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This is a carcinoma that arises from the epithelial cells of the parathyroid gland. It is rare but an important cause of hypeparathyroidism which leads to hypercalcemia. Like parathyroid adenomas, it may be identified by elevated serum calcium levels. However, occasionally, a hypercalcemic crisis may occur with serum calcium reaching levels of 14 mg/dl, levels usually much higher than seen for benign parathyroid adenomas. The result of increased parathyroid hormone and serum calcium includes renal stones, diminished renal function, bone resorption (osteitis fibrosa cystica) and osteoporosis. These tumors are usually larger than adenomas and may present with a palpable mass lesion in the neck in 1/3 of cases.


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INCIDENCE 0.5-2% of cases of primary hyperparathyroidism
AGE RANGE-MEDIAN Mean 45 years
Ranges 28-72 years


Allelic Loss in Parathyroid Neoplasia Can Help Characterize Malignancy.

Hunt JL, Carty SE, Yim JH, Murphy J, Barnes L.

From the Department of *Pathology and daggerSurgery, University of Pittsburgh Medical Center, Pittsburgh, PA.

Am J Surg Pathol. 2005 Aug;29(8):1049-1055. Abstract quote  

Parathyroid carcinoma can be difficult to diagnose, and the final pathologic diagnosis relies on clinicopathologic correlation. Clinical features of malignancy include high preoperative calcium levels and an intraoperative impression that the gland is adherent to local structures.
Histologic features of malignancy include increased mitoses, vascular invasion, and broad bands of fibrosis.

This study used molecular genotyping to assess parathyroid neoplasia for loss of heterozygosity across a panel of known tumor suppressor genes that have been previously identified as being important in the pathogenesis of parathyroid diseases. Parathyroid adenomas, hyperplasia, and carcinomas were included in the study, and a fractional allelic loss was calculated for each lesion. Losses of 1q25, 7q13.3, 10q23, 13q14.3, and 11p15.5 were particularly prevalent. In addition, almost all adenomas and carcinomas had loss of the markers for 1p.

The benign parathyroid diseases (adenomas and hyperplasia) had low mean fractional allelic loss (11% and 15%, respectively). The parathyroid carcinomas, in contrast, showed high mean fractional allelic loss (63%). This difference in the mutational profile suggests that this type of assay may be useful as an adjunctive diagnostic test in cases of parathyroid neoplasia.



Ill-defined mass densely adherent to the surrounding soft tissues

Surgeon plays an important role in determining this extraglandular extension


Mean 3 cm
Mean 6.7 gms

Gray tan tumor with firm cut surface

Primary parathyroid tumors of the mediastinum: a clinicopathologic and immunohistochemical study of 17 cases.

Moran CA, Suster S.

Department of Pathology, M.D. Anderson Cancer Center, Houston, TX 77030, USA.

Am J Clin Pathol. 2005 Nov;124(5):749-54. Abstract quote  

We describe 17 cases (9 women, 8 men; aged 36 to 72 years) of primary parathyroid tumors occurring primarily in the anterior mediastinum. Clinically and radiologically, all patients had an anterior mediastinal tumor.

All patients had metabolic disturbances with calcium and phosphorus. Of 17 patients, 13 had clinical primary hyperparathyroidism, 1 had secondary hyperparathyroidism due to polycystic kidney disease, and 1 had a history of prostatic carcinoma and 1 of chronic obstructive pulmonary disease. In 1 patient, the tumor was found at autopsy. Grossly, the tumors varied in size from 2 to 7 cm in greatest dimension.

Histologically, 2 tumors showed features of parathyroid carcinoma, and 15 tumors showed more conventional features of parathyroid adenomas. Six tumors were predominantly oncocytic, 6 were composed predominantly of chief cells, and 3 had mixed cellular composition. Immunohistochemical studies for chromogranin, synaptophysin, low-molecular-weight keratin (CAM 5.2), and parathyroid hormone were performed in 10 cases (8 parathyroid adenomas and 2 parathyroid carcinomas). All the tumors examined showed variable positive reaction for those antibodies.

The cases highlight the importance of keeping primary parathyroid tumors in the differential diagnosis of anterior mediastinal tumors.



