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Diagnostics2026-06-22 · 22 min read

Mast Cell Tumors in Dogs: Grading, When to Worry, and What Treatment Actually Costs

Clinical guide to canine mast cell tumors (MCTs). Understand Patnaik vs. Kiupel grading, staging, surgical resection vs. Stelfonta vs. Palladia, openFDA adverse event data, and cost comparisons.

Ran Chen
Ran Chen
Founder, VetMedGuide. Life-sciences operator and 10× global market-access lead.
Published

Mast cell tumors (MCTs) represent the most common cutaneous malignancy in dogs, accounting for up to 21% of all skin cancers in canine patients. These tumors are often called the "great imitators" because they can present in a bewildering variety of shapes, sizes, and appearances—ranging from small, benign-looking hairless bumps to large, ulcerated, or fluctuating masses. For both veterinary professionals and dog owners, a diagnosis of a mast cell tumor starts a complex decision-making process. The central questions are: How aggressive is this tumor? Has it spread? What is the best treatment path? And what will it realistically cost?

To navigate these questions, veterinary teams rely on a combination of cytological diagnostics, histopathological grading, clinical staging, and targeted therapeutics. While surgical excision remains the cornerstone of local control for many tumors, newer medical advancements—specifically the intratumoral agent tigilanol tiglate (Stelfonta) and the small-molecule tyrosine kinase inhibitor toceranib phosphate (Palladia)—have significantly expanded the oncology toolkit.

This clinical guide provides a comprehensive overview of canine cutaneous mast cell tumors. We detail the mechanics of Patnaik vs. Kiupel grading, outline the standard staging workup, compare the primary treatment pathways, present a real-world cost map, analyze pharmacovigilance data from openFDA, and answer critical client questions.

Quick answer

Canine mast cell tumors (MCTs) are graded histologically via the Patnaik (I-III) and Kiupel (Low/High) systems. Low-grade/Patnaik I-II tumors have an excellent prognosis with surgical excision alone (median survival >3 years, metastasis <10%). High-grade/Patnaik III tumors have high metastatic potential (55-96%) and a median survival of 2-4 months. Treatment pathways range from surgical resection ($1,000–$3,500) to intratumoral injection of Stelfonta ($800–$1,500 per vial, yielding 75% complete response in one injection and 87-88% with two) or oral Palladia maintenance ($300–$600/month). Analysis of 1,062 openFDA Palladia dog reports highlights diarrhea (21.00%), vomiting (18.17%), and anorexia (15.44%) as the top adverse reactions, while 1,916 Stelfonta reports show lack of efficacy (44.36%), injection site swelling (35.07%), and wounds (20.15%).

Anatomy and Pathology of Mast Cells

To understand mast cell tumors, one must understand the normal cell of origin. Mast cells are specialized granulocytes derived from bone marrow hematopoiesis that migrate into tissues, primarily residing at interfaces between the internal and external environments, such as the skin, gastrointestinal tract, and respiratory tract. Under normal physiological conditions, mast cells are central to the immune system's response to allergens and parasites. They contain abundant cytoplasmic granules rich in bioactive substances, including histamine, heparin, proteolytic enzymes (such as chymase and tryptase), and various pro-inflammatory cytokines.

When a mast cell degranulates, these chemical mediators are released into the surrounding tissue. Histamine binds to H1 and H2 receptors, causing localized vasodilation, increased vascular permeability, pruritus (itching), and gastric acid secretion. Heparin interferes with the local coagulation cascade. Proteases degrade the extracellular matrix.

In neoplastic mast cells, these degranulation events can be triggered by minor physical manipulation, trauma, extreme temperature shifts, or systemic stressors. Neoplastic degranulation leads to characteristic clinical signs:

  • Darier's Sign: The classic swelling, erythema (redness), and wheal formation surrounding a mast cell tumor after physical manipulation.
  • Fluctuating Mass Size: Owners often report that the bump "swells up and then shrinks down to nothing" over a matter of hours or days. This is not tumor growth and regression, but rather localized edema caused by histamine release, followed by fluid resorption.
  • Gastrointestinal Ulceration: Systemic release of histamine travels through the bloodstream and binds to gastric parietal cell H2 receptors, leading to hypersecretion of hydrochloric acid. This causes gastric hyperacidity, nausea, vomiting (often containing digested blood or "coffee grounds"), melena (dark, tarry stools), and life-threatening gastrointestinal perforation.

