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1/18/2018
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Soft Tissue Tumor Boot Camp
Rajiv M. Patel, M.D.
Associate Professor of Pathology & Dermatology
University of Michigan, Ann Arbor, MI
General comments
• More STT are initially sampled by core needle, FNA or other limited biopsy techniques to decrease patient morbidity
– Smaller specimens more challenging to interpret
• Sampling
• Problems with IHC
• A competent consultant is your friend
• Under diagnosis often poses greater risk than over diagnosis
• Misclassification is possible if several types of tumors share morphologic features
• “When you hear hoof beats think of horses, not zebras”
– Always rule out carcinoma, melanoma, lymphoma & mesothelioma before committing to a mesenchymal tumor diagnosis
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General histologic approach
• Ensure lesion tissue present!
• Evaluate:1. Growth pattern & architecture in conjunction with tumor cell cytology
• Look for clues to a specific diagnosis (e.g., Verocay bodies, lipoblasts)
2. Presence or absence of mitoses or necrosis
3. Use ancillary studies when necessary (e.g., IHC, molecular)
• If features are classic for a particular entity….go for it!
• If definitive diagnosis cannot be made determine if lesion is:1. Benign or malignant
2. Low-grade, or high-grade malignant
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Regarding ancillary testing
• Make the diagnosis or put together a limited differential based on H&E appearance & pattern-based approach
• Universal IHC screening panel– Keratin, S100, SMA, desmin, CD34
• Check internal & external positive controls
• Look at entire slide!
• Know what constitutes a positive result for a given stain
• Stain looks positive in the cells of interest?
• In limited specimens negative staining may not reflect status of entire neoplasm
• Most relevant molecular tests can utilize FFPE tissue
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Reporting
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• Biopsy
– Clear diagnosis & grade if possible
• Descriptive comment with differential if the above not possible
• Resections
– Without adjuvant Tx
• If previously sampled review bx & confirm dx and adequacy of sampling
• Confirm any previous grading. Any higher grade areas present?
• Margin status
– With neoadjuvant
• % residual tumor viability
• Margin status
• All three numbers are summated to determine degree of differentiation
Grade 1 : 2-3
Grade 2 : 4-5
Grade 3 : 6-8
• Proven to correlated well with survival
• Mitotic Count. In the most mitotically active area, ten successive high-power fields (at 400x magnification=0.1734 mm2) using a 40x objective.
1 0-9 mitoses per 10 HPFs
2 10-19 mitoses per 10 HPFs
3 >20 mitoses per 10 HPFs
• Tumor necrosis. Evaluated on gross examination and validated with histological sections
0 No tumor necrosis
1 <50% tumor necrosis
2 >50% tumor necrosis
• Degree of Differentiation. 1-3
FNCLCC Grading
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A Pattern-Based Approach
Pattern-based approach: What does it mean?
• Histomorphology-based
– Epithelioid
– Round cell
– Pleomorphic
– Spindle cell
– Myxoid
• Age-based
– Generally STT (particularly sarcomas) that arise in children, do not tend to afflict adults with the same frequency and vice versa (e.g.;, FHI in infants, or MFS in older adults); there are always exceptions
• Location-based
– Certain lesions tend to arise at particular anatomic sites (e.g., periungual SAF)
• Combination of the 3 highest diagnostic yield
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Morphology
• Evaluate all tissue on slide
• Size & depth
• Relation to overlying skin & fascia
• Borders (circumscription, encapsulation)
• Cellular differentiation
• Atypia
• Mitoses (abnormal forms?)
Growth Patterns
• Infiltrative vs. circumscribed
• Cellular
• Zonal
• Fascicular
• Palisading
• Multinodular
• Diffuse
Stroma & Vasculature
• Myxoid
• Fibrotic/hyalinized
• Actinic damage
• Secondary elements
• Background vasculature (lobular, stag-horn)
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Special Studies
• Special stains (PAS+/-)
• IHC
• Cytogenetics-FISH, RT-PCR
• EM (rarely used now)
• NGS (becoming more common)
• Other laboratory studies
Another generality
• Pleomorphic vs. Monomorphic Sarcomas
– Pleomorphic sarcomas have complex karyotypes & multiple genetic abnormalities
– Monomorphic (translocation-associated) have a single molecular abnormality that is oncogenic
Clinical Information Morphology
Special Studies
Diagnosis
Integrated Approach
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Examples of major histologic patterns
• Epithelioid
• Round cell
• Pleomorphic
• Monomorphic spindle cell
• Myxoid
Epithelioid pattern
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11-year-old female with an ulcerated scalp mass
Diagnosis?
• Granuloma annulare?
• Necrobiosis lipoidica?
• Rheumatoid nodule?
• Dermatofibroma?
• Scar?
• Something else?
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Cytokeratin AE1/3
CD34
IHC Epithelioid NeoplasmsAntigen CA Melanoma/
EMPNSTLymphoma ES EAS ELMS
CK + +/- melanoma,- EMPNST
- + +/- -
S-100/SOX10 - + - - - -
SMA - - - - - +
Desmin - - - - - +
CD34 - - - + +/- -
CD45 - - + conventional B & T-cell lymphoma,
- most ALCL
- - -
CD30 - - - most conventional B & T-cell
lymphoma, + ALCL
- - -
CD31/ERG - - - - + -
ALCL, anaplastic large cell lymphoma; EAS, epithelioid angiosarcoma; ES, epithelioid sarcoma; CA, carcinoma; CK, cytokeratin; EMPNST, epithelioid malignant peripheral nerve sheath tumor; ELMS, epithelioid leiomyosarcoma
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Diagnosis?
