Molecular testing has moved from specialist referral to everyday cancer care, yet in many laboratories it still sits outside the routine anatomic pathology workflow. This article is for pathologists, lab managers and molecular scientists who want to bring molecular pathology into the routine workflow, from block selection to the integrated report.
Why molecular pathology belongs in the routine workflow
When molecular testing is treated as a separate service, problems appear at the joins. Blocks are selected without enough information, requests are lost between departments, results return on a different report from the morphology, and clinicians have to assemble the picture themselves.
An integrated workflow treats molecular testing as a continuation of the diagnostic process. The pathologist who makes the diagnosis is usually the person best placed to choose the right block, judge tumor content, and interpret molecular findings in the context of morphology and immunohistochemistry.
Pre-analytic factors start at the bench
The quality of molecular results depends heavily on what happened to the tissue long before extraction.
Fixation
Formalin fixation preserves morphology but chemically modifies and fragments nucleic acids. Delayed or prolonged fixation can further degrade DNA and RNA. Consistent fixation practices, and recording fixation details, support both biomarker testing and molecular analysis.
Decalcification
Strong acid decalcification can severely damage nucleic acids. For bone specimens that may need molecular testing, many laboratories prefer gentler methods such as EDTA-based decalcification, or keep a portion of tissue undecalcified when possible. These decisions are made at grossing, so grossing staff need to know which cases are likely to need molecular work. The bench habits in grossing best practices apply here.
Small biopsies
Lung, pancreas and other small biopsies may need diagnosis, immunohistochemistry and molecular testing from very little tissue. Ordering thoughtfully, cutting efficiently and avoiding unnecessary stains help preserve material for the tests that matter most.
Selecting the right block and tissue
Choosing material for molecular testing is a diagnostic act. The pathologist should:
- Select the block with the most viable tumor and the least necrosis.
- Estimate tumor cellularity in the selected area, since many assays have minimum tumor content requirements.
- Mark the area for macrodissection when tumor occupies only part of the section.
- Note factors that could affect the result, such as extensive necrosis, crush artifact or decalcification.
- Record which block and slides were sent, so the choice can be reviewed later.
Tumor cellularity estimates are known to vary between observers. Simple measures, such as agreeing how to estimate, reviewing difficult cases together and calibrating periodically, improve consistency.
Ordering and tracking molecular tests
Who orders, and when
Some institutions use reflex testing, where defined diagnoses automatically trigger certain molecular tests. Others rely on clinician or pathologist requests. Reflex protocols reduce delays and missed tests but must be clearly defined and agreed with oncology. Whichever model you use, write it down and make it visible to everyone involved.
Tracking across sections and laboratories
Molecular work often happens in a separate section or an external reference laboratory. That creates a tracking problem: blocks leave, slides are cut, extracts are created, and results come back days or weeks later.
- Register the molecular request against the original case.
- Track blocks and slides sent out, and their return.
- Record sample adequacy decisions.
- Link the returned result to the case automatically where possible.
- Alert the pathologist and clinician when results arrive.
Integration with hospital and reference laboratory systems reduces manual transcription, which is a known source of error for long variant descriptions. The options are discussed in integrating the LIS with hospital systems.
Interpreting and reporting molecular results
Molecular reports should be understandable to clinicians who are not molecular specialists. Good practice includes:
- Standard nomenclature. Variants are commonly described using HGVS nomenclature, which supports unambiguous communication.
- Clinical significance. For somatic variants in cancer, joint consensus recommendations from AMP, ASCO and CAP describe a tiered approach to classifying clinical significance.
- Limitations. State the assay type, what it can and cannot detect, and any sample-related limitations such as low tumor content.
- Context. Relate molecular findings to the morphology and immunohistochemistry.
Molecular results often complement or confirm immunohistochemistry. Discordance between the two deserves review, and well-run immunohistochemistry workflow management makes it easier to trace both results back to their source material.
The integrated report
An integrated report presents histology, immunohistochemistry and molecular findings together, with an overall interpretation. Some tumor classifications now combine morphologic and molecular features in the diagnosis itself, which makes integration a necessity rather than a courtesy. When molecular results arrive after the initial report, issue a clearly labeled addendum and notify the clinician.
Quality management for molecular pathology testing
Molecular assays require their own validation, controls and external quality assessment, in addition to the general quality system. Practical points:
- Validate each assay for the specimen types you accept, including small biopsies and cytology material if applicable.
- Monitor failure rates and their causes, such as insufficient tumor or poor nucleic acid quality.
- Track turnaround time from request to integrated report, not just laboratory processing time.
- Review cases where molecular and morphologic findings disagree.
Failure rates in particular point back to pre-analytic steps, which is why molecular quality cannot be separated from grossing and histology. A rise in failed extractions is often the first visible sign of a fixation or decalcification problem upstream.
Share those findings with the whole chain. Grossing staff and histotechnologists rarely see what happens to the blocks they prepare once they leave for molecular testing, and a short regular summary of failures and their causes closes that loop.
Key takeaways
- Treat molecular testing as part of the diagnostic workflow, not a separate service.
- Fixation and decalcification choices made at grossing directly affect molecular results.
- Block selection, tumor cellularity and macrodissection are pathologist decisions to document.
- Track requests, blocks and results across sections and external laboratories.
- Report with standard nomenclature, clear limitations and an integrated interpretation.
Bringing molecular pathology into routine work is mainly about connecting steps that already exist. PATHOLOGY+ links case registration, specimen and block tracking, and reporting with addenda in one platform; book a demo to see it with your own workflow in mind.