Open Journal of Pathology, 2012, 2, 107-112
Published Online October 2012 (
Copyright © 2012 SciRes. OJPathology
Primary Adrenal Tumors—Five Years Single Centre
Rashmi D. Patel*, Aruna V. Vanikar, Kamlesh S. Suthar, Kamal V. Kanodia
Department of Pathology, Laboratory Medicine and Transfusion Services and Immunohematology, G. R. Doshi and K. M. Mehta
Institute of Kidney Diseases & Research Centre (IKDRC)-Dr. H. L. Trivedi Institute of Transplantation Sciences (ITS), Civil Hospi-
tal Campus, Ahmedabad, India.
Email: *, *
Received April 2nd, 2012, revised July 3rd, 2012, accepted July 21st, 2012
Primary adrenal tumors are less commonly encountered in clinic. They may be functional/non-functional and noted
incidentally when investigating for other problems. However there is no study available in Asian countries, and espe-
cially India regarding the incidence and natural history of these tumors. We carried out a study on adrenal tumors noted
in our set-up for last five years to document the prevalence of adrenal tumors, their presentation along with the most
common tumor followed by incidence of other tumors and their clinical and pathological presentation. This was a ret-
rospective study in our hospital from June 2006 to 2011. 29 adrenalectomies performed over 5 years. Their clinical
presentation and investigations were recorded and analyzed. Adrenal tumors accounted for 0.6% of total surgical
specimens, 18 out of 29 belonged to males. Majority (85.2%) of the patients were adults with mean age, 39.8 years.
Majority (79.3%) had presented with symptoms, incidentalomas were found in 20.7% patients out of which 2 belonged
to potential kidney donors. Nonfunctioning tumors were noted in 58.6% patients. Pheochromocytoma was the com-
monest tumor noted in 68.9% followed by adrenal cortical adenoma in 13.7%, carcinoma in 6.9% and lipoma, myeloli-
poma and ganglioneuroma, 3.45% each. All the patients are doing well over a mean follow-up of 2.5 years. To our
knowledge this is the first study on incidence and natural history of primary adrenal tumors which are less commonly
encountered and usually have good prognosis.
Keywords: Adrenal Tumors; Pheochromocytoma; Hypertension; Incidentaloma
1. Introduction
Primary adrenal tumors encountered in clinical practice
are functioning/nonfunctioning tumors. Asymptomatic
adrenal masses discovered incidentally (incidentalomas)
are becoming increasingly frequent with availability of
advanced imaging modalities like Computed Tomography
(CT) Scan/magnetic resonance imaging (MRI). These
techniques can now define adrenal masses as small as 0.5
cm in size and prevalence is up to 4% of abdominal
studies [1-3]. Adrenal tumors are surgically removed due
to the fear of malignant changes/hormonal disturbances
created by them. Histopathology still remains the gold
standard in their diagnosis. No statistical data about in-
cidence of adrenal tumors, especially in India are avail-
able. We present 5 years single centre experience of ad-
renal tumors received in our surgical pathology section.
2. Material and Methods
Totally 29 adrenalectomies were received between Janu-
ary 2006 to December 2010 and analyzed histopa-
thologically. Their case records were studied for clinical
presentation and correlation with radiological [Ultra-
sonography (USG) CT, MRI] and pathological investiga-
tions. Functional status was evaluated by baseline hor-
monal assessment which included serum potassium, cor-
tisol, aldosterone, urinary Vanillyl mandelic acid (VMA)
and metanephrine levels.
All tumors were subjected to gross pathology, light
microscopy and immunohistochemistry (IHC) evalua-
3. Results
Adrenal tumors accounted for 0.6% of total surgical
specimens. Out of 29 specimens 18 belonged to males.
Majority (85.2%) of the patients were adults (n = 25)
with mean age, 39.8 ± 10.2 years (range: 21 - 58 years)
and 4 were children with mean age, 10.1 ± 6.3 years
(range: 9 months to 14 years). Majority (79.3%, n = 23)
of the patients had presented with symptoms; incidenta-
lomas were found in 20.7% (n = 6) patients. Two out of 6
*Corresponding author.
Primary Adrenal Tumors—Five Years Single Centre Experience
incidentalomas belonged to potential kidney donors.
