20 - 118: VASCULAR TUMORS Flashcards
most significant risk factor for development of infantile hemangioma (IH)
LBW <2500g
Characteristic of infantile hemangiomas, except
a. presence at birth
b. presence of a nascent IH
c. presence of area of pallor
d. presence of telangiectasias
a. presence at birth – absence at birth
S1 IH corresponds to anomalies in the
a. cerebral, cerebrovascular, ocular
b. less associated with extracutaneous features
c. airway involvement
d. cardiovascular abnormalities
a. cerebral, cerebrovascular, ocular
most common extracutaneous features of PHACE
cardiac anomalies
Areas most highly associated with PHACE
S3 – and S1
area that carries 60% of symptomatic airway disease
S3
Multifocal IH are considered if the patient presents with ___ or more IH
c. 6 p 2045
MC complication of IH
a. GI bleeding
b. early onset vascular stroke
c. Ulceration
d. DVT
c. Ulceration
rare complication in infants with diffuse infantile hemangiomas
a. Hypothyroidism
b. Hyperthyroidism
c. Hypercalcemia
d. Hypocalcemia
a. Hypothyroidism
Alternative drug to propranolol that lacks bronchial reactivity
Atenolol
β1-selective antagonist
most common tumor of infancy
Infantile hemangiomas
most significant risk factor for IH development
Low birth weight
characteristic features of IH
- ABSENT at birth or presence of a nascent IH often an area of pallor, telangiectasias or duskiness
There is _____% risk increase of infantile hemangioma for every _______ g decrease in birth weight
40%
500g
peak Infantile hemangioma growth period
5.5 and 7.5 weeks of age
Most common location of IH
Head and neck
but can be found on any cutaneous or mucosal site
Fill in the blanks.
Almost all IHs with a superficial component become apparent in the _______ month of life, and most will at least double in size within the first _______months of life.
- become apparent in the First month of life
- double in size within the first 2 months of life
While 80% of growth has occurred by _____months of age, 80% of IHs have completed all growth by ______ months of age
- 80% of growth has occurred by 3 months of age
- 80% of IHs have completed all growth by 5 months of age
The late proliferative stage of ongoing slower growth that occurs after peak rapid growth typically ends by _______ months of age
9 months
Evidence of involution, often referred to as ________
graying
- involves change to a dull red, then gray or milky-white color, followed by flattening and softening
Evidence of involution, often referred to as graying, is usually apparent by what age?
usually apparent by 1 year of age
More than 90% of IHs have completed involution by what age?
3.5 to 4 years of age
True or False:
DEEP IHs are more likely to develop residual skin changes following involution compared with SUPERFICIAL IHs
FALSE
Superficial IHs are more likely to develop residual skin changes following involution compared with deep IHs
A less-common subtype of IH is distinguished by its minimal-to-absent proliferation and telangiectatic surface
IH with minimal or abortive growth
the presence of facial segmental IH is associated with risk of what?
PHACE (posterior fossa brain malformations, hemangiomas of the face, arterial anomalies, cardiac anomalies, and eye abnormalities)
Segmental IHs on the lower body confer risk of what syndrome?
myelopathy and genitourinary anomalies in LUMBAR (lower body hemangioma and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies) syndrome
term used to those that are not clearly identifiable as localized or segmental IH; some authors consider them to be “subsegmental”
Indeterminate IHs
Multifocal (multiple localized) IHs are less common, with fewer than 3% of infants presenting with _________ or more IHs.
