Makindo Medical Notes

❓ Cancer of Unknown Primary (CUP) – a diagnosis where malignant cells are identified but the primary tumour site cannot be found. 🔍 In some patients, the primary lesion is never discovered despite extensive investigations.

📘 About

• Uncommon diagnosis, accounts for ~3–5% of all cancers.
• Primary tumour may be too small, destroyed by immune response, or removed during previous surgery.

⚙️ Aetiology

• Primary cancer may be very small and slow-growing.
• The immune system may have eradicated the original lesion.
• The primary tumour may have been excised incidentally during earlier surgery.

🧪 Cytology

• 🟨 Squamous cell carcinoma (~5%).
• 🟦 Undifferentiated carcinoma / neuroendocrine tumour (~30%).
• 🟥 Adenocarcinoma / poorly differentiated carcinoma (~65%).

🔍 Clinical Features

• Common metastatic sites: 🫁 chest, 🥼 adrenals, 🦴 bone, 🧠 brain.
• Ask about bowel and upper GI symptoms (colorectal, gastric origin).
• Full skin check 🩺 to rule out melanoma.

🧫 Pathology

• Excisional biopsy: Entire lump removed.
• Incisional biopsy: Portion of lump/tissue removed.
• Core biopsy (preferred): Tissue cylinder removed via wide needle.
• FNA: Cells/fluid aspirated via fine needle.

🧭 Investigations – “Hunting the Primary”

• 🧪 Bloods: FBC, U&E, LFTs, TFTs, PSA, directed tumour markers.
• 🖥️ CT chest/abdomen/pelvis with contrast.
• 🦴 Bone scan if symptoms suggest skeletal spread.
• 🧲 MRI chest/abdomen/pelvis (second-line for clarification).
• 🔥 PET-CT for metabolically active disease.
• 👩 Mammogram in women.
• 📹 Endoscopy (upper GI, colonoscopy) if symptoms or suspicion.
• 🎯 Directed tumour markers (CA-125, CgA, AFP, β-hCG, PSA).
• Core biopsy of most accessible lesion for histology & molecular analysis.

🧬 Immunohistochemistry (IHC) Panels – Common Markers

• 🩷 Breast: ER, GCDFP-15, mammaglobin, HER-2, GATA-3.
• 🫁 Lung: TTF-1, surfactant protein A, napsin A.
• 🧔 Prostate: PSA, PAP, AMACR.
• 🧬 Lymphoma: LCA, CD3, CD20, CD45, PAX5, Bcl-2, cyclin D1.
• 👩‍🦰 Ovarian/Müllerian: ER, WT-1, PAX8.
• 💪 Sarcoma: Desmin, CD31, SMA, MyoD1, myogenin.
• 🧠 Neuroendocrine: Chromogranin, synaptophysin, CD56.
• 🍼 Germ Cell: β-hCG, AFP, OCT3/4, CD30.
• 💧 Urothelial: CK7, CK20, GATA-3.
• 🍽️ Colorectal: CK7, CK20, CDX2, SATB2, CEA.
• 🩺 Renal: RCC, CD10, PAX8.
• 🧪 Hepatocellular: HepPar-1, Glypican-3, Arginase-1.
• ⚫ Melanoma: S100, HMB-45, SOX10.
• 🦋 Thyroid: Thyroglobulin, TTF-1, PAX8.

🩺 Management

• Multidisciplinary care via Oncology MDT is essential.
• Palliative chemotherapy may be considered in selected cases (e.g. responsive histologies).
• Supportive care – analgesia, symptom control, palliative services – is crucial for QoL.

📖 References

• MD Anderson – Cancer of Unknown Primary Algorithm