Breast cancer histology

Grade - modified Bloom-Richardson (grades I-III)

Grade I = good prognosis; grade III = bad prognosis.

• Tubule formation = happy sign.
• Mitotic count per high-power field.
• Nuclear size and pleomorphism (enlargement and variation are bad).

DCIS

90% of DCIS are identified on mammography as suspicious calcifications, linear, clustered, segmental, focal, or mixed distribution. DCIS is divided into comedo (i.e. cribriform, micropapillary, solid) and noncomedo subtypes, which prognosticates on the likelihood of progression or local recurrence:

DCIS Characteristic	Comedo	Noncomedo
Nuclear grade	High	Low
ER	-	+
HER2 overexpression	Present	Absent
Distribution	Continuous	Multifocal
Necrosis	Present	Absent
Local recurrence	High	Low
Prognosis	Worse	Better

LCIS

Arises from the terminal duct apparatus and shows a diffuse distribution throughout the breast, which explains its presentation as a nonpalpable mass in most cases.

Infiltrating ductal carcinoma

The most commonly diagnosed breast tumour (75%). Has a tendency to metastasise via lymphatics. Has no specific histologic characteristics other than invasion through the basement membrane. DCIS is a frequently associated finding on pathologic examination. Typically metastasises to axillary LNs first.

Infiltrating lobular carcinoma

Much lower incidence (15%). Characterised histologically by the 'Indian file' arrangement of small tumour cells. Like ductal carcinoma, infiltrating lobular carcinoma typically metastasises to axillary LNs first. However, it also has a tendency to be more multifocal. Despite this, the prognosis is comparable to that of ductal carcinoma.

Medullary carcinoma

Relatively uncommon (5%). Generally occurs in younger women. Most present with a bulky palpable mass with axillary lymphadenopathy. Diagnosis depends on a histological triad:

1. Sheets of anaplastic tumour cells with scant stroma.
2. Moderate or marked stromal lymphoid infiltrate.
3. Histological circumscription or a pushing border.

DCIS may be observed in the surrounding normal tissues. Typically ER-, PR- and HER2-. TP53 is commonly mutated.

Mucinous carcinoma

Rather rare (fewer than 5%). Usually presents in the 60s as a palpable mass or appears mammographically.

Excellent prognosis (80% 10-year survival).

Mucin production is the histological hallmark with 2 main forms, type A and B, with AB lesions possessing features of both. Type A represents the classic variety with larger quantities of extracellular mucin, whereas type B shows endocrine differentiation.

DCIS is not a frequent occurrence, although it may be found. Most are ER+ and PR+. HER2 overexpression in rare. These carcinomas predominantly express glycoproteins MUC2 and MUC6.

Tubular carcinoma

1-2%. Single layer of epithelial cells with low-grade nuclei and apical cytoplasmic snoutings arranged in well-formed tubules and glands. L

ow incidence of LN involvement and very high overall survival rate. Because of its good prognosis, patients are often treated only with breast-conserving surgery and local radiation therapy.

Papillary carcinoma

1-2%. Women older than 60y. Centrally located in the breast and can present as a bloody nipple discharge. Strongly ER+ and PR+.

2 common types: Cystic (non-invasive) and micropapillary ductal carcinoma (invasive). The cystic type has a low mitotic activity, which results in a more indolent course and good prognosis. Micropapillary ductal carcinoma has a more aggressive phenotype, even though 70% are ER+. LN metastasis is seen frequently.

Metaplastic breast cancer (MBC)

1%. Older women. Higher incidence in blacks. Combination of adenocarcinoma + mesenchymal and epithelial components.

A wide variety of histologic patterns including:

• Spindle cell carcinoma
• Carcinosarcoma
• Squamous cell carcinoma of ductal origin
• Adenosquamous carcinoma, etc.

The diverse group of malignancies is identified as a single entity based on a similarity in clinical behavious. When compared with infiltrating ductal carcinomam MBC tumours are larger, more rapidly growing, commonly LN-negative, and typically ER-, PR-, HER-.

Mammary Paget disease

Relatively rare (1-4%). Peak incidence in the 50s.

This adenocarcinoma is localised within the epidermis of the nipple-areola complex and composed of the histologic hallmark Paget cells within the basement membrane. Paget cells are large, pale epithelial cells with hyperchromatic, atypical nuclei, dispersed between the keratinocytes singly or as a cluster of cells.

Lesions are predominantly unilateral, developing insidiously as a scaly, fissured, oozing, or erythematous nipple-areola complex. Retraction or ulceration of the nipple is often noted, along with symptoms of itching, tingling, burning or pain.

