Diagnosis and variants Abdominal fibromatosis Acquired tufted angioma Acral myxoinflammatory fibroblastic sarcoma Adenomatoid tumor Adult

rhabdomyoma Aggressive angiomyxoma Alveolar soft part sarcoma Amyloidoma Angiolipoma - Cellular angiolipoma - Spinal angiolipoma Angiomatoid fibrous histiocytoma Angiomatosis (Diffuse hemangioma) Angiomyofibroblastoma Angiomyoma Angiosarcoma - Cutaneous angiosarcoma without lymphedema - Angiosarcoma associated with lymphedema - Angiosarcoma of the breast - Angiosarcoma of soft tissue - Radiation-induced angiosarcoma Arterial spiders Arteriovenous hemangioma Atypical fibrous histiocytoma Atypical fibroxanthoma Atypical vascular lesion Bacillary angiomatosis Calcifying aponeurotic fibroma Calcifying fibrous pseudotumor Cardiac rhabdomyoma Cavernous hemangioma - Sinusoidal hemangioma Cellular angiofibroma Cherry angioma Chondroid lipoma Clear cell sarcoma of tendon and aponeurosis Clear cell sarcoma-like tumor of gastrointestinal tract Crystal-storing histiocytosis Cutaneous leiomyoma Cutaneous myxoma Dedifferentiated liposarcoma Dermatofibrosarcoma protuberans - Pigmented DFSP (Bednar tumor) Desmoplastic fibroblastoma Desmoplastic melanoma Desmoplastic small round cell tumor Diffuse lipomatosis Diffuse malignant mesothelioma Elastofibroma - Elastofibrolipoma EBV-associated smooth muscle tumor

M/F F>M M=F M>F F>M F>M M>F

Age Young Children 30-50 30-60 >40 15-35 15-50

10-40 0-20 F>>M F>M 30-60 M>F F>M F>>M M>F 40+ 60-70 20-40 Any

20-50 Elderly M>F M>F F>M M=F F>M M=F F>M 20-40 20-40

8-14 10-30 Infants Children

M>F M=F M>F M>F M>F M>F F>M

Early 20-40 50-70 20-50 40-70 Older 15-35 0-2 45-75 50-70 Children

Epithelioid angiomatous nodule Epithelioid hemangioendothelioma Epithelioid hemangioma Epithelioid sarcoma - Proximal-type epithelioid sarcoma Epithelioid sarcoma-like hemangioendothelioma Extra-abdominal fibromatosis Extra-cranial meningioma Extra-gastrointestinal stromal tumor Extra-skeletal chondroma Extra-skeletal Ewing's sarcoma/PNET Extra-skeletal mesenchymal chondrosarcoma Extra-skeletal myxoid chondrosarcoma Extra-skeletal osteosarcoma Extra-spinal ependymoma Fetal rhabdomyoma - Myxoid fetal rhabdomyoma - Intermediate fetal rhabdomyoma - Neural variant of fetal rhabdomyoma Fibroma of the tendon sheath - Pleomorphic fibroma of the tendon sheath Fibrodysplasia ossificans progressiva Fibromatosis colli Fibrosarcoma, classic type Fibrous hamartoma of infancy Fibrous histiocytoma (dermatofibroma) - Aneurysmal fibrous histiocytoma - Cellular fibrous histiocytoma - Epithelioid fibrous histiocytoma - Lipidized fibrous histiocytoma Florid vascular proliferation of the colon Ganglion cell choristoma Ganglion cyst Ganglioneuroma Gardner fibroma Genital rhabdomyoma Giant cell fibroblastoma Giant cell tumor of low malignant potential Giant cell tumor of tendon sheath - Diffuse type - Localized type - Malignant Gingival fibromatosis Glial heterotopia Glomangioma Glomangiomatosis Glomangiomyoma Glomeruloid hemangioma Glomus tumor - Malignant glomus tumor - Glomus tumor of uncertain malignant potential - Symplastic glomus tumor

