Sandbox:Hannan

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]

Overview

Vascular Anomalies
Vascular Tumors	Vascular Malformations
Benign Locally aggressive or Borderline Malignant	Simple	Combined°	of major named vessels	associated with other anomalies
	Capillary malformations Lymphatic malformations Venous malformations Arteriovenous malformations* Arteriovenous fistula*	Capillary venous malformation , Capillary lymphatic malformation Lymphatic venous malformation, Capillary lymphatic venous malformation Capillary arteriovenous malformation Capillary lymphatic arteriovenous malformation others	See details	See list

° defined as two or more vascular malformations found in one lesion

* high flow lesions

Classification

Classification of Vascular Malformations

Vascular malformations

Simple

Combined

of major named vessels

asscoiated with other anomalies

Combined vascular malformations* CM + VM Capillary-venous malformation CVM CM + LM Capillary-lymphatic malformation CLM CM + AVM Capillary-arteriovenous malformation CAVM LM + VM Lymphatic-venous malformation LVM CM + LM + VM Capillary-lymphatic-venous malformation CLVM CM + LM + AVM Capillary-lymphatic-arteriovenous malformation CLVM CM + VM + AVM Capillary-venous-arteriovenous malformation CVAVM CM + LM + VM + AVM Capillary-lymphatic-venous-arteriovenous malformation CLVAVM

Anomalies of major named vessels (also known as "channel type" or "truncal" vascular malformations)

Vascular malformations associated with other anomalies Klippel-Trenaunay syndrome CM + VM +/-LM + limb overgrowth Parke's Weber syndrome CM + AVF + limb overgrowth Servelle-Martorell syndrome Limb VM + bone undergrowth Sturge-Weber syndrome Facial + leptomeningeal CM + eye anomalies +/-bone and/or soft tissue overgrowth Maffucci syndrome VM +/-spindle-cell hemangioma + enchondroma CLOVES syndrome LM + VM + CM +/-AVM+ lipomatous overgrowth Proteus syndrome CM, VM and/or LM + asymmetrical somatic overgrowth Bannayan-Riley-Ruvalcaba sd lower lip CM + face and neck LM + asymmetry and partial/generalized overgrowth Limb CM + congenital non-progressive limb overgrowth Macrocephaly-CM (M-CM / MCAP) Microcephaly-CM (MICCAP)

Capillary malformations

Lymphatic malformations

Venous malformations

Arteriovenous malformations

Arteriovenous fistula

Nevus simplex / salmon patch, “angel kiss”, “stork bite”

Common (cystic) LM Macrocystic LM Microcystic LM Mixed cystic LM

Common VM

Sporadic

Sporadic

Cutaneous and/or mucosal CM (also known as “port-wine” stain) Nonsyndromic CM CM with CNS and/or ocular anomalies (Sturge-Weber syndrome) CM with bone and/or soft tissues overgrowth Diffuse CM with overgrowth (DCMO)

Generalized lymphatic anomaly (GLA) Kaposiform lymphangiomatosis (KLA)

Familial VM cutaneo-mucosal (VMCM)

In HHT

In HHT

Reticulate CM CM of MIC-CAP (microcephaly-capillary malformation) CM of MCAP (megalencephaly-capillary malformation-polymicrogyria)

LM in Gorham-Stout disease

Blue rubber bleb nevus (Bean) syndrome VM

In CM-AVM

In CM-AVM

CM of CM-AVM

Channel type LM

Glomuvenous malformation (GVM)

Others

Others

Cutis marmorata telangiectatica congenita (CMTC)

“Acquired” progressive lymphatic anomaly (so called acquired progressive "lymphangioma")

Cerebral cavernous malformation (CCM)

Others

Primary lymphedema

Familial intraosseous vascular malformation (VMOS)

Telangiectasia Hereditary hemorrhagic telangiectasia (HHT) Others

Others

Verrucous venous malformation (formerly verrucous hemangioma)

Others

Tables

Anomalies of major named vessels (also known as "channel type" or "truncal" vascular malformations)
Affect lymphatics veins arteries Anomalies of origin course number length diameter (aplasia, hypoplasia, stenosis, ectasia / aneurysm) valves communication (AVF) persistence (of embryonal vessel)

Combined vascular malformations*
CM + VM	capillary-venous malformation	CVM
CM + LM	capillary-lymphatic malformation	CLM
CM + AVM	capillary-arteriovenous malformation	CAVM
LM + VM	lymphatic-venous malformation	LVM
CM + LM + VM	capillary-lymphatic-venous malformation	CLVM
CM + LM + AVM	capillary-lymphatic-arteriovenous malformation	CLAVM
CM + VM + AVM	capillary-venous-arteriovenous malformation	CVAVM
CM + LM + VM + AVM	capillary-lymphatic-venous-arteriovenous m.	CLVAVM

