Primary adrenal lymphoma: Radiological; pathological, clinical correlation

European Journal of Radiology 81 (2012) 401–405

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Primary adrenal lymphoma: Radiological; pathological, clinical correlation Liangping Zhou a,∗ , Weijun Peng a , Chaofu Wang b , Xiaohang Liu a , Yijun Shen c , Kangrong Zhou d a

Department of Radiology, Fudan University Cancer Hospital, Shanghai, 270 DongAn Road, Shanghai 200032, China Department of Pathology, Fudan University Cancer Hospital, Shanghai, 270 DongAn Road, Shanghai 200032, China c Department of Urology, Fudan University Cancer Hospital, Shanghai, 270 DongAn Road, Shanghai 200032, China d Department of Radiology, Fudan University Zhongshan Hospital, Shanghai, 180 Fenglin Road, Shanghai 200032, China b

a r t i c l e

i n f o

Article history: Received 2 August 2010 Received in revised form 13 November 2010 Accepted 18 November 2010 Keywords: Lymphoma Adrenal glands Computed tomography (CT) Magnetic resonance (MR) imaging

a b s t r a c t Objective: The purpose of this study was to analyze CT and MR imaging (MRI) manifestation of primary adrenal lymphoma in order to better understand of this rare disease. Materials and methods: Six patients (4 men, 2 women; median age, 65.5 years) with pathologically proven primary adrenal lymphoma were retrospectively reviewed. Imaging findings (CT&MRI, n = 3; only CT, n = 3) were analyzed and correlated with clinical and pathologic findings. Results: All cases were pathologically proven primary adrenal diffuse large B-cell lymphoma with bilateral lesions in 3 cases respectively. Maximum diameters of the 9 lesions were 6.1–14.8 cm, median 10.5 cm. Seven lesions were round, oval or oblong, and 2 lesions irregular. Seven lesions were well-defined and 2 had ill-defined margins. Unenhanced CT density of 9 lesions and MR signal intensity of T1 weighted images of 6 lesions were similar to that of muscle, and all 6 lesions were hyperintense on T2-weighted MR images. Following intravenous injection of contrast media, 6 lesions had mild enhancement and 3 lesions had moderate enhancement on parenchymal phase imaging. Enhancement was homogenous in three, slightly inhomogeneous in four, and heterogeneous in two. Seven lesions, in 5 cases, infiltrated the adjacent tissues or organs in patients with large tumors. Conclusion: Primary adrenal lymphoma usually manifests as large, well-defined, soft-tissue masses replacing the adrenal gland with homogeneous or slightly inhomogeneous enhancement. Large tumors especially tend to infiltrate adjacent structures. © 2010 Elsevier Ireland Ltd. All rights reserved.

1. Introduction

2. Materials and methods

Secondary involvement of the adrenal glands with non-Hodgkin lymphoma has been reported to occur in up to 25% of patients during the course of their disease [1]. However, primary adrenal lymphoma is extremely rare and accounts for just 1% of all nonHodgkin’s lymphoma cases [2]. Less than 100 cases of primary adrenal lymphoma had been reported in the English literatures, most are single, or just a few cases reported and literature reviewed [2–7]. To our knowledge, the imaging features of CT and MR imaging have received limited attention [8–12]. In this retrospective study, we describe CT and MR imaging findings of six patients with primary adrenal lymphoma, and correlate with clinical and pathologic results.

A retrospective review of radiological and pathological database during a 12 year period (1998–2009) discovered 32 patients with adrenal lymphoma at our two institutions. Documentation was by adrenalectomy in 7 patients, adrenal needle biopsy in 6 patients and clinical history and follow-up in 19 patients. Among them, 6 patients were diagnosed as primary adrenal lymphomas while the remaining 26 cases as secondary adrenal lymphomas. The criteria used for a diagnosis of primary adrenal lymphoma were based upon prior reports as follows “histology confirmed to be unilateral or bilateral adrenal lymphoma with no evidence of disease elsewhere for at least 6 months after diagnosis” [3,11,13]. Patients consisted of four males, two females, and clinical findings were summarized (Table 1). Ages ranged from 43 to 77 years, median age is 65.5 years. Most common presenting symptoms were abdominal pain (3/6) and/or fever (2/6). All of the 6 cases were non-Hodgkin’s lymphoma (NHL) with the subtypes of diffuse large B-cell lymphoma (DLBCL) proven by adrenalectomy (5 patients) and adrenal needle biopsy (1 patient). Pathological analysis showed tumor cells proliferated diffusely with vacuole nuclei and conspic-

