Essential Pathology Topics: Systemic Diseases & Neoplasms

Atherosclerosis: Pathogenesis & Complications

A chronic inflammatory disease of medium and large arteries, caused by endothelial injury and lipid accumulation.

Key Risk Factors:

• Hypertension
• Hyperlipidemia
• Smoking
• Diabetes

Lesions evolve from fatty streaks → fibrous plaques → complicated plaques.

Common Complications:

• Myocardial Infarction (MI)
• Stroke
• Aneurysm
• Peripheral Artery Disease

Histologically, it shows lipid cores, calcification, and fibrous caps.

Hypertensive Disease: Organ Damage & Malignant Forms

Chronic blood pressure (BP) elevation causes vascular and organ damage.

Consequences Include:

• Arteriolosclerosis
• Left Ventricular (LV) hypertrophy
• Stroke
• Chronic Kidney Disease

Malignant hypertension (diastolic BP >120 mmHg) causes fibrinoid necrosis and acute organ failure. Retina shows papilledema; kidneys show a “flea-bitten” surface in malignant cases.

Non-Rheumatic Endocarditis: Types & Risks

This category includes infective endocarditis (IE) (bacterial, acute/subacute) and non-bacterial thrombotic endocarditis (NBTE).

Infective Endocarditis:

• Acute IE: Rapid, destructive, usually caused by Staphylococcus aureus.
• Subacute IE: Slower progression, often caused by Streptococcus viridans.

NBTE is seen in conditions like Systemic Lupus Erythematosus (SLE) (Libman-Sacks endocarditis) and cancer. Vegetations pose a significant risk for embolism, valve destruction, and sepsis.

Myocarditis, Metabolic Heart Diseases & Pericarditis

Myocarditis:

Inflammation of the myocardium, often viral (e.g., Coxsackievirus), but can also be autoimmune or drug-related. Features include interstitial inflammation, myocyte necrosis, arrhythmias, and heart failure.

Metabolic Heart Diseases:

Examples include thyrotoxic heart disease, characterized by tachycardia and hypertrophy.

Pericarditis:

Inflammation of the pericardium, which can be:

• Acute: Fibrinous, serous, or purulent.
• Chronic: Constrictive or adhesive, potentially leading to tamponade or heart failure.

Cardiomyopathies & Congenital Heart Defects

Cardiomyopathies:

Primary myocardial disorders affecting heart muscle function:

• Dilated Cardiomyopathy: Most common type, characterized by systolic dysfunction.
• Hypertrophic Cardiomyopathy: Involves diastolic dysfunction, often genetic.
• Restrictive Cardiomyopathy: Features stiff myocardium and impaired filling.

Congenital Heart Diseases:

Include septal defects (e.g., Atrial Septal Defect (ASD), Ventricular Septal Defect (VSD)), Tetralogy of Fallot, and transpositions of the great arteries. Heart failure is the end stage of many cardiac conditions, classified as left-sided/right-sided or systolic/diastolic, and presents with hypertrophy, dilation, and congestion.

Vasculitis Syndromes & Aneurysms

Vasculitis:

Inflammation of vessel walls, classified by vessel size:

• Large Vessel Vasculitis: Giant cell arteritis, Takayasu arteritis.
• Medium Vessel Vasculitis: Polyarteritis nodosa, Kawasaki disease.
• Small Vessel Vasculitis: Wegener’s granulomatosis (GPA), Microscopic polyangiitis.

Aneurysms:

Abnormal dilations of blood vessels.

• True Aneurysm: Involves all layers of the vessel wall.
• False Aneurysm: A breach in the vessel wall, with blood contained by surrounding tissue.

Causes include atherosclerosis, infections, and trauma. Phlebothrombosis refers to venous thrombosis without inflammation, while thrombophlebitis involves inflammation.

Pulmonary Infections: Bronchitis & Pneumonias

Bronchitis:

Acute or chronic inflammation of the bronchi, often caused by viral or bacterial agents.

