. Rhabdomyosarcoma. OrthopaedicsOne Articles. In: OrthopaedicsOne - The Orthopaedic Knowledge Network. Created Jun 12, 2010 17:05. Last modified Nov 04, 2011 11:08 ver.3. Retrieved 2019-07-20, from https://www.orthopaedicsone.com/x/tw0CAg.
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
- 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
- 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
- Lower eyelid location reported in a 3-month-old
- Unusual locations
- Erosion of bone in hand or foot lesions
- MRI: deep-seated intramuscular mass
- 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%)
- 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
- 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
- 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
- Ewing’s sarcoma
- Poorly differentiated angiosarcoma
- Synovial sarcoma
- Malignant melanoma
- Granulocytic sarcoma
- 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
- Lung (67% when metastases are present)
- LNs(depends on location and type--alveolar > embryonal)
- Bone marrow (aspirate as part of staging work-up)
- 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
- Poor prognostic indicators
Andrassy RJ, Corpron CA, Hays D, Raney RB, Wiener ES, Lawrence W Jr, Lobe TE, Bagwell C, Maurer HM: Extremity sarcomas: an analysis of prognostic factors from the Intergroup Rhabdomyosarcoma Study III: J Pediatr Surg 31:191-6,1996.
Ariel IM, Briceno M: Rhabdomyosarcoma of the extremities and trunk: analysis of 150 patients treated by surgical resection. J Surg Oncol 7:269-87,1975.
Boulad F, Karnan NA, LaQuaglia MP, Heller G, Lindsley KL, Rosenfield NS, Abramson SJ, Gerald WL, Small TN, Gillio AP, Gulati SC, O’Reilly RJ, Ghavimi F: High-dose induction chmoradiotherapy followed by autologous bone marrow transplantation as consolidation therapy in rhabdomyosarcoma, extraosseous Ewing’s sarcoma, and undifferentiated sarcoma. J Clin Oncol 16:1697-706,1998.
Cessna MH, Zhou H, Perkins SL, Tripp SR, Layfield L, Daines C, Coffin CM: Are myogenin and MyoD1 expression specific for rhabdomyosarcoma? A study of 150 cases. with emphasis on spindle cell mimics. Am J Surg Pathol 25:1150-7,2001.
Chen B, Dias P, Jenkins JJ, III, Savell VH, Parham DM: Methylation alterians of the MyoD1 upstream region are predictive of subclassification of human rhabdomyosarcomas. Am J Pathol 152:1071-9,1998.
Coffin CM: The new International Rhabdomyosarcoma Classification, its progenitors, and considerations beyond morphology. Adv Anat Pathol 4:1-16,1997.
Coffin CM, Rulon J, Smith L, Bruggers C, White FV: Pathologic features of rhabdomyosarcoma before and after treatment: a clinicopathologic and immunohistochemical analysis. Mod Pathol 10:1175-87,1997.
Cohen M, Ghosh L, Schafer ME: Congenital embryonal rhabdomyosarcoma of the hand and Apert’s syndrome. J Hand Surg 12A:614-7,1987.
Crist W, Gehan EA, Ragab AH, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, Heyn R, : The Third Intergroup rhabdomyosarcoma study. J Clin Oncol 13:610-30,1995.
Cui S, Hano H, Harada T, Takai S, Masui F, Ushigome S: Evaluation of new monoclonal anti-MyoD1 and anti-myognein antibodies for the diagnosis of rhabdomyosarcoma. Pathol Int 49:62-8,1999.
Dias P, Chen B, Dilday B, Palmer H, Hosoi H, Singh S, Wu C, Li X, Thompson J, Parham D, Qualman S, Houghton P: Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass. Am J Pathol 156:399-408,2000.
Dias P, Parham DM, Shapiro DN, Webber BL, Houghton PJ: Myogenic regulatory protein (MyoD1) expression in childhood solid tumors: diagnostic utility in rhabdomyosarcoma. Am J Pathol 137:1283-91,1990.
Engel ME, Mouton SC, Emms M: Paediatric rhabdomyosarcoma; MyoD1 demonstration in routinely processed tissue sections using wet heat pretreatment (pressure cooking) for antigen retrieval. J Clin Pathol 50:37-9,1997.
Enzinger FM, Weiss SW: Rhabdomyosarcoma. In Soft Tissue Tumors FM Enzinger and SW Weiss (Eds), C.V. Mosby Co., St. Louis (3rd ed) 1995, pp 539-578.
