Vascular tumors Flashcards
When do vascular malformations occur?
They are present at birth
What is the clinical progression of vascular malformations?
These are capillary, venous, lymphatic or arteriovenous malformations, therefore they do not rapidly enlarge like hemangiomas (not true neoplasms)
They may persist and become more verrucous over time (PWS)
What is the GLUT-1 staining in vascular malformations?
GLUT-1 negative
What disorders can vascular malformations be associated with?
Maffucci syndrome, Klippel-Trenaunay, Sturge-Weber, Blue rubber bleb (cavernous hemangioma), kasabach-merritt syndrome and proteus syndrome
What is the histology of the nevus flammeus?
Dilated capillary-sized vessels
What are the histologic hallmarks of an angiokeratoma?
Hyperkeratosis, acanthosis, ectatic, thin-walled vessels that are in contact w/ the epi.
when you see these think a bloody looking seborrheic keratosis
What are the 5 types of angiokeratoma?
- Angiokeratoma of Mibelli: 10-15 y/o; fingers and toes
- Angiokeratoma of Fordyce: older men (scrotum) or women (vulva)
- Angiokeratoma corporis diffusum: multiple lesions in childhood/adolescence; bathing suite distribution; a/w Fabry disease and other enzyme deficiencies
- Angiokeratoma circumscriptum: In children, F>M, aggregates of lesions forming plaques
- Solitary and multiple angiokeratomas: children and adults; can arise anywhere; can be related to chronic irritation or trauma of superficial dermal vessels
What type of angiokeratomas is a/w Fabry’s disease?
Angiokeratoma corporis diffusum: look for multiple lesions in childhood or adolescence in a bathing suit distribution
What is the clinical description of lymphangioma?
Frog spawn clinically
These are often noted to come and go somewhat
What stains are used for vascular/lymphatic endothelium?
CD31, CD34, PAL-E, factor VIII, Ulex
What stains are used for lymphatic only tumors?
VEGFR-3, poloplanin, LYVE-1, prox-1; D2-40, thrombomodulin
Do vascular malformations like nevus flameus ever go away?
These can fade (forehead and central face), however, are largely permanent
Grows in proportion to the child, does not spontaneous involute
What is the clinical presentation of venous malformations?
These are congenital (cavernous hemangioma). They appear as blue-purple papules on nodules on infants.
They don’t have a proliferative phase and do not regress over time like capillary hemangiomas
What is the histology of venous malformations?
Large dilated vascular channels with flat endothelium in the deep dermis/subcutis. You can see thrombosis and calcifications of the walls.
What conditions are venous malformations associated with?
Blue rubber bleb nevus syndrome and Maffucci’s syndrome (enchondromas of bone, chondrosarcoma risk, spindle-cell hemangioendothelioma, may be due to parathyroid receptor mutation in some cases)
What are the most common locations for glomerulovenous malformation (glomangioma)?
Most commonly located on the extremities and trunk
It presents as painless, blue, or violaceous macules, nodules, or plaques
What is the histology of glomangioma?
Think lots of vessels with one to two layers of glomus cells around the prominent vessels. So when you look the vessels look thicker because they have the glomus cells
As compared to glomus tumors, these are mostly vessels with some glomus cells, whereas the glomus tumors are tumors of glomus cells with some surrounding inconspicuous vessels
What are the most common locations for lymphangioma cicumscriptum?
Proximal limbs, girdle
What is the clinical presentation of deep lymphangiomas?
These are soft swellings int he skin, epidermis should be normal (deep)
Variants included: cavernous lymphangioma, cystic hygroma
What syndromes are deep lymphangiomas associated with?
Cystic hydromas (lymphangiomas) are seen in the neck and axilla area in turner’s syndrome, down syndrome, Noonan’s syndrome
What is the clinical description of verrucous hemangioma?
They occur at birth to childhood
Most commonly located on the legs
They appear as bluish-red soft papules, plaques or nodules that become wart-like, may develop satellite lesions
If removed they frequently recur due to deep component
What is the histology of verrucous hemangioma?
Numerous small and large vessels in dermis and subcutis, irregular papillomatosis and overlying verrucous hyperplasia changes
What is the clinical presentation of venous lakes?
Elderly, occur on the ear, face, lip, neck
What is the histology of a venous lake?
Single large dilated vascular channel in the upper dermis, thin fibrous wall and flat endothelial lining; thrombus; sun-damaged skin
What is the clinical progression of infantile hemangioma?
Most common on the head, neck, trunk, and over the parotid gland.
They tend to enlarge in size, sometimes rapidly in the first year and then regress over 5-7 years
What is the histology of infantile hemangioma?