Epithelioid sarcoma
EMA
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INI-1
Epithelioid Sarcoma (ES)
• First described by Franz Enzinger in 1970
• Most common in adolescents and young adults
• Two main variants:
– Classic Epithelioid Sarcoma (CES)
– Proximal Epithelioid Sarcoma (PES)
Classic Epithelioid Sarcoma (CES)
• Peak incidence in 2nd decade
• Male preponderance
• Mainly affect hands, fingers and lower arm, followed by lower leg
• Presents as single or multiple firm nodules (usually <3cm in MD), +/- ulceration
• Mainly superficial with involvement of tendons, aponeuroses and dermis
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Histology - CES
• Vaguely circumscribed cellular nodules
• Central necrosis, imparting a pseudogranulomatous appearance
• Epithelioid and spindle cells with eosinophilic cytoplasm and vesicular nuclei with small nucleoli
• Variable nuclear atypia
• Aggregates of chronic inflammatory cells at the periphery
• Hyalinised stroma
• Dystrophic calcification +/- metaplastic bone formation in ≈ 20% of cases
• Some cases have haemorrhage and pseudoangiomatous spaces
• Spindled variant resembles CDF
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• Co-expression of “epithelial markers” (CK & EMA) and vimentin
• CK expressed include both LMW and HMW cytokeratins
• 50-60% of cases CD34 +ve
• May be Factor XIIIa-positive mimicking DF
ES: Immunohistochemistry
INI1
Loss of INI1 (SMARCB1 protein) expression in >95% of cases
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INI-1 (SMARCB1)
• hSNF51/INI1/SMARCB1/BAF47 gene
• Tumor suppressor
• Loss of expression hallmark of pediatric rhabdoid tumors and atypical teratoid rhabdoid tumors of CNS
• Loss in >90% of epithelioid sarcomas, but not in almost all other sarcomas and carcinomas
• Genetics: complex rearrangements esp. 22q11, but SMARCB1 mutations not frequent, 8q gains frequently observed
Epithelioid Sarcoma-Proximal Type
Proximal Epithelioid Sarcoma (PES)
• Affects older patients
• Involves deep soft tissues of trunk, pelvis, perineum & genital region, buttock & hip, head & neck
• Larger than superficial examples of CES
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Histology - PES
• Multinodular pattern
• Sheets of large cells with pleomorphic vesicular nuclei containing prominent nucleoli
• Rhabdoid morphology more common
• Focal necrosis (spotty necrosis)
• Rare cases of ES have myxoid stroma
• Some cases with hybrid features of both CES & PES described
PES
ES prognosis
• ≈ 40-80% recur and 35-50% metastasise
• CES recur in more proximal tissues as multiple nodules
• Not graded by the FNCLCC system
• Adverse prognostic factors: male sex, older age, proximal location, size >5cm, deep location, multifocality, ↑mitoses, vascular invasion, lymph node involvement, necrosis and proximal type morphology
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ES: Differential Diagnosis
• Necrobiotic granulomata (rheumatoid nodule, granuloma annulare)
– CK-, INI1 retained
• Cellular fibrous histiocytoma (CFH)
– Rule of thumb: Consider ES when contemplating CFH of distal extremity (ES may be FXIIIa+)
• CK-, INI1 retained
• Carcinoma (primary/metastatic)
– CD34-, INI1 retained
• Malignant rhabdoid tumour – mostly in children, has diffuse morphology and show mutation of INI1 gene
• Epithelioid vascular tumours
• Myoepithelial lesions
– Express keratins
– carcinoma (can also show loss of INI1)
Granuloma annulare
Epithelioid Vascular Tumours
• Epithelioid haemangioma
• Epithelioid haemangioendothelioma
• Pseudomyogenic haemangioendothelioma (ES-like haemangioendothelioma)
• Epithelioid angiosarcoma
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Epithelioid Haemangioma (EH)
• AKA angiolymphoid hyperplasia with eosinophilia and histiocytoid haemangioma
• Most widely documented in the skin and subcutis (head)
• Also described in bone, lymph nodes, lung, penis, eye, tongue, breast, arteries, colon, heart, spleen, and testis
• Skeleton probably 2nd most common location
Clinical: EH
• In the skin & superficial tissues presents as a solitary or cluster of small, pink to reddish-brown dome shaped nodules
• Adults commonly affected
• Patients with bone lesions have an average age of 35yrs
• EH of skin & subcutis is multifocal in up to 50%
• More than 18% of cases developing in the skeleton are polyostotic
• Simultaneous involvement of skin & bone is uncommon. Nielsen P et al (Am J Surg Path 2009) reported two out of 50 patients with discontinuous lesions of bone, skin, artery, and lymph nodes
EH - Pathology
• Grossly, the tumours are solid, well circumscribed, reddish-tan, haemorrhagic and lobulated
• Associated with a larger calibre, damaged thick-walled vessel in ≈ 60% of cases
• Vaguely lobular proliferation of vessels with epithelioid endothelial cells with abundant eosinophilic cytoplasm showing focal “tombstone” pattern +/- intracytoplasmic vacuoles
• Some vessels lack well defined lumina
• Inflammatory cell infiltrate including numerous eosinophils
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CD31
Differential Diagnosis
• Kimura’s disease
• Epithelioid haemangioendothelioma
• Epithelioid angiosarcoma
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EH vs. Kimura’s Disease (KD)
EH• Slight female predominance• No racial predilection• Lymphadenopathy uncommon• Peripheral eosinophilia in app.
20% of cases• IgE levels normal• Superficial, circumscribed,
occasional lymphoid follicles, prominent vessels and non prominent stromal fibrosis
KD• Male predominance• Asians more commonly affected• Lymphadenopathy common• Peripheral eosinophilia
invariably present• Increased IgE levels• Deep seated, non
circumscribed, vessels not prominent, abundant lymphoid follicles and prominent stromal fibrosis
Epithelioid Haemangioendothelioma (EHE)
• Described by Weiss and Enzinger in 1982
• Adults, M=F
• Subcutaneous soft tissues of extremities –commonest site
• Other sites: skin, oral cavity, lung, liver, penis etc.
• Visceral EHE may exhibit a rather indolent clinical course
• Solitary, sometimes multifocal
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EHEEHE
EHE
EHE
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EHE - Histology
• Multiple nodules• Usually ass. with arterioles and venules• Cords, trabeculae or solid nests/sheets of epithelioid
cells• Eosinophilic cytoplasm +/- cytoplasmic
vacuoles/lumina• Myxohyaline to myxochondroid stroma• Low grade nuclear features but subset of cases in
the soft tissue (25-30%) have high nuclear grade, necrosis & frequent mitoses(“malignant EHE”)
EHE
Positive for:• CD31• CD34• FLI1• ERG• CK & EMA (40%)
CD31
CD34
AE1/AE3
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EHE: Molecular
• Cytogenetics
– >90% Epithelioid hemangioendotheliomas have t(1;3)(p36;q25)
– Fusion of WWTR1 and CAMTA1
– WWTR1: transcriptional coactivator highly expressed in endothelial cells
– CAMTA1: DNA binding transcriptional regulatory protein usually expressed in brain
– Possible therapeutic target
MR Tanas et al. Sci Transl Med. 2011;3:98ra82.
