14-year-old female Dutch Warmblood horse (Equus ferus caballus)The horse had a history of an approximately 1 cm mass within the lower left cheek that was excised 3
months prior to presentation and diagnosed as a trichoblastoma. The mass had recurred and was rapidly enlarging at
the time of presentation. On palpation, a 5 X 3 X 2 cm, bilobed, firm mass was present within the left cheek at the
level of the first three mandibular cheek teeth (307 to 309). The mass elevated both the intact overlying skin and
underlying intact oral mucosa. Some pain appeared to be associated with the mass, and the horse was intermittently
depressed. An initial incisional biopsy was followed by complete surgical excision 12 days after presentation.
A 5.5 x 3.0 cm by 2.5 cm thick section of skeletal muscle with an associated section of overlying
skin was submitted. Within the subcutis and muscle on cut section, there was a multilobulated, pink, fleshy mass
extending to the surgical margins.
Mass, left cheek: Examined is an unencapsulated, poorly demarcated, multilobulated,
densely cellular mass composed of lobules and tracts of neoplastic cells that infiltrate adjacent skeletal muscle and
connective tissue and extend to the tissue margins. The cells within the bulk of the mass are arranged in sheets,
cords, and packets within a moderately abundant fine fibrovascular stroma. Cells in these areas are polygonal with
distinct cell borders, small amounts of wispy eosinophilic to clear cytoplasm, and large round central nuclei with
finely stippled chromatin. In scattered areas (not present on every slide), the cells are pleomorphic, very large, lack
distinct cell borders, and are often multinuceated and have bizarre nuclei and prominent nucleoli. There are 0-3
mitoses per 10 high power fields (8 per 50 high power fields) in all regions. Along the thick fibrous septae,
neoplastic cells abut and bulge into large irregular, occasionally blood-filled, endothelial-lined clefts. Clusters of
neoplastic cells are occasionally present within these vascular lumina.
Neoplastic cells exhibited strong cytoplasmic immunoreactivity for smooth muscle actin and vimentin and variable
to strong cytoplasmic immunoreactivity for desmin. A well-defined basal lamina surrounding the individual tumor
cells was demonstrated by positive immunoreactivity for laminin outlining the cytoplasmic border of each cell.
Neoplastic cells were diffusely negative for pan-cytokeratin, cytokeratin 14, synaptophysin, CD11c, skeletal myosin,
factor VIII-ra, and S100 α and β. With factor VIII-ra, a single layer of endothelium could be variably demonstrated
separating the tumor from the lumina of vessels and clefts. With S100, several immunoreactive nerves were present
within the tumor.
Mass, left cheek: Malignant glomus tumor (glomangiosarcoma)
Malignant glomus tumor (glomangiosarcoma)
Glomus tumors are thought to arise from modified smooth muscle cells of the glomus
body, a type of arteriovenous anastomosis or shunt which is involved in regulating temperature.(6,10) Glomus bodies
are composed of an afferent arteriole and small venules connected by a series of small channels (Sucquet-Hoyer
canals), surrounded by dense collagenous tissue, and closely associated with small nerve branches. Within the walls
of the anastomosing canals are epithelioid cells with ultrastructural and immunocytologic features similar to smooth
muscle cells, called glomus cells, which are thought to be the cell of origin for glomus tumors.(4,10)
Glomus tumors have best been characterized in humans where their locations correspond to the most common sites
for glomus bodies, i.e. subungual regions and skin of the extremities. Other reported sites of glomus tumors in
humans include dermis, subcutis and soft tissues in other locations, as well as bone, nerve, stomach, colon, nasal
cavity, and trachea.(6,10) Glomus tumors of the head and neck account for only approximately 6% of the cases in
humans.(10) A similar distribution has been seen in dogs and cats, with most of the few reported cases occurring in
the digits.(2,3,7,9) Of the 3 known cases of glomus tumors in horses, one occurred as an osteolytic lesion within the
third phalanx deep to the hoof wall, a presentation very similar to that seen in humans,(1) while two others, this and
another unpublished case from UC Davis, occurred in the cheek and skin of the neck, respectively. The distribution
of normal glomus bodies in horses has not been well-characterized, although they occur frequently in the skin of the
A feature of glomus tumors of the subungual region in humans, and less commonly of these tumors in other sites, is associated intense pain, presumably a result of innervation with substance P-containing nerve fibers.(6,10) In human medicine, this feature is diagnostically useful as few types of skin tumors are painful. Some degree of soreness was thought to be associated with this tumor, which was immediately adjacent to the facial nerve grossly and included several nerve fibers histologically. Interestingly, the other equine glomus tumor in the UC Davis case files was removed because it appeared to be painful to the horse when touched.
