2014 JOURNAL OF MEDICAL RESEARCHVol.1 No.1Vol.1Jul.–Dec. 2014ERA’S JOURNAL OF MEDICAL RESEARCHJul.–Dec. No.1ERA’S
CYTo loGY oF ADRENAl lESIoNS
Prof. Manoj Jain
Department of Pathology, SGPGIMS, Lucknow
Address for Correspondence
Cystic and solid lesions in the adrenal glands commonly present as mass lesions and have varied Prof. Manoj Jain
etiology as infectious diseases, benign eysts, adrenal neoplastic lesions and metastasis. Smaller Department of Pathology
sized and nonfunctional small adrenal lesions, incidentaloma,are being picked up with the Sanjay Gandhi Post Graduate
advancement in the radiological diagnostic modalities and widespread use of CT scans and USG. Institute of Medical Sciences
Main use of the FNA of adrenal lesions is to ascertain origin and character of cystic and solid LPhone No. : 0522–2494244,
adrenal masses, distinguishing benign adrenal nodules from metastatic tumors and diagnosis of E–mail : firstname.lastname@example.org
infectious diseases commonly presenting as adrenal insufficiency (disseminated histoplasmosis).
Radiological guided FNAC of adrenal gland provides an easy and quick method for the diagnosis
of these lesions.
Key Words : Adrenal gland, Mass lesions, Guided FNAC, Cytology.
A working knowledge of the pathophysiology of the gland
and familiarity with the clinical and laboratory data are
important while dealing with FNAC of adrenal lesions and
examining the gross and microscopic features of the biopsied
or resected adrenal gland. Vastly different pathophysiologic
mechanisms may lead to the same clinical syndromes. With
the advancement of imaging modalities and smaller size
of sampled adrenal gland (core needle biopsies/ guided
FNAC) and picking up and resection of non–functional
incidentelomas, poses additional diagnostic challenges to the
pathologist. (1)Figure 1. Part of adrenal gland and corresponding hormones and
BRIEF ANAToMYrelated syndromes
The adrenal glands are paired endocrine organs consisting of
both cortex and medulla, which differ in their development, shape and is gray–tan and <10% of gland volume (1% in
structure, and function. In the normal adult each adrenal gland neonates) and is more prominent with cortical atrophy. (2)
measures approximately 5 × 3 × 1 cm. Left gland is crescentic Laboratory evaluation of adrenocortical function: Blood
and right gland is pyramidal in shape in adults. Normal weight Levels:
in adults is 4–6 grams each after dissection of fat, acute stress
reduces lipid content and weight, prolonged stress induces Peptides: The plasma levels of ACTH, angiotensin II, Plasma
hypertrophy and hyperplasia and increases weight. Adrenal Corticotropin–Releasing Hormone
gland has a complete fibrous capsule, which may merge with Steroids: Cortisol and aldosterone are both secreted
capsule of kidney (either gland), and liver (right sided gland). episodically. Measurement of the sulfate conjugate of DHEA
Beneath the capsule of the adrenal is the narrow layer of zona may be a useful index of adrenal androgen secretion. (3)
glomerulosa (ZG). An equally narrow zona reticularis (ZR)
abuts the medulla. Intervening is the broad zona fasciculata Urine Levels: Measurement of urinary free cortisol
(ZF), which makes up EJMRabout 75% of the total cortex. Cortex Stimulation Tests: are useful in the diagnosis of hormone
is bright yellow due to lipid. ZG is composed of small angular deficiency (adrenal insufficiency) states.