Because of these risks, supportive care is vital. For any dog suspected of having a mast cell tumor, particularly if the mass is large, ulcerated, or scheduled for biopsy or surgery, antihistamine therapy is initiated. This typically includes an H1 blocker (such as diphenhydramine at 2 mg/kg BID-TID) and an H2 blocker or proton pump inhibitor (such as famotidine at 1 mg/kg BID or omeprazole at 1 mg/kg SID) to shield the gastrointestinal tract.

How are canine mast cell tumors graded under Patnaik vs. Kiupel?

Histopathological grading is the single most powerful predictor of biological behavior and survival for canine cutaneous mast cell tumors. Pathologists evaluate the cellular architecture of the tumor after biopsy or surgical removal. However, veterinary medicine uses two co-existing grading systems, which can sometimes create confusion for primary-care practitioners and owners.

The Patnaik System (1984)

The Patnaik system is a three-tier classification scheme that divides tumors into Grades I, II, and III:

  • Grade I (Well-Differentiated): These tumors are confined to the dermis, exhibit minimal cellular pleomorphism, have rare mitotic figures, and contain abundant, large granules. They behave in a benign fashion, with local excision almost always being curative. Metastasis is extremely rare (<2%).
  • Grade II (Moderately Differentiated): These tumors extend into the subcutaneous tissue. They show moderate cellular pleomorphism and have a low-to-moderate mitotic index. Their biological behavior is highly variable and notoriously difficult to predict. Some behave like Grade I tumors and never recur, while others behave aggressively and metastasize.
  • Grade III (Poorly Differentiated): These tumors exhibit marked cellular pleomorphism, high mitotic indices, cellular atypia, and sparse, small granules. They are highly aggressive, display rapid local growth, and have an extremely high rate of metastasis to regional lymph nodes, the spleen, the liver, and the bone marrow.

The primary limitation of the Patnaik system is the Grade II category. Historically, approximately 60% to 75% of all canine mast cell tumors are classified as Grade II. Because their behavior is unpredictable, clinicians were often left in a gray zone—unsure whether to recommend aggressive chemotherapy or simply monitor the surgical site.

The Kiupel System (2011)

To address the Patnaik gray zone and reduce inter-pathologist variability, Dr. Matti Kiupel and an international group of veterinary pathologists proposed a two-tier system: Low-Grade and High-Grade.

A tumor is classified as High-Grade if it meets at least one of the following criteria in 10 high-power fields (HPFs) under a microscope:

  1. Mitotic Index: 7 or more mitotic figures.
  2. Multinucleated Cells: 3 or more multinucleated cells (cells containing 3 or more nuclei).
  3. Bizarre Nuclei: 3 or more atypical, highly abnormal, or bizarre nuclei.
  4. Karyomegaly: Pronounced variation in nuclear size (nuclear diameter exceeding at least two times that of adjacent mast cells in at least 10% of cells).

All tumors that do not meet any of these criteria are classified as Low-Grade.

Clinical Comparison: Patnaik vs. Kiupel

Pathologists now routinely report both grades (e.g., "Patnaik Grade II, Kiupel Low-Grade"). This dual reporting helps clinicians make highly refined decisions. A Patnaik Grade II tumor that is classified as Kiupel Low-Grade has a very low risk of metastasis (typically <5%) and can be managed with local therapy alone. If that same Patnaik Grade II tumor is Kiupel High-Grade, the metastatic risk jumps significantly, and systemic therapy is recommended.

Patnaik Grade Kiupel Grade Biological Behavior Metastatic Potential Median Survival Time (MST) Recommended Approach
Grade I Low-Grade Benign / Localized <2% >3 Years (often curative) Local surgical excision with clean margins
Grade II Low-Grade Mildly Aggressive 2% to 10% >3 Years Local surgical excision; active monitoring
Grade II High-Grade Highly Aggressive 30% to 50% 6 to 12 Months Surgical excision + systemic chemotherapy
Grade III High-Grade Extremely Aggressive 55% to 96% 2 to 4 Months Palliative surgery + systemic therapy

The clinical utility of this dual-grading system is grounded in the AAHA Oncology Guidelines for Dogs and Cats (2023), which emphasize that histopathological grading must guide the decision of whether to pursue staging and adjuvant therapy.

