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PA7.1,PA22.1-5 | Diagnostic Cytology & Clinical Pathology — PBL Case

CLINICAL SETTING

Manohar, a 55-year-old male primary school headmaster from a semi-urban town in Tamil Nadu, presents to the district hospital with a two-week history of progressively worsening breathlessness, right-sided dull aching chest pain, and swelling of both legs. He has no fever. His wife notes that his urine has become 'frothy and reddish-brown' over the same period. He is a known hypertensive (on amlodipine), non-diabetic, and non-smoker. He takes no NSAIDs or herbal medications. He has no prior history of renal or cardiac disease. On examination: Blood pressure 168/106 mmHg bilaterally. Pulse 96/min regular. Respiratory rate 22/min. JVP normal. Percussion note is stony dull at the right lung base with absent breath sounds; chest X-ray confirms a right pleural effusion. Both legs show 2+ pitting oedema to the knees. Urine dipstick: protein 3+, blood 3+, nitrite negative, leucocyte esterase negative. His wife also mentions, almost as an afterthought, that the couple has been trying to conceive for two years without success, and that Manohar's younger brother was recently told his thyroid 'is not working properly.'

Trigger 1: Red Urine and a Chest Full of Fluid

Urine dipstick: protein 3+, blood 3+. Urine appears smoky-brown. Urine specific gravity 1.028. Urine microscopy report: RBC >100/HPF — majority dysmorphic (acanthocytes); RBC casts present; granular casts present. Protein 3+ on dipstick. No bacteria or pus cells. Right pleural tap performed: 850 mL straw-coloured fluid removed. Pleural fluid biochemistry: protein 18 g/L, LDH 95 IU/L. Serum protein 58 g/L, serum LDH 310 IU/L. Serum albumin 22 g/L. Serum creatinine 2.8 mg/dL. Serum urea 68 mg/dL.

DISCUSSION POINTS

  • Manohar's urine microscopy shows dysmorphic RBCs and RBC casts. What do these two findings together tell you about the anatomical origin of his haematuria, and what underlying disease process do they indicate?
  • Apply Light's criteria to Manohar's pleural fluid and classify it as transudate or exudate. Now reconcile this with his serum albumin of 22 g/L — is there a contradiction, and how do you explain it?
  • Manohar's urine protein is 3+ on dipstick and his serum albumin is 22 g/L. What syndrome does this represent, and what is the pathophysiological mechanism linking the renal protein loss to his leg oedema and his pleural effusion?
  • Looking at his creatinine and urea together: what does the urea:creatinine ratio suggest about the type of renal dysfunction — and does his clinical picture fit prerenal, renal intrinsic, or postrenal pathophysiology?
Click to reveal Trigger 2: The FNAC Report and the Thyroid Brother (discuss previous trigger first!)

Trigger 2: The FNAC Report and the Thyroid Brother

A renal biopsy is recommended, but before it can be performed, Manohar is found to have a 1.8 cm nodule in the right lobe of the thyroid on incidental neck ultrasound. An FNAC of the thyroid nodule is performed under ultrasound guidance. Cytology report: 'Cellular smear showing follicular cells in macrofollicular pattern with abundant colloid; no nuclear grooves, nuclear inclusions, or nuclear crowding; no mitoses; background Hurthle cells noted. Bethesda Category II — Benign.' Manohar's brother (45 years old) presents the same afternoon requesting advice. He has fatigue, weight gain of 6 kg over one year, constipation, cold intolerance, and mild hair thinning. TFT panel: TSH 48 mIU/L (normal 0.4–4.0 mIU/L); free T4 3.8 pmol/L (normal 9–25 pmol/L); free T3 1.9 pmol/L (normal 3.5–7.8 pmol/L); anti-TPO antibody: strongly positive (>600 IU/mL).

DISCUSSION POINTS

  • The cytology report describes a Bethesda Category II thyroid FNAC. Describe the staining technique used for thyroid FNAC and the key cytological features that distinguish a benign nodule from a papillary carcinoma on a Pap-stained smear.
  • What is the advantage of FNAC over excision biopsy for thyroid nodule evaluation, and in what clinical situation would the cytology result require surgical follow-up despite a Category II benign report?
  • Interpret the brother's TFT panel: what is the pattern, what is the most likely diagnosis, and what is the autoimmune mechanism underlying this condition?
  • The brother has anti-TPO antibodies. Explain how this autoantibody arises in the context of the broader hypersensitivity classification — which type of hypersensitivity best describes this mechanism of thyroid damage?
Click to reveal Trigger 3: Semen Analysis, Renal Biopsy, and Putting It All Together (discuss previous trigger first!)

Trigger 3: Semen Analysis, Renal Biopsy, and Putting It All Together

Manohar's renal biopsy report: 'Light microscopy shows diffuse mesangial hypercellularity with capillary wall thickening; immune deposits confirmed by immunofluorescence (IgG, C3 granular subepithelial deposits — 'full house' pattern); electron microscopy shows 'humps' on the subepithelial aspect of the glomerular basement membrane.' Semen analysis is performed (WHO 2021 reference criteria): volume 2.1 mL; sperm concentration 7 × 10⁶/mL (RL ≥16); total motility 30% (RL ≥42%); progressive motility 18% (RL ≥30%); normal morphology 1% (RL ≥4%). Manohar is told his renal biopsy diagnosis, started on prednisolone and ACE inhibitor, and advised about prognosis. His wife asks whether his kidney disease is contributing to their fertility problem.

