Rhabdomyoblast

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A rhabdomyoblast is a cell type which is found in some rhabdomyosarcomas. [1] When found histologically, a rhabdomyoblast aids the diagnosis of embryonal, alveolar, spindle cell/sclerosing, and pleomorphic rhabdomyosarcomas; however, in a tumor, expression of the rhabdomyoblast phenotype is not the only factor in diagnosing a rhabdomyosarcoma. [2] [3] Mesenchymal malignancies can exhibit this phenotype as well. [3] Immunohistochemistry techniques allow for the sensitive detection of desmin, vimentin, muscle specific actin, and MyoD1. [4] Similarly the rhabdomyoblast phenotype can be detected morphologically. [3]

Contents

Rhabdomyoblasts are early stage mesenchymal cells, having the potential to differentiate into a wide range of skeletal cells. [5] Each stage of differentiation exhibits unique and distinguishable histological characteristics. In its initial form, stellate cells with amphiphilic cytoplasm and ovular central nuclei are observed. Commonly referred to as rhabdoid features, the maturing rhabdomyoblast will likely exhibit low levels of eosinophilic cytoplasm in proximal distances to the nucleus. [6] As maturation and differentiation progress, the cell's cytoplasmic levels of white blood cells increase; additionally, elongated shapes, commonly depicted as “tadpole”, “strap” and "spider cells", are observed. In the concluding phase of differentiation, the white blood cell rich cytoplasm appears bright and exhibits cross-striation. [5] The highly regulated organization of actin and myosin microfilaments in contractile proteins results in this appearance. [7]

With advancements in the medical field, the number of tumors connected to the rhabdomyoblastic phenotype has increased. [3] Recently, the lesion cells of 10 inflammatory tumors were found to possess the rhabdomyoblastic phenotype. [3] Continued research is necessary for precise molecular characterization of the rhabdomyoblastic phenotype and its use in patient case management. [3]

Post-Treatment rhabdomyoblast emergence

Cancer encompasses the group of diseases classified by abnormal cell growth. [8] While cases of cancer have increased, likely due to better methods of detection and potentially increased exposure to carcinogens, cancer has been present throughout human history. [9] [10] [11] The earliest written acknowledgment of cancer took place in 1600 BC in Edwin Smith Papyrus, an ancient Egyptian medical treatise. [11] The efficacy and availability of cancer treatments has tremendously improved since the disease's origin. Treatment options for various cancers consist of, but are not limited to, chemotherapy, radiation, and palliative care. [12] The type of treatment used is determined by a combination of factors, including recommendations provided by health professionals, patient preferences, and biological properties of the cancer.

Following cancer treatment, specifically through chemotherapy and radiation, lesions composed almost exclusively of mature rhabdomyoblasts can emerge. [13] This phenomenon, referred to as cytodifferention, in pediatric rhabdomyosarcoma has been accepted in the medical field for several decades. [13] The increase of differentiated rhabdomyoblasts can be attributed to the degradation of undifferentiated tumor cells. [14] In clinical settings, the emergence of post-chemotherapy rhabdomyoblast differentiation in cases of pediatric embryonal rhabdomyosarcoma is an encouraging prognosis, as it potentially signifies the tumor's increased response to the provided therapy. [14] Outlier case reports have been presented, including the aggressive prognosis of embryonal rhabdomyosarcoma and the simultaneous development adipocyte-like cells. [14] [15] Other favorable prognosis factors following target therapies exist and may serve as a more reliable indicator until sufficient data regarding rhabdomyosarcoma cases are available. [14] Medical professionals have suggested that well defined rhabdomyoblasts with a low mitotic index serve as a marker to terminate additional treatment regimens. [14] The mitotic index of a sample can be calculated by summing the number of somatic cells in prophase, metaphase, anaphase, and telophase, then dividing by the total number of quantifiable somatic cells.

Presence in pediatric neoplasms

Neoplasia, the formation of a neoplasm, can result in the expression of tumors and ultimately progress into cancers. The detection of rhabdomyoblasts is fundamental in the diagnosis of rhabdomyosarcomas, but rhabdomyoblast differentiation can be detected in several pediatric neoplasms. [5] It is important to note that rhabdomyoblastic differentiation is not a characteristic unique to rhabdomyosarcomas; in order for optimal treatment to be administered, the neoplasm containing rhabdomyoblasts should be carefully and correctly classified. [5]

Rhabdomyosarcoma

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]

Rhadbodomyofibrosarcoma

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]

Peripheral nerve sheath tumors

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]

Ectomesenchymoma

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]

Nephroblastoma

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

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]

Other head and neck malignancies

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]

Related Research Articles

<span class="mw-page-title-main">Sarcoma</span> Cancer originating in connective tissue

A sarcoma is a malignant tumor, a type of cancer that arises from cells of mesenchymal origin. Connective tissue is a broad term that includes bone, cartilage, muscle, fat, vascular, or other structural tissues, and sarcomas can arise in any of these types of tissues. As a result, there are many subtypes of sarcoma, which are classified based on the specific tissue and type of cell from which the tumor originates.