Glomus tumors in humans can be classified as solid, angiomatous, or myxoid types.(6) Except for multiple angiomatous glomus tumors in the bladder of a cow,(5) glomus tumors in animals, including this case, have generally been of the solid type.(2,3,7,9) They have several characteristic features which were seen in this case, including an intimate relationship with blood vessels, which may only be evident at the periphery, a round or cuboidal epithelioid cell shape with a punched out round nucleus and eosinophilic cytoplasm, and a network of basement membranes around each cell.(6,10) Immunohistochemistry for laminin was used in this case to demonstrate the basal lamina surrounding the neoplastic cells. Primary differential diagnoses for this tumor included trichoblastoma (the initial diagnosis), other epithelial neoplasms, or a neuroendocrine tumor, all of which were ruled out with additional immunohistochemical stains. Typical of glomus tumors, the neoplastic cells were positive for smooth muscle actin and vimentin and negative for cytokeratins, synaptophysin, factor VIII, and S100. The cells were variably positive for desmin, which has occasionally been reported in human and canine glomus tumors.(10)
In humans, malignant glomus tumors (glomangiosarcomas) are very rare, but have been defined by being larger than 2 cm with a deep location, having atypical mitotic figures, or having marked nuclear atypia and mitoses >5 per 50 high power fields (hpf). The tumor in this horse was considered to be malignant based on recurrence and rapid growth, invasiveness of deep tissues, large size, and areas of marked cellular atypia. Mitotic figures were also 8 per 50 hpf. Although clusters of neoplastic cells appeared to be present within vascular channels, true intravascular invasion was difficult to assess because of the close association of the tumor with blood vessels. No metastases were evident at presentation. The horse was treated with intralesional injections of cisplatin every 2-4 weeks post-surgery, with a total of 4 treatments planned. However, the mass recurred prior to the final injection, and the horse was euthanized (necropsy not performed at our institution).
Left cheek, fibrovascular tissue: Glomus tumor.
Despite the history of recurrence and rapid growth, conference participants felt the tumor
was a benign entity based on the section presented in conference, and a discussion on the features of malignancy
was held. Cytomorphologic features mentioned by the contributor such as areas of cellular atypia, atypical mitoses,
and local invasiveness were not seen by conference participants, who felt the tumor showed no overt signs of
The differentiation between benignancy and malignancy is one of the most important roles of the pathologist, and tumors can sometimes defy typical classifications, so a best effort must be made on a diagnosis. Standard features to differentiate a benign tumor from its cancerous counterpart are the amount of differentiation or presence of anaplasia, the rate of growth, and the presence of local invasion and metastasis. The moderator commented that often with a surgical biopsy, which can be accompanied by a limited or no history as was the case with conference participants, the pathologist gets no information on metastasis, and local invasion may not be observed if no adjacent normal tissue is present(8).
Differentiation is the degree to which neoplastic cells resemble the cell or tissue of origin, both in appearance and function. Anaplasia is when the tumor is poorly differentiated, and it is believed that the undifferentiated cells with immature stem-cell-like properties with a loss of differentiation capacity. Anaplastic tumors may also exhibit lack of cell and nuclear uniformity, or pleomorphism; abnormal nuclear morphology with hyperchromasia, high nuclearto- cytoplasmic ratio, irregular shape, and variable nucleoli; bizarre mitoses or a high mitotic rate; loss cellular polarity with haphazard organization; tumor giant cells; and large areas of ischemic necrosis. The rate of growth in malignant tumors is often erratic, ranging from slow to rapid, and this is a difficult parameter to measure and use for the evaluation of malignancy. The local aggressiveness of a tumor is a good indicator of malignancy, as benign tumors are often expansile, while malignant tumors invade or efface the surrounding normal tissue. Malignant tumors are often poorly demarcated and lack an obvious cleavage plane. Finally, the presence of metastasis is an indisputable marker of malignancy, as benign tumors by definition to do not metastasize. Metastasis is achieved through either the seeding of body cavities and surfaces, as in carcinomatosis, or hematogenous or lymphatic spread. While generally carcinomas spread via lymphatic routes and sarcomas spread via hematogenous routes, the interconnectedness of the two vascular systems often blurs these lines. In lymphatic spread, neoplastic cells follow the natural route of lymphatic drainage. In hematogenous spread, veins are more easily penetrated by neoplastic cells, and spread usually occurs in the closest capillary bed. However, pulmonary capillary beds or primary pulmonary tumors allow easier access to arterial spread(8).
