Different pathological findings in each of four parathyroid glands in a long-standing hemodialysis patient

A 51-year-old male patient with chronic renal failure, who had required dialysis for 22 years, presented with a cervical mass. Laboratory data were consistent with secondary hyperparathyroidism due to chronic renal failure. Cervical exploration was performed with excision of four parathyroid glands and autotransplantation of the normal gland into the forearm. The cervical tumor of the right inferior gland demonstrated parathyroid carcinoma histologically. Adenoma of the right superior gland and hyperplasia of the left superior gland were also recognized. The left inferior gland was normal. A few cases of parathyroid carcinoma in patients on maintenance hemodialysis have been previously reported. However, this is the first report in which all four parathyroid glands revealed different pathological findings: carcinoma, adenoma, hyperplasia and normal gland. Chronic stimulation of the parathyroid glands to release parathyroid hormone might have caused the variety of findings in the four parathyroid glands.     

Lectins in diagnosis of bladder carcinoma.

With the purpose of studying changes in the expression of glycoconjugate structures in nonmalignant and cancerous lesions of urothelium the lectins ConA, TKA, PNA, DBA, STA, LFA, UEA, MPA, RCA, LCA, GSA1, SBA, GSA2, WGA, PHA and Lot were tested in formalin-fixed, paraffin-embedded tissue sections of (1) cold biopsies from normal urothelium and bladder cancer of different grades (G1-G3) in humans, (2) normal transitional epithelium and N-butyl-N(4-hydroxybutyl)nitrosamine (BBN)-induced bladder cancer in animal experiments (Wistar rat), and (3) human transitional cancer cell line HT 1376. In human urothelium TKA and SBA were positive markers demonstrating positive staining reactions in all tumor grades without binding to normal epithelium. They stained also the human transitional carcinoma cell line HT 1376 (G3). In Wistar rats DBA, ConA, LCA, SBA, GSA2 and WGA had a specific affinity to BBN-induced carcinoma. Findings of positive lectin marker in transitional cell cancer may offer progress in diagnostics and therapy.     

Study of parathyroid transcription factor Gcm2 expression in parathyroid lesions

Glial cells missing 2 (Gcm2) is a master regulatory gene of parathyroid gland development, and it is exclusively expressed in the parathyroid gland. Diagnostic application of anti-Gcm2 antibody has not been reported yet. In this study, a total of 58 cases of parathyroid lesions including 40 adenomas, 2 atypical adenomas, 2 carcinomas, 9 hyperplastic lesions, 4 parathyroid cysts, and 1 case of recurrent hyperplasia of an autograft gland were stained with anti-Gcm2 antibody. Anti-Gcm2 was also applied to a variety of endocrine tumors, including thyroid tumors and nonendocrine tumors, and normal tissues from a variety of organs, including the parathyroid and thyroid glands. Gcm2 nuclear expression was seen in all the normal parathyroid glands, and cystic, hyperplastic, and neoplastic parathyroid lesions in a diffuse manner, whereas no Gcm2 expression was seen in any other normal tissues and tumors, including those of the thymus and thyroid gland. Anti-Gcm2 antibody is a highly sensitive and specific marker for parathyroid lesions. Although the immunohistochemistry stain for parathyroid hormone is a useful marker, its reaction tends to be variable in extent and intensity in parathyroid neoplasia, and it is often negative in parathyroid cysts, and Gcm2 would serve as a useful adjunct marker.     

Lectin-Binding Sites in Normal Human Testis/Lektinbindungsstellen normaler humaner Hoden

Nine fluorescein isothiocyanate (FITC)-labelled lectins have been used to investigate the distribution of glycoconjugates in unfixed frozen and Bouin-fixed sections of normal human testis. Interstitial cells and lamina propria of seminiferous tubuli were stained by PNA, HPA, RCA II, SBA, ConA, and WGA indicating an abundance of the following glycoconjugates: N-GlcNAc, N-GalNAc, Gal, and Man. The germinative cells were stained cytoplasmatically by ConA (Alpha-D-Man/-Glc). Sertoli cells showed the same pattern with ConA. Early spermatids fixed PNA and RCA II in the acrosomal region. Elongated spermatids fixed WGA on their acrosomes and fainty on the flagellae too indicating abundance of N-GlcNAc residues. The findings argue for differentiation-related modifications of lectin-binding sites on germinative cells and the usefulness of Bouin-fixed samples for lectin histochemistry.     

