Functioning oxyphil cell adenomas of the parathyroid gland. A study of 15 cases

Parathyroid adenomas composed predominantly of chief cells are the most frequent cause of primary hyperparathyroidism. Until as recently as 1978, the rare oxyphil cell parathyroid adenoma was generally considered nonfunctioning. A retrospective review of 500 consecutive patients at the Massachusetts General Hospital with a diagnosis of hyperparathyroidism associated with parathyroid adenoma during the years 1979-1987 yielded 15 (3.0%) oxyphil cell adenomas. A total of 65 case reports of hyperparathyroidism associated with a diagnosis of oxyphil cell adenomas were reviewed, applying the same diagnostic criteria used in case selection for the present series. These criteria include: (a) at least 90% composition of the adenoma by oxyphil cells; (b) biopsy or excision of a second histologically normal parathyroid gland to help rule out hyperplasia; and (c) postoperative alleviation of hypercalcemia. More than 50% of the previously reported cases did not conform to these criteria. The findings in the present study further document the entity of hyperparathyroidism caused by oxyphil cell parathyroid adenomas and suggest criteria guidelines for this rare diagnosis.     

Clear cell variant of thyroid carcinoma

Three carcinomas composed of a variable proportion of clear cells, oxyphil cells, and cells with combined oxyphil and clear cell features are reported. Cytologically, these tumors were included in the category of oxyphil cell variant of follicular carcinoma. In regard to pattern, two were entirely follicular, and one had follicular and papillary areas. The biologic behavior of these tumors, however, was consistent with that of follicular carcinomas. The clear cell change could be the result of chronic TSH overstimulation. This may explain the variable histological patterns, nuclear features, and biologic behavior associated with these tumors. These tumors bear a striking histologic resemblance to metastatic renal cell carcinoma and clear cell neoplasms from other sites. Immunocytochemical stain for thyroglobulin proved to be a specific and sensitive method for identification of these tumors.     

Oxyphil cell adenoma as a cause of hyperparathyroidism

A 57 year old woman with primary hyperparathyroidism was found to have an oxyphil cell adenoma. With removal of the adenoma, the elevated serum calcium level returned to normal. This patient and others previously reported in the literature serve as examples to support the view that oxyphil cells are functional and can, on occasion, cause primary hyperparathyroidism.     

Oxyphil parathyroid carcinomas: a clinicopathologic and immunohistochemical study of 10 cases

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.     

Histopathological study of the parathyroid gland in renal hyperparathyroidism

From July 1973 to July 1984, 50 patients underwent parathyroidectomy because of secondary hyperparathyroidism due to chronic renal failure. One hundred fifty-eight excised parathyroid glands in 41 of these patients were submitted to the histopathological examinations in the relations to their clinical features which revealed the following findings. Inspite of secondary hyperparathyroidism, eleven of 41 patients showed four unevenly enlarged parathyroid glands with one or two glands weighing less than 100mg. The glands were divided into three adenomas, 101 diffusely and 54 nodulary hyperplastic glands. The nodular type hyperplasia, which had a greater proportion of clear chief cells, vacuolated chief cells, transitional oxyphil cells and oxyphil cells, was more hyperplastic than the diffuse type. The patients with the nodular type showed more advanced clinical features in the secondary hyperparathyroidism.     

The positive effect of adenoma weight and oxyphil cell content on preoperative localization with 99mTc-sestamibi scanning for primary hyperparathyroidism

BACKGROUND: Although the sensitivity of sestamibi scanning (MIBI) is high in patients with solitary parathyroid adenomas, negative sestamibi scan results are inevitable. The exact mechanism of visualization of abnormal and hyperfunctioning parathyroid tissue is not yet clear. The aims of this clinical study were (1) to evaluate positive and negative sestamibi scan results with regard to adenoma weight and oxyphil cell content and (2) to compare the effects of adenoma weight and oxyphil cell content on the results of sestamibi scanning. PATIENTS: The patients were divided in 2 groups according to their sestamibi scan results. Group 1 consisted of 27 patients with positive sestamibi scan results, and group 2 consisted of 20 patients with negative sestamibi scan results. Parathyroid adenoma weight and oxyphil cell content were determined in all patients. RESULTS: The weight and oxyphil cell content of the parathyroid adenomas in the patients of group 1 were significantly higher than those in the patients of group 2 (P = .001). An adenoma weight >600 mg and an oxyphil cell content >20% increased the rate of obtaining a positive sestamibi scan result 10- and 4-fold, respectively. CONCLUSIONS: Both adenoma weight and oxyphil cell content were found to significantly correlate with positive sestamibi scan results. In patients with high-weight adenomas, adenoma weight was the most significant factor in obtaining positive MIBI scan results, whereas in patients with low adenoma weights, high oxyphil cell content was the most significant factor in obtaining positive MIBI scan results.     

