Histology

Atherosclerosis Atherosclerosis

Definition: A specific type of arteriosclerosis characterized by the formation of plaques (atheromas) within the arterial wall, leading to thickening and hardening. The fibrolipid plaque, called atheroma, can protrude into the vessel, obstruct it, and weaken the media layer.

Artery Wall Layers

Intima Layer: Inner layer, in contact with blood, made of endothelium

Media Layer: Middle layer, variable thickness, composed of muscle fibers, separated from intima by internal elastic lamina

Adventitia Layer: External part, connective tissue, contains vasa vasorum, separated from media by external elastic lamina.

Atherosclerosis Pathogenesis

Starts with endothelial damage, which increases permeability in the intima. This allows lipids (e.g., LDL) to deposit, recruiting macrophages and stimulating smooth muscle cell migration and proliferation from the media to the intima. This leads to the formation of a necrotic inner core (from cell death) surrounded by inflammatory cells and a thin endothelium (fibrous cap).

Atheroma Components

Cellular part: Smooth muscle cells, macrophages, and leukocytes. Extracellular matrix: Collagen, elastic fibers (can be destroyed), proteoglycans

Atherosclerosis Clinical Manifestations

Ischemic Syndromes resulting from obstruction or plaque rupture: Heart: Myocardial infarction, chronic ischemic heart disease, sudden cardiac death (from coronary arteries).
Brain: Cerebral infarction, ischemic encephalopathy (from cerebral arteries).
Limbs: Claudicatio intermittens, gangrene (from iliac or popliteal arteries). Intestine: Intestinal infarcts (from mesenteric arteries).
Aorta: Aneurysms.

Fatty Streaks

Early atherosclerotic lesions, typically asymptomatic if not protruding into the lumen. They can form in the first decade of life and represent initial lipid deposition on the endothelium, especially near turbulent blood flow areas like main branch origins.

Atherosclerotic Complications

Rupture (intraplaque or extraplaque) leading to sudden hemorrhage or thrombus formation and subsequent embolism

Stenosis

(obstruction of >65% of lumen) causing insufficient blood flow and ischemic consequences

Aneurysm

Definition: A localized, abnormal, blood-filled balloon-like bulge in the wall of a blood vessel or the heart, due to weakening of the wall. It is a permanent expansion.

True vs. False Aneurysm

True Aneurysm: Involves the thinning or alteration of the entire vessel wall. False (Pseudo-aneurysm) / Dissection Aneurysm: Consists of a fissuring of the intima with leakage of blood into the vessel wall (blood flows through the media layer).

Aneurysm Causes

Atherosclerosis (main cause of abdominal aortic aneurysms), trauma, Infection (mycotic aneurysms, e.g., 3rd stage syphilis affecting vasa vasorum), Systemic diseases (e.g., Marfan syndrome, Ehlers-Danlos syndrome, vasculitis), hypertension

Aneurysm Morphology Classification

Saccular: Involve a segment of vessel circumference, 5-20 cm, often thrombosed. Fusiform: Largest aneurysms (up to 20 cm diameter), progressive gradual expansion of entire circumference. Berry (Sacciform): Small, roundish dilatations, usually in Willis polygon, about 1 cm, typically cerebral.

Aneurysm Risk of Rupture

Directly correlated with diameter: < 4 cm: 0% risk, 4-5 cm: 1% per year. 5-6 cm: 11% per year. 6cm: 25% per year. Average increase: 0.2-0.3 cm per year. Rupture can lead to hemorrhage (retroperitoneal, abdominal, sub-arachnoid).

Syphilitic (Luetic) Aneurysms

Affect individuals with 3rd stage syphilis. Caused by inflammation of vasa vasorum due to Treponema pallidum, leading to impaired blood flow and weakening of the media tunic (ischemic phenomena). Often affects the first portion of the aorta (ascending aorta and arch). Can cause dilatation of the aortic valve leading to insufficiency and compression of mediastinal structures (lungs, esophagus, recurrent laryngeal nerve).

Aortic Dissection

Definition: Blood splits the laminar planes of the media to form a blood-filled channel within the aortic wall. It is a very serious and dangerous pathology. Caused by a first tear in the intima layer, allowing blood to delaminate the media tunica.

