Atypical Parathyroid Adenoma Research Articles

Primary hyperparathyroidism due to atypical parathyroid adenoma presenting with peroneus brevis tendon rupture

Primary hyperparathyroidism due to atypical parathyroid adenoma presenting with peroneus brevis tendon rupture

Intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenoma

Distinction of parathyroid cancer from atypical parathyroid adenoma (APA) at operation is difficult. The aim of this study was to determine whether parathyroid cancer and APA have different operative findings and long-term outcomes. A retrospective review was undertaken of patients with suspicious or malignant parathyroid tumours treated between 1974 and 2005. Parathyroid cancer was defined as a lesion with vascular or tissue invasion, and APA as a neoplasm with broad fibrous bands, trabecular growth, mitosis and nuclear atypia. Twenty-seven patients with suspicious or malignant parathyroid tumours were identified. After histological review, parathyroid cancer was confirmed in 11 patients (group 1) and 16 tumours were classified as APA (group 2). The clinical presentation and operative findings of the two types of tumour were indistinguishable. At initial surgery, seven patients in group 1 underwent en bloc resection, and four had parathyroidectomy. Four of the seven patients who had en bloc resection had recurrences. No recurrences were observed in the other seven patients in group 1 at a median follow-up of 65 months. In group 2, eight patients had en bloc resection and eight had parathyroidectomy; no patient had recurrence at a median follow-up of 91 months. Operative findings cannot distinguish APA from parathyroid cancer reliably. Without evidence of macroscopic local invasion, the value of en bloc resection at initial surgery remains debatable.

Radiographic Appearance Of Primary Hyperparathyroidism With Atypical Parathyroid Adenoma

Classical radiological descriptions of primary hyperparathyroidism are infrequently seen with early diagnosis and management in recent times. A patient with brown tumor in primary hyperparathyroidism secondary to an atypical parathyroid adenoma is presented.

Myxoid lipoadenoma of parathyroid gland: a case report and literature review

Myxoid lipoadenoma of the parathyroid gland is a rare variant of parathyroid adenoma. We present the case of a 40-year-old man with asymptomatic hypercalcemia who underwent surgical removal of a parathyroid adenoma. Histologically, the tumor consisted of monomorphous round-to-oval chief cells arranged in several architectural patterns including solid sheet-like, trabecular, and follicular. The tumor stroma was prominently myxoid with interspersed mature adipose tissue. Immunohistochemistry confirmed expression of thyroid transcription factor and parathyroid hormone by all tumor cells and a low proliferation rate with a Ki-67 labeling index of at most 5%. Although the lesion exhibited characteristics that have been previously associated with "atypical parathyroid adenoma," such as dense fibrous bands within the tumor and a trabecular growth pattern, there was no further evidence, neither histologically nor clinically, for malignant behavior of the tumor.

Diagnosis of Parathyroid Tumors in Familial Isolated Hyperparathyroidism with HRPT2 Mutation: Implications for Cancer Surveillance

Mutations of the HRPT2 gene have recently been implicated in the development of parathyroid carcinoma. The objective of this study was early diagnosis of parathyroid tumor in a family with germline HRPT2 mutation. In a 40-yr-old male previously treated for parathyroid atypical adenoma, we screened the 17 translated HRPT2 exons and their exon-intron boundaries and found a germline frameshift mutation in exon 7 (685delAGAG) predicting a premature stop codon at nucleotides 767-769. Nine family members (age, 33.9 +/- 19.8 yr, mean +/- SD) also carry the mutation, but eight have had normal serum calcium. Biochemical and ultrasonographic evaluation uncovered a 27-yr-old hypercalcemic carrier niece with an atypical parathyroid adenoma, and a 43-yr-old normocalcemic carrier sister was found by ultrasonography to have an extrathyroidal nodule, which proved to be parathyroid carcinoma. The index case, 12 yr after surgery, was normocalcemic, but ultrasonography revealed an extrathyroidal nodule in the contralateral hemithyroid tissue that proved to be atypical adenoma. Our report confirms that germline mutations of HRPT2 gene may be associated with multiple parathyroid neoplasms. Our experience suggests that longitudinal surveillance by serum biochemistry alone may not be 100% sensitive, and addition of routine neck ultrasonography is a readily accepted adjunct that may facilitate earlier disease detection in some families.