∗ Corresponding author. Tel.: +86 21 64433384; fax: +86 21 64433384. E-mail address: [email protected] (L. Zhou). 0720-048X/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2010.11.026

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Table 1 Clinicopathological features of patients with primary adrenal lymphoma. Case/sex/ age

Tumor type

Presenting symptom(mo)

Side (size, cm)

Adrenal insufficiency

B symptoms

Diagnosis method

Treatment

Treament results

FU(mo)

1/M/56 2/M/40 3/F/70 4/M/77 5/M/72 6/M/61

DLBCL DLBCL DLBCL DLBCL DLBCL DLBCL

WL(2.0) Abd pain(1.0) Abd pain Fever(6.0) Abd pain(1.0) HE Fever(4.0)

R(6.1) L(7.9) R(10.8) L(12.3) L(14.8) R(10.1) L(11.3) L(6.3) L(7.5)

Present Present Absent Absent Absent Absent

Fatigue, WL Fever, Fatigue, WL Fever, Fatigue, WL Fatigue, WL Absent Fever, Fatigue, WL

Adrenalectomy Adrenalectomy Adrenalectomy Adrenalectomy Adrenalectomy Needle biopsy

CEOP*4 CHOP*3 CHOP*4 CHOP*6 CHOP*4 CHOP*6

Progression Progression CR Progression CR PR

DOD(10) DOD(7) AWD(36) DOD(8) AWD(28) DOD (22)

Abd, abdominal; AWD, alive with disease; CEOP, Cyclophosphamide, epidoxorubicin, vincristine, and prednisolone; CHOP: cyclophosphamide, doxorubicin, vincristine and prednisolone; CR, complete remission; DOD, died of disease; DLBCL: diffuse large B-cell lymphoma; F, female; FU, follow-up; L, left; M, male; mo, month; NS, night sweating; PR, partial response; R, right; WL, weight loss.

uous nucleoli (Fig. 1d). Immunohistochemically, the tumor cells were positive for CD20 (Fig. 1e). 2.1. CT and MRI Of the 6 patients, 3 underwent both CT and MRI examinations, and 3 CT examinations alone. The CT and MRI technique varied somewhat owing to the varied imaging equipment and the retrospective nature of the study. However, intravenous contrastenhanced images had been obtained for studies in all patients. Four patients were examined with single-detector spiral CT (GE Hispeed CT/i), 2 with multi-detector spiral CT (Somatom S40), with a 3–7-mm collimation and 3–7-mm intervals. Contrast-enhanced CT images were obtained during arterial phase (25–30 s) and parenchymal phase (55–70 s) after the intravenous injection of 100 ml Ultravist 300 or Ominipaque 300 with a power CT injector at the rate of 2–3 ml/s. All patients were examined with a 1.5 T twin speed superconducting MR system (GE Signa with EXCITE II), with 5–8 mm slice thickness and 0.5–2.0 mm gap spacing. Dynamic contrast-enhanced FSPGR axial T1 weighted imaging (TR 150–180 ms, TE1.4–1.7 ms) with fat-suppression were scanned 20–120 s after the intravenous injection of 15 ml Magnevist with a power MR injector at the rate of 2 ml/s. 2.2. Image analysis CT and MR images were analyzed by two radiologists with 13 years’ and 8 years of experience in genitourinary radiology, respectively. Evaluation was performed by consensus, and the reviewers were aware of the clinical data. The following imaging features of primary adrenal lymphoma were evaluated: lesions size, shape, and sharpness/irregularity of radiographic margins. CT values of images obtained during unenhanced, arterial phase and parenchymal phase were measured. The appearance of the lesions on MR images was categorized as hypointense, isointense or hyperintense as compared to normal paravertebral muscle. After intravenous injection of contrast media, the tumors with similar

enhancement degree to that of muscles, livers and kidneys were graded mild, moderate or marked enhancement, respectively. The patterns of tumor enhancement were divided into 3 types: homogeneous, slightly inhomogeneous, and heterogeneous. Infiltration of adjacent structure by the tumor and remote disseminations were recorded.

