SOFT TISSUE TUMORS OF CANINE SKIN AND SUBCUTIS
A discussion about soft tissue tumors/soft tissue sarcomas is in the 2020 fascicle on Tumors of Soft Tissue.
The term soft tissue tumor or soft tissue sarcoma is a group diagnosis and not a diagnosis of a specific entity. Wherever possible the specific entity should be diagnosed. The generic term would therefore be used when one cannot make a specific diagnosis.Soft tissue tumor or soft tissue sarcoma is a group diagnosis. It was used for spindle cell tumors of the skin of dogs that were thought to be sarcomas - orginally included malignant peripheral nerve sheath tumors (at the time included perivascular wall tumors), fibrosarcoma, liposarcoma, malignant fibrous histiocytoma and undifferentiated sarcoma (Kuntz et al 1997). Kuntz et al (1997) reported on the application of the human grading scheme (which as far as I know is no longer used) on 75 tumors that included malignant peripheral nerve sheath tumors (36 dogs), fibrosarcomas (26 dogs), undifferentiated sarcomas (6 dogs), myxosarcomas (5 dogs), and malignant fibrous histiocytomas (2). All other types were excluded. 13 of the 75 had metastasis with a median interval of 365 days. Dogs with a mitotic count of 20 or higher were 5 times more likely to develop metastasis. 4 of 31 (13%) with Grade I tumors metastasised, and 2 of 27 (7%) with Grade II tumors metastasized. 7 of 17 (41%) of Grade III tumors metastasised. Excluded diagnosis includes osteosarcoma, hemangiosarcoma, rhabdomyosarcoma, and synovial cell sarcoma (which also now no longer exists is a diagnosis). Nerve sheath tumors of the brachial plexus were also excluded. Also excluded were mandibular and maxillary sarcomas.
We now know that malignant nerve sheath tumors are as rare as hen's teeth. The majority of what was called malignant nerve sheath tumor are perivascular wall tumors, and perivascular wall tumors have information about their own prognosis. Malignant fibrous histiocytoma no longer exists as a diagnosis and most of those cases were either histiocytic sarcoma or undifferentiated pleomorphic sarcoma.
The category is now referred to as 'soft tissue tumors' when the tumor has a low mitotic count (or is a grade 1 or grade 2 tumor according to Kuntz et al 1997). Soft tissue sarcoma is reserved for tumors with a high mitotic count (above 9 or 19 depending on the study). Whereever possible, a specific diagnosis and prognosis should be used. There are publications providing prognostic information for perivascular wall tumors, fibrosarcomas, myxosarcoma, and histiocytic sarcomas. These are indicated below.
I personally no longer use the grading scheme. There are more accurate and better studies of outcome for many included in the group diagnosis of soft tissue sarcoma. Additionally, the prognostic information provided by the original grading paper was not confirmed in subsequent publications, the metastatic rate was much higher then other papers and publications did not identify a difference between grades.
Relationship to metastasis
The original publication by Kuntz et al (1997) identified metastasis in 4 of 31 (13%) cases of Grade I tumors , and 2 of 27 (7%) with Grade II tumors. 7 of 17 (41%) of Grade III tumors metastasised. These values seem unusually high and may represent a bias of cases examined at that academic centre. This has not been verified in many studies with many more patients.
Bray et al (2014) reported metastasis in 40 of 350 cases (11.4%) using imaging, histology or a combination. The median metastasis free interval was 550 days.
Surgical dose and outcome
Many of the publications on margins are based on histologic tumour free distance. Relating surgical dose to outcome is much more important, and even when reported, did not include deep margin evaluation - just lateral margins.
McSporran (2009) reported on 139 tumors graded histologically - 71 grade I, 59 grade II, and 9 grade III. Marginal excision was a histologic tumor free distance of < or = 1 mm. A mitotic count of >9 had the highest likelihood of recurrence.
Bray et al (2014) examined surgical dose and outcome. Of the 350 cases, there were 231 (66%) grade I tumors, 95 (27.1%) grade II, and 22 (6.3%) grade III tumors. Histologic tumor free distance was not possible because of the nature of the samples. Tumor reoccurrence was in 73 (dogs and death attributed to the tumor occurred in 58 cases (16.5%); 25 dogs died with but not because of the tumor. Reoccurrance was significantly related to mitotic count (>19), necrosis (and grade. Surgical dose was not significantly correlated to recurrence. Surgical margins had a selection bias and the majority of cases had marginal excisions at least lateral margins; deep margins were unknown. Wider margins were taken when the diagnosis was made. In short, knowledge of surgical dose was problematic, and the assumption that surgical dose was not related to outcome is especially problematic. "This recalibration of treatment advice is dependent on veterinarians recognizing that a spectrum of tumor behavior exists, and understanding that preoperative testing will improve patient selection and treatment planning. Our results would suggest that much education is still required."
