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Primary malignant lymphoma of the saphenous vein
Primary malignant lymphoma of the saphenous vein Francesco Rulli, MD,a Anna Neri, MD,a Giulio Bigotti, MD,b Raffaele Tartaglione, MD,b Giampiero Ausili Cefaro, MD,b and Attilio Maria Farinon, MD, FACS,a Rome, Italy We herein present a case of primary malignant lymphoma of the saphenous vein. A 72-year-old man suffered from tumor and pain of the anteromedial aspect of the left upper thigh. Local thigh ultrasound scanning and computed tomography revealed a mass within the superior third of the internal saphenous vein. The patient underwent surgical exploration and removal of the saphenous vein between the groin and the upper third of the leg. The resected vessel was surrounded and infiltrated by a whitish, rubbery tissue all along its course. The histologic findings were consistent with high-grade, diffuse, large-cell lymphoma of peripheral B lymphocyte origin, primarily arising in the saphenous vein. Antiactin monoclonal antibodies depicted the venous vascular wall infiltrated by tumor cells, confirming the lymphomatous localization within the saphenous vein. The patient is now alive and free of tumor 10 months after the operation. (J Vasc Surg 2002;35:168-71.)
Primary tumors arising from the vessel wall are rare, and, although primary cardiac malignant lymphoma has been reported,1-3 a malignant lymphoma originating from a vein is exceptional. A case of primary malignant lymphoma of the superior vena cava has been described in 1998.4 Herein we report a malignant lymphoma primarily localized within the wall of the internal saphenous vein, which is, to the best of our knowledge, the first presented in the medical literature. CASE REPORT A 72-year–old white man was admitted to the Department of Surgery of the University of Rome “Tor Vergata” (Columbus Hospital) on June 5, 2000. He complained of progressive pain of the left upper thigh in the crural area. He had no history of immunosuppression or methotrexate treatment of rheumatoid arthritis. Furthermore, human immunodeficiency virus and Epstein-Barr virus exposures were excluded. Physical examination showed a medial thigh mass and a moderate swelling of the ipsilateral leg. Routine laboratory tests revealed highly increased serum lactate-dehydrogenase (609 IU/L; normal, <460 IU/L) and fibrinogen (723 mg/dL; normal, 200400 mg/dL) levels. Local thigh ultrasound scanning and computed tomography (CT) showed a dishomogeneous mass of 4.5 cm in diameter, with particular echogenicity and density (Fig 1, A, B, C) without invasion of adjacent femoral vessels. The mass was extraluminal at all CT levels examined and showed indistinct margin and no cleavage planes between the tumor and the great saphenous vein. The color Doppler scan revealed a normal flow in the femoral vessels but no flow in the internal saphenous vein (Fig 1, D). CT total body did not reveal lymphadenopathy or
organomegaly. Because the mass was quite painful and a source of discomfort to the patient, we decided to remove it immediately and without further work-up. In surgical exploration of the thigh, the saphenous vein from the saphenofemoral junction to the upper third of the leg was surrounded and infiltrated by whitish, rubbery tissue all along its course. The vessel was removed through a longitudinal incision from the groin to the upper medial third of the leg. The excision of the tumor was not challenging, and local exeresis was performed on grossly free margins. In particular, the common femoral vein at its junction with the great saphenous vein was free of tumor, and no enlarged lymph nodes were detected upon palpation. The gross specimen consisted of a saphenous vein that was surrounded and infiltrated by a whitish to brownish, rubbery tissue all along its course (Fig 2, upper panel). Histologically a large vascular structure was seen (Fig 2, lower panel), which was diffusely infiltrated by a lymphoid proliferation sometimes admixed with histiocytes (Fig 3). The lymphoid cells were large and immunohistochemically stained by monoclonal antibodies (MoAbs) anti-CD10 and anti-BCL2. C-Myc was also positive, whereas the neoplastic cells were CD3-negative and CD79A-negative. Antiactin MoAbs highlighted the venous vascular wall infiltrated by tumor cells. The findings were consistent with a high-grade, diffuse, large-cell lymphoma of peripheral B lymphocyte origin, primarily arising in the saphenous vein. The postoperative course was uneventful. Polichemotherapy was administered for six cycles (cyclophosphamide, vincristine, and prednisolone every 28 days). Follow-up CT after polichemotherapy did not show recurrence or lymph node enlargement. The patient is now alive and free of tumor 10 months after the operation.
