Rapid Review·General Pathology
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NEOPLASIA
T1Must knowImmunohistochemical & Histochemical Stains, Liquid Biopsy
P223
Focus on
Using intermediate filaments to reveal a metastasis's origin, plus the special dyes that name a bug or a deposit.
Key takeaways
Immunohistochemistry
Why IHC exists
it determines the primary site of origin for a metastatic tumor and characterizes tumors that are otherwise impossible to classify. The intermediate filament a cell keeps making betrays the lineage it came from.| Stain | Target | Tumors Identified |
|---|---|---|
| Cytokeratin | Epithelial cells | Carcinomas, e.g. squamous cell carcinoma |
| Vimentin | Mesenchymal tissue | Sarcomas, but also endometrial carcinoma, RCC, meningioma |
| Desmin | Muscle | Rhabdomyosarcoma, leiomyosarcoma |
| GFAP | Neuroglia | Astrocytoma, glioblastoma |
| Neurofilament | Neurons | Neuroblastoma |
| Chromogranin and synaptophysin | Neuroendocrine cells | Small cell lung carcinoma, carcinoid, neuroblastoma |
| S-100 | Neural crest cells | Melanoma, schwannoma, Langerhans cell histiocytosis |
| PECAM-1 / CD31 | Endothelial cells | Angiosarcoma |
| PSA | Prostatic epithelium | Prostate cancer |
| TRAP | Tartrate-resistant acid phosphatase | Hairy cell leukemia |
Histochemical stains
Histochemical stains, each tied to one thing worth naming
- Acid-fast: Mycobacterium, Nocardia, Cryptosporidium parvum.
- Giemsa: Plasmodium, Trypanosoma, Leishmania, Borrelia, Chlamydia.
- H&E: nuclei blue (basophilic); cytoplasm and ECM pink (eosinophilic).
- India ink and mucicarmine: Cryptococcus neoformans. India ink gives a clear halo, mucicarmine stains the capsule red.
- Oil Red O and Sudan black: fat, used for fat emboli and fecal fat in steatorrhea.
- PAS: glycogen and mucin. Whipple disease is PAS-positive foamy macrophages in the lamina propria.
- Prussian blue: iron, for ringed sideroblasts, hemochromatosis, and hemosiderin-laden macrophages.
- Congo red: amyloid, with apple-green birefringence.
- Silver: H. pylori, spirochetes, Leishmania, Pneumocystis jirovecii.
Liquid biopsy and testing panels
Liquid biopsy
Liquid biopsy
a noninvasive test on blood or urine using circulating tumor DNA (ctDNA), ctRNA, or circulating tumor cells (CTCs).- Used for molecular profiling (EGFR in lung cancer), treatment monitoring, and post-treatment surveillance in colorectal cancer.
- Aids early metastatic detection and personalized therapy without a tissue sample.
Testing panels
Cancer testing panels and what each one predicts
- Tumor mutational burden: total mutations in the cancer, which predicts response to immune-checkpoint inhibitors.
- Microsatellite instability: assesses mismatch repair deficits, the hallmark of Lynch syndrome, and guides prognosis and treatment in colorectal and endometrial carcinoma.
- PD-L1 expression: in NSCLC and urothelial carcinoma, selects patients for anti-PD-1/PD-L1 therapy.
- Homologous recombination deficiency: BRCA-associated breast and ovarian cancer, which predicts response to PARP inhibitors through synthetic lethality.
A metastatic tumor in the liver stains positive for S-100 and negative for cytokeratin. Which primary tumor should you look for?
Melanoma. S-100 marks neural crest cells, and a negative cytokeratin argues against a carcinoma.
How it's tested
A poorly differentiated metastasis of unknown primary is the entire point of these stains: cytokeratin-positive means carcinoma; vimentin-positive means sarcoma; S-100-positive means melanoma or schwannoma; chromogranin or synaptophysin positive means neuroendocrine.
The classic vignette is an S-100-positive metastasis in a patient with no known primary. That is amelanotic melanoma, which need not be pigmented at all.
Go deeper
First Aid "Immunohistochemical stains" table; Pathoma Ch. 3. Anchor the origin map (cytokeratin = carcinoma, vimentin = sarcoma, desmin = muscle, GFAP = glia, chromogranin/synaptophysin = neuroendocrine, S-100 = neural crest) — the tool for typing an anaplastic "tumor of unknown origin."
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