|Year : 2015 | Volume
| Issue : 1 | Page : 101-105
Peripheral venous malformations and pulmonary hypertension: A case report and literature review
Nambakam Tanuja Subramanyam1, Girish P Vakrani2, R Veena1, Shashidaran1
1 Department of General Medicine, Vydehi Institute of Medical Sciences and Research Center, Bangalore, Karnataka, India
2 Department of Nephrology, Vydehi Institute of Medical Sciences and Research Center, Bangalore, Karnataka, India
|Date of Web Publication||13-Apr-2015|
Dr. Nambakam Tanuja Subramanyam
A-29, Vydehi Hospital staff quarters, 82, EPIP area, Whitefield, Bangalore - 560 066, Karnataka
Source of Support: None, Conflict of Interest: None
Extensive pure peripheral venous malformations are rare. We report occurrence of peripheral venous malformations associated with pulmonary hypertension in a middle-aged male, who had nodular, irregular, soft, compressible, painless, non-pulsatile swellings over dependant positions such as forearms, hands, axilla, and genitalia, with overgrowth of hands and fingers enlarging slowly since early childhood. He had right ventricular failure signs. Plain films showed soft-tissue mass with diffuse calcifications (phleboliths). Doppler study showed low flow vascular channels, compressible hypoechoic lesions along with occasional hyperechoeic lesion corresponding with phleboliths. Magnetic resonance imaging (MRI, T1-weighted) showed polypoidal mass with heterogenous hypo to intermediate signal with no flow voids. T2-weighted MRI showed high-signal intensity mass. Computed tomography (CT) pulmonary angiogram showed pulmonary hypertension, no thrombi or vascular malformation. He was treated with angiotensin-converting enzyme inhibitors, diuretics, amiodarone, antiplatelets, and venous stockings. Specific therapy such as sclerosis and surgical resection could not be done as he was discharged against medical advice.
Keywords: Peripheral venous malformations, phleboliths, pulmonary hypertension
|How to cite this article:|
Subramanyam NT, Vakrani GP, Veena R, Shashidaran. Peripheral venous malformations and pulmonary hypertension: A case report and literature review. Arch Med Health Sci 2015;3:101-5
|How to cite this URL:|
Subramanyam NT, Vakrani GP, Veena R, Shashidaran. Peripheral venous malformations and pulmonary hypertension: A case report and literature review. Arch Med Health Sci [serial online] 2015 [cited 2020 Feb 21];3:101-5. Available from: http://www.amhsjournal.org/text.asp?2015/3/1/101/154957
| Introduction|| |
Extensive pure peripheral venous malformations are rare. We report occurrence of peripheral venous malformations associated with pulmonary hypertension in a 49-year-old middle-aged male.
| Case Report|| |
We report a case of 49-year-old male with a history of NYHA class 3 breathlessness since 2 months. He was on digoxin started elsewhere. There was history of painless nodular swellings in dependant positions such as forearms, hands, axilla, and genitalia, enlarging slowly since early childhood causing difficulty in performing routine work. There was no history of pain, ulcers, bleeding in the swellings or history suggestive of paroxysmal nocturnal dyspnea, leg swelling, abdomen distention, palpitation, or chest pain.
Physical examination revealed bilateral pitting pedal edema and nodular, irregular, soft, compressible, painless, non-pulsatile swellings over dependant positions such as forearms, hands, axilla, and genitalia [Figure 1]. There was overgrowth of hands and fingers. There was no local change in temperature, ulceration, bruit, or thrill in the swellings.
Pulse was 45 beats/minute, regular and blood pressure was 150/90 mmHg. No clubbing was seen. Respiratory system examination showed bilateral basal crepitations. Cardiac examination showed raised jugular venous pulse, loud P2, and grade 2 parasternal haeve. Abdominal examination showed tender mild hepatomegaly, and the nervous system was unremarkable.
Initial investigations showed hemoglobin was 13.37 g/dl (normal range 12-15 g/dL), total leucocytes were 6370/cmm (normal range 3500-9500/cmm), platelet count was 1.67 lakh/cmm (normal range 1.6-4 lakh/cmm), ESR was 52 mm/hour (normal range 0-20 mm/hour). Serum creatinine was 0.8 mg/dl (normal range 0.6-1.5 mg/dL), and troponin was negative. Viral serology (HCV, HIV, and HBsAg) was negative. Urine analysis showed bland sediment. Chest radiograph showed right heart enlargement; lung fields were normal. Ultrasound of abdomen showed normal abdominal organs. Electrocardiograph showed ventricular bigemini. Echocardiogram showed enlarged right atria, ventricle, pulmonary artery, asymmetric thickening of interventricular septum, moderate tricuspid regurgitation, systolic pulmonary artery pressure of 60 mmHg, and pulmonary hypertension [Figure 4].