DISCUSSION Vergata,”a
From the Department of Surgery, University of Rome “Tor and the Institutes of Pathology and Radiology, Catholic University of Sacred Heart,b Rome, Italy. Competition of interest: nil. Reprint requests: Francesco Rulli, MD, Department of Surgery, University of Rome “Tor Vergata,” c/o Complesso Integrato Columbus, via Moscati 1, 00168 Rome, Italy (e-mail [email protected]). Copyright © 2002 by The Society for Vascular Surgery and The American Association for Vascular Surgery. 0741-5214/2002/$35.00 + 0 24/4/119753 doi:10.1067/mva.2002.119753
168
This is, to our knowledge, the second case of primary malignant lymphoma of a vein. The first one was published in 1998 by Nomori et al,4 who described a case of superior vena cava localization. In any case, malignant tumors arising from venous walls of the lower extremity are uncommon. Histologically they are divided into two groups—hemangioendotheliomas of intermediate malignancy and leiomyosarcomas.5 To these groups we should add primary malignant lym-
JOURNAL OF VASCULAR SURGERY Volume 35, Number 1
Rulli et al
A
C
B
D
169
Fig 1. Primary malignant lymphoma of the saphenous vein. A, The ultrasound scan shows solid, hypoechoic palpable mass with a central hyperechoic area. B, Medial to the mass is a neoplastic tissue with a peculiar cerebroid appearance involving soft tissues. C, Local CT showed dishomogeneous mass (arrow) with peripheral enhancement, without invasion of femoral vessels. D, Color Doppler scan showed a normal flow in the femoral vessels.
phoma, considering the case we observed. Patients with scleroderma have been reported to show an increased incidence of lung, breast, hematopoietic, and lymphoproliferative malignancies6; in most patients, scleroderma occurs first and is followed by development of a lymphoma. Scleroderma developed in the patient with primary malignant lymphoma of the superior vena cava4 41 months after the operation. No scleroderma has yet developed in our patient. As is well known, extranodal non-Hodgkin’s lymphoma usually develops in organs containing recognizable areas of lymphoid tissue such as tonsils, stomach, small bowel, and skin. Some recent studies have pointed to the concept of mucosa-associated lymphoid tissue to explain the occurrence of lymphomas in certain extranodal tis-
sues,7,8 and primary tumors in unusual locations that do not contain lymph nodes or easily apparent lymphoid aggregates, such as the breast, have been reported.9 Regarding the spread modalities of the neoplasms that eventually enter in the differential diagnosis with primary venous lymphoma, in a series of 13 primary venous leiomyosarcomas, metastases developed in five patients.10 In another condition, intravascular lymphomatosis (ILV), metastatic diffusion seems to be more common because most of the reported patients showed widespread disease and involvement of the central nervous system.11 In the case we have described, no lymph node structures involved by the lymphoma were found, either in the inguinal region or in the leg compartments adjacent the saphenous vein, thus confirming that the site of origin is to
JOURNAL OF VASCULAR SURGERY January 2002
170 Rulli et al
A
A
B
B
Fig 2. Primary malignant lymphoma of the saphenous vein. Upper panel, Saphenous vein appears surrounded and infiltrated by a whitish to brownish, neoplastic tissue that extends all along its course. Lower panel, The wall of the vein is infiltrated and replaced by a monomorphous large lymphoid cell proliferation that invades up to the intimal layers. At the top of the field the vascular lumen is seen (hematoxyline-eosine × 250).
