What Do Lymphovascular (LVI) and Perineural Invasion (PNI) Mean in a Pathology Report?
In this article
If a pathology report says LVI (lymphovascular invasion) or PNI (perineural invasion), the pathologist saw tumor cells under the microscope inside a lymphatic or blood vessel or inside, around or along a nerve, respectively. This does not mean the cancer has spread; it means a route for spread exists and that the risk estimate changes accordingly. Both findings are linked to a less favorable course in many cancers; however, their meaning varies by cancer type and neither one decides treatment on its own. A report that says "not identified" does not mean the risk is zero either.
Who is this article for? Patients and relatives who see these terms in a pathology report, health professionals who read such reports, and anyone curious about how a pathology report is read. This article is not medical advice; no treatment decision should be made on the basis of this text. Only the oncologist and pathologist who follow you can assess what your report means.
What are LVI and PNI?
Both are findings the pathologist sees under the microscope in a tissue sample (a biopsy or surgical specimen); that is, a description, not a diagnosis. Spread of the tumor into the tissue around it (invasion) is a separate concept. LVI and PNI say that tumor cells have reached a specific structure, a vessel or a nerve.
| LVI (lymphovascular invasion) | Tumor cells seen inside a lymphatic vessel or a blood vessel. This general term is used when lymphatic and blood vessels cannot be told apart |
| Lymphatic invasion | Involvement of a lymphatic vessel only |
| Vascular invasion (angioinvasion) | Involvement of a blood vessel, usually a vein |
| LVSI | "Lymphovascular space invasion"; the term used instead of LVI especially in gynecologic cancer reports |
| PNI (perineural invasion) | Tumor cells seen inside, around or along a nerve. In many studies the definition is: tumor cells encircling at least one third of a nerve's circumference, or tumor cells in any of the three layers of the nerve sheath |
| How is it written in the report? | "Present / identified / positive", "not identified / absent / negative", or "indeterminate". In TNM staging, lymphatic invasion is coded L0/L1 and venous invasion V0/V1/V2 (0: not identified) |
One distinction matters: in breast cancer reporting standards, perineural invasion is not recorded as LVI; they are separate findings. PNI is also a microscopic finding. In some cancers, nerve involvement can cause symptoms such as pain, numbness or weakness; but "PNI present" in a report does not by itself say that such a symptom exists or will occur.
Why do these findings matter?
Vessels and nerves are possible routes of spread for tumor cells. In one source's words, LVI means not that the cancer "has spread" but that a route for spread exists and the likelihood is higher; some people with LVI never have spread, and some without LVI do. So both findings are a risk marker, not a definitive result.
- LVI is linked to a less favorable outcome in many cancers. It is said to raise the risk of lymph node spread in cancerous polyps and to be a recognized high-risk factor for recurrence in testicular germ cell tumors. In liver cancer (hepatocellular carcinoma), vascular invasion changes the stage itself.
- PNI has also been linked to worse outcomes in many cancers; but whether it is an independent prognostic factor is disputed in some cancers (for example prostate), because studies differ in definition and method.
- Both findings are assessed together with other information such as stage, grade, surgical margin status and lymph node result.
Reading guide: "LVI present" = tumor cells were seen inside a vessel, which may be a route of spread. "LVI not identified" = not seen in the sections examined; because only the sections submitted to the laboratory are examined, this does not rule out invasion with certainty. In either case, the weight of the finding varies with the cancer type and the other findings.
How does the pathologist identify these findings?
The findings are first looked for in routine sections stained with hematoxylin–eosin (H&E). But this assessment is not always easy: as tissue is processed, shrinkage can create a gap around a cluster of tumor cells that resembles a vessel (retraction artifact). This gap can look like a real vessel.
- When needed, immunohistochemistry is used: D2-40 shows lymphatic vessel endothelium, and CD31, CD34 and ERG show blood vessel endothelium. An elastic tissue stain may also be used to confirm a vein.
- The report has an "indeterminate" category; it can be chosen when the finding is probable but not certain.
