Soft Tissue

Rapidly involuting congenital hemangiomas (RICH) ●● Tumor fully grown at birth, regresses rap-

idly (by 1 year)

Non-involuting congenital hemangiomas (NICH) ●● Tumor fully grown at birth, does not

regress, grows proportionately with child

Epithelioid hemangiomas

●● Small vessels lined by epithelioid endothelial cells

Glomus tumors

●● Arise from modified smooth muscle cells of glomus body

endothelium ●● Positive for smooth muscle actin (SMA)

stain

Glomangioma

Glomangiomatosis

Glomangiomyoma

●● Features of glomus tumor and angioleiomyoma

Intermediate grade

Hemangioendotheliomas

cells in myxohyaline background ●● Stain positively with CD31, CD34, and fac-

tor VIII-related antigen

Kaposiform hemangioendothelioma

●● Multiple masses in head/neck, extremities, intestinal tract, and retroperitoneum

D2-40, SMA ●● Does not harbor HHV-8 ●● Associated with Kasabach-Merritt syn-

drome, lymphangiomatosis

tract, lung ●● Low-grade, spindle cell lesion, entrapped

erythrocytes ●● Immunoreactive with CD31, CD34, HHV-8

Epithelioid hemangioendothelioma

Angiosarcomas

VASCULAR MALFORMATIONS

●● Conglomeration of vessels of variable caliber

●● Lumina show thrombi in different stages of organization

●● Simple slow flow: Capillary, lymphatic, venous

Syndromes associated with vascular malformations

Von Hippel-Lindau syndrome

●● Hemangioblastoma of cerebellum, renal cell carcinoma

Blue rubber bleb nevus syndrome

●● Multifocal venous malformations affecting skin and gastrointestinal tract

Maffucci syndrome

●● Multiple enchondromas, hemangiomas, and lymphangiomas

●● Higher risk of central nervous system (CNS), pancreatic, and ovarian malignancies

Proteus syndrome

nary embolism

Sturge-Weber syndrome

●● Hemangioma in distribution of trigeminal nerve

Kasabach-Merritt syndrome

●● Thrombocytopenia due to sequestration of platelets in lesion

●● Vascular malformation with lymphatic channels, positive staining with D2-40

Gorham-Stout syndrome

Osler-Rendu-Weber syndrome

●● Hereditary hemorrhagic telangiectasia and arterio-venous malformations

LYMPHATIC TUMORS

Cystic lymphangioma (hygroma)

structures ●● Gorham-Stout syndrome: Bone involvement

by lymphangioma leads to vanishing bone syndrome

●● Variably sized lymphatic spaces lined by endothelium

FIBROUS, MYOFIBROBLASTIC, AND PERICYTIC TUMORS

Scars, keloids, and fasciitis

tion therapy

Hypertrophic scar

Keloid

more prevalent in Africans

ing cut surface ●● Spindle cell areas forming short fascicles,

interspersed by less cellular areas and mucoid-myxomatous extracellular material

●● Mitotic figures (none atypical), mild cytologic atypia, interstitial hemorrhage, and scattered inflammatory cells

Cranial fasciitis

Myositis ossificans

(10-15 cm) ●● No anaplasia, no atypical mitoses ●● Three zones

●❑ Central zone: Proliferating plump myofibroblasts, histiocytes, and blood vessels

Fibrodysplasia ossificans progressiva

heterotopic bone ●● ACVR1/ALK2 mutation

Infantile myofibromatosis (myofibroma)

3 cm ●● Head/neck/extremities ●● Spontaneous regression ●● Non-encapsulated nodular mass, central

hemorrhage ●● Centrally, hemangiopericytoma-like histol-

ogy (CD34+)

●● Peripherally, spindle-shaped cell fascicular proliferation (SMA+)

Myopericytoma

spindle cells

Infantile fibromatosis

desmoid fibromatosis ●● Stain positively with CD34

Fibrous hamartoma of infancy

nal regions, extremities ●● Bland mature spindle cells, mature adipose

tissue, small bundles of immature spindle cells

Inclusion body fibromatosis (infantile digital fibroma)

●● Small nodular mass located in digits and toes (sparing big toe/thumb)

(stain red with trichrome)

Desmoid-type fibromatosis (desmoid tumor, musculoaponeurotic fibromatosis)

●● Association with Gardner syndrome and familial adenomatous polyposis (FAP)

●● Spindle fibroblasts/myofibroblasts in collagenous, pale myxoid background

●● Infiltrative margins, scattered lymphoid nodules at interface with normal tissue

●● Surgical margins important due to very high recurrence rate

●● Sporadic/familial desmoids have nuclear expression of beta-catenin

Gardner-nuchal fibroma

cal/paraspinal region ●● Nuclear positivity for beta-catenin and

cyclin -D1

Juvenile hyaline fibromatosis

●● Painful papulonodular lesion of skin/soft tissue

(resemble cartilage)

