NK/T-cell lymphoma of bilateral adrenal glands in a patient with pyothorax
© Tsukahara et al.; licensee BioMed Central Ltd. 2012
Received: 31 July 2012
Accepted: 26 August 2012
Published: 29 August 2012
Primary lymphoma of adrenal glands is rare, and non-B-cell lymphoma associated with pyothorax is also very rare. Here we report the first autopsy case of non-B-cell lymphoma in bilateral adrenal glands of a 79-year-old woman with pyothorax who had an aggressive clinical course. Immunohistochemically, tumor cells showed CD3+, CD45RO+, CD5-, CD7-, CD4-, CD8-, CD10-, CD20-, CD30-, CD79a-, CD138-, CD56-, granzyme B-, TIA-1+ and ALK-. In addition, tumor cells were strongly EBER1-positive by in situ hybridization. In genomic DNA of tumor cells, T-cell receptor rearrangements were not detected by southern blotting. We finally diagnosed this case as extranodal NK/T-cell lymphoma (nasal type).
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Lymphoma in the adrenal gland is rare, accounting for less than 1% of non-Hodgkin lymphomas. The features of lymphoma in adrenal glands are: (i) peak age of onset is elderly (mean age of 68 years), (ii) bilateral adrenal glands are involved in 60% of cases, (iii) adrenal failure occurs in 66% of cases, (iv) B-cell type is predominantly observed in 90% of cases and (v) prognosis is poor . On the other hand, pyothorax-associated lymphoma, which is also rare (only 2% of patients with pyothorax), commonly shows the following features: (i) pathogenesis is related to pyothorax resulting form tuberculosis and artificial pneumothorax, (ii) common site of the tumor is around the pleural cavity, (iii) period of onset is more than 20 years, (iv) B-cell type is typical and strongly positive for Epstein-Barr virus, and (v) prognosis is poor . However, non-B-cell type lymphoma occurring in adrenal glands of a patient with pyothorax has not been reported.
Here we report the first case of NK/T-cell lymphoma in bilateral adrenal glands in a patient with pyothorax.
A 79-year-old Japanese woman presented with cough and bloody sputum in July 2011. She had been followed since 1990 by a pulmonologist under the diagnosis of chronic pyothorax resulting from tuberculosis, and warfarin had been administered under the diagnosis of atrial fibrillation since 2009. There was no obvious evidence of existing immunodeficiency.
Materials and methods
The autopsy specimen was fixed with 10% buffered formaldehyde and embedded in paraffin. Sections were cut to 2um in thickness and stained with hematoxylin and eosin. Immunohistochemistry was performed using primary antibodies against cytokeratin, vimentin, CD3, CD45RO, CD5, CD7, CD4, CD8, CD10, CD20, CD79a, CD138, CD56, granzyme B, TIA-1, ALK and Ki-67. Ki-67 index was calculated as the ratio of Ki-67-positive cell number to 1,000 tumor cells. In situ hybridization was performed using an anti-sense probe of Epstain-Barr virus (EBV)-encoded RNA 1 (EBER1). Southern blotting for detection of T cell receptor rearrangement in genome DNA of fresh frozen tumor tissue using probes against Jß1 and Jß2 of TCR ß chain and Jγ of TCR γ chain was performed by BML, Inc (Tokyo, Japan).
Histologic and genomic findings
These findings indicated that the tumor had characteristics of peripheral T-cell origin or natural killer (NK)/T-cell origin. The findings of CD3+, CD45RO + and CD56- could indicate peripheral T-cell lymphoma. In contrast, the findings of TIA-1+, EBER1+ and no TCR rearrangement could indicate NK/T-cell lymphoma. Considering the findings of TIA-1+, EBER1+ and no TCR rearrangement, histological type of the tumor was finally diagnosed as CD56-negative extranodal NK/T-cell lymphoma (nasal type).
