The morphological
criteria for parathyroid adenocarcinoma include:
Capsular and blood
vessel invasion, desmoplastic stroma with fibrous bands, trabecular
growth pattern, thickening and hyalinization of the capsule, spindle
shaped tumour cells, elevated mitotic count and aberrant mitoses.
Of these features, the presence of fibrous bands stands out as the most
helpful for the diagnosis of malignancy, being present in 90%
of 67 cases studies (Schantz & Castleman 1973).
Caution should be
exercised in the interpretation of fibrous bands since these may
sometimes occur as part of regressive phenomenon in adenomas, in which
case they may be associated with deposition of hemosiderin and
surrounded by chronic inflammatory cells.
Assessment of
mitotic activity either by mitotic counts, flow cytometry, or by immunohistochemistry has been proposed as a means of predicting
malignancy in parathyroid neoplasia.
While there is a statistical tendency for the adenocarcinoma
- particularly those with aggressive
behaviour - to have higher proliferative activity than adenomas,
overlap in the result ranges limits diagnostic utility in the
individual case.
The main problem appears to be that some parathyroid adenomas,
increasingly recognized to be clonal and a true neoplasm,
have high proliferative indices.
In one interesting study, nuclear
chromatin texture, even when subject to detailed image analysis,
failed to distinguish benign and malignant parathyroid neoplasms.
Capsular invasion
is an important distinguishing feature for parathyroid adenocarcinoma,
being present in approximately two thirds of cases, often associated
with a capsule which itself is thicker than that encountered in
parathyroid adenomas. However, care should be taken not to confuse
occasional entrapped clusters of cells, particularly in the capsules of adenomas which
have undergone cystic degeneration, for true invasion. While clear-cut vascular invasion is only encountered in 10-15% of
parathyroid adenocarcinomas, when present it is a useful sign of malignancy.
The growth
pattern in parathyroid adenocarcinoma may be trabecular, rosette-like
or sheet-like. Nuclear palisading may be present. While the tumour
cells are generally larger than those in adenomas, there may be little
nuclear pleomorphism.
Electron
microscopic studies have failed to show any unique features
correlating with malignancy in parathyroid neoplasms.
Analysis of the p53 gene mutation is of
uncertain value in the prediction of malignancy in parathyroid neoplasia. In one study it was demonstrated in neither adenomas
nor carcinomas. In another study two out of nine carcinomas were p53
immunopositive of which one had p53 allelic loss while the other was genetically
non-informative,
while none of the adenomas had allelic loss.
Loss of Retinoblastoma (Rb)
protein has been reported in some parathyroid carcinomas while
adenomas appear to be Rb positive.
A number of
benign and malignant lesions can mimic parathyroid adenocarcinoma.
The
clear cells in the wall of parathyroid cyst, atypical oxyphil
parathyroid adenoma, various metastatic tumours particularly of clear
cell type, and implantation of parathyroid tissue at previous surgery
for benign conditions may mimic parathyroid adenocarcinoma.
The
presence of mitotic figures within a parathyroid adenoma,
(provided that they are not atypical) is not in itself as indicator of
malignancy.
Groups of large
atypical cells in parathyroid neoplasms,
particularly close to foci of hemorrhage, do not indicate malignancy
and are , paradoxically, more common in adenomas.
When a diagnosis
of parathyroid adenocarcinoma is established, the prognosis is
poor with an approximate 50% 10 year survival, with more patients dying
from severe hypercalcemia than the physical effects of metastatic
disease.
Multiglandular parathyroid carcinoma: a case report and brief review. South
Med J. 2007 Aug;100(8):841-4.
A 53-year-old man
with no past medical history was admitted with complaints of hematuria,
flank and abdominal pain of one week duration. He also complained of
an enlarging new neck mass one month before presentation. The
laboratory assessment showed a calcium level of 17.3 mg/dL (normal
8.5-10.5 mg/dL), serum albumin 2.9 g/dL (normal 3.0-5.0 g/dL), serum
creatinine 3.4 mg/dL (normal 0.5-1.2 mg/dL). A neck ultrasound showed
a complicated left neck mass. He was hydrated for one week with
improvement in his labs, showing a decrease in serum calcium to 9.3
mg/dL and a serum creatinine of1.8 mg/dL. He underwent a total
thyroidectomy and parathyroidectomy. The pathology showed
multiglandular parathyroid carcinoma. It is important for the
physician and surgeon dealing with primary hyperparathyroidism to look
for parathyroid carcinoma. A better knowledge and understanding of
this condition would aid in early diagnosis and
possibly increase the survival rate.