- The international reporting guideline for breast cancer (ICCR) states that good fixation and processing are the main way to limit retraction artifact, that a routine H&E section is the best method, and that additional stains generally add little but may be considered in difficult, critical cases. Because D2-40 also stains myoepithelial cells, it does not resolve the confusion around in situ carcinoma.
| Method | Cases with LVI | Note |
|---|---|---|
| H&E alone | 25 (50%) | 13 of the 25 cases were not confirmed with D2-40 |
| D2-40 | 14 (28%) | Agreement with H&E: kappa 0.4 ("fair", limited agreement) |
Read this table with caution. The study is small and comes from a single center; it cannot be generalized to "half of the LVI seen on H&E is not real". What it shows is that the interpretation of LVI on a routine section can vary with the observer and the method. A practical guide for endometrium likewise notes that non-uniform criteria cause differences between observers and that vessel-like "pseudo-LVSI" appearances make diagnosis harder.
What it means by cancer type
The clinical weight of LVI and PNI is not the same in every cancer. The table below summarizes the points we could verify in the sources; each row is not the full guideline for that cancer type.
| Cancer type | Finding | What the sources say |
|---|---|---|
| Colon (stage II) | LVI, PNI | Among the high-risk features NCCN lists for stage II are lymphatic/vascular and perineural invasion (as relayed in a 2023 BMC Cancer paper, NCCN version 1.2022). Adjuvant chemotherapy is recommended for stage II patients with high-risk features; however, there is no high-quality evidence supporting the choice of chemotherapy by feature, and observation also remains an option |
| Endometrium | LVSI | Reported in two tiers: none/focal and substantial. Substantial LVSI is part of the 2023 FIGO staging and informs adjuvant treatment recommendations |
| Cervix | LVSI | A component of the intermediate-risk criteria (Sedlis) used for postoperative radiotherapy. We could not verify the criteria's thresholds in the sources we reviewed; therefore we did not write them |
| Breast | LVI | According to ICCR, LVI is an independent adverse predictor of local recurrence and survival; in stage IIA/IIB with axillary dissection it may affect the use of postoperative radiotherapy. Subclassifying as "extensive / limited" is optional because there is no agreed definition |
| Head and neck squamous cell cancers | PNI | NCCN (version 3.2021) lists vascular or nerve invasion among high-risk factors for postoperative radiotherapy; the ASCO 2019 consensus advises against neck radiotherapy in pN0/pN1 disease after adequate neck dissection unless there is an indication based on primary tumor features (for example PNI) (intermediate-level evidence) (as relayed in a 2022 Sci Rep paper) |
| Pancreas | PNI | According to a review it is common in pancreatic tumors; in patients with PNI, 5-year survival is reported as under 10% and the risk of liver metastasis as higher |
| Prostate | PNI | Linked to adverse clinicopathological parameters; its independent prognostic role is disputed because the studies' definitions and methods differ. The need for a more standardized definition is stressed |
| Intrahepatic cholangiocarcinoma | PNI | Seen in 20–31% of patients; linked to shorter overall survival and recurrence-free survival |
Colon cancer: PNI and LVI numbers
In the same retrospective multicenter series of 931 patients, PNI remained an independent factor for overall survival in multivariable analysis (HR 2.166; 95% CI 1.282–3.660). For disease-free survival it stayed borderline (HR 1.583; p=0.058). In the same study, the benefit of postoperative chemotherapy varied with the presence of PNI; no such interaction was found for LVI. The study is retrospective (100 disease-free survival and 71 overall survival events); the result does not determine what is recommended to an individual patient.
Endometrial cancer: what is called "substantial" LVSI?
Risk of pelvic lymph node recurrence, 5 years (%)
Patients who did not receive external beam radiotherapy in the PORTEC-1 and PORTEC-2 trials; by the number of vessels involved in LVSI.
The difference between 1–3 vessels and no LVSI was not significant (p=0.51); in the group with 4 or more vessels the difference was significant (p<0.001). Similar results were seen in the Danish Gynecological Cancer Database cohort. Bar lengths are drawn relative to the highest value.
