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Year : 2012  |  Volume : 55  |  Issue : 4  |  Page : 461-466
Spectrum of adrenal lesions on fine needle aspiration cytology

Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

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Date of Web Publication4-Mar-2013


Background: Fine needle aspiration (FNA) cytology of adrenal gland is not a commonly performed technique and is limited primarily to tertiary care centers. However, it is a sensitive and specific procedure in the workup of patients with adrenal gland's mass lesions. Though cytomorphological features for various lesions have been described, there are a limited number of studies in cytologic literature. Aims: We report our 7 years of experience in FNAC of adrenal lesions. We have not only described the cytomorphological details of different lesions, but also tried to discuss the various diagnostic difficulties encountered during reporting of adrenal fine needle aspirations. Materials and Methods: All ultrasound-guided percutaneous aspirations of adrenal gland received in the department between the years 2002 and 2009 were reviewed. There were a total of 52 FNA samples of adrenal masses from 35 patients in 7 years. The lesions were categorized as non-neoplastic and neoplastic categories. Neoplastic lesions were further divided into benign and malignant lesions. Results: In our study, FNA proved to be 100% specific for diagnosing malignant lesions. The overall inadequacy rate was 11.4% with no major complications of the procedure. A wide variety of non-neoplastic as well as neoplastic lesions were identified.

Keywords: Adrenal lesions, fine needle aspiration, cytology

How to cite this article:
Rana C, Krishnani N, Kumari N. Spectrum of adrenal lesions on fine needle aspiration cytology. Indian J Pathol Microbiol 2012;55:461-6

How to cite this URL:
Rana C, Krishnani N, Kumari N. Spectrum of adrenal lesions on fine needle aspiration cytology. Indian J Pathol Microbiol [serial online] 2012 [cited 2021 Oct 25];55:461-6. Available from: https://www.ijpmonline.org/text.asp?2012/55/4/461/107781

   Introduction Top

Fine needle aspiration cytology (FNAC) of adrenal gland is a less frequently performed technique in cytology services. [1] Many investigators in past have reported their experience with percutaneous image guided (computed tomographic (CT) or ultrasonographic (US)) FNA of adrenal and have underscored the value of FNA in adrenal glands. [2],[3] However, there are studies which have demonstrated that FNA biopsy of adrenal glands is a specific and sensitive procedure in the workup of patients with adrenal gland lesions. [4],[5],[6] FNA not only allows the confirmation of surgical conditions like primary and metastatic malignancies, benign neoplasms, and cystic lesions, but also helps to diagnose the medical disorders which can be cured without surgery, like infections, e.g., tuberculosis (TB) and histoplasmosis. In the present studym we report our experience with FNA of adrenal glands and the spectrum of lesions which were encountered in a tertiary care referral center.

   Materials and Methods Top

All image-guided percutaneous needle aspirations of adrenal masses received in the cytopathology section of Department of Pathology, Sanjay Gandhi Institute of Medical Science and Research, India, between the years 2002 and 2009 were reviewed.

FNA of the adrenal masses was performed via a posterior, anterior, or transhepatic approach under CT or US guidance, using 18- to 22-gauge spinal needles. Four to eight smears including air-dried and alcohol-fixed smears were prepared in each case from the aspirated material. Alcohol-fixed smears were stained with hematoxylin and eosin (H and E) and Papanicolaou (PAP) stains, while air-dried smears were stained with May Graunwald Giemsa (MGG). Special stains like periodic acid Schiff (PAS), silver methanamine, Ziehl Neelsen (ZN), periodic acid after diastase (PAD), periodic acid after diastase and Alcian blue (PAD-AB), grimelius, etc., were used as and when required. Histological confirmation was looked for in all cases.

   Results Top

A total of 52 FNA samples of adrenal masses were received from 35 patients in 7 years. The patients presented as symptomatic or incidental adrenal lesions during routine radiological surveys for some other complaints. No serious complications of the procedure were observed.