Calcifying aponeurotic fibromatosis

hyalinized stroma, granular calcifications ●● Highly recurrent

Juvenile nasopharyngeal angiofibroma

proliferation, intervening vascular spaces, pushing borders

●● Associated with FAP, positive nuclear expression for beta-catenin

Fibromatosis colli

matosis

Inflammatory myofibroblastic tumor

intestinal tract, multifocal ●● Associated constitutional symptoms: Fever,

weight loss, failure to thrive ●● Dense spindle cell proliferation (myofibro-

blasts), extensive infiltration by lymphocytes and plasma cells

●● Paucicellular histology with scattered inflammatory cells

Adult-type fibrosarcoma

Congenital infantile fibrosarcoma (CIFS)

mesoblastic nephroma and secretory breast carcinoma also

●● Uniform to primitive appearing spindled fibroblasts in fascicular/non-fascicular pattern

Low-grade fibromyxoid sarcoma

lar myxoid areas ●● Hyalinizing giant rosettes ●● Diffusely positive for vimentin and focally

positive for epithelial membrane antigen (EMA)

Solitary fibrous tumor and hemangiopericytoma

●● Intermediate-grade, rarely metastasizing tumors

enous stroma ●● Positive staining for vimentin and CD34

Dermatofibrosarcoma protuberans and giant cell fibroblastoma

arises in mid-deep dermis and extends into subcutaneous tissue/deep fascia

●● Both tumors show proliferation of spindle cells, pale myxoid stroma

●● Scattered floret like giant cells in cleft-like spaces

FIBROHISTIOCYTIC TUMORS

Benign fibrous dermatofibroma

●● Proliferation of bland spindle-shaped fibroblasts and histiocytes

Juvenile xanthogranuloma

●● Xanthomatous histiocytes and Touton giant cells

Giant cell tumor (GCT) of tendon sheath

Nodular tenosynovitis

ated giant cells

Extra-articular villonodular tenosynovitis

Pigmented villonodular synovitis

hypercellular stroma, hemosiderin pigment laden histiocytes

Angiomatoid fibrous histiocytoma

●● Low-grade malignant tumors, slow growing

mitotic activity ●● Blood-filled spaces, lymphoid nodules ●● Positive staining with vimentin, CD99, des-

min, CD68, and EMA ●● EWSR1-ATF1 translocation ●● Low rate of metastasis, local recurrence

Plexiform fibrohistiocytic tumor

dled fibroblasts in collagenous stroma ●● Scattered osteoclast like giant cells, lym-

phocytic inflammatory infiltrate ●● Positive for CD68 ●● Locally recurrent, low metastatic rate

ADIPOCYTIC (LIPOMATOUS) TUMORS

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN)

●● Germline mutation in tumor suppressor gene located on 10q

●● Proteus syndrome; formation of hamartomatous growths

Macrodystrophia lipomatosa and macrodactyly

hamartomatous growth of fibrous, vascular, neural tissue

●● Macrodactyly; lipofibromatous hamartoma of median nerve

Congenital intraspinal lipoma

tissue ●● Differential diagnosis with Currarino syn-

drome (sacral anomalies, tethered spinal cord or lipoma, presacral teratoma and various anorectal anomalies, point mutations in HLXB9 homeobox gene)

Lipomas

Angiolipoma

fibrin thrombi

Lipoblastoma

oid change, no atypia ●● Delicate arborizing capillary network, mast

cells, lobular architecture ●● Fat cells show positive staining with S100 ●● PLAG1 gene amplified/rearranged (8q13)

Myxoid liposarcoma

round cells, lipoblasts, myxoid background, lacy vasculature

Hibernoma

mic vacuoles

Arrhythmogenic right ventricular cardiomyopathy

●● Fatty infiltration and replacement of right ventricle of heart by fat

PERIPHERAL NERVE SHEATH TUMORS (PNST)

Neurofibroma

subcutaneous, and deep soft-tissue masses) ●● Non-encapsulated, diffuse, and plexiform

subtypes ●● Wavy spindle cells ●● Focally positive for S100 stain

Schwannoma

nerve by schwannoma ●● Diffuse staining with S100 ●● Encapsulated tumors ●● Cellular spindle cell pattern with Verocay

bodies (Antoni A) ●● Hypocellular myxoid foci (Antoni B)

Malignant peripheral nerve sheath tumor (MPNST)

plastic cells ●● If associated with small collections of rhab-

domyoblasts; triton tumor ●● Positive staining with vimentin, S100, CD57

Perineurioma

●● Soft-tissue mass arising in major nerve/ brachial plexus

Nerve sheath myxoma (neurothekeoma)

Granular cell tumor (GCT)

on alveolar border of maxilla/mandible in neonates

●● Nests of granular cells, pale/eosinophilic granular cytoplasm

●● Positive staining with CD68, S100 (neural variant), alpha-inhibin

Glioneuronal heterotopia

PERIVASCULAR EPITHELIOID CELL NEOPLASM (PECOMA)

