S p e c i a l A r t i c l e s • C l i n i c a l Pe r s p e c t i ve Chauhan et al. Lymphoma Presenting With Tumor Thrombus
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Special Articles Clinical Perspective
Tumor Thrombus as a Rare Presentation of Lymphoma: A Case Series of 14 Patients Anil Chauhan1 Naveen Garg2 Christine O. Menias 3 Catherine E. Devine 2 Priya R. Bhosale2 Aparna Balachandran2
OBJECTIVE. We present a case series of 14 patients with lymphoma presenting with tumor thrombus to highlight this rare but important manifestation of lymphoma. CONCLUSION. The dominant mass leading to tumor thrombus formation was nodal disease in nine patients and extranodal disease in five patients. Lymphoma should be considered in the differential diagnosis in the setting of tumor thrombus with solid organ involvement when there are other imaging features suggestive of lymphoma.
Chauhan A, Garg N, Menias CO, Devine CE, Bhosale PR, Balachandran A
umor thrombus has been described as being associated with many solid organ malignancies, including hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), adrenal cortical carcinoma, a testicular carcinoma, and neuroendocrine tumors [1]. In many of these malignancies, such as HCCs and RCCs, the presence of tumor thrombus alters the treatment plan for the patient [2, 3]. Lymphoma typically manifests with lymphadenopathy (above or below the diaphragm) with or without solid organ involvement. On imaging, investigators have reported that the lymphomatous mass tends to respect anatomic landmarks such as the vascular structures around them. For example, a lymphomatous mass classically engulfs blood vessels and may narrow them without directly invading them [4]. Although lymphoma is a risk factor for venous thrombosis, lymphoma is more often a risk factor for bland thrombus [5]. Tumor thrombus formation has been reported in the literature as an extremely rare presentation in patients with lymphoma [1, 5–9]. Recognizing this association is especially important in patients with extranodal solid organ lymphoma who present with tumor thrombus. Tumor thrombus in these patients can be misdiagnosed as a nonlymphomatous primary tumor, and this misdiagnosis can lead to inappropriate treatment. To our knowledge, there are eight case reports (nine cases) of tumor thrombus described as a secondary finding from lymphoma that include imaging correlation of the lymphoma and tumor thrombus in the pub-
Keywords: CT, lymphoma, MRI, PET/CT, solid organ, tumor thrombus DOI:10.2214/AJR.14.12782 Received March 3, 2014; accepted after revision August 25, 2014. 1
Department of Radiology, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. Address correspondence to A. Chauhan ([email protected]).
2 Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX. 3
Department of Radiology, Mayo Clinic, Scottsdale, AZ.
WEB This is a web exclusive article. AJR 2015; 204:W398–W404 0361–803X/15/2044–W398 © American Roentgen Ray Society
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lished report [1, 5–11]. We present a case series of 14 patients with a known diagnosis of lymphoma who presented with tumor thrombus as a secondary finding on CT, MRI, PET/CT, or a combination of these modalities from both nodal and extranodal disease to highlight this rare but important manifestation of lymphoma on imaging. Materials and Methods Patient Population This study was approved by the institutional review board, and a waiver of consent was obtained for this retrospective study. A search of the department’s electronic database of the reports in the radiology information system was performed for records dated from January 1, 2000 to January 1, 2013. The reports of CT, MRI, and PET/ CT studies were searched. The keywords used for the search were the following: “tumor thrombus” and “lymphoma,” “lymphoproliferative disorder,” or “lymphomatous.” The search yielded a total of 16 patients with imaging reports that mentioned a confirmed or suspected tumor thrombus. The clinical history and imaging findings of these 16 patients were evaluated by two boardcertified fellowship-trained radiologists; each observer had more than 10 years of experience in oncologic imaging at the time of the study. Two of the 16 patients were excluded after application of our criteria for the diagnosis of tumor thrombus, which we discuss later, because they were thought to have bland thrombus; thus, a total of 14 patients were included in this study. The two cases initially questioned as tumor thrombus in reporting were excluded because they were thought to be cases of bland thrombus. One
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Lymphoma Presenting With Tumor Thrombus case was thought to be bland thrombus because of the presence of mass effect without tumor extending near the left gonadal vein. The other case was thought to be bland thrombus because of the separation of the vein from the primary nodal disease.
Imaging At the time of the diagnosis of tumor thrombus, 10 of 14 patients had undergone both contrast-enhanced CT (CECT) and unenhanced PET/CT, one patient had undergone both contrast-enhanced MRI and PET/CT, and three patients had undergone only CECT.
Pathology The two observers reviewed the pathologic diagnosis listed in the medical records of all patients.
Diagnosis of Tumor Thrombus Tumor thrombus was diagnosed if at least one of the following criteria was present: thrombus was seen as a direct extension of the surrounding mass; enhancement of the thrombus in the vessel was similar to the enhancement of the primary disease and the thrombus was in close contiguity to the primary disease; or the thrombus showed FDG avidity similar to that of the primary nodal or extranodal disease in the vicinity and expansion of the involved vessel was noted.
Results A total of 14 patients (five males and nine females) constituted the study population. The patients ranged in age from 17 to 77 years (mean age, 55.1 years.) The demographic characteristics, relevant clinical information, and imaging features are provided in Table 1. All patients met two criteria (seven patients) or three criteria (seven patients) for the diagnosis of tumor thrombus. The most common subtype of lymphoma associated with the tumor thrombus was diffuse large B-cell lymphoma (DLBCL; five patients), followed by follicular lymphoma (FL; three patients), combination of FL and DLBCL (two patients), Hodgkin disease (two patients), mycosis fungoides (T-cell lymphoma; one patient), and HIV-associated plasmacytic lymphoma (one patient). Based on these results and consistent with the 2008 World Health Organization (WHO) classification [12], the most common lymphomas associated with tumor thrombus are the lymphomas associated with a mature Bcell origin (DLBCL, FL, mixed FL and DLBCL, and plasmacytic lymphoma; 11 patients), followed by lymphomas associated with Hodgkin disease (two patients) and lymphoma with a mature T-cell origin (one patient).