The age ranged from 17 to 83 years, with a mean age of 48.9 years and median of 52 years. There were 25 males (71.4%) and 10 females (28.6%) (M:F = 2.5:1). FNA smears from four cases (11.4%) were unsatisfactory and nondiagnostic. Histological confirmation was available in 17 patients. Adequate treatment follow-up was available in the remaining cases.

On the basis of cytological findings, the diagnostic aspirates were divided into two broad categories, neoplastic and non-neoplastic. The neoplastic lesions were further sub-classified into malignant lesions and benign lesions. These malignant lesions were grouped into metastatic and primary adrenal lesions [Table 1].
Table 1: Spectrum of lesions on FNA of adrenal gland (n=35)

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Malignant Adrenal Lesions

Among the diagnostic smears (31 cases), the FNA was 100% specific for diagnosis of malignant lesions. There were no false-positive or false-negative cases.

There were 15 cases of malignant neoplasms diagnosed by FNA of adrenal glands [Table 1]. Among these, 10 cases were confirmed on histological examination. Follow-up was available in all the 15 cases. There were 4 primary lesions and 12 metastatic neoplasms. The primary lesions included one adrenocortical carcinoma, one pheochromocytoma, and two cases of neuroblastoma. The metastatic malignancies consisted of five lymphomas and seven carcinomas [Table 1].


There was one case of pheochromocytoma which presented as right adrenal mass. The clinical complaints comprised palpitations and episodic hypertension. A right adrenal mass was identified on ultrasound. Biochemical examination revealed elevated 24 h urinary normetanephrines (1051 miug/24 h).

FNA smears showed loose clusters as well as scattered polygonal cells having anisokaryosis, finely dispersed chromatin, and moderate amount of granular cytoplasm with indistinct cell borders. Adrenalectomy was done and histopathologic examination confirmed the diagnosis of pheochromocytoma.

Adrenocortical carcinoma

A 14-year-old girl was admitted in our institute for evaluation of obesity, hirsutism, and primary amenorrhea. On examination, she had cushingoid features like facial plethora, buffalo hump, acanthosis, truncal obesity, and clitoromegaly. Abdominal ultrasound revealed a 8-9 cm mass in right adrenal, which had a heterogeneous intensity with areas of calcification and necrosis. Biochemical tests revealed high basal serum cortisol (568.1 nmol/l) with no suppression on high- as well as low-dose dexamethasone (596.1 nmol/l and 605.7 nmol/l, respectively).

FNA smears from adrenocortical carcinoma showed clusters as well as dispersed population of neoplastic cells in a hemorrhagic background. The tumor cells had pleomorphic hyperchromatic nuclei, prominent nucleoli, and moderate to abundant vacuolated to granular cytoplasm [Figure 1]. Mitotic figures were seen. Adrenalectomy was done and histopathologic examination confirmed the cytological diagnosis of adrenocortical carcinoma along with presence of metastatic deposits in the inguinal lymph nodes. This was a unique case of adrenocortical carcinoma occurring in a young girl.
Figure 1: Adrenocortical carcinoma (MGG; oil immersion) - Clusters as well as dispersed population of polygonal atypical cells with pelomorphic hyperchromatic nuclei, prominent nucleoli, and moderate amount of granular cytoplasm

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Five out of 35 cases (14.3%) were of non-Hodgkin's lymphoma of adrenal gland secondary to involvement of intra-abdominal lymph nodes in 4 and breast in 1 case [Table 2]. In all these cases, there was bilateral and extensive adrenal involvement. Two patients developed hemiparesis as a result of spread to brain which led to lacunar infarct. Similarly, one another case had testicular involvement which was also diagnosed on non-Hodgkin's lymphoma on FNAC. The fifth case had bilateral breast lumps which were diagnosed as malignant lymphoma on FNAC.
Table 2: FNA cytodiagnosis of adrenal secondaries (n=12)