Sebaceous Carcinoma of the Salivary Gland in a Cat

Sebaceous carcinoma of the submandibular salivary gland is described in a cat; tumour cells were characterized histologically by moderate amounts of pale eosinophilic or vacuolated cytoplasm. Tumour cells were stained with antibody to cytokeratins (CKs 5, 6, 8, 17 and 19) and with lectins Con A and wheat germ agglutinin (WGA); this occurs in many other types of salivary gland tumour and is a feature of normal salivary gland acinar cells.     

The role of hyperplasia in multiple parathyroid adenomas

BACKGROUND: Parathyroid adenoma is the most common cause of primary hyperparathyroidism (pHPT). Adenomas usually involve only a single gland, and the remaining glands are normal or suppressed. Multiple parathyroid adenomas have been reported to occur in as high as 11% of patients with pHPT. The significant incidence of multiple adenomas with histologic similarities to hyperplasia has raised the possibility that adenoma is a continuation of the hyperplasia state. To test this theory, we used molecular genetics to compare clonality and proliferative activity of parathyroid adenoma with its corresponding normal glandular tissue. Furthermore, we devised a scheme to definitively distinguish between the different parathyroid states on a molecular level, because histologic distinction is unreliable. METHODS: The study included three patients with a diagnosis of singular parathyroid adenoma and three with double parathyroid adenomas. Paraffin-embedded surgical specimens of both adenomas and normal glands were retrieved from each patient. Clonal analysis of the phosphoglycerolkinase (PGK) gene has suggested that parathyroid adenomas are monoclonal. Clonality of parathyroid adenomas and normal parathyroid glands was studied by polymerase chain reaction-based restriction fragment length polymorphic analysis for the PGK gene. Proliferative activity of the specimens was also analyzed using the immunohistochemical markers PCNA and Ki-67. RESULTS: All adenomas were monoclonal and all normal parathyroid glands were polyclonal for the PGK gene in both the single and double adenoma specimens. All adenomas stained positive for proliferative activity. In the three patients with singular adenoma, proliferative activity was not detected in the normal parathyroid tissue. However, in the double adenoma group, two of the three patients showed hyperproliferative activity in the normal glands. CONCLUSION: Proliferative activity consistent with hyperplasia was present in some normal glands of multiple adenoma patients. Our observation supports the theory that multiple adenomas may be a continuation of the hyperplasia state.     

Lectin affinity of the seminiferous epithelium in healthy and cryptorchid post-pubertal boars

