The polydipsic cancer patient

12 The polydipsic cancer patient



INTRODUCTION


Polydipsia is defined as when an animal drinks in excess of 100 ml/kg/day, although a high degree of suspicion for polydipsia can be reached when daily water intake exceeds 80 ml/kg. Interestingly, many owners are much more aware of the polyuric aspect of polydipsic patients, which is probably not surprising, especially if the patient is incontinent. Because investigation of polydipsic patients encompasses many possible different medical and oncological conditions, it is vital that a logical and step-wise approach is taken with such patients. Very broadly, polydipsic patients can be grouped in many different ways but the flow diagram in Figure 12.1 gives one possible framework to investigate polydipsic patients along with the major differential diagnoses for each group.



From this it will become apparent that neoplasia is a major cause of polydipsia and polyuria. This can be due to a direct effect of the tumour via the production of non-constitutive hormones such as parathyroid-hormone-related peptide, as can be seen in anal sac carcinoma, or by production of excessive amounts of a constitutive hormone such as cortisol, as seen in adrenal-dependent hyperadrenocorticism. Neoplasia can affect plasma osmolality and viscosity (such as in multiple myeloma), cause renal damage (such as in tumour-associated glomerulonephritis), affect hepatic function (as seen in diffuse hepatocellular carcinomas) and also possibly via mechanisms that are, as yet, not fully understood.



CLINICAL CASE EXAMPLE 12.1 – MEDIASTINAL LYMPHOMA IN A DOG










Theory refresher


Lymphoma is one of the more common tumours seen in dogs, estimated to account for between 7 and 24% of all reported canine tumours. It is most commonly seen in middle-aged to older dogs and there appears to be no gender predisposition for the disease. Lymphoma and lymphosarcoma are interchangeable terms, although as lymphatic tissue is technically mesenchymal in origin, the term lymphosarcoma is technically more correct. The neoplastic cells develop from a clonal expansion of lymphocytes located in any of the sites within which lymphoid cells may be found. As a result, there are many different forms of the disease and currently several different classification systems, which can make interpretation of pathology reports difficult! However, in practical terms, the classification systems do not really change the initial clinical approach to the disease, which is to:






Diagnosis can frequently be made simply by cytology on aspirates obtained, either from peripheral lymph nodes, or by ultrasound-guided aspiration of internal organs. It is highly recommended to attempt this in all cases before considering obtaining surgical samples for histopathological diagnosis, as cytology is simpler, cheaper and the results are available more quickly. If ever there is a question over the accuracy of a cytological result then it should be confirmed by histopathology, but cytology is usually the method by which lymphoma is diagnosed in the authors’ clinics. The major drawback with cytological evaluation is that it does not allow an accurate assessment of the tumour grade to be undertaken but as illustrated above, the grade rarely impacts significantly on the treatment.


The clinical usefulness of cytology can be enhanced by having flow cytometry undertaken at the same time. Flow cytometry is a technique in which cells are sorted according to their size and then investigated to see what external molecular markers they carry by using monoclonal antibodies that bind to cell surface molecules. Flow cytometry can be extremely useful in the diagnosis of lymphoproliferative diseases, as there are some markers such as CD45, that clearly label a cell as being a leucocyte. There are markers that are unique to B lymphocytes (e.g. CB21 and CD79a) or T lymphocytes (e.g. CD3, CD4, CD8) and markers that are only found on immature cells (e.g. CD34), thereby identifying the cell as being a blast. By using this specific identification technique, cells can be accurately identified; both by their specific family subtype but also by their stage of maturity and therefore are determined as neoplastic or normal. Flow cytometry has been shown to be especially helpful in the differentiation between thymoma and lymphoma, which cytologically can be a challenge as the thymus contains lymphoid cells in various stages of maturation as a natural physiological feature (see Fig. 8.8). Thymomas can also cause a dog to become hypercalcaemic in a minority of cases (up to 30% in one series), so the identification of hypercalcaemia in a patient with a mediastinal mass does not rule out a diagnosis of thymoma. It has been shown that thymomas in dogs can be identified by undertaking flow cytometry on cells obtained by ultrasound-guided aspirates of mediastinal masses and identifying more than 10% of the cells as having both CD4 and CD8 staining, whereas lymphoma cases stained for these markers on less than 2% of cells. This is why this technique was performed in this clinical case example.


