Management Considerations for Incidental Adrenal, Splenic and Pulmonary Nodules

Rodney L. Page MS, DVM: Diplomate ACVIM (Internal Medicine & Oncology)
College of Veterinary Medicine, Cornell University

Introduction

Increased use of abdominal ultrasonography has enhanced our ability to identify clincial and subclinical adrenal and splenic abnormalities. Likewise, recommendations for aggressive screening of geriatric dogs with survey radiographs are being developed to increase longevity. Such a shift in screening technology and early detection has created a clinical dilemma in assymptomatic patients: what is the significance of these lesions and what common sense recommendations can be made for additional diagnostic evaluation and followup. The detection of incidental adrenal lesions should prompt additional provocative testing to confirm an endocrine abnormality since few adrenal lesions are benign in dogs and cats. However, small (<3 cm diameter) incidental lesions in the spleen may be benign processes not requiring immediate intervention. Solitary pulmonary nodules should be aggressively staged and dealt with early.

Adrenal Abnormalities

Unexpected adrenal masses are identified in approximately 1 % of abdominal ultrasound evaluations. However, discovery of adrenal lesions increases in dogs undergoing a complete abdominal ultrasound evaluation for a non-specific illness. For instance, in a recent retrospective review, 20/40 dogs later confirmed to have pheochromocytomas had suspect adrenal lesions despite the absence of clinical signs specifically related to that disorder. Those pheochromocytomas not identified on ultrasound were < 1 cm in diameter. Thus, increased attention to adrenal glands during ultrasound examination should increase the discovery of adrenal-specific lesions.

A recent compilation of adrenal lesions from several pathologic and clinical data bases provide useful estimates of the prevalence of benign and malignant adrenal gland tumors in dogs and cats . Approximately 35-40% of geriatric beagles from research colonies had histopathologic evidence of nodular hyperplasia following a complete necropsy. Primary adrenal tumors (cortical and medullary) were reported in 5-19% of these dogs. Surprisingly, 33% of histopathologic adrenal lesions in research beagles were metastases. The most common tumors identified with adrenal metastases were lymphoma, hemangiosarcoma and melanoma. In contrast, primary adrenal tumors were reported in approximately 0.17-0.76% of pet dogs (1-2 % of all canine tumors) and 0.03% of cats (0.2% of feline tumors) from the Veterinary Medical Data Base. It is interesting that only 3-5 % of canine adrenal lesions in this data base were metastases. The apparent discrepancy between clinical and histologic evidence of adrenal gland neoplasia is likely due to: 1) previously insensitive methods to noninvasively identify and characterize adrenal lesions antemortem, 2) difficulty obtaining tissue for biopsy due to the size and location of the adrenal gland, and, 3) the long latency period associated with some primary adrenal tumors that may remain assymptomatic or occult. The subclinical incidence of adrenal metastases in dogs suggest that adrenal glands should be screened routinely for involvement, particularly in dogs with melanoma and hemangiosarcoma.

More sensitive methods of adrenal imaging will also aid in the characterization of lesions. In humans, carcinomas are generally larger than adenomas, invasive into surrounding structures and have different imaging qualities on CT or MR. Pheochromocytomas likewise have different imaging characteristics. Preliminary evidence in dogs supports this finding as well. Adenomas of the adrenal gland were generally < 2 cm in diameter and carcinomas were of any size, but often > 2 cm. Calcification does not appear to be predictive for either adenoma or carcinoma although pheochromocytomas do not calcify. Expanded use of imaging modalities such as CT and MR in dogs and cats will likely provide additional data on the characteristics of specific adrenal lesions for use in diagnosis and treatment planning.

Incidental adrenal lesions should be investigated clinically if they are diagnosed. Non-neoplastic adrenal lesions such as cysts or granulomas are very rare in dogs and cats and the high incidence of metastatic lesions justifies a thorough endocrinologic screening and evaluation for non-adrenal neoplasms. Incidental adrenal masses may appear to be nonfunctional at the time of diagnosis although it seems more likely they are actually subclinically functional. The diagnosis may be pursued aggressively with a surgical biopsy or may be more conservatively managed (frequent imaging, endocrine testing, blood pressure screening, etc.). However, management of neoplasia before it has become clinically apparent is clearly the best time to intervene.

