Soft Tissue Sarcomas: What the Category Includes, What the Grade Means, and Why Subtype Often Cannot Be Determined
Pathology Deep Dive · Canine, Feline · Soft Tissue Oncology
Soft tissue sarcoma is one of the most frequently encountered diagnoses in veterinary oncology — and one of the most frequently misunderstood. It is not a single disease. It is a broad category encompassing a diverse group of malignant tumors arising from mesenchymal tissues: connective tissue, fat, smooth muscle, peripheral nerves, blood vessels, and other non-epithelial, non-hematopoietic structures. What unites them is their mesenchymal origin and their shared tendency toward local invasion, frequent recurrence with incomplete excision, and variable but generally lower metastatic rate compared to carcinomas. What separates them — in terms of subtype, behavior, and treatment — is often not determinable from the histology alone. Understanding what soft tissue sarcoma means on a pathology report, what the grade tells you, and why your report may not specify a subtype is essential for interpreting these results accurately.
What tumors fall under the soft tissue sarcoma category
The soft tissue sarcoma category in veterinary pathology encompasses a wide range of histologically distinct but biologically related tumors. The most commonly encountered in dogs and cats include the following.
Peripheral nerve sheath tumor (PNST) — arising from Schwann cells, perineurial cells, or endoneurial fibroblasts along peripheral nerve branches. Most commonly encountered at the brachial plexus and cutaneous nerve branches in dogs. Older terminology — neurofibrosarcoma, malignant schwannoma — referred to what is now classified as malignant PNST. A closely related entity, hemangiopericytoma, was historically diagnosed as a distinct tumor in dogs but is now understood to represent a morphologic pattern rather than a specific entity — most tumors formerly called hemangiopericytoma are currently classified as PNST or undifferentiated sarcoma based on IHC and morphology. The name change matters because it reflects a more accurate understanding of histogenesis and aligns with the current WHO classification framework.
Fibrosarcoma — arising from fibroblasts, producing collagen, and typically presenting as a firm subcutaneous or deep soft tissue mass. In cats, spontaneous fibrosarcoma is distinguished from injection-site sarcoma (FISS), which shares fibrosarcomatous histology but is a biologically distinct entity with a more aggressive clinical course, higher local recurrence rate, and molecular features — including PDGFR dysregulation and a characteristically immunosuppressive tumor microenvironment — that set it apart from spontaneous soft tissue sarcomas. FISS is covered in detail in a prior Pathology Deep Dive post in this series. For the purposes of this post, fibrosarcoma refers to spontaneous tumors in dogs and cats arising outside the injection-site context.
Leiomyosarcoma — arising from smooth muscle, most commonly in the gastrointestinal tract, spleen, uterus, and retroperitoneum in dogs and cats.
Liposarcoma — arising from adipocytes or lipoblasts, less common than lipoma but distinguished by infiltrative growth, local recurrence potential, and a histologic appearance that ranges from well-differentiated (lipoma-like) to pleomorphic.
Rhabdomyosarcoma — arising from skeletal muscle precursors, uncommon in dogs and cats but occurring most often in young animals at sites including the tongue, larynx, and urinary bladder. The embryonal and alveolar subtypes carry different prognoses and are distinguished histologically and immunohistochemically.
Myxosarcoma — arising from mesenchymal cells producing abundant mucoid matrix. Characterized by a gelatinous to mucoid gross appearance and a morphologically distinctive myxoid stroma on histology. Behavior tends to be locally aggressive with lower metastatic rate than higher-grade STS subtypes.
Undifferentiated / pleomorphic sarcoma — high-grade tumors with such marked pleomorphism and poor differentiation that a specific line of origin cannot be assigned even with IHC. Formerly called malignant fibrous histiocytoma in older literature; the current terminology reflects the acknowledged uncertainty about histogenesis in these tumors.
For most of these subtypes, the primary management principle is the same: surgical excision with the widest achievable margins, with grade-informed decisions about staging and adjuvant therapy. Rhabdomyosarcoma subtypes carry subtype-specific prognostic implications that warrant specific designation where achievable.
What grade means in soft tissue sarcomas
Histologic grade is the most clinically actionable finding in an STS pathology report. In veterinary medicine, soft tissue sarcomas are most commonly graded using a three-tier system adapted from the Guillou/Coindre grading scheme used in human soft tissue pathology, evaluating three parameters: differentiation (how closely the tumor resembles its normal tissue of origin), mitotic count (mitotic figures per 10 high-power fields), and necrosis (estimated percentage of tumor showing necrotic change). Each parameter contributes a score, and the combined score places the tumor in grade I, II, or III.
| Parameter | Score range | |
|---|---|---|
| Differentiation | Well differentiated (1) to undifferentiated (3) | 1–3 |
| Mitotic count / 10 HPF | 0–9 (1), 10–19 (2), ≥20 (3) | 1–3 |
| Necrosis | None (0), <50% (1), ≥50% (2) | 0–2 |
| Grade I (low) | Total score 2–3 — low metastatic risk | |
| Grade II (intermediate) | Total score 4–5 — intermediate risk | |
| Grade III (high) | Total score 6–8 — high metastatic risk | |
Grade correlates with metastatic risk more reliably than with local recurrence risk. Local recurrence is primarily determined by surgical margin status — a grade I sarcoma with incomplete excision will recur locally at a rate that a grade III sarcoma with wide clear margins will not. Metastatic potential, however, scales with grade: published data in dogs indicates metastatic rates of approximately 7 to 10% for grade I, 25 to 35% for grade II, and 50 to 75% or higher for grade III soft tissue sarcomas. These figures are approximations and vary by subtype and anatomic location, but the directional relationship is consistent.
