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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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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

jesse.jenkins@stjude.orgPhone: (901)495-3516

Fax: (901)495-3100Web site: www.Cure4Kid.org