Aortic Dissection Causes

Hypertension (major risk factor, especially in 40-60 y/o), Connective tissue disorders (e.g., Marfan syndrome, often in younger people 20-30 y/o), Iatrogenic (e.g., catheterization), Pregnancy (due to weakness of media layer and hypertension).

Aortic Dissection Morphology

Cystic medial degeneration (loss of elastic fibers, mucoid material deposition). Small rupture (1-5 cm) at intima, usually within 10 cm of aortic valve, transversal or oblique with sharp margins. Can extend proximally and distally.

Aortic Dissection Classification

Stanford Type A: Involves ascending aorta.
Stanford Type B: Localized after epi-aortic vessel origin (thoracic to abdominal aorta). DeBakey Classification: Type I (ascending + descending), Type II (ascending only), Type III (descending only).

Aortic Dissection Clinical Course

Retrosternal lancinating pain (can simulate MI). Rupture can lead to cardiac tamponade (hemorrhage into pericardial cavity), sudden death. Other hemorrhages: pleural cavity (thoracic), retroperitoneal (abdominal). Can cause ischemic lesions if cerebral or coronary vessels are affected. Death rate: 30-40%.

Heart Failure Heart Failure (as a consequence)

A condition where the heart cannot pump enough blood to meet the body's needs. It is described as a consequence of other primary conditions, rather than a standalone primary disease definition in the sources.

Heart Failure - Ischemic Heart Disease

Chronic ischemic heart disease often manifests insidiously with progressive heart failure due to cumulative ischemic damage. Myocardial infarction can lead to left ventricular failure or cardiogenic shock, severe cases having high mortality.

Heart Failure - Valvular Disease

Calcific aortic stenosis can lead to congestive heart failure due to increased pressure in the left ventricle. Papillary muscle rupture during MI causes acute mitral insufficiency, leading to pulmonary edema and eventually right heart failure. Pulmonary hypertension (due to recurrent PE) can lead to chronic right heart failure.

Ischemic Heart Disease (IHD) Ischemic Heart Disease (IHD) Definition

A generic term for pathologies characterized by myocardial ischemia, an imbalance between blood supply to the heart and the oxygen requirement of the myocardium.

IHD Causes

In over 90% of cases, it is caused by a reduction of blood flow in the coronary arteries due to atherosclerotic plaques ("coronary heart disease"). Isolated hypoxemia rarely causes problems if perfusion is normal. Myocardial hypertrophy can exacerbate ischemia.

Coronary Flow

Relies on the pressure difference between diastolic aorta and coronary sinus. Affected by aortic valve insufficiency, shock, or massive hemorrhage.

IHD Clinical Forms

Angina Pectoris (transient ischemia)

Sudden Cardiac Death (unexpected, within 1 hr, often due to high-grade stenosis and arrhythmias)

Myocardial Infarction (MI) (necrosis of heart muscle due to prolonged ischemia)

Chronic Ischemic Heart Disease (progressive heart failure due to cumulative ischemic damage).

Angina Pectoris Types

Stable Angina: Predictable, relieved by rest/nitroglycerin, due to increased metabolic demands (stress, tachycardia). Prinzmetal's (Variant) Angina: Occurs at rest, due to coronary artery spasm, relieved by vasodilators. Unstable Angina: Increasing frequency/intensity, not relieved by rest/nitroglycerin, can precede MI.

Myocardial Infarction (MI)

Definition: Necrosis of heart muscle due to prolonged ischemia. About 1.5 million people/year in the USA have an MI, 1/3 die. Irreversible cellular damage occurs after 20 minutes of ischemia.

MI Classification/Patterns

Transmural: Necrosis involves the full thickness of the ventricular wall (endocardium to epicardium), usually caused by thrombosis on atherosclerotic plaque. Subendocardial (Nontransmural): Limited to the inner 1/3 or 1/2 of the myocardium, the most at-risk zone. Can be caused by rapid lysis of a thrombus or severe hypotension.

