Parathyroid cancer/FHH/Operation Flashcards
(27 cards)
Parathyroid Cancer
- accounts for less than 1% of all patients with primary
- most often occurs sporadically but may also occur in patients with familial HPT, most notably the HPT-JT and familial isolated HPT.
- (CDC73) tumor suppressor gene (also known as HRPT2)
» HPT-JT
» Sporadic - CGM2 mutations
» Familial isolated HPT
Parathyroid cancer
- almost a uniformly functional tumor
- median age at diagnosis is 57 years
- symptomatic
- skeletal manifestations, nephrolithiasis, and renal insufficiency
- nephrolithiasis and bone disease occur concomitantly
» Dont happens in primary HPT - likely to present with HC.
- 50% palpable neck mass
when to suspect cancer
- suspected in patients with HPT, hoarseness, and unilateral vocal cord paralysis
- serum calcium levels greater than 14 mg/dL, serum intact PTH levels that are 3 to 10 times normal, and increased alkaline phosphatase levels
nonfunctional parathyroid cancers
- Most patients with nonfunctional parathyroid cancer present with a palpable neck mass.
- Calcium and PTH levels are normal.
- The prognosis is typically worse because of detection at an advanced stage.
The definitive diagnosis
is made on the basis of invasion of adjacent tissue or regional or systemic metastases.
As a result, parathyroid cancer is usually diagnosed at the time of operation
Parathyroid cancers are large tumors that are most often more than 3 cm in maximum dimension.
At operation how to know it
solid firm mass
grayish white appearance
firm consistency
The normal tissue planes between the parathyroid mass and the thyroid lobe are absent
invasion of surrounding structures, most commonly the thyroid gland and the strap muscles, but the recurrent laryngeal nerve, trachea, and esophagus may be also be involved
Vs Adenoma
In contrast, a benign parathyroid adenoma is a soft tumor that has a definite connective tissue plane separating it from the thyroid gland, allowing for easy dissection of the tumor from surrounding tissues.
Treatment of patients with parathyroid cancer
1- medical management of severe hypercalcemia
2- en bloc resection of the cancer and any adjacent involved structures
3- to not disrupt the capsule of the tumor
-If the recurrent laryngeal nerve is resected, immediate reconstruction with a primary repair or an ansa cervicalis graft can be considered.
-Tracheal invasion is managed by local en bloc resection and either tracheostomy, primary repair or muscle coverage to deal with the defect in the trachea
-For esophageal invasion confined to the muscle layers, partial resection of the esophageal wall is completed.
-A small full-thickness esophageal resection with muscle flap reinforcement may be necessary
What about LNs ?
- Cervical lymph node metastases are uncommon
- central or lateral compartments of the neck, is reserved for patients with lymph node metastases identified on preoperative physical examination, sonographic evaluation, or at operation
Recurrence
- Recurrence rates are high
- 40% to 70% of patients
- within 2 to 5 years
- Locoregional recurrence is most common
- systemic metastases are not infrequent, most commonly affecting the lung and bone
- Mets should be resected if possible to control hypercalcemia
- radioresistant and chemotherapy is ineffective
- Patients die of either metastatic disease or complications of chronic intractable hypercalcemia.
Familial Primary Hyperparathyroidism
- genetic counseling and testing in patients with :
> > primary HPT younger than 40 years of age with multigland disease
> > and in patients with clinical manifestations or a family history that is suggestive of a familial syndrome
MEN 1 genetic testing
> > in primary HPT patients younger than 40 years old with multigland disease or persistent or recurrent primary HPT.
MEN1
- is the most common familial form of primary HPT
- 2% to 4% of patients with primary HPT
- autosomal dominant disorder
- germline, loss-of-function mutation in the MEN1 tumor suppression gene.
- HPT is the most common feature of MEN1
- most MEN1 patients developing HPT in their third decade
- Almost all MEN1 patients develop primary HPT by 50 years
- are most likely to develop multigland disease.
MEN4
- rare inherited syndrome
- lack the MEN1 gene mutation
- mutations in the CDKN1B gene
> > Subtotal parathyroidectomy (or total parathyroidectomy and heterotopic autotransplantation) and transcervical thymectomy is recommended for treatment of primary HPT in patients with MEN1 or MEN4
MEN2A
-MEN2A occurs due to a gain-of-function germline mutation in the RET proto-oncogene.
-Primary HPT in MEN2A has a penetrance of 15% to 35%
-Primary HPT in MEN2A occurs as a single adenoma (30% to 50%)
-In patients with a known RET mutation, screening for primary HPT and pheochromocytoma should occur annually
- codons 634 and 883 (“high risk”), evaluation should occur by age 11
- other RET mutations (“moderate risk”), evaluation for primary HPT should occur by age 16
surgical management of HPT in MEN2A
The surgical options include :
(1) resection of visibly enlarged parathyroid glands
(2) subtotal parathyroidectomy
(3) total parathyroidectomy with immediate heterotopic autotransplantation
- recommend resection of only visibly enlarged glands in MEN2-associated HPT
- Pheochromocytoma must be ruled out or addressed prior to surgery for MEN2-associated primary HPT.
HPT-JT
-autosomal dominant
-primary HPT, ossifying fibromas of the mandible and maxilla, renal cysts, hamartomas, Wilms tumors, and uterine tumors
-mutation in the CDC73 gene
-second or third decade
-single gland disease in approximately 90%
-Parathyroid carcinoma develops in 15% to 20%
-can be treated with focused parathyroidectomy guided by IOPTH measurement when the tumor is localized preoperatively
- parathyroid cancer are treated with an en bloc resection of the tumor and anything that the tumor is invading
When to do Genetic evaluation for HPT JT
Genetic evaluation and testing for the CDC73 gene are recommended for
- all patients with parathyroid carcinoma
- for patients with primary HPT and ossifying fibromas of the mandible and maxilla
- young patients with primary HPT and multigland disease in the absence of a MEN1 gene mutation.
Familial isolated HPT
-autosomal dominant
-lack of syndromic manifestations
-multiple potential causative genetic
-MEN1 gene»_space; associated with multigland disease
-the CDC73 gene»_space; often associated with single gland disease
- 18% of patients with familial isolated HPT have a mutation in the GCM2 proto-oncogene»_space; associated with multigland disease and higher risk of parathyroid cancer.
Tx ?
- Because of the high incidence of multigland disease, consideration should be given to bilateral neck exploration.
- It is our preference to proceed with a bilateral neck exploration and only resect enlarged glands and use IOPTH monitoring as an adjunct
Recurrence Rate for familial primary HPT
familial primary HPT is associated with a higher rate of recurrence following parathyroidectomy and a lower overall cure rate.
Recurrence rates following parathyroidectomy vary from 17% to 46% in MEN1
6% to 11% in MEN2A
15% to 20% in HPT-JT
11% in familial isolated HPT
Persistent and Recurrent
Persistent HPT is defined as failure to achieve normocalcemia within 6 months of parathyroidectomy.
Recurrent primary HPT is defined as recurrent hypercalcemia after an interval of normal calcium levels for at least 6 months following parathyroidectomy.
Reoperation risk
Rates of hypoparathyroidism and recurrent laryngeal nerve injury are higher after parathyroid reexploration.
Family hx is important why ?
A family history is important to help understand whether the patient is more likely to have single or multigland disease
