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.