Tumor thrombus was present on the initial staging examinations in 10 of the 14 patients. In the remaining four patients, the tumor thrombus was present on follow-up (restaging) examinations. The first of the four patients had episodes of gastrointestinal bleeding and was off therapy when the follow-up examinations showed progression with evidence of tumor thrombus. The second patient was in the ICU and was off therapy when the follow-up examinations showed progression with evidence of tumor thrombus. The third patient was considered to be in remission when a follow-up examination showed disease with evidence of tumor thrombus. The fourth patient was receiving treatment when a follow-up examination showed evidence of tumor thrombus. The dominant mass leading to tumor thrombus formation was nodal disease in nine of 14 patients and was extranodal disease in the remaining five patients. Of the five patients with extranodal disease, three patients had the mass centered within the liver, and two patients had the mass centered within the kidney. Patients with venous tumor thrombus involving the jugular veins, inferior vena cava (IVC), or iliac veins did not present with
TABLE 1: Demographic, Clinical, and Imaging Characteristics of the Patients With Lymphoma Presenting as Tumor Thrombus Patient No.
Age (y)
Sex
Indication for Imaging
Diagnosis
Imaging Modalities
Nodal or Extranodal Mass With Tumor Thrombus
Vessels Involved
1
17
F
Staging
Hodgkin disease
CECT, PET/CT
Nodal
Right IJV
2
77
F
Staging
DLBCL
CECT, PET/CT
Nodal
Right IJV
3
61
F
Staging
DLBCL
CECT, PET/CT
Nodal
Right superior pulmonary vein, left atrium
4
48
M
Staging
DLBCL
CECT, PET/CT
Extranodal (liver)
Left PV, right PV, main PV
5
73
F
Staging
DLBCL
CECT, PET/CT
Extranodal (liver)
Left PV, main PV
6
40
M
Staging
Mycosis fungoides (T-cell lymphoma)
CECT, PET/CT
Extranodal (liver)
IVC
7
72
M
Staging
FL and DLBCL
Contrast-enhanced MRI, PET/CT
Extranodal (kidney)
Left renal vein
8
29
M
Staging
Plasmacytic lymphoma
CECT, PET/CT
Extranodal (kidney)
Right renal vein, IVC
9
75
F
Restaging
10
64
F
Staging
11
43
F
Restaging
FL FL and DLBCL Hodgkin diseasea
CECT
Nodal
Splenic vein, main PV
CECT, PET/CT
Nodal
Main PV, superior mesenteric vein, splenic vein
CECT
Nodal
IVC
12
68
F
Staging
DLBCL
CECT, PET/CT
Nodal
IVC
13
48
F
Restaging
FL
CECT, PET/CT
Nodal
Left common iliac vein
14
57
M
Restaging
FL
CECT
Nodal
Right external iliac vein, right common iliac vein
Note—CECT = contrast-enhanced CT, IJV = internal jugular vein, DLBCL = diffuse large B-cell lymphoma, PV = portal vein, IVC = inferior vena cava, FL = follicular lymphoma. aNodular sclerosing.
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Chauhan et al. extremity edema or congestion. In these patients, the diagnosis of tumor thrombus was made using only imaging findings. The IVC and main portal vein were the most commonly involved veins in our study group; each involved in four of the 14 patients (Table 1). Imaging Characteristics of Lymphomatous Tumor Thrombus Head and neck—Two patients (patients 1 and 2 in Table 1) had tumor thrombus from lymphomatous nodal masses into the internal jugular vein (Fig. 1). Chest—Patient 3 presented with a large mediastinal mass and had a tumor thrombus invading the right superior pulmonary vein and left atrium (Fig. 2). Abdomen: extranodal mass—Five patients (patients 4–8) had tumor thrombus arising from lymphomatous involvement of extranodal solid organs. Patients 4 and 5 had a dominant hepatic mass with tumor thrombus extending into the portal venous system (Figs. 3 and 4). Patient 6 had a dominant mass in the liver with tumor thrombus extending into the IVC. Patients 7 and 8 had dominant renal masses (left kidney in patient 7 and right kidney in patient 8). Patient 7 had direct extension of the tumor into left renal vein, which was best seen on MRI (Fig. 5), without extension into the IVC. Patient 8 had direct extension of tumor into the IVC at the level of upper pole of right kidney through right inferior renal vein (Fig. 6). Abdomen: nodal mass—Four patients (patients 9–12) presented with tumor thrombus in the abdomen secondary to a dominant nod-
al mass. In patient 9, the tumor directly invaded the splenic vein and then extended into the portal-splenic venous confluence (Fig. 7). In patient 10, direct tumor extension into the portal-splenic venous confluence and extensive spread throughout the mesenteric venous system were noted (Fig. 8). Patients 11 and 12 had dominant nodal masses in the abdomen with direct extension into the IVC (Fig. 9). Pelvis—Patients 13 and 14 presented with dominant pelvic nodal masses with direct extensions into the iliac venous system: the left common iliac vein in patient 13 and the right common and right external iliac veins in patient 14. Discussion Tumor thrombus—either from a primary nodal mass [1, 5, 6] or from a primary extranodal mass [7–11]—is an unusual but important manifestation of lymphoma and has been reported only in isolated case reports in the imaging literature (Table 2). Raising awareness of this entity in the radiology and surgical communities is important. An awareness of this manifestation of lymphoma is also important when evaluating patients with suspected RCC because treatment is often nephrectomy without obtaining a biopsy of the solid renal mass. In this series of 14 patients, tumor thrombus related to lymphoma was found in different locations in the body. In all of our patients, the tumor thrombus was seen as a direct extension from a dominant nodal or extranodal mass in the vicinity. The mechanism of the tumor thrombus formation in lymphoma is unclear because this entity is rare. The previous case reports regarding lymphoma presenting with tu-
