hyperparathyroidism

2. Are thyroid and parathyroid lesions wrongly reported
in a thyroid pathology sample?
Does ultrasound help to differentiate adenoma lesions
from parathyroid carcinoma?

3. Parathyroid carcinoma is rare,
representing<1% of primary
hyperparathyroidism cases.
Parathyroid carcinoma (PC) is an
uncommon malignancy,
less than 1000 recorded cases
reported in literature since described
by de Quervain in 1904

5. We report a 50-year-old male patient who was referred to our department for a right
thyroid nodule, incidentally detected on carotid Doppler ultrasound scan, with a
fine-needle aspiration cytology showing a follicular lesion. At the time of our
evaluation, neck ultrasound showed a 1.3 cm right hypoechoic thyroid nodule with
irregular margins and the absence of enlarged bilateral cervical lymph nodes. Thyroid
function tests were normal. Serum calcium was normal and plasma PTH slightly
above the upper limit of the normal range. The patients underwent right lobectomy.
The intraoperative frozen-section pathological examination raised the suspicion of a
PC. Definitive histology showed a markedly irregular infiltrative growth of the tumor
with invasion of the thyroid tissue and cervical soft tissues.

6. Immunostaining for thyroglobulin was negative, whereas staining for chromogranin A
and PTH showed a strong reactivity. Based on the microscopic findings and the
immune histochemical profile, the tumor was diagnosed as a PC. Postoperative
serum calcium and phosphate levels were in the normal range. This is the first
case of a nonfunctioning sporadic PC misdiagnosed prior of surgery as a follicular thyroid
nodule. The parathyroid nature of the neck lesion could not be suspected before surgery.
Fine-needle aspiration cytology (FNAC) may fail to distinguish a parathyroid tumor from a
benign thyroid nodule because at FNAC, parathyroid and thyroid lesions have some
morphological similarities. Histological criteria are not always sufficient for the differential
diagnosis, which can definitely be established using immunohistochemistry.

8. Retrospective data of patients referred for evaluation of parathyroid
disease between 2001 and 2018 were reviewed. The goal was to
describe the clinical presentation, histopathologic characteristics,
and treatment outcomes of parathyroid carcinoma.

9. We reviewed 219 patients referred for parathyroid disease;175 patients
were found to have hyperparathyroidism, 14 patients were managed for
hypoparathyroidism, and 30 patients were found to have normal parathyroid
function. Of the 175 patients with hyperparathyroidism, 149 individuals had
primary hyperparathyroidism, including 9 patients with parathyroid carcinoma;
22 cases were secondary hyperparathyroidism; 3 were tertiary
hyperparathyroidism; one patient had familial hypocalciuric hypercalcemia. Of
the parathyroid cancer cases, one was excluded as the pathology sample from
another institution was not available for review.

10. We identified 8 cases of parathyroid carcinoma from the
outpatient practice
of a quaternary care Endocrine Oncology practice in Toronto,
Canada.

11. The clinical presentation was as follows: 5/8 cases (62.5%) of symptomatic
hypercalcemia and 3/8 cases (37.5%) of a suspicious thyroid nodule. Hypercalcemia
was evident in all 7 case with pre-operative calcium measurements. Histopathologic
features included: vascular invasion in 7/8 cases (87.5%) and immunohistochemical
loss of either parafibromin,retinoblastoma, or p27 in all 8 cases. Additional treatment
included: external beam radiotherapy in 5/8 cases (62.5%), chemotherapy for 2/8
patients (25%), and additional surgery for 3/8 patients (37.5%). Only 2 patients (25%)
had long-term remission following surgical treatment, and the others had either
persistent (3 patients) or recurrent disease(3 patients). Five patients developed
metastatic disease, all involving lung. In one of two patients treated with Sorafenib
there was evidence of regression of lung metastases. One patient died of disease
progressin.

14. One of these patients (patient #3), had been investigated for weight
loss and constipation, leading to
the diagnosis of hyperparathyroidism, and a neck ultrasound revealed a
3.5 cm hypoechoic nodule in the lower pole of the right thyroid that was
suspicious for differentiated thyroid cancer on fine-needle aspiration
biopsy. The patient underwent total thyroidectomy and the pathology
was consistent with angioinvasive and widely invasive parathyroid
carcinoma arising from the right parathyroid gland and involving the
thyroid and the painted resection margins.

15. If PC is pre-operatively suspected, FNA
should be avoided due to the risk of tumor
dissemination along the needle tract, with higher
risk of recurrence;biopsy has resulted in capsular
rupture and PT tissue diffusion.

16. Ultrasonography showed that parathyroid carcinomas tend to be
large, inhomogeneous, hypoechoic masses with lobulated contours.
In contrast, parathyroid adenomas were small, homogeneous,
hypoechoic masses with smooth borders. The mean (range) DW
ratios for parathyroid carcinomas were 1.21 (0.91-2.5) and 0.64 (0.33-
1.47) for adenomas; the difference was statistically significant
(p<0.0001). The DW ratio was ≥1 in 15 (94%) of the 16 cases of
carcinoma, whereas only 3(5%) of the 61 adenomas had a similar
ratio.

17. Ultrasonographic examination is useful not only for
preoperative localization but also for differentiating
parathyroid carcinoma from adenoma. Parathyroid tumors
with irregular margins, inhomogeneous echogenicity, and a
DW ratio ≥1 are likely to be malignant.

19. A 53-year-old female was referred for the exclusion of metabolic bone disease.
She presented with low back pain that had persisted for the past 6 months and
elevated serum alkaline phosphatase (1,253 IU/L). Four years previously, she had
been diagnosed at a local hospital with a 2.3-cm thyroid nodule, which was
determined to be pathologically benign. Radiofrequency ablation was performed
at the same hospital because the nodule was still growing during the follow-up
period 2 years before the visit to our hospital, and the procedure was unsuccessful
in reducing the size of the nodule.

20. The results of the laboratory tests in our hospital were as follows: serum calcium,
14.6 mg/dL; phosphorus, 3.5 mg/dL; and intact parathyroid hormone (iPTH),
1,911 pg/mL. Neck ultrasonography and 99mTc sestamibi scan detected a 5-cm
parathyroid neoplasm in the left lower lobe of the patient’s thyroid; left
parathyroidectomy was performed. This case indicated that thyroid
ultrasonographers and pathologists need to be experienced enough to differenti-
ate a parathyroid neoplasm from a thyroid nodule; 99mTc sestamibi scan, serum
calcium, and iPTH levels can help to establish the diagnosis of parathyroid
neoplasm

25. Parathyroid adenomas are frequently mistaken cytologically for a
follicular lesion of the thyroid. Most patients with a parathyroid
adenoma have hypercalcemia, which is a clue to the correct
diagnosis. Immunohistochemistry for thyroglobulin and parathyroid
hormone can be helpful if a non thyroid origin is suspected.