Vascular lesions in pediatric patients

Juan Putra, MD
Department of Pathology, Boston Children’s Hospital
Harvard Medical School
 Acknowledgements
Cincinnati
Children’s
Medical Center

Anita Gupta MD

Alyaa Al-Ibraheemi, MD Harry Kozakewich, MD

 International Society for the Study of
Vascular Anomalies (ISSVA)

• Formalized in 1992
• Membership around 600
• Interdisciplinary society
• Meetings biennially
 Nomenclature
• Anomaly includes tumors and malformations
• Tumors are masses and arise by cellular hyperplasia
• Malformation is error in morphogenesis usually
evident at birth and grows commensurately with the
child (not always true)
• Distinction between tumor and malformation is not
always clear-cut
• “Hemangioma” should not be used in a generic sense
• Concepts and terminology evolving
 Vascular tumor (ISSVA classification, 2014)
Benign Intermediate/borderline
• Infantile hemangioma • Hemangioendothelioma
• Congenital hemangioma (CH) – Kaposiform
– Rapidly involuting CH – Retiform
– Non-involuting CH – Composite
– Partially involuting CH • Papillary intralymphatic
• Tufted angioma angioendothelioma
• Spindle cell hemangioma • Kaposi sarcoma
• Epithelioid hemangioma
• Pyogenic granuloma Malignant
• Others • Angiosarcoma
• Epithelioid hemangioendothelioma
Know about your patient!
 Case 1

1-year-old female with an enlarging left cheek

lesion, first noticed a few weeks after birth
Courtesy of Dr. Harry Kozakewich
GLUT-1
 Infantile hemangioma

• The most common tumor of infancy (4-10%)

– Caucasian >> African American and Asian
• Female predominance
• Most common in cervicofacial locations
• Presented during the first few weeks of life as a
solitary cutaneous lesion that progressively enlarges
over months and then gradually regresses
• May be multiple and/or involve visceral organs
 PHACE and LUMBAR associations
Posterior fossa and other brain abnormalities Lumbosacral and limb hemangioma
Hemangioma(s) of cervico-facial region Urogenital anomalies
Myelopathy
Arterial cerebrovascular anomalies
Bony abnormalities
Cardiac defects Anorectal and arterial abnormalities
Eye anomalies, endocrine Renal anomalies
 Infantile hemangiomas

Proliferative
Involuting
SIZE

1st 2nd 3rd

1 year 2 years 3 years

Prenatal Birth Postnatal

AGE
 Infantile hemangiomas

2 months 24 months 10 years

Wassef M et al. Pediatrics. 2015; 136(1): e203-214

Infantile hemangioma- proliferative phase

Courtesy of Dr. Harry Kozakewich

Infantile hemangioma- involuting phase

Darrow DH et al. Pediatrics. 2015; 136(4): e1060-104

Infantile hemangioma- CD31
Infantile hemangioma- GLUT-1
 Management

• Beta-blockers (propranolol) – first line treatment

– Vasoconstriction
– Inhibition of angiogenesis
– Stimulation of apoptosis
• Corticosteroids
• Laser treatment and surgery
 Case 2

2 year old male with persistent

shoulder lesion present since birth
Case 2

GLUT1 negative

Wassef M et al. Pediatrics. 2015; 136(1): e203-214

 Congenital hemangiomas

• Benign vascular tumors that, unlike infantile

hemangiomas, are present and fully grown at birth
• Somatic mutation involving GNAQ
• Histology: capillary lobules where endothelial cells do
not express Glut-1 and are associated with large
extralobular veins, arteries, and lymphatics.
• Classification (based on involution)
– Rapidly involuting CH (RICH): complete involution in 6-14
months
– Non-involuting CH (NICH): lesions might enlarge
– Partially-involuting CH (PICH): decrease in size in 12-30 months
and then stabilize
 Congenital hemangiomas

A large scalp vascular mass was present at birth in this infant

https://www.uptodate.com/contents/rapidly-involuting-congenital-hemangioma-rich-and-noninvoluting-congenital-hemangioma-nich#H13843143
 Congenital hemangiomas

Infantile Hemangioma
NICH

SIZE
RICH, FT PICH

RICH

1st 2nd 3rd

1 year 2 years 3 years

Prenatal Birth Postnatal

AGE

RICH, FT: Rapidly involuting congenital hemangioma, fetal type

RICH: Rapidly involuting congenital hemangioma
PICH: Partially involuting congenital hemangioma
NICH: Non-involuting congenital hemangioma
Rapidly involuting congenital hemangioma