M=F F>M M>F

10-90 20-40 10-35

F>M

15-40 Adults 30-60 0-30 15-35 35-60 35-80

M>F M>F F>M M>F M>F

M>F M>F M>F M=F M>F M>F M>F

0-1 Adults 20-50 0-6 Newborn 20-50 0-2 20-50

F>M M=F M=F F>>M M>F

25-45 5-40 Young Young 0-10

F>M F>M F>M M=F

4-76 30-50 12-79 Young Infants Children Children

M=F

20-40

Granular cell reaction Granular cell tumor F>M 30-60 - Congenital granular cell tumor F>M Infants Hemangioma of peripheral nerves 0-40 Hemangiopericytoma-like tumor of nasal passages Hemangiopericytoma / solitary fibrous tumor M=F Adults Hemosiderotic fibrohistiocytic lipomatous lesion Adults Hereditary hemorrhagic telangiectasia Children Hibernoma M>F 20-40 Histoid leprosy Hobnail hemangioma Young Hobnail hemangioendothelioma Any Idiopathic retroperitoneal fibromatosis M>F 20-70 Infantile digital fibromatosis F>M 0-3 Infantile fibromatosis (lipofibromatosis) M>F 0-8 Infantile fibrosarcoma M>F 0-2 - Infantile rhabdomyofibrosarcoma 0-3 Infantile hemangiopericytoma 0-1 Inflammatory myofibroblastic tumor F>M 0-45 Inflammatory pseudotumor M~F 30-50 Intra-abdominal fibromatosis F>M 20-35 Intramuscular hemangioma M=F 0-30 Intramuscular lipoma / Intermuscular lipoma M>F 30-60 Intramuscular myxoma F>M 40-70 Intranodal palisaded myofibroblastoma Intravenous leiomyomatosis F Pre-MP Ischemic fasciitis F>M 70-90 Juvenile hemangioma Infants Juvenile hyaline fibromatosis M>F 0-5 Juvenile xanthogranuloma Infants Juxta-articular myxoma M>F 20-50 Kaposi sarcoma - Classic Kaposi sarcoma M>F 50-70 - Endemic Kaposi sarcoma F>M - Iatrogenic Kaposi sarcoma - AIDS-related Kaposi sarcoma M>F Younger Kaposiform hemangioendothelioma Children Keloid M=F 15-50 Knuckle pads M=F 30-60 - Pachydermatodactyly Leiomyoma of deep soft tissue M=F Leiomyomatosis peritonealis disseminata F Pre-MP Leiomyosarcoma F>M - Retroperitoneal/abdominal leiomyosarcoma F>M 60-70 - Leiomyosarcoma of somatic soft tissue M=F - Cutaneous leiomyosarcoma M>F 40-70 - Leiomyosarcoma of vascular origin F>F 50 Lipoblastoma / Lipoblastomatosis M>F 0-35 Lipoma M>F 40-60 - Fibrolipoma, sclerotic lipoma, myxolipoma, chondrolipoma, osteolipoma Lipoma of joint (lipoma arborescens) M>F Adults Lipoma of tendon sheath M=F 15-35

Localized massive edema Low-grade fibromyxoid sarcoma - Hyalinizing spindle cell tumor with giant rosettes Lumbosacral lipoma Lymphangioma - Acquired progressive lymphangioma - Cystic lymphangioma Lymphangiomatosis Malakoplakia Malignant extrarenal rhabdoid tumor Malignant fibrous histiocytoma - Storiform-pleomorphic MFH - Myxoid MFH - Giant cell MFH - Inflammatory MFH Malignant mesenchymoma Malignant peripheral nerve sheath tumor Mammary-type myofibroblastoma Melanotic neuroectodermal tumor of infancy Melanotic schwannoma Morton's neuroma Mucosal neuroma Multicystic peritoneal mesothelioma Muscular fibrosis Mycobacterial pseudotumor Myelolipoma Myofibroma / myofibromatosis Myofibrosarcoma (myofibroblastic sarcoma) Myolipoma Myopericytoma Myositis ossificans - Fibro-osseous pseudotumor of the digits Myxofibrosarcoma - Epithelioid myxofibrosarcoma Myxoid liposarcoma - Round cell liposarcoma Nasopharyngeal angiofibroma Nerve sheath ganglion Neural fibrolipoma (lipofibromatous hamartoma) Neuroblastoma and ganglioneuroblastoma Neurofibroma - Localized neurofibroma - Plexiform neurofibroma - Diffuse neurofibroma - Pigmented neurofibroma Neuromuscular hamartoma Neurothekeoma - Cellular neurothekeoma Nevus flammeus Nevus lipomatosus cutaneous superficialis Nodular fasciitis - Cranial fasciitis

M>F M>F F>M M>F M>F M=F

Wide 20-40 0-10 0-2 Children Children

M>F

50-70

M~F M>F

20-50 60-70 0-1

F>M F>M 0-20 Young 0-3 >40 Wide 30-40 40-60

M>F M>F F>M

M>F Young F>M Young 40-70 M>F 25-45 M>>F 10-20 M>F M>F M=F 0-30 0-5 20-30 Children

Children Children

M=F M=F

0-20 20-40 Infants

- Intravascular fasciitis - Ossifying fasciitis Nuchal-type fibroma Odontogenic myxoma Olfactory neuroblastoma Ossifying fibromyxoid tumor of soft parts Pacinian neuroma Palisaded encapsulated neuroma Palmar fibromatosis Papillary endothelial hyperplasia Parachordoma / mixed tumor / soft tissue myoepithelioma Paraganglioma - Carotid body paraganglioma - Jugulotympanic paraganglioma - Vagal paraganglioma - Mediastinal paraganglioma - Retroperitoneal paraganglioma Paraganglioma-like dermal melanocytic tumor Pelvic lipomatosis Penile fibromatosis Perineurioma - Intraneural perineurioma - Extraneural perineurioma - Sclerosing perineurioma - Reticular perieurioma Perivascular epithelioid cell neoplasm (PEComa) - Angiomyolipoma - Lymphangiomyoma / lymphangiomyomatosis Phosphaturic mesenchymal tumor Plantar fibromatosis Pleomorphic fibroma of the skin Pleomorphic hyalinizing angiectatic tumor of soft parts Pleomorphic liposarcoma Plexiform fibrohistiocytic tumor Polymorphous hemangioendothelioma Polyvinylpyrridoline (PVP) granuloma Proliferative fasciitis Proliferative myositis Proteus syndrome Pyogenic granuloma Reactive nodular fibrous pseudotumor Reticulohistiocytoma (solitary) Reticulohistiocytosis (multicentric) Rhabdomyomatous mesenchymal hamartoma Rhabdomyosarcoma - Embryonal rhabdomyosarcoma (ERMS) - ERMS, spindle cell type - ERMS, botryoid type - Alveolar rhabdomyosarcoma - Pleomorphic rhabdomyosarcoma - Sclerosing rhabdomyosarcoma Rosai-Dorfman disease (extranodal)