mor thrombus have not suggested a potential mechanism for the development of tumor thrombus in these patients [1, 5–11]. Eight of the nine previous cases [1, 5–11] have shown DLBCL (i.e., originating from mature B-cell lymphoma) as the subtype of lymphoma presenting as tumor thrombus (Table 2). Wagner et al. [7] classified the renal lymphoma in their case report on the basis of its histiocytic features as of B-cell subtype. In our study, the majority of tumors associated with tumor thrombus (79%) were related to those with a mature B-cell origin (WHO classification). An analysis of the subtypes of lymphoma and their associations with venous tumor thrombus and prognosis could be an area of future prospective research. Tumor thrombus in the presence of extranodal disease involving a solid organ presents a diagnostic dilemma. Diagnoses such as HCC or RCC are favored in patients with primary hepatic or renal masses associated with tumor thrombus. In the case reported by Wagner et al. [7], the diagnosis of RCC was made on the basis of radiologic findings and the patient underwent nephrectomy; however, the postoperative pathologic findings revealed diffuse histiocytic B-cell lymphoma, which would have been treated with chemotherapy rather than nephrectomy [7]. The significant treatment differences between RCC and renal lymphoma underscore the importance of keeping lymphoma in the differential diagnosis of a renal mass [10, 11, 13, 14] and of recognizing that venous tumor thrombus can occur in the setting of lymphoma [7, 10, 11]. Nonlymphomatous causes were considered as the primary diagnosis in all five of our patients with extra-
TABLE 2: Descriptive Findings of Previously Reported Cases of Lymphoma Presenting as Tumor Thrombus Reference
Patient
Nodal or Extranodal Disease
First Author
Age (y)
Sex
Pathology
1993
Wagner
44
M
B-cell lymphoma
Extranodal (kidney)
Renal vein, IVC
1998
Yoneyama
55
F
DLBCL
Extranodal (liver)
Main PV, right PV, left PV
[5]
2004
Matsumoto
62
F
DLBCL
Nodal (mesentery)
Main PV, superior mesenteric vein
[6]
2006
Kanemura
55
M
DLBCL
Nodal (porta hepatis)
Main PV
[1]
2007
Lai
26
F
DLBCL and Hodgkin disease
Nodal (mediastinum)
Superior vena cava, right atrium
[9]
2009
Natsuizaka
78
M
DLBCL
Extranodal (liver or spermatic cord)
Main PV, right PV, left PV
No.
Year Reported
[7] [8]
Vessels Involved
[11]
2011
Samlowski
62
F
DLBCL
Extranodal (kidney)
Renal vein, IVC
[10]
2013
Chen
69
F
DLBCL
Extranodal (kidney)
Renal vein, IVC
[10]
2013
Chen
70
F
DLBCL
Extranodal (kidney)
Renal vein, IVC
Note—IVC = inferior vena cava, DLBCL = diffuse large B-cell lymphoma, PV = portal vein.
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Lymphoma Presenting With Tumor Thrombus nodal disease based on the initial staging examination. However, the biopsy results raised the possibility of the diagnosis of lymphoma, which was confirmed. The presence of nodal disease elsewhere on imaging may also lead to the suspicion of lymphoma in these patients. Additional clinical history and laboratory results in patients at risk of malignancy, such as patients with a history of cirrhosis or a high α-fetoprotein level, would favor HCC over lymphoma. In patients with renal masses, there is currently no laboratory test available to lead to the correct diagnosis. In these patients, adenopathy elsewhere should raise the possibility of lymphoma, and tissue sampling should be considered before determining treatment. The limitations of our study include the small sample size and the retrospective nature of the study. However, the intent of our study was to present an imaging spectrum to make radiologists aware of the association of tumor thrombus in patients with lymphoma. A future direction would be performing a prospective study with immunohistochemical and pathologic analyses of the lymphoma to assess for mechanisms of tumor thrombus and to evaluate prognosis in the presence of tumor thrombus. Conclusion Lymphoma can rarely present with tumor thrombus. This diagnosis should be consid-
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ered in the differential diagnosis of solid organ involvement with tumor thrombus, particularly in the presence of other imaging features suggestive of lymphoma. References 1. Lai P, Bomanji JB, Mahmood S, et al. Detection of tumour thrombus by 18F-FDG-PET/CT imaging. Eur J Cancer Prev 2007; 16:90–94 2. Minagawa M, Makuuchi M. Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. World J Gastroenterol 2006; 12:7561–7567 3. Heidenreich A, Ravery V; European Society of Oncological Urology. Preoperative imaging in renal cell cancer. World J Urol 2004; 22:307–315 4. Sheth S, Horton KM, Garland MR, Fishman EK. Mesenteric neoplasms: CT appearances of primary and secondary tumors and differential diagnosis. RadioGraphics 2003; 23:457–473 5. Matsumoto S, Mori H, Takaki H, Ishitobi F, Shuto R, Yokoyama S. Malignant lymphoma with tumor thrombus in the portal venous system. Abdom Imaging 2004; 29:460–462 6. Kanemura N, Tsurumi H, Yamada T, Kojima Y, Kasahara S, Moriwaki H. Diffuse large B-cell lymphoma with tumor thrombosis in the portal vein. Int J Hematol 2006; 84:282–283 7. Wagner JR, Honig SC, Siroky MB. Non-Hodgkin’s lymphoma can mimic renal adenocarcinoma with inferior vena caval involvement. Urology 1993; 42:720–723; discussion, 723–724
