Soft tissue lesions

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Soft tissue lesions

• Aaron Auerbach

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These lectures were prepared with the help of Dr.
Julie Fanburg-Smith
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Phenotypes

• Fibroblastic
• Lipomatous
• Vascular
• Nerve Sheath
• Skeletal Muscle
• Smooth Muscle
• Bone or Cartilage
• Uncertain Phenotype

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Immunophenotype

• Fibroblastic SMA/MSA focal CD34 in fibroblasts
• Lipomatous S100fat and lipoblasts,
  CD34spindled areas
• Vascular CD31, CD34, SMA for pericytes, HHV8 for
  KS
• Nerve Sheath S100, CD34, NFP, GFAP, EMA
• Skeletal Muscle Desmin, MyoD1, myf4
• Smooth Muscle SMA, MSA, Desmin
• Alveolar Soft Part Sarcoma PAS crystals, no
  consistent IHC
• Epithelioid Sarcoma Keratin, EMA, Vimentin, CD34
• Synovial Sarcoma Keratins, CK7, EMA
• Clear Cell Sarcoma HMB45 gtS100 protein

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Molecular changes
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Adipocytic Tumors
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Classification of Adipocytic Tumors

• Reactive Fat necrosis, Fat atrophy, Silicone
  granuloma, Massive localized lymphedema of the
  morbidly obese , Adiposa Dolorosa
• Benign Lipomas Classic (Intramuscular,
  Lipomatosis), Spindle Cell/ Pleomorphic,
  Angiolipoma, Chondroid, Lipoleiomyoma,
  Angiomyolipoma, Lipoblastoma, Hibernoma
• Intermediate Atypical Lipoma/WDLS
• Malignant Liposarcomas Well-differentiated,
  Round Cell/Myxoid, Pleomorphic

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Classic Lipoma

• Fatty mass, surrounded by pseudocapsule

Cells with different sizes and shapes can be
seen It can look busy
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Intramuscular Lipoma
harder to excise, higher local recurrence rate
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Lipomatosis involves either 3 different muscle
groups or 3 different planes (dermis, subq, deep
tissue) Madelung lipomatosis involves multiple
lipomas in a posterior neck and shoulder
distribution ETOH
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Adiposa dolorosa
lipomatosis causing extremity enlargement
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Spindle Cell/Pleomorphic Lipoma

• 60 year old male
• Posterior shoulder/back/neck
• Multiple/familial, changes in chromosomes 13 and
  16 similar in spindle cell lipoma and pleomorphic
  lipoma

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Spindle Cell Lipoma/Pleomorphic Lipoma

• 5 features
• 1. Fat
• 2. Spindled cells
• 3. Collagen bundles (thick ropey)
• 4. Mast cells
• 5. Myxoid back ground
• FLORET CELLS for pleomorphic

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Spindle cell lipoma
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Spindle cell lipoma, abundant thick collagen
Abundant myxoid change
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Floret giant cells
Pleomorphic lipoma
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Angiolipoma

• young adults male forearm,trunk
• capillary sized vessels at periphery of lobule
• fibrin thrombi in the lumen
• painful

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Angiolipoma
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Angiolipoma
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Chondroid lipoma

• Adult female (80), thigh, arm shoulder,
  subcutaneous or intramuscular
• Mature fat, epithelioid chondroid cells in
  myxoid matrix, resembles chondrosarcoma and
  liposarcoma
• Similar genetics to hibernoma

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Chondroid lipoma
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Hibernoma

• Brown fat
• S100 protein positive
• No such thing as malignant hibernoma

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Central nuclei Multiple vacuoles
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Angiomyolipoma

• 3 components
• 1) thick walled vessels
• 2) immature specialized smooth muscle cells
  which may be pleomorphic
• 3)mature fat
• 1/3 have tuberous sclerosis.
• Desmin, HMB45 positive

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HMB45
Desmin
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Liposarcoma Variants

• Well differentiated liposarcoma (50)
  Dedifferentiated Liposarcoma (5)
• When they dedifferentiate they can metastasize
• Myxoid / round cell liposarcoma (30-40)
• Clinically and genetically similar
• Pleomorphic liposarcoma lt 5

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Myxoid Liposarcoma
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Round Cell Liposarcoma
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Pleomorphic Liposarcoma
Empty fat has been leached out
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Features of atypical lipomatous tumor /well
differentiated liposarcoma
Widened septa Low power busy appearance Heterog
eneous cell size and shape Lipoblasts may be
seen Hallmark finding lipocytic atypia
WDLS intramuscular, groin, retroperitoneum
Atypical lipomatous tumor Superficial subcutis
not groin, intramuscular or retroperitoneum.

