Histopathology Final Exam Review

Liquefactive Necrosis

	Histological Findings	Questions	Case Scenario(s)
Normal Brain	Neuropil, glial cells, neuron cell bodies
Necrotic Brain	Portions of gyri are pale where brain substance has disappeared Many macrophages with granular material in cyto and hemosiderin Early response is PMNs, then macs dominate and liquefaction ensues	Source of hemosideri? RBC breakdown What will brain look like in a year? Reactive astrocytes give rise to scar tissue	Embolic occlusion of cerebral aa.

Adipose Tissue Necrosis

	Histological Findings	Questions	Case Scenario(s)
Normal Omentum	Largely adipose tissue (cyto look empty) Thin ct and single layer of mesothelium
Enzymatic necrosis	Adipose tissue has white, chalky flecks Lobules are occupied by light purple material, surrounded by a band of leukocytes Purple areas are necrotic cells—no nuclei In addition to halo of inflammatory cells, there is a layer of fibrin and PMNs on outer surface Thick layer of fibrinopurulent exudate	What is saponification? Pancreatic lipase à cleaves TG à yields FA à combine with Ca, Mg, etc. à saponification à fills cyto of dead cells	History of severe abominal pain prior to death
Ischemic fat necrosis	Coagulative
Traumatic fat necrosis	Very large spaces—puddles of cytoplasmic lipid from smashed adipocytes Macrophages at margins of puddles		Common in surgically resected specimens

Heart Changes

	Histological Findings	Questions	Case Scenario(s)
Normal Heart	Intercalated disks, branching Central nuclei, striations May have lipofuscin pigment
Coagulative necrosis	Broad areas of necrotic myocardium alternating with normal myocardium Irregular clusters of blue—aggregates of PMNs (eosinophilic), indicate leukocytic response instead of postmortem autolysis Nuclei are karyolitic Cell boundaries maintained in coagulative necrosis	Serum enzymes changes? Creatine kinase Long term? Scarring Congestive heart failure: myocarditis or cardiomyopathy; anemia; rhythm disturbances Results? Hypertrophy, hypoxia, forward failure (LV), backward failure (RV, LV)	Heart attack—ischemia, infarct
Myocardial Infarct	Abnormally mottled appearance with irregular pale patches (areas of liquefactive necrosis) Macs contain lipofuscin pigment Fibrinous pericarditis: clumps of fibrin on epicardial surface; sometimes accompanies myocardial infarct; would be manifested by friction rub	How to tell it’s LV? Thicker wall, trabeculae; epicardial surface smooth (with fat) Cause of ischemia? Coronary artery occlusion Consequences? Death (usu from arrythmia); loss of heart function; infarct may grow; wall is weak, may rupture (tamponade); scarring	History of ischemic heart disease

Kidney Changes

	Histological Findings	Questions	Case Scenario(s)
Normal Kidney	Many tubules fill field
Coagulative necrosis	Pale staining areas among deep staining parenchyma; anucleate cells Inflammatory reaction at border between normal and abnormal; blood infiltrates parenchyma	Cause? Embolic shower (multiple insult)—LH Result? White scars	Hematuria, proteinuria, flank pain; kidney still functions
Atheroemboli	Arterial branches contain cholesterol clefts within vessel lumen Foreign body reaction to cholesterol gives rise to granulation tissue which fills lumen; multinucleated giant cells Post mortem autolysis—no inflammatory reaction around dead cells	“Ordinary” atherosclerosis: plaque is part of wall Age? Chronic inflammatory reaction Source of emboli? Often abdominal aorta or coronary arteries Other manifestations of atheroembolism? Decreased urine flow, renal failure; extremities are common destination, or brain	Death after coronary artery bypass surgery

