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Rhabdomyoma

Classification
Abbreviations Definitions The extracardiac rhabdomyomas are divided into adult, fetal, and genital types.
 * Adult rhabdomyoma (AR)
 * Fetal rhabdomyoma (FR)
 * By definition, this is a group of benign soft tissues tumors showing skeletal muscle differentiation. The tumors are separated into two major categories: cardiac and extracardiac.
 * The adult type generally develop in the head and neck area (>70%)


 * The fetal type are further separated into myxoid or intermediate types (also sometimes interchangeably called cellular, juvenile, or intermediate)


 * The genital type usually develop in middle-aged women, affecting either the vagina or vulva

Etiology/Pathogenesis
The tumors are thought to arise from the unsegmented mesoderm which is derived from the 3rd and 4th branchial arches. Importantly, it is not derived from myotomes. Although uncommon, a few fetal rhabdomyomas are associated with the nevoid basal cell carcinoma syndrome (also called Gorlin syndrome). This is an autosomal dominant inheritance pattern in which the PTCH1 gene shows a mutation. The patients will have odontogenic keratocysts, basal cell carcinoma, and abnormalities of bones, skin, nervous, and reproductive systems.

Signs and Symptoms
Site Presentation
 * AR: Neck, larynx (supraglottic, glottis), and hypopharynx
 * FR: Orbit, tongue, soft palate, periauricular, larynx, nasopharynx, chest, or abdominal wall Presentation
 * AR: Dysphagia, dyspnea, hoarseness
 * FR: Soft tissue or mucosal mass (orbit, ear, oral cavity)
 * Ophthalmologic findings, periauricular mass, difficulty swallowing

Macroscopic
The majority of the tumors are solitary, but may appear to be multinodular or multicentric.
 * AR: Unencapsulated, submucosal tumor with a rounded or lobular, well defined border, tan to grayish red-brown on cut surface.
 * FR: When they affect mucosal sites, they are often polypoid or pedunculated, given a grey-white, mucoid or glairy cut surface.

Size

 * AR: Median: 3 cm; range: 1.5-8.0 cm
 * FR: Median 3 cm; range 1.0-12.5 cm

Adult Rhabdomyoma

 * Sheets, nests, or lobules
 * Closely packed, large polygonal cells separated by delicate fibrovascular stroma
 * Abundant eosinophilic, granular, &/or vacuolated cytoplasm (due to glycogen)
 * Vacuolation creates spiderweb-like appearance due to radially oriented strands of cytoplasm separating vacuoles
 * Small, rounded, centrally, or peripherally located nuclei
 * Cytoplasmic cross striations
 * Crystalline-like cytoplasmic structures called jackstraw inclusions (rod-like)
 * Mitoses, necrosis, and pleomorphism are absent

Myxoid type

 * Bland, primitive oval to spindled cells with indistinct cytoplasm and slight nuclear hyperchromasia
 * Associated with immature skeletal muscle fibers
 * Delicate, elongated skeletal muscle cells reminiscent of fetal myotubules
 * Small uniform nuclei
 * Uni- or bipolar eosinophilic cytoplasmic extensions
 * Haphazardly arranged in abundant fibromyxoid stroma
 * Rare mitoses and no atypical forms
 * No pleomorphism or necrosis

Intermediate type

 * Greater degree and greater number of cells with skeletal muscle differentiation
 * Large, ganglion cell-like rhabdomyoblasts with vesicular nuclei and prominent nucleoli
 * Cross striations frequent and easy to identify
 * Interlacing ribbon or strap-like rhabdomyoblasts with abundant deeply acidophilic cytoplasm
 * Broad fascicles of delicate spindled rhabdomyoblasts
 * Infiltration and entrapment of adipose tissue and skeletal muscle
 * Rare areas of fibroblastic proliferation
 * Mitoses usually not identified, but when present, can be increased (up to 14/50 HPFs)
 * Absent: Nuclear pleomorphism, atypical mitoses, cambium layer (seen in rhabdomyosarcoma)
 * Transitional forms between myxoid and intermediate types may be seen

Histochemistry

 * PAS(+), diastase-resistant glycogen granules
 * PTAH highlights cross striations and crystals

Immunohistochemistry

 * Positive for a variety of skeletal muscle markers: Desmin, myoglobin, MYOD1, myogenin.

Genetic Testing

 * Reciprocal translocation of chromosome 15 and 17
 * Variety of changes in 10q

Differential diagnoses
The histologic differential diagnosis is quite broad, including several benign and malignant soft tissue type tumors. These include, although not limited to, granular cell tumor, paraganglioma, oncocytoma, myoepithelioma, and rhabdomyosarcoma.

Diagnosis
The diagnosis of this tumor requires a biopsy of the tumor, which is then examined by a surgical pathologist or cytopathologist to render a diagnosis.

Management
The treatment of choice is a complete surgical excision (removal), which generally results in an excellent long term prognosis. Unfortunately, it is often difficult to completely remove the tumors, especially when they are in the larynx. In this location, there is up to a 40% recurrence or persistence if it is not completely removed.

Epidemiology
These tumors are incredibly uncommon, with only a few hundred diagnosed each year.

There is a difference in age at presentation based on the specific tumor type:


 * AR: Mean: 6th decade; range: 16-82 years
 * FR: ~ 50% within 1st year of life (congenital), with an overall median age at presentation of 4.5 years.

There is a sex difference based on the specific tumor type:


 * AR: Male > > female (3-4:1)
 * FR: Male > female (2:1)