Correlation between
clinical and histological findings in parathyroid tumors suspicious
for carcinoma.
Am Surg. 2006 May;72(5):419-26.
Carcinoma of the
parathyroid is a rare malignancy that can be cured surgically if the
proper diagnosis and treatment is given initially. Arriving to the
clinical suspicion of a malignancy preoperatively is by far the most
important step for a good prognosis. Our goal is to review the
correlation between clinical and final histopathological findings that
can arouse the suspicion of such malignancy and their true predictive
value in the diagnosis. All patients that underwent surgical removal
of the parathyroid mass between March of 1992 and March of 2003 were
reviewed retrospectively at Providence Hospital and Medical Centers.
Among 168 patients who underwent parathyroid excision, 14 (8.3%) had
hyperplasia of the parathyroid, 121 (72%) had benign adenoma, 25
(14.8%) had other benign lesions, and 8 (4.7%) patients had primary
carcinoma of the parathyroid confirmed by pathology. Our mean serum
calcium level was 11.57 mg/dL, which was lower than the mean level (12
mg/dL) for benign hyperparathyroidism. The mean tumor size was 2.18
cm, smaller than the proposed for malignant criteria, and none of the
eight patients (0%) had any symptoms of hypercalcemia at the time of
diagnosis. Seven of eight patients (87.5%) had frank signs of invasion
together with other histological features, and two patients had
associated papillary carcinoma of the thyroid. Five patients from our
series did not meet clinical criteria for malignancy (tumor size > 3
cm, palpable mass, and serum calcium > 14 mg/dL), but had undisputable
histological findings (high mitotic pattern, fibrous trabeculae,
capsular invasion, vascular invasion, and nodular involvement). On the
other hand, 17 patients with benign histology had tumors greater than
3 cm, and an additional 18 had palpable masses on physical
examination. We believe that these patients need to be followed
closely. The patients with diagnosis of parathyroid carcinoma, their
kindred, and those with large adenomas may benefit from genetic
screening for HRTP2 gene mutations in search of early detection of
tumors suspicious for malignancy. This is based on the fact that we
did not find correlation between the clinical presentation and the
histological features in our patients with proven malignancy.
Parathyroid carcinoma: a case series.
Ann Acad Med Singapore. 2005 Aug;34(7):443-6.
INTRODUCTION: We
present 3 patients with parathyroid carcinoma and describe their
presentations, clinical profiles, and management. MATERIALS AND
METHODS: A case series review of medical records. RESULTS: Two women
and 1 man (age range, 32 to 57 years) had parathyroid cancer and
primary hyperparathyroidism (PHPT). One patient presented with
osteitis fibrosa, 1 with renal stone and a neck mass, and 1 with
recurrence of PHPT after excision of supposedly benign parathyroid
adenoma 4 years ago. All had severe hypercalcaemia and elevated
parathyroid hormone levels that ranged from 4 to 43 times above the
normal range. Exploration of the neck clearly identified 1 parathyroid
tumour with local invasion; 2 other specimens showed capsular and
vascular invasion on frozen section and final histology. All 3
patients underwent parathyroidectomy and ipsilateral hemithyroidectomy.
Parathyroid size ranged from 1.3 to 4 cm and no lymph node metastasis
was identified. No patient had tumour recurrence after a follow-up
period of 1 year. CONCLUSION: Parathyroid carcinoma is a rare
endocrine malignancy. Suspicious features include marked
hypercalcaemia, neck mass, and local recurrence. Parathyroidectomy
with ipsilateral hemithyroidectomy and nodal clearance gives the best
chance of reducing local tumour recurrence.
Parathyroid carcinoma: a 22-year experience.
Head Neck. 2004 Aug;26(8): 716-26.
PURPOSE:
Because parathyroid carcinoma is rare, clear consensus is not
available regarding the optimal management of patients with this
condition. Treatment strategies generally derive from clinical and
anecdotal experiences. We report our experience with this entity.
