This document discusses various types of vascular tumors, including benign tumors like hemangiomas and lymphangiomas, intermediate tumors like hemangioendotheliomas, and malignant tumors such as Kaposi sarcoma and angiosarcomas. It covers the histological and clinical features used to classify and diagnose these different vascular neoplasms. Key information includes that benign tumors form well-organized vessels, while malignant tumors are more cellular and proliferative without such organization. Immunohistochemistry can help identify the endothelial cell origin of these proliferations.

2. VASCULAR TUMORS
Surg Lt Cdr Rabia Ahmed
MBBS, FCPS, FRCPath (UK)
Consultant Histopathologist
Assistant Professor
BUHS, Karachi

3. Vascular tumors
• Tumors of blood vessels and lymphatics include:
• Benign
• Intermediate
• Malignant
• Vascular neoplasms arise either from:
• Endothelium (e.g. hemangioma, lymphangioma, angiosarcoma)
• Cells that support or surround blood vessels (e.g., glomus tumor)
• Tumor-like lesions
• Congenital or developmental malformations
• Non-neoplastic reactive vascular proliferations (e.g., bacillary angiomatosis) can also
manifest as that may present diagnostic challenges

5. Vascular tumors
• In general, benign and malignant vascular neoplasms are distinguished by the following features:
• Benign tumors
• Composed of vascular channels filled with blood cells or lymph
• Lined by a monolayer of normal-appearing endothelial cells
• Malignant tumors
• More cellular
• Show cytologic atypia, are proliferative
• Usually do not form well-organized vessels
• Confirmation of the endothelial derivation of such proliferations may require
immunohistochemical detection of EC-specific markers, CD34 and Vwf.

6. Vascular tumors
• Vascular Ectasias
• A generic term for any local dilation of a structure
• Telangiectasia
• A permanent dilation of preexisting small vessels (capillaries, venules, and arterioles, usually
in the skin or mucous membranes) that forms a discrete red lesion
• Can be congenital or acquired and are not true neoplasms

7. Vascular tumors
• Nevus flammeus (a “birthmark”)
• The most common form of vascular
ectasia
• Light pink to deep purple flat lesion on
the head or neck composed of dilated
vessels
• Most ultimately regress spontaneously
• “Port wine stain”
• A special form of nevus flammeus
• These lesions tend to grow during
childhood, thicken the skin surface, and
do not fade with time

8. Vascular tumors
• Sturge Weber syndrome
• Also called encephalotrigeminal
angiomatosis
• Uncommon congenital disorder
• Nevus flammeus (a “birthmark”) lesions
occurring in the distribution of the
trigeminal nerve
• Associated with facial port wine nevi,
ipsilateral venous angiomas in the cortical
leptomeninges, mental retardation,
seizures, hemiplegia, and radiologic
opacities of the skull
• A large facial telangiectasia in a child with
mental deficiencies may indicate the
presence of additional vascular
malformations

9. Vascular tumors
• Spider telangiectasias
• Non-neoplastic vascular lesions
• Radial, often pulsatile arrays of dilated
subcutaneous arteries or arterioles (the
“legs” of the spider) about a central core
(the spider’s “body”) that blanch with
pressure
• Commonly occur on the face, neck, or
upper chest
• Most frequently are associated with
hyperestrogenic states
• In pregnant women or patients with
cirrhosis

10. Vascular tumors
• Hereditary hemorrhagic telangiectasia
(Osler-Weber-Rendu disease)
• Autosomal dominant disorder
• Caused by mutations in genes that
encode components of the TGF-ß
signaling pathway in ECs
• Malformations composed of dilated
capillaries and veins that are present at
birth
• They are widely distributed over the skin
and oral mucous membranes, as well as
in the respiratory, gastrointestinal, and
urinary tracts
• The lesions can spontaneously rupture,
causing serious epistaxis (nosebleed),
gastrointestinal bleeding, or hematuria.