Oxyphil cells of parathyroid glands in chronic renal failure may not secrete parathyroid hormone

To evaluate the function of parathyroid oxyphil cell in chronic renal failure, we studied the histopathological findings of 148 parathyroid glands of 42 patients (29 males, 13 females) on maintenance hemodialysis. The individual and total weights of resected parathyroid specimens in each patient were recorded. Using the morphometrical analyzing system, we measured the oxyphil cell area and total area in each excised section taken through the maximum diameter, to estimate them in each patients. According to the fractional ratio (R:oxyphil cell area/total area), patients were divided into four groups: group I (R less than 1%), group II (1% less than or equal to 5%), group III (5% less than or equal to R less than 10%) and group IV (10% less than or equal to R). There were no differences in age, duration of hemodialysis and serum C-PTH level among the different groups. There was a positive correlation not only between total glandular weight and serum C-PTH level, but also between total glandular weight and total area, and also a positive correlation was found between serum C-PTH level and total area. No tendency was found between oxyphil cell area and serum C-PTH level. However, in 15 patients whose oxyphil cell area was more than 10 mm2, there was a negative correlation between the area and serum C-PTH level. Also, in 16 patients whose R was more than 5%, there was a negative correlation between the rate and serum C-PTH level. These results suggested that oxyphil cell in chronic renal failure might not secrete PTH.     

Predictors of an accurate preoperative sestamibi scan for single-gland parathyroid adenomas

OBJECTIVE: To investigate why some patients with single parathyroid adenomas have negative preoperative sestamibi scans. DESIGN: Retrospective review. SETTING: Tertiary care center. PATIENTS: Twenty-one patients with false-negative (FN) scans were compared with 22 patients with true-positive (TP) scans. All patients had single parathyroid adenomas. INTERVENTIONS: Neck exploration and removal of parathyroid adenomas. MAIN OUTCOME MEASURES: Age; sex; preoperative serum calcium and parathyroid hormone levels; gland weight; location; and pathologic features. RESULTS: There was no significant difference in age or preoperative serum calcium or parathyroid hormone levels. Gland weight was greater in the TP group compared with the FN group (mean +/- SD, 1336 +/- 1603 mg vs 475 +/- 365 mg; P = .04); 13 (62%) of the 21 glands in the FN group were located in the upper position, compared with 6 (27%) of the 22 glands in the TP group (P = .03). Ten of the 22 glands in the TP group consisted predominantly of oxyphil cells, compared with 2 of the 21 glands in the FN group (P = .02). A multivariate logistic regression model yielded the following factors that predicted an accurate scan: higher percentage of oxyphil cells (P = .03), heavier gland (P = .03), female sex (P = .04), and gland location in the lower position (P = .04). CONCLUSIONS: Smaller-volume parathyroid adenomas and those in the upper position are less likely to be localized with sestamibi scans. A TP scan correlates with oxyphil cell predominance, supporting a role for the mitochondrial-rich cell in sestamibi uptake and retention.     

Parathyroid pathology in hyperparathyroidism secondary to chronic renal failure

Weights and histopathological changes in parathyroid glands were evaluated in relation to clinical and biochemical parameters in 42 patients who underwent parathyroidectomy for hyperparathyroidism (HPT) secondary to chronic renal failure. There was a positive relation (r = 0.71, p less than 0.01) between duration of renal insufficiency and total parathyroid glandular weight. The glandular weight was also closely related to the serum levels of parathyroid hormone (r = 0.67, p less than 0.01). No correlation was found between total parathyroid glandular weight or histopathological findings and clinical symptoms, serum levels of calcium, phosphate, alkaline phosphatases, calcium X phosphorus product or radiological evidence of bone disease. The enlargement of the glands was mostly uniform in the individual patient and all patients showed multiple gland involvement. This indicates that when parathyroid surgery is performed in patients with uraemia and secondary HPT, a radical approach, i.e. total parathyroidectomy with autotransplantation or subtotal parathyroidectomy, should always be used. In smaller glands only diffuse hyperplasia of parenchymal cells was generally found; fat cells were present in near-normal amounts. With increasing glandular weight, fat cells were more sparse and nodularity was common. In general, the proportion of oxyphil cells increased parallel with the total glandular weight, suggesting that this cell type is sensitive to stimulation. As a group, patients undergoing conservative renal treatment had suffered longer with renal disease, had larger parathyroid glands with more nodularity, and had more oxyphil cells than those undergoing parathyroidectomy while on haemodialysis.     

