Does Neoplasm of Uncertain Behavior Mean Cancer?

A neoplasm of uncertain behavior is not cancer, but it is not clearly benign either. The label describes a tumor that a pathologist could not confidently place into the “definitely harmless” or “definitely malignant” category after examining it under a microscope. It sits in a gray zone between the two, which is why the diagnosis can feel so unsettling to receive. What it means for you depends heavily on where the tumor is, what it looks like at the cellular level, and what additional testing reveals over time.

What the Diagnosis Actually Means

When doctors classify a tumor, they assign it a behavior code. A code of 0 means benign, 2 means in situ (abnormal cells that haven’t spread), and 3 means malignant. Code 1 sits between benign and malignant, and that is the code assigned to neoplasms of uncertain behavior. Borderline and precursor thyroid tumors, for instance, were specifically assigned behavior code 1 because they are biologically indolent and do not behave like full-blown carcinomas, yet they are not entirely benign either.¹

The designation exists because biology does not always sort neatly into two buckets. A tumor can have some worrying features, like an unusual number of dividing cells or an atypical growth pattern, without meeting all the criteria for a malignant diagnosis. Pathologists looking at uterine smooth muscle tumors, for example, label them as having uncertain malignant potential when only one of the classic “red flag” features is present, rather than the full set required for a diagnosis of leiomyosarcoma.² The diagnosis is honest about a limit of current knowledge rather than forcing certainty where none exists.

Why Pathologists Cannot Always Tell

Under the microscope, tumors reveal clues about their nature: how fast cells are dividing, whether cells look abnormal, whether the growth invades surrounding tissue. For many tumors, these clues point clearly one way or the other. But some tumors send mixed signals. In melanocytic skin lesions, for instance, ambiguous features can make it genuinely difficult for even expert pathologists to agree on whether a growth is a benign mole, an atypical proliferation, or an early melanoma.³ These ambiguous lesions have been given dedicated terms like “melanocytic tumor of uncertain malignant potential” precisely because forcing a binary classification would be misleading.⁴

A study of melanocytic tumors found that only three microscopic features reliably distinguished tumors that eventually behaved aggressively from those that stayed quiet: the presence of dividing cells, dividing cells near the base of the tumor, and an inflammatory reaction. All three were more common in the tumors that later caused problems.⁵ That is a surprisingly short list, and it illustrates why pathologists sometimes cannot predict with confidence how a given tumor will behave.

How Often These Tumors Turn Out to Be Cancer

This varies enormously depending on the organ. One of the most concrete data sets comes from a breast unit that reviewed 92 cases initially diagnosed as neoplasms of uncertain behavior. After surgical excision and further pathological analysis, about two-thirds turned out to be benign, roughly a third turned out to be malignant, and a small fraction (around 3%) remained in the intermediate “malignant potential” zone. Among those with malignant results, about 69% needed a second surgery to fully control the disease.⁶

Those numbers are specific to one breast unit and one set of referral patterns, so they should not be taken as universal. But they illustrate an important point: the “uncertain behavior” label is a temporary holding category that often resolves once more tissue is examined. In many cases the answer is reassuring. In some it is not. The label itself does not predict the outcome so much as it flags that the outcome is not yet known.

Borderline Ovarian Tumors

Borderline ovarian tumors are one of the best-studied examples. They tend to appear in younger women, are usually caught at an early stage, and carry an overall favorable prognosis, with a ten-year survival rate around 95%.⁷ Compared to invasive ovarian cancer, these tumors behave much more gently. But “favorable” does not mean “risk-free.” About 11% of borderline ovarian tumors recur, and when they do, roughly one in four to one in three of those recurrences show a transformation into something more aggressive.⁸

What makes borderline ovarian tumors tricky is the long timeline. Recurrence and even death from the disease can show up as late as 20 years after initial treatment.⁹ This means that long-term follow-up is part of the deal, even when the initial outlook is excellent. Conservative surgery, where the uterus and at least part of one ovary are preserved, is considered safe and effective for women who want to maintain fertility. The biggest risk factor for recurrence from that approach is the conservativeness of the surgery itself, but recurrences after conservative surgery tend to be borderline again rather than invasive, making them treatable with good outcomes.

