118 - Vasular Tumors Flashcards
Vascular anomalies are broadly divided into
Vascular malformations
Vascular tumors
Errors of vascular morphogenesis
Vascular malformation
Vascular tumors are subdivided into
Benign
Locally aggressive or borderline
Malignant
Benign Vascular Tumors
Infantile hemangioma Congenital hemangioma Tufted hemangioma Spindle-cell hemangioma Epithelioid hemangioma Pyogenic granuloma
Locally Aggressive Vascular Tumors
Kaposiform hemangioendothelioma Retiform hemangioendothelioma PILA, Dabska tumor Composite hemangioendothelioma Kaposi sarcoma
Malignant Vascular Tumors
Angiosarcoma
Epithelioid hemangioendothelioma
Simple Vascular Malformations
Capillary malformation Lymphatic malformation Venous malformation Arteriovenous malformation Arteriovenous fistula
Combined Vascular Malformations
CVM, CLM
LVM, CLVM
CAVM
CLAVM
Most common tumor of infancy
Infantile hemangioma
Infantile hemangiomas are more common in (males/females)
Females
Appears to be the most significant risk factor for IH development
Low birth weight (especially those weighing less than 2500g)
Prenatal risk factors for IH development
Advanced maternal age (older than 30 years of age)
Preeclampsia
Placenta previa
Other placental anomalies
80% of IHs have completed all growth by _____ of age
5 months
The late proliferative stage of ongoing slower growth that occurs after peak rapid growth typically ends by _____ of age
9 months
Deep IHs are more likely to have a (shorter/longer) proliferative phase
Longer
Evidence of involution of IH, often referred to as _____, involves change to a dull red, then gray or milky-white color, followed by flattening and softening
Graying
Graying in IH is usually apparent by _____ of age
1 year
More than 90% of IHs have completed involution by ______ of age
3.5 to 4 years
(Superficial/Deep) IHs are more likely to develop residual skin changes following involution
Superficial
Cutaneous IH classification based on tumor depth
Superficial
Deep
Combined/mixed
Cutaneous IH classification based on distribution
Localized
Segmental
Indeterminate
Multifocal
Most common of the morphologic subtypes of IH
Superficial
Facial segmental IH is associated with risk of
PHACE syndrome
PHACE/S syndrome
Posterior fossa brain malformations Hemangiomas of the face Arterial anomalies Cardiac anomalies Eye abnormalities Sternal defects
Segmental IHs on the lower body confer risk of
Myelopathy and genitourinary anomalies in LUMBAR syndrome
LUMBAR syndrome
Lower body hemangioma and other cutaneous defects Urogenital anomalies Ulceration Myelopathy Bony deformities Anorectal malformations Arterial anomalies Renal anomalies
Multifocal IHs present with ______ or more IHs
6
Involvement of the following areas should alert clinicians to possible increased risk of complications
Central face (especially the nose and perioral skin) Periocular area Neck Mandibular region Perineum
Complications of IH
Ulceration Severe bleeding Scarring Pain Infection Airway obstruction Congestive heart failure Visual compromise
Facial segmental IH patterns have been labeled as 4 segments
Frontotemporal (S1)
Maxillary (S2)
Mandibular (S3)
Frontonasal (S4)
Segments most highly associated with PHACE
Frontotemporal (S1)
Mandibular (S3)
Most common extracutaneous features of PHACE
Congenital vascular anomalies
PELVIS syndrome
Perineal hemangioma External genitalia malformations Lipomyelomeningocele Vesicorenal abnormalities Imperforate anus Skin tag
SACRAL syndrome
Spinal dysraphism Anogenital anomalies Cutaneous anomalies Renal and urologic anomalies Angioma of lumbosacral localization
Most commonly associated extracutaneous abnormality in segmental IHs on the lower body involving the perineum or lumbosacral area
Myelopathy, presenting as tethered cord or lipomyelo(meningo)cele
Infants with periocular hemangiomas are at risk for
Anisometropia
Amblyopia
Permanent visual loss
Most common ocular complication of periocular hemangiomas
Amblyopia
Most favorable prognostic sign to herald normal vision following involution is
Absence of asymmetrical refractive error