One study proposed defining "substantial LVSI" as four or more LVSI-involved vessels in at least one H&E slide. This threshold is a numerical proposal offered to help pathologists, especially in borderline cases. Endometrial LVSI is strongly associated with lymph node metastasis; it is an independent risk factor for lymph node recurrence and distant metastasis.
Limits of the evidence. In breast cancer, a small retrospective series of 263 patients reported that what was independently associated with recurrence was vascular invasion, not lymphatic (recurrence: 5.5% in those with no invasion; 20.0% in those with both lymphatic and vascular invasion). By contrast, ICCR notes that lymphatic and blood vessels are hard to tell apart and that true blood vessel involvement in the breast is rare. So the evidence for interpreting by vessel type is still inconsistent. In cervical cancer, in a retrospective series of 861 intermediate-risk patients, LVSI was the only independent prognostic factor (LVSI together with deep stromal invasion: HR 1.88 for recurrence); but no significant difference in 5-year recurrence-free survival was seen between those who received postoperative additional treatment and those who did not (no additional treatment 87.1%, radiotherapy alone 84.2%, chemoradiotherapy 89.6%; p=0.27). This is the result of a single retrospective series and does not change guidelines.
How does it affect the treatment plan?
LVI or PNI alone does not determine treatment. Together with tumor type, grade, stage, surgical margin, lymph node status and other findings, it may lead the team to raise these questions:
- Should additional treatment after surgery (chemotherapy or radiotherapy) be considered?
- Is additional lymph node examination needed?
- Should follow-up be more frequent?
In some cancers the finding is directly part of the stage or of a written criterion (for example substantial LVSI in the endometrium, vascular invasion in liver cancer). In others it only refines the risk estimate. A finding regarded as unfavorable in one cancer should not be expected to carry the same weight in another.
Six common misunderstandings:
- "There is LVI, so the cancer has spread." No. LVI shows that a route of spread exists; it does not show the spread itself. Spread is assessed separately with lymph node results and imaging.
- "There is no LVI/PNI, so there is no risk." No. Not being identified in the sections examined does not rule out invasion with certainty.
- "PNI is present, so there will be nerve pain." No. PNI is a microscopic finding; it may cause no symptoms.
- "It means the same thing in every cancer." No. Its weight and how it is used differ in cancers such as colon, endometrium, head and neck, and pancreas.
- "The report is certain and unchangeable." The assessment can depend on the observer; in uncertain cases an additional stain or a second opinion may be requested.
- "The finding alone determines treatment." No. The decision is made by reading the whole report and the patient's situation together.
Questions you can ask your oncologist
If LVI or PNI appears in your report, you can ask:
- Does it say LVI/PNI was identified, not identified, or "indeterminate"?
- Which vessel type (lymphatic, venous) is involved? Could they not be told apart?
- Was an additional stain (immunohistochemistry) used for the result in the report?
- In cancers such as endometrial cancer: is the finding "focal" or "substantial"? How many vessels are involved?
- Were the lymph nodes examined, and what are the results?
- How does this finding affect my stage and treatment plan? Is additional treatment recommended, or is follow-up enough?
- If the report is uncertain, does it make sense to get a second pathology opinion?
The situation in Türkiye. For this article we did not check how LVI/PNI is reported in pathology laboratories in Türkiye, how additional stains are used, or access to second opinions; we have drawn no assumptions. The wording in a report can vary from laboratory to laboratory ("LVİ/PNİ", "lymphovascular invasion", "perineural invasion", "present/absent"). The best person to explain how to interpret the report is your oncologist, who works together with the pathologist. For the place of molecular tests in the other parts of the report, see our article on next-generation sequencing (NGS) (in Turkish), and for one way to reach new treatments, our article on taking part in clinical trials (in Turkish).
DROZDOGAN Academy Commentary
LVI and PNI are two small but meaningful lines of a pathology report: they give a clue about the routes by which a cancer can spread. But their weight varies by cancer type, the assessment can depend on the observer, and neither decides treatment on its own.
⚡ Why it matters
These two terms appear often in pathology reports and are easily misunderstood (this assessment is ours). Read correctly, they let the patient have a clearer conversation with the oncologist: the difference between "has spread" and "a route of spread exists" puts anxiety and questions about additional treatment in the right place.
