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PA19.{1-3,5-6} | Lymphadenopathy & Lymphomas — PBL Case

CLINICAL SETTING

Ramu, a 38-year-old sugarcane farmer from a village in Uttar Pradesh, presents to the district hospital with a two-month history of painless, slowly enlarging swellings on the right side of his neck. He noticed the first swelling four months ago but ignored it, attributing it to a tooth problem that resolved. Over the past six weeks, the swellings have multiplied and some have begun to feel soft in the centre. He reports low-grade fever in the evenings ('slight warmth'), drenching night sweats that require him to change his vest, and has lost about 5 kg without reducing his diet. He has a dry cough for two months but no haemoptysis. He has never been tested for tuberculosis. He tends cattle and lives in a joint family in a poorly ventilated two-room house with six others. On examination: temperature 37.9°C, pulse 88/min, respiratory rate 18/min. Right posterior cervical and right submandibular lymph nodes: four nodes, largest 3.5 × 2.5 cm, firm to hard, non-tender, beginning to mat; one node appears to have a softened centre with slight overlying skin discolouration. No axillary or inguinal lymphadenopathy. Chest auscultation normal. Spleen not palpable. Mantoux (PPD) test: 18 mm induration at 72 hours. Chest X-ray: right hilar prominence, no parenchymal infiltrate.

Trigger 1: Initial Presentation

The district hospital physician reviews Ramu: a 38-year-old farmer with two months of painless cervical lymphadenopathy (matting, softening, skin discolouration), constitutional symptoms (fever, night sweats, weight loss), a strongly positive Mantoux, right hilar prominence on X-ray, and a TB-risk household environment. No splenomegaly, no generalised lymphadenopathy. The physician must decide how to approach this lymphadenopathy, what it likely represents, and what tissue procedure is indicated.

DISCUSSION POINTS

  • Use the six clinical discriminators for lymphadenopathy evaluation (distribution, number of groups, consistency, tenderness, matting/fixation, skin changes) to characterise Ramu's nodes — which features point toward an infective/granulomatous cause and which features might raise concern for malignancy?
  • The Mantoux test is 18 mm — interpret this result in context. What is the immunological mechanism underlying the Mantoux reaction, and what hypersensitivity type is it? Does a positive Mantoux confirm active tuberculous lymphadenitis?
  • Matting of lymph nodes (multiple nodes fusing into a confluent mass) and central softening (fluctuance) are characteristic of TB lymphadenitis — what is the pathological process that produces matting and central fluctuance in this disease?
  • The physician is considering FNAC versus excision biopsy. For Ramu's presentation of probable TB lymphadenitis, which procedure is first-line, and under what circumstances would an excision biopsy be mandatory instead?
Click to reveal Trigger 2: Investigations (discuss previous trigger first!)

Trigger 2: Investigations

FNAC of the largest right cervical node is performed. Cytology report: 'Smear shows clusters of epithelioid cells, Langhans-type multinucleated giant cells, and a background of caseous-type necrotic material (amorphous eosinophilic debris). No viable lymphoid cells in the necrotic areas. AFB smear (Ziehl-Neelsen stain): acid-fast bacilli seen in 1 of 10 high-power fields (scanty positive). FNAC Impression: Granulomatous lymphadenitis with caseous necrosis — consistent with tuberculous lymphadenitis.' Sputum AFB smear × 2: negative. GeneXpert MTB/RIF on the FNAC material: MTB detected; Rifampicin resistance: NOT detected. The diagnosis of tuberculous lymphadenitis (scrofula) is confirmed. However, the physician notices on follow-up at 4 weeks that while the TB nodes have begun to shrink on anti-TB therapy, a NEW 2.5 cm left axillary node has appeared. The patient is afebrile. The new node is non-tender, firm, rubbery, and has no overlying skin changes.

