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Phlebology OnlineFirst, published on October 8, 2014 as doi:10.1177/0268355514555210
Short Report
Neoplastic zebras of venous thrombosis: Diagnostic challenges in vascular medicine
Phlebology 0(0) 1–5 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355514555210 phl.sagepub.com
A Cornejo1, A Lekah2 and AK Kurklinsky3
Abstract Venous thrombosis is a common medical problem. Imaging differentiation of neoplasms and venous clots may prove challenging. We report three cases of ‘‘mistaken identities’’ of venous thrombi and neoplasms on the basis of clinical findings and different imaging modalities: ultrasound, computed tomography, and magnetic resonance imaging. Imaging studies are not always reliable and consideration of clinical features, including pretest probability, is necessary for correct diagnosis. A combination of imaging modalities and biopsies is needed for correct diagnosis in some cases.
Keywords Deep venous thrombosis, venous thromboembolism, venous thrombosis, veins, hemangioendothelioma, schwannoma, melanoma
Case reports Case 1 A 58-year-old man presented with a 14-month history of left lower leg pain. He was earlier diagnosed elsewhere by venous duplex compression ultrasound (US) with deep venous thrombosis (DVT) and received warfarin anticoagulation for eight months with no improvement. Repeat US upon referral did not confirm DVT, but a 1.5 cm mass mimicking a venous thrombus was found in the left gastrocnemius vein (Figure 1(a)). Magnetic resonance imaging (MRI) showed an indeterminate rounded lesion along the course of the gastrocnemius vessels (Figure 1(b)). Thrombophilia panel tests were negative. Ultrasound-guided tissue core biopsy of the left calf mass was positive for epithelioid hemangioendothelioma (EH). He received radiation therapy to the calf and underwent resection of the mass with negative margins (Figure 1(c)). Clinical examination and MRI images 14 months later showed no local neoplasm recurrence.
examination. A 1.5 cm 1.5 cm superficial freely mobile mass was located over the proximal medial aspect of the left forearm between the skin and the fascia. Its color and consistency were similar to a varicose vein. There was no local transillumination or pulsatility. Tinel’s sign was negative. Epitrochlear lymph nodes were not palpable. The referring physician suspected a tumor. Ultrasound scan revealed a superficial heterogeneous fusiform hyperechoic mass associated with either a tributary of the basilic vein or a nerve (Figure 2(a) and (b)). Computed tomography (CT) scan showed a small well-circumscribed mass most consistent with a benign neurogenic tumor such as schwannoma or neurofibroma (Figure 2(c) and (d)). Using blunt dissection and no-touch technique, the mass was excised en bloc. Operative report confirmed close proximity of the medial antebrachial cutaneous nerve to the mass lesion. Pathology revealed an organizing venous thrombus without evidence of a tumor.
1
Case 2
Hospital Metropolitano in Quito, Ecuador Department of Diagnostic Radiology, Mayo Clinic, Rochester, USA 3 Division of Cardiovascular Medicine, Mayo Clinic, Jacksonville, USA
A 44-year-old woman presented with discrete local swelling in the left forearm slowly increasing for two years. She denied any paresthesias. There was no history of neurofibromatosis and no axillary freckling on
Corresponding author: Andrew K Kurklinsky, Division of Cardiovascular Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Email: [email protected]
2
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Figure 1. (a) Gray-scale US image of the posterior left upper calf demonstrates a round, mass-like lesion in the gastrocnemius vein. (b) Sagittal MRI image confirms the presence of a round lesion along the gastrocnemius vessels (arrow), which has non-specific imaging characteristics and remains indeterminate. (c) Gross pathology image of the mass.
Case 3 A 72-year-old man with a history of metastatic melanoma with recent chemotherapy and radiation, Hodgkin’s disease, and coronary artery disease presented to the emergency room with fevers, chills, confusion, and leg swelling. Fever responded to antibiotic therapy but the infectious workup was negative. Persistent swelling of the right calf was evaluated by US and suggested acute DVT in one of the lumens of the paired right posterior tibial veins (Figure 3(a) and (b)). Low-molecular weight heparin therapy produced no response in several weeks. Positron emission tomography (PET)/CT scan was ordered to search for possible melanoma recurrence and metastases. It revealed hypermetabolic lesions consistent with metastases, one located at the site previously identified by US (Figure 3(c) and (d)). Palliative care was ultimately pursued.
