Systemic symptoms

Systemic manifestations include weight loss, stunted growth, lethargy and weakness of the affects child.

Specific symptoms

Specific signs and symptoms vary on the basis of the primary site if the tumor. Some common sites and their presenting signs include:

• Eyes: Tumors behind or around the eyes or orbital cavity may present with symptoms such as bulging of the eyes called proptosis or disconjugate gaze [4], visual defects, swelling or puffiness around the eyes and sometimes pain.
• Nasal or oral cavity: RMS in the nasal cavity may cause congestion or blockage, anosmia and bleeding. If it is present in the oral cavity it may cause pain or difficulty in swallowing. If the tumor extends from either cavity to the brain, neurological symptoms may start appearing.
• Auditory canal: RMS in the ear or auditory canal may present with hearing loss, pain and swelling. A mass may or may not be palpable.
• Parameningeal: Upper respiratory symptoms or pain [5].
• Extremities: RMS in the muscles of the arms or legs may present with a solid lump which may be mistaken for a swelling due to injury. The mass may or may not be painful.
• Urogenital tract: RMS is the urinary bladder or elsewhere in the urinogenital tract may present with symptoms such as incontinence, hesitancy and urgency in urination.

• Anemia

  This finding has important clinical implications, as EPO is frequently employed to ameliorate chemotherapy-related anemia. [bloodjournal.org]

  Maintenance treatment actually resulted in less anemia; neutropenia and thrombocytopenia (ie, less need for transfusions); fewer infectious episodes; and no cardiac, hepatic, gastrointestinal, or renal toxicity compared to the prior intensive chemotherapy [ascopost.com]

  Laboratory findings showed leukocytosis, anemia and thrombocytopenia. [medlib.mef.hr]

  Pain may be present and if metastatic disease exists, symptoms of bone pain, respiratory difficulty, anemia, thrombocytopenia, and neutropenia may be present. [skullbaseinstitute.com]

  Severe megaloblastic anemia: Vitamin deficiency and other causes Daniel S. Socha, MD, Sherwin I. DeSouza, MD, Aron Flagg, MD, Mikkael Sekeres, MD, MS and Heesun J. [ccjm.org]

• Asymptomatic

  We describe a unique case of a rhabdomyosarcoma of the middle ear cavity in a four-year-old boy, presenting as an otherwise asymptomatic ipsilateral Horner's syndrome. [ncbi.nlm.nih.gov]

  Signs and symptoms of Alveolar Rhabdomyosarcoma include: In the initial growing phase of the tumors, they are normally asymptomatic As the tumor grows rapidly, its presence is felt by pain and a sensation of mass. [dovemed.com]

  Epidemiology [ edit ] 350 children per year in US Most common soft tissue sarcoma of childhood 2/3 occur Clinical presentation depends on site, but frequently an asymptomatic mass Most common locations are H&N, GU, and extremities Local spread along fascial [en.wikibooks.org]

  At the time of admission to our service, the patient presented facial asymmetry with an asymptomatic, fetid swelling on the left side (Figure 2A). [scielo.isciii.es]

  Familial dilated cardiomyopathy: cardiac abnormalities are common in asymptomatic relatives and may represent early disease. J Am Coll Cardiol 1998 ;31: 195 - 201 7. Mestroni L, Rocco C, Gregori D, et al. [nejm.org]

• Increased Susceptibility to Infections

  These include hair loss, fatigue, nausea, and increased susceptibility to infection. Patients are also at risk of long-term side effects that can manifest months or years after successful treatment. [docdoc.com.sg]

  These include hair loss, nausea, fatigue, and increased susceptibility to infection. Your doctor will help you to manage these side effects. Longer term side effects can also occur later on in life. [drugs.com]

• Short Stature

  Bloom syndrome Bloom syndrome, which is also called Bloom-Torre-Machacek syndrome, is an inherited disorder that is characterized by short stature and elevated rates of most cancers. [medicalnewstoday.com]

• Constipation

  […] child look cross-eyed Bladder, urinary tract, vagina, or testicle May cause blood in the urine and make urinating difficult Bleeding from the vagina Mass growing from the vagina Rapid growth around the testicles Abdomen or pelvis Abdominal pain Vomiting Constipation [cancer.net]

  Trunk of the body: if the tumor is in the abdomen (belly), it may cause constipation, painful bowel movements, bloody urine, difficulty urinating, or swelling of the groin area. [nationwidechildrens.org]

  Tumors in the abdomen can cause vomiting, pain, or constipation. Tumors in the neck, chest, arms, legs, back, or groin can cause lumps or swelling. [webmd.com]