Eusebi V, Rilke F, Ceccarelli C, Fedeli F, Schiaffino S, Bussolati G: Fetal heavy chain skeletal myosin. An oncofetal antigen expressed by rhabdomyosarcoma. Am J Surg Pathol 10:680-6,1986.
Furlong MA, Mentzel T, Fanburg-Smith JC: Pleomorphic rhabdomyosarcoma in adults: a clincopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle-specific markers. Mod Pathol 14:595-603,2001.
Ghavimi F, Mandell LR, Heller G, Hajdu SI, Exelby P: Prognosis in childhood rhabdomyosarcoma of the extremity. Cancer 64:2233-2237,1989.
Hastings R, Newbury-Ecob R, Ng A, Taylor R: A further patient with Noonan syndrome due to a SOS1 mutation and rhabdomyosarcoma. Genes Chromosomes Cancer. 2010 Jul 6.
Hays DM: Rhabdomyosarcoma. Clin Orthop 289:36-49,1993.
Hays DM, Lawrence W, Jr, Wharam M, Newton W Jr, Ruymann FB, Beltangady M, Maurer HM:Primary reexcision for patients with "microscopic residual" tumor following initial excision of sarcomas of the trunk and extremity sites. J Pediatr Surg 24:5-9,1989.
Hays DM, Raney RB, Crist WM, Lawrence WW Jr, Ragab A, Wharam MD, Webber B, Gehan E, Johnston J, Maurer HM: Secondary surgical procedures ot evaluate primary tumor status in patienst with chemotherapy-responsive stage III and IV sarcomas: a report from the Intergroup Rhabdomyosarcoma Study. J Pediatr Surg 25:1100-5,1990.
Hays DM, Soule EH, Lawrence W, Jr, Gehan EA, Maurer HM, Donaldson M, Raney RB, Tefft M: Extremity lesions in the intergroup rhabdomyosarcoma study (IRS-I): a preliminary report. Cancer 49:1-8,1982.
Hays DM, Soule EH, Lawrence W, Jr, : Rhabdomyosarcoma: surgical therapy in extremity lesions in children. Orthop Clin North Am 8:883-902,1977.
Jones AE, Albano EA, Lovell MA, Hunger SP: Metastatic alveolar rhabdomyosarcoma in multiple endocrine neoplasia type 2A. Pediatr Blood Cancer. 2010 Jun 8.
Jones TR, Norton MS, Johnstone PA, Kane E, Shin AY: Pleomorphic rhabdomyosarcoma in an adult forearm: a case report. J Hand Surg 27A:154-9,2002.
Jung JH, Lee JE, Shin JH, Lim YT, Choi HY: Lower eyelid rhabdomyosarcoma ina 3-month-old infant. J AAPOS. 2010 Jun;14(3):285-287.
Kumar S, Perlman E, Harris CA, Raffeld, M, Tsokos M: Myogenin is a specific marker for rhabdomyosarcoma: an immunohistochemical study in paraffin-embedded tissues. Mod Pathol 13:988-93,2000.
La TH, Wolden SL, Rodeberg DA, Hawkins DS, Brown KL, Anderson JR, Donaldson SS: Regional nodal involvement and patterns of spread along in-transit pathways in children with rhabdomyosarcoma of the extremity: A report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys. 2010 Jun 11.
LaQuaglia MP: Extremity rhabdomyosarcoma: biological principles, staging, and treatment. Sem Surg Oncol 9:510-9,1993.
LaQuaglia MP, Ghavimi F, Penenberg D, Mandell LR, Healey JH, Hadju SI, Exelby PR: Factors predictive of mortality in pediatric extremity rhabdomyosarcoma. J Ped Surg 25:238-43,1990.
LaQuaglia MP, Heller G, Ghavimi F, Casper ES, Vlamis V, Hajdu S, Brennan MF: The effect of age at diagnosis on outcome in rhabdomyosarcoma. Cancer 73:107-17,1994.
Lawrence W, Jr, Gehan EA, Hays DM, : Prognostic significance of staging factors of the UICC staging system in children rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study (IRS III). J Clin Oncol 5:46-54,1987.
Lawrence W Jr, Hays DM, Heyn R, Tefft M, Crist W, Beltangady M, Newton W Jr, Wharam M: Lymphatic metastases with childhood rhabdomyosarcoma. A report from the Intergroup Rhabdomyosarcoma Study. Cancer 60:910-5,1987.
Lawrence W, Jr, Hays DM, Moon TE: Lymphatic metastasis with childhood rhabdomyosarcoma. Cancer 39:556-61,1977.
