Abstract
We present a case of an 80-year-old patient with three concurrent multiple atypical parathyroid adenomas. The patient was managed with bilateral parathyroid exploration and concurrent parathyroidectomy. Postoperative recovery was uneventful. Atypical parathyroid adenomas are a rare entity that are clinically difficult to distinguish from parathyroid carcinoma. Histological characteristics are similar however atypical adenomas lack complete capsular or vascular invasion and cannot be considered malignant. All reported cases of atypical parathyroid adenoma are solitary lesions. We present the first case of multiple concurrent atypical parathyroid adenomas.
Keywords: ear, nose and throat/otolaryngology; calcium and bone; general surgery; head and neck surgery; otolaryngology / ENT
Background
Atypical parathyroid adenomas are a rare histological entity distinct from typical adenomas or carcinomas. Atypical adenomas share multiple characteristics to parathyroid adenocarcinoma including fibrous bands, enhanced mitotic activity, pronounced trabecular growth, tumour necrosis and adherence to adjacent tissues. However they lack complete capsular invasion or presence of metastases and can not be classified as malignant lesions.1
Clinically, parathyroid adenomas and adenocarcinomas present with raised serum parathyroid hormone level (PTH) and calcium levels indicative of primary hyperparathyroidism. Parathyroid carcinomas are associated with very high serum calcium levels while parathyroid adenoma typically present with mild-to-moderate elevation. Atypical adenomas are described as more heterogeneous. Typically presenting with moderately elevated calcium levels in between what is expected of adenoma and carcinoma.2 Variable calcium levels at presentation, including very high calcium levels, can make preclinical distinction from parathyroid carcinoma difficult.1 Atypical parathyroid adenomas of the parathyroid gland are rare and typically solitary lesions.1–3
We report a rare case of multiple concurrent atypical parathyroid adenomas; to the best of our knowledge this is the first such case of multiple concurrent atypical parathyroid adenomas in the literature.
Case presentation
An 80-year-old female patient presented to her General Practitioner with anterior neck swelling. The patient was otherwise asymptomatic. There was no history of irradiation or family history of endocrinopathies. The patient had no swallowing or respiratory symptoms and no signs of hyper or hypothyroidism. Clinical examination revealed a nodular and enlarged thyroid gland. She was investigated for thyroid nodules in the primary care setting.
Investigations
Ultrasound scan of the neck confirmed benign thyroid nodules. It also identified two small exophytic lesions. One lesion was lying posterior to the right hemithyroid; the second lesion was between the left hemithyroid and carotid artery. This was suggestive of bilateral parathyroid adenomas. Subsequent blood tests showed an elevated serum corrected calcium 2.91 mmol/L and a raised PTH of 21.9 pmol/L.
Localisation imaging was undertaken. Sestamibi scan suggested a right lower parathyroid adenoma but no evidence of a left-sided adenoma. Contrast-enhanced CT scan of the neck and thorax showed evidence of a right lower parathyroid mass but no evidence of a left-sided lesion.
Bone densitometry confirmed underlying osteoporosis (T scores in the lumbar spine of −3.5, femoral neck −3 and radius −4.1). She did not show clinical signs of hypercalcaemia.
Differential diagnosis
Primary hyperparathyroidism secondary to parathyroid adenoma was considered the primary differential diagnosis.
Treatment
The primary treatment of primary hyperparathyroidism is parathyroidectomy. Non-concordant localisation studies (ultrasound, sestamibi and CT) necessitate bilateral parathyroid exploration in accordance with American Association of Endocrine Surgeon Guidelines.4 The patient, therefore, underwent bilateral parathyroid exploration. Intraoperative findings identified an enlarged lower right parathyroid, a large left upper parathyroid and a large upper right-sided retro-oesophageal parathyroid that was wrapped around and adherent to the recurrent laryngeal nerve. Intraoperatively all three lesions were excised and sent for intraoperative frozen section. Intraoperative frozen sections revealed the right lower parathyroid to be of normal cellularity and the right upper and left upper parathyroids to be hypercellular. The left lower parathyroid was not enlarged in any imaging modality and not removed to reduce the risk of postoperative hypoparathyroidism.
Outcome and follow-up
The patient recovered well after surgery with normal laryngeal function postoperatively, as confirmed by nasal endoscopy. Calcium levels returned to normal on day 1 post-surgery. The patient was discharged with a normal calcium level. The patient experienced an acute drop in her serum calcium levels 2–4 weeks after surgery. This was identified at routine outpatient follow-up and postoperative calcium monitoring. She was not symptomatic. The patient responded well to oral calcium supplementation. Calcium levels normalised (corrected calcium of 2.38 mmol/L), with a normal postoperative PTH level (1.9) following oral supplementation.
