Non-Rhabdomyosarcomatous Soft Tumors Tissue & Germ Cell Tumors of Childhood Other Than Jesse J. Jenkins, III, M.D. Director of Pathology for the International Outreach Program

St. Jude Children’s Research Hospital 1 2

Soft Tissue Tumors • Heterogenous with diverse patterns – Extracellular matrix proteins • collagen Soft Tissue Tumors • laminin • chondroitin sulfate – Cytoskeletal elements Can be easy or very difficult to • keratin diagnose! • vimentin – Energy storing & enzymatic proteins • myoglobin • creatine kinase

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Soft Tissue Tumors Soft Tissue Tumors

• Histopathologic diagnosis • Cytoskeleton/Matrix Relation – Morphology defined by – Defines tumor cell shape • Cell shapes • Dense collagen - compresses (narrow, elongated) • Spatial organization • Chondroid matrix - surrounds in lacunar fashion – Patterns produced • Myxoid matrix - allows polygonal expansion • Organization of cellular elements • Interaction with surrounding tissues

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1 Soft Tissue Tumors Soft Tissue Tumors

• Complex structures • Recognizable distinguishing characteristics – Produced or induced by tumor – Light microscopy (still the primary standard) • Epithelial slits (synovial , nerve sheath – Electron microscopy (decreasingly used) tumors) – Immunohistochemistry (now the secondary • Blood vessels (hemangiopericytoma) standard) • Inflammatory cells (recruited by all of them) – Mast cells – Cytogenetics – Lymphocytes – Molecular diagnostics (increasingly important)

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Soft Tissue Tumors Soft Tissue Tumors •Benign •Benign – Scar – Fibrohistiocytic lesions – • Fibrous – Proliferative fasciitis & myositis • Giant cell fibroblastoma • Plexiform fibrohistiocytic tumor – Myositis ossificans • Juvenile xanthogranuloma – Fibrodysplasia ossificans progressiva • Xanthoma – Various Fibromatoses • Tenosynovial giant cell tumor – Fibrous pseudotumor (inflammatory – Vascular lesions pseudotumor) • More than 16 varieties described – Angiofibroma – lesions

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Soft Tissue Tumors Soft Tissue Tumors • Intermediate Clinical Behavior •Benign –Fibromatoses – Nerve sheath lesions • At least 5 varieties • At least 7 varieties – Vascular lesions –Fatty lesions • Epithelioid hemangioendothelioma • /lipoblastomatosis • Spindle cell hemangioendothelioma • Fibrous hamartoma of infancy • Giant cell angioblastoma • Kaposi sarcoma • of infancy • Dermatofibrosarcoma protuberans

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2 Soft Tissue Tumors Soft Tissue Tumors • Malignant – • Malignant – Hemangiopericytoma – (malignant melanoma of soft parts – Malignant peripheral nerve sheath tumor –Angiosarcoma – Epithelioid sarcoma – – Malignant fibrous histiocytoma – –Fibrosarcoma – Extraskeletal mesenchymal chrondrosarcoma – Myofibrosarcoma – Extraskeletal myxoid chondrosarcoma – Alveolar soft part sarcoma

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One Month Old Boy

Right Upper Quadrant Mass

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4 Infantile Hemangioendothelioma Final Diagnosis • Cavernous angioma Liver tumor • Angioendothelioma • Capillary hemangioma Infantile Hemangioendothelioma

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Infantile Hemangioendothelioma Infantile Hemangioendothelioma

• 90% in first 6 months of life • Jaundice • Males < Females • Thrombocytopenia • Often multinodular • Heart failure (up to 25%) • Involves other organs commonly – Skin (20-40%) –Lung – Lymph nodes –Bone

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One Month Old Girl Soft Tissue Mass in Left Calf

Open Biopsy

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Soft Tissue of Left Calf Thirteen Year Old Girl Open Biopsy

Congenital (Infantile) Fibrosarcoma Mass in Right Thigh

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Mass in thigh Mass in thigh

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6 Alveolar Soft Part Sarcoma • Adolescence & early adulthood • 40% in deep thigh or buttock • Everywhere else has been reported Final Diagnosis • Indolent growth & no pain • 20% metastatic rate at diagnosis – Lung, Bone, Brain Alveolar Soft Part Sarcoma • Uniform histology – Organoid clusters of bland cells – Thin fibrovascular septa – Central necrosis give alveolar pattern

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Alveolar Soft Part Sarcoma Soft Tissue Sarcomas References • No consistent immunophenotype – Myogenin/MyoD1 but cytoplasmic • Coffin CM, Dehner LP, O’Shea PA. –+/-desmin Pediatric Soft Tissue Tumors. A Clinical, • Rhomboid, PAS+ crystals in 22-80% but Pathological, and Therapeutic Approach. pathognomonic 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 Germ Cell Tumors

• 2 to 3 per 1,000,000 births in USA • Biphasic age distribution • Primordial germ cell origin – First peak at 2 years of age • Heterogenous group of tumors • Extragonadal and gonadal – Mature teratoma • Site- and age-specific differences in – Immature teratoma (20% have yolk sac carcinoma) biology, prognosis, and therapy – Yolk sac carcinoma • Biphasic age distribution – Second peak at 15-20 years of age – First peak at 2 years of age • Mostly gonadal – Second peak at 15-20 years of age

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7 Germ Cell Tumors One Month Old Girl

• Teratoma • Immature teratoma • Embryonal carcinoma • Gastroschisis • Germinoma (dysgerminoma; seminoma) • Sacrococcygeal region mass • Choriocarcinoma • Yolk sac carcinoma (endodermal sinus tumor) • Gonadoblastoma

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8 Primitive neural tube formation

Final Diagnosis

Sacrococcygeal teratoma (immature teratoma, grade I)

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Immature Teratoma Immature Teratoma • Virtually all grade 1 and 2 are benign in • No i(12p) in childhood cases children • Immaturity in one or more of the three • Extraovarian sites extremely rare - ? layers but usually neuroepithelial tissue sufficient numbers to evaluate the grading • Grades (?) system – 0 = no immaturity • Elevated serum α-fetoprotein – 1 = no more than one low power field – Usually means small foci of yolk sac carcinoma – 2 = >1 to <4 low power fields that may not stain with immunoperoxidase – 3 = many consecutive fields – May mean fetal liver (or hepatoid pattern yolk

51 sac carcinoma) - ?? immature tissue or tumor 52

One Month Old Boy

Presacral Tumor Mass with Pulmonary Metastases

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Yolk Sac Carcinoma FINAL DIAGNOSIS • Commonest malignant GCT in prepuberal children Needle biopsy of presacral tumor: • Pre-existing teratoma in most Yolk sac carcinoma • Usually elevated alpha fetoprotein • Lots of confusing histologic patterns and overlap with embryonal carcinoma

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10 Jesse J. Jenkins, III, M.D. Department of Pathology St. Jude Children’s Research Hospital 332 North Lauderdale Street Memphis, Tennessee 38105-2794 USA [email protected] Phone: (901)495-3516 Fax: (901)495-3100 Web site: www.Cure4Kid.org 61

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