METHODS: We included all patients with parathyroid carcinoma seen at
The University of Texas M. D. Anderson Cancer Center since January 1,
1980. The medical records and pathology specimens were reviewed and
verified in all cases. RESULTS: Since 1980, 27 patients (16 men and 11
women) registered at M. D. Anderson Cancer Center with parathyroid
carcinoma and a minimum follow-up of 2 years. The age at initial
diagnosis (mean +/- SD) was 46.7 +/- 15.3 years. All patients were
seen with hypercalcemia (mean calcium, 13.4 +/- 1.5 mg/dL). Eighteen
patients had locally invasive disease, eight had localized disease,
and one had distant metastasis. Parathyroid cancer was treated with
complete surgical excision with curative intent in 18 patients. In the
other nine patients, who had clinical and/or radiographic evidence of
soft tissue extension, the tumor was treated by comprehensive "en
bloc" soft tissue resection. Of six patients who received adjuvant
radiotherapy after initial surgery, only one had a local relapse. In
contrast, of 20 patients who did not receive adjuvant radiotherapy, 10
had a local relapse, excluding the one patient who had distant
metastases. The 5-year survival was 85%, and the 10-year survival was
77%. Five patients died of parathyroid carcinoma; all deaths were
hypercalcemia related. CONCLUSIONS: Parathyroid carcinoma can be an
indolent disease with morbidity and mortality related to hypercalcemia.
Adjuvant radiotherapy may improve local control and limit the
occurrence of local relapse. A comprehensive multidisciplinary
approach with surgery, radiation therapy, and medical treatment for
hypercalcemia is needed to optimize patient outcome.
Parathyroid
carcinoma. Therapeutic strategies derived from 20 years of experience.
Minerva Endocrinol. 2001 Mar;26(1):23-9.
BACKGROUND:
Carcinoma of the parathyroid is a rare endocrine tumour which can be
difficult to diagnose even for expert anatomopathologists. METHODS: A
retrospective study was carried out on all the cases of parathyroid
pathology observed between January 1980 and October 2000: parathyroid
carcinoma was diagnosed in 17 (3.59%) out of 478 patients treated for
hyperparathyroidism. We describe their clinical presentation,
treatment and results obtained. The patients included 9 women and 8
men, with a male/female ratio of 1.14 and a mean age at diagnosis of
56.9 years (range 30-83). All the patients, except one, the only
non-secreting case, presented hypercalcemia, and 10 patients presented
serum calcium levels above 3 mmol/L. The symptoms at onset included:
nephrolithiasis in 10 cases, osteoporosis in 4 (3 of which presented
uremic syndromes), gastrointestinal symptoms (gastritis) in 1 case, a
palpable cervical mass in 1 patient and recurrent nerve palsy in one
case suffering from familial IPT. A variety of imaging techniques were
used for the preoperative localisation: high-resolution
ultrasonography of the neck was carried out in all 17 patients and was
positive in 15 cases; scintigraphy (99mTcO4/201Tl or 99mO4/MIBI) was
carried out in 16 patients and was positive in 14; CAT was positive in
6 out of 17 patients. Three patients underwent the first operation in
another hospital and were referred to our department for resistance or
recidive. Initial surgery was restricted to simple parathyroidectomy
in 4 cases; parathyroidectomy was extended to the entire gland in 3
patients with uremic syndrome and to the ipsilateral thyroid lobe in 7
cases. Three patients underwent parathyroidectomy extended en bloc to
the adjacent structures, and recurrent lymph node dissection was also
performed in 2 of these patients. Lymph node involvement was never
demonstrated during the first operation. The dimensions of the tumour
varied from 1 to 6.7 cm; we found signs of invasion of the
neighbouring structures in 3 patients. RESULTS: Parathyroid carcinoma
was correctly diagnosed during the first operation in 14 cases (this
diagnosis was suspected in 10 cases following intraoperative frozen
session), whereas the first diagnosis was of benign disease in 3
patients. Blood levels of calcium, phosphorus and PTH returned to
normal after the first operation in 13 patients. These values
diminished, but did not return to normal in 2 cases. Two patients
relapsed, respectively 5 and 175 months after the first operation. A
total of 10 reoperations were performed in 4 patients with
persistent/recurrent symptoms (from a minimum of 1 to a maximum of 4).