Pneumonias:

Infection of the lung parenchyma.

• Lobar Pneumonia: Uniform involvement of a lung lobe, progressing through four stages: congestion, red hepatization, grey hepatization, and resolution.
• Bronchopneumonia: Patchy involvement affecting multiple lobes.

Potential Complications:

Abscess formation, empyema, bacteremia, and fibrosis.

Lung Tumors: Carcinoma & Mesothelioma

Primary Lung Carcinoma:

The leading cause of cancer-related deaths.

• Types: Adenocarcinoma (peripheral, most common), Squamous cell carcinoma (central), Small cell carcinoma (aggressive, neuroendocrine), and Large cell carcinoma.

Mesothelioma:

A malignant tumor strongly linked to asbestos exposure, with a poor prognosis. Molecular markers (e.g., EGFR, ALK) often guide targeted therapy. Lung cancers frequently metastasize to the brain, liver, and bone.

Common Symptoms:

Cough, hemoptysis, weight loss, and pleural effusion.

Oral Cavity & Salivary Gland Pathology

Stomatitis:

Inflammation of the oral mucosa, which can be infectious, autoimmune, or trauma-induced.

Sialadenitis:

Inflammation of salivary glands, often due to mumps or ductal obstruction.

Tumors:

• Benign Salivary Gland Tumors: Pleomorphic adenoma (most common), Warthin tumor.
• Malignant Salivary Gland Tumors: Mucoepidermoid carcinoma, Adenoid cystic carcinoma.

Clinical Features:

May include a mass, pain, dry mouth, or facial nerve involvement.

Esophageal Disorders: Reflux, Barrett's & Cancers

Common Esophageal Conditions:

• Achalasia: Failure of the lower esophageal sphincter (LES) to relax.
• Hiatal Hernia
• Diverticula: Such as Zenker’s and traction diverticula.
• Reflux Esophagitis (GERD): Mucosal damage caused by acid reflux.

Barrett’s esophagus is a premalignant condition involving metaplasia (squamous epithelium transforming to columnar).

Esophageal Malignancies:

• Squamous Cell Carcinoma: Typically in the upper/mid esophagus, linked to smoking and alcohol.
• Adenocarcinoma: Usually in the lower third, often arising from Barrett’s esophagus.

Gastritis & Peptic Ulcer Disease: Causes & Complications

Acute Gastritis:

Transient mucosal inflammation, often triggered by NSAIDs, alcohol, or stress.

Chronic Gastritis:

Usually caused by H. pylori infection or autoimmune factors, leading to mucosal atrophy, intestinal metaplasia, and dysplasia.

Peptic Ulcers:

Occur in the stomach and duodenum, predominantly due to H. pylori or NSAID use.

Complications:

Bleeding, perforation, and obstruction. Histologically, ulcers show necrotic debris, inflammation, granulation tissue, and fibrosis.

Stomach Tumors: Benign & Malignant Gastric Carcinoma

Benign Gastric Tumors:

Include non-neoplastic (e.g., hyperplastic polyps) and neoplastic (e.g., adenomas) types.

Gastric Carcinoma:

A common and often deadly malignancy.

• Types: Intestinal type (gland-forming, generally better prognosis) and Diffuse type (signet-ring cells, linitis plastica).

Risk Factors:

H. pylori infection, nitrosamines, smoking, and chronic gastritis.

Spread:

Commonly to the liver, Virchow’s node, and Krukenberg tumors (ovaries). Early stages are often asymptomatic.

Inflammatory Bowel Disease: Crohn's & Ulcerative Colitis

IBD encompasses Crohn’s disease and Ulcerative colitis, both chronic, relapsing inflammatory disorders of the gastrointestinal (GI) tract.

Crohn’s Disease:

Characterized by transmural inflammation, skip lesions, and granulomas; can affect any segment of the GI tract, especially the terminal ileum.