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8. Yoneyama F, Nimura Y, Kamiya J, et al. Primary lymphoma of the liver with bile duct invasion and tumoral occlusion of the portal vein: report of a case. J Hepatol 1998; 29:485–488 9. Natsuizaka M, Kudo M, Suzuki M, et al. Diffuse large B-cell lymphoma with massive portal vein tumor thrombosis in a patient with alcoholic cirrhosis: a case report and literature review. Intern Med 2009; 48:805–808 10. Chen L, Richendollar B, Bunting S, Campbell S, Zhou M. Lymphomas and lymphoproliferative disorders clinically presenting as renal carcinoma: a clinicopathological study of 14 cases. Pathology 2013; 45:657–663 11. Samlowski EE, Dechet C, Weissman A, Samlowski WE. Large cell non-Hodgkin’s lymphoma masquerading as renal carcinoma with inferior vena cava thrombosis: a case report. J Med Case Rep 2011; 5:245 12. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 2011; 117:5019–5032 13. Hayakawa A, Shimotake N, Kubokawa I, et al. Primary pediatric stage III renal diffuse large B-cell lymphoma. Am J Case Rep 2013; 14:34–37 14. Kato Y, Hasegawa M, Numasato S, Monma N, Fujioka T. Primary mucosa-associated lymphoid tissue-type lymphoma arising in the kidney. Int J Urol 2008; 15:90–92
Fig. 1—77-year-old woman with diffuse large B-cell lymphoma (patient 2 in Table 1). A, Axial contrast-enhanced CT image obtained for initial staging shows enhancing mass in right neck engulfing right external and internal carotid arteries (arrow). Posteriorly, mass invades right internal jugular vein (arrowhead) and presents as large tumor thrombus. B, Fused axial PET/CT image shows intense FDG avidity of neck mass.
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Chauhan et al.
A
B
Fig. 2—61-year-old woman with history of diffuse large B-cell lymphoma (patient 3 in Table 1). A, Axial contrast-enhanced CT image obtained for initial staging shows large infiltrative mass centered in right hilum and invading right superior pulmonary vein and left atrium (arrow) as tumor thrombus. B, Fused axial PET/CT image shows intense FDG avidity of mass.
A
B
Fig. 3—48-year-old man with history of diffuse large B-cell lymphoma (patient 4 in Table 1). A, Axial contrast-enhanced CT image obtained for initial staging shows mass involves liver along gallbladder fossa. Image also shows another similarly enhancing mass (arrow) in main portal vein bifurcation that extends into right portal vein as tumor thrombus. B, Fused axial PET/CT image shows intense FDG avidity of mass and of tumor thrombus.
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Lymphoma Presenting With Tumor Thrombus
A
B
Fig. 4—73-year-old woman with history of diffuse large B-cell lymphoma (patient 5 in Table 1). A, Axial contrast-enhanced CT image obtained for initial staging shows large infiltrative mass involving left hepatic lobe and secondarily invading left portal vein up to main portal vein (arrow) as tumor thrombus. B, Fused axial PET/CT image shows intense FDG avidity of mass and of tumor thrombus.
A
B
C
Fig. 5—72-year-old man with history of mixed diffuse large B-cell lymphoma and follicular lymphoma (patient 7 in Table 1). A, Coronal unenhanced CT image obtained for initial staging shows infiltrative mass involving left kidney. B, Coronal contrast-enhanced MR image confirms CT finding (A) and also shows mass extending into left renal vein (arrow) as tumor thrombus. C, Fused axial PET/CT image shows intense FDG avidity of mass.
A
B
C
Fig. 6—29-year-old man with history of plasmacytic lymphoma (patient 8 in Table 1). A and B, Axial (A) and coronal (B) contrast-enhanced CT images obtained for initial staging show large right renal mass. Coronal image also shows that mass extends into inferior renal vein and inferior vena cava (arrow, B) as tumor thrombus. C, Fused axial PET/CT image shows intense FDG avidity of mass.
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Chauhan et al. Fig. 7—75-year-old woman with history of follicular lymphoma (patient 9 in Table 1). Restaging axial contrast-enhanced CT image shows complex mass centered at gastrosplenic ligament and infiltrating into spleen laterally. Medially, mass is seen as invading splenic vein up to portal venous confluence (arrow) as tumor thrombus.
Fig. 8—64-year-old woman with history of mixed diffuse large B-cell lymphoma and follicular lymphoma (patient 10 in Table 1). A, Coronal contrast-enhanced CT image obtained for initial staging shows infiltrative mesenteric mass invading superior mesenteric vein through its tributaries (arrow) as tumor thrombus. B, Fused coronal PET/CT image shows intense FDG avidity of mass including intense FDG avidity of tumor thrombus.
Fig. 9—68-year-old woman with history of diffuse large B-cell lymphoma (patient 12 in Table 1). A and B, Axial (A) and coronal (B) contrastenhanced CT images obtained for initial staging show retroperitoneal lymphadenopathy invading into inferior vena cava (arrows) as tumor thrombus.