EHE: Molecular
Subset of EHE have TFE3 gene rearrangement
• WWTR1 - CAMTA1 negative
• +ve for TFE3 by IHC (in addition to endothelial markers)
• -ve for CK & HMB45
• TFE3 gene rearrangement demonstrated by FISH
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EHE: Behavior
• Considered tumor of intermediate malignancy– Frequent recurrence (10-15%)
– Lymph node and pulmonary metastasis (up to 30%)
– Overall mortality: 10-20%
• 5 year survival 50-85%
• 10 year survival 42-55%
• Treatment– Wide local excision
– Amputation
– Lymph node dissection
Malignant EHE
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EHE Risk Stratification (Deyrup A et al. AJSP 2008)
Criteria for malignancy (malignant EHE):
•>3cm in size
•>3 mitotic figures per 50HPF
– 59% disease specific survival in pts. with above characteristic vs. 100% DSS in pts. with tumours lacking the features
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Differential Diagnosis
Depends on site involved:
• Epithelioid haemangioma
• Carcinoma (both primary & metastatic)
• Chondrosarcoma & ESMC
• Leiomyosarcoma (epithelioid LMS)
• Angiosarcoma (epithelioid AS)
EHE: Key Points
• Any age but peak incidence 4th-5th decade
• F > M
• Myxohyaline matrix, nests, cords, chains, single file epithelioid cells, angiocentric growth, +/- intracytoplasmic vacuoles
• LMWCK 25%
• Inclusive of HG, LR 10-15%, Met 25%, mortality 10-15%
• Overall 5-year survival 73%
• WWTR1-CAMTA1 & YAP1-TFE3 specific fusions
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• Rare entity originally described in 2003
• Equally involves superficial or deep soft tissue
• Can present as ulcerated lesion
• Striking resemblance to ES
Pseudomyogenic (epithelioid sarcoma-like) Hemangioendothelioma (PMHE)
(Am J Surg Pathol 27:48-57, 2003.)
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PMHE
• Very rare
• Some cases probably included in cases published as:
– Fibroma-like variant of epithelioid sarcoma
(Mirra JM et al, Cancer 1992; 69:1382-95)
– Spindle cell variant of epithelioid sarcoma
Clinical: PMHE
• M>F (4:1)
• 2nd-5th decade – mean 30yrs
• Multiple nodules
• Lower limbs> upper limbs >trunk >head
• Painful/non-painful
Histopathology: PMHE
• Poorly circumscribed
• Infiltrative border
• Dermal, dermal + subcutis, dermal + subcutis + muscle
• Round, oval or spindled cells with vesicular nuclei and inconspicuous nucleoli
• Fascicles
• Focal myxoid stroma
• Ample eosinophilic cytoplasm →rhabdomyoblastic appearance
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Fascicles
Poorly circumscribed
Histopathology: PMHE
• Neutrophils frequently present
• Minimal nuclear pleomorphism
• Rare mitotic figures
• Necrosis is uncommon
• Some cases show intravascular invasion
• Subtle evidence of vascular differentiation consisting of focal intracytoplasmic lumen
• No overt vascular channels
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Neutrophils
PMHE
Hornick and Fletcher Am J Surg Pathol 35:190-201, 2011
IHC: PMHE
Positive for:
– AE1/AE3
– ERG
– EMA
– FLI-1
– CD31(50%)
– SMA
– (MNF116)
Negative for:
– CD34
– Desmin
– S100
INI1 expression retained
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AE1/3 Fli-1
CD31 INI-1
Hornick and Fletcher Am J Surg Pathol 35:190-201, 2011
PMHE
• Balanced translocation t(7;19)(q22;q13) found as sole anomaly in 3 lesions of same pt.(Trombetta et al Cancer Cytogenet 2011)
• Unbalanced t(7)t(7;19) in another case
Behavior: PMHE
• Relatively indolent
• Risk of local recurrence
• Regional metastasis vs. multifocal disease
• No distant metastasis
• No disease related deaths
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Epithelioid AS
Angiosarcoma (AS)
• Conventional (idiopathic)
• Iatrogenic/Secondary:
– Lymphoedema assoc.
– Post radiation
– Thorotrast
– Foreign material
– PVC in hepatic AS
– In ass. with nerve sheath tumour
Conventional AS
• Elderly pts
• Sun-damaged skin
• Head & neck
• M>F
Histopathology: AS
• Solid sheets of atypical, mitotically active epithelioid cells
• Can be mostly spindled
• Vasoformation can be inconspicuous, usually seen at the periphery
• Can be easily mistaken for other tumours if index of suspicion low!
• Positive for vascular markers (CD31, ERG, CD34+/-)
• May be strongly keratin positive
• Subset show loss of INI1
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AS IHC
• Use more than one endothelial marker
– CD31 – not entirely specific, also expressed by histiocytes
– CD34 – less sensitive than CD31 & not specific
– Fli-1 – poor specificity; expressed by carcinomas, AFX/PDS, MM
– ERG – sensitive & relatively specific
• May be strongly keratin positive
• Subset show loss of INI1
Epithelioid AS
CD31
Epithelioid angiosarcoma CD31
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• ERG = ETS-related gene
• ETS family of transcription factor
• Expressed in normal endothelial cells
• Expressed by haemangiomas, lymphangiomas, almost all angiosarcomas, EHE and PMHE
• Also +ve in AML, subset of EWS + some prostatic adenocarcinoma
ERG
Clear Cell/Signet Ring Cell AS
Am. J. Dermatopathol.2013; 35; 671–675. Histopathology 2015, 66, 856–863.
• Foamy cell
• Granular cell
Dermatopathol. 2014; 36; 669–672
J. Cutan. Pathol. 2010; 37; 901–906
J. Cutan. Pathol. 2012; 39; 476–478, 475
Other Morphological Variants of Epithelioid AS
Histopathology 2015, 66, 856–863
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Mimics of epithelioid AS
Melanoma Epithelioid fibrous histiocytoma
Myoepithelial Tumours of Skin & Soft Tissues
• Relatively recently described & therefore not well recognised
• Encompasses tumours previously labelled as:
– Parachordoma
– Mixed tumours
– Chondroid syringoma
– Ectomesenchymal chondromyxoid tumour
• WHO currently considers the tumours to be part of a histological spectrum
• Most are benign
Myoepithelial Tumours of Skin and Soft Tissues
• ~25% mixed tumours
• ~42% myoepitheliomas
• ~32% myoepithelial carcinoma or malignant mixed tumours
Stout, 1959; Kilpatrick, 1997; Fernandez-Figueras, 1998; Michal 1999; Kutzner, 2001; Mentzel, 2003; Hornick, 2003; Flucke, 2011
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Apocrine Mixed Tumor-Chondroid Syringoma
• Uncommon tumor composed of epithelial & mesenchymal elements
• Solitary, slow-growing nodule on the head & neck
• Middle-age to elderly
• Slight male predilection
• Well-circumscribed 0.5-3 cm in diameter
• Benign but atypical & malignant variants described
• Lipomatous (apocrine) mixed tumor when fat is conspicuous
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MNF116
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p63
pCEA
Myoepithelial Tumours of Soft Tissues: Clinical
• Affects mainly adults (mean 38 years)
• ~20% of cases in patients younger than 20 yrs.