Uterine Smooth Muscle Tumors of Uncertain Malignant Potential

Uterine STUMPs are a distinct headache. These tumors sit between ordinary fibroids (leiomyomas, which are very common and benign) and leiomyosarcomas (which are rare and aggressive). A STUMP has some features that are worrying but falls short of a definitive sarcoma diagnosis. The management of STUMPs remains controversial, particularly for younger women who want to have children, because the tumors generally behave in a non-aggressive way and patients survive far longer than those with leiomyosarcomas.¹⁰

Patients diagnosed with a STUMP are typically counseled about the possibility that the tumor could recur, and that a recurrence could present as a leiomyosarcoma. Close surveillance, often more frequent than a standard annual exam, is recommended, sometimes with input from a gynecologic oncologist.¹¹

One factor that has drawn attention is how the tumor is removed. A systematic review found that unprotected morcellation, a technique that fragments the tumor during surgical removal, was independently associated with a nearly threefold increase in the risk of recurrence. Roughly 57% of patients who underwent hysterectomy with unprotected morcellation experienced a recurrence, compared to lower rates with other surgical approaches.¹² This finding has practical implications: if you are told you have a STUMP and surgery is planned, how the tumor is handled matters significantly for your long-term risk.

Skin and Thyroid Versions

The uncertain-behavior category pops up in many organs beyond the breast, ovary, and uterus. In dermatology, the terms MELTUMP (melanocytic tumor of uncertain malignant potential) and SAMPUS (superficial atypical melanocytic proliferation of uncertain significance) describe skin growths that resist easy classification as moles or melanomas.⁴ These diagnoses present a real challenge for dermatologists, who must decide how aggressively to excise or monitor a lesion when the pathology report does not give a clear answer.³

In the thyroid, a tumor formerly called “noninvasive encapsulated follicular variant of papillary thyroid carcinoma” was reclassified in 2016 and renamed NIFTP (noninvasive follicular thyroid neoplasm with papillary-like nuclear features). The word “carcinoma” was deliberately removed from the name because the tumor’s behavior did not warrant a cancer label.¹³ Before the reclassification, patients with this tumor were sometimes treated with total thyroid removal and radioactive iodine, the standard protocol for thyroid cancer. The reclassification opened the door to more conservative management, sparing some patients from aggressive treatments they did not need.¹ This is one of the clearest examples of how the uncertain-behavior label can directly protect patients from overtreatment.

How Treatment Decisions Are Made

Because the label spans such a wide range of tumors, there is no single treatment protocol. Treatment depends on the organ, the specific features the pathologist observed, and the patient’s age, fertility goals, and preferences. Across most sites, the approach leans conservative compared to how a confirmed malignancy would be treated, precisely because the tumor has not earned the full cancer diagnosis.

For borderline ovarian tumors, fertility-sparing surgery is considered safe for most women when paired with thorough staging.⁸ For thyroid borderline tumors, a lobectomy (removing half the thyroid) is often sufficient instead of total thyroidectomy followed by radioactive iodine.¹ For uterine STUMPs, the range extends from myomectomy (removing just the tumor) in women who want to preserve fertility, to hysterectomy in those who do not. The common thread is that surveillance after treatment tends to be longer and more vigilant than for a clearly benign tumor, reflecting the residual uncertainty about behavior.

Why Cancer Registries Track These Tumors

You might see references to neoplasms of uncertain behavior in cancer statistics, which adds to the confusion about whether the label means cancer. Cancer registries, the databases that track tumor incidence across populations, often include uncertain-behavior tumors in their records. Bladder cancer registries, for example, typically include both in situ and uncertain-behavior tumors alongside confirmed malignancies.¹⁴ This is done for completeness and surveillance, not because every uncertain-behavior tumor is considered cancer. But it does mean that if you are looking at bladder cancer incidence data from different countries, the numbers may not be directly comparable because some registries include these borderline tumors and others do not.

Genetic testing billing codes also use the “neoplasm of uncertain behavior” designation. When Medicare claims data were analyzed, this diagnosis code commonly appeared alongside orders for genetic and molecular tests, particularly in the context of blood cancers.¹⁵ In that context, the code is essentially a placeholder that says the clinical team is still working out what they are dealing with. It triggers testing that could help resolve the uncertainty, not a cancer treatment plan.

The Psychological Burden of an Ambiguous Diagnosis

Living with a diagnosis that says “we’re not sure” can be genuinely distressing. The medical system is built around decisive action: you have this, here is what we do about it. When the answer is “it might be something, it might not be, and we need to watch and wait,” the emotional toll is real. Research on cancer patients more broadly has found that when clinicians acknowledge and respond to patient uncertainty and negative emotions, patients report better mental health, better physical health, and less psychological distress.¹⁶

Effective communication between patients and providers is especially important for reducing uncertainty and promoting well-being.¹⁷ If you have received this kind of diagnosis, it is worth asking your doctor to explain, in concrete terms, what the specific risks are for your type of tumor, what the surveillance plan looks like, and what would trigger a change in approach. A named uncertainty with a plan is far easier to cope with than a vague sense that nobody knows what is going on.

Can Better Technology Resolve the Uncertainty

One reason this diagnostic category persists is that the tools pathologists have traditionally relied on, mainly looking at tissue under a microscope, hit a ceiling when tumors have ambiguous features. Several newer approaches are being tested to push past that ceiling.

