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CASE REPORT
Year : 2020  |  Volume : 17  |  Issue : 2  |  Page : 89-93

Parathyromatosis in a patient with parathyroid carcinoma and hypercalcemic crisis: Findings on MIBI scan and 4D CT


1 Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
3 Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India
4 Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
5 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission01-Apr-2020
Date of Acceptance03-Apr-2020
Date of Web Publication17-Jul-2020

Correspondence Address:
Dr. Nishikant Avinash Damle
Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/trp.trp_21_20

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  Abstract 


Parathyroid carcinoma is a rare tumor associated with significantly high levels of parathyroid hormone (PTH) and primary hyperparathyroidism (HPT) and is difficult to distinguish from parathyroid adenoma, which is a much more common cause of HPT. Parathyromatosis is a rare condition in which several nodules of hyperfunctioning parathyroid tissue form in the neck and mediastinum, and it presents as recurrent hyperparathyroidism. We describe the case of a 44-year-old woman with recurrent hyperparathyroidism who presented with hypercalcemic crisis and biochemical investigations showed a severely raised serum intact parathyroid hormone (iPTH) level of 2513 pg/ml and serum calcium level of 17 mg/dl. A four-dimensional computed tomography (4D CT) of the neck was done, which showed few arterially enhancing nodular lesions in the right paratracheal and retrotracheal location at the level of thoracic inlet showing washout in delayed images suggestive of recurrent/residual parathyroid lesions. A technetium-99 m methoxyisobutylisonitrile (Tc-99 m MIBI) scan was done, and the planar neck anterior early images showed an area of increased radiotracer uptake in the right lower neck region with persistent uptake in the delayed images. Single photon emission computed tomography/ computed tomography (SPECT/CT) images showed a soft-tissue lesion in the right paratracheal region at the level of C7 vertebra showing increased radiotracer uptake suggestive of a recurrent/residual parathyroid lesion. Exploration and excision of the recurrent parathyroid mass was planned, and the right paratracheal mass with nodes above the aortic arch along with the subcutaneous and intramuscular lesions were excised. Postoperative serum calcium was 7.8 mg/dl, and serum iPTH was 135 pg/ml. Histopathological examination of the excised tissue showed the features of parathyroid carcinoma. Thus, Tc-99 m MIBI scan and 4D CT were critical in evaluating this case of parathyroid carcinoma with recurrent hyperparathyroidism and planning its management.

Keywords: 4D CT, hypercalcemic crisis, parathyroid carcinoma, parathyromatosis, Tc-99m MIBI


How to cite this article:
Prakash S, Damle NA, Kandasamy D, Gupta Y, Kumar C, Agarwal S, Yadav R, Boro H, Alam S, Yadav D. Parathyromatosis in a patient with parathyroid carcinoma and hypercalcemic crisis: Findings on MIBI scan and 4D CT. Thyroid Res Pract 2020;17:89-93

How to cite this URL:
Prakash S, Damle NA, Kandasamy D, Gupta Y, Kumar C, Agarwal S, Yadav R, Boro H, Alam S, Yadav D. Parathyromatosis in a patient with parathyroid carcinoma and hypercalcemic crisis: Findings on MIBI scan and 4D CT. Thyroid Res Pract [serial online] 2020 [cited 2020 Aug 10];17:89-93. Available from: http://www.thetrp.net/text.asp?2020/17/2/89/289998




  Introduction Top


Parathyroid carcinoma is rare and makes up for <1% of all cases of primary hyperparathyroidism (HPT).[1] Although majority of parathyroid carcinoma cases are functional tumors[2] and present with HPT, they are difficult to diagnose because of their rarity and also because they closely mimic parathyroid adenoma, which is the most common cause of HPT.[3] However, serum calcium levels usually higher than 14 mg/dl and serum intact parathyroid hormone (iPTH) levels that are 10–15 fold higher than the normal range have been reported.[4] Thus, hypercalcemic crisis is common in cases of parathyroid carcinoma. Imaging methods such as ultrasound, computed tomography (CT), sestamibi scan with or without single photon emission CT/ CT (SPECT/CT), and F-18 fluorodeoxyglucose positron emission tomography with CT (F-18 FDG PET/CT) have been used for initial diagnosis and for detecting the recurrence of parathyroid carcinoma.[5]En bloc resection as the initial surgery has been advocated as the gold-standard treatment approach.[6] More than 50% of patients with parathyroid carcinoma show persistent or recurrent disease.[7] Hyperfunctioning parathyroid tissue scattered throughout the neck known as parathyromatosis leads to recurrent hyperparathyroidism and requires repeated surgery.[8] Here, we report the MIBI scan and four-dimensional CT (4D CT) findings in a patient with parathyroid carcinoma who underwent multiple surgeries for persistent hyperparathyroidism and presented with hypercalcemic crisis and parathyromatosis.