  Other symptoms may include: Painless tumour in the scrotum (paratesticular tumour) Mass in the vagina Blood in urine Frequent urination Visible mass in the pelvis or abdomen Constipation Nausea Vomiting Headache Bleeding in the rectum, vagina, nose or [docdoc.com.sg]

• Abdominal Mass

  Here, we present an apt example of a young girl with large abdominal mass which was diagnosed as ovarian rhabdomyosarcoma (RMS). Besides, her excellent response to RMS regimen further reinforces the findings. [ncbi.nlm.nih.gov]

  Clinical findings were consistent with a diagnosis of cardio-facio-cutaneous syndrome (CFC-s), and a huge abdominal mass was evident on computed tomography scan. A biopsy was performed, and embryonal rhabdomyosarcoma was diagnosed. [doi.org]

  The diagnosis of hepatic cyst with RMS was supported by the long history of a stable abdominal mass and the histopathology findings. [journals.lww.com]

  GU cancers cause abdominal pain, a palpable abdominal mass, difficulty urinating, and hematuria. Extremity cancers appear as firm, indiscrete masses anywhere on the arms or legs. [merckmanuals.com]

• Jaundice

  Biliary duct localization is extremely rare, but it is the most common cause of malignant obstructive jaundice in pediatric patients. [ncbi.nlm.nih.gov]

  […] vision, deafness (on the side where lesion is present), inflammation of nasal cavity (sinusitis), nosebleeds, congestion, headaches, vomiting, constipation, blocked urinary bladder, scrotal mass, blood/fluid discharge from vagina, yellowing of the eyes (jaundice [dovemed.com]

  […] abdominal mass, vaginal discharge, and palpable painless masses • Extremities - 20% of cases – Swelling, palpable adenopathy, and pain.526 Tumors on the • Trunk, pelvis, and abdomen can present with – Nerve root compression, palpable mass or adenopathy, jaundice [slideshare.net]

  Biliary tract tumors are even rarer, typically presenting with obstructive jaundice. Other rare sites of presentation include: liver, brain, trachea, heart, breast, and ovary. [clinicaladvisor.com]

  […] conjunctival erythema and chemosis, and severe mucopurulent discharge Malignant otitis externa: Erythematous, swollen, and inflamed external auditory canal; local lymphadenopathy Bacteremia: Fever, tachypnea, and tachycardia; hypotension and shock; jaundice [emedicine.medscape.com]

• Myopathy

  […] with early respiratory failure, Hypertrophic cardiomyopathy, Myopathy, early-onset, with fatal cardiomyopathy, Limb-Girdle Muscular Dystrophy, Recessive, Dilated Cardiomyopathy, Dominant, Distal myopathy Markesbery-Griggs type, - 178,599,800(-) T/A/C [genecards.org]

  In addition, TTN mutations have been implicated in congenital myopathies involving cardiac and skeletal muscle, hereditary myopathy with early respiratory failure, tibial muscular dystrophy, and limb-girdle muscular dystrophy. 12-15 Figure 1. [nejm.org]

  PMID 30810839 Centronuclear myopathy with cardiomyopathy due to recessive titinopathy. Martinez-Thompson JM, et al. Muscle Nerve, 2019 Apr. PMID 30681174 Expanding the importance of HMERF titinopathy: new mutations and clinical aspects. [ncbi.nlm.nih.gov]

• Irritability

  Dry Skin Very dry skin can make the nose look red and irritated. Some people develop this dryness and irritation from frequently wiping their nose. Dry skin conditions, such as eczema, can also make the nose look red, scaly, or irritated. [medicalnewstoday.com]

  Rubbing the face tends to irritate the reddened skin. Some cosmetics and hair sprays may aggravate redness and swelling. Facial products such as soap, moisturizers and sunscreens should be free of alcohol or other irritating ingredients. [medicinenet.com]

  Many people with rosacea also experience dry, irritated, swollen eyes and red, swollen eyelids. This is known as ocular rosacea. In some people, the eye symptoms precede the skin symptoms. Enlarged nose. [mayoclinic.org]

  Conversely, topical Retin-A has the potential to worsen rosacea due to enhanced irritation and sensitivity of increasingly erythematous and heavy telangiectatic skin. [ncbi.nlm.nih.gov]

• Metrorrhagia

  Typical presentations of nonmetastatic disease, by location, are as follows: Orbit: Proptosis or dysconjugate gaze [2] Paratesticular: Painless scrotal mass Prostate: Bladder or bowel difficulties Uterus, cervix, bladder: Menorrhagia or metrorrhagia Vagina [emedicine.medscape.com]

• Urinary Retention

  Method: We report a 20-year-old girl who presented with back pain, progressive paraparesis, and urinary retention. She had muscular weakness in her lower extremities and absent deep tendon reflex. [omicsonline.org]

A complete workup of a patient suspected to have RMS includes a detailed history and physical examination.

