Primary adrenal lymphoma is rare, but clinically important. We report a unique case of adrenal lymphoma which showed extensive cystic change mimicking a pseudocyst. Seventy-three-year-old man visited our hospital for healthcare check-up, and was found to have a large adrenal cystic mass. He was received adrenalectomy on the impression of an adrenal pseudocyst. On gross examination, the mass was a unilocular cyst with no solid mass formation. Microscopically, the cyst wall had no epithelial lining, but was infiltrated by some atypical large lymphoid tumor cells. The cystic space was filled with coagulative necrotic material with the tumor cell shadow. The most of the tumor cells expressed leukocyte common antigen, CD20, PAX5, Ki-67, and Epstein-Barr virus (EBV)-encoded RNA, which was consistent with EBV-positive diffuse large B-cell lymphoma of the elderly. No extra-adrenal involvement was observed in imaging studies. We concluded that primary adrenal lymphoma should be considered as a rare but important cause of adrenal cysts.
Adrenal cyst is rare and usually an incidentally detected asymptomatic condition. Most adrenal cysts are benign. The presence of a solid portion can be evidence for the suspicion of malignancy. Therefore, an entire cystic mass of an adrenal gland might be assumed benign. However, final diagnosis can only be made after surgical excision.
Primary adrenal lymphoma is rare, compared to secondary involvement of extra-adrenal lymphomas or other types of malignancies in adrenal glands. Most of the adrenal malignant tumors or adrenal lymphomas were reported to be entirely solid, or to harbor a considerable amount of solid portion.[3-5] Here, we report a unique case of a 73-year-old man with an entirely cystic adrenal mass detected on computed tomography (CT), and finally diagnosed as Epstein–Barr virus (EBV)-positive diffuse large B cell lymphoma of the elderly after surgical excision.
A 73-year-old man was hospitalized for further examination of left adrenal cystic mass detected in healthcare check-up. He was previously healthy, except for hypertension on medication. One year ago, he had facial flushing, abdominal distention and dyspnea on exertion, which lead him to the healthcare check-up. On CT scan, an 8.0 × 7.3 cm-sized, left adrenal cystic mass with peripheral wall enhancement and calcification was incidentally observed (Fig. 1a). Radiologic differential diagnosis included pseudocyst with hematoma, adrenal complicated cyst, and pheochromocytoma with extensive cystic change.
Physical examination revealed no other remarkable findings including fever, night sweat, weight loss, anorexia, rash, pruritus, malaise or skin hyperpigmentation. On complete blood cell count with differential count, no abnormal finding was observed. Blood or urine hormone levels including metanephrine, norepinephrine, cortisol, aldosterone, and adrenocorticotropic hormone were not remarkable. Alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19–9 levels on serum were within normal limits.
Laparoscopic adrenalectomy was performed to rule out adrenal cystic tumor. On surgical field, a well-demarcated round cystic mass in left adrenal gland was observed with adhesion to kidney and adjacent fat tissue. Intraoperative aspiration of cystic content showed yellowish pus-like material. Postoperative impression was pseudocyst.
Gross examination revealed well-defined unilocular cyst (Fig. 1b,c). The cystic space was filled with yellowish necrotic material. The cyst wall was irregular in thickness, and adhered to adjacent soft tissue. Histologic sections revealed diffuse necrosis with tumor cell shadow and only a small number of viable atypical tumor cells (Fig. 2a). The tumor cells had high nuclear cytoplasmic ratio, coarse chromatin, occasional mitosis and some prominent large, centrally located, eosinophilic nucleoli. Immunohistochemical studies showed that leukocyte common antigen, CD20, CD79a, and PAX5 were positive in large atypical cells, whereas pan-cytokeratin, CD3, CD4, and CD8 were negative. Ki-67 proliferation index was more than 90% in viable tumor cells. EBV in situ hybridization for EBV-encoded RNA also showed diffuse positivity in most of the viable tumor cells (Fig. 2b–d). These findings were compatible with EBV-positive diffuse large B cell lymphoma of the elderly, which was newly described in World Health Organization (WHO) classification in 2008.
