Spindle cell rhabdomyosarcoma is a rare variant of embryonal rhabdomyosarcoma that has a predilection for young males and most commonly involves the paratesticular region followed by head and neck. Histopathology demonstrates elongated spindle cells with fusiform to cigar-shaped nuclei and indistinct eosinophilic cytoplasm arranged in fascicles or whorls. Although the tumor demonstrates increased cellularity and moderate atypia, the microscopic and architectural patterns can allow this tumor to be confused with multiple entities, such as leiomyosarcoma, spindle cell carcinoma, desmoplastic melanoma, or fibrosarcoma, with important therapeutic implications. Immunohistochemical workup demonstrates sarcomeric differentiation with reactivity for desmin, myogenin, and MyoD1 markers. Compared with other subtypes, the spindle cell variant in children is associated with a favorable outcome; however, in the adult population there does not appear to be any prognostic advantage.

Rhabdomyosarcoma (RMS) is the most common childhood and adolescent sarcoma showing features of skeletal muscle differentiation. It is classified into 3 histologic subtypes (embryonal, alveolar, and pleomorphic) by their unique characteristics, with the embryonal type comprising most of these cases.1  Spindle cell rhabdomyosarcoma (SC-RMS), 1 of the 3 embryonal rhabdomyosarcoma variants, was first recognized in the pediatric population in 1992 by the German-Italian Cooperative Sarcoma Study.2  It affects mainly young males, occurs predominantly in the paratesticular region, and is characterized by a fascicular proliferation of spindle cells with rhabdomyoblastic differentiation. In the population examined, it has a better prognosis, as supported by additional reports from the Intergroup Rhabdomyosarcoma studies3,4  (5-year survival of 95.5% and 88%). Following description of this variant, a few small studies were published presenting this tumor in the adult population, where it appears to have a more aggressive clinical course than previously described.57  Even though embryonal rhabdomyosarcoma is common, the spindle cell variant is considered rare (only 3% of all RMS cases in Intergroup Rhabdomyosarcoma Study4). Recently, some authors8  have suggested a higher incidence in adults than initially recognized, although the overall number of cases described is low. Proper identification is important as patients with RMS may benefit from specific neoadjuvant chemotherapy, whereas chemotherapy is of more questionable value in the treatment of other types of sarcomas.

In the initial studies, SC-RMS showed a strong predilection for young patients (mean age approximately 7 years)9  in the paratesticular region followed closely by head and neck.2,3  In adults, the tumor demonstrates a preference for the head and neck region with a minority of cases arising in other locations such as subcutaneous and deep soft tissues of the extremities6,7  and visceral organs as seen in occasional case reports.1012  The clinical presentation is usually that of a rapidly growing, painless, soft tissue mass with specific symptoms related to the location and infringement on surrounding structures, which can produce urinary retention, diplopia, unilateral deafness, proptosis, and sinusitis. Although many cases appear de novo, 1 case report13  associates the disease with prior radiation therapy.

The size of these lesions can vary significantly, with a range of 1.5 to 35 cm.6  Tumors located in the paratesticular region allow for earlier detection, whereas pelvic tumors tend to be larger.14  In 1 case involving an 11-year-old girl with a facial mass evaluated in our department, the tumor reached 27 cm (Figure 1, A). Spindle cell rhabdomyosarcoma can be either well or poorly circumscribed and there are no specific macroscopic features to distinguish this tumor. The cut surface reveals a firm, white to tan mass with a whorled appearance, which can mimic leiomyoma or leiomyosarcoma, especially when presenting in the uterus of an adult female.11  Necrosis, a common finding, along with cystic degeneration and interspersed areas of hemorrhage, can also be secondarily induced by preoperative embolization procedures (Figure 1, B).

Figure 1.

A, Gross appearance of a spindle cell rhabdomyosarcoma evaluated in our department. B, Close-up view of the same case demonstrating necrosis and cystic degeneration.

Figure 2. Light microscopy shows eosinophilic spindle cells arranged in long fascicles. The cells are minimally pleomorphic with tapered nuclei (hematoxylin-eosin, original magnification ×20).

Figure 1.

A, Gross appearance of a spindle cell rhabdomyosarcoma evaluated in our department. B, Close-up view of the same case demonstrating necrosis and cystic degeneration.

Figure 2. Light microscopy shows eosinophilic spindle cells arranged in long fascicles. The cells are minimally pleomorphic with tapered nuclei (hematoxylin-eosin, original magnification ×20).

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Histopathology is dominated by a uniform cellular proliferation of elongated, spindle cells arrayed in fascicles or whorls demonstrating a herringbone growth pattern reminiscent of leiomyosarcoma.9  The cells have centrally located nuclei with blunted or fusiform ends, small to inconspicuous or prominent nucleoli, and eosinophilic fibrillar cytoplasm (Figure 2). Mitotic figures are easily appreciated, including atypical forms. Admixed with this population can be a second cell type of immature rhabdomyoblasts,14  usually comprising a small percentage of the total tumor. These cells exhibit eccentric nuclei and bright cytoplasmic eosinophilia; on occasion, cytoplasmic cross-striations can be observed. The presence of these cells should be an intimation of the diagnosis.

