Undifferentiated Lymphadenopathy — Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mr David Okafor is a 58-year-old Nigerian-born taxi driver presenting with a six-week history of a painless left supraclavicular node, three months of drenching night sweats, a 6 kg unintentional weight loss and early satiety. He has hypertension and gastro-oesophageal reflux on amlodipine and pantoprazole. ^[1]

His main problems are:

1. A generalised lymphadenopathy with supraclavicular, mediastinal, para-aortic and iliac nodes on the CT, with B symptoms and a raised LDH — the leading diagnosis is lymphoma, with the differential of disseminated tuberculosis given the positive IGRA and his country of origin, and metastatic carcinoma from an intra-abdominal primary given the left supraclavicular node.
2. The hepatosplenomegaly, consistent with a systemic haematological or infiltrative process.
3. The positive IGRA, indicating a latent tuberculosis that must be managed before any immunosuppressive or cytotoxic therapy.
4. The constitutional decline — the weight loss and the low albumin. ^[1]

My immediate priority is a tissue diagnosis — the next step is an excisional biopsy of the most accessible abnormal node, with the tissue sent fresh for the histology, the immunohistochemistry, the flow cytometry and the molecular studies. I would not give corticosteroids at any point before the biopsy. I would investigate for tuberculosis in parallel — the node will be sent for the acid-fast bacilli stain, the culture and the PCR. I would stage the disease with a PET-CT after the histology, per the Lugano classification, and prognosticate with the revised International Prognostic Index if the diagnosis is a diffuse large B-cell lymphoma." ^[1]

Examiner probing questions and model answers

Q1: "Why an excisional biopsy rather than a fine-needle aspiration?" ^[1]

"The FNA samples cells, not architecture, and it is inadequate for the primary diagnosis of lymphoma. The excisional biopsy preserves the nodal architecture — the follicular versus diffuse pattern, the growth pattern, the capsule — and it provides ample tissue for the immunohistochemistry, the flow cytometry and the molecular studies that sub-classify the lymphoma and direct therapy ^[5]. An FNA might identify 'atypical lymphoid cells,' but it cannot distinguish the Hodgkin from the non-Hodgkin lymphoma, it cannot distinguish the diffuse large B-cell from the follicular, and it cannot provide the cell-of-origin or the translocation status that the modern therapy requires. The principle is that the choice of biopsy technique is as important as the decision to biopsy — FNA is acceptable for the suspected metastatic carcinoma or the infective node, but the excisional biopsy is the gold standard for the suspected lymphoma, and Mr Okafor's leading diagnosis is lymphoma."

Q2: "He has a positive IGRA. How does that change your management?" ^[1]

"The positive IGRA indicates a latent tuberculosis infection, common in a man born in a high-prevalence country. It raises two issues. First, I must exclude active tuberculosis before I consider any immunosuppressive or cytotoxic therapy — the lymphoma, if confirmed, will be treated with immunochemotherapy that would reactivate a latent TB, and the TB itself is in the differential of the lymphadenopathy. I send three sputum samples for the acid-fast bacilli and the PCR, and the node is sent for the AFB stain, the culture and the PCR. Second, I will treat the latent TB (the rifampicin for 4 months or the isoniazid for 6 to 9 months per the local guideline) after the active TB is excluded and before or during the lymphoma therapy, in consultation with the infectious diseases team. The teaching point is that the latent TB is not the explanation for the B symptoms or the LDH — the night sweats, the weight loss and the LDH are more consistent with the lymphoma — but it is a comorbidity that must be managed alongside the lymphoma to prevent the reactivation." ^[1]

Q3: "How would you stage him once the histology is back?" ^[1]