Ulcerative Colitis:

Limited to the colon, with continuous inflammation starting from the rectum, affecting only the mucosa and submucosa.

Complications:

Fistulas (Crohn’s), toxic megacolon (UC), and an increased risk of dysplasia progressing to carcinoma.

Intestinal Tumors: Adenomas, Colorectal Carcinoma & GISTs

Benign Intestinal Tumors:

Mainly adenomas (tubular, villous, tubulovillous), which are precancerous lesions.

Malignant Intestinal Tumors:

Colorectal carcinoma often develops from the adenoma-carcinoma sequence, commonly found in the sigmoid colon and rectum.

Risk Factors for Colorectal Carcinoma:

Diet, Inflammatory Bowel Disease (IBD), and familial syndromes (e.g., Familial Adenomatous Polyposis (FAP), Lynch syndrome).

Gastrointestinal Stromal Tumors (GISTs):

Rare tumors arising from interstitial cells of Cajal, frequently found in the stomach or intestine; they typically express c-KIT (CD117).

Cirrhosis: Alcoholic & Post-Necrotic Forms

Alcoholic Liver Disease:

Progresses from steatosis → alcoholic hepatitis → cirrhosis. Features include hepatocyte ballooning, Mallory bodies, and perivenular fibrosis.

Post-Necrotic Cirrhosis:

Develops following massive hepatic necrosis, often due to viral hepatitis or toxins.

Both types of cirrhosis exhibit micronodular to macronodular changes, ultimately leading to portal hypertension, liver failure, and an increased risk of hepatocellular carcinoma.

Gallbladder & Biliary Tract Diseases

Cholelithiasis (Gallstones):

Composed of cholesterol or pigment stones.

Risk Factors:

Often summarized as "four F's": Female, Fat, Forty, Fertile.

Cholecystitis:

Inflammation of the gallbladder, usually caused by obstruction.

• Acute Cholecystitis: Sudden pain, fever, can lead to perforation.
• Chronic Cholecystitis: Recurrent attacks, wall thickening, and Rokitansky-Aschoff sinuses.

Biliary Tumors:

Mainly adenocarcinoma, which is aggressive and has a poor prognosis.

Pancreatitis & Pancreatic Tumors: Pathology

Acute Pancreatitis:

Caused by enzymatic autodigestion, often due to gallstones or alcohol; leads to fat necrosis and hemorrhage.

Chronic Pancreatitis:

Characterized by fibrosis, calcification, and exocrine insufficiency.

Pancreatic Tumors:

• Adenocarcinoma of the Pancreatic Head: A very aggressive malignancy, often presenting with painless jaundice and weight loss.

It carries a poor prognosis and frequently involves KRAS and p53 mutations.

Glomerular Diseases: Nephrotic & Nephritic Syndromes

Glomerular injury can manifest as either:

• Nephrotic Syndrome: Characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia.
• Nephritic Syndrome: Characterized by hematuria, hypertension, and oliguria.

Common Pathological Patterns:

Proliferation, basement membrane thickening, and sclerosis. These diseases can result from immune complex deposition, anti-glomerular basement membrane (anti-GBM) disease, or systemic illnesses (e.g., Systemic Lupus Erythematosus (SLE), diabetes).

Primary Glomerulonephritis: Specific Types

This section focuses on less common primary glomerular diseases:

• Membranoproliferative Glomerulonephritis (MPGN): Features a thickened basement membrane and a characteristic "tram-track" appearance.
• Focal Glomerulonephritis (FGN) and Focal Segmental Glomerulosclerosis (FSGS): Involve segmental sclerosis and are common in patients with HIV and heroin users.
• IgA Nephropathy (Berger's Disease): The most common primary glomerulonephritis worldwide, presenting with episodic hematuria.

Chronic Glomerulonephritis ultimately leads to end-stage renal disease.