<span class="mw-page-title-main">Rhabdomyosarcoma</span> Cancer originating in precursors to muscle cells

Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts.

<span class="mw-page-title-main">Sertoli–Leydig cell tumour</span> Medical condition

Sertoli–Leydig cell tumour is a group of tumors composed of variable proportions of Sertoli cells, Leydig cells, and in the case of intermediate and poorly differentiated neoplasms, primitive gonadal stroma and sometimes heterologous elements.

<span class="mw-page-title-main">Desmoplastic small-round-cell tumor</span> Aggressive and rare cancer

Desmoplastic small-round-cell tumor (DSRCT) is an aggressive and rare cancer that primarily occurs as masses in the abdomen. Other areas affected may include the lymph nodes, the lining of the abdomen, diaphragm, spleen, liver, chest wall, skull, spinal cord, large intestine, small intestine, bladder, brain, lungs, testicles, ovaries, and the pelvis. Reported sites of metastatic spread include the liver, lungs, lymph nodes, brain, skull, and bones. It is characterized by the EWS-WT1 fusion protein.

Pleuropulmonary blastoma (PPB) is a rare cancer originating in the lung or pleural cavity. It occurs most often in infants and young children but also has been reported in adults. In a retrospective review of 204 children with lung tumors, pleuropulmonary blastoma and carcinoid tumor were the most common primary tumors. Pleuropulmonary blastoma is regarded as malignant. The male:female ratio is approximately one.

<span class="mw-page-title-main">Blastoma</span> Type of cancer arising from precursor cells

A blastoma is a type of cancer, more common in children, that is caused by malignancies in precursor cells, often called blasts. Examples are nephroblastoma, medulloblastoma, and retinoblastoma. The suffix -blastoma is used to imply a tumor of primitive, incompletely differentiated cells, e.g., chondroblastoma is composed of cells resembling the precursor of chondrocytes.

<span class="mw-page-title-main">Undifferentiated pleomorphic sarcoma</span> Medical condition

Undifferentiated pleomorphic sarcoma (UPS), also termed pleomorphic myofibrosarcoma, high-grade myofibroblastic sarcoma, and high-grade myofibrosarcoma, is characterized by the World Health Organization (WHO) as a rare, poorly differentiated neoplasm. WHO classified it as one of the undifferentiated/unclassified sarcomas in the category of tumors of uncertain differentiation. Sarcomas are cancers derived mesenchymal stem cells that typically develop in bone, muscle, fat, blood vessels, lymphatic vessels, tendons, and ligaments. More than 70 sarcoma subtypes have been described. The UPS subtype of these sarcomas consists of tumor cells that are poorly differentiated and may appear as spindle-shaped cells, histiocytes, and giant cells. UPS is considered a diagnosis that defies formal sub-classification after thorough histologic, immunohistochemical, and ultrastructural examinations fail to identify the type of cells involved.

<span class="mw-page-title-main">Mixed Müllerian tumor</span> Medical condition

A malignant mixed Müllerian tumor, also known as malignant mixed mesodermal tumor (MMMT) is a cancer found in the uterus, the ovaries, the fallopian tubes and other parts of the body that contains both carcinomatous and sarcomatous components. It is divided into two types, homologous and a heterologous type. MMMT account for between two and five percent of all tumors derived from the body of the uterus, and are found predominantly in postmenopausal women with an average age of 66 years. Risk factors are similar to those of adenocarcinomas and include obesity, exogenous estrogen therapies, and nulliparity. Less well-understood but potential risk factors include tamoxifen therapy and pelvic irradiation.

Sarcoma botryoides or botryoid sarcoma is a subtype of embryonal rhabdomyosarcoma, that can be observed in the walls of hollow, mucosa lined structures such as the nasopharynx, common bile duct, urinary bladder of infants and young children or the vagina in females, typically younger than age 8. The name comes from the gross appearance of "grape bunches".

Alveolar rhabdomyosarcoma (ARMS) is a subtype of the rhabdomyosarcoma family of soft tissue cancers whose lineage is from mesenchymal cells and are related to skeletal muscle cells. ARMS tumors resemble the alveolar tissue in the lungs. Tumor location varies from patient to patient, but is commonly found in the head and neck region, male and female urogenital tracts, the torso, and extremities.

Malignant ectomesenchymoma(MEM) is a rare, fast-growing tumor of the nervous system or soft tissue that occurs in children and young adults. MEM is part of a group of small round blue cell tumors which includes neuroblastoma, rhabdomyosarcoma, non-Hodgkin's lymphoma, and the Ewing's family of tumors.

