22 Miscellaneous Adrenal Neoplasms (Cysts, Myelolipoma, Hemangioma, Lymphangioma)

contents

22.1 Adrenal Cysts . . . 223 22.1.1 True Cyst . . . 224 22.1.2 Pseudocysts . . . 225 22.1.3 Parasitic . . . 225 22.2 Myelolipoma . . . 225 22.3 Hemangioma . . . 227 22.4 Lymphangioma . . . 228

References . . . 228

Adrenal neoplasms that are non-functional and have benign characteristics on imaging studies may pose a management dilemma. This is particularly true of the uncommon neoplasms that have an uncertain natural history. These tumors usually present as adrenal inci- dentalomas, with an incidence of 1–4% on imaging studies.With liberal computed tomography (CT) scan- ning and advanced imaging techniques, they are be- coming a more frequent entity. While the majority of adrenal incidentalomas are adenomas or metastases [14], this chapter will focus on the diagnosis and man- agement of the less common adrenal neoplasms.

The best studies to obtain to aid in the diagnosis of these neoplasms are CT scanning and magnetic reso- nance imaging (MRI). A non-enhanced CT scan is the most common modality used in adrenal imaging.

Density criteria are used to assist in characterizing the adrenal pathology.The helical scanning techniques us- ing smaller slices (3 mm) have improved the accuracy in assessing density. MRI with chemical shift imaging has excellent contrast resolution, allowing imaging of tumors as small as 0.5 cm.The T1-weighted images are the best for assessing anatomic detail. Accurate imag- ing and interpretation of these neoplasms is critical because the majority are clinically benign and do not require an operation.

If an operation is recommended; the patient can usually undergo a laparoscopic adrenalectomy. An

open adrenalectomy should be performed if there is any suspicion for a primary malignancy. The role of fine-needle aspiration for cytology is limited second- ary to sparse cellularity. Prior to any surgical or other invasive procedure (aspiration), the lesion must be evaluated for function. Functional studies should in- clude a 24-h urine for cortisol, metanephrines, cate- cholamines and vanillylmandelic acid to assess for either a cortisol-producing neoplasm or a pheochro- mocytoma. A serum potassium level and possibly an aldosterone level should be obtained to screen for an aldosterone-producing tumor.

22.1 Adrenal Cysts

The first adrenal cyst of record was described in 1670 by Greiselius,a Viennese anatomist [4].Since that time, adrenal cysts have been rare, with an incidence of less than 0.1% [1]. They account for 4–22% of adrenal in- cidentalomas [14]. Occurring more commonly in women, they are equally distributed bilaterally. They can occur at any age, but children may actually have a cystic neuroblastoma. Overall, adrenal cysts are most accurately identified and evaluated with CT scanning.

The most common presentation is as an inciden- taloma. In a review of 286 cases, they were found inci- dentally in 34% of patients (Table 1) [16]. Other pre- sentations included: abdominal pain in 19%, abdomi- nal mass in 10%, pain and a mass in 10% and hypertension in 9% [16]. Patients with hypertension may also have a cystic pheochromocytoma, which supports the importance of functional studies.

In 1966,Foster classically divided adrenal cysts into four categories: endothelial cysts,pseudocysts,epithe- lial cysts and parasitic cysts (Table 2) [3,6].The largest review was reported in 1999 by Neri and Nance, which included 515 patients with adrenal cysts (Table 3) [16].

They found that most adrenal cysts were pseudocysts (56%), followed by endothelial (24%), unspecified be-

(Cysts, Myelolipoma, Hemangioma, Lymphangioma)

Melanie L. Richards

nign (12%), epithelial (6%) and parasitic (2%). Many simply classify adrenal cysts as either a true cyst or a pseudocyst.

There are varying opinions regarding the manage- ment of adrenal cysts. Some authors have recom- mended aspiration of asymptomatic small non-func- tioning cysts and surgical excision of cysts greater than 5 cm diameter [13].Tung recommended attempts at aspiration in all symptomatic benign cysts, reserv- ing surgery for recurrence after aspiration [21]. The current recommendation is for continued observation

Presentation Number of

patients (%)

Incidental 97 (34%)

Abdominal pain 53 (19%)

Abdominal mass 30 (10%)

Abdominal pain and mass 30 (10%)

Hypertension 26 (9%)

Flank pain 17 (6%)

Hypertension and a symptom or sign 13 (5%)

Back pain 7 (2%)

Trauma 7 (2%)

Loin pain 2 (1%)

Shock (ruptured angiomatous cysts) 2 (1%)

Vague 2 (1%)

Table 2. Foster’s 1966 classification of adrenal cysts [6]

Histologic type Frequency

Parasitic cysts (hydatid cysts) 7%

Epithelial cysts 9%

Embryonal cysts Cystic adenomas

True glandular (mesothelial)

Endothelial cysts 45%

Lymphangiomatous 42%

Angiomatous 3%

Pseudocysts 39%

Table 3. Classification of adrenal cysts in 515 patients [16]

Classification (%) Subtype Case number (%)

Parasitic (2%) Echinococcus 12 (2%)

