non-rhabdomyosarcomatous soft soft tissue tumors tissue ... filetissue sarcomas & germ cell...
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Non-Rhabdomyosarcomatous Soft Tissue Sarcomas & Germ Cell
Tumors of Childhood
Jesse J. Jenkins, III, M.D.Director of Pathology
for theInternational Outreach Program
St. Jude Children’s Research Hospital 2
Soft Tissue Tumors
Other Than Rhabdomyosarcoma
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Soft Tissue Tumors
Can be easy or very difficult to diagnose!
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Soft Tissue Tumors• Heterogenous with diverse patterns
– Extracellular matrix proteins• collagen• laminin• chondroitin sulfate
– Cytoskeletal elements• keratin• vimentin
– Energy storing & enzymatic proteins• myoglobin• creatine kinase
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Soft Tissue Tumors
• Histopathologic diagnosis– Morphology defined by
• Cell shapes• Spatial organization
– Patterns produced• Organization of cellular elements• Interaction with surrounding tissues
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Soft Tissue Tumors
• Cytoskeleton/Matrix Relation– Defines tumor cell shape
• Dense collagen - compresses (narrow, elongated)• Chondroid matrix - surrounds in lacunar fashion• Myxoid matrix - allows polygonal expansion
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Soft Tissue Tumors
• Complex structures– Produced or induced by tumor
• Epithelial slits (synovial sarcoma, nerve sheath tumors)
• Blood vessels (hemangiopericytoma)• Inflammatory cells (recruited by all of them)
– Mast cells– Lymphocytes
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Soft Tissue Tumors
• Recognizable distinguishing characteristics– Light microscopy (still the primary standard)– Electron microscopy (decreasingly used)– Immunohistochemistry (now the secondary
standard)– Cytogenetics– Molecular diagnostics (increasingly important)
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Soft Tissue Tumors• Benign
– Scar– Nodular fasciitis– Proliferative fasciitis & myositis– Myositis ossificans– Fibrodysplasia ossificans progressiva– Various Fibromatoses– Fibrous pseudotumor (inflammatory
pseudotumor)– Angiofibroma
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Soft Tissue Tumors• Benign
– Fibrohistiocytic lesions• Fibrous histiocytoma• Giant cell fibroblastoma• Plexiform fibrohistiocytic tumor• Juvenile xanthogranuloma• Xanthoma• Tenosynovial giant cell tumor
– Vascular lesions• More than 16 varieties described
– Smooth muscle lesions
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Soft Tissue Tumors
• Benign– Nerve sheath lesions
• At least 7 varieties
– Fatty lesions• Lipoblastoma/lipoblastomatosis• Fibrous hamartoma of infancy
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Soft Tissue Tumors• Intermediate Clinical Behavior
– Fibromatoses• At least 5 varieties
– Vascular lesions• Epithelioid hemangioendothelioma• Spindle cell hemangioendothelioma• Giant cell angioblastoma• Kaposi sarcoma• Fibrosarcoma of infancy• Dermatofibrosarcoma protuberans
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Soft Tissue Tumors• Malignant
– Synovial sarcoma– Hemangiopericytoma– Malignant peripheral nerve sheath tumor– Epithelioid sarcoma– Malignant fibrous histiocytoma– Fibrosarcoma– Myofibrosarcoma– Alveolar soft part sarcoma
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Soft Tissue Tumors
• Malignant– Clear cell sarcoma (malignant melanoma of soft
parts– Angiosarcoma– Liposarcoma– Leiomyosarcoma– Extraskeletal mesenchymal chrondrosarcoma– Extraskeletal myxoid chondrosarcoma
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One Month Old Boy
Right Upper Quadrant Mass
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Final Diagnosis
Liver tumor
Infantile Hemangioendothelioma
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Infantile Hemangioendothelioma
• Cavernous angioma• Angioendothelioma
• Capillary hemangioma
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Infantile Hemangioendothelioma
• 90% in first 6 months of life• Males < Females• Often multinodular• Involves other organs commonly
– Skin (20-40%)– Lung– Lymph nodes– Bone
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Infantile Hemangioendothelioma
• Jaundice• Thrombocytopenia• Heart failure (up to 25%)