Oxyphil tumors of the thyroid: follow-up of 42 surgical cases.

Histopathologic and clinical follow-up data on 42 patients observed 2-20 years after operations for oxyphil neoplasms of the thyroid are presented. In eight patients histologic signs of malignancy were found but only two patients showed a clinically malignant course with development of distant metastases. The results do not indicate that oxyphil thyroid neoplasms are especially prone to assume a malignant course with the mode of treatment applied. Our policy is to remove any differentiated epithelial thyroid neoplasm with at least lobectomy. Total thyroidectomy is reserved for cases with capsular penetration, blood vessel invasion and/or metastases.     

Intracellular lipid droplets in functioning transitional parathyroid oxyphil adenomas. A caveat.

Histochemical demonstration of intracellular lipid droplets on frozen section has been used to distinguish normal parathyroid tissue from that of adenoma and chief cell hyperplasia. Differentiation is based on the observation that the cells of adenoma and chief-cell hyperplasia largely lack intracellular lipid, which is present in the suppressed chief cells of normal glands in patients with adenoma. We present two functional transitional oxyphil adenomas that contained abundant intracellular lipid. Failure to recognize that transitional oxyphilic adenomas may contain focal accumulation of intracellular lipid droplets could lead to confusion in histologic interpretation.     

Oncocytoma of tongue in a child.

Oncocytoma, or oxyphil adenoma, is an uncommon benign tumor arising from the major salivary glands, and its occurrence from the minor salivary glands is rate. We present a case of oncocytoma of tongue occurring in a child.     

Oxyphilic clear cell carcinoma of the ovary. A report of nine cases

Nine clear cell carcinomas (CCC) of the ovary with a prominent component of cells with abundant eosinophilic cytoplasm are reported. The majority of these tumors--which we have designated "oxyphilic clear cell carcinomas"--were misinterpreted by the referring pathologists as tumors of other types. Each specimen, however, had one or more features establishing it as a clear cell carcinoma, including tubules and cysts lined by cuboidal, hobnail, or flattened cells; nests and sheets of cells with abundant clear cytoplasm containing glycogen; and an adjacent adenofibromatous component. Two tumors were bilateral. The ages of the patients (average, 55 years), their clinical presentation, and the gross appearance of the neoplasms were similar to those of clear cell carcinomas in general. The diagnosis of clear cell carcinoma should always be considered in the differential diagnosis of an ovarian tumor with oxyphil cells, particularly if the patient is postmenopausal. Thorough sampling should be undertaken in such cases to identify other, more typical foci of clear cell carcinoma in order to avoid misdiagnosis.     

Negative Imaging Studies for Primary Hyperparathyroidism Are Unavoidable: Correlation of Sestamibi and High-Resolution Ultrasound Scanning with Histological Analysis in 150 Patients

Background Preoperative localization studies with Tc^99m-sestamibi have become an integral step in the preoperative assessment of patients with primary hyperparathyroidism (PHPT). This enables scan-directed minimally invasive parathyroidectomy (MIP) to be the preferred treatment for PHPT in many units. This study aimed to identify factors that lead to negative imaging studies in patients with PHPT. Methods Over a 3-year period consecutive unselected patients with PHPT underwent Tc^99m-sestamibi scanning and high-resolution ultrasound (US) scanning by the same radiologist. When localization studies were concordant, patients underwent MIP. Those patients with negative imaging studies underwent bilateral neck exploration. Histology slides were independently reviewed and the proportion of chief cells and oxyphil cells within each adenoma was estimated. Results One hundred and fifty-eight patients underwent localization studies (38 men and120 women, aged 61.8 ± 15.2 years). Sestamibi scans were negative in 52 (32%) and positive in 106 (68%) patients. There was a higher incidence of hyperplasia in the group of patients with negative sestamibi scans (4 out of 52 vs. 4 out of 103, P < 0.05, χ² test). In patients with negative sestamibi scans the majority of adenomas were formed predominantly from chief cells (26 out of 36) while the majority of patients with adenomas composed predominantly of oxyphil cells had positive scans (21 out of 23) (P < 0.05, χ² test). The weight of parathyroid adenomas was higher when sestamibi scans were positive (median: 1,180 vs. 517 mg, P < 0.05, Student’s t-test). Conclusion Successful preoperative localization of parathyroid adenomas using Tc^99m-sestamibi scanning is influenced by the cytological predominance of individual tumors. Negative scans might therefore be unavoidable in a subgroup of patients.     