DISCUSSION POINTS

  • Describe the complete microscopic picture of tuberculous lymphadenitis systematically: what do you see at low power (the pattern) and high power (the specific cells), naming each component and its pathological significance?
  • What is caseous necrosis — how does it differ from coagulative necrosis histologically and biochemically, and what specific pathophysiological mechanism produces it in TB (hint: consider the cytotoxic T-lymphocyte response to the centre of the granuloma)?
  • Construct the differential diagnosis of granulomatous lymphadenitis: list at least four conditions that produce granulomas in lymph nodes, and for each state the key distinguishing feature (presence or absence of caseation, ZN stain, specific cell, serum marker).
  • A new axillary lymph node appearing while the cervical TB nodes are responding to treatment is an unexpected finding — what possibilities should be considered, and why does this mandate an excision biopsy rather than a repeat FNAC?
Click to reveal Trigger 3: Diagnosis & Management (discuss previous trigger first!)

Trigger 3: Diagnosis & Management

An excision biopsy of the left axillary node is performed. Histopathology report: 'Lymph node architecture is effaced. There is a diffuse proliferation of large lymphoid cells with vesicular nuclei, 2–3 prominent nucleoli, and moderate pale cytoplasm. Mitotic figures frequent. Background shows scattered macrophages engulfing apoptotic debris, imparting a 'starry-sky' pattern. No Reed-Sternberg cells. No caseating granulomas. IHC: CD20+, CD10+, BCL6+, MUM1−, CD30−, CD15−, CD3−. Ki-67: 95%. FISH: MYC translocation detected — t(8;14)(q24;q32). Diagnosis: Diffuse Large B-Cell Lymphoma with MYC translocation (provisional Burkitt-like / high-grade B-cell lymphoma with MYC rearrangement).' The haematology-oncology team is urgently involved. Staging CT shows retroperitoneal and mesenteric lymphadenopathy. LDH is 4× the upper limit of normal. Ramu is continued on anti-TB therapy and simultaneously referred for urgent immunochemotherapy (R-CHOP or DA-EPOCH-R). The team explains that TB and lymphoma can co-exist — lymphoma itself can cause immunosuppression that reactivates latent TB or impairs clearance of active TB.

DISCUSSION POINTS

  • Compare Hodgkin lymphoma and Non-Hodgkin lymphoma across the key parameters — cell of origin, age distribution, spread pattern (contiguous vs non-contiguous), presence of Reed-Sternberg cells, B-symptoms, immunophenotype, and overall treatability.
  • The starry-sky pattern is produced by tingible-body macrophages engulfing apoptotic tumour cells — in what lymphoma subtypes is this pattern characteristic, and what does a Ki-67 of 95% mean for the biology and urgency of treatment?
  • The t(8;14) translocation juxtaposes the MYC oncogene with the immunoglobulin heavy chain gene promoter — explain the pathogenetic mechanism by which this translocation transforms a B cell, and why the same translocation mechanism (IG promoter hijacking) is shared by follicular lymphoma [t(14;18)] and mantle cell lymphoma [t(11;14)].
  • Ramu's case illustrates that TB and lymphoma co-exist. How does lymphoma-associated immunodeficiency predispose to opportunistic infection, and what surveillance is needed in a patient receiving immunochemotherapy who is also on anti-TB treatment?

Group Task Assignments

Group 1: Lymphadenopathy evaluation framework

  • Construct a clinical evaluation table for lymphadenopathy using six discriminators (distribution, consistency, tenderness, matting, skin changes, associated symptoms) and apply it to three vignettes: (a) a 7-year-old with tender, fluctuant submandibular nodes after a dental abscess; (b) Ramu's presentation; (c) a 55-year-old with hard, fixed, supraclavicular nodes and weight loss.
  • Explain the difference between FNAC and excision biopsy in lymph node evaluation — for what conditions is FNAC sufficient, and in what situations is excision biopsy mandatory? Why can FNAC never be used alone to diagnose lymphoma?