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One Month Old GirlSoft Tissue Mass in Left Calf
Open Biopsy
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Soft Tissue of Left CalfOpen Biopsy
Congenital (Infantile) Fibrosarcoma
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Thirteen Year Old Girl
Mass in Right Thigh
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Mass in thigh
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Mass in thigh
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Final Diagnosis
Alveolar Soft Part Sarcoma
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Alveolar Soft Part Sarcoma• Adolescence & early adulthood• 40% in deep thigh or buttock• Everywhere else has been reported• Indolent growth & no pain• 20% metastatic rate at diagnosis
– Lung, Bone, Brain• Uniform histology
– Organoid clusters of bland cells– Thin fibrovascular septa– Central necrosis give alveolar pattern
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Alveolar Soft Part Sarcoma
• No consistent immunophenotype– Myogenin/MyoD1 but cytoplasmic– +/- desmin
• Rhomboid, PAS+ crystals in 22-80% but pathognomonic
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Soft Tissue SarcomasReferences
• Coffin CM, Dehner LP, O’Shea PA. Pediatric Soft Tissue Tumors. A Clinical, Pathological, and Therapeutic Approach. Williams & Wilkins, Baltimore, 1997.
• Weiss SW, Goldblum JR. Enzinger and Weiss’s Soft Tissue Tumors. Fourth Edition. Mosby, St. Louis, 2001.
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Germ Cell Tumors• 2 to 3 per 1,000,000 births in USA• Primordial germ cell origin• Heterogenous group of tumors• Site- and age-specific differences in
biology, prognosis, and therapy• Biphasic age distribution
– First peak at 2 years of age– Second peak at 15-20 years of age
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Germ Cell Tumors
• Biphasic age distribution– First peak at 2 years of age
• Extragonadal and gonadal– Mature teratoma– Immature teratoma (20% have yolk sac carcinoma) – Yolk sac carcinoma
– Second peak at 15-20 years of age• Mostly gonadal
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Germ Cell Tumors
• Teratoma• Immature teratoma• Embryonal carcinoma• Germinoma (dysgerminoma; seminoma)• Choriocarcinoma• Yolk sac carcinoma (endodermal sinus tumor)• Gonadoblastoma
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One Month Old Girl
• Gastroschisis• Sacrococcygeal region mass
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Primitive neural tube formationPrimitive neural tube formation
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Final Diagnosis
Sacrococcygeal teratoma (immature teratoma, grade I)
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Immature Teratoma
• No i(12p) in childhood cases• Immaturity in one or more of the three
layers but usually neuroepithelial tissue• Grades (?)
– 0 = no immaturity– 1 = no more than one low power field– 2 = >1 to <4 low power fields– 3 = many consecutive fields
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Immature Teratoma• Virtually all grade 1 and 2 are benign in
children• Extraovarian sites extremely rare - ?
sufficient numbers to evaluate the grading system
• Elevated serum α-fetoprotein– Usually means small foci of yolk sac carcinoma
that may not stain with immunoperoxidase– May mean fetal liver (or hepatoid pattern yolk
sac carcinoma) - ?? immature tissue or tumor
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One Month Old Boy
Presacral Tumor Mass with Pulmonary Metastases
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57 58α fetoprotein
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FINAL DIAGNOSIS
Needle biopsy of presacral tumor:Yolk sac carcinoma
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Yolk Sac Carcinoma
• Commonest malignant GCT in prepuberal children
• Pre-existing teratoma in most• Usually elevated alpha fetoprotein• Lots of confusing histologic patterns and
overlap with embryonal carcinoma
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Jesse J. Jenkins, III, M.D.Department of Pathology
St. Jude Children’s Research Hospital332 North Lauderdale Street
Memphis, Tennessee 38105-2794USA
[email protected]: (901)495-3516
Fax: (901)495-3100Web site: www.Cure4Kid.org