Soft Tissue Pathology The Sort of Thing You Get in Exams! Dr. Petra Dildey Royal Victoria Infirmary Newcastle upon Tyne

50y old male patient, soft tissue mass left popliteal fossa. Case 38551/03: 50y old male patient, soft tissue mass left popliteal fossa.

Case 38551/03

Case 38551/03

Case 38551/03

Myxoid Liposarcoma Myxoid and round cell same category Adults; deep-seated in extremities (thigh) Histology: multinodular with increased cellularity at periphery of nodules myxoid matrix, occ. with mucin pools typical delicate branching vessels bland round to oval mesenchymal cells and univacuolated lipoblasts progression to round cell LPS histological continuum Genetics: t(12;16)(q13;p11), t(12;22)(q13;q12)

33y old male patient, 4cm deep soft tissue tumour right forearm. Case 18319/05: 33y old male patient, 4cm deep soft tissue tumour right forearm.

Case 18319/05

Case 18319/05

Case 18319/05

Case 18319/05

Low Grade Fibromyxoid Sarcoma Rare soft tissue sarcoma Young to middle-aged adults; extremities and trunk; deep Histology: circumscribed, low to moderate cellularity alternating fibrous and myxoid stroma bland spindle cells, whorled pattern arcades of blood vessels occ. giant collagen rosettes Genetics: t(7;16)(q33;p11)

48y old female patient, 6.5cm intramuscular tumour left buttock. Case 35841/03: 48y old female patient, 6.5cm intramuscular tumour left buttock.

Case 35841/03

Case 35841/03

Intramuscular Myxoma Important DD for myxoid soft tissue tumours Middle-aged to older adults; large muscles of limb girdles Histology: macro circumscribed, but micro infiltrative extensive myxoid matrix, hypocellular bland stellate- and spindle-shaped cells NO mitoses, pleomorphism, necrosis

77y old male patient, 4cm superficial mass right upper arm. Case 34761/09: 77y old male patient, 4cm superficial mass right upper arm.

Case 34761/09

Case 34761/09

Case 34761/09

Myxofibrosarcoma Rel. common fibroblastic sarcoma; myxoid MFH Elderly patients; limbs and limb girdles; subcutaneous and deep Histology: multinodular with fibrous septa myxoid stroma atypical spindle-/stellate-shaped cells, occ. pseudolipoblasts curvilinear vessels

66y old male patient, haemorrhagic soft tissue tumour right calf. Case 19222/04: 66y old male patient, haemorrhagic soft tissue tumour right calf.

Case 19222/04

Case 19222/04

Case 19222/04

Extraskeletal Myxoid Chondrosarcoma Rare soft tissue sarcoma Middle-aged to older adults; extremities, limb girdles and other sites; often haemorrhagic Histology: multinodular chondromyxoid matrix cords and networks of cells eosinophilic cytoplasm, uniform nuclei, few mitoses focal S100, occ. cytokeratin and EMA Genetics: t(9;22(q22;12), t(9;17)(q22;q11), t(9;15)(q22;q21)

Case 30750/03: 15y old male patient, large pelvic mass and lymphadenopathy as well as mediastinal and lung lesions on CT. Groin node biopsied.

Case 30750/03

Case 30750/03

Case 30750/03 MyoD1

Alveolar Rhabdomyosarcoma Small round blue cell tumour 10-25 years; often extremities, all other sites possible Histology: 3 subtypes: typical, solid, mixed nests separated by fibrovascular septa small round nuclei, scant cytoplasm horse-shoe giant cells common Myogenin, MyoD1, desmin positive Genetics: t(1;13)(p36;q14), t(2;13)(q35;q14)

Case 7739/06: 36y old female patient, large tumour tail of pancreas with liver metastases.

Case 7739/06

Case 7739/06

Case 7739/06

Case 7739/06

Case 7739/06 CK

Case 7739/06 Desmin

Desmoplastic Small Round Cell Tumour Small round blue cell tumour showing divergent differentiation Children and adolescents, esp. male; abdominal cavity, retroperitoneum, pelvis Histology: nests of variable size surrounded by desmoplastic stroma small uniform cells with round nuclei, occ. rhabdoid inclusions epithelial, smooth muscle and neural markers positive, esp. CK, EMA and desmin (dot-like), WT1 Genetics: t(11;22)(p13;q12)

Case 24640/04: 42y old male patient, small nodule in the subcutis of the right buttock.