Competencies: PA19.1

Group 2: Tuberculous lymphadenitis — pathology in depth

  • Draw and label the complete microscopic architecture of a tuberculous lymph node: show the zones at low power (intact cortex/paracortex, granuloma zones) and identify at high power: epithelioid macrophages, Langhans giant cell (describe the nuclear arrangement), caseous necrosis centre, and surrounding lymphocyte cuff.
  • Describe the gross specimen of TB lymphadenitis step-by-step using the structured approach (size, consistency, cut surface, colour, content) and correlate each gross feature with its microscopic counterpart (matting = periadenitis + fibrosis; caseous centre = central necrosis).

Competencies: PA19.2, PA19.5

Group 3: Hodgkin lymphoma — specimen identification and pathology

  • Describe the gross and microscopic features of nodular sclerosis Hodgkin lymphoma — the most common subtype. Include: collagen band description, lacunar cell morphology, Reed-Sternberg cell hallmark features (owl-eye nucleoli, size, binucleate), and the reactive background composition.
  • Draw and label a Reed-Sternberg cell and its four variants (Hodgkin cell, lacunar cell, lymphocytic/histiocytic cell, mononuclear RS cell), stating the subtype of Hodgkin lymphoma in which each is most characteristically seen.

Competencies: PA19.5, PA19.6

Group 4: NHL pathogenesis, translocations, and key subtypes

  • Build a translocation reference table for B-cell lymphomas: for t(14;18), t(8;14), and t(11;14) — state the lymphoma type, the gene fused to the IG promoter, the protein overproduced, and the biological consequence (BCL2 anti-apoptosis, MYC proliferation, cyclin D1 cell cycle entry).
  • Compare follicular lymphoma and DLBCL: cell of origin, architecture (follicular vs diffuse), Ki-67 (low vs high), clinical behaviour (indolent vs aggressive), and first-line treatment approach.

Competencies: PA19.3, PA19.6

Group 5: Hodgkin vs Non-Hodgkin lymphoma — integrated comparison and diagnostic algorithm

  • Construct a comparison table of Hodgkin lymphoma vs Non-Hodgkin lymphoma across 8 parameters: cell of origin, age group, spread pattern (contiguous vs non-contiguous), Reed-Sternberg cell presence, B-symptoms frequency, extranodal involvement, IHC panel (CD15, CD30, CD20, CD3), and prognosis.
  • Design a diagnostic algorithm for a patient presenting with painless lymphadenopathy: starting from clinical assessment, progressing through FNAC vs biopsy decision, morphology reading (granuloma vs effaced architecture), and IHC panel interpretation to reach a specific diagnosis for Ramu's two sequential nodes.

Competencies: PA19.1, PA19.3, PA19.6

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [PA19.1] What are the causes of lymphadenopathy, and what are the clinical features (distribution, consistency, tenderness, matting, skin changes, associated constitutional symptoms) that differentiate reactive/infective lymphadenopathy from lymphoma? What is the role and limitation of FNAC versus excision biopsy?
  2. [PA19.2] What is the pathogenesis of tuberculous lymphadenitis (M. tuberculosis → macrophage phagocytosis → Th1 cell-mediated immunity → granuloma formation → caseous necrosis), and what are its gross and microscopic features including the specific cells and stains used for confirmation?
  3. [PA19.3] What are the pathogenesis (EBV, chromosomal translocations, immunodeficiency), pathology, and key differentiating features of Hodgkin lymphoma versus Non-Hodgkin lymphoma, including the Reed-Sternberg cell, spread patterns, B-symptoms, immunophenotype, and selected aggressive subtypes (DLBCL, Burkitt)?
  4. [PA19.5] How do you identify and describe the features of tuberculous lymphadenitis in a gross specimen (size, matted nodes, caseous centre) and in a microscopic section (epithelioid granulomas with Langhans giant cells, caseous necrosis, cuff of lymphocytes, ZN stain for AFB)?
  5. [PA19.6] How do you identify and describe the features of Hodgkin lymphoma in a gross specimen (enlarged rubbery nodes, fish-flesh cut surface, collagen bands) and in a microscopic section (Reed-Sternberg cells with owl-eye nucleoli, lacunar cells in nodular sclerosis, polymorphous reactive background, IHC: CD15+, CD30+, CD45−)?