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Imaging of F-18 FDG PET/CT and follow up of bilateral invasive adrenal diffuse large B cell lymphoma mimicking adrenocortical carcinoma

Although secondary involvement of the adrenal gland has been reported to occur in up to 25% of patients with non-Hodgkin’s lymphoma (NHL), primary adrenal lymphomas (PALs) represent only about 3% of primary extranodal lymphomas. The primary diagnostic modalities include computed tomography (CT), ultrasonography, and magnetic resonance imaging (MRI). Due to the rarity of PAL, there have been only several two case reports of F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) as the staging workup. Here, we describe a patient with primary bilateral adrenal diffuse large B-cell lymphoma initially mimicking adrenocortical carcinoma (ACC) on CT. We achieved complete remission after treatment with rituximab (R)-CHOP and identified an early response to this therapeutic regimen via interim F-18 FDG PET/CT.

one-month history of epigastric pain and dyspepsia. He was diagnosed with hypertension eight years previously, and consequently was being treated with oral antihypertensive medication.
Five years earlier, he had been diagnosed with seropositive rheumatoid arthritis and Raynaud's syndrome, and had used non-steroidal anti-inflammatory drugs (NSAIDs) as needed. At admission, his blood pressure was 120/80 mmHg, his pulse rate was 89 BPM, and his body temperature was 36.2℃. He had ingested alcohol for 20 years and did not smoke. On physical examination, he reported radiating pain in his back.
A complete blood count showed a hemoglobin level of 14.6 g/dL, hematocrit of 43.2%, white blood cell count of 5,290/mL, and platelet count of 230,000 /µL. To rule out pain originating from his pancreas, amylase, lipase, and CA 19-9 testing were performed and found to be within normal limits. His sodium level was slightly decreased at 136 mM/L (normal range, 138-148 mM/L), but potassium, chloride, and calcium levels were all normal.
Chest radiography was normal with no hilar lymphadenopathy. Abdominopelvic CT (APCT) scans demonstrated large bilateral adrenal masses, which were probably the cause of his radiating back pain. The left adrenal gland measured 5.0 x 6.2 x 6.0 cm and the right adrenal gland measured 3.7 x 5.7 x 5.0 cm. The left adrenal gland mass was heterogeneously enhanced and invaded to the left crus. Another small, enhanced lymph node (LN) measuring 2.0 cm was also noted around the superior pole of the left kidney. The right adrenal gland mass was also heterogeneously enhanced, directly invaded segment 1 (S1) of the liver, and partially invaded the right crus. A 2.8-cm enlarged LN in the retrocaval area and several enlarged LNs with some necrosis in the aortocaval and left paraaortic area were also noted ( Fig. 1).
Laboratory tests to evaluate the bilateral adrenal masses were also performed. Serum β2-microglobulin concentration was slightly increased The findings of the EGD and colonoscopy were also normal. Relying only on laboratory and radiologic findings, we could not differentiate between ACC and PAL. Adjacent organ invasion and heterogeneous enhancement after IV contrast medium was administered suggested a provisional diagnosis of ACC. A CT-guided biopsy of the left adrenal mass was performed for definitive diagnosis. The mass was diagnosed as diffuse large B-cell lymphoma, which was immunohistochemically positive for CD20 but negative for CD3, CD5, CD10, and CD30 ( Fig. 3a, b). The Ki-67 labeling index was about 90% (Fig. 3c). A bone marrow biopsy was negative for lymphomatous involvement. The clinical staging by the Ann Arbor system was IV A and the international prognostic index placed him in the low intermediate risk group.
He was administered R-CHOP chemotherapy, consisting of rituximab (375 mg/m2 IV), cyclo-  2b). After completing six cycles of R-CHOP chemotherapy, the size was even more decreased on CT with no abnormal metabolism noted on F-18 FDG PET/CT (Fig. 2c). This patient continues to be followed up without definitive evidence of recurrence.

DISCUSSION
The differential diagnosis of adrenal tumors includes primary tumors originating from the adre-  type is diffuse large B-cell lymphoma. 2 PAL is most common in elderly men; the mean age at diagnosis is 68 years and the male-to-female ratio is 2.2:1.
Clinical symptoms of PAL include fever, weight loss, localized pain, and symptoms of adrenal insufficiency. 3 Immune dysfunction may be a predisposing factor in some patients. 4  There has been a lack of uniform consensus on the definition of PAL in the past. 12 Recently, however, there have been efforts to better define this disease entity. 13  In addition, the previously reported cases only showed adrenal involvement without other areas of abnormal uptake. Unfortunately, both ACC and PAL are highly FDG-avid so we cannot differentiate these two malignant tumors by F-18 FDG PET/CT; however, F-18 FDG PET/CT can reveal staging, local recurrence, and the result of treatment follow-up. 15 Our case showed successful treatment response, with decreased FDG avidity in adrenal lesions and metastatic lymph nodes, and the involved adrenal glands returning to their original size and configuration.
In conclusion, PAL is a very rare entity, so only limited cases using F-18 FDG PET/CT have been reported. Our patient showed highly FDG-avid PAL mimicking adrenocortical carcinoma before biopsy. He had nearly complete remission after three cycles of R-CHOP, and the size was even more decreased after six cycles of R-CHOP. These results suggest the possibility for evaluation of early responsiveness of chemotherapy using F-18 FDG PET/CT.