Little DJ, Ballo MT, Zagars GK, Pisters PW, Patel SR, El-Naggar AK, Garden AS, Benjamin RS: Adult rhabdomyosarcoma: outcome following multimodality treatment. Cancer 95:377-88,2002.
Lobe TE, Wiener ES, Hays DM, Lawrence WH, Andrassy RJ, Johnston J, Wharam M, Webber B, Ragab A: Neonatal rhabdomyosarcoma: the IRS experience. J Pediatr Surg 29:1167-70,1994.
Maurer HM, Beltangady M, Gehan E, : The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 61:209-20,1988.
Maurer HM, Moon T, Donaldson M, : Intergroup Rhabdomyosarcoma Study. Cancer 40:2015-25,1977.
McMulkin HM, Yanchar NL, Fernandez CV, Giacomantonio C: Sentinel lymph node mapping and biopsy: a potentially valuable tool in the managment of childhood extremity rhabdomyosarcoma. Pediatr Surg Int 19:453-6,2003.
Milanovic R, Zganjer M, Cizmic A, Pajic A: Rhabdomyosarcoma of the hand. Med Pediatr Oncol 37:481-2001.
Newton W, Jr, Gehan EA, Webber BL, Marsden HB, van Unnik AJ, Hamoudi AB, Tsokos MG, Shimada H, Harms D, Schmidt D, : Classification of rhabdomyosarcomas and related sarcomas. Pathologic aspects and proposal for a new classification--an Intergroup Rhabdomyosarcoma Study. Cancer 76:1073-85,1995.
Newton W, Jr, Soule E, Hamoudi A, : Histopathology of childhood sarcomas, Intergroup Rhabdomyosarcoma Studies I and II: Clinico-pathological correlation. J Clin Oncol 6:67-75,1988.
Ortega JA, Wharam M, Gehan EA, Ragab AH, Crist W, Webber B, Wiener ES, Haeberlen V, Maurer HM: Clinical features and results of therapy for children with paraspinal soft tissue sarcoma: a report of the Intergroup Rhabdomyosarcoma Study. J Clin Onocl 9:796-801,1991.
Pappo AS, Etcubanas E, Santan VM, Rao BN, Kun LE, Fontanesi J, Roberson PK, Bowman LC, Crist WM, Shapiro DN: A phase II trial of ifosfamide in previously untreated children and adolescents with unresectable rhabdomyosarcoma. Cancer 71:2119-25,1995.
Parham DM, Webber B, Holt H, Williams WK, Maurer H: Immunohistochemical study of childhood rhabdomyosarcomas and related neoplasm: reults of an Intergroup Rhabdomyosarcom study project. Cancer 67:3072-80,1991.
Philippe PG, Rao BN, Rogers DA, : Sarcomas of the flexor fossae in children: is amputation necessary? J Ped Surg 27:964-7,1992.
Piersigilli F, Danhaive O, Auriti C: Blueberry muffin baby due to alveolar rhabdomyosarcoma with cutaneous metastasis. Arch Dis Child Fetal Neonatal Ed. 2010 Jun 14.
Pittore B, Fancello G, Cossu Rocca P, Ledda GP, Tore G: Rhabdomyosarcoma: a rare laryngeal neoplastic entitiy.
Raney RB, Jr, Ragab AH, Ruymann FB, : Soft tissue sarcoma of the trunk in childhood: results of the Intergroup Rhabdomyosarcoma Study. Cancer 49:2612-6,1982.
Ranson JL, Pratt CB, Shanks E: Childhood rhabdomyosarcoma of the extremity: results of combined modality therapy. Cancer 40:2810-6,1977.
Tabrizi P, Letts M: Childhood rhabdomyosarcoma of the trunk and extremities. Am J Orthop 28:440-6,1999.
Takahashi T, Machida K, Honda N, Hosono M, Kashimada A, Murata O, Osada H, Nishimura K: Adult embryonal rhabdomyosarcoma in axilla. Radiat Med 21:135-7,2003.
Tallini G, Parham DM, Dias P, Cordon-Cardo C, Houghton PJ, Rosai J: Myogenic regulatory protein expression in adult soft tissue sarcomas: a sensitive and specific marker of skeletal muscle differentiation. Am J Pathol 144:693-701,1994.
Xarchas K, Paparassiliou N, Tsoutseous N, Burke FD: Rhabdomyosarcoma of the hand. Two case reports and a review of the literature. J Hand Surg 21B:325-9,1996.