M=F M>F F>M M=F M>F M=F M>F M=F M>F F>M F>M M=F M=F M>F M

< 30 20-50 Young 40-60 50

>30 10-40 40-60 40-50 >40 30-45 20-40 45-60 Young Adults Young

M=F M>F

F>M 30-40 F>M 40s F>>M 40s M=F F>M F>M Any 40s 50s Elderly 0-30

M=F M=F M=F M=F M>F

40-70 45-65 All Adults

M>>F 0-1 M>F 0-25 0-10 M>F Young 10-25 >45 18-50

M>F M~F

Schwannoma Schwannomatosis Sclerosing epithelioid fibrosarcoma Silica reaction Spindle cell hemangioma Spindle cell/pleomorphic lipoma Spindle cell liposarcoma Steroid lipomatosis Symmetric lipomatosis Synovial chondromatosis Synovial hemangioma Synovial sarcoma Traumatic neuroma Tumoral calcinosis Vascular transformation of lymph nodes Venous hemangioma Well-differentiated liposarcoma - Lipoma-like well differentiated liposarcoma - Sclerosing well differentiated liposarcoma - Inflammatory well differentiated liposarcoma - Lipoleiomyosarcoma Well-differentiated papillary mesothelioma Xanthoma

M=F M=F M=F

20-50 Wide Young 45-60 Varies Adults Young 15-40 Young

M>F

M>F

M>F M=F

M=F

50-70

F>M

20-40

Location Abdominal wall Fingers, hands, toes, feet, ankles Genital tract, rarely others Head/neck (pharynx, oral cavity) Vulva, inguinal region, scrotum Lower extremities, head/neck Anywhere Forearm, trunk, upper arm

Positive IHC and special stains

Vimentin; +/- CD68 CK, calretinin, D2-40, WT1, CK5/6 Desmin, MSA, +/- focal SMA Vimentin, desmin, MSA, SMA TFE3, +/- S-100; PAS-D (crystals) Congo red CD31/CD34 (vascular component)

Arms, legs Vulva, vagina Extremities, head, trunk, oral Skin, superficial soft tissue, other Head/neck (scalp, forehead), leg Extremities (arm) Breast Leg, trunk, arm, head/neck Abdomen, breast skin

+/- CD68, desmin, CD99 Desmin, ER, PR

CD31, CD34, thrombomodulin

CD31, vWF, +/- keratin

Arms, legs Head/neck (nose, cheek, ear) Breast Skin, organs, soft tissue Palm, fingers, feet Extremities, trunk Heart ventricles Upper portion of body Inguino-scrotal, vulvo-vaginal Trunk, extremities Extremities, limb girdle Foot, ankle, knee, thigh, hand Small bowel, stomach, colon Genital region/nipples; elsewhere Trunk, legs, head/neck Retroperitoneum Trunk, legs, arms Shoulder, arm Head, neck Abdominal cavity, pelvis Extremities, trunk, head/neck Pleura, peritoneum, pericardium Subscapular area Mediastinum Solid organs

Warthin-Starry (organisms) +/- SMA, MSA, desmin, CD34 MSA, desmin, +/- HMB-45

CD34, +/- SMA, desmin, ER, PR PAS, Oil red O, S-100, CD68 S-100, HMB-45, Melan-A, NSE CD68 SMA Vimentin, CD34; Alcian blue CD34, apolipoprotein D Focal SMA and MSA S-100, clusterin; +/- MiTF CK, vimentin, desmin, carboxy WT1 CK5/6, calretinin, WT1, D2-40 Elastic stains EBER, SMA

Skin Soft tissue, lung, liver, bone, skin Head/neck, ear Hand, fingers, forearm, wrist, knee Pelvis, perineum, genital tract Extremities Shoulder, chest/back, thigh Scalp, vertebral axis Omentum, mesentery Fingers, hands, toes, feet Upper thigh, buttock, arm, shoulder Orbit, head/neck, thigh, legs Thigh, popliteal fossa, limb girdle Thigh, pelvis, shoulder, RP Sacrococcygeal region Head/neck (auricular area) Head/neck (orbit, tongue, palate) Fingers, hands Spreads throughout body Sternocleidomastoid muscle Thigh, knee, arms, trunk Axilla, upper arm, thigh Arms, legs

CD31, CD34, vWF CK, EMA, vimentin; +/- CD34 +/- desmin, SMA CK, vimentin, CD31, FLI1 B-catenin, SMA, MSA CKIT, CD34, +/- SMA CD99, FLI1, S-100, synaptophysin S-100 (cartilage); NSE, CD99, Sox9 Vimentin; +/- focal, weak S-100 Osteocalcin Desmin, MSA

SMA, MSA, CD68

Vimentin; maybe focal SMA, MSA Actin, +/- CD34 Factor XIIIa; +/- desmin, SMMS

Ankle Skin Dorsal wrist, fingers, foot, toes Posterior mediastinum, RP Head/neck, other Vagina, vulva, cervix, male tract Thigh, inguinal region, chest