Characteristically, there are thick fibrous bands, mitotic activity, capsular invasion, and vascular invasion

Fibrous bands and mitotic figures present in 90% of cases

Cytologically, composed of predominately chief cells with trabecular, rosettes, or sheet-like growth pattern

Oncocytic Occasionally seen with oncocytic change within majority of cells
Oxyphil Parathyroid Carcinomas
A Clinicopathologic and Immunohistochemical Study of 10 Cases

Lori A. Erickson, M.D.; Long Jin, M.D.; Mauro Papotti, M.D.; Ricardo V. Lloyd, M.D., Ph.D.

From the Departments of Laboratory Medicine and Pathology (L.A.E., L.J., R.V.L.), Mayo Clinic, Rochester, Minnesota, U.S.A.; and the Department of Pathology (M.P.), University of Torino, Torino, Italy.

Am J Surg Pathol 2002;26:344-349 Abstract quote

Oxyphil parathyroid carcinomas are uncommon neoplasms, and the clinicopathologic features of these tumors are largely unknown.

We evaluated the clinicopathologic features of oxyphil parathyroid carcinomas and the expression of cytokeratin 14 (CK14), the high-affinity glucose transporter-4 (Glut-4), as well as the cell cycle proteins p27 and Ki67 and compared these with oxyphil parathyroid adenomas and chief cell parathyroid adenomas and carcinomas. Formalin-fixed, paraffin-embedded archival tissues from primary (n = 6) and recurrent (n = 4) oxyphil carcinomas were analyzed and compared with chief cell parathyroid carcinomas (n = 12), oxyphil parathyroid adenomas (n = 38), and chief cell parathyroid adenomas (n = 17) by immunohistochemistry for CK14, Glut-4, p27, and Ki67 using the avidin-biotin peroxidase system. Patients with primary oxyphil and chief cell carcinoma presented with high levels of serum calcium (n = 15.5 and 13.7 mg/dL, respectively). Approximately half the patients in each group died of disease. The Ki67 labeling index was higher (4.9 vs 1.9) and the p27 index lower (23 vs 66) in primary oxyphil carcinoma compared with primary oxyphil adenomas. CK14 was expressed in most oxyphil adenomas (35 of 38 cases) but not in oxyphil carcinomas (0 of 10 cases). Glut-4 was more commonly expressed in both groups of adenomas compared with carcinomas.

These results show that oxyphil parathyroid carcinomas are functional malignancies similar to chief cell carcinomas and are associated with hypercalcemia, recurrence, and death. Expression of CK14 is very different in oxyphil adenomas compared with carcinomas. Although distinction between parathyroid adenomas and carcinomas can only be made by histopathologic and clinical findings, these results suggest that immunostaining for CK14, p27, and Ki67 may provide additional information to help distinguish between difficult cases of parathyroid adenomas and carcinomas. These findings also indicate that the same histopathologic features should be used to diagnose oxyphil and chief cell parathyroid carcinomas.



Recurrence of tumor within 2 years of diagnosis is poor prognostic sign

Cause of death in 72% of cases related to parathyroid disease including hyperparathyroidism with severe hypercalcemia, extensive metastases, renal disease, and acute pancreatitis

Aneuploid tumors identified by flow cytometry may be associated with more aggressive behavior than diploid tumors


Analysis of Parathyroid Neoplasms by Interphase Fluorescence In Situ Hybridization.

Erickson LA, Jalal SM, Harwood A, Shearer B, Jin L, Lloyd RV.

Department of Laboratory Medicine and Pathology (*Anatomic Pathology and daggerCytogenetics), Mayo Clinic and Mayo Foundation, Rochester, MN.
Am J Surg Pathol. 2004 May;28(5):578-584. Abstract quote  

Recent studies have indicated that numerical chromosomal abnormalities, including changes in cyclin D1 and p53, may be involved in parathyroid tumorigenesis.

