Epithelial proliferation with features neuroendocrine features, most supportive of adrenocortical origin, adenoma vs. adenocarcinoma.  

At the time of submission, an adrenal mass/mass effect was not described. Based on this cytologic appearance, an adrenal cortical population was suspected. Differentiation between sampling proliferative/hyperplastic or possibly ectopic adrenocortical tissue, a benign adrenal adenoma, or malignant adrenal carcinoma is not possible cytologically.¹ While unlikely in this case, an ovarian sex-stromal/sex-cord stromal tumor can appear cytologically similarly.

Adrenal neoplasia is uncommon in cats, accounting for 0.2% of feline neoplasms.² These tumors include adrenal cortical (e.g., adenoma and adrenocortical carcinoma) and medullary tumors (pheochromocytoma). Cortical tumors are further characterized as functional (producing excess hormones such as aldosterone, cortisol, sex hormones, or rarely hypersecretion of more than one hormone) or non-functional.³ Not all functional tumors however secrete enough hormones to cause systemic signs (e.g., Cushing’s syndrome due to cortisol or Cohn’s syndrome due to aldosterone) and/or secrete unusual steroid hormones that are not measured by routine clinical pathology laboratory methodology. Nevertheless, adrenal hormone panels may be beneficial in some cases. Of the possible clinical syndromes associated with adrenal tumors in cats, primary hyperaldosteronism is the most common. In a retrospective study of 33- cats, the most common adrenal tumor type in cats was adrenal cortical carcinoma.² Regardless of tumor type, surgical excision of feline adrenal tumors in one study resulted in good long-term survival.² Cytology and even histology alone cannot characterize biological behaviour of adrenal neoplasms. Only macro- or microscopic invasiveness and metastatic tendency detectable by diagnostic imaging, gross findings, and histopathology are considered reliable indicators of malignancy.¹ In this case, it was unclear cytologically if the sampled tissue represented an effaced lymph node or primary mass/mass effect given the clinical history. No further diagnostics were pursued in this case.

As mentioned above, ovarian sex-stromal tumors exhibit a similar cytologic appearance, resembling cellular constituents of the ovary endocrine apparatus with the potential to be hormonally active.⁴ In spayed females this would be considered less likely however if there is residual functional ovarian tissue (i.e., ovarian remnant syndrome – ORS), the possibility for malignant transformation exits.⁵ Given the potential for hormonal secretion and cytologic overlap, imaging to evaluate the adrenal glands (normal vs. mass/mass effect) and assessment for abnormal tissue, with histopathology, and potentially immunohistochemistry of the sampled lesion, would likely be required for definitive differentiation.  Of note, in cats, granulosa cell tumors are the most common ovarian sex-stromal tumor and relatively frequently metastasize.

1. Cytology of adrenal tum Bertazzolo W, Didier M, Gelain ME, Rossi S, Crippa L, Avallone G, Roccabianca P, Bonfanti U, Giori L, Fracassi F. Accuracy of cytology in distinguishing adrenocortical tumors from pheochromocytoma in companion animals. Vet Clin Pathol. 2014; 43:453-9.
2. Daniel G, Mahony OM, Markovich JE, Appleman E, Monaghan KN, Lawrence YA, Fiocchi EH, Weaver K, Johnston A, Barton B. Clinical findings, diagnostics and outcome in 33 cats with adrenal neoplasia (2002-2013). J Feline Med Surg. 2016; 18:77-84.
3. Guerios SD, Souza CHM, Bacon NJ. Adrenocortical tumor in a cat secreting more than one type of corticosteroid. J Feline Med Surg Open Rep. 2015 1;1(2):2055116915617970.
4. Agnew DW, MacLachlan NJ. Tumors of the Genital Systems. In: Meuten DJ, ed. Tumors in Domestic Animals. 5^th Hoboken, NJ: John Wiely & Son, Inc.; 2016: 689-701.

For more information on feline hyperaldosteronism, these references may be helpful.

Hyperaldosteronism:

Ash RA, Harvey AM, Tasker S. Primary hyperaldosteronism in the cat: a series of 13 cases. J Feline Med Surg. 2005;7:173-82.

Langlois DK, Mazaki-Tovi M, Harro CC, Refsal KR. Multiple corticosteroid abnormalities in cats with hyperaldosteronism. J Vet Intern Med. 2021;35:2152-2158.