Intimal sarcoma of the superficial femoral arterywith osteosarcomatous differentiationJames L. Ebaugh, MD, MPH,a,b Minsheng Yuan, MD, PhD,c Jeffery Hu,c Ahchean Chen, MD, PhD,c

and Joseph D. Raffetto, MD,a,b West Roxbury and Boston, Mass

Sarcomas of the large vessels usually present centrally in the aorta, pulmonary artery, and inferior vena cava. Peripheralarterial sarcomas are exceptionally rare. They have been reported in the iliac and common or profunda femoral arteries,and are frequently undifferentiated. In this study, we describe a differentiated intimal sarcoma of the superficial femoralartery with abundant osteosarcoma within the specimen. Before knowing the diagnosis, treatment was for a presumedpseudoaneurysm using excision and bypass. Postoperatively, the patient received palliative radiation therapy. The tumor’slocation and histopathology are unique. A differentiated intimal sarcoma has never been reported in the superficialfemoral artery, and it represents the second peripheral arterial intimal sarcoma reported with osteosarcomatous

differentiation. (J Vasc Surg 2011;53:1394-7.)

sDpa

cpuptslaapLwdc

P

irt

sttmaattsew

Sarcomas of the great vessels and their branches have apredilection for the pulmonary artery, inferior vena cava,and aorta, whereas peripheral arterial sarcomas are excep-tionally rare. Most peripheral arterial sarcomas are leiomy-osarcomas1 or angiosarcomas,2 with only one reported caseof a differentiated intimal sarcoma in a peripheral artery, thecommon femoral artery.3 We report a case of an intimalsarcoma in the superficial femoral artery (SFA) with un-usual histopathology.

CASE REPORT

An 87-year-old man presented with left lower extremityedema that he had for the past several days. Venous duplex scanshowed an acute left lower extremity deep venous thrombosis(DVT), and a secondary finding of a 3.7 cm multilobular, heter-ogenous, pulsatile mass consistent with either an aneurysm orpseudoaneurysm of the SFA. The patient stated that this left thighmass had been present for several weeks and denied any trauma.His medical history included bilateral lower extremity weaknessfrom multiple lower back operations in the 1960s for spinal steno-sis, and a left total knee arthroplasty 8 years ago. He was onCoumadin for atrial fibrillation and his international normalizedratio was 2.7. Physical examination showed a 3 to 4 cm nontender,pulsatile medial midthigh mass and normal peripheral pulses. Theanterior knee arthroplasty incision extended proximally to thedistal extent of the pulsatile thigh mass. Knee plain films showed nobony abnormalities in the vicinity of the aneurysm.

From the Boston VA Healthcare System, Surgical Service, West Roxburya;the Division of Vascular and Endovascular Surgery, Brigham and Wom-en’s Hospital, Harvard Medical School, Bostonb; and Boston VA Health-care System, Department of Pathology, West Roxbury.c

Competition of interest: none.Reprint requests: James L. Ebaugh, MD, MPH, Boston VA Healthcare

System, Surgical Service, 1400 VFW Parkway, West Roxbury, MA 02132(e-mail: james.ebaugh2@med.va.gov).

The editors and reviewers of this article have no relevant financial relationshipsto disclose per the JVS policy that requires reviewers to decline review of anymanuscript for which they may have a competition of interest.

0741-5214/$36.00

pPublished by Elsevier Inc. on behalf of the Society for Vascular Surgery.doi:10.1016/j.jvs.2010.11.098

1394

A magnetic resonance angiogram of the lower extremitieshowed what seemed to be a distal SFA pseudoaneurysm (Fig 1).ifferential diagnosis included direct arterial injury related to hisrior knee surgery with chronic pseudoaneurysmal degeneration vsmycotic or true aneurysm.

