10/25/19 Vascular Lesions to Look Out For Adnan Mir, MD, PhD Dermpath Diagnostics Port Chester, New York Assistant Professor Pediatric Dermatology and Dermatopathology Dermpath New York Medical College Diagnostics Disclosures I have no relevant financial conflicts of interest I will not mention off-label uses of FDA-approved medications 62 year old man Site: Left cheek Clinical: Facial fullness for seven months Asympatomatic R/o Morbihan, rosacea, seborrheic dermatitis 1 10/25/19 61 year old woman Site: Left cheek Clinical: Bleeding ulcer on abdomen Obesity, Pulmonary HTN Harker et al, J Cut Pathol 2017 Jan;44(1) 2 10/25/19 Cutaneous Angiosarcoma Angiosarcoma of the face/scalp first described in 1964 as malignant angioendothelioma of the skin 1% of sarcomas, 1/100,000 incidence Distinct behavior and presentation among angiosarcomas: Face, scalp – Wilson-Jones Lymphedema – Stewart-Treves Radiation-induced Epithelioid 3 10/25/19 Cutaneous Angiosarcoma Clinical presentation Typically asymptomatic Bruise-like Violaceous papules, plaques, nodules Clinical impressions often: Hematoma, rosacea, eczema, seborrheic dermatitis, hemangioma, xanthelasma, cellulitis, angioedema Cutaneous Angiosarcoma Epidemiology and predisposing factors Average age 70 M:F = 2:1 Chronic sun exposure? Overall, unknown etiology Cutaneous Angiosarcoma Pathophysiology Mutations detected in P53 (>50%) KRAS PTPRB Angiogenesis PLCG1 Upregulated: NTSR1, ANKRD1, CDKN2C, KDR 4 10/25/19 Cutaneous Angiosarcoma Histologic features Infiltrative growth pattern Well-differentiated Inter-anastamosing Easily identified endothelial channels cells and vascular spaces Beware of sampling error Dissect collagen, surround adnexae Poorly-differentiated Multi-layering of variably Epithelioid or spindled cytology atypical cells Elina Shustef et al. J Clin Pathol 2017;70:917-925 5 10/25/19 Cutaneous Angiosarcoma Workup CD34 Fairly sensitive – Low specificity CD31 Very sensitive – Better specificity ERG Very sensitive – Even better specificity Fli1 Very sensitive – also expressed in LMS, AFX, melanoma, SCC Others Claudin-5, vWF, BNH9, FVIII-related Ag, D2-40, VegFR3 c-MYC Secondary angiosarcoma CD98 Expression correlates with worse prognosis Cutaneous Angiosarcoma Other tools C-Myc amplification by FISH Some data showing more common in post-radiation than primary Questionable practical use Cep8 Harker et al, J Cut Pathol 2017 Jan;44(1) C-MYC Cutaneous Angiosarcoma Differential Diagnosis Angiolymphoid hyperplasia with Sinusoidal hemangioma eosinophils Spindle cell hemangioma Infantile hemangioma Targetoid hemosiderotic Kaposi sarcoma hemangioma Hemangioendotheliomas Progressive lymphangioma Pyogenic granuloma Poorly-differentiated sarcomas 6 10/25/19 32 year old woman Site: Left breast Clinical: Hemangioma vs amelanotic melanoma vs SK vs other 7 10/25/19 Picked up the phone…. Is there a history of breast cancer/radiation? Yes – in the vicinity of the biopsied lesion History of Cowden syndrome with breast and thyroid cancer Atypical Vascular Lesion First described in 1994 by Fineberg and Rosen Presumed to be ectatic lymphatic vessels after breast cancer radiation/surgery Atypical hemangiomas Acquired progressive lymphangioma Benign lymphangiomatous papules Lymphangioma circimscriptum Benign lymphangioendothelioma 8 10/25/19 Atypical Vascular Lesion History and presentation Occurs 1-6 years after breast radiation Single or multiple (agminated or dispersed) Well-circumscribed erythematous to skin-colored papule May resemble a lymphangioma or bruise Atypical Vascular Lesion 2005 - Brenn and Fletcher – AVLs have malignant potential 2008 – Patton et al – there are two types of AVL – lymphatic and vascular types Atypical Vascular Lesion Vascular Type Lymphatic Type Less common More common Higher risk of malignancy Low risk of malignancy Irregular, capillary-sized vessels Thin-walled vessels Extravasated RBCs/hemosiderin D2-40-negative D2-40-positive SMA-positive SMA-negative 9 10/25/19 Atypical Vascular Lesion Vascular Type Lymphatic Type Less common More common Higher risk of malignancy Low risk of malignancy Irregular, capillary-sized vessels Thin-walled vessels Extravasated RBCs/hemosiderin D2-40-negative D2-40-positive SMA-positive SMA-negative Excise with 1-cm margin Observe vs Excise AVL vs Angiosarcoma AVL Angiosarcoma Dermal Invade subcutis Can have some anastomosis Anastamosing Monolayer of endothelial cells Multi-layered endothelial cells Minimal atypia Variable atypia Minimal necrosis, mitotic activity Mitotically active, necrosis c-MYC - Secondary AS usually c-MYC + 68 year old African man Site: Left lateral foot Clinical: Dysplastic nevus 10 10/25/19 Kaposi Sarcoma in an HIV-negative patient Diagnosis Clinical diagnosis is terrible 11 10/25/19 Kaposi Sarcoma Histologic variants Patch Kaposi Sarcoma Histologic variants Patch