Additional studies including positron emission tomography-CT, bone marrow biopsy showed no other involvement of lymphoma with normal levels of lactate dehydrogenase on serum. The patient received four cycles of chemotherapy with the rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in the state of no measurable disease, and was then lost to follow-up 4 months after diagnosis with no evidence of recurrence.
Most adrenal cysts are benign. They are usually incidentally detected. Clinically, how large the solid part is an important clue to consider the possibility of adrenal malignancies in imaging studies or operation findings, in contrast to adrenal non-neoplastic cysts or benign neoplasm. Malignancies presenting as adrenal cysts are very rare. Most adrenal cysts are pseudocysts, endothelial cysts, and epithelial cysts. Pseudocysts are usually large unilocular cysts, with walls composed of dense, fibrous connective tissue, devoid of a recognizable endothelial layer. The walls are usually 1–5 mm thick, but may be up to 3 cm in rare cases. Therefore, the present case is a unique clinical situation because malignant lymphoma presented with an entirely cystic lesion mimicking pseudocyst. This case emphasizes the importance of clinical suspicion and surgical excision to confirm the diagnosis for adrenal cysts.
Malignant tumor generally harbors highly active proliferative capacity, leading to a solid mass formation. However, extensive central necrosis caused by rapid tumor growth far exceeding the range of vascular supply might lead to the formation of an entirely cystic lesion. In the present case, extreme central necrosis with an irregular wall masqueraded as a pseudocyst in radiologic imaging, surgical field and gross examination. Sufficient sampling of irregular wall tissues in gross section, meticulous microscopic examination with a high level of suspicion, and immunohistochemistry targeting the differentiation of high grade lymphoma could lead to the clear diagnosis of this rare and critical entity.
It is not uncommon for malignant lymphoma to involve adrenal glands. Most adrenal lymphomas are secondary involvement of extra-adrenal lymphoma. Although primary adrenal lymphoma has been regarded as very rare, over 100 cases have been reported on the Pubmed database and 12 published reports on the Koreamed database. Most cases presented with solid heterogeneous or homogeneous adrenal masses or enlargements in image studies, but entirely cystic lesion, as shown in the present case, has not been specifically described.[3, 9-12] The present case might be an extreme end of the spectrum of adrenal lymphoma presentation.
In the reported cases and reviews for primary adrenal lymphoma, most cases were diffuse large B-cell lymphoma of non-germinal center phenotype with bcl-6 gene rearrangement and bilateral adrenal involvement in about 50% to 70%.[13, 14] Interestingly, unilateral cases tended to be left-sided in Mozos’ series, as the present case. Elderly men in their seventh decade were frequently involved with symptoms of fever, weight loss, local pain, and adrenal insufficiency.[13-15] Most patients had stage IE disease without nodal involvement, which makes it difficult to detect the disease.[13, 16] The patients were treated with combination chemotherapy or surgery followed by chemotherapy in addition to corticosteroid replacement.[13, 14]
Although EBV-association was sporadically described in some reports of primary adrenal lymphoma,[11, 13] many clinical reports did not mention it.[3, 10, 12, 14, 17] In 2008 the WHO classification, EBV-positive diffuse large B cell lymphoma of the elderly was described as an independent entity occurring in patients of >50 years and no history of immunodeficiency or prior lymphoma. It frequently involves extranodal sites, and shows poor prognosis.[6, 18] The presence of B symptoms and age >70 were reported as reliable poor prognostic factors, in contrast to international prognostic index or histopathologic subtypes. It might be assumed that high frequency of EBV-association in primary adrenal lymphoma is associated with its predilection to old age.
General prognosis of primary adrenal lymphoma was poor in published cases and reviews.[12, 17, 19] The mean survival ranged from 4 to 34 months with poorer outcomes in cases of chemoresistance.[12, 17, 19] Some clinical factors including old age, adrenal insufficiency at presentation, larger tumor size, higher lactate dehydrogenase level, and extra-adrenal involvement were proposed as indicators for poor prognosis.
In summary, we described a unique case of primary adrenal diffuse large B cell lymphoma, which mimicked an adrenal pseudocyst in imaging study, surgical field and gross examination. The awareness of this rare presentation, as well as careful pathologic examination, would help to make the correct diagnosis and properly manage the patients.