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PA33.1-4 | Skin — Case Study

CLINICAL SCENARIO

A 68-year-old male farmer presents with a 3-month history of a slowly enlarging, irregularly pigmented lesion on the back of his left hand. He reports years of outdoor work without sun protection. The lesion has areas of ulceration and a raised, pearly border on one margin. This case-study assignment asks you to work through the differential diagnosis of common skin tumours — squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and malignant melanoma — using clinical features, histopathological reasoning, and molecular pathogenesis.

You will present a structured clinico-pathological analysis: synthesise the history and morphology into a prioritised differential, predict the expected histology for your leading diagnosis, apply ABCDE criteria and Breslow/Clark staging where relevant, explain the underlying molecular events (UV-induced DNA damage, TP53, PTCH1, or BRAF/NRAS pathways), and appraise the natural history and metastatic risk. The assignment is designed for peer review: a classmate will evaluate your reasoning and provide constructive feedback before faculty assessment.

Instructions

  1. Read the clinical vignette carefully. Note the patient's age, occupation, anatomical site, lesion duration, morphological features (pigmentation, ulceration, border character), and any implied risk exposures.
  1. Complete each scaffolded section in order (see Scaffolding Sections below). Use your own words; do not copy textbook definitions verbatim.
  1. Section 1 — Clinical Summary: Summarise the key positive and negative findings from the history and examination in no more than 100 words. Identify the three most likely diagnoses in descending order of probability with a one-sentence justification for each.
  1. Section 2 — Differential Diagnosis Reasoning: Discuss the distinguishing clinical features of BCC, SCC, and malignant melanoma that support or argue against each diagnosis in this patient. Use the ABCDE criteria (Asymmetry, Border, Colour, Diameter, Evolution) where applicable.
  1. Section 3 — Histopathology: State your leading diagnosis and describe the expected microscopic findings on H&E-stained biopsy. For BCC, describe palisading basaloid cells and retraction artefact. For SCC, describe dysplastic squamous cells, keratin pearls, and invasion pattern. For melanoma, describe atypical melanocytes, pagetoid spread, and dermal invasion. Report Breslow thickness and Clark level if melanoma is your leading diagnosis.
  1. Section 4 — Molecular Pathogenesis: Explain the molecular mechanism most relevant to your leading diagnosis. Cover at least two of the following: UV-induced C→T transitions at dipyrimidine sites, TP53 loss-of-function in SCC, PTCH1/Hedgehog pathway disruption in BCC, BRAF V600E / NRAS mutations in melanoma, and the role of immunosuppression or chronic inflammation.
  1. Section 5 — Natural History and Metastatic Risk: Describe the expected biological behaviour of your leading diagnosis. Include typical local growth pattern, risk of regional lymph node involvement, and distant metastatic potential. Compare briefly with the metastatic risk of the other two diagnoses on your differential.
  1. Section 6 — Management Implications of Pathological Diagnosis: State one key management decision that hinges on the pathological diagnosis (e.g., margin assessment for excision, sentinel lymph node biopsy for melanoma >1 mm Breslow, Hedgehog inhibitor eligibility for locally advanced BCC).
  1. Section 7 — Peer Review Response (complete AFTER receiving peer feedback): Summarise the feedback you received, state whether you agree or disagree with each point, and describe any revision you made to your reasoning.
  1. Word limit: 600–900 words across Sections 1–6. Section 7 is additional (not counted in the word limit). Submit as a single document with clearly labelled section headings.

Length: 600–900 words (Sections 1–6). Section 7 is additional and not counted.

What to Submit

Section 1 — Clinical Summary

Summarise the key clinical findings in 3–5 sentences. Rank your top three diagnoses in order of probability and give a one-sentence rationale for each ranking based on the patient's age, site, morphology, and exposure history.

Section 2 — Differential Diagnosis Reasoning

Systematically compare BCC, SCC, and malignant melanoma for this lesion. Apply the ABCDE criteria where relevant. Identify the single clinical feature in this vignette that most strongly favours your leading diagnosis over the others.

Section 3 — Histopathology

Describe the microscopic findings you would expect on the biopsy of your leading diagnosis. Be specific: name the cell types, architectural patterns (e.g., islands, nests, sheets), and at least two characteristic microscopic features. If melanoma is your leading diagnosis, report the Breslow thickness category that would change management and the corresponding Clark level.

