Parathyroid Proliferative Disorders

Parathyroid Proliferative Disorders
Parathyroid Adenomas Primary Parathyroid Hyperplasia Parathyroid Carcinomas

(85%) (15%) (5%)
Patients typically present with evidence of primary hyperparathyroidism with

elevated serum calcium levels and elevated serum parathyroid hormone levels.
Wieneke JA, Smith A. Parathyroid Adenoma. Head and Neck Pathology. 2008;2(4):305-308.

Clinical Features
• Patients with primary hyperparathyroidism may present
with clinical evidence of elevated serum calcium levels
which include :
Non-specific symptoms : fatigue, pain and weakness as
well as polydipsia, polyuria, and nephrolithiasis.
GIT : constipation, anorexia, nausea, and vomiting.
Extreme hypercalcemia : cardiac arrhythmias, coma and

death.
• Osseous manifestations (varying from initial
decrease in bone density to full blown osteitis
fibrosa cystica)
• Renal manifestations
• Rarely hypertension, acute and chronic
pancreatitis, peptic ulcer, and mental
disturbances.
Radiology
• Normal parathyroid glands are too small to be
detected on imaging (usually 5 × 3 × 1 mm,), but
parathyroid disease typically results in enlargement of
the glands allowing for visualization.
• Sonography and 99mTc-sestamibi scintigraphy are the
primary imaging modalities utilized for the
visualization of diseased glands.
• Scintigraphy is approximately 90% sensitive for
localizing a parathyroid adenoma, and can easily
demonstrate glands greater than 500 mg.

• Ultrasound imaging demonstrates parathyroid
adenomas as typically homogeneously
hypoechoic lesions compared with the
adjacent thyroid, and they can easily be
detected when they are larger than 1 cm
• Doppler imaging typically demonstrates a
characteristic extrathyroidal feeding vessel
entering the parathyroid gland at one of the
poles.
Parathyroid adenoma
•The weight of parathyroid adenomas

varies but in general, approximately 1 g
(the weight of a normal parathyroid gland
is typically less than 50 mg).
•Cut surface is typically smooth, soft, and

reddish brown in color, distinguished from
the yellow-brown color of normal
parathyroid tissue.
•Usually solid, rarely cystic.

Treatment
• Parathyroidectomy, a surgical procedure with a high success
rate, is currently the treatment of choice. Pathological
parathyroid tissue excision can be achieved by surgical and non-
surgical ablative therapy (selective percutaneous ethanol
injection and transcatheter ablation of pathological parathyroid
tissue).
• Therapeutic alternatives to parathyroidectomy are
antiresorptive drugs (bisphosphonates, oestrogens and
selective oestrogen receptor modulators) and inhibitors of PTH
secretion (calcimimetics). A combination of drugs with diverse
mechanisms of action may have a synergistic effect in the
symptomatic control of PHP.
Iglesias P1, Díez JJ.. Current treatments in the management of patients with primary
hyperparathyroidism. Postgrad Med J. 2009 Jan;85(999):15-23.
Parathyroid Carcinoma
• PTC is a very rare disease, represents a diagnostic
and therapeutic challenge and diagnosed in <1% of
patients with elevated serum parathormone levels.
• Can equally affect both genders
• Mean age of onset is 50 years
• The aetiology remains unknown, although genetic
predisposition factors, such as primary
hyperparathyroidism (PHP) with jaw tumour, or risk
factors such as irradiation have been described.
C. Rodriguez a , S. Nadéri a , C. Hans b, C. Badoual a. Parathyroid carcinoma: A difficult histological diagnosis.