be identified in the vessel wall. Our staging preoperative work-up included only a CT scan because the lymphomatous nature of the disease was not suspected before surgery and biopsies were not carried out. One might object that our case could represent a primary soft tissue lymphoma arising in the periadventitial tissues that, for unknown reasons, has invaded the saphenous vein wall and extended all along its course. Even if we cannot rule out this possibility, we believe that if this were indeed true, it would not change the uniqueness of such clinical presentation considering that no primary soft tissue lymphomas with such exceptional features have to date been reported. In fact, primary soft tissue lymphomas, even if rare, can occur in the soft tissues of the extremity, but as a mass without the localization and spread observed in our case.12 In any
Fig 3. Primary malignant lymphoma of the saphenous vein. Upper panel, Low-power view of the lymphoid infiltrate (arrows) at a different level along the course of the saphenous vein shows a mainly periadvential location in close connection with the venous muscular wall (hematoxyline-eosine × 100). Lower panel, High-power view of the lymphoma shows a uniform proliferation of large cells with prominent nuclei and nucleoli consistent with the diagnosis of high-grade large cell lymphoma (Giemsa stain × 400).
JOURNAL OF VASCULAR SURGERY Volume 35, Number 1
event, antiactin MoAbs highlighted the venous vascular wall infiltrated by tumor cells, thus confirming the lymphomatous localization within the saphenous vein. In such a rare case, surgical treatment in terms of extent of excision and tumor-free margins should include wide local resection of the mass. In summary, we can say that the treatment of the presented case did not differ from that of other anatomical-site primary lymphoma. In fact, this kind of management, together with multidrug chemotherapy, is the recommended treatment.12 Gallium-67 imaging has been advocated to define residual disease and predict outcome,13 but we did not perform it because this diagnostic tool is not routinely used at our institution. It is important to remark that 10% elevation in the serum lactate-dehydrogenase, age >60 years, and bulky disease are independent prognostic factors for overall survival in patients treated for aggressive lymphoma.14 In general, the most important clinical differential diagnosis should then be made with primary venous leiomyosarcoma, a rare but lethal disease that can arise in a large vein, including the great saphenous vein,6 and that is present as a tumor mass. In these cases, surgical treatment should include wide local excision with free margins and eventually postoperative adjuvant therapy. Because of the possibility of invasion of adjacent organs, surgery may be technically challenging and may be responsible for perioperative morbidity and mortality.6 In conclusion, it seems important to remark that primary lymphoma of a large vein is a pathologic condition involving the layers of the wall and, eventually, the periadventitial tissues and must not be confused with ILV, a rare malignancy characterized by neoplastic proliferation of lymphoid cells within the lumens of arteries, small veins, and capillaries.15 Although ILV should be suspected in adult patients with unclear meningoencephalitic syndrome, confusional state, dementia, or other unexplained neurologic conditions with signs of a systemic disease,16 vein lymphoma, based on the two cases in the world literature (including our case), is to be considered in the case of a soft tissue mass localized within the wall and periadventitial tissues of a major venous vessel.