Atypical Cystic Adenoma of The Parathyroid Gland: Case Report and Review of Literature

To describe the clinical course of a patient with atypical cystic parathyroid adenoma manifesting as hypercalcemic parathyroid crisis. We present a case report and review the relevant literature on parathyroid cysts and atypical cystic parathyroid adenomas. A 76-year-old woman was evaluated for weakness, weight loss, urinary incontinence, and memory disturbances. She had severe hypercalcemia (calcium level, 18.3 mg/dL) in conjunction with an elevated parathyroid hormone level of 1,472 pg/mL. She received aggressive hydration, pamidronate, and calcitonin. Ultrasonography revealed a large cystic structure (5.8 cm) at the lower pole of the left thyroid lobe. She underwent surgical exploration of the neck, total thyroidectomy for multinodular disease of the thyroid, and subtotal parathyroidectomy. Intraoperatively, 25 mL of fluid was aspirated from the cystic mass, and the parathyroid hormone level in the fluid was 7,400,000 pg/mL. The final pathologic diagnosis was an atypical cystic parathyroid adenoma. Parathyroid cysts are uncommon and should be considered in the differential diagnosis of a neck mass. Although most parathyroid cysts are nonfunctional, 10% to 15% of such cysts are functional and can rarely manifest as acute parathyroid crisis. Atypical cystic parathyroid adenomas are rare and have an unpredictable clinical course. They exhibit some features of carcinoma but lack the indisputable evidence of malignant disease, such as angioinvasion or metastatic involvement. Treatment options for parathyroid cysts include aspiration, injection of sclerosing agents, and surgical excision.

Brown tumor of the mandible as first manifestation of atypical parathyroid adenoma

1. Hoye RC, Herrold KM, Smith RR, et al: A clinicopathological study of epidermoid cancer. Cancer 15:741, 1962 2. Geowen GF, Desuto-Nagy G: The incidence of sites of distant metastasis in head and neck carcinoma. Surg Gynecol Obestet 116:603, 1963 3. Alavi S, Namazie A, Sercarz JA, et al: Distant lymphatic metastasis from head and neck cancer. Ann Otol Rhinol Laryngol 108:860, 1999 4. Mukherji SK, Armao D, Joshi VM: Cervical nodal metastases in squamous cell carcinoma of the head and neck. What to expect. Head Neck 23:995, 2001

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

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. HUM PATHOL 34:54-64. Copyright 2003, Elsevier Science (USA). All rights reserved.

Parathyroid cytology: avoiding diagnostic pitfalls.

Interpretation of parathyroid fine-needle aspirates (FNA) remains problematic not only because this type of specimen is rare but also because the pertinent literature is very limited. We systematically reviewed parathyroid FNAs in our files and sought to delineate additional diagnostic criteria. Review of all thyroid and parathyroid aspirates from January 1990 to June 1998 disclosed 12 parathyroid lesions. The final diagnoses included four parathyroid adenomas, one intrathyroidal hyperplastic parathyroid, one intrathyroidal parathyroid adenoma, one atypical parathyroid adenoma (all confirmed by histologic screening or immunocytochemistry), and five parathyroid cysts (all confirmed by immunoassay). Papanicolaou and Diff Quik-stained smears of the parathyroid FNAs were reviewed. The cytologic features were compared and contrasted with those of thyroid FNAs to establish criteria for differential diagnoses. The FNAs of the five parathyroid cysts yielded virtually acellular fluid with a characteristic water-clear appearance and markedly elevated levels of parathyroid hormone. The remaining seven aspirates consisted of moderately cellular smears that showed an admixture of architectural features. Common patterns included cohesive three-dimensional groups, disorganized sheets, papillary fragments, microfollicles, and a single case showing lymphoidlike smears. Although the cells were generally small and round to oval, all cases demonstrated mild to moderate anisokaryosis. The nuclei were hyperchromatic E with coarsely granular chromatin reminiscent of that of small lymphocytes. Occasional nucleoli were noted. Although the cytoplasm was usually pale blue and finely granular with ill-defined borders, two cases showed well-delineated cytoplasmic membranes. Less common findings included cytoplasmic granulation, vacuolization, and rare oxyphilic cells. Naked nuclei were noted in the background of all of the aspirates to varying degrees. Other background findings included the presence of colloidlike material, macrophages, and lymphocytes. One interesting finding that to date has not been reported is the presence of nuclear overlapping (100%) and nuclear molding (71%), which is an uncommon finding in thyroid aspirates. FNAs of the parathyroid can be easily confused with that of the thyroid, not only because of the clinical similarity between these two types of lesions but also because of the overlap in cytomorphologic features of the aspirated cells. Although no one single cytomorphologic feature is diagnostic, a combination of cytologic parameters noted earlier should raise the possibility of a parathyroid lesion. Aspirates of parathyroid cysts show acellular water-clear fluid with elevated parathyroid hormone measurements.