Secondary Glomerular Diseases: Systemic Causes

Glomerular damage can occur secondary to various systemic diseases:

• Lupus Nephritis: Caused by immune complex deposits.
• Diabetic Nephropathy: Characterized by nodular glomerulosclerosis (Kimmelstiel-Wilson lesions).
• Amyloidosis: Involves Congo red positive deposits in the glomeruli.
• Myeloma Nephropathy: Due to light chain deposition.
• Hereditary Glomerular Diseases: E.g., Alport syndrome (a type IV collagen defect).

Tubular & Interstitial Kidney Disorders

Acute Tubular Necrosis (ATN):

The most common cause of acute renal failure, occurring as ischemic or toxic types.

Chronic Renal Failure:

Leads to uremia, anemia, and electrolyte disturbances.

Nephrosclerosis:

Results from long-standing hypertension.

• Benign Nephrosclerosis: Characterized by hyaline arteriolosclerosis.
• Malignant Nephrosclerosis: Features hyperplastic ("onion-skin") arteriolitis.

Tubular diseases also encompass toxic injuries, infections, and metabolic causes.

Cervical Lesions & Cancer: HPV, CIN & Carcinoma

This topic includes cervicitis, polyps, and Cervical Intraepithelial Neoplasia (CIN), which are dysplastic changes graded I–III. CIN is primarily caused by high-risk Human Papillomavirus (HPV) types (16, 18). Carcinoma in situ may progress to invasive cervical cancer, most commonly squamous cell carcinoma. A Pap smear is critical for early detection. Spread can involve the parametrium, bladder, and rectum.

Gestational Trophoblastic Disease (GTD) Types

GTD is a group of tumors originating from placental trophoblasts:

• Complete Hydatidiform Mole: Characterized by a 46 XX (paternal origin) karyotype, no embryo, significantly elevated hCG levels, and a "snowstorm" appearance on ultrasound.
• Partial Hydatidiform Mole: Triploid, with some fetal parts present.
• Invasive Mole: Penetrates the uterine wall.
• Choriocarcinoma: A highly malignant tumor with hematogenous spread, responsive to chemotherapy.

Treatment involves curettage and monitoring of hCG levels.

Thrombocytopenia & Coagulation Disorders

Thrombocytopenia:

Low platelet count due to:

• Decreased production (e.g., aplastic anemia).
• Increased destruction (e.g., Immune Thrombocytopenic Purpura (ITP)).
• Sequestration (e.g., hypersplenism).

Platelet Function Disorders:

Can be congenital (e.g., Glanzmann thrombasthenia, Bernard-Soulier syndrome) or acquired (e.g., due to certain drugs).

Coagulation Disorders:

Include hemophilia A (Factor VIII deficiency), hemophilia B (Factor IX deficiency), liver disease, vitamin K deficiency, and Disseminated Intravascular Coagulation (DIC).

Laboratory Tests:

Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and bleeding time are used for diagnosis.

Leukemias: Acute & Chronic Forms

Leukemias are malignant proliferations of white blood cells, classified as acute (involving immature blasts) or chronic (involving more mature cells).

Acute Leukemias:

• Acute Lymphoblastic Leukemia (ALL): More common in children.
• Acute Myeloid Leukemia (AML): More common in adults.

Present with symptoms like anemia, infections, and bleeding.

Chronic Leukemias:

• Chronic Lymphocytic Leukemia (CLL): Typically affects the elderly.
• Chronic Myeloid Leukemia (CML): Affects middle-aged individuals, often associated with the Philadelphia chromosome t(9;22).

Bone marrow is hypercellular with blast infiltration. Treatment involves chemotherapy and targeted therapy.

Lymphadenitis: Acute & Chronic Inflammation

Lymphadenitis refers to the inflammation of lymph nodes.

Acute Lymphadenitis:

Caused by local infection, presenting as swollen, tender nodes.

Chronic Lymphadenitis:

Can be granulomatous (e.g., in tuberculosis, sarcoidosis) or involve follicular hyperplasia (reactive). Histologic types aid in differentiating infectious from neoplastic causes. It is important to distinguish lymphadenitis from lymphoma on biopsy.