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Smears from all these cases were cellular and showed predominantly dispersed population of medium- to large-sized neoplastic lymphoid cells. These cells had high n/c, round to irregular nuclei, condensed chromatin, and scant cytoplasm [Figure 2]. Adrenal trucut biopsy was done in two cases on which immunohistochemical panel for lymphoma was applied and these cases were diagnosed as B-cell non-Hodgkin's lymphoma.
Figure 2: Adrenal lymphoma (MGG; oil immersion) cytomorphology shows predominantly dispersed population of medium- to large-sized neoplastic lymphoid cells with high n/c, round to irregular nuclei, condensed chromatin, and scant cytoplasm

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Metastatic carcinoma

Seven of 35 cases (20%) were diagnosed as representing metastatic carcinomas to adrenal glands. All these patients had a known history of extra-adrenal malignancies at the time of aspiration from adrenal gland. The metastatic carcinoma comprised two cases each of lung carcinoma and renal cell carcinoma, and one case each of urothelial carcinoma, colonic adenocarcinoma, and prostatic adenocarcinoma [Table 2]. Cytological features of these malignancies were similar to the features of the primary tumor [Figure 3].
Figure 3: Metastatic carcinoma (MGG; oil immersion) cytomorphology of metastatic colorectal carcinoma - Cohesive clusters of atpical cells with plemoprhic hyperchromatic nuclei, coarse chromatin, conspicuous nucleoli, and vacuolated cytoplasm

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Benign Adrenal Lesions

Adrenal TB

Four of 35 cases (11.4%) of disseminated TB presented as adrenal mass along with presence of adrenal insufficiency. Three cases had bilateral adrenal enlargement while one case had unilateral involvement. All these patients were known cases of pulmonary TB and were on anti-tubercular therapy (ATT) during the time of FNA. FNA from the mass was done to confirm TB and rule out other lesions like malignancy.

FNA smears from three cases showed epithelioid cell granulomas and multinucleated giant cells and two of them had in addition necrosis in the background [Figure 4]a. One case showed only necrosis along with degenerated cells [Figure 4]b. ZN stain was performed in all these cases, which turned out to be noncontributory as the patients were already on ATT. Special stains for fungal elements were negative. Based on cytomorphology and a history of TB, they were diagnosed as consistent with TB. Thus, our diagnosis of TB was confirmed on follow-up.
Figure 4: Adrenal tuberculosis (MGG; oil immersion). (a) Granuloma composed of slipper-shaped epithelioid cells along with intermixed lymphocytes. (b) Multinucleated giant cells

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Adrenal histoplasmosis

The nine cases of histoplasmosis presented with bilateral adrenal enlargement and nonspecific constitutional symptoms like fever, weight loss, loss of appetite, and abdominal pain.

Smears from three cases showed predominantly necrosis with degenerated cells. The remaining five cases displayed clusters as well as dispersed population of histiocytes. Giant cells and epithelioid granulomas were also seen [Figure 5]a. All these cases showed fungal elements on PAS stain [Figure 5]b. These fungal elements were uniform yeast-like organisms, ranging in size from 3 to 5 μm in diameter, displaying narrow based budding. Hyphae and pseudohyphae were not seen. The cytopathologic features were consistent with Histoplasma capsulatum. ZN stain for acid-fast bacilli was negative.
Figure 5: Adrenal histoplasmosis (MGG; oil immersion). (a) Numerous intracellular budding yeasts (Histoplasma capsulatum) on May Graunwald Geimsa stain. (b) Periodic acid Schiff's stain displaying many intracellular and extracellular yeasts (Histoplasma capsulatum)

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Aspirate material was simultaneously sent for culture in six cases which showed growth of H. capsulatum. In rest of the three cases, culture was not sent as the suspected diagnosis was malignancy. Adrenal trucut biopsy was available in one case which also showed fungal profiles consistent with Histoplasma. One case each had involvement of bone marrow and testis by Histoplasma, apart from adrenal histoplasmosis. All the patients received antifungal treatment and improved.


