Tumors

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