  Case Report Top


A 44-year-old female presented to the endocrinology clinic with multiple episodes of vomiting. She had a prolonged history of symptoms of hyperparathyroidism spanning 9 years which included bone pains, fracture neck of the femur, renal stones, and an episode of acute pancreatitis. Her initial hospital admission 9 years back was for the treatment of fracture of the right neck of the femur. In view of pathological fracture, FDG PET/CT was done at another hospital to look for the primary pathology, and it raised suspicion of a right inferior parathyroid adenoma. Biochemical investigations showed that her serum calcium was 11.3 mg/dl; serum phosphate was 2 mg/dl; and serum iPTH was 724.02 pg/ml. She was diagnosed with HPT and underwent right inferior parathyroidectomy and DHS fixation of the right neck of the femur. Postoperative bio-chemical investigations were done, and her serum Calcium had reduced to 6.7 mg/dl, and iPTH had normalized to 48.47 pg/ml. Follow-up investigation 1 year after the first surgery showed increased serum calcium of 11.3 mg/dl, iPTH level of 681.7 pg/ml. She was admitted again and technetium-99 m methoxyisobutylisonitrile (Tc-99 m MIBI) scintigraphy was done which again revealed the features suggestive of right inferior parathyroid adenoma. Residual parathyroid adenoma was suspected, and she underwent reexcision of all remaining parathyroid tissue at the right inferior polar region and right hemithyroidectomy apparently to excise any adherent tissue, but there was no postoperative fall in serum calcium or iPTH levels. The postoperative serum calcium was 11.3 mg/dl, and serum iPTH was 656 pg/ml. Histopathological examination of the excised tissue was inconclusive. In the following two years, the patient had persistently high-serum calcium (~12.3 mg/dl) and iPTH levels (~653.6 pg/ml), but imaging by MIBI scan showed no parathyroid adenoma. In the following years, the patient was lost to follow-up and experienced worsening of bone pains and flank pain. The patient came to our hospital after an episode of acute pancreatitis which was managed conservatively. Furthermore, her biochemical investigations revealed a very high serum calcium level of 17 mg/dl, serum iPTH– 2513 pg/ml, and serum phosphate – 3.08 mg/dl. Recurrent HPT with hypercalcemic crisis was diagnosed, and parathyroid carcinoma was suspected to be the root cause. She was referred for a Tc-99 m MIBI parathyroid scintigraphy. Planar neck anterior early images showed an area of increased radiotracer uptake in the right lower neck region [Figure 1]a with persistent uptake in the delayed images [Figure 1]b. She also underwent a whole-body scan at 1 h postradiotracer injection to look for potential metastatic sites, and the whole-body planar images did not show any other abnormal areas of tracer uptake [Figure 2]. SPECT/CT images of the neck showed soft-tissue density lesion in the right paratracheal region at the level of C7 vertebra anterolateral to the longus colli muscle and anteromedial to the right common carotid artery, measuring 13 cm × 9 mm in the largest dimension [Figure 1]c with increased radiotracer uptake [Figure 1]d which was suggestive of a recurrent/residual parathyroid carcinoma. 4D CT neck with IV contrast showed few arterially enhancing nodular lesions in the right paratracheal and retrotracheal location at the level of thoracic inlet, largest measuring 13 mm × 9 mm [Figure 3]a showing washout in delayed images [Figure 3]b suggestive of recurrent/residual parathyroid carcinoma or nodes. Subcutaneous and intermuscular nodules were also seen in the right lower cervical region superficial to the paratracheal mass. Visualized bones showed osteopenic changes and multiple well-defined lytic lesions in the skeleton. Clinical presentation, biochemical investigations, and imaging results established a presumptive diagnosis of recurrent parathyroid carcinoma. The patient was planned for an exploration and excision of recurrent parathyroid mass and intraoperative findings revealed a conglomerated mass comprising multiple maroon-colored friable nodules present in the right paratracheal region as explained in 4DCT. The mass was adherent to the internal jugular vein (IJV), trachea, and esophagus. The IJV was ligated and divided. The mass was reaching up to arch of the aorta confirming parathyroid carcinoma. The right paratracheal mass along with all suspicious nodes superior to the arch of the aorta was excised. The subcutaneous and intermuscular nodules were also removed. Postoperatively, the serum calcium level had reduced to 7.8 mg/dl and serum iPTH had come down to 135 pg/ml. The excised tissue was sent for histopathological examination. Specimen of the right-sided parathyroid mass measuring 6 cm × 4.5 cm × 1.5 cm showed multiple whitish tumor deposits on serial slicing, measuring 5.5 cm × 4 cm × 1 cm reaching up to the external capsule grossly. Multiple sections examined from the tumor showed the features of parathyroid carcinoma. The tumor was focally breaching the peripheral painted resected surface. Subcutaneous neck nodules (1 cm × 1 cm × 0.6 cm) showed a tumor with similar morphology. Vacular emboli were also seen [Figure 4].
Figure 1: Planar neck anterior early images showing an area of increased radiotracer uptake (arrow) in the right lower neck region (a) with persistent uptake (arrow) in the delayed images (b). Computed tomography (CT) of neck showing soft-tissue mass lesion (arrow) in the right paratracheal region (c). With increased tracer uptake (arrow) on fused single photon emission CT/ CT (SPECT/ CT) images (d)