MI Clinical Diagnosis

Symptoms: Sudden retrosternal pain (may irradiate to left arm/shoulder), nausea, vomiting, sweating, burning sensation, epigastric pain (10-15% asymptomatic). Lab Data: Increased cardiac troponins (I and T), increased Creatine Kinase (CK-MB). Instrumental: ECG, Echocardiography, Cardiac Scintigraphy.

MI Early Complications

Arrhythmias (most common cause of sudden death after MI), Left ventricular failure (can lead to cardiogenic shock), Systemic embolization from mural thrombosis, Pericarditis (epistenocardial, fibrinous/fibrino-hemorrhagic, after transmural infarct), Myocardial rupture (ventricular wall, ventricular septum, or papillary muscle).

MI Late Complications

Ventricular aneurysms: Follow extensive transmural infarcts, involving all 3 layers of the ventricular wall. Can lead to overlapping wall thrombosis and embolization. Dressler syndrome: Immunological reaction (autoimmune pleuropericarditis) after transmural infarction. Neurodystrophic syndromes.

Valvular Heart Disease Valve Anatomy

Atrioventricular valves: Mitral (2 leaflets), Tricuspid (3 leaflets) with chordae tendineae and papillary muscles
Semilunar valves: Aortic, Pulmonary (3 leaflets). Layers: Fibrous zone, Spongy zone, Elastic/Ventricular zone, all covered by endothelium.

Valvular Pathophysiology

Stenosis: Inability of the valve to open fully, preventing normal blood flow. Insufficiency/Regurgitation: Inability of the valve to close fully, favoring retrograde blood flow. Can be pure (only stenosis/insufficiency) or mixed, isolated or combined. Functional reflux can occur due to excessive ventricular dilatation.

Valvular Disease Clinical Manifestations

Murmurs on auscultation. Severity depends on valve involved, etiology, degree, time of appearance, and compensating mechanisms. Acquired causes are more frequent than congenital, often involving mitral and/or aortic valves (left side).

Calcific Aortic Stenosis

Most common cause of aortic stenosis. Occurs in older adults (senile) or younger individuals with congenital bicuspid aortic valves. Small calcified masses on valve cusps, especially at the base, leading to rigidity and preventing full opening. Leads to concentric hypertrophy of the left ventricle, angina pectoris, syncope, and congestive heart failure.

Rheumatic Heart Disease (RHD)

Results from Acute Rheumatic Fever (ARF), an immune-mediated disease following group A streptococcal pharyngitis. ARF causes pancarditis (endocarditis, myocarditis, pericarditis) and is pathologically characterized by Aschoff bodies (pathognomonic myocardial lesions). Chronic RHD is the long-term consequence, leading to permanent valve deformities, especially mitral "fish mouth" stenosis, due to thickening, commissural fusion, chordae tendineae shortening/fusion, and diffuse fibrosis.

Infective Endocarditis (IE)

Infection of the endocardium, typically involving heart valves. Characterized by vegetations: friable, bulky masses of fibrin, platelets, microbes. Can be Acute (aggressive, S. aureus, healthy hearts) or Subacute (less virulent, Strep. viridans, already damaged valves). Complications: leaflet perforations, tendon cord rupture, septic embolizations.

Non-Infective Endocarditis

Nonbacterial Thrombotic Endocarditis (NBTE): Sterile vegetations on normal valves, associated with hypercoagulable states, often in debilitated/malignancy patients. Can embolize. Libman-Sacks Endocarditis: Sterile vegetations in Systemic Lupus Erythematosus (SLE), usually on undersurfaces of atrioventricular valves, cords, or mural endocardium. Warty appearance. Carcinoid Heart Disease: Due to bioactive compounds from carcinoid tumors, affects right heart valves if hepatic metastasis present, causing intimal plaque-like thickenings.

Prosthetic Heart Valves

Can be Mechanical (e.g., Bjork-Shiley, Carbomedics) or Bioprosthetic (xenografts from animals or homografts/autographs from humans). Complications: Thromboembolism (typical of mechanical, requires anticoagulation), Infective Endocarditis (more frequent for biological, with abscess formation), Structural degeneration (common for biological), Dehiscence, Hemolytic anemia, Mechanical flow obstructions.