CD34, nuclear B-catenin, +/- CD99 Desmin, MSA CD34 CD68, SMA, TRAP

Knee, ankle/foot, wrist, fingers Fingers, toes, ankle/foot, knee Gingiva Scalp, other Hand, forearm

CD68, HAM56; CD45 (giant cells)

GFAP

Finger, palm, wrist, forearm, organs

Actin, +/- desmin; type IV collagen Actin, type IV collagen

Dermis, subcitus, muscle, organs Gingiva Nerves Nasal cavity Thigh, pelvic fossa, RP, pleura Foot, ankle Face, lips, oral mucosa, tongue Thigh, shoulder, back, neck, chest Subcutis, dermis Extremities Distal extremities Retroperitoneum Fingers, toes Head/neck, shoulder, upper arm Foot, ankle, hand, wrist Oral cavity, subcutis Lung, mesentery, omentum Mostly GU organs Pelvis, mesentery Muscles of lower extremity (thigh) Thigh, shoulder, upper arm Thigh, shoulder, buttocks, upper arm Groin, submandibular Uterus, can reach heart Shoulder, chest Head/neck, parotid Head/neck, fingers, trunk Head/neck, trunk Knee, shoulder, elbow, hip, ankle Extremities (legs, arms), organs

AFB PAS (granules), S-100, NSE, CD68 negative for S-100 SMA, MSA; +/- desmin, CD34 CD34, CD99; +/- bcl2, EMA, actin

S-100, Oil red O Fite-Faraco CD31, VEGFR3, D2-40 CD34, CD31, vWF, VEGFR3 Actin; trichrome for inclusion bodies +/- SMA, MSA SMA, desmin; - myoglobin SMA, MSA; +/- desmin, ALK SMA, MSA, desmin, CK, +/- ALK B-catenin

Vimentin; Alcian blue (background) Actin, vimentin Focal actin, CD68 VEGF, CD31, vWF, SMA, GLUT1 Hyaline material: PAS, Alcian blue CD68, CD31, factor XIIIa, A1AT CD31, LANA1 (HHV8), VEGFR3

Lines of cleavage, mucosa, organs Superficial and deep soft tissue Face, shoulders Knuckles Extremities; retroperitoneum Peritoneum Retroperitoneum, abdomen Lower extremities Extremities (extensor surfaces) IVC, pulmonary artery, other Extremities, head/neck, trunk Upper back, neck, extremities Knee, shoulder, hip, elbow Wrist, hand, ankle, foot

CD31, CD34, FLI1, D2-40 Vimentin

ER, PR (gynecologic type) SMA, MSA, +/- desmin, caldesmon

Medial extremities Legs/thigh, chest wall Legs/thigh Lumbosacral Head, neck, axilla, pectoral, other

Focal SMA, MSA; +/- desmin, CK Rounded cells: S-100, NSE VEGFR3, D2-40 +/- Factor VIII-related antigen CD31 PAS-D Vimentin, EMA, CK, INI1 loss +/- focal keratin, desmin, NF

Multiple GU organs, retroperitoneum Paraspinal region, neck, others Legs, thigh, arms, retroperitoneum

Retroperitoneum Sciatic nerve, brachial plexus Breast, other Jaw, others Midline/autonomic nerves Metatarsals (3rd-4th, 2nd-3rd) Lips, mouth, eyelid, intestines Uterus, cul-de-sac, bladder surface Quadriceps Lymph nodes, other Adrenal, rarely other Head/neck, trunk Head/neck Retroperitoneum, abdomen Lower extremities Limbs, head, neck Digits Extremities Extremities, thigh, popliteal area Nasopharynx External popliteal nerve Hand (left > right), wrist, forearm Sympathetic ganglia, incl. adrenal No site predilection Head/neck

+/- CD68 +/- S-100 (focal), nestin, Leu-7, p53 Desmin, actin, CD34 CK, HMB-45; NSE, synaptophysin S-100, HMB-45

CK, EMA, calretinin, CK 5/6 AFB, CD68, S-100; +/- desmin Actin SMA, calponin, +/- desmin, MSA SMA, desmin, trichrome SMA, h-caldesmon; +/- desmin Vimentin, actin +/- SMA, MSA

CD31, CD34, SMA, AR, B-catenin

NSE, NF, S-100, synapto, chromo S-100 (focal)

Melanin markers (pigmented cells) Brachial and sciatic nerve trunks Head, neck, shoulder Mid-forehead, eyelid, nape of neck Pelvic girdle (in multifocal cases) Arm, trunk Scalp/skull S-100, PGP9.5 negative for S-100

SMA, MSA

Arm, head/neck Nuchal area Tissue around maxilla or mandible Sinonasal (nasal vault) Extremities, trunk, head/neck Digits Face Palms Head, neck, fingers, trunk Thigh, calf, upper arm, forearm Carotid artery bifurcation Temporal bone/middle ear Head/neck (around vagus nerve) Pulmonary artery, aortic arch Retroperitoneum Perirectal, perivesical Penis Upper extremity Trunk, extremities, deep tissue Hand Uterus, soft tissue, viscera, bone Kidney, soft tissue Lung, mediastinum, retroperitoneum EMA EMA, claudin-1, GLUT1 EMA, GLUT1; +/- SMA, MSA CD34, nuclear B-catenin, +/- CD99 CK19 NSE, CD56, synapto/chromo Vimentin, S-1000; +/- Leu-7, NSE

