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]

Short Case Discussion

The systematic lymph node examination

Examiner instruction: "Examine this patient's lymph nodes. Present your findings and offer a differential diagnosis." [1]

Candidate's model answer: [1]

*"My routine is the neck, the axillae, the epitrochlear nodes, the inguinal nodes, the popliteal fossae — the integrated examination that does not stop at the node the patient noticed. Before I touch the patient, I take five seconds at the end of the bed: is the patient cachectic, pale, icteric? Are there skin lesions — the rash of secondary syphilis, the erythema nodosum of sarcoid? Are there surgical scars — a previous biopsy, a previous thyroid or breast surgery? [1]

The neck. I inspect for asymmetry and scars, then I palpate in sequence: the occipital nodes (draining the scalp), the pre-auricular and post-auricular nodes, the submental and submandibular nodes (draining the floor of mouth and the tongue tip), the upper, middle and lower deep cervical nodes along the anterior border of the sternocleidomastoid (draining the oral cavity, the oropharynx, the nasopharynx, the larynx and the thyroid), the posterior triangle along the posterior border of the sternocleidomastoid (draining the back of the scalp and the nasopharynx — the nasopharyngeal primary classically spreads here), and the supraclavicular fossae. The supraclavicular fossa I palpate from behind the patient, with the head flexed forward to relax the sternocleidomastoid, and my fingers placed deep to the clavicle — the registrar who palpates from the front with the head extended misses the node. [1]

The axillae. With the patient's arm supported by my hand, I palpate against the chest wall in all five axillary positions: the apical (high in the axilla), the central (the bulk of the axilla), the pectoral (anterior), the lateral (against the humerus), and the subscapular (posterior). The registrar who examines the axilla with the arm raised and unsupported misses the central and apical nodes. [1]

The epitrochlear nodes. With the elbow flexed to 90 degrees, I palpate 2 to 3 cm above the medial epicondyle, in the groove between the biceps and the triceps. Any palpable epitrochlear node above 5 mm is abnormal. [1]

The intraclavicular nodes. Just below the clavicle, in the deltopectoral groove. [1]

The inguinal nodes. The horizontal group along the inguinal ligament, and the vertical group along the saphenous vein. [1]

The popliteal fossae. [1]

I then extend the examination to the primary drainage sites — the skin of the head, neck and scalp (examined through the hair, because the melanoma or the squamous cell carcinoma of the scalp is easily missed), the oral cavity and the oropharynx (the tongue, the floor of mouth, the buccal mucosa, the palate, the tonsils), the breast (both breasts and both axillae), the thyroid, the abdomen for hepatosplenomegaly, the testes, and the skin of the limbs. [1]

For each node I characterise five features: the size (with a ruler, never an estimate), the consistency (soft, rubbery, hard), the mobility (mobile, tethered, fixed), the tenderness, and the overlying skin."* [1]

Examiner: "Why do you examine the supraclavicular fossa from behind the patient?" [1]

"Because the supraclavicular nodes lie deep to the clavicle and the sternocleidomastoid, and they are best palpated from behind with the head flexed forward to relax the sternocleidomastoid. The fingers are placed in the supraclavicular fossa, deep to the clavicle, and the patient may be asked to cough or to perform a Valsalva manoeuvre, which pushes a deep node up against the examining fingers. The registrar who palpates from the front with the head extended is palpating the overlying sternocleidomastoid, not the node. The supraclavicular node is the single highest-risk location — a left supraclavicular node (the Virchow node) drains the abdominal cavity via the thoracic duct and classically signals a gastric, pancreatic or other intra-abdominal malignancy; a right supraclavicular node drains the mediastinum, the right lung and the oesophagus. Any supraclavicular node of any size in an adult is a red flag and mandates biopsy." [1]

Examiner: "What is the significance of an epitrochlear node?" [1]

"Any palpable epitrochlear node above 5 mm is abnormal [1]. The epitrochlear node drains the medial forearm and the ulnar aspect of the hand. The differential includes secondary syphilis (the classic association), lymphoma (especially the non-Hodgkin lymphoma), infectious mononucleosis, and the skin infection of the hand or forearm. An epitrochlear node is a red flag in the same way that a supraclavicular node is — it is never a normal reactive node — and the registrar who dismisses one as reactive has missed a significant finding."

Examiner: "What is the single most important lesson from this examination for a registrar managing lymphadenopathy?" [1]

"The single most important lesson is that the examination is not complete until all node groups have been examined, and the examination extends to the primary drainage sites and the systemic signs. The registrar who examines only the node the patient noticed has examined only a fraction of the patient. The supraclavicular node, the epitrochlear node and the systemic hepatosplenomegaly are the findings that change the differential and the urgency, and they are found only by the systematic examination. The corollary is the characterisation of the node — the size with a ruler, the consistency (soft, rubbery, hard), the mobility, the tenderness, the matting — because these features, with the location and the B symptoms, drive the decision to biopsy." [1]