●● Immunophenotyping similar to angiomyolipomas of kidney and sugar tumor of lung

●● Immunopositive for SMA, HMB-45, and microphthalmic transcription factor

ophilic/clear cytoplasm

GASTROINTESTINAL STROMAL TUMOR (GIST)

or PDGFR1 ●● Positive staining with CD117, CD34 ●● Stomach/small intestine most common sites ●● Association with Carney triad ●● Spindle/epithelioid cells mixed morphology

SKELETAL AND SMOOTH MUSCLE NEOPLASMS

Rhabdomyoma

masses in ventricles

Focal myositis

●● Inflammatory mass in deep soft tissue of extremities

●● Surrounding skeletal muscle shows degenerative/regenerative changes

Smooth muscle tumors

●● Leiomyoma of soft tissue, smooth muscle hamartoma

Rhabdomyosarcoma (RMS)

●● Metastasize to regional lymph nodes, bone marrow, and lungs

●● RMS may be associated with other tumors; ectomesenchymoma (RMS+ PNET), triton tumor (RMS+ MPNST)

●● In uterine cervix RMS shows heterologous cartilage

Embryonal RMS

nuclear hyperchromasia, atypical mitoses scattered larger tumor cells with abundant eosinophilic cytoplasm

●● Sarcoma botryoides (cambium layer of small primitive tumor cells underneath epithelial surface)

myogenin, desmin ●● Molecular genetics: LOH on 11p15.5

Alveolar RMS

fibrovascular stroma, septal growth pattern ●● Loose sheets of tumor cells with interven-

ing multinuclear tumor cells

●● Positive staining for vimentin, diffuse nuclear positivity for desmin, myoD1, and myogenin

●● Molecular genetics; PAX3-FKHR, t(2;13), and PAX7-FKHR, t(1;13)

●● PAX3 is more common; carries a worse prognosis

Ectomesenchymoma

Rhabdomyosarcoma and neuroectodermal ●● Head/neck, external genitalia

SARCOMAS OF UNCERTAIN HISTOGENESIS

Ewing sarcoma-primitive neuroectodermal tumor (EWS-PNET)

wall, paraspinal region, viscera ●● Second decade of life ●● Nested lobular pattern of monotonous

round/polygonal cells ●● Central round nuclei, finely vacuolated/

clear glycogen-containing cytoplasm ●● Positive staining for vimentin (perinuclear

cytoplasmic/dot like) and CD99 (membranous pattern)

Desmoplastic small round cell tumor

fibrous stroma ●● Positive staining with vimentin, cytokera-

tin (perinuclear), desmin, WT1

Clear cell sarcoma of soft tissue (malignant melanoma of soft parts)

●● EWS fusion partner with ATF1, translocation t(12;22)

●● Phenotypically melanoma-containing melanosomes

●● Does not have mutation of BRAF4 kinase (d/d cutaneous melanoma)

●● Located in lower extremities, near tendon sheath/aponeurosis

inclusions

●● Positive staining with S100, HMB45, Melan-A, CD99

Extraskeletal myxoid chondrosarcoma

Myoepithelial tumor of soft tissue

oid chondrosarcoma ●● Positive staining for AE1/AE3, EMA, S100

Malignant rhabdoid tumor

central nervous system ●● Soft-tissue primary sites: Head, neck, and

mediastinum ●● Filamentous eosinophilic cytoplasmic

inclusions in rhabdoid cells ●● Positive staining for EMA, vimentin ●● Negative staining for BAF47 (due to inacti-

vated INI1 gene)

Atypical teratoid rhabdoid tumor (ATRT)

Carcinoma with t(15;19) translocation

NUT rearrangement t(15;19), NUT-BRD4 oncogene

located in mediastinum) ●● Sheets of undifferentiated cells, hemor-

rhage, necrosis, apoptosis, mitosis

Alveolar soft part sarcoma

cell carcinoma in children ●● Deep soft tissue of proximal lower extrem-

ity, head/neck ●● Nests of uniform polygonal tumor cells,

prominent nucleoli, surrounded by delicate stromal envelopes

(nuclear positivity is diagnostic)

Epithelioid sarcoma

hand/forearm, superficial dermal location ●● Proximal (axial type): Immunophenotype/

genotypic features similar to malignant rhabdoid tumor, very aggressive clinical course, located in deep soft tissue

●● Mantle of epithelioid cells, central necrosis/ hyalinization

●● Differential diagnosis with necrobiosis lipoidica (CD68+)

●● Positive staining with vimentin, cytokeratin, EMA

Synovial sarcoma

●● t(X;18) translocation, fusing SYT and SSX1/ SSX2

tion in spindle cell background, dystrophic calcification

●● Positive staining for spindle cell component; vimentin (diffuse)

●● Positive staining for epithelial component; EMA(diffuse), CK7(Individual tumor cells), Bcl2, CD99

prognosis