Beard area hemangiomas carry a 60% risk of causing
Symptomatic airway disease
Recommended for infants presenting with 5 or more cutaneous IHs
Screening hepatic and abdominal ultrasound
Most common extracutaneous site for IH
Liver
Focal hepatic hemagiomas are not true IHs, but are analogous to
RICH occurring in the liver
Diffuse infantile hepatic hemangiomas can cause
Abdominal compartment syndrome
Severe hypothyroidism
Most common complication of IH
Ulceration
Sensitive marker of impending ulceration in IH
Early gray-white discoloration in patients younger than 3 months
Development of new blood vessels from existing blood vessels
Angiogenesis
De novo development of blood vessels
Vasculogenesis
Studies show IH to be if fetal, rather than maternal origin, and demonstrate immature mesenchymal features with similarities to the _____, an early embryologic vascular structure
Cardinal vein
Most reliable histologic marker of IH
Red blood cell glucose transporter protein
GLUT1
GLUT1 expression is absent in the normal cutaneous vasculature but is found in
Placental blood vessels as well as in other so-called barrier tissues, such as the blood-brain barrier
Postulated to trigger neovasculogenesis in infants
Hypoxia
Hepatic hemangioma demonstrates high levels of _____ activity, which accelerates the degradation of thyroid hormone
Type III iodothyronine deiodinase
The most important factor to affect prognosis in complicated IH is
Timing of specialist referral for management
Only medication approved by the US FDA for the treatment of complicated IH
Propranolol
In _____, it is recommended to use the lowest effective dose, consider a slower dose titration, and to give the medication in 3 divided doses
PHACE
Common side effects of propranolol
Sleep disturbance
Acrocyanosis
Asymptomatic transient decrease in blood pressure or heart rate
Rarely observed potential important adverse effects of propranolol
Hypoglycemia Symptomatic hypotension or bradycardia Wheezing Bronchospasm Diarrhea
In determining a patient’s candidacy for propranolol, family history must be obtained to ensure absence of
Congenital heart disease
Arrhythmia
Maternal connective tissue disease
Dosing of propranolol for IH
Start at 1 mg/kg/day in 2 divided doses
Increase by 0.5 mg/kg/day increments every 3 to 7 days to a target dose between 2 and 3 mg/kgday
Main benefit of atenolol (beta1-selective antagonist)
Lack of bronchial reactivity
Advantage of nadolol (nonselective beta-antagonist)
Inability to cross the blood-brain barrier
Nonselective beta blocker available in an ophthalmic preparation approved for the treatment of pediatric glaucoma
Eight to 10 times more potent than propanolol
Topical timolol
Corticosteroid are most effective during the _____ phase of IH
Proliferative
Dosing of prednisone or prednisolone for IH
2 to 3 mg/kg/day typically for 4-8 weeks followed by a tapering of varying length
Short-term complications of systemic corticosteroids
Cushingoid facies Personality changes (irritability/fussiness) Gastric irritation Fungal infection Diminished gain of height and weight
Other complications of systemic corticosteroids
Hypertension
Steroid-induced myopathy
Immunosuppression
Transient adrenal insufficiency
Children taking more than _____ mg/kg/day of prednisone for longer than _____ days are considered to have a deficit in cell-mediated immunity
2
14
Reported adverse events of intralesional corticosteriods for periocular hemangiomas
Retinal artery embolization
Blindness
PDL is primarily limited by its minimal depth of penetration (less than _____)
2 mm
Even earlier excision may be indicated in cases where clinical characteristics, such as _____ dictate that scarring will inevitably occur
Pedunculated IH
Severe, recalcitrant ulceration
Extremely thick dermal involvement
_____ years serve as a na appropriate threshold for decisions regarding surgery
Four
Raised, violaceous tumor with large, radiating veins or with overlying telangiectasia and a halo of pallor
Involute spontaneously by or before 14 months of age
Rapidly involuting congenital hemangioma