Ectomesenchymoma is a rare, fast-growing tumor of the nervous system or soft tissue that occurs mainly in children, although cases have been reported in patients up to age 60. Ectomesenchymomas may form in the head and neck, abdomen, perineum, scrotum, or limbs. Also called malignant ectomesenchymoma.

<span class="mw-page-title-main">WHO classification of tumours of the central nervous system</span>

The WHOclassification of tumours of the central nervous system is a World Health Organization Blue Book that defines, describes and classifies tumours of the central nervous system (CNS).

Large cell lung carcinoma with rhabdoid phenotype (LCLC-RP) is a rare histological form of lung cancer, currently classified as a variant of large cell lung carcinoma (LCLC). In order for a LCLC to be subclassified as the rhabdoid phenotype variant, at least 10% of the malignant tumor cells must contain distinctive structures composed of tangled intermediate filaments that displace the cell nucleus outward toward the cell membrane. The whorled eosinophilic inclusions in LCLC-RP cells give it a microscopic resemblance to malignant cells found in rhabdomyosarcoma (RMS), a rare neoplasm arising from transformed skeletal muscle. Despite their microscopic similarities, LCLC-RP is not associated with rhabdomyosarcoma.

<span class="mw-page-title-main">Sarcomatoid carcinoma</span> Medical condition

Sarcomatoid carcinoma, sometimes referred to as pleomorphic carcinoma, is a relatively uncommon form of cancer whose malignant cells have histological, cytological, or molecular properties of both epithelial tumors ("carcinoma") and mesenchymal tumors ("sarcoma"). It is believed that sarcomatoid carcinomas develop from more common forms of epithelial tumors.

Embryonal rhabdomyosarcoma (EMRS) is a rare histological form of cancer in the connective tissue wherein the mesenchymally-derived cells (rhabdomyoblasts) resemble the primitive developing skeletal muscle of the embryo. It is the most common soft tissue sarcoma occurring in children. Embryonal rhabdomyosarcoma is also known as PAX-fusion negative or fusion-negative rhabdomyosarcoma, as tumors of this subtype are unified by their lack of a PAX3-FOXO1 fusion oncogene. Fusion status refers to the presence or absence of a fusion gene, which is a gene formed from joining two different genes together through DNA rearrangements. These types of tumors are classified as embryonal rhabdomyosarcoma "because of their remarkable resemblance to developing embryonic and fetal skeletal muscle."

<span class="mw-page-title-main">Endodermal sinus tumor</span> Medical condition

Endodermal sinus tumor (EST) is a member of the germ cell tumor group of cancers. It is the most common testicular tumor in children under three, and is also known as infantile embryonal carcinoma. This age group has a very good prognosis. In contrast to the pure form typical of infants, adult endodermal sinus tumors are often found in combination with other kinds of germ cell tumor, particularly teratoma and embryonal carcinoma. While pure teratoma is usually benign, endodermal sinus tumor is malignant.

Vulvar tumors are those neoplasms of the vulva. Vulvar and vaginal neoplasms make up a small percentage (3%) of female genital cancers. They can be benign or malignant. Vulvar neoplasms are divided into cystic or solid lesions and other mixed types. Vulvar cancers are those malignant neoplasms that originate from vulvar epithelium, while vulvar sarcomas develop from non-epithelial cells such as bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Epithelial and mesenchymal tissue are the origin of vulvar tumors.

References

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  13. 1 2 Clevenger JA, Foster RS, Ulbright TM (October 2009). "Differentiated rhabdomyomatous tumors after chemotherapy for metastatic testicular germ-cell tumors: a clinicopathological study of seven cases mandating separation from rhabdomyosarcoma". Modern Pathology. 22 (10): 1361–1366. doi: 10.1038/modpathol.2009.108 . PMID   19633644. S2CID   205199458.
  14. 1 2 3 4 5 Jeyaraju M, Macatangay RA, Munchel AT, York TA, Montgomery EA, Kallen ME (2021-11-08). Ahmed AA (ed.). "Embryonal Rhabdomyosarcoma with Posttherapy Cytodifferentiation and Aggressive Clinical Course". Case Reports in Pathology. 2021: 1800854. doi: 10.1155/2021/1800854 . PMC   8592761 . PMID   34790419.
  15. ↑ Balitzer D, McCalmont TH, Horvai AE (2015-12-10). "Adipocyte-Like Differentiation in a Posttreatment Embryonal Rhabdomyosarcoma". Case Reports in Pathology. 2015: 406739. doi: 10.1155/2015/406739 . PMC   4689918 . PMID   26783483.
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  20. ↑ Nael A, Siaghani P, Wu WW, Nael K, Shane L, Romansky SG (2014). "Metastatic malignant ectomesenchymoma initially presenting as a pelvic mass: report of a case and review of literature". Case Reports in Pediatrics. 2014: 792925. doi: 10.1155/2014/792925 . PMC   4227373 . PMID   25405050.
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