Final histology revealed a hypercellular appearance in all three excised parathyroid glands. All specimens were composed predominantly of chief cells without cytological atypia, mitoses or necrosis and with cystic changes. Dense acellular fibrous bands infiltrated by large and small nests of chief tumour cells were present in each specimen. Figure 1 demonstrates histological findings for the right upper parathyroid lesion. Figure 2 demonstrates findings for the right lower parathyroid lesion and figure 3 the left upper. There was no evidence of capsular or vascular invasion and a normal rim of parathyroid tissue present. This was consistent with three concurrent multiple atypical parathyroid adenomas and no evidence of malignancy.
Figure 1.
H&E staining of right upper atypical parathyroid adenoma. Hypercellular pattern with an infiltration and fibrous bands.
Figure 2.
H&E staining of right lower atypical parathyroid adenoma. Hypercellular pattern with an infiltration and fibrous bands.
Figure 3.
H&E staining of left upper atypical parathyroid adenoma. Hypercellular pattern with an infiltration and fibrous bands.
The patient and histology was discussed within the thyroid/parathyroid multidisciplinary meeting and the consensus was for yearly follow-up and parathyroid hormone monitoring.
Discussion
Solitary parathyroid adenomas are the most common cause of hyperparathyroidism accounting for 85% of presentations. Multiple adenomas are the next most common presentation. Parathyroid carcinomas and atypical adenomas are rare.1 Atypical parathyroid adenoma is a difficult entity to diagnose both clinically and histologically. Clinical and intraoperative findings may be indistinct from carcinoma and histology shares many features with parathyroid carcinoma.1 Both may exhibit fibrous bands, trabeculae and increased mitotic features. Capsular and vascular invasion remain the key differentiators at histology. Differentiation between atypical adenoma and carcinoma is important as they have distinct disease courses and management pathways.
Interestingly cases of atypical adenoma appear to have calcium levels intermediate to benign adenomas and carcinomas, however, may have less clinical manifestations of hypercalcaemia.5 There is thought to be some phenotypic variation between typical adenomas, atypical adenomas and carcinomas, however the molecular pathogenesis of atypical adenoma is still not clear.6
While atypical parathyroid adenoma is a rare entity it has been well documented. Review of the literature identified six distinct papers reporting 27 cases. In all cases reviewed none report the presence of concurrent multiple atypical adenomas. One case reports the presence of a concurrent typical adenoma. Findings are summarised in table 1.1 2 5 7–9
Table 1.
Published cases of atypical parathyroid adenoma
| Author | Year | Cases (n) | Sex | Age at diagnosis | Calcium level at diagnosis mmol/L | PTH level at diagnosis pmol/L | Histological features | Multiple parathyroid pathology | Recurrent disease |
| Ipopolito et al3 | 2007 | 16 | 11F 5M |
32–81 (median 58) | – | – | – | Nil | 0/16 |
| Fernadez-Ranvier et al5 | 2007 | 7 | 3F 4M |
46–66 (mean 55.8) |
3.38–5 (mean 3.38) | 14.8–99.8 (mean 31.5) |
Fibrous trabeculae 5 Trabecular pattern 2 Mitotic features 2 Nuclear polymorphisms 1 |
1 concurrent adenoma | 1/7 |
| Mishra and Newman1 | 2014 | 1 | M | 36 | 5.8 | 354 | – | Nil | 0/1 |
| Juárez-León et al9 | 2015 | 1 | F | 18 | 3.1 | 270 | Partial capsular invasion | Nil | 0/1 |
| Christakis et al7 | 2016 | 1 | F | 32 | 2.9 | 53 | Thick bands Lobular feature |
1 recurrent adenoma | 0/1 |
| Mohan et al8 | 2017 | 1 | F | 21 | 2.55 | 33.4 | Pleomorphic nuclei Minimal mitotic features Partial capsular invasion |
Nil | 0/1 |
Learning points.
Atypical parathyroid adenoma is a challenging clinical diagnosis.
Atypical parathyroid adenoma shares many features with parathyroid malignancy and histological differentiation is key in the further management of these patients.
Atypical parathyroid adenoma may present with an intermediate raised serum calcium level.
Multiple atypical parathyroid adenoma is a rare but important clinical entity.
Acknowledgments
We would like to thank and acknowledge Dr Mohammad Ameen and Professor Silvana Di Palma for providing histopathology assessment and images in this case.
Footnotes
Contributors: All authors contributed to the writing of this case report. JF wrote the manuscript with assistance from KV and supervision from NC. NC was the consultant in charge of the patients care.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: None declared.
Patient consent for publication: Obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.
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