For uterine STUMPs, researchers have begun exploring whether deep learning, a type of artificial intelligence, can predict which tumors will recur by analyzing features in tissue slides that human eyes might miss. A recent multicenter pilot study found that deep-learning-based features extracted directly from standard histological slides could help predict progression-free survival and identify high-risk patients, a task that has had limited success with other methods.¹⁸ The study is early-stage, but it points toward a future where the “uncertain” part of the diagnosis might shrink as computational tools get better at reading biological signals from tissue.

Molecular testing is another frontier. Tumors that look alike under the microscope can carry very different genetic mutations, and some of those mutations are strong indicators of whether a growth will behave aggressively. The reclassification of certain thyroid tumors from carcinoma to borderline was driven partly by molecular evidence showing that the genetic profile of these indolent tumors looked different from true papillary carcinomas.¹³ As molecular profiling becomes cheaper and more accessible, more tumors currently stuck in the “uncertain” category may get moved into definitive benign or malignant classifications.

When Diagnostic Errors Happen

The uncertain-behavior label is sometimes confused with a diagnostic error, but they are not the same thing. A pathologist assigning the label is being transparent about what the tissue shows. Actual diagnostic errors, where a growth is misclassified because something went wrong, are a separate concern. In dermatology and dermatopathology, errors can occur at multiple stages, from the biopsy technique and clinical judgment to the pathologist’s interpretation to how follow-up is managed afterward.¹⁹ Delayed melanoma diagnosis and incomplete biopsies are among the more common documented issues.

For a patient, the practical distinction matters. If you receive an uncertain-behavior diagnosis, asking for a second pathology opinion is reasonable and widely accepted in medicine, especially for tumors in the gray zone. A second set of expert eyes looking at the same tissue can sometimes resolve the ambiguity. When the ambiguity genuinely cannot be resolved, the uncertain-behavior label is the most honest answer available, and the right response is a surveillance plan, not a demand for a definitive classification that the biology does not support.

How Tumors Evolve Over Time

One reason that a tumor classified as uncertain today might behave differently years from now is that tumors are not static. They evolve. Cancer in general develops through repeated cycles of cells dividing, acquiring new genetic changes, and being selected for or against by the environment around them.²⁰ A tumor that currently sits in the borderline zone may, over time, accumulate mutations that push it toward malignancy. Or it may not. This is why surveillance matters even for tumors with a favorable prognosis and why borderline ovarian tumors, for instance, are followed for decades rather than years.

This biological reality also explains why removing tumors cleanly and avoiding fragmentation during surgery is so important for uncertain-behavior tumors. Scattering tumor cells during a procedure gives them new tissue environments to settle in, and those transplanted cells get their own chances to evolve. The elevated recurrence risk associated with unprotected morcellation in uterine STUMPs is likely tied to exactly this mechanism.

1
PubMed Central. How to handle borderline/precursor thyroid tumors in management of patients with thyroid nodules
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PubMed. Pathology of uterine leiomyosarcomas and smooth muscle tumours of uncertain malignant potential
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PubMed Central. Atypical Melanocytic Proliferations: A Review of the Literature
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Journal of the American Academy of Dermatology. Ambiguous melanocytic lesions: A retrospective cohort study of incidence and outcome of melanocytic tumor of uncertain malignant potential (MELTUMP) and superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) in the Netherlands
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The American Journal of Surgical Pathology. Melanocytic Tumors of Uncertain Malignant Potential
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PubMed Central. The Diagnosis, Treatment, Prognosis and Molecular Pathology of Borderline Ovarian Tumors: Current Status and Perspectives
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PubMed Central. Diagnosis, treatment, and follow-up of borderline ovarian tumors
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PubMed Central. Uterine smooth muscle tumors of uncertain malignant potential (STUMP): pathology, follow-up and recurrence
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PubMed. Uterine smooth muscle tumors of uncertain malignant potential: a case presentation
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PubMed Central. Recurrence of Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Systematic Review of the Literature
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PubMed Central. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a problematic entity
14
PubMed Central. Systematic review of population-based bladder cancer registries: How criteria heterogeneity affects the comparison of incidences
15
Nature. Utilization of genetic tests: analysis of gene-specific billing in Medicare claims data
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PubMed Central. Managing uncertainty and responding to difficult emotions: Cancer patients’ perspectives on clinician response during the COVID-19 pandemic
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PubMed Central. Examining the role of pre‐visit anxiety on patient uncertainty and breast cancer patient–provider communication
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PubMed. Deep Learning Can Accurately Predict the Prognosis of Gynecologic Smooth Muscle Tumors of Uncertain Malignant Potential: A Multicenter Pilot Study
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PubMed Central. Real-world Medicolegal Issues in Dermatology and Dermatopathology
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PubMed Central. Clonal evolution in cancer