Rhabdomyosarcoma


Table of Contents

DEFINITION AND PATHOGENESIS

  • Juvenile types
    • Embryonal rhabdomyosarcoma (70-80%): mainly affects children < 15 years of age occurring in the head and neck, GU tract, retroperitoneum and extremities
    • (Botryoid type: a variant of the embryonal type characterized by a grapelike growth pattern not occurring in the extremities, but in hollow visceral organs)
    • Alveolar rhabdomyosarcoma (10-20%): usually occurs between ages 10-25, responsible for a second incidence peak
    • Occurs with greater incidence in the extremities
  • Adult type
    • Pleomorphic rhabdomyosarcoma: peak incidence >45 years of age, occurring most commonly in the thigh
    • Pretreatment staging system
      • Stage    Site*   Invasiveness    Size    Nodes    Metastases
      • 1       favorable   T1 or T2       a or b    N0, N1        M0
      • 2     unfavorable T1 or T2     a (<5cm)     N0           M0
      • 3     unfavorable T1 or T2     b (>5cm)  N0, N1        M0
      • 4        any site   T1 or T2     a or b      N0, N1        M1
        * all extremity sites unfavorable
    • Intergroup Rhabdomyosarcoma Study Clinical groups
    • I Localized, complete resection, no LNs
      • a) confined to nuscle/organ or origin
      • b) tumor infiltration beyond muscle/organ of origin
    • II Localized/regional disease, complete macroscopic resection
      • a) resection with microscopic margin, no LNs
      • b) complete resection of tumor and LNs
      • c) tumor and LNs resected with microscopic margins
    • III < wide resection with macroscopic residual
    • IV Distant metastases at dx

IMPORTANCE

  • The most common soft tissue sarcoma of children, addolescents, and young adults, although only 14.6% occur in the extremities
  • Accounts for 4-8% of all pediatric malignancies
    • 20% involve the extremities

CLINICAL FEATURES

  • Rare >45 years of age (except pleomorphic type which occurs 40-80 yrs of age)
  • May present at birth
  • M:F = 1.5:1
  • Discovery frequently associated with a traumatic episode (falsely diagnosed as a hematoma or benign tumor)
  • Most are deep-seated intramuscular masses
  • Often asymptomatic
  • Alveolar subtype reported in a neonate with Beckwith-Wiedemann Syndrome with multiple nodular and vesicular lesions on the face, limbs, and abdomen, resembling "blueberry muffin baby"
  • Head/neck locations
  • Unusual locations

RADIOLOGIC FEATURES

  • Erosion of bone in hand or foot lesions
  • MRI: deep-seated intramuscular mass

GROSS PATHOLOGY

  • Poorly defined, infiltrating into surrounding structures in extremity lesions
  • Firm, rubbery, and grayish-white in appearance ± necrosis or cystic degeneration

HISTOLOGIC AND MOLECULAR FEATURES

  • Rhabdomyoblasts have eosinophilic cytoplasm that is filamentous and granular ± transverse striations, contractile elements
  • Alveolar types: embryonal types = 4:3
  • Embryonal types (46-60%)
    • Poorly-differentiated to well-differentiated looking like fetal muscle tissue with variation in cellularity denseness and alternating cellular and myxoid areas
    • Scant interstitial collagen
    • Elongated and rounded rhabdomyoblasts with hyperchromatic nuclei, eosinophilic cytoplasm, and fibrillary material around the nucleus ± cross striations (50-60%)
    • + PAS ± diastase for intracellular glycogen in well-differentiated tumors("spider-web" cells are rhabdomyoblasts with glycogen washed out by the fixative and strands extending to the cellular periphery)
    • Iron hematoxylin, PTAH, Masson trichrome shows cross striations
    • "Broken-straw" sign = angulation of narrow, ribbon-shaped muscle fibers
  • Alveolar types (20-41%)(50% of extremity locations)
    • Aggregates of tumor cells with "alveolar" spaces separated by loose fibrous septa are typical but areas may be solid cells, especially at the periphery of a tumor
    • Rounded nuclei and indistinct cytoplasm
    • Rhabdomyoblasts in only 30% ± cross striations (20-30%)
    • Multinucleated giant cells are prominant
    • Entrapment of normal muscle tissue
  • Pleomorphic types (~13%)(adult-type)
    • Difficult to distinguish from other pleomorphic sarcomas (eg, MFH)
    • Rarely with cross striations
  • Undifferentiated (15-20%)
  • Botryoid
  • Spindle cell
  • Rhabdomyosarcoma with rhabdoid features
  • Immunohistochemistry and special stains
    • Desmin and myoglobin (beware of false + in entrapped normal muscle)
    • + PAS for glycogen
    • Myogenic transcriptional regulatory proteins
    • + myogenin
    • + MyoD1
  • Cytogenetics
    • Li-Fraumeni syndrome associated with rhabdomyosarcoma
    • Reported in Noonan syndrome due to a SOS1 mutation
    • Metastatic alveolar rhabdomyosarcoma reported in Multiple Endocrine Neoplasia Type 2A
    • Expression of MyoD1 geneLoss of 11p15 heterozygosity in embryonal subtype
    • Translocation t(2;13) or t(1;13) with fusion gene Pax 3-FKHR or Pax 7-FKHR fusion genes respectively in alveolar subtype
  • EM
    • Variable appearance resembling stages of embryonal muscle tissue development
    • Myofilaments and polyribosomes
    • Golgi apparatus is prominent

DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS

  • Poorly differentiated round or spindle cell sarcomas
  • Neuroblastoma
  • Neuroepithelioma
  • Ewing’s sarcoma
  • PNET
  • Poorly differentiated angiosarcoma
  • Synovial sarcoma
  • Malignant melanoma
  • Granulocytic sarcoma
  • Lymphoma
  • Small cell carcinoma
  • Benign lesions
    • Granular cell tumor