Ovarian cancer

3 cell types make up the normal ovary: Surface epithelial cells (multipotential); sex cord/stromal cells (multipotential); germ cells (totipotential).

Risk factors: Nulliparity and Fx. OCP reduces the risk :)

Genetics: 5-10% of all ovarian cancers are familial. Most are caused by mutations in BRCA1 and BRCA2. The average lifetime risk for ovarian cancer approximates 30% for BRCA1 carriers; somewhat lower in BRCA2 carriers.

Sporadic cancers:

• BRCA1 and BRCA2 mutations are seen in only 10% of sporadic ovarian cancers.
• HER2/NEU is overexpressed in 35%, and is associated with a poor prognosis.
• K-RAS protein is overexpressed in up to 30%, mostly mucinous cystadenocarcinomas.
• p53 is mutated in about 50% as with other cancers.

Surface epithelial cells

• Serous
• Mucinous
• Endometrioid
• Clear cell
• Brenner
• Cystadenofibroma

Germ cell

• Teratoma
• Dysgerminoma
• Endodermal sinus tumour
• Choriocarinoma

Sex cord-stroma

• Fibroma
• Cranulosa-theca cell tumour
• Sertoli-Leydig cell tumour
  

Surgery is also out.

All OK :)

Medicine is out.

My first result is out. I was reading in bed when my mobile groaned on my bedside table. I groaned too. Who was it now? ‘Medicine is out’, said the message. Oh, I see.

I allowed myself to fall back into bed and became very aware of my beating heart and of a whirlpool of doom forming in my gut. Slowly I got out of bed and walked calmly to the computer. I almost whistled to convince myself that I was completely calm and in control of the freaky situation. I took the book with me, so that I could pretend to read while my computer switched itself on, the browser coughed into motion and esims loaded.

But I couldn’t read, so I prayed instead. A D, please please please! Give me a D! A D! A D! While I went on with my sad mantra I entered esims. And there it was, my result.

I prayed for a D because the last time I did well in my exams (four whole years ago), I prayed for a C when I wanted a B. And I actually got an A and a B in the subjects that mattered. So I repeat, like a superstitious monkey, the small things that led me to success four years ago. I beg for the minimum I need to scrape by to perhaps get something better.

I almost forgot: My result was OK. OKish.

ARDS - acute respiratory distress syndrome

Info from Burkitt pg 179

Characterised by rapid, shallow breathing, severe hypoxaemia, stiff lungs, diffuse pulmonary opacity on CXR.

Pathophysiology

1. Insult to the lung.
2. Increased permeability of pulmonary capillaries + damaged type I pneumocytes.
3. Leakage of protein-rich fluid into alveolar interstitium (interstitial oedema).
4. Lung compliance is reduced - stiff lungs.
5. Reduced alveolar ventilation.
6. Leakage of fluid into alveolar spaces until they are filled.
7. Disruption of V/Q ration, causing R to L shunting of blood.
8. The intra-alveolar fluid later condenses to form a hyaline membrane which lines the alveoli. This is histologically similar to the natal form of the disease.
9. If the patient recovers, the interstitial damage may result in diffuse interstitial fibrosis.

Note that cardiac failure plays no party in the development of ARDS, although cardiac failure may later complicate ARDS.

Clinical features

• Rapid shallow respiration.
• Only scattered crepitations on auscultation.
• Usually no cough, no chest pain, no haemoptysis.
• ABG reveals low PaO2 but usually normal PaCO2 unless very severe.
• CXR may be normal initially, with interstitial markings progressively increasing to complete or partial 'white out'.
• May be difficult to distinguish from cardiac failure. Cardiac diameter is usually normal in ARDS, and heart failure usually responds to diuretic therapy.

Treatment

The overall objective is to maintain respiratory function and cardiovascular stability while the underlying causes e.g. sepsis is treated. This should be carried out in ITU.

Most patients need mechanical ventilation with PEEP (positive end-expiratory pressure).

Fluid balance is complex; they need a CVP. Cardiac output can be measured with TOE (trans-oesophageal echo).

One of the treatment aims is to produce a negative fluid balance and thus help minimise accumulation of fluid in the lung and interstitial tissue. Loop diuretic infusions or continuous veno-venous haemofiltration can be used to achieve this.

In these patients, diuretics alone do not control pulmonary oedema but instead aggravate the hypovolaemia and shock associated with the underlying cause.

Renal failure is a common complication, sometimes prevented by early use of drugs such as dopamine.

Mortality rate for complicated ARDS approaches 90%.

Causes

Direct insults to the lung = ARDS Causes.

Systemic insults to the lung = STAN BEC DEAD.

Respiratory complications of surgery

Up to 15% of patients suffer from respiratory complications associated with general anaesthesia and major operations. The most common of these are atelectasis and pneumonia.