The present study describes the sugar content of the seminiferous epithelium, using lectin histochemistry, in healthy boars and in boars with unilateral and bilateral abdominal cryptorchidism. In healthy boars the apical cytoplasm of Sertoli cells exhibited abundant glucosyl (Con A and WGA lectins), galactosyl (HPA, DBA, SBA and PNA lectins), and fucosyl (AAA lectin) residues. Spermatogonia and spermatocytes contained abundant glucosyl (Con A and WGA lectins) and fucosyl (AAA lectin) residues. In spermatids, galactosyl (SBA and PNA lectins) and glucosyl (Con A and WGA lectins) residues increased progressively throughout spermiogenesis, and fucosyl (AAA lectin) residues decreased. As compared with healthy boars, the scrotal testis of unilateral cryptorchid boars showed decreased amounts of fucosyl (AAA lectin) and galactosyl (HPA and DBA lectins) residues on the Sertoli cell apical cytoplasm; spermatocytes exhibited higher content of glucosyl (Con A lectin) residues and spermatids showed altered nature of glucosyl (Con A and WGA lectins) and galactosyl (SBA and PNA lectins) complexes. In abdominal testes of unilateral and bilateral cryptorchid boars, immature Sertoli cells and spermatogonia showed decreased fucosyl (AAA lectin), and increased glucosyl (Con A and WGA lectins) and galactosyl (SBA and PNA lectins) contents. These results suggest that the seminiferous epithelium of healthy boars has polarized activity with the apical compartment implicated in germ cell-Sertoli cell adhesion and interaction, in transport of ions, substrates and fluids, and in acrosomal differentiation. In scrotal testes, unilateral abdominal cryptorchidism could lead to defective germ cell-Sertoli cell adhesion, impaired acrosomal differentiation and increased ionic transport in the apical compartment of the seminiferous epithelium. Unilateral and bilateral cryptorchidism could induce increased ionic transport and membrane permeability in the seminiferous epithelium of abdominal testes.     

Surgical strategy in nonfamilial primary parathyroid hyperplasia: long-term follow-up of thirty-nine cases

The extent and result of surgery in 39 cases of nonfamilial primary parathyroid hyperplasia followed from 2 to 20 years are reported. Thirteen patients had been subjected to subtotal parathyroidectomy leaving no gland intact, while 26 had undergone less extensive surgery leaving at least one grossly normal or near-normal gland intact without biopsy. In the former group two patients (15%) developed permanent hypoparathyroidism requiring vitamin D treatment. In the latter group there were two patients (8%) with persistent hypercalcemia, which might have been avoided with a subtotal parathyroidectomy. Judging from these results, we believe that an individualized surgical approach is justifiable in nonfamilial primary parathyroid hyperplasia. Subtotal parathyroidectomy, leaving no gland intact, is advocated as the method of choice only when all four glands are enlarged. If one or more glands are grossly normal or near normal, factors such as degree of hypercalcemia, symptoms, age, general condition, and life expectancy should be taken into consideration when the extent of the operation is decided. A more conservative operation leaving at least one grossly normal gland intact without biopsy appears to be sufficient for cure in most of these cases and minimizes the risk for development of permanent hypoparathyroidism.     

Familial form of primary cancer of the parathyroid glands. A disease entity or incidental association?]

Three cases of parathyroid neoplasms in familial hyperparathyroidism are reported. There were not associated with other endocrine glands or parathyroid glands lesions. Parathyroid gland carcinoma was diagnosed in 2 cases. Review of 7 cases of familial parathyroid carcinoma, diagnosed in 5 different families and issued from the literature, indicates that it can be associated to multiple endocrine neoplasia or other parathyroid lesions. The familial parathyroid carcinoma entity needs further studies before to be fully recognised.     

The in vitro effect of calcitriol on parathyroid cell proliferation and apoptosis

Calcitriol treatment is used to reduce parathyroid hormone levels in azotemic patients with secondary hyperparathyroidism (HPT). Whether long-term calcitriol administration reduces parathyroid gland size in patients with severe secondary hyperparathyroidism is not clear. The aim of the study was to evaluate in vitro the effect of calcitriol on parathyroid cell proliferation and apoptosis in normal parathyroid glands and in adenomatous and hyperplastic human parathyroid glands. Freshly harvested parathyroid glands from normal dogs and hyperplastic and adenomatous glands from patients with secondary (2 degrees) and primary (1 degree) HPT undergoing parathyroidectomy were studied. Flow cytometry was used to quantify the cell cycle and apoptosis of parathyroid cells. Apoptosis was also evaluated by DNA electrophoresis and light and electron microscopy. In normal dog parathyroid glands, culture with calcitriol (10(-10) to 10(-7) M) for 24 h produced a dose-dependent inhibitory effect on the progression of cells into the cell cycle and into apoptosis. When glands from patients with 2 degrees HPT were cultured for 24 h, only high calcitriol concentrations (10(-7) M) inhibited the progression through the cell cycle and the induction of apoptosis. In parathyroid adenomas (1 degrees HPT), even a high concentration of calcitriol (10(-7) M) had no significant effect on the cell cycle or apoptosis. The present study shows that in vitro, calcitriol inhibits in a dose-dependent manner in normal parathyroid glands both parathyroid cell proliferation and apoptosis. However, in secondary hyperplasia, only high concentrations of calcitriol inhibited cell proliferation and apoptosis. In 1 degree HPT, even high concentrations of calcitriol had no effect. Because calcitriol simultaneously inhibits both cell proliferation and apoptosis, a reduction in the parathyroid gland mass may not occur as a direct effect of calcitriol treatment.     

Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein

The histologic spectrum of proliferative parathyroid lesions (hyperplasia, adenoma, and carcinoma) often overlap, and differentiation between these lesions may at times be difficult. p27kip1 (p27) is a cyclin-dependent kinase inhibitor that helps regulate the transition from the G1 to the S phase of the cell cycle. Significantly higher levels of p27 expression have been detected in some normal tissues than in their neoplastic counterparts. The authors analyzed a series of parathyroid lesions to determine if expression of this cell cycle protein may be useful in distinguishing between parathyroid hyperplasia, adenomas, and carcinomas. Formalin-fixed paraffin-embedded tissues from randomly selected patients (22 histologically normal parathyroid glands, 33 cases of hyperplasia, 43 adenomas, and 17 carcinomas) were analyzed for expression of p27 by immunostaining. All cases were also immunostained for Ki67 with antibody MIB-1. The distribution of immunoreactivity was analyzed by quantifying the percentage of positive nuclei that was expressed as the labeling index (LI). In situ hybridization (ISH) for p27 mRNA was done using a cRNA probe with 30 of these cases. Normal parathyroid glands had the highest p27 LI (89.6 +/- 1.4), followed by hyperplasia (69.6 +/- 7.5), adenomas (56.8 +/- 3.4), and carcinomas (13.9 +/- 2.6). ISH showed no differences in p27 mRNA, indicating that the expression of the p27 gene was controlled at a posttranslational level in parathyroid tissues. Ki67 expression was significantly higher in carcinomas (LI = 8.4 +/- 1.9) than in adenomas (LI = 2.7 +/- 0.2) and hyperplasia (LI = 3.3 +/- 0.4). These results suggest that both p27 and Ki67 may be helpful in the diagnosis of histologically difficult parathyroid lesions.     

The problems encountered in the surgical management of primary hyperparathyroidism.

The problems encountered in the diagnosis and treatment of primary hyperparathyroidism were studied in 69 cases. The accuracy of imaging for hyperplasia was less than that for adenoma or carcinoma and the major causes for multiple operations were a failure to locate the four glands and mediastinal adenoma. The intravenous administration of high doses of calcitonin could reduce the serum calcium level of patients in hypercalcemic crisis. Carcinoma required ipsilateral modified radical neck dissection because of lymph node metastases, and non-medullary thyroid carcinoma was often associated with primary hyperparathyroidism. We found removal of the parathyroid adenoma and biopsy or extirpation of only one macroscopically normal gland to be a fully satisfactory procedure after bilateral neck exploration and attempting to identify at least four glands.     

The problems encountered in the surgical management of primary hyperparathyroidism

The problems encountered in the diagnosis and treatment of primary hyperparathyroidism were studied in 69 cases. The accuracy of imaging for hyperplasia was less than that for adenoma or carcinoma and the major causes for multiple operations were a failure to locate the four glands and mediastinal adenoma. The intravenous administration of high doses of calcitonin could reduce the serum calcium level of patients in hypercalcemic crisis. Carcinoma required ipsilateral modified radical neck dissection because of lymph node metastases, and non-medullary thyroid carcinoma was often associated with primary hyperparathyroidism. We found removal of the parathyroid adenoma and biopsy or extirpation of only one macroscopically normal gland to be a fully satisfactory procedure after bilateral neck exploration and attempting to identify at least four glands.     