Congenital Heart Disease Congenital Heart Disease (Limited Information)

The sources provide limited detailed information on congenital heart diseases as primary conditions. They are mentioned as: Causes of aneurysms (e.g., berry aneurysms in Willis polygon). Rarely a cause of ischemic problems if perfusion is normal. Possible cause of sudden cardiac death. Bicuspid aortic valves are a congenital malformation prone to calcific stenosis. Tetralogy of Fallot is noted as a combination of valvular and other cardiac malformations.

Embolism and Pulmonary Infarction Thrombosis

Definition: Formation of a solid mass of blood constituents within the vascular system (arteries, veins, heart chambers).

Virchow's Triad

Three factors predisposing to thrombus formation:
1. Endothelial Damage (most important, can cause thrombosis alone, e.g., MI, atherosclerosis, vasculitis, heart valves)
2. Alterations of Normal Blood Flow (stasis or turbulence, e.g., aneurysms, MI, valve stenosis, hyperviscosity syndromes)
3. Hypercoagulability States (primary/genetic or secondary/acquired, e.g., DIC, lupus anticoagulant).

Fates of a Thrombus

Resolution (fibrinolysis), Detachment (embolism), Increase in length, Organization and recanalization.

Embolism

Definition: Passage of an abnormal mass (solid, liquid, gas) through the bloodstream, blocking a vessel.

Types of Emboli

Thromboembolism (most common), fat embolism, air embolism, amniotic fluid, tumor cell, foreign body

Pulmonary Embolism (PE)

Origin: 95% originates from deep venous thrombosis (DVT) in lower extremities (popliteal, femoral, iliac veins). Can be multiple. Consequences: Can lead to hemorrhagic infarction (red-dark, wedge-shaped) or just local ischemia depending on size and collateral circulation. Massive PE with "saddle" embolus can cause sudden death from acute right ventricular failure. Recurrent PE can lead to pulmonary hypertension and chronic right heart failure. Symptoms include stabbing pain, dyspnea, hemoptysis, fever, cough.

Systemic Embolism

Origin: From the left heart (MI, atrial fibrillation, IE, prosthetic valves) or aortic aneurysms. Affects: Lower extremities (75%), brain (10%), intestines, kidneys, spleen. Leads to infarction in the target organ.

Fatty Embolism

Origin: From long bone fractures or soft tissue trauma, usually in older patients with osteoporosis or large burns. Symptoms: Respiratory distress, neurological symptoms, petechial rash. Caused by mechanical obstruction and chemical damage from fatty acids.

Amniotic Fluid Embolism

Condition: Affects women immediately post-partum or in first days after delivery. Very rare but dangerous (86% mortality). Cause: Infusion of amniotic fluid and its components (fetal epithelial scales, hair, vernix caseosa, bile) into maternal circulation due to placental membrane tears or uterine vein rupture. Oxytocin from uterus can cause vasoconstriction, adding to obstruction.

Gaseous Embolism

Cause: Bubbles of air or gas blocking blood flow. Can occur during childbirth/abortions, IV injections, pneumothorax (torn vessel), chest wall injury. Decompression sickness (Caisson disease): Typical of divers/deep-sea divers due to sudden changes in atmospheric pressure, causing gas (helium, nitrogen) to form bubbles in circulation. Forms: Acute (breathing difficulties, coma/death), Chronic (multiple foci of ischemic necrosis, especially skeletal system).

Lung Tumors Lung Cancer (Bronchogenic Carcinoma)

Definition: Malignant tumors arising from lung tissue. Most common cause of cancer deaths globally.

Lung Cancer Etiology

Tobacco (major risk factor, 10-60x greater risk, contains ~1000 carcinogens, passive smoking also a risk), Industrial Exposure, air pollution, genetic factors.

Lung Cancer Histological Types

• Non-Small Cell Lung Carcinomas (NSCLC) (80%): Adenocarcinoma (most common, peripheral, slower growth, better prognosis, associated with EGFR, KRAS, ALK mutations, acinar/papillary/micropapillary/lepidic patterns),

• Squamous Cell Carcinoma (strongest association with smoking, central, can cause cavitation)

• Large Cell Carcinoma (undifferentiated, diagnosis by exclusion, aggressive, fast growth, often metastatic)

• Small Cell Lung Carcinoma (SCLC) (15%): Strongly associated with smoking, central, highly aggressive, early metastasis, often paraneoplastic syndromes, neuroendocrine differentiation. Combined carcinomas (10%).

