Alveolar Rhabdomyosarcoma in a Juvenile Labrador Retriever: Case Report and Literature Review
A 7 mo old Labrador retriever presented for evaluation of facial swelling associated with a 5 cm oral mass extending caudally from the upper third premolar on the left side. Cytology revealed an atypical population of round cells of undetermined origin. A diagnosis of alveolar rhabdomyosarcoma (RMS) was reached via histopathology and confirmed with positive immunohistochemical staining for desmin. In humans, RMSs have a well-described round cell cytologic appearance. Few descriptions of veterinary cases of RMS exist. This report describes the cytologic appearance of alveolar RMS in a young dog and both summarizes and compares findings throughout the veterinary and human literature.
Introduction
Rhabdomyosarcoma (RMS) is an uncommon type of soft-tissue sarcoma seen in a wide variety of species including humans, dogs, cattle, sea lions, and birds.1,2 In human medicine, RMSs are the most common sarcoma observed in children, but are generally rare in adults.3 These tumors appear to be more common in young veterinary patients as well.4–9 RMSs show varying degrees of striated muscle differentiation, and may develop from either muscle stem cells or mesenchymal stem cells.10 Tumors may arise from any location in the body. Canine tumors have been noted in the tongue, oral cavity, ocular orbit, heart, and genitourinary system.4–9 Bone marrow involvement mimicking acute leukemia with or without a solid tumor has also been reported in people.11 Histologically, RMS can be divided into four categories: alveolar, embryonal, botyroid, and pleomorphic.3 Some consider botyroid to be a subclassification of embryonal RMS and therefore classify RMS into only three categories. The first three types of RMSs are most commonly seen in younger animals whereas pleomorphic RMS is more commonly seen in adults. Alveolar RMS is more aggressive than other types and carries a worse prognosis.12
In the last 2 decades, guidelines for cytopathologic diagnosis of human RMS have been developed as cytopathology is considered a reliable diagnostic tool for this tumor. Cytologic differentiation between types of RMS is not considered to be reliable.13,14 In the veterinary literature, there are few descriptions of the cytologic appearance of RMS. In this article, the authors present a case of an alveolar RMS in a dog and assess the applicability of the human criteria for cytologic diagnosis of RMS in dogs.
Case Report
A 7 mo old castrated male Labrador retriever presented to the referring veterinarian for examination of a left-sided facial swelling. The facial swelling, which was first noted 3 mo earlier, was treated empirically as a lacrimal gland blockage and then as a tooth root abscess. Because the facial swelling was progressive, fine-needle aspirates (FNAs) were submitted to a pathologist for evaluation.
FNAs were moderately cellular with numerous individualized and loose packets of round to oval cells with variably distinct cell margins and a small amount of lightly basophilic cytoplasm (Figures 1, 2). Cells were 12–18 μm in diameter, and contained a single round nucleus with a finely stippled chromatin pattern. Some nuclei contained one to two nucleoli. There was moderate anisocytosis and anisokaryosis. Many tiny basophilic cytoplasmic fragments were identified in the background of the sample. An increase in neutrophils was noted as well as occasional medium length extracellular rod-shaped bacteria. A cytologic diagnosis of atypical round or mesenchymal cellular proliferation with evidence of mild neutrophilic inflammation was made. Biopsy was recommended for further characterization of the lesion.
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5693
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5693
Following the completion of the initial cytology reports, the patient presented to a referral veterinary hospital for further diagnostics. The oral mass was found to be approximately 5 cm in diameter with irregular margins, extending caudally from the third premolar on the left side. The swelling associated with the mass was causing marked facial deformity (i.e., the left eye was partially closed and the left third premolar was displaced). The mass extended past the palate midline and was necrotic, ulcerated, and bleeding. The left mandibular lymph node was also enlarged. Several punch biopsies of the mass were obtained, and impression smears were made before placing the biopsy tissue in formalin.
Impression smears were highly cellular with a prominent population of atypical round to (rarely) elongate cells, identical to those noted in the aspirates. A marked increase in neutrophils was noted with numerous intracellular and extracellular medium-length bacterial rods. Based on the description of the mass and the cytologic appearance of the sample, a cytologic diagnosis of malignant neoplasia with marked septic neutrophilic inflammation was made. Given the age of the patient, consideration was given to a primitive neuroectodermal tumor or other germ-line tumor.
Histopathologic examination of the biopsy samples revealed atypical round to spindloid cells arranged in short intersecting fascicles, sheets, and alveolar patterns with a supporting stroma. Atypical cells contained scant cytoplasm with an oval nucleus and one to two small nucleoli. A mitotic rate of 8–10 mitotic figures/high-power field was noted. Histopathologic diagnosis was a high-grade sarcoma most consistent with alveolar RMS (Figures 3, 4). Immunohistochemical staining with desmin was performed, and the sample was positive for desmin staining, confirming a muscle origin (Figure 5).
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5693
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5693
Citation: Journal of the American Animal Hospital Association 47, 6; 10.5326/JAAHA-MS-5693
Due to the guarded to poor prognosis and the clinical aggressiveness of the lesion, treatment of the tumor was declined. The owner elected to take the patient home for euthanasia.