The Staging Workup: How Far Has it Spread?

Staging determines the extent of tumor spread (metastasis) throughout the body. While grading tells you how the tumor behaves under a microscope, staging tells you where the tumor is physically located.

Not every dog with a mast cell tumor requires a complete staging workup. For a single, small, slowly growing mass that cytologically appears well-differentiated, a veterinarian may choose to perform surgical excision first and wait for histopathology. However, staging is strongly indicated when:

  • The tumor is high-grade (Kiupel High-Grade or Patnaik Grade III).
  • The mass is rapidly growing, ulcerated, or larger than 3 cm.
  • Multiple cutaneous masses are present.
  • The regional lymph nodes are enlarged or firm.
  • Systemic signs are present (vomiting, anorexia, weight loss).
  • The tumor is located in a known high-risk site (mucocutaneous junctions, muzzle, perineum, inguinal region, or nail bed).

A complete staging workup includes:

  1. Fine-Needle Aspirate (FNA) and Cytology of the Mass: The initial diagnostic test. On a cytology slide, mast cells appear as round cells with characteristic purple/blue metachromatic granules. The background often contains numerous eosinophils (attracted by mast cell chemokines). For clinics looking to perform this test in-house, establishing a standardized in-house cytology of cutaneous mast cell tumors is essential for rapid preliminary identification.
  2. FNA and Cytology of the Sentinel/Regional Lymph Node: This is a crucial staging step. Even if a lymph node feels normal in size, microscopic metastasis can be present in up to 30% of cases. Identifying lymph node metastasis (Stage II) changes the surgical plan and indicates the need for systemic chemotherapy.
  3. Abdominal Ultrasound: Mast cell tumors do not typically metastasize to the lungs. Instead, they spread through the lymphatic system and blood vessels to abdominal organs—specifically the spleen and liver. An ultrasound evaluates these organs for structural changes. If abnormalities are seen, ultrasound-guided FNAs of the spleen and liver are performed. It is important to note that a normal-looking spleen or liver can still harbor mast cell metastasis, so biopsies or aspirates are the only definitive way to rule out organ involvement.
  4. Three-View Thoracic Radiographs: While pulmonary metastasis is rare, chest radiographs are useful to rule out chest lymph node enlargement and to evaluate the patient's heart and lungs prior to general anesthesia.
  5. Complete Blood Count (CBC) and Blood Smear Review: To evaluate for systemic inflammation, anemia (which can indicate gastrointestinal bleeding from H2 activation), and circulating mast cells (mastocythemia), which is a rare sign of advanced Stage V disease.

Staging results are categorized using the World Health Organization (WHO) staging system for canine mast cell tumors:

  • Stage I: One cutaneous tumor confined to the dermis without lymph node involvement.
  • Stage II: One cutaneous tumor with regional lymph node metastasis.
  • Stage III: Multiple cutaneous tumors or large, infiltrating tumors with or without lymph node metastasis.
  • Stage IV: Any tumor with distant metastasis (spleen, liver, bone marrow, or blood).

When is Stelfonta appropriate compared to surgical excision?

Once the grading and staging are complete, the veterinary team must choose the appropriate treatment pathway. The primary options for local tumor control are surgical excision and intratumoral injection.

Surgical Excision (The Gold Standard)

For the vast majority of localized cutaneous mast cell tumors, surgical excision remains the first-line treatment. The goal of surgery is complete removal of the tumor with clean margins. Mast cell tumors grow by sending out microscopic cords of cells into the surrounding tissue, which are invisible to the surgeon's eye. Therefore, wide margins are required.

Historically, the standard rule was to remove 3 cm of healthy tissue laterally and one fascial plane deep. Modern oncology has refined this rule. Today, a proportional margin approach is commonly used: the lateral margin width is equal to the diameter of the tumor, up to a maximum of 2 cm. For low-grade tumors, a lateral margin of 1 cm is often sufficient, but a deep margin of at least one clean fascial plane remains non-negotiable.

If histopathology returns with "clean margins," the local recurrence rate is less than 5% for low-grade tumors. If margins are "dirty" or "narrow" (<1 mm), options include a second surgery to scarify the margins, scar tissue removal, local radiation therapy, or close active monitoring.