Vascular malformations associated with other anomalies
Klippel-Trenaunay syndrome *		CM + VM +/-LM + limb overgrowth
Parkes Weber syndrome		CM + AVF + limb overgrowth
Servelle-Martorell syndrome		limb VM + bone undergrowth
Sturge-Weber syndrome		facial + leptomeningeal CM + eye anomalies +/-bone and/or soft tissue overgrowth
Limb CM + congenital non-progressive limb overgrowth
Maffucci syndrome		VM +/-spindle-cell hemangioma + enchondroma
Macrocephaly-CM (M-CM / MCAP) *
Microcephaly-CM (MICCAP)
CLOVES syndrome *		LM + VM + CM +/-AVM+ lipomatous overgrowth
Proteus syndrome		CM, VM and/or LM + asymmetrical somatic overgrowth
Bannayan-Riley-Ruvalcaba sd	lower lip CM + face and neck LM + asymmetry and partial/generalized overgrowth

Vascular Tumors

Locally aggressive or borderline vascular tumors

Kaposiform hemangioendothelioma

• Locally Aggressive tumor that originates on skin and occurs primarily in childhood. It is characterized by a single or multiple masses with following characteristics:

     ** Deep reddish-purple color
     ** Shiny, firm texture
     ** Warm to the touch
     ** Swollen and painful

• May be complicated by Kasabach-Merritt phenomenon (KMP), characterized by consumption coagulopathy, thrombocytopenia, and hemolytic anemia. Typical features also include low fibrinogen and elevated D-dimers.
• Somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations have been found in some KHE.
• Invasion of bone, retroperitoneum, and mediastinum has occured in some cases but no case of metastasis has been reported yet.
• Diagnostic work up may include blood tests, biopsy, contrast enhanced ultrasound and MRI or CT scan imaging.
• Treatment Options include steroid, vincristine, interferon alpha, anti-platelet agents, sirolimus-containing therapies and surgery.

Retiform hemangioendothelioma

• First described in 1994 as a form of low grade angiosarcoma, Retiform hemangioendothelioma commonly presents as a slow growing asymptomatic solitary nodule or plaque on distal extremities in 2nd-4th decade of life.
• Must be differentiated from Angiosarcoma.
• High level of local recurrence but very low potential for metastasis.
• Diagnostic work up includes histopathological studies, that shows arborizing blood vessels are arranged in retiform pattern , and MRI.
• Surgery is the treatment of choice, though 2/3rd cases recur. Adjuvant radiotherapy and ddjuvant chemotherapy with recombinant interferon alpha and low dose cisplatin have also been reported in selected cases.

Papillary intralymphatic angioendothelioma (PILA), Dabska tumor

• First described in 1969 by Dabska,this rare vascular neoplasm generally occurs in soft tissues but can also occur in bone. They usually appear as painless inflammatory irregular or nodular lesions below the skin surface.
• The distinctive feature on histopathology is the intravascular growth of well-differentiated endothelial cells presenting as a matchstick columnar configuration.
• They are locally aggressive but rarely metastasize. Locally recurrence after surgery is very common.
• Diagnostic studies may include histopathological studies, fine needle aspiration, MRI and Ct scan.
• Wide local excision is the treatment of choice. However any combination of steroids, chemotherapy, radiation therapy, and invasive procedures can be used to treat this tumor.

Composite hemangioendothelioma

• A rare vascular neoplasms, characterized by an admixture of benign, low-grade malignant, and malignant vascular components, the ratio of each component can vary. They can occur in any age group.
• They occur predominantly as long-standing lesions in the dermis and subcutis of the extremities, but can also occur at other sites, including the oral cavity and in viscera such as kidney and spleen.
• It may recur locally and has the potential to metastasize. Recurrence was found to be in 8/10 cases in some studies.
• Diagnostic work up must include biopsy because of heterogeneity of lesions and it must be differentiated from other vascular tumors.
• Surgical excision is the treatment of choice although some patients have been treated with interferon and electron beams.

Pseudomyogenic hemangioendothelioma

• A locally aggressive tumor with endothelial differentiation that usually presents as multiple asymptomatic discontinuous lesions, often at extremities.
• SERPINE1-FOSB fusions are characteristic that result in over-expression of truncated form of FOSB. FBJ murine osteosarcoma viral oncogene homolog B, also known as Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B, FOSB or FosB, is a protein that, in humans have been implicated as regulators of cell proliferation, differentiation, and transformation.
• It may mimic epithelioid sarcoma on histology but metastasis is very rare and prognosis is excellent.
• Diagnostic work up includes X-ray, MRI, CT scan and biopsy of the lesion.
• Excision is the typical treatment but chemotherapeutic agents including gemcitabine/taxane and mammalian target of rapamycin inhibitor , mTOR inhibitors such as sirolimus , VEGFR1-4/PDGFRA inhibitors such as telatinib have been used with success in various studies.

Polymorphous hemangioendothelioma

• A rare vascular neoplasm, Polymorphous hemangioendothelioma occurs in lymph nodes, but a few cases have been found in extra-nodal sites such as the mediastinum, spinal cord, and liver. It is a very rare cause of persistent lymphadenopathy. The data on natural history and clinical presentation is limited due to very few number of cases reported.
• Characterized by a polymorphous blend of solid, primitive vascular and angiomatous areas in varied proportions on microscopic examination.
• Diagnotic work up includes histopathological examination, MRI and Ct scan.
• Wide local excision has been used for treatment, with radiation therapy in case of recurrence.

