Rhabdomyosarcoma

Rhabdomyosarcoma, often abbreviated RMS, is a malignant tumour of skeletal muscle.

General

• Most common paediatric sarcoma.
  • Classically in the head and neck region.
• Most common sarcoma in Li-Fraumeni syndrome.
• ~6% of all childhood cancer.

Classification

Histologic

1. Alveolar rhabdomyosarcoma.
   • Usually young adults/adolescents.
   • Early mets common.
   • Usu. arises in regions with skeletal muscle.
2. Embryonal rhabdomyosarcoma.
   • Usual <10 years old.
   • Typically locally invasive.
   • Usu. arises in regions without skeletal muscle.

Less common types:

1. Undifferentiated rhabdomyosarcoma.
2. Botryoid - may be considered a subtype of embryonal RMS.
3. Spindle cell - may be considered a subtype of embryonal RMS.

Notes:

• How to remember the special types BUS: botryoid, undifferentiated, spindle.
• The above is the international classification. Several classification of RMS exist - see: Classifications of Rhabdomyosarcoma.

Molecular and histologic

1. Translocation-positive alveolar RMS.
2. Translocation-negative alveolar RMS.
3. Embryonal RMS.

Notes:

• Translocation-negative alveolar RMS shares gene expression profiling characteristics with embryonal RMS -- suggesting these can be grouped together.

Gross

Sarcoma botryoides (embryonal RMS) - distinctive appearance:

• Grapes on the vine-like clusters.
  • Found in urinary bladder, vagina.

Image:

• Sarcoma Boytriodes (flickr.com).

Microscopic

Alveolar rhabdomyosarcoma

Features:

• Alveolus-like pattern -- key low-power feature.
  • Fibrous septae lined by tumour cells.
    • Cells may "fall-off" the septa, i.e. be detached/scattered in the alveolus-like space.
    • Space between fibrous sepate may be filled with tumour = solid variant of alveolar rhabdomyosarcoma.
• Rhabdomyoblasts - essentially diagnostic.
  • Eccentric nucleus.
  • Moderate amount of intensly eosinophilic cytoplasm.
  • Striations -- if you're really lucky; these are not common.

Other features:

• Nuclear pleomorphism - common.
• Mitoses - common.

Notes:

• Well-differentiated rhabdomyoblasts are uncommon in alveolar RMS.

DDx:

• Alveolar soft part sarcoma.

Images:

• WC:
  • Alveolar RMS - intermed. mag. (WC).
  • Alveolar RMS - very high mag. (WC).
• www:
  • Alveolar RMS - several images (upmc.edu).

Embryonal rhabdomyosarcoma

Features:

• Randomly arranged small cells.
• Myxoid matrix.
• Strap cells:
  • Tadpole-like morphology.
• Rhabdomyoblasts - essentially diagnostic.
  • Eccentric nucleus.
  • Moderate amount of intensly eosinophilic cytoplasm.
  • Striations -- if you're really lucky; these are not common.

DDx:

• Small round cell tumours.
• Pleuropulmonary blastoma.

Images:

• Embryonal RMS - several images (upmc.edu).

Subtypes of embryonal RMS

There are two common subtypes of embryonal RMS. Both of them have a better prognosis that embryonal RMS not otherwise specified (NOS).

Common subtypes:

1. Botryoid subtype (AKA sarcoma botryoides):
   • Gross: Grape-like morphology.
   • Microscopic: Non-proliferating layer deep to the surface ("Cambium layer").
2. Spindle cell subtype.
   • General: may mimic leiomyosarcoma (complete with vesicular pattern) -- which is not common in the pediatric population.
   • Microscopic: vesicular growth pattern, spindle cells.

Notes:

• Cambium layer = cellular region deep to epithelial component.
  • Can be thought of as the opposite of a "Grenz zone" -- which is a paucicellular zone between tumour and epithelium.

Anaplasia

Criteria:

1. Hyperchromatic nuclei with size variation greater or equal to 3x.
2. Multipolar (atypical) mitotic figures.

Subclassification:

1. Focal - a few cells.
2. Diffuse - cluster or sheets of anaplasia.

Notes:

• Not subtle - can identify at low power.
• Seen in 10-15% of RMS.
  • More common in older individuals.
• Poorer prognosis in embryonal RMS.
  • No change in prognosis in alveolar RMS.

IHC

Panel of muscle markers -- DAM:

• Desmin (best marker).
• Actin.
• Myogenin.

Subtyping via IHC

PST proposes the following (presumably based on Makawitz et al.):

IHC	Translocation positive alveolar RMS	Embryonal RMS	Translocation negative alveolar RMS
myogenin	+ve -- diffuse	+ve -- focal	+ve -- diffuse
EGFR	-ve	+ve	-ve
P-cadherin	+ve	-ve	-ve
IGF2	-ve	+ve	+ve

A paper by Wachtel at al. proposes the use of:

• AP2beta and P-cadherin +ve in translocation positive alveolar RMS, and
• EGFR and fibrillin-2 +ve in embryonal RMS and translocation negative alveolar RMS.

Electron microscopy

Features:

• Sarcomeric like structures - usu. in "bent" cells; cells that are U-shaped.

Molecular diagnostics

Alveolar rhabdomyosarcoma

Common translocations (~85% of cases):

• t(1,13).
  • PAX7/FKHR fusion gene.
  • Seen in approx. 15% of cases.
• t(2,13).
  • PAX3/FKHR fusion gene.
  • Seen in approx. 70% of cases.

Notes:

• t(1,13) vs. t(2,13) -- t(1,13) usually: younger age, extremity lesion, localized disease, better survival.
• Several uncommon translocations exist.

See also

• Small round cell tumours.
• Soft tissue lesions.
• Pediatric pathology.