Difficulty obtaining a biopsy has also hampered characterization of adrenal lesions. The clinical evaluation of the patient with a suspected adrenal mass often provides sufficient justification to initiate medical therapy and the need for biopsy is not strong. Furthermore, a nonsurgical biopsy with ultrasound or computed tomography guidance is not often attempted in small adrenal nodules due to the highly vascular nature, size and potential complications associated with the procedure. Finally, the histologic or cytologic identification of adrenal adenomas, macronodular hyperplasia, carcinoma and even pheochromocytoma may be difficult to confirm even with adequate tissue. Therefore, histologic criteria such as grade of malignancy that are indicative of response to treatment in other tumor types have not been developed in canine or feline adrenal tumors as they have for many other tumor types.

Splenic Nodules

Identification of splenic nodules in dogs undergoing abdominal ultrasonography is relatively common. Small nodules identified in older dogs (>8 yrs) are benign in the majority of instances. Prior to the wide-spread use of ultrasound the prevalence of splenic nodules were only appreciated when they were palpable or when dogs presented with signs consistent with splenic hemangiosarcoma. It has been estimated that of all the splenic nodules identified by clinical palpation or abdominal radiography, approximately 40% -60% are tumors. Other diagnoses included lymphoid hyperplasia, hematoma and non-specific changes associated with congestion, hemorrhage, extramedullary hematopoiesis and hemosiderin deposition. Hemangiosarcoma accounted for approximately 2/3f of the neoplasms of the spleen. Anaplastic sarcoma was also diagnosed occasionally.

With the advent of ultrasound the identification of small (1.0 cm) splenic nodules has become routine. In addition to lymphoid hyperplasia other benign processes that are associated with small splenic nodules include splenic infarction or abscess. The dilemma of whether to proceed with additional diagnostic procedures for such lesions can be frustrating.

Additional diagnostic procedures may be considered if the dog or cat being evaluated has one of the following major risk factors: 1) breed at high risk for splenic neoplasia such as German shepherd dogs or golden retrievers, 2) a concurrent condition associated with high likelihood of splenic involvement such as hemangiosarcoma at other sites, mast cell tumors, lymphoma, myeloma and systemic infectious diseases such as rickettsial and fungal infections. Aspiration of nodules may be possible for those located superficially or if they are substantial in size (> 2 cm). However, aspiration of a small hemangiosarcoma may result in contamination of the abdominal cavity with tumor cells. Inaccessible lesions may require laparotomy and such a procedure may be warranted in high risk groups. Clearly, the splenic pathology should be considered in the context of any other clinical circumstances.

In a dog without such risk factors a re-evaluation of the spleen should be conducted in 4-6 weeks to document changes in specific nodules of concern. Any significant change in size over this period should prompt a suggestion for additional diagnostics such as an ultrasound-guided fine needle aspirate or a laparotomy. It should be remembered that a change in diameter from 1.0 to 1.2 cm is associated with a doubling in volume for a spherical mass. Therefore, careful documentation of nodule size should be conducted at each examination. Nodules associated with benign processes should not increase during this time frame. The appearance of new lesions within this time period should be pursued with a laparotomy.

Incidental Pulmonary Lesions

Approximately 1 in 500 survey thoracic radiographs contain an incidental pulmonary nodule in people. The evaluation of such a finding is dependent on the size of the mass identified, the age of individual and high risk factors for pulmonary disease such as tabacco smoke or poor air quality exposure. The likelihood of discovering an incidental pulmonary lesion in veterinary medicine is unknown. The shift toward regular screening evaluations for asymptomatic geriatric dogs and cats may elucidate the problem in a general population. However, identification of an unexpected pulmonary nodule may present some clinical dilemmas.