We analyzed a series of parathyroid neoplasms with DNA fluorescent probes to evaluate the diagnostic and prognostic utility of numerical abnormalities of chromosomes 1, 6, 9, 11, 13, 15, 17, and 22 and cyclin D1 and p53 gene loci. Interphase fluorescence in situ hybridization (FISH) analysis was performed on paraffin-embedded tissue sections from 15 parathyroid adenomas and 18 parathyroid carcinomas. Directly labeled fluorescent DNA probes for the centromere region of chromosomes 1, 6, 9, 11, 15, and 17, and locus-specific probes for chromosome 22 and chromosome 13 and for cyclin D1 and p53 gene loci were used for dual-probe hybridization. Sixty-seven percent (10 of 15) parathyroid adenomas and 78% (14 of 18) of parathyroid carcinomas showed chromosome gains. Seventy-three percent (11 of 15) of parathyroid adenomas and 33% (6 of 18) of parathyroid carcinomas showed chromosome losses. Normal parathyroid tissues used as controls showed no chromosomal abnormalities. Parathyroid hyperplasias averaged 1.8 gains and 0.2 losses per case.

Parathyroid adenomas averaged 2.8 gains and 0.8 losses per case, and parathyroid carcinomas averaged 3.6 gains and 0.6 losses per case. In summary, chromosome abnormalities, both gains and losses, are common in parathyroid adenomas and carcinomas. Parathyroid carcinomas tend to show gains of more chromosome than adenomas. Chromosome 11 was the most frequent chromosome loss identified in parathyroid adenomas and a frequent chromosomal gain in parathyroid carcinomas.

These results indicate that gain of chromosome 11 is associated with more aggressive biologic behavior in parathyroid neoplasms.

Parathyroid neoplasms: Clinical, histopathological, and tissue microarray-based molecular analysis.

Stojadinovic A, Hoos A, Nissan A, Dudas ME, Cordon-Cardo C, Shaha AR, Brennan MF, Singh B, Ghossein RA.

Departments of Surgery and Pathology and the Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, NY.


Hum Pathol 2003 Jan;34(1):54-64 Abstract quote

We studied 45 patients with typical and 8 with atypical parathyroid adenomas as well as 20 with parathyroid carcinomas. Clinical, pathological, and molecular analyses were conducted on all adenomas. Clinical data were analyzed for 20, histopathologic slides for 16, and tissue specimens for 8 patients with carcinoma. Molecular expression profiles were investigated by immunohistochemistry (IHC) for Ki-67, p53, mdm2, p21, Bcl-2, cyclin D1, and p27 on paraffin-embedded tissues arrayed on tissue microarrays. Trabecular growth and vascular, capsular, and soft-tissue invasion were characteristic of parathyroid carcinomas but not of typical adenomas. No adenomas recurred. Seventy-four percent of carcinomas recurred, most in the neck.

Seventy-nine percent of patients with such illness died of disease after an indolent, multiply recurrent course responsive to repeated resections; the 5-year survival rate was 50%. High Ki-67 proliferative index was seen in 2% of adenomas and 25% of carcinomas, whereas p27 expression was present in 80% of adenomas and 18% of carcinomas. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), was observed in 76%, 29%, and 0% of typical and atypical adenomas and carcinomas, respectively. The complexity of molecular phenotypes increased with tumor aggressiveness.

Parathyroid carcinoma is an aggressive disease with a propensity for multiple recurrences. It is characterized by capsular, vascular, and soft-tissue invasion. Recurrence portends poor outcome.

Molecular markers, Ki-67 and p27, may distinguish parathyroid carcinoma from adenoma. The molecular phenotype, p27(+)Bcl-2(+)Ki-67(-)mdm2(+), appears to be unique to nonmalignant parathyroid tumors, and multimarker phenotypes are more complex in carcinomas.

SURVIVAL 50% cured by en block resection

When recurrence or metatases occurs, usually heralded by hypercalcemia

Recurrence usually occurs within 3 years after initial surgery, average survival after this is 7-8 years

35% develop metastases:
Cervical lymph nodes 30%
Lung 40%
Liver 10%

TREATMENT En bloc resection at the time of surgery
Usually not radiosensitive

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Parathyroid glands

Parathyroid Adenoma

Parathyroid Hyperplasia

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Last Updated November 16, 2005

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