• No sex predilection
• Deep soft tissues of thigh > calf >upper limb >head & neck
• Slow growing painless mass
• Most <5cm in MD
• Most benign
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Myoepithelial Tumours of Soft Tissues: Histopathology
• Often well circumscribed and lobulated or multinodular
• Cords, trabeculae and solid nests of epithelioid, ovoid and spindled cells with eosinophilic to clear cytoplasm
• Some hepatoid, plasmacytoid or vacuolated morphology
• Variably myxoid and chondromyxoid stroma
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Myoepithelial Tumours of Soft Tissues: Histopathology
• ~20% show ductal differentiation
• ~10% show cartilaginous and/or osseous differentiation
• ~5% show “chordoma-like” features
• Syncytial variant seen in skin
• Rare cases show squamous or fat metaplasia
Cutaneous syncytial ME
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Myoepithelioma: IHC
AE1/3 SMA
S100 SOX10
Myoepithelioma: IHC
GFAP INI1
Myoepithelial Tumours of Soft Tissues: IHC
GFAP +ve in ~ 50%
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Myoepithelial Tumours of Soft Tissues: IHC
• Negative for brachury
• INI1/SMARCB1 lost in ~20% of cases (most carcinomas)
• PLAG-1 +ve in most mixed tumours
• HMGA2 –ve in ST mixed tumours
Myoepithelial Tumours of Soft Tissues: Molecular
• EWSR1 gene rearrangement in ~40% of cases
– Fusion partners – POU5F, PBX1, ZNF44, ATF1, PBX3, KLF17
– FUS may substitute for EWSR1
• PLAG1 gene rearrangement in most mixed tumours
Brandal 2008; Brandal, 2009; Antonescu, 2010; Flucke, 2012; Agaram, 2014, Puls 2014; Huang 2015
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EWSR1 FISH
Myoepithelial Carcinoma of Soft Tissues
• Clinically aggressive – recurrence/metastases in ~40% of cases
• Constitute a significant proportion of ST myoepithelial tumours occurring in children
• Criteria for malignancy not well defined:
– Nuclear atypia
– Prominent nucleoli
– Mitoses, necrosis or infiltrative pattern – not considered reliable
Myoepithelial Carcinoma of Soft Tissues
• Malignant myoepithelioma in skin malignant mixed tumor (very, very rare-aggressive)
• Morphologically & immunophenotypically similar to salivary gland counterparts
• Soft tissue cases predominate in pediatric population
• 75% of ST cases arise in limbs, typically subcutaneous
• Recur & metastasize 40-50% of cases to lungs, lymph nodes, bone & soft tissue
• EWSR1 translocation common outside salivary glands
• PLAG-1 in mixed tumors
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Myoepithelial Carcinoma
Myoepithelial Carcinoma
Myoepithelial Carcinoma
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Ki-67
Keratin
S-100
SMA
Differential diagnosis
• Extraskeletal myxoid chondrosarcoma
• Chondrosarcoma
• Chordoma
• Chondroid lipoma
More ST with Epithelioid Variants
• Mammary myofibroblastoma
• Myxofibrosarcoma
• Rhabdomyosarcoma
• Clear cell sarcoma
• PEComa
• IMT
• Undifferentiated Pleomorphic Sarcoma with epithelioid morphology
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Epithelioid LMS
Desmin
SMA
Key points: Epithelioid pattern
• Epithelioid morphology not uncommon in soft tissue tumours (STT)
• Small proportion of STT have epithelioid morphology as the most distinctive and/or predominant feature (e.g., vascular lesions)
• STT with epithelioid morphology are a heterogeneous group of tumours, often with overlapping features
• Morphologically and immunohistochemically overlap with non-mesenchymal/epithelial tumours
• The resemblance of the tumours to each other and overlapping features with non-mesenchymal tumours present a diagnostic challenge
• Always rule out carcinoma, melanoma, lymphoma and melanoma before diagnosing and epithelioid mesenchymal neoplasm
Key points: Epithelioid pattern
• A 5 stain screening panel including keratin, S100, SMA, desmin& CD34 is a good place to start. Order lots of unstained sections!
• Some of the most important mesenchymal tumors with this pattern include ES, epithelioid vascular tumors, epithelioid MPNST & myoepitheliomas
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Round cell pattern
22-year-old male with a violaceous nodule of the right
thigh
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Abundant cleared-out cytoplasm secondary to glycogen deposition
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Small Round Blue Cell Tumor IHC
AB SCCA MM ML Ewing-PNET
RMS PDSS DRCT
PANK + +/- - +/- Rare + +
S-100 - + - +/- Rare +/- -
CD45 - - + - - - -
TdT - - + - - - -
Desmin - +/- - Rare + - +
CD99 - - +/- + +/- + Rare
AB, antibody; SCCA, small cell carcinoma; MM, melanoma; ML, lymphoma; PNET, primitive neuroectodermal tumor; RMS, rhabdomyosarcoma; PDSS, poorly differentiated synovial sarcoma; DRCT, desmoplastic small round cell tumor
CD 99
Results of additional ancillary testing…
• IHC negative for TdT, CD3, CD5, CD20, CD45, Mart-1, S-100, WT-1, CD57, panCK, CK20, desmin, synaptophysin, chromogranin
• EWSR1 FISH positive
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Diagnosis?
