Alveolar Rhabdomyosarcoma



Alveolar Rhabdomyosarcoma


Khin Thway, BSc, MBBS, FRCPath





Key Facts


Terminology



  • High-grade malignant round cell neoplasm showing partial differentiation towards skeletal muscle


Etiology/Pathogenesis



  • Characteristic PAX-FOXO1 balanced translocations in most



    • t(2;13)(q35;q14) (majority)


    • t(1;13)(p36;q14) in 10-15%


Clinical Issues



  • Accounts for approximately 30% of rhabdomyosarcomas


  • Predominantly adolescents and young adults


  • Sites: Deep soft tissue of extremities, head and neck, and trunk


  • Can present with widespread dissemination


  • Tend to be high-stage lesions at presentation


Microscopic Pathology



  • Poorly differentiated round cells


  • Hyperchromatic nuclei, scanty cytoplasm


  • Alveolar-like spaces formed by central loss of cohesion


  • Multinucleate giant tumor cells in some cases


  • Fibrovascular septa separate nests


  • Rhabdomyoblasts can be present


  • Solid variant



    • Lacks alveolar architecture


  • Mixed alveolar and embryonal rhabdomyosarcoma



    • Behavior and classification as ARMS


  • Desmin usually strong and diffuse


  • Myogenin and MYOD1 are sensitive and specific for skeletal muscle differentiation






Alveolar rhabdomyosarcoma from the postnasal space is seen. Respiratory-type epithelium overlies fibrous tissue extensively infiltrated by sheets and nests of monomorphic round cell tumor.






The tumor is composed of round cells with peripheral cellular preservation image, but central discohesion and necrosis image as well, somewhat resembling the appearance of pulmonary alveoli.


TERMINOLOGY


Abbreviations



  • Alveolar rhabdomyosarcoma (ARMS)


Definitions



  • High-grade malignant round cell neoplasm characterized by recurrent chromosomal translocations showing variable differentiation toward skeletal muscle


ETIOLOGY/PATHOGENESIS


Genetic Events



  • Characteristic balanced translocations



    • Produce chimeric fusion proteins



      • These act as aberrant transcription factors


      • Regulate expression of specific target genes


  • Target cell/cell of origin still unknown


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Accounts for approximately 30% of rhabdomyosarcomas


    • 2nd most common rhabdomyosarcoma



      • After embryonal RMS


  • Age



    • Predominantly adolescents and young adults


    • Peak incidence: 10-25 years


    • Rare in adults > 45 years


    • Congenital in small number of cases


  • Gender



    • M = F


  • Ethnicity



    • No ethnic or geographical predilections


Site



  • Deep soft tissue


  • Most common in extremities


  • Head and neck


  • Trunk


  • Pelvis


  • Retroperitoneum


  • Perineum


Presentation



  • Suddenly enlarging mass



    • Local symptoms pertaining to site of origin



      • Proptosis or cranial nerve deficits (head and neck)


      • Paresthesia or paresis (paraspinal areas of trunk)


    • Can present with widespread dissemination



      • Lymphadenopathy or marrow infiltration


      • Rarely may present without obvious primary


  • Deep mass


Treatment



  • Multimodality approach


  • RMS is sensitive to both chemotherapy and radiation therapy


  • Systemic chemotherapy



    • In conjunction with surgery, radiation therapy, or both modalities


  • Radiotherapy



    • To maximize local control


  • Surgery



    • Excise primary tumor when possible, without major functional or cosmetic defects


    • Complete resection often difficult or impossible


Prognosis



  • Tend to be high-stage lesions at presentation


  • Prognosis of ARMS significantly worse than for embryonal RMS



    • Accurate distinction between RMS subtypes is therefore crucial for appropriate management



MACROSCOPIC FEATURES


General Features



  • Fleshy mass


  • Infiltrative margins


  • Tan cut surface


  • Hemorrhage


  • Necrosis


MICROSCOPIC PATHOLOGY


Histologic Features



  • Poorly differentiated round cells



    • Medium size


    • Hyperchromatic nuclei


    • Scanty cytoplasm


  • Sheets and nests



    • Alveolar-like spaces formed by central loss of cohesion


    • Central cells poorly preserved and necrotic


    • Many appear freely floating


  • Fibrovascular septa separate nests


  • Rare clear cell appearance



    • Due to cytoplasmic glycogen


    • Vacuolated cells may be confused with lipoblasts


  • Rhabdomyoblasts can be present



    • Less frequent than in embryonal RMS


  • Multinucleate giant tumor cells in some cases



    • Peripheral or wreath-like nuclei


  • Very rarely atypical cells, similar to anaplastic variant of embryonal RMS


  • Tumor metastases often show alveolar pattern


  • Solid variant



    • Sheets and islands of densely packed tumor cells



      • Cytomorphology of typical ARMS


      • Lack alveolar pattern


    • Occasional small nests may be present


    • Foci of more typical ARMS may be seen on careful examination


    • More likely to be fusion(-) for PAX3/7-FOXO1


    • Very rarely atypical cells, similar to anaplastic variant of embryonal RMS


  • Mixed alveolar and embryonal rhabdomyosarcoma



    • Foci of embryonal morphology



      • Spindle cells or myxoid stroma


    • Behavior and classification as ARMS


Lymph Nodes



  • Nodal metastases may be presenting factor


Predominant Pattern/Injury Type



  • Neoplastic


Predominant Cell/Compartment Type



  • Mesenchymal, muscle, skeletal


Genetics

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Jul 9, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Alveolar Rhabdomyosarcoma

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