Rulli et al
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REFERENCES 1. Zaharia L, Gell PS. Primary cardiac lymphoma. Am J Clin Oncol 1991;14:142-5. 2. Roller MB, Manoharan A, Lvoff R. Primary cardiac lymphoma. Acta Haematol 1991;85:47-8. 3. Costantino A, West TE, Gupta M, Loghmanee F. Primary cardiac lymphoma in a patient with acquired immune deficiency sindrome. Cancer 1987;60:2801-5. 4. Nomori H, Nara S, Morinaga S, Soejema K. Primary malignant lymphoma of superior vena cava. Ann Thorac Surg 1998;66:1423-4. 5. Reix T, Sevestre H, Sevestri-Pietri MA, Szychta P, Pietri J. Primary malignant tumors of the venous system in the lower extremities. Ann Vasc surg 1998;12:589-96. 6. Hall SW, Gillespie JJ, Tencznski TF. Generalized lipodystrophy, scleroderma, and Hodgkin’s disease. Arch Intern Med 1978;138:1303-4. 7. Ferguson DJ. Intraepithelial lymphocytes and macrophages in the normal breast. Virchows Arch A Pathol Anat Histopathol 1985;407:369-78. 8. Isaacson PG, Spencer J. Malignant lymphoma of mucosa associated lymphoid tissue. Histopathology 1987;11:445-62. 9. Sokolov T, Shimonov M, Blickstein D, Nobel M, Antebi E. Primary lymphoma of the breast: unusual presentation of breast cancer. Eur J Surg 2000;166:390-3. 10. Dzsinch C, Gloviczki P, van Herden JA, Nagorney DM, Pairolero PC, Johnson CM, et al. Primary venous leiomyosarcoma: a rare but lethal disease. J Vasc Surg 1992;15:595-603. 11. Bogomolski-Yahalom V, Lossos IS, Okun E, Sherman Y, Lossos A, Polliak A. Intravascular lymphomatosis—an indolent or aggressive entity? Leukemia Lymphoma 1998;29:585-93. 12. Travis WD, Banks FM, Reiman HM. Primary extranodal soft tissue lymphoma. Am J Surg Pathol 1987;11:359-66. 13. Kaplan WD, Jochelson MS, Herman TS, Nadler LM, Stomper PC, Takvorian T, et al. Gallium-67 imaging: a predictor of residual tumor viability and outcome in patients with diffuse large-cell lymphoma. J Clin Oncol 1990;8:1966-70. 14. Wilder RB, Rodriguez MA, Ha CS, Pro B, Hess MA, Cabanillas F, et al. Bulky disease is an adverse prognostic factor in patients treated with chemotherapy comprised of cyclophosphamide doxorubicin, vincristine, and prednisone with or without radiotherapy for aggressive lymphoma. Cancer 2001;91:2440-6. 15. Pfelger L, Tappeiner J. Zur kenntnis der systemisierten endotheliomatose der cutanen blutgefasse [Germany]. Hautarzt 1959;10: 359-63. 16. Baumann TP, Hurwitz N, Karamitopolou-Diamantis E, Probst A, Herrmann R, Steck AJ. Diagnosis and treatment of intravascular lymphomatosis. Arch Neurol 2000;57:374-7. Submitted May 24, 2001; accepted Aug 14, 2001.
Primary tumors arising from the vessel wall are rare, and, although primary cardiac malignant lymphoma has been reported,1-3 a malignant lymphoma originating from a vein is exceptional. A case of primary malignant lymphoma of the superior vena cava has been described in 1998.4 Herein we report a malignant lymphoma primarily localized within the wall of the internal saphenous vein, which is, to the best of our knowledge, the first presented in the medical literature. CASE REPORT A 72-year–old white man was admitted to the Department of Surgery of the University of Rome “Tor Vergata” (Columbus Hospital) on June 5, 2000. He complained of progressive pain of the left upper thigh in the crural area. He had no history of immunosuppression or methotrexate treatment of rheumatoid arthritis. Furthermore, human immunodeficiency virus and Epstein-Barr virus exposures were excluded. Physical examination showed a medial thigh mass and a moderate swelling of the ipsilateral leg. Routine laboratory tests revealed highly increased serum lactate-dehydrogenase (609 IU/L; normal, <460 IU/L) and fibrinogen (723 mg/dL; normal, 200400 mg/dL) levels. Local thigh ultrasound scanning and computed tomography (CT) showed a dishomogeneous mass of 4.5 cm in diameter, with particular echogenicity and density (Fig 1, A, B, C) without invasion of adjacent femoral vessels. The mass was extraluminal at all CT levels examined and showed indistinct margin and no cleavage planes between the tumor and the great saphenous vein. The color Doppler scan revealed a normal flow in the femoral vessels but no flow in the internal saphenous vein (Fig 1, D). CT total body did not reveal lymphadenopathy or