Familial isolated primary hyperparathyroidism with parathyroid carcinomas: clinical and molecular features.

Familial isolated primary hyperparathyroidism (FIHP) is a rare hereditary disorder. We present four patients from a single family with FIHP, and genetic analysis of their parathyroid adenomas and parathyroid carcinoma. DNA was extracted from tumours resected at surgery. Tumours were examined for loss of heterozygosity (LOH) with microsatellite polymorphic markers. The 27-year-old proband (Patient 1) died of parathyroid carcinoma with metastases to the lungs and chest wall. Sixteen years later, his 34-year-old sister (Patient 2) presented with a neck tumour and primary hyperparathyroidism. Family screening revealed parathyroid tumours in his 36-year-old sister (Patient 3) and 29-year-old cousin (Patient 4). Histological examination of resected tumours showed parathyroid carcinoma and adenoma in Patient 2, a parathyroid adenoma in Patient 3, and an atypical parathyroid adenoma in Patient 4. Autopsy of the proband ruled out multiple endocrine neoplasia (MEN) type 1, and the three patients who underwent parathyroidectomy did not exhibit any abnormalities in the pancreas or the pituitary gland. Analysis of tumour DNA from one parathyroid carcinoma (Patient 2), the atypical parathyroid adenoma (Patient 4), and two parathyroid adenomas (Patients 2 and 3) showed limited LOH on chromosomes 13q12.3-q32 in an adenoma of Patient 2 and 9p21-p22 and 13q12.3-q32 in an adenoma of Patient 3. These results suggest the possible contribution of tumour suppressor genes including the retinoblastoma gene and the hereditary breast cancer susceptibility gene (BRCA2) on 13q to parathyroid tumours in this family.

Atypical adenoma of the parathyroid gland. A case report.

Background: Atypical parathyroid adenoma is a borderline neoplasm defined by histological findings, while its cytological characteristics have not been described so far.Case: A 43-year-old man was diagnosed as primary hyperparathyroidism due to parathyroid tumor by medical check-up as a momentum. Although the extirpated tumor was welldemarcated by fibrous capsule, a few small tumor nests were observed in the capsule, which fulfilled the histological diagnostic criteria of atypical adenoma. Some of the tumor cells had giant and/or hyperchromatic nuclei, with intranuclear cytoplasmic inclusions in part, which may be used in favor of an estimation of adenoma rather than carcinoma. In addition, there were few mitotic figures in the tumor tissue and Ki-67 labeling index was as low as that in the conventional parathyroid adenomas.Conclusion: It is suggested that the present case is biologically akin to the conventional adenoma and that nuclear atypy and low proliferative activity are useful findings to estimate parathyroid neoplasms to be benign in the cytological specimens.

Diagnosis of parathyroid adenomas: efficacy of measuring parathormone levels in needle aspirates of cervical masses.

The purpose of this study was to assess the value of measuring parathormone levels in percutaneous needle aspirates of suspicious cervical lesions in patients with hyperparathyroidism to confirm whether the lesion represents abnormal parathyroid tissue. The study group consisted of 66 patients with hyperparathyroidism in whom 80 cervical lesions were aspirated and levels of parathormone in the aspirates were measured. CT guidance was used for two patients and sonographic guidance for the remainder. The lesions selected for aspiration were demonstrated on either sonography or CT and had either an unusual position (separate from the thyroid gland or were intrathyroidal) or configuration (irregular shape or atypical heterogeneous sonographic texture). In 15 patients, an indeterminate, posteriorly located intrathyroidal mass was detected and felt most likely to represent a thyroid nodule by sonographic criteria. These masses were aspirated to rule out atypical parathyroid adenomas. In patients who had been previously explored for hyperparathyroidism and presented with persistent or recurrent hypercalcemia, all indeterminate, cervical, potentially parathyroid masses were aspirated for parathormone determination. The level of parathormone in each aspirate was measured by using an immunoradiometric assay. Levels of parathormone were increased in the aspirates in 37 of the 45 patients in whom sonography showed classic lesions suggestive of parathyroid adenoma. This included the 25 patients who had previously undergone exploratory surgery. At surgery, all 37 had parathyroid adenomas in the indicated locations, for a specificity of 100%. In six patients, the results of the aspiration were false-negative. Parathyroid adenomas were suspected on sonograms and confirmed at surgery, but no parathormone was detected in the aspirate. Results of aspiration of indeterminate lesions were true-negative in two patients who had both characteristic and indeterminate lesions on sonography and in the 15 patients who had indeterminate lesions that were felt to be of thyroid origin. Aspirates contained no parathormone, and surgical findings confirmed the lesions were not of parathyroid origin. Our results show that increased levels of parathormone in percutaneous needle aspirates of cervical masses in patients with hyperparathyroidism confirm the mass is a parathyroid adenoma. Although absence or low levels of parathormone in the aspirates usually excludes a parathyroid adenoma, this is not absolute as sometimes the needle may miss the mass, rendering the parathormone value invalid (false-negative).