Nonfunctioning tumors were noted in 58.6% (n = 17)
patients (Table 1).
3.1. Pathological Evaluation
Adrenal cortical tumors were more common than me-
dullary tumors accounting for 89.5% cases. Pheochro-
mocytoma was the commonest adrenal tumor noted in
68.9% (n = 20) followed by adrenal cortical adenoma in
13.7% (n = 4), carcinoma in 6.9% (n = 2) and lipoma,
myelolipoma and ganglioneuroma, 3.45% (n = 1) each.
3.1.1. Ph eochromocytoma
The mean age was 35.7 ± 14.2 years with male predilec-
tion, affecting 14 males. Both sides were equally affected
and all were unilateral. Hypertension was observed in
70% (n = 14) patients who were on three anti-hyperten-
sives before surgery. Elevated urinary VMA was noted in
55% (n = 11) with mean values, 14.3 ± 3.4 mg/24hours
(reference range: 2 - 8 mg/24hr). Urinary metanephrin
was elevated in 35% (n = 7) with mean value of 1.65 ±
0.29 mg/24hours (reference range: 0 - 0.9 mg/24hours).
Urinary cortisol was elevated in 36.4 % (n = 4) patients
with mean value of 240 ± 42.43 microgram/24hours
(reference range: 60 - 160 microgram/24hours). All of
them showed gradual decrease in need of anti-hyperten-
sives which were stopped after 6 - 8 months of surgery.
All patients are doing well without any anti-hyperten-
sives over a mean follow-up of 2.53 ± 1.42 years. Their
urinary hormonal levels also returned to normal range 3
weeks after surgery.
Gross and Hi stopath ol ogy:
The tumors were soft to firm in consistency with mean
weight 99.7 ± 100 grams, size 7.14 ± 2 cm, well circum-
scribed with variegated appearance, yellow brown col-
ored and showing rare areas of hemorrhage and necrosis
(Figure 1(a)).
Histopathology revealed tumor cells arranged in or-
ganoid pattern or fascicles showing extensive areas of
“Zell ballen” appearance. Individual tumor cells were
large, polygonal with mild atypia having fine granular
eosinophilic cytoplasm and centrally placed large nuclei
with prominent nucleoli (Figure 2(a)). Haemorrhage and
necrosis were noted in variable amounts. The tumor was
well circumscribed and surrounded by thick fibrous cap-
sule in all cases. Atypical mitotic figures were noted in
85.7 % (n = 18) and bizarre giant cells in 66.6% (n = 14)
tumors. They were all exhibiting positivity to chromo-
granin and synaptophysin. However none showed fea-
tures of malignancy in the form of capsular invasion or
distant metastasis.
(a) (b)
(c) (d) (e)
Figure 1. Gross appearance (cut surface) of adrenal tumors.
(a) Pheochromocytoma with golden brown appearance; (b)
Cortical Carcinoma: Nodular grey-white-black dashed line
denoting tumor, white line denoting hemorrhagic area of
adrenal gland; (c) Lipoma: Homogenous yellow fatty with
myxomatous jellylike appearance; arrow depicting adrenal
gland in periphery; (d) Myelolipoma: Variegated with
hemorrhagic and yellowish fatty areas; arrow depicting
adrenal gland in periphery; (e) Ganglioneuroma: Homoge-
nous grey-white appearance.
Table 1. Demographics of adrenal tumors.
Lesion Number
Mean (SD) age
(years) (range) Gender
M:F HT/DM F/NF Mean(SD) size
(cm) (range)Mean (SD) weight
(gm) (range) Incidental Mean (SD) follow up
(years ) (range)
Pheochromocytoma 20 35.7 (14.2)
(12 - 58) 14:6 HT-15
DM-2 8/12 7.14 (2.21)
(4 - 13)
99.75 (100.16)
(10 - 400) 1 2.53 (1.42)
(0.78 - 5.52)
Adrenal adenoma 4 37.5 (8.66)
(30 - 45) 1:3 - 1/3
5.17 (0.85)
(4 - 6)
35.4 (26.2)
(15 - 60) 2 2.84 (1.76)
(1.35 - 5.02)
Adrenal cortical
carcinoma 2 22.9 (31.3)
(0.75 - 45) 1:1 - 1/1 8 (2.83)
(6 - 10)
145 (77.78)
(90 - 200) 1 0.95 (0.24)
(0.78 - 1.12)
Lipoma 1 43 1:0 HT 0/1 15 810 1 2.73
Myelolipoma 1 46 0:1 HT 1/0 10 315 - 0.98
Ganglioneuroma 1 33 1:0 HT 0/1 10 300 1 0.82
HT-Hypertension, DM-Diabetes Mellitus, F/NF-Functional/Non Functional.