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Well-differentiated Liposarcoma
Lipcytic atypia
lipoblasts
WIDENED SEPTA
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Dedifferentiated Liposarcoma gt10x power
field alipogenic area
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Immunohistochemistry in Adipocytic Tumors

• S100 protein in fat cells and lipoblasts
• CD34 positive in spindled component of fatty
  tumors
• Desmin positive if the component has smooth
  muscle features, like in myolipoma or
  angiomyolipoma, sometimes a component of
  dedifferentiated liposarcoma

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Pseudolipoblasts

• Fat necrosis
• Fat atrophy
• Silicone reaction
• Hibernoma cells
• Chondroid lipoma
• Frozen section artifact
• Signet ring cells
• Neoplasm with myxoid change

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Fat Necrosis
Ischemic No histiocytes too quick
Peripancreatic Eosinophilic degen
lipogranulomas
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Pseudolipoblast in fat necrosis
True lipoblast in well- differentiated liposarcoma
Histiocyte engulfing fat In fat necrosis
Nucleus scalloped by vacuoles
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TRUE ATYPICAL CELL
HISTIOCYTE
Multiple nuclei Eosinophilic cytoplasm
Single nuclei Little cytoplasm
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Silicone granuloma
Cystic spaces
CD163
Breast implants or joint replacement Large cystic
spaces histiocytes, polarize, spectrophometry
CD163
CD163
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Fat atrophy
malnutrition or injection sites the fatty
lobules retain their structure
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Nerve Sheath Tumors

• Will cover
• Neurofibroma
• Neurofibromatosis
• Malignant peripheral nerve sheath tumor (MPNST)
• Schwannoma
• Will not discuss
• Neuromas
• Neurothekeoma
• Granular Cell Tumor
• Perineurioma

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Neurofibroma

• Sporadic or in the setting of Neurofibromatosis
  type 1
• Arise within nerve
• Collagen fibers

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more cellular in center, than edematous periphery
Center
Periphery
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S100--schwann cells
CD34-fibroblasts
NFP positive
NFP--Residual neurites (neuroaxons)
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Neurofibroma SubtypesThis will be on the boards
Plexiform 100 assoc with NF1 Bag of
worms Diffuse actual assoc with NF1 largely
unknown (gt10) Wagner-Meissner bodies
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Diffuse Neurofibroma

• Ill-defined subcutaneous mass
• Honeycomb pattern, reminiscent of DFSP
• Wagner-Meissner bodies are the hallmark
• Typically DOES NOT undergo malignant
• transformation by itself usually only if
  associated with plexiform.

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Diffuse neurofibroma
WAGNER-MEISSNER BODIES
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S100
CD34
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Plexiform Neurofibroma

• 100 patients will have NF1
• Gross bag of worm distortion of nerve with
  associated hypertrophy of the adjacent bone or
  soft tissue, overlying skin hyperpigmentation
• Histologically complex tortuous aggregate of
  intraneural neurofibroma(s)
• Clinicopathologic diagnosis
• May undergo malignant transformation

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Gross Bag of worms
Plexiform pattern
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Neurofibromatosis Type I

• Von Recklinghausens Disease (1882) AD or new
  mutation of NF1 gene tumor suppressor gene on
  chromosome 17
• 3-5 with NF1 develop MPNST
• (no neurofibromin found in MPNST)

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NF1

• café-au-lait macules appear shortly after birth
• neurofibromas can be plexiform type
• Axillary/inguinal freckling
• Optic glioma (pilocytic astrocytoma)
• Lisch nodules (iris hamartomas)
• Bone changes osteoporosis, kyphoscoliosis,
  pseudoarthrosis
• Family history
• Loss of neurofibromin Nf1 (surpesses Ras)

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Cellular Neurofibroma
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Malignant changes in neurofibroma