Bray JP, Polton GA, McSporran KD, Bridges J, Whitbread TM. Canine soft tissue sarcoma managed in first opinion practice: outcome in 350 cases. Vet Surg. 2014; 43: 774-782.
Kuntz CA, Dernell WS, Powers BE, Devitt C, Straw RC, Withrow SJ. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). J Am Vet Med Assoc. 1997 Nov 1;211(9):1147-51. PMID: 9364229.
Roccabianca P, Schulman FY, Avallone G, Foster RA, Scruggs JL, Dittmer K, Kiupel M. Volume 3, Tumors of Soft Tissue, In Surgical Pathology of Tumors of Domestic Animals. Ed. M Kiupel. 2020.
Capillaries have endothelial cells, pericytes, and basement membrane
Larger vessels (PCV) have endothelial cells, myopericyte and BM
Largest vessels have endothelium, subendothelial cells, smooth muscle, and surrounding myopericyte and fibroblasts.
Pericytes – vimentin, pan actin, SMA
Myopericytes - vimentin, pan actin, SMA, desmin, calponin
Smooth muscle - vimentin, pan actin, SMA, desmin, calponin, smoothelin, heavy caldesmon,
Glomus tumors are well-demarcated expansile masses composed of tightly packed round cells. Their cytoplasm is pale eosinophilic and the nuclei are round. Anisocytosis and anisokaryosis are mild, and the mitotic count are usually low. The tumor has vascular channels that are compressed and indistinct. Clusters of cells may bulge into the lumen of blood vessels with an endothelial lining. Glomus cells express vimentin and α-smooth muscle actin. Desmin expression can be seen in scattered cells. PAS positive basal lamina surrounds single neoplastic cells. This is also laminin and collagen IV positive by immunohistochemistry.
Dagli ML, Oloris SC, Xavier JG, dos Santos CF, Faustino M, Oliveira CM, Sinhorini IL, Guerra JL. Glomus tumour in the digit of a dog.
Furuya Y, Uchida K, Tateyama SJ. A case of glomus tumor in a dog. Vet Med Sci. 2006; 68: 1339-1341.
Shinya K, Uchida K, Nomura K, Ozaki K, Narama I, Umemura TJ. Glomus tumor in a dog.Vet Med Sci. 1997; 59: 949-950.
Histopathology
Perivascular wall tumors (PWT) resemble cells around small blood vessels - arterioles, capillaries and venules. The classical patterns of PWT are
Perivascular whorls.
These are whorls around a central vessel lumen that is often collapsed and the vascular lumen may no longer be visible.
Placentoid pattern
This is multiple neoplastic lobules separated by an empty space and containing central capillaries.
Staghorn (antler-like) vessels
These are thin-walled, branching and dilated vascular structures.
Bundles of spindle cells arising directly from the vascular wall.
Self explanatory!
Immunohistochemistry
One of the major issues of immunohistochemistry in PWT is the technique used. The original manuscript and some subsequent papers performed immunohistochemistry on frozen sections; immunophenotyping of these in formalin fixed tissues is problematic. Confirmation of some types requires electron microscopy.
These tumors are invariably vimentin positive (not particularly helpful) and many express PDGFR. Muscle markes including SMA may be positive (my experience with formalin fixed tissue is not good). Some are S100 positive. They are negative for GFAP, Olig-2 and NGFR.
Prognosis
These tumors are traditionally lumped with soft tissue tumors/sarcoma and are graded as such. Despite this, the original metastatic rate was not confirmed in much larger studies, and most dont always reoccur with marginal excision. There does not appear to be a practical reason to subdivide then into specific entities (hemangiopericytoma, myopericytoma, angioleiomyoma, angiofibroma and angiomyofibroblastoma)
Bostock and Dye (1980) had followup information for perivascular wall tumors (called hemangiopericytoma) and there was 1 metastasis in 86 skin tumors.
Stefanello et al (2011) reported on the outcome of 53 dogs with 55 cPWT and which were not recurrent when examined initially. 'Clean' margins were defined as >3mm, clean but close were 1-3mm. If the mass was <5cm diameter, the survival time was >90%. 10 dogs had a reoccurrence and 2 dogs developed metastases - both to the lungs - identified 180 and 365 days after surgery. Size of the neoplasm was an important prognostic variable - larger was more likely to reoccur and ultimately resulted in reduced probability of survival (50% at 2 years).