Discussion
Cytologically, human RMSs are grouped into “round cell neoplasia” or “small blue cell neoplasia” categories. Primary cytologic differential diagnoses in young animals include hematolymphoid round cell neoplasia and nonhematolymphoid round cell neoplasia, including primitive neuroectodermal tumors/Ewing sarcoma (PNET/ES).13–15 Although a cytologic diagnosis of RMS is considered reliable, it is not possible to definitively differentiate subtypes without histopathology. Cytologically, RMSs contain mostly individualized cells, many of which are round to oval and have a lymphoid or plasmacytoid appearance, which is thought to be compatible with the appearance of early rhabdomyoblasts.15 Occasional multinucleate cells with a strap-like appearance or with a “wreath-like” arrangement of nuclei may also be present.15 The proportion of different cell types can vary in individual tumors. Increased numbers of mitotic figures are commonly noted.14 Spindloid cells are rarely present in alveolar RMSs, but are seen more frequently in the other subtypes, and tissue with a classic striated muscle appearance are rarely noted in any of the tumor types.14
There is relatively little literature about the cytologic appearance of RMS in veterinary species. Two cases have reported predominately spindle-shaped cells, and two more recent cases reported the high cellularity and substantial round cell component seen in humans.6,16–18 Tissue consistent with striated muscle was not noted in three of the five veterinary cases with cytologic information. Although multinucleated cells were not a prominent feature the present case, they were noted in a recent article of a botyroid RMS from the tongue of a dog.6 Only one other case of cytology from an alveolar RMS in a veterinary species has been reported.18 In this case, atypical lymphoid-appearing round cells also predominated, with rare binucleate cells and increased mitotic figures.
Differential diagnoses for nonhematolymphoid small blue/round cell tumors include PNET/ES, neuroblastoma, and lymphoma. Human cytologic comparisons have found that PNET/ES and neuroblastomas tend to be more cohesive, and in PNET/ES, rosette formations are often noted.15 PNET/ES often contain a mixed population consisting of both dark apoptotic cells and cells with a large, pale-staining nucleus.15 Multinucleated cells are not a cytologic feature of either PNETs or neuroblastomas.15 There is little information on the cytomorphology of PNETs in dogs, but several reports give histologic descriptions of Ewing-like sarcoma in dogs, which is very similar cytologically to what is seen in people.19
In many cases, histopathology alone is sufficient to diagnose RMSs. In other cases, immunohisotochemistry, electron microscopy, and gene rearrangements (in humans) may be necessary to confirm the diagnosis. RMSs may exhibit variably staining for vimentin, desmin, and myoglobin. Myogenin and Myogenin differentiation 1 are thought to be specific for muscle differentiation, although desmin and muscle-specific actin are often substituted in veterinary medicine.20–22 The degree of cellular differentiation can impact the staining quality of the tumors. Vimentin is expressed earliest in muscle differentiation, followed by desmin and myoglobin.20 Recent articles in the human literature have found that significant numbers of RMSs may be also be focally positive for epithelial (cytokeratins) and/or neuroendocrine markers (synaptophysin and chromagranin-A).21,22 Additionally, some veterinary RMSs have evidence of immunoreactivity to neuronal markers, including neuron-specific enolase, S-100 protein and glial fibrillary acidic protein.23 It is not clear whether this is simply due to aberrant expression of cellular markers, lack of specificity of some immunohistochemical markers, or if there is actual epithelial/neuroendocrine/neural differentiation of the primitive neoplastic cells. Electron microscopy may serve as a useful diagnostic adjunct by demonstrating mitochondrial-laden cells and, rarely, cross-striations in tumors with myofibril differentiation. High numbers of mitochondria are also observed in oncocytomas; however, immunohistochemical staining patterns and the absence of cross striations differentiate these tumors from RMSs.4
Conclusion
Veterinary RMSs appear to be cytologically similar to human RMSs and should be considered as a possible differential diagnosis for a solid tumor with a round cell appearance in a young animal. Given the clinical aggressiveness of alveolar RMS, cytologic diagnosis (or suspicion for this tumor) may lead to improved assessment of prognosis and patient care in affected animals. Further investigation of cytologic characteristics of veterinary RMSs is indicated to improve clinical diagnostic efficacy.
Cytology of a fine-needle aspirate (FNA) of the oral mass demonstrating individualized round cells. Modified Romanowski stain, original magnification ×500.
Cytology of a FNA demonstrating loosely cohesive packets with individualized round cells. Modified Romanowski stain, original magnification ×500.
Histology of the oral mass demonstrating an alveolar pattern. Hematoxylin and eosin (H&E) stain, original magnification ×100.
Histology of the oral mass demonstrating an alveolar pattern. H&E stain, original magnification ×400.
The mass had cytoplasmic positivity for desmin. Original magnification ×500.
Contributor Notes
L. Snyder's present affiliation is Marshfield Laboratories, Marshfield, WI.