"I would stage with a PET-CT, per the Lugano classification ^[5]. The PET-CT is the standard for the staging and the response assessment of the FDG-avid lymphomas — the Hodgkin, the diffuse large B-cell, the follicular and the mantle cell. The Ann Arbor staging (I to IV) provides the anatomical framework. The routine bone marrow biopsy is no longer indicated if the PET-CT shows no marrow involvement and the diagnosis is Hodgkin lymphoma or diffuse large B-cell lymphoma — a change that spares the patient a painful and often non-contributory procedure. I would prognosticate with the revised International Prognostic Index if the diagnosis is diffuse large B-cell lymphoma — the R-IPI uses the age over 60, the stage III or IV, the more than one extranodal site, the performance status 2 to 4, and the elevated LDH, and it stratifies the outcome into the very good, the good and the poor risk groups ^[4]. Mr Okafor's LDH is elevated, his stage is likely IV by the CT, and his performance status would need to be assessed — he is likely in the good or the poor R-IPI group, and this frames the discussion of the prognosis."

Q4: "Could this be metastatic gastric cancer? He has a left supraclavicular node." ^[1]

"Yes, it is in the differential. The left supraclavicular node — the Virchow node — drains the abdominal cavity via the thoracic duct, and it classically signals a gastric, pancreatic, hepatic, renal or testicular primary. The early satiety and the weight loss raise the gastric cancer possibility. However, the picture overall is more consistent with a lymphoma than a gastric cancer: the generalised lymphadenopathy (the supraclavicular, the mediastinal, the para-aortic, the iliac nodes are all involved), the hepatosplenomegaly, and the raised LDH. A gastric cancer would more typically give a single dominant left supraclavicular node with the intra-abdominal primary, not the generalised nodal pattern. I would request an upper endoscopy as part of the work-up if the histology of the node is metastatic adenocarcinoma — but I expect the histology to show lymphoma, and the endoscopy is not the first step. The teaching point is that the Virchow node is a red flag that mandates the biopsy, and the histology directs the search for the primary — I do not speculate on the primary before the biopsy, because the biopsy answers the question." ^[1]

Q5: "What is your plan for his long-term management after the diagnosis?" ^[1]

"The plan is integrated and stage-dependent. If the diagnosis is a diffuse large B-cell lymphoma, the standard therapy is the R-CHOP for six cycles, with the intrathecal prophylaxis if there is a high-risk subtype. The PET-CT response assessment after 2 to 4 cycles and at the end of therapy uses the Deauville scale. If the diagnosis is a Hodgkin lymphoma, the therapy is the ABVD or the escalated BEACOPP for the high-risk, with the PET-CT response-adapted therapy. If the diagnosis is an indolent lymphoma (the follicular), the therapy may be deferred (the watch-and-wait) if the disease is asymptomatic, or the rituximab with or without the chemotherapy if it is symptomatic. The latent TB is treated alongside. The supportive care — the nutrition, the psychosocial support, the fertility preservation (the sperm banking before the chemotherapy) — is integrated from the start. And the communication — the honest discussion of the diagnosis, the prognosis and the treatment plan, with the patient and the family, in the language he understands, with the interpreter if needed — is the foundation of the long-term management." ^[1]

Q6: "What is the single most important lesson from this case for a registrar managing undifferentiated lymphadenopathy?" ^[1]

"The single most important lesson is that the biopsy is the priority, and the choice of biopsy matters. Mr Okafor has a supraclavicular node with B symptoms and a raised LDH — the leading diagnosis is lymphoma, and the next step is an excisional biopsy, not an observation period and not an FNA. The registrar who observes a supraclavicular node, or who accepts an FNA diagnosis, has lost time and compromised the diagnostic tissue. The corollary is the parallel work-up — the tuberculosis is in the differential, and the latent TB is a comorbidity that must be managed before the immunosuppressive therapy. The integrated approach — the red-flag screen, the correct biopsy, the parallel work-up of the differential, the staging per the Lugano classification, and the prognostication per the R-IPI — is what keeps the complex lymphadenopathy patient safe and gets the diagnosis right the first time." ^[1]