Epithelial (6%) Congenital glandular/retention 6 (1%)

Cystic adenoma 14 (3%)

Epithelial unspecified 8 (2%)

Endothelial (24%) Lymphangiomatous 83 (16%)

Angiomatous 13 (3%)

Unspecified or mixed angio and lymph 23 (5%)

Pseudocyst (56%) Hemorrhagic 188 (37%)

In adenoma 7 (1%)

Pheochromocytoma 21 (4%)

Malignant tumor

– Neuroblastoma 11 (2%)

– Adrenocortical carcinoma 5 (1%)

– Metastatic 1 (<1%)

– Unspecified 1 (<1%)

Pyogenic 3 (<1%)

Unspecified pseudocyst 55 (11%)

Unspecified benign (12%) 64 (12%)

of small benign-appearing asymptomatic adrenal cysts [3]. Surgical excision or enucleation of benign cysts can safely be performed laparoscopically.

22.1.1 True Cyst

A true cyst may be a benign or malignant lesion con- taining epithelial or endothelial cells. The endothelial cysts include lymphangiomatous (lymphangiectatic or serous) (Fig. 1) and angiomatous (hemangioma) cysts. These cysts are typically small and multiple. The epithelial cysts are also referred to as “glandular”cysts.

Since normal adrenal contains no glandular or ductal

structures, it has been proposed that these epithelial

cysts are derived from embryonic rests. This category includes cystic adenomas, glandular retention cysts and embryonal cysts.

22.1.2 Pseudocysts

Pseudocysts are the most common clinically diagnosed

adrenal cysts. A pseudocyst lacks an epithelial lining and is often a result of hemorrhage or infarction. Cal- cification within the wall of a cyst is suspicious for ei- ther a pseudocyst or a parasitic cyst. Rarely, a benign or malignant adrenal tumor may undergo cystic de- generation and result in a pseudocyst. Recently, it has been shown that hemorrhagic adrenal pseudocysts of- ten contain thin-walled vascular channels [20]. Im- munohistochemical studies of these channels are con- sistent with a vascular origin, suggesting that many of these hemorrhagic cysts are endothelial cysts. A 47- year literature review by Torres identified 107 patients with 111 vascular adrenal cysts; 79% were hemor- rhagic pseudocysts and 21% were endothelial cysts [20]. The differentiation may be difficult because or- ganizing thrombus may form endothelial cells. Histo- logically, hemorrhagic pseudocysts may also display papillary endothelial hyperplasia [10]. Papillary en- dothelial hyperplasia may be confused with an an- giosarcoma. It is differentiated from an angiosarcoma by the lack of endothelial cell atypia, the presence of a hyaline core and the absence of gross invasion of ad- jacent tissues.

Most patients may complain of a vague discomfort;

others may have severe pain that results from an in- tracystic hemorrhage or rupture. Adrenal cysts may also become infected. Infected cysts may also present

with pain and these patients will often have a leuko- cytosis. Surgical resection is recommended for symp- toms or a suspicion of malignancy.

22.1.3 Parasitic

Parasitic infections, most commonly a hydatid cyst,

can also present as adrenal cysts. These cysts are the result of an Echinococcus tapeworm infestation. Echi-

causing cystic echinococcosis. Echinococcosis is un- common in northern Europe and North America. It is endemic to areas of South America, the Mediter- ranean, the Middle East, Africa, Australia and New Zealand. Of all patients with echinococcus, less than 0.5% will have adrenal involvement [6].These patients may have an eosinophilia or a hypogammaglobine- mia. Serology for echinococcus can be obtained to aid in the diagnosis of a hydatid cyst. The enzyme-linked immunosorbent assay (ELISA) and the indirect hemagglutination test are the most sensitive screening tests. Testing for antibodies to echinococcus will con- firm the diagnosis.A CT scan is also a highly sensitive and accurate method to aid in the diagnosis because it can identify daughter cysts.

Patients will often remain asymptomatic until the cyst has increased in size to over 5 cm. Aspiration is generally not recommended because there is a risk of cyst disruption and subsequent dissemination of a parasitic infection.There is no adequate medical treat- ment for cystic echinococcal infections.These patients should be surgically treated with an adrenalectomy. It is critical to avoid spillage of cyst contents, not only to prevent spread of the disease, but to avoid an allergic anaphylaxis.

22.2 Myelolipoma

Adrenal myelolipomas were first described in 1905 by Gierke [7]. These rare tumors are reported in 0.08–2% of the population [5]. They are benign, non-functional and usually asymptomatic (Fig. 2).

They are most often found incidentally as solitary lesions on imaging studies or at autopsy. Rarely, they may present with symptoms secondary to hemor- rhage, infarction or from compression of adjacent structures. There are a few reports of associated en- docrine function, most often a 21-hydroxylase defi- ciency or Cushing’s syndrome [22]. Adrenal insuffi- ciency, primary hyperaldosteronism and pheochro-

(Courtesy of D. Linos, M.D.)

mocytoma have also been found in association with adrenal myelolipomas.

