Incidentally Discovered Mass Lesions (Case 35)

Case: A 42-year-old woman presented to her family physician with right lower quadrant discomfort of 2 days’ duration and was sent for a CT scan of the abdomen and pelvis to “rule out appendicitis.” The CT scan revealed a normal appendix and no acute abnormality. The patient’s acute problem was self-limited, and she felt better the following day. However, the radiologist noted an “incidental finding,” and the family physician was promptly notified.

Differential Diagnosis

Speaking Intelligently

An incidentally discovered mass, or “incidentaloma,” will be experienced by every physician, both during training and during practice. The unsuspected mass that appears on imaging done for some other purpose can present a great conundrum for clinicians. As our population ages and both the frequency and resolution of radiologic imagery increase, there will consequently be more incidental mass findings. Clinicians must be prepared to manage these safely and effectively. The focus of evaluation is a balance of minimizing untoward stress or risk to the patient without missing something important that requires additional diagnostic evaluation.

PATIENT CARE

Clinical Thinking

• Incidental lesions force the clinician to “work backwards,” by re-examining the patient’s history and clinical picture to determine whether the finding validates a concern, warrants a more extensive evaluation, or requires surveillance.

History and Physical Examination

• Specific points of history, possible findings on examination, and specific tests for diagnosis are covered separately under Clinical Entities below.

Clinical Entities

Medical Knowledge

Adrenal Mass
Pφ	An adrenal “incidentaloma” is an adrenal mass > 1 cm in size that is discovered on radiologic imaging performed for reasons unrelated to the adrenal glands.
TP	Prevalence of an incidental adrenal mass found on abdominal CT imaging is 4% and in those aged ≥ 70 years is ∼7%. A compelling theory is that as people age there is increased likelihood of undergoing imaging and that the effects of local ischemia and atrophy lead to the development of cortical nodules or lesions.
Dx	Three questions should be investigated when evaluating an incidental adrenal mass: (1) Is the tumor active or functional? (2) Does the radiologic phenotype suggest malignancy? (3) Is there a history of a previous malignant lesion? Radiologic phenotypic features that aid our characterization of the mass include size, shape, symmetry, and heterogeneity or homogeneity of tissue density measured in Hounsfield units (HU). Adenomas tend toward smooth edges, symmetry, and homogeneous density. FNA of the mass is recommended only in patients with suspicious radiologic phenotypic malignant features in the background of a prior oncologic process. FNA is also reasonable in patients refusing the recommendation for surgery, if the findings would alter management. FNA should proceed only after a pheochromocytoma has been ruled out, as hypertensive crisis and physiologic collapse may occur.
Tx	If any of the above diagnostic questions can be answered affirmatively, then a multidisciplinary approach is prudent, inclusive of an endocrinologist, surgeon, and medical oncologist. Refer to the following Clinical Entities on specific workup for hypercortisolism, hyperaldosteronism, pheochromocytoma, and primary adrenocortical adenocarcinoma. Excess production of androgen or sex hormones is rarely asymptomatic and is not included in our discussion on incidental adrenal masses. Incidental adrenal lesions that are inactive and measuring over 4–6 cm warrant both radiologic and biochemical follow-up. Radiologic follow-up is fashioned to elicit whether the lesion is either dormant or rapidly proliferating; radiologic evaluations are recommended at 6-, 12-, and 24-month intervals. Annual biochemical assays, over a 5-year duration, are warranted for any nonfunctional adrenal mass measuring over 4–6 cm because there is a positive relationship between adrenal mass size and hormonal functionality. See Cecil Essentials 67.

Cortisol-Secreting Adrenal Mass
Pφ	These lesions display autonomous glucocorticoid production and can be termed subclinical hypercortisolism (SCS) when the patient is asymptomatic or lacks the signs and symptoms of the Cushing syndrome.
TP	SCS is the most common biochemical abnormality detected in patients with an adrenal incidentaloma (∼9%) and can be accompanied by arterial hypertension, obesity, dyslipidemia, glucose intolerance, and osteoporosis.
Dx	An overnight 1-mg dexamethasone suppression test is done to screen for elevated cortisol levels in patients with suspected Cushing syndrome or SCS; a serum cortisol > 5 µg/dL after a 1-mg (low-dose) dexamethasone suppression test is considered positive (specificity 91%). If the screening test is positive, then confirmatory testing is warranted. This can be done with measurement of a 24-hour urinary free cortisol (UFC), midnight salivary cortisol, or a 48-hour 2-mg (high-dose) dexamethasone suppression test.
Tx	Medical therapy remains the mainstay of treatment. Surgical adrenalectomy is reserved for patients who are young (<40 years) and those with recent onset or worsening hypertension, glucose intolerance, dyslipidemia, obesity, or osteoporosis. See Cecil Essentials 67.

