Page 604 - Withrow and MacEwen's Small Animal Clinical Oncology, 6th Edition

582 PART IV Specific Malignancies in the Small Animal Patient

concentrations barely below, rather than within, the normal refer- favorable because the disease tends to be slowly progressive, clini-
ence range. This reduces the risk of hypercalcemia and provides cal signs may be mild, and renal failure may be a less common
outcome than previously suspected.
337
the stimulus for recovery of function of the remaining normal

VetBooks.ir parathyroid glands. Once the serum calcium has been stable for Pancreatic Beta-Cell Tumors (Insulinomas)
at least 1 to 2 weeks in an outpatient, the dose of calcitriol can be
reduced gradually, with careful monitoring. The time for return
of normal parathyroid function is unpredictable, therefore clients Pancreatic beta-cell tumors are rare in humans and cats and
should expect frequent rechecks of calcium levels for several weeks uncommon in dogs. 372–375 These tumors often are functional,
to months after treatment of hyperparathyroidism. but the neoplastic beta cells fail to inhibit insulin secretion appro-
A small percentage of patients have persistent hypercalcemia priately at low blood glucose concentrations. Thus the hallmark
after parathyroidectomy. This likely is due to a nodule of another of insulinoma is a normal or increased blood insulin concentra-
parathyroid gland that was not discovered at the time of surgery, tion in the presence of low blood glucose levels. Molecular studies
or to hyperplasia or neoplasia in ectopic parathyroid tissue. Ecto- of a feline insulinoma revealed abnormal glucokinase and hexo-
pic parathyroid tissue is a frustrating clinical problem. Anecdot- kinase expression, suggesting that these changes may contribute
ally the author (SB) has found a parathyroid adenoma under the to enhanced glucose sensitivity and an abnormal insulin secre-
tongue in one patient. A rapid parathyroid assay now is available tory response in insulinoma cells. 374 Although the clinical signs
for intraoperative measurement of PTH. 357 This may be help- of insulinoma result from hypoglycemia associated with unregu-
ful for confirming that the offending parathyroid tissue has been lated insulin secretion, immunocytochemical analysis reveals
removed successfully intraoperatively. 367 When ectopic parathy- that these tumors often produce many additional hormones,
roid tissue cannot be located easily, MRI or CT can be attempted. including glucagon, somatostatin, pancreatic polypeptide, GH,
However, the nodules typically are small and may be difficult to IGF-1, and gastrin. 374,376–380 A more recent study demonstrated
diagnose. that some canine insulinomas express genes more typically asso-
Ultrasound-guided ablative techniques also have been reported ciated with the exocrine pancreas; the study also revealed that
to treat primary hyperparathyroidism. Ultrasound-guided radio- these tumors contain small subpopulations of cells with mixed
frequency ablation (RFA) was first reported in 2001 in 11 dogs. endocrine-exocrine features, termed amphicrine cells. 381
One treatment was required in six dogs, two treatments in two In humans 90% of insulinomas are solitary and benign, and
dogs, and the treatment was unsuccessful in three dogs. 368 In 5% to 10% are associated with multiple endocrine neoplasia type
another study persistent or recurrent disease was reported in 31% 1 (MEN1). Insulinomas in dogs are much more likely to be malig-
of 32 dogs; larger nodules and/or concurrent hypothyroidism were nant, although morphologic classification into adenoma or adeno-
associated with treatment failure. 369 Ultrasound-guided ethanol carcinoma does not consistently reflect the biologic behavior of
ablation also has been reported as a minimally invasive method these tumors. 375,378,382 Metastatic lesions are detected in approxi-
to treat primary hyperparathyroidism. This technique first was mately 50% of canine insulinomas, with the regional lymph nodes
reported in eight dogs, with seven dogs requiring one treatment and liver most commonly affected. Pulmonary metastases are
and one dog requiring two treatments. Hypercalcemia resolved in rare in dogs. 379,383–387 The World Health Organization (WHO)
all cases, but one dog developed recurrent hypercalcemia 1 month recommendations have been used to stage canine pancreatic
later and was treated with surgical removal of the mass. 370 Another tumors. 384 Stage I tumors involve only the pancreas, with no evi-
larger study reported ethanol ablation of parathyroid nodules in dence of local or distant lymph node involvement and no distant
27 dogs; hypercalcemia resolved in 85% of the cases, but three metastasis (T1N0M0); stage II tumors have lymph node involve-
dogs required a second treatment. 371 A direct comparison of the ment (T1N1M0); and stage III tumors have distant metastasis
three techniques for the treatment of primary hyperparathyroid- (T1N1M1 or T1N0M1).
ism was reported retrospectively. That study found that control
of hypercalcemia was achieved in 94%, 72%, and 90% of cases Beta-Cell Tumors in Dogs
treated with parathyroidectomy, ethanol ablation, and RFA,
respectively. 339 The cellular and molecular events causing beta-cell tumors in dogs
The long-term prognosis after surgical or ablative treatment are unknown; however, studies of these tumors have provided
for hyperparathyroidism is very good both for control of hyper- insights into tumor biology and molecular genetics. Canine insu-
calcemia and for the tumor itself. Metastatic disease is extremely linomas have been shown to express somatostatin receptors, which
rare, and the complication of hypocalcemia generally is amena- may have implications for both diagnosis and therapy. 388 Local
ble to medical therapy. Histopathology most commonly reveals production of GH and IGF-1 also have been demonstrated in
a parathyroid adenoma or hyperplastic nodule, although histo- canine insulinomas, with a higher level of expression of GH and
logic classification is not straightforward. 340 In rare cases a para- IGF-1 mRNA in metastases compared to primary tumors. 380,389
thyroid adenocarcinoma has been diagnosed. These are functional It has been suggested that the locally produced hormones may
parathyroid nodules, and in a report of 19 dogs with parathyroid have autocrine or paracrine effects on cell proliferation, and tumor
adenocarcinoma, no features of the disease differed from those of growth and progression. Furthermore, it is speculated that locally
a benign functional adenoma except for the finding of carcinoma produced somatostatin has inhibitory effects on insulinomas
on histopathology. The prognosis in these cases was excellent both within the pancreas, but that these effects are decreased in metas-
for tumor control and for resolution of hyperparathyroidism. 344 tases leading to increased GH production. 389 Gene expression
Approximately 10% of dogs treated for hyperparathyroidism profiling of canine insulinomas and their metastases have dem-
experience a recurrence of the disease. 340 If this occurs, a second onstrated differential expression of genes between low-metastatic
surgery or ablative procedure should be performed. The short- and high-metastatic subsets of insulinomas with genes for acinar
term prognosis for dogs and cats that do not undergo definitive enzymes being more substantially down-regulated in the more
surgical or ablative therapy for hyperparathyroidism still may be malignant subset of tumors. In addition, pathways involved in