Liver Changes

	Histological Findings	Questions	Case Scenario(s)
Normal Liver	Granular cytoplasm Cells arranged in cords/strands with bile caniliculi in between Portal triads, central vv.
Steatosis	Paler than usual color A few dark foci Cytoplasmic vacuolization of hepatocytes— cells are loaded with lipid drops (pale, foamy) Dark foci are dead hepatocytes and PMNs Patches of hemorrhage may be evident	Why do vacuoles look empty? Fat dissolves in fixation What else may look empty? H20, glycogen How to differentiate? Frozen section or diff. stain Is steatosis reversible? Yes, it’s a form of cell injury	54 yo alcoholic with enlarged liver, paler than usual color with a few mottled foci scattered throughout
Hemochroma-tosis	Accumulation of hemosiderin in hepatocytes, bile duct epithelium, macs, and connective tissue Patches of regeneration Caused by excess iron absorption	Other situations for hemosiderin? Hemorrhage (pigment in macs) Other brown pigments? Bilirubin (RBC); lipofuscin (wear and tear); melanin (melanocytes) Cirrhotic livers: Scarring, nodules	Enlarged, firm liver with diabetes (“bronze diabetics” from hemosiderin)
Suppurative necrosis	Patches of light staining areas, edema Lots of PMNs—suppurative necrosis, abscess Granulation tissue surrounds necrotic area Fibrin clot in blood vessel with many leukocytes—evidence of organization at edges		Hepatic infection, eg. Typhoid fever or systemic strep
Changes related to cardiac failure	Pattern of alternating light and dark areas Lighter areas: around central vv; smaller hepatocytes, widened sinusoids; produced by chronic impairment of blood outflow Ischemic necrosis caused by low arterial perfusion (eg. with decreased LV output)—pyknosis and karyolysis visible	Central hemorrhagic necrosis: combination of poor perfusion and passive congestion, results in necrotic centrilobular areas stuffed with blood Noncardiac causes of same changes? Obstructed hepatic vv or vena cava	Patients with RH failure (2° to LH failure) RUQ pain, hepatojugular reflux, jaundice, incr hepatic enzymes

Lung Changes

	Histological Findings	Questions	Case Scenario(s)
CMV infection	Pale staining debris (many macs, some other leukocytes, RBC, exudate fluid) within alveolar spaces Some intra-alveolar hemorrhage Infected cells—very large with huge intranuclear inclusions (headlights)	Other tissues with CMV? Kidney, lung, GI, pancreas, etc. Who is susceptible to exposure? Everyone Cytopathic or oncogenic? Cytopathic	Immunocompromised, eg. HIV
Metastatic Calcification	Calcium deposits in tissue (basophilic) that range from crystalline to granular Deposits found in alveolar walls and walls of large vessels Also have cell debris in alveolar spaces	Metastatic Calcification: Abnormal Ca and PO4 in blood; form in viable tissue Dystrophic calcification: Local biochemical abnormality; form in dead tissue
Acute Purulent Broncho-pneumonia	Alveolar spaces filled with edema fluid—pink, acellular, from blood Many PMNs from blood as well	Cause? Bacterial; can resolve Chest xray? Opaque Complications? Death if untreated	Hospitalized in comatose state before death
Acute Passive Congestion and Edema	Air spaces filled with edema fluid—pink, homogenous to slightly granular material; low protein content, may have fibrin or air bubbles Congestion (vascular engorgement)—excessive RBC in alveolar septa, giving lung purple hue, some extravasated into air spaces from high hydrostatic pressure (hemorrhage by diapedesis) Foci of inflammation—PMNs (maybe suppuration), some organization	Clinical manifestations? Shortness of breath or labored breathing; moist rales on auscultation, abnormal chest xray Passive congestion: LV failure à congestion à increased hydrostatic pressure Active congestion: direct injury, inflammation	Death from sepsis Suppurative lesions suggest infection
Chronic Passive Congestion	Alveolar septa engorged with RBC, prominent hemorrhage by diapedesis Brown induration: MANY intra-alveolar clumps of hemosiderin in macs; macs may have just phagocytosed crud instead	Source of hemosiderin? Blood breakdown; found in areas of hemorrhage being mopped up, or in thrombi undergoing resolution/organization	Cardiac conditions involving LV—bad valve, ischemia/infarct
Pulmonary Arterial Embolus and Infarct	Gross appearance: very red, little/no air; sharply demarcated area of infarct at periphery (elevated and white) Ischemic/coagulative necrosis of alveoli—no nuclei, no caps, still have outline of walls; filled with blood in varying stages of disintegration Irregular leukocytic infiltration in and around infarct; zone of organization at margin Dense blood clots in pulmonary arterial branches with some organization Usually don’t infarct b/c dual blood supply (bronchial and pulmonary aa.)	Age? Organized embolus indicates chronic condition How to tell thrombus from embolus? Look same histologically, but grossly, caliber of embolus doesn’t always match vessel Rare to have primary thrombosis in lung Saddle embolus: occludes r and l pulmonary aa; instant death from acute R heart failure	Bedridden Trouble breathing