organomegaly. Because the mass was quite painful and a source of discomfort to the patient, we decided to remove it immediately and without further work-up. In surgical exploration of the thigh, the saphenous vein from the saphenofemoral junction to the upper third of the leg was surrounded and infiltrated by whitish, rubbery tissue all along its course. The vessel was removed through a longitudinal incision from the groin to the upper medial third of the leg. The excision of the tumor was not challenging, and local exeresis was performed on grossly free margins. In particular, the common femoral vein at its junction with the great saphenous vein was free of tumor, and no enlarged lymph nodes were detected upon palpation. The gross specimen consisted of a saphenous vein that was surrounded and infiltrated by a whitish to brownish, rubbery tissue all along its course (Fig 2, upper panel). Histologically a large vascular structure was seen (Fig 2, lower panel), which was diffusely infiltrated by a lymphoid proliferation sometimes admixed with histiocytes (Fig 3). The lymphoid cells were large and immunohistochemically stained by monoclonal antibodies (MoAbs) anti-CD10 and anti-BCL2. C-Myc was also positive, whereas the neoplastic cells were CD3-negative and CD79A-negative. Antiactin MoAbs highlighted the venous vascular wall infiltrated by tumor cells. The findings were consistent with a high-grade, diffuse, large-cell lymphoma of peripheral B lymphocyte origin, primarily arising in the saphenous vein. The postoperative course was uneventful. Polichemotherapy was administered for six cycles (cyclophosphamide, vincristine, and prednisolone every 28 days). Follow-up CT after polichemotherapy did not show recurrence or lymph node enlargement. The patient is now alive and free of tumor 10 months after the operation.
DISCUSSION Vergata,”a
From the Department of Surgery, University of Rome “Tor and the Institutes of Pathology and Radiology, Catholic University of Sacred Heart,b Rome, Italy. Competition of interest: nil. Reprint requests: Francesco Rulli, MD, Department of Surgery, University of Rome “Tor Vergata,” c/o Complesso Integrato Columbus, via Moscati 1, 00168 Rome, Italy (e-mail [email protected]). Copyright © 2002 by The Society for Vascular Surgery and The American Association for Vascular Surgery. 0741-5214/2002/$35.00 + 0 24/4/119753 doi:10.1067/mva.2002.119753
168
This is, to our knowledge, the second case of primary malignant lymphoma of a vein. The first one was published in 1998 by Nomori et al,4 who described a case of superior vena cava localization. In any case, malignant tumors arising from venous walls of the lower extremity are uncommon. Histologically they are divided into two groups—hemangioendotheliomas of intermediate malignancy and leiomyosarcomas.5 To these groups we should add primary malignant lym-
JOURNAL OF VASCULAR SURGERY Volume 35, Number 1
Rulli et al
A
C
B
D
169
Fig 1. Primary malignant lymphoma of the saphenous vein. A, The ultrasound scan shows solid, hypoechoic palpable mass with a central hyperechoic area. B, Medial to the mass is a neoplastic tissue with a peculiar cerebroid appearance involving soft tissues. C, Local CT showed dishomogeneous mass (arrow) with peripheral enhancement, without invasion of femoral vessels. D, Color Doppler scan showed a normal flow in the femoral vessels.