cells with a high nuclear to cytoplasmic ratio, ZF with large Tests of Glucocorticoid Reserve: Within minutes after
clear lipid laden cells arranged in columns and ZR comprises administration of ACTH, cortisol levels increases. This
eosinophilic (compact) cells with little lipid storage arranged responsiveness can be used as an index of the functional
in cord around vascular sinusoids. Medulla has ellipsoid reserve of the adrenal gland for production of cortisol. (4)
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Tests of Mineralocorticoid Reserve and Stimulation of the •
Renin–Angiotensin System: When the dietary sodium intake •
is normal, stimulation testing requires the administration of Ganglioneuroma
Ganglioneuroblastoma (malignant ganglioneuroma)
a potent diuretic, such as 40–80 mg furosemide, followed by •
2–3h of upright posture. The normal response is a two– to •
Metastasis in adrenal gland
fourfold rise in plasma aldosterone levels. (11, 12, 14)•
Suppression Tests: Suppression tests to document hyper–•
secretion of adrenal hormones, involve measurement of the •
target hormone response after standardized suppression of its •
tropic hormone. (13, 17, 18)
Adrenocortical begign lesions (adenoma/nodular
Indications of FNA in adrenal lesion: Main use of FNA of hyperplasia): Adrenal hyperplasia and adenoma or
adrenal lesions is to ascertain origin and character of cystic & indistinguishable on cytology. Cytomorphology of benging
solid adrenal masses, distinguishing benign adrenal nodules adrenal cortical nodule or adenoma reveals numerous naked
from metastatic tumors (the adrenal gland is a common nuclei on a “frothy”, granular background and occasional intact
site of metastasis from tumors elsewhere in the body) and cells with indistinet cell border and bubbly cytoplasm. (18)
diagnosis of infectious diseases commonly presenting as
adrenal insufficiency (disseminated histoplasmosis). With Adrenocortical carcinoma: Differentiation from
widespread use of CT scans & USG, many smaller lesions of adrenocortiocal adenoma and adrenocortical denmoma
adrenal (incidentalomas)are being pickup and subjected to requires Weiss criteria on histology. Cytomorphological
guided FNA/ trucut biopsies. (14, 18)features which indicates adrenocrotical carcinoma are
numerous isolated cell with intact cytoplasm, presence of
Procedure & usefulness of FNA in adrenal lesions: FNA moderate to marked nuclear atypia, mitosis, atypical mitosis
of adrenal gland is done under imaging (CT/US guided) by and necrotic debris. To differentiate adrenocortical carcinoma
either percutaneously or by Direct/ transhepatic approach. from renal cell carcinoma, pheochromoctyoma and metsasis,
Relatively safe procedure and complications include mild–use of immunocytochemistry is very important. (Table 1). (14).
minimal hematuria, self–limited hypotension and bradycardia.
Rare serious complications include pneumothorax and Table 1 : Immunostains in adrenal lesions:
hemothorax. FNA smears of adrenal should be very gently PHEoCHRoMoCYToMA (INTRA–ADRENAl
smeared because adrenal cortical cells have extremely fragile PARAGANGlIoMAS):
cytoplasm. Guided FNA smears are dry and wet fixed and
stained with MGG, Papanicolaou & H & E stains. Cell blocks A presumptive diagnosis of pheochromocytoma is based
may be prepared to perform immunohistochemistry, which on the combination of an adrenal mass, hypertension,
is at times crucial in differentiating adrenocortical lesions and elevated blood and urinary levels of catecholamines.
with metastasis in adrenal gland. (15, 17)Cytologic preparations are highly cellular and contain cells
FNA in adrenal lesions has an accuracy of around 97%, and arrangedpleomorphism in loose can clusters be marked, and as with isolated small polygonal cells. Cellular cells
good negative predictive value, particularly for lesions larger admixed with large spindle–shaped cells with abundant
than 3 cm. False–positive results are uncommon. Rarely, fibrillary cytoplasm. Nuclei are pleomorphic and irregular
the cells of a benign adrenal nodule or adenoma may be in contour. The chromatin is finely stippled; intranuclear
misinterpreted as metastatic small cell carcinoma. The non cytoplasmic pseudoinclusions and prominent nucleoli may
diagnostic rate is around 14%. (16)be present. Red cytoplasmic granules may be present on
ADRENAl INCIDENTEloMA:MGG stain. With alcohol–fixed, Pap–stained preparations, the
cytoplasm has a characteristic, deep red–to–purple, granular
Advancements in medical imaging have led to the incidental appearance. Pheochromocytoma can resemble an adrenal
discovery of non–functional adrenal masses of varying cortical neoplasm. Immunostains help in differentiating
sizes (incidentalomas) in asymptomatic individuals (or in these lesions (Table 1). (20)
individuals in whom the presenting complaint is not directly
related to the adrenal gland. Incidence is approximately ADRENAl MYElolIPoMA:
4%. They are usually detected after 35 years of age. The vast Adrenal myelolipoma are uncommon benign neoplasm
majority of adrenal incidentalomas are small non–secreting and composed of adipose tissue and benign hematopoietic
cortical adenomas of no clinical importance. (17)elements. FNA smears show fat with interspersed marrow
Adrenal lesions:elements including nucleated red blood cells, megakaryocytes,
• Adrenocortical hyperplasia, nodular hyperplasiaand granulocytes and their precursors (all three lineages).