✅ What is strong
For PNI in colon cancer, a large systematic review (58 studies, about 22,900 patients) reports a consistent unfavorable association. In the endometrium there is a numerical threshold (at least 4 vessels) based on PORTEC data, and substantial LVSI features in staging and treatment recommendations. In breast and head and neck, the reporting and guideline wording is clear.
⚠️ What is weak
Definitions and methods vary between studies; the assessment of LVI can differ between observers and distinguishing vessel type is hard. The independent role of PNI in prostate is disputed. Data on predicting response to additional treatment in colon are retrospective. In the sources we reviewed, some guideline thresholds (for example the cervical Sedlis criteria) could not be verified.
🩺 What it means in practice for patients and physicians
When you see these terms in a report, there is no need for panic, and false reassurance should not be sought either. What matters is in which cancer type, at which stage and together with which other findings the finding is interpreted. Taking questions to your oncologist in writing, and discussing a second pathology opinion if the report is uncertain, are reasonable steps.
❓ Open questions
In which cancers, and with what threshold, will the "extensive" versus "limited" distinction for LVI be standardized? In which cancers will the independent prognostic role of PNI become definite? Will AI-assisted assessment reduce the differences between observers? The answers to these questions are not in this article's sources.
Bottom line: LVI means tumor cells seen inside a vessel; PNI means tumor cells seen inside, around or along a nerve. Both are a marker of a route of spread and of risk, not of spread itself; they are interpreted according to cancer type and the other findings. A report that says "not identified" does not mean the risk is zero, and one that says "present" does not mean the cancer has spread.
Frequently asked questions
- What is LVI and what does it mean?
- It is tumor cells seen inside a lymphatic vessel or a blood vessel. It does not mean the cancer has spread; it shows that a route for spread exists and that the likelihood is higher.
- What is PNI?
- It is tumor cells seen inside, around or along a nerve. In many studies it is defined as at least one third of the nerve's circumference being encircled, or tumor cells being present in any layer of the nerve sheath.
- If there is LVI or PNI, has the cancer spread?
- No. Both are risk markers. Spread is assessed separately with lymph node results and imaging.
- If the report says LVI "not identified", is there no risk?
- No. Because only the submitted sections are examined, not being identified does not rule out invasion with certainty.
- If there is LVI or PNI, is chemotherapy needed?
- The finding alone does not decide. In stage II colon cancer it is counted among high-risk features and postoperative chemotherapy is discussed; this decision is made by the oncologist together with tumor type, stage and other findings.
- What does "substantial LVSI" mean in endometrial cancer?
- One study proposed defining it as four or more LVSI-involved vessels in at least one H&E slide. In this group the risk of pelvic lymph node recurrence after surgery is markedly higher (26.3% in those who did not receive radiotherapy, 3.3% in those without LVSI).
- What can be done if the report is uncertain?
- You can discuss with your oncologist whether an additional stain was used and whether getting a second pathology opinion is appropriate.
Glossary
- LVI (lymphovascular invasion)
- Tumor cells seen inside a lymphatic or blood vessel.
- LVSI
- Lymphovascular space invasion; used as the equivalent of LVI especially in gynecologic cancers.
- PNI (perineural invasion)
- Tumor cells seen inside, around or along a nerve.
- Invasion
- Tumor cells reaching the surrounding tissue or a specific structure (vessel, nerve) from where they started.
- Angioinvasion
- Invasion of a blood vessel (mostly a vein).
- H&E (hematoxylin–eosin)
- The routine stain used to examine tissue under the microscope.
- Immunohistochemistry
- A method that stains specific proteins in tissue with antibodies; markers such as D2-40 (lymphatic vessels) and CD31/CD34/ERG (blood vessels) are used.
- Retraction artifact
- A gap resembling a vessel that forms around a cluster of tumor cells from shrinkage during tissue processing.
- Stage II colon cancer
- A tumor that has advanced in the colon wall but has not reached lymph nodes; in this stage, features such as LVI and PNI are taken into account in deciding on additional chemotherapy.