Two cases of parathyroid carcinoma in patients on long-term hemodialysis

Two cases of parathyroid carcinoma, in a 46-year-old male on maintenance hemodialysis for 135 months and a 55-year-old female on maintenance hemodialysis for 64 months were reported. In both cases, the parathyroid carcinoma showed local invasion and the other glands were hyperplasia and/or adenoma, which would support the concept of malignant transformation occurring in parathyroid hyperplasia. The concurrence of parathyroid carcinoma with hyperplasia and/or adenoma is a pertinent feature in patients on maintenance dialysis, although it is rare in primary parathyroid carcinoma.     

Expression of TRAIL and Fas in Primary Hyperparathyroidism

Aim: Differentiating between parathyroid lesions is still difficult and ambiguous. In cases of primary hyperparathyroidism, appropriate and prompt diagnosis is of great importance for effective treatment and follow-up. A great amount of mechanisms contribute to the pathogenesis of primary hyperparathyroidism, such as disturbance in balance between pro- and anti-apoptotic factors. Therefore, we examined whether immunohistochemical expression of apoptotic factors, TNF-related apoptosis-inducing ligand (TRAIL) and Fas, could have clinical utility as a marker of proliferative lesions of parathyroid gland. Materials and methods: Parathyroid specimens of 58 consecutive patients who had undertaken surgery due to primary hyperparathyroidism were incubated with purified mouse monoclonal antihuman antibodies: anti-TRAIL and anti-Fas. Staining was considered positive when at least 5% of the cells showed immunoreactivity. Results: The percentage of cells which were positively stained for TRAIL in parathyroid hyperplasia was 9.65%, in parathyroid adenoma 8.31%, and in normal controls 2.24%. Immunoreactivity for TRAIL was detected in 91.89% of parathyroid hyperplasias, 85.71% of parathyroid adenomas, and none in healthy glands. The percentage of cells with a positive reaction to Fas in parathyroid hyperplasia was 8.92%, in parathyroid adenoma 8.09%, and in normal tissue 1.9%. The expression of Fas was found in 94.59% of parathyroid hyperplasias, 90.48% of parathyroid adenomas, and none in healthy glands. Conclusions: In our study, hyperplasias demonstrated the highest expression of TRAIL and Fas, whereas in adenomas it was increased compared to normal tissue, but lower than in hyperplasias. These factors could be an additive tool in the differential diagnosis of parathyroid lesions.     

Surgery for parathyroid adenoma and hyperplasia: Relationship of histology to outcome

Recent histopathologic evidence challenges the teaching that enlargement of a solitary parathyroid gland is invariably caused by an adenoma, whereas multiple gland enlargement results from hyperplasia. We have re-examined the parathyroid tissue obtained from 152 consecutive patients undergoing surgery for primary hyperparathyroidism and compared it with their clinical outcome. Our approach was to excise enlarged glands and biopsy the remainder. In 124 patients (82%) at least three glands were biopsied or removed. The ratio of adenoma to hyperplasia was reversed by our histologic re-examination; adenomas were found in only 27 patients (25 single, two double), whereas hyperplasia was found in 117 patients (one gland, 87 patients; two glands, 16 patients; three glands, five patients; four glands, nine patients). Normal tissue only was reported in eight patients. During a 2-year follow-up, five patients (3%) developed hypocalcemia and none developed recurrent hypercalcemia. Our results indicate that a full neck exploration with removal of all enlarged glands is more important than the histologic diagnosis in planning a successful surgical strategy for primary hyperparathyroidism.     