Plain films showed soft-tissue mass with diffuse calcifications (phleboliths) and hypertrophy of fingers [Figure 2]. Doppler study showed low-flow vascular channels, compressible hypoechoic solid lesions along with occasional hyperechoeic lesion corresponding with phleboliths, and isoechoeic subcutaneous thickening. There was monophasic low-velocity blood flow. Magnetic resonance imaging (MRI) of upper limbs, axilla (T1-weighted) showed polypoidal mass with heterogenous hypo to intermediate signal with no flow voids. Axial T2-weighted MRI showed high signal-intensity mass [Figure 3]. Computed tomography (CT) pulmonary angiogram showed pulmonary hypertension and no thrombi or vascular malformation. MRI of brain and spine were normal [Figure 5].
|Figure 2: Plain x ray showing soft tissue mass with diffuse calcifications (phleboliths)|
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|Figure 3: MRI of upper limbs, axilla (T1 weighted) showed polypoidal mass with heterogeneous hypo to intermediate signal with no flow voids. Axial T2 weighted MR image showed high signal intensity mass|
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These swellings appeared to be low-flow venous vascular malformations as they had slow steady enlargement since early childhood with no bruit or thrill but had diffuse calcifications and compressible hypoechoic lesions with no flow voids associated with pulmonary hypertension.
Digoxin was stopped, and he was started on medical management such as angiotensin-converting enzyme inhibitors (ACEI), diuretics, amiodarone, antiplatelets, and application of venous stockings. Ventricular bigemini was corrected, and his symptoms improved.
D-dimer assay and specific therapy such as sclerosis and surgical resection could not be done as he was discharged against medical advice.
| Discussion|| |
As our case has childhood onset of vascular malformation, it is prudent to discuss differential diagnosis in detail.
The International Society for the Study of Vascular Anomalies Classification (ISSVA) system [Table 1] divides vascular anomalies into 2 primary biological categories:
|Table 1: International society for the study of vascular anomalies classification system|
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Vasoproliferative neoplasms have increased endothelial cell turnover (i.e., they proliferate and undergo mitosis) because they are neoplasms. Vascular malformations do not have increased endothelial cell turnover. Instead, vascular malformations are structural abnormalities of the capillary, venous, lymphatic, and arterial system that grow in proportion to the child. ,
- Vasoproliferative or vascular neoplasms and
- Vascular malformations. 
Vascular or vasoproliferative neoplasms (Etiopathogenesis and clinical features)
Infantile hemangiomas present between 2 weeks to 2 months of life, undergoing a proliferative growth phase until they reach their full size, whereas congenital hemangiomas are distinguished by being fully formed at birth. 
Recent Hypotheses and Observations Regarding the Pathogenesis of Hemangiomas
Evidence suggests that vasoproliferative tumors result from vasculogenesis (formation of primitive blood vessels from angioblasts).  Immature stem/progenitor cells are identified within the anomaly that may originate from the placenta. 
They have a predictable clinical course, including rapid proliferation during the first year of life (proliferative phase), followed by gradual involution over 1-7 years (involuting phase), and then complete regression after 8 years (involuted phase).  The skin is the most common location, especially in hemangiomas of the head and neck (60%), trunk (25%), and extremities (15%). 
Congenital hemangiomas differ from infantile hemangiomas in that they congenital hemangiomas are fully developed at birth. These are usually solitary and present on the head and limbs near a joint, unlike infantile hemangiomas, which may occur anywhere in the body. 
Tufted angioma (TA) and Kaposiform hemangioendothelioma (KH)
TA and KH are rare vasoproliferative tumors that present at or shortly after birth. The imaging characteristics of TA and KH are similar to other vasoproliferative neoplasms [Table 2], although KH tends to be larger, more ill-defined, and infiltrative and is more often associated with impressive flow voids because of numerous feeding and draining vessels. 
|Table 2: Key Imaging Features of the Most Common Pediatric Vascular Anomalies|
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Vascular malformations (Etiopathogenesis and clinical features)
Vascular malformations are congenital morphogenic anomalies of various vessels that can present at any age.  They are subdivided into 2 categories:
- Slow- or low-flow malformations and
- Fast- or high-flow malformations [Table 1]. Low-flow malformations contain combinations of capillary, venous, and lymphatic components.
High-flow malformations contain arterial components in combination with other vascular structures.  Vascular malformations are always present at birth and enlarge in proportion to the growth of the child. They do not involute and remain present throughout the patient's life, as in our case. 
Slow flow vascular malformations
Venous, lymphatic, and venolymphatic malformations are the most common types of vascular malformations with an overall prevalence of up to 1% in the general population. The venous portions of malformations contain abnormally formed and dilated superficial or deep veins, the walls of which are thin because the veins lack smooth muscle. 
The lymphatic portions of these malformations are formed from collections of lymph vessels filled with serous fluid. 
