The Turkish Journal of Gastroenterology
Turk J Gastroenterol 2011; 22 (6): 643-647
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|Primary adrenal non-Hodgkin’s lymphoma:
Report of two cases
|Ali EZER1, Alper PARLAKGÜMÜÞ1, N. Emrah KOCER1, 2, Tamer ÇOLAKOÐLU1, G. Nihal NURSAL1, 3,
|Departments of 1General Surgery, 2Pathology and 3Nuclear Medicine, Baþkent University, School of Medicine, Ankara
|Keywords: Primary adrenal lymphoma, adrenal mass, non-Hodgkin lymphoma.
Primary adrenal lymphoma is very rare. It is characterized by a high incidence of bilateral adrenal involvement of diffuse large Bcell
lymphoma. It can be diagnosed with endocrine evaluation, imaging studies and histopathological examination. We present two
cases of primary adrenal lymphoma. One is a 74-year-old female patient with right primary adrenal lymphoma and the other is a
62-year-old male patient with bilateral primary adrenal lymphoma associated with normal adrenal function. In both cases, radiological
features led to an initial misdiagnosis. The surgical exploration demonstrated masses invading the retroperitoneal space,
and the biopsy revealed diffuse large B-cell lymphoma. In conclusion, primary adrenal lymphoma should be kept in mind in the differential
diagnosis of adrenal masses. In cases of suspicious primary adrenal lymphoma, percutaneous computerized tomographyor
ultrasonography-guided needle biopsy can help to avoid unnecessary surgeries.
Autopsy studies have revealed that 25% of the patients
with non-Hodgkin’s lymphoma (NHL) have involvement
of the adrenal gland during the course of
their disease (1,2). However, NHL originating from
the endocrine glands accounts for only 3% of extranodal
malignant lymphomas and usually appears
only in the thyroid gland. Therefore, primary adrenal
malignant lymphoma is rare (3). It is difficult to
diagnose adrenal lymphoma before surgery due to
its nonspecific clinical appearance and imaging findings.
Histologically, diffuse large B-cell lymphoma
is the most frequent type of primary adrenal
lymphomas (PALs) (4). Most patients with PAL have
bilateral disease on admission and most of them
have adrenal insufficiency subsequent to destruction
of more than 90% of adrenal parenchyma by the
disease (5). We present two cases of primary adrenal
NHL associated with normal adrenal function.
A 62-year-old man was referred to our hospital
with a two-week history of progressive anorexia,
nausea, vomiting, weight loss, and fatigue. His
medical history was unremarkable. There was no
palpable mass in the abdomen. His vital signs were
all within normal limits: body weight 61 kg, blood
pressure 120/70 mmHg, respiratory rate
20/min, pulse rate 74/min, and body temperature
36.8°C. There was no superficial lymphadenopathy
or organomegaly. Initial laboratory findings
revealed a normal complete blood count, but erythrocyte
sedimentation rate was 59 mm/hour (normal
range: 0-20 mm/h) and C-reactive protein
(CRP) was 41 mg/L (normal range: 0-6 mg/L). A
serum biochemistry profile was all within normal
limits except lactate dehydrogenase (LDH) of 306
IU/L (100-240). Further findings including serum
cortisol level, urine vanillylmandelic acid and serum
aldosterone were all within normal range.
For further diagnosis, abdominal plain computed
tomography (CT) was performed and showed bilateral
adrenal massive homogeneous soft tissue
masses measuring 9.7 cm x 6.1 cm x 5.3 cm on the
right and 11.2 cm x 5.6 cm x 6.1 cm on the left. No
other abdominal lesions or lymphadenopathy was
detected. Since radiological findings were not suggestive
of lymphoma, the patient underwent surgery.
The masses in both adrenal glands were found
to invade the neighboring organs and vessels
on operation and could not be resected. Biopsy was
obtained from both adrenal glands. Histopathological
examination revealed diffuse proliferation of
atypical cells with large hyperchromatic nuclei
and narrow eosinophilic cytoplasm. Infiltration
extended to the adipose tissue. In the immunohistochemical
study, tumor cells were positive for leukocyte
common antigene (LCA), CD20, CD79a,
and Pax-5, while CD3 and CD30 were negative
(Figure 1a, 1b). There was no bone marrow involvement.