Highly cellular vascular lumina w/ slit-like and small openings. You can see central draining lumens in each lubule often
The more early lesions appear more cellular and the later lesions appear more w/ ectatic vessels
What do infantile hemangiomas stain + for?
GLUT-1
What are the two forms of formed hemangiomas that appear at birth and how do they stain?
Rapidly involuting congenital hemangioma (RICH) is GLUT-1 negative
Non-involuting congenital hemangioma (NICH) is also negative for GLUT-1
What is the clinical presentation of a rapidly involuting congenital hemangioma (RICH)?
Fully developed at birth, then involutes rapidly the first months of life
Important: can show thrombocytopenia, low fibrinogen, and elevated fibrin degradation products but these are transient and NOT like the Kassabach-Merrit effect
What is the clinical of non-involuting congenital hemangioma (NICH)?
These are fully formed at birth and grow slowly with the child over time, proportional to the size of the infant.
What difference is seen with RICH/NICH?
The tumors have thicker vessel walls and the endothelium may appear hobnail-like
What are some risk factors for infantile hemangioma?
Prematurity, females, and placental abnormalities
What hemangiomas pose risk for the airway in a newborn?
Hemangiomas along the pre-auricular cheek along the mandible, lower lip, chin or anterior neck (beard distribution)
What is the concern for periorbital hemangioma?
Concern for astigmatism (from pressure on globe), and amblyopia (caused by obstruction of visual axis)
What is diffuse neonatal hemangiomatosis and when does it occur?
Occurs in birth to infancy
It presents with multiple cutaneous capillary hemangiomas and visceral hemangiomas
Associated with PHACES syndrome
What is the prognosis of diffuse neonatal hemangiomatosis?
Usually fatal
Death occurs due to high output cardiac failure from AV shunts, especially in the liver, CNS involvement and bleeding from Kasabach-Merritt syndrome
What is the most common location of sinusoidal hemangioma?
Acquired, benign lesions in adults (especially women)
Located on the trunk, breast, limbs
What is the histology of sinusoidal hemangiomas?
Located in the subcutis or dermis.
There is a lobular architecture of thin-walled interconnecting vascular channels in a sinusoidal pattern. There is little stroma
What is the histology of a cherry angioma?
Polypoid lesions with congested, ectactic vessels and scant stroma
Clues include loss of rete ridges and atrophy of epidermis. May have a collarette around the periphery
What conditions are glomeruloid hemangiomas associated with?
POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) or multicentric Castleman’s syndrome (giant lymph node hyperplasia)
What is the histology of glomeruloid hemangiomas?
Look for grape-like aggregates of small capillary vessels that make it look like the glomerulus.
Look for two cell populations, one with large vesicular nuclei, an open chromatin pattern and a large amount of cytoplasm and a second group with small basal nuclei, a dense chromatin pattern and scant cytoplasm
What is the clinical appearance of glomeruloid hemangioma?
Most common on the trunk and limbs
Presents as eruptive, multiple, red/purple papules
What is intravascular papillary endothelial hyperplasia of Masson?
It is common on the head/neck
common in angiokeratomas but can happen in any vascular space
It is basically recanalizing thrombus within a vascular space. So fibrin in thrombus, and papillary projections with hyalinized cores
What growth factor levels are increased in glomeruloid hemangioma?
VEGF
What is the histology of microvenular hemangiomas?
Monomorphous elongated blood vessels with small lumens.
Surrounding pericytes seen
Clinical appearance of microvenular hemangioma?
Acquired vascular tumor
Occurs in young to middle-aged adults
Single, slow-growing purple/red papule or nodule
What is the other name for a hobnail hemangioma?
Targetoid hemosiderotic hemangioma
What is the clinical appearence of hobnail hemangioma/targetoid hemosiderotic hemangioma?
Young to middle-aged men
Occurs on trunk and limbs
Has a targetoid violaceous central papule with an area of palor and brown surrounding ring
Histology of hobnail hemangioma?
In the superficial dermis: plump, hobnail endothelial cells that protrude into the lumen; fibrin thrombi, hemosiderin
In the deeper dermis the vessels become more slit-like; RBC extravasation and hemosiderin deposition is seen
What is the differential for hob-nailing?
Think DR. HAPpy
D = Dabska’s tumor
R = Retiform hemangioendothelioma
H = Hobnail hemangioma
A = angiolymphoid hyperplasia with eosinophilia
P = PILA (papillary intralymphatic angioendothelioma)
Where are spindle-cell hemangio-endotheliomas located?
Hand
What is the histology of the spindle-cell hemangioendothelioma?
Located in the dermis/subcutis
Has 3 components: 1. vascular component of thin-walled cavernous channels 2. solid area of spindle cells with slit-like vascular spaces 3. plump endothelial cells
What is thought to cause spindle-cell hemangioendothelioma and what is it associated with?
