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PA3.4 | Inflammation Morphology — Practical — SDL Guide (Part 3)

Chronic Inflammation — Microscopic Features

Chronic inflammation is defined by a mononuclear infiltrate — lymphocytes, plasma cells, and macrophages — often with tissue remodelling.

Key cells and their nuclear signatures:
• Lymphocyte: small, round, dark nucleus, scant cytoplasm — the most numerous cell in most chronic inflammatory infiltrates
• Plasma cell: eccentric nucleus with clock-face (cartwheel) chromatin and a clear perinuclear hof (Golgi zone) — the antibody-secreting cell
• Macrophage/histiocyte: kidney-shaped or oval nucleus, abundant pale cytoplasm — phagocytic workhorse; when activated, may show cytoplasmic vacuoles (lipid-laden 'foamy macrophage')

Associated tissue changes:
• Fibrosis: collagen deposition by activated fibroblasts — pink, acellular bands on H&E; indicates attempted repair
• Granulation tissue: combination of new thin-walled capillary loops, fibroblasts, and mixed inflammatory cells — the substrate of healing
• Glandular or epithelial hyperplasia in some chronic inflammatory sites (e.g. chronic gastritis)

Chronic inflammation often has scattered neutrophils too, especially at active ulcer edges — this is called 'active chronic inflammation' and is important to recognise in gastric and bowel biopsies.

IMPORTAN: Eosinophils in the infiltrate suggest allergic/parasitic aetiology or IBD — their presence is worth noting.

A four-panel histology diagram shows chronic inflammatory infiltrate in gastric mucosa, key mononuclear cell types, tissue remodelling, and active chronic inflammation with neutrophils and eosinophils. — **Panel A:** High-power H&E-style gastric mucosa overview showing gastric gland, lamina propria, chronic inflammatory infiltrate, fibrosis, and granulation tissue.. **Panel B:** Key mononuclear cells: lymphocyte, plasma cell with eccentric clock-face nucleus and perinuclear hof, macrophage or histiocyte, and foamy macrophage with cytoplasmic vacuoles.. **Panel C:** Associated tissue changes: activated fibroblast, collagen deposition, fibrosis, thin-walled capillary loops, granulation tissue, and mixed inflammatory cells.. **Panel D:** Active chronic inflammation at ulcer edge with mononuclear infiltrate plus scattered neutrophils, and eosinophils suggesting allergic, parasitic, or IBD-associated inflammation..

SELF-CHECK

You are examining a colonic biopsy. At 40× you see: cells with small dark round nuclei (most numerous), cells with eccentric nuclei showing peripheral clumped chromatin and a pale cytoplasmic zone, and occasional cells with kidney-shaped nuclei. There is also increased pink fibrous material between crypts. What is the most appropriate diagnosis?

A. Acute colitis — the dominant cell is neutrophil

B. Granulomatous colitis — the kidney-shaped nuclei indicate giant cells

C. Normal colonic mucosa — all cells described are physiological

D. Chronic inflammation with fibrosis — lymphocytes, plasma cells, and macrophages with collagen deposition

Reveal Answer

Answer: D. Chronic inflammation with fibrosis — lymphocytes, plasma cells, and macrophages with collagen deposition

Small dark round = lymphocytes; eccentric nucleus with clock-face chromatin + perinuclear hof = plasma cells; kidney-shaped = macrophages. Increased fibrous material = fibrosis. Together: chronic inflammation with fibrosis. The kidney-shaped nucleus of a macrophage must not be confused with a giant cell, which has multiple nuclei arranged in a specific pattern.

Granulomatous Inflammation — The Granuloma in Detail

A granuloma is a focal aggregate of activated macrophages (epithelioid histiocytes) surrounded by lymphocytes, with or without giant cells and central necrosis.