With the absence of any lymphadenopathy
elsewhere or any other site of involvement,
the patient was accepted and treated as PAL. Before
the therapy began, positron emission tomography
(PET)-CT was obtained (Figure 1c). He was
administered R-CHOP chemotherapy, including
rituximab (375 mg/m2 intravenous [IV]), cyclophosphamide
(750 mg/m2 IV), doxorubicin (50
mg/m2 IV), and vincristine (1.4 mg/m2 IV) on day 1,
and prednisolone (100 mg P.O.) on days 1-5 every
3 weeks. PET-CT scan performed after administration
of six cycles of R-CHOP chemotherapy showed
that the previous adrenal masses had nearly
disappeared (Figure 1d).
Computed tomography (CT) of the thorax and the
abdomen in the ninth month demonstrated multiple
masses in both suprarenal glands, left paraaortic,
perirenal, perisplenic, and subdiaphragmatic
regions, lungs, and liver. Bone marrow aspiration
biopsy showed atypical lymphocyte infiltration.
The patient received a total of eight cycles of
chemotherapy. Since suprarenal failure occurred,
the cortisone dose was increased. The patient died
of sepsis in the eleventh month.
A 74-year-old woman was referred to our hospital
with a three-week history of abdominal pain, anorexia,
nausea, vomiting, and fatigue. Abdominal
ultrasonography (US) showed right hypoechoic adrenal
masses. Upper abdominal magnetic resonance
imagine (MRI), performed for further diagnosis,
showed right adrenal homogeneous soft tissue
mass 7 x 7 x 6 cm in size. There were no other
abdominal lesions or lymphadenopathy. The patient
had a five-year history of diabetes mellitus
and underwent coronary by-pass seven years ago.
No palpable mass was found in the abdomen. In
the initial laboratory investigations, complete blood
count was normal, but erythrocyte sedimentation
rate was 50 mm/h (normal range: 0–20 mm/h).
A serum biochemistry profile was all within normal
limits except LDH of 573 IU/L and albumin of
3.17 g/dl. Further findings including serum cortisol
level, urine vanillylmandelic acid and serum
aldosterone were all within normal ranges.
The mass in the right suprarenal region was found
to invade the vena cava inferior, duodenum, aorta,
and liver. It was considered unresectable. Biopsy
was obtained. Pathological examination revealed
NHL (diffuse B-cell lymphoma with CD20 positivity)
(Figure 2a, 2b). Thoracic CT scan did not
show any lymph nodes. Bone marrow aspiration
biopsy eliminated a secondary lymphoma. Before
the therapy began, PET-CT images were obtained
(Figure 2c). She received R-CHOP chemotherapy,
including rituximab (375 mg/m2 IV), cyclophosphamide
(750 mg/m2 IV), doxorubicin (50 mg/m2 IV),
and vincristine (1.4 mg/m2 IV) on day 1, and prednisolone
(100 mg P.O.) on days 1-5 every 3 weeks.
After six cycles of R-CHOP chemotherapy were
completed, there was no evidence of tumor on follow-
up fluorodeoxyglucose (FDG)-PET scans (Figure 2d). To date, the patient has been followed regularly
in our outpatient clinic for the past 10
months, with no evidence of tumor recurrence.
Primary adrenal non-Hodgkin’s lymphoma (PAL)
is a rare neoplastic disease, and there have been
approximately 116 reports about it in the literature
so far (4). It has a very poor prognosis, clinical
features and radiological/laboratory investigations
may not facilitate a firm diagnosis of the disease,
and there is no clear treatment protocol.