Potentially a reactive process arising from local, abnormal blood flow
Seen in Maffucci’s syndrome and Klippel-Trenaunay syndrome
Where do angioma serpiginosum arise?
On a woman’s leg (before puberty)
Clinical appearence of angioma serpiginosum?
Multiple, pin-size puncta that expand with age
What is the histology of angioma serpiginosum?
Ectatic, congested, thin-walled capillaries in the papillary dermis
What is the clinical appearance of angiolymphoid hyperplasia w/ eosinophilia?
Occurs on young to middle-aged adults
Occurs around the ears, forehead, and scalp
Lesions are pink to red-brown papules/nodules that pare painful pruritic or pulsatile
What is the histology of angiolymphoid hyperplasia w/ eosinophilia?
Central thick-walled areas that looks hobnail-like or cobblestone-like. There is a circumscribed collection of vessels and inflammatory cells w/ lymphocytes and eosinophils (mast cells, plasma cells) and there is often edema around the stroma of the vessels.
Note that the capillaries have large epithelioid endothelial cells w/ intracytoplasmic vacuoles (primitive vascular lumens)
What is the histology of kimura disease?
Deep lymphoid nodules w/ eos, peripheral eos, elevated IgE, large subcutaneous lymphoid nodules and lymphadenopathy
What are the most common locations for pyogenic granulomas?
Children and young adults, gingiva (pregnancy), lips, fingers, face
What things are associated with pyogenic granulomas?
Drugs: retinoids, indinavir, OCP
Pregnancy (especially in gingiva or oral mucosa)
What is the histology of pyogenic granuloma?
Early: solidly packed endothelial cells
Later: ectatic vessels, erosion, and crusting
Epidermal collertte is common and you can commonly have an impetiginized surface.
What is on the differential of pyogenic granuloma and how can it be distinguished?
Bacillary angiomatosis can appear similarly clinically and histologically. However, it will have neutrophil infiltrates and not have ulceration
Who gets tufted angiomas and where are they located?
Children to young adults
Neck and the upper trunk are the most common areas
What are some clinical clues of tufted hemangioma and what syndrome can they be associated with?
There is often hypertrichosis overlying a tufted angioma.
-Platlet trapping can occure and may produce Kasabach-Merrit syndrome
What is the histology of tufted angioma?
Think of tufts of small vessels. It gives a “Cannonball” appearance that compresses vessels. There are multiple separated cellular lobules with spindle-shaped and polygonal cells
What is the ddx of tufted angioma?
Glomeruloid angioma: these have more degenerated erythrocytes and tufts protruding into crescent-like paces
Where do the cells of the glomus tumor arise from?
The Suquet-Hoyer canal
What is the most common location for acquired solitary glomus tumors?
These occur in adults and subungual are the most common site
What is the clinical appearance and most common location of multinucleate cell angiohistocytoma?
Women > 40 years old
Most common location is the legs (especially calves and thighs and the hands)
Slow-growing, grouped, red-to violet papules that can resemble Kaposi’s sarcoma
What is the histology of multinucleate cell angiohistocytoma?
Increased narrow dermal vessels
Large angulated multinucleated giant cells with palisading nuclei and eosinophilic cytoplasm is the main finding
What is the clinical presentation of acroangiodermatitis?
Pseudo-Kaposi sarcoma
- Lower extremities (prominent on first and second toes), purple papules/nodules with variable scale/stasis derm
- Associated with chronic venous insufficiency, limb paralysis, amputation, congenital AV malformation
Histology of acroangiodermatitis?
Proliferation of small vessels in edematous dermis; increased fibroblasts; plump endothelium; hemosiderin
What are the 4 variants of Kaposi sarcoma?
- Classic: 50-60 y/o men, jews, eastern European, Mediterranean, extremities, edema first
- African endemic: tropical Africa, associated w/ EBV and HHV-8 (encodes a IL6 homolog, possible growth factor)
- Immunosuppressive: renal transplants, chemotherapy, long-term corticosteroids
- Epidemic (HIV-associated): mucosa, trunk, head, neck, arms. May have internal organ involvement (GI, lungs), involved with no skin lesions
What is the histology of Kaposi’s sarcoma?
Features change depending on the stage
Early-patch state Kaposi sarcoma: Bizarre staghorn, ectatic, lymphatic-like vessels, plasma cells
Later-patch/plaque Kaposi sarcoma: Busy dermis surrounding adnexal structures and preexisting vessels, pale appearance of busy area (appears understained), promontory sign
-Plaque-stage Kaposi is characterized by vascular wrapping. New vessels wrap and surround pre-existing vascular and adnexal structures. The preexisting structure commonly protrudes into a lakelike ectatic space
Nodular Kaposi sarcoma: Nodule composed of fascicles of parallel spindle cells, erythrocytes between spindle cells, eosinophilic globules, mitoses, hemosiderin
What is the promontory sign seen in Kaposi’s sarcoma?