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Special Articles Clinical Perspective
Tumor Thrombus as a Rare Presentation of Lymphoma: A Case Series of 14 Patients Anil Chauhan1 Naveen Garg2 Christine O. Menias 3 Catherine E. Devine 2 Priya R. Bhosale2 Aparna Balachandran2
OBJECTIVE. We present a case series of 14 patients with lymphoma presenting with tumor thrombus to highlight this rare but important manifestation of lymphoma. CONCLUSION. The dominant mass leading to tumor thrombus formation was nodal disease in nine patients and extranodal disease in five patients. Lymphoma should be considered in the differential diagnosis in the setting of tumor thrombus with solid organ involvement when there are other imaging features suggestive of lymphoma.
Chauhan A, Garg N, Menias CO, Devine CE, Bhosale PR, Balachandran A
umor thrombus has been described as being associated with many solid organ malignancies, including hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), adrenal cortical carcinoma, a testicular carcinoma, and neuroendocrine tumors [1]. In many of these malignancies, such as HCCs and RCCs, the presence of tumor thrombus alters the treatment plan for the patient [2, 3]. Lymphoma typically manifests with lymphadenopathy (above or below the diaphragm) with or without solid organ involvement. On imaging, investigators have reported that the lymphomatous mass tends to respect anatomic landmarks such as the vascular structures around them. For example, a lymphomatous mass classically engulfs blood vessels and may narrow them without directly invading them [4]. Although lymphoma is a risk factor for venous thrombosis, lymphoma is more often a risk factor for bland thrombus [5]. Tumor thrombus formation has been reported in the literature as an extremely rare presentation in patients with lymphoma [1, 5–9]. Recognizing this association is especially important in patients with extranodal solid organ lymphoma who present with tumor thrombus. Tumor thrombus in these patients can be misdiagnosed as a nonlymphomatous primary tumor, and this misdiagnosis can lead to inappropriate treatment. To our knowledge, there are eight case reports (nine cases) of tumor thrombus described as a secondary finding from lymphoma that include imaging correlation of the lymphoma and tumor thrombus in the pub-
Keywords: CT, lymphoma, MRI, PET/CT, solid organ, tumor thrombus DOI:10.2214/AJR.14.12782 Received March 3, 2014; accepted after revision August 25, 2014. 1
Department of Radiology, University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. Address correspondence to A. Chauhan ([email protected]).
2 Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, TX. 3
Department of Radiology, Mayo Clinic, Scottsdale, AZ.
WEB This is a web exclusive article. AJR 2015; 204:W398–W404 0361–803X/15/2044–W398 © American Roentgen Ray Society
W398
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lished report [1, 5–11]. We present a case series of 14 patients with a known diagnosis of lymphoma who presented with tumor thrombus as a secondary finding on CT, MRI, PET/CT, or a combination of these modalities from both nodal and extranodal disease to highlight this rare but important manifestation of lymphoma on imaging. Materials and Methods Patient Population This study was approved by the institutional review board, and a waiver of consent was obtained for this retrospective study. A search of the department’s electronic database of the reports in the radiology information system was performed for records dated from January 1, 2000 to January 1, 2013. The reports of CT, MRI, and PET/ CT studies were searched. The keywords used for the search were the following: “tumor thrombus” and “lymphoma,” “lymphoproliferative disorder,” or “lymphomatous.” The search yielded a total of 16 patients with imaging reports that mentioned a confirmed or suspected tumor thrombus. The clinical history and imaging findings of these 16 patients were evaluated by two boardcertified fellowship-trained radiologists; each observer had more than 10 years of experience in oncologic imaging at the time of the study. Two of the 16 patients were excluded after application of our criteria for the diagnosis of tumor thrombus, which we discuss later, because they were thought to have bland thrombus; thus, a total of 14 patients were included in this study. The two cases initially questioned as tumor thrombus in reporting were excluded because they were thought to be cases of bland thrombus. One
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Lymphoma Presenting With Tumor Thrombus case was thought to be bland thrombus because of the presence of mass effect without tumor extending near the left gonadal vein. The other case was thought to be bland thrombus because of the separation of the vein from the primary nodal disease.
Imaging At the time of the diagnosis of tumor thrombus, 10 of 14 patients had undergone both contrast-enhanced CT (CECT) and unenhanced PET/CT, one patient had undergone both contrast-enhanced MRI and PET/CT, and three patients had undergone only CECT.
Pathology The two observers reviewed the pathologic diagnosis listed in the medical records of all patients.
Diagnosis of Tumor Thrombus Tumor thrombus was diagnosed if at least one of the following criteria was present: thrombus was seen as a direct extension of the surrounding mass; enhancement of the thrombus in the vessel was similar to the enhancement of the primary disease and the thrombus was in close contiguity to the primary disease; or the thrombus showed FDG avidity similar to that of the primary nodal or extranodal disease in the vicinity and expansion of the involved vessel was noted.
Results A total of 14 patients (five males and nine females) constituted the study population. The patients ranged in age from 17 to 77 years (mean age, 55.1 years.) The demographic characteristics, relevant clinical information, and imaging features are provided in Table 1. All patients met two criteria (seven patients) or three criteria (seven patients) for the diagnosis of tumor thrombus. The most common subtype of lymphoma associated with the tumor thrombus was diffuse large B-cell lymphoma (DLBCL; five patients), followed by follicular lymphoma (FL; three patients), combination of FL and DLBCL (two patients), Hodgkin disease (two patients), mycosis fungoides (T-cell lymphoma; one patient), and HIV-associated plasmacytic lymphoma (one patient). Based on these results and consistent with the 2008 World Health Organization (WHO) classification [12], the most common lymphomas associated with tumor thrombus are the lymphomas associated with a mature Bcell origin (DLBCL, FL, mixed FL and DLBCL, and plasmacytic lymphoma; 11 patients), followed by lymphomas associated with Hodgkin disease (two patients) and lymphoma with a mature T-cell origin (one patient).
