- Email: [email protected]
CT images in primary adrenal lymphoma
European Journal of Radiology Extra 68 (2008) e83–e87
18
F-FDG PET/CT images in primary adrenal lymphoma
Junping Wang a,∗ , Haoran Sun a,1 , Renju Bai a,1 , Shuo Gao b , Yajun Li b a
Department of Radiology, General Hospital of Tianjin Medical University, Tianjin 300052, China b PET-CT Center, General Hospital of Tianjin Medical University, Tianjin 300052, China Received 30 March 2008; accepted 13 June 2008
Abstract Primary adrenal lymphoma (PAL) is an extremely rare entity and primary adrenal insufficiency (PAI) is a common complication. The majority of cases reported previously were of B-cell origin. Here, we describe an additional PAL of B-cell origin with 18 F-FDG PET/CT images. The patient was a 74-year-old man who presented with clinical and laboratory features of PAI. Abdominal ultrasonography (US) showed bilateral adrenal masses. Whole-body 18 F-FDG PET/CT showed intensely increased glucose metabolism in bilateral bulky adrenal masses. Pathological diagnosis was non-Hodgkin lymphoma of B-cell origin. Combination chemotherapy was unsuccessful and our patient died of CNS involvement 6 months later. The present case indicated that PAL should be included in the differential diagnosis of bilateral adrenal masses, especially in patients with PAI. We report the case and review the literature for this disease in detail. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Primary adrenal lymphoma; Primary adrenal insufficiency; 18 F-FDG; PET; CT
1. Introduction Secondary involvement of the adrenal glands with nonHodgkin lymphoma has been reported to occur in up to 25% of patients during the course of disease [1]. However, PAL is extremely rare. So far, only less than 80 cases have been reported in English literature [2]. Most of the patients with PAL usually present with bilateral adrenal masses with no evidence of extraadrenal spreading. Among the cases, US, CT, and MRI were the imaging modalities used to describe the lesion. Recently, whole-body 18 F-FDG PET/CT has shown promising results in differentiating benign from metastatic adrenal masses in patients with known or suspected malignancies. We report the rare case of PAL in which whole-body 18 F-FDG PET/CT played an important role in the diagnosis. 2. Case report A 74-year-old man was transferred to our hospital because of progressive anorexia, nausea, vomiting, weight loss, fatigue and
∗ 1
Corresponding author. Tel.: +86 22 60362497. E-mail address: [email protected] (J. Wang). Contributed equally for the paper.
1571-4675/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrex.2008.06.010
pigmentation for 2 months. Bilateral huge hypoechoic adrenal masses had been found on abdominal US at other hospital. He denied any abdominal discomfort or symptoms of airway or urinary tract infection. His past history was unremarkable except receiving calcium channel blockers to control hypertension for 10 years. Physical examinations on admission revealed a chronically ill patient with a clear consciousness. No palpable mass was found in the abdomen. His vital signs were all within normal limits: body weight 64 kg, blood pressure 120/78 mmHg, respiratory rate 18/min, pulse rate 67/min, and body temperature 37.0 ◦ C. Pertinent physical findings revealed some hyperpigmentation spots over his lower lip. There was no superficial lymphadenopathy or organomegaly. Initial laboratory findings revealed a normal full blood count and erythrocyte sedimentation rate. Serum tumor markers including carcinoembryonic antigen (CEA), ␣-fetoprotein (AFP) and prostatic specific antigen (PSA) were all within normal limits. A serum biochemistry profile disclosed a sodium concentration of 125 mmol/L (normal range: 135–145 mmol/L), potassium concentration of 5.8 mmol/L (normal range: 3.5–5.5 mmol/L), serum lactate dehydrogenase 586 g/dL (normal range: 109–245 g/dL), and 2 microglobulin 4.3 mg/L (normal range: 0.91–2.2 mg/L). PAI was suspected due to the complaint of progressive anorexia, nausea, vomiting, weight loss, fatigue, pigmentation and the findings of hyponatremia and hyperkalemia. It was confirmed
e84
J. Wang et al. / European Journal of Radiology Extra 68 (2008) e83–e87
Fig. 1. (a) Plain abdominal CT scan shows large, irregular, homogeneous soft tissue masses in bilateral adrenal area, normal bilateral adrenal glands could not be seen. (b) and (c) Axial PET scan and PET–CT fusion image (axial view of same level as CT scan) shows intense FDG uptake in bilateral adrenal masses.