- Postoperative (adjuvant) treatment
- Chemotherapy or radiotherapy given after surgery to reduce the risk of recurrence.
Transparency note. Verified: definitions of LVI and PNI, reporting categories and L/V codes (mypathologyreport.ca; ICCR breast guideline); the comparison of H&E and immunohistochemistry (Iranian Journal of Pathology, 2020, 50 cases); PNI and LVI frequencies in colon and HRs for PNI (Li et al., BMC Cancer 2023; the systematic review numbers are a citation relayed by this paper, the review itself could not be accessed); the threshold for substantial LVSI in the endometrium and the PORTEC rates (Peters et al., Int J Gynecol Pathol 2021; from the abstract page); the statement on 2023 FIGO and treatment recommendations (summary of the 2024 practical guidance by Gilks, Bosse et al.); references to NCCN and ASCO in head and neck (as relayed in Wang et al., Sci Rep 2022); the PNI review (Front Oncol 2025); the prostate PNI review (Cancers 2022, abstract only); the cervical series (Cao et al., Int J Gynecol Cancer, from the DOI it appears to be 2020). Secondary relay only: the NCCN and ASCO texts themselves could not be accessed; the statements were taken from the papers above. Not verified, and therefore not written in: the current full text of NCCN, ESMO and ASCO guidelines; the numerical thresholds of the cervical Sedlis criteria; the frequency of PNI in prostate and its place in treatment decisions; the frequency of PNI in pancreas (the review had no number); a separate code for PNI in TNM ("Pn") was not verified in these sources, so we wrote only the L and V codes; reporting practices in Türkiye; overlap with existing articles on drozdogan.com (not checked). Small inconsistencies: in breast cancer, a retrospective series of 263 patients (Anticancer Res 2014) found vascular invasion independent but not lymphatic invasion, while ICCR notes that distinguishing vessel type is difficult; the two should be read together. Also, ICCR says additional stains generally add little for the breast, while the small study from Iran reported that D2-40 did not confirm about half of the H&E findings; they may be addressing different questions. Assessments and commentary belong to this article. This article is not medical advice; no treatment decision should be made on the basis of this text.
References
- MyPathologyReport.ca. Lymphovascular Invasion (LVI): Definition. mypathologyreport.ca
- ICCR. Lymphovascular invasion in primary breast carcinoma (Core and Non-core). iccr-cancer.org
- Li K, Zhao F, et al. Interaction analysis of high-risk pathological features on adjuvant chemotherapy survival benefit in stage II colon cancer patients: a multi-center, retrospective study. BMC Cancer. 2023;23:797. bmccancer.biomedcentral.com
- Peters EEM, et al. Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer. Int J Gynecol Pathol. 2021. themednet.org
- Gilks CB, Bosse T, et al. Practical guidance for assessing and reporting lymphovascular space invasion (LVSI) in endometrial carcinoma. 2024. researchexchange.ocrahope.org
- Cao L, Wen H, Feng Z, et al. Role of adjuvant therapy after radical hysterectomy in intermediate-risk, early-stage cervical cancer. Int J Gynecol Cancer. ijgc.bmj.com
- Wang J, Su X, Zhang X, et al. Postoperative radiotherapy to the neck for pN1 status HNSCC patients after neck dissection. Sci Rep. 2022;12:13696. pmc.ncbi.nlm.nih.gov
- Significance and mechanisms of perineural invasion in malignant tumors. Front Oncol. 2025;15. frontiersin.org
- The Role of Perineural Invasion in Prostate Cancer and Its Prognostic Significance. Cancers. 2022. pmc.ncbi.nlm.nih.gov
- Vosough Z, Hosseini A, et al. D2-40 A Helpful Marker in Assessment of Lymphatic Vessel Invasion in Carcinoma of Breast. Iran J Pathol. 2020;16(2):96–102. pmc.ncbi.nlm.nih.gov
- Breast cancer vascular and lymphatic invasion and recurrence (retrospective, 263 patients). Anticancer Res. 2014;34(3):1255. ar.iiarjournals.org
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