Lung Cancer Precursor Lesions

For Squamous Cell Carcinoma: Squamous metaplasia then squamous dysplasia (to carcinoma in situ). For Adenocarcinoma: Atypical adenomatous hyperplasia. For neuroendocrine tumors: Diffuse idiopathic neuroendocrine cells hyperplasia.

Lung Cancer Diagnosis

Imaging (CT scan, PET), Biopsy (Bronchoscopy with bronchial biopsy, EBUS for nodes, transthoracic needle biopsy for peripheral lesions),
Cytology (Sputum, bronchial washing/brushing, FNA, pleural/pericardial effusion). Cell Block can convert aspirated cells into histological-like exams for IHC/molecular analysis.

Lung Cancer Staging (TNM)

T (Tumor): Size and local extension (pleural/mediastinal involvement), N (Nodes): Presence and localization of metastasis in local lymph nodes (localization, not number, is key for prognosis), M (Metastasis): Distant metastasis, including contralateral lung nodules. Staging guides prognosis and treatment.

Lung Cancer Molecular Alterations (Predictive Factors)

Primarily analyzed in Adenocarcinoma.

• KRAS mutation (25% of adenocarcinomas, mutually exclusive with others, G12C mutation being targeted)

• EGFR mutation (more frequent in non-smokers, women, Asian ethnicity)

• ALK rearrangement (target for tyrosine kinase inhibitors, detected by IHC then FISH confirmation)

• ROS1 rearrangement (less frequent, target for tyrosine kinase inhibitors).

Lung Cancer Immunotherapy Markers

PD-L1/PD-1 receptor expression: Tumors can produce PD-1 on neoplastic cells

Carcinoid Tumor (Lung)

Low-grade neuroendocrine tumor. Usually central, better prognosis than SCLC. Affects younger, non-smokers. Can be typical (low mitotic count, no necrosis) or atypical (higher mitotic count, necrosis). Clinical symptoms (cough, hemoptysis, breathing difficulties) and carcinoid syndrome (diarrhea, skin rash, cyanosis, carcinoid heart disease) due to neuroendocrine secretion.

Hamartoma (Lung)

Common benign lesion. Peripheral nodule in adult males. Contains cartilage, fat, and bronchial epithelium (tissues normally in lung but in different localization). Well-circumscribed with sharp borders.

Solitary Pulmonary Nodule (SPN)

Definition: Radiological term, "coin lesion", < 3 cm diameter, surrounded by normal lung parenchyma. Significance: Must be considered malignant until proven otherwise. Requires biopsy (transthoracic) for morphological and immunohistochemical analysis. Can correspond to malignant neoplasms or benign lesions (infective, congenital).

Colorectal Cancer Colon Normal Histology

Mucosa layer: Glandular epithelium (goblet cells), lamina propria, muscularis mucosae. Submucosa: Contains vascular and lymphatic vessels. Muscularis propria: Inner circular, external longitudinal (teniae coli). Serosa layer: Mesothelial cells, vessels, nerves.

Polyps (Colon)

Any lesion protruding into the lumen. Non-Neoplastic Polyps:

• Hyperplastic (common, usually <5mm, left colon, no malignant potential, star-shaped lumen),

• Inflammatory (pseudopolyps, due to chronic inflammation like IBD),

• Lymphoid,

• Hamartomatous (developmental anomalies, e.g., Peutz-Jeghers, juvenile polyps). Neoplastic Polyps (Adenomas): Tubular (most common, small, pedunculated)

• Villous (less common, larger, sessile, higher malignant potential)

• Tubulovillous (mixed).

Sessile Serrated Adenomas (SSA/SSP)

Successor lesions of microvesicular hyperplastic polyps. Characterized by crypt architectural alterations (inverted T/L-shaped bases, dilated crypts, serration extending to lower third). Absence of overt cytologic dysplasia. Associated with V600E BRAF mutation and high CpG island methylation (CIMP-H). Possess significant malignant potential, precursors of sporadic MSI-H CRCs. Dysplasia can arise within SSAs.

