Vascular anomalies
|
Vascular Anomalies |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2], Anmol Pitliya, M.B.B.S. M.D.[3]
Overview
Vascular anomalies constitute a wide array of disorders ranging from benign lesions such as infantile hemangioma to aggressive malignant tumors such as angiosarcoma. Commonly used misnomers and confusing nomenclature has often presented difficulties for accurate diagnosis and appropriate management. International Society for the Study of Vascular Anomalies (ISSVA) has now classified vascular anomalies into vascular tumors and vascular malformations with an unclassified category for lesions that show clinical and histological characteristics unique from disorders classified in vascular tumors and vascular malformations.
Classification
| Vascular Anomalies | ||||
|---|---|---|---|---|
| Vascular Tumors | Vascular Malformations | |||
| Simple vascular malformation | Combined vascular malformation* | Vascular malformation of major named vessels | Vascular malformation associated with other anomalies | |
|
|
For details, Click here |
For details, Click here | For details, Click here |
|
* Defined as two or more vascular malformations found in one lesion | ||||
Classification of Vascular Tumors
| Vascular tumors | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Benign | Locally aggressive or borderline | Malignant | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Infantile hemangioma / Hemangioma of infancy | Kaposiform hemangioendothelioma* | Angiosarcoma | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Congenital hemangioma* | Retiform hemangioendothelioma | Epithelioid hemangioendothelioma | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Tufted angioma* | Papillary intralymphatic angioendothelioma (PILA), Dabska tumor | Others | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Spindle-cell hemangioma | Composite hemangioendothelioma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Epithelioid hemangioma | Pseudomyogenic hemangioendothelioma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pyogenic granuloma (also known as lobular capillary hemangioma) | Polymorphous hemangioendothelioma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hemangioendothelioma not otherwise specified | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
'
| Kaposi sarcoma | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Others | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*congenital hemangioma (rapidly involuting type) and tufted angioma may be associated with thrombocytopenia and/or consumptive coagulopathy in some cases. Many experts consider tufted angioma and kaposiform hemangioendothelioma to be part of a spectrum rather than distinct entities
Classification of Vascular Malformations
| Vascular malformations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Simple vascular malformations | Combined vascular malformations | Vascular malformations of major named vessels | Vascular malformations asscoiated with other anomalies | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*
| (also known as "channel type" or "truncal" vascular malformations)
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Capillary malformations (CM) | Lymphatic malformations (LM) | Venous malformations (VM) | Arteriovenous malformation(AVM) | Arteriovenous fistula | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Nevus simplex / salmon patch, “angel kiss”, “stork bite” |
| Common VM | Sporadic | Sporadic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Generalized lymphatic anomaly (GLA) Kaposiform lymphangiomatosis (KLA) | Familial VM cutaneo-mucosal (VMCM) | In HHT | In HHT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Others | Verrucous venous malformation (formerly verrucous hemangioma) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Others | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
| Anomalies of major named vessels
(also known as "channel type" or "truncal" vascular malformations) |
|---|
Affect
Anomalies of
|
| Provisionally unclassified vascular anomalies |
|---|
| Intramuscular hemangioma * |
| Angiokeratoma |
| Sinusoidal hemangioma |
| Acral arteriovenous "tumour" |
| Multifocal lymphangioendotheliomatosis with thrombocytopenia / cutaneovisceral
angiomatosis with thrombocytopenia (MLT/CAT) |
| PTEN (type) hamartoma of soft tissue / "angiomatosis" of soft tissue
(PHOST) |
| Fibro adipose vascular anomaly (FAVA) |
* Distinct from infantile hemangioma, from intramuscular common VM, PHOST/AST, FAVA and AVM. Some lesions may be associated with thrombocytopenia and/or consumptive coagulopathy.
| 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 | |
| Causal genes of vascular anomalies | |
|---|---|
| ACVRL1 | Telangiectasia, AVM and AVF of HHT2 |
| AKT1 | Proteus syndrome |
| BRAF | Pyogenic granuloma PG |
| CAMTA1 | Epithelioid hemangioendothelioma EHE |
| CCBE1 | Primary generalized lymphatic anomaly (Hennekam lymphangiectasia-lymphedema syndrome) |
| ELMO2 | Familial intraosseous vascular malformation VMOS |
| ENG | Telangiectasia, AVM and AVF of HHT1 |
| EPHB4 | CM-AVM2 |
| FLT4 | Nonne-Milroy syndrome (gene also named VEGFR3) |
| FOS | Epithelioid hemangioma EH |
| FOSB | Pseudomyogenic hemangioendothelioma |
| FOXC2 | Lymphedema-distichiasis |
| GATA2 | Primary lymphedema with myelodysplasia |
| GJC2 | Primary hereditary lymphedema |
| Glomulin | Glomuvenous malformation |
| GNA11 | Congenital hemangioma CH
CM with bone and/or soft tissue hyperplasia Diffuse CM with overgrowth DCMO |