Focal B-catenin; +/- SMA, MSA CK8/18, EMA, S-100 NSE, NF, synapto/chromo; S-100

HMB-45, Melan-A, SMA, +/- desmin Actin, desmin, HMB-45, Melan A HMB-45 FGF23 Plantar aponeurosis SMA Extremities, trunk MSA, +/- CD34 and CD99 Ankle/foot, lower leg, thigh, perineum Vimentin, CD34, factor XIIIa Retoperotineum, extremities +/- keratin, actin, desmin, S-100 Arms, legs CD68, SMA Liver, spleen, lymph nodes Arm, trunk Trunk, shoulder Varies Gingiva, fingers, lips, face, tongue Mesentery Anywhere Face/neck (chin) Head/neck, GU tract, RP Head/neck (orbit, parameninges) Paratesticular, head/neck Vagina, bladder, nasopharynx Extremities, head/neck Extremities (thigh), RP, chest Congo red, mucicarmine, iron SMA, MSA

Actin, desmin, CD117 CD68, SMA; +/- A1AT, lysozyme CD68, A1At, lysozyme, PAS-D MSA, desmin, myogenin, myoD1 MSA, desmin, titin, troponin D Myogenin MSA, desmin, myoglobin, myoD1 MyoD1; focal myogenin, desmin S-100; +/- CD1a

Head, neck, flexor surfaces Legs, limb girdle, trunk Inguinal region, abdominal wall Distal extremities (hand) Posterior neck, shoulder, back

S-100, Leu-7, GFAP EMA; rarely S-100, NSE PAS-D CD34, Bcl-2

Neck, cheeks, breast, arm, axilla Joints (knee, hip, elbow, shoulder) Para-articular regions of extremities Near joints: hip, shoulder, elbow Lymph nodes (axilla) Extremities, retroperitoneum Groin, retroperitoneum Retroperitoneum Omentum, mesentery, pelvis Depends on type MDM2, CDK4 CK7, CK19, EMA, TLE1, CD99, bcl2

Molecular Inheritance linked to EDR, ENG, FLT4?

12q13-15 (HMGA2) mutation t(X;17) TFE3-ASPL

t(12;16) ATF1-FUS or t(12;22) ATF1-EWSR1

Possible link to CMC1 on 5q

t(11;16) t(12;16) EWS-ATF1 t(12;16) EWS-ATF1 Germline 1q43 mutation (link to HLRCC) PRKAR1A mutation (Carney complex patients) MDM2, CDK4 t(17;22) COL1A1-PDGFB

t(11;22) EWS-WT1

Rearrangements of 22q11 (INI1), 8q, 18q11 Aberration of 22q11 (INI1)

KIT, PDGFRA t(11;22) EWS-FLI1; t(21;22) EWS-ERG; others t(9;22) EWS-NOR1 or t(9;17) RBP56-NOR1

PTCH

Possible mutations at 4q27-31 or 17q21-22

t(17;22) COL1A1-PDGFB

t(1;2) COL6A3-CSF1 t(1;2) COL6A3-CSF1

Truncating glomulin mutation at 1p21-22

HHT1 on 9q, HHT2 on 12q 11q13-21 (GARP?) rearrangement

t(12;15); + 8, 11, 17, 20

+/- ALK +/- ALK

GNAS1 mutations

Nonrandom X-inactivation patterns

8q11-13 (PLAG1) rearrangement 12q13-15 (HMGIC) aberrations, others

t(7;16) FUS-CREB3L2 t(7;16) FUS-CREB3L2

Aberration of 22q11 (INI1) various gains, losses

NF1, other gains/losses

t(12;16) FUS-CHOP; rarely t(12;22); p53 B-catenin

del(1p); MYCN amplification in some

NF1

CMC1 on 5q in some lesions 11 deletion (in Michelin tire baby syndrome)

Germline mutation in SDH

Can have TSC1 and TSC2 deletions

PTEN in some patients

LOH at 11p15.5; trisomy 8

t(2;13) PAX3-FKHR; t(1;13) PAX7-FKHR

Mutated gene on chromosome 22 +/- FUS

loss of 16q, 13q

t(X;18) SYT-SSX1, SYT-SSX2, or SYT-SSX4 GALNT3 or FGF23 mutation (familial cases) VMCM1 mutation on chromosome 9 Giant and ring chromosomes (12q13-15)

Behavior / Notes Benign; linked to pregnancy, FAP, or trauma; typically 3-10 cm; can recur locally Benign; may be same lesion as kaposiform hemangioendothelioma Intermediate; has a predilection to recur; metastases rare Benign; usually < 2 cm; usually solitary Benign; can be multifocal; does not regress; can recur Benign but locally aggressive; can exceed 20 cm; recurs often Malignant; grows slowly; poor prognosis; metastasizes early; age and tumor size prognostic Benign; can be associated with hematopoietic neoplasms, other conditions Benign; subcutaneous; painful to palpation; usually multiple; rarely > 2 cm

