General  News

Case of the Month: August 2023



Gemma, a 10 year old FN golden retriever

Clinical history:

Presented with seizures.

No abnormalities were found on examination of cerebrospinal fluid and serological screening for Toxoplasma sp. and Neospora sp. were negative. Haematology and biochemistry was within normal limits, including bile acid stimulation test. A CT scan was performed to look for extra-cranial causes of the seizures and identified a mass in the left adrenal gland.



Cytological evaluation of the mass showed moderate cellular yield with many cells present as free nuclei which were often in a palisading arrangement, rarely in acinar-like formations. Cells that were intact appeared rounded to occasionally polygonal in shape and occasionally formed clusters. Nuclei were uniformly round with smooth to focally clumped chromatin and occasionally a prominent nucleolus. Moderate anisocytosis and anisokaryosis was apparent. No overt inflammation or infection was identified.


Consistent with adrenal medullary tumour; phaeochromocytoma

Figure 1. Typical appearance of a neuroendocrine tumour, in this case canine phaeochromocytoma
Figure 2. Free nuclei in a palisading arrangement

But why?

The tendency for neoplastic cells to present as ‘free nuclei’ on cytology is typically attributed to neuroendocrine tumours, although some carcinomas will have a ‘neuroendocrine appearance’. ‘Rowing-up’ or ‘pallisading’ arrangement is a feature of such populations and often cells will form ‘acinar-like’ arrangements or ‘rosettes’. For adrenal tumours, this appearance supports a diagnosis of adrenal medullary neoplasia, most likely a phaeochromocytoma. This case was a bit tricky, as the clustering behaviour seen was more prominent than expected; further confirmation of the diagnosis with measurement of urine catecholamines or with histopathology was advised. Elevated urine metanephrine levels supported the diagnosis.

Figure 3. More nuclear palisading!

A bit about canine phaeochromocytomas:

This is a tumour that develops from chromaffin cells in the adrenal medulla. In dogs they are usually benign but may be locally invasive. Occasionally metastases is reported in regional lymph nodes, liver and lungs. Chromaffin cells are responsible for secreting catecholamine hormones (epinephrine and norepinephrine). Some phaeochromocytomas will produce excessive levels of these hormones that may lead to clinical symptoms, most prominently the effects of systemic hypertension. Presenting history may be non-specific (restlessness, weakness, collapse, PUPD).  Elevated catecholamines in the urine (or plasma) can help to support a diagnosis, however not all tumours are functional and release of hormones may be episodic. In non-functional tumours, symptoms may relate to local tissue compression or invasion by the tumour as it grows. If measurement of catecholamines is not informative then cytological evaluation is a reliable way to differentiate phaeochromocytoma from adrenocortical tumours in dogs. However imaging and histopathology is needed to assess the biological behaviour of the tumour and whether there is local invasion at a macroscopic and a microscopic level. It is also important to consider the potential risks with aspiration of adrenal medullary tumours when approaching sampling, since manipulation and aspiration could lead to acute systemic effects of catecholamine release or potential bleeding. Measurement of urine normetanephrine can be a useful initial tool for investigation where phaeochromocytoma is suspected, before more invasive procedures are undertaken.


Figure 4. Intact cells varying from rounded to polygonal in shape
Figure 5. Clustering arrangements are not a typical feature of canine phaeochromocytoma but were observed in this case