Collagen fibers are frequently intermingled between the spindle cells; however, the degree is highly variable. The extent of collagen production has led some authors4  to subclassify SC-RMS into collagen-rich and collagen-poor forms. In the collagen-poor form, the cells are disposed in bundles or fascicles with abundant cellularity and little or no stroma, resembling leiomyosarcoma. In the collagen-rich form, the cellularity is reduced by abundant fine collagen fibers with a “storiform” pattern giving it a more sclerotic appearance. The subclassification does not appear to affect clinical outcome; nonetheless, a pathologist should be aware of the different presentations of this tumor.

Given the large differential diagnosis for SC-RMS, immunohistochemistry plays a pivotal role in identification of this lesion. While there is some debate over whether rhabdomyosarcomas indeed arise from skeletal muscle cells, the staining pattern is consistent with that differentiation. Spindle cell rhabdomyosarcoma consistently reacts with myogenic markers such as desmin, titin, troponin D, myoglobin, MyoD1 (Figure 3, A) and myf-4 (myogenin) (Figure 3, B). The proportion of desmin-positive cells may vary from case to case depending on the number of differentiated cells, and desmin expression is usually mirrored by muscle-specific actin immunoreactivity. Because desmin immunostain exhibits occasional nonspecific reactivity in smooth muscle cells and myofibroblasts, as well as other tumors such as desmoplastic small round cell tumor, desmin immunostain should never be used as a sole marker for diagnosis, but as part of a panel of immunostains.15  While all rhabdomyosarcomas will stain with these markers, this variant appears to demonstrate a higher degree of differentiation owing to the consistency of the expression of late myogenesis markers, specifically titin and troponin.3,9  Myogenin and MyoD1 are myogenic nuclear transcription factors present early in skeletal muscle differentiation and are currently used as a standard approach to diagnosis, with sensitivity exceeding 95% and specificity of virtually 100%.14  They are considered more sensitive and specific than desmin, with myogenin showing no reactivity in other spindle cell proliferations, such as nodular fasciitis, malignant peripheral nerve sheath tumor, leiomyosarcoma, or myofibrosarcoma, which may come in the differential diagnosis.16  The diagnostic utility of Myo-D1 could be limited by technical challenges with background and cytoplasmic nonspecific staining; however, at our institution we have not experienced enough difficulty with this stain to discontinue its use.

Figure 3.

A, MyoD1 immunostain shows diffuse nuclear staining. B, Myogenin immunostain shows focal positivity with nuclear staining (original magnifications ×10 [A] and ×20 [B]).

Figure 3.

A, MyoD1 immunostain shows diffuse nuclear staining. B, Myogenin immunostain shows focal positivity with nuclear staining (original magnifications ×10 [A] and ×20 [B]).

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In occasional reports, SC-RMS has shown variable aberrant staining for Wilms tumor 1 (WT1), and CD99.7 To complicate the picture, rare cases with focal reactivity for keratins and epithelial membrane antigen have been described.6,8  Strong reactivity for c-kit (CD117) was reported, suggesting possible implications of the c-kit pathway in tumorigenesis and therapy.17  Negative reactivity for S100, h-caldesmon, CD34, and glial fibrillary acidic protein help in the differential diagnosis with other types of sarcomas (Table).

Immunoprofiles of Similar Spindle Cell Neoplasms

Immunoprofiles of Similar Spindle Cell Neoplasms
Immunoprofiles of Similar Spindle Cell Neoplasms

While embryonal RMS has been thoroughly studied for cytogenetic abnormalities, the studies focusing specifically on SC-RMS are scarce and do not bring any clear genetic data to link this subset with either embryonal or alveolar RMS. Two studies have focused on individual tumor cases and demonstrated presence of abnormal karyotypes with hypotriploid modal chromosome number and rearrangements affecting chromosomes 1, 8, 12, 21, and 2218  and involvement of 2q36-q37 in a subpopulation of cells in another case.19  The absence of a “signature” translocation with loss of heterozygosity and gains and losses of chromosomes is more common in embryonal type of rhabdomyosarcoma.8,14  Minimal overlap between reported cytogenetic analyses may be due to the rarity and complexity of this tumor, as well as scarcity of studies looking at this aspect.