| GNA14 | Tufted angioma TA
Pyogenic granuloma PG Kaposiform hemangioendothelioma KHE |
| GNAQ | Congenital hemangioma CH
CM "Port-wine" stain, nonsyndromic CM CM of Sturge-Weber syndrome |
| IDH1 | Maffucci syndrome
Spindle-cell hemangioma |
| IDH2 | Maffucci syndrome
Spindle-cell hemangioma |
| KIF11 | Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation syndrome |
| KRIT1 | Cerebral cavernous malformation CCM1 |
| Malcavernin | Cerebral cavernous malformation CCM2 |
| MAP2K1 | Arteriovenous malformation AVM (sporadic) |
| MAP2K1 | Ateriovenous fistula AVF (sporadic) |
| MAP3K3 | Verrucous venous malformation (somatic) |
| MYC | Post radiation angiosarcoma |
| NPM11 | Maffucci syndrome |
| PDCD10 | Cerebral cavernous malformation CCM3 |
| PIK3CA | Common (cystic) LM (somatic)*
Common VM (somatic)* Klippel-Trenaunay syndrome* Megalencephaly-capillary malformation-polymicrogyria (MCAP)* CLOVES syndrome* CLAPO syndrome* Fibro adipose vascular anomaly FAVA |
| PTEN | Bannayan-Riley-Ruvalcaba syndrome
PTEN (type) Hamartoma of soft tissue / "angiomatosis" of soft tissue |
| PTPN14 | Lymphedema-choanal atresia |
| RASA1 | CM-AVM1
Parkes Weber syndrome |
| SMAD4 | Telangiectasia, AVM and AVF of Juvenile polyposis hemorrhagic telangiectasia JPHT |
| SOX18 | Hypotrichosis-lymphedema-telangiectasia |
| STAMBP | Microcephaly-CM (MIC-CAP) |
| TEK (TIE2) | Common VM (somatic)
Familial VM cutaneo-mucosal VMCM Blue rubber bleb nevus (Bean) syndrome (somatic) |
| TFE3 | Epithelioid hemangioendothelioma EHE |
| VEGFC | Primary hereditary lymphedema |
| VEGFR3 | Nonne-Milroy syndrome (gene also named FLT4) |
*Some of these lesions, associated with overgrowth, belong to the PIK3CA related overgrowth spectrum PROS
Provisionally unclassified vascular anomalies
Intramuscular hemangioma
- Characterized by benign proliferation of vascular channels. Majority of lesions occur in subcutaneous adipose tissues, followed by muscles. Thigh and calf are most common sites of occurrence. Majority of the lesions are asymptomatic. Typical clinical presentation includes chronic pain and swelling that both may increase with exercise of affected muscle due to increased blood flow. Other clinical manifestations may include pulsations, discoloration over the lesion, lesion enlargement when in dependent position, increased temperature, muscle contracture, tenderness, and muscle weakness and fatigue.[1][2][3][4][5][6]
- Intramuscular hemangiomas may be associated with Kasabach-Merritt syndrome characterized by thrombocytopenia and/or consumptive coagulopathy. This lesion may also lead to functional impairment, congestive cardiac failure due to arteriovenous shunting, pressure symptoms, skin necrosis and may also erode bone.[5]
- Etiology and pathophysiology are not clearly defined but majority of the lesions are congenital while a one fifth may be associated with trauma.[7]
- MRI is the diagnostic study of choice although X-RAY and ultrasound may be used as initial studies. Treatment is generally not indicated for asymptomatic lesions. Management options for symptomatic, complicated lesions and for cosmetic reasons may include laser ablation, systemic corticosteroids, cryotherapy, embolization, radiation, compression sclerotherapy, and surgical excision although surgical excision is usually treatment of choice in majority of the cases.[7][5][6][1][2][3][4]
Angiokeratoma
- A muco-cutaneous vascular lesion with wart-like papular appearance characterized by dilated capillaries in the dermis and hyperkeratotis of the overlying epidermis. Clinically it may manifest as solitary or multiple hyperkeratotic papules that may be localized or generalized, most typically on scrotum, thighs, lower extremity, abdomen, trunk, tongue, penis and labia majora. Majority of the lesions are asymptomatic but some may ulcerate and/or bleed.[8][9][10]
- It may be classified into following entities:[10]
- Fordyce’s angiokeratoma (arising on the genitals)
- Mibelli’s angiokeratoma (dorsum of toes and fingers)
- Angiokeratoma circumscriptum naeviforme (unilateral large keratotic plaques)
- Angiokeratoma corporis diffusum (ACD) (generalized lesions between umbilicus and the knee)
- Angiokeratomas are more prevalent among males as compared to females. Increased venous pressure and radiation therapy have been cited as possible causes. Angiokeratomas have been associated with enzyme deficiencies such as alpha-galactosidase A (Fabry disease), α-fucosidase (fucosidosis), neuraminidase (sialodosis), aspartyl glycosaminase (aspartyl glucosaminuria), β-mannosidase (β- mannosidosis), α-N-acetyl galactosaminidase (Kansaki disease), and β-galactosidase (adult onset GM1 gangliosidosis).[10][8][9][11][12]
- The diagnosis is mainly clinical but biopsy may be required. Associated enzyme deficiencies and systemic disorders must be ruled out. Treatment is generally not indicated but if so required then excision, electrocautery, cryotherapy, or laser ablations are the options.[8][12][10][13][11]
Sinusoidal hemangioma
- A variant of cavernous hemangioma characterized histopathologically by presence of dilated thin-walled vascular channels, that vary in size, exhibiting nodular proliferation with sinusoidal arrangement. Pseudopapillary structures may also be present. Clinically majority of the lesions manifest in female adults as single, well-defined, painless, subcutaneous nodule with bluish color. Most frequent locations are trunk, extremities and breasts. Painless swelling is the most common patient complaint.[14][15]