Laboratory test

A number of tests are conducted to diagnose RMS. These may include:

• Complete blood count (CBC)
• Lumbar puncture
• Biopsy of the mass
• Biopsy of the bone marrow to check for metastasis 
• Urinalysis to check for hematuria which may indicate urinary tract involvement
• Liver function tests
• Fluorescent in situ hybridization (FISH)
• Polymerase chain reaction (PCR)

Imaging

Imaging helps us grade and stage the tumor, if present. Imaging studies include:

• X-ray of the chest
• X-ray of the head and neck
• CT scan of the site if mass
• CT scan of the chest or other areas to check for metastasis
• MRI
• Bone scan to check for metastasis

Test results

Imaging studies may reveal the exact location and size of the mass as well as metastasis, if any. Biopsy will confirm that it is RMS.
Presence of proteins such as myogenin and myoD1 in tumor cells are diagnostically valuable because these proteins are transcription factors that are normally present only in developing striated muscles and disappear once development is complete.

In patients with localised disease, overall 5% survival rates have improved to more than 80% with the combined use of surgery, radiation therapy and chemotherapy. As shown in the Intergroup Rhabdomyosarcoma Study (IRS)-IV reported in 2001, 5 year survival rates increased from 25% in 1973 to 73% [6].

A link between rhabdomyosarcoma and tungsten alloy embedded in muscle (eg. bullet or missile fragments) has been shown by a study. However it should be noted that the tungsten alloy contains 6% of nickel which happens to be a carcinogen [7]. Alternate methods of using the alloy without harmful effects of nickel have been suggested.

Currently the treatment of choice is surgery with radiation therapy, provided that the tumor is at a surgically accessible site. This is followed by chemotherapy that acts to destroy any leftover cancer cells as well as to prevent recurrence and metastasis.
In a phase II trial of 87 patients having RMS who had suffered a first relapse or disease progression and whose disease progression was unfavourable, temsirolimus proved superior to bevacizumab [7] [9]. At 6 months, the response rate also favoured temsilorimus (47.4% vs. 27.5%). The rate of progressive disease was also better with temsilorimus (28% vs. 10%) [7] [9].

In certain subpopulations with preexisting renal abnormality that predispose them to nephrotoxicity, cyclophosphamide is often added (VAC protocol). The overall survival rate for this group is more than 90% [10].

Like all other malignant tumors, the prognosis of RMS depends upon the subtype, location and size or the cancer. Distant metastasis, although very rare, may be present which may negatively affect the prognosis.

If caught on early, and if given complete and appropriate treatment, a child suffering from RMS may lead a long relatively healthy life.

The incidence of anaplasia in patients with RMS may be higher than previously described and may be of prognostic significance in children with intermediate risk-RMS, as its presence appears to negatively affect prognosis [4].

Complications with respect to the disease itself include first and foremost metastasis to other organs. This way not only the primary site of the tumor will be diseased but failure or insufficiency of the organ to which metastasis has occurred will appear. Other such complications may arise due to the bulging mass as it may press the surrounding and underlying structures leading to their injury, ischemia and other damage.

Complications with respect to treatment of the cancer include the adverse effects of chemotherapy and radiation therapy. The tumor may be present in a site inaccessible for surgery, thus complicating the disease.

The exact cause of a rhabdomyosarcoma is heretofore unknown. However some risk factors such as gene mutations may possibly play a role in its development. But even risk factors are usually absent in most children presenting with this disease. Studies reveal that some families have a tendency to develop this cancer but the exact carrying link has not yet been discovered.

Incidence

Only around 350 cases of RMS are diagnosed every year in the United States in people below 21 years of age. It is estimated that only 4:1 million children aged 15 or less will develop this cancer annually.

Sex

Rhabdomyosarcoma is slightly more common in boys.

Age

Although it may arise at any age, RMS is common in people in their 1st and 2nd decade of life and most common in children aged 5 years or less.

RMS can arise anywhere in the body where there is striated muscle but it is most commonly, around 40% of total cases, found in the head and neck muscles. The second most common area in both males and females is the urinogenital tract occurring about 25% of total cases. RMS may also arise from the upper or lower limbs in 20% of cases, making the extremities the third most common location.

Types

The most recent classification system, the International Classification of Rhabdomyosarcoma was created by the Intergroup Rhabdomyosarcoma Study [2]. This classification is based on the histologic subtype of RMS. According to it, 5 subtypes have been proposed. These are:

• Botryoid rhabdomyosarcoma 
• Spindle cell rhabdomyosarcoma 
• Embryonal rhabdomyosarcoma 
• Alveolar rhabdomyosarcoma 
• Undifferentiated sarcoma

There are other subtypes as well, like pleomorphic rhabdomyosarcoma or sclerosing rhabdomyosarcoma, but they do not fit into this classification. Of all the subtypes, the 2 most common are embryonal and alveolar RMS. Patients older than 10 years with embryonal histology and all patients with alveolar histology have 5 year survival rates of less than 30% [3].

