SOFT TISSUE PATHOLOGY

FIBROBLASTIC LESIONS

NODULAR FASCIITIS (S153)

Clin:

• § -young, hx of recent trauma
• § -cheek, forearm, subcutaneous
• § -rapidly arising mass

Gross:

• § -poorly circumscribed or infiltrativeà WC rather…
• § -no capsule

Micro:

• § -WC but no capsule
• § -myxoid with fibroblasts
• § -zonation with cellular periphery
• § -keloidal collagen
• § -microcysts/macrocysts
• § -extravasation of RBCs, granulation-like tissue (bv at periphery)à no hemosiderin
• § -can be mitotically active up to 1/1
• § -never dark or pleomorphic, never involve skin except on face
• § -lymphocytes but no plasma cells or PMN

 

PROLIFERATIVE FASCIITIS/MYOSITIS (S154)

• § Micro: like nodular fasciitis but has ganglion-like cells

 

MYOSITIS OSSIFICANS (S159)

• § Clin: areas of rubbing (butt, elbows, shoulder), assoc/ trauma
• § Gross: tan mass with gritty periphery and soft glistening centre
• § Micro: (similar to what breast lesion, why?)
• § Zonation effect:
• § central zone w/ myxoid loose tissue & fibroblasts
• § woven bone with osteoblasts
• § lamellar bone
• § Ddx: parosteal osteosarcoma (has opposite direction of maturation and less orderly)

 

FIBROMATOSES (S163/WHO)

• § More in kids
• § Mature FB with uniform nuclei
• § No nucleoli
• § Rich collagenous matrix
• § No infiltration
• § No mets

Classification

Superficial

• § -plantar
• § -palmar
• § -Peyronie’s (penile)

Deep (desmoid tumours)

• § -abdominal
• § -intraabdominal wall
• § -extraadominal wall

Micro:

• § -bland fibroblast cells with variable amts of collagen
• § -FEW bv
• § -NO hemosiderin
• § ***need to sample desmoid tumours widely to rule out fibrosarcoma***
• § Clin: deep tissues of the extremities

DESMOID-TYPE FIBROMATOSIS

FIBROSARCOMA

Micro

• § Variable cellularity
• § Spindle cells with central dark needle-like nuclei
• § Variable mitoses
• § No ugly large pleomorphic cells
• § Unencapsulated
• § Short and compact fascicles
• § Herringbone (acute angle), chevron pattern
• § -overlapping nuclei, ↑ mitoses, nucleoli

 

SCLEROSING EPITHELOID FIBROSARCOMA

• § Clin: lower extremities
• § Micro: cords or nests of epithelioid cells + dense sclerotic stroma
• § -mitoses

 

SOLITARY FIBROUS TUMOUR (S163)

Micro:

• § -hypocellular and hypercellular spindle cells arranged in a “patternless pattern”
• § Plump FB
• § Mature collagenous stroma
• § HPC vasculature
• § -keloidal type collagen

IHC

• § Bcl-2+
• § CD34+

 

BENIGN FIBROHISTIOCYTOMA AND DFSP

DF	DFSP
§ Small § larger § mid-upper dermis § deep dermis to SQ(fat infilt.) § foamy mf, hemosiderin-laden hf, Touton GC § no
§ collagen trapping with dense collagen § no § prominent vascularity (eg.sclerosing hemangioma) § no § no § storiform and monomorphic § no § ↑ mitoses § FXIII+ / CD34- § FXIII- / CD34+ § Location: proximal extremities, retroperitoneum § Better prognosis: superficial, small, prominent chronic inflammatory infiltrate § Gross: may be large § Micro: § IHC: vimentin, CD68, Factor 13a § Ddx: AFX, DFSP § -assoc/ post-radiation sarcoma, scars or foreign bodies § -highly pleomorphic tumor cells, storiform pattern, § -chronic lymphoplasmacytic infiltrate, bone or cartilage § hemorrhagic cyst like spaces + ↑chr. infm § +++ nφ, pφ § -phagocytosed nφ in tumor cytoplasm § -curvilinear vessels with condensation of stroma around vessels § ->50% myxoid § Location: Intramuscular, cardiac, cutaneous § Micro:Bland, stellate spindle cells in myxoid matrix § Clin and genetics: Young adults, thigh § -t(12;16), TLS-CHOP gene rearrangement § Micro: hypocellular myxoid with spindle cells, lymphangioma-like fluid, chicken wire vascularity § -Poorly differentiated myxoid liposarcoma § Micro: lipoblasts fat cells + atypical cells with eosinophilic cytoplasm § -T(12;16), TLS-CHOP gene rearrangement § Clin: Extremities of old people § Micro: Pleomorphic atypical cells + curvilinear bv + >50% myxoid areas + mitoses

MALIGNANT FIBROUS HISTIOCYTOMA (MFH)