Making the correct diagnosis is of critical importance owing to the wide range of treatment modalities of this particular variant. The differential diagnosis is influenced by the patient's age and tumor location. In children and adolescents, most soft tissue malignancies are rhabdomyosarcomas.20  Spindle cell rhabdomyosarcoma provides a diagnostic challenge by virtue of its similarity to other spindle cell neoplasms, mostly of smooth muscle, fibromyoblastic, and nerve origin. High on the differential diagnosis list is leiomyosarcoma; owing to morphologic similarities between these neoplasms, SC-RMS is mentioned in old publications as “leiomyomatous” embryonal RMS.4  The spindle cells comprising most SC-RMS are morphologically similar to smooth muscle cells and to complicate matters further, they show variable staining for certain smooth muscle markers like actin (smooth muscle and muscle specific) and desmin.6  The eosinophilic cytoplasm, with blunted central nuclei and tapered ends arranged in densely arrayed whorls, further support the confusion. If cytoplasmic cross-striations or rhabdomyoblasts are present, they can point toward additional immunohistochemical workup, which confirms the skeletal muscle differentiation. Adult and infantile fibrosarcoma will also have similar spindled cells, and both tumors can demonstrate herringbone architecture, but immunoreactivity for myogenin or MyoD1 in SC-RMS should help in that distinction. In the adult population, desmoplastic melanoma and spindle cell (sarcomatoid) squamous cell carcinoma are substantially more common in the head and neck region and should be considered first in this age group. A large variety of myofibroblastic and histiocytic proliferations, such as nodular fasciitis, malignant fibrous histiocytoma, inflammatory myofibroblastic tumor, low-grade myofibroblastic sarcoma, or myofibrosarcoma, do not stain for myogenin.16  In the case of an inflammatory myofibroblastic tumor, Anaplastic lymphoma kinase-1 (ALK-1) positivity may also be of use. Malignant peripheral nerve sheath tumor (MPNST) and malignant triton tumor (MPNST with rhabdomyoblastic differentiation), potential candidates on morphologic grounds alone, arise often from a large peripheral nerve in patients with known neurofibromatosis. As with any soft tissue spindle neoplasm, immunohistochemistry can play a prominent role in the final diagnosis, and reactivity for S100 stain is of great help when present (Table). However, S100 staining is not infrequently negative in these tumors and differentiating between a malignant triton tumor and SC-RMS can be extremely difficult by histopathology alone; sometimes only a diagnosis of neurofibromatosis for the patient will aid in the diagnosis.

The SC-RMS that was seen at our department (mentioned previously) had originally been diagnosed as a leiomyoma and was treated with only local excision. The tumor recurred within less than 1 year and was larger than the previous excision. At this time the diagnosis of leiomyosarcoma was given with resection. Again, within less than 1 year the mass had recurred with a significant size increase and morbidity. Only at the time of the third resection was the diagnosis of spindle cell rhabdomyosarcoma made. The patient received resection with a successful skin graft placement and appropriate chemotherapy and radiation. She has been recovering well with a positive attitude. This case demonstrates how important it is to consider this entity in the differential diagnosis of spindle cell lesions; had she received the correct diagnosis initially, she might have been spared the degree of disfiguration and morbidity that she experienced.

By far the most significant distinction associated with spindle cell rhabdomyosarcoma is the prognosis. Pediatric SC-RM has been shown to have a highly favorable prognosis in comparison to other forms of RMS.2,3  In this population, paratesticular lesions appear to have an even better prognosis than tumors of nonparatesticular sites,3,4  most likely related to earlier diagnosis in this location. It is important to note that major prognostic factors in these tumors are resectability, tumor size (which also correlates with resectability), histologic subtype, and tumor stage.20  Owing to complex anatomy of the head and neck region and the local aggressiveness of the tumor, it is often difficult to obtain adequate free surgical margins, which hamper local control of the disease. In the adult population, SC-RMS has a poorer prognosis, whereby 40% of patients have experienced uncontrolled local disease, 25% developed metastases, and 17% died of the disease.6  Similar results are seen in smaller case reports.5,7 

Spindle cell rhabdomyosarcoma are treated aggressively with similar protocols as for other RMS and owing to their rarity, very little research has been done on the use of a different approach for this variant. The standard protocols involve combined therapy including surgery, chemotherapy, and adjuvant radiation. Staging of rhabdomyosarcomas is based on resection and clinical findings, which include site of origin, presence or absence of residual disease, lymph node involvement, and distant metastases. On the basis of these aspects, the Intergroup Rhabdomyosarcoma Study Postsurgical Clinical Grouping System21  classifies RMS in 4 different groups. A specific grouping system for SC-RMS has not been identified and this variant falls into the general grouping system. Group I contains completely resected tumors without lymph node involvement, group II is composed of cases with complete resection and lymph node involvement or microscopic residual disease, group III includes patients with gross residual disease, and group IV contains tumors with distant metastases. This grouping system is used to plan additional radiation therapy for the tumor.

In children with any rhabdomyosarcoma, this multimodality approach has led to a cure rate of approximately 70%. Children who survive the first 5 years have been found to have an excellent long-term prognosis.22  However, in adults, the 5-year survival approached only 53% in 1 study.8 

Spindle cell rhabdomyosarcoma is a distinct variant of embryonal rhabdomyosarcoma that demonstrates a predominant spindle cell population with or without admixed foci of rhabdomyoblasts. Clinical setting and morphology should trigger appropriate immunohistochemical workup, which can be of great aid in distinguishing this entity from multiple other spindle cell neoplasms. This tumor carries a better prognosis than other rhabdomyosarcomas in children and correct identification has impact on therapy.

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