• Nuclear atypia (by itself not worrisome)
• ?cellularity or focal fascicular growth
• ? mitoses
• Immunos ? S100 CD34

fascicular growth
Atypia, mitosis fascicular growth
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Malignant Peripheral Nerve Sheath Tumor

• Sporadic or NF1
• In NF1, earlier onset, ?morbidity
• Diff dx melanoma
• Both S100, but MPNST not for other melanoma
  markers

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Geographic necrosis
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MPNST Immunos

S100 protein
GFAP (rare in melanoma)
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Rhabdomyoblasts in MPNST Desmin positive
DES
MALIGNANT TRITON TUMOR MPNST RMS
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Schwannoma

• -Encapsulated
• -eccentric to nerve
• -surrounded by perineurium (EMA).
• -Antoni A (cellular, Verocay bodies)
• -Antoni B (hypocellular, perivascular hyaline)
• -Cellular type lacks Antoni B, well-formed
  Verocay, and has pericapsular lymphocytic cuffing

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Bilateral acoustic schwannoma

• -germ line mutation in NF2 gene on
• Chr22
• -resulting in absence of gene product
• merlin
• -meningiomas, gliomas

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SCHWANNOMAAntoni A
Verocay bodies
Verocay bodies
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SCHWANNOMA
ANTONI B MYXOID AREAS WITH PERIVASCULAR
HYALINIZATION
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CELLULAR SCHWANNOMA
PERICAPSULAR LYMPHOCYTIC CUFFING
FASCICULAR GROWTH PATTERN
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Schwannoma immuno

• S100 diffuse
• CD34 only in Antoni B
• NFP not within tumor
• Cellular schwannoma has diffuse S100 protein,
  GFAP, and occasionally keratin

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SCHWANNOMA
S100
CD34 only in antoni B
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EMA at periphery in capsule (perineurium)
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Fibroblastic and Fibrohistiocytic Tumors
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(Myo)Fibroblastic Tumors

• Nodular Fasciitis
• Proliferative Fasciitis (ADF)
• Fibrous Histiocytoma (Cellular)
• Fibromatosis
• DFSP/FS
• MFH

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Nodular fasciitis
Most common pseudosarcoma Rapid growth History
of trauma ages 15-40 extremities
Morphology Usually fascia at one edge Myxoid
degeneration Tissue culture like
myofibroblasts Extravasated red blood cells Older
lesions - keloid-like collagen. Mitosis No
necrosis, only reactive atypia
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Fascia
Fascia at one edge
Tissue culture myofibroblasts
EXTRAVASATED RBCs
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Nodular fasciitis
KELOIDAL COLLAGEN
REACTIVE ATYPIA/ MITOSES
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Proliferative fasciitis

• Solitary lesion
• Adults 40-70
• Less often trauma, compared to nod fasc
• Benign, excise

Morphology Ganglion cell like myofibroblasts Actin
Diff Dx RMS, but prolif fasc is desmin
Ganglioneuroblastoma, but prolif fasc is S100
and GFAP-
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GANGLION-CELL-LIKE MYOFIBROBLASTS
Eccentric nuclei w prominent basophilic
nucleolus slightly granular cytoplasm
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Im skipping atypical decubital fibroplasia b/c
of time constraints
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Fibrous histiocytoma

• Dermpath calls it dermatofibroma
• Classic 1 local recurrence rate
• Cellular 26 local recurrence rate

Morphology Storiform/short fascicular growth
pattern Pushing, stellate border Production of
collagen giant cells Perivascular lymphocytes
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SHORT FASCICULAR AND STORIFORM GROWTH PATTERNS
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PUSHING STELLATE BORDER
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Cellular FH
cellular
necrosis
HEMORRHAGE AND HEMOSIDERIN
hemosiderin
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Fibromatosis
Superficial fibromatoses Palmar/Plantar Deep
fibromatoses (Desmoid) Extraabdominal or
abdominal Intraabdominal 13 assoc with Gardners
syndrome Morphology Elongate blood
vessels Parallel myofibroblasts Beta catenin
(nuclear) Inactivation of APC tumor supressor
gene in Gardner or sporadic fibromatosis leads to
accumulation of beta-catenin Gardners
syndrome 1.Osteomas 2.Fibromatosis 3.Fibromas
4.GI adenomas
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ELONGATE VESSELS
ELONGATE VESSELS
EL
PARALLEL MYOFIBROBLASTS
Infiltrates sk muscle
Beta catenin
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Dermatofibrosarcoma Protuberans (DFSP) --Low
grade fibrohistiocytic tumor --Dermis,
subcutaneous tissue --Lesion parallel to skin
surface
PARALLEL PATTERN
SKIN
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STORIFORM
HONEYCOMB PATTERN Entraped fat
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DFSP with fibrosarcomatous transformation (FS)