- Abnormalities of vasculogenesis and angiogenesis have been proposed as possible pathogenesis but it is not well-established.[15]
- Combination of clinical manifestations and histopathological features is used for diagnosis. Surgery (wide excision of tumor) is the treatment of choice if treatment is required.[15][16]
Acral arteriovenous "tumour"
- Congenital or acquired lesion manifesting clinically as asymptomatic mass or may present with pulsatile swelling, headache, localized throbbing pain, tinnitus and bleeding. Histopathologically they are characterized by arterio-venous connection without connecting capillary with or without intracranial component. The lesion derived its name from its acral distribution.[17][18]
- Etiology can be classified as following: Congenital, traumatic, infectious and inflammatory and familial.[17]
- Although diagnosis can be made clinically, angiography is the gold standard diagnostic modality to diagnose and define the extent of the lesion. Management regimen may include surgical excision, ligation of the supplying arteries, embolization, and intralesional sclerosing injection.[18]
Multifocal lymphangioendotheliomatosis with thrombocytopenia / cutaneovisceral angiomatosis with thrombocytopenia (MLT/CAT)
- Rare congenital disorder characterized by proliferation of vascular channels in multiple organs associated with thrombocytopenia of variable degree. Lesions may manifest themselves on skin, gastrointestinal tract, lungs, brain, bone, liver, spleen and muscles. Majority of cutaneous lesions present as multiple red to blue papules, plaques, nodules on trunk and extremities. Gastrointestinal bleeding due to multiple hemorrhagic lesions is the cause of mortality in majority of the patients. Similar lesions in brain and lungs may cause severe cerebral edema and pulmonary hemorrhage.[19][20]
- Disease may manifest without cutaneous involvement or thrombocytopenia. Biopsy typically reveals proliferation of well differentiated vascular channels with intravascular papillary structure and thrombi, sometimes with hobnail appearance of lining endothelial cells.[19][20]
- Biopsy followed by histopathological and immunohistochemical are required for diagnosis. Management is not well-established and disorder has a poor prognosis with high mortality. Recently sirolimus and bevacizumab have been used to treat this diorder with some success.[19][20][21][22]
Fibro adipose vascular anomaly (FAVA)
- Vascular disorder typically manifesting as infiltration of muscles by fibrofatty tissues, atypical venodilation associated with localized pain, and contracture of the affected muscles. Majority of the lesions involve calf muscles and may present as painful mass, contracture of the extremity, and decreased dorsiflexion at ankle joint. Skin is not typically involved. Histological studies demonstrates fibrous and adipose tissue and congregations of venous channels with abnormal lymphatic component.[23][24]
- Somatic activating mutations in PIK3CA that encodes phosphatidylinositol 3-kinase (PI3K), an enzyme functioning in cell growth, proliferation, differentiation, and survival.[25]
- Clinical and radiological findings are often sufficient to form the diagnosis. Inconclusive cases my require biopsy. Surgical resection is the often the preferred treatment and is more effective than sclerotherapy, the alternative therapy.[23][24]
Vascular malformations associated with other anomalies
Klippel-Trenaunay syndrome
- First described by Klippel and Trenaunay in 1900, this congeital syndrome is characterized by presence of capillary malformations, venous malformations, and soft tissues and bone hypertrophy. Lymphatic malformations may or may not be present. Capillary malformations typically present in form of capillary hemangioma and can occur anywhere on the body while venous and lymphatic malformations, and soft tissue and bone hypertrophy usually involves the extremities.[26][27][28][29][30]
- Clinical manifestations are unilateral in 85% of the cases and may include localized pain and discomfort, leg length discrepancy due to hemihypertrophy, developmental delay, limb abnormalities such as polydactyly, macrodactyly, syndactyly, thrombophlebitis, osteomyelitis, pathological fractures, heart failure, erysipelas, venous thrombosis due to malformations, pulmonary embolism, gastrointestinal bleeding due to venous overload in the internal iliac vein and ophthalmic abnormalities such as telangiectasia, orbital varix, strabismus, oculosympathetic palsy, Marcus-Gunn pupil, iris coloboma and heterochromia, cataracts, persistent fetal vasculature and varicosities.[29][30][28][31]
- Etiology and pathogenesis have not been established yet. Some suggestions include PIK3CA mutations, polygenic inheritance, VG5Q mutation and obstruction of the venous system.[26][29][31]
- Diagnosis can be made on clinical manifestations and can be confirmed by Doppler ultrasound and magnetic resonance angiography. Management depends on clinical manifestations.[29][31][28][29]
Parkes Weber syndrome
- Characterized by a cutaneous flush with underlying multiple micro-AVFs (arteriovenous fistulas), in association with soft tissue and skeletal hypertrophy of the affected limb. Clinical Presentation enlarged arteries and veins, capillary or venous malformations, cutaneous blush, arteriovenous fistulas, and enlargement of limb.
- Mutation in the RASA1 gene has been found to be associated with this syndrome.
- To learn more about Parkes Weber syndrome, click here.