phoma, considering the case we observed. Patients with scleroderma have been reported to show an increased incidence of lung, breast, hematopoietic, and lymphoproliferative malignancies6; in most patients, scleroderma occurs first and is followed by development of a lymphoma. Scleroderma developed in the patient with primary malignant lymphoma of the superior vena cava4 41 months after the operation. No scleroderma has yet developed in our patient. As is well known, extranodal non-Hodgkin’s lymphoma usually develops in organs containing recognizable areas of lymphoid tissue such as tonsils, stomach, small bowel, and skin. Some recent studies have pointed to the concept of mucosa-associated lymphoid tissue to explain the occurrence of lymphomas in certain extranodal tis-
sues,7,8 and primary tumors in unusual locations that do not contain lymph nodes or easily apparent lymphoid aggregates, such as the breast, have been reported.9 Regarding the spread modalities of the neoplasms that eventually enter in the differential diagnosis with primary venous lymphoma, in a series of 13 primary venous leiomyosarcomas, metastases developed in five patients.10 In another condition, intravascular lymphomatosis (ILV), metastatic diffusion seems to be more common because most of the reported patients showed widespread disease and involvement of the central nervous system.11 In the case we have described, no lymph node structures involved by the lymphoma were found, either in the inguinal region or in the leg compartments adjacent the saphenous vein, thus confirming that the site of origin is to
JOURNAL OF VASCULAR SURGERY January 2002
170 Rulli et al
A
A
B
B
Fig 2. Primary malignant lymphoma of the saphenous vein. Upper panel, Saphenous vein appears surrounded and infiltrated by a whitish to brownish, neoplastic tissue that extends all along its course. Lower panel, The wall of the vein is infiltrated and replaced by a monomorphous large lymphoid cell proliferation that invades up to the intimal layers. At the top of the field the vascular lumen is seen (hematoxyline-eosine × 250).
be identified in the vessel wall. Our staging preoperative work-up included only a CT scan because the lymphomatous nature of the disease was not suspected before surgery and biopsies were not carried out. One might object that our case could represent a primary soft tissue lymphoma arising in the periadventitial tissues that, for unknown reasons, has invaded the saphenous vein wall and extended all along its course. Even if we cannot rule out this possibility, we believe that if this were indeed true, it would not change the uniqueness of such clinical presentation considering that no primary soft tissue lymphomas with such exceptional features have to date been reported. In fact, primary soft tissue lymphomas, even if rare, can occur in the soft tissues of the extremity, but as a mass without the localization and spread observed in our case.12 In any
Fig 3. Primary malignant lymphoma of the saphenous vein. Upper panel, Low-power view of the lymphoid infiltrate (arrows) at a different level along the course of the saphenous vein shows a mainly periadvential location in close connection with the venous muscular wall (hematoxyline-eosine × 100). Lower panel, High-power view of the lymphoma shows a uniform proliferation of large cells with prominent nuclei and nucleoli consistent with the diagnosis of high-grade large cell lymphoma (Giemsa stain × 400).
JOURNAL OF VASCULAR SURGERY Volume 35, Number 1
event, antiactin MoAbs highlighted the venous vascular wall infiltrated by tumor cells, thus confirming the lymphomatous localization within the saphenous vein. In such a rare case, surgical treatment in terms of extent of excision and tumor-free margins should include wide local resection of the mass. In summary, we can say that the treatment of the presented case did not differ from that of other anatomical-site primary lymphoma. In fact, this kind of management, together with multidrug chemotherapy, is the recommended treatment.12 Gallium-67 imaging has been advocated to define residual disease and predict outcome,13 but we did not perform it because this diagnostic tool is not routinely used at our institution. It is important to remark that 10% elevation in the serum lactate-dehydrogenase, age >60 years, and bulky disease are independent prognostic factors for overall survival in patients treated for aggressive lymphoma.14 In general, the most important clinical differential diagnosis should then be made with primary venous leiomyosarcoma, a rare but lethal disease that can arise in a large vein, including the great saphenous vein,6 and that is present as a tumor mass. In these cases, surgical treatment should include wide local excision with free margins and eventually postoperative adjuvant therapy. Because of the possibility of invasion of adjacent organs, surgery may be technically challenging and may be responsible for perioperative morbidity and mortality.6 In conclusion, it seems important to remark that primary lymphoma of a large vein is a pathologic condition involving the layers of the wall and, eventually, the periadventitial tissues and must not be confused with ILV, a rare malignancy characterized by neoplastic proliferation of lymphoid cells within the lumens of arteries, small veins, and capillaries.15 Although ILV should be suspected in adult patients with unclear meningoencephalitic syndrome, confusional state, dementia, or other unexplained neurologic conditions with signs of a systemic disease,16 vein lymphoma, based on the two cases in the world literature (including our case), is to be considered in the case of a soft tissue mass localized within the wall and periadventitial tissues of a major venous vessel.