There was also a case of myelolipoma which was identified as an incidentaloma on ultrasound. The patient was being evaluated for pain in upper abdomen for 2 years. There was no history of palpitation, hypertension, or visual disturbances. Biochemical tests were within normal limits. Guided FNA smears showed fibroadipocytic fragments along with intermixed hemopoietic elements comprising megakaryocytes, myeloid and erythroid series of cells [Figure 6]. Resected specimen was available which confirmed myelolipoma on histopathology.
Figure 6: Myelolipoma (MGG; oil immersion). Hemopoietic elements comprising megakaryocytes, myeloid and erythroid series of cells in a hemorrhagic background

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A 30-year-old female presented with dull pain in left hypochondrium for 2 months. On physical examination, a well-defined firm to hard irregular large lump was palpable in the left hypochondrium, which was reaching up to the midline. Radiologically, a large adrenal mass 25 × 20 cm was identified, displacing the transverse mesocolon and adherent to left kidney.

Aspiration smears prepared were found to be markedly hemorrhagic and paucicellular. It showed few fibroadipocytic fragments only. Because the aspiration done was from the center of the lesion [Figure 7], a diagnosis of no e/o malignancy was given. Histologically, this case was diagnosed as angiomyolipoma.
Figure 7: Angiomyolipoma (MGG; ×400). Fibroadipocytic fragments in a hemorrhagic background

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   Discussion Top

FNAC of adrenal gland is not a frequently performed technique. It is performed mostly in tertiary care centers. However, with an increased expertise in precise localization of adrenal masses with newer radiological techniques, FNA is becoming increasingly important in the diagnosis of adrenal masses. With the help of ultrasound and CT scan, lesions as small as 3 cm and 1cm, respectively, can be picked up with ease. [7]

Many investigators have reported their experiences in the past with percutaneous image-guided biopsy and have shown the inadequacy rates as high as 37%. [4],[5],[6],[8] However, in the present study, inadequacy rate was 11.4%. Good radiological localization, multiple passes (2-3), and awareness of cytomorphological features of the different entities of adrenal gland can help to arrive at a diagnosis in majority of cases.

Percutaneous FNA of adrenal mass is an invasive procedure and is known for significant morbidity with reported complications like pneumothorax, septicemia and hemorrhage in 8-13% cases; [1],[9] however, with correct technique, complications can be reduced. No such complication was reported in any of the 35 cases in the present study.

The increasing use of improved imaging techniques as a part of diagnostic workup for metastasis in patients with cancer has resulted in the detection of increased number of adrenal mass lesions, both benign and malignant.

FNA of adrenal gland is performed under three situations: (1) incidentally detected mass on abdominal imaging, (2) symptomatic mass lesions, and (3) staging workup or follow-up of cancer patient. [6] Whatever may be the situation, the primary aim is always to distinguish between the primary adrenal neoplasm and a metastatic disease.

The overall sensitivity of adrenal FNA in detecting the presence of the malignancy has been reported to be up to 85%. [10],[11] In our series, the FNA was 100% specific for malignant lesions and correctly diagnosed 83.3% of the adrenal masses. There were no false-positive or false-negative cases for these malignant lesions.

Problems in Arriving at a Diagnosis

Malignant adrenal tumors

Cytological diagnosis of adrenocortical carcinoma is difficult. Firstly, the usual differential diagnoses include metastatic melanoma, renal cell carcinoma, and hepatocellular carcinoma. [12] Secondly, pleomorphism and hypercellularity are not the reliable features to distinguish between adrenal adenoma and adrenocortical carcinoma. An attempt has been made in cytology literature to distinguish adrenocortical carcinoma from adenomas. [13],[14],[15] However, features like tumor size >5 cm, absence of any other primary site, polygonal cells with prominent nucleoli, granular cytoplasm, presence of frequent mitosis and necrosis, suggest adrenocortical carcinoma. [11],[15],[16] Cells of a benign lesion tend to form cohesive clusters and often have stripped nuclei. Although focal anisonucleosis and mild nuclear atypia may be found, mitosis and necrosis are exceedingly rare in benign lesions. Based on these distinguishing factors, we could diagnose one case of adrenocortical carcinoma on cytology, which was confirmed on subsequent histological examination [Figure 1].