Discussion Venous thrombosis is a common pathology,1 and duplex compression US is the most common first-line imaging diagnostic modality. Most cases of calf vein thrombosis involve the posterior tibial or peroneal veins and isolated gastrocnemius and soleal vein thrombosis (IGSVT) comprises 10–25% of all leg DVTs.2
There is no consensus on the best treatment modality for IGSVT, but systemic anticoagulation is an accepted practice.2 With advancements of ultrasound technology, routine detection of thrombi in gastrocnemius and soleal veins became possible,2 but the specificity of ultrasound and clinical assessment is imperfect.2,3 A number of tumors may have a presentation similar to venous clots, both clinically and in imaging studies, resulting in diagnostic errors. These cases illustrate misidentification of venous clots and neoplasms. In our practice, ultrasound scanning protocols are based on the guidelines developed collaboratively by the American College of Radiology, the American Institute of Ultrasound in Medicine, and the Society of Radiologists in Ultrasound. Our peripheral venous ultrasound protocol requires sufficient venous compression by the transducer in the transverse plane to completely obliterate the normal venous lumen. The extent and location of the sites where the veins fail to compress completely are recorded. After the entire venous segment has been evaluated in the transverse plane, the examiner rotates the probe and rescans the segment in the longitudinal plane with color and spectral Doppler to support the presence or absence of an abnormality. Abnormal findings require additional images to document the complete extent of the abnormalities. If the cause of the symptoms is not readily discernable by the standard examination, additional clinical evaluation
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Figure 2. (a) Color Doppler and (b) gray-scale US images of the left anterior proximal forearm show a subcutaneous, focal, heterogeneous, solid mass in the vicinity of the basilic vein and the medial antebrachial cutaneous nerve. (c) Non-enhanced axial and (d) Contrast-enhanced sagittal CT images demonstrate a well-circumscribed, round, low attenuation mass with a thin-peripheral rim of enhancement (arrows) in the subcutaneous tissues of the left anterior proximal forearm. This mass might be associated with a vessel or nerve in the region and remains indeterminate.
and imaging modalities may be pursued. In the above reported cases, an earlier correct diagnosis could not be made due to the challenging similarity between venous thrombi and neoplasms. EH is a rare neoplasm that can arise from any vascularized tissue and has potential to metastasize. It belongs to a group called ‘‘vascular tumors of intermediate malignancy.’’4 It is characterized by epithelioid endothelial cells, and in the beginning it may appear as DVT. It usually presents in both sexes in middle age and is rare in pediatric population.4 The neoplasm presents as a painful and poorly circumscribed mass involving subcutaneous soft tissue in the extremities. Occasionally, well-formed large vessels are seen in the central areas of the lesion. The lumen of the vessel may appear occluded by necrotic material and dense
collagen bundles.5 Fine needle aspiration cytology is used for the diagnosis of soft tissue tumors like EH. Immunohistochemistry is also helpful in the differential diagnosis with other tumors because VW factor, CD-31 and CD-34 markers are present in this neoplasm.5,6 Hemangioendotheliomas are low-to-intermediate grade neoplasms with metastasis rates up to 30%, most commonly to the lung, and the mortality ranging 17–65%. Although radiation therapy may be used, surgical excision with clear margins is the best treatment.4,5 Schwannoma in most cases is a benign nerve sheath neoplasm and malignant transformations are extremely rare.7,8 It is usually a solitary lesion, but may present as multiple lesions, especially when associated with neurofibromatosis type I (von Recklinghausen disease).
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Figure 3. (a) Color Doppler and (b) Gray-scale ultrasound images of the medial right midcalf demonstrate a mass-like lesion in one of the paired right posterior tibial veins resembling a thrombus. (c) Coronal and (d) Axial PET/CT scan images suggest that a tiny culprit hypermetabolic lesion in the region of the posterior tibial veins in the medial midcalf is consistent with a metastasis (arrow). Another larger metastatic focus is seen in the right popliteal fossa (arrowhead).