DISCUSSION POINTS

  • Using WHO 2021 criteria, classify Manohar's semen analysis abnormalities with the correct terminology for each parameter that falls below the reference limit. Which single parameter is most predictive of natural conception outcome?
  • The biopsy shows subepithelial immune deposits with IgG, C3, and electron-dense humps. Name the glomerulonephritis, explain the immunopathological mechanism of subepithelial complex deposition, and classify this by the Gell and Coombs hypersensitivity type.
  • Manohar's wife asks if his kidney disease explains their infertility. Explain the mechanisms by which nephrotic syndrome and the underlying immune disease could affect male fertility — consider both the systemic effects of nephrotic syndrome and any direct gonadal effects of the underlying disease.
  • Construct a systematic interpretation algorithm for a combined panel consisting of urinalysis (dipstick + microscopy) + LFT + RFT + TFT — describe the stepwise approach a clinician should take to interpret each panel and integrate the findings into a unified diagnostic conclusion.

Group Task Assignments

Group 1: Urine analysis — physical, chemical, and microscopic

  • Prepare a systematic approach to urinalysis interpretation: starting from physical properties (colour, appearance, specific gravity) through dipstick chemistry to microscopy findings (cells, casts, crystals). For each component, give one clinical disease example where that finding is the key diagnostic clue.
  • Construct a comparison table of nephritic versus nephrotic syndrome using the following axes: urine findings, proteinuria quantity, haematuria, oedema mechanism, and common causes.

Competencies: PA22.1

Group 2: Body fluid analysis — pleural, CSF, and synovial fluid

  • Apply Light's criteria to three hypothetical pleural fluid samples and classify each as transudate or exudate, then propose the most likely diagnosis for each. Include one case of cardiac failure, one of parapneumonic effusion, and one of malignant effusion.
  • Prepare a comparison table of normal versus bacterial meningitis versus viral meningitis versus TB meningitis CSF findings using the following axes: appearance, opening pressure, WBC count and type, protein, glucose, and glucose ratio.

Competencies: PA22.2

Group 3: FNAC technique, staining, and cytological criteria

  • Describe the standard FNAC technique including needle gauge, aspiration method, smear preparation, and immediate fixation — compare wet fixation (Pap stain) versus air-dry fixation (MGG stain) in terms of what each stain is best suited to demonstrate.
  • List the cytological criteria of malignancy (nuclear and cytoplasmic) that a pathologist looks for in a cytology smear, and explain how liquid-based cytology (LBC) improves on conventional smear preparation.

Competencies: PA7.1

Group 4: TFT and semen analysis interpretation

  • Describe the four main TFT patterns (primary hypothyroidism, primary hyperthyroidism, secondary hypothyroidism, subclinical hypothyroidism) using TSH/FT4/FT3 values, and give the most common Indian disease cause for each pattern.
  • Using WHO 2021 criteria, define the following semen analysis terminology: oligospermia, asthenospermia, teratospermia, oligoasthenoteratospermia (OAT syndrome) — and explain what percentage improvement in which parameter has the greatest clinical impact on fertility outcomes.

Competencies: PA22.3

Group 5: LFT and RFT panel interpretation

  • Construct a stepwise framework for interpreting a liver function test panel: identify the dominant pattern (hepatocellular vs cholestatic vs mixed), classify the jaundice type, and list three disease examples for each pattern.
  • Describe the use of serum creatinine, urea, urine sodium, and fractional excretion of sodium (FENa) in distinguishing prerenal AKI from intrinsic renal (ATN) AKI, and apply these criteria to two clinical scenarios.

Competencies: PA22.4, PA22.5

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [PA7.1] What are the techniques and staining methods used in cytology, what are the cytological criteria of malignancy, and what are the specific clinical applications and limitations of FNAC compared with histopathological biopsy?
  2. [PA22.1] How is urine analysed systematically from physical properties through dipstick chemistry to microscopy, and how do the patterns of urinary abnormality (dysmorphic RBCs, RBC casts, granular casts, waxy casts) correlate with specific renal diseases?
  3. [PA22.2] How are body fluids (pleural, peritoneal, CSF, synovial) classified as transudate versus exudate, what are Light's criteria, and how do the cellular and biochemical findings in each fluid type correlate with specific disease states?
  4. [PA22.3] What are the WHO 2021 reference limits for semen analysis, what terminology is used for each abnormality, and how are thyroid function test patterns interpreted to diagnose primary versus secondary thyroid disease?
  5. [PA22.4] What are the three functional groups of liver function tests, how are hepatocellular, cholestatic, and mixed patterns distinguished, and how is viral hepatitis serology interpreted in the context of acute versus chronic infection?
  6. [PA22.5] What do serum creatinine, urea, and eGFR measure, how are prerenal, renal, and postrenal causes of AKI distinguished, and what are the key differences between AKI and CKD on clinical and laboratory grounds?