Rulli et al
171
REFERENCES 1. Zaharia L, Gell PS. Primary cardiac lymphoma. Am J Clin Oncol 1991;14:142-5. 2. Roller MB, Manoharan A, Lvoff R. Primary cardiac lymphoma. Acta Haematol 1991;85:47-8. 3. Costantino A, West TE, Gupta M, Loghmanee F. Primary cardiac lymphoma in a patient with acquired immune deficiency sindrome. Cancer 1987;60:2801-5. 4. Nomori H, Nara S, Morinaga S, Soejema K. Primary malignant lymphoma of superior vena cava. Ann Thorac Surg 1998;66:1423-4. 5. Reix T, Sevestre H, Sevestri-Pietri MA, Szychta P, Pietri J. Primary malignant tumors of the venous system in the lower extremities. Ann Vasc surg 1998;12:589-96. 6. Hall SW, Gillespie JJ, Tencznski TF. Generalized lipodystrophy, scleroderma, and Hodgkin’s disease. Arch Intern Med 1978;138:1303-4. 7. Ferguson DJ. Intraepithelial lymphocytes and macrophages in the normal breast. Virchows Arch A Pathol Anat Histopathol 1985;407:369-78. 8. Isaacson PG, Spencer J. Malignant lymphoma of mucosa associated lymphoid tissue. Histopathology 1987;11:445-62. 9. Sokolov T, Shimonov M, Blickstein D, Nobel M, Antebi E. Primary lymphoma of the breast: unusual presentation of breast cancer. Eur J Surg 2000;166:390-3. 10. Dzsinch C, Gloviczki P, van Herden JA, Nagorney DM, Pairolero PC, Johnson CM, et al. Primary venous leiomyosarcoma: a rare but lethal disease. J Vasc Surg 1992;15:595-603. 11. Bogomolski-Yahalom V, Lossos IS, Okun E, Sherman Y, Lossos A, Polliak A. Intravascular lymphomatosis—an indolent or aggressive entity? Leukemia Lymphoma 1998;29:585-93. 12. Travis WD, Banks FM, Reiman HM. Primary extranodal soft tissue lymphoma. Am J Surg Pathol 1987;11:359-66. 13. Kaplan WD, Jochelson MS, Herman TS, Nadler LM, Stomper PC, Takvorian T, et al. Gallium-67 imaging: a predictor of residual tumor viability and outcome in patients with diffuse large-cell lymphoma. J Clin Oncol 1990;8:1966-70. 14. Wilder RB, Rodriguez MA, Ha CS, Pro B, Hess MA, Cabanillas F, et al. Bulky disease is an adverse prognostic factor in patients treated with chemotherapy comprised of cyclophosphamide doxorubicin, vincristine, and prednisone with or without radiotherapy for aggressive lymphoma. Cancer 2001;91:2440-6. 15. Pfelger L, Tappeiner J. Zur kenntnis der systemisierten endotheliomatose der cutanen blutgefasse [Germany]. Hautarzt 1959;10: 359-63. 16. Baumann TP, Hurwitz N, Karamitopolou-Diamantis E, Probst A, Herrmann R, Steck AJ. Diagnosis and treatment of intravascular lymphomatosis. Arch Neurol 2000;57:374-7. Submitted May 24, 2001; accepted Aug 14, 2001.