Stelfonta (Tigilanol Tiglate): The Non-Surgical Alternative

Approved by the FDA in 2020, Stelfonta (tigilanol tiglate) is a novel, plant-derived, intratumoral injection. It is extracted from the seed of the blushwood tree (Fontainea picrosperma) found in the Australian rainforest.

Stelfonta is a protein kinase C (PKC) activator. When injected directly into the tumor, it triggers a rapid and highly localized inflammatory response, disrupts the tumor's blood supply, and causes localized tissue necrosis. Over the course of 7 to 14 days, the tumor literally sloughs away, leaving an open, healthy wound that heals via second intention (granulation and re-epithelialization) without surgical closure.

Stelfonta Selection Criteria

Stelfonta is not a universal replacement for surgery. It is highly regulated by its FDA label:

  • Location: It is indicated for cutaneous mast cell tumors anywhere on the body, or subcutaneous mast cell tumors located at or distal to the elbow or hock.
  • Size: The tumor volume must not exceed 10 cubic centimeters (computed as L × W × H × 0.5).
  • Metastasis: The tumor must be non-metastatic (Stage I).
  • Restrictions: It must not be injected into tumors that are heavily ulcerated, or those involving the eyelids, mouth, or perineum where tissue sloughing would compromise vital structures.

Efficacy and Clinical Outcomes

According to the Stelfonta FDA label trials, a single injection achieves a 75% complete response rate (meaning the tumor is completely gone with no active cells remaining) by Day 28. For dogs that do not achieve a complete response, a second injection can be administered, raising the overall complete response rate to 87% to 88%.

However, clinicians and owners must prepare for the visual reality of Stelfonta treatment. Because it works by tissue destruction, it creates a significant local wound. The injection site will swell, bruise, turn black, and slough. While this looks alarming, clinical trials show that these wounds heal completely with standard wound care and pain management, and the cosmetic outcome is often surprisingly good.

Oral Maintenance: Toceranib Phosphate (Palladia)

For tumors that are unresectable, metastatic, or recurrent, systemic therapy is necessary. Toceranib phosphate (Palladia), manufactured by Zoetis, was the first FDA-approved tyrosine kinase inhibitor (TKI) for dogs.

Palladia works by targeting and blocking several receptor tyrosine kinases, including:

  • KIT: A receptor that is mutated and constitutively active in up to 30% of high-grade mast cell tumors, driving uncontrolled cell division.
  • VEGFR2 (Vascular Endothelial Growth Factor Receptor): Blocking VEGFR2 inhibits tumor angiogenesis (the growth of new blood vessels), starving the tumor of nutrients.
  • PDGFR (Platelet-Derived Growth Factor Receptor): Another receptor involved in cell proliferation and angiogenesis.

Palladia is administered orally at home, typically three times a week (every other day). Because it is a chemotherapy drug, owners must wear chemotherapy-resistant gloves when handling the tablets and when cleaning up the dog's waste.

What are the common side effects of Palladia and Stelfonta based on FDA adverse event data?

To provide clients with accurate safety counseling, we analyzed the public adverse event reports submitted to the FDA CVM. Systemic pharmacovigilance reports are valuable because they capture real-world clinical outcomes outside of tightly controlled manufacturer trials.

Toceranib (Palladia) Adverse Event Profile

Our analysis of 1,062 openFDA adverse event reports for toceranib (Palladia) in canine patients reveals that gastrointestinal side effects are the most dominant risk. Because Palladia inhibits VEGFR, it can cause subclinical mucosal ischemia in the stomach and intestines, making the GI tract highly sensitive.

The top reported clinical signs in the database are:

  • Diarrhea: 21.00% of cases (223 reports)
  • Vomiting: 18.17% of cases (193 reports)
  • Anorexia: 15.44% of cases (164 reports)
  • Anemia (NOS): 9.98% of cases (106 reports)
  • Neutropenia: 9.32% of cases (99 reports)
  • Lameness / Joint Pain: 9.13% of cases (97 reports)
  • Death by Euthanasia: 9.04% of cases (96 reports)

Outcomes in the database:

  • Ongoing: 44.82% (476 cases)
  • Outcome Unknown: 11.11% (118 cases)
  • Died (Natural Death): 10.73% (114 cases)
  • Recovered/Normal: 8.85% (94 cases)
  • Euthanized: 4.90% (52 cases)

Clinical Insight: The high rate of euthanasia and natural death in the Palladia cohort reflects the advanced, often metastatic or end-stage oncological status of the patients receiving the drug, rather than direct drug toxicity alone. However, gastrointestinal ulceration and neutropenia can be life-threatening if ignored. If a dog on Palladia develops watery diarrhea, vomiting, or a fever, the drug must be stopped immediately, and supportive care (fluids, gastroprotectants, antibiotics) initiated.