Granulomatous Inflammation

	Histological Findings	Questions	Case Scenario(s)
Normal Spleen	PALS around central artery White pulp, red pulp, sinusoids
Caseous Necrosis Spleen	Pale pink areas surrounded by light cellular halo (epithelioid cells) Pale areas are granular cell debris of disintegrating, necrotic cells May have multinucleated giant cells Infectious agents reached spleen via blood or by trauma	Granulomatous inflammatory reaction: Discrete nodular accumulations, well circumscribed, epithelioid cells, maybe multinucleate giants Usual fate? Remain for long time; stay as abscess or undergo dystrophic calcification	Systemic infection, eg. TB
Noncaseating, spleen	Multiple pink nodules, surrounded by blue halo of inflammatory cells Epithelioid cells and multinucleated giants, surrounded by lymphocytes	Other granuloma situations? Fungal, intracellular pathogen that can’t be digested	Immune sarcoidosis
Foreign body type	Clusters of foreign material surrounded by scar and many multinucleate giant cells	Does all foreign material evoke this reaction? Only if persistsent/indigestible	Suture

Other Inflammation/Healing

	Histological Findings	Questions	Case Scenario(s)
Cellulitis, foot	Diffuse cellular infiltrate, mostly deep (in adipose) Many PMNs—distorted nuclei, pale cyto	What distinguished cellulitis? Tons of diffusely distributed PMNs	Spreading infection
Appendicitis, acute	Mucosa missing or necrotic in diseased areas—it’s actually gangrenous in some places Dense inflammatory infiltrate, mostly PMNs	Suppurative= PMNs plus liquefactive necrosis Purulent=many PMNs Fibrinopurulent=PMNs plus fibrin Complications? Perforationàperitonitis, abscess	LRQ pain Treat with appendectomy
Pseudomem-branous Colitis	Some areas of mucosa have fibrinopurulent exudate (fibrin and PMNs) and superficial necrosis	Psudomembrane=patch of exudate adherent to damaged mucosa	Antibiotic treatment
Gout, bone and soft tissue	Irregular nodular deposits within bone and into soft tissue, surrounded by inflammatory infiltrate (macs and multinucleates)	What characterizes gout? Urate deposits Gross apprearance: pea green; crystals	Arthritis (in synovial fluid); tophi (tissues)
Organizing Fibrinupurulent Peritonitis, colon	Serosal surface has HUGE inflammatory reaction—very, very thickened by granulation tissue (capillary buds, young fibroblasts) Fibrinopurulent at peritoneal side	Age? At least a few days (granulation tissue) Fate of exudate? No resolution, but have scar form (organization), can lead to adhesions	Peptic ulcer that penetrated, soiling peritoneal cavity
Proud flesh, vagina	Overgrowth of granulation tissue at site of wound healing Proliferating vessels, young fibroblasts, edematous ground substance, prominent plasma cells, other leukocytes	Significance? Wound cannot heal unless it’s removed because epithelium can’t grow over it	Hysterectomy, red nodule at apex of vagina
Chronic Ulcer, skin and subcutis	Cutaneous surface interrupted by deep penetrating defect with layer of fibrinopurulent exudate on outer surface, underlying zone of maturing granulation tissue, and shell of dense fibrous tissue (mature scar) Chronic inflammation with advanced scarring and continued exudation	Age? It takes months for mature scar to form Sequence of events to heal? Must clear cause of fibrinopurulenceà reepithelializationà scar forms	Nonhealing scalp lesion
Scar, skin	Dermal appendages absent, dense connective tissue in place of dermis Epidermis has flattened rete pattern	Significance? Skin is much weaker in this area
Keloid	Nodule of overgrown scar tissue—mostly made of coarse, glassy collagen	Significance? Overdeposition of collagen	Complication of healing
Traumatic neuroma	Tangle of regenerating nerve fibers entrapped in dense collagen	Significance? May have pain, loss of nerve function	Complication of healing