Aldosterone-Secreting Adrenal Mass
Pφ	Almost 1% of incidental adrenal masses are aldosterone-secreting adenomas, warranting biochemical evaluation in those with hypertension or other signs or symptoms consistent with autonomous aldosterone production.
TP	Patients with hypertension should undergo evaluation for hyperaldosteronism. In those with hypokalemia and mild hypernatremia, you may elicit a history of nocturia, polyuria, muscle cramping, and palpitations.
Dx	Measure the ambulatory morning plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio while the patient is upright. A PAC/PRA ratio > 20 is consistent with hyperaldosteronism (note: spironolactone and mineralocorticoid antagonists can result in false positive results). A positive screen is followed with confirmatory measurement of mineralocorticoid secretory autonomy with oral sodium loading, IV saline infusion, or a fludrocortisone suppression test.
Tx	Any lesion autonomously producing aldosterone should be referred for surgical removal. See Cecil Essentials 13, 67.

Pheochromocytoma
Pφ	Pheochromocytoma is associated with high rates of morbidity and mortality.
TP	History may include episodic (paroxysmal) rapid heart rate, tremor, headache, or diaphoresis. These episodes may be precipitated by anxiety, extreme postural changes, or medications (metoclopramide and anesthetic agents).
Dx	Initial evaluation should include measurement of plasma free metanephrines (sensitivity 98% and specificity 92%), and/or 24-hour total urinary metanephrines and fractionated catecholamines. A total plasma catecholamine of at least 2000 pg/mL is diagnostic of a pheochromocytoma. Generally a positive plasma fractionated metanephrine test deserves confirmation with either urinary fractionated metanephrines or a clonidine suppression test. When plasma free metanephrines, 24-hour urinary metanephrines, and fractionated catecholamines are elevated, the sensitivity is 100% and specificity 96.7%, with a negative predictive value of 100%. False positive results can occur in patients with congestive heart failure, cerebrovascular accident, acute alcohol or clonidine withdrawal, cocaine use, or use of medications such as tricyclic antidepressants, phenoxybenzamine, bromocriptine, labetalol, and α1-adrenergic receptor blockers.
Tx	The mainstay of treatment for pheochromocytoma is surgical resection after several weeks of α-adrenergic blockade. See Cecil Essentials 13, 67.

Primary Adrenocortical Adenocarcinoma
Pφ	Primary adrenocortical adenocarcinoma is found in 4.7% of patients and is metastatic in 2.5%. The prognosis is very poor, with mean survival at the time of diagnosis of only 18 months.
TP	There may be a history of some degree of discomfort secondary to mass effect or other vague symptoms related to secretion of any the adrenals’ hormonally active substances. Patients may have signs of osteopenia, osteoporosis, hypertension, glucose intolerance, diabetes mellitus, hyperlipidemia, and leukocytosis or lymphopenia. Only 50% to 60% of adrenocortical adenocarcinomas are hormonally active. Furthermore, patients with hormonally inactive adrenocortical adenocarcinomas rarely present with weight loss, fever, or anorexia, or other symptoms of back or abdominal pain.
Dx	The mass size and radiologic appearance are the two major predictors of malignant disease. A diameter > 4 cm is consistent with an adrenocortical carcinoma with a sensitivity of 90% (specificity only 24%). Risk of malignancy rises with increasing size of adrenal masses: those <4 cm confer 2% risk for malignant potential, 4–6 cm 6% risk for malignant potential, and >6 cm a 25% risk for malignant potential. Based on size alone, surgical removal is advocated for adrenal masses > 4–6 cm. Once adrenocortical carcinoma is suspected, size matters even more, because the smaller the lesion at the time of diagnosis, the lower will be the tumor stage, which correlates with a better overall prognosis.
Tx	Referral to both medical and surgical oncologists is appropriate. See Cecil Essentials 67.

Ovarian Mass

Pφ

Any adnexal mass identified by a primary-care physician or gynecologist should be considered potentially malignant in patients in any age group.

In terms of gynecologic cancer, ovarian cancer is the leading cause of death. In 2007 an estimated 22,500 women were newly diagnosed and there were more than 15,000 deaths. Mortality rises with advanced stage; the 5-year survival in those with stage I cancer approaches 90%, while the 5-year survival in those with stage III or IV is between 30% and 55%.

Most incidentally discovered adnexal masses are benign, especially those that are unilocular cystic masses in premenopausal or perimenopausal women. Cystic lesions measuring >5–6 cm should be followed up radiologically in the premenopausal age group, as they are at risk of torsion. Referral to a gynecologic oncologist is recommended when complex cysts of any size are found in postmenopausal women (risk of malignancy 3%). Tumor volume doubling time for ovarian cancer is <3 months; thus, repeat imaging (ultrasound or MRI) should occur in 6 weeks on any lesions with solid components or any lesion in postmenopausal women.