Intermediate; anemia, pyrexia, weight loss; rarely recurs or metastasizes Benign; causes pain and swelling; almost always recurs Benign; overlaps with other benign genital stromal tumors; can rarely be malignant Benign; usually < 2 cm; half of cases cause pain; recurrence very rare Malignant; behavior varies based on site and etiology; linked to many possible factors Malignant; most common angiosarcoma subtype; metastasizes often; size is prognostic Malignant; usually in post-mastectomy patients; metastasizes often Malignant; rapidly growing; often metastatic at time of presentation; grade is prognostic Malignant; often syndrome-associated; can be large; often recurs or metastasizes Malignant; develop 3-5 years after radiation; often recurs or metastasizes Benign; acquired in altered physiologic states Benign; more a clinical than a pathologic diagnosis Intermediate; < 2 cm; low rates of recurrence, metastasis Benign/intermediate; solitary; < 2 cm; secondary to radiation; recurrence rare Benign; < 1 cm; usually develop within 3 years of radiation Benign; caused by Bartonella infection in immunocompromised patients Benign; slow-growing, < 3 cm, gritty; high recurrence rate Benign; 3-5 cm; gritty; can recur Benign; often multiple; can cause cardiac symptoms; regress; linked to tuberous sclerosis Benign; large, can be deep; do not regress; linked to Kasabach-Merritt, other syndromes Benign; solitary, well-demarcated Benign; overlaps with angiomyofibroblastoma-like tumor of male genital tract Benign; few millimeters in size; may be linked to infection or chemical exposure Benign; slow-growing; 1-11 cm Malignant; 2-6 cm; can be grossly pigmented; size prognostic; often recur or metastasize Malignant; often metastasize Benign; linked to monoclonal immunoglobulin production Benign; pilar type 1-2 cm, painful, can be multifocal; genital type solitary and rarely painful Benign; linked to Carney's complex; usually 1-5 cm; often recur Malignant; often recurs or metastasizes; site is most important prognostic factor Intermediate; slow, persistent growth; high rate of recurrence; metastases uncommon Benign; slow-growing, < 4 cm Malignant; nodal spread rare; often recurs; may have better prognosis than typical melanoma Malignant; poor prognosis; often metastasizes widely Benign; linked to osseous hypertrophy, tuberous sclerosis; tends to recur Malignant; symptoms depend on location; linked to asbestos, SV40; dismal prognosis Benign; often history of manual labor; often bilateral (subclinically?) 1 reported case Benign(?); seen in immunocompromised patients; half of patients have multiple lesions

Benign; may be variant of epithelioid hemangioma Intermediate; can arise in vessels; rarely multifocal; low rate of recurrence or metastasis Benign; reactive?; patients can have peripheral eosinophilia; can recur; rarely regress Malignant; typically 3-6 cm; possible trauma link; often recurs multiple times or metastasizes Malignant; possibly linked to malignant extrarenal rhabdoid tumor Intermediate; can recur or metastasize Benign; 5% multicentric; usually 5-10 cm Benign; two types depending on origin and site Benign or malignant (criteria: cellularity, mitoses, necrosis); linked to Carney triad, NF1 Benign; slow-growing; painless; solitary; < 3 cm; can recur Malignant; typically in Caucasians; usually 5-10 cm; often metastasizes; prognosis improving Malignant; grows rapidly; metastasizes often Malignant; slow-growing; late recurrence and metastasis common Malignant; 5-10 cm; related to radiation, potentially trauma; recurs and metastasizes often Intermediate; link to spina bifida and similar abnormalities; can metastasize Benign; associated with nevoid basal cell carcinoma syndrome; does not regress

Benign; grows slowly over several years, < 2 cm, can recur Benign but progressive,debilitating, and typically fatal within 10-15 years; can be familial Benign; causes torticollis; 1-3 cm; grows rapidly; may spontaneously regress; does not recur Malignant; slow-growing, painless, 3-8 cm; recurs, metastasizes; possibly injury-related Benign; solitary; grows rapidly (3-5 cm); does not regress; may recur Benign, possibly reactive; 1/3 multiple; can recur; metastases extremely rare Benign; can evolve rapidly; higher risk of local recurrence Benign; higher risk of local recurrence Benign; larger than normal fibrous histiocytoma Benign; secondary to intussusception and prolapse Benign; incidental finding Benign; half of cases linked to trauma; typically 1.5-2.5 cm; recurrence rare Benign; ganglioneuromatous polyposis can occur in NF1 and MEN Iib Benign; linked to Gardner syndrome; may recur; see nuchal-type fibroma Benign; usually < 3 cm; does not regress Intermediate; painless nodule; 1-8 cm; can recur; not known to metastasize; link to DFSP Intermediate; can recur; not known to metastasize Benign; cause pain, tenderness, joint symptoms; unencapsulated; often recurs Benign; slow-growing; circumscribed; may be reactive or neoplastic; can recur Malignant; can recur or metastasize Benign; many forms, some linked to syndromes; tends to recur; can be familial Benign Benign; malformation; not painful Benign; deep, extensive, painful lesions Benign Benign; seen in POEMS syndrome and multicentric Castleman's disease Benign; usually solitary; usually < 1 cm; causes sudden, radiating pain; infrequently recur Malignant; can metastasize Indeterminate; follow-up lacking on known examples Benign