Cutaneous Ewing Sarcoma
Ewing sarcoma
• High-grade, small blue cell tumor affecting the long bones or vertebrae in children and young adults; male predominance
• ES and primitive neuroectodermal tumors (PNET)/peripheral neuroepithelioma are closely related tumors, considered as a single entity in the last WHO classification (Ewing Family of Tumors)
• 10-20% of cases are extraskeletal
• 5y survival: 68% for localized tumors, 39% for metastatic disease
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Primary cutaneous Ewing sarcoma
• Female predominance, later age (median 17 years), better outcome
• Might be due to early diagnosis and smaller tumor size
• Median tumor size 2.3 cm
• Predilection sites: lower limbs (38%), upper limbs (26%), head (20%) and trunk (16%)
• DD: Cutaneous metastases of osseous ES
• Metastasis in ca 10%, overall survival ca. 90%
Primary cutaneous Ewing sarcoma: Histology
• Rather small, sharply circumscribed, basophilic, dermal or subcutaneous tumor
• Monomorphous, confluent lobules or sheets of densely packed small round blue cells with clear eosinophilic cytoplasm, fine chromatin, small nucleoli
• Rich vascularization, extensive capillary network (+/- visible)
• Mitotic activity usually not prominent
• Histopathologic features indistinguishable from ES/PNET of the bone
• Useful feature: high glycogen content of tumor cells, strong PAS+
Primary cutaneous Ewing sarcoma: IHC / molecular
• IHC: 100% membranous CD99, 90% FLI-1
• CD99 is highly sensitive but lacks specificity: should always be used as part of a panel of immunostains
• ERG specific for tumors with ERG rearrangement
• May express epithelial markers, 25% + with AE1/AE3 (diagnostic pitfall)
• Translocation EWSR1: EWSR1-FLI1 (>95%), EWSR1-ERG (2%), can have false negative (other rearrangements possible)
• Detected via FISH or RT-PCR in fixed, paraffin-embedded tissues
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EWS (22q12) Break-apart probe
t(11;22), t(21;22) – EWS/PNET (FLI1/EWS, ERG/EWS)
t(11;22), t(21;22) - DSRCT (WT-1/EWS, ERG/EWS)
t(12;22) – Clear Cell Sarcoma (ATF1/EWS)
t(9;22) – ES Myxoid Chondrosarcoma (CHN/EWS)
t(16;22) – Myxoid/Round Cell Liposarcoma (CHOP/EWS)
Ewing & Ewing-like family tumors translocationsGene fusions, chromosomal rKaryotype Anatomic location Morphology expression markers references
Ewing sarcomaEWSR1-FLI1 t(11;22)(q24;q12) Bone or soft tissues
or cutaneousEwing sarcoma orso-called 'atypicalEwing sarcoma'
+++ FLI1 Delattre et al. (1994)
EWSR1-ERG t(21;22)(q22;q12) +++ ERG Sorensen et al. (1994)
EWSR1-ETV1 t(7;22)(p22;q12) Bone or soft tissues +++NSE, S100, DES, EMA Jeon al. (1995)
EWSR1-ETV4 t(7;22)(p21;q12) Extraosseous +++ Kaneko et al. (1996)EWSR1-FEV t(2;22)(q35;q12) Extraosseous +++ Peter et al. (1997)
Round cell sarcoma with EWSR1 -non ETS rearrangementEWSR1-NFATC2 t(20;22)(q13;q12) Bone So-called 'atypical
Ewing sarcoma'+++ None Szuhai et al. (2009)
EWSR1-SP3 t(2;22)(q31;q12) Bone or soft tissues So-called 'atypicalEwing sarcoma'
+++ NSE Wang et al. (2007)
EWSR1-PATZ1 inv(22) in t(1;22) Chest wall PNET +++ DES, keratins Mastrangelo et al. (2000)EWSR1-SMARCA5 t(4;22)(q31;q12) Lumbar spine So-called 'atypical
Ewing sarcoma'+++ NSE,
SynaptophysiSumegi et al. (2011)
Round cell sarcoma with non EWSR1-ETS rearrangementFUS-ERG t(16;21)(p11;q22) Chest wall Ewing sarcoma +++ ERG, NSE Shing et al. (2003)FUS-FEV t(2;16)(q35;p11) Bone (clavicle) Ewing sarcoma +++ None Ng et al. (2007)
Round cell sarcoma with CIC-DUX4 rearrangementCIC-DUX4 t(4;19)(q35;q13) Soft tissues URCS or so-called
'atypical Ewing sarcoma'
Weak focal WT1 Kawamura-Saito et al. (2006)
t(10;19)(q26;q13) ETV4
Round cell sarcoma with BCOR-CCNB3 rearrangementBCOR-CCNB3 inv(X)(p11) Bone URCS 50%+++ CCNB3 Pierron et al. (2012)
Undifferentiated round cell sarcomaNone (yet!) Non recurrent Variable URCS - Variable Fletcher (2008)
Abbreviations: PNET, peripheral neuroectodermal tumor: URCS, undifferentiated round cell saroma, +++, strong membranous expression; -, no expression.
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DDx small round blue cell tumors
• Ewing sarcoma/PNET (bone/soft tissue or cutaneous)
• Neuroblastoma
• Alveolar rhabdomyosarcoma
• Lymphoblastic lymphoma
• Desmoplastic small round cell tumor (DSRCT)
• Metastatic pulmonary small cell carcinoma and cutaneous neuroendocrine carcinoma (Merkel cell carcinoma)
• Mesenchymal chondrosarcoma
• Small cell osteosarcoma
• Poorly differentiated synovial sarcoma
Neuroblastoma
• Third most common pediatric tumor
• 96% before age 5, 25% are congenital
• Arise along sympathetic chain
• Up to 90% of patients have elevated urinary catecholamine metabolites
• CD99 -, neuroendocrine markers +
• No EWSR1 aberrations; MYCN amplification, deletion 1p
Neuroblastoma
Sheets of small round cells with little cytoplasm divided into small lobules by fibrovascular stromaRound dark nuclei
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Homer-Wright rosettes
Alveolar rhabdomyosarcoma
• Rare aggressive neoplasm of children and young adults
• Deep soft tissues of extremities
• Overall 5yr survival <50%
• Does not respond well to traditional chemotherapy
• Conventional: Immunoreactivity for desmin or myogenin/MyoD1 should be present; 15% CD99 +
• t(1;13) or t(2;13) characteristic of alveolar rhabdomyosarcoma
Alveolar rhabdomyosarcoma
Alveolar or solid growth pattern, variable rhabdomyoblastic differentiationUniform small round blue cellsFibrovascular septa, discrete nests, center discohesive, multinucleated giant cells
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Myogenin
Lymphoblastic lymphoma
• Usually children
• Aggressive; 2/3 curable with chemotherapy
• 85% B-cell, 10-20% T-cell
• IHC: B-cell markers, TdT (rarely negative), CD99 (membranous), CD179a/b+
• Surface IgG, cytoplasmic IgM, CD15, CD30, CD45 -
Lymphoblastic lymphoma
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Desmoplastic small round cell tumor (DSRCT)
• Malignant SRBCT with striking desmoplasia
• Mesothelial-lined spaces, rarely other locations
• Males 15-35 years of age
• >75% DOD in <5yrs
DSRCT
Sharply outlined islands of tumor cells separated by a desmoplastic stroma containing myofibroblasts and prominent vascularity
Metastatic pulmonary small cell carcinoma and MCC
• DD particularly when patients >45 y and superficial
• Metastatic PSCC r/o if no pulmonary involvement clinic/Rx
• Metastatic PSCC TTF1+ (- in Ewing)
• MCC has large cells, closely packed nuclei and little cytoplasm, frequently arranged in a trabecular pattern.
