NK/T-cell lymphoma of bilateral adrenal glands in a patient with pyothorax

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 [1]. 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 [2]. 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.

At the initial presentation, a large cystic lesion, pleural fluid and bilateral independent adrenal tumors (55 mm x 31 mm on the right side and 57 mm x 32 mm on the left side) were detected by thoracic and abdominal computed tomography (CT) scans, respectively (Figure 1A, 1B). Tuberculosis bacterium was not detected in the sputum using PCR. Serum LDH was elevated to 1,038 U/L. Although use of warfarin was immediately stopped and coagulation therapy was performed using carbazochrome sodium sulfonate hydrate and tranexamic acid, the symptoms were not improved. Nineteen days after initial presentation, bloody sputum was successfully decreased by bronchial artery embolization. The next day, however, hyponatremia (Na: 113 mEq/L) occurred, followed by increases of serum IL-2R (1,185 U/mL) and serum NSE (117.9 ng/mL). An abdominal CT scan showed an increase in sizes of the bilateral adrenal tumor masses (57 mm x 54 mm on the right side and 74 mm x 45 mm on the left side). Two days later, under the diagnosis of adrenal failure caused by the tumors, augmentation of corticosteroid and correction of hyponatremia were started. Serum concentrations of cortisol, sodium and potassium were controlled well. However, seven days after the initiation of treatment, the patient had symptoms of general malaise and chest pain as well as atrial fibrillation with a rapid ventricular response. Serum LDH was increased to 3,650 U/L from 1,038 U/L at the initial presentation. Despite administration of anti-arrhythmic agents, blood pressure decreased to less than 70 mmHg, and then cyanosis and hypouresis occurred. Thirty-three days after initial presentation (11 days after initiation of therapy for adrenal failure), the patient died. Autopsy was performed five hours after death.

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).

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 [14]. 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 [15]. 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 [16].

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 [17].

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 [8]. 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 [5].

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.