Malignant small round cell tumors can be pose a precise diagnostic challenge. The usual differential diagnosis in adrenal lesions includes neuroblastoma, Wilms tumor, metastatic small round cell tumor, and embryonal rhabdomyosarcoma. [17],[18] Knowledge of certain distinguishing features can help in making the diagnosis:

  1. Neuroblastoma shows features like presence of rosette with central fine fibrillary material.
  2. Presence of lymphoglandular bodies in the background suggests the diagnosis of lymphoma.
  3. Presence of cells with dense cytoplasm, eccentric nucleus, and triangular, star-shaped, or tadpole-like cells may be recognized as rhabdomyoblasts and suggest the diagnosis of embryonal rhabdomyosarcoma
  4. Presence of glomeruloid bodies, small blastemal cells, and mesenchymal elements points toward the diagnosis of Wilms tumor in children. Monophasic Wilms can further pose a diagnostic challenge.
As far as the diagnosis of metastatic carcinoma is concerned, it is a little easier as the features resemble morphologic appearance of the primary tumor.

Benign adrenal lesions

The diagnosis of myelolipoma is fairly easy. Pheochromocytoma can also be diagnosed with certain reliability; however, we were not able to make the diagnosis of angiomolipoma on cytology though malignant lesion was excluded with certainty. The smears were predominantly hemorrhagic with few fibroadipocytic fragments. On review of slides, the predominant components seen were blood vessels and adipocytes. The myoid component was very less which was missed on initial look. However, with experience, it can be picked on aspiration.

Infective adrenal lesions

In the present series, infective pathology comprised 37.1% cases. All the cases presented as adrenal mass or enlargement, along with nonspecific clinical complaints. There were 9 cases (25.7%) of histoplasmosis and 4 cases (11.4%) of TB.

In India, TB is the most common cause of adrenal insufficiency, and in all varieties of clinical TB, adrenal involvement is seen in 46-56% instances. [19] However, in this study, histoplasmosis of adrenal was more common as compared to TB. It is important to differentiate between histoplasmosis and TB as their management is entirely different. They also need to be differentiated from primary as well as metastatic malignant conditions.

   Conclusion Top

In the present study, we present our experience on FNA of adrenal glands and describe the spectrum of lesions along with their cytomorphological features and diagnostic difficulties. A good co-ordination between pathologist, radiologist, and the clinician not only helps in increasing the adequacy rate, but also helps to arrive at a diagnosis by providing relevant clinical as well as radiological details. FNA adrenal gland is an effective method of making a rapid diagnosis, and hence can play a crucial role in treatment, especially in infective conditions where early diagnosis is required.

   References Top

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2.Montali G, Solbiati L, Bossi MC, De Pra L, Di Donna A, Ravetto C. Sonographically guided fine-needle aspiration biopsy of adrenal masses. AJR Am J Roentgenol 1984;143:1081-4.  Back to cited text no. 2
3.Nguyen GK, Akin MR. Fine needle aspiration cytology of kidney, renal pelvis and adrenal. Clin Lab Med 1998;18:429-59.  Back to cited text no. 3
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9.Moreira SG Jr, Pow-Sang JM. Evaluation and management of adrenal masses. Cancer Control 2002;9:326-34.  Back to cited text no. 9
10.Katz RL. Kidney, adrenal, reteroperitoneum. In: Bibbo M, editor. Comprehensive cytopathology. Philadelphia: WB Saunders; 1991.p. 771-806.  Back to cited text no. 10
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15.Saboorian MH, Katz RL, Charnsangavej C. Fine needle aspiration cytology of primary and metastatic lesions of the adrenal gland: A series of 188 biopsies with radiologic correlation. Acta Cytol 1995;39:843-51.  Back to cited text no. 15
16.Wu HH, Cramer HM, Kho J, Elsheikh TM. Fine needle aspiration cytology of benign adrenal cortical nodules: A comparison of cytologic findings with those of primary and metastatic adrenal malignancies. Acta Cytol 1998;42:1352-8.  Back to cited text no. 16
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Correspondence Address:
Narendra Krishnani
Department of Pathology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.107781

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2]

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