11. Hemangiomas
• Hemangiomas are very common tumors
• Composed of blood-filled vessels
• Constitute 7% of all benign tumors of infancy and childhood
• Most are present from birth and initially increase in size
• Many eventually regress spontaneously
• While hemangiomas typically are localized lesions confined to the head and neck
• They occasionally may be more extensive (angiomatosis)
• Can arise internally
• Nearly one third of these internal lesions are found in the liver
• Malignant transformation is rare

12. Hemangiomas
• Capillary hemangiomas
• The most common type
• Occur in the skin, subcutaneous tissues, and mucous membranes of the oral cavities and lips,
as well as in the liver, spleen, and kidneys
• Histologically, they are composed of thin-walled capillaries with scant stroma
• Juvenile hemangiomas (so-called “strawberry hemangiomas”)
• Extremely common (1 in 200 births)
• Can be multiple
• Grow rapidly for a few months but then fade by 1 to 3 years of age
• Complete regression by 7 years of age in majority of cases

13. Hemangiomas
• Pyogenic granulomas
• Are capillary hemangiomas
• Manifest as rapidly growing red
pedunculated lesions
• On the skin, gingival, or oral mucosa
• Microscopically, they resemble exuberant
granulation tissue
• They bleed easily and often ulcerate
• Roughly one fourth of the lesions develop
after trauma
• Reaching a size of 1 to 2 cm within a few
weeks
• Curettage and cautery usually are
curative

14. Hemangiomas
• Pregnancy tumor (granuloma gravidarum)
• Is a pyogenic granuloma
• Occurs infrequently in the gingiva of
pregnant women
• May spontaneously regress (especially
after pregnancy) or undergo fibrosis
• Occasionally require surgical excision

15. Hemangiomas
• Cavernous hemangiomas
• Composed of large, dilated vascular
channels
• Are more infiltrative
• Frequently involve deep structures
• Do not spontaneously regress
• On histologic examination
• The mass is sharply defined but
unencapsulated
• Composed of large blood-filled vascular
spaces separated by connective tissue
stroma

16. Hemangiomas
• Cavernous hemangiomas
• Intravascular thrombosis and dystrophic calcification are common
• Lesions may be locally destructive
• Surgical excision is required in some cases
• They can be cosmetically troublesome
• Vulnerable to traumatic ulceration and bleeding
• Brain hemangiomas are problematic - symptoms related to compression of adjacent tissue or
may rupture
• One component of von Hippel-Lindau disease - in which vascular lesions are commonly found
in the cerebellum, brain stem, retina, pancreas, and liver

18. Lymphangiomas
• Lymphangiomas are the benign lymphatic
counterpart of hemangiomas
• Simple (capillary) lymphangiomas
• Slightly elevated or sometimes
pedunculated lesions
• Up to 1 to 2 cm in diameter
• Occur predominantly in the head, neck,
and axillary subcutaneous tissue
• Histologically, lymphangiomas are
composed of networks of endothelium-
lined spaces that are distinguished from
capillary channels only by the absence of
blood cells

19. Lymphangiomas
• Cavernous lymphangiomas (cystic hygromas)
• Typically are found in the neck or axilla of
children
• More rarely in the retroperitoneum
• Can be large (up to 15 cm), filling the axilla
or producing gross deformities of the neck
• Composed of massively dilated lymphatic
spaces lined by endothelial cells and
separated by intervening connective tissue
stroma containing lymphoid aggregates
• The tumor margins are indistinct and
unencapsulated, making definitive
resection difficult.
• Of note, cavernous lymphangiomas of the
neck are common in Turner syndrome.

20. Glomus Tumors (Glomangiomas)
• Glomus tumors are benign
• Exquisitely painful tumors
• They most commonly are found in the distal
portion of the digits, especially under the
fingernails.
• Arising from specialized SMCs of glomus
bodies, arteriovenous structures involved in
thermoregulation.
• Distinction from cavernous hemangiomas is
based on clinical features and
immunohistochemical staining for smooth
muscle markers.
• Excision is curative

21. Bacillary Angiomatosis
• A vascular proliferation in immune-compromised
• Hosts (e.g., patients with AIDS) caused by opportunistic gram-negative bacilli of the Bartonella
family
• The lesions can involve the skin, bone, brain, and other organs
• Two species have been implicated:
• Bartonella henselae, whose principal reservoir is the domestic cat; this organism causes cat-
scratch disease (a necrotizing granulomatous inflammation of lymph nodes) in
immunocompetent hosts
• Bartonella quintana, which is transmitted by human body lice; this microbe was the cause of
“trench fever” in World War I