In humans, size of the pulmonary mass is positively correlated with the likelihood of malignancy. A mass of 4 cm or larger in diameter is considered most likely to be a tumor. Nodules smaller than 4 cm are assessed in conjunction with the individuals age and risk factors. Computed tomographic patterns of calcification in incidental nodules is correlated with the histopathologic pattern. Specific patterns which demonstrate an orderly and controlled calcification pattern are most likely associated with non-neoplastic processes such as granulomas of infectious or inflammatory cause. A non-uniform calcification pattern often corresponds to neoplastic nodule formation. In addition to evaluation of the calcification pattern, evaluation of smaller nodules, not distinguishable by survey radiographs, may conducted throughout the entire lung field using computed tomorgraphy or magnetic resonance. Any lymph node enlargement may also be determined more clearly prior to diagnostic procedures.

In dogs and cats, it is presumed that the incidence of non-neoplastic processes that give rise to solitary pulmonary nodules is less than in humans. Infectious causes, such as pulmonary bacterial abscess, feline toxoplasmosis, and lung worm granulomas may be considered in the differential diagnosis. Until we have sufficient data, the majority of solitary nodules should be considered neoplastic in geriatric animals until proven to be something else. Primary pulmonary tumors in dogs and cats present as solitary nodules most of the time. The prognosis is related to size of the nodule and lymph node involvement. Early detection (i.e., small nodule) and removal is associated with longer control than when a large nodule is detected.

Identification of a pulmonary nodule should prompt a discussion with the owner regarding follow-up evaluations and diagnosis. Even with a small nodule (1-2 cm diameter) it is suggested that evaluation be pursued. A CT or MR of the thorax is indicated with all solitary nodules in the lungs. This will confirm that the nodule is truly solitary and whether the hilar lymph nodes are enlarged. If CT or MR in unavailable to the owner a second thoracic radiograph should be recommended in 4-6 weeks. Similar techniques should be used and evaluation of the nodule should be conducted using the same position (left or right laterals depending on the correct side for best visualization). It is important to remember that tumor volume doubles rapidly as the linear measurements increase. For instance: a 1 cm diameter mass doubles in volume when the diameter measure 1.2 cm! (1.3 x 1.3 x 1.3 = 2.1 cc) It is difficult to be this accurate from one survey film to the next unless all parameters are identical. Any change in the diameter of the mass should be considered significant. A CT-determine tumor volume is generally more accurate.

A diagnosis of the pulmonary nodule can be made by fine needle aspirate using guidance with either ultrasound or CT. The decision to conduct a fine needle aspirate of a lung nodule is based on accessibility of the nodule. A peripheral nodule that is of significant size can be readily aspirated. The vailidity of the aspirate will depend on the cellular uniformity of the nodule. It is not uncommon to have inflammatory reactions to pulmonary tumors that would confound the diagnosis. After considering the results of the aspiration the decision about surgical intervetion needs to be made. If the cytologic diagnosis confirms neoplasia the decision would be to resect the mass and surrounding lung lobe if the patient is the appropriate stage and health. If the cytologic diagnosis suggests inflammation additional diagnostic tests may be considered such as culture of the aspirate, serum titer determination of specific infectious agents, etc. A decision to perform a lobectomy may be made in either scenario. However, in many instances the decision to perform a thoracotomy is made without any attempts at fine needle aspiration, even for accessible nodules. This decision is based on the size and location of the nodule, the absence of other evidence of tumor presence (CT), the patients health status and the owners desires. Avoiding a fine needle aspirate would also prevent the accidental seeding of tumor cells along the biopsy track. Without a CT the thoracotomy should be approached as an exploratory procedure to determine if smaller nodules exist throughout the lung field or lymph node enlargement exists. The risks of thoracotomy should be considered and the procedures conducted at facilities that have experienced staff and adequate facilities. An alternative to thoracomy is thoracoscopy. This technique is rapidly gaining popularity for diagnostic and therapeutic use in humans and has been conducted in larger dogs and horses.

Early detection of cancer has resulted in prolonged survival times due to improved management such as definitive surgical resection. In order to take advantage of early interventions, screening programs need to be developed that are based on sound medical evidence We should rapidly evaluate the advantages the current screening tools and move from identification of "incidental nodules" to "intentional early diagnosis".