原位保留甲状旁腺血供及甲状旁腺自体移植术

目的 介绍甲状腺肿瘤手术中保护甲状旁腺血供及甲状旁腺自体移植的方法及疗效.方法 46例全甲状腺切除或近全切除手术中,血管化甲状旁腺保留24例,单纯自体甲状旁腺移植5例,1～2枚甲状旁腺血管化保留同时其余甲状旁腺Ⅰ期自体移植17例.结果 应用此法行全甲状腺切除或近全切除患者中,有2例原位血管化保留甲状旁腺及3例血管化保留+自体甲状旁腺移植患者术后48～72 h内出现一过性低血钙,予以补钙后3 d左右恢复正常.2例单纯甲状旁腺自体移植患者术后出现低血钙,服用钙尔奇D/罗盖全4周～8周后复查血钙维持在正常水平.术后出现永久性甲状旁腺功能低下的仅1例(2.2%).结论 血管化甲状旁腺保留及自体甲状旁腺移植可大大降低全甲状腺切除或近全切除手术导致甲状旁腺功能低下的发生率.     

Development and progression of secondary hyperparathyroidism in chronic kidney disease: lessons from molecular genetics

The identification of the calcium-sensing receptor (CaSR) and the clarification of its role as the major regulator of parathyroid gland function have important implications for understanding the pathogenesis and evolution of secondary hyperthyroidism in chronic kidney disease (CKD). Signaling through the CaSR has direct effects on three discrete components of parathyroid gland function, which include parathyroid hormone (PTH) secretion, PTH synthesis, and parathyroid gland hyperplasia. Disturbances in calcium and vitamin D metabolism that arise owing to CKD diminish the level of activation of the CaSR, leading to increases in PTH secretion, PTH synthesis, and parathyroid gland hyperplasia. Each represents a physiological adaptive response by the parathyroid glands to maintain plasma calcium homeostasis. Studies of genetically modified mice indicate that signal transduction via the CaSR is a key determinant of parathyroid cell proliferation and parathyroid gland hyperplasia. Because enlargement of the parathyroid glands has important implications for disease progression and disease severity, it is possible that clinical management strategies that maintain adequate calcium-dependent signaling through the CaSR will ultimately prove useful in diminishing parathyroid gland hyperplasia and in modifying disease progression.     

Parathyroid anatomy in hyperplasia.

Pathologically enlarged parathyroid glands offer the surgeon a vital medium for studying parathyroid anatomy. The advantages include gland magnification, rapid-section diagnosis to aid dissections, and postoperative clinical and laboratory responses to check for "missed" or supernumerary glands. In this series, each of 71 patients had at least four hyperplastic glands. Both mediastinal and intrathyroidal glands occurred in nine instances (13%), supernumerary glands in eight (11%), and ectopic neck glands in seven (10%). In total, anomalous parathyroid glands occurred in almost half (46%) of these patients with parathyroid hyperplasia.     

纳米炭负显影及甲状旁腺自体移植在甲状腺乳头状癌手术中的应用

目的探讨纳米炭混悬注射液负显影联合甲状旁腺自体移植对甲状旁腺保护的临床意义。 方法回顾性分析2014年5月至2017年05月收治的134例甲状腺乳头状癌(TPC)患者临床资料,将67例注射纳米炭混悬注射液行甲状旁腺负显影及自体移植患者作为纳米炭组,67例常规手术患者作为对照组。应用SPSS17.0进行统计学处理,比较两组患者术后甲状旁腺误切率,手术后暂时性及永久性甲状旁腺功能减退的发生率,采用χ²检验,P<0.05差异有统计学意义。 结果纳米炭组甲状旁腺误切率10.44%(7/67)、暂时性甲状旁腺功能减退发生率10.44%(7/67)、永久性甲状旁腺功能减退发生率4.47%(3/67)明显低于对照组31.34%(21/67)、31.34%(21/67)、21.89%(14/67)差异有统计学意义(P<0.05)。 结论TPC根治术中通过纳米炭混悬注射液进行甲状旁腺负显影联合自体移植术,可有效减少甲状旁腺损伤,降低永久性甲状旁腺功能减退的发生率,提高手术安全性。