Microfluorometric measurements of cytoplasmic calcium in chief and oxyphil parathyroid cells of adenomatous and hyperplastic glands and of normal-sized glands associated with adenomas

The effects of extracellular calcium on the cytoplasmic Ca2+ concentration (Ca2+i) were studied by dual-wavelength microfluorometry in individual human parathyroid cells obtained from adenomatous glands and normal-sized glands associated with adenomas in hypercalcemic hyperparathyroidism (HPT), as well as from enlarged glands of patients with uremia with HPT. In comparison with the normal parathyroid tissue, chief cells of the adenomatous and hyperplastic glands showed significantly lower Ca2+, and also right-shifted responses of Ca2+i to increases in the extracellular calcium concentration within the 0.5 to 3.0 mmol/L range. This pathophysiologic disturbance apparently was independent of the cell size. Oxyphil cells of nodules from the hyperplastic glands had lower Ca2+i and responded less to increments in extracellular Ca2+ than the chief cells from the surrounding parts of the same glands. Also the chief cells from the normal-sized glands associated with single adenomas exhibited a disturbance of the regulation of Ca2+i, which was less pronounced than that in the cells of the adenomas. These findings support the presence of relative calcium insensitivity of Ca2+i in chief and oxyphil parathyroid cells from adenomatous and hyperplastic glands. This derangement may also be found in all parathyroid glands of individuals with adenomatous HPT.     

Influence of 1,25-dihydroxycholecalciferol on parathyroid activity in patients with primary hyperparathyroidism.

Parathyroid morphology and blood chemistry were studied in five patients with primary hyperparathyroidism treated with 1,25-dihydroxycholecalciferol (1,25-DHCC) for 2 to 11 days before planned operation. Before the institution of treatment all patients were hypercalcemic, whereas the serum immunoreactive parathyroid hormone (iPTH) concentration either was elevated or normal. During the treatment the urinary phosphate excretion was significantly increased, whereas the calcium excretion and the serum concentrations of calcium and phosphate were unaffected or only slightly changed. Serum iPTH decreased during the first days of treatment, but returned then to increased levels close to the pretreatment ones. The treatment was tolerated well by the patients. Light and electron microscopy of the removed parathyroid glands disclosed one adenoma in each of the five patients, the other glands exhibiting either a slight hyperplasia or a normal appearance. Both the adenomatous and the non-adenomatous parathyroid tissue showed a predominance of dark chief cells and three of the adenomas exhibited a varying number of atrophic and oxyphil cells. The non-adenomatous glands were composed of atrophic and dark chief cells. Signs of low functional activity were ultrastructurally observed in the parathyroid parenchymal cells. It is suggested that 1,25-DHCC treatment of patients with primary hyperparathyroidism inhibits parathyroid hormone secretion.     

高磷通过局部环氧化酶2途径刺激尿毒症患者甲状旁腺细胞增生

目的 探讨尿毒症时高磷是否通过局部环氧化酶2( COX2)途径刺激人甲状旁腺细胞增生和功能亢进.方法 收集19例行甲状旁腺切除术的尿毒症患者甲状旁腺组织,通过免疫组化和免疫共染法观察COX2和增殖细胞核抗原(PCNA)的表达和分布.进行人甲状旁腺细胞原代培养,分别予高磷和正常磷干预,48 h后检测两组细胞上清液甲状旁腺激素(iPTH)水平;应用Western印迹和实时PCR方法观察细胞中COX2及PCNA的表达.结果 在获取的62枚尿毒症甲状旁腺结节中43枚为结节性增生,19枚为弥漫性增生,均观察到大量PCNA阳性细胞和COX2高表达.在弥漫性和结节性增生的甲状旁腺组织中,分别有80.60％及85.20％的COX2阳性细胞同时表达PCNA.在体外原代培养的尿毒症患者甲状旁腺细胞中,高磷能显著增加iPTH分泌,同时显著上调COX2及PCNA蛋白和基因表达.结论 高磷可能通过局部COX2表达和代谢途径参与尿毒症甲状旁腺细胞增生和功能亢进.     

