A 43 year old woman with a

history of lung cancer 2 years

ago presents with back pain …..
Keratin
 Diagnosis

Metastatic carcinoma?.....

Chordoma?.....

Osteosarcoma?.....
Epithelioid Vascular Tumors of
Bone and Soft Tissue

Andrew E Rosenberg, MD
Department of Pathology
University of Miami
Miami, Florida
Arosenberg@miami.edu

pathotim 2018
 Definition –Endothelial Cell

Cells that line blood and lymphatic vessels.

Classically classified as simple squamous cell
Phenotype and function vary upon location
More than 2 kg. of endothelial cells in human adult body
Cover 4000 – 7000 square meters
Definition – Epithelioid Vascular Tumor

A proliferation of
neoplastic cells whose
phenotype recapitulates
endothelial cells that
line blood or lymph
vessels and which are
large, polyhedral and
contain abundant
eosinophilic cytoplasm
 Biological Potential of
Epithelioid Vascular Tumors
Reactive Benign Low-grade High-grade
Malignant Malignant

Bacillary angiomatosis Epithelioid hemangioma Epithelioid Epithelioid angiosarcoma

Spindle cell hemangioma hemangioendothelioma Malignant EHE
Kaposiform Psuedomyogenic
hemangioendothelioma hemangioendothelioma
 Epithelioid Vascular Tumors
Morphology Ultrastructure
Genetics Immuoprofile

Translocations Vimentin, keratin

Amplifications EMA, SMA, CD34
CD31, ERG, FLI-1
Factor 8, D2-40
 Epithelioid Vascular Tumors
Genetics
Epithelioid Epithelioid
hemangioma angiosarcoma
t(19q13.2;19q13.32) PTPRB/PLCG1 mutations
ZFP36-FOSB fusion gene C-myc amplification

Spindle cell Psuedomyogenic Epithelioid

hemangioma hemangioendothelioma
IDH1/IDH2 mutations t(7;19(q22;q13)
SERPINE and FOSB fusion gene
hemangioendothelioma
t(1;3) WWTR1-CAMTA1
fusion gene
t(x;11) TFE3-YAP1
fusion gene
 Embryology of the
Vascular System
Hensen’s node
Primitive streak
Area vasculosa
Epiblast

Endoderm
Migrating cells Hypoblast Yolk
Blastocoel
mesoderm
Formation of blood vessels de novo is a process known as vasculogenesis
Blood islands are the earliest discernible vascular structures that give rise to a
primitive vascular network in the yolk sac
Angioblasts are progenitor cells that has the characteristics of endothelial cells
Vasculogenesis begins in the embryo on approximately Day 18
 Vasculogenesis

Angioblast

Xu K and Cleaver Semin Cell Dev Biol 2011;22:993-1004

Vasculogenesis

Keratin 7
Keratin 17
Keratin 18

Xu K and Cleaver Semin Cell Dev Biol 2011;22:993-1004

 Bacillary Angiomatosis
Reactive vascular proliferation in response to
arthropod borne infection with Bartonella sp.
(henselae, quintana)
Patients frequently immunocompromised (HIV))
Bacillary Angiomatosis
 Bacillary Angiomatosis
Treatment
Antibiotics – erythromycin, tetracycline
Prognosis
Good – depends on cause of immuno
suppression
 Epithelioid Hemangioma
Age: 3rd-5th decade
Gender: F>M
Location: Superficial soft tissue of head and
neck, skeleton, lymph node, lung, heart, testis
Presentation: Single or multiple (regional) pruritic,
plaques or nodules; painful bone mass
 Epithelioid Hemangioma Genetics
Gene Fusions involving FOS gene family – 75-80%
Finkel–Biskis–Jinkins murine osteosarcoma viral oncogene homolog
Cell proliferation, differentiation, and transformation

FOS
59% (10/17) Huang et al, Amer J Surg Pathol 2015
70% (5/7) van IJzendoorn DG, Genes Chromosome Cancer 2015
different gene partners (LMNA, Vimentin)