Tumor thrombus was present on the initial staging examinations in 10 of the 14 patients. In the remaining four patients, the tumor thrombus was present on follow-up (restaging) examinations. The first of the four patients had episodes of gastrointestinal bleeding and was off therapy when the follow-up examinations showed progression with evidence of tumor thrombus. The second patient was in the ICU and was off therapy when the follow-up examinations showed progression with evidence of tumor thrombus. The third patient was considered to be in remission when a follow-up examination showed disease with evidence of tumor thrombus. The fourth patient was receiving treatment when a follow-up examination showed evidence of tumor thrombus. The dominant mass leading to tumor thrombus formation was nodal disease in nine of 14 patients and was extranodal disease in the remaining five patients. Of the five patients with extranodal disease, three patients had the mass centered within the liver, and two patients had the mass centered within the kidney. Patients with venous tumor thrombus involving the jugular veins, inferior vena cava (IVC), or iliac veins did not present with
TABLE 1: Demographic, Clinical, and Imaging Characteristics of the Patients With Lymphoma Presenting as Tumor Thrombus Patient No.
Age (y)
Sex
Indication for Imaging
Diagnosis
Imaging Modalities
Nodal or Extranodal Mass With Tumor Thrombus
Vessels Involved
1
17
F
Staging
Hodgkin disease
CECT, PET/CT
Nodal
Right IJV
2
77
F
Staging
DLBCL
CECT, PET/CT
Nodal
Right IJV
3
61
F
Staging
DLBCL
CECT, PET/CT
Nodal
Right superior pulmonary vein, left atrium
4
48
M
Staging
DLBCL
CECT, PET/CT
Extranodal (liver)
Left PV, right PV, main PV
5
73
F
Staging
DLBCL
CECT, PET/CT
Extranodal (liver)
Left PV, main PV
6
40
M
Staging
Mycosis fungoides (T-cell lymphoma)
CECT, PET/CT
Extranodal (liver)
IVC
7
72
M
Staging
FL and DLBCL
Contrast-enhanced MRI, PET/CT
Extranodal (kidney)
Left renal vein
8
29
M
Staging
Plasmacytic lymphoma
CECT, PET/CT
Extranodal (kidney)
Right renal vein, IVC
9
75
F
Restaging
10
64
F
Staging
11
43
F
Restaging
FL FL and DLBCL Hodgkin diseasea
CECT
Nodal
Splenic vein, main PV
CECT, PET/CT
Nodal
Main PV, superior mesenteric vein, splenic vein
CECT
Nodal
IVC
12
68
F
Staging
DLBCL
CECT, PET/CT
Nodal
IVC
13
48
F
Restaging
FL
CECT, PET/CT
Nodal
Left common iliac vein
14
57
M
Restaging
FL
CECT
Nodal
Right external iliac vein, right common iliac vein
Note—CECT = contrast-enhanced CT, IJV = internal jugular vein, DLBCL = diffuse large B-cell lymphoma, PV = portal vein, IVC = inferior vena cava, FL = follicular lymphoma. aNodular sclerosing.
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Chauhan et al. extremity edema or congestion. In these patients, the diagnosis of tumor thrombus was made using only imaging findings. The IVC and main portal vein were the most commonly involved veins in our study group; each involved in four of the 14 patients (Table 1). Imaging Characteristics of Lymphomatous Tumor Thrombus Head and neck—Two patients (patients 1 and 2 in Table 1) had tumor thrombus from lymphomatous nodal masses into the internal jugular vein (Fig. 1). Chest—Patient 3 presented with a large mediastinal mass and had a tumor thrombus invading the right superior pulmonary vein and left atrium (Fig. 2). Abdomen: extranodal mass—Five patients (patients 4–8) had tumor thrombus arising from lymphomatous involvement of extranodal solid organs. Patients 4 and 5 had a dominant hepatic mass with tumor thrombus extending into the portal venous system (Figs. 3 and 4). Patient 6 had a dominant mass in the liver with tumor thrombus extending into the IVC. Patients 7 and 8 had dominant renal masses (left kidney in patient 7 and right kidney in patient 8). Patient 7 had direct extension of the tumor into left renal vein, which was best seen on MRI (Fig. 5), without extension into the IVC. Patient 8 had direct extension of tumor into the IVC at the level of upper pole of right kidney through right inferior renal vein (Fig. 6). Abdomen: nodal mass—Four patients (patients 9–12) presented with tumor thrombus in the abdomen secondary to a dominant nod-
al mass. In patient 9, the tumor directly invaded the splenic vein and then extended into the portal-splenic venous confluence (Fig. 7). In patient 10, direct tumor extension into the portal-splenic venous confluence and extensive spread throughout the mesenteric venous system were noted (Fig. 8). Patients 11 and 12 had dominant nodal masses in the abdomen with direct extension into the IVC (Fig. 9). Pelvis—Patients 13 and 14 presented with dominant pelvic nodal masses with direct extensions into the iliac venous system: the left common iliac vein in patient 13 and the right common and right external iliac veins in patient 14. Discussion Tumor thrombus—either from a primary nodal mass [1, 5, 6] or from a primary extranodal mass [7–11]—is an unusual but important manifestation of lymphoma and has been reported only in isolated case reports in the imaging literature (Table 2). Raising awareness of this entity in the radiology and surgical communities is important. An awareness of this manifestation of lymphoma is also important when evaluating patients with suspected RCC because treatment is often nephrectomy without obtaining a biopsy of the solid renal mass. In this series of 14 patients, tumor thrombus related to lymphoma was found in different locations in the body. In all of our patients, the tumor thrombus was seen as a direct extension from a dominant nodal or extranodal mass in the vicinity. The mechanism of the tumor thrombus formation in lymphoma is unclear because this entity is rare. The previous case reports regarding lymphoma presenting with tu-