6
This subtype of IHs are 11 times more likely to experience complications and 8 times more likely to receive treatment
segmental hemangiomas
possible complications of infantile hemangioma
ulceration, severe bleeding, scarring, pain and infection
High-risk Infantile Hemangioma Features
Enumerate the 4 segments of facial segmental IH
S1: frontotemporal
S2: maxillary
S3: mandibular
S4: frontonasal
this segment of facial segmental IH is associated with cerebral, cerebrovascular, and ocular anomalies
S1: frontotemporal segment
this segment of facial segmental IH is less-frequently associated with extracutaneous involvement
maxillary segment (S2)
this segment of facial segmental IH is correlated with airway IH, ventral developmental defects, and cardiovascular abnormalities
mandibular segment (S3)
this segment of facial segmental IH encompasses the high-risk territory of the nose, including the nasal tip, and confers risk of cerebral and cerebrovascular involvement
frontonasal segment (S4)
facial segments most highly associated with PHACE
frontotemporal (S1) and mandibular (S3) segments
most common extracutaneous features in PHACE
Congenital vascular anomalies
segmental IHs on the lower body involving the perineum or lumbosacral area are risk factors for associated spinal, bony, and genitourinary anomalies
LUMBAR syndrome describes the constellation of lower body hemangioma and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies
most commonly associated extracutaneous abnormality in LUMBAR syndrome presenting as tethered cord or lipomyelo(meningo)cele
Myelopathy
most common ocular complication, occurring in 40% to 60% of infants with untreated periocular IH
Amblyopia
IHs larger than ______in diameter confer greater risk of amblyopia, significantly lowering the threshold to initiate treatment.
1 cm
The most favorable prognostic sign to herald normal vision following involution
absence of asymmetrical refractive error
most common extracutaneous site for IH
Liver
T/F.
Focal hepatic hemangiomas are not true IHs.
Multifocal and diffuse hepatic hemangiomas are true IHs.
True
most common complication of IH
ulceration
- occurring in greater than 20% of infants in a referral setting, typically during the proliferative phase, with a median age of onset of 4 months
sensitive marker of impending ulceration of IH
Early gray-white discoloration in patients younger than 3 months
most reliable histologic marker of IH, which is expressed in all stages of IH
GLUT1, a red blood cell glucose transporter protein
only medication approved by the United States Food and Drug Administration (FDA) for the treatment of complicated IH
Propranolol
Molecular mechanisms of propranolol in effectively treating IH include lesional capillary vasoconstriction (visible IH color change within first 48 hours of use), angiogenesis inhibition (arresting growth), and induction of apoptosis (bringing about IH regression).
refers to errors of vascular morphogenesis
Vascular malformations
give examples of benign vascular TUMORS
give examples of locally aggressive vascular tumors
give examples of malignant vascular tumors
give examples of vascular malformations
classification of infantile hemangioma based on depth
- superficial,
- deep,
- combined/mixed
classification of infantile hemangioma based on distribution
- localized,
- segmental,
- indeterminate,
- multifocal
most common of the morphologic subtypes of infantile hemangiomas
superficial IHs
subtype of IH that presents as bright fuchsia pink to “strawberry” red vascular plaques or nodules; they involve the papillary dermis
Superficial IHs
characterize deep IH
- present as a partially compressible, localized subcutaneous tumors with variable prominence depending upon depth in the skin, and either appear with a slight blue hue or the same color as the surrounding skin; they may be noted, on average, 1 month later than superficial IHs.
- Less frequently, deep IHs are not appreciated until the infant is a few months of age.
- more likely to have a longer proliferative phase
- later onset of involution compared with their superficial counterparts
PHACE stands for?
posterior fossa brain malformations, hemangiomas of the face, arterial anomalies, cardiac anomalies, and eye abnormalities
IHs that are not clearly identifiable as localized or segmental
Indeterminate IHs
one of the most important factors affecting risk of extracutaneousmanifestations of IH
Anatomic location
What is the associated risk or complication when IH is located on facial, large segmental area?
PHACE (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, sternal clefting) syndrome
What is the associated risk or complication when IH is located on the Nasal tip, ear, large facial area (especially with prominent deep component)?
Permanent scarring, cartilage destruction, disfigurement
What is the associated risk or complication when IH is located on the Periorbital and retrobulbar area?
Ocular axis occlusion, astigmatism, amblyopia, tear-duct obstruction
What is the associated risk or complication when IH is located on the Segmental (S3)/”beard area,” central neck?
Airway infantile hemangioma
What is the associated risk or complication when IH is located on the Perioral area?
Ulceration, disfigurement, feeding difficulties
What is the associated risk or complication when IH is segmental overlying lumbosacral spine?