• Skin surface
• DFSP below skin surface has entrapped fat
• Line of demarcation
• Fibrosarcoma beneath (fascicular growth pattern,
  herring bone pattern, no entrapped fat, ?CD34)

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DFSP WITH FS
Skin surface DFSP dermacation Fibrosarcoma
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DFSP WITH FS
HERRINGBONE/FASCICULAR PATTERN
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CD34
CD34 DFSP CD34- Fibrosarcoma
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Bedar tumor (DFSP with melanin pigment)
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Elastofibroma

• Scapula
• fibroblast-like cells, abundant collagen,
  abnormal elastic fibers

Elastin stain
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MPH.pleomorphic sarcoma

• Pleomorphic sarcoma
• RMS- Myoid
• LMSdesmin
• Liposarcoma
• AngiosarcomaCD34

• MFH

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Classification of Vascular Tumors

• Benign
• Hemangioma
• Lymphangioma
• Intermediate
• Hemangioendotheliomas
• Malignant
• Angiosarcoma
• Kaposi sarcoma

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Hemangioma facts

• --Infants/kids, head and neck,
• --can regress
• --Cavernous hemangioma assoc w Kasabach-Merritt
  syndrome

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Lymphangioma

• Cystic hygroma Turners syndrome (XO).
• D240 immuno

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Angiosarcoma

• Skin liver bone spleen
• Post mastectomy w/ lymphadema
• Primary breast
• Radiation induced (5yrs after rads)
• Get vascular markers

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Kaposi sarcoma

• --AIDS/immunosuppressed
• --Morphology
• fascicles of spindle cells
• slit-like vascular spaces
• PAS positive diastase resistant hyaline
  globules,
• extravasated RBCs
• --HHV8

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Spindle cells, RBCs
Hyaline globules
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What is your diagnosis for the next3 slides?
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SMA
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Desmin
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What is the most likely diagnosis?
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Leiomyosarcoma
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LMS morphology

• intersecting fascicles of spindle cells
• Nucleus cigar shaped
• /-perinuclear vacuoles

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What is your dx?
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What is your diagnosis?
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RMS
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Cross striations
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Myogenic regulatory proteins most specific
markers for RMS
MYOD1
MYOGENIN
MYOD1
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What is your dx?
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ALVEOLAR RMS

• Extremities gt Head/Neck
• Nests/Clusters discohesive or solid
• Fibrous vascular septa, often hyalinized
• Small round blue cells sparse cytoplasm

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Botryoid RMS

• Genital
• Gross grape-like
• Polypoid mass
• Cellular cambium layercellular
• Deeper--acellular

Cambium layer
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GIST

• --Mostly stomach, but found throughout the GI
  tract
• --Immunos
• CD117 gt90
• CD34 80
• Smooth muscle actin 20
• Desmin 5
• --Tx Imatinib (Gleevec)

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KIT
CD117
CD34
SMA
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Alveolar soft part sarcoma

• organoid pattern,
• tumor nests outlined by
• sinusoidal vascular channels
• PAS crystals,
• EM rhomboid crystals
• TFE3 (fusion protein)
• Vimentin negative
• sometimes for desmin,
• myoD1.

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Epithelial sarcoma

• Sarcoma with epithelioid morphology
• Sites fingers/extremities
• Eosinophilic epithelioid cells surrounding
  central necrosis
• Immuno Keratin, EMA, Vimentin, CD34

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Epithelial sarcoma
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Questions ?

• I skipped synovial sarcoma, clear cell sarcoma,
  DSRCT, mesench chondrosarc and Ewings sarcoma due
  to time constraints.