European Annals of Otorhinolaryngology, Head and Neck diseases (2012) 129, 157—159
Clinical Features
• The clinical presentation is variable, usually comprising
renal failure
• A palpable neck mass is present in 15 to 75% of cases.
• Parathyroid carcinomas are hyperfunctional and
characterized by severe elevations of serum calcium(with
the mean values between 14 and 15 mg/dL) with
associated renal and bone symptoms.
• Very few cases of nonfunctional parathyroid cancers have
been reported in the literature accounting for
approximately 1.9% of parathyroid tumors and represent a
prognostic indicator of poor outcome.
Gabriele Ricci, Marco Assenza, Marco Barreca, et al., “Parathyroid Carcinoma: The Importance of High Clinical
Suspicion for a Correct Management,” International Journal of Surgical Oncology, vol. 2012, Article ID 649148, 5
pages, 2012.
• Recurrent laryngeal nerve palsy
• The most frequent complaints are fatigue, weakness,
anxiety, nausea, vomiting, polyuria, and polydipsia
• Renal colic, bone pain, and pathological fractures are also
common features of parathyroid cancer
• Pancreatitis and peptic ulcer disease secondary to the
relentless hypercalcaemia may occur further
It is important to note the high incidence of concomitant bone and stone disease that
occurs in parathyroid cancer, that is very unusual in primary hyperthyroidism.
pages, 2012.
pages, 2012.
Gender Predilection More common in women Equally affects both
genders
Levels are lesser severe hypercalcemia and
serum ALP levels at higher
levels
local recurrence and
metastatic disorder s
BASER, H., KARAGOZ, A., OKUS, A., CAYCI, M., EREN KARANIS, M., SEVIMLI BURNIK, F., BASER, S..
Differential Diagnosis of Atypical Parathyroid Adenoma and Parathyroid Carcinoma in a Case
With Severe Hypercalcemia. Journal of Medical Cases, North America, 4, may. 2013.
Histology
• Presence of vascular invasion (in the capsule or

adjacent tissues);
• Capsular invasion with extension to adjacent tissues
and/or;
• Presence of metastases
• Histological features like presence of coagulation
necrosis, large nucleoli and more than five mitotic
figures per ten high-power fields indicate an aggressive
clinical course
IHC
• Immuno-histochemistry using an anti-PTH antibody has
not been demonstrated to be useful for the diagnosis of
malignancy. It confirms the parathyroid origin of the
tumour.
• A proliferation index, evaluated by the Ki 67 antibody,
higher than 5% is associated with a higher risk of
malignancy and recurrence.
• Overexpression of cyclin D1 or inactivation of the
retinoblastoma gene cannot be used to reliably
differentiate parathyroid adenoma from parathyroid
carcinoma .
Intraoperative macroscopic appearance
• Lobulated firm mass, surrounded by fibrous

grayish-white capsule that adheres tenaciously
to thyroid lobe or adjacent cervical tissues
(strap muscles, recurrent laryngeal nerve,
esophagus, and trachea)
• The most common sites of invasion were the :
ipsilateral thyroid gland 89%
strap muscles 71%
ipsilateral recurrent laryngeal nerve 26%
oesophagus 18%, and
trachea 17%.
Differential Diagnosis
• The main differential diagnosis is parathyroid
adenoma, but parathyroid hyperplasia,
anaplastic thyroid cancer or, more rarely,
metastasis of renal cell carcinoma, must also
be excluded.
Treatment
• Treatment is essentially surgical with “en bloc”
resection including the tumour, the ipsilateral
thyroid lobe, ipsilateral recurrent laryngeal
and jugular and carotid lymph nodes, and
pretracheal adipose tissue.
• The efficacy of adjuvant therapy has not been
clearly demonstrated.
pages, 2012.
• Sandelin and coll. showed that patients treated
initially with more extensive surgery had a longer
survival and a longer relapse-free period than
patients treated with tumor resection alone .(K.
Sandelin, G. Auer, L. Bondeson, L. Grimelius, and L. O. Farnebo, “Prognostic factors in
parathyroid cancer: a review of 95 cases,” World Journal of Surgery, vol. 16, no. 4, pp. 724–
731, 1992.)
• Similarly the analysis of literature of Koea and