The clinical presentation of low-flow vascular malformations varies because of the many combinations of venous and lymphatic components as well as variation in size and location. Predominantly, venous lesions may present at birth, but they are also seen in later years, as in our case. Predominantly, lymphatic malformations are often apparent at birth, and nearly all are present by 2 years of age. The natural history of venolymphatic malformations consists of slow steady enlargement. As in our case, venolymphatic malformations present with soft, easily compressible blue masses that may swell in dependent positions or when venous pressures increase (i.e., crying or valsalva). They may be small and localized or extensive with infiltration throughout an anatomical region. Although venous malformations most often involve the face, limbs, and/or trunk, they may be found within the internal viscera, bones, and skeletal muscle.  Many venous malformations cause pain and decreased range of motion and deformity. Often patients will suffer from increasing symptoms in late childhood or early adulthood. 
Imaging of low-flow vascular malformations involves ultrasound for general characterization of cystic (mostly lymphatic) versus solid (mostly venous) components. 
The appearance of a low-flow vascular malformation on MRI depends on the composition of lymphatic and venous components. The venous portions of a malformation will appear as a collection of serpentine structures separated by septations, as in our case. These serpentine structures represent slow-flowing blood in the venous channels and appear as high-signal intensity on T2-weighted images and low- to intermediate-signal intensity on T1-weighted images Phleboliths may be present as in our case and appear as round, low-signal intensity lesions on MRI.  Gadolinium-enhanced T1-weighted images may show enhancement of the slow-flowing venous channels. Lymphatic components of the malformation may contain cystic structures of various sizes ranging from macrocystic to microcystic. These cystic structures typically appear as high-signal intensity on T2-weighted MRI and do not exhibit central enhancement with gadolinium. 
MRI is often performed to determine lesion extent and plan for treatment. Phleboliths, a specific feature of venous components of vascular malformations, may be seen on plain radiographs when calcified, as in our case [Figure 2], and on MRI before or after calcification, as in our case. Both ultrasonography (US) and MRI are able to demonstrate the typical multispacial, multicystic, and/or partially solid nature of slow-flow venolymphatic malformations, allowing a diagnosis. 
Treatment of predominantly venous malformations is determined by the extent and location of the lesion. Although many are managed expectantly, some require treatment because they are painful, are in a location where they can cause significant morbidity, or are threatening vital organs (i.e., airway compromise). Therapeutic options range from observation and compression garments for palliation of pain and swelling, to sclerotherapy of mostly cystic mass using ethanol, sodium tetradecyl sulfate, ethibloc, bleomycin, cyclophosphamide, doxycycline, alcohol solution of zein, and OK-432 and finally, surgical excision. 
High-flow vascular malformations
Arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) are typically congenital and acquired malformations, respectively. They are characterized by a cluster of arterial and venous channels without a significant solid identifiable mass.  Histologically, AVMs and AVFs consist of dysplastic arteries that drain into arterialized veins.
AVMs and AVFs may present with pain, ulceration, ischemic changes, bleeding, embolism, and congestive heart failure. On physical examination, they may be warm pink pulsating patches on the skin with an underlying vascular murmur or thrill. Common locations include intracranial, intraosseous, muscle and subcutaneous fat.
Lesions are often multispacial and hypervascular on color Doppler US. Color Doppler sonography indicates a direct connection between the arterial and the venous systems. Lesion extent is best determined with MRI, which shows numerous flow voids (because of turbulence) and hyperintense signal on gradient echo as well as angiographic sequences. On MRI, the lesions appear as a tangle of multiple flow voids that indicate high flow on gradient-echo images. 
Therapy for high-flow malformations is preceded by angiography for complete mapping of vessels.  The first-line therapy for AVMs and AVFs is embolization. ,
Imaging approach to vascular anomalies
Many vascular anomalies can be diagnosed by history and physical examination, making imaging unnecessary.
US and MRI are the 2 most widely used modalities of choice. Typically, US is able to determine the basic type of lesion, direct initial management, and plan further imaging evaluation. 
MRI is helpful to further characterize sonographic findings and determine the extent of larger lesions for planning medical, interventional, and/or surgical therapy.
Radiography has limited utility in evaluating vascular anomalies, but when obtained, it may show organomegaly, soft tissue masses, and/or phleboliths, as in our case.
Association of venous malformations and pulmonary hypertension
Venous malformations are associated with spontaneous thrombosis and thrombolysis. , This is associated with size, depth, and presence of palpable phleboliths. This phenomenon is named Localized Intravascular Coagulopathy (LIC). D-dimer levels are often very high, even if these otherwise healthy patients do not have other conditions to increase D-dimer levels, e.g. cancer, inflammatory disease, thrombophilia, ischemic heart disease, arterial aneurysm or dissection, or pregnancy. This is an important LIC, which can lead to embolism causing pulmonary arterial hypertension. 
| Conclusion|| |
With this case report, we want to give a message that even pure peripheral venous malformations, which are of rare occurrence, can occur with complications such as pulmonary hypertension.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]