mor thrombus have not suggested a potential mechanism for the development of tumor thrombus in these patients [1, 5–11]. Eight of the nine previous cases [1, 5–11] have shown DLBCL (i.e., originating from mature B-cell lymphoma) as the subtype of lymphoma presenting as tumor thrombus (Table 2). Wagner et al. [7] classified the renal lymphoma in their case report on the basis of its histiocytic features as of B-cell subtype. In our study, the majority of tumors associated with tumor thrombus (79%) were related to those with a mature B-cell origin (WHO classification). An analysis of the subtypes of lymphoma and their associations with venous tumor thrombus and prognosis could be an area of future prospective research. Tumor thrombus in the presence of extranodal disease involving a solid organ presents a diagnostic dilemma. Diagnoses such as HCC or RCC are favored in patients with primary hepatic or renal masses associated with tumor thrombus. In the case reported by Wagner et al. [7], the diagnosis of RCC was made on the basis of radiologic findings and the patient underwent nephrectomy; however, the postoperative pathologic findings revealed diffuse histiocytic B-cell lymphoma, which would have been treated with chemotherapy rather than nephrectomy [7]. The significant treatment differences between RCC and renal lymphoma underscore the importance of keeping lymphoma in the differential diagnosis of a renal mass [10, 11, 13, 14] and of recognizing that venous tumor thrombus can occur in the setting of lymphoma [7, 10, 11]. Nonlymphomatous causes were considered as the primary diagnosis in all five of our patients with extra-
TABLE 2: Descriptive Findings of Previously Reported Cases of Lymphoma Presenting as Tumor Thrombus Reference
Patient
Nodal or Extranodal Disease
First Author
Age (y)
Sex
Pathology
1993
Wagner
44
M
B-cell lymphoma
Extranodal (kidney)
Renal vein, IVC
1998
Yoneyama
55
F
DLBCL
Extranodal (liver)
Main PV, right PV, left PV
[5]
2004
Matsumoto
62
F
DLBCL
Nodal (mesentery)
Main PV, superior mesenteric vein
[6]
2006
Kanemura
55
M
DLBCL
Nodal (porta hepatis)
Main PV
[1]
2007
Lai
26
F
DLBCL and Hodgkin disease
Nodal (mediastinum)
Superior vena cava, right atrium
[9]
2009
Natsuizaka
78
M
DLBCL
Extranodal (liver or spermatic cord)
Main PV, right PV, left PV
No.
Year Reported
[7] [8]
Vessels Involved
[11]
2011
Samlowski
62
F
DLBCL
Extranodal (kidney)
Renal vein, IVC
[10]
2013
Chen
69
F
DLBCL
Extranodal (kidney)
Renal vein, IVC
[10]
2013
Chen
70
F
DLBCL
Extranodal (kidney)
Renal vein, IVC
Note—IVC = inferior vena cava, DLBCL = diffuse large B-cell lymphoma, PV = portal vein.
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Lymphoma Presenting With Tumor Thrombus nodal disease based on the initial staging examination. However, the biopsy results raised the possibility of the diagnosis of lymphoma, which was confirmed. The presence of nodal disease elsewhere on imaging may also lead to the suspicion of lymphoma in these patients. Additional clinical history and laboratory results in patients at risk of malignancy, such as patients with a history of cirrhosis or a high α-fetoprotein level, would favor HCC over lymphoma. In patients with renal masses, there is currently no laboratory test available to lead to the correct diagnosis. In these patients, adenopathy elsewhere should raise the possibility of lymphoma, and tissue sampling should be considered before determining treatment. The limitations of our study include the small sample size and the retrospective nature of the study. However, the intent of our study was to present an imaging spectrum to make radiologists aware of the association of tumor thrombus in patients with lymphoma. A future direction would be performing a prospective study with immunohistochemical and pathologic analyses of the lymphoma to assess for mechanisms of tumor thrombus and to evaluate prognosis in the presence of tumor thrombus. Conclusion Lymphoma can rarely present with tumor thrombus. This diagnosis should be consid-
A
ered in the differential diagnosis of solid organ involvement with tumor thrombus, particularly in the presence of other imaging features suggestive of lymphoma. References 1. Lai P, Bomanji JB, Mahmood S, et al. Detection of tumour thrombus by 18F-FDG-PET/CT imaging. Eur J Cancer Prev 2007; 16:90–94 2. Minagawa M, Makuuchi M. Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus. World J Gastroenterol 2006; 12:7561–7567 3. Heidenreich A, Ravery V; European Society of Oncological Urology. Preoperative imaging in renal cell cancer. World J Urol 2004; 22:307–315 4. Sheth S, Horton KM, Garland MR, Fishman EK. Mesenteric neoplasms: CT appearances of primary and secondary tumors and differential diagnosis. RadioGraphics 2003; 23:457–473 5. Matsumoto S, Mori H, Takaki H, Ishitobi F, Shuto R, Yokoyama S. Malignant lymphoma with tumor thrombus in the portal venous system. Abdom Imaging 2004; 29:460–462 6. Kanemura N, Tsurumi H, Yamada T, Kojima Y, Kasahara S, Moriwaki H. Diffuse large B-cell lymphoma with tumor thrombosis in the portal vein. Int J Hematol 2006; 84:282–283 7. Wagner JR, Honig SC, Siroky MB. Non-Hodgkin’s lymphoma can mimic renal adenocarcinoma with inferior vena caval involvement. Urology 1993; 42:720–723; discussion, 723–724