by the findings of a low serum cortisol level of 3.1 g/dL at 06:30 a.m. (normal range: 5–17.5 g/dL), a high ACTH level of 768.8 pg/mL (normal range: 0–46 pg/mL), and a low cortisol level of 13.1 g/dL 1 h after the cosyntropin stimulation test. Further findings including urine vanillymandelic acid and serum aldosterone in supine/supine position were all within normal range. Immediately he received hormone replacement therapy with intravenous hydrocortisone 100 mg every 8 h daily and the patient’s general conditions improved rapidly while his diagnostic workup proceeded. For further diagnosis, abdominal plain computed tomography (CT) was performed and it showed bilateral adrenal massive homogeneous soft tissue masses measuring 5.3 cm × 5.1 cm × 5.9 cm on the right and 7.7 cm × 6.1 cm × 4.2 cm on the left (Fig. 1a). No other abdominal lesions or lymphadenopathy were detected. Plain CT of the chest showed no lymphadenopathy or any pulmonary lesions. Based on the CT findings, a provisional diagnosis of adrenal metastases or possible lymphomatous involvement of the adrenal glands was made. A whole-body 18 F-FDG PET/CT scan was acquired for further staging of the disease and it showed intense 18 F-FDG accumulation in bilateral adrenal glands (Fig. 1b and c). There was no abnormal 18 F-FDG uptake in the rest of the body (Fig. 2a). Based on the localized intense FDG uptake only in the adrenal glands, a diagnosis of primary bilateral adrenal lymphoma was made. CT-guided core biopsy of the left adrenal mass was performed in order to determine the nature of the tumor and it revealed non-Hodgkin lymphoma (Fig. 3a). Immunostaining for common leukocyte antigen showed B-cell marker (CD20) positive (Fig. 3b) and T-cell marker (CD45RO) negative (Fig. 3c). Bone marrow aspiration and cerebrospinal fluid analysis were negative for lymphomatous cells. Primary bilateral adrenal lymphoma with PAI was diagnosed. The patient was given four cycles of cyclophosphamide, vincristine, daunorubicin, and prednisolone (CHOP)-based chemotherapy. Unfortunately he died of progression of PAL and CNS involvement 6 months later (Fig. 4).
3. Discussion PAL is extremely uncommon. A diagnosis of PAL should be considered in a patient presenting with bilateral adrenal masses without nodal involvement and absence of a leukemic blood picture as well as other organs involvement [3,4]. Because of the
rarity of this disease, the clinical and pathologic features, imaging characteristic, therapeutic regimen and prognosis have not been defined in detail. We reviewed the literature of the reported cases in detail, which may help to understand this disease better. 3.1. Clinical features PAL commonly affects elderly men, with a median age of 65 years old and a male to female ratio of about 2.1–7:13. Common symptoms include fever, weight loss, and abdominal/lumbar pain, which are nonspecific [3]. Some cases were incidentally discovered by abdominal US or CT scan. Approximately 50–70% of patients with bilateral PAL have clinical or biochemical evidence of PAI [2], as seen in our patient. The clinical symptoms of PAI include fatigue, anorexia, weight loss, postural hypotension and pigmentation on skin or mucous membrane, and so on. And the laboratory findings of PAI include hyponatremia, hyperkalemia, low plasma/urinary cortisol, and the absence of a plasma cortisol response to tetracosactrin, etc. Because more than 90% of the bilateral adrenal glands are destroyed before clinical symptoms or laboratory findings of PAI develop, it is not commonly seen in unilateral PAL or in the early stage of bilateral PAL [5]. The diffuse type of infiltration and the complete destruction of the architecture of the adrenal glands by the tumor may be responsible for the finding of PAI in patient with PAL. And literature review suggests that there is no correlation between the size of the tumor and PAI [4]. 3.2. Histopathology The etiology of PAL is still not clear currently. The most common hypothesis for the origin of this disease is hematopoietic tissue resting in the adrenal glands akin to adrenal myelolipoma [4]. Another author believes that the adrenal glands in man contain no lymphoid tissue, and the follicle centre cell origin of PAL suggests the tumor may have risen on a background of previous autoimmune adrenalitis, consistent with the finding of PAI [6]. The confirmatory diagnosis of PAL is based on pathological examination. Ultrasound- or CT-guided core biopsy or surgical biopsy through laparoscopy or laparotomy is required to definite histopathological diagnosis. Histologically, the most common type of PAL is diffuse large B cell. Other less common histological types are mixed large and small cell, small noncleaved cell,
J. Wang et al. / European Journal of Radiology Extra 68 (2008) e83–e87
e85
Fig. 2. (a) Whole-body PET MIP images (coronal views) show intense 18 F-FDG uptake in bilateral adrenal masses. There are no other areas of abnormal 18 F-FDG uptake. These findings are suggestive of primary adrenal lymphoma.
