Post on 14-Sep-2020
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PathologieProf. Dr. med. Katharina Glatz
Soft Tissue Tumors of the SkinFibrohistiocytic Tumors: Histopathology 2010, 56:148-165
2020-03-02
DERMATOFIBROMA VARIANTS
Clinically important variants and differential diagnoses F. XIIIa
Variants of Dermatofibroma
Clinically important variantsHistopathology 2000; 36:529-539Histopathology 2010; 56:148-165
Cellular Dermatofibroma
Characteristics5% of dermatofibromasInfiltration of superficial subcutisCellular spindle cell fasciclesIncreased proliferative activityCentral tumor necrosisMore frequently SMA+Peripheral expression of CD34and Desmin DD: DFSP
Up to 26% local recurrence
Complete excision
Histopathology 2010; 56:148-165
Aneurysmal Dermatofibroma
Characteristics<2% of dermatofibromasPredilection for lower limbsRapid recent growth due to hemorrhageLarge and cellularInfiltration of deep soft tissuesBlood filled spaces without endothelial lining
19% local recurrence(usually less than 2% in conventional FH)
Complete excision
Histopathology 2010; 56:148-165
Atypical Dermatofibroma
CharacteristicsBackground of common DFSpindled fibroblast/myofibroblast-like cellsPleomorphic histiocyte-like cellsMultinucleated giant cells3 mitoses/10 HPF on averageOccasional atypical mitosesNecrosis and deep infiltration possible
14% local recurrenceRarely distant metastases
Complete excision
Histopathology 2010; 56:148-165 American Journal of Surgical Pathology 2002; 26(1):35-46
Dermatofibroma of the Face
CharacteristicsVery rare localisationRarely suspected by the clinicianIll-defined Infiltration of deep structuresMore aggressive subtypesSMA+ spindle cell fascicles
High rate of recurrence (18.5%)(usually less than 2% elsewhere)
Complete/wide excision
Am J Dermatopathol 2001; 23:419-426
49 y ♂
Adnexal tumor on the proximal calf
HMB-45 S100
Factor XIIIa
ALK-1
Diagnosis:Epithelioid cell histiocytoma
• initially described in 1989
– “epithelioid cell histiocytoma”
• considered a morphologic variant of cutaneous fibroushistiocytoma
• at least 50% epithelioid morphology
• some distinct features:– “grenzzone” generally lacking
– tends to lack lateral entrapment of collagen
– usually lacks a prominent infiltrate of foamy histiocytes and lymphocytes
– EMA + (65%)
• such differences have led some authors to suggest that epithelioid fibrous histiocytoma may be a distinct entity
Morphologic Features
Histopathology. 2010; Mod Pathol. 2015
Int J Biochem Cell Biol. 2014; J Cutan Pathol. 2014; Br J Dermatol. 2015
Molecular Evidence
IHC:
• ALK (5A4; Leica Biosystems)
• ROS1 (D4D6; Cell Signaling Technology)
– in ALK – cases onlyMod Pathol. 2015
• FISH (dual-color break-apart probe; Abbott Molecular) in 14 ALK + and 4 ALK - cases
• Rearrangement in all evaluable ALK + cases
– 12 cases balanced ALK rearrangement
– one case unbalanced (with loss of the 5′ signal)
– percentage of nuclei with rearrangement 20-70%
• No rearrangement in ALK - cases
Molecular Evidence
Differential
Diagnoses
IHC/
Molecular
Findings
Reference
Cellular neurothekeoma +NKI/C3, CD10, PGP9.5
-S100, Melan A, GFAP
Am J Surg Pathol.
2007;
31(7):1103-14
Cutaneous syncytial
myoepithelioma
+ EMA, S100, GFAP, SMA, p63
- ALK
EWSR1 rearrangement
Am J Surg Pathol.
2013;
37(5):710-8
Epithelioid sarcoma +EMA, CK, CD34
INI1 loss
Am J Surg Pathol.
2009; 33(4):542-50
Spitz tumors + HMB45, MelanA, S100
ALK, ROS1, NTRK1, BRAF, RET kinase fusions
Nat Commun.
2014;5:3116
"Wiesner" nevus + HMB45, MelanA, S100
BAP1 loss, BRAF V600E mut.
Am J Surg Pathol.
2013; 37(2):193-9
«Wiesner nevus»
«Wiesner Nevus»
BRAF V600E
BAP1
Melanocytic tumors with germline mutations in BAP1 first described by Thomas Wiesner. Marker for a hereditary BAP1-associated cancer syndrome.Nat Genet 2011; 43(10): 1018–1021.
Sporadic combined BAP1-/BRAFmut. melanocytic tumors. Am J Surg Pathol. 2013; 37(2):193-9
Angiomatoid Fibrous Histiocytoma
WHO blue books skin
0.3% of all soft tissue tumorsSubcutaneous tumorIntermediate malignant potentialAll ages (peak first two decades)
50% desmin +, MYOD1-, Myogenin-EMA, CD99, CD68 +/-
EWSR1-CREB1 fusion in > 90%
Dermatofibrosarcoma Protuberans
DFSP1% of all sarcomasLow grade, locally aggressivefibroblastic neoplasmCD34+ S100- Desmin- CK-COL1A1-PDGFB fusion gene
Important variantsMyxoid DFSPSuperficial plaque-likeFibrosarcomatous
Pathology 2014; 46(2):149-159
Fibrosarcomatous DFSP
Characteristics10-20% of DFSPsMetastases Abrupt or gradual transformationExpansive growth Cellular fascicles Increased atypiaIncreased proliferationLoss of CD34 expressionIncreased p53 expression
Imatinib mesylate as therapeutic optionJ Clin oncol 2005;23:866-873
Pathology 2014; 46(2):149-159Ki-67 CD34
SPINDLE CELL TUMORS IN SUN-DAMAGED SKIN
AFX, pleomorphic dermal sarcoma and DD
Atypical Fibroxanthoma (AFX)
J Cutan Pathol 2010; 37(3):301-309.
Atypical Fibroxanthoma (AFX)
J Cutan Pathol 2010; 37(3):301-309. Morphological and immunohistochemical characteristics of AFX...
Atypical Fibroxanthoma (AFX)
Diagnosis of exclusion
No confirmative IHC (CD68, CD10, CD99 not helpful!)
Minimal Panel:negative reaction: CK22, CK5/6, ERG, Desmin
S100 (dendritic cells+)
Additional markers depending on morphology
AFX or Pleomorphic Dermal Sarcoma?
AFX versus pleomorphicdermal sarcoma?Superficial biopsy
?
Atypical Fibroxanthoma (AFX)
AFX versus pleomorphicdermal Sarcoma?
Do not answer this question in a superficial biopsy!Ask for complete excision!
Atypical Fibroxanthoma (AFX):
Growth into superficial subcutaneoustissue with expansile and well demarcateddeepest margin allowed
Growth around the nerve, but withoutInfiltration of the perineural space
Diagnosis of exclusion
Complete local excision is curativeSmall risk for local recurrenceNo metastasesNo Mortality
J Cutan Pathol 2010; 37(3):301-309. Morphological and immunohistochemical characteristics of atypical fibroxanthoma...
Pleomorphic Dermal Sarcoma
Pleomorphic Dermal Sarcoma:
Invasion of deep subcutis/muscle/fascia> 2cmTumor necrosis 53%L1 26%, Pn1 29%
Risk for local recurrenceMetastasisRare Mortality
J Cutan Pathol 2010; 37(3):301-309.Am J Surg Pathol 2012; 36(9):1317-26.