• MCC mainly in the dermis or subcutis, and 2/3 occur in patients >60 y
• MCC CK20+, CD99-
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Mesenchymal chondrosarcoma
• Bone or soft tissue, extraosseous location in ca. 20%
• Adolescents and young adults, but broad age range
• Biphasic pattern with islands of cartilage surrounded by sheet of small round cell (may spindle), hemangiopericytoma-like vascular pattern
• NSE, S‐100, CD99 & SOX9 +, Fli‐1 and ERG –
• HEY1‐NCOA2 fusion
Mesenchymalchondrosarcoma
Biphasic pattern: islands of cartilage surrounded by sheet of small round cell, hemangiopericytoma-like vascular pattern
Mesenchymalchondrosarcoma
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Small cell osteosarcoma
• Very rare form of osteosarcoma
• Adolescents in metaphysis of long bones
• Diagnosis can be made if osteoid identified only, but may be only focally present in the tumor/missed in small biopsy specimens
• Most express neural markers (NSE, CD57), some CK, actin
• CD99 may be positive
Small cellosteosarcoma
Uniform small round cells, osteoid, some spindled
Small cellosteosarcoma
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Poorly differentiated synovial sarcoma
• Malignant mesenchymal tumor with epithelial differentiation
• 10% soft tissue tumors
• Young adults, but any age
• Around the knee most common site, but any location
• High-grade sarcoma, significant potential for metastases and adverse outcome
• 5 yr. survival approximately 55%
• Biphasic, monophasic, poorly differentiated (round cell)
Synovial sarcoma
• CD99 expression common, particularly in PD tumors
• TLE-1 is a robust marker for SS• t(X;18) (p11.2;q11.2) (SYT-
SS1/2)
ES vs. alveolar rhabdomyosarcoma vs. poorly differentiated synovial sarcoma
Ewing sarcoma ARMS PDSS
Age 10‐25 yrs 10‐25 yrs 10‐30 yrs
Site Extremities/trunk Extremities/trunk Extremities
Histology Monotonous/small nucleoli
Alveolar pattern/giant cells
Epithelial structures
CD99 95% 25% 65%
CK/EMA 30% 50% 90%
Myogenin no >95% no
Fli‐1 80% no no
TLE‐1 no no >95%
FISH EWSR1 break‐apart FOXO1A break‐apart SYT break‐apart
RT‐PCR EWSR1‐FLI1/ERG PAX3/PAX7‐FOXO1A SYT‐SSX1/2
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Take home messages round cell pattern
• Wide differential, including epithelial, melanocytic, & hematopoetic neoplasms
– Rule these out before diagnosing a mesenchymal tumour
– Differential is often age dependent
• CD99, PanCK, S100, desmin, CD45 & TdT IHC narrows differential & informs use of additional ancillary tests
– Molecular testing for definitive classification increasingly important (e.g., CIC-DUX4,BCOR-CCNB3 sarcomas)
Pleomorphic pattern
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80-year-old female with an ulcerated left upper cheek
lesion
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IHC panel for common pleomorphic cutaneous SCT
Cytokeratin(wide
spectrum, HMW,
CK5/6)
S-100, SOX10
Melanocytic markers (HMB-45, Melan-A)
SMA Desmin
Endothelial markers (CD31,
CD34,ERG)
Sarcomatoid SCC + - - - - -
Desmoplastic melanoma
-/+ + -/+ - -/+ -
AFX - - - -/+ - -
Leiomyosarcoma -/+ -/+ - + +/- -/+
Angiosarcoma -/+ - - - - +
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S100
panCK
p63
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Diagnosis?
Atypical fibroxanthoma/ pleomorphic dermal sarcoma
Atypical fibroxanthoma (AFX)
• Histologically identical to malignant fibrous histiocytoma (MFH), but with largely benign behavior
• Almost always occurs in sun damaged skin
• Must be small (<1-1.5 cm), confined to dermis/subcutis, and completely visualized
• Diagnosis of exclusion
• No specific immunostains
• If does not meet criteria should be called pleomorphic dermal sarcoma (PDS) because higher risk of recurrence and mets
• Almost uniformly excellent prognosis following conservative tx; in one of largest series only 9/140 pts had recurrence; none had mets
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Atypical fibroxanthoma (AFX)
• Expansile dermal nodule on sun-damaged skin
• Less than 1.5 to 2 cm
• Confined to dermis or only minimal subcutaneous involvement
• Does not have extensive necrosis
• Bizarre cells with marked pleomorphism and easily identifiable mitotic figures
• Negative for S100, keratins, sma, desmin, CD34 & other vascular markers
AFX
AFX
AFX
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AFX
Atypical fibroxanthoma (AFX): DDx
• Sarcomatoid carcinoma: keratin positive; dysplasia in overlying epidermis
• Malignant melanoma: S100 positive; melanoma in situ
• Pleomorphic dermal sarcoma (AKA superficial undifferentiated pleomorphic sarcoma): larger than 2 cm, significant extension into subcutis or necrosis
• Spindle cell angiosarcoma (scalp): CD31 & ERG positive; areas of typical AS
• Leiomyosarcoma: perinuclear vacuoles, actin positive, desmin +/-
• Kaposi sarcoma: typically HIV +, HHV8 +
Sarcomatoid SCC
panCK
p63
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Desmoplastic melanoma
S100
Spindle cell angiosarcoma
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Typical AS at periph. of spindle cell AS
Pilar LMS
Pilar LMS
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KS
KS
HHV-8KS
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DM vs. AFX vs. SSCC vs. AS vs. KS
DM AFX SSCC AS LMS KS
Clinical
H&N H&N VariableRapid onset
Variable
Typically HIV
+/immunosuppressed
Pattern Packeted,short fasc.