Kaposi sarcoma

• An AIDS-associated vascular malignancy that usually presents as mucocutaneous lesions but can also occur in viscera such as lungs. It can remain confined to skin but widespread visceral involvement may occur.
• There are three known variants
  • One variant occurs spontaneously in Jewish and Italian males in Europe and the United States.
  • Another more aggressive variant is endemic in young children is endemic in Africa.
  • A third form occurs in about 0.04% of kidney transplant patients. There is also a high incidence in AIDS patients. HHV-8 is the suspected cause.
• To learn more about KS, click here.

Malignant vascular tumors

Angiosarcoma

• Angiosarcoma(AS) is malignancy that presents with a very heterogeneous distribution in the human body with aggressive clinical course, and may appear in multiple locations, from breast to liver or skin.
• Associated with MYC gene amplification and protein overexpression. Myc is a family of regulator genes and proto-oncogenes that code for transcription factors.
• Complete surgical excision and radiotherapy are the main treatments, with a minor role of chemotherapy.
• To learn more about angiosarcoma click here.

Epithelioid hemangioendothelioma

• A rare vascular tumor, described for the first time in 1975 by Dail and Liebow,that usually affects lung, liver and bones, although may occur many other sites in body including head and neck, breasts and lymph nodes.
• Usually Asymptomatic but patient may present with respiratory symptoms, bone pains or other symptoms depending on the site of the tumor.
• Majority are characterized by a reciprocal t(1;3)(p36;q25) translocation. The t(1;3) results in fusion of a gene known as WWTR1 (or TAZ) to CAMTA1. These genes code for transcription factors.
• Imaging is crucial in forming both diagnosis and management plan. Recognition of the expression of vascular markers (Fli-1 and CD31 are endothelial-specific markers), and the microscopic evidence of vascular differentiation is of primary importance as well.
• Surgery has been used as primary treatment modality depending upon the location of the tumor, with radiotherapy being used in some cases.

Vascular malformations

Simple vascular malformations

Capillary malformations (CM)

Nevus simplex

• Also called "salmon patch" , “angel kiss”, “stork bite”, this common anomaly presents as single or multiple blanchable, pink-red patches with poorly defined borders in newborn infants. It may affect up to 60% of new born infants.
• Typically are found at the nape of the neck , on the forehead between the eyebrows or on the eyelids. Although asymptomatic, they often become more noticeable during crying or temperature changes.
• Fades within one to two years, though some lesions can persist on the back of the neck. No treatment is needed except when asked by the patient.
• Imaging studies are recommended to evaluate for underlying spinal dysraphism if lumbosacral nevus simplex is present with another lumbosacral abnormality such as dermal sinus or pit, lipoma, patch of hypertrichosis, or deviated gluteal cleft.

Cutaneous and/or mucosal CM (“port-wine” stain)

• "A vascular malformation of developmental origin characterized pathologically by ectasia of superficial dermal capillaries, and clinically by persistent macular erythema." They occur on face for majority of times and may vary from pale pink to deep red or purple, ranging from few millimeters to centimeters in diameter. Lesions are usually flat, are not painful and do not regress spontaneously.
• Can be classified as follows:
  • Nonsyndromic CM
  • CM with CNS and/or ocular anomalies (Sturge-Weber syndrome)
  • CM with bone and/or soft tissues overgrowth
  • Diffuse CM with overgrowth (DCMO)
• Usually occur as sporadic isolated lesions, following the embryonic vasculature of the face. Majority of lesions are caused by somatic mutations in GNAQ (Guanine nucleotide-binding protein G(q) subunit alpha) and its paralogue GNA 11. Somatic activating mutation in GNAQ c.548G>A, p.Arg183Gln has been demonstrated in majority of lesions. A novel GNAQ, c.547C>G, p.Arg183Gly variant has also been found to be associated with some lesions.
• May be associated with other abnormalities including glaucoma, and soft tissue and bone overgrowth and with various syndromes including Sturge-Weber syndrome, Klippel-Trenaunay syndrome, Parkes-Weber syndrome, Servelle-Martorell syndrome, Proteus syndrome, CLOVES syndrome, Bannayan-Riley-Ruvalcaba syndrome, Capillary malformation-arteriovenous malformation syndrome, Macrocephaly-capillary malformation syndrome, Microcephaly-capillary malformation syndrome, Beckwith-Wiedemann syndrome.
• Diagnosis is mainly clinical depending upon history and examination. New born screening for other congenital and genetic anomalies may be indicated including urgent ophthalmology review and a brain MRI.
• The pulsed dye laser (PDL) treatment is considered to be the gold standard. Surgery is considered when PWS is associated with bone and soft tissues overgrowth.
• To learn more about PWS click here.