Fig. 3. Biopsy specimen of the left adrenal gland stained with hematoxylin and eosin shows diffuse proliferation of large atypical lymphoid cells replacing normal adrenal tissue. (a, 200×). Immunostaining for common leukocyte antigen shows B-cell marker (CD20) positive (b, 200×) and T-cell marker (CD45RO) negative (c, 200×).
e86
J. Wang et al. / European Journal of Radiology Extra 68 (2008) e83–e87
Fig. 4. Axial (a) and coronal (b) contrast-enhanced T1 -weighted MR images show a large intensely enhanced right frontal mass with surrounding edema.
undifferentiated, and others [2]. Based on immunostaining, the majority of PAL originated from B cell, and only 10 cases of T-cell origin were reported so far [2,3]. 3.3. Diagnosis and differential diagnosis The increasing use of US, CT, and MRI renders a large number of incidentally discovered adrenal masses. Therefore, it is important to differentiate benign from malignant adrenal masses and diagnose PAL during its early stages. PAL usually presents with bilateral adrenal masses (73%) with moderate to severe adrenal enlargement (sizes ranging from 4 to 17 cm2 .) Kumar reviewed the 70 patients with PAL, 56 had bilateral adrenal involvement [3]. Most cases appear as complex masses with a variable density on plain CT scan. In some cases, CT has demonstrated a cystic appearance due to necrosis, whereas a few cases have also shown a homogenous density. PAL was described to be low signal intensity on T1 -weighted imaging and high signal intensity with areas of mixed signal intensity on T2 -weighted imaging. On MR chemical shift imaging, signal intensity of PAL does not decrease on out-phase images. On contrast enhancement examination, PAL commonly enhances slightly and heterogeneously. PAL should be differentiated from other adrenal masses, including metastases, tuberculosis, pheochromocytoma, nonfunctioning adenoma, adrenal cortical carcinoma, and others. Patients with adrenal tuberculosis commonly have a long history of years or decades. The lesions generally appear as heterogeneously low signal intensity masses on T2 -weighted imaging because of caseate, and calcification can be seen on plain CT. Nonfunctioning adenomas are rich of lipid, plain CT demonstrates low-density masses, contrast material washes out rapidly on dynamic enhanced CT/MR scan. On MR chemical shift imaging, signal intensity of the lesions decreases obviously on out-phase images by cancellation of the signal from fat and water, which is a specific characteristic of adenomas. Generally, adenomas could be able to be differentiated from other adrenal masses easily [7].
Pheochromocytomas secrete a great deal of catecholamines which cause specific manifestations and laboratory findings. The masses demonstrate obviously high signal intensity on T2 -weighted imaging. Contrast-enhanced T1 -weighted imaging shows that the parenchyma of the masses is enhanced obviously. Definite diagnosis could be made easily by clinical presentations and imaging findings [8]. Adrenal cortical carcinoma is usually big in size. Hemorrhage, necrosis, cyst, and calcification are common. Vessels adjacent to the tumor are always encased or invaded [9]. Both adrenal metastases and PAL are bilateral adrenal soft tissue masses with similar appearance on US, CT, and MRI. It is difficult to distinguish between them. Adrenal metastases were mostly from lung cancers. CT with high-resolution anatomic imaging technique is used as the first-line diagnostic modality for screening and determining the nature of the adrenal lesions. Signal intensities on MR T2 -weighted imaging and chemical shift sequences are most commonly used to differentiate benign from malignant adrenal masses. Unlike US, CT and MRI, 18 F-FDG PET/CT is based on increased glucose metabolism in malignant lesions. Recently, 18 F-FDG PET/CT has shown great potential in differentiating malignant from benign adrenal lesions. Erasmus et al. evaluated 33 adrenal masses in 27 patients with bronchogenic carcinomas. The sensitivity for detecting metastasis was 100% and the specificity was 80% [10]. 18 F-FDG PET/CT can simultaneously obtain characteristics of metabolism and morphology of the lesions, whole-body 18 F-FDG PET/CT scan can identify whether the adrenal malignant masses are metastatic and detect their primary malignancies. Because most PAL have adrenal involvement only, without any lymph nodes or organs involvement, it demonstrates intense 18 F-FDG uptake only in bilateral adrenal masses. In our patient, whole-body 18 F-FDG PET/CT demonstrated intense 18 F-FDG uptake in bilateral adrenal masses and no evidence of abnormal uptake in extraadrenal regions. Because 18 F-FDG is taken up only by viable/residual tumor and is not taken up by necrotic tumor and fibrosis, it also has an important role in staging, monitoring response to treatment, and detecting recurrence of PAL [3].
