Takaya Kodama

Diffuse sclerosing variant of papillary carcinoma of the thyroid. Clinical importance, surgical treatment, and follow-up study

A diffuse sclerosing variant is not very rare among papillary carcinomas of the thyroid when the patients are female and younger than 30 years of age. the variant is characterized by diffuse involvement of one or both thyroid lobes, with dense sclerosis, patchy lymphocytic infiltration, and abundant psammoma bodies. Controversy still exists concerning its prognosis. We reviewed our experience with 14 patients treated between 1958 and 1988. All patients were young females, their age being from 10 to 28 years with a mean of 19.6. Hashimotos thyroiditis had been suspected in nine patients before they came to our clinic. Nowadays the diagnosis of this cancer is possible when we have this entity in mind and detect abundant psammoma bodies either by ultrasonography or by soft‐tissue roentgenography of the neck. Total thyroidectomy with modified neck dissection was carried out in eight patients, subtotal thyroidectomy with neck dissection in five, and lobectomy with neck dissection in one. All of them are alive and well without distant metastasis at a mean follow‐up of 16 years. Because most of the patients with this variant of papillary carcinoma are young women and the prognosis is favorable, a complete resection without causing later recurrence, but also cosmetic and complication‐free surgery, should be considered.

Flow cytometric dna analysis of parathyroid tumors with special reference to its diagnostic and prognostic value in parathyroid carcinoma

The nuclear DNA content of paraffin‐embedded parathyroid tumors from 49 patients with proven primary hyperparathyroidism was determined by flow cytometric analysis. The lesions included 14 primary and 11 locally recurrent or metastatic lesions from 16 carcinoma patients, 28 single adenomas from 28 patients, and 15 hyperplastic glands from five patients with familial multiple endocrine neoplasia type 1. No abnormal DNA stemline was found in any of the hyperplastic glands. One (3.6%) of the adenomas was aneuploid. There was no difference in ploidy patterns between the primary and recurrent lesions of the carcinomas and five (31%) of the carcinomas expressed aneuploidy. Four of the five patients with aneuploid carcinoma had recurrences including pulmonary metastases. One of them died of this disease 12 years after the initial operation, and all except one of the others are hypercalcemic even after removal of the successive recurrent or metastatic tumors. Of the 11 patients with diploid carcinoma, four had either local recurrence or pulmonary metastasis. Two of them are living with normocalcemia 3 and 6 years, respectively, after removal of the recurrent tumors and the others are alive with mild hypercalcemia. The remaining seven patients with diploid carcinoma, however, have no recurrence 2 to 5 years after the initial operation. Thus aneuploid parathyroid carcinomas are likely to show more malignant behavior than those with a diploid DNA pattern. All of the patients with adenoma and hyperplasia have been normocalcemic after a mean follow‐up‐interval of 37 months. This study indicates that flow cytometric analysis of nuclear DNA content is a valuable adjunct to histologic examination in the diagnosis of parathyroid carcinoma and the prediction of the clinical outcome.

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.

A LIGHT AND ELECTRON MICROSCOPIC STUDY ON THE PANCREATIC DUCTAL SYSTEM

To Investigate morphological features of the human pancreatic ductal system, light and electron microscopic studies were performed, on the comparative basis with those of several species of mammals. The human pancreas possessed relatively well–developed ductal system, as compared with those of other mammals. Furthermore, it had unique centroacinr cells containing numerous mitochondria. The mode of innervation to the ducts, and cytological features such as cilia formation and mucin production were also revealed. Several kinds of endocrine cells including A, B, D1, ECn, presumptive EC1, and presumptive EC2 or K could be identified, but a few remained unclassiflable. The above findings are considered to be prerequisite for understanding the physiology, especially of bicarbonate production, and pathology, especially of oncogenesis of the exocrine and endocrine pancreas. ACTA PATHOL. JPN. 33: 297–321, 1983.

Identification of carcinoembryonic antigen in the C‐Cell of the normal thyroid

Carcinoembryonic antigen (CEA) activity was confirmed in the C‐cell of the normal thyroid by immunohistochemical techniques. This suggests that CEA production in medullary carcinoma of the thyroid is not initiated by carcinogenesis, but reflects a function of the normal C‐cell. It is not yet clear whether CEA production in the C‐cell may be influenced by carcinogenesis. The C‐cell is the first APUD cell that was confirmed to have CEA activity.