Tigilanol Tiglate (Stelfonta) Adverse Event Profile

Our analysis of 1,916 openFDA adverse event reports for tigilanol tiglate (Stelfonta) in canine patients shows a profile dominated by the drug's local tissue-destruction mechanism.

The top reported signs are:

  • Lack of Efficacy (NOS): 44.36% of cases (850 reports)
  • Injection Site Swelling: 35.07% of cases (672 reports)
  • Wound Formation: 20.15% of cases (386 reports)
  • Injection Site Pain: 15.45% of cases (296 reports)
  • Pain (General): 14.87% of cases (285 reports)
  • Swelling (General): 14.72% of cases (282 reports)
  • Injection Site Necrosis: 12.06% of cases (231 reports)
  • Swollen Limb: 10.91% of cases (209 reports)
  • Injection Site Complication (NOS): 10.86% of cases (208 reports)
  • Injection Site Bruising: 10.54% of cases (202 reports)

Outcomes in the database:

  • Outcome Unknown: 61.64% (1,181 cases)
  • Recovered/Normal: 23.96% (459 cases)
  • Ongoing: 5.43% (104 cases)
  • Died (Natural Death): 3.81% (73 cases)
  • Euthanized: 3.76% (72 cases)

Clinical Insight: The 44.36% "Lack of Efficacy" rate in the database is significantly higher than the 12% to 25% failure rate reported in manufacturer trials. This discrepancy suggests that in real-world clinical settings, Stelfonta is sometimes used outside its labeled indications—such as for larger, ulcerated, or subcutaneous tumors where achieving a complete response is harder. Additionally, the 20.15% wound rate and 35.07% swelling rate are expected clinical consequences of the drug's mechanism rather than accidental toxicities.

What are the real-world costs of canine mast cell tumor treatment?

Treatment costs are a major factor in veterinary oncology, and helping clients understand their financial options is an important role for the primary-care team. Costs vary depending on the patient's size, tumor location, and geographic region.

Below is a detailed cost comparison mapping the three primary pathways: surgical excision, Stelfonta injection, and Palladia maintenance.

Cost Component Surgical Excision (General Practice) Surgical Excision (Specialist Surgeon) Stelfonta Injection Pathway Palladia Maintenance (Monthly)
Initial Diagnostics & Staging $500 – $900 $800 – $1,500 $500 – $900 $600 – $1,200 (including baseline labs)
Procedure / Drug Cost $1,000 – $2,000 (anesthesia & surgery) $2,500 – $4,500 (complex reconstruction) $800 – $1,500 (per vial of Stelfonta) $300 – $600 (monthly drug cost, weight-dependent)
Pathology / Post-Op Labs $200 – $350 (histopathology) Included or $200 – $350 Included in follow-up $150 – $300 (monthly monitoring CBC/chem)
Supportive Meds & Follow-Up $100 – $250 (pain meds, antibiotics) $200 – $400 $150 – $300 (concomitant steroid/pain protocol) $50 – $100 (antiemetics, antidiarrheals)
Complication Costs (Est.) $300 – $800 (seroma, dehiscence) $500 – $1,500 $200 – $500 (extended wound management) $500 – $1,500 (severe neutropenia/GI bleed)
Total Estimated First-Month Cost $1,800 – $3,250 $3,800 – $6,750 $1,650 – $3,000 $1,100 – $2,200
Ongoing Monthly Cost $0 (assuming clean margins) $0 $0 (if complete response achieved) $450 – $900 (ongoing drug + monitoring)

Financial Considerations

  • Surgical Reconstruction: If a tumor is located on a limb or the face where there is little loose skin, closing the wound after removing wide margins can be difficult. A specialist surgeon may be required to perform skin grafts or reconstructive flaps, which significantly increases the surgical cost.
  • Stelfonta Vial Calculation: Stelfonta is dosed by the size of the tumor, but it is sold in 2 mL vials (containing 1 mg of tigilanol tiglate per mL). If a dog has a larger tumor requiring more than one vial, or if multiple tumors are treated, the cost will scale accordingly.
  • Palladia Weight Scaling: A Chihuahua may only need one 10 mg tablet three times a week, costing under $150 a month, while a Great Dane may require multiple 50 mg tablets per dose, driving the monthly drug cost over $600.