1 month 8 months
Rapidly involuting congenital hemangioma

Always GLUT-1 negative

Courtesy of Harry P. Kozakewich

Non-involuting congenital hemangioma

Courtesy of Harry P. Kozakewich

Non-involuting congenital hemangioma

Always GLUT-1 negative

Courtesy of Harry P. Kozakewich

 Management

• Treatment is unnecessary unless there are

complications (ulceration, bleeding)
– Pulsed-dye laser treatment
– Surgery (with/without arterial embolization)
 Case 3

9-day-old male with vascular mass in the

left lower extremity and thrombocytopenia
Case 3
CD34
D2-40
 Kaposiform hemangioendothelioma

• Locally aggressive vascular neoplasm occurring

primarily in neonates and children
• Kaposiform – histologically similar to Kaposi sarcoma
• Hemangioendothelioma – borderline malignant
behavior
• Rare (less than 1 in 100,000 children in the U.S.)
• Most commonly involved extremities followed by
trunk, retroperitoneal, and cervicofacial regions
• Thrombocytopenia and consumptive coagulopathy?
– Kasabach-Meritt phenomenon
 Kasabach-Merritt phenomenon

• Thrombocytopenia due to intralesional platelet

entrapment
• Seen in up to 70% of kaposiform hemangioendotheliomas
– Lesions greater than 8 cm
– Lesions in the retroperitoneum, mediastinum, or multiple
anatomical regions
• 30-40% mortality rate
Kaposiform hemangioendothelioma
Kaposiform hemangioendothelioma

Putra J, Gupta A. Pathology. 2017; 49(4): 356-362

Kaposiform hemangioendothelioma

Putra J, Gupta A. Pathology. 2017; 49(4): 356-362

Kaposiform hemangioendothelioma

PROX-1 D2-40

Putra J, Gupta A. Pathology. 2017; 49(4): 356-362

 Management

• Resection is difficult because of the extent of the lesion

• Corticosteroids
• Chemotherapies
– vincristine, cyclophosphamide, actinomycin, doxorubicin, and
gemcitabine
• Radiation therapy
• Mechanistic target of rapamycin (mTOR) inhibitor -
sirolimus
 Histologic differential diagnosis

• Infantile hemangioma
• Congenital hemangioma
• (Acquired) tufted angioma
• Deep-seated pyogenic granuloma
 Tufted angioma

• Milder and superficial version of kaposiform hemangioendothelioma

• Similar histology and immunophenotype as kaposiform hemangioendothelioma
• Few cases are associated with Kasabach-Merritt phenomenon

Wassef M et al. Pediatrics. 2015; 136(1): e203-214

Putra J, Gupta A. Pathology. 2017; 49(4): 356-362
Deep-seated pyogenic granuloma

Putra J et al. J Cutan Pathol. 2017; 44(6):516-522

 Case 4
12-year-old female with painful and
enlarged calf
• 16 patients (13 female; 3 female)
• Age range: neonate to 28 years
• Locations:
• Calf (n=10)
• Forearm/wrist (n=3)
• Thigh (n=3)
• Painful lesion (seen in 15 patients)
• PIK3CA mutations
J Pediatr Orthop 2014;34:109–117
 Fibro-adipose vascular anomaly

• Differential diagnosis:
– Venous malformation
– PTEN-associated hamartoma
• Therapeutic implications:
– Fibro-adipose vascular anomaly: resection and physical
therapy (risk for contracture)
– Venous malformation: sclerotherapy (first line
management)
 Venous malformation

• Most often involve skin, subcutis, skeletal muscle

• Most are non-familial, solitary, and localized
• Visceral lesions most often in liver and brain
• Malformed venous channels of any size
• Special types:
– Blue rubber bleb nevus syndrome
– Cerebral cavernous malformation
– Verrucous venous malformation
Venous malformation
 PTEN hamartoma of soft tissue

• Cowden syndrome; Bannayan-Riley-Ruvalcaba syndrome

• 34 patients (22 F, 12 M)
• Age range: 3 to 42 years (median of 12 years)
• Genetic mutation confirmed in 16 patients
• Pain and swelling in the lower extremity (most common)

Am J Surg Pathol. 2012 May ; 36(5): 671–687

PTEN hamartoma of soft tissue
PTEN hamartoma of soft tissue
PTEN hamartoma of soft tissue
 Summary

GLUT1 (+)
Infantile Hemangioma
NICH

SIZE
GLUT1 (-)
RICH, FT PICH

RICH

1st 2nd 3rd

1 year 2 years 3 years

Prenatal Birth Postnatal

AGE
 Summary

• Kaposiform hemangioendothelioma
– Deep and extensive; nodular, D240 (+)
– Kasabach-Merritt phenomenon
– Mild form: tufted angioma

• Fibroadipose vascular anomaly

– Painful calf lesion
– PIK3CA mutation
– Differential diagnosis:
• Venous malformation
• PTEN soft tissue hamartoma
Thank you