Recidive presented characteristics of local invasiveness in one case
and the persistence was supported by micro-insemination of the
pre-thyroid compartment and muscles in another two cases. At
reoperation, lymph node metastasis was associated with local recidive
only in one case. Two patients underwent radiotherapy after surgery
and one received chemotherapy. At the last check-up (October 2000), 14
patients were alive and disease-free (82.25%). Two presented slight
persistent hypercalcemia (with values ranging between 2.65 and 2.80
mmol/L), but without any macroscopic localisation of disease (11.76%).
Only 1 patient died (5.88%) (one year after the first operation and 7
months after the last one). Death was caused by uncontrollable
hypercalcemia supported by widespread metastasis to the bones and
lungs. The 5 and 10-year survival rates were calculated as 94.12%.
CONCLUSIONS: In conclusion, high blood levels of calcium and PTH, a
palpable mass at the neck, with recurrent nerve paralysis, aspects of
local invasiveness should alert the surgeon and guide him towards
surgery that includes resection of the parathyroid en bloc with the
adjacent structures, although there is no proof that a more extensive
surgery is correlated with a more favourable prognosis. Being the
majority of recidive functional, monitoring serum calcium and PTH
levels offers a useful market which precedes their macroscopic
demonstration.
Primary hyperparathyroidism due to parathyroid carcinoma.
Arch Med Res. 1997
Summer;28(2):303-6.
Most cases of
primary hyperparathyroidism are due to either a parathyroid adenoma or
to parathyroid hyperplasia. Parathyroid carcinoma is a very rare cause
of hyperparathyroidism. Although the diagnosis of parathyroid
carcinoma is usually established based on pathological criteria of
vascular and capsular invasion, some clinical and biochemical features
differentiate it from benign forms of hyperparathyroidism. We report
the case of a middle-aged woman with a long standing history of
nephrolithiasis, who presented with a palpable neck mass, weight loss,
severe hypercalcemia and hypophosphatemia, as well as very high serum
levels of intact parathyroid hormone. Surgical neck exploration
revealed a large tumor that invaded trachea, esophagus, reccurrent
laryngeal nerve, right apical pleura and right carotid artery.
Pathological examination confirmed the invasive nature of the tumor.
Along with the case report, we review the literature and discuss the
diagnostic and therapeutic options of this rare condition.
Parathyroid carcinoma: clinical and pathologic features in 43
patients.
Medicine (Baltimore).1992 Jul;71(4):197-205.
Parathyroid
carcinoma accounts for 0.5 to 5% of all cases of hyperparathyroidism.
We reviewed the clinical, surgical, and pathologic features observed
in all patients with parathyroid carcinoma evaluated at the Mayo
Clinic from 1920 through 1991. Forty-three patients (22 women, 21 men;
mean age, 54 yrs, range 29-72) were identified, including 2 with
familial hyperparathyroidism. Information on initial presentation was
available in 40 patients: 15 (38%) presented with polydipsia or
polyuria, 11 (27%) with myalgias or arthralgias, 7 (17%) with weight
loss, and 4 (10%) with nephrolithiasis; 3 patients (7%) were
asymptomatic at presentation. Of 31 patients in whom the initial neck
examination was recorded, 14 (45%) had a palpable neck mass. The mean
serum calcium and serum phosphorus levels were 14.6 mg/dl and 2.3
mg/dl, respectively. Parathyroid hormone levels were elevated in 21 of
21 patients (mean elevation, 10.2 times upper limit of normal).
Complications included nephrolithiasis in 14 of 25 patients (56%),
bone disease in 20 of 22 patients (91%) and both in 8 of 15 patients
(53%). All patients underwent primary surgical resection of
parathyroid carcinoma. Twenty-six of 43 patients (60%) required a
second operation with 18 patients requiring multiple re-explorations.
At the second operation, residual tumor was found in the neck (68%),
mediastinum (16%), or both (12%). Six patients received radiation
therapy to the neck (5 patients) or bones (1 patient) for recurrent or
metastatic disease. Of these, 1 patient appeared cured of parathyroid
carcinoma by radiation therapy 11 years after documented tumor
invasion of his trachea. Repeated excision of tumor recurrences was an
effective means of controlling hypercalcemia in these patients.