Embryonal rhabdomyosarcoma

This is the most common subtype and occurs more in younger children. Histologically, the tumor appears to resemble a 6-8 week embryo.

Alveolar rhabdomyosarcoma

The second most common subtype, alveolar RMS occur in 20% of patients with RMS. Histologically, the tumor appears to resemble a 10-12 week embryo. It is more common in older children.

Metastasis

Although RMS is a malignant tumor, it rarely exhibits distant metastasis. Only 1 out 5 children with RMS would show distant metastasis to the brain, liver or other such organs.

There are no known set of precautions that may help combat this disease. But it can be assumed that prevention may be similar to that of other cancers. Avoiding exposure to harmful radiations, toxins, drugs and alcohol, particularly during pregnancy, may prevent the occurrence of this sarcoma.

Rhabdomyosarcoma (RMS) is a malignant tumor that arises from striated muscles. It is the most common soft tissue cancer found in children. According to Rubin, it is derived from primitive mesenchyme that retained its capacity of skeletal muscle differentiation [1].

Since striated muscles are present almost all over the body, a rhabdomyosarcoma may arise anywhere in muscles that are attached to the bone, because that is where (most) striated muscles are located. This means a RMS may arise from the head and neck, arms, legs, etc. however, RMS may often arise from regions not having a lot of striated muscles particularly the head and neck area.

Rhabdomyosarcoma makes up to 3% of all cancers occurring in children.

Rhabdomyosarcoma is a malignant tumor that has no cure and no known prevention. It arises from connective tissue or the striated muscle cells, most commonly in the head and neck region. It is a very rare cancer, occurring mostly in children only. General symptoms include weight loss, fatigue and sometimes the presence of a palpable mass. Other signs and symptoms vary on the basis of the site of the primary tumor. Treatment is based on the subtype, of which there are more than 7, and serves to increase life expectancy and quality. A combination of surgery, radiation therapy and chemotherapy is used to fight the spread of this cancer.

1. Rubin E, Farber EL, eds. Pathology. Vol 1. Philadelphia:. J B. Lippincott Company;1994: 1343-4.
2. Newton WA, Gehan EA, Webber EL, et al. (September 1995). Classification of Rhabdomyosarcoma and Related Sarcomas. Pathological Aspects and Proposal for a new classification- an Intergroup Rhabdomyosarcoma Study. Cancer 76(6) 1073-85. 
3. Anderson JR, Ruby E, Link M. Identification of a favourable subset of patients with metastatic Rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group. Proceedings of the American society of Clinical oncology. Alexandria VA: American Society of Clinical Oncology:1997;A1836:510a.
4. Barr FG. Molecular genetics and pathogenesis of Rhabdomyosarcoma. J Pediatr Hematol Oncol. Nov-Dec 1997;19(6)4831-91
5. Williamson D, Missiaglia E, de Rhynies A, Pierron G, Thuille B, Palenzuela G, et al. Fusion gene-negative alveolar Rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal Rhabdomyosarcoma. J Clin Oncol. May 1 2008;28(13)2151-8 
6. Qualman S, Lynch J, Bridge J, Parham D, Teot L, Meyer W, et al. Prevalence and clinical impact of anaplasia in childhood Rhabdomyosarcoma: a report from the Soft tissue sarcoma Committee of the Children's Oncology Group. Cancer. Dec 2008;113:3242-3247
7. Chris WM, Anderson JR, Meza JL. Intergroup Rhabdomyosarcoma Study-IV: results of patients with nonmetastatic disease. J Clin Oncol. June 15 2001; 19(12):3091-102 
8. Kalinich JF, Emond CA, Dalton TK, Mog SR, Coleman GD, Kordell JE, Miller AC, McClain DE. Embedded Weapons- Grade Tungsten Alloy Shrapnel Rapidly Induces Metastatic High-Grade Rhabdomyosarcomas in F344 Rats. Environmental Health Perspectives 2005 113 (6): 729-734. 
9. National Collaborating Centre for Cancer. Guidance on Cancer Services: improving outcomes for people with sarcoma. London (UK): National I statute of Health and Clinical Excellence (NICE): March 2006. 138p.
10. Arndt CA, Nascimento AG, Schroeder G. Treatment of intermediate risk Rhabdomyosarcoma and undifferentiated sarcoma with alternating cycles of vincristine/doxorubicin/cyclophosphamide and etoposide/ifosfamide. Eur J Cancer. July 1998;34(8):1224-9