Krantz et al (2019) examined the records of 167 tumors they called hemangiopericytomas and considered them perivascular wall tumors. Marginal excision was defined as <3mm. Metastasis - 0 dogs. Reoccurrence was 23 cases. Of the 158 tumors removed with wide resection (no neoplasm at margin at surgery, 44.9% had 'clean' histological margins, 46.2% had <3mm histological margins, and 8.9% had neoplastic cells at the histological margins. Recurrence occurred in 2.8% of those with 'clean' margins, 17.8% with narrow, and 35.7% of those with dirty margins.
Chili et al (2021) reported on 102 dogs with PWT concentrating on local reoccurrence and survival after diagnosis. Lack of metastasis was a selection criterium. 27% of dogs had local reoccurrence, and 13% of dogs died of tumour related causes.9 of the dogs had a Grade III tumor. There were 10 dogs with metastasis - 6 had local recurrence and metastasis and 4 had distant metastasis only. 7 dogs with metastasis to the lungs, 2 to lymph node, 1 to skin, 1 to rib (n = 1), and 1 to peritoneum. Reoccurrence was correlated with higher mitotic count (higher for each unit increase), grade (II and III) and necrosis more than 50% based on hazard ratios. Local reoccurrence was in cases with a HTFD of 3 mm or less. Tumor related cause of death was in 10 dogs.
Avallone G, Helmbold P, Caniatti M, Stefanello D, Nayak RC, Roccabianca P. The spectrum of canine cutaneous perivascular wall tumors: morphologic, phenotypic and clinical characterization. Vet Pathol. 2007; 44: 607-620.
Avallone G, Stefanello D, Ferrari R, Roccabianca P. The controversial histologic classification of canine subcutaneous whorling tumours: The path to perivascular wall tumours. Vet Comp Oncol. 2020; 18: 3-8
Bostock DE, Dye MT. Prognosis after surgical excision of canine fibrous connective tissue sarcomas. Vet Pathol. 1980; 17: 581-588.
Chiti LE, Ferrari R, Boracchi P, Morello E, Marconato L, Roccabianca P, Avallone G, Iussich S, Giordano A, Ferraris EI, Agnoli C, Dondi F, Giacobino D, Godizzi F, Stefanello D. Prognostic impact of clinical, haematological, and histopathological variables in 102 canine cutaneous perivascular wall tumours. Vet Comp Oncol. 2021 Jan 2. doi: 10.1111/vco.12673. Epub ahead of print. PMID: 33386693.
Kravitz A, Davis G, Bastian RP, Fittipaldi K. Outcome and Prognostic Indicators for Hemangiopericytomas in Dogs: 167 Cases (2009-2016). J Am Anim Hosp Assoc. 2019; 55: 194-200.
Palmieri C, Avallone G, Cimini M, Roccabianca P, Stefanello D, Della Salda L. Use of electron microscopy to classify canine perivascular wall tumors. Vet Pathol. 2013; 50: 226-233.
Stefanello D, Avallone G, Ferrari R, Roccabianca P, Boracchi P. Canine cutaneous perivascular wall tumors at first presentation: clinical behavior and prognostic factors in 55 cases. J Vet Intern Med. 2011; 25: 1398-1405.
In humans Solitary fibrous tumor (SFT) is a mesenchymal tumor with uncertain differentiation and intermediate malignant potential. SFTs can arise at any location (pleural or extrapleural) and display a wide histopathological spectrum, frequently with hemangiopericytoma‐like vessels. Several other histological patterns have also been described, including round cell, giant‐cell‐containing, epithelioid, myxoid, fat‐forming, pleomorphic and dedifferentiated variants.3,8,9,22–30 Many of the histological variants reveal a focal patternless architecture, and variably fibro‐collagenous stroma.1–9,22–30 NAB2‐STAT6
was discovered as a novel fusion gene of SFTs, and STAT6 immunoexpression has been established as a surrogate marker of the NAB2‐STAT6 gene fusion, expression of this protein representing a very sensitive and specific diagnostic tool.
There are benign and malignant types.
Desmoid type Fibromatosis
In humans, desmoid-type fibromatosis is a locally aggressive neoplasm composed of long sweeping fascicles of bland fibroblasts/myofibroblasts admixed with thin-walled blood vessels. Different forms include those with dense keloidal collagen, myxoid zones, and areas reminiscent of nodular fasciitis.
Subtypes areconventional,
hyalinized/hypocellular,
staghorn vessel,
myxoid, keloidal,
nodular fasciitis-like
hypercellular.Lipofibromatosis
This is just like fibromatosis but with lipocytes in varying amounts.
In humans these tumors have a consistent gene fusion, MYH9–USP6
Initialism/
IMT
Ellies tumour!