Deoxyribonucleic acid cytometry helps identify parathyroid carcinomas.

It may be difficult in some patients with parathyroid tumors to distinguish between parathyroid carcinoma and parathyroid adenoma on the basis of clinical and histopathological findings. Patients initially diagnosed as having a parathyroid adenoma have subsequently occasionally developed metastases, and thereby their tumor was proven to be a carcinoma. To determine whether the nuclear DNA content would correlate with the clinical course and pathology of parathyroid tumors DNA cytometry was performed on parathyroid carcinomas (9 patients), histologically atypical adenomas (10 patients), adenomas associated with severe hypercalcemia [serum calcium, greater than or equal to 13.0 mg/dL (greater than or equal to 3.24 mmol/L); 11 patients], typical benign adenomas (11 patients), and incidentally removed normal parathyroid glands (6 patients). Sections were cut from the original paraffin-embedded surgical specimens and stained for nuclear DNA using the azure A Feulgen reaction. Nuclear DNA stain content was measured using an integrating image cytometer, and the results were plotted as histograms. Adjusted optical density (AOD) values were measured (in arbitrary units) to estimate the DNA content of whole nuclei in the specimens. The mean nuclear DNA content in the parathyroid carcinomas [24.6 +/- 2.1 (+/- SE) AOD] was significantly greater than that in the three groups of parathyroid adenomas (P less than 0.005, by unpaired t test) and in the normal parathyroid glands (P less than 0.0005). The mean nuclear DNA content in the atypical adenomas (15.8 +/- 1.6 AOD), profoundly hypercalcemic adenomas (16.8 +/- 1.3 AOD), and typical adenomas (16.0 +/- 1.1. AOD) were similar, and all were significantly greater than that in the normal parathyroid glands (11.5 +/- 0.7 AOD, P less than 0.05). Five distinct DNA histogram patterns were present in the parathyroid specimens from these 47 patients. Four of the 9 parathyroid carcinomas had an aneuploid DNA pattern, an abnormal pattern not found in any of the other groups; 2 of these tumors were originally diagnosed as atypical parathyroid adenomas. Both patients developed recurrent disease, and 1 died from a hepatic metastasis. Therefore, DNA cytometry provides valuable information in differentiating some parathyroid carcinomas from adenomas and diagnosing certain parathyroid carcinomas before the appearance of grossly invasive or metastatic tumor.

CT evaluation of parathyroid adenomas: diagnostic criteria and pitfalls.

Sixty-three patients with biochemically proven primary hyperparathyroidism underwent CT of the neck and upper chest prior to surgery. All examinations were prospectively evaluated. Parathyroid adenomas were correctly identified on CT in 81% of patients. Thyroid adenomas, tortuous vessels, the esophagus, and atypical parathyroid adenomas may be potential sources of error in the diagnosis of parathyroid adenomas.

90. Diagnostic Imaging in Parathyroid Cancer and Atypical Parathyroid Adenoma

90. Diagnostic Imaging in Parathyroid Cancer and Atypical Parathyroid Adenoma

Parathyroid cytopathology

Cytologic criteria for diagnosing parathyroid adenomas and hyperplasia have not been elucidated. This report will present the cytomorphology of parathyroid tissue in the spectrum of normal, hyperplastic, and neoplastic states. We examined clinical needle aspirates from three patients with parathyroid lesions as well as 15 needle aspirations or touch preparations from surgical specimens. The series included three with hyperparathyroidism secondary to chronic renal failure, four with primary chief cell hyperplasia, nine with typical adenomas, and two with atypical adenomas. Normal parathyroid glands were also studied. Most parathyroid lesions could be distinguished from thyroid lesions by frequent thick fragments of cohesive cells with frayed edges and typical nuclear features. In general, the nuclei were small (6-8 mu) and round with regular coarse granular chromatin. Occasional larger nuclei (10-30 mu) with similar chromatin were observed in some cases. Oxyphil cells with abundant granular cytoplasm were present in some cases; one case with mostly oxyphil cells was difficult to differentiate from a thyroid neoplasm. Pseudocolloid was found in seven cases. Criteria for the differentiation between parathyroid hyperplasia and adenomas were not discovered. In addition, the cytology and differential diagnosis of atypical parathyroid adenomas are described and illustrated.