Although features of PAL have not been described
well, it usually presents with bilateral, large masses,
sometimes accompanied by adrenal insufficiency
or hypercalcemia. The disease most frequently
affects older men. In fact, the mean age at diagnosis
is 68 years and the male-to-female ratio is
2.2:1. Among clinical symptoms of PAL are fever,
weight loss, local pain, and symptoms of adrenal
insufficiency (6). Immune dysfunction may predispose
to PAL in some patients (7). Wang et al. (8),
in their review of 55 PAL patients, showed that 8
(15%) had a concurrent or past history of carcinoma,
2 (4%) had human immunodeficiency virus
(HIV) infection, and 7 (13%) had concomitant autoimmune
disease. They also noted that the most
frequent type of PAL is diffuse large B-cell on histological
The increase in the use of US, CT and MRI has resulted
in a large number of incidentally discovered
adrenal masses. Therefore, differentiation of benign
from malignant adrenal masses and diagnosis
of PAL during its early stages are of importance.
Although imaging modalities help in the diagnosis
of adrenal masses, making a firm diagnosis
is difficult due to nonspecific findings, especially
when there is unilateral involvement. Only pathological
examination confirms the diagnosis of PAL.
Ultrasound- or CT-guided core biopsy or surgical
biopsy through laparoscopy or laparotomy is necessary
to make a definitive histopathological diagnosis.
In the event of suspected PAL, Tru-cut biopsy
or fine needle biopsy can obviate unnecessary
surgery for biopsy.
Adrenal insufficiency can be due to infiltration of
malignant cells into the adrenal glands. Approximately
90% of the adrenal cortex is supposed to be
destructed for adrenal insufficiency to become apparent.
Therefore, not all cases of neoplasms involving
the adrenal glands result in adrenal insufficiency
(9). Adrenal insufficiency crisis causes severe
life-threatening consequences. Therefore, immediate
hormone replacement therapy must be given
when primary adrenal insufficiency is suspected.
Although adrenal insufficiency may not appear
at the beginning, it may develop in later stages,
and surgeons should be alert for acute adrenal insufficiency.
In the presented Case 1, there was no
sign of adrenal insufficiency initially in the adrenal
function test, but over the course of the treatment
the patient developed marked general weakness
and lethargy, and the laboratory study showed
hyponatremia (to 126 mEq/L) and hyperkalemia
(to 5.9 mEq/L). We thought that these manifestations
were likely due to adrenal insufficiency,
and they were rapidly corrected with continuous
small doses of prednisolone.
It has been reported in the literature that advanced
age, primary adrenal insufficiency as an initial
sign, tumor size, LDH level, and involvement of other
organs can be poor prognostic indicators (10).
Since PAL is a rare entity, therapeutic regimens
have not been defined in detail, and most patients
are treated with regimens similar to those used for
other types of lymphoma. Among the treatment alternatives
used are surgery, combination chemotherapy
and radiation. PAL is usually lethal and
early death may occur during chemotherapy. There
have been a few cases of complete and partial
remissions with a longer mean duration of survival
(5,6). The cases presented here received rituximab-
CHOP chemotherapy, which was used to treat
PAL by Kim et al. (11). Case 1 showed almost
complete remission following the sixth cycle. However,
the disease showed an invasive involvement
in the ninth month. The patient died of sepsis
after receiving the eighth cycle of chemotherapy
in the eleventh month. Case 2 showed complete
remission following six cycles of chemotherapy.
Follow-up PET-CT did not indicate any involvement.
The disease progression differed between
these two cases despite their having received
the same chemotherapy. Based on only two cases,
it can be difficult to make comments. However, it
seems that cases of unilateral adrenal lymphoma
may have longer survival. Poor prognosis in the
case of bilateral adrenal lymphoma can be attributed
to adrenal insufficiency.
Positron emission tomography (PET)-CT has been
widely employed in recent years. CT and MRI are
different from FDG-PET in that the latter is based
on increased glucose metabolism in malignant lesions.
PET-CT offers a powerful combination of
functional and attenuation information to reveal
characteristics of adrenal lesions (12).
In conclusion, PAL should be kept in mind in the
differential diagnosis of patients presenting with
unilateral or bilateral huge adrenal malignant
masses without nodal involvement in the absence
of other malignancies. In addition, fine needle biopsy
may help to avoid unnecessary surgery. Surgeons
should be cautious regarding adrenal insufficiency
crisis, which is likely to arise in the followup
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