Benign; linked to surgical trauma Benign; typically < 3 cm; poorly circumscribed; can be multifocal; very rarely malignant Benign; typically 1-2 cm; often regress Benign; often painful Benign; can cause nasal obstruction or epistaxis; can be locally aggressive Intermediate; can cause hypoglycemia; malignant examples can recur, metastasize Benign; can recur; possible link to pleomorphic hyalinizing angiectatic tumor of soft parts Benign; lesions frequently hemorrhage Benign; slow-growing; 5-15 cm; has prominent vascularity; does not recur Benign; linked to sulfone-treated lepromatous leprosy; expansive subcutaneous nodule Intermediate; can recur; lymph node metastases uncommon Benign; obstructs ureters or aorta; sometimes due to drugs or malignancy Benign; < 2 cm; many recur; regresses; X-linked dominant inheritance? Benign; usually asymptomatic; can become large; may recur; possible trauma link Malignant, can recur/metastasize; good prognosis; 1/3 present at birth Malignant, can metastasize; very few reported cases Benign; rarely multiple; may regress; can recur or rarely metastasize Usually benign; 5-10 cm; can be multiple; can cause anemia, elevated ESR Benign; often history of trauma; relationship to IMT? Benign; often > 10 cm; some mesenteric cases linked to Gardner's syndrome Benign; often painful; can impair local function; can recur Benign; can be greater than 20 cm Benign; painless, fluctuant; linked to Mazabraud syndrome; typically 5-10 cm Benign Benign; associated with recent pregnancy, enlarged uterus, pelvic pain; can recur Benign; mass overlying bone in debilitated patients (< 6 months) Benign; type of capillary hemangioma; one-fifth of cases multiple; enlarge, then regress Benign; multiple; can be up to 10 cm; do not regress Benign; often multiple; usually regress spontaneously; can occur in adulthood Benign; usually 2-6 cm; recurrence not uncommon Malignant; caused by HHV8; can be aggressive; prognosis depends on numerous factors Malignant; prevalent in Poland, Russia, Italy, parts of Africa; linked to immunocompromise Malignant; heterogeneous disease; seen in children with bulky lymphadenopathy Malignant; typically develops several months after a renal transplant Malignant Intermediate; associated with Kasabach-Merritt phenomenon; rarely metastasizes Benign; induced by injury, trauma, or infection in dark-skinned patients Benign; often asymptomatic; linked to palmar and plantar fibromatosis Benign; often calcified; can be > 10 cm; must be distinguished from leiomyosarcoma Benign; linked to pregnancy; nodules can be several cm; can regress or recur Malignant; prognosis varies by site Malignant; usually > 5 cm; aggressive local extension and metastases Malignant; often vessel-associated; can recur and metastasize Malignant; usually < 2 cm; excellent prognosis; can recur but infrequently metastasize Malignant; causes site-based symptoms; worse prognosis in vena cava lesions Benign; may grow slowly or quickly; usually 3-5 cm; can recur in diffuse disease Benign; slow-growing, soft mass; rarely > 10 cm; can be multiple or familial; may recur Benign; causes effusions, joint swelling; possibly a reactive process Benign; often bilateral; can cause local symptoms

Benign; patients morbidly obese; overlying skin thickened, hyperkeratotic; can recur Malignant; slow-growing, painless, 1-18 cm; recurs often; can metastasize after decades Benign; causes myelopathy or radiculopathy in 2/3 of cases; imaging is essential Benign; can wax and wane; in utero cases linked to Turner, other syndromes Benign; spontaneous in children, follows injury/irradiation in adults; may recur Benign; patients can have multiple bone lesions; prognosis depends on disease extent Malignant; typically < 5 cm; poor prognosis; often metastasizes widely Malignant; can grow slowly or quickly; 5-10 cm; recurs and metastasizes often Most common subtype Better prognosis than storiform-pleomorphic type; recurs more than metastasizes Fever, leukocytosis; grossly yellow; may be dedifferentiated liposarcoma Malignant; term is variably applied and does not refer to a lone entity; not a WHO diagnosis Malignant; roughly half of cases associated with NF1; large; often recurs, metastasizes Benign; can be bilateral Intermediate; locally destructive; can increase VMA; often recurs; can metastasize Intermediate; link to Carney syndrome; heavily pigmented; can metastasize Benign; non-tumorous fibrosing process secondary to wearing high heels Benign; link to MEN Iib; usually multiple Benign; causes nonspecific symptoms; can recur; can uncommonly lead to patient death Benign; congenital or acquired (injection-related); severely affects movement Benign; immunocompromised patients Benign; usually 3-7 cm, but can be giant Benign but may cause organ failure; multicentricity more common; regress Malignant; slow-growing, painless, 1-12 cm; recurs, rarely metastasizes Benign; can be up to 15 cm if deep Benign; solitary; painless; can be intravascular; very rarely recur or metastasize Benign; self-limiting; may regress; usually related to trauma Benign; painful, localized; often related to trauma Malignant; often subcutaneous; grade influences behavior; recurs more than metastasizes Malignant; often metastasizes; age, round cell areas, and necrosis worsen prognosis Malignant; significant round cell areas imparts worse prognosis in myxoid liposarcomas Benign; facial deformity, epistaxis; may recur destructively; linked to FAP? Benign; degenerative process Benign; slow-growing; causes compression neuropathy; can be seen with macrodactyly Malignant; symptoms vary; urine catecholamines increase; detailed classification systems Benign; not associated with neurofibromatosis 1; slow-growing, painless Benign but can have malignant transformation; pathognomonic of neurofibromatosis 1

Benign; causes neurologic symptoms Benign Entity contested Benign; very common; typically regress; can be indicative of many syndromes Benign; can be multiple or solitary; typically does not recur Benign; reactive; rapid growth (1-2 weeks), slight pain, solitary, < 2 cm Related to birth trauma?