In rare cases, a vessel wall may be involved.7–9 They are typically located along the course of peripheral nerves, appearing as well defined, skin colored nodules within the deep dermis or subcutis of the flexor aspects of extremities.7 Diagnosis requires fine needle aspiration biopsy with immunohistochemistry. All Schwannomas should demonstrate reactivity for S-100 protein.7 Most patients present with local pain and undergo surgical removal of the tumor; however, local recurrence is not uncommon.9
Conflict of interest
Conclusion
References
Tumors and venous thrombi may be mistaken on imaging studies. Correct identification of tumors located near vessels or nerves may be particularly challenging because of the local extension. Additional imaging modalities and biopsy can assist with diagnosis.
1. Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008; 28: 370–372. 2. Lautz TB, Abbas F, Walsh SJ, et al. Isolated gastrocnemius and soleal vein thrombosis: should these patients receive therapeutic anticoagulation? Ann Surg 2010; 251: 735–742.
All authors meaningfully contributed to the preparation of the manuscript and had an opportunity to review the manuscript prior to its submission. None of the authors has any conflicts of interest to declare in connection with this manuscript.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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[1–5] [PREPRINTER stage]
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3. Moua J, Nussbaum E, Kim Y-S, et al. The persistent thrombus: complications, diagnosis, and novel treatment intervention. Pediatr Crit Care Med 2011; 12: e416–e419. 4. Henton JMD and Kang N. Epithelioid hemangioendothelioma: occasionally encountered and potentially harmful. J Plast Reconstruct Aesthet Surg 2013; 66: 131–133. 5. Requena L and Kutzner H. Hemangioendothelioma. Semin Diagn Pathol 2013; 30: 29–44. 6. Sehgal S, Agarwal R, Verma S, et al. Fine needle aspiration cytology of epithelioid hemangioendothelioma of soft tissue. Diagn Cytopathol 2013; 41: 179–182.
7. Gaudi S, Mills O, Goyette EF, et al. Intravascular schwannoma. Am J Dermatopathol 2011; 33: 850–854. 8. Joyce M, Laing AJ, Mullet H, et al. Multiple schwannomas of the posterior tibial nerve. Foot Ankle Surg 2002; 8: 101–103. 9. MacCollin M, Woodfin W, Kronn D, et al. Schwannomatosis: a clinical and pathologic study. Neurology 1996; 46: 1072–1079.
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(PHL)
[1–5] [PREPRINTER stage]
Phlebology OnlineFirst, published on October 8, 2014 as doi:10.1177/0268355514555210
Short Report
Neoplastic zebras of venous thrombosis: Diagnostic challenges in vascular medicine
Phlebology 0(0) 1–5 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355514555210 phl.sagepub.com
A Cornejo1, A Lekah2 and AK Kurklinsky3
Abstract Venous thrombosis is a common medical problem. Imaging differentiation of neoplasms and venous clots may prove challenging. We report three cases of ‘‘mistaken identities’’ of venous thrombi and neoplasms on the basis of clinical findings and different imaging modalities: ultrasound, computed tomography, and magnetic resonance imaging. Imaging studies are not always reliable and consideration of clinical features, including pretest probability, is necessary for correct diagnosis. A combination of imaging modalities and biopsies is needed for correct diagnosis in some cases.
Keywords Deep venous thrombosis, venous thromboembolism, venous thrombosis, veins, hemangioendothelioma, schwannoma, melanoma
Case reports Case 1 A 58-year-old man presented with a 14-month history of left lower leg pain. He was earlier diagnosed elsewhere by venous duplex compression ultrasound (US) with deep venous thrombosis (DVT) and received warfarin anticoagulation for eight months with no improvement. Repeat US upon referral did not confirm DVT, but a 1.5 cm mass mimicking a venous thrombus was found in the left gastrocnemius vein (Figure 1(a)). Magnetic resonance imaging (MRI) showed an indeterminate rounded lesion along the course of the gastrocnemius vessels (Figure 1(b)). Thrombophilia panel tests were negative. Ultrasound-guided tissue core biopsy of the left calf mass was positive for epithelioid hemangioendothelioma (EH). He received radiation therapy to the calf and underwent resection of the mass with negative margins (Figure 1(c)). Clinical examination and MRI images 14 months later showed no local neoplasm recurrence.
