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.
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