Servelle-Martorell syndrome
- Also called phlebectatic osteohypoplastic angiodysplasia, this rare syndrome is characterized by venous malformations such as abnormal location of vein, partial or complete absence of valves, and/or venous hypoplasia or aplasia and undergrowth of bone. These abnormalities may also be associated with limb hypertrophy and arterial malformations.[32]
- Clinical manifestations may include cutaneous compressible lesions due to malformations, cellulitis, lesion limb shortening, joint and soft tissue pain and swelling, tortuous limbs, reduced muscle mass, venous thrombosis, consumption coagulopathy, pathological fractures and bone tenderness.[32]
- Combination of clinical and radiological findings is used to form the diagnosis, MRI can assess the involvement and extent of lesions. Treatment is mainly conservative with surgery being used in some cases to excise and/or correct malformations.[32][33]
Sturge-Weber syndrome
- Congenital syndrome characterized by capillary malformations involving face and laptomeninges and eye abnormalities. There may also be bone and/or overgrowth.
- Clinical manifestations may include seizures, port-wine stain on the forehead and upper eyelid of one side of the face, muscle weakness, developmental delays and mental retardation, glaucoma, and buphthalmos.
- Associated with mutations in GNAQ gene that encodes for members of G protein family.
- To learn more about Sturge-Weber syndrome, click here.
Maffucci syndrome
- A rare disorder characterized by presence of venous malformations associated with multiple enchondromas, benign cartilage-forming tumors, and multiple soft tissue hemangiomas and lymphangiomas. These benign tumors have tendency to undergo malignant transformation in maffuci syndrome. People with maffuci syndrome are also at increased risk of developing other malignant tumors such as glioma, glioblastoma, acute myeloid leukemia, intrahepatic cholangiocarcinomas, hepatocellular carcinoma, pancreatic, and breast malignancies. Clinical manifestations depend on the coexisting lesions.[34][35][36]
- Mutations in isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2), enzymes involved in metabolism of isocitrate and α-ketoglutarate, and TP53, a cell-cycle regulator, have been found in tumors in maffuci syndrome.[37][38]
- Patients should be evaluated to check for malignant transformation. Some recommend CT scans and PET scans at regular intervals.[36][35][39][36]
- To learn more about maffuci syndrome, click here.
CLOVES syndrome
- CLOVES is an acronym for congenital lipomatous overgrowth, vascular malformations, epidermal nevi, skeletal and spinal anomalies. Vascular malformations in this syndrome include venous, capillary and lymphatic malformations with or without combined arteriovenous malformations. Pulmonary thromboembolism and respiratory failure are the cause of mortality in majority of the patients. Lipomatous and vascular abnormalities are often segmental and asymmetric in distribution and present typically on chest and abdominal wall.[40][41][42][43]
- Clinical and imaging findings may include swellings due to lipomatous growths, skin discoloration, port wine stain, bilateral epidermal nevi,leg length discrepancy, developmental limb anomalies such as increased gap between the first and second toes, hemorrhage, seizures, ascites, pleural effusions, hypotension, bilateral multicystic venous and lymphatic malformations, chest wall venous dilatation, multiple congenital hemangiomas, asymmetric septal hypertrophy, renal hypoplasia, dislocated knees, scoliosis, and neural tube defect.[40][43][42]
- Activating mutations in PICK3CA gene that encodes part of PI3K has been thought to be associated with this syndrome. These mutations may help enable the cells to grow independent of growth factors.[40][41][44]
- This syndrome can be detected prenatally and its manifestations have been identified on prenatal ultrasound and fetal MRI. Treatment options include supportive management, surgical debulking and scletherapy but treatment is often complicated by severity of the disease resulting in anemia, coagulopathy and poor wound healing.[40][41]
Proteus syndrome
- Congenital syndrome characterized by asymmetric overgrowth of multiple tissues in limbs, hamartomas and vascular lesions such as capillary malformations, venous malformations, lymphatic malformations. Cerebriform connective tissue nevi, a pathognomonic lesion if present alone, are helpful in diagnosing Proteus syndrome. It may affect multiple organs such as eyes, spleen, liver, thymus, intestine, and lungs, and may cause facial dysmorphia. Some benign and malignant neoplasms such as testicular papillary adenocarcinoma and mesothelioma.[45][46][47]
- Clinical manifestations and findings may include hemihypertrophy, asymmetry of the limbs, scoliosis, subcutaneous tumors, soft tissues tumors such as lipoma, limb abnormalities such as macrodactyly, hyperpigmented lesions on skin, verrucous epidermal nevi, lung diseases, pulmonary embolism, venous thrombosis, glaucoma, strabismus, nystagmus, pseudopapileudema, cardiac defects such as ARVC, healed myocardial infarctions, cardiomyopathies, cardiac lipomas, and central nervous system findings. These findings may be detected prenatally or at birth but majority of the patients present after 6 months of birth.[45][46][47][48]
- Somatic mutations in AKT1 gene that encodes proteins functioning in AKT/PI3K signaling pathway has been proposed to be the cause of this syndrome. This pathway functions in cell growth, differentiation and survival.[47][49]
- Diagnosis is based on clinical and radiological findings and must meet general and specific criteria. Management consists of clinical and psychological assistance. This may include orthopedic consultation to stop or delay bone growth, physical rehabilitation, surgical correction of deformities such as scoliosis, dermatology consultation fro skin lesions, workup and followup for vein thrombosis and pulmonary embolism, intervention for developmental delay, and evaluation for associated neoplasms at regular intervals.[45][50]
- To learn more, click here.