Endovascular treatment of the aneurysm with a stent graft wasonsidered, but to decompress the femoral vein and relieve theatient’s significant edema we opted for open surgery. The patientnderwent resection of the aneurysm with oversewing of theroximal and distal arteries. A short jump graft from the distal SFAo the above-knee popliteal artery was performed using a reversedaphenous vein. Inside the mass was a significant amount ofobulation and chronic inflammation (Fig 2, a) but no purulence,nd otherwise had the appearance of a typical true SFA or poplitealneurysm. No frozen sections were sent. Due to a drop in hislatelet count, he was switched from unfractionated heparin toepirudin pending a heparin-induced platelet antibody test, whichas negative. The patient made an uneventful recovery and wasischarged on postoperative day 10 with Coumadin for the asso-iated DVT.

athologic features

Gross findings. The surgical specimen consisted of anrregular, firm artery varying in color from yellow to darked-brown, measuring 5.0 � 1.5 cm with variable wallhickness.

Conventional microscopy. The tumor (Fig 3, a)eemed to arise within the lumen of the vessel and infil-rated along the arterial wall with extension into the adven-itia. There were areas suggestive of in situ tumor where thealignant cells seemed to be confined within the intima

nd apposed beneath the endothelium. There were alsoreas of surface organizing thrombus that could have con-ributed to the clinical impression of the aneurysm. Theumor was composed of malignant spindle cells with exten-ive osteosarcomatous differentiation containing abundantxtracellular osteoid matrix (Fig 3, b). Additionally, thereere some areas indistinguishable from undifferentiated

leomorphic sarcoma or malignant fibrous histiocytoma

mod

Whit

orph

JOURNAL OF VASCULAR SURGERYVolume 53, Number 5 Ebaugh et al 1395

(Fig 3, c). The final pathologic diagnosis was high-gradeintimal sarcoma with osteosarcomatous differentiation.

Immunohistochemistry. Tumor cells stained strongly

Fig 1. a, Magnetic resonance angiogram of bilateral lowdropout artifact from prior left total knee replacement (acenter of the mass.

Fig 2. a, Intraoperative photo showing the lobulationpostoperative magnetic resonance image of residual tumor.

Fig 3. Hematoxylin and eosin stained sections: a, Intimhigher power images shown in (boxed b) and (boxed cfocus of osteoid (arrow; �20). c, Undifferentiated pleom

positive for vimentin, which is found in both benign and o

alignant mesenchymal tumors, but they were negative forther immunohistochemical stains. Negative staining foresmin and smooth muscle actin ruled out smooth muscle

tremities, left anterior oblique projection. Notice signal. b, Magnetic resonance coronal tomogram through the

hronic inflammation within the tumor. b, One monthe arrow shows bypass; arrowheads show residual tumor.

oma in lower power (�2), with boxes corresponding toOsteosarcomatous differentiation showing extracellularic area in higher power (�20).

er exrrow)

and c

al sarc). b,

rigin, while negative staining for pancytokeratin, S100

eucsdmapsipa

sdp5itp

isorvmiburtsrsm

12cgpmmpRmgiicm

tmo

JOURNAL OF VASCULAR SURGERYMay 20111396 Ebaugh et al

protein, and CD45-leukocyte common antigen ruled outmetastatic carcinoma, metastatic melanoma, and lym-phoma, respectively.4-6 Absence of CD31 and CD34 stain-ing argued against sarcoma of endothelial cell origin such asmalignant endothelioma and angiosarcoma. High prolifer-ative index (Ki-67 staining) supported the diagnosis of ahigh-grade malignant tumor.

Clinical course. Metastatic workup with computedtomography (CT) of the chest, abdomen, and pelvis wasnegative, but magnetic resonance imaging (MRI) of thethigh 1 month later showed a residual 7 � 5 � 3 cm tumorwithin the vastus medialis (Fig 2, b). Due to chronic dis-ability and advanced age, an above-knee amputation wasrecommended for curative resection. This was delayed sev-eral weeks due to the patient’s slow convalescence from thefirst surgery.

Several days before the amputation, 2 months after hispathologic diagnosis was made, the patient developedpneumonia, pleural effusions, urosepsis, and a non-ST seg-ment myocardial infarction, postponing the surgery. Achest CT showed multiple new bilateral pulmonary nod-ules, consistent with metastatic disease, and the thigh massenlarged and became tender, with a CT showing it had nowgrown to 11 � 10 � 7 cm, with extrinsic bypass graftcompression. Palliative radiation therapy (6600 CGy over 6weeks) was initiated to prevent bypass graft thrombosis andfor pain relief, with only modest effect. The patient passedaway 7 months after his initial presentation with no autopsyperformed.