Copyright © 2012 SciRes. OJPathology
Primary Adrenal Tumors—Five Years Single Centre Experience 109
(a) (b) (c)
(d) (e) (f) (g)
Figure 2. Adrenal tumor photomicrographs (H & E stain,
×100). (a) Pheochromocytoma: Tumor cells in “Zell-ballen”
pattern, inset: cytoplasmic positivity with chromogranin; (b)
Cortical Adenoma: Appearing mixture of zona glomerulosa
and fasciculate; (c) Cortical Carcinoma: Diffuse sheets of
large polygonal cells; inset (×200): showing mitotic activity;
(d) Cortical Carcinoma: Vimentin positivity with capsular
invasion; (e) Lipoma: Well-encapsulated mature adipose
tissue tumor with adjacent normal parenchyma; (f) Myelo-
lipoma: Proliferating mature adipose tissue with haemato-
poietic elements; (g) Ganglioneuroma: Mature ganglion and
Schwann-like cells arranged in fascicles; inset (×200) NSE
3.1.2. Adrenal Cortical Adenoma
The next common tumor found was adrenal cortical
adenoma in 4 patients, 3 females and 1 male with mean
age, 37.5 ± 8.66 years. One of them, a 30 years old female
presented with Cushing’s syndrome and others were
nonfunctioning. One out of these was an incidentaloma
noted in a 45 years old lady who was a potential kidney
donor. Both sides were equally affected. The kidney do-
nor was subjected to donor nephrectomy after tumor re-
moval and all are doing well over a mean follow-up of
2.84 ± 1.76 years.
Gross and Hi stopath ol ogy:
The tumors were soft to firm in consistency with mean
weight 35.4 ± 26.2 grams, size 5.17 ± 0.85 cm, well-
encapsulated and grey brown colored. Small foci of
hemorrhage were seen.
Histopathology revealed tumor cells appearing to be
mixture of zona glomerulosa and fasciculata arranged in
sheets or organoid pattern. The tumor was well encapsu-
lated with areas of haemorrhage and necrosis and not
infiltrating in to surrounding parenchyma. The adrenal
parenchyma adjacent to tumor showed unremarkable
morphology (Figure 2(b)). No atypia or mitotic activity
was noted. They were negative for epithelial membrane
antigen and positive for synaptophysin and vimentin.
3.1.3. Adrenal Cortical Carcinoma
We found 2 patients with adrenal cortical carcinoma, a 9
months old male baby with a functional tumor, 10 cm in
size, weighing 200 grams. The child had virilizing effect
with hormonal activity showing serum testosterone of
6.38 ng/dL (normal value: 0.03 - 0.68 ng/mL at 1 - 12
years age) and urinary cortisol value of 14.75 microgram/
24 hours (normal range: 4.3 - 17.6 microgram/24hours).
Three months after surgery his hormone levels returned
to normal with unremarkable sonography finding. The
second patient was a 45 years old lady who was a poten-
tial kidney donor with 6 cm incidentally detected non-
functioning tumor in right adrenal gland weighing 90
grams. She was rejected as potential donor and over a
follow-up of 1 year she is asymptomatic.
Gross and Hi stopath ol ogy:
The tumors were firm, nodular in consistency weigh-
ing 200 and 90 gms respectively and measuring 10 and 6
cms respectively, well circumscribed and greyish white
colored (Figure 1(b)). The tumor of the infant was very
necrotic and friable.