Bannayan-Riley-Ruvalcaba syndrome
- An overgrowth syndrome characterized by vascular malformations, macrocephaly, multiple benign neoplasm and pigmented lesions on the skin. Speckled pigmented macules on genitalia are one of the most significant diagnostic characteristics. People with this syndrome may have increased risk of developing neoplasms in many organs such as thyroid, breasts, and female genital tract although it has not been confirmed.[51][52][53]
- Typical manifestations and findings may include multiple lipomas, hemangiomas, intestinal hamartomatous polyposis, vascular malformations such as arteriovenous malformations and capillary malformations, developmental delay, macrocephaly (>97 percentile), penile pigmented macules, thyroid abnormalities such as multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer and Hashimoto’s thyroiditis, high-arched palate, protuberant frontal bone, hypertelorism, strabismus, macrosomia, hypotonia, joint hyperextensibility, hypoglycemia, convulsions, café-au-lait spots, prominent forehead, malar hypoplasia and micrognathia.[51][52][53]
- Mutations in PTEN gene have been thought to be the cause. This gene encodes an enzyme that acts as tumor suppressor by stopping cell division and inducing apoptosis. Both autosomal-dominant transmission and sporadic occurrence have been reported.[51]
- Diagnosis is based on clinical findings, the most important of these findings being penile pigmented maculae, hamartomatous intestinal polyposis and macrocephaly. Management consists of psycho-social counseling and treatment of manifestations such as surgical and dermatological interventions, spinal stimulation for intractable gastrointestinal pain and screening for [[[malignancies]] associated with PTEN mutations such as annual thyroid ultrasound and mammography.[51][53]
- To learn more, click here.
CLAPO syndrome
- CLAPO syndrome, a syndrome that has been diagnosed in 6 patients) is acronym for capillary malformation of the lower lip, lymphatic malformations of the face and neck, asymmetry, and partial or generalized overgrowth. Manifestations may include cutaneous lesions on head and neck and asymmetrical overgrowth.[54][55]
- Somatic activating PIK3CA mutations have been found in patients with CLAPO syndrome. This gene encodes proteins that function in cell-signaling pathways.[54][55]
References
- ↑ 1.0 1.1 Wang CS, Wu PK, Chiou HJ, Chen CF, Chen WM, Liu CL, Chen TH (August 2014). "Nonpalpable intramuscular hemangioma treated with hookwire localization and excision". J Chin Med Assoc. 77 (8): 426–9. doi:10.1016/j.jcma.2014.02.017. PMID 25028288.
- ↑ 2.0 2.1 Doddanna SJ, Dawar G, Rallan NS, Agarwal M (2014). "Intramuscular cavernous hemangioma: a rare entity in the buccinator muscle". Indian J Dent Res. 25 (6): 813–5. doi:10.4103/0970-9290.152211. PMID 25728120.
- ↑ 3.0 3.1 Righini CA, Berta E, Atallah I (February 2014). "Intramuscular cavernous hemangioma arising from the masseter muscle". Eur Ann Otorhinolaryngol Head Neck Dis. 131 (1): 57–9. doi:10.1016/j.anorl.2013.03.003. PMID 23845293.
- ↑ 4.0 4.1 Alami B, Lamrani Y, Addou O, Boubbou M, Kamaoui I, Maaroufi M, Sqalli N, Tizniti S (January 2015). "Presumptive intramuscular hemangioma of the masseter muscle". Am J Case Rep. 16: 16–9. doi:10.12659/AJCR.890776. PMC 4298281. PMID 25590509.
- ↑ 5.0 5.1 5.2 Brown RA, Crichton K, Malouf GM (June 2004). "Intramuscular haemangioma of the thigh in a basketball player". Br J Sports Med. 38 (3): 346–8. PMC 1724833. PMID 15155443.
- ↑ 6.0 6.1 Patnaik S, Kumar P, Nayak B, Mohapatra N (2016). "Intramuscular Arteriovenous Hemangioma of Thigh: A Case Report and Review of Literature". J Orthop Case Rep. 6 (5): 20–23. doi:10.13107/jocr.2250-0685.612. PMC 5404154. PMID 28507959.
- ↑ 7.0 7.1 Wierzbicki JM, Henderson JH, Scarborough MT, Bush CH, Reith JD, Clugston JR (September 2013). "Intramuscular hemangiomas". Sports Health. 5 (5): 448–54. doi:10.1177/1941738112470910. PMC 3752185. PMID 24427416.
- ↑ 8.0 8.1 8.2 Hussein RS, Kfoury H, Al-Faky YH (2014). "Eyelid angiokeratoma". Middle East Afr J Ophthalmol. 21 (3): 287–8. doi:10.4103/0974-9233.134702. PMC 4123288. PMID 25100920.
- ↑ 9.0 9.1 Trickett R, Dowd H (October 2006). "Angiokeratoma of the scrotum: a case of scrotal bleeding". Emerg Med J. 23 (10): e57. doi:10.1136/emj.2006.038745. PMC 2579622. PMID 16988295.
- ↑ 10.0 10.1 10.2 10.3 Chowdappa V, Narasimha A, Bhat A, Masamatti SS (May 2015). "Solitary Angiokeratoma: Report of Two Uncommon Cases". J Clin Diagn Res. 9 (5): WD01–2. doi:10.7860/JCDR/2015/12163.5946. PMC 4484136. PMID 26155544.
- ↑ 11.0 11.1 Ghosh SK, Ghosh S, Agarwal M (2015). "Multiple giant angiokeratoma of Fordyce on the shaft of the penis masquerading as keratoacanthoma". An Bras Dermatol. 90 (3 Suppl 1): 150–2. doi:10.1590/abd1806-4841.20153876. PMC 4540534. PMID 26312700.