Myelopathy, genitourinary anomalies
What is the associated risk or complication when IH is located on the Perineal, axilla, neck, perioral area?
Ulceration
What is the associated risk or complication when IH is multifocal?
Visceral involvement (especially liver, GI tract)
LUMBAR syndrome describes the constellation of what manifestations?
lower body hemangioma and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies
this event is postulated to trigger neovasculogenesis in infants with IH
hypoxia
At present, the most supported explanation suggests that hypoxia (in utero or in local tissue) is key to stimulation of circulating endothelial progenitor cells (CD34+, CD133+ stem cells), subsequent vasculogenesis with ensuing proliferation to maintain tissue oxygenation homeostasis, and eventual increased apoptosis (beginning by end of first year of life) to initiate involution
what stains can you request in IH?
Ki-67 and GLUT-1
IHs are also CD31+ and CD34+
- In early IH, markers of cellular proliferation such as Ki-67 denotes proliferation of endothelium and pericytes and normal appearing mitotic figures appear abundant
- When necessary to confirm the diagnosis on histopathologic specimen, GLUT1 immunostaining is positive in the endothelial cells lining IH capillaries at all stages of IH growth, distinguishing IH from other vascular tumors and all vascular malformations
what should you evaluate if there is presence of a segmental IH of the head, neck, and/or scalp?
evaluation for possible PHACE to include** MRI and MRA of the head/neck/chest,** formal ophthalmologic evaluation, and echocardiogram
prognosis of IH
- The prognosis of most IHs is excellent, with spontaneous involution and little to no sequelae, but a significant minority of IH result in permanent disfigurement or medical sequelae
- Following involution, approximately half of all treated patients will attain normal skin, while the other half can have residual atrophy, scarring, telangiectasias, or fibrofatty softtissue remnant.
- The most important factor to affect prognosis in complicated IH is timing of specialist referral for management, including initiation of therapy and workup as necessary.
Key criteria to warrant consideration of beta-blocker treatment initiation for IH
- facial deformity,
- active or impending functional impairment,
- early prevention of anticipated permanent sequelae,
- mitigation of the need for surgery
Common side effects of propranolol
- sleep disturbance, acrocyanosis, and asymptomatic transient decrease in blood pressure or heart rate
- Rarely observed potential important adverse effects include hypoglycemia, symptomatic hypotension or bradycardia, wheezing, bronchospasm, and diarrhea
current proposed factors favoring inpatient initiation of propranolol
- young age (the study on which FDA approval of propranolol was granted included infants as young as 5 weeks of age with outpatient initiation),
- comorbid medical conditions (eg, respiratory or cardiovascular),
- inadequate social support, or
- any preexisting concerns for blood glucose
youngest age allowable to receive outpatient initiation of propranolol
5 weeks
propranolol dosing for IH
Dosing is typically started at 1 mg/kg/day in 2 divided doses and increased by 0.5 mg/kg/day increments every 3 to 7 days to a target dose between 2 and 3 mg/kg/day.
- Most practitioners use 2 mg/kg/day.
- Slower dose escalation or lower target dose may be warranted in the setting of PHACE syndrome, ulceration or other comorbid conditions.
a nonselective β-antagonist which has an advantage of its inability to cross the blood–brain barrier, thereby decreasing concerns for any potential neurocognitive side effects compared with propranolol
nadolol
- nonselective beta blocker available in an ophthalmic preparation approved for the treatment of pediatric glaucoma
- this is 8 to 10 times more potent than propranolol
- it has been reported as an effective option for IH
Topical timolol
When used, prednisone or prednisolone is given at what dose for IH?
2 to 3 mg/kg/day, typically for 4-8 weeks followed by a tapering of varying length, depending on the age of the child and indication for treatment
Vincristine’s use in the treatment of vascular tumors is now reserved for what tumors?
complicated kaposiform hemangioendothelioma (KHE) and tufted angioma (TA)
Proposed indications for surgical intervention of IH during infancy
- anatomically favorable site amenable to resection,
- a contraindication or failure of pharmacotherapy, or a
- high risk of ultimately necessary resection with similar scar regardless of timing of surgery
When is screening for PHACE warranted?