Disturbances of Circulation

Varices, Esophagus	Varicose veins: markedly dilated veins throughout wall, esp in submucosa—engorged with blood, associated with hemorrhage Some contain thrombi, some of which have begun organization May have necrotic areas which resulted from pressure of device inflated within esophageal lumen to stop bleeding	Cause? Prolonged engorgement of veins, eg. portal hypertension (usu secondary to cirrhosis); collaterals between stomach and esophagus become engorged	Death from massive upper GI hemorrhage
Subdural Hematoma	Dura: dense fibrous membrane Beneath dura is capsule that formed around hematoma—compact and collagenous, contains inflammatory cells Below that is looser, less collagenous tissue—scattered RBC and hemosiderin-containing macs Process immediately adjacent to dura is oldest	Ultimate fate if survive? Large hematomas organize and form scar How is this different from a simple bruise? Small bruise is mopped up completely, no scar Other hemosiderin situations? Excess iron	Functional loss (acts like a tumor) Alcoholic—more chance of trauma
Organizing Venous Thrombi	Large veins distended with blood, held in distended state by thrombi Normal veins would appear collapsed in section	How to tell in vivo thrombus? Lines of Zahn Age? At least a few days if have organization Contributing factors? Immobile, poor circulation	Sudden death—pulmonary embolus

Neoplasia

	Histological Findings	Questions	Case Scenario(s)
Adenoma, Parathyroid gland	Circumscribed nodule of epithelial cells with patches of normal parathyroid tissue just outside Normal tissue: chief cells and oxyphils; marbled with adipose tissue Nodule: no adipose tissue; marked increase in cellularity; mostly oxyphils, very uniform appearance	How to differentiate from hyperplasia? This is a sharply circumscribed nodule; presence of normal cells; hyperplasia is more diffuse Benign? Uniformity, lack of pleomorphism, sharply circumscribed	Hypercalcemia, enlarged gland, high PTH
Adenoma, colon	Lesion is entirely mucosal Normal epithelium: straight, regular crypts; lots of mucus; basal nuceli Adenomatous epithelium: increased cellularity; irregular crypts; little mucus; nuclei more dense and stratified	Polyp: bulbous projection from surface Nonneoplastic polyp? Inflammatory or edematous Sessile adenoma: grows on broad base; no stalk Pedunculated adenoma: has stalk Carcinoma? Dysplastic cells would invade	Usually silent, maybe bleeding Almost always lead to cancer
Cortial adenoma, Adrenal gland	Normal adrenal: zonal arrangement Normal cortex: zona glomerulosa, fasciculata, reticularis Nodule: no zonal arrangement; mostly fasciculata cells	Benign? Uniform and bland; no pleomorphism Cortical hyperplasia: involves both glands; generalized overgrowth of multiple nodules Benign medullary neoplasm? Pheochromocytoma	Cushing’s syndrome, hypercortisolism, low serum ACTH
Adenocarcinoma, colon	Sessile mass projects from surface Epithelium: crypt architecture bizarre and complex; nuclear crowding; cells invade submucosa	Malignant? Dysplastic glandular formations within muscularis propria (transmural invasion) Why adeno-? Glandular	Early screening and colonoscopy improve prognosis
Invasive Squamous Cell Carcinoma, uterine cervix	Normal: SSE, normal maturation from basal layer to surface; no pleomorphism, very low N/C ratio Carcinoma: masses of epithelium invade; high N/C ratio; highly dysplastic (cells jumbled, no normal maturation; nuclei large, hyperchromatic, pleomorphic; mitotic figures throughout)	How to tell it’s squamous cell? Cells grow in solid sheets/nests; do not make tubules or glands; focal keratinization Risk factors? HPV For lung or oropharyngeal? Tobacco and alcohol
Leiomyoma, uterus	Numberous circumscribed nodules—densely cellular, high concentration of nuclei, stain more blue Normal myometrium: interlacing fascicles of smooth m. cells Neoplasm: also has interlacing bundles of spindle-shaped cells	Malignant=leiomyosarcoma	Hypermenorrhea
Lipoma, colon	Yellow nodule below intact mucosa; muscle wall distorted Lesion: mature adipose tissue, can’t be distinguished from normal fat cells; grossly, can see circumscribed lump of adipose tissue		Lump
Leimyosarcoma, Soft Tissue	Origin of neoplasm could be any tissue containing smooth muscle Interlacing fascicles of smooth m. cells; nuclei vary in size and stain more than normal	Malignant? Definite nuclear pleomorphism—large, irregular, hyperchromatic, occasional mitotic figures	Lesion on scalp
Liposarcoma, soft tissue of lower extremity	Light staining nodular lesion bordered by deeper staining tissue Lobules of cellular neoplasm extend into adjacent, distorted skeletal m. Neoplasm: some identifiable adipocytes; others have multiple cytoplasmic lipid droplets; others less differentiated; bottom line is high cellularity, nuclear pleomorphism, and invasiveness	Malignant neoplasm of cartilage? Chondrosarcoma Bone? Osteosarcoma Primary or metastatic? Look at origin/type of cells; more than one focus—malignant
Metastatic Adenocarcinoma, liver	Nodular lesions replace and compress hepatic parenchyma Nodules: proliferating epithelial cells forming trabecular and ductal (glandular) spaces Epithelial cells are crowded, stratified, hyperchromatic, pleomorphic Granular material in center of nodules is necrotic neoplastic cells	Adenocarcinoma? Glandular, malignant Would there be primary adenocarcinoma in liver? Maybe from bile duct cells