DISEASE COURSE AND TREATMENT

  • Alveolar subtype with more aggressive clinical behavior/worse outcome than embryonal subtype
  • Chemotx + wide resection + chemotherapy ± XRT after careful staging
    • Dictated by Intergroup Rhabdomyosarcoma Study (IRS) protocols
  • Aggressive regional LN sampling, if +, further proximial node evaluation
  • Response to chemotx overall is good; "second look" surgeries have been advocated
    • Vincristine, actinomycin-D, cyclophosphamide, ± adriamycin, ifosfamide
    • De novo multiple drug resistance has been reported
  • Metastases
    • Lung (67% when metastases are present)
    • LNs(depends on location and type--alveolar > embryonal)
    • Bone marrow (aspirate as part of staging work-up)
    • Heart
    • Brain
    • Abdominal organs
  • Prognosis depends on stage at time of diagnosis with up to 83% 5 year survival with localized disease and with histological type (alveolar type has a worse prognosis), and with ability to gain a wide margin and complete resection
  • Unresectable lesions will have <10% long term survivors
  • Embryonal histologic subtype has the most favorable prognosis
  • More distally located tumors generally have a better prognosis
  • Extemity lesions have a worse prognosis than orbital or GU lesions
  • 12% 5-yr risk of regional failure
    • Poor prognostic indicators
      • Female gender
      • LN involvement at dx

SPECIAL CONSIDERATION

  • A

    • y

  • A

    • A

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Malignant Schwannoma  

Quote
"It is much more important to know what sort of a patient has a disease than what sort of a disease a patient has." Sir William Osler

Figures
Figure 1a. A 27-year-old man received an unplanned excision of a chest wall rhabdomyosarcoma at an outside facility through a transverse posterior chest wall incision, contaminating the posterior shoulder musculature. A PA chest radiograph appears normal.
Figure 1b. The axial CT reveals the intercostal mass extending into the thorax. On close inspection, a large amount of swelling is seen medial to the scapula. A small amount of intramuscular air is present near the midline.
Figure 1c. A whole body bone scan reveals the soft tissue uptake in the posterior right upper back region, medial to the scapula.
Figure 1d. On the pre-chemotherapy axial fat-saturated MR image, the mass, not including the contaminated tissues, measures 10.4 x 8.6 x 3.7 cm in size. This is a tumor that should have been treated with a needle biopsy and a carefully planned resection.
Figure 1e. The gadolinium enhanced T1-weighted axial MR reveals the intercostal nature of the mass, as well as the medial shoulder musculature contamination.
Figure 1f. The patient received 2 cycles of Adriamycin and ifosfamide followed by restaging studies. The tumor clearly involves the 4-5 and 6-7 intercostal spaces.
Figure 1g. On the coronal STIR MR image, the intercostal space above 4-5 and a medial lesion is evident. An extensile chest wall resection is needed but because of the previous unplanned excision, resection with clear margins will be difficult.
Figure 1h. Now it is evident, on this restaging fat-suppressed axial MR image, just how much soft tissue contamination occurred. Enhancement occurs in the residual tumor and in the tissues surrounding the previous excision contaminated tissues.
Figure 1i. On low-power, the cellularity of the tumor is clearly evident. The tumor abuts normal skeletal muscle in the upper left of the field. Not shown here, are positive stains for desmin and muscle specific actin.
Figure 1j. On a higher field view, there are 30 mitoses/10 hpf and there is marked nuclear pleomorphism. The eosinophilic cytoplasm is evident.
Figure 1k. The transverse incision and the musculature contaminated by the unplanned excision was problematic and required wide excision of the previous incision and all the musculature previously exposed during the unplanned procedure.
Figure 1l. A double lumen ET tube was used to drop the lung during the resection when necessary. The parietal pleura was resected as part of the specimen and the visceral pleura was left with the lung.
Figure 1m. The gross specimen with the skin ellipse is seen here.
Figure 1n. The ventral side of the gross specimen reveals the multiple nodules visible beneath the parietal pleura, showing just how close the closest margins were.
Figure 1o. The defect created by the resection of the ribs 2-6 is substantial, especially because the soft tissue coverage had to be resected to gain negative margins. The closest margin was the pleural margin where the margin was 1 mm.
Figure 1p. A bovine pericardial xenograft was utilized to repair the large parietal pleural defect.
Figure 1q. An osteomyocutaneous latissimus flap, using ribs 10-12 was lifted up to fill the defect.
Figure 1r. Here, the osteomyocutaneous flap is lifted up to the extent of the defect from the resection.
Figure 1s. Here, the titanium rib plates have been used to secure the ribs together.
Figure 1t. The entire defect was not covered with ribs as seen here inferiorly. The remaining part of the defect was covered by the latissimus.
Figure 1u. The skin paddle from the osteomyocutaneous rotational flap is seen here. Most of the donor site could be closed primarily and only a portion required a STSG.
Figure 1v. The postoperative chest radiograph reveals the reconstructed chest wall and internal fixation used.
Figure 1w. The resected specimen showed no post-chemotherapeutic necrosis. In addition to the spindled cell areas, a pleomorphic component seen here was quite evident.
Figure 1x. Here, the pleomorphic nature of the cells are seen.
Figure 1y. The diagnosis of rhabdomyosarcoma is hinted at by the small amount of eosinophilic cytoplasm within the pleomorphic cells. It is not confirmed until immunohistochemistry stains are done however.
Figure 1z. On the left, desmin staining is strongly positive. On the right, myogenin is intranucularly positive, counterstained with fast green.
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J. David Pitcher, Jr., MD 60056 days ago
Christian Veillette 200563 days ago