Case 24640/04

Case 24640/04

Case 24640/04

Nodular Fasciitis Small fibroblastic proliferation All age groups, mostly young adults; subcutis!, anywhere in body; rapid growth Histology: partly loose/feathery, partly cellular tissue-culture fibroblasts mitotically active collagen bundles, hyalinisation, giant cells SMA positive, desmin negative

50y old female patient, small subcutaneous tumour forearm. NEQAS Case 261: 50y old female patient, small subcutaneous tumour forearm.

NEQAS Case 261

NEQAS Case 261

NEQAS Case 261

Proliferative Fasciitis A small fibroblastic proliferation similar to nodular fasciitis, but with large ganglion-like cells Middle-aged and older adults; subcutis, esp. extremities; rapid growth Histology: ill-defined tissue-culture fibroblasts myxoid/collagenous stroma large, ganglion-like cells with prominent nucleoli

Case 3821/03: 18y old female patient, calcified soft tissue mass right thigh, recent increase in size, vague history of trauma.

Case 3821/03

Case 3821/03

Case 3821/03

Myositis Ossificans Localized, reparative lesion Any age, mostly young adults; anywhere; history of trauma; rapid growth Histology: zonation! centre resembling nodular fasciitis then immature unmineralized bone periphery mature bone

61y old female patient, 4cm tumour in gastric fundus. Case 17062/04: 61y old female patient, 4cm tumour in gastric fundus.

Case 17062/04

Case 17062/04

Case 17062/04 CD117 (c-kit)

GIST KIT-positive mesenchymal tumours primarily of the GI-tract Middle-aged and older adults; stomach, small bowel, rectum & colon in that order (rare oesophagus and elsewhere) Histology: fascicular architecture spindle cells or epithelioid cells, rarely pleomorphic CD117 (c-kit), DOG1, CD34, occ. SMA, desmin, S100 behaviour depending on site, max. diameter, mitoses

60y old male patient, 10cm tumour around left common iliac vessels. Case 5365/04: 60y old male patient, 10cm tumour around left common iliac vessels.

Case 5365/04

Case 5365/04

Case 5365/04 SMA Desmin

Leiomyosarcoma Soft tissue type Middle-aged and older adults; retroperitoneum, large vessels and other soft tissue sites Histology: typical fascicular pattern eosinophilic cytoplasm and blunt-ended nuclei hyalinization, myxoid change SMA, desmin and caldesmon occ. poorly differentiated, pleomorphic areas (“dedifferentiated”)

33y old female patient, soft tissue tumour abdominal wall. Case 14986/04: 33y old female patient, soft tissue tumour abdominal wall.

Case 14986/04

Case 14986/04

Case 14986/04

Fibromatosis Superficial and deep fibroblastic proliferations Age depending on type; superficial: palmar, plantar etc., deep: extra-/intraabdominal Histology: think of it! infiltrative margin cellularity variable, fascicular architecture bland spindle cells collagen occ. hyalinized, prominent small arteries SMA positive, desmin negative, beta-catenin

9y old female patient, 13 cm tumour caecum. Case 28715/05: 9y old female patient, 13 cm tumour caecum.

Case 28715/05

Case 28715/05

Case 28715/05

Case 28715/05 ALK

Inflammatory Myofibroblastic Tumour Heterogenous group of tumours; primarily, a visceral and soft tissue tumour in children and adolescents often with ALK gene rearrangement Lung, abdomen, bladder most common sites Histology: myofibroblasts in fascicular or storiform pattern matrix myxoid to collagenized inflam. infiltrate of lymphocytes, plasma cells, eosinophils SMA, occ. desmin and CK, ALK in 50%

45y old female patient, 5cm soft tissue tumour left calf. Case 3356/04: 45y old female patient, 5cm soft tissue tumour left calf.

