Yoshihide Fujimoto

Diagnosis and Treatment of Patients with Parathyroid Carcinoma: An Update and Review

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism. However, to our best knowledge, at least 163 cases of functioning parathyroid carcinoma appeared in the English literature from 1981 to 1989. We summarize the available information obtained from the reports of those patients and compare it with previous descriptions of the disease. The etiology of parathyroid carcinoma is usually obscure, but the possibility of a radiation-induced malignant change in the parathyroid gland became evident in a few patients. Clinical manifestations, including age, sex, symptoms, and biochemical findings in this review were comparable to those in previous reviews. Noninvasive localization studies such as ultrasonography may offer a diagnostic clue to parathyroid carcinoma. Measurement of DNA content is a useful adjunct for making the histologic diagnosis of parathyroid carcinoma and prediction of the clinical outcome. Since the initial operation offers the best chance for cure, preoperative suspicion and intra-operative recognition of the parathyroid cancer are essential. The initial operation should been bloc resection of the tumor, avoiding rupture of the tumor capsule and spillage of tumor cells. As parathyroid carcinoma is a slow-growing but tenacious malignancy, repeated resection of local recurrent tumors or even distant métastases is effective for palliation of recurrent hypercalcemia and occasional cure. When hypercalcemia is refractory to surgical therapy or no recurrent tumor can be identified, other modalities of therapy must be considered. New drugs to control hypercalcemia by inhibiting bone resorption may hold promise in patients with recurrent parathyroid carcinoma.RésuméLe cancer de la parathyroÏde est une cause rare dhyperpararthyroÏdie. A notre connaissance, au moins 163 cas de cancer avec hyperparathyroÏdie ont été publiés dans la littérature Anglosaxonne entre 1981 et 1989. Nous avons résumé ici ces observations pour les comparer aux descriptions antérieures à 1981. Létiologie du cancer de là parathyroÏde reste inconnue, mais la possibilité dune transformation maligne secondaire à une irradiation a pu Être retenue dans quelques cas. Les manifestations cliniques, lâge, le sexe, les symptÔmes, ainsi que les données biochimiques, étaient tout à fait similaires à ceux davant 1981. La localisation de la parathyroÏde pathologique par les ultrasons, méthode noninvasive, peut Être utile au diagnostic. La quantification du taux dADN est également utile pour le diagnostic histologique de cancer et pour prédire lévolution. Puisque lintervention initiale réprésente pour lé patient les meilleurs chances de guérison, la suspicion préopératoire et la reconnaissance peropératoire du cancer de la parathyroÏde sont essentielles. Lintervention doit comporter la résection en bloc de la tumeur, en évitant la rupture de la capsule et la diffusion des cellules tumorales. Puisque le cancer de la parathyroÏde est un cancer qui évolue lentement, il est toujours possible de proposer des résections locales répétées ou celle des métastases à distance pour contrÔler lhypercalcémie, voire pour obtenir une guérison. Lorsque lhypercalcémie persiste malgré le traitement chirurgical, et quaucune récidive tumoral ne peut Être identifiée, dautres modalités thérapeutiques peuvent Être envisagées. De nouveaux médicaments pour contrÔler lhypercalcémie, en inhibant la résorption osseuse, semblent prometteuses en cas de récidive.ResumenEl carcinoma paratiroideo es causa rara de hiperparatiroidismo primario. Sin embargo, segÚn nuestro mejor conocimiento, por lo menos 163 casos de carcinoma paratiroideo funcionante han aparecido en la literatura en el idioma ingles entre 1981 y 1989. Hemos resumido la información disponible en los reportes sobre esos pacientes para compararla con descripciones previas de la enfermedad. La etiología del carcinoma paratiroideo es generalmente oscura, aunque la posibilidad de degeneration maligna inducida por irradiación aparece evidente en algunos casos. Las manifestaciones clínicas, incluyendo edad, sexo, síntomas y hallazgos bioquimicos en los pacientes en nuestra serie son comparables con aquellos en revisiones previas. Estudios no invasivos de localización, taies como ultrasonografía, pueden significar la clave diagnóstica en el carcinoma paratiroideo. La medición del contenido de DNA es un método Útil complementario para establecer el diagnóstico histológico del carcinoma paratiroideo y en la prediction del resultado clínico. Puesto que la operatión inicial ofrece la mejor oportunidad de curación, la sospecha preoperatoria y el reconocimiento intraoperatorio del cáncer paratiroideo son de importancia esencial. La operación inicial debe consistir en la resección en bloque del tumor, evitando la ruptura de la cápsula y la contaminación con células tumorales. Siendo que el carcinoma paratiroideo es una enfermedad de crecimiento lento pero tenaz, la resección repetida de tumores localmente recurrentes, o aÚn de metastasis distantes, es eficaz en la paliación de la hipercalcemia recurrente o aÚn en su curación ocasional. Cuando la hipercalcemia aparece refractaria a la terapia quirÚrgica o cuando no es posible identificar tumor recurrente, se deben considerar otras modalidades terapéuticas. Nuevas drogas para el control de la hipercalcemia por inhibición de la resorción ósea pueden ser promisorias en pacientes con carcinoma paratiroideo recurrente.