Benign; linked to diabetes; may recur; see Gardner fibroma Benign but can be locally destructive; recurrence common Malignant; causes local symptoms; late recurrence and metastasis common Intermediate; typically 3-5 cm; usually benign, but can recur or metastasize Benign; linked to trauma; typically painful; Pacinian structures are typically > 1.5 mm Benign; not linked to syndromes Benign; 50% bilateral, can impair use of hand; linked to diabetes, alcohol Benign; small (average 2 cm); exuberant form of organizing thrombus; sometimes recurs Intermediate; can be histologically malignant; can recur, sometimes late; metastases rare Usually benign; cause hypertension if functional; can be familial; uncommonly metastasizes

Occasionally multifocal or metastatic Can occur in patients with Carney's triad; higher rate of recurrence, metastasis, and death Can be multiple and/or occur in patients with Carney's triad Benign Benign; causes local genitourinary symptoms; can lead to recurrent DVT Benign; causes penile curvature; linked to palmar and plantar fibromatosis Benign Benign; causes muscle weakness Benign; circumscribed; can reach 20 cm; rarely recurs Benign Benign Intermediate; rarely linked to tuberous sclerosis complex; can recur or metastasize Benign; often associated with tuberous sclerosis complex; can involve lymph nodes benignly Benign; associated with tuberous sclerosis complex; can cause severe pulmonary symptoms Intermediate; causes osteomalacia, phosphaturia, hyperphosphatemia; can metastasize Benign; 33% bilateral; linked to palmar fibromatosis, diabetes, alcohol Benign; 0.5-2 cm Intermediate; grows slowly; recurrences common; does not metastasize Malignant; high recurrence and metastasis rate; age, size, and location affect outcome Intermediate; 1-3 cm, ill-defined; recurrences frequent; metastases rare No longer a distinct entity per the WHO Benign Benign; rapid growth (3 weeks), usually < 3 cm Benign; sporadic; wide range of manifestations Benign; type of capillary hemangioma; reactive?; one-third occur after trauma; can recur Benign; rarely multiple; recurrence uncommon Benign; waxes and wanes; can be paraneoplastic; weight loss, crippling arthritis Benign; usually < 2 cm; does not regress; linked to congenital anomalies Malignant; intermediate prognosis among rhabdomyosarcoma Malignant; superior prognosis among rhabdomyosarcomas Malignant; superior prognosis among rhabdomyosarcomas Malignant; poor prognosis among rhabdomyosarcomas Malignant; rapidly growing, large (> 10 cm), painless; metastasizes early; poor prognosis Benign; may be associated with lymphadenopathy; can resolve spontaneously

Benign; typically sporadic, but linked to NF2; rarely undergo malignant transformation Benign; patients have multiple painful schwannomas Malignant; 5-10 cm; may recur or metastasize; link to LGFMS? Benign; exuberant reaction to large amount of injected silica (polarizable) Benign; may be multifocal; usually asymptomatic; often recur; linked to Mafucci syndrome Benign; slow-growing; rarely multiple or familial; can reach 14 cm Benign; may be due to endogenous or exogenous steroids Benign; linked to alcoholism and liver disease; causes neuropathy; can be familial Benign Benign; may be diffuse; may be trauma-related Malignant; often recurs or metastasizes, though rates lowering due to better treatment Benign; non-neoplastic response to injury; typically < 5 cm; can be painful Benign; often multifocal; can be familial; slow-growing; 5-15 cm; calclium level normal Benign Benign; malformation; can be superficial or deep; may be linked to cavernous hemangioma Malignant; slow-growing, often large; recur but do not metastasize; can dedifferentiate

Benign if localized; aggressive if widespread (can metastasize); possible link to asbestos Benign; reactive, seen in hyperlipidemic patients; asymptomatic in and of themselves

Subtypes

verrucous hemangioma

Pilar, genital

Epithelial, sarcomatoid, mixed

Usual type, fibroma-like

Fibrochondroma, osteochondroma, myxochondroma, chondroblastoma-like

Oncocytic

Lipomatous, meningeal, with giant cells

Typical; myxoid; lipoma-like; spindle cell

Retiform, Dabska-type

Pelvic, mesenteric Capillary type, cavernous type

Somatic, gynecologic

Usual, myxoid, inflammatory, granular cell

Subcutaneous, deep; sometimes termed based on site

Head/neck type, intra-abdominal type, cutaneous type

Malignant Triton tumor, glandular, epithelioid, superficial epithelioid

Epithelioid neurofibroma

Port-wine stain Subcutaneous, intramuscular, fascial types

Nasopharyngeal, laryngeal, orbital, gangliocytic, of cauda equina, cardiac

Epithelioid

Traditional, small-cell/epithelioid (not official terms)

Pregnancy-related (granuloma gravidarum) ; intravenous

Embryonal rhabdomyosarcoma with anaplasia

Clear cell rhabdomyosarcoma

Ancient, cellular, plexiform, epithelioid

Biphasic, monophasic fibrous, monophasic epithelial

Eruptive, tuberous, tendinous, xanthelasma, plane