DISCUSSION

This is the first known case of a peripheral arterialdifferentiated intimal sarcoma arising from the SFA. Thetumor also displayed osteosarcomatous differentiation, anextremely rare histology for this type of tumor.5

Primary neoplasms of the major blood vessels are di-vided into three categories based on their site of origin:from the large veins, the pulmonary artery (PA), or theaorta and its branches.4,5 Over 60% of reported sarcomas ofthe aorta and its branches are intimal sarcomas,4,5 arisingfrom the tunica intima of large blood vessels, rather thanfrom endothelial, medial, or adventitial cells. Other com-mon sites for intimal sarcoma include the PA and inferiorvena cava,4,5 although the majority of sarcomas of themajor veins are derived from medial smooth muscle.4,7

Hemangioendotheliomas (angiosarcomas) of endothelialorigin and mural tumors derived from the media andadventitia represent the majority of the remaining classes ofperipheral arterial tumors.5 To differentiate intimal sarco-mas from these other two, histology and immunohisto-chemistry patterns are used. Angiosarcomas show endothe-lial cells on microscopy and stain positively for vimentin,factor VIII, and CD 34. Leiomyosarcomas, on the otherhand, have characteristic spindle-shaped cells and stainpositively for desmin and actin. Intimal sarcomas, whichhave an unknown cell of origin, usually show undifferenti-

ated cells with variable immunophenotyping.4-6 a

Large vessel intimal sarcomas tend to occur in thelderly with a history of peripheral vascular disease, andsually present with advanced disease with an aggressiveourse.5 Many are centrally located, and can present as aymptomatic thoracic aneurysm,8 or with dyspnea,9 suddeneath,10 or distal embolization.1,4,11 Aortic intimal sarco-as have also been reported at the site of prior vascular

nastomoses.4,5,12 Peripheral arterial tumors frequentlyresent with edema, local pain, claudication, motor orensory loss, signs of peripheral embolization, or as annguinal mass.1-3 This patient presented with a nontender,ulsatile mass in his medial thigh, and painful edema fromn associated DVT.

Imaging of peripheral arterial tumors, if the diagnosis isuspected before surgery, includes a preoperative MRI toetermine resectability. A CT of the chest, abdomen, andelvis is mandatory in these patients in light of the reported0% to 70% incidence of metastatic disease at the time of

nitial diagnosis.1,5,13 These studies are also useful in de-ecting an unknown primary, because arterial tumors thatresent peripherally could be metastases.

Treatment of peripheral arterial intimal sarcoma is sim-lar to that of primary aortic sarcomas.4,12,13 If the diagno-is of a malignancy is known preoperatively, surgery consistsf local node sampling and en bloc resection with arterialeconstruction with an interposition graft or bypass. Adju-ant therapy using doxorubicin and ifosfamide is recom-ended after resection regardless of margin status, and also

n the presence of embolic or metastatic disease.14 Externaleam radiation therapy can be used to treat residual ornresectable tumors, although due to the low numbers ofeported cases, any benefit from chemotherapy, radiationherapy, or a combination of the two is difficult to demon-trate.5,14 Despite advances in surgery, chemotherapy, andadiation therapy, the 1-year survival rate with large vesselarcoma has remained 13%, with a mean survival of 14onths.12,13

In a review of 180 primary sarcomas of large arteries,09 (61%) were classified as intimal sarcomas, and of these,8 (26%) were differentiated.5 Differentiated intimal sar-omas show a spectrum of histopathological morpholo-ies with variable immunophenotying. Commonly re-orted types include angiosarcoma, leiomyosarcoma,yxofibrosarcoma, epithelioid hemangioendothelioma,yxoid chondrosarcoma, and undifferentiated pleomor-

hic sarcoma (or malignant fibrous histiocytoma).1,4,5

arer differentiations such as osteosarcoma and rhabdo-yosarcoma have been reported in PA4,15 and aortic ori-

in16,17 intimal sarcoma. Osteosarcomatous differentiationn a peripheral arterial intimal sarcoma has been describedn a patient with radiation-induced intimal sarcoma of theommon femoral artery,3 but never as a spontaneous tu-or, and never in the SFA, as in our case.