- ↑ 12.0 12.1 Rees R, Freeman A, Malone P, Garaffa G, Muneer A, Minhas S (May 2009). "Case study: the surgical management of angiokeratoma resulting from radiotherapy for penile cancer". ScientificWorldJournal. 9: 339–42. doi:10.1100/tsw.2009.23. PMC 5823195. PMID 19468654.
- ↑ Vijay MK, Arava S (2014). "Solitary angiokeratoma of tongue: a rare entity clinically mistaken as a malignant tumor". Indian J Pathol Microbiol. 57 (3): 510–1. doi:10.4103/0377-4929.138810. PMID 25118768.
- ↑ Halawar SS, Venugopal R, Varsha B, Kavya B (May 2013). "Intramuscular sinusoidal hemangioma with Masson's lesion". J Oral Maxillofac Pathol. 17 (2): 315–7. doi:10.4103/0973-029X.119762. PMC 3830250. PMID 24250102.
- ↑ 15.0 15.1 15.2 Ciurea M, Ciurea R, Popa D, Pârvănescu H, Marinescu D, Vrabete M (2011). "Sinusoidal hemangioma of the arm: case report and review of literature". Rom J Morphol Embryol. 52 (3): 915–8. PMID 21892538.
- ↑ Konda P, Bavle RM, Makarla S, Muniswamappa S (January 2016). "Intramuscular sinusoidal haemangioma with secondary Masson's phenomenon". BMJ Case Rep. 2016. doi:10.1136/bcr-2013-201457. PMC 4716435. PMID 26729822.
- ↑ 17.0 17.1 Gupta R, Kayal A (2014). "Scalp arteriovenous malformations in young". J Pediatr Neurosci. 9 (3): 263–6. doi:10.4103/1817-1745.147587. PMC 4302550. PMID 25624933.
- ↑ 18.0 18.1 Özkara E, Özbek Z, Özdemir AÖ, Arslantaş A (2018). "Misdiagnosed Case of Scalp Arteriovenous Malformation". Asian J Neurosurg. 13 (1): 59–61. doi:10.4103/1793-5482.181137. PMC 5820896. PMID 29492122.
- ↑ 19.0 19.1 19.2 Droitcourt C, Boccara O, Fraitag S, Favrais G, Dupuy A, Maruani A (August 2015). "Multifocal Lymphangioendotheliomatosis With Thrombocytopenia: Clinical Features and Response to Sirolimus". Pediatrics. 136 (2): e517–22. doi:10.1542/peds.2014-2410. PMID 26148948.
- ↑ 20.0 20.1 20.2 Zegpi MS, Zavala A, del Puerto C, Cárdenas C, González S (2012). "Newborn with multifocal lymphangioendotheliomatosis with thrombocytopenia". Indian J Dermatol Venereol Leprol. 78 (3): 409. doi:10.4103/0378-6323.95494. PMID 22565464.
- ↑ Kline RM, Buck LM (April 2009). "Bevacizumab treatment in multifocal lymphangioendotheliomatosis with thrombocytopenia". Pediatr Blood Cancer. 52 (4): 534–6. doi:10.1002/pbc.21860. PMID 19101995.
- ↑ Lanöel A, Torres Huamani AN, Feliú A, Sala MJ, Alvarez M, Cervini AB (July 2016). "Multifocal Lymphangioendotheliomatosis with Thrombocytopenia: Presentation of Two Cases Treated with Sirolimus". Pediatr Dermatol. 33 (4): e235–9. doi:10.1111/pde.12879. PMID 27282436.
- ↑ 23.0 23.1 Fernandez-Pineda I, Marcilla D, Downey-Carmona FJ, Roldan S, Ortega-Laureano L, Bernabeu-Wittel J (2014). "Lower Extremity Fibro-Adipose Vascular Anomaly (FAVA): A New Case of a Newly Delineated Disorder". Ann Vasc Dis. 7 (3): 316–9. doi:10.3400/avd.cr.14-00049. PMC 4180696. PMID 25298836.
- ↑ 24.0 24.1 Alomari AI, Spencer SA, Arnold RW, Chaudry G, Kasser JR, Burrows PE, Govender P, Padua HM, Dillon B, Upton J, Taghinia AH, Fishman SJ, Mulliken JB, Fevurly RD, Greene AK, Landrigan-Ossar M, Paltiel HJ, Trenor CC, Kozakewich HP (January 2014). "Fibro-adipose vascular anomaly: clinical-radiologic-pathologic features of a newly delineated disorder of the extremity". J Pediatr Orthop. 34 (1): 109–17. doi:10.1097/BPO.0b013e3182a1f0b8. PMID 24322574.
- ↑ "www.issva.org" (PDF).
- ↑ 26.0 26.1 Abdolrahimzadeh S, Scavella V, Felli L, Cruciani F, Contestabile MT, Recupero SM (2015). "Ophthalmic Alterations in the Sturge-Weber Syndrome, Klippel-Trenaunay Syndrome, and the Phakomatosis Pigmentovascularis: An Independent Group of Conditions?". Biomed Res Int. 2015: 786519. doi:10.1155/2015/786519. PMC 4588354. PMID 26451379.
- ↑ Withana M, Rodrigo C, Shivanthan MC, Warnakulasooriya S, Wimalachandra M, Gooneratne L, Rajapakse S (November 2014). "Klippel-Trenaunay syndrome presenting with acanthocytosis and splenic and retroperitoneal lymphangioma: a case report". J Med Case Rep. 8: 390. doi:10.1186/1752-1947-8-390. PMC 4289367. PMID 25427442.
