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PA30.1-5 | Breast — PBL Case

CLINICAL SETTING

Suresh, a 55-year-old railway guard from a small town in Maharashtra, presents to the surgical OPD with a 6-month history of bilateral breast swelling that he has been hiding from his family, explaining it away as 'weight gain.' He is visibly embarrassed. He was diagnosed with hypertension and chronic heart failure two years ago and is on spironolactone 100 mg/day and digoxin. He does not drink alcohol. On examination, there is a 2.5 cm rubbery, firm retroareolar disc of tissue in the right breast and a 1.5 cm similar disc on the left — both are subareolar, mobile, and slightly tender. There are no skin changes, no nipple discharge, and no axillary lymphadenopathy. Meanwhile, his 26-year-old daughter, Priya, accompanies him. She had visited this same OPD last week with a rapidly enlarging right breast lump discovered three months ago; that biopsy result has now returned.

Trigger 1: Why is a Man's Breast Growing?

The surgical registrar reviews Suresh's medication list carefully. Spironolactone is an aldosterone antagonist widely used for heart failure; it also acts as an anti-androgen. His serum testosterone is in the low-normal range; oestradiol is normal for his age. Liver function tests are entirely within normal limits. A clinical breast examination confirms soft, bilateral subareolar glandular tissue without skin dimpling, nipple retraction, or fixity. Breast ultrasound shows bilateral hypoechoic, fan-shaped, subareolar tissue without a discrete mass, suspicious calcifications, or lymphadenopathy. Fine-needle aspiration of the right retroareolar disc yields a cellular sample showing proliferating ductal cells without atypia, surrounded by fibroblastic stroma.

DISCUSSION POINTS

  • Define gynaecomastia and distinguish it from pseudogynecomastia. What is the core hormonal imbalance that drives true gynaecomastia at the cellular level, and which receptor on ductal epithelial cells is the effector?
  • Spironolactone causes gynaecomastia in 10–20% of male patients on long-term therapy. Explain the pharmacological mechanism by which spironolactone shifts the oestrogen-androgen balance to produce breast ductal hyperplasia.
  • What are the two histological phases of gynaecomastia (florid and fibrous), and how does the ultrasound appearance of subareolar fan-shaped hypoechoic tissue reflect the underlying histopathological process?
  • List three other drug classes — beyond spironolactone — that commonly cause drug-induced gynaecomastia and give the mechanism for one of them. Why must clinicians rule out a testicular or adrenal tumour before attributing gynaecomastia to medication alone?
Click to reveal Trigger 2: Priya's Biopsy — A Different Story (discuss previous trigger first!)

Trigger 2: Priya's Biopsy — A Different Story

Priya's biopsy report is handed to the registrar. She is 26 years old and presented with a right breast lump that reached 6 cm in three months — unusually rapid growth for her age. Clinically, it was mobile, bosselated, and non-tender. The core needle biopsy showed leaf-like fronds of hypercellular stroma projecting into duct-like epithelial-lined spaces, with 14 mitoses per 10 high-power fields, stromal nuclear pleomorphism, and foci of stromal necrosis. The overlying epithelium is benign. No in-situ or invasive carcinoma is identified. A wide local excision with 1 cm margins is planned. Separately, a 55-year-old woman in the adjacent bed has just been told her core biopsy shows 'invasive lobular carcinoma' — she asks the ward medical student what that means.

DISCUSSION POINTS

  • Priya's biopsy describes a fibroepithelial tumour with leaf-like architecture and a hypercellular, mitotically active stroma. Using the WHO three-tier grading system for this tumour, assign a grade based on the five histological parameters, and state the appropriate surgical margin.
  • Contrast the phyllodes tumour and a fibroadenoma at each level: age of presentation, gross appearance, stromal cellularity, clinical behaviour, and recommended surgical management — explaining why simple enucleation is inadequate for phyllodes.
  • The 55-year-old woman's invasive lobular carcinoma infiltrates in single-file cords without forming a discrete mass. Explain the molecular basis of this growth pattern. Which protein is lost, what gene encodes it, and why does its loss cause cells to behave differently from ductal carcinoma?
  • The admitting clerk notes the woman's mammogram was reported as 'negative' 18 months ago despite a palpable lump. What property of invasive lobular carcinoma makes it mammographically occult, and what imaging modality is more sensitive for its detection?
Click to reveal Trigger 3: The Nipple Sign That Cannot Be Ignored (discuss previous trigger first!)