Pleomorphic-storiform MFH

Angiomatoid MFH

Inflammatory MFH

MYXOID MFH (MYXOFIBROSARCOMA)

MYXOID LESIONS

MYXOMA

MYXOID LIPOSARCOMA

ROUND CELL LIPOSARCOMA

MYXOID MFH (MYXOFIBROSARCOMA)

 

LIPOBLASTOMA/LIPOBLASTOMATOSIS

• § Clin: May be confused with myxoid liposarcoma
• § Age <5 yrs
• § Benign lipoblastoma: well circumscribed
• § Lipoblastomatosis: deep-seated and ill-defined
• § Gross: soft, lobulated
• § Micro: resembles fetal fat; has lipoblasts, distinct lobulation, plexiform vascular pattern and abundant myxoid stroma, but is NOT myxoid liposarcoma
• § Location: wrist, hand
• § Micro: pseudocyst surrounding myxoid matrix
• § Location: perineum, large bulbous mass
• § Micro: fibroblasts in myxoid matrix, thick bv
• § Ddx: FE polyp (not as deep, more bizzare atypia)

GANGLION

AGGRESSIVE ANGIOMYXOMA

CHORDOMA

Location:

-sacral, coccygeal

-sphenooccipital

-cervical (chondroid chordoma)

Gross: myxoid-blue and hemorrhagic

Micro: myxoid matrix with cords of small round cells with vacuolated cytoplasm, fibrous strands separating into tumour cells into lobules or cords

-physalipherous (bubbly) cells

Variants:

Chondroid chordoma→chondroid differentiation, better prognosis)

Dedifferentiated chordoma: differentiation into high grade spindle lesion

LIPOMATOUS-LIKE LESIONS

HIBERNOMA

• § Gross: Brown
• § Micro: large cells with central nucleus and many small vacuoles

 

LIPOMA

• § Micro: -mature adipose tissue, no atypia
• § Location: painful in young people with small SQ lesion on arm
• § Micro: blood vessels with fibrin thrombi + fat cells

ANGIOLIPOMA

 

MYELOLIPOMA

• § Location: adrenal gl.
• § Micro: mature adipose tissue +

 

HEMATOPOETIC TISSUE

ANGIOMYOLIPOMA (AML)

• § -often associated with tuberous sclerosis
• § most behave in a benign fashionà excision is curative
• § Gross:hemorragic, yellow (fat)à may look like RCC, XGP , malakoplakia
• § Micro:tortuous thickened blood vessels,
• § mature fat, smooth muscle cells which seem to eminate from bv
• § -epithelioid cells centred around the bv
• § if prominent may give rise to “epithelioid angiomyolipoma”
• § -HMB-45 +, MelanA + : esp. in the epithelioid cells

 

SPINDLE CELL LIPOMA

• § Clin: back and neck of old men
• § Micro: keloidal type collagen, uniform spindle cells set in a mucinous or myxoid background, fat cells
• § Micro: floret giant cells (hyperchromatic, multinucleated, wreath like nuclei)

PLEOMORPHIC LIPOMA

 

ATYPICAL LIPOMA/ WELL DIFF. LIPOSARCOMA

• § Location: periphery (AS) and retroperitoneum
• § (WDLS)
  Micro: spindle cells + lipoblasts
• § Clin: local recurrence

LIPOSARCOMA

• § Location: Lower extremities
• § Gross: large well circumscribed
• § Micro: Lipoblasts (signet ring like or central nuclear scalloped appearance)
• § Clin: Usually in recurrent or metastatic foci
• § Micro: high grade, resembles MFH; may have heterologous elements (bv, skeletal muscle)
• § Micro: spindle cells + large, pleomorphic lipoblasts with multiple bizarre nuclei
• § -mitoses
• § -see above

DEDIFFERENTIATED LIPOSARCOMA

PLEOMORPHIC LIPOSARCOMA

MYXOID LIPOSARCOMA

 

MUSCLE TUMOURS

SMOOTH MUSCLE ORIGIN

LEIOMYOMA

-uterus, subcutis

• § Micro: blunt ended, elongated nuclei, minimal atypia, few mitotic figures, no tumor necrosis
• § extremities
• § Gross: large, necrosis, hemorrhage, soft
• § Micro: mitoses, tumor cell necrosis or  10 cm
• § -blunt cigar shaped nuclei

LEIOMYOSARCOMAS

IHC: vimentin, desmin, SMA

SKELETAL MUSCLE ORIGIN:

