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

• Book Royalties

Financial disclosures

Benign Vascular Tumors

• 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%

Epithelioid Hemangioma

• 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

Microscopic features

IHC

• Positive for vascular markers • CD31, CD34, ERG• Also positive for D2-40

• Pitfall!! • Immunoreactivity for EMA and keratins may be

seen

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

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

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

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

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

• In dermis or subcutis with so-called cannonball pattern of spherical well-dermacated 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

Microscopic features

Vascular Tumors of

Intermediate Malignancy

• 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

Kaposiform

Hemangioendothelioma

• 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

Microscopic features

• 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

Immunohistochemistry

• 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

Prognosis

D2-40

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

• 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

Microscopic features

• Immunophenotype that resembles normal lymphatic endothelium • CD31, CD34, ERG • VEGFR3, podoplanin

• Lack of actin-positive cuff of pericytes

IHC

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”

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

Radiologic findings

Diagnostic Pathology: Soft Tissue Tumors 2nd Ed 2015, Elsevier

Microscopic findings

Histopathology 2016

May;68:776-95

Immunohistochemistry POSITIVE

CKAE1/3 ERGCD31 (variable)

NEGATIVE

CD34

INI-1 (SMRCB1) is retained

AE1/AE3

ERG

AE1/AE3 INI1 CD31

Other Differential Diagnosis

• Spindle cell squamous cell carcinoma• Cellular benign fibrous histiocytoma• Smooth muscle neoplasms• Epithelioid Hemangioendothelioma

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

• WHO 2013 definition• “Locally aggressive, rarely metastasizing vascular

neoplasm, containing an admixture of histologically distinct components”

• Chiefly in adults • 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%)

Composite

Hemangioendothelioma

CD31 Synaptophysin

D2-40 Synaptophysin

Malignant Vascular

Tumors

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

• 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!!!!

Clinical Features

Microscopic findings

Diagnostic Pathology: Vascular 2016 Elsevier

Immunohistochemistry

POSITIVE

• CD31

• CD34

• ERG

• AE1/AE3 in 25% of

cases

NEGATIVE

• S100 protein

• Desmin

• EMA

CD31

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

CAMTA1

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

TFE3

• Alveolar soft part sarcoma• Xp11 translocation renal cell carcinoma• “melanotic” Xp11 translocation renal cell

carcinoma • A subset of PEComas• Epithelioid hemangioendotheliomas

Antonescu et al, Genes, Chromosomes and Cancer 52, 772-784, 2013

CAMTA1TFE3

CD31

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.

• 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.

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.

FISH MYC

Angiosarcoma

Case 1 Case 2

Angiosarcomas

Atypical Vascular lesion (AVL)

Conclusion

• MYC immunohistochemistry is therefore useful in differentiating atypical or benign

vascular lesions occurring in irradiated

skin from secondary postradiation

angiosarcomas.

CD31 ERG

• Email: Konstantinos.Linos@hitchcock.org

• @ @ KonstantinosLin