StoriformStoriform, fascicles
Fascicles Fascicles Fascicles
MorphologySpindled Pleomorphic
Pleomorphic to spindled
Spindled Spindled Spindled
IHCS100,
SOX10+, CK-
S100, SOX10-, CK-,
SMA -/+, p63-/+
S100, SOX10-,
CK+, SMA-/+, p63+
S100, SOX10-CK+/-,
CD31 & ERG+
S100, SOX10, CK,
SMA, desmin+/-
S100, SOX10, CK,
HHV8, CD31, ERG+
Clue Sun-damage,
AJMH, Lymphs
Sun-damage, no epidermal
component
AK or in-situ SCC
Areas of typical
AS
Perinuclear vacuoles
HIV +, plasma
cells
80-year-old male with rapidly growing cutaneous nodule on
thorax
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Pleomorphic lipoblast
Pleomorphic spindle cell
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Diagnosis?
Primary cutaneous pleomorphic liposacoma
Pleomorphic liposarcoma
• WHO definition: Pleomorphic high-grade sarcoma with a variable number of pleomorphic lipoblasts
• Uncommon form of liposarcoma that rarely occurs in the skin and subcutis, usually deep soft tissues– Most common superficial variant of liposarcoma
• Aggressive
• 5% of liposarcomas, 20% pleomorphic sarcomas
• Extremities
• Elderly, M=F
• Overall mortality 50%
• Wide local excision +/- adjuvant chemotherapy
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Sites: retroperitoneum (7), scrotum (2), buttock (2), and abdominal cavity (1)11/12 MDM2 amplification
Sites: retroperitoneum (7), proximal lower extremity (3), chest wall (1), and neck (1)12/12 MDM2 amplification
• 16 superficial (dermal and subcutaneous)
• 2/16 metastasized, 1 died
• Even superficial tumors may follow an aggressive course
• Multivariate analysis: age > 60 years, central location, tumor size, and mitotic rate predictors for an adverse outcome
• Cave adequate sampling (lipoblastic zones/ cellular zones)
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Results cutaneous /subcutaneous pleomorphic LS
• Tumors located on the extremity (n=15), trunk (n=7), and head & neck (n=7)
• involved the dermis (n=4), dermis & subcutis (n=10), and subcutis (n=15)
• All were mitotically active high-grade sarcomas with either a pleomorphic spindled (n=24) or an epithelioid pattern (n=5) with variable extent of lipogenic differentiation
• MDM2 gene amplification was present in 3 of 26 cases
• Follow-up in 24 cases (median 48 mo): local recurrences (4/24) but no metastasis or death from disease.
• Conclusion: cutaneous and subcutaneous PLs, despite their high grade, have a much more favorable outcome compared with their deep-seated counterparts, most likely due to their small size and superficial location. The low incidence of MDM2 gene amplification indicates that most superficial PLs are unrelated to WDL/DL.
Differential: Pleomorphic liposarcoma
• Tumors with pleomorphic lipoblasts or pseudolipoblasts
– Other pleomorphic sarcomas that infiltrate fat (e.g., LMS, RMS, MPNST)
– Dedifferentiated liposarcoma or chondrosarcoma
Take home messages pleomorphic pattern
• Pleomorphic cutaneous soft tissue tumours: rule out sarcomatoid carcinoma, spindle cell/desmoplastic melanoma, spindle cell AS & LMS
• Pleomorphic sarcomas of soft tissue & bone: rule out component of a dedifferentiated liposarcoma (particularly retroperitoneal lesions) or chondrosarcoma, respectively– Thoroughly sample to find identifiable low grade component or
clues to specific dx (e.g. pleomorphic lipoblasts in PLS)
• Other sarcomas may be predominantly pleomorphic but also have identifiable low-grade areas (e.g., LMS, MPNST & RMS)– Line of differentiation may only be discernable with IHC
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Monomorphic spindle cell pattern
55-year-old female with a 6cm neck mass
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Diagnosis?
Solitary fibrous tumor
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Solitary fibrous tumor
• Described by Klemprerer & Rabin 1931
• Synonymous with hemangiopericytoma
– Not a tumor of pericytes
• Middle-aged adults
• First described in pleura, but wide anatomic distribution
– Subcutaneous (40%)
– Head & neck (10%)
• May present with hypoglycemia
– Produces insulin like growth factor I or II
• Small unpredictable risk of metastasis
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Pathologic features: Solitary fibrous tumor
• Well-circumscribed, 1-25cm (median 5-8 cm)
• Wide range of histologic features, ranging from cellular to fibrous with intermediate forms between the two ends of the spectrum
– Spindled to ovoid cells arranged in alternating hyper- & hypocellular areas in a “patternless pattern”, cellular variants more monomorphic
– Myxoid & microcystic change, nuclear palisading, chronic inflammation and mast cells common
– “Staghorn” branching vessels may be seen in all variants
– Predominantly myxoid SFT difficult to recognize
• Mitoses sparse & necrosis rare
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• CD34 (95%)
• CD99
• BCL2
• EMA (33%)
• SMA (33%)
• Some cases may show focal S100, CK or desmin positivity
• STAT6 (translocation)
Solitary Fibrous Tumour: IHC
STAT6
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Add stat6 paper
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Solitary fibrous tumor
• Criteria for malignancy– Increased cellularity
– Mitotic activity (>4 mitoses/10HPF)
– Necrosis
– Some dedifferentiate
• Unpredictable clinical course, but most benign– 5-10% recur or metastasize (lungs, bone liver)
– Vast majority that are aggressive are histologically malignant, but rarely benign SFT metastasize
• Complete excision with tumor-free margins– Radiotherapy for local control of malignant examples should be considered
Differential: SFT
• Synovial sarcoma– Almost always CD34-, t(X;18) SYT-SSX, STAT6-
• MPNST– Less circumscribed & less positive for CD34, arise from nerves
• LGFMS– More uniform, less cellular and well circumscribed, MUC4+, STAT6-
• Desmoplastic mesothelioma (fibrous/pleural SFT)– CK+, CD34 & STAT6-, cytologic atypia
• Deep fibrous histiocytoma (subcutaneous SFT)– More prominent & uniform storiform growth pattern, secondary elements,
CD34 & STAT6-
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Deep FH
Deep DF
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80-old-man with a nodule on the right dorsal foot, Rule out BCC
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AE1/3
Synovial Sarcoma
• Malignant mesenchymal tumor with epithelial differentiation
• 10% STS
• Young adults, but any age
• Around the knee most common site, but any location
• High-grade sarcoma, significant potential for metastases and adverse outcome
• 5 yr survival approximately 55%
Synovial Sarcoma
• Most litigated STT!