Despite the history of recurrence and rapid growth, conference participants felt the tumor was a benign entity based on the section presented in conference, and a discussion on the features of malignancy ensued. Cytomorphologic features of malignancy, such as areas of cellular atypia, atypical mitoses, and local invasiveness, lack of cellular differentiation, and evidence of metastasis, were not appreciated by conference participants The moderator commented that often with a surgical biopsy, limited or no history and the relatively small amount of tissue evaluated in a single histologic slide may make the differentiation between benign and malignant tumors elusive.
The moderator offered his approach to the characteristics of malignancy in order of most reliable to least as follows: By its very definition, evidence of metastasis means that a tumor is malignant. However, this information is often not present, and the next best feature to indicate metastasis is the presence of intravasation of the neoplasm, which underscores its aggressive nature. The next most reliable feature of malignancy is focal tissue invasion, characterized by neoplastic cells breaking through basement membranes, or inciting a desmoplastic response, inflammation or other features of host reaction. The least reliable criterion of malignancy is the cytologic appearance of neoplastic cells. When evaluating malignancy based on cellular features, evidence of cell behavior is more important that their appearance, such as the presence of bizarre mitotic figures; however, this can be difficult to completely ascertain based on the two-dimensional cut through a three-dimensional nucleus.
Glomus tumors are often difficult to characterize based on histomorphology alone, and this was an excellent example, having definitive features of a glomus tumor, including characteristic bulging into vascular channels.
1. Brounts SH, Adams SB, Vemireddi V, Holland CH: A malignant glomus tumour in the foot of a horse.
Equine Vet Educ 20: 24-27, 2008
2. Dagli MLZ, Oloris SCS, Xavier JG, dos Santos CF, Faustino M, Oliveira CM, Sinhorini IL and Guerra JL: Glomus tumour in the digit of a dog. J Comp Path 128: 199-202, 2003
3. Furuya Y, Uchida K, Tateyama S: A case of glomus tumor in a dog. J Vet Med Sci 68: 1339-1341, 2006
4. Ludewig T: Occurrence and importance of glomus organs (Hoyer-Grossers organs) in the skin of the equine and bovine mammary gland. Anat Histol Embryol 27: 155-159, 1998
5. Roperto S, Borzacchiello G, Brun R, Perillo A, Russo V, Urraro C, Roperto F: Multiple glomus tumors of the urinary bladder in a cow associated with bovine papillomavirus type 2 (BPV-2) infection. Vet Pathol 45: 39-42, 2008
6. Rosai J: Soft tissues. In: Surgical Pathology, 9th ed., pp. 2288-2290. Mosby, St. Louis, MO, 2004
7. Shinya K, Uchida K, Nomura K, Ozaki K, Narama I, Umemura T: Glomus tumor in a dog. J Vet Med Sci 59: 949-950, 1997
8. Stricker TP, Kumar V. Neoplasia. In: Kumar V, Abbas AK, Fausto N, Aster JC, eds., Robbins and Cotran Pathologic Basis of Disease. 8th ed. Philadelphia, PA: Saunders Elsevier; 2010:262-271.
9. Uchida K, Yamaguchi R, Tateyama S: Glomus tumor in the digit of a cat. Vet Pathol 39:590-592, 2002
10. Weiss SW, Goldblum JR: Perivascular tumors. In: Soft Tissue Tumors, 5th ed., pp. 751-757. Mosby, St. Louis, MO, 2008