Society of Gynecologic Oncologists and American College of Obstetrics and Gynecology guidelines for referral in women with a newly detected adnexal mass (2002)
Premenopausal woman	Postmenopausal woman
CA-125 > 200 U/mL	CA-125 > 35 U/mL
Ascites	Ascites
Evidence of abdominal or distant metastasis	Evidence of abdominal or distant metastasis
Family history of breast or ovarian cancer (in a first-degree relative)	Family history of breast or ovarian cancer (in a first-degree relative)
	Nodular or fixed pelvic mass
Reprinted from Journal of the American College of Radiology, 4/10, Miller JC, et al., Evaluating adnexal lesions: Which need follow-up?, pages 725–729, 2007, with permission from American College of Radiology. http://www.sciencedirect.com/science/journal/15461440.

Operative indications and referral are warranted in patients who are symptomatic and those who display increasing size of the lesion over time. See Cecil Essentials 57.

Renal Mass
Pφ	Incidental renal tumors have emerged as a new clinical entity with modern imaging. Small renal masses measure <4 cm and enhance on imaging. Renal masses are covered in greater detail in Chapter 25.
TP	The frequency of small renal masses has risen quite steeply. A recent review by the US National Cancer Data Base (NCDB) shows that the proportion of tumors measuring <4 cm increased by >10% between 1993 and 2004.
Dx	There are no concrete guidelines on evaluation, management, and surveillance of small renal masses. The consensus is that elderly or infirm patients, with an expected short life expectancy, can undergo surveillance with imaging every 6–12 months. Several studies have supported a positive correlation between renal cell tumor growth and increasing malignancy and higher tumor grade. Percutaneous biopsy (PCB) has been utilized to distinguish benign from malignant lesions, but this falls short on accuracy (20% remain indeterminate) and thus should be used only if the result will change management.
Tx	Pathologic grading is traditionally done at the time of surgical removal. Surgical excision has been the mainstay of treatment for renal masses especially in those under the age of 70 years with a significant life expectancy. Young, healthy individuals with lesions that are >1 cm generally are referred for surgical removal. Treatment options include radiofrequency ablation and cryoablation, although long-term data on efficacy are not yet available. Nephron-sparing surgery (NSS) is appropriate for many patients. See Cecil Essentials 30, 57.

Hepatic Mass
Pφ	Liver lesions can be quite common. Most of them will be benign and appear as a simple cyst, hemangioma, focal fat, or focal nodular hyperplasia (FNH). Incidental liver masses are challenging in patients with cirrhosis, fibrosis, and hemochromatosis, as there is a slightly higher propensity for malignant potential.
TP	These lesions are discovered at the time of right upper quadrant ultrasound or upon CT performed for reasons other than those related to liver abnormalities.
Dx	Workup of incidental liver lesions follows an algorithm based on the clinical and radiologic pictures correlating positively with malignant potential. Classic benign lesions contain fat or serous contents (simple cyst, hemangioma, FNH). Patients with a previous history or risk factors for hepatic malignancy warrant MRI with contrast, or helical CT with contrast, including delayed portal venous phases. Patients with lesions that correlate both clinically and radiologically with malignancy should be evaluated with serum tumor markers and/or percutaneous core biopsy.
Tx	Malignant confirmation warrants referral to both surgical and medical oncologists for directed treatment and management.

Solitary Pulmonary Nodule
Pφ	A solitary pulmonary nodule is an approximately round lesion that is between 1 and 3 cm in diameter and completely surrounded by pulmonary parenchyma. When warranted, workup is critical because of the high mortality rate (85%) in those with lung cancer. Pulmonary nodule is covered in greater detail in Chapter 17.
TP	Concern for malignant potential should be raised in those with a social history of smoking (total pack-years is directly proportional to incidence of cancer). Other risk factors include prior malignancy (testicular, melanoma, sarcoma, or colon), pulmonary fibrosis, and HIV infection.
Dx	Stable radiologic findings over a 2-year period support a benign etiology. Reviewing old images is prudent and may negate further workup. Lesions with spiculated margins and calcifications that are stippled, eccentric, diffuse, or amorphous warrant further workup with either FNA or core biopsy (if lymphoma is suspected). CT with IV contrast that demonstrates nodule enhancement <15 HU is strongly indicative of a benign etiology (positive predictive value, ∼99%). An excellent prediction model is available at http://www.chestx-ray.com.
Tx	If malignant features are present, staging must be performed to determine the appropriate treatment. See Cecil Essentials 24.