The mitotic count is the most reproducible and prognostically powerful component of the grade. A mitotic index of 20 or more per 10 HPF in any STS is a significant finding that warrants prominent reporting and carries direct implications for staging workup and adjuvant therapy discussions.
A note on hemangiopericytoma: a name you may still encounter
Hemangiopericytoma deserves specific mention because the name persists in clinical use even though the diagnosis has largely been reclassified. Historically, hemangiopericytoma was used in veterinary pathology to describe a common canine cutaneous and subcutaneous spindle cell tumor with a characteristic whorling or storiform growth pattern around vascular channels, arising most often on the limbs of older dogs. The term implied origin from pericytes — contractile cells surrounding blood vessel walls — but this histogenesis was never convincingly established.
With the adoption of more rigorous IHC criteria and updated WHO classification standards, most tumors formerly called hemangiopericytoma are now classified as PNST or undifferentiated spindle cell sarcoma depending on their IHC profile and morphologic features. Some pathologists still use the hemangiopericytoma designation for tumors with the characteristic morphologic pattern in the appropriate clinical context, while others have transitioned fully to the current classification. If your report uses this term, it is referring to a low- to intermediate-grade spindle cell sarcoma at a cutaneous or subcutaneous site — typically in an older dog — with behavior that is primarily local and generally favorable with adequate excision. The management implications align with those of a low-grade PNST or soft tissue sarcoma at the same site.
Why subtype often cannot be determined
One of the most common clinician questions about an STS report is: why doesn't it tell me what kind of sarcoma this is? The answer lies in the biology of these tumors and the limitations of the diagnostic tools available on standard FFPE tissue.
Soft tissue sarcomas from different lines of origin frequently share overlapping histologic and immunohistochemical features. A spindle cell sarcoma with a collagenous stroma could be a fibrosarcoma, a PNST, a leiomyosarcoma with spindle cell morphology, or an undifferentiated sarcoma. The IHC markers used to distinguish between them — S100 for neural origin, smooth muscle actin and desmin for myogenic differentiation, CD34 for vascular or neural origin — are not specific to a single line of origin and frequently overlap. S100 is expressed in neural, melanocytic, adipocytic, and other cell types. Smooth muscle actin can be focally expressed in fibroblastic and myofibroblastic tumors that are not true leiomyosarcomas.
When IHC results are overlapping or nonspecific, and when the morphology does not clearly favor one subtype over another, the pathologist will report the tumor as soft tissue sarcoma, subtype not further classifiable. This is not a diagnostic failure. It is an accurate statement of what the available evidence supports. Assigning a subtype that is not histologically and immunohistochemically defensible does the clinician no favors — it creates false confidence in a designation that may not reflect the tumor's actual biology.
For most soft tissue sarcomas in dogs and cats, the subtype designation does not change the primary management approach. Surgery with the widest achievable margins, followed by grade-informed decisions about staging and adjuvant therapy, is the standard approach regardless of whether the tumor is classified as fibrosarcoma, PNST, or undifferentiated sarcoma. Where subtype does carry specific management implications — rhabdomyosarcoma subtypes in particular — the pathologist will note this and the IHC workup will be directed accordingly.
What the pathology report should communicate
A complete STS pathology report should provide: confirmation of malignant mesenchymal origin (sarcoma), histologic grade with the individual component scores (differentiation, mitotic count, necrosis) clearly stated, mitotic count per 10 HPF as a standalone figure, margin status with closest measured margin distance, a subtype designation where histologically and immunohistochemically supportable or an explicit statement that subtype cannot be assigned, and any additional features of prognostic relevance such as vascular invasion, necrosis pattern, or depth of invasion.
The mitotic count is worth noting as a standalone figure alongside the composite grade. Because the grading system assigns the same score to any mitotic count within a bracket — a count of 10 and a count of 19 both score as 2 in the Guillou/Coindre system — the raw count provides more granular information than the score alone. A tumor sitting at the high end of a mitotic bracket is not necessarily a different clinical entity than one at the low end, but having the actual count on record supports future comparison and clinical decision-making, particularly when assessing response to treatment or monitoring for progression.
Margin status: the most actionable finding
For soft tissue sarcomas, surgical margin status is the single most actionable histopathologic finding and should be read with the same attention as the grade. Complete excision with histologically clear margins is the strongest predictor of local disease control. Incomplete excision — tumor at or within 1 to 2 mm of the inked margin — carries significantly higher local recurrence rates regardless of grade.
STS frequently extend beyond their apparent gross boundaries along fascial planes and tissue compartments. A tumor that appears grossly encapsulated may have microscopic projections beyond the capsule that are not sampled in the planes of section evaluated. This is particularly true for PNSTs, which grow along nerve sheaths, and for myxosarcomas, which infiltrate through loose connective tissue. A margin reported as clear on the evaluated sections may not be clear in all planes — a caveat worth noting in the report when the tumor's growth pattern raises concern.
Eric Snook, DVM, PhD, DACVP — Vetopathy. Soft tissue sarcoma reports include histologic grade with component scores, mitotic count, margin assessment, and subtype designation where supportable. Questions about a specific report? Direct pathologist contact is available.