examination. A 1.5 cm 1.5 cm superficial freely mobile mass was located over the proximal medial aspect of the left forearm between the skin and the fascia. Its color and consistency were similar to a varicose vein. There was no local transillumination or pulsatility. Tinel’s sign was negative. Epitrochlear lymph nodes were not palpable. The referring physician suspected a tumor. Ultrasound scan revealed a superficial heterogeneous fusiform hyperechoic mass associated with either a tributary of the basilic vein or a nerve (Figure 2(a) and (b)). Computed tomography (CT) scan showed a small well-circumscribed mass most consistent with a benign neurogenic tumor such as schwannoma or neurofibroma (Figure 2(c) and (d)). Using blunt dissection and no-touch technique, the mass was excised en bloc. Operative report confirmed close proximity of the medial antebrachial cutaneous nerve to the mass lesion. Pathology revealed an organizing venous thrombus without evidence of a tumor.
1
Case 2
Hospital Metropolitano in Quito, Ecuador Department of Diagnostic Radiology, Mayo Clinic, Rochester, USA 3 Division of Cardiovascular Medicine, Mayo Clinic, Jacksonville, USA
A 44-year-old woman presented with discrete local swelling in the left forearm slowly increasing for two years. She denied any paresthesias. There was no history of neurofibromatosis and no axillary freckling on
Corresponding author: Andrew K Kurklinsky, Division of Cardiovascular Medicine, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Email: [email protected]
2
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Figure 1. (a) Gray-scale US image of the posterior left upper calf demonstrates a round, mass-like lesion in the gastrocnemius vein. (b) Sagittal MRI image confirms the presence of a round lesion along the gastrocnemius vessels (arrow), which has non-specific imaging characteristics and remains indeterminate. (c) Gross pathology image of the mass.
Case 3 A 72-year-old man with a history of metastatic melanoma with recent chemotherapy and radiation, Hodgkin’s disease, and coronary artery disease presented to the emergency room with fevers, chills, confusion, and leg swelling. Fever responded to antibiotic therapy but the infectious workup was negative. Persistent swelling of the right calf was evaluated by US and suggested acute DVT in one of the lumens of the paired right posterior tibial veins (Figure 3(a) and (b)). Low-molecular weight heparin therapy produced no response in several weeks. Positron emission tomography (PET)/CT scan was ordered to search for possible melanoma recurrence and metastases. It revealed hypermetabolic lesions consistent with metastases, one located at the site previously identified by US (Figure 3(c) and (d)). Palliative care was ultimately pursued.
Discussion Venous thrombosis is a common pathology,1 and duplex compression US is the most common first-line imaging diagnostic modality. Most cases of calf vein thrombosis involve the posterior tibial or peroneal veins and isolated gastrocnemius and soleal vein thrombosis (IGSVT) comprises 10–25% of all leg DVTs.2
There is no consensus on the best treatment modality for IGSVT, but systemic anticoagulation is an accepted practice.2 With advancements of ultrasound technology, routine detection of thrombi in gastrocnemius and soleal veins became possible,2 but the specificity of ultrasound and clinical assessment is imperfect.2,3 A number of tumors may have a presentation similar to venous clots, both clinically and in imaging studies, resulting in diagnostic errors. These cases illustrate misidentification of venous clots and neoplasms. In our practice, ultrasound scanning protocols are based on the guidelines developed collaboratively by the American College of Radiology, the American Institute of Ultrasound in Medicine, and the Society of Radiologists in Ultrasound. Our peripheral venous ultrasound protocol requires sufficient venous compression by the transducer in the transverse plane to completely obliterate the normal venous lumen. The extent and location of the sites where the veins fail to compress completely are recorded. After the entire venous segment has been evaluated in the transverse plane, the examiner rotates the probe and rescans the segment in the longitudinal plane with color and spectral Doppler to support the presence or absence of an abnormality. Abnormal findings require additional images to document the complete extent of the abnormalities. If the cause of the symptoms is not readily discernable by the standard examination, additional clinical evaluation
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Figure 2. (a) Color Doppler and (b) gray-scale US images of the left anterior proximal forearm show a subcutaneous, focal, heterogeneous, solid mass in the vicinity of the basilic vein and the medial antebrachial cutaneous nerve. (c) Non-enhanced axial and (d) Contrast-enhanced sagittal CT images demonstrate a well-circumscribed, round, low attenuation mass with a thin-peripheral rim of enhancement (arrows) in the subcutaneous tissues of the left anterior proximal forearm. This mass might be associated with a vessel or nerve in the region and remains indeterminate.
