Pituitary Metastasis of Pancreatic Origin in a Dog Presenting with Acute-Onset Blindness

Introduction

There is very little published information regarding metastatic neoplastic lesions involving the canine pituitary gland, with only three case reports describing four affected dogs.^1–3 Physical examination in all four dogs revealed abnormalities indicative of a multifocal disease process.^1–3 MRI findings were only available in one report and revealed multiple lesions in the brain suggestive of metastatic disease.³ In a large postmortem study of secondary brain tumors in dogs, only 6 of 177 patients were reported to have metastasis to the pituitary gland.⁴ Details of the findings on physical and MRI examination were missing for those six dogs.⁴ In humans, pituitary metastases are uncommon and a pancreatic origin is very rare.⁵ This is the first report in a dog of an exocrine pancreatic carcinoma with widespread metastasis including the pituitary gland and that fully describes the clinical, imaging, and histopathologic features of the case.

Case Report

An 11 yr old castrated male English springer spaniel was referred for evaluation of a 24 hr history of blindness. The owners reported lethargy during the previous month, but no other clinical signs. On presentation, complete physical and ophthalmologic fundus examinations demonstrated no abnormalities. Neurologic examination revealed a disorientated patient that was bumping into objects. Cranial nerve examination showed a bilaterally absent menace response, no response to the cotton ball test, mydiatric pupils, reduced pupillary light reflexes, and a normal dazzle reflex. Gait, postural reactions, and spinal reflexes were normal. Clinical neurologic findings suggested a single lesion localizing to bilateral retinas, optic nerves, optic tracts, or optic chiasm.

Complete blood count and serum biochemical analysis results were within normal ranges. Electroretinography^a was normal, ruling out retinal involvement. MRI examination of the brain was performed under general anesthesia using a 1.5 Tesla unit^b and revealed a well-circumscribed, rounded, midline, 8 mm mass centered on the pituitary gland. This mass was isointense to gray matter in T1- and T2-weighted images. The normal hyperintense appearance of the neurohypophysis was lost with only a subtle linear hyperintense area dorsal to the mass, suggestive of a distorted neurohypophysis. After IV contrast administration^c, enhancement was seen only at the dorsal and caudal periphery of the mass, which was considered to represent pituitary tissue displaced and compressed by a mainly nonenhancing mass. It was not possible to clearly differentiate adenohypophysis from neurohypophysis. The mass extended rostrally and compressed the optic chiasm (Figures 1A–E).

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Differential diagnoses included either a primary neoplastic process (such as pituitary adenoma, pituitary carcinoma, lymphosarcoma, craniopharyngioma and germ cell tumor) or possibly metastatic disease. Other less likely differentials included a harmartoma or granulomatous inflammatory process. Further diagnostic tests were offered, but the owners elected euthanasia with no further investigations.

Postmortem examination identified a firm, white, oblong mass in the head of the pancreas measuring 4 cm × 1.5 cm × 1.5 cm and multiple similar masses were present in the lungs, liver, and omentum, ranging in size from 0.5 cm to 2 cm in diameter. A small, white mass was found within, and largely effacing, the normal architecture of the pituitary gland, with impingement on the adjacent optic nerves. Histologically, in all examined masses, the tumor cells were largely arranged in sheets and packets with occasional acinus formation and were supported by a minimal amount of fibrovascular stroma. The tumor cells were polygonal or ovoid with a moderate to large amount of eosinophilic, sometimes finely vacuolated cytoplasm that had well-defined margins. Nuclei were large, ovoid, and paracentral with sparse, reticulated and partially marginated chromatin and one to two large, central, deeply eosinophilic nucleoli. There was marked anisokaryosis and anisocytosis, with two to four mitotic figures per high power (magnification ×400) field. The neoplastic masses contained multiple, often extensive, areas of necrosis, and numerous large intravascular tumor emboli were often observed within adjacent blood vessels. Within the pituitary gland the tumor was effacing most of the normal architecture with the exception of a narrow area of the pars distalis (Figure 2). On the basis of the clinical, postmortem, and histologic findings the patient was diagnosed with a solid-type, poorly differentiated exocrine pancreatic carcinoma with widespread metastasis, including the pituitary gland, lungs, liver, and omentum.