J. Wang et al. / European Journal of Radiology Extra 68 (2008) e83–e87
3.4. Treatment and prognosis Although most patients with PAL have a very poor prognosis, early diagnosis and treatment can prolong disease-free survival in patients. Treatment of PAL is similar to treatment of other types of lymphoma. The therapeutic modalities include bilateral adrenalectomy, multiagent chemotherapy, radiotherapy, or a combination of them [2]. Since adrenal insufficiency crisis leads to severe life-threatening consequences, immediate hormone replacement therapy must be given if PAI is suspected. The regimens of combination chemotherapy that have been used include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CHO and prednisolone, CVP (cyclophosphamide, vincristine, and prednisone), and MACOP (adding methotrexate and bleomycin) with varying success [3]. Some investigators suggest that surgical debulking with subsequent chemotherapy is the best approach [4]. Radiation seems to be ineffective in those patients [11,12]. Despite every effort in treatment, these lesions have poor prognosis and patients usually die within 1 year [4,13]. They frequently died of severe infection, pulmonary embolism, or NHL progression [14]. Several inauspicious prognostic factors for PAL are old age, initial presentation with adrenal insufficiency, large tumor burden, elevated serum lactic dehydrogenase, and 2 -microglobulin, and involvement of other organs during following up [4]. Concerning our patient, all unfavourable prognostic factors mentioned above were present. Combination chemotherapy was unsuccessful and our patient died of CNS involvement 6 months later. It is interesting to note that PAL exhibits a propensity for late CNS involvement. And this observation raises the possibility that it will be useful in future clinical trials to add CNS prophylaxis in the treatment of patients with PAL [15]. 4. Conclusions PAL is a very rare but interesting disease entity. Bilateral adrenal masses should raise the suspicion of PAL, especially in patients with clinical or laboratory features of PAI. Whole-body 18 F-FDG-PET/CT could reveal the masses with characteristic
e87
manifestations, it is of great value in differentiating adrenal metastases from PAL, and it also play an important role for staging, and evaluation of the response to treatment in this disease. References [1] Rosenberg SA, Diamond HD, Jaslowitz B, et al. Lymphosarcoma: a review of 1269 cases. Medicine 1961;40:31–84. [2] Tomoyose T, Nagasaki A, Uchihara JN, et al. Primary adrenal adult Tcell leukemia/lymphoma: a case report and review of the literature. Am J Hematol 2007;82:748–52. [3] Kumar R, Xiu Y, Mavi A, et al. FDG-PET imaging in primary bilateral adrenal lymphoma: a case report and review of the literature. Clin Nucl Med 2005;30(4):222–30. [4] Dutta P, Bhansali A, Venkatesan R, et al. Primary adrenal lymphoma. Endocrinologist 2005;15(6):340–2. [5] Diamanti-Kandarakis E, Chatzismalis P, Economou F, et al. Primary adrenal lymphoma presented with adrenal insufficiency. Hormones (Athens) 2004;3(1):68–73. [6] Ellis RD, Read D. Bilateral adrenal non-Hodgkin’s lymphoma with adrenal insufficiency. Postgrad Med J 2000;76(898):508–9. [7] Wang WH, Bai RJ, Sun HR, et al. Evaluation of dynamic enhanced CT scanning in the differentiation of adrenal adenoma with non-adenoma. J Clin Radiol 2003;22:475–8. [8] Sun HR, Bai RJ, Wu EH. MR imaging of the pheochromocytoma. J Clin Radiol 2000;19:155–8. [9] Ribeiro J, Ribeiro RC, Fletcher BD. Imaging findings in pediatric adrenocortical carcinoma. Pediatr Radiol 2000;30:45–51. [10] Erasmus JJ, Patz Jr EF, McAdams HP, et al. Evaluation of adrenal masses in patients with bronchogenic carcinoma using 18F-fluorodeoxyglucose positron emission tomography. AJR 1997;168:1357–60. [11] Wang J, Sun NC, Renslo R, et al. Clinically silent primary adrenal lymphoma: a case report and review of the literature. Am J Hematol 1998;58(2):130–6. [12] Sasagawa I, Sadamori N, Itoyama T, et al. Primary adrenal lymphoma with chromosomal abnormalities. Acta Haematol 1995;94:156–62. [13] Barbaros U, Erbil Y, Bozbora A, et al. Primary adrenal lymphoma presenting as bilateral adrenal masses. Endocrinologist 2006;16(2): 75–6. [14] Hsu CW, Ho CL, Sheu WH, et al. Adrenal insufficiency caused by primary aggressive non-Hodgkin’s lymphoma of bilateral adrenal glands: report of a case and literature review. Ann Hematol 1999;78(3):151–4. [15] Mantzios G, Tsirigotis P, Veliou F, et al. Primary adrenal lymphoma presenting as Addison’s disease: case report and review of the literature. Ann Hematol 2004;83(7):460–3.