Trigger 3: The Nipple Sign That Cannot Be Ignored

The ward round proceeds to a 60-year-old retired schoolteacher, Kamala, who was referred by her family physician after four months of an eczematoid, crusting eruption of the right nipple-areola complex that did not respond to two courses of topical antifungals. She has no palpable breast lump. A punch biopsy of the nipple skin is taken. Histology reveals large, pale, vacuolated cells with prominent nucleoli scattered individually within the epidermis, without forming glands. ER staining of these intraepidermal cells is strongly positive. MRI of the breast identifies a 1.2 cm DCIS focus in the right subareolar region, with no invasive component. In the same corridor, a junior student asks about the difference between DCIS and LCIS, which the tutor uses as a teaching moment.

DISCUSSION POINTS

  • Kamala's biopsy shows intraepidermal malignant cells with pale vacuolated cytoplasm and strong ER positivity. Identify this condition and explain its pathological relationship to the underlying DCIS focus found on MRI.
  • Contrast DCIS and LCIS across five parameters: clinical presentation, mammographic detectability, laterality risk, malignant potential, and histological appearance (including the key feature that distinguishes LCIS cells from DCIS cells).
  • The Nottingham grading system for invasive breast carcinoma scores three histological features. Name the three features, their scoring range, and the total score thresholds that define Grade 1, 2, and 3 — and explain why grade is a stronger independent prognostic factor than tumour size alone in node-negative disease.
  • A patient's IHC results return: ER 85%, PR 60%, HER2 1+ (IHC), Ki-67 5%. Assign the molecular subtype, predict the likely response to endocrine therapy versus chemotherapy, and explain what additional test would be needed if HER2 were reported as 2+ instead of 1+.

Group Task Assignments

Group 1: Gynaecomastia — pathogenesis and drug causes

  • Construct a systematic clinical algorithm for evaluating a male patient presenting with bilateral breast enlargement, including the questions to ask (drugs, liver disease, testicular mass, age), investigations to order, and when to biopsy.
  • List and categorise by mechanism the ten most common drug causes of gynaecomastia in India (including spironolactone, digoxin, antipsychotics, anti-androgens, ketoconazole).

Competencies: PA30.4

Group 2: Phyllodes tumour grading and fibroepithelial tumour distinction

  • Draw a side-by-side comparison of fibroadenoma and phyllodes tumour on gross and microscopic morphology, clearly labelling the leaf-like architecture and stromal cellularity that distinguishes them.
  • Apply the WHO five-parameter grading system to three hypothetical cases and justify the grade assigned for each; include the implication for surgical margin in each case.

Competencies: PA30.1, PA30.3, PA30.5

Group 3: Invasive breast carcinoma subtypes and molecular classification

  • Construct a table of invasive breast carcinoma subtypes (IDC NST, ILC, medullary, mucinous, tubular, inflammatory, Paget disease) with one distinguishing gross, one microscopic, and one clinical feature per subtype.
  • Map IHC results (ER, PR, HER2, Ki-67) to the four molecular subtypes (Luminal A, Luminal B, HER2-enriched, Triple-negative/TNBC) and indicate the primary treatment strategy for each.

Competencies: PA30.2, PA30.5

Group 4: Prognostic factors and TNM staging of breast carcinoma

  • Apply the Nottingham Histological Grade to a descriptive case and calculate the total score; explain why grade, nodal status, and hormone receptor status together outperform tumour size as a prognostic predictor.
  • Stage three hypothetical breast carcinoma patients using the AJCC anatomic TNM 8th edition and identify which factors would move a patient from Stage II to Stage III.

Competencies: PA30.2

Group 5: Benign breast disease and triple assessment

  • Describe the triple assessment framework (clinical examination, imaging, pathology) and the 1–5 grading scale, explaining what grade 3 (equivocal) demands in clinical practice.
  • Identify the three benign breast conditions that mimic carcinoma on clinical examination and imaging (fat necrosis, periductal mastitis, radial scar) and explain the distinguishing pathological feature of each.

Competencies: PA30.1, PA30.5

Learning Issues

Research these questions and bring your findings to the discussion.

  1. [PA30.1] What is the hormonal basis, pathological spectrum, and clinical presentation of benign breast diseases including fibrocystic change, fibroadenoma, intraductal papilloma, acute mastitis, and fat necrosis?
  2. [PA30.2] What are the epidemiology, molecular pathways, in-situ lesions (DCIS and LCIS), invasive subtypes, Nottingham grading criteria, IHC-based molecular classification, TNM staging, and routes of spread of breast carcinoma?
  3. [PA30.3] What distinguishes a phyllodes tumour from a fibroadenoma on gross and microscopic morphology, and how does the WHO three-tier grading system determine surgical management?
  4. [PA30.4] What is the pathogenesis of gynaecomastia, which drugs and systemic conditions produce it, and what are the histological appearances of the florid and fibrous phases?
  5. [PA30.5] What are the key gross and microscopic morphological features that allow identification of fibroadenoma, phyllodes tumour, DCIS, LCIS, invasive ductal carcinoma NST, invasive lobular carcinoma, and Paget disease of the nipple on pathology slides?