Components of a tuberculoid granuloma (prototype):

Epithelioid histiocytes (centre): elongated, pale/eosinophilic nuclei with folded margins, indistinct cell borders (cells appear to merge) — so named because they resemble epithelial cells
Langhans giant cells: multinucleate macrophage fusions with nuclei arranged in a peripheral horseshoe or ring pattern — classically around the granuloma edge; MUST be distinguished from foreign-body giant cells (nuclei randomly scattered centrally)
Central caseation: if present, strongly suggests TB or fungal aetiology; amorphous, pink, cheese-like, anucleate — no ghost outlines (unlike coagulative necrosis)
Lymphocyte cuff: rim of small lymphocytes outside the epithelioid zone, maintaining the cell-mediated immune response

Granulomas WITHOUT caseation (non-caseating granulomas) suggest sarcoidosis, foreign-body reaction, Crohn's disease, or fungal/atypical mycobacterial infection.

Remember: the granuloma is a T-cell–driven, macrophage-dominated response — it means the agent is poorly degradable (TB bacilli, fungi, silica, suture material).

A multi-panel histology diagram showing the structure of a tuberculoid granuloma, its epithelioid histiocytes, giant cell patterns, and the distinction between caseating and non-caseating granulomas. — **Panel A:** Single well-formed tuberculoid granuloma with central caseation, epithelioid histiocyte zone, Langhans giant cell, and outer lymphocyte cuff.. **Panel B:** Magnified epithelioid histiocytes showing elongated folded nuclei, pale eosinophilic cytoplasm, and indistinct cell borders.. **Panel C:** Comparison of Langhans giant cell with peripheral horseshoe nuclei versus foreign-body giant cell with randomly scattered central nuclei.. **Panel D:** Caseating granuloma suggesting TB or fungal infection compared with non-caseating granuloma suggesting sarcoidosis, Crohn disease, foreign-body reaction, or atypical infection..

CLINICAL PEARL

Langhans vs. Foreign-body giant cell — a classic trap:
• Langhans giant cell: nuclei at the periphery in a horseshoe or ring → think TB/fungal granuloma
• Foreign-body giant cell: nuclei scattered centrally (haphazard) → think suture, silica, talc
The nuclear arrangement is the exam discriminator. The cell formation mechanism is the same (macrophage fusion), but the stimulus and clinical meaning differ completely.

SELF-CHECK

In a lymph node biopsy from a patient with cough and weight loss, you see: aggregates of pale, elongated cells with indistinct margins (resembling epithelium), ringed by small lymphocytes, with a central zone of structureless pink material. No nuclear ghost outlines are visible in the central zone. What are the cells, what is the central material, and what is the most likely aetiology?

A. Neutrophils / fibrinous exudate / bacterial lymphadenitis

B. Epithelioid histiocytes / caseation necrosis / tuberculosis

C. Plasma cells / amyloid / chronic lymphadenopathy

D. Reed-Sternberg cells / necrosis / Hodgkin lymphoma

Reveal Answer

Answer: B. Epithelioid histiocytes / caseation necrosis / tuberculosis

Pale elongated cells with indistinct margins in clusters = epithelioid histiocytes. Structureless pink material without nuclear ghosts = caseation necrosis (coagulative necrosis would retain ghost outlines; liquefactive necrosis would be more cellular-debris-rich). Caseating granuloma in a lymph node + constitutional symptoms = tuberculosis until proven otherwise.

Gross Pathology — Matching Macroscopic to Microscopic

Gross recognition is tested in 'spot diagnosis' stations. Correlate each gross appearance with its microscopic counterpart:

Gross appearance	Macroscopic clue	Microscopic correlate
Abscess	Creamy-yellow, fluctuant cavity; firm wall	Liquefactive necrosis + neutrophils; pyogenic membrane → granulation tissue
Fibrinous pericarditis	Roughened, shaggy, dull surfaces; 'bread-and-butter' when separated	Fibrin strands on serosal surface; scattered neutrophils
Chronic peptic ulcer	Oval punched-out base; indurated overhanging edges; clean base	Four-zone ulcer: exudate / necrosis / granulation tissue / fibrosis
Granulomatous lymph node	Enlarged, matted; cut surface shows grey-white foci, possibly central softening	Caseating granulomas: epithelioid cells + Langhans giant cells + lymphocytes + caseation

Tip for gross exams: hold the specimen at arm's length first (gestalt impression), then examine the cut surface systematically: colour, consistency, margins, cavities.