and imaging modalities may be pursued. In the above reported cases, an earlier correct diagnosis could not be made due to the challenging similarity between venous thrombi and neoplasms. EH is a rare neoplasm that can arise from any vascularized tissue and has potential to metastasize. It belongs to a group called ‘‘vascular tumors of intermediate malignancy.’’4 It is characterized by epithelioid endothelial cells, and in the beginning it may appear as DVT. It usually presents in both sexes in middle age and is rare in pediatric population.4 The neoplasm presents as a painful and poorly circumscribed mass involving subcutaneous soft tissue in the extremities. Occasionally, well-formed large vessels are seen in the central areas of the lesion. The lumen of the vessel may appear occluded by necrotic material and dense
collagen bundles.5 Fine needle aspiration cytology is used for the diagnosis of soft tissue tumors like EH. Immunohistochemistry is also helpful in the differential diagnosis with other tumors because VW factor, CD-31 and CD-34 markers are present in this neoplasm.5,6 Hemangioendotheliomas are low-to-intermediate grade neoplasms with metastasis rates up to 30%, most commonly to the lung, and the mortality ranging 17–65%. Although radiation therapy may be used, surgical excision with clear margins is the best treatment.4,5 Schwannoma in most cases is a benign nerve sheath neoplasm and malignant transformations are extremely rare.7,8 It is usually a solitary lesion, but may present as multiple lesions, especially when associated with neurofibromatosis type I (von Recklinghausen disease).
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Figure 3. (a) Color Doppler and (b) Gray-scale ultrasound images of the medial right midcalf demonstrate a mass-like lesion in one of the paired right posterior tibial veins resembling a thrombus. (c) Coronal and (d) Axial PET/CT scan images suggest that a tiny culprit hypermetabolic lesion in the region of the posterior tibial veins in the medial midcalf is consistent with a metastasis (arrow). Another larger metastatic focus is seen in the right popliteal fossa (arrowhead).
In rare cases, a vessel wall may be involved.7–9 They are typically located along the course of peripheral nerves, appearing as well defined, skin colored nodules within the deep dermis or subcutis of the flexor aspects of extremities.7 Diagnosis requires fine needle aspiration biopsy with immunohistochemistry. All Schwannomas should demonstrate reactivity for S-100 protein.7 Most patients present with local pain and undergo surgical removal of the tumor; however, local recurrence is not uncommon.9
Conflict of interest
Conclusion
References
Tumors and venous thrombi may be mistaken on imaging studies. Correct identification of tumors located near vessels or nerves may be particularly challenging because of the local extension. Additional imaging modalities and biopsy can assist with diagnosis.
1. Heit JA. The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol 2008; 28: 370–372. 2. Lautz TB, Abbas F, Walsh SJ, et al. Isolated gastrocnemius and soleal vein thrombosis: should these patients receive therapeutic anticoagulation? Ann Surg 2010; 251: 735–742.
All authors meaningfully contributed to the preparation of the manuscript and had an opportunity to review the manuscript prior to its submission. None of the authors has any conflicts of interest to declare in connection with this manuscript.
Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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3. Moua J, Nussbaum E, Kim Y-S, et al. The persistent thrombus: complications, diagnosis, and novel treatment intervention. Pediatr Crit Care Med 2011; 12: e416–e419. 4. Henton JMD and Kang N. Epithelioid hemangioendothelioma: occasionally encountered and potentially harmful. J Plast Reconstruct Aesthet Surg 2013; 66: 131–133. 5. Requena L and Kutzner H. Hemangioendothelioma. Semin Diagn Pathol 2013; 30: 29–44. 6. Sehgal S, Agarwal R, Verma S, et al. Fine needle aspiration cytology of epithelioid hemangioendothelioma of soft tissue. Diagn Cytopathol 2013; 41: 179–182.
7. Gaudi S, Mills O, Goyette EF, et al. Intravascular schwannoma. Am J Dermatopathol 2011; 33: 850–854. 8. Joyce M, Laing AJ, Mullet H, et al. Multiple schwannomas of the posterior tibial nerve. Foot Ankle Surg 2002; 8: 101–103. 9. MacCollin M, Woodfin W, Kronn D, et al. Schwannomatosis: a clinical and pathologic study. Neurology 1996; 46: 1072–1079.
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