This is the first case of non-B-cell lymphoma in bilateral adrenal glands in a patient with pyothorax. Tumor cells had the characteristics of both peripheral T-cell lymphoma and NK/T-cell lymphoma. In addition, no tumor lesions were detected around the pyothorax. The tumor showed highly malignant characteristics and showed an aggressive clinical course.
Commonly, adrenal lymphoma shows histological characteristics of B-cell type, mainly diffuse large B-cell lymphoma (DLBCL). Therefore, this case of non-B-cell lymphoma is a rare case. Six cases of peripheral T-cell lymphoma and five cases of NK/T-cell lymphoma have been reported [3, 4]. On the other hand, most pyothorax-associated lymphomas have shown findings of DLBCL occurring in the pleural cavity in addition to strong positive findings of EBV. Nine cases of peripheral T-cell lymphoma associated with pyothorax have been reported [5–13], but no cases of NK/T-cell lymphoma associated with pyothorax have been reported. Only one case of lymphoma occurring in both adrenal glands in a patient with pyothorax has been reported . In that case, a small lesion of lymphoma was also detected around the pyothorax lesion, and the histological type was diagnosed as DLBCL. Thus, non-B-cell lymphoma in adrenal glands in a patient with pyothorax such as the present case is an extremely rare condition.
For differential diagnosis, (i) “peripheral T-cell lymphoma, not otherwise specified”, (ii) “extranodal NK/T-cell lymphoma (nasal type)” and (iii) chronic active Epstein-Barr virus infection (CAEBV) were considered. As described above, the tumor had characteristics of both peripheral T-cell and NK/T-cell lymphomas. The findings of CD3 + CD45RO + CD56- could indicate peripheral T-cell lymphoma. On the other hand, the findings of cytotoxicity-associated molecule TIA-1+, no TCR rearrangement and EBV + could indicate NK/T-cell lymphoma. The present case could not strictly be categorized into either. However, considering the findings of TIA-1+, EBER1+ and no TCR rearrangement, we finally diagnosed this lymphoma as extranodal NK/T-cell lymphoma (nasal type). Recently, Miles et al. reported a case of CD56-negative extranodal NK/T-cell lymphoma . In that case, neoplastic lymphoid cells expressed CD3, TIA-1 and EBER1 with an unusual lack of CD56. In addition, the patient had no typical symptoms of infectious mononucleosis-like illness, hypersensitivity to mosquito bites or other symptoms supporting CAEBV .
Our patient died only 33 days after initial presentation. Generally, the prognosis of both peripheral T-cell lymphoma and NK/T-cell lymphoma is poor. Nonnasal NK/T-cell lymphoma, such as this case, shows an aggressive clinical course. Chen et al. reported that the mean survival period of nonnasal NK/T-cell lymphoma patients was 3.5 months (from 1 week to 3 years) after initial presentation .
In pyothorax-associated lymphoma, transformation of lymphocytes caused by EBV infection and proliferative stimulation via inflammatory cytokines including interleukin-6 in the microenvironment of chronic pyothorax might be the major cause of tumorigenesis . In a narrow sense, the association between pyothorax and the present lymphoma of adrenal glands is still unknown because no tumor lesions were detected in the pleural cavity. Obviously, there is a possibility that the pyothorax existed incidentally. Nevertheless, the possibility that both the long-standing pyothorax lesion and EBV infection contributed to the tumor-initiating ability of tumor cells in the present case cannot be ruled out. Asakage et al. reported a case of EBV-positive T-cell lymphoma of the stomach in a patient with pyothorax. In that patient, no tumors were detected around the pleural cavity, as in the present case .
We have reported the first case of CD56-negative extranodal NK/T-cell lymphoma in bilateral adrenal glands in a patient with pyothorax. The tumor displayed highly malignant characteristics with a distressful clinical course. There is a possibility that chronic inflammation in the microenvironment of the pyothorax and EBV infection contributed to the tumor-initiating ability of tumor cells in the present case.
Written informed consent was obtained from the family of the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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