How to recognize and treat parathyroid carcinoma.

Parathyroid carcinoma is a rare tumor and its clinical course is variable. Differentiation of patients with parathyroid carcinoma from those with parathyroid adenoma is often difficult both preoperatively and at operation. For good results, the surgeon must recognize this disorder and perform an en bloc resection at the initial surgery. A neck dissection is necessary only when there is evidence of regional node metastases. After surgery, periodic follow-up of the serum calcium and iPTH levels is essential. When hypercalcemia recurs or the serum iPTH increases, localization studies with the use of thallium-201 scanning help detect local recurrence and regional lymph node metastases, but unfortunately, this method often fails to localize pulmonary metastases. Chest radiographs and CT scanning are useful for delineating pulmonary metastases. A wide excision of locally recurrent tumor, an en bloc radical neck dissection and mediastinum dissection for lymphatic metastases, and an aggressive surgical resection of lung metastases are recommended. Although these operations are rarely curative, they usually offer definite palliation of the marked hypercalcemia, often for a considerable period. Drugs to lower the serum calcium level and systemic chemotherapy are currently of only limited benefit, and radiation therapy is generally ineffective.

Surgical treatment of ten cases of parathyroid carcinoma: Importance of an initial en bloc tumor resection

AbstractThis report examines the charcteristics of 10 patients surgically treated for unequivocal parathyroid carcinoma. Seven cases were from our series of 165 patients with primary hyperparathyroidism. Routine determination of serum calcium level by an automated analyzer occasionally led to early tumor detection. A spectrum of clinical and pathological variation was evident in our series. One of 3 patients with simple tumor resection and 1 of 4 patients with wide local excision in the initial operation showed local recurrence. Regional lymph node metastases without local recurrence occurred in another patient 3 years after the initial wide local resection and he was treated by neck and mediastinal dissections.nThree additional parathyroid carcinoma patients with simple tumor resection were referred to us from elsewhere for recurrent hypercalcemia. Aggressive surgical resections of locally recurrent tumors or metastatic nodules brought marked alleviation of hypercalcemic symptoms, although none was curative.nAlthough the prognosis of parathyroid carcinoma greatly depends on the biological malignancy of the tumor in individual cases, our ongoing data confirm the importance of thorough identification and en bloc removal of the tumor at the time of the initial operation. A neck dissection is necessary when there is evidence of lymph node metastasis.RésuméCet article est consacré à 10 malades traités pour cancer parathyroïdien. Sept cas traités de première main proviennent dune série, observée par les auteurs, de 165 malades atteints dhyperparathyroïdisme. Le dosage systématique du taux de la calcémie a permis parfois la découverte précoce du cancer alors que des variations cliniques et pathologiques diverses furent constatées. Un des trois malades qui avaient subi lexérèse simple de la tumeur et un des quatre sujets qui avaient subi une exérèse locale large ont présenté une récidive locale. Lapparition dadénopathies régionales métastatiques sest manifestée chez un autre opéré trois ans après une résection locale large; il fut traité par une dissection radicale cervicale et médiastinale.Trois cas supplémentaires de cancer parathyroïdien, de seconde main, ont été réopérés pour récidive dhypercalcémie. La résection large de la tumeur récidivante ou des ganglions envahis se solda par une amélioration des symptômes dhypercalcémie mais ne fut pas suivie de guérison.Bien que le pronostic du cancer parathyroïdien dépende essentiellement de la malignité biologique de la tumeur dans chaque cas, notre expérience confirme limportance de lidentification parfaite et de lexérèse en bloc de la tumeur lors de lintervention initiale. La dissection cervicale simpose quand les ganglions sont manifestement le siège de métastases.ResumenEn este informe se analizan las características de 10 pacientes con carcinoma inequívoco de paratiroides sometidos a tratamiento quirúrgico. Siete de estos casos provienen de nuestra serie de 165 pacientes con hiperparatiroidismo primario. La determinación rutinaria del nivel de calcio sérico por medio del analizador automático ocasionalmente hizo posible la detección temprana del tumor.Se pudo evidenciar un perfil de alteraciones clínicas y patológicas en los pacientes que constituyen nuestra serie. Uno de los 3 pacientes sometidos a simple reacción primaria del tumor y uno de cuatro sometidos a amplia excisión en el momento de la operación inicial exhibieron recurrencia local. Metástasis ganglionares regionales sin recurrencia local se presentaron en otro paciente tres años después de una amplia resección local inicial, y éste fue tratado con disecciones cervical y mediastinal.Tres pacientes adicionales con carcinoma paratiroideo nos fueron referidos de fuera debido a hipercalcemia recurrente. Resecciones quirúrgicas agresivas de los tumores localmente recurrentes o de los nódulos metastásicos resultaron en marcada mejoría de los síntomas hipercalcémicos, aun cuando ninguna fue curativa.Aun cuando el pronóstico del carcinoma paratiroideo depende de la malignidad biológica de caso individual, nuestros datos confirman la importancia de una identificación completa y de la resección en bloque del tumor durante la operación inicial. La disección cervical es necesaria cuando hay evidencia de metastasis en los ganglios linfáticos.

