an overview of cutaneous vascular neoplasms · 2018-11-03 · an overview of cutaneous vascular...
TRANSCRIPT
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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
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• Book Royalties
Financial disclosures
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Benign Vascular Tumors
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• 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
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• 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
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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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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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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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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
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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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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
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• 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
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Vascular Tumors of
Intermediate Malignancy
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• 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
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• 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
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• 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
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• 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
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D2-40
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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
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• 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
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• Immunophenotype that resembles normal lymphatic endothelium • CD31, CD34, ERG • VEGFR3, podoplanin
• Lack of actin-positive cuff of pericytes
IHC
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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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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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Radiologic findings
Diagnostic Pathology: Soft Tissue Tumors 2nd Ed 2015, Elsevier
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Microscopic findings
Histopathology 2016
May;68:776-95
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Immunohistochemistry POSITIVE
CKAE1/3 ERGCD31 (variable)
NEGATIVE
CD34
INI-1 (SMRCB1) is retained
AE1/AE3
ERG
AE1/AE3 INI1 CD31
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Other Differential Diagnosis
• Spindle cell squamous cell carcinoma• Cellular benign fibrous histiocytoma• Smooth muscle neoplasms• Epithelioid Hemangioendothelioma
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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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• 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
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CD31 Synaptophysin
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D2-40 Synaptophysin
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Malignant Vascular
Tumors
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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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• 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
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Microscopic findings
Diagnostic Pathology: Vascular 2016 Elsevier
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Immunohistochemistry
POSITIVE
• CD31
• CD34
• ERG
• AE1/AE3 in 25% of
cases
NEGATIVE
• S100 protein
• Desmin
• EMA
CD31
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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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CAMTA1
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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
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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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Antonescu et al, Genes, Chromosomes and Cancer 52, 772-784, 2013
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CAMTA1TFE3
CD31
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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.
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• 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.
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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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FISH MYC
Angiosarcoma
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Case 1 Case 2
Angiosarcomas
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Atypical Vascular lesion (AVL)
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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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CD31 ERG