(Neoplasia, cont’d)	Histological Findings	Questions	Case Scenario(s)
Metastatic Squamous Cell Carcinoma, lymph node	Pink nodule replaces normal tissue—consists of epithelial cells in a fibrous background Epithelial cells have abundant cyto and are arranged in cohesive sheets/nests; nuclei pleomorphic and hyperchromatic	Metastatic? Presence of epithelial cells in lymph node Squamous cell? NO glandular formation; whorls of keratin
Teratoma, ovary	Multi-potential: differentiates in diverse directions; eg. adipose tissue, SSE epithelium, hair follicles, sebaceous glands, CNS tissue	Significance? None in ovary; testis—often malignant
Hemartoma, lung	Practically no normal tissue present—lump is jumble of hyaline cartilage and respiratory epithelium, some ct This is NOT neoplastic—embryological origin, no progressive growth	Hemartoma: mass of disorganized but mature tissue indigenous to the site Choristoma: next of mature tissue in ectopic location

Other Cell and Tissue Injury

	Histological Findings	Questions	Case Scenario(s)
Gangrene, Foot	Coagulative necrosis plus infection Inflammatory reaction found ONLY at line of demarcation between viable and dead tissue	Long term? Toes cast off
Condyloma, perianal region	Coarse papillary projections—massive proliferation of SSE Squamous epithelium much thicker than normal—papilloma virus stimulates proliferation Koilocytosis—presence of squamous cells with perinuclear halo and irregular nucleus	What other lesions do HPV cause? Common wart, squamous papilloma of upper respiratory tract What can result? Carcinoma, especially in female reproductive tract Transmission? Venereal	Large wart from region of anus
Atherosclerosis (w/ dystrophic calcification), artery	Lumen is markedly narrowed by atherosclerotic plaque (in arterial wall) Plaque consists of amorphous material, cholesterol deposits, cells from arterial media, and collagen Basophilic Ca found within plaques (dystrophic)	Why do cholesterol clefts look empty? Cholesterol dissolves in processing Other dystrophic calcification? Valves, pulmonary hilar lymph nodes, ducts, caseous necrosis Consequences? Ischemia, infarct	Hypertension
Ischemic Colitis	Gradient of abnormality in colonic wall indicates low flow state (shock) Ulcer: localized defect in mucosa; crypts disappear, lamina propria filled with fibrin and leukocytes Inflammatory reaction and associated hemorrhage extend into submucosa; looks like cobblestones or thumbprinting	What situations? Hypoperfusion; thrombosis or embolus Clinical manifestations? Radiographic changes; acute abdomen; irritation (cramping, bloat, diarrhea)	Death from cardiac failure