Relation of biochemical, cytologic, and morphologic parameters to the result of gammagraphy with technetium 99m sestamibi in primary hyperparathyroidism

The aim of this study was to analyze the possible relation of biochemical, cytologic, and morphologic parameters to the results of parathyroid gammagraphy with Tc 99m sestamibi in primary hyperparathyroidism. We studied 46 consecutive patients with primary hyperparathyroidism who were undergoing surgery. All the patients were given a preoperative parathyroid gammagraphy with Tc 99m sestamibi and a complete preoperative biochemical study. During the surgical intervention we recorded the weight and size of the pathologic glands to calculate the volume of each. We also determined the percentage of the chief and oxyphil cells in the pathologic glands. Tc 99m sestamibi sensitivity is higher in adenomas (91%) than in hyperplasia (67%) or double adenomas (50%). No relation was found between biochemical or cytologic parameters and gammagraphic results. Weight and gland volume were significantly greater for adenomas than for hyperplasia (P < 0.0014 and P < 0.0004, respectively), and statistically significant differences in both of them were observed between the glands with positive and negative sestamibi.     

Solitary parathyroid microadenoma

In our experience with operations for primary hyperparathyroidism, a recurring problem centers on patients whose solitary adenomas are too small to be appreciated at the initial exploration. We have seen four patients with parathyroid microadenomas, which we define as lesions less than 6 mm in diameter in externally undeformed parathyroid glands. Two such patients were fortuitously cured at the initial exploration even though the operative findings were inconclusive. One, a 25-year-old man, underwent excision of an externally normal gland that contained a 3 by 2 by 2 mm microadenoma. He is eucalcemic since the operation. The other patient, a 70-year-old woman with hypercalcemia, responded to prednisone. She then underwent a neck exploration at which the diagnosis of sarcoidosis was confirmed by lymph node biopsy examination. A 4 by 2 by 2 mm parathyroid microadenoma was incidentally removed. The patient is normocalcemic receiving low-dose steroid treatment since the operation. In a third patient, a 34-year-old practical nurse, three explorations were needed to find a parathyroid gland, which was negative for adenoma on frozen-section microscopy. The solitary adenoma, 6 by 3 by 3 mm, was appreciated only on permanent sections. The majority of oxyphil microadenomas should be suspected to be nonfunctioning, as in a 59-year-old woman in whom the lesion coexisted with primary chief cell parathyroid hyperplasia. The hyperparathyroidism responded well to three and a half-gland resection. The 2 by 2 by 2 mm oxyphil adenoma was also removed. Solitary parathyroid adenomas can be subtle and small. Appraisal of parathyroid disease at the operating table is not always straightforward. As more patients with early hyperparathyroidism appear on routine calcium screening, we may expect to see increasing numbers of challenging solitary parathyroid microadenomas.     

腹腔镜保留肾单位手术治疗早期肾癌的临床研究（附32例报告）

目的探讨腹腔镜保留肾单位手术治疗早期肾癌的方法和疗效。方法采用腹腔镜技术，术中使用超声刀、电凝钩对32早期。肾癌患者行保留肾单位手术，患者年龄31～72岁，平均49±1．8岁。肿瘤平均直径1．5±4．5cm，平均（2．8±0．8）cm。25例行后腹腔镜保留肾单位手术，7例行经腹途径腹腔镜保留肾单位手术，影像学检查示32例肿瘤突出于肾脏表面，肾上极10例，肾下极13例，肾脏中部5例，近肾盂部位4例；偏背侧18例，腹侧14例。结果32例除1例转开放手术外，余31例为腹腔镜保留肾单位的肾肿瘤切除术。平均手术时间（105±15．4）min，平均出血量（120±21．6）ml，6例术中输血400ml。2例术后发生尿漏，予负压吸引15d后引流量小于20ml后拔出肾周引流管。术后住院时间平均7～17d，平均（9±2）d。术后病理报告：肾透明细胞癌28例，肾颗粒细胞癌3例，嗜酸性细胞癌1例。随访时间3-53个月，平均（21±4）个月，肿瘤无复发。结论腹腔镜保留肾单位术治疗早期肾癌安全、可行。