Rhabdomyoblast

Sarcomas are cancers that originate from connective tissues. Rhabdomyosarcoma is a sarcoma composed of skeletal muscle cells; irregular growth in the primitive form of these skeletal muscle cells, rhabdomyoblasts, are commonly associated with Rhabdomyosarcoma.[3] Being the most common sarcoma among the childhood population, the level of rhabdomyoblast differentiation is variable between and within Rhabdomyosarcoma subtypes.[3] The rhabdomyoblast displays only condensed eosinophilic cytoplasm at the undifferentiated state, but becomes more defined with increased differentiation.[3] Variations in cytoplasmic shape range from stretched to polygonal.[3] Immunochemistry is needed to prove the presence of rhabdomyoblast differentiation.[3] Detection for MyoD1 and myogenin is used frequently. Staining sensitivity is highly variable from subtype to subtype.[3] For instance the myogenin staining is far less efficient than Myod1 in the spindle cell rhabdomyosarcoma subtype.[3] Variable levels of desmin are also reported among rhabdomyosarcomas.[3]

It has previously been suggested that there are four subtypes of rhabdomyosarcoma. Recent studies have advocated for the emergence of three additional subtypes: those with Myod1 mutations, TFCP2 mutations, and VGLL2/NCOA2 fusions.[3] In general, the severity of rhabdomyosarcomas vary based on the tumor location and other factors; the five year survival rates rang from 35% to 95%.[16]

Infantile rhadbodomyofibrosarcoma is an extremely rare sarcoma variant.[5] Only being present in children under the age of three, the rare sarcoma shares many features with infantile fibrosarcoma.[5][17] Concerns arise due the similarities between these two sarcomas; rhadbodomyofibrosarcomas have a more aggressive and costly prognosis than that of fibrosarcomas through distant metastasis and recurrence.[17] There are troubling beliefs that rhadbodomyofibrosarcomas may be underdiagnosed, resulting in potential under treatment.[17] Histologically, rhadbodomyofibrosarcomas display a wide variety of rhabdomyoblasts within spindle cell proliferation.[5] These neoplastic cells yield positive results for vimentin, smooth muscle actin, and desmin stains; however, myoglobin, myoD1 and myogenin stains yield negative test results.[5] Thus, the detection of rhabdomyoblasts can play a key role in distinguishing rhadbodomyofibrosarcomas from fibrosarcomas.[17]

Malignant peripheral nerve sheath tumors are aggressive soft tissue sarcomas occurring on the exterior lining of nerves.[5] These nerves extend outward from the spinal cord to the rest of the body. Commonly, tumors develop promptly on extremities due to a mutation of the tumor suppressor, neurofibromin.[18] These developments do not possess precise sub-cellular characteristics.[5] Histological tests indicate epithelial and mesenchymal cell differentiation; neoplastic skeletal muscle displays rhabdomyoblasts during differentiation.[5] A subcategory of malignant peripheral nerve sheath tumors in particular, malignant triton tumors, have an enhanced expression of rhabdomyoblast differentiation.[5] Its name was coined due to the tumor's ability to promote the growth of limbs on the backs' of triton salamanders in animal transplant models.[5] The quantity of rhabdomyoblasts present throughout the stroma is variable, with defining characteristics being eosinophilic rich cytoplasm and an unusual polygonal-like shape.[5] Microscopically, the cytoplasmic content makes the rhabdomyoblast easily identifiable at low power due to its sharp contrast with the pale background of Schwannian cells.[19] The severity and rapidness of progression in malignant triton tumors exceeds that of other malignant peripheral nerve sheath tumors; the short term survival rates of those with malignant triton tumors are significantly lower than the alternative.[5] These more consequential prognoses can sometimes be detected through rhabdomyoblast characterization.[5] The differentiation of rhabdomyoblasts in malignant triton tumors from that of rhabdomyosarcomas may be difficult; this difficulty can be further compounded by the association of patients with neurofibromatosis 1 and increased risk of rhadbodomyofibrosarcoma.[19] The detection of benign nerve sheath tumors, a dense Schwannian cell background, negative test results for desmin, myogenin and MyoD1 are reliable indicators of a malignant triton tumor.[19]

Malignant ectomesenchymomas are rare sarcomas found in children; they contain neuroectodermal and mesenchymal neoplastic elements.[20] The abnormal growth has an unusual prognosis, stemming from the developing neural crest tissue during embryogenesis.[5] A finite number of malignant ectomesenchymoma cases have previously been reported, with the majority presenting in young males.[5] Extensive research is needed for a more detailed report; however, embryonal rhabdomyosarcoma and rhabdomyoblast differentiation have been detected histologically.[5] The development of malignant ectomesenchymomas are still not fully understood; it has been suggested, due to consistent genetic abnormalities, that the neoplasm may be a variant embryonal rhabdomyosarcoma.[21]

A 'nephroblastoma, also referred to as Wilms' tumor, arises from blastemal cells and induces abnormal cellular differentiation in children.[5] The tumor is the most common pediatric genitourinary tumor, affecting approximately 1 in every 8,000-10,000 children.[5] Upon examination, a solid mass with regions indicative of necrosis are typically seen.[5] Some cases present a projection of the tumor into the renal pelvis. This progression suggests skeletal muscle differentiation, establishing differential diagnosis hardships with rhabdomyosarcoma.[5] Various degrees of skeletal differentiation in the stroma are observed. Rhabdomyoblasts are observed in the most frequent divergent cell line.[5] The rare deviation of Wilms' tumor, fetal rhabdomyomatous nephroblastoma, is composed predominantly of differentiating rhabdomyoblasts.[5] This variant can also be identified by defined striations and central nuclei.[22] Fetal rhabdomyomatous nephroblastoma is known to be unresponsive to chemotherapy; surgery has proven to be the optimal treatment method.[22] For this reason, its identification is significant for proper patient treatment.[22]

Pleuropulmonary blastoma development occurs in children; its presentation can occur via pulmonary or pleural based neoplasms.[5] Clinically, its presence in children induces respiratory distress, a non-productive cough, fever, and chest pain.[5] Three evolutions of pleuropulmonary blastomas are known and categorized based on prognostic elements.[23] Type 1 pleuropulmonary blastomas are composed of purely cystic tumors.[5] Type 1 pleuropulmonary blastomas have the potential to progress into type 2 and type 3, which consist of a mixture of cystic and solid tumors and purely solid tumors respectively.[5] In the type 1 categorization, the exterior region of the cyst may contain rhabdomyoblastic differentiation in addition to the early stages of abnormal tissue growth.[5] Type 2 and type 3 categorizations contain a blastematous and mesenchymal component.[5] The mesenchymal portion may exhibit elongated rhabdomyoblasts in sheets or clusters; this appearance is a product of the common rhabdomyosarcomatous proliferation.[5] Detection of these features can be confirmed with the use of immunochemistry.[5]

Rhabdomyoblastic differentiation has been detected in several other malignancies associated with the head and neck area.[19] Additional malignancies include sarcomatoid carcinoma, undifferentiated (anaplastic) thyroid carcinoma, salivary carcinosarcoma, olfactory neuroblastoma, teratocarcinosarcoma, malignant teratoma, melanoma, liposarcoma and more.[19] This identifies the potential for misdiagnosis, as rhabdomyoblastic differentiation is present in several neoplasms.[19]