Hodgkin Lymphoma: Characteristics & Subtypes

Hodgkin Lymphoma is characterized by the presence of distinctive Reed-Sternberg cells within a mixed inflammatory background.

Subtypes Include:

• Nodular sclerosis (most common)
• Mixed cellularity
• Lymphocyte-rich
• Lymphocyte-poor

It exhibits a bimodal age distribution. Spread is typically predictable, involving contiguous lymph node groups.

Symptoms:

Painless lymphadenopathy and "B symptoms" (fever, weight loss, night sweats). Generally has a good prognosis with chemotherapy and radiation.

Plasma Cell Disorders: Myeloma & Related Conditions

This category includes Multiple Myeloma, a malignant proliferation of plasma cells that produce monoclonal immunoglobulin (M protein).

Key Features of Multiple Myeloma (CRAB):

• Calcium elevation (hypercalcemia)
• Renal failure
• Anemia
• Bone lesions (lytic lesions)

Bence-Jones proteins are detectable in the urine. Other related conditions include Plasmacytoma, Waldenström’s macroglobulinemia (characterized by IgM paraprotein), and less common, aggressive Peripheral T-cell/NK-cell neoplasms.

Pituitary Gland Disorders: Hyper/Hypopituitarism

Disorders of the Pituitary Gland Include:

• Hyperpituitarism: Usually caused by a pituitary adenoma (e.g., prolactinoma leading to galactorrhea and amenorrhea).
• Hypopituitarism: Can result from infarction (e.g., Sheehan’s syndrome), tumors, or trauma.

Pituitary Adenomas:

May be functional (producing hormones like GH, ACTH, TSH) or non-functional. Symptoms vary depending on the specific hormone excess or deficiency.

Thyroid Tumors: Benign & Malignant Types

Benign Thyroid Tumors:

Follicular adenoma is a common benign tumor, characterized by being encapsulated and non-invasive.

Malignant Thyroid Tumors:

• Papillary Carcinoma: Most common type, generally has a good prognosis, characterized by "orphan Annie eye" nuclei and psammoma bodies.
• Follicular Carcinoma: Tends to spread hematogenously.
• Medullary Carcinoma: Arises from C-cells, secretes calcitonin, and is associated with Multiple Endocrine Neoplasia type 2 (MEN2).
• Anaplastic Carcinoma: A highly aggressive tumor with a very poor prognosis.

Adrenal Gland Disorders: Hyper/Hypoadrenalism & Tumors

Hyperadrenalism:

• Cushing Syndrome (excess cortisol): Caused by an adrenal adenoma, carcinoma, or an ACTH-producing tumor.
• Conn Syndrome (excess aldosterone): Primary hyperaldosteronism leading to hypertension and hypokalemia.
• Adrenogenital Syndromes: Characterized by androgen excess.

Hypoadrenalism:

• Addison’s Disease: Often autoimmune or due to tuberculosis, resulting in weakness and hyperpigmentation.

Adrenal Tumors:

Include adrenal adenomas, carcinomas, and pheochromocytomas (which produce excess catecholamines, causing hypertension).

Endocrine Pancreas: Diabetes & Islet Cell Tumors

Diabetes Mellitus:

• Type 1 Diabetes: Autoimmune destruction of pancreatic β-cells, leading to insulin dependence.
• Type 2 Diabetes: Characterized by insulin resistance, strongly linked to obesity.

Chronic Complications of Diabetes:

Microangiopathy, nephropathy, neuropathy, and retinopathy.

Islet Cell Tumors (Neuroendocrine Tumors - NETs):

• Insulinoma: Causes hypoglycemia.
• Gastrinoma (Zollinger-Ellison Syndrome): Produces excess gastrin, leading to severe peptic ulcers.
• Other types include glucagonoma, somatostatinoma, and VIPoma.