22. Bacillary Angiomatosis
• They most commonly are found in the distal portion of the digits, especially under the fingernails
• Skin lesions take the form of red papules and nodules, rounded subcutaneous masses
• Histologically, there is a proliferation of capillaries lined by prominent epithelioid ECs, which
exhibit nuclear atypia and mitoses
• Other features include infiltrating neutrophils, nuclear debris, and purplish granular collections of
the causative bacteria
• The bacteria induce host tissues to produce hypoxiainducible factor-1a (HIF-1a), which drives
VEGF production and vascular proliferation
• The infections (and lesions) are cured by antibiotic treatment

23. Bacillary Angiomatosis

24. Kaposi sarcoma
• Kaposi sarcoma (KS) is a vascular neoplasm
• Caused by Kaposi sarcoma herpes virus (KSHV or HHV-8)
• It is most common in patients with AIDS
• Four forms of KS, based on population demographics and risks, are recognized:
• Classic KS
• Endemic African KS
• Transplantation-associated KS
• AIDS-associated (epidemic) KS

25. Kaposi sarcoma
• Classic KS
• Disorder of older men of Mediterranean, Middle Eastern, or Eastern European descent
(especially Ashkenazi Jews)
• Uncommon in the United States
• Associated with malignancy or altered immunity but is not associated with HIV infection
• Manifests as multiple red-purple skin plaques or nodules
• Usually on the distal lower extremities
• These progressively increase in size and number and spread proximally
• The tumors typically are asymptomatic
• Remain localized to the skin and subcutaneous tissue

26. Kaposi sarcoma
• Endemic African KS
• Occurs in younger (under 40 years of age) HIV-seronegative individuals
• Can follow an indolent or aggressive course
• It involves lymph nodes much more frequently than in the classic variant
• A particularly severe form, with prominent lymph node and visceral involvement, occurs in
prepubertal children; the prognosis is poor, with an almost 100% mortality within 3 years

27. Kaposi sarcoma
• Transplantation-associated KS
• Occurs in solid organ transplant recipients in the setting of T-cell immunosuppression
• In these patients, the risk for KS is increased 100-fold
• It pursues an aggressive course and often involves lymph nodes, mucosa, and viscera;
cutaneous lesions may be absent
• Lesions often regress with attenuation of immunosuppression, but at the risk for organ
rejection

28. Kaposi sarcoma
• AIDS-associated (epidemic) KS
• AIDS-defining illness
• Worldwide it represents the most common HIV-related malignancy
• Occurs in HIV-infected individuals with a 1000-fold higher incidence than in the general
population
• Often involves lymph nodes and disseminates widely to viscera early in its course
• Most patients eventually die of opportunistic infections rather than from KS

29. Kaposi sarcoma
• AIDS-associated (epidemic) KS
• Virtually all KS lesions are infected by KSHV (HHV-8)
• KSHV is a γ-herpesvirus
• It is transmitted both through sexual contact and potentially via oral secretions and
cutaneous exposures
• KSHV and altered T-cell immunity probably are required for KS development
• In older adults, diminished T-cell immunity may be related to aging
• It also is probable that acquired somatic mutations in the cells of origin contribute to tumor
development and progression.

30. Kaposi sarcoma
• AIDS-associated (epidemic) KS
• KSHV causes lytic and latent infections in Ecs
• A virally encoded G protein induces VEGF production, stimulating endothelial growth, and
cytokines produced by inflammatory cells recruited to sites of lytic infection also create a
local proliferative milieu
• In latently infected cells, KSHV encoded proteins disrupt normal cellular proliferation controls
(e.g., through synthesis of a viral homologue of cyclin D) and prevent apoptosis by inhibiting
p53
• Thus, the local inflammatory environment favors cellular proliferation, and latently infected
cells have a growth advantage
• In its early stages, only a few cells are KSHV-infected, but with time, virtually all of the
proliferating cells carry the virus