RHABDOMYOSARCOMA

• § Clin: most common soft tissue sarcoma of childhood/adolescence

EM

• § Well-formed Z-bands
• § Thick and thin myofilaments
• § Incomplete sarcomere

Variants

• § Alveolar RMS
  • Ø Solid
  • Ø Anaplastic
• § Micro
  • Ø Fibrous septa separating loosely cohesive RMB into alveolar spaces
  • Ø +/-MGC
• § Embryonal RMS
  • Ø Botryoides sarcoma
  • Ø Spindle cell
  • Ø Anaplastic
• § Micro
  • Ø Myxoid stroma
  • Ø Round to spindle cells
  • Ø Hyperchromatic nuclei
  • Ø RMB with cross-striations
  • Ø Botryoid variant has cambium layer and primitive cells in deep stroma
• § Pleomorphic RMS

ALVEOLAR RHABDOMYOSARCOMA

-extremities/paraspinal

-teenagers

-N-myc amp in 50% → poor prog??? This is for neuroblastoma…

• § Micro: “alveoli”→ thin fibrous septae lined by small round blue cells
• § -deep eosinophilic cytoplasm + occ GCs are diagnostic features
• § Molecular:

t(2,13) [PAX3-FKHR]

• § t(1;13) [PAX7-FKHR]

Ddx: Merkel cell (negative for muscle markers), metastatic neuroendocrine carcinoma

EMBRYONAL RHABDOMYOSARCOMA

-H/N, paratesticular, extremities <10yrs.

-good prog. if localized

Gross: poorly circumscribed, white, soft, infiltrative

• § Micro: small, spindle shaped cells

cellular around blood vessels

IHC: occ c-kit & myogenin

Botyroides

Gross: submucosal mass in walls of hollow, mucosal lined structures (vagina, bladder, eyelid)

-grape-like mass

• § Micro:

cambium layer (dense zone of undifferentiated tumor cells immediately beneath epithelium) Spindle cell

Anaplastic

PLEOMORPHIC RHABDOMYOSARCOMA

-adults, abdo/retroperitoneum

-poor prognosis

Gross: can be large

Micro: multinucleated, bizarre cells, rhabdomyoblasts with cross-striations

General

• § IHC: muscle markers: myoglobin, MyoD1, desmin, myogenin, MSA, SMA

EM: rhabdomyoblasts contain sarcomeres (thick and thin filaments)

 

 

PERIPHERAL NERVE SHEATH TUMOURS

SCHWANNOMA

Location: periphery

Micro:

-thick capsule

alternating hypercellular (Antoni A) & hypocellular (Antoni B) regions

-verucay body pattern

• § IHC: S100

Ancient Schwannoma

• § -above features PLUS…
• § -cystic degeneration, fibrosis
• § -hemosiderin
• § -aypia

Cellular Schwannoma

• § -hypercellular → just Antoni A areas!

NEUROFIBROMA

Location: peripheral, within nerve

Micro: spindle cells, fascicular pattern, mast cells,

• § -no capsule, no verucay bodies
• § IHC: S100

Neurofibromatosis

Genetics:

• § NF1→ neurofibrillin, ch17
• § NF2→ merlin, ch22
• § gene NF1→ chromosome 17
• § neurofibromas throughout body plexiform or solitary
• § cafe au lait spots→ hyperpigmented spots (increased melanin in basal layer)
• § Lisch nodules→ pigmented nodules on the iris
• § pheochromocytoma

NF1

NF2

• § gene NF2→ chromosome 22q12

•               bilateral acoutic (actually vestibular)CNVIII schwannomas

•               multiple meningiomas

• § gliomas → usu. ependymomas

 

MALIGNANT PERIPHERAL NERVE SHEATH TUMOUR (MPNST)

Clin: often assoc/ NF1

Gross: large mass producing a fusiform enlargement of a major nerve (often sciatic)

Micro: monomorphic serpentine cells, frequent mitoses, atypia

-mitoses are an important indicator of malignancy

IHC: S100 IS SPORADIC!

GRANULAR CELL TUMOUR

-degenerative change that can occur in Schwann cells, smooth muscle cells or tumors

Location: anywhere “classic”=tongue,

Micro: oncocytic, granular PAS+ cytoplasm

• § IHC: S100

 

UNUSUAL TUMOURS

SYNOVIAL SARCOMA

Clin: deep seated mass in young adults (usu. not assoc/ joint)

Prog: 10 year survival 40%; recurs locally, 10% mets to lung and pleura, bone

-poor differentiation→poor outcome

Gross: well circumscribed, pink

• § Micro:

Biphasic variant:

• § Epithelial component: Glands. Cells have abundant pink cytoplasm w/ open vesicular nuclei
• § Stromal component: hypercellular with scant cytoplasm and overlapping (blastemal-like)

Monophasic variant:

• § Stromal component only. May be assoc/ ropy collagen, HPC pattern, calicifications

 

• § Genetics: t(X;18) SYT:SSX1 or 2
• § IHC: CD99, EMA, CK(epithelial), vimentin
• § SS: glds have mucicarmine and PAS + substance -reticulin highlights biphasic pattern
• § EM: thin spaces with microvilli