Adenoma-Carcinoma Sequence

Adenomas precede carcinoma. Risk of carcinoma is directly proportional to the number and size of adenomas and the presence of a villous component. Excision of adenomas reduces the incidence of carcinomas.

Familial Adenomatous Polyposis (FAP)

Caused by APC gene mutation (tumor suppressor). Characterized by at least 100 adenomas, developing at an early age. Leads to adenocarcinoma in 100% of cases by age 30. Prophylactic colectomy is common. Variants include Turcot syndrome and Gardner's syndrome.

Hereditary Non-Polyposis Colorectal Carcinoma Syndrome (Lynch, HNPCC)

Most frequent form of hereditary colorectal cancer (2-3%). Caused by germline mutation of MMR genes ("mismatch repair"), particularly MLH1 and MSH2. Leads to microsatellite instability. Often affects the right colon, multiple tumors (synchronous or metachronous), flat or serrated adenomas. Prognosis generally favorable.

Colorectal Cancer Clinical Features

Typically affects individuals aged 60-70. Symptoms vary by location: Left Colon: Alterations of bowel habits, obstruction (stenotic mass), massive bleeding. Right Colon: Occult bleeding (anemia), usually discovered later due to less obstructive symptoms. Other symptoms: weight loss, perforation/peritonitis/fistulas.

Colorectal Cancer Histology/Grading

Invasive carcinoma shows gland anastomoses, reduced mucosecretion, and loss of stroma between glands. Grading (G1, G2, G3) based on differentiation (ability to recognize architecture)

Colorectal Cancer Metastasis

Primarily spreads lymphatically to regional lymph nodes. Right colon cancers: More frequently metastasize through the vena porta to the liver. Left colon/rectum cancers: More frequently metastasize to pelvic nodes and through the inferior vena cava to the lung.

Colorectal Cancer Staging (TNM)

T (Tumor): Based on the deepness of infiltration into the colonic wall layers, not major dimension. N (Nodes): Based on the total number of nodes involved by metastasis

Breast Diseases Breast Normal Anatomy

6-10 main ducts ending in lobules (duct + acini). Ducts drain to nipple via galactophore ducts. Terminal Ductular-Lobular Unit (TDLU): Site of origin for most breast neoplasias (carcinoma, fibroadenoma, cysts). Ducts covered by single layer epithelium and external myoepithelial cells (contractile). Stroma is loose connective tissue. Male Breast: Primarily ductal structures, lacks acini and stroma.

Gynecomastia

Breast gland development in males, usually only ductal structures, due to hormonal imbalance.

Acute Non-Specific Mastitis

Inflammation during lactation, typically caused by S. Aureus or streptococci. Can lead to localized abscesses or diffuse infection. Severe cases can cause diffuse necrosis, fibrosis, and nipple/skin retraction, mimicking carcinoma.

Periductal Mastitis (Zuska's Disease) / Mammary Duct Ectasia

Inflammation of subareolar ducts, recurrent, common in smokers. Mammary Duct Ectasia (Plasma Cell Mastitis): Dilated ducts with chronic inflammation (often plasma cells), typically older women. Leads to nipple discharge, retraction, periareolar mass. Etiology unknown, possibly duct obstruction or hyperprolactinemia.

Fat Necrosis (Breast)

Caused by trauma or surgery. Can mimic carcinoma on palpation/imaging due to fibrotic changes and calcific deposits. Initially shows hemorrhage and colliquative necrosis, followed by acute inflammation, macrophages, foreign body giant cells, calcium crystals, and blood pigment.

Fibrocystic Changes (Non-Proliferative)

Most common breast alteration (over 50% of surgeries). Simple Fibrocystic Alteration: Multiple bilateral lesions, increased fibrous stroma, dilated ducts with cysts (macrocysts >3mm, microcysts, "blue dome cysts"). Palpable thickened, micronodular areas. Microcalcifications common. No increased risk of carcinoma. Adenosis: Increase in number of acini per lobule. Sclerosing Adenosis: Adenosis distorted by fibrous tissue, can mimic carcinoma. Slight increase in carcinoma risk (1.5-2x).