31. Kaposi sarcoma
• In classic Kaposi sarcoma (and sometimes in
other variants), the cutaneous lesions
progress through three stages: patch,
plaque, and nodule
• Patches
• Pink, red, or purple macules
• Typically confined to the distal lower
extremities
• Microscopic examination reveals dilated,
irregular, and angulated blood vessels
lined by ECs and an interspersed
infiltrate of chronic inflammatory cells,
sometimes containing hemosiderin

32. Kaposi sarcoma
• Plaques
• Lesions spread proximally and become
larger, violaceous, raised plaques
• It is composed of dilated, jagged dermal
vascular channels lined and
surrounded by plump spindle cells
• Other prominent features include
extravasated red cells, hemosiderin-
laden macrophages, and other
mononuclear cells

33. Kaposi sarcoma
• Nodules
• More overtly neoplastic, lesions appear
• These are composed of plump,
proliferating spindle cells, mostly
located in the dermis or subcutaneous
tissues, often with interspersed slit like
spaces
• The spindle cells express both EC and
SMC markers
• Hemorrhage and hemosiderin
deposition are more pronounced, and
mitotic figures are common
• The nodular stage often is
accompanied by nodal and visceral
involvement, particularly in the African
and AIDS-associated variants

34. Kaposi sarcoma

35. Kaposi sarcoma
• The course of disease varies widely according to the clinical setting
• Most primary KSHV infections are asymptomatic
• Classic KS is—at least initially—largely restricted to the surface of the body and surgical resection
usually is adequate for an excellent prognosis
• Radiation therapy can be used for multiple lesions in a restricted area
• Chemotherapy yields satisfactory results for more disseminated disease, including nodal
involvement
• In KS associated with immunosuppression, withdrawal of therapy (with or without adjunct
chemotherapy or radiotherapy) often is effective
• For AIDS-associated KS, HIV anti-retroviral therapy generally is beneficial, with out without
additional therapy
• IFN-γ and angiogenesis inhibitors also have proved variably effective

36. Hemangioendotheliomas
• Comprise a wide spectrum of borderline vascular neoplasms
• Clinical behaviors intermediate between those of benign, well-differentiated hemangiomas and
aggressively malignant angiosarcomas
• Epithelioid hemangioendothelioma
• A tumor of adults arising in association with medium- to large-sized veins
• The clinical course is highly variable
• While excision is curative in a majority of the cases
• Up to 40% of the tumors recur
• 20% to 30% eventually metastasize
• 15% of patients die of their tumors

37. Angiosarcomas
• Malignant endothelial neoplasms
• Ranging from highly differentiated tumors resembling
• Hemangiomas to wildly anaplastic lesions
• Older adults are more commonly affected, without gender predilection
• Lesions can occur at any site, but most often involve
• Involve skin, soft tissue, breast, and liver
• Aggressive tumors that invade locally and metastasize
• Current 5-year survival rates are only about 30%

38. Angiosarcomas
• Can arise in the setting of lymphedema
• Classically in the ipsilateral upper extremity
several year after radical mastectomy (i.e.,
with lymph node resection) for breast cancer
• In such instances, the tumor presumably
arises from lymphatic vessels
(lymphangiosarcoma)
• Angiosarcomas can also be induced by
radiation
• Rarely are associated with long-term (years)
indwelling foreign bodies (e.g., catheters)

39. Angiosarcomas
• Hepatic angiosarcomas
• Associated with certain carcinogens
• Including arsenical pesticides and
polyvinyl chloride (one of the best known
examples of human chemical
carcinogenesis)
• Multiple years typically transpire
between exposure and subsequent
tumor development

40. Angiosarcomas
• Skin angiosarcomas
• Begin as small, sharply demarcated, asymptomatic red nodules
• More advanced lesions are large, fleshy red-tan to gray-white masses
• Margins blend imperceptibly with surrounding structures
• Necrosis and hemorrhage are common
• On microscopic examination
• Extent of differentiation is extremely variable
• Ranging from plump atypical ECs that form vascular channels to undifferentiated
spindle cell tumors without discernible blood vessels
• The EC origin can be demonstrated in the poorly differentiated tumors by staining for the EC
markers CD31 and von Willebrand factor

41. Angiosarcomas

42. Haemangiopericytoma
• Arise from pericytes
• Myofibroblast type cells associated with capillaries and venules
• Solitary fibrous tumor in pleura

43. Thank you