A case of gastric carcinoma associated with excessive granulocytosis. Production of a colony-stimulating factor by the tumor.

A patient with gastric carcinoma exhibited an excessive granulocytosis (58,000/μl) preoperatively, in the absence of overt infection. After resection of the primary tumor, the peripheral leukocyte count decreased promptly to the normal value. In a search for a colony‐stimulating factor (CSF), the tumor was transplanted into nude mice. A marked neutrophilia was observed in the tumor‐bearing mice, suggesting the production of CSF by the tumor. Media conditioned by the primary culture of the tumor cells revealed the presence of CSF activity as well. CSF‐producing carcinomas have been detected in various organs; nevertheless, no cases of gastric carcinoma have hitherto been described. It is of particular interest that in this patient hypercalcemia was not observed, although it often accompanied CSF‐producing tumors reported previously. Therefore, it is suggested that this tumor secreted pure CSF and that the CSF produced by the tumor did not necessarily induce hypercalcemia.

Localization and surgical resection of metastatic parathyroid carcinoma

Six cases of recurrent parathyroid carcinoma were reviewed. Four patients presented with local recurrence, which followed a simple tumor resection more frequently than an en bloc initial operation. The fact that the mode of recurrence varied made preoperative localization difficult. In 3 earlier patients (1978–1980), careful palpation of the neck and venous sampling for parathyroid hormone concentrations were the means of localization. In 4 recent patients (1980–1985), including 1 of the former 3, thallium-201 scan was the most useful method for detecting the local recurrence and the regional lymph node metastases, but the method failed to localize the lung metastases. Chest x-rays and computed tomographic (CT) scan were useful in delineating metastatic pulmonary lesions. Wide excision of the local recurrent tumor, once or twice, was curative in 3 of the 4 patients. En bloc radical dissection of the neck and mediastinum in 1 patient resulted in normocalcemia for the past 2 years. Thoracotomies carried out in 2 patients with multiple pulmonary metastases were palliative in 1 case for 5 years and curative at least at the present time (3 months after the operation) in the other case. Thus, the results in our series justify aggressive surgical treatment for the recurrence of parathyroid carcinoma.RésuméSix case de récidive de cancer parathyroïdien ont été observés par les auteurs. Quatre dentre eux présentaient une récidive locale plus souvent après exérèse de la tumeur quaprès exérèse en bloc. Le mode de récidive fut variable et de ce fait la localisation préopératoire de la lésion fut difficile. De 1978 à 1980 la récidive fut localisée par la palpation soigneuse du cou et par la détermination de la concentration de lhormone parathyroïdienne dans des échantillons de sang veineux. De 1980 à 1985 chez un groupe de 4 malades comprenant lun des précédents le diagnostic fut porté par le scan au thallium-201 qui permet de découvrir le siège de la récidive locale et les éventuelles métastases ganglionnaires mais qui est incapable de mettre en évidence les métastases pulmonaires. En revanche lexploration radiologique du thorax et la tomodensitométrie permettent de les déceler. Lexérèse large de la récidive tumorale locale exerça une action curative sur 3 des 4 malades. La dissection radicale du cou et du médiastin chez un malade sest traduite depuis 2 ans par une calcémie normale. Les thoracotomies entreprises chez 2 malades avec des métastases pulmonaires multiples se sont soldées dans un cas par une survie de 5 ans et dans un autre cas par une survie qui dure depuis 3 mois. Les résultats de cette série justifient pour les auteurs une attitude chirurgicale agressive en présence dune récidive de cancer parathyroïdien.ResumenSeis casos de carcinoma paratiroideo recurrente fueron revisados. Cuatro pacientes se presentaron con recurrencia local; ésta apareció después de resección simple del tumor con mayor frecuencia que después de resección en bloque como operación inicial. El modo de recurrencia fue variable, lo cual hizo que la localización preoperatoria fuera difícil. En 3 pacientes del comienzo de esta serie (1978–1980) la palpación cuidadosa del cuello y el muestreo de sangre venosa para determinar concentraciones de hormona paratiroidea constituyeron los métodos de localización. En nuestros 4 pacientes recientes (1980–1985), incluyendo 1 de los 3 primeros, la exploración con talio-201 fué el método más útil para detectar la recurrencia local y las metástasis ganglionares regionales, pero el método en cuanto a la localización de metastasis pulmonares falló. Las radiografías y la tomografía computadorizada fueron de utilidad en la identificación de lesiones metastásicas en el pulmón. La resección amplia del tumor local recurrente, una o dos veces, resultó curativa en 3 de 4 pacientes. La disección en bloque del cuello y del mediastino resultó en normocalcemia durante los últimos 2 años en un paciente. Toracotomía en 2 pacientes con metástasis pulmonares fue paliativa en un caso durante 5 años y curativa, por lo menos hasta el momento (3 meses después de la operación), en el otro. En conclusión, los resultados en nuestra serie justifican el tratamiento quirúrgico agresivo en el manejo del carcinoma paratiroideo recurrente.