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Discussion

Pituitary metastases are rare in dogs with only 10 reported cases in the literature including lymphosarcoma (n = 2), metastatic carcinoma of unspecified origin (n = 2), histiocytic sarcoma (n = 1), malignant melanoma (n = 1), transmissible venereal tumor (n = 2), and thyroid carcinoma (n = 2).^1–4 In human patients with malignant tumors, metastases to the pituitary gland are considered to be uncommon, with estimated rates of 1–3.6%.⁶ Neoplasms from almost every tissue have been reported to metastasize to the pituitary gland in human patients, with breast and lung tumors being the most common. In a retrospective review of pituitary metastasis, only 5 of 380 cases had a pancreatic origin.⁵ Pancreatic neoplasia is uncommon in dogs, but when present, malignant tumors of exocrine epithelial origin are the most frequently reported type.⁷ Widespread metastasis of pancreatic exocrine carcinomas has been reported in dogs with organ involvement, including liver, lungs, kidneys, spleen, peritoneum, regional lymph nodes, and central nervous system, but not the pituitary gland.⁸

Clinically, the four previously reported dogs with pituitary metastases had systemic signs suggesting metastatic disease, including masses in the neck area and mammary glands, enlarged lymph nodes, and a preputial mass and swelling.^1–3 Remarkably, in the present case, the dog presented for blindness rather than signs relating either to the primary tumor or other metastatic lesions. This is similar to human patients where pituitary metastasis may often be the first manifestation of an occult primary tumor, and visual impairment is one of the most frequent presenting complaints in patients with pituitary metastasis.^6,9 Other commonly reported signs in humans include diabetes insipidus, headache, and anterior pituitary dysfunction.^5,6,9

The MRI findings in this case were suggestive of a neoplastic process, and metastatic disease was not excluded as a differential diagnosis. However, canine pituitary metastases are rare, and only one case report of two dogs with pituitary metastases of thyroid origin details the MRI findings.³ In that report, other lesions were present in the brain parenchyma making a metastastic process in these dogs the most likely differential.³ The described pituitary metastasis had the same signal intensity as the surrounding parenchyma in T1- and T2-weighted images, which enhanced after contrast administration and extended from the sella turcica dorsally.³ The mass in the present case also showed isointensity to brain parenchyma in T1- and T2-weighted images and had an extrasellar extension, but had no contrast enhancement. There were no other masses in the brain cavity. Thus a diagnosis of metastatic disease in the present case was challenging, especially as one of the main characteristics of intracranial metastases is contrast enhancement or at least ring enhancement.¹⁰ Nevertheless, metastatic disease was still included as a differential as the imaging characteristics were not suggestive of the tumor types typically originating at this site. The most common tumor at this site is a macroadenoma, which is characterized by hyperintensity in T2-weighted images with marked and heterogeneous contrast enhancement, none of which were present in this case.¹¹ Meningioma was considered unlikely as the mass did not show either the characteristic homogenous contrast enhancement or any attachment to the dura.¹² Germ cell tumor was also considered unlikely as those tumors tend to affect the suprasellar region and show prominent contrast enhancement.¹² Further, the craniopharyngiomas reported in humans affecting the pituitary gland tend to have mixed solid and cystic characteristics with homogenous enhancement of the solid portion.¹³ In humans, while MRI evaluation has not been totally successful in distinguishing pituitary metastases from adenomas, a few characteristics have been reported as helpful in differentiating them, including enlargement of the sella turcica, a dumbbell shape, a sellar enhancing mass, loss of high intensity from the posterior pituitary, isointensity on T1- and T2-weighted images, invasion of the cavernous sinus, and sclerotic changes around the sella turcica.^5,6 Thus, the authors concluded that the main MRI findings of canine pituitary metastases based on the previous case report and the present case are isointensity on T1- and T2-weighted images, extrasellar extension, and variable contrast enhancement.

In humans, the neurohypophysis appears to be more commonly affected, but breast metastases have an affinity for the adenohypophysis.^14–16 Generally, four pathways of metastatic spread to the pituitary gland are hypothesized: direct bloodborne metastasis to the neurohypophysis; bloodborne metastasis to the pituitary stalk with growth into the adeno- and neurohypophysis; bloodborne metastasis to the clivus, dorsum sellae, or cavernous sinus that then spreads into the pituitary gland; and leptomeningeal spread with involvement of the pituitary capsule.¹⁷ Neither by MRI nor histopathology was it possible in this case to accurately identify the initial location of the metastasis, as the tumor was effacing most of the pituitary gland architecture, except for a narrow area of the pars distalis.

It has been reported that 76% of dogs with secondary intracranial neoplasia have pulmonary metastasis and nearly 25% of dogs with primary brain tumors had an unrelated, but potentially clinically significant form of neoplasia identified on postmortem examination.^4,18 In the present case the owners elected euthanasia after the MRI and no further investigations were performed. However, thoracic radiographs and abdominal ultrasound would have been beneficial prior to brain imaging highlighting the importance of performing screening tests (thoracic radiographs and abdominal ultrasound) in dogs with suspected intracranial tumors.

Conclusion

Pituitary metastases are uncommon but should be included as a differential diagnosis for dogs presenting with acute-onset blindness and also for single pituitary masses as they can be the first manifestation of an occult primary tumor.