Parathyroid

Carcinoma
SUDHIR V NAIR MS, MCH
A S S O C I AT E P R O F E S S O R
H E A D A N D N E C K O N C O S U R G E RY
TATA M E M O R I A L C E N T E R
Parathyroid glands produce parathyroid hormone (PTH), which
regulates the circulating level of calcium
There are typically 4 parathyroid glands, but more numbers can be
found occasionally.
Etiology
Rare disease
Rare cause of primary hyperparathyroidism (< 2%)
Etiology of parathyroid carcinoma is not known
Very rarely associated with multiple endocrine neoplasia type 1
Can occurring in an adenoma, hyperplastic gland, or in patients with
history of neck irradiation.
Occurs with equal frequency in men and women
Clinical features
Mean age – 44 to 54 years
Mean serum calcium concentration – 14.6 to 15.9 mg/dL
Mean serum parathyroid hormone (PTH) concentrations 5- to 10-fold higher than the
upper limit of normal (PPV of 81%).
Higher levels of Alkaline Phosphatase & HCG.
Serum calcium concentration above 14 mg/dL – 65 to 75%
Parathyroid crisis – 12 percent
Neck mass – 34 to 52 percent
Bone disease – 34 to 73 percent
Renal disease – 32 to 70 percent
Pancreatitis – 0 to 15 percent
No symptoms – 2 to 7 percent
Predilection to single inferior gland
Lymph node metastases at initial presentation in one third.
Distant metastases - usually to liver and bone
Parathyroid Carcinoma Challenges in Diagnosis and Treatment
Arash Mohebati, MD, Ashok Shaha, MD, Jatin Shah, MD; Hematol Oncol Clin N Am 26 (2012) 1221–1238
Molecular Pathogenesis
mutations of both oncogenes and tumor suppressor genes
Mutation of the HRPT2 (also called CDC73) tumor suppressor
◦ HRPT2 is located on chromosome 1 
◦ Also seen in Hyperparathyroidism-jaw tumor syndrome - 15% develops
parathyroid carcinoma.
◦ 77% of sporadic parathyroid carcinoma – a potential diagnostic tool.
◦ Cyclin D1
◦ overexpressed in 18% to 40% of adenomas
◦ Upto 91% of parathyroid carcinoma specimens

◦ Loss of Rb and BRAC1 genes

◦ Loss of p53
Imaging studies
Ultrasonography , USG guided FNAC
◦ lobulated, hypoechoic, and relatively large, with illdefined borders compared
with adenomas
◦ lesions larger than 15 mm.

Sestamibi scanning – hyperfunctioning parathyroid

Computed tomography (CT),
Single-photon emission CT, magnetic resonance imaging (MRI) and
Positron emission tomography
Parathyroid carcinoma proposed TNM definitions AJCC UICC 2017
T category T criteria
TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

Tis Atypical parathyroid neoplasm (neoplasm of uncertain malignant potential)*

T1 Localized to the parathyroid gland with extension limited to soft tissue

T2 Direct invasion into the thyroid gland

T3 Direct invasion into recurrent laryngeal nerve, esophagus, trachea, skeletal muscle, adjacent lymph nodes, or thymus

T4 Direct invasion into major blood vessel or spine

* Defined as tumors that are histologically or clinically worrisome but do not fulfill the more robust criteria (ie, invasion, metastasis) for carcinoma.
They generally include tumors that have two or more concerning features, such as fibrous bands, mitotic figures, necrosis, trabecular growth, or
adherence to surrounding tissues intraoperatively. Atypical parathyroid neoplasms usually have a smaller dimension, weight, and volume than
carcinomas and are less likely to have coagulative tumor necrosis.

Regional lymph nodes (N)

N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis

N1a Metastasis to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes) or superior mediastinal lymph
nodes (level VII)

N1b Metastasis to unilateral, bilateral, or contralateral cervical (levels I, II, III, IV, or V) or retropharyngeal nodes

Distant metastasis (M)

M category M criteria
M0 No distant metastasis
M1 Distant metastasis
Preoperative medical
management
Treatment of hypercalcemia
◦ Prompt aggressive hydration with normal saline
◦ intravenous bisphosphonates
◦ pamidronate, zoledronic acid
◦ Use of a Calcimimetic (Cinacalcet)- 30 mg twice daily to
begin with.
◦ Denosumab :Monoclonal Antibody; Bone-Modifying
Agent.
◦ potent inhibitor of bone resorption
 Surgery
Resectable disease
◦ Surgery is the mainstay of therapy 

Extent of resection -
◦ Preoperatively diagnosed
◦ Parathyroidectomy with surrounding tissues (Hemi thyroidectomy)
◦ Avoid tumor spillage.
◦ If RLN is grossly involved by tumor, it needs to be sacrificed
◦ When cervical nodes are involved, a therapeutic modified neck
dissection is necessary
◦ Limited data on ipsilateral neck node dissection in the absence of
nodes
Pathological features
Firm and greyish nodules showing capsular and vascular invasion –
◦ Local invasion of contiguous structures (ipsilateral thyroid)

Lymph node or distant metastases

Trabecular or rosettelike cellular architecture
mitotic figures,
Thick fibrous bands
IHC
◦ Parafibromin immunostaining – more in adenomas. Reduced in carcinoma
◦ Galactin-3, PGP9.5, and Ki67 – good specificity.
◦ Postoperatively diagnosed 
◦ Reoperation with ipsilateral thyroidectomy is frequently
performed
◦ Metastatic disease
◦ surgical resection of distant metastases may be
considered.
Postoperative
management
Close monitoring of the patient's serum calcium 
“hungry bone syndrome” – increased influx of calcium in to bones
immediately after parathyroid gland excision leading to severe
hypocalcemia.
◦ intravenous (IV) calcium for patients with symptoms or ECG Changes.
◦ Correction of hypomagnesemia
◦ oral calcium supplementation

Adjuvant radiotherapy
◦ it is considered in patients who are at high risk of locoregional recurrence.
Unresectable disease
prognosis is generally poor
major morbidity and mortality result from severe hypercalcemia
◦ hydration 
◦ intravenous bisphosphonates
◦ Use of a Calcimimetic (Cinacalcet)- 30 mg twice daily to begin with.
◦ Denosumab :Monoclonal Antibody; Bone-Modifying Agent.
◦ potent inhibitor of bone resorption
◦ Chemotherapy - limited role. Flurouracil.
◦ Targeted therapy - clinical trials.
GENETIC TESTING
Genetic HRPT2 testing – for most patients with sporadic parathyroid
carcinoma.
If HRPT2 shows mutations
◦ Index patient with parathyroid carcinoma : all parathyroid glands at
increased risk for developing new malignant tumors.
◦ Family members:
◦ If negative : it will reduce the anxiety
◦ If positive : active surveillance – testing for PTH and S.Ca once in 6 months.
Parathyroid carcinoma is a rare cause of primary hyperparathyroidism
More likely to have symptoms,
◦ a neck mass
◦ bone and kidney disease
◦ marked hypercalcemia and
◦ very high serum parathyroid hormone concentrations

Diagnosis usually made at the time of surgery

Surgery is the mainstay of therapy
Treatment of hypercalcemia – in unresectable disease
◦ Dedicated physician or endocrine department

Genetic evaluation - HRPT2 mutations

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