Histopathology revealed diffuse sheets of tumor cells
that were large, polygonal with moderate to marked
atypia. Individual cells had fine granular eosinophilic
cytoplasm and centrally placed large nuclei with promi-
nent nucleoli. Extensive hemorrhage and necrosis were
noted. Few dilated cystic spaces filled with RBCs were
also seen with 5 mitotic figures/high power field with
atypical mitotic figures amongst them. The tumor was
well circumscribed and surrounded by thick fibrous cap-
sule. The adrenal parenchyma adjacent to tumor showed
unremarkable morphology. The tumor in lady had pro-
minent capsular invasion. Vimentin was strongly positive
and low molecular weight keratin was negative in both
(Figures 2(c) and (d)).
3.1.4. Adrenal Li po ma
A 43 years old male with hypertension and past history
of myocardial infarction was found to have non-func-
tional tumor 15 cm in size, weighing 810 grams (Figure
1(c)). On gross examination the external surface was
smooth and grey-yellow colored, and the adjacent adre-
nal gland measuring 6 × 1.5 × 0.5 cm in size was unre-
markable. The cut surface was homogenous, yellow and
fatty with myxomatous areas with jelly-like appearance
and soft to firm in consistency. Microscopy revealed a
well-encapsulated tumor composed of mature adipose
tissue with myxoid degenerative changes and normal
adrenal parenchyma (Figure 2(e)). He is also doing well
after 2.73 years of surgery.
3.1.5. Adrenal Myelolipoma
It was noted in 1 patient who was a 46 years old lady
with functional tumor showing high urinary cortisol of
229.6 microgram/24 hours and normal urinary VMA.
The tumor was weighing 315 grams, measuring 10 × 9.6
× 6 cm in size. Outer surface showed variegated ap-
Copyright © 2012 SciRes. OJPathology
Primary Adrenal Tumors—Five Years Single Centre Experience
pearance, few hemorrhagic areas were seen along with
yellowish fatty areas. Cut surface showed variegated ap-
pearance, hemorrhagic along with fatty area with ad-
jacent uninvolved strip of adrenal gland (Figure 1(d)).
Histopathology showed proliferating mature adipose
tissue with haematopoietic elements containing myelo-
cytes and metamyelocytes and remaining part of adrenal
gland showed focal hemorrhage (Figure 2(f)). She is
doing well over a follow-up of 0.98 yr.
3.1.6. Ganglioneu roma
We found ganglioneuroma in a 33 years old male who
presented with epigastric pain with cholelithiasis and
incidentally was found to have adrenal mass during USG.
The tumor was large, weighing 300 grams, measuring 10
× 9 × 7 cm in size, nodular, irregular grey colored, con-
gested and partially covered with fatty tissue. Cut section
showed a well circumscribed tumor mass with homoge-
nous grey-white appearance (Figure 1(e)). Microscopy
examination revealed normal adrenal cortical and me-
dullary tissue with adjacent well circumscribed benign
tumor mass of mature ganglion cells and Schwann-like
cells arranged in fascicles, staining strongly with neu-
ron-specific enolase and s-100 proteins. No immature
cells or malignancy was noted (Figure 2(g)). Over a fol-
low-up of 0.82 years he is doing fine.
4. Discussion
Adrenal gland tumors require a multi-disciplinary ap-
proach. The incidence in India is not available; in US the
incidence of adrenal mass is approximately 5% [4]. The
average age of a person diagnosed with an adrenal gland
tumor is between 45 and 50; however, these tumors can
occur at any age. More women than men tend to be di-
agnosed with adrenal gland tumors. Our study differs
from this observation. We have seen adrenal tumors af-
fecting little earlier at mean age of 39.8 ± 10.2 years and
males are more often diagnosed to have this tumor. One
of the reasons could be that ours being a male dominated
society, women even if they are suffering may not have
been reported since they do not come to the hospital for
treatment. Our study shows that approximately 80% of
adrenal tumors are detected due to symptoms related/
unrelated to tumors and 55% are usually functional.
The incidence of adrenal incidentaloma is about 20%.