Synonyms
Synonyms include inflammatory fibrosarcoma, inflammatory pseudotumour, Ellies tumour
Histopathology
This is a mass of bland fibroblasts that form a well demarcated expansile mass and which infiltrate at the periphery. There are histiocytic / dendritic cells, lymphocytes and plasma cells that intermingle.
Immunohistochemistry
IHC profile includes
100% of spindle cells vimentin diffuse cytoplasmic staining
100% of spindle cells Claponin
20% SMA positive cytoplasmic and surface
20% desmin predominantly surface
Negative – panCK, GFAP, s100, Melan A, CD18,
Prognosis
They do well with removal
Knight C; Fan E; Riis R; McDonough S. Inflammatory Myofibroblastic Tumors in Two Dogs Vet Pathol 2009; 46: 273-276.
In humans there is an “abundance of plump spindle and stellate fibroblasts arranged in an intercellular matrix that may be relatively scant or myxoid”
Price EB Jr, Silliphant WM, Shuman R. Nodular fasciitis: a clinicopathologic analysis of 65 cases. Am J Clin Pathol. 1961;35: 122-36
Shimizu S, Hashimoto H, Enjoji M. Nodular fasciitis: an analysis of 250 patients. Pathology. 1984 Apr;16(2):161-6.
Conventional Fibroma and Fibrosarcoma
Bostock and Dye (1980) examined fibrous tumors of dogs and found that mitotic count was predictive of metastasis. They behaved in a similar fashion to perivascular wall tumors (hemangiopericytomas). There were 74 skin fibrosarcomas and 7 were metastatic. Mitotic count was the only significant determinant of median survival. A mitotic count of 9 or more per 10HPF had a median survival of of 49 weeks and 118 with a count less than 9.
Kuntz et al (1997) had 26 cases in their 75 selected tumors of soft tissue. With all their tumors, a mitotic count of greater than 19 (20 or more) were more likely to metastasise.
Bostock DE, Dye MT. Prognosis after surgical excision of canine fibrous connective tissue sarcomas. Vet Pathol. 1980; 17: 581-588.
Kuntz CA, Dernell WS, Powers BE, Devitt C, Straw RC, Withrow SJ. Prognostic factors for surgical treatment of soft-tissue sarcomas in dogs: 75 cases (1986-1996). J Am Vet Med Assoc. 1997; 211: 1147-1151.
Keloidal Fibroma and Fibrosarcoma
Mikaelian and Gross (2002) reported on 16 dogs with keloidal fibromas and fibrosarcomas. 3 were fibrosarcomas. Of the 13 with fibromas there was followup in 5 and none reoccurred or metastasised, .
Mikaelian I, Gross TL. Keloidal fibromas and fibrosarcomas in the dog. Vet Pathol. 2002 ; 39: 149-153.
Myofibroblastic Fibroma and Fibrosarcoma
Bostock and Dye reported on 10 myxosarcomas. Non had metastasis. Reoccurrance was important in prognosis.
Iwakli et al (2019) reported the outcome of 32 dogs with myxosarcomas. Those with a mitotic count less than 10 per 2.37 mm² had a mean survival time of 1393 (20 to 2345) days. 3 of 20 dogs with this mitotic count had metastasis. If the mitotic count was 10 to 19, 2 of 3 dogs had metastasis, and if the mitotic count was greater than 19, 3 of 6 dogs had metastasis. Thus 8 in 29 dogs with followup had metastasis to a local lymph node or lung and if so, the MST was 119 (0-643) days.The mean survival time in dogs with the mitotic count greater than 10 was 433 (169-831) days.
Iwaki Y, Lindley S, Smith A, Curran KM, Looper J. Canine myxosarcomas, a retrospective analysis of 32 dogs (2003-2018). BMC Vet Res. 2019 Jun 27;15(1):217. doi: 10.1186/s12917-019-1956-z. PMID: 31248415; PMCID: PMC6595552.
Dermatofibroma is usually a solitary lesion of the dermis. The proliferation is typical of a fibroma elsewhere.
Angiolipoma
Fibrolipoma
Adenolipoma
Chondrolipoma
Osteolipoma
Spindle cell lipoma
Infiltrative lipoma
Infiltrative lipomas are just like regular lipoma but they infiltrate surrounding tissue. Their location determines the prognosis. While they do no metastasise, local reoccurrence is an issue.
Bergman et al (1994) reported on 15 dogs with infiltrative lipoma. Prognosis is related to reoccurrence which is related to surgical accessibility. This infiltrative lipomas of the hind limb have a high liklihood of reoccurrence.
Bergman PJ, Withrow SJ, Straw RC, Powers BE. Infiltrative lipoma in dogs: 16 cases (1981-1992). J Am Vet Med Assoc. 1994;205(2):322-324.