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8. Yoneyama F, Nimura Y, Kamiya J, et al. Primary lymphoma of the liver with bile duct invasion and tumoral occlusion of the portal vein: report of a case. J Hepatol 1998; 29:485–488 9. Natsuizaka M, Kudo M, Suzuki M, et al. Diffuse large B-cell lymphoma with massive portal vein tumor thrombosis in a patient with alcoholic cirrhosis: a case report and literature review. Intern Med 2009; 48:805–808 10. Chen L, Richendollar B, Bunting S, Campbell S, Zhou M. Lymphomas and lymphoproliferative disorders clinically presenting as renal carcinoma: a clinicopathological study of 14 cases. Pathology 2013; 45:657–663 11. Samlowski EE, Dechet C, Weissman A, Samlowski WE. Large cell non-Hodgkin’s lymphoma masquerading as renal carcinoma with inferior vena cava thrombosis: a case report. J Med Case Rep 2011; 5:245 12. Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 2011; 117:5019–5032 13. Hayakawa A, Shimotake N, Kubokawa I, et al. Primary pediatric stage III renal diffuse large B-cell lymphoma. Am J Case Rep 2013; 14:34–37 14. Kato Y, Hasegawa M, Numasato S, Monma N, Fujioka T. Primary mucosa-associated lymphoid tissue-type lymphoma arising in the kidney. Int J Urol 2008; 15:90–92
Fig. 1—77-year-old woman with diffuse large B-cell lymphoma (patient 2 in Table 1). A, Axial contrast-enhanced CT image obtained for initial staging shows enhancing mass in right neck engulfing right external and internal carotid arteries (arrow). Posteriorly, mass invades right internal jugular vein (arrowhead) and presents as large tumor thrombus. B, Fused axial PET/CT image shows intense FDG avidity of neck mass.
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Chauhan et al.
A
B
Fig. 2—61-year-old woman with history of diffuse large B-cell lymphoma (patient 3 in Table 1). A, Axial contrast-enhanced CT image obtained for initial staging shows large infiltrative mass centered in right hilum and invading right superior pulmonary vein and left atrium (arrow) as tumor thrombus. B, Fused axial PET/CT image shows intense FDG avidity of mass.
A
B
Fig. 3—48-year-old man with history of diffuse large B-cell lymphoma (patient 4 in Table 1). A, Axial contrast-enhanced CT image obtained for initial staging shows mass involves liver along gallbladder fossa. Image also shows another similarly enhancing mass (arrow) in main portal vein bifurcation that extends into right portal vein as tumor thrombus. B, Fused axial PET/CT image shows intense FDG avidity of mass and of tumor thrombus.
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Lymphoma Presenting With Tumor Thrombus
A
B
Fig. 4—73-year-old woman with history of diffuse large B-cell lymphoma (patient 5 in Table 1). A, Axial contrast-enhanced CT image obtained for initial staging shows large infiltrative mass involving left hepatic lobe and secondarily invading left portal vein up to main portal vein (arrow) as tumor thrombus. B, Fused axial PET/CT image shows intense FDG avidity of mass and of tumor thrombus.
A
B
C
Fig. 5—72-year-old man with history of mixed diffuse large B-cell lymphoma and follicular lymphoma (patient 7 in Table 1). A, Coronal unenhanced CT image obtained for initial staging shows infiltrative mass involving left kidney. B, Coronal contrast-enhanced MR image confirms CT finding (A) and also shows mass extending into left renal vein (arrow) as tumor thrombus. C, Fused axial PET/CT image shows intense FDG avidity of mass.
A
B
C
Fig. 6—29-year-old man with history of plasmacytic lymphoma (patient 8 in Table 1). A and B, Axial (A) and coronal (B) contrast-enhanced CT images obtained for initial staging show large right renal mass. Coronal image also shows that mass extends into inferior renal vein and inferior vena cava (arrow, B) as tumor thrombus. C, Fused axial PET/CT image shows intense FDG avidity of mass.
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Chauhan et al. Fig. 7—75-year-old woman with history of follicular lymphoma (patient 9 in Table 1). Restaging axial contrast-enhanced CT image shows complex mass centered at gastrosplenic ligament and infiltrating into spleen laterally. Medially, mass is seen as invading splenic vein up to portal venous confluence (arrow) as tumor thrombus.
Fig. 8—64-year-old woman with history of mixed diffuse large B-cell lymphoma and follicular lymphoma (patient 10 in Table 1). A, Coronal contrast-enhanced CT image obtained for initial staging shows infiltrative mesenteric mass invading superior mesenteric vein through its tributaries (arrow) as tumor thrombus. B, Fused coronal PET/CT image shows intense FDG avidity of mass including intense FDG avidity of tumor thrombus.
Fig. 9—68-year-old woman with history of diffuse large B-cell lymphoma (patient 12 in Table 1). A and B, Axial (A) and coronal (B) contrastenhanced CT images obtained for initial staging show retroperitoneal lymphadenopathy invading into inferior vena cava (arrows) as tumor thrombus.
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