What Is Histopathology? A Complete Guide for Researchers and Clinicians

Histopathology is the microscopic examination of tissue to study the manifestations of disease. Whether you're diagnosing cancer, assessing organ damage, or validating a preclinical drug candidate, histopathology remains an essential tool in both clinical and research settings.

In this guide, we’ll explore what histopathology involves, how it differs from histology, the key techniques used, and its expanding role in modern biomedical science.

Low-magnification view of a mouse lung reveals multiple well-demarcated tumor nodules disrupting the normal alveolar architecture. The neoplastic foci are densely cellular with loss of normal parenchyma, consistent with multifocal pulmonary tumor development. Click the image to view Whole Slide Imaging.

What Is Histopathology?

Histopathology is a branch of pathology focused on examining biological tissues under a microscope to identify abnormal changes caused by disease. Through stained tissue sections, pathologists assess cellular and structural alterations that reflect inflammation, degeneration, neoplasia, or infection.

These insights are critical for clinical diagnosis and pharmaceutical R&D, where histopathology supports drug safety, efficacy, and tissue-level validation.

Wild-type PASD Staining

Disease Model PASD staining

Wild-type (left) and disease model (right) liver sections stained with PAS-D. The wild-type shows minimal PAS reactivity after diastase digestion, consistent with normal glycogen levels. In contrast, the disease model retains magenta staining, suggesting accumulation of diastase-resistant PAS-positive materials—possibly altered glycoproteins or mucopolysaccharides. Click the image to view Whole Slide Imaging.

Histology vs. Histopathology: What’s the Difference?

Although often used interchangeably, histology and histopathology refer to different concepts:

• Histology focuses on the normal microscopic anatomy of tissue.

• Histopathology examines tissue that has been altered by disease.

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For example:

• A histological study might describe the layered architecture of healthy colon epithelium.

• A histopathological study could reveal crypt abscesses or dysplasia in ulcerative colitis.

Understanding this distinction is critical in both research and diagnostic contexts.

A coronal brain section stained with the Golgi method reveals distinct neuronal morphology. Neurons and dendritic processes are clearly visible in the cortex, hippocampus, and subcortical regions, enabling high-resolution analysis of brain connectivity. Click the image to view Whole Slide Imaging.

The Histopathology Workflow: Step by Step

A standard histopathology pipeline includes:

1. Tissue Collection & FixationSamples are collected (e.g., biopsy or necropsy) and fixed in formalin to preserve structure.

2. Processing & Paraffin EmbeddingWater is removed and replaced with paraffin to stabilize the tissue for sectioning.

3. Sectioning (Microtomy)Thin slices (4–6 μm) are cut using a microtome and mounted on glass slides.

4. StainingThe most common is Hematoxylin and Eosin (H&E), but special and immunostains are frequently used.

5. Microscopic ReviewA trained pathologist evaluates slides for cellular abnormalities.

6. ReportingObservations are recorded in a histopathology report or annotated digitally.

   
   

At iHisto, this entire workflow is optimized for speed, consistency, and optional digital slide delivery.

Dual IHC staining highlights E-Cadherin (brown, DAB) in epithelial tumor cells and α-SMA (pink/red) in stromal myofibroblasts, clearly separating tumor and stromal compartments. Click the image to view Whole Slide Imaging.

Common Histopathology Techniques

🟣 H&E Staining

The gold standard for general morphology. Hematoxylin stains nuclei blue; eosin stains cytoplasm pink.

🟠 Special Stains

Used to highlight specific tissue elements like collagen (Masson's Trichrome), mucin (PAS), bacteria (Gram), or iron (Prussian Blue).

🟢 Immunohistochemistry (IHC)

Protein-level detection using antibodies, widely used in oncology, neuroscience, and immunology.

🔵 Digital Pathology & Whole Slide Imaging

Glass slides are scanned into high-resolution digital files for remote access, AI analysis, and archiving.

GFAP immunostaining (brown) reveals astrocytes and their processes in the mouse brain. The hematoxylin counterstain (blue) aids in tissue contrast. Click the image to view Whole Slide Imaging.

Why Histopathology Matters in Research & Biotech

Histopathology is essential for:

• Clinical Diagnosis: Cancer grading, inflammatory and autoimmune conditions

• Preclinical Research: Toxicology, efficacy, model validation

• Translational Science: Connecting molecular profiles with tissue phenotype

• Drug Development: IND-supporting studies, biomarker validation

• Biotech Outsourcing: Regulatory-ready CRO/CDMO support

At iHisto, combines expert pathology services with high-throughput capacity and rapid digital delivery.

The Future of Histopathology: Digital, AI-Powered, and Spatial

Histopathology is undergoing a digital transformation:

• AI Analysis: Tools like HALO and Aiforia deliver reproducible quantification

• Multiplex Imaging: Platforms like Akoya PhenoImager visualize dozens of biomarkers

• Spatial Biology: Resolves gene/protein data within tissue context

• Cloud Pathology: Enables remote collaboration and global consultations

These advances are reshaping histopathology into a precision data science platform.

Choosing the Right Histopathology Service Partner

When selecting a histopathology provider, look for:

✅ Expertise in complex staining and rare tissue types

✅ Rapid turnaround and high-volume throughput

✅ Whole Slide Imaging and AI compatibility

✅ Custom protocol support

✅ Batch-to-batch consistency

iHisto, based in the Boston area, serves biotech, academic, and CRO teams with high-quality histopathology from pilot to scale.

Conclusion

Histopathology remains one of the most powerful tools in modern biomedical science. Its ability to reveal cellular and structural disease changes is unmatched—and its impact only grows with digital pathology and AI.

Whether you're building disease models, validating drug candidates, or analyzing preclinical tissues, histopathology provides the cellular context that science demands.

Ready to accelerate your histopathology project?

Contact iHisto to learn how our digital histology solutions can move your research forward—from tissue to insight.

FAQ

What is histopathology used for?

Histopathology is used to examine tissue under a microscope to diagnose diseases, monitor treatment effects, and support biomedical research. It is essential in cancer diagnosis, drug development, and toxicology studies.

How is histopathology different from histology?

Histology refers to the study of normal tissue structure, while histopathology focuses on diseased or abnormal tissue. Histopathology reveals how disease alters cells and tissue architecture.

What stains are commonly used in histopathology?

The most common stain is hematoxylin and eosin (H&E). Other stains include PAS, Masson's trichrome, Prussian blue, and immunohistochemistry (IHC) markers like Ki-67 or CD3.

What is the histopathology process?

The process includes tissue fixation, paraffin embedding, sectioning, staining, and microscopic examination. Advanced labs also offer digital slide scanning and AI-assisted analysis.

Can histopathology be done digitally?

Yes, many labs scan slides into high-resolution whole slide images (WSI), enabling digital review, remote consultation, and AI-based quantification. This is known as digital pathology.