Infiltrative angiolipoma
Intermuscular lipoma
Hibernoma
These are reported in the orbit of dogs. They are well circumscribed and demarcated tumors that resemble brown fat. Anisokaryosis is minimal, mitoses are infrequent and they dont metastasise. The cells have either a granular cytoplasm (mitochondria) or a vacuole.
They express UCP-1, and variably myogenin and MYOD1
Lipomatosis
Liposarcomas have either neoplastic mature lipocytes, cells with a lipid globule and or lipoblasts.
Liposarcomas are vimentin +, UCP1+, and variably S100+, SMA+, desmin+, and myogenin+, MDM2+ and CDK4+
In a study of 25 liposarcomas, 23 of 25 expressed UCP1, 7 of 25 expressed SMA, 7 expressed desmin and 3 expressed myogenin. This was independent of phenotype. This shows an overlap with hibernoma and rhabdomyosarcoma
LaDouceur EEB, Stevens SE, Wood J, Reilly CM. Immunoreactivity of Canine Liposarcoma to Muscle and Brown Adipose Antigens. Vet Pathol. 2017; 54: 885-891.
Avallone G, Roccabianca P, Crippa L, Lepri E, Brunetti B, Bernardini C, Forni M, Olandese A, Sarli G. Histological Classification and Immunohistochemical Evaluation of MDM2 and CDK4 Expression in Canine Liposarcoma. Vet Pathol. 2016; 53: 773-780.
Baez JL et al (2004) reported on 56 dogs with liposarcoma. There were 6 visceral and 50 skin and soft tissues. The median survival time was 694 days. The cause of death was known in 25, of which 10 were tumor related. One was metastatic on radiographs and 2 of 8 with skin and soft tissue tumors had ultrasound metastasis to the liver and spleen.
Well differentiated liposarcoma
This is essentially a lipoma that is multilobulated and with many lipocytes and lipoblasts. On immunohistochemistry, it should be MDM2 postive
Dedifferentiated liposarcoma
This liposarcoma has many spindle cells with rare lipid vacuoles. It is a rare type. On immunohistochemistry, it should be MDM2 positive.
Myxoid liposarcoma
Alcian blue (pH 2.5) positive material is present and many areas are myxosarcoma like. It is the lLeast common of 3 main types. On immunohistochemistry, it should be MDM2 negative.
Pleomorphic liposarcoma
Marked cellular pleomorphism including uninuclear and multinuclear neoplastic giant cells. Lipoblasts and lipid vacuoles are present but there is lLittle lipid. On immunohistochemistry, it should be MDM2 negative
Avallone G, Roccabianca P, Crippa L, Lepri E, Brunetti B, Bernardini C, Forni M, Olandese A, Sarli G. Histological Classification and Immunohistochemical Evaluation of MDM2 and CDK4 Expression in Canine Liposarcoma. Vet Pathol. 2016; 53: 773-780.
Baez JL, Hendrick MJ, Shofer FS, Goldkamp C, Sorenmo KU. Liposarcomas in dogs: 56 cases (1989-2000). J Am Vet Med Assoc. 2004; 224: 887-891.
Doria-Torra G, Martínez J, Domingo M, Vidaña B, Isidoro-Ayza M, Casanova MI, Vidal E. Liposarcoma in animals: literature review and case report in a domestic pig (Sus scrofa). J Vet Diagn Invest. 2015; 27: 196-202.
Hemangiomas are categorised based on morphology and location. If the bewildering array of different types causes your eyes to involuntary roll, you are not alone.
Cavernous hemangioma
Capillary hemangioma
Capillary like vascular channels
Often in lobules
Not exophytic
Inflammed lobular capillary hemangioma
Exophytic tumor
often ulcerated and the inflammation is from ulceration and thus is on the surface.
lobular arrangement of capillary like vascular channels
Usually has a feeder vessel for each lobule.
Overlying epidermal hyperplasia and hyperkeratosis is common.
Mixed capillary - cavernous hemangioma
Spindle cell hemangioma
This is an exceedingly rare tumor. It is variously called Kaposi-like vascular tumor and Kaposiform hemangioendothelioma. It is usually well circumscribed, and the leading edge has endothelium lined spaces that tend to radiate outward. These are separated by losely arranged spindle cells and other vascular spaces that are irregular. Centrally, the spaces can be cavernous and sometimes thrombosed. The arrangement of vascular spaces and spindle cells resembles but is distinctly different to granulation tissue.
Vincek V, Zaulyanov L, Mirzabeigi M. Kaposiform hemangioendothelioma: the first reported case in a nonhuman animal species. Vet Pathol. 2004; 41: 695-497.