18
F-FDG PET/CT images in primary adrenal lymphoma
Junping Wang a,∗ , Haoran Sun a,1 , Renju Bai a,1 , Shuo Gao b , Yajun Li b a
Department of Radiology, General Hospital of Tianjin Medical University, Tianjin 300052, China b PET-CT Center, General Hospital of Tianjin Medical University, Tianjin 300052, China Received 30 March 2008; accepted 13 June 2008
Abstract Primary adrenal lymphoma (PAL) is an extremely rare entity and primary adrenal insufficiency (PAI) is a common complication. The majority of cases reported previously were of B-cell origin. Here, we describe an additional PAL of B-cell origin with 18 F-FDG PET/CT images. The patient was a 74-year-old man who presented with clinical and laboratory features of PAI. Abdominal ultrasonography (US) showed bilateral adrenal masses. Whole-body 18 F-FDG PET/CT showed intensely increased glucose metabolism in bilateral bulky adrenal masses. Pathological diagnosis was non-Hodgkin lymphoma of B-cell origin. Combination chemotherapy was unsuccessful and our patient died of CNS involvement 6 months later. The present case indicated that PAL should be included in the differential diagnosis of bilateral adrenal masses, especially in patients with PAI. We report the case and review the literature for this disease in detail. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Primary adrenal lymphoma; Primary adrenal insufficiency; 18 F-FDG; PET; CT
1. Introduction Secondary involvement of the adrenal glands with nonHodgkin lymphoma has been reported to occur in up to 25% of patients during the course of disease [1]. However, PAL is extremely rare. So far, only less than 80 cases have been reported in English literature [2]. Most of the patients with PAL usually present with bilateral adrenal masses with no evidence of extraadrenal spreading. Among the cases, US, CT, and MRI were the imaging modalities used to describe the lesion. Recently, whole-body 18 F-FDG PET/CT has shown promising results in differentiating benign from metastatic adrenal masses in patients with known or suspected malignancies. We report the rare case of PAL in which whole-body 18 F-FDG PET/CT played an important role in the diagnosis. 2. Case report A 74-year-old man was transferred to our hospital because of progressive anorexia, nausea, vomiting, weight loss, fatigue and
∗ 1
Corresponding author. Tel.: +86 22 60362497. E-mail address: [email protected] (J. Wang). Contributed equally for the paper.
1571-4675/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrex.2008.06.010
pigmentation for 2 months. Bilateral huge hypoechoic adrenal masses had been found on abdominal US at other hospital. He denied any abdominal discomfort or symptoms of airway or urinary tract infection. His past history was unremarkable except receiving calcium channel blockers to control hypertension for 10 years. Physical examinations on admission revealed a chronically ill patient with a clear consciousness. No palpable mass was found in the abdomen. His vital signs were all within normal limits: body weight 64 kg, blood pressure 120/78 mmHg, respiratory rate 18/min, pulse rate 67/min, and body temperature 37.0 ◦ C. Pertinent physical findings revealed some hyperpigmentation spots over his lower lip. There was no superficial lymphadenopathy or organomegaly. Initial laboratory findings revealed a normal full blood count and erythrocyte sedimentation rate. Serum tumor markers including carcinoembryonic antigen (CEA), ␣-fetoprotein (AFP) and prostatic specific antigen (PSA) were all within normal limits. A serum biochemistry profile disclosed a sodium concentration of 125 mmol/L (normal range: 135–145 mmol/L), potassium concentration of 5.8 mmol/L (normal range: 3.5–5.5 mmol/L), serum lactate dehydrogenase 586 g/dL (normal range: 109–245 g/dL), and 2 microglobulin 4.3 mg/L (normal range: 0.91–2.2 mg/L). PAI was suspected due to the complaint of progressive anorexia, nausea, vomiting, weight loss, fatigue, pigmentation and the findings of hyponatremia and hyperkalemia. It was confirmed
e84
J. Wang et al. / European Journal of Radiology Extra 68 (2008) e83–e87
Fig. 1. (a) Plain abdominal CT scan shows large, irregular, homogeneous soft tissue masses in bilateral adrenal area, normal bilateral adrenal glands could not be seen. (b) and (c) Axial PET scan and PET–CT fusion image (axial view of same level as CT scan) shows intense FDG uptake in bilateral adrenal masses.