Case 3356/04

Case 3356/04

Case 3356/04

Schwannoma Benign nerve sheath tumour All ages; almost any nerve Histology: capsule! thick-walled, hyalinized vessels! Antoni A and B areas, Verocay bodies cystic degeneration, hyalinization, nuclear atypia, calcification, foam cells, haemorrhage cellular, ancient and plexiform variants

63y old female patient, 17.5cm mass left upper quadrant of abdomen. Case 7859/04: 63y old female patient, 17.5cm mass left upper quadrant of abdomen.

Case 7859/04

Case 7859/04

Case 7859/04

Case 7859/04 CD34

Solitary Fibrous Tumour Cellular SFT syn. to haemangiopericytoma Middle-aged adults; extrapleural variant at any site Histology: circumscribed, patternless alternating hypo- and hypercellular areas hyalinized collagen haemangiopericytomatous vascular pattern small bland cells, few mitoses CD34 90%, CD99 70%, BCL2 30%, occ. EMA & SMA

69y old male patient, deep soft tissue mass left thigh. Case 14005/03: 69y old male patient, deep soft tissue mass left thigh.

Case 14005/03

Case 14005/03

Case 14005/03

Case 14005/03

Dedifferentiated Liposarcoma In up to 10% of well-diff. liposarcomas Adults; retroperitoneum, spermatic cord and other sites Histology: often abrupt transition well-differentiated component dedifferentiated component, low or high grade mostly “MFH”-type, but also heterologous differentiation IHC: CDK4, MDM2

59y old female patient, 3.3kg / 26cm tumour retroperitoneum. Case 21561/07: 59y old female patient, 3.3kg / 26cm tumour retroperitoneum.

Case 21561/07

Case 21561/07

Case 21561/07

Case 21561/07

Case 21561/07 HMB45 SMA

Angiomyolipoma Part of PEComas, can be associated with tuberous sclerosis Adults, women>men; mostly kidneys Histology: mature fat / smooth muscle / thick-walled blood vessels smooth muscle often focally epithelioid IHC: HMB45, MelanA, SMA, occ. desmin monotypic epithelioid variant!

21y old female patient, 4cm mass in left tibialis anterior muscle. Case 28802/10: 21y old female patient, 4cm mass in left tibialis anterior muscle.

Case 28802/10

Case 28802/10

Case 28802/10

Case 28802/10

Chondroid Lipoma A unique benign fatty tumour Young adults, 80% women; prox. limbs & limb girdles; deep & subcutaneous Histology: lobulated, circumscribed, nests and cords of cells epithelioid multivacuolated cells, cells with eosinophilic granular cytoplasm, mature adipocytes myxoid and occ. hyaline matrix, vascular Genetics: t(11;16)(q13;p12-13)

14y old female patient, small soft tissue tumour left knee. Case 158/07: 14y old female patient, small soft tissue tumour left knee.

Case 158/07

Case 158/07

Case 158/07

Case 158/07 SMA

Myofibroma Solitary or multicentric (myofibromatosis) All ages, commonly in infants & children; solitary: skin, muscle, multiple: skin, viscera, muscle, bone Histology: apparently biphasic plump myofibroblasts in whorls/bundles primitive small round or short spindle cells haemangiopericytomatos vascular pattern hyalinization, calcification, necrosis, haemorrhage SMA positive, desmin negative

10y old boy, 2cm nodule right groin. Case 4899/08: 10y old boy, 2cm nodule right groin.

Case 4899/08

Case 4899/08

Case 4899/08

Case 4899/08

Case 4899/08 EMA Desmin

Angiomatoid Fibrous Histiocytoma Peculiar small tumour in skin or subcutis Children and young adults; extremities, trunk, head & neck, often at sites of normal LN Histology: 3 components capsule with lymphoplasmacytic infiltrate blood-filled cystic spaces proliferation of fibrohistiocytic or myofibroblastic cells desmin, EMA, CD68, CD99 in half of cases Genetics: t(12;22)(q13;q12), t(12;16)(q13;p11), t(1;22)(q33;q12)

65y old male patient, recurrent deep soft tissue tumour left thigh. Case 34141/04: 65y old male patient, recurrent deep soft tissue tumour left thigh.