Screening for PHACE is recommended in the setting of segmental IH on the head, in infants without classic segmental IH or with a small IH who have a major anomaly seen in PHACE (eg, coarctation of the aorta or supraumbilical raphe) and in infants with **2 major criteria for PHACE **as outlined in consensus guidelines from 2016
Hemangiomas that are fully formed tumors at the time of birth and do not proliferate in postnatal life
congenital hemangiomas
They are benign and much less common than IH
3 major subtypes of congenital hemangiomas
- rapidly involuting (RICH),
- noninvoluting (NICH),
- partially involuting congenital hemangioma
areas of predilection of congenital hemangiomas
head, neck, and extremities
- RICH often appears as a raised, violaceous tumor with large, radiating veins or with overlying telangiectasia and a halo of pallor
- Central ulceration may be present
Most RICHs involute spontaneously by or before how many months of age and usually leave residual atrophic anetodermic scar tissue?
14 months of age
Somatic activating missense mutations in what genes are reported to cause RICH and NICH?
GNAQ and GNA11
Indications for treatment of congenital hemangiomas
ulceration, impairment of vital function and congestive heart failure
Excision, with or without preoperative embolization, should definitely be considered for ulceration, which can lead to severe hemorrhage, and for postinvolutional skin changes if disfiguring
what is the GLUT1 staining of congenital hemangioma?
negative
Infantile hemangioma is positive
- most commonly seen on the neck, trunk, and extremities.
- They may present as a subtle stain-like area that later thickens, as a large, plaque-like, infiltrated, red or dusky blue-purple lesion, or as an exophytic, firm, rubbery, violaceous, cutaneous nodule
- Tenderness and overlying hyperhidrosis may occur.
Tufted angioma
- infiltrative, aggressive tumor classified as locally aggressive or borderline in the ISSVA classification
- It may present as a brown-red stain at birth which begins to thicken and become purpuric, or as plaques or deep-seated nodules and bulky tumors.
- Most cases involve the skin and musculature
- It can occur on the extremities, especially overlying joints, trunk, head, neck.
- Deeper viscera including cervicothoracic, abdominal, and the retroperitoneum can be affected
KAPOSIFORM HEMANGIOENDOTHELIOMA
refers to the presence of platelet trapping within a vascular tumor resulting in profoundly severe thrombocytopenia (typically less than 30000/µL) and associated **microangiopathic hemolytic anemia **and **consumption of clotting factors **resulting in **low fibrinogen, elevated D-dimers, **and varying degrees of decreased coagulation factors
Kasabach-Merritt Phenomenon
what laboratory abnormalities are seen in Kasabach-Merritt Phenomenon?
- severe thrombocytopenia (typically less than 30000/µL)
- microangiopathic hemolytic anemia
- low fibrinogen
- elevated D-dimers
- decreased coagulation factors
Which vascular tumors may present with Kasabach-Merritt Phenomenon as complication?
Kaposiform Hemangioendothelioma and Tufted Angioma
KHE>TA
rare benign vascular tumor most often seen with Maffucci syndrome
Spindle-cell hemangioma
- IDH1 and IDH2 genetic mutation
- It can occur at any age and site but the extremities are the most commonly affected.
- The histology is of a nodular, dense, spindle cell proliferation associated with dilated dysplastic veins.
considered first-line treatment of Kaposiform Hemangioendothelioma
Systemic corticosteroids often used in combination with vincristine, especially in the setting of KMP
Ticlopidine and aspirin are reported as adjunctive therapies with variable benefit
- usually presents as a solitary, red, rapidly growing papule or nodule, often with a subtle collarette of scale
- Typical locations include the cheek or forehead, but virtually any body site including the mucous membranes may be affected
pyogenic granuloma
The presence of “hobnail” endothelial cells inside tumoral vessels is the sine qua non of this tumor
Papillary intralymphatic angioendothelioma (PILA), also known as Dabska tumor