Epithelioid hemangioma
Angiokeratoma
Infiltrative hemangioma
These invariably have adipocytes with the vascular channels.
Epithelioid hemangioendothelioma
Retiform hemangioendothelioma
Kaposiform hemangioendothelioma
Haemangiosarcoma Vet pathol1992 29:323 Hargis.
Solar radiation induced if lightly haired, poor pigmentation.
S/Q - 3 of 5 dogs with subcutis HSA have internal neoplasia
Dermal 25 of 52 with dermal HSA died of disease, reoccurrence of local disease - don’t know metastasis, couldn’t find out - no pms.
Ward H, Fox LE, Calderwood-Mays MB, Hammer AS, Couto CG. Cutaneous hemangiosarcoma in 25 dogs: a retrospective study. J Vet Intern Med. 1994; 8(5): 345-348.
JVDI 16: 522-526 (2004)
76 in skin or subcutis, outcome in 60
18 dermis – 2 caused death
22 in dermis and S/C 9 caused death
10 in subcutus, 0 caused death
Eric J. Bulakowski, Jeff C. Philibert, Sheri Siegel, Craig A. Clifford, Rebecca Risbon, Kara Zivin, and Kim L. Cronin Evaluation of outcome associated with subcutaneous and intramuscular hemangiosarcoma treated with adjuvant doxorubicin in dogs: 21 cases (2001 2006) Journal of the American Veterinary Medical Association July 01, 2008, Vol. 233, No. 1: 122-128.
Animals—21 dogs.
Procedures—Records of dogs with histologically confirmed hemangiosarcoma, no detectable metastasis at initial evaluation, and adequate local tumor control were included. Age, sex, number of treatments, treatment interval, radiation therapy, and concurrent use of cyclophosphamide or deracoxib were evaluated for associations with disease-free interval (DFI) or survival time. Three to 6 cycles of doxorubicin were planned. Disease-free interval was defined as time of definitive surgery to time of local recurrence, metastasis, or both. Survival time was defined as the beginning of the DFI to time of death.
Results—17 tumors were subcutaneous, and 4 were intramuscular. Median age was 9 years. Median weight was 31.1 kg (68.4 lb). Five dogs received adjuvant radiation therapy. Median DFI for subcutaneous tumors was 1,553 days (95% confidence interval [CI], 469 days to not estimable). Median DFI for intramuscular tumors was 265.5 days (95% CI, 123 to 301 days). Median survival time for subcutaneous tumors was 1,189 days (95% CI, 596 days to not estimable). Median survival time for intramuscular tumors was 272.5 days (95% CI, 123 to 355 days). For dogs with subcutaneous tumors, younger age (< 9 years) was associated with longer DFI and survival time. Dogs with subcutaneous tumors that did not receive radiation therapy had longer DFI.
Conclusions and Clinical Relevance—Dogs with subcutaneous hemangiosarcoma had a more favorable outcome, compared with dogs with intramuscular hemangiosarcoma, when treated with adequate local control and adjuvant doxorubicin.
Kai-Biu Shiu, Andrea B. Flory, Christie L. Anderson, Jackie Wypij, Corey Saba, dvm, dacvim; Heather Wilson, Ilene Kurzman, Ruthanne Chun 2011 Predictors of outcome in dogs with subcutaneous or intramuscular hemangiosarcoma. JAVMA 2011 287: 472-
Objective—To identify prognostic factors in a large group of dogs with subcutaneous or intramuscular hemangiosarcoma (HSA) or both.
Design—Multi-institutional retrospective cohort study.
Animals—71 dogs with subcutaneous or intramuscular HSA.
Procedures—Medical records of affected dogs were reviewed. The following factors were evaluated for an association with outcome: dog age and sex, clinical signs, anemia, thrombocytopenia, neutrophilia, tumor stage at diagnosis, achievement of complete excision, intramuscular involvement, presence of gross disease, tumor recurrence, and treatment.
Results—Of the 71 cases identified, 16 (29%) had intramuscular tumor involvement. For all dogs, median time to tumor progression and overall survival time (OST) were 116 and 172 days, respectively; 25% survived to 1 year. Univariate analysis identified presence of clinical signs or metastasis at diagnosis, dog age, tumor size, use of any surgery, and presence of gross disease as predictors of time to tumor progression and OST. There was no significant difference in survival time between dogs with respect to type of HSA. Multivariate analysis confirmed that adequate local tumor control, tumor diameter ≤ 4 cm, presence of metastasis at diagnosis, and presence of gross disease were significantly associated with OST.