Case 34141/04

Case 34141/04

Case 34141/04

Case 34141/04 Myogenin MyoD1 Desmin

Pleomorphic Rhabdomyosarcoma Rare RMS subtype in adults Adults >45years; deep-seated in extremities most common Histology: haphazardly arranged bizarre cells with severely pleomorphic nuclei and deeply eosinophilic cytoplasm tadpole and strap cells, occ. cross-striations desmin, MyoD1, Myogenin

Case 33584/03: 35y old male patient, 12cm tumour in right iliac fossa adjacent to right psoas muscle, kidney and adrenal gland.

Case 33584/03

Case 33584/03

Case 33584/03

Case 33584/03 DPAS

Alveolar Soft Part Sarcoma Rare soft tissue sarcoma Adolescents and young adults; extremities (adults) and head and neck (children); slow growth Histology: distinct nested pattern, central discohesion round uniform nuclei, granular cytoplasm vascular invasion! DPAS-positive crystals TFE3, occ. muscle markers Genetics: t(X;17)(p11;q25)

Cases 17157/02 & 37608/03: 17157/02: 61y old female patient, rapidly growing recurrent soft tissue tumour left foot. 37608/03: 32y old male patient, growing painful soft tissue mass right thigh.

Case 17157/02

Case 17157/02

Case 17157/02

Case 37608/03

Case 37608/03

Case 37608/03

Case 37608/03 EMA

Synovial Sarcoma Relatively frequent soft tissue sarcoma Young adults; deep-seated in extremities, but any site possible Histology: cellular! biphasic, monophasic epithelial element in solid nests, glands spindle cells in vague fascicles hyalinisation, calcification, ossification EMA, cytokeratin (7 & 19), BCL2, CD99, S100 Genetics: t(X;18)(p11;q11), t(X;20)(p11;q13)

68y old female patient, recurrent tumour scalp. Case 8960/04: 68y old female patient, recurrent tumour scalp.

Case 8960/04

Case 8960/04

Case 8960/04

Case 8960/04 CD31

Angiosarcoma Mostly cutaneous, rarely soft tissue Skin: lymphoedema, post-irradiation; adults; site dep. on aetiology Soft tissue: any age; any site; with syndromes Histology: multinodular, haemorrhagic, dissecting growth pattern anything from well-formed vessels to solid sheets often marked endothelial atypia and mitoses CD31, CD34, Fli-1, Factor 8 variably positive

18y old female patient, 5cm soft tissue tumour around the right ankle. Case 7503/01: 18y old female patient, 5cm soft tissue tumour around the right ankle.

Case 7503/01

Case 7503/01

Case 7503/01

Case 7503/01 S100

Clear Cell Sarcoma Soft tissue sarcoma with melanocytic differentiation Young adults; deep-seated in extremities; slow growth Histology: nested and fascicular architecture polygonal and spindle-shaped cells wreath-like giant cells low mitotic rate S100 and melanocytic markers positive Genetics: t(12;22)(q13;q12)

Case 24689/09: 64y old male patient, 2cm tumour medial aspect left wrist associated with tendon sheath.

Case 24689/09

Case 24689/09

Case 24689/09 CK EMA

Case 24689/09 CD34

Epithelioid Sarcoma Distinctive sarcoma with epithelioid morphology Classic type: 10-40 years; hands, forearms, lower legs, feet Proximal type: older age; pelvis, perineum, genital tract; aggressive Histology: multinodular, central necrosis large epithelioid cells with eosinophilic cytoplasm, vesicular nuclei, small nucleoli CK-profile (8,18,19), EMA, vimentin, CD34 DD: carcinoma, granuloma annulare, rheum. nodule

Minimum Dataset Soft Tissue Sarcomas Clinical: site, depth from surface Trimming: one block per 10mm tumour, max. 12 blocks sample margins <30mm (exceptions) sample fat in retroperitoneal/abdominal/scrotal sarcomas IHC: Ki67, myogenic differentiation Genetic data Report: type/subtype, grade (FNCLCC), margins, tissue planes involved, maximum size

Finally – the End!