3. Results Radiologic findings are summarized (Table 2). The maximum diameters of 9 lesions were 6.1–14.8 cm, the median were 10.5 cm. On axial images, seven lesions were round, oval or oblong, 2 lesions were irregular. Seven lesions were well-defined and 2 were illdefined. On coronal reconstructed CT or MR images, 6 of 9 lesions manifested as triangular masses (Figs. 1c and 2d). Unenhanced CT density of 9 lesions were 26–43HU (median: 35HU) which were similar to that of muscle (Fig. 1a). 4 of 6 (66.7%) tumors were slightly hypointense and 2 (33.3%) were isointense on T1-weighted MR images, and all 6 (100%) were hyperintense on T2-weighted MR images (Figs. 2a and b and 3a). After intravenous injection of contrast media, 9 lesions (100%) had mild enhancement on arterial phase imaging (CT value: 42–58HU, median: 45HU), and 6 (66.7%) lesions had mild enhancement and 3 (33.3%) lesions had moderate enhancement on parenchymal phase imaging (CT value: 54–74HU, median: 58HU), with enhancement patterns as homogenous in 3 (33.3%) tumors (Fig. 1b and c), slightly inhomogeneous in 4 (44.4%) (Fig. 2c and d) and heterogeneous in 2 (22.2%) (Fig. 3b), respectively. 4 of 6 (66.7%) lesions demonstrate the areas of mild enhancement which manifested as hypointense on T2 weighted MR images (Fig. 2a and d). Seven lesions in 5 cases infiltrated the ipsilateral kidneys and vascular vessels (Figs. 1c, 2c and d). Five of seven (71.4%) lesions exceed 10 cm in diameter. The remaining two lesions without adjacent infiltration were 6.1 cm and 6.3 cm in the maximum diameter respectively. One patient had the lymphadenopathy in the adjacent retroperitoneal area without disseminated lymphadenopathy.

Table 2 Imaging features of patients with primary adrenal lymphoma. Case

1 2 3 4 5 6

Side

Right Left Right Left Left Right Left Left Left

Size (cm)

6.1 8.2 10.8 12.3 14.8 10.5 11.3 6.3 7.5

Figure

Round Oval Oval Oval Oblong Irregular Irregular Round Oval

Edge

WD ID WD WD WD WD ID WD WD

CT Value (HU)

MR Signal Intensity

UE

AP

PP

T1WI

T2WI

Enhancement EnhancedDegree

Patterns

26 28 31 35 42 37 36 34 43

47 45 39 43 58 45 47 42 56

75 76 54 56 67 55 58 57 78

Slight hypointensity Slight hypointensity Slight hypointensity Slight hypointensity NE Isointensity Isointensity NE NE

Hyperintensity Hyperintensity Hyperintensity Hyperintensity

Moderate Moderate Slightly Slightly Slightly Slightly Slightly Slightly Moderate

Heterogeneous Heterogeneous Slightly inhomogeneous Slightly inhomogeneous Homogeneous Slightly inhomogeneous Slightly inhomogeneous Homogeneous Homogeneous

Hyperintensity Hyperintensity

Adjacent infiltration

Absent LK, LRV RRV, LCV LK, LRV LK, LRV, LRH, RPL RK, RRV, LCV LK, LRV Absent LK

AP, arterial phase; HU, Housefield unit; ID, ill-defined; LK, left kidney; LRH, left renal hilar; LRV, left renal vessels; NE, not examination; PP, parenchymal phase; RK, right kidney; RPL, retroperitoneal lymphadenectasis; RRV, right renal vessels; UE, unenhanced; WD, well-defined.

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Fig. 1. 70-Year-old woman with primary left adrenal non-Hodgkin’s lymphoma. Axial unenhanced CT (a) and enhanced CT (b) show a left adrenal mass with slightly homogeneous enhancement but without obvious necrosis. Triangular shape of the adrenal is maintained. Infiltration of left kidney noted on coronal reconstructed image (c). Histopathologic photograpy (H&E staining, original magnification at 400×) (d) and Immunohistochemical photograpy (S & P method, original magnification at 400×) (e).

4. Discussion Primary adrenal lymphoma is a rare extranodal lymphoma representing only 3% of extranodal lymphomas [2,11,14]. Disseminated whole body lymphoma may sometimes present as adrenal involvement firstly which may be confused with primary adrenal lymphoma. Primary extranodal lymphoma (which includes primary adrenal lymphomas) is classified as stage IE according to the Ann Arbor classification to distinguish them from the disseminated

form of the disease (stage IV), which carries a poorer prognosis [15]. The criteria for a diagnosis of primary adrenal lymphoma have not been clearly defined. However, most authors suggested the following criteria: “(1) histologically proven unilateral or bilateral adrenal lymphoma without nodal involvement, (2) absence of a leukemic blood picture and (3) lack of involvement of other organs for at least 6 months after diagnosis” [3,11,13]. Primary adrenal lymphoma commonly affects elderly men; with a median age of 65 years old in the 70 cases review by

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Fig. 3. 56-Year-old man with primary bilateral adrenal NHL. On axial fatsuppressed T2-weighted MR images (a) and axialcontrast-enhanced fat-suppressed T1-weighted MR images (b), both masses show moderate heterogeneous enhancement suggesting necrosis or cystic degeneration.