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Figure 2: Whole-body planar images (anterior and posterior) on Technetium-99 m methoxyisobutylisonitrile scan taken at 1 h showing no other areas of abnormal uptake

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Figure 3: Four-dimensional computed tomography neck with IV contrast showing few arterially enhancing nodular lesions in the right paratracheal (star) and retrotracheal location (arrow) at the level of thoracic inlet and subcutaneous deposits (arrowhead) on the right side (a) showing washout in delayed images (b)

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Figure 4: Aspirate from the nodule was moderately cellular showing cells arranged in vascularized fragments (May–Grünwald–Giemsa stain, ×100) and as microfollicles (inset; May–Grünwald–Giemsa stain, ×400). (a) Sections from the resection specimen showed the features of parathyromatosis. Cellular parathyroid tissue was interspersed as islands within fibro-adipose tissue (H and E, ×40). (b) There were areas of hypercellularity (H and E, ×400), but significant atypia or mitotic activity not seen. (c) MIB-1 labeling index was low (1%–2% in highest proliferative area) (IHC, ×600). (d) Vascular emboli were seen (e, H and E, ×400). CD 34 highlighted the endothelial cells (f, IHC, ×200)

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  Discussion Top


Parathyroid carcinomas are rare and tend to occur a decade earlier than adenoma and have equal incidence in both genders.[9] Genetic associations have been reported between parathyroid carcinoma and inactivating mutations of CDC73 tumor-suppressor gene, loss of nuclear expression of parafibromin,[10] and HRPT2 mutations.[11]

Patients with parathyroid carcinoma have clinical features similar to that of parathyroid adenoma such as weakness, fatigue, nervousness, depression, weight loss, bone disease, abdominal pain, nephrolithiasis, pancreatitis, and peptic ulcer disease.[12] They have higher chances of presenting with severe bone involvement such as bone pain, osteopenia, osteoporosis, osteofibrosis, and pathologic fractures and renal involvement such as nephrolithiasis and renal insufficiency than adenomas.[13] Concomitant bone and renal involvement is more common in cases of parathyroid carcinoma and parathyroid adenomas.[14] Serum calcium levels usually higher than 14 mg/dl and serum iPTH levels that are 10-15 fold higher than the normal range have been reported.[4]

Imaging methods such as Tc-99 m MIBI SPECT/CT, MRI, and CT may help in localizing the parathyroid carcinoma and are recommended before invasive parathyroidectomy to allow precise and accurate localization of the parathyroid lesion.[15],[16],[17] In a study reported by Chen et al.,[18] Tc99 m-MIBI SPECT/ CT showed a high sensitivity for parathyroid carcinoma lesions. In our patient, MIBI scan was positive for the recurrent lesion, and SPECT/ CT gave us the exact location of the lesion. 4D CT was helpful in localizing the recurrent mass as well as the malignant nodes and other deposits.

Histopathological distinction between malignant and benign parathyroid tumors cannot be definitively established unless there is evidence of invasion of extratumoral vessels, perineural spaces, or adjacent structures such as thyroid.[19] In most cases, the diagnosis of parathyroid carcinoma is made intraoperatively.[20]

The management for parathyroid carcinoma is primarily surgical[21],[22] with complete resection and microscopically negative margins offering the best chance of cure.[7] Despite a potentially curative resection, parathyroid carcinoma has a high recurrence rate of more than 50% with the disease-free interval varying from 2 to 3 years to as long as 20 years.[23] We observed multiple recurrences in our patient with a severely elevated serum iPTH level of 2513 pg/ml and serum calcium level of 17 mg/dl which dropped to 7.8 mg/dl and 135 pg/ml, respectively, postsurgical exploration and excision of the recurrent malignant mass along with the malignant subcutaneous and intramuscular nodules. Imaging studies such as Tc-99 m MIBI, CT, and sometimes, F-18 FDG PET/CT for restaging may be performed where possible before reoperation.[5],[24],[25] The surgical excision of recurrent lesions have also been shown to have further recurrences, and most patients succumb to the effects of hypercalcemia than from tumor burden or infiltration.[26] Thus, it is important to regularly follow-up patients with biochemical and imaging investigations.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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