Proliferative Changes Without Atypia

Epithelial Hyperplasia: Increase in number of epithelial cell layers in ducts. Mild/moderate/florid forms have no or minimal increased risk. Intraductal Papilloma: Benign papillary growth within ducts, can cause bloody nipple discharge. Solitary papillomas are benign, multiple increase relapse/carcinoma risk. Radial Scar: Sclerosing ductal proliferation around a central fibro-elastic area, can mimic carcinoma clinically/radiologically. No association with carcinoma. Fibroadenoma: Most common benign tumor. Double component (glandular and stromal). Well-circumscribed, mobile nodule, common before age 30.

Atypical Hyperplasia (Proliferative Changes with Atypia)

Atypical Ductal Hyperplasia (ADH) or Atypical Lobular Hyperplasia (ALH): Proliferation of epithelial cells with some features of carcinoma in situ. Significant increase in risk for carcinoma (5 times up to 10)

Breast Cancer Risk Factors

Family history (mother, sister, aunt with BC, especially young age), BRCA1/BRCA2 gene mutations (can explain family cases, 3% of all BCs, early development), Prolonged exposure to endogenous estrogens (early menarche, late menopause, obesity, increased food lipids), Advanced age at first pregnancy

Breast Cancer Clinical Presentation

Typically non-palpable lesions discovered by mammography (micro-calcifications). Less frequently, a palpable mass. Sometimes associated with nipple discharge (especially bloody, though most discharge is benign).

Breast Cancer Classification

Based on cell types and architectural characteristics. Based on basal membrane infiltration: Invasive (infiltrate surrounding stroma) or Non-invasive (confined within ducts or lobules, e.g., Ductal Carcinoma In Situ (DCIS), Lobular Carcinoma In Situ (LCIS)).

Ductal Carcinoma In Situ (DCIS)

Non-invasive. Detected by mammographic micro-calcifications. Histologically shows ducts occupied by proliferating cells, often with a cribriform pattern. Can have central necrosis (comedocarcinoma-type).

Invasive Breast Carcinoma Histological Types

No Special Type (NST) / Ductal Invasive Carcinoma: Most common invasive type. Irregular borders, retraction, desmoplastic stroma (hard). Invasive Lobular Carcinoma: Cells invade in single rows, do not form masses, loss of E-cadherin adhesion molecule. Medullary Carcinoma: Solid nests with high atypia, heavy lymphocytic infiltrate, better response to chemotherapy. Mucinous Carcinoma: Polylobated borders, mucinous content, better prognosis. Tubular Carcinoma: Well-differentiated, can be difficult to distinguish from sclerosing adenosis. Paget Disease of the Nipple: Associated with in situ or invasive carcinoma, neoplastic cells in basal layer of nipple/areola epithelium, causing purulent/bloody discharge or erythematous lesion. Metaplastic Carcinoma: Aggressive, other neoplastic differentiations (squamous, sarcoma), tendency for vascular metastasis. Inflammatory Carcinoma: Neoplastic cells spread through skin lymphatic vessels, leading to "orange peel" skin appearance, advanced stage.

Breast Cancer Prognostic Factors

Histological type, Grading (Scarff-Bloom-Richardson, based on tubule formation, nuclear pleomorphism, mitotic count, angioinvasion, diameter, lymph node status, distant metastasism stage, cellular kinetics, expression of gene biomarkers

Breast Cancer Diagnostic Procedures

Self-examination, Mammography screening (most sensitive/specific, shows non-palpable masses and microcalcifications, radiolucent in older women allows better detection), Biopsy (ago-biopsy under mammography/ultrasound guide for tissue core), Ago aspiration (thinner needle for cells/cytology), Cytological smear (Papanicolaou or H&E stain, classified C1-C5). Biopsy/excision needed to confirm if in situ or invasive.

Breast Cancer Prognosis

Generally better prognosis with: < 2 cm tumor size without axillary metastases, low histological grade, DCIS/LCIS, no vascular invasion, hormone receptor positivity (ER, PgR), HER2 negativity (unless targeted therapy is given), low proliferative index (Ki-67). Prognosis is not completely predictable and depends on the combination of factors. Significant improvement in life quality with early diagnosis and personalized therapies.