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PA19.1-6 | Tuberculous Lymphadenitis — Pathology & Specimen — Part 1
CLINICAL SCENARIO
A 19-year-old female student presents with a 6-week history of painless swelling on the right side of her neck. Examination reveals a cluster of firm, matted lymph nodes in the posterior triangle. She has no fever but has lost 4 kg over two months. Fine-needle aspiration cytology (FNAC) is planned.
Before the needle touches skin, two questions: What immunological battle is being fought inside that node? And if you received the slide, what exactly would you be looking for? By the end of this module, you will answer both with confidence.
WHY THIS MATTERS
India contributes the highest absolute number of TB cases globally (2.8 million new cases/year — WHO 2023). Of all extrapulmonary sites, lymph nodes are the most frequently involved. Scrofula — cervical tuberculous lymphadenitis — is the classic presentation your outpatient clinic, ENT OPD, and surgical wards will throw at you repeatedly.
Beyond sheer frequency, this lesion is the teaching specimen of choice for granulomatous inflammation. The morphological vocabulary — granuloma, epithelioid histiocyte, Langhans giant cell, caseous necrosis — is the shared language of Pathology, Medicine, Dermatology, and Surgery. PA19.5 explicitly requires you to identify these features in a gross specimen and on a microscopic slide, making this module directly OSCE-tested.
RECALL
Before we build forward, anchor three Year-1 concepts:
- Type IV hypersensitivity (cell-mediated, delayed): T-lymphocyte driven, no antibody involvement, peak reaction at 48–72 hours. Classic examples: tuberculin (Mantoux) test, contact dermatitis, graft rejection.
- Macrophage activation: Resting monocyte-derived macrophages become activated on exposure to cytokines (especially IFN-γ), acquiring enhanced microbicidal capacity (reactive oxygen species, nitric oxide, lysosomal enzymes).
- Mycobacterium tuberculosis survival strategy: The bacillus resists phagosomal killing by blocking phagosome–lysosome fusion. This chronic intracellular persistence is precisely why the immune response escalates to granuloma formation.
Hold these three concepts. They are the engine of everything that follows.
Pathogenesis: Why a Granuloma Forms
When M. tuberculosis reaches a lymph node (via lymphatic drainage from a primary pulmonary focus or direct inoculation), it is phagocytosed by resident macrophages. Unable to destroy the bacillus, the macrophage presents mycobacterial antigens (lipoarabinomannan, ESAT-6 peptides) via MHC class II to CD4+ Th1 lymphocytes.
Activated Th1 cells release IFN-γ (the master activating cytokine), TNF-α, and IL-2. IFN-γ transforms ordinary macrophages into epithelioid histiocytes — large, elongated cells with abundant pink cytoplasm and oval nuclei, resembling epithelial cells under the microscope (hence the name). This transformation is the hallmark of Type IV hypersensitivity.
When epithelioid histiocytes fuse (driven by IFN-γ and IL-4), they form Langhans giant cells — multinucleate cells with nuclei characteristically arranged in a horseshoe or peripheral wreath pattern at the edge of the cytoplasm. This distinguishes them from foreign-body giant cells (nuclei scattered centrally, no orderly arrangement).
The cumulative structure — a central zone of activated macrophages and giant cells surrounded by a cuff of CD4 lymphocytes and fibroblasts — is the tuberculous granuloma (also called tubercle or follicle). This is a delayed hypersensitivity granuloma, driven by persistent antigen that the immune system cannot clear.
Caseous Necrosis: The Defining Feature
As the granuloma matures, the central zone undergoes a unique form of cell death: caseous necrosis (from Latin caseus — cheese). This is structureless, acellular, eosinophilic (pink) material that, grossly, looks and feels like crumbly white cheese. It is the pathological signature of TB.
The mechanism involves three converging forces:
1. Macrophage-mediated cytotoxicity — activated macrophages secrete toxic oxygen radicals and proteases that kill both the bacillus and surrounding host cells.
2. TNF-α — drives apoptosis and tissue necrosis within the granuloma core.
3. Ischaemia — the granuloma's fibrous capsule compresses feeding vessels; the avascular centre becomes hypoxic and necrotic.