Does pet insurance cover Stelfonta and Palladia for dog mast cell tumors?

This is one of the most common questions owners ask upon diagnosis. The short answer is: Yes, standard pet insurance policies cover mast cell tumor treatments, including surgery, Stelfonta, and Palladia, provided that the tumor is not classified as a pre-existing condition.

However, owners must navigate several specific policy details:

  1. Pre-Existing Condition Clauses: If the dog had a skin mass, bump, or skin allergy documented in their veterinary medical record before the policy's effective date or during the initial waiting period (typically 14 days), any subsequent mast cell tumor diagnosis will be denied as pre-existing. This is true even if the previous bump was never biopsied or was noted as a benign cyst.
  2. Pre-Authorization: Before initiating expensive treatments like Stelfonta or starting long-term Palladia therapy, veterinarians should submit a pre-authorization request to the insurance company. This request includes the diagnosis, histopathology report, and the veterinarian's estimated treatment plan. The insurer will review the file and confirm in writing what percentage of the cost they will cover, preventing unexpected out-of-pocket expenses.
  3. Deductibles and Co-Pays: Most policies reimburse between 70% and 90% of the actual veterinary bill after the annual deductible is met. For a $3,000 Stelfonta treatment or surgery, a policy with a 90% reimbursement rate and a $250 deductible will cover approximately $2,475 of the cost.
  4. Coverage Limits: Some older or basic plans have per-condition or annual limits. Because cancer treatment can quickly reach these limits, it is important to review the policy details. Standard modern plans from major insurers (such as Trupanion, Nationwide, or Embrace) typically offer unlimited lifetime coverage.

For more information on how pet insurance handles claim workflows, waiting periods, and exclusions, see pet insurance pre-existing conditions and direct-pay pet insurance workflow.

FAQ: Common Client Questions

How long does a dog live after a mast cell tumor is removed?

The survival time depends almost entirely on the tumor's histologic grade and whether it has spread. For dogs with low-grade or Patnaik Grade I-II tumors that are completely removed with clean margins, the prognosis is excellent, and median survival times exceed 3 years—in many cases, the surgery is curative. For dogs with high-grade or Patnaik Grade III tumors, the median survival time is only 2 to 4 months without treatment, and approximately 6 to 12 months when surgery is combined with chemotherapy or Palladia.

Can a mast cell tumor shrink and grow?

Yes. Neoplastic mast cells release histamine, which causes local blood vessels to dilate and leak fluid, leading to localized swelling. When this fluid is reabsorbed by the body, the mass appears to shrink. This rapid fluctuation in size is a classic clinical sign of a mast cell tumor, but it does not mean the tumor itself is growing and shrinking.

What does a mast cell tumor look like in a dog?

Mast cell tumors do not have a single, classic appearance. They are often called the "great imitators." They can look like a benign fatty lipoma, a small pink hairless bump, a red inflamed hive, or a large, ulcerated, bleeding mass. Any new skin lump on a dog should be evaluated by a veterinarian with a fine-needle aspirate.

Is Stelfonta painful for the dog?

The injection process itself is performed under mild sedation and local nerve blocks because Stelfonta causes rapid inflammation that can be uncomfortable. In the 2 to 4 days following the injection, the site will be painful, swollen, and bruised. Veterinarians prescribe a mandatory protocol of corticosteroids (prednisone), pain medications (such as gabapentin or NSAIDs), and gastroprotectants to manage these symptoms and prevent systemic degranulation.

Does my dog need chemotherapy if the surgery removed the tumor?

If the pathology report indicates a low-grade tumor that was completely removed with clean margins, chemotherapy is not indicated. However, if the tumor is high-grade (Kiupel High-Grade or Patnaik Grade III), or if there is evidence of lymph node or organ metastasis, chemotherapy (such as vinblastine/prednisone or Palladia) is strongly recommended to target systemic microscopic spread, even if the primary surgical site has healed.

Sources

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OncologyClinical Pathology
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