Cerebrovascular Diseases: Hemorrhage & Ischemic Stroke

Cerebral Hemorrhage:

Rupture of blood vessels in the brain, often due to hypertension.

Cerebral Ischemia/Infarction:

• Global Ischemia: Due to systemic hypoperfusion (e.g., cardiac arrest).
• Focal/Regional Ischemia: Caused by thromboembolism, resulting in an ischemic stroke.

Infarcts can be pale (non-hemorrhagic) or red (hemorrhagic). Neurons are highly sensitive to ischemia, with the earliest changes ("red neurons") appearing within 12–24 hours.

CNS Infections: Meningitis, Encephalitis & Abscess

This category includes meningitis, encephalitis, and related lesions.

Meningitis Types:

• Bacterial Meningitis: Characterized by purulent exudate and neutrophilic infiltrate; common agents include Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae.
• Viral Meningitis: Involves a lymphocytic response and is typically self-limited.
• Tuberculous Meningitis: Granulomatous inflammation, often affecting the base of the brain.

Encephalitis:

Often viral (e.g., HSV, arboviruses), leading to cerebral edema and necrosis.

Other CNS Infections:

Include brain abscess, Progressive Multifocal Leukoencephalopathy (PML), Subacute Sclerosing Panencephalitis (SSPE), and prion diseases (e.g., Creutzfeldt-Jakob Disease (CJD) with spongiform degeneration).

Herpesvirus Infections: HSV, VZV & CMV Pathology

Common Herpesviruses:

• Herpes Simplex Virus (HSV-1/HSV-2): Causes cold sores and genital lesions; remains latent in sensory ganglia.
• Varicella-Zoster Virus (VZV): Causes chickenpox in children and reactivates as shingles (with a dermatomal distribution).
• Cytomegalovirus (CMV): Common in immunocompromised individuals, characterized by large cells with "owl’s eye" intranuclear inclusions.

All herpesviruses can cause severe disease in neonates or immunosuppressed patients (e.g., encephalitis, pneumonitis).

Dysenteries: Bacillary & Amoebic Forms

Bacillary Dysentery:

Caused by Shigella species, which invade the colon mucosa, leading to bloody diarrhea and ulceration.

Amoebic Dysentery:

Caused by Entamoeba histolytica, forming characteristic flask-shaped ulcers in the colon and potentially leading to liver abscesses.

Both types present with abdominal pain, fever, and mucus/blood in the stool. Histology reveals mucosal ulceration and inflammation.

Primary Tuberculosis: Ghon Complex & Granulomas

Caused by Mycobacterium tuberculosis. Primary TB represents the first exposure, often asymptomatic, forming a Ghon complex (a lung lesion plus hilar lymph node involvement).

Histological Features:

Caseating granulomas and Langhans giant cells. Primary TB may resolve, progress to progressive primary TB, or become latent. Diagnosis involves Ziehl-Neelsen stain, culture, and PCR.

Secondary Tuberculosis: Reactivation & Miliary TB

Secondary TB is the reactivation of latent tuberculosis, typically occurring in the apical regions of the lungs. It elicits a more intense immune response, leading to cavitary lesions and fibrosis. The infection may spread locally or systemically, resulting in miliary TB.

Extrapulmonary Involvement:

Can affect kidneys, spine (Pott disease), and meninges.

Symptoms:

Cough, weight loss, night sweats, and hemoptysis. Histology is similar to primary TB but with more extensive necrosis.

Vector-Borne Infections: Malaria & Lyme Disease

Malaria:

Caused by Plasmodium spp., transmitted via the Anopheles mosquito. Red blood cell lysis leads to cyclical fever, anemia, and splenomegaly. Severe forms, particularly with P. falciparum, can cause cerebral malaria.

Lyme Disease:

Caused by Borrelia burgdorferi, transmitted by tick bites. Progresses through stages: erythema migrans (target-like rash) → neurologic/cardiac signs → chronic arthritis.

Diagnosis:

Blood smear for malaria, serology for Lyme disease.