Flow cytometric DNA analysis of parathyroid tumors. Implication of aneuploidy for pathologic and biologic classification

The previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between DNA content and histopathology, resulting from differences in technical methods and data analysis. This study measured nuclear DNA of parathyroid tumors by flow cytometry in fresh material and determined whether DNA aneuploidy really assists in making a pathologic diagnosis of carcinoma or not. From May 1987 through April 1989, 65 consecutive patients operated on for primary hyperparathyroidism had DNA analysis of the freshly excised parathyroid tumors. Three of the patients had metastatic lesions of parathyroid carcinoma in the lung, cervical lymph nodes, and lung and mediastinal lymph nodes, respectively. Pathologic classifications of the lesions from the other 62 patients were 54 adenomas, four carcinomas, and four hyperplasias. In all the latter patients, hyperplasia was associated with a multiple endocrine neoplasia syndrome. Unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60% of the primary lesions of the carcinomas, in 9% of the adenomas and in 50% of the hyperplasias. Therefore, parathyroid carcinomas were more apt to be aneuploid than were adenomas (P = 0.0015, both‐sided testing). In each of the cases of aneuploid hyperplasia, a small aneuploid peak was found. The high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential. Cell distribution analysis did not provide any significant information beyond ploidy level. In conclusion, DNA flow cytometric analysis of DNA ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms.

Mid-mediastinal parathyroid lesions: preoperative localization and surgical approach in two cases.

Although hyperfunctioning mediastinal parathyroid lesions that require median sternotomy or thoracotomy for removal are occasionally present, the majority are located in the anterior mediastinum closely associated with the thymus. Only eight cases of ectopic hyperfunctioning parathyroid tumors in the middle mediastinum have been reported. We experienced two cases of either persistent or recurrent hyperparathyroidism in which abnormal parathyroid tissue was located in the aorticopulmonary window. One of the patients had a parathyroid adenoma and the other had metastatic lesions of parathyroid carcinoma. In both cases, thallium scanning proved useful in identifying the lesions while computed tomography scan was effective for mediastinal three-dimensional localization. In one case, single photon emission computed tomography imaging with thallium proved beneficial for both identification and localization of the middle mediastinal lesion. The surgical approach used in both cases was different. In one case, left thoracotomy was performed, after which the ligamentum arteriosum was divided, and an adenoma anterior to the left main bronchus and posterior to the left pulmonary artery removed. In the other case, two metastatic tumors of parathyroid carcinoma anterior to the right main bronchus and posterior to the right pulmonary artery were resected through a median sternotomy and opening of the pericardium.

MORPHOLOGICAL BEHAVIOR OF CARCINOMA OF THE PANCREAS

The incidence and the behavior of endocrine cells In carcinomatous tissues were studied in 84 autopsy cases and 10 surgical or autopsy cases of pancreatic carcinoma, by light and electron microscope, respectively. It was found that the islets persistently survived in the carcinomatous tissues. In large duct type carcinomas, the islets showed unique familiarity with the carcinomatous ducts, which may be interpreted as suggesting interactions between ductal cells and islet cells in pancreatic carcinogenesis. Aside from these survivor islet cells, carcinomas exhibited different degree and kind of differentiation to endocrine cells, depending upon their histological types. Namely, neoplastic argyrophil cells were found at the incidence of 82% (large duct type carcinoma), 39% (small duct), 43% (adenosquamous), and 18% (undifferentiated one). Moreover, argyrophil cells with their apexes stretching far to the neoplastic lumen were found only in large duct type carcinoma and cystadenocarcinoma. In three cases of carcinoid or oat cell type carcinoma, argyrophil cells were diffusely scattered and irregular in shape. These findings further justify the classification, reported in the previous article. The differentiation to endocrine cells was confirmed also by electron microscope.

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.

MORPHOLOGICAL LESIONS OF THE PANCREATIC DUCTS

Morphological lesions of the pancreatic ducts were studied in 113 control autopsy cases, and 84 cases of primary pancreatic carcinoma. The lesions were classified into pyloric gland metaplasia, focal pseudo‐proliferation, goblet cell metaplasia, squamous metaplasia, and atypical proliferation. Diabetes mellitus or glycosuria, alcohol intake, and smoking do not seem to have any close associations with these lesions or pancreatic carcinoma. Pyloric‐gland and squamous metaplasias were found at nearly comparable incidences both in control and carcinoma cases, but marked atypical proliferations, which were indistinguishable from carcinoma in situ or intraductal spreading of carcinoma, were more frequently observed in the carcinoma cases. Pyloric gland metaplasia was the most common among the various lesions, and considered to represent nonspecific change of the pancreatic duct. However, it was suggested that some of the metaplastic lesions might be transformed into atypical proliferations and further into carcinoma in situ. The expected latent period from the appearance of in situ lesion to overt pancreatic carcinoma may be a clue to early diagnosis and effective surgical treatment, but possible multiplicity of carcinoma in situ or intraductal spreading of carcinoma even at its early stage will burden further problems on its treatment. On rare occasions, argyrophil cells were found In the pyloric gland metaplasia, and its significance was discussed in relation to the genesis of Zollinger‐Ellison tumor.