Monday 7 May 2007
Wikimedia: Oxyphil parathyroid adenoma
JRC:2676 : Parathyroid adenoma (58 y/o female).
JRC:9382 : Parathyroid adenoma (vs hyperplasia).
JRC:9385 : Parathyroid adenoma (vs hyperplasia).
JRC:9386 : Parathyroid adenoma (with fibrosis).
JRC:9387 : Parathyroid adenoma.
JRC:9390 : Parathyroid adenoma.
JRC:9391 : Parathyroid adenoma.
JRC:14578 : Parathyroid adenoma.
JRC:15047 : Parathyroid adenoma.
Definition: A parathyroid adenoma is a benign tumor of the parathyroid gland. It can cause hyperparathyroidism.
Parathyroid adenomas are benign neoplasms composed of chief cells, oncocytes or transitional oncocytes with frequent admixtures of these cell types.
Although most adenomas involve a single gland, occasional cases of double adenomas have been reported.
Double adenomas appear to have a nonuniform anatomic distribution with a predilection for the superior parathyroid glands, which are remnants of the fourth branchial pouch.
The average weight of adenomas in patients without significant bone disease is 1 g with many < 0.5 g, whereas tumors in patients with significant bone disease tend to be larger.
The term ‘microadenoma’ refers to tumors weighing < 0.1 g.
Foci of cystic change tend to occur in large adenomas and are relatively common in the tumors associated with the hyperparathyroidism-jaw tumor syndrome (HPT-JT syndrome).
Microscopically, most adenomas are composed of chief cells. Although microadenomas are nonencapsulated, larger tumors are usually surrounded by a fibrous capsule. A rim of normocellular parathyroid tissue is often present at the periphery of adenomas, although this feature may not be apparent in large tumors.
The component cells may be arranged in cords, nests, sheets and follicles and frequently have a palisaded arrangement around blood vessels.
The nuclei are round and densely stained and are typically larger than those present in the adjacent non-neoplastic parathyroid tissue.
Scattered hyperchromatic and pleomorphic nuclei exhibiting so-called ‘endocrine atypia’ are relatively common, as are multinucleated tumor cells.
Mitotic activity may be present in up to 70% of adenomas and the proliferative fraction, as assessed with Ki-67, is generally < 4%.
The tumor cells are positive for cytokeratins, PTH and chromogranin A, whereas stains for thyroglobulin and thyroid transcription factor-1 are negative.
Some parathyroid adenomas may have a prominent follicular architecture. The follicles contain a colloid-like material and may be distinguished from normal and neoplastic thyroid tissue by the presence of birefringent calcium oxalate crystals that may be present in the latter.
This approach is particularly useful during frozen examination.
Adenoma variants include:
oxyphil parathyroid adenoma / oncocytic adenoma
parathyroid clear cell adenoma
parathyroid adenoma with spindle cell features
parathyroid adenoma with papillary architecture
parathyroid lipoadenoma (parathyroid hamartoma )
oxyphil parathyroid adenoma (oxyphil cell adenomas of parathyroid glands)
Adenomas represent clonal proliferations and are similar in this regard to a significant proportion of primary and secondary parathyroid hyperplasias.
One of the molecular abnormalities described in these tumors involves the cyclin D1 (CCND1/PRAD1) oncogene on 11q13. Overexpression of this oncogene results from pericentric inversion of chromosome 11p, with placement of the CCND1 gene under the control of tissue-specific enhancer elements of the PTH gene promoter sequences. Translocations of this type were initially reported in 5% of adenomas.
FISH analyses have reported translocations in up to 8% of cases. However, overexpression of cyclin D1 occurs in up to 40% of adenomas, suggesting mechanisms other than translocations for overexpression. Such mechanisms could include amplification, rearrangements with other enhancers or promoters or transcriptional activation.
Loss of one MEN1 allele has been observed in up to 40% of sporadic parathyroid adenomas, with an inactivating mutation of the second allele occurring in 50% of these tumors.
Abnormalities of the MEN1 gene have also been observed in small adenomas, suggesting that alterations of this gene represent an early event in parathyroid tumorigenesis.
Other genes including RET, the vitamin D receptor and the calcium-sensing receptor (CaSR) have also been studied for pathogeneic mutations in adenomas, but none has been found to date.
Comparative genomic hybridization studies have shown loss of 11q as the most frequent alteration in adenomas. In addition, losses of 1p, 6q, 9p, 11p, 13q and 15q and gains in 7, 16p and 19p occur commonly.
- 9p22-24 gain (43%)
- 9q34 gain (43%).
- Xq26 gain (43%)
- 4q21-28 gain (29%)
- 8p22-23 (29%)
- 16p gain (11%) (9589690)
- 19p gain (9%) (9589690)
- 11p loss (26%) (9589690)
- 11q loss (34%) (9589690)
- whole chromosome 11 loss (14%)
- 20q12-13 loss (14%)
- 1p loss (9589690)
- 1q loss (9589690)
- 6q loss (9589690)
- 9p loss (9589690)
- 9q loss (9589690)
- 13q loss (9589690)
- 15q loss (9589690)
gene rearrangement and overexpression of the PRAD1/cyclin D1 oncogene
11q13 LOH (24%)
Sammarelli G, Zannoni M, Bonomini S, Delsignore R, Rizzoli V, Sianesi M, Caramatti C. A translocation t(4; 13)(q21;q14) as single clonal chromosomal abnormality in a parathyroid adenoma. Tumori. 2007 Jan-Feb;93(1):97-9. PMID: 17455879
Garcia JL, Tardio JC, Gutierrez NC, Gonzalez MB, Polo JR, Hernandez JM, Menarguez J. Chromosomal imbalances identified by comparative genomic hybridization in sporadic parathyroid adenomas. Eur J Endocrinol. 2002 Feb;146(2):209-13. PMID: 11834430
Agarwal SK, Schrock E, Kester MB, Burns AL, Heffess CS, Ried T, Marx SJ. Comparative genomic hybridization analysis of human parathyroid tumors. Cancer Genet Cytogenet. 1998 Oct 1;106(1):30-6. PMID: 9772906
Palanisamy N, Imanishi Y, Rao PH, Tahara H, Chaganti RS, Arnold A. Novel chromosomal abnormalities identified by comparative genomic hybridization in parathyroid adenomas. J Clin Endocrinol Metab. 1998 May;83(5):1766-70. PMID: 9589690
Cryns VL, Yi SM, Tahara H, Gaz RD, Arnold A. Frequent loss of chromosome arm 1p DNA in parathyroid adenomas. Genes Chromosomes Cancer. 1995 May;13(1):9-17. PMID: 7541648