 

CLEAR CELL SARCOMA (OF TENDONS AND APONEUROSES)

(MELANOMA OF SOFT PARTS)

Clin: adolescents/young adults

-deep tumor, near tendon, fascia

Clinical course: frequent local recurrences; eventually nodal and distant metastases

Gross: well circumscribed, gray and gritty

• § Micro:
• § -unique pattern:
• § -nests & fasicles
• § -uniform nuclei with central nucleolus, cytoplasm is often clear but may be eosinophilic
• § -may have floret giant cells
• § -often have melanin
• § Genetics: t(11:22) ATF:EWS (not seen in melanoma)
• § IHC: S100, HMB45, occ MelanA
• § EM: melanosomes
• § DD: melanoma

 

ALVEOLAR SOFT PART SARCOMA

Clin: young adults

-mets up to 30yrs. later in lungs, veins

• § Micro:
• § -also unique pattern:
• § -nests of tumor cells surrounded by fibrous stroma may contain thin microvasculature (less than clear cell sarcoma)
• § -nests look alveolar if discohesive
• § -uniform nuclei with central nucleolus, cytoplasm eosinophilic with PAS+ granules
• § -often have melanin?
• § Genetics: X;17 ASPL:TFE3
• § IHC: desmin, MyoD1(cyto)?
• § EM: rhomboid membrane-bound crystals w/ x-grid pattern

 

DESMOPLASTIC SMALL CELL TUMOUR

Clin: young adults

-testes, pleura, pelvic serosa

• § Micro:
• § -islands of small round tumor cells trapped in a desmoplastic stromaà reminiscent of carcinoid
• § Genetics: t(11;22) EWS:WT1
• § IHC: WT1+ and neuromusculoepithelial+ (desmin+, CK+/EMA+, NSE+)

 

EPITHELIOID SARCOMA

Clin: extremities of young adults, often ulcerated hand mass

• § Micro:
• § -cytologically bland
• § -epithelioid tumor cells in granuloma like fashion around areas of necrosis (nodules with central necrosis)
• § Genetics: t(11;22) EWS:WT1à probably wrong because it’s DSRCT…
• § IHC: keratin, vimentin, CD34
• § Ddx: granuloma (due to necrosis)

 

SARCOMAS THAT MET. TO REGIONAL LYMPH NODES

• § MFH
• § RMS
• § SS
• § Clear cell sarcoma

 

DIFFERENTIAL DIAGNOSIS OF GIANT CELL LESIONS IN SOFT TISSUE

1.  GCT of tendon sheath

2.  GCT of soft tissue

• § 3.  PVNS

 

INFLAMMATORY MYOFIBROBLASTIC TUMOR

Micro

• § Spindle cell proliferation (MFB and FB)
• § Inflammatory background (eosinophils, plasma cells, lymphocytes)
• § 3 possible patterns
  • Ø Myxoid or edematous stroma[1]
  • Ø Compact fascicles of spindle cells[2]
  • Ø Scar-like[3]
• § Ganglion-like cells (vesicular nuclei, pink macronucleoli)

Malignant transformation[4]

• § Atypia (oval vesicular nuclei, macronucleoli)
• § Variable mitoses including atypical ones

Gross

• § WC

Clinical

• § Before age 20 mostly
• § Lung, mesentery, omentum
• § Constitutional symptoms (fever, mass, weight loss, pain, growth failure)[5]

IHC

• § VIM+ always
• § SM markers (all 3)+ variably (focal or diffuse+)
• § Skeletal markers-
• § S100-
• § ALK+ in 50%

EM

• § FB and MFB

Prognosis

• § Difficult ot predict by histology

 

 

Tumor	Cytogenetic Abnormality	Genetic Abnormality
Extraosseous Ewing sarcoma and primitive neuroectodermal tumor	t(11:22)	FLI-1-EWS
Liposarcoma-myxoid and round cell type	t(12:16)	CHOP/TLS
Synovial sarcoma	t(x;18)	SYT-SSX
Rhabdomyosarcoma- alveolar type	t(2;13)	PAX3-FKHR
	t(1;13)	PAX7-FKHR
Desmoplastic small round cell tumor	t(11;22)	EWS-WT1
Clear cell sarcoma	t(12;22)	EWS-ATF1
Alveolar soft part sarcoma	t(X;17)	TFE3-ASPL
Burkitt lymphoma	t(8;14)	c-myc-IgH
Chronic myelogenous leukemia	t(9;22)	c-abl-bcr
Mantle cell lymphoma	t(11;14)	bcl-1-IgH
Follicular lymphoma	t(14;18)	IgH-bcl2

Extraskeletal myxoid chondrosarcoma	t(9;22)
Dermatofibrosarcoma protuberans	t(17:22)
Congenital fibrosarcoma	t(12;15)

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