lymph node metastases rare, prognosis excellent
 Virtually all are ER+/PR+/HER2-
o Common features of invasive cancers
 Tend to become adherent and fixed to pectoral muscles or deep fascia of
chest wall and the overlying skin, causing retraction or dimpling of skin or
 Involvement of lymphatics may result in localised lymphedema, causing skin
thickening around exaggerated hair follicles, giving peau d’orange
o Treatment:
 Excision (Wide local excision, hook-needle localisation, mastectomy)
 Removal of axilla lymph node (sentinel node biopsy, axillary dissection)
 Radiotherapy
 Adjuvant therapy (cytotoxic, hormonal, Herceptin)
o Prognostic factors
 Predicts disease recurrence and death
 Patient-related factors: age, menopausal status, comorbidities
 Tumour-related factors: LN staging, tumour size, grade, histological type,
lymphvascular invasion
o Predictive factors
 Predicts benefit from adjuvant therapies
 ER/PR/HER2 both prognostic and predictive

Stromal malignancies

 Phyllodes tumour
o Morphology:
 Biphasic epithelial and mesenchymal neoplasm of breast characterised by
variably cellular stroma and benign double-layered epithelial cells which
form ‘leaf-like’ structures
 Stromal component can show heterologous differentiation, resembling
fibroblasts and myofibroblasts
o Most follow benign course, <10% locally invasive
 Metaplastic carcinoma
o A group of neoplasms characterised by differentiation of neoplastic epithelium into
squamous cells and/or mesenchymal-looking elements
Yau Jun Wern (Year 3)

Includes squamous cell carcinoma, spindle cell carcinoma, low-grade
adenosquamous carcinoma, metaplastic carcinoma with mesenchymal component
o Lymph node metastasis significantly less than invasive carcinoma
o Distant metastasis can be found without lymph node metastasis
o May have lower response to adjuvant chemotherapy and worse prognosis
 Sarcoma
o Rare
o Angiosarcoma is most common primary sarcoma
 Occurs in 3 scenarios:
 Sporadic/primary
 After local radiation treatment
 Chronic lymphedema following mastectomy  Stewart-Treves
 Clinical presentation: ill-defined, haemorrhagic lesion
 Morphology:
 Well-differentiated: resembles vessels with bland cells
 Poorly-differentiated: sheets of malignant cells with no vascular
 Diagnosis: Either discernable vascular channels or immunostains
demonstration vascular differentiation
 Treatment: Wide surgical excision (with deep resection margin)
 Metastasise to lungs, skin, bone and liver. Axillary nodes involvement rare


 Either as primary tumour or secondary to systemic lymphoma

 Primary lymphoma
o Rare (<0.5%)
o Limited to breast and regional lymph nodes in patient with no history of lymphoma
o Most common subtype is diffuse large B cell lymphoma
o ALK-negative anaplastic large cell lymphoma (ALCL) associated with breast implants
 Presents with unilateral seroma
 Good prognosis

Metastasis to breast

 Most common in adult females: melanoma, lung carcinoma

 Most common in adult males: prostate carcinoma
 Signet ring carcinoma (in gastric) are histologically similar to invasive lobular carcinoma (but
latter is ER+/PR+/CDX2-)
 Women with breast carcinomas are at increased risk of developing 2nd primary in
contralateral breast
o Metastasis usually have extensive lymph vessel involvement and/or positive axillary
lymph nodes


1. Lecture notes
2. Robbins Basic Pathology (9th ed): Female Genital System and Breast, page 710