Jagged, vascular channels with plump endothelial cells surrounding existing vessels, especially patch stage. Sometimes you can see Dorf balls which are pink amorphous globules in vessels
What are the two forms of hemangiopericytoma?
- Congenital or infantile: Birth to fist year of life; boys, Head, neck, extremities, trunk, are the most common locations,
- Adult type: adults, arises in deep soft tissue, lower extremities, pelvis
What is the histology of hemangiopericytoma?
Endothelial-lined vessels surrounded by a proliferation of pericytes
- Concentric or curlicue pattern of spindle cells
- Staghorn etatic vascular spaces
- Most represent examples of a solitary fibrous tumor with staghorn vessels
infantile forms are less likely to be malignant. Larger size and higher mitotic rate may suggest more aggressive/malignant form
What is PILA/papillary intralymphatic angioendothelioma?
These are a low-grade variant of angiosarcoma in children (likely lymphatic differentiation). In children 4 months to 15 years. looks like diffuse swelling or intradermal tumor.
Low malignant potential
What is the name for angiosarcoma that arises in a lymphedematous limb?
Stewart-Treves syndrome
What are the 4 variants of angiosarcoma?
- Idiopathic cutaneous angiosarcoma: males, face/scalp, bluish-violaceous nodules/plaques (rosacea-like, bruise that won’t resolve; metastatic risk
- AS complicating lymphedema (Stewart-Treves): usually 12.5 yrs after surgery, puruplish-red macular or polypoid tumor
- Post-irradiation AS: a/w radiotherapy (12-21 yrs after tx)
- Miscellaneous: pre-exisitng benign vascular tumor, port wine staine, etc
What is the most common location of epithelioid hemangioendothelioma?
They tend to be on the extremities of young people
Histology of epithelioid hemangioendothelioma?
Dilated vascular channels with solid epithelioid and spindle cell areas, intracytoplasmic lumens, variable pleomorphism and mitotic activity, surrounding cells are epithelioid
Where do retiform hemangioendothelioma occur?
On the extremities of young adults
What is the histology of retiform hemangioendothelioma?
Look for arborizing blood vessels that almost looks like the rete testis (you’ll see retiform looking crack like spaces with surrounding collagen and cells)
What is the clinical appearance of angiosarcoma?
Look for bruiselike lesions on the forehead or scalp of an older patients. The epithelioid variants can be nodular
What is the clinical presentation of diffuse dermal angiomatosis and what can it look like?
Diffuse dermal angiomatosis can look like angiosarcoma
It is an acquired benign vascular proliferation in response to stasis or ischemia. So it usually happens in association with an arteriovenous fistula or large pendulous breasts. Pts are often heavy smokers.
What is the clinical appearance of diffuse dermal angiomatosis?
It looks like a poorly circumscribed violaceous plaques with frequent ulceration.
What is the histology of diffuse dermal angiomatosis?
It has new vessels dissecting between collagen bundles, there is no atypia or mitoses
What is the histology of angiosarcoma?
Think blood + busy dermis + vessels (the vessel cells “pile-up” on each other and arch or bridge vessels)
- They are poor circumscribed, have irregularly dissecting vessels lined with pleomorphic endothelial cells
- There is increased mast cells
How do you distinguish angiosarcoma from atypical vascular lesions from radiation?
c-MYC staining –> amplified in angiosarcoma but not in atypical vascular lesions occurring after radiation therapy
What staining might you use for angiosarcoma?
CD34 (no specific, clear stain), CD31 (very specific, but background staining common), ERG-1 (nuclear stain), Ulex europaeus lectin (clean staining, marks endothelium and epithelium), D2-40 stains lymphatic vessels, most angiosarcomas, most tumors associated with kasaback-merritt), c-myc (important to distinguish between angiosarcoma and atypical vascular proliferation from radiation)
What might you stain a glomangioma with?
These will stain w/ smooth muscle actin and vimentin because the glomus cells are modified smooth muscle cells
What stain would you use to differentiate angiosarcoma from benign vascular lesions?
MAPK is negative in angiosarcoma
How do you differentiate angiosarcoma from Paget’s?
CEA (negative in angiosarc, + in pagets)
What is the most specific stain for non-radiation induced angiosarcoma?
ERG
What is the most specific stain for radiation-induced angiosarcoma?
C-myc
What are the things associated with hobnailing?
Dabaska tumor, retiform hemangioma, hobnail hemangioma, anigolymphoid hyperplasia with eos, PILA