by the findings of a low serum cortisol level of 3.1 g/dL at 06:30 a.m. (normal range: 5–17.5 g/dL), a high ACTH level of 768.8 pg/mL (normal range: 0–46 pg/mL), and a low cortisol level of 13.1 g/dL 1 h after the cosyntropin stimulation test. Further findings including urine vanillymandelic acid and serum aldosterone in supine/supine position were all within normal range. Immediately he received hormone replacement therapy with intravenous hydrocortisone 100 mg every 8 h daily and the patient’s general conditions improved rapidly while his diagnostic workup proceeded. For further diagnosis, abdominal plain computed tomography (CT) was performed and it showed bilateral adrenal massive homogeneous soft tissue masses measuring 5.3 cm × 5.1 cm × 5.9 cm on the right and 7.7 cm × 6.1 cm × 4.2 cm on the left (Fig. 1a). No other abdominal lesions or lymphadenopathy were detected. Plain CT of the chest showed no lymphadenopathy or any pulmonary lesions. Based on the CT findings, a provisional diagnosis of adrenal metastases or possible lymphomatous involvement of the adrenal glands was made. A whole-body 18 F-FDG PET/CT scan was acquired for further staging of the disease and it showed intense 18 F-FDG accumulation in bilateral adrenal glands (Fig. 1b and c). There was no abnormal 18 F-FDG uptake in the rest of the body (Fig. 2a). Based on the localized intense FDG uptake only in the adrenal glands, a diagnosis of primary bilateral adrenal lymphoma was made. CT-guided core biopsy of the left adrenal mass was performed in order to determine the nature of the tumor and it revealed non-Hodgkin lymphoma (Fig. 3a). Immunostaining for common leukocyte antigen showed B-cell marker (CD20) positive (Fig. 3b) and T-cell marker (CD45RO) negative (Fig. 3c). Bone marrow aspiration and cerebrospinal fluid analysis were negative for lymphomatous cells. Primary bilateral adrenal lymphoma with PAI was diagnosed. The patient was given four cycles of cyclophosphamide, vincristine, daunorubicin, and prednisolone (CHOP)-based chemotherapy. Unfortunately he died of progression of PAL and CNS involvement 6 months later (Fig. 4).
3. Discussion PAL is extremely uncommon. A diagnosis of PAL should be considered in a patient presenting with bilateral adrenal masses without nodal involvement and absence of a leukemic blood picture as well as other organs involvement [3,4]. Because of the
rarity of this disease, the clinical and pathologic features, imaging characteristic, therapeutic regimen and prognosis have not been defined in detail. We reviewed the literature of the reported cases in detail, which may help to understand this disease better. 3.1. Clinical features PAL commonly affects elderly men, with a median age of 65 years old and a male to female ratio of about 2.1–7:13. Common symptoms include fever, weight loss, and abdominal/lumbar pain, which are nonspecific [3]. Some cases were incidentally discovered by abdominal US or CT scan. Approximately 50–70% of patients with bilateral PAL have clinical or biochemical evidence of PAI [2], as seen in our patient. The clinical symptoms of PAI include fatigue, anorexia, weight loss, postural hypotension and pigmentation on skin or mucous membrane, and so on. And the laboratory findings of PAI include hyponatremia, hyperkalemia, low plasma/urinary cortisol, and the absence of a plasma cortisol response to tetracosactrin, etc. Because more than 90% of the bilateral adrenal glands are destroyed before clinical symptoms or laboratory findings of PAI develop, it is not commonly seen in unilateral PAL or in the early stage of bilateral PAL [5]. The diffuse type of infiltration and the complete destruction of the architecture of the adrenal glands by the tumor may be responsible for the finding of PAI in patient with PAL. And literature review suggests that there is no correlation between the size of the tumor and PAI [4]. 3.2. Histopathology The etiology of PAL is still not clear currently. The most common hypothesis for the origin of this disease is hematopoietic tissue resting in the adrenal glands akin to adrenal myelolipoma [4]. Another author believes that the adrenal glands in man contain no lymphoid tissue, and the follicle centre cell origin of PAL suggests the tumor may have risen on a background of previous autoimmune adrenalitis, consistent with the finding of PAI [6]. The confirmatory diagnosis of PAL is based on pathological examination. Ultrasound- or CT-guided core biopsy or surgical biopsy through laparoscopy or laparotomy is required to definite histopathological diagnosis. Histologically, the most common type of PAL is diffuse large B cell. Other less common histological types are mixed large and small cell, small noncleaved cell,
J. Wang et al. / European Journal of Radiology Extra 68 (2008) e83–e87
e85
Fig. 2. (a) Whole-body PET MIP images (coronal views) show intense 18 F-FDG uptake in bilateral adrenal masses. There are no other areas of abnormal 18 F-FDG uptake. These findings are suggestive of primary adrenal lymphoma.