Section 4 — Molecular Pathogenesis

Explain the two-step or multi-step molecular pathway driving your leading diagnosis. Identify the initiating DNA lesion caused by chronic UV exposure, the key tumour suppressor or oncogene involved, and how these changes lead to uncontrolled proliferation or invasion.

Section 5 — Natural History and Metastatic Risk

Describe the biological behaviour of your leading diagnosis from initiation to potential metastasis. Compare its metastatic risk qualitatively (low / moderate / high) with the other two diagnoses on your differential. Name the most likely route of spread (lymphatic vs haematogenous) if dissemination occurs.

Section 6 — Management Implications of Pathological Diagnosis

Identify ONE management decision that depends critically on the pathological diagnosis and staging. Explain the specific threshold or criterion (e.g., Breslow >1 mm for SLNB, surgical margin width for SCC, BRAF V600E mutation testing for systemic therapy eligibility) and why accurate histopathology is essential for this decision.

Section 7 — Peer Review Response

After receiving your peer's assessment form: (a) list the two strongest pieces of feedback, (b) state whether you agree or disagree with each and why, and (c) describe any specific change you made — or would make — to your analysis as a result.

Grading Rubric — Skin Case Study Rubric
Criterion Points Full-marks descriptor
Differential Diagnosis Reasoning — Applies clinical features (ABCDE, site, patient profile) to construct and justify a prioritised differential; distinguishes BCC, SCC, and melanoma on evidence, not pattern-matching. 8 pts All three diagnoses addressed with specific evidence from the vignette; ABCDE criteria applied correctly; leading diagnosis clearly justified against the other two with nuanced clinical reasoning.
Histopathological Accuracy — Correctly describes the microscopic features of the leading diagnosis, including cell morphology, architectural pattern, and at least two diagnosis-specific features; Breslow/Clark included when melanoma is chosen. 7 pts Accurate and specific histopathology with correct cell types, architectural features (e.g., palisading and retraction for BCC; keratin pearls and invasion for SCC; pagetoid spread and Clark/Breslow for melanoma); language is precise and consistent with H&E interpretation.
Molecular Pathogenesis — Explains the UV-damage initiation step and the key molecular pathway (TP53 / PTCH1-Hedgehog / BRAF-NRAS-MAPK) appropriate to the leading diagnosis, with a mechanistic link to tumour behaviour. 6 pts Correct UV-induced mutation type (C→T at dipyrimidines) stated; appropriate pathway identified (e.g., PTCH1 loss → unrestrained Hh signalling → BCC); mechanism links molecular change to the hallmark behaviour (proliferation, invasion, or immune evasion); no factual errors.
Natural History and Metastatic Risk — Accurately characterises the biological behaviour and metastatic potential of the leading diagnosis and compares it with the other two tumours. 4 pts Local growth pattern, route and risk of nodal spread, and distant metastatic potential all described accurately for the leading diagnosis; comparison with BCC/SCC/melanoma is qualitatively correct (e.g., BCC almost never metastasises; SCC ~2–5% regional; melanoma varies with Breslow); route of spread correctly identified.
Management Implication of Pathological Diagnosis — Identifies a specific, evidence-based management decision that is contingent on pathological diagnosis or staging, with a clear threshold or criterion stated. 3 pts A concrete, correct management decision is identified (e.g., SLNB for melanoma >1 mm Breslow; wide local excision margin 4–6 mm for SCC vs 3–4 mm for BCC; Vismodegib/Sonidegib eligibility for advanced BCC; BRAF V600E testing for stage III–IV melanoma); the specific criterion or threshold is stated and correctly linked to pathology.
Peer Review Quality — Engages constructively with peer feedback: accurately summarises the feedback received, provides a reasoned agree/disagree response, and describes a concrete revision or explains why none is warranted. 2 pts Peer feedback accurately summarised for both points; agree/disagree decision supported by a specific medical or reasoning argument for each; a concrete revision is described or a well-justified reason for no change is given.

PEER REVIEW

You will be assigned one classmate's submission anonymously. Read their work in full before scoring. Use the assignment rubric to evaluate each criterion independently — do not adjust scores based on overall impression. For each criterion, write 2–3 sentences: (1) state what they did well, (2) identify the most important gap or error, and (3) suggest a specific improvement. Avoid vague praise ('good work') and avoid rewriting their answer for them. Your feedback will be read by the author before faculty grading, so aim for accuracy and professional tone. Your own grade for this peer-review component is based on the quality of your feedback, not on how the author responds to it.