Intermediate and high-grade15 intimal sarcoma sub-ypes behave aggressively and have a high incidence ofetastases at the time of diagnosis.5,13 There was extensive

steosarcoma within this neoplasm, which usually suggests

more benign course. Despite this, the rapid postoperative

1

1

1

1

1

1

1

1

JOURNAL OF VASCULAR SURGERYVolume 53, Number 5 Ebaugh et al 1397

tumor growth and short survival of our patient implies thatthis differentiation does not alter the poor prognosis.

Special thanks to Ming Tao, MD, for assistance withthe pathology images.

REFERENCES

1. Sakpal SV, Mehta R, Babel N, Chamberlain RS. Peripheral arteryleiomyosarcoma. J Vasc Surg 2009;49:217-21.

2. Sattout AH, Deolekar MV, Tait WF, Williams GT. Femoral arteryangiosarcoma presenting with distal embolization: report of a case. SurgToday 2008;38:541-4.

3. [No authors listed]. Case records of the Massachusetts General Hospi-tal. Weekly clinicopathological exercises. Case 26-1993. A 73-year-oldman with an enlarging inguinal mass 10 years after treatment forprostate and colon cancers. N Engl J Med 1993;329:43-8.

4. Burke AP, Virmani R. Sarcomas of the great vessels. A clinicopathologicstudy. Cancer 1993;71:1761-73.

5. Sebenik M, Ricci A Jr, DiPasquade B, Mody K, Pytel P, Jee KJ, et al.Undifferentiated intimal sarcoma of large systemic blood vessels: reportof 14 cases with immunohistochemical profile and review of literature.Am J Surg Pathol 2005;29:1184-93.

6. Wick MR. Immunohistochemical approaches to the diagnosis of undif-ferentiated malignant tumors. Ann Diagn Pathol 2008;12:72-84.

7. Kevorkian J, Cento DP. Leiomyosarcoma of large arteries and veins.Surgery 1973;73:390-400.

8. Terra RM, Fernandez A, Bammann RH, Junqueira JJ, Capelozzi VL.

Pulmonary artery sarcoma mimicking a pulmonary artery aneurysm.Ann Thorac Surg 2008;86:1354-5. S

9. Hsing JM, Thakkar SG, Borden EC, Budd GT. Intimal pulmonaryartery sarcoma presenting as dyspnea: case report. Int Semin Surg Oncol2007;29:4-14.

0. Jiang WX, Gao CR, Sun JH, Bunai Y. Sudden cardiac death caused bya primary intimal sarcoma of the left coronary artery. Int J Leg Med2009;123:503-6.

1. Pompilio G, Tartara P, Varesi C, Biglioli P. Intimal-type primarysarcoma of the thoracic aorta: an unusual case presenting with left armembolization. Eur J Cardiothorac Surg 2002;21:574-6.

2. Shuster TA, Dall’Olmo CA, Spadone D, Silver D. Abdominal aorticsarcoma: report of a case with long-term survival and review of theliterature. Ann Vasc Surg 2002;16:545-9.

3. Seelig MH, Klingler PJ, Oldenburg WA, Blackshear JL. Angiosarcomaof the aorta: report of a case and review of the literature. J Vasc Surg1998;28:732-7.

4. Mayer F, Aebert H, Rudert M, Königsrainer A, Horger M, Kanz L, etal. Primary malignant sarcomas of the heart and great vessels in adultpatients — a single-center experience. Oncologist 2007;12:1134-42.

5. Tavora F, Miettinen M, Fanburg-Smith J, Franks TJ, Burke A. Pulmo-nary artery sarcoma: a histologic and follow-up study with emphasis ona subset of low-grade myofibroblastic sarcomas with a good long-termfollow-up. Am J Surg Path 2008;32:1751-61.

6. Miracco C, Laurini L, Santopietro R, DeSanti MM, Sassi C, Neri E, etal. Intimal-type primary sarcoma of the aorta. Report of a case withevidence of rhabdomyosarcomatous differentiation. Virchow Arch1999;435:62-6.

7. Szekely E, Kulka J. Primary intimal type leiomyosarcoma with rhab-domyosarcomatous differentiation of the thoracic aorta. Virchow Arch2000;437:208-9.

ubmitted Aug 13, 2010; accepted Nov 12, 2010.