• Adrenal cortical adenomas, Conn’s adenomaDifferential diagnosis includes angiomyoliopma of the
• Adrenocortical carcinomakidneyelements andwhich absence is distinguished of smooth by musclepresence cells of andhematopoietic negative
• Pheochromocytoma (intra–adrenal paraganglioma)HMB45 immunostain. (21)
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METASTATIC TUMoRS IN ADRENAl GlAND:RCC. Metastatic adenocarcinomas from the lung, kidney,
FNA of the adrenal gland is useful to confirm or rule out an breast, and other sites can look like an adrenal cortical
adrenal metastasis in a patient with a history of cancer and carcinoma. Immunostains are helpful in distinguishing
also in distinguishing metastatic tumor nodules with benign adrenocortical lesions from metaststasis eg; TTF–1 for
adrenocortical conditions. The most common metastases metastatic adenocarcinoma or small cell carcinoma of the
encountered by FNA are from lung cancers, melanoma, and Lung, S–100 and HMB–45 for melanoma (Table 1). (5, 6)
Table 1 : Immunostains in adrenal lesions:
Adrenocortical Ca /adenoma hyperplasia Pheochrome–cytoma Renal Cell carcinoma Metastasis
Adrenal infections: are usually part of systemic disease and
any infection can occur in the adrenal glands. (7)
Tuberculosis accounts for approx 70% of Addison’s disease
in developing countries. On FNA tuberculosis of adrenal
show extensive caseating necrosis and poorly formed
granulomatous response. (8)
Fungal infections of adrenal are discovered in working up a
PUO or adrenal cortical insufficiency. Adrenal insufficiency
usually occurs when >90% of the adrenal is destroyed. fungal
infections of adrenal include histoplasmosis, blastomycosis,
coccidiomycosis and cryptococcosis. Commonest fungal
infection of adrenal is histoplasmosis. Disseminated
histoplasmosis presents as bilateral adrenal mass and
may present as adrenal insufficiency. On cytomorphology Figure 2. Guided FNA smear from adrenal showing large atypical
histoplasomosis show caseating necrosis, blunted polygonal cells from case of adrenal cortical carcinoma.
granulomatous response and organisms may aggregate in (MGG X100 original magnification)
macrophages. Characteristic features of histoplasma are
tiny 2– to 4–μm oval yeasts that reproduce by budding and
parasitize macrophages. Awareness of histoplasmosis and
early diagnosis with FNA is important as timely antifungal
treatment (amphotericin B) prevents mortality and morbidity
(Table 2). (9, 10)
Table 2 : Adrenal histoplasmosis at SGPGI Experience
AgeMedian 55 yrs ; range (45–66 years)
Fever, Wt LossAll cases
Bilateral adrenal 8/8 Figurepolygonal 3. Guidedcells from FNA case smear of adrenal from adrenal lymphoma. showing large atypical
Adrenal Insufficiency EJMR3/8(MGG X100 original magnification)
DiagnosisGuided FNA 6/8, Histology 2/8
Treatment:Amphotericin B–2weeks, followed by
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7. Dusenbery D, Dekker A: Needle biopsy of the adrenal gland:
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