• Monophasic and Biphasic
• Biphasic pattern with epithelioid cell component forming glands, & a spindle cell component resembling fibrosarcoma
• AE1/3, CK7, CK19, EMA, TLE1+, focal S-100 30%
• t(X;18) SYT-SSX
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SS
SS
SS
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SSSS
Ancillary Studies
• Limited LMW & HMW cytokeratins and EMA
• TLE1 (not absolutely specific, but diffuse positivity a good bet)
• 30% S-100 protein expression
• CD34 negative (I have seen one exception)
• CD99 expression common, particularly in PD tumors
• t(X;18) (p11.2;q11.2) (SYT-SS1/2)
TLE-1
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TLE-1
• TLE proteins (human homologues of Groucho)
• Transcriptional corepressors that inhibit Wnt signaling and other cell fate determination signals
• Established role in repressing differentiation
• Imperfectly specific
Terry J, Saito T, Subramanian S, et al. Am J Surg Pathol. 2007 Feb;31(2):240‐6
SYT (18q11) - Break Apart Probe
Synovial sarcoma positive result
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Differential: Synovial sarcoma
• MPNST– Lacks SYT/SSX translocation, arises from nerves
• Cellular schwannoma– Strong and diffuse S100
• Fibrosarcomatous DFSP– Areas of classic DFSP
• Cellular blue nevi– Melanocytic markers
• Solitary fibrous tumor– CD34 & STAT6+
• Small round blue cell tumors (poorly differentiated SS)
Cellular Blue Nevus Family
• Present in childhood to middle age
• Buttock, sacroccygeal region most common, followed by scalp, face, dorsal hands and feet
• Heavily pigmented lesions, often mistaken for melanoma clinically
• Amelanotic BN, flesh colored papules
• Benign
CBN
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CBN
CBNS-100
CBNHMB45
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DFSP
Fibrosarcomatous DFSP
• Sarcomatous foci should constitute at least 5-10% of tumor
• Fascicular rather than storiform growth
• Increased mitotic rate (7-15 mits/10hpf)
• Significance is unclear
Fibrosarcomatous DFSP
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Fibrosarcomatous DFSP: fascicular growth
Fibrosarcomatous DFSP: increased mitoses
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MPNST
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MPNST
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MPNST
PDSS
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PDSS
PDSS
Take home messages monomorphic spindle cell pattern
• Highly cellular mesechymal spindle cell tumors with fascicular growth patterns not uncommonly encountered
• Most common ddx: MPNST, cellular schwannoma, synovial sarcoma, SFT & fibrosarcomatous DFSP
• Combining light microscopy & IHC a specific line of differentiation can usually be detected
• In difficult cases molecular studies may be needed to differentiate translocation-associated monomorphic spindle cell neoplasms for morphologic mimics
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Myxoid pattern
Myxoid SST: Key features to evaluate
• Cellularity– Extremely low= myxoma, relatively high= fasciitis
• Arrangement of cells with respect to one another– Little cell-cell contact= MLS, touching= ESMC
• Nuclear pleomorphism– Absent= intramuscular myxoma, high degree of atypia= MFS
• Underlying vasculature– Low vascularity= intramuscular myxoma, intricate vasculature= MLS & MFS
• (Alcian blue pH 2.5) evaluation of myxoid stroma (rarely)– Hyaluronic acid-rich= intramuscular myxoma, MLS, MFS (pretreatment with
hyaluronidase results in loss of positivity)
– Chondroitin sulfate-rich= ESMC & chordoma (hyaluronidase resistant positivity)
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Case 9: 30-year-old male telephone lineman with 2.5cm right palmar mass, first noticed after hitting his hand while roofing. Increasing in size over the
last 10 months
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302
303
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305
306
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Diagnosis?
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Myxoinflammatory fibroblastic sarcoma (MIFS)
MIFS: Clinical
• Distinct low-grade sarcoma of distal extremities characterized by a mixture of myxoid, inflammatory & hyalinized zones
• Acral sites; 2/3 upper extremity, 1/3 lower extremity, rarely proximal trunk
• Potential for destructive local recurrence; rare lymph node & lung metastases
• Middle-aged adults; no sex predilection
• Slow-growing, occasionally painful mass
• Frequent local recurrence, occasionally necessitating amputation; adjuvant radiotherapy for selected cases
MIFS: Pathologic Features
• Hyalinized, inflammatory & myxoid zones
• Bizarre tumor cells with giant macronucleoli (virocyte- & Reed-Sternberg-like)
• Pseudolipoblasts in myxoid areas
• Mixed acute and chronic inflammation
• Low mitotic rate
• Infrequent necrosis
• CD34 + 20%, occasional focal CK & SMA
• 18% TGFBR3 &/or MGEA5 rearrangements*– Hemosiderotic fibrolipomatous tumor
– Pleomorphic hyalinizing angiectatic tumor
*Boland & Folpe. Hemosiderotic fibrolipomatous tumor, pleomorphic angiectatic tumor and myxoinflammtory fibroblastic sarcoma: Related or not? Adv Anat Pathol 2017 Apr 3 (Epub ahead of print)
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MIFS
MIFS
MIFS
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MIFS: Differential
• Infection/inflammatory process– Special stains and cultures+
• Myxofibrosarcoma– Distinct vessels, more atypia, less inflammation
• Giant cell tumor of tendon sheath– Rarely myxoid and admixed with areas of typical GCTT, osteoclast type giant
cells and secondary elements often present
• Hodgkin lymphoma– Hematolymphoid markers positive, not as myxoid
• Inflammatory myofibroblastic tumor– Marks with smooth muscle markers and ALK in a subset, no virocyte- or
ganglion-like atypical cells typically present, more spindled, less myxoid
M. Cheloniae
M. Cheloniae
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GCTTS
GCTTS
GCTTS
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Hodgkin lymphoma
Hodgkin lymphoma
CD30 CD15
MFS-Myxoid MFH
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MFS-Myxoid MFHMFS-Myxoid MFH
IMT
IMT
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Take home messages myxoid pattern
• Certain features are more important to assess for this pattern
• Clinical – Younger patients (MLS), older patients (MFS)
• Growth pattern– Mutinodular (ESMC, MFS, MIFS), diffuse (fasciitis), infiltrative (aggressive
angiomyxoma)
• Presence or absence of vasculature– Little to none (myxoma), plexiform (MLS), curvilinear (MFS), arcuate (LGFMS)
• Cellularity– Low (myxoma), high (MFS)
– Cells touching (ESMC), little cell-to-cell interaction (MLS)
• Inflammation– MIFS (chronic inflammation), Intramuscular myxoma (absent)
Acknowledgements
• Thank you to my colleagues Steve Billings and Patrick Shenjere for sharing PPT slides used in this talk.
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Congrats soldier you have graduated from boot camp!