Fig. 3. Biopsy specimen of the left adrenal gland stained with hematoxylin and eosin shows diffuse proliferation of large atypical lymphoid cells replacing normal adrenal tissue. (a, 200×). Immunostaining for common leukocyte antigen shows B-cell marker (CD20) positive (b, 200×) and T-cell marker (CD45RO) negative (c, 200×).
e86
J. Wang et al. / European Journal of Radiology Extra 68 (2008) e83–e87
Fig. 4. Axial (a) and coronal (b) contrast-enhanced T1 -weighted MR images show a large intensely enhanced right frontal mass with surrounding edema.
undifferentiated, and others [2]. Based on immunostaining, the majority of PAL originated from B cell, and only 10 cases of T-cell origin were reported so far [2,3]. 3.3. Diagnosis and differential diagnosis The increasing use of US, CT, and MRI renders a large number of incidentally discovered adrenal masses. Therefore, it is important to differentiate benign from malignant adrenal masses and diagnose PAL during its early stages. PAL usually presents with bilateral adrenal masses (73%) with moderate to severe adrenal enlargement (sizes ranging from 4 to 17 cm2 .) Kumar reviewed the 70 patients with PAL, 56 had bilateral adrenal involvement [3]. Most cases appear as complex masses with a variable density on plain CT scan. In some cases, CT has demonstrated a cystic appearance due to necrosis, whereas a few cases have also shown a homogenous density. PAL was described to be low signal intensity on T1 -weighted imaging and high signal intensity with areas of mixed signal intensity on T2 -weighted imaging. On MR chemical shift imaging, signal intensity of PAL does not decrease on out-phase images. On contrast enhancement examination, PAL commonly enhances slightly and heterogeneously. PAL should be differentiated from other adrenal masses, including metastases, tuberculosis, pheochromocytoma, nonfunctioning adenoma, adrenal cortical carcinoma, and others. Patients with adrenal tuberculosis commonly have a long history of years or decades. The lesions generally appear as heterogeneously low signal intensity masses on T2 -weighted imaging because of caseate, and calcification can be seen on plain CT. Nonfunctioning adenomas are rich of lipid, plain CT demonstrates low-density masses, contrast material washes out rapidly on dynamic enhanced CT/MR scan. On MR chemical shift imaging, signal intensity of the lesions decreases obviously on out-phase images by cancellation of the signal from fat and water, which is a specific characteristic of adenomas. Generally, adenomas could be able to be differentiated from other adrenal masses easily [7].
Pheochromocytomas secrete a great deal of catecholamines which cause specific manifestations and laboratory findings. The masses demonstrate obviously high signal intensity on T2 -weighted imaging. Contrast-enhanced T1 -weighted imaging shows that the parenchyma of the masses is enhanced obviously. Definite diagnosis could be made easily by clinical presentations and imaging findings [8]. Adrenal cortical carcinoma is usually big in size. Hemorrhage, necrosis, cyst, and calcification are common. Vessels adjacent to the tumor are always encased or invaded [9]. Both adrenal metastases and PAL are bilateral adrenal soft tissue masses with similar appearance on US, CT, and MRI. It is difficult to distinguish between them. Adrenal metastases were mostly from lung cancers. CT with high-resolution anatomic imaging technique is used as the first-line diagnostic modality for screening and determining the nature of the adrenal lesions. Signal intensities on MR T2 -weighted imaging and chemical shift sequences are most commonly used to differentiate benign from malignant adrenal masses. Unlike US, CT and MRI, 18 F-FDG PET/CT is based on increased glucose metabolism in malignant lesions. Recently, 18 F-FDG PET/CT has shown great potential in differentiating malignant from benign adrenal lesions. Erasmus et al. evaluated 33 adrenal masses in 27 patients with bronchogenic carcinomas. The sensitivity for detecting metastasis was 100% and the specificity was 80% [10]. 18 F-FDG PET/CT can simultaneously obtain characteristics of metabolism and morphology of the lesions, whole-body 18 F-FDG PET/CT scan can identify whether the adrenal malignant masses are metastatic and detect their primary malignancies. Because most PAL have adrenal involvement only, without any lymph nodes or organs involvement, it demonstrates intense 18 F-FDG uptake only in bilateral adrenal masses. In our patient, whole-body 18 F-FDG PET/CT demonstrated intense 18 F-FDG uptake in bilateral adrenal masses and no evidence of abnormal uptake in extraadrenal regions. Because 18 F-FDG is taken up only by viable/residual tumor and is not taken up by necrotic tumor and fibrosis, it also has an important role in staging, monitoring response to treatment, and detecting recurrence of PAL [3].
