An Overview of Cutaneous Vascular Neoplasms
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1 An Overview of Cutaneous Vascular Neoplasms By Konstantinos Linos MD, FCAP, FASDP Bone, Soft Tissue and Dermatopathology Assistant Professor of Pathology Dartmouth-Hitchcock Medical Center Geisel School of Medicine at Dartmouth Hanover, NH, USA
2 Financial disclosures Book Royalties
3 Benign Vascular Tumors
4 Epithelioid Hemangioma Most commonly present on the Head & Neck area Often periauricular Middle-aged adults, female predominance However wide range of cutaneous location Rarely intravascular Also affects bone Can be multifocal in 25%
5 Microscopic features Circumscribed dermal or subcutaneous lobular proliferations of well-formed capillaries Usually surrounds a large vessel Inflammatory infiltrate Lymphocytes (sometimes germinal centers), eosinophils, histiocytes and plasma cells Involved capillaries retain lumina Lined by epithelioid cells Variably hobnail Mitoses may be seen but not atypical
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9 IHC Positive for vascular markers CD31, CD34, ERG Also positive for D2-40 Pitfall!! Immunoreactivity for EMA and keratins may be seen
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16 Cutaneous Epithelioid Angiomatous Nodule Most cases solitary as small violaceous superficial nodules Occasional multiple or eruptive forms Unilobular dermal and circumscribed Large solid sheets of epithelioid endothelial cells Intracytoplasmic vacuoles No significant pleomorphism Conspicuous mitotic activity but no atypical
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20 Symplastic Hemangioma Degenerative-type pleomorphism of vascular smooth muscle and interstitial cells Pre-existing long-standing vascular neoplasm Probably due to inflammation or hypoxia Extremities or face of young to elderly adults No sex predilection Characteristically bizarre pleomorphic cells within the walls of vascular channels Occasional mitotic figures are seen
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22 Spindle Cell Hemangioma Superficial subcutaneous or dermal erythematous to violaceous nodule Predilection for distal extremities of young adults, especially hands Sometimes multiple small nodules Subset of cases a/w Maffucci Syndrome Multiple spindle cell hemangiomas Enchondromas Increased risk for chondrosarcoma A/w IDH mutations
23 Microscopic Features Circumscribed subcutaneous or dermal tumors Half partially intravascular Biphasic composition Cavernous vascular spaces Solid spindle cell areas Cavernous vessels may contain phleboliths Spindle cell areas with slit-like spaces and intracytoplasmic lumina Mitotic activity and atypia low
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29 Acquired Tufted Angioma Aka Angioblastoma of Nakagawa Most frequently in early childhood as progressive enlarging macule in head & neck area Cases with Kasabach-Merritt Syndrome have been described Less frequently than kaposiform hemangioendothelioma
30 Microscopic features In dermis or subcutis with so-called cannonball pattern of spherical welldermacated nodules Dilated lymphatic channels at the periphery Single endothelial cell layer surrounded by SMA positive pericytes Pericytes can be prominent and have a spindled appearance D2-40 positive in lymphatics and partially in capillary network
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33 Vascular Tumors of Intermediate Malignancy
34 Kaposiform Hemangioendothelioma Vary rare tumor of infancy and childhood Most frequently as multinodular lesions in peripheral soft tissue or skin Followed by retroperitoneum Subset of cases a/w lymphangiomatosis Most patients in the first two years Has been reported in adults
35 Microscopic features Plexiform mass of lobules separated by fibrous septa Capillary hemangioma-like areas alternating with spindle cells Spindle cells slit-like lumina with mild atypia and few mitoses Glomeruloid structures characteristic Small vessels surrounded by pericytes and hyaline globules At the periphery striking lymphatic proliferation with ectatic vascular spaces
36 Immunohistochemistry Endothelial cells express CD31, CD34 and ERG SMA highlights the pericytes Lymphatic markers (VEFG3, D2-40, Prox1) are positive both in the lymphatic channels at the lobule periphery and spindle cells GLUT1 is negative
37 Prognosis May show regional perinodal soft tissue involvement Not been reported to produce distal metastases Can be infiltrative and retroperitoneal cases can extensively infiltrate surrounding organs Can induce Kasabach-Merritt Syndrome Thrombocytopenia and consumption coagulopathy Related to tumor size and location 10% lethal secondary to KMS complications
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41 D2-40
42 Papillary Intralymphatic Hemangioendothelioma (PILA) Aka Dabska tumor Closely related to retiform hemangioendothelioma Most in infants and children Some cases congenital Up to 25% in adults Single slowly growing nodule or plaque Most cases skin and superficial tissue of head and neck, trunk or extremities
43 Microscopic features Numerous and dilated, thin-walled lymphatic like spaces line by bland hobnail endothelial cells Intravascular papillae lined by hobnail endothelial cells as well Papillae containing a collagenous core Mononuclear inflammatory component may be present Usually not prominent
