Update on Cutaneous Mesenchymal Tumors. Thomas Brenn
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1 Update on Cutaneous Mesenchymal Tumors Thomas Brenn
2 Cutaneous Mesenchymal Tumours Wide morphological and biological spectrum Myofibroblastic, smooth muscle, neural, vascular, apidocytic, undifferentiated; rare rhabdomyoblastic or osseous Spindle cell, epithelioid, pleomorphic, vasoformative, fat forming Benign to intermediate and high-grade malignant Vast majority is benign Distinctive behavior of malignant tumors presenting in the skin High grade cutaneous sarcomas exceptionally rare
3 Case History 80 year-old male rapidly enlarging, crateriform nodule on the scalp clinical suspicion of keratoacanthoma or squamous cell carcinoma unremarkable past medical history diagnostic curettage was a performed
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10 SMA CD10
11 AE1/3 desmin CD34 S100
12 Immunohistochemistry NEGATIVE MNF116 CK5/6 AE1/3 EMA P63 Desmin S100 Melan a CD31 CD34 ERG
13 Diagnosis: Pleomorphic Dermal Sarcoma
14 Follow-up: Negative Re-excision Pulmonary metastasis 8 months after biopsy Rapidly progressive disseminated disease Patient died 12 months after biopsy
15 Pleomorphic Dermal Sarcoma Closely related to AFX: Same clinical setting, similar clinical presenting features Similar histologic and immunohistochemical features Similar underlying genetic events BUT Invasion of subcutis, tumor necrosis, LVI and PNI confer potential for aggressive behaviour
16 Pleomorphic Dermal Sarcoma -Clinical Features- Sun-damaged skin Head and neck; scalp Elderly Strong male predilection Rapid growth Ulceration and bleeding 2.5 cm median Miller K, et al. Am J Surg Pathol. 2012; 36(9):
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25 Pleomorphic Dermal Sarcoma -Immunohistochemistry- Diagnosis of exclusion No positive discriminatory histological or immunohistochemical features Consistently negative: S100 multiple CK, especially HMW-CK Desmin CD34
26 CD68 CD10 SMA EMA
27 S100 Melan A Fli-1 CD31
28 Pleomorphic Dermal Sarcoma -Genetics- Frequent mutations in TP53 and TERT promoter FAT1 NOTCH1/2 CDKN2A But no difference AFX vs PDS Griewank KG, et al. Mod Pathol. 2014; 27(4): Helbig D, et al. Oncotarget. 2016; 7(16): Griewank KG, et al. Mod Pathol Mar;31(3):
29 Pleomorphic Dermal Sarcoma -Prognosis- Risk for local recurrence (30%) Metastasis (10-20%) to skin, soft tissue, Lung Rare mortality (up to 20%) Behavior likely more aggressive but f/u limited due to advanced age at presentation and significant co-morbidities Miller K, et al. Am J Surg Pathol. 2012; 36(9): Tardío JC, et al. J Cutan Pathol. 2016; 43(2):
30 Pleomorphic Dermal Sarcoma -Prognosis- Presence of metastatic disease associated with high associated mortality (50%) Wang WL, et al. Am J Dermatopathol. 2015; 37(6):
31 Wang WL, et al. Am J Dermatopathol. 2015; 37(6):
32 Pleomorphic Dermal Sarcoma -Treatment- Complete excision with negative margins Consideration for adjuvant RTX if surgical clearance cannot be achieved Clinical follow-up
33 Atypical Fibroxanthoma / PDS Beware: Partial sampling, shave, curettage bx
34 AFX / PDS -Differential Diagnosis- Pleomorphic tumors on sun-damaged skin: Melanoma Poorly differentiated SCC Poorly differentiated angiosarcoma MPNST, DFSP, Leiomyosarcoma
35 Spindle Cell Squamous Cell Carcinoma MNF116
36 Spindle Cell Melanoma S100 Melan a
37 Pleomorphic Dermal Sarcoma Cutaneous Angiosarcoma Thum C, et al. Ann Diagn Pathol. 2013;17(6):502-7.
38 Pleomorphic Dermal Sarcoma -DDx- Cutaneous angiosarcoma: Significant clinical and morphological overlap Important distinction due to aggressive behaviour of cutaneous angiosarcoma
39 Pleomorphic Dermal Sarcoma Cutaneous Angiosarcoma CD31 CD31 Fli-1 Fli-1
40 Pleomorphic Dermal Sarcoma Cutaneous Angiosarcoma ERG ERG
41 Case History 81 year-old female Tumor on left arm?scc
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43 CD10 cytokeratin S100 Melan A
44 Diagnosis: Atypical Fibroxanthoma?
45 Melan A
46 Melan A S100
47 Diagnosis: Dedifferentiated (sarcomatoid) melanoma
48 Dedifferentiated melanoma The availability of CD10 and PC1 as positive markers of AFX means it is no longer just a diagnosis of exclusion.
49 Dedifferentiated melanoma
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52 Case History 40 year old male with a 5 cm nodular tumor on the right lateral hip,?eic
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59 CD34 CD34
60 Diagnosis: Pigmented DFSP with fibrosarcomatous and myoid differentiation ( Bednar tumor )
61 Dermatofibrosarcoma Protuberans Clinical Presentation Young adults (20-40 years) Trunk > head & neck and proximal extremities Slowly growing plaque >> nodule Longstanding history Size: ~5cm, often underestimated clinically
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67 CD34
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69 Dermatofibrosarcoma Protuberans Cytogenetics Reproducible cytogenetic abnormality: t(17;22) Col1A1 and PDGFB genes Rarely Col6A3 and PDGFD genes (breast tumors) Dickson BC, et al. Genes Chromosomes Cancer Sep;57(9): Dadone-Montaudié B, et al. Mod Pathol Nov;31(11):
70 Prognosis and Treatment High rate of local recurrence Low metastatic potential Surgery: Wide local excision Modified Mohs surgery at anatomically difficult sites
71 Dermatofibrosarcoma Protuberans Variants Fibrosarcomatous DFSP Pleomorphic DFSP DFSP with myoid nodules Giant Cell Fibroblastoma Pigmented DFSP ( Bednar tumor ) Myxoid DFSP Atrophic DFSP
72 Myxoid DFSP
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76 CD34
77 Fibrosarcomatous DFSP
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