Kumar et al. [11], similar to our experience, median age of 65.5 years. Bilateral involvement occurred in 73% of the study and in half our patients. B symptoms (include fever, night sweating, fatigue, and weight loss) were similar in our small group (5/6) patients. To date, only one case of primary Hodgkin’s lymphoma (HL) arising from adrenal gland has been reported [16]. The remaining of primary adrenal lymphomas in the literatures is NHL, with B-cell type being much more common than T-cell. In one review, only 5% were of T-cell origin [17,18]. Approximately 50% of patients actually develop symptoms of adrenal insufficiency, such as pigmented skin and mucous membrane, fatigue, anorexia, and constipation, and occurred in 2/6 of our patients. Primary adrenal lymphoma generally manifests as large, softtissue masses, replacing the adrenal glands with the maximal diameters often exceeding 6 cm [8–12]. In this study, most (7/9) of adrenal lymphomas are round or oval and smooth with welldefined margins, even in the largest lesions as seen in our experience. Despite their large size, imaging often reflects preservation of the native triangular appearance of the normal adrenal gland. This may represent the characteristics of diffuse lymphoFig. 2. 77-Year-old man with primary bilateral adrenal NHL. Bilateral adrenal irregular soft masses are displayed on axial fat-suppressed T2-weighted MR image (a), axial T1-weighted MR image (b), and axial contrast-enhanced T1-weighted fatsuppressed MR image (c). Note the hypointensity areas on axial fat-suppressed T2-weighted MR image (arrows). Both the kidneys are infiltrated, and on coronal T2-weighted MR image (d) a right adrenal mass is noted and the adrenal gland retains its triangular shape and the space between the left kidney and the spine are occupied by the left adrenal mass which is extended to the left renal hilar (arrows).

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mous infiltration of the gland. Several papers noted that adrenal lymphoma may present as adrenal thickening similar to appearance of adrenal hyperplasia [19–21]. On unenhanced CT, primary adrenal lymphoma manifests as isodense or slightly hypodense with normal muscle as the standard for comparison. On unenhanced MRI exam, primary adrenal lymphoma appears as iso- or hypointense to normal muscle on T1-weighted images and hyperintense to normal muscle on T2-weighted images. Most of the masses demonstrated mild to moderate enhancement after intravenous administration of contrast media. Unfortunately, there is significant overlap between the imaging appearances of primary adrenal lymphoma and other adrenal diseases [9–12]. The lack of significant inhomogenatous or frank necrosis can assist in distinguishing from metastases and primary adrenal cortical carcinoma. Additionally, in this study, 4/6 lesions demonstrated the areas of hypointensity on T2-weighted images with mild enhancement on parenchymal phase images. White et al. observed a similar appearance of images in the bone and soft tissue lymphoma which represent internal fibrotic components of the tumor [22]. This feature may also be a distinguishable sign to characterize a primary adrenal lymphoma. Unfortunately, some primary adrenal lymphomas may manifest as masses with necrotic or cystic components and heterogeneous, moderate enhancement [9,10], as occurred in one of our cases (Fig. 3), making it impossible to differentiate from primary adrenal cortical carcinoma, pheochromocytomas, or metastatic disease. When large, primary adrenal lymphoma may infiltrate the adjacent structures including the renal parenchyma and renal liver regions. The typical growth patterns within the retroperitoneum should suggest lymphoma, as it is more likely to infiltrate and insinuate around the upper pole of the kidney and adjacent vessels, as compared to metastatic disease with a more destructive appearance. In conclusion, adrenal lymphoma is an unusual manifestation of adrenal pathology. It is characterized by large tumors, exceeding 10 cm in diameter, with a growth pattern of infiltration. Masses generally expand and infiltrate the glands, maintaining their triangular appearances. Imaging characteristics include hypodensity in unenhanced CT and hypodense/isotense in T1-weighted MR and hyperdense in T2-weighted MR images. On enhanced CT and MR images, the lesions generally show mildly or moderate enhancement being homogenous or just mildly inhomogenous. Conflicts of interest This paper is neither the entire paper nor any part of its content has been published or has been accepted elsewhere. The manuscript has been read and approved by all the authors and the criteria for authorship have been met. There are no financial or other conflicts of interests; there are no suggestions such as referring possible unqualified reviewers due to conflict of interests.

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