A four-panel pathology diagram matching gross appearances of abscess, fibrinous pericarditis, chronic peptic ulcer, and granulomatous lymph node to their microscopic correlates. — **Panel A:** Abscess: creamy-yellow cavity, firm wall, liquefactive necrosis, neutrophils, pyogenic membrane, granulation tissue. **Panel B:** Fibrinous pericarditis: rough dull pericardial surfaces, shaggy fibrin strands, bread-and-butter separation, serosal fibrin, scattered neutrophils. **Panel C:** Chronic peptic ulcer: oval punched-out ulcer, indurated overhanging edges, clean base, exudate, necrosis, granulation tissue, fibrosis. **Panel D:** Granulomatous lymph node: enlarged matted nodes, grey-white foci, central softening, caseating granuloma, epithelioid cells, Langhans giant cells, lymphocytes. **Footer:** Gross exam approach: gestalt impression at arm’s length, systematic cut surface inspection, colour, consistency, necrosis.

SELF-CHECK

At a gross pathology station you are shown a lymph node cut surface with grey-white foci and one area of central softening. The examiner asks: 'What would you expect to see under the microscope?' Which answer is most complete?

A. Dense fibrin strands on a serosal surface with neutrophils — fibrinous pleuritis

B. Diffuse neutrophil infiltration with liquefactive necrosis — suppurative lymphadenitis

C. Epithelioid histiocytes in granulomas with Langhans giant cells, lymphocyte cuff, and central caseation — tuberculosis

D. Small dark lymphocytes replacing normal architecture — reactive hyperplasia

Reveal Answer

Answer: C. Epithelioid histiocytes in granulomas with Langhans giant cells, lymphocyte cuff, and central caseation — tuberculosis

Grey-white foci with central softening in a lymph node = caseating granulomas. Central softening = liquefaction of caseous material. Microscopically: epithelioid histiocytes + Langhans giant cells + caseation + lymphocyte cuff = tuberculoid granuloma. This is the most common gross-to-micro correlation in Indian university examinations for PA3.4.

Quick Differential at a Glance

A four-step histology decision-tree diagram differentiating acute, chronic, granulomatous, suppurative, fibrinous, serous, ulcerative, phlegmonous, caseating, and non-caseating inflammation patterns. — **Panel A:** Dominant inflammatory cell decision point showing neutrophils for acute inflammation, lymphocytes and plasma cells for chronic inflammation, and epithelioid cell clusters for granulomatous inflammation.. **Panel B:** Acute inflammation patterns showing suppurative abscess with pus and liquefactive necrosis, fibrinous exudate on a serosal surface, serous dilute exudate, ulcer with four-zone wall defect, and phlegmon with diffuse unwalled spread.. **Panel C:** Granulomatous inflammation comparison showing caseating granuloma with amorphous anucleate necrosis suggesting TB or fungal infection, and non-caseating granuloma suggesting sarcoid, foreign body reaction, or Crohn disease.. **Panel D:** Multinucleated giant cell nuclear arrangements showing peripheral horseshoe nuclei in Langhans giant cell and central haphazard nuclei in foreign-body giant cell..

Use this decision tree at the microscope:

Step 1 — What is the dominant cell?
``Neutrophils → ACUTE inflammation Lymphocytes/Plasma cells → CHRONIC inflammation Epithelioid clusters → GRANULOMATOUS inflammation`

Step 2 — If ACUTE, what pattern?`Pus/liquefactive necrosis → Suppurative / Abscess Fibrin on serosal surface → Fibrinous Dilute exudate, few cells → Serous Four-zone wall defect → Ulcer Diffuse, no walling-off → Phlegmon`

Step 3 — If GRANULOMATOUS, caseation present?`Yes (amorphous, anucleate) → TB / Fungal No → Sarcoid / Foreign body / Crohn's`

Step 4 — Check giant cell nuclear arrangement:`Peripheral horseshoe → Langhans (TB) Central, haphazard → Foreign-body``

This four-step framework answers 95% of PA3.4 examination questions.