Kaposi Sarcoma Histologic variants Plaque 12 10/25/19 Kaposi Sarcoma Histologic variants Nodular Kaposi Sarcoma Histologic variants Nodular Kaposi Sarcoma Histologic variants Anaplastic Grayson and Pantanowitz, Diagn Pathol 2008;3:31 13 10/25/19 Kaposi Sarcoma Histologic variants Lymphangioma-like Can be associated with bullae, hyperkeratosis, lymphedema Grayson and Pantanowitz, Diagn Pathol 2008;3:31 Kaposi Sarcoma in an HIV-negative patient Etiology Kaposi sarcoma-related herpesvirus Subtypes A-E – different subtypes can be more aggressive Transmitted through prolonged/repeated salivary transfer Cell of origin still unknown Kaposi Sarcoma in an HIV-negative patient Classifications Classic KS in elderly men Endemic KS in young men and children from Central Africa Indolent nodular disease Aggressive invasive disease Pediatric disease with lymphadenopathy Other immunosuppressed classes 14 10/25/19 14 year old girl Site Right preauricular Clinical Cyst vs pilomatricoma 15 10/25/19 Epithelioid angiomatous nodule Red to bluish to violaceous nodules Head, neck, trunk, extremities Typically solitary, may be ‘agminated’ Possibly a variant of epithelioid hemangioma Follow a benign course 16 10/25/19 Epithelioid angiomatous nodule Histologic features Sheets of large, epithelioid cells Variably-shaped and distributed vascular spaces No/minimal atypia Occasional mitotic activity Sparse lymphocytic inflammation, occasionally with eosinophils Epithelioid angiomatous nodule Histologic features Sheets of large, epithelioid cells Variably-shaped and distributed vascular spaces No/minimal atypia Occasional mitotic activity Sparse lymphocytic inflammation, occasionally with eosinophils Epithelioid angiomatous nodule Differential diagnosis Capillary hemangiomas Bacillary angiomatosis Epithelioid hemangioendothelioma Pleomorphism, no vascular spaces Epithelioid angiosarcoma Pleomorphism, atypical mitoses 17 10/25/19 Epithelioid angiomatous nodule Differential diagnosis Capillary hemangiomas Bacillary angiomatosis Epithelioid hemangioendothelioma Pleomorphism, no vascular spaces Epithelioid angiosarcoma Pleomorphism, atypical mitoses 3 year old boy Site Back Clinical Lymphoma vs pseudolymphoma vs other 18 10/25/19 Tufted Angioma/Kasposiform Hemangioendothelioma Natural History Predominantly in infants (50% at birth, most others within year 1 of life) Acquired adult forms described (~10%) Usually persistent lesion with benign course (may regress spontaneously or with treatment) Trunk and neck > extremities > head An Bras Dermatol. 2017 Sep-Oct; 92(5): 742–743 19 10/25/19 Tufted Angioma Further history The patient had a history of thrombocytopenia requiring repeated transfusions Kasabach-Merritt syndrome – consumptive coagulopathy Potentially fatal An Bras Dermatol. 2017 Sep-Oct; 92(5): 742–743 Tufted Angioma Histologic features Clumps of tightly-packed endothelial cells in dermis and subcutis. Rare deep invasion Tufted Angioma Histologic features Clumps of tightly-packed endothelial cells in dermis and subcutis. Rare deep invasion Narrow vascular spaces, around the periphery of each aggregate D2-40 positive 20 10/25/19 Tufted Angioma Histologic features Clumps of tightly-packed endothelial cells in dermis and subcutis. Rare deep invasion Narrow vascular spaces, around the periphery of each aggregate D2-40 positive Round to ovoid nuclei, rare mitoses Hypertrophy of eccrine glands common Tufted Angioma Differential Diagnosis Infantile hemangioma Kaposi sarcoma Angiosarcoma Kaposiform hemangioendothelioma Tufted Angioma Differential Diagnosis Infantile hemangioma Kaposi sarcoma Angiosarcoma Kaposiform hemangioendothelioma Int J Clin Exp Pathol. 2015; 8(10): 13711–13718 21 10/25/19 Tufted Angioma vs Kasposiform Hemangioendothelioma TA KHE Clinical Clinical Well-circumscribed Poorly circumscribed Small/solitary Large, confluent Sometimes regress Never regress Histological Histological Nodular Fusional nodules Rarely invades deep to SC Often invades muscle Rare mitotic activity More common mitoses Selected References Am J Surg Pathol. 2013 Oct;37(10):1580-5. J Clin Pathol. 2017 Nov;70(11):917-925. J Am Acad Dermatol. 2010 Aug;63(2):337-40. Hum Pathol. 2014 Apr;45(4):709-16. Am J Clin Dermatol. 2017 Aug;18(4):529-539. Diagn Pathol. 2008 Jul 25;3:31. Surg Pathol Clin. 2015 Sep;8(3):331-51. Am J Dermatopathol. 2008 Feb;30(1):16-20. Our teaM at UT Southwestern, coMposed of DerMatopathologists and Pediatric Pathologists, is conducting a survey regarding pediatric derMatopathology. Should you have any questions regarding this survey, please contact Tyler Enos ([email protected]). Access the survey using the QR Code below. To launch the survey: Open the caMera app on your sMartphone or tablet Hold the caMera up to the QR code for 2-3 seconds Click on the banner or notification to launch the survey 22.