Critically, caseous necrosis is not liquefactive (unlike pyogenic abscesses) and not coagulative (unlike infarcts). Under the microscope, it is amorphous, finely granular, and ghost cell outlines are absent — you cannot identify any cellular remnants in established caseum.
Evolution of a single tubercle: (1) Exudative phase → cellular infiltrate, no necrosis. (2) Productive/granulomatous phase → epithelioid granuloma with peripheral lymphocytes. (3) Caseous phase → central necrosis. (4) Fibrocalcific phase → dystrophic calcification (Ghon lesion equivalent in nodes).
IMPORTANT: In lymph nodes, necrosis tends to be confluent — multiple granulomas coalesce, producing large zones of caseous material rather than discrete tiny foci.
Histopathology of Tuberculous Lymphadenitis: Caseating Granuloma
SELF-CHECK
In a tuberculous granuloma, caseous necrosis differs from a pyogenic abscess because the necrotic material is:
A. Liquefied, with intact neutrophils and bacteria
B. Acellular, amorphous, and finely granular — no ghost cell remnants
C. Coagulative, preserving ghost outlines of dead cells
D. Haemorrhagic, owing to vascular disruption by the bacillus
Reveal Answer
Answer: B. Acellular, amorphous, and finely granular — no ghost cell remnants
Caseous necrosis is structureless and amorphous — unlike coagulative necrosis (which preserves tissue architecture) and liquefactive necrosis (which yields pus). The 'cheesy' consistency reflects protein denaturation and lipid release from mycobacterial cell walls (mycolic acid content). No ghost cell outlines are visible because the necrosis is complete.
Gross Features of Tuberculous Lymphadenitis
In the clinic and at autopsy/surgical resection, you may be handed a specimen or a pot. Know what you are looking for.
Size and number: Multiple lymph nodes, often >2 cm. Cervical chain most commonly affected (posterior triangle and submandibular groups); also axillary and mesenteric (tabes mesenterica).
Matting: Nodes lose their individual capsules as periadenitis (inflammation of perinodal fat and capsule) causes them to fuse. On palpation and on cut section, they form a matted mass — a conglomerate rather than discrete spheres.
Cut surface: Fresh caseous material is dull, cheesy, yellow-white, and crumbly — grossly resembles cottage cheese or very old cheddar. More advanced lesions show chalky-white calcification.
Cold abscess: When caseous material liquefies (liquefaction is a secondary event in older lesions — bacillary products + host lipases), it may track along fascial planes and point at the skin surface. Because TB lacks the pyrogens of pyogenic bacteria, the overlying skin is neither red nor hot — hence cold abscess. This is a classic surgical and clinical term.
Collar-stud abscess: In the neck, liquefied caseum may penetrate the deep cervical fascia but remain tethered to the skin — producing a dumbbell-shaped collection above and below the fascia, connected by a narrow neck. The surface bulge resembles a collar stud (now often called a shirt-stud abscess).
Sinus tract: If the cold abscess points and ruptures spontaneously through skin, a chronic discharging sinus forms — a persistent tract lined with granulation tissue, discharging caseous or sero-purulent material.
Gross Pathology of Tuberculous Lymphadenitis
SELF-CHECK
You receive a surgical specimen: a bisected lymph node with a dull yellow-white crumbly centre and a fused capsule merging with adjacent fat. The most likely diagnosis is:
A. Reactive follicular hyperplasia
B. Metastatic squamous cell carcinoma with central necrosis
C. Tuberculous lymphadenitis with caseation
D. Suppurative lymphadenitis (pyogenic abscess)
Reveal Answer
Answer: C. Tuberculous lymphadenitis with caseation
The combination of matted capsule (periadenitis), cheesy yellow-white crumbly material (caseation), and the absence of a liquid centre (not liquefactive yet) is classic for TB. Metastatic carcinoma can show central necrosis but will have firm, white tumour tissue at the periphery and lacks the cheese-like texture. Pyogenic abscesses are liquefied and creamy-white (pus), and the node is not matted — it is simply fluctuant.