- ↑ 28.0 28.1 28.2 Ricks CB, Grandhi R, Ducruet AF (October 2014). "Klippel-Trenaunay syndrome and cavernous malformations". BMJ Case Rep. 2014. doi:10.1136/bcr-2014-207486. PMC 4187537. PMID 25293688.
- ↑ 29.0 29.1 29.2 29.3 29.4 Baba A, Yamazoe S, Okuyama Y, Shimizu K, Kobashi Y, Nozawa Y, Munetomo Y, Mogami T (February 2017). "A rare presentation of Klippel-Trenaunay syndrome with bilateral lower limbs". J Surg Case Rep. 2017 (2): rjx024. doi:10.1093/jscr/rjx024. PMC 5400491. PMID 28458832.
- ↑ 30.0 30.1 Tetangco EP, Arshad HM, Silva R (August 2016). "Klippel-Trenaunay Syndrome of the Rectosigmoid Colon Presenting as Severe Anemia". ACG Case Rep J. 3 (4): e161. doi:10.14309/crj.2016.134. PMC 5126491. PMID 27921060.
- ↑ 31.0 31.1 31.2 Chagas C, Pires L, Babinski MA, Leite T (2017). "Klippel-Trenaunay and Parkes-Weber syndromes: two case reports". J Vasc Bras. 16 (4): 320–324. doi:10.1590/1677-5449.005417. PMC 5944310. PMID 29930667. Vancouver style error: initials (help)
- ↑ 32.0 32.1 32.2 Karuppal R, Raman RV, Valsalan BP, Gopakumar T, Kumaran CM, Vasu CK (May 2008). "Servelle-Martorell syndrome with extensive upper limb involvement: a case report". J Med Case Rep. 2: 142. doi:10.1186/1752-1947-2-142. PMC 2394530. PMID 18454870. Vancouver style error: initials (help)
- ↑ Langer M, Langer R (May 1982). "[Radiologic aspects of the congenital arteriovenous malformations, Klippel-Trenaunay type, and Servelle-Martorell type (author's transl)]". Rofo (in German). 136 (5): 577–82. doi:10.1055/s-2008-1056105. PMID 6284617.
- ↑ McCarthy CM, Blecher H, Reich S (June 2015). "A case of myelopathy because of enchondromas from Maffucci syndrome with successful surgical treatment". Spine J. 15 (6): e15–9. doi:10.1016/j.spinee.2015.03.006. PMID 25777744.
- ↑ 35.0 35.1 Tsao YP, Tsai CY, Chen WS (December 2015). "Maffucci Syndrome". J. Rheumatol. 42 (12): 2434–5. doi:10.3899/jrheum.150216. PMID 26628708.
- ↑ 36.0 36.1 36.2 Prokopchuk O, Andres S, Becker K, Holzapfel K, Hartmann D, Friess H (February 2016). "Maffucci syndrome and neoplasms: a case report and review of the literature". BMC Res Notes. 9: 126. doi:10.1186/s13104-016-1913-x. PMC 4769492. PMID 26920730.
- ↑ Moriya K, Kaneko MK, Liu X, Hosaka M, Fujishima F, Sakuma J, Ogasawara S, Watanabe M, Sasahara Y, Kure S, Kato Y (March 2014). "IDH2 and TP53 mutations are correlated with gliomagenesis in a patient with Maffucci syndrome". Cancer Sci. 105 (3): 359–62. doi:10.1111/cas.12337. PMC 4317937. PMID 24344754.
- ↑ Pansuriya TC, van Eijk R, d'Adamo P, van Ruler MA, Kuijjer ML, Oosting J, Cleton-Jansen AM, van Oosterwijk JG, Verbeke SL, Meijer D, van Wezel T, Nord KH, Sangiorgi L, Toker B, Liegl-Atzwanger B, San-Julian M, Sciot R, Limaye N, Kindblom LG, Daugaard S, Godfraind C, Boon LM, Vikkula M, Kurek KC, Szuhai K, French PJ, Bovée JV (November 2011). "Somatic mosaic IDH1 and IDH2 mutations are associated with enchondroma and spindle cell hemangioma in Ollier disease and Maffucci syndrome". Nat. Genet. 43 (12): 1256–61. doi:10.1038/ng.1004. PMC 3427908. PMID 22057234.
- ↑ Al-Katib S, Al-Faham Z, Grant P, Palka JC (June 2015). "The Appearance of Maffucci Syndrome on 18F-FDG PET/CT". J Nucl Med Technol. 43 (2): 131–2. doi:10.2967/jnmt.114.146480. PMID 25537758.
- ↑ 40.0 40.1 40.2 40.3 Emrick LT, Murphy L, Shamshirsaz AA, Ruano R, Cassady CI, Liu L, Chang F, Sutton VR, Li M, Van den Veyver IB (October 2014). "Prenatal diagnosis of CLOVES syndrome confirmed by detection of a mosaic PIK3CA mutation in cultured amniocytes". Am. J. Med. Genet. A. 164A (10): 2633–7. doi:10.1002/ajmg.a.36672. PMC 4496426. PMID 25044986.