J. Wang et al. / European Journal of Radiology Extra 68 (2008) e83–e87
3.4. Treatment and prognosis Although most patients with PAL have a very poor prognosis, early diagnosis and treatment can prolong disease-free survival in patients. Treatment of PAL is similar to treatment of other types of lymphoma. The therapeutic modalities include bilateral adrenalectomy, multiagent chemotherapy, radiotherapy, or a combination of them [2]. Since adrenal insufficiency crisis leads to severe life-threatening consequences, immediate hormone replacement therapy must be given if PAI is suspected. The regimens of combination chemotherapy that have been used include CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), CHO and prednisolone, CVP (cyclophosphamide, vincristine, and prednisone), and MACOP (adding methotrexate and bleomycin) with varying success [3]. Some investigators suggest that surgical debulking with subsequent chemotherapy is the best approach [4]. Radiation seems to be ineffective in those patients [11,12]. Despite every effort in treatment, these lesions have poor prognosis and patients usually die within 1 year [4,13]. They frequently died of severe infection, pulmonary embolism, or NHL progression [14]. Several inauspicious prognostic factors for PAL are old age, initial presentation with adrenal insufficiency, large tumor burden, elevated serum lactic dehydrogenase, and 2 -microglobulin, and involvement of other organs during following up [4]. Concerning our patient, all unfavourable prognostic factors mentioned above were present. Combination chemotherapy was unsuccessful and our patient died of CNS involvement 6 months later. It is interesting to note that PAL exhibits a propensity for late CNS involvement. And this observation raises the possibility that it will be useful in future clinical trials to add CNS prophylaxis in the treatment of patients with PAL [15]. 4. Conclusions PAL is a very rare but interesting disease entity. Bilateral adrenal masses should raise the suspicion of PAL, especially in patients with clinical or laboratory features of PAI. Whole-body 18 F-FDG-PET/CT could reveal the masses with characteristic
e87
manifestations, it is of great value in differentiating adrenal metastases from PAL, and it also play an important role for staging, and evaluation of the response to treatment in this disease. References [1] Rosenberg SA, Diamond HD, Jaslowitz B, et al. Lymphosarcoma: a review of 1269 cases. Medicine 1961;40:31–84. [2] Tomoyose T, Nagasaki A, Uchihara JN, et al. Primary adrenal adult Tcell leukemia/lymphoma: a case report and review of the literature. Am J Hematol 2007;82:748–52. [3] Kumar R, Xiu Y, Mavi A, et al. FDG-PET imaging in primary bilateral adrenal lymphoma: a case report and review of the literature. Clin Nucl Med 2005;30(4):222–30. [4] Dutta P, Bhansali A, Venkatesan R, et al. Primary adrenal lymphoma. Endocrinologist 2005;15(6):340–2. [5] Diamanti-Kandarakis E, Chatzismalis P, Economou F, et al. Primary adrenal lymphoma presented with adrenal insufficiency. Hormones (Athens) 2004;3(1):68–73. [6] Ellis RD, Read D. Bilateral adrenal non-Hodgkin’s lymphoma with adrenal insufficiency. Postgrad Med J 2000;76(898):508–9. [7] Wang WH, Bai RJ, Sun HR, et al. Evaluation of dynamic enhanced CT scanning in the differentiation of adrenal adenoma with non-adenoma. J Clin Radiol 2003;22:475–8. [8] Sun HR, Bai RJ, Wu EH. MR imaging of the pheochromocytoma. J Clin Radiol 2000;19:155–8. [9] Ribeiro J, Ribeiro RC, Fletcher BD. Imaging findings in pediatric adrenocortical carcinoma. Pediatr Radiol 2000;30:45–51. [10] Erasmus JJ, Patz Jr EF, McAdams HP, et al. Evaluation of adrenal masses in patients with bronchogenic carcinoma using 18F-fluorodeoxyglucose positron emission tomography. AJR 1997;168:1357–60. [11] Wang J, Sun NC, Renslo R, et al. Clinically silent primary adrenal lymphoma: a case report and review of the literature. Am J Hematol 1998;58(2):130–6. [12] Sasagawa I, Sadamori N, Itoyama T, et al. Primary adrenal lymphoma with chromosomal abnormalities. Acta Haematol 1995;94:156–62. [13] Barbaros U, Erbil Y, Bozbora A, et al. Primary adrenal lymphoma presenting as bilateral adrenal masses. Endocrinologist 2006;16(2): 75–6. [14] Hsu CW, Ho CL, Sheu WH, et al. Adrenal insufficiency caused by primary aggressive non-Hodgkin’s lymphoma of bilateral adrenal glands: report of a case and literature review. Ann Hematol 1999;78(3):151–4. [15] Mantzios G, Tsirigotis P, Veliou F, et al. Primary adrenal lymphoma presenting as Addison’s disease: case report and review of the literature. Ann Hematol 2004;83(7):460–3.