Shaw reported an overall 8% evidence of local
recurrence after en bloc resection compared to a
51% incidence after a standard parathyroidectomy.
pages, 2012.
• Controversy exists as to whether the patient in whom malignancy is
recognized after tumorectomy requires reoperation with resection of
all structures adjacent to where the tumour was originally located.
Some investigators have suggested that in these cases reoperation
may be postponed until tumor recurrence is recognized by rising
calcium levels .
• Current literature, however, suggests that conservative resection is
associated with a significant risk of capsule rupture and subsequent
local dissemination of the tumor, therefore reoperation with
ipsilateral total thyroid loboistmectomy is recommended .
• For the same reason a preoperative aspiration biopsy or an
intraoperative incisional biopsy of the mass must be avoided,
otherwise local dissemination of tumor cells may occur
pages, 2012.
• Some authors reported that despite infiltration
macroscopically or adherence of the tumor to
adjacent structures is often associated with
malignant tumors, it could be sometimes
present in benign lesions .
• The data of literature and our experience
showed that it is preferable to treat all these
patients as parathyroid carcinoma than to miss
the opportunity for surgical cure.
pages, 2012.
• Although the reported incidence of cervical
lymph node metastasis is <20% the most of
authors recommended routine dissection of
trachea-esophageal groove, but an extensive
lateral neck dissection is indicated only when
there is macroscopic spread to the anterior
cervical nodes
pages, 2012.
Hungry Bone Syndrome
• One well recognized surgical complication in patients in whom the tumor is
completely excised is the development of the “hungry bone syndrome.”The
sudden postoperative withdrawal of PTH induces abrupt cessation of
osteoclastic bone resorption without affecting osteoblastic activity.
Consequently, an increased bone uptake of calcium, phosphate and
magnesium is observed.
• Risk factors for the syndrome include: large parathyroid adenomas, age >
60 years, and high pre-operative PTH levels, calcium and alkaline
phosphatase. In high risk individuals careful vigilance for clinical symptoms
of hypocalcaemia and close follow up of laboratory parameters are
warranted during the immediate postoperative period. Treatment is with
large doses of oral or intravenous calcium and oral calcitriol, at least
initially.
Gabriella Captur et al. Parathyroid carcinoma: clinical course, diagnosis and management.
Malta Medical Journal Volume 22 Issue 02 2010
• Parathyroid carcinoma is not a radiosensitive tumour and
the role of radiotherapy is generally restricted to neck
irradiation after surgery for recurrence, in order to prevent
re-growth. Use of either radiotherapy or chemotherapy
should be considered only when a patient is not a candidate
for surgery and hypercalcaemia cannot be controlled.
• The role of chemotherapy in the management of
parathyroid carcinoma is limited although there are scant
reports of success with synthetic oestrogens, 5-fluorouracil,
cyclophosphamide and dacarbazine-containing regimes
Control of intractable hyperglycaemia
• When the tumor is no longer amenable to

surgical intervention, treatment becomes
limited to the control of hypercalcaemia
through hydration, calcimimetic agents
(cinacalcet) or intravenous bisphosphonates
(pamifronate, zoledronic acid).
Immunotherapy
• Immunisation with human, modified human
and bovine PTH peptides stimulated the
production of autoantibodies against human
PTH giving rise to PTH-antibody immune
complexes. This strategy has been successful
in reducing hypercalcaemia, improving clinical
status30 and in one case it was even shown to
reduce tumour load.
Prognosis
• The recurrence rate of PTC ranges between 30
and 67%.
• The 5-year survival is 40 to 86% and the 10-
year survival is 49%
• Metastases occur in regional lymph nodes
(30–40%), lungs (20–40%) and, more rarely, in
the mediastinum, bone, pleura, pericardium
or pancreas.
pages, 2012.
• Diagnosis is made on a combination of clinical,
radiological and histological signs in the
context of an atypical presentation of PT
tumour and, whenever possible, before the
appearance of metastases.
• However, it is not uncommon for a final
diagnosis of malignancy to be established only
at the stage of recurrence or metastases.
pages, 2012.
Note
Patients with MEN syndromes, most commonly MEN
1, frequently will have parathyroid proliferative
disorder as part of their syndrome. Nearly 90% of
patients with MEN 1 have parathyroid hyperplasia.
Parathyroid adenoma and carcinoma can also be
seen as part of these syndromes. While the vast
majority of patients with parathyroid proliferative
disorder present with sporadic disease, the
possibility of an MEN syndrome should always be
kept in mind when evaluating these patients.

Parathyroid Proliferative Disorders

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Parathyroid Proliferative Disorders

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Parathyroid Proliferative Disorders

Parathyroid Adenomas Primary Parathyroid Hyperplasia Parathyroid Carcinomas

Patients typically present with evidence of primary hyperparathyroidism with

Wieneke JA, Smith A. Parathyroid Adenoma. Head and Neck Pathology. 2008;2(4):305-308.

GIT : constipation, anorexia, nausea, and vomiting.

Extreme hypercalcemia : cardiac arrhythmias, coma and

Wieneke JA, Smith A. Parathyroid Adenoma. Head and Neck Pathology. 2008;2(4):305-308.

•The weight of parathyroid adenomas

•Cut surface is typically smooth, soft, and

•Usually solid, rarely cystic.

Wieneke JA, Smith A. Parathyroid Adenoma. Head and Neck Pathology. 2008;2(4):305-308.

C. Rodriguez a , S. Nadéri a , C. Hans b, C. Badoual a. Parathyroid carcinoma: A difficult histological diagnosis.

• Presence of vascular invasion (in the capsule or

• Lobulated firm mass, surrounded by fibrous

• Similarly the analysis of literature of Koea and

• When the tumor is no longer amenable to

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