Histopathology studies show these tumors to con- sist of both fat and hematopoietic or myeloid tissue (Fig.3).It is this finding that suggests that these tumors originate from reticuloendothelial cells of the blood capillaries. These cells may undergo adrenocortical cell metaplasia in response to stimuli such as necrosis, hemorrhage, infection or stress [19]. It has also been postulated that these tumors originate from the em- bolization of hemopoietic stem cells and ectopic myeloid hyperplasia [23]. The association with other functional tumors has led other authors to suggest that adrenal myelolipomas are within the spectrum of a multiple endocrine neoplasia [2].

These benign tumors are easily identified by their well-encapsulated fatty appearance on CT scanning (Fig. 4). They have a low density, typically with nega- tive Hounsfield units (–100 to –200) and may have ar- eas of calcification. The presence of gross fat, with a density below –30 HU confirms the diagnosis [12].The fatty-appearing adrenal myelolipomas should be dif- ferentiated from teratomas, liposarcomas, adenomas, metastatic lesions and primary adrenal malignancy.

Retroperitoneal lipomas and renal angiomyolipomas are also in the radiologic differential. If the diagnosis is uncertain, an MRI may be useful to assess tissue planes for invasion or to identify the origin of extra- adrenal tumors.

These tumors are rare and the largest series of ad- renal myelolipomas consisted of 21 tumors in 20 pa- tients [8]. Four patients underwent an adrenalectomy;

two for abdominal pain, one for Cushing’s syndrome and one for a large tumor (10.5 cm). The patient with Cushing’s syndrome did have both an adrenal myelolipoma and an adrenal adenoma. Fifteen non- operative patients were evaluated over a mean follow- up period of 3.2 years. Thirteen of these patients re- mained asymptomatic and two patients had vague ab- dominal complaints. Serial CT scans were obtained in 12 patients. The mean tumor size increased from 5.1 cm (range 2.2–12 cm) to 5.6 cm (range 2.5–17 cm).

Fifty percent of patients had tumors that had increased in size. Tumor size did not appear to correlate with symptoms and no adverse outcomes occurred with non-operative management. These authors felt that routine imaging was unnecessary, but that patients should be followed clinically in order to monitor for clinically significant growth.

Depending on the level of suspicion for malignan- cy; the patient may be explored or a fine-needle aspi- ration may be performed in a patient with normal ad-

(Courtesy of D. Linos, M.D.)

Fig. 3. A thin rim of adrenocortical cells adjacent to bone marrow tissue and mature adipose tissue in a myelolipoma [25]. H&E stain, ¥200

Fig. 4. Non-contrast CT scan showing bilateral adrenal masses with fat densities similar to retroperitoneal or sub- cutaneous fat consistent with myelolipomas [22]

renal function. Otherwise, these tumors are benign and do not require surgical intervention unless they are symptomatic.

22.3 Hemangioma

Adrenal hemangiomas are rare and benign. There have been approximately 50 cases reported in the world literature since the first adrenalectomy for a he- mangioma by Johnson and Jeppesen in 1955 [11, 15].

They are usually small, non-functional and asympto- matic. Large tumors (25 cm) have been reported and these are at risk for bleeding. Histologically, most have a cavernous appearance with the presence of hyper- vascularization (Figs.5,6).The patients are often in the 5th through 7th decade of life. They are twice as likely to occur in women [18].

The diagnosis can be made on both CT and MRI studies. A CT scan with contrast will show peripheral enhancement and a central area of low attenuation.

(Fig.7).This central area may fill with contrast with de- layed imaging. These lesions typically contain calcifi- cations, which may be speckled in appearance. These calcifications may have the appearance similar to a phlebolith. MRI imaging will show a low T1 signal and a moderate to high T2 signal. If there are areas of hem- orrhage or necrosis, these will enhance on T1-weight- ed images [9].

Adrenalectomy has been recommended by some authors [17].However,most reserve adrenalectomy for symptomatic tumors, tumors that are suspicious for a malignancy such as a hemangiosarcoma and for larg- er tumors at risk for bleeding. Patients with a sympto- matic or large tumor with benign characteristics are candidates for laparoscopic adrenalectomy.

Fig. 5. Gross specimen of a 9.5-cm left adrenal gland con- taining a cavernous hemangioma. (Thiele 2001 [19a])

Fig. 6. Hypervascularization and normal adjacent adrenal tissue in an adrenal hemangioma [24]. H&E stain, ¥100

Fig. 7. Contrast-enhanced CT scan showing a low-density mass with peripheral enhancement in the right adrenal gland consistent with a hemangioma [24]

22.4 Lymphangioma

The lymphangioma is one of the most common cystic adrenal neoplasms (Fig. 8). Classified as endothelial cysts, they account for 16% of all adrenal cysts (Table 3). Only the hemorrhagic pseudocyst is more prevalent. Lymphangiomas are typically small and most are reported as incidental findings at autopsy.

These lesions are multiloculated and many have calci- fications present on imaging studies.The cyst contents may range from clear to milky to hemorrhagic. They

are difficult to differentiate from organizing hemor- rhagic pseudocysts because both lesions may contain endothelial cells.Surgery is rarely indicated in these le- sions because they are usually small and asympto- matic.

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