44 IHC Immunophenotype that resembles normal lymphatic endothelium CD31, CD34, ERG VEGFR3, podoplanin Lack of actin-positive cuff of pericytes
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47 Retiform Hemangioendothelioma Superficially located, mainly occurs in adults Elongated-shaped vessels resembling rete testis Similarly to PILA lined by hobnail endothelial cells and a/w lymphocytes Intravascular papillary projections absent or very few Closely related to PILA Hobnail Hemangioendotheliomas
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49 Epithelioid sarcoma-like/pseudomyogenic hemangioendothelioma Typically young adults with marked male (4:1) predilection Rare soft tissue of intermediate biological potential Propensity for local recurrence or frequent (and characteristic) development of additional nodules in the same region Metastasis is rare Conservative management is the mainstay of therapy
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51 Radiologic findings Diagnostic Pathology: Soft Tissue Tumors 2nd Ed 2015, Elsevier
52 Microscopic findings Histopathology 2016 May;68:776-95
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55 Immunohistochemistry POSITIVE CKAE1/3 ERG CD31 (variable) AE1/AE3 NEGATIVE CD34 INI-1 (SMRCB1) is retained AE1/AE3 INI1 CD31 ERG
56 Other Differential Diagnosis Spindle cell squamous cell carcinoma Cellular benign fibrous histiocytoma Smooth muscle neoplasms Epithelioid Hemangioendothelioma
57 Molecular Recurrent balanced translocation t(7;19)(q22;q13) Fusion of SERPINE1 and FOSB genes To date this translocation has not been identified in other soft tissue tumors
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62 WHO 2013 definition Locally aggressive, rarely metastasizing vascular neoplasm, containing an admixture of histologically distinct components Chiefly in adults Composite Hemangioendothelioma Very rare pediatric or congenital cases Predominantly skin and superficial soft tissues High rate of local recurrence (50%) Low risk of lymph node (6%) or distant metastases(1%)
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68 CD31 Synaptophysin
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70 D2-40 Synaptophysin
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72 Malignant Vascular Tumors
73 Epithelioid Hemangioendothelioma (EHE) and CAMTA1 Rare low-grade, malignant vascular neoplasm that shows endothelial differentiation Less aggressive than angiosarcoma Risk of metastasis in ~ 20-30% of cases Death in approximately 15% of cases
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75 Clinical Features Affects patients of all ages but rare during childhood Typically solitary lesion on the extremities Can involve larger preexisting vessels Multiple cutaneous nodules!!!!metastasizing deep soft tissue or osseous EHE should be ruled out!!!!
76 Microscopic findings Diagnostic Pathology: Vascular 2016 Elsevier
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79 Immunohistochemistry POSITIVE CD31 CD34 ERG AE1/AE3 in 25% of cases NEGATIVE S100 protein Desmin EMA CD31
80 Molecular Recurrent translocation t(1;3)(p36;q25) involving WWTR1 (3q25) and CAMTA1 (1p36) Approximately 90% of EHE with classic morphology and not identified in histologic mimics A subset shown to harbor YAP1-TFE3
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83 CAMTA1
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86 TFE3 TFE3 is a member of the microphthalmia (MiT) family of transcription factors, which includes MiTF, TFEB, TFEC, and TFE3 Although TFE3 is ubiquitously expressed in humans, native TFE3 protein is usually not detected by routine immunohistochemical methods
87 TFE3 Alveolar soft part sarcoma Xp11 translocation renal cell carcinoma melanotic Xp11 translocation renal cell carcinoma A subset of PEComas Epithelioid hemangioendotheliomas
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89 Antonescu et al, Genes, Chromosomes and Cancer 52, , 2013
90 CD31 TFE3 CAMTA1
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92 Angiosarcoma Angiosarcoma arises in four typical clinical settings: Chronically sun-damaged skin, particularly the scalp or face Sporadic visceral angiosarcoma In the setting of chronic lymphedema (eg, after mastectomy in Stewart-Treves syndrome) In areas of prior therapeutic radiation, such as for the management of breast carcinoma.
93 Atypical vascular proliferations, which have been described under various nomenclature designations, occur in areas of prior radiation In some cases may be difficult to distinguish from vasoformative angiosarcoma.
94 MYC MYC proto-oncogene is a transcription factor located on the long arm of chromosome 8 (8q24.21) Nuclear expression of MYC occurs in the vast majority of secondary angiosarcomas Only very rarely seen in primary angiosarcoma Not detected in atypical or benign vascular lesions occurring in irradiated skin.
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98 Angiosarcoma FISH MYC
99 Angiosarcomas Case 1 Case 2
100 Atypical Vascular lesion (AVL)
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102 Conclusion MYC immunohistochemistry is therefore useful in differentiating atypical or benign vascular lesions occurring in irradiated skin from secondary postradiation angiosarcomas.
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106 CD31 ERG
107 KonstantinosLin
21/07/2017. Hobnail endothelial cells are not the same as epithelioid endothelial cells
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