[2,3,5] The symptoms depend on functional status and
what hormone is over-produced. Tumors arising from
adrenal cortex are adrenal adenomas and carcinomas,
whereas tumors of adrenal medulla are neuroblastoma,
pheochromocytoma, genglioneuroblastoma and gangli-
oneuroma. Other tumors like lipoma, myelolipoma, ade-
nomatoid tumor, benign mesenchymal tumors, sarcoma,
malignant lymphoma and melanoma are very rare. Our
study also matches with the observation of others re-
garding tumor type, pheochromocytoma accounting for
about 69% of all adrenal tumors followed by adenoma
noted in approximately 11.5%, carcinoma in 7.7% and
others noted rarely. Both the clinical and biochemical
features of pheochromoctyomas result largely from the
over-production of catecholamine with over half of pa-
tients developing marked hypertension. They occur at all
ages but are most common in forth through sixth decades
of life [6]. In our study also we found that hypertension
was the commonest symptom however we found wide
age range of 12 to 58 years with younger mean age of
35.7 ± 14.2 years of our patients. Accompanying com-
plaints of weight loss, headache and palpitations are
fairly common presentation [6-8]. Malignant pheochro-
mocytomas account for 10% - 25% of cases and are char-
acterized by bone, lung, liver or splenic metastasis. Re-
cently gene expression analysis raised the possibility that
molecular markers might predict clinical tumor behavior
[8]. We have not come across any malignant phaeochro-
mocytoma in our study. Adrenal adenoma, a benign le-
sion usually affects women, which has also been our ob-
servation showing all females with this tumor with age
range of 30 - 45 years. Adrenal cortical carcinoma is rare,
highly aggressive tumor, incidence ranging for 0.5 to 12
per million (0.6 to 2 per million). It accounts for 0.05%
to 2% of all malignancies. There is bimodal age distribu-
tion with peak incidence in the first and fifth decades of
the life. The gender distribution amongst patients with
adrenal carcinoma appears to vary in different series, still
females are commonly affected [3,9,10]. Virilization by
androgen secreting tumors is common phenomenon in
children, its rate is much lower in adults [11-13]. In chil-
dren it has less aggressive clinical course and responds
better with surgery and other therapeutic modalities as
compared to adults. Both our patients are doing well over
a follow up of 1 year approximately, unlike other studies
showing a median survival of 18 months after diagnosis
Adrenal lipomatous tumors are uncommon, accounting
for 4.8% of the primary adrenal tumors noted in the 30
years period [14-16]. Most of these tumors are asympto-
matic and found incidentally. Theories of pathogenesis
include metaplastic origin, retention of embryonic rests
or extramedullary origin. Myelolipoma accounts for 2.6
to 15% of primary adrenal tumor, usually noted in adults
with age range of 41 - 84 years [17-19]. Ganglioneuroma
is a rare benign tumor of adrenal gland arising from neu-
ral crest cells. GN is common in children and in sympa-
thetic nervous system, posterior mediastinum and retrop-
eritoneum, very rare in adults and in adrenal gland with
equal gender distribution. A preference of thoracic
(41.5%) followed by abdominal-non-adrenal (37.5%) and
adrenal GN (21%) as been observed in one series. Most
of the GN are non-functioning, asymptomatic, incident-
tally detected by imaging procedures as in our study also.
Copyright © 2012 SciRes. OJPathology
Primary Adrenal Tumors—Five Years Single Centre Experience 111
However a patient may have abdominal pain, gastroen-
teritis, weight loss, hypertension and diarrhea. Histologi-
cally two benign subtype of GN- mature and maturing
have been noted malignant transformation has also been
reported [20-23].
To our knowledge this is the first Indian study on
natural history of adrenal tumors. Although not so com-
mon, they are encountered in routine practice, overall
they are amenable to surgical modalities and have good
prognosis. Pheochromocytomas are the commonest ad-
renal tumors in our set-up. Larger studies are required to
find the incidence in our part of the world.
5. Acknowledgements
Treating clinicians: Pranjal R. Modi and S. J. Rizvi, Pro-
fessors in Urology and Transplantation, Veena R. Shah:
Prof. & HOD, Anesthesia and Critical Care, Hargovind L.
Trivedi: Department of Nephrology & Transplantation
Medicine, Jyotsana Suthar: Librarian who helped in lit-
erature search.
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Primary Adrenal Tumors—Five Years Single Centre Experience
Copyright © 2012 SciRes. OJPathology
10, 2001, pp. 1905-1913.
CT: Computed tomography
GN: Ganglioneuroma
IHC: Immunohistochemistry
MRI: Magnetic resonance imaging
NSE: Neuron specific enolase
USG: Ultrasonography
VMA: Vanillyl mandelic acid