Surgery rarely has a role in the management of lymphoma, because (a) the disease generally shows a good response to chemotherapy and (b) because frequently a single lymphoma lesion will be part of a systemic multicentric disease even if gross evidence of the disease cannot be easily identified. Surgery can obviously be useful in solitary, stage I disease and also in obtaining lymph node tissue for biopsy if cytological evaluation does not elucidate the diagnosis. The question of whether chemotherapy should be administered to a patient following the diagnosis of a splenic lymphoma excised at laparotomy to investigate splenomegaly is a slightly difficult one, but the opinion of the authors is that splenic lymphoma should probably be considered a manifestation of multicentric disease. Therefore, should this scenario develop, a full investigation should be undertaken postsurgery to try to establish the exact clinical stage of the disease but frequently the use of systemic chemotherapy will be warranted.


If histopathology is undertaken, the classification system in Box 12.1 is the one most frequently referred to in the UK.



What the various classification systems have been useful to show is that:






B-cell lymphoma is the more common variant over T-cell lymphoma but it is also possible to have mixed B- and T-cell tumours and also occasionally lymphoma which shows no clear B- or T-cell immunophenotyping, so-called ‘null cell’ lymphoma. From a clinical point of view, dogs that appear not to have significant signs of illness (substage ‘a’) will frequently respond better to treatment than dogs with obvious signs of clinical illness (substage ‘b’), both in terms of remission rates and remission times.


Hypercalcaemia is more commonly associated with T-cell lymphoma (although it does develop in B-cell patients) and the identification of hypercalcaemia used to be thought of as a negative prognostic indicator. However, it is now clear that it is the B- or T-cell delineation that has the negative prognostic indications rather than the hypercalcaemia per se. The hypercalcaemia is induced by the production of parathyroid-hormone-related peptide (PTHrP) by the neoplastic cells, as documented in the case presented. PTHrP is elevated in many tumours (with the subsequent development of hypercalcaemia) but it is most commonly associated with lymphoma, anal sac adenocarcinoma and multiple myeloma. The other main differential diagnoses for hypercalcaemia in the dog and cat are given in Box 12.2.




Prognosis


The prognosis for lymphoma patients is variable and depends upon many factors, so it is often difficult to be precise when giving such information to an owner. The tumour cell type (B or T) is important as explained previously, as is the clinical subtype staging (‘a’ or ‘b’). The clinical staging of the multicentric form of the disease also has some bearing, in that dogs with stage V disease often have a poorer outcome, but in general, dogs with stage I–IV disease will respond in a similar way to treatment. For animals with non-multicentric lymphoma, there are few good studies that provide consistent data with regard to prognosis with the exception of cutaneous lymphoma. However, animals with primary CNS lymphoma have been reported to respond to external beam radiotherapy.


The choice of treatment protocol for the multicentric form of lymphoma may also affect the prognosis in some cases. It has been shown that dogs treated with a doxorubicin-containing protocol in general have a reduced risk of relapse and death when compared to dogs treated with a non-doxorubicin-containing protocol. Furthermore, multidrug protocols generally result in longer remission times and greater survival figures when compared to single-agent treatments. Pretreatment with steroids should be avoided if at all possible, as steroids appear to increase the risk of multidrug resistance gene expression, leading to reduced success rates with other chemotherapeutic agents. However, many factors need to be considered when choosing the correct protocol for each case, such as treatment cost, treatment frequency and duration, the suitability of the patient for injectable treatments and the risk of toxic side effects, to name but a few. Therefore, a summary of the most commonly used treatment choices is given below:


Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on The polydipsic cancer patient
Premium Wordpress Themes by UFO Themes