A compound adrenal medullary tumor (pheochromocytoma and ganglioneuroma) and a cortical adenoma in the ipsilateral adrenal gland: a case report with enzyme histochemical and immunohistochemical studies

Neoplasms of all the adrenal parenchymatous elements [i.e., a compound adrenal medullary tumor (MT) consisting of pheochromocytoma (Pheo) and ganglioneuroma (GN) and a cortical adenoma] were found in the right adrenal gland of a 53-year-old man. A mature GN element was predominant in the MT, and nodules of small polygonal Pheo cells were scattered in GN. No neuroblastomatous element or malignant Pheo was found. The cortical adenoma consisted of compact cells and clear cells; it showed 3 beta hydroxysteroid dehydrogenase, glucose-6-phosphate dehydrogenase, and succinate dehydrogenase activity. The nonneoplastic cortex was slightly atrophic and showed weaker activity of the enzymes, suggesting that the adenoma was cortisol-producing. The cortex surrounding the MT was invaded and replaced by either GN or Pheo. In some places, however, hypertrophic compact cells constituted the cortex and were in contact with ACTH-immunoreactive chromaffin cells. A few of the latter were also positive for other proopiomelanocortin (POMC)-derived peptides. Pheo cells in the other parts were negative for POMC-derived peptides.

Parathyroid carcinoma of the oxyphil cell type. A report of two cases, light and electron microscopic study

Parathyroid adenomas are subdivided into chief cell and oxyphil cell variants. However, the parathyroid carcinomas described thus far have been only of the chief cell type. Two cases of oxyphil cell carcinoma of the parathyroid gland are reported, with light and electron microscopic study. The patients presented apparent clinical hyperparathyroidism with x‐ray finding of generalized fibrous osteitis and palpable parathyroid tumors. Initially, a pathologic diagnosis of parathyroid adenoma was made in both of them. However, in due course, pulmonary metastases developed in one patient and a local recurrence occurred in the other, 5 and 8 years after the primary operation, respectively. Review of the microscopic slides showed that both primary tumors met the criteria of parathyroid carcinoma. A matter of interest in both cases is that the neoplasms were composed principally of oxyphil cells. Electron microscopic study confirmed the existence of typical oxyphil cells packed with numerous mitochondria.

Autoantibodies in Malignant Lymphoma of the Thyroid Gland

THE discovery of autoimmune thyroiditis by Witebsky and Rose1 and Roitt and Doniach2 has been confirmed by others3 , 4 and has established the thyroid gland as one of the commonest sites for the development of autoimmunization. Autoimmune hemolytic anemia and other immunologic disturbances are often associated with neoplastic disorders of the lymphoid system such as lymphosarcoma. It has not previously been known that a malignant lymphoma localized in the thyroid gland can produce thyroid autoantibodies. This report reviews the clinical and laboratory data of 6 patients with malignant lymphoma of the thyroid gland and discusses the mechanisms of production and maintenance .xa0.xa0.

Family study of serum carcinoembryonic antigen in inherited medullary carcinoma of the thyroid

Serum carcinoembryonic antigen (CEA) and calcitonin were assayed in 8 patients with medullary carcinoma of the thyroid (MCT) and 14 unaffected family members, from 4 pedigrees of Sipples syndrome and one pedigree with inherited MCT. Serum CEA ranged from 5.4 to 44.5 ng/ml in the patients, but less than 2.5 ng/ml in the unaffected. This is in contrast with retinoblastoma and cancer family syndrome, where not only the patients but also unaffected family members show high serum CEA, and cytoplasmic or selective maternal inheritance of serum CEA level is presumed. In inheritable MCT, serum CEA increases in association with the development of MCT, and serum CEA level per se is not inherited. Cancer 44:661‐664, 1979.

Soft Tissue Roentgenography in Diagnosis of Thyroid Cancer

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