Somatic activating missense mutations in the genes _____ are reported to cause RICH and NICH
GNAQ
GNA11
Also called angioblastoma of Nakagawa
Tufted angioma
Demonstrate vascular tufts of tightly packed capillaries, randomly dispersed throughout the dermis in a typical “cannonball distribution” with crescenteric spaces surrounding the vascular tufts, and lymphatic-like spaces within the tumor stroma
Tufted angioma
CD31+
D2-40, LYVE1, PROX1 are partially positive
Tufted angioma
Kaposiform hemangioendothelioma does not occur in the
Liver
Presence of platelet trapping within a vascular tumor resulting in a profoundly severe thrombocytopenia (typically less than 30000/microliter) ad associated with 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
Kasabach-Merritt Phenomenon is a complication almost exclusively of
Tufted angioma
Kaposiform hemangioendothelioma
Involvement of KHE across more than _____ anatomic region increases the risk of developing KMP
1
KHE presenting at a later age, with superficial tumors or tumors involving only bone, appears to have a (lower/higher) risk of KMP
Lower
Considered first-line treatment for KHE and are often used in combination with vincristine
Systemic corticosteroids
Rare benign vascular tumor most often seen with Maffucci syndrome
Spindle-cell hemangioma
Genetic mutation associated with Maffucci syndrome
IDH1
IDH2
Nodular, dense, spindle cell proliferation associated with dilated dysplastic veins
Spindle-cell hemangioma
Solitary, red, rapidly growing papule or nodule, often with a subtle collarette of scale
Typical locations include the cheek and forehead
Pyogenic granuloma
Band-Aid disease - often develop an eroded surface, with subsequent bleeding which can be profuse
Pyogenic granuloma
Multiple cutaneous vascular papules and plaques that are usually congenital with development of new lesions over time
Multifocal lymphagioendotheliomatosis with thrombocytopenia
Most infants affected with _____ have intermittent thrombocytopenia and lesions in the GI tract, leading to GI bleeding
Multifocal lymphagioendotheliomatosis with thrombocytopenia
Thin-walled vessels, some hobnailed endothelial cells, and intraluminal papillary projections
Multifocal lymphagioendotheliomatosis with thrombocytopenia (similar to Dabska tumor)
Also known as Dabska tumor
Papillary intralymphatic angioendothelioma
Dermal nodule or a diffuse violaceous swelling on the head, neck, or extremities that is seen almost exclusively in the pediatric age group
Papillary intralymphatic angioendothelioma/Dabska tumor
Enlarged vessels with thick walls surrounded with lymphoid aggregates and smaller lymphatic vessules
Papillary intralymphatic angioendothelioma/Dabska tumor
The presence of _____ is the sine qua non of papillary intralymphatic angioendothelioma/Dabska tumor
“Hobnail” endothelial cells inside tumoral vessels
Occurs primarily in adults and has a significant overlap with PILA/Dabska tumor
Retiform hemangioendothelioma
Retiform pattern of long, arborizing blood vessels lined by monomorphic hobnail endothelial cells
Prominent lymphocytic infiltrate with focal presence of hyaline collagenous core comprising papillae
Retiform hemangioendothelioma
Combination of benign and malignant vascular components
Identification of at least 2 hemangioendothelioma variants is necessary to render this diagnosis
Composite hemangioendothelioma
Violaceous papule, often surrounded by a pale rim and peripheral ecchymotic halo, which fades with time
Targetoid hemosiderotic hemangioma
Dilated intraluminal papillary projections dissecting into collagen bundles in the subcutis
Extravasated erythrocytes and hemosiderin are present
Targetoid hemosiderotic hemangioma
Also called sudoriparous angioma
Congenital eccrine angiomatous hamartoma
Ill-defined plaques with increased lanugo hair and sweating at the site of the lesion
Congenital eccrine angiomatous hamartoma
Closely packed eccrine sweat glands associated with dilated capillaries, a few dysplastic venous channels, and a dense collagenous matrix
Congenital eccrine angiomatous hamartoma
