What Is Histopathology? A Complete Guide for Preclinical Research

Histopathology is the microscopic examination of biological tissues to observe the cellular changes caused by disease. Whether you are validating a preclinical drug candidate, assessing organ toxicity, or diagnosing cancer, histopathology remains the gold standard in both clinical and pharmaceutical research settings.

In this guide, we’ll explore the complete histopathology workflow, clarify how it differs from routine histology, break down key staining techniques (like H&E and IHC), and discuss 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 (derived from the Greek histos for tissue) is a specialized branch of pathology. Unlike cytopathology, which examines loose cells, histopathology preserves the tissue architecture, allowing pathologists to see how cells interact with their surrounding environment.

Through the analysis of stained tissue sections (typically biopsies or surgical resections), experts can identify specific morphological changes—such as inflammation, necrosis, fibrosis, or neoplasia. In the context of pharmaceutical R&D, these tissue-level insights are indispensable for validating preclinical drug safety and efficacy before human trials begin.

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 in casual conversation, histology and histopathology serve distinct purposes in the research pipeline:

• Histology focuses on the normal microscopic anatomy of tissue. It provides the essential baseline for what "healthy" looks like.

• Histopathology examines tissue that has been altered by disease or experimental treatment.

Feature	Histology	Histopathology
Primary Focus	Normal, healthy tissue anatomy	Diseased tissue & cellular abnormalities
Key Objective	To establish a baseline reference	To diagnose disease or assess drug toxicity
Research Application	Basic biology, atlas creation	Cancer research, efficacy studies, toxicology
Typical Observation	Regular cell layers & structures	Inflammation, necrosis, tumors, fibrosis

For example: A routine histology study might describe the organized, layered architecture of a healthy colon epithelium. In contrast, a histopathological analysis would identify specific disruptions—such as crypt abscesses in ulcerative colitis or tumor margins in an oncology study.

Why It Matters: Understanding this distinction is critical. In preclinical studies, you often need high-quality histology to prove your controls are healthy, and precise histopathology to quantify how well your drug treats the disease.

Golgi-stained coronal brain section showing normal neuronal morphology — a prime example of Histology. 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 & Fixation

   Samples are collected (e.g., biopsy) and fixed in formalin to create FFPE blocks, preserving tissue structure.

2. Processing & Embedding

   Water is removed and replaced with paraffin to stabilize the tissue for precision cutting.

3. Sectioning (Microtomy)

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

4. Staining

   While H&E is the gold standard, advanced research often requires Immunohistochemistry (IHC) or Special Stains.

5. Microscopic Review

   A board-certified pathologist evaluates the slides for cellular abnormalities.

6. Reporting

   Observations are recorded in a detailed report or digitized via Whole Slide Imaging for remote access.

   
   

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, we combine 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 today to discuss your study design and receive a custom proposal.

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.