Conclusions and Clinical Relevance—Subcutaneous and intramuscular HSA remains a heterogeneous group of tumors that generally carries a poor prognosis. Adequate local control of smaller tumors with no associated clinical signs or metastasis may have the best chance of long-term survival. (J Am Vet Med Assoc 2011;238:472–479)
Median OST (d)
Variable Present Absent Hazard ratio P value
Signalment
Age — — 1.126 0.034
Body weight — — 0.994 0.625
Findings at initial evaluation
Tumor size — — 1.041 0.030
Clinical signs 98 237 2.075 0.013
Anemia 98 226 1.911 0.034
Thrombocytopenia 130 193 1.294 0.415
Neutrophilia 122 193 1.247 0.476
Metastasis 115 246 2.089 0.012
Tumor size
# 4 cm 364 131 0.426 0.014
. 4 cm and # 6 cm 212 167 0.931 0.842
. 6 cm 130 294 2.284 0.006
Histologic findings
Intramuscular involvement 136 212 1.430 0.268
Mitotic index — — 1.116 0.090
Complete surgical margins achieved 399 130 0.460 0.017
Treatment
Surgery 246 49 0.194 , 0.001
Radiotherapy 166 167 1.065 0.844
Chemotherapy 226 111 0.681 0.162
Outcome
ALC 399 120 0.437 0.007
Gross disease 89 399 4.325 , 0.001
Local recurrence 399 328 1.182 0.702
A. Szivek, R. E. Burns, B. Gericota, V. K. Affolter, M. S. Kent C. O. Rodriguez Jr and K. A. Skorupski (2012) Clinical outcome in 94 cases of dermal haemangiosarcoma in dogs treated with surgical excision: 1993–2007*. Veterinary Comparative Oncol 2012, 10: 65-73
Abstract
Canine dermal haemangiosarcoma (HSA) is believed to have a better prognosis compared to HSA in other organs, but outcome has only been reported in a small number of dogs. The purpose of this study was to assess outcome and prognostic factors in a larger cohort of dogs with dermal HSA. Clinical data was collected retrospectively for 94 dogs and histopathology was reviewed in 53 dogs. Median overall survival time was 987 days. Dogs of predisposed breed with ventral location and histologic solar changes had longer survivals. Loco-regional recurrence occurred in 72/94 (77%) dogs. Predisposed breeds with ventral location and multiple masses were more likely to develop recurrence. Non-predisposed breeds with invasive tumours were more likely to develop metastasis. Results suggest that dogs with solar-induced dermal HSA may have high recurrence rates, but prolonged survivals. Dogs with non-solar tumours may be at increased risk for metastasis and shorter survival.
94 dogs, 53 had biopsy material for review.
61 had ventral location
67 had single masses
53 had biopsies for review
Dermis only. 27
Dermis and Sc 26
37 dogs had actinic changes
Clean but close was 5mm
32 of 94 cases had metastasis; abdominal organs affected in 20. Occirred a medium of 326 days after diagnosis.
Median survival overall was 987 days with a 1-year survival of 79%, 2-year survival of 60% and 3-year survival of 44%.
E. D. Lombardini* and B. A. Summers (2013) Two Canine Malignant Vascular Tumours with Features of Human Retiform Haemangioendothelioma J Comp Path 2013, 148: 225-230
Summary
Within the human medical literature, retiform haemangioendothelioma (RHE) is an established and wellrecognized histopathological variant of endothelial tumours, but to date RHE has not been reported in animals. These tumours are characterized by the presence of elongate, arborizing vascular channels lined by neoplastic endothelium with prominent, often bulging (‘hobnail’) nuclei supported by a dense collagenous matrix and accompanied by abundant lymphoplasmacytic inflammation. Immunohistochemically, the neoplastic cells typically express endothelial markers such as von Willebrand factor and CD31. Human RHEs are categorized as low-grade malignancies. This report describes two canine vascular tumours with canine vascular tumours with features consistent with RHE. In both cases there was suspected or known widespread tumour metastasis.
Lymphangioma is a well circumscribed expansile lesions comprised of channels with well differentiated endothelium. The channels should have little blood/red cells.
Sato Y. Cutaneous pedunculated lymphangioma in a dog. J Small Anim Pract. 2021; 62: 713.
Lymphangiosarcoma is a rare tumor, particularly in dogs. It is a progressive disease that is difficult to control, and metastasis can occur in about one half of affected dogs - to local lymph node, spleen, kidney, lung, and various other locations.
Confirmation of lymphatic endothelial cells can be done with lymphatic vessel endothelial receptor-1 (LYVE-1) and porspero-related homeobox gene-1 (PROX-1).
Curran KM, Halsey CH, Worley DR. Lymphangiosarcoma in 12 dogs: a case series (1998-2013). Vet Comp Oncol. 2016; 14: 181-190.
