Non-Rhabdomyosarcomatous Soft
Tissue Sarcomas & Germ Cell
Tumors of Childhood
Jesse J. Jenkins, III, M.D.
Director of Pathology
for the
International Outreach Program
St. Jude Children’s Research Hospital
Soft Tissue Tumors
Other Than Rhabdomyosarcoma
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Soft Tissue Tumors
• Heterogenous with diverse patterns
– Extracellular matrix proteins
• collagen
• laminin
• chondroitin sulfate
Soft Tissue Tumors
– Cytoskeletal elements
Can be easy or very difficult to
diagnose!
• keratin
• vimentin
– Energy storing & enzymatic proteins
• myoglobin
• creatine kinase
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Soft Tissue Tumors
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Soft Tissue Tumors
• Histopathologic diagnosis
• Cytoskeleton/Matrix Relation
– Morphology defined by
– Defines tumor cell shape
• Cell shapes
• Spatial organization
• Dense collagen - compresses (narrow, elongated)
• Chondroid matrix - surrounds in lacunar fashion
• Myxoid matrix - allows polygonal expansion
– Patterns produced
• Organization of cellular elements
• Interaction with surrounding tissues
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Soft Tissue Tumors
Soft Tissue Tumors
• Complex structures
• Recognizable distinguishing characteristics
– Produced or induced by tumor
– Light microscopy (still the primary standard)
– Electron microscopy (decreasingly used)
– Immunohistochemistry (now the secondary
standard)
– Cytogenetics
– Molecular diagnostics (increasingly important)
• 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
Soft Tissue Tumors
• Benign
• Benign
– Scar
– Nodular fasciitis
– Proliferative fasciitis & myositis
– Myositis ossificans
– Fibrodysplasia ossificans progressiva
– Various Fibromatoses
– Fibrous pseudotumor (inflammatory
pseudotumor)
– Angiofibroma
– Fibrohistiocytic lesions
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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
Soft Tissue Tumors
• Intermediate Clinical Behavior
• Benign
– Fibromatoses
– Nerve sheath lesions
• At least 5 varieties
• At least 7 varieties
– Vascular lesions
– Fatty lesions
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• Lipoblastoma/lipoblastomatosis
• Fibrous hamartoma of infancy
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Epithelioid hemangioendothelioma
Spindle cell hemangioendothelioma
Giant cell angioblastoma
Kaposi sarcoma
Fibrosarcoma of infancy
Dermatofibrosarcoma protuberans
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Soft Tissue Tumors
Soft Tissue Tumors
• Malignant
• Malignant
– Synovial sarcoma
– Hemangiopericytoma
– Malignant peripheral nerve sheath tumor
– Epithelioid sarcoma
– Malignant fibrous histiocytoma
– Fibrosarcoma
– Myofibrosarcoma
– Alveolar soft part sarcoma
– 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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Infantile Hemangioendothelioma
Final Diagnosis
• Cavernous angioma
• Angioendothelioma
• Capillary hemangioma
Liver tumor
Infantile Hemangioendothelioma
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Infantile Hemangioendothelioma
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90% in first 6 months of life
Males < Females
Often multinodular
Involves other organs commonly
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Infantile Hemangioendothelioma
• Jaundice
• Thrombocytopenia
• Heart failure (up to 25%)
– 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
Open Biopsy
Thirteen Year Old Girl
Congenital (Infantile) Fibrosarcoma
Mass in Right Thigh
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Mass in thigh
Mass in thigh
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Alveolar Soft Part Sarcoma
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Final Diagnosis
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
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
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Soft Tissue Sarcomas
References
• No consistent immunophenotype
• 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.
– Myogenin/MyoD1 but cytoplasmic
– +/- desmin
• Rhomboid, PAS+ crystals in 22-80% but
pathognomonic
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Germ Cell Tumors
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Germ Cell Tumors
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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
• 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
– First peak at 2 years of age
– Second peak at 15-20 years of age
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Germ Cell Tumors
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One Month Old Girl
Teratoma
Immature teratoma
Embryonal carcinoma
Germinoma (dysgerminoma; seminoma)
Choriocarcinoma
Yolk sac carcinoma (endodermal sinus tumor)
Gonadoblastoma
• Gastroschisis
• Sacrococcygeal region mass
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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
children
• Extraovarian sites extremely rare - ?
sufficient numbers to evaluate the grading
system
• Elevated serum α-fetoprotein
• 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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– 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 52
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One Month Old Boy
Presacral Tumor Mass with
Pulmonary Metastases
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α fetoprotein
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α fetoprotein
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Yolk Sac Carcinoma
FINAL DIAGNOSIS
• 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
Needle biopsy of presacral tumor:
Yolk sac carcinoma
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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
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