Pre-existing lung disease greatly increases the risk of complications. Severely ill patients, including those with acute pancreatitis, and burns or trauma victims, are susceptible to the development or ARDS.

Effects of anaesthesia and surgery on respiratory function
Anaesthesia and surgery predispose to postoperative complications by altering lung function and compromising normal defence mechanisms as follows:

• Lung tidal volume may be reduced by as much as 50%, depending on the incision site. Thoracic, upper abdominal and lower abdominal incisions (in decreasing order of effect) reduce lung volume.
  
  
• Lung expansion is reduced by the supine posture during and after operation, pain, abdominal distension, abdominal constriction by bandages and the effects of sedative drugs.
  
  
• Ventilation rate usually increases and there is loss of normal periodic hyperinflation.
  
  
• Diminished ventilation and pulmonary perfusion result in reduced gaseous exchange.
  
  
• Airway defences are compromised by loss of the cough reflex and diminished ciliary activity, which both lead to accumulation of secretions.
  
  
• Problems associated with laparoscopic abdominal surgery - the pneumoperitoneum and head-down position lead to diaphragmatic splinting, a reduction in functional residual capacity and changes in intrathoracic blood volume. These lead to atelectasis, pulmonary shunting and hypoxaemia.

Atelectasis

Atelectasis or alveolar collapse occurs when airways become obstructed and air is absorbed from the air spaces distal to the obstruction.

Bronchial secretions are the main cause of this obstruction. Predisposing factors include shallow ventilation, loss of periodic hyperinflation, inhibition of coughing and pooling of mucus. All of these are particular problems after thoracic or abdominal surgery.

The resulting V/Q mismatch produces a degree of R to L shunting of the blood and tends to cause a fall in PaO2.

If the obstructed airways are small, there is only minor segmental collapse, in which case localising signs are minimal and x-ray appearance is unremarkable. Despite this, the overall extent of collapse may be large and cause significant hypoxia.

Obstruction of a major airway causes collapse and consolidation of a whole lobe, resulting in the typical clinical signs of dullness to percussion and reduced breath sounds or bronchial breathing.

CXR will show the lobe to be contracted and opacified with mediastinal shift and compensatory expansion of other lobes.

Most cases of atelectasis are relatively mild and pass undiagnosed, although the patient may be slow to recover from operation.

The patient may be cyanosed, resulting from mild hypoxaemia, and have a mild tachypnoea, tachycardia and low-grade pyrexia, which all resolve spontaneously within a few days. Sputum culture (if any is produced) is usually negative but infection may complicate severe cases.

Prevention and Rx:

1. Preop and postop physiotherapy. This includes deep breathing exercises, regular adjustments of posture and vigorous coughing. During physiotherapt, wounds should be supported by the patient's hand.
2. Analgesia, e.g. infiltration of the wound with local anaesthetic or epidural analgesia, facilitates physiotherapy and mobility.
3. Nebulised bronchodilators e.g. salbutamol may assist the patient to cough up secretions.
4. Severe cases of diffuse atelectasis may require endotracheal intubation and positive-pressure ventilation.
5. Lobar or whole lung collapse requires intensive physiotherapy and sometimes flexible bronchoscopy to aspirate occluding mucus plugs.

Pneumonia

Bronchopneumonia is the usual form of chest infection seen in surgical patients. It occurs secondarily to chronic lung disease, chronic smoking or following atelectasis or aspiration of gastric contents.

Haemophilus and Strep. pyogenes are the common infecting organisms but coliforms may be responsible in elderly, debilitated or seriously ill patients.

Pseudomonas bronchopneumonia occurs in patients on ventilators or with bronchiectasis.

Infection is manifest by pyrexia, tachypnoea, tachycardia, increased leucocyte count.

Mucopurulent sputum is thick, copious and green.

Antibiotics, usually amoxicillin or co-trimoxazole, are given on a best-guess basis until sputum culture and sensitivities are available.

Physiotherapy and encouragement to cough are equally important for recovery.

Incomplete - Missing aspiration pneumonitis, aspiration pneumonia, ARDS. INfo from Burkitt pg 177.

Thyroid adenoma

from http://www.fpnotebook.com/Endo/Hemeonc/ThyrdAdnm.htm.

1. Simple or colloid Macrofollicular Adenoma

• Most common type
• Follicles of normal size

2. Embryonal (Trabecular) adenoma

• Mostly stroma and minimal follicles

3. Fetal Microfollicular Adenoma

• Small follicles with minimal colloid
• Follicular cancer found in 5% of cases

4. Hurthle Cell Adenoma (uncommon)