Halsey CH, Worley DR, Curran K, Charles JB, Ehrhart EJ. The use of novel lymphatic endothelial cell-specific immunohistochemical markers to differentiate cutaneous angiosarcomas in dogs. Vet Comp Oncol. 2016; 14: 236-244.
Rhabdomyosarcoma is a rare tumor of dogs.
Connell et al (2020) reported on 25 cases. 16 had metastasis on presentation. Many were diagnosed as round cell tumors originally.
Connell DR, Rodriguez CO Jr, Sternberg RA, Singh K, Barger A, Garrett LD. Biological behaviour and ezrin expression in canine rhabdomyosarcomas: 25 cases (1990-2012). Vet Comp Oncol. 2020; 18: 675-682. 32246519.
The general neoplasia page has information about NST that apply to all species. Please check this first for general characteristics and diagnosis.
Neurolemmoma (Schwannoma)
Neurofibroma
Schöniger and Summers reported on 12 dogs with nerve sheath tumors - neurofibroma. Their criteria were:
- high and poor cell areas – Antoni A and B
- nuclear pallasading
- Verocay bodies
- Hyalinised microvessels
- Nerve fibres at edge or within mass
- S100 + strong and diffuse in Schwann cells
- Schwannomas have typical fusiform cells
Subtypes are localized or plexiform (multinodular) then classic, collagenous, cellular and pigmented.
Neurofibromas have buckled or wavy nuclei – S100 cells are Schwann cells which are part of the tumour.
Are composed of Schwann cells, neurofibrocytes and perineural cells.
Subtypes are localized, plexiform or diffuse (infiltrative) then then classic, collagenous, cellular and pigmented.Schöniger S; Summers BA(2009) Localized, Plexiform, Diffuse, and Other Variants of Neurofibroma in 12 Dogs, 2 Horses, and a Chicken. Vet Pathol 2009 46: 904-915.
Perineurioma
Neurofibromatosis
Malignant nerve sheath tumor
There is an issue with the definition of malignant nerve sheath tumor. Invasion, high mitotic count, pleomorphism and other features are often used.
Stokes et al (2023) used the definition of tumor arising from brachial or lumbar sacral plexus. Thus they used the diagnosis of MPNST for any nerve sheath tumor of that location. Criteria for inclusion was amputation and tumor resection. The grading scheme of 'soft tissue sarcoma' was used. Bottom line - their NST were graded and compared to survival data. They used the R0, R1 and R2 systems to identify margins. Statistics were t-test based. Their 30 dogs were high grade 16, intermediate grade - 10 dogs and low grade 13%. 1 had osteoid formation, There was no correlation between grade and margin, or between surgery and margin. Most dogs died of their disease regardless of treatment or grade.
Stokes R, Wustefeld-Janssens BG, Hinson W, et al. Surgical and oncologic outcomes in dogs with malignant peripheral nerve sheath tumours arising from the brachial or lumbosacral plexus. Vet Comp Oncol. 2023; 21: 739-747.
Granular cell tumor
In dogs, these are invariably found in the oral cavity.
Patnaik (1993) reported on the presence of a granular cell tumor in the skin of the thorax in one dog. It was infiltrative. It was vimentin and anti trypsin positive, and negative for S100 and NSE
Patnaik AK. Histologic and immunohistochemical studies of granular cell tumors in seven dogs, three cats, one horse, and one bird. Vet Pathol. 1993 Mar;30(2):176-85.
Traumatic neuroma
This is not a neoplasm! It is a cluster of axons and their accompaning myelin sheath - Schwann cells that occur at sites of amputation, which is usually at a tail doc or toe amputation site.
Chondrosarcoma of the soft tissues of the skin are exceptionally rare.
There is a single case report of a myxoid chondrosarcoma in the skin of a young dog. It was metastatic.
Kojima D, Hatai H, Oyamada T, Park CH. Extraskeletal myxoid chondrosarcoma with systemic metastasis in a five-month-old Irish setter dog. J Vet Med Sci. 2012; 74: 1045-1049.
Craig et al (2020) reports person communications from Dr Brian Murphy that myxoma may very rarely be found in the lymph node. Generally though the majority of of dogs do not have metastatic disease.
Craig LE, Krimer PM, O'Toole AD. Synovial Cysts and Myxomas in 16 Cats. Vet Pathol. 2020; 57: 554-558.
In may ways, UPS is a diagnosis of exclusion. Histiocytic sarcoma, pleomorphic perivascular wall tumor, pleomorphic fibrosarcoma, pleomorphic liposarcoma and other pleomorphic sarcomas should be eliminated.
UPS may stain for actins and desmin suggesting they are myofibroblastic. Some have dendritic cells and even multinucleated macrophages that are CD18 and CD204+.