- ↑ 41.0 41.1 41.2 Sarici D, Akin MA, Kurtoglu S, Tubas F, Sarici SU (2014). "A Neonate with CLOVES Syndrome". Case Rep Pediatr. 2014: 845074. doi:10.1155/2014/845074. PMC 4221976. PMID 25400966.
- ↑ 42.0 42.1 Alomari AI, Burrows PE, Lee EY, Hedequist DJ, Mulliken JB, Fishman SJ (August 2010). "CLOVES syndrome with thoracic and central phlebectasia: increased risk of pulmonary embolism". J. Thorac. Cardiovasc. Surg. 140 (2): 459–63. doi:10.1016/j.jtcvs.2010.04.023. PMID 20537357.
- ↑ 43.0 43.1 Gopal B, Keshava SN, Selvaraj D (2015). "A rare newly described overgrowth syndrome with vascular malformations-Cloves syndrome". Indian J Radiol Imaging. 25 (1): 71–3. doi:10.4103/0971-3026.150166. PMC 4329693. PMID 25709171.
- ↑ Kurek KC, Luks VL, Ayturk UM, Alomari AI, Fishman SJ, Spencer SA, Mulliken JB, Bowen ME, Yamamoto GL, Kozakewich HP, Warman ML (June 2012). "Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome". Am. J. Hum. Genet. 90 (6): 1108–15. doi:10.1016/j.ajhg.2012.05.006. PMC 3370283. PMID 22658544.
- ↑ 45.0 45.1 45.2 Rocha R, Estrella M, Amaral D, Barbosa AM, Abreu M (2017). "Proteus syndrome". An Bras Dermatol. 92 (5): 717–720. doi:10.1590/abd1806-4841.20174496. PMC 5674710. PMID 29166516. Vancouver style error: initials (help)
- ↑ 46.0 46.1 El-Sobky TA, Elsayed SM, El Mikkawy DM (December 2015). "Orthopaedic manifestations of Proteus syndrome in a child with literature update". Bone Rep. 3: 104–108. doi:10.1016/j.bonr.2015.09.004. PMC 5365241. PMID 28377973.
- ↑ 47.0 47.1 47.2 Hannoush H, Sachdev V, Brofferio A, Arai AE, LaRocca G, Sapp J, Sidenko S, Brenneman C, Biesecker LG, Keppler-Noreuil KM (January 2015). "Myocardial fat overgrowth in Proteus syndrome". Am. J. Med. Genet. A. 167A (1): 103–10. doi:10.1002/ajmg.a.36773. PMC 4275354. PMID 25377688.
- ↑ Sarman ZS, Yuksel N, Sarman H, Bayramgurler D (June 2014). "Proteus syndrome: report of a case with developmental glaucoma". Korean J Ophthalmol. 28 (3): 272–4. doi:10.3341/kjo.2014.28.3.272. PMC 4038735. PMID 24882963.
- ↑ Lindhurst MJ, Yourick MR, Yu Y, Savage RE, Ferrari D, Biesecker LG (December 2015). "Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome". Sci Rep. 5: 17162. doi:10.1038/srep17162. PMC 4675973. PMID 26657992.
- ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Biesecker LG, Sapp JC. PMID 22876373. Vancouver style error: initials (help); Missing or empty
|title=(help) - ↑ 51.0 51.1 51.2 51.3 Gontijo GM, Pinto CA, Rogatto SR, Cunha IW, Aguiar S, Alves CA (2013). "Bannayan-Riley-Ruvalcaba syndrome with deforming lipomatous hamartomas in infant--case report". An Bras Dermatol. 88 (6): 982–5. doi:10.1590/abd1806-4841.20132730. PMC 3900354. PMID 24474112.
- ↑ 52.0 52.1 Peiretti V, Mussa A, Feyles F, Tuli G, Santanera A, Molinatto C, Ferrero GB, Corrias A (2013). "Thyroid involvement in two patients with Bannayan-Riley-Ruvalcaba syndrome". J Clin Res Pediatr Endocrinol. 5 (4): 261–5. doi:10.4274/Jcrpe.984. PMC 3890226. PMID 24379037.
- ↑ 53.0 53.1 53.2 Sagi SV, Ballard DD, Marks RA, Dunn KR, Kahi CJ (January 2014). "Bannayan Ruvalcaba Riley Syndrome". ACG Case Rep J. 1 (2): 90–2. doi:10.14309/crj.2014.11. PMC 4435287. PMID 26157835.
- ↑ 54.0 54.1 Downey C, López-Gutiérrez JC, Roé-Crespo E, Puig L, Baselga E (July 2018). "Lower lip capillary malformation associated with lymphatic malformation without overgrowth: Part of the spectrum of CLAPO syndrome". Pediatr Dermatol. 35 (4): e243–e244. doi:10.1111/pde.13514. PMID 29766551.
- ↑ 55.0 55.1 Rodriguez-Laguna L, Ibañez K, Gordo G, Garcia-Minaur S, Santos-Simarro F, Agra N, Vallespín E, Fernández-Montaño VE, Martín-Arenas R, Del Pozo Á, González-Pecellín H, Mena R, Rueda-Arenas I, Gomez MV, Villaverde C, Bustamante A, Ayuso C, Ruiz-Perez VL, Nevado J, Lapunzina P, Lopez-Gutierrez JC, Martinez-Glez V (August 2018). "CLAPO syndrome: identification of somatic activating PIK3CA mutations and delineation of the natural history and phenotype". Genet. Med. 20 (8): 882–889. doi:10.1038/gim.2017.200. PMID 29446767.