ZFP36-FOSB fusions
14% (2/14) Antonescu CR et al, Amer J Surg Pathol 2014
atypical histology (increased cellularity, occasional areas of
necrosis and mild nuclear pleomorphism)
dis-proportionate number occurring in the penile location
(Antonescu CR, Genes Chromosomes Cancer 2014)
 Epithelioid Hemangioma With
FOS Gene Rearrangements
Anatomic depth Location
Bone - 60% Extremities - 71%
Soft tissue - 35% Trunk - 18%
Cutaneous - 5% Head and neck - 6%
Histologic variants Penis - 6%
Cellular variants - 70%
Typical variants - 30%
ALHE - 0%
Huang SC et al, Am J Surg Pathol 2015
Epithelioid Hemangioma
 Epithelioid Hemangioma
14 2% 2%
12

10
M:F = 1:1
17%
4%
# cases

8
19%
6

4
10%
2

0 17%
1 2 3 4 5 6 7 8

Age in decades
12%
Age Range 10-62 (av. 37)
Epithelioid Hemangioma
Epithelioid Hemangioma
Epithelioid Hemangioma
Epithelioid Hemangioma
Epithelioid Hemangioma
Epithelioid Hemangioma
CD31
 Epithelioid Hemangioma
Treatment
Conservative excision
curettage, en bloc resection
10-20% local recurrence
Prognosis
Excellent; local recurrence
mulitcentric vs metastasis
 Psuedomyogenic
Hemangioendothelioma
Synonyms – epithelioid sarcoma-like
hemangioendothelioma
Locally aggressive, rarely metastasizing
endothelial neoplasm
Arises in soft tissue more commonly than
bone; 20% of patients have bone
involvement, pure bone lesions rare
 Psuedomyogenic
Hemangioendothelioma
Age – children and young adults
Gender – male predominance
Location – skin, soft tissue – multiple
anatomic depths, long bones, axial skeleton,
usually multicentric
Genetics – t(7;19(q22;q13) - fusion of
SERPINE and FOSB genes
 Epithelioid
Hemangioendothelioma
Age: 2nd - 5th decades
Location: Soft tissue -
angiocentric, lung, liver,
skeleton (lower
extremity>spine>pelvis>
humerus; multifocal 50%)
Presentation: Enlarging
painful mass
 Epithelioid Hemangioendothelioma
Genetics
Classic and Malignant
WTR1-CAMTA1 fusion – 90% A
Vasoformative 1
t(1;3)(p36.3;q24)
3

TFE3-YAP1

t(11;X)(q22.1;p11.3
 Epithelioid
Hemangioendothelioma
Epithelioid Hemangioendothelioma
Epithelioid Hemangioendothelioma

Bone Liver
Liver

Soft tissue Lung

 CD31 Keratin

CAMTA1 TFE3
Epithelioid Hemangioendothelioma
Treatment
Surgical excision, systemic therapy,
radiation
Prognosis
Guarded, local recurrence, metastases 10-
50% (regional lymph nodes, lung, skeleton)
5 year survival 73%; outcome related to size,
grade multifocality, visceral involvement
 Epithelioid Angiosarcoma
Aggressive sarcoma
Age: Develops in adults
Location: Skin, soft tissue, bone, adrenal,
thyroid, bladder, lung, gastrointestinal tract
Prexisting disease: radiation, Mafucci’s
syndrome, von Recklinghausen’s disease-
type 1, Klippel-Trenaunay syrome
Genetics: Mutations in PTPRB and PLCG1,
amplification cMYC
CD 31 Keratin
 Epithelioid Angiosarcoma

Biologic behavior: Progressive

growth
Treatment: Wide excision
Prognosis: 50% locally recur
50-75% metastasize – most
patients die of disease
 Epithelioid Vascular Tumors
Uncommon tumors
Majority are benign
Molecular techniques facilitate
diagnosis
Epithelioid vascular tumors can be
confused with a variety of other types
of tumors
 A 43 year old woman with a
history of lung cancer 2 years
ago presents with back pain …..
Keratin