Akito Noguchi

CERVICAL THYMOMA and INCIDENCE OF CERVICAL THYMUS

A case of cervical thymoma in a 51‐year‐old female is reported. The tumor was located on the left side of the anterior neck just beneath the left lower lobe of the thyroid gland and there was no connection to the mediastinal thymus gland. It was well encapsulated and lobulated on the cut‐surface. Histologically, the tumor showed a mixed proliferation of lymphocytes and epithelial cells. Mitoses were frequently seen. Several tiny fragments of ectopic thymic tissue were found around the tumor. Cervical thymic tissue, considered to be the original site of the cervical thymoma, was studied and found macroscopically in 12 out of 657 patients with Basedows disease (1.8%).

LIGHT AND ELECTRON MICROSCOPIC STUDY OF NONFUNCTIONING PARATHYROID CARCINOMA

A case of nonfunctioning parathyroid carcinoma in a 69‐year‐old female has been studied by light and electron microscopy. The tumor, located on the left side of the anterior neck, was well encapsulated by connective tissue but showed invasion to the capsule and to the thyroid. The tumor cells exhibited a trabecular arrangement surrounded by capillary networks but focally showed several ductal structures. They were polygonal in shape, had a large nucleus showing frequent mitosis and poor cytoplasm containing glycogen. Some tumor cells had clear and abundant cytoplasm, and resembled water‐clear cells of the parathyroid. Immunohistochemically, no thyroglobulin was demonstrated in the tumor tissue. Electronmicroscopically, the tumor cells with high N/C ratio contained poorly developed cell organelles and abundant glycogen particles. They were poor in secretory granules and had no conglomeration of lipid. Desmosomes and tonoflbrils were observed. The ratio of the reported number of nonfunctioning parathyroid carcinoma to that of functioning one in Japan was compared with that in western countries. No difference of the ratio was found between these two, when identical criteria were employed.

THYROID CARCINOMA IN BENIGN THYROID DISEASES An Analysis from Minute Carcinoma

The relative frequency of thyroid carcinoma in benign thyroid diseases such as toxic diffuse goiter (toxic goiter), adenomatous goiter (goiter), adenoma, and chronic thyroiditis (thyroiditis) was studied using 3,219 surgically removed thyroid glands. Coexistence of carcinoma and benign diseases was found in 257 glands. Among them, 157 glands had minute carcinoma (diameter of cancer nodule is smaller than 10 mm) and 100 glands had advanced carcinoma (larger than 10.1 mm in diameter). The incidence of carcinoma including minute carcinoma was 29.4% in goiter (98/333), 21.0% in thyroiditis (11/53), 8.6% in adenoma (55/638), and 5.3% in toxic goiter (98/1852). Chi‐square test also revealed that the rate of carcinoma not only advanced carcinoma but also minute carcinoma was higher in goiter than in the other diseases (P<0.01, respectively). Among the patients aged under 39, the incidence of advanced carcinoma and minute carcinoma in thyroiditis were the highest, respectively (83% and 100% in thyroiditis, 9.0% and 11.4% in goiter, 2. 6% and 1.9% in adenoma, and 0.7% and 3.4% in toxic goiter), however, among the patients aged over 40, they were secondary lower and the lowest, respectively (19% and 16.8% in goiter, 5.2% and 7.5% in adenoma, 4.2% and 6.7% in thyroiditis, and 1.4% and 7.5% in toxic goiter). We concluded that adenomatous goiter accompanies carcinoma more frequently than other benign thyroid diseases and the high incidence of carcinoma in chronic thyroiditis is probably due to a preoperative selection of the patients. ACTA PATHOL. JPN. 35: 781–788, 1985.

Ultrastructural Localization Of Endogenous Peroxidase In The Human Thyroid Gland Under Normal And Hyperfunctioning Conditions

Ultrastructural localization of human thyroid peroxidase in normal and hyperfunctioning states has been studied. Peroxidase activity was visualized ultrastructurally with a cytochemical reaction using 0.05% diaminobenzidine‐tetrahydrochloride, and hydrogen peroxide with a final concentration of 0. 0025%, 0.005%, or 0.01%, respectively, and 2% osmium tetroxide. Reaction product demonstrating the enzyme was clearly observed in cell organelles with a final concentration of hydrogen peroxide at 0.0025% or 0.005%. In the normal portion of thyroid, follicular cells demonstrated the reaction product, located mainly in rough‐surfaced endoplasmic reticulum and perinuclear cisternae and in addition a small amount of the product was found in Golgi cisternae and small vesicles dispersed throughout the subapical cytoplasm. The reaction product significantly increased in amount in the cell organelles described above and in addition, a characteristic heavy deposition of the product was observed at the external surface of the microvilli in the follicular cells of thyroid obtained from the patients with treated Basedows disease. ACTA PATHOL. JPN. 34: 553–561, 1984.

MINUTE CARCINOMA OF THE THYROID and ITS DEVELOPMENT TO ADVANCED CARCINOMA

The relationship between the size of carcinomas and their histological characteristics such as encapsulation and sclerosis was studied using 157 cases of thyroid minute carcinomas with diameters less than 10 mm. When the diameter of the tumor was less than 1 mm, encapsulated carcinomas were not found, but they were presented in a group with a larger diameter. Sclerosing carcinomas were more frequently distributed in the group with a diameter less than 5 mm. With increasing tumor size, the carcinomas were reduced markedly in number and only two cases of sclerosing carcinoma were observed with a diameter more than 8 mm. It was concluded that thyroid minute carcinomas arise as nonencapsulated carcinoma, either sclerosing or nonsclerosing, followed by encapsulation at a later time and that some of the nonsclerosing carcinomas become apparent clinically, whereas most of the sclerosing carcinomas remain clinically silent throughout the entire life of the host. ACTA PATHOL. JPN. 35 : 377–383, 1985.

IMMUNOELECTRON MICROSCOPIC LOCALIZATION OF THYROGLOBULIN (TG) IN THE THYROID GLAND IN BASEDOW'S DISEASE

An electron microscopic immunohistochemical localization of thyroglobulin (TG) using PAP methods from Epok‐812 embedded tissues has been made in human thyroids obtained from 15 patients with treated Basedows disease aged 13 to 43 years. Follicular cells vary considerably in shape and content of cytoplasmic organelles depending mainly upon the size of follicles. Reaction product for TG coincided well with previous investigations studied by electron microscopic autoradiography and is strongly positive in most follicular lumina having no relation to their size, reabsorbed colloid droplets or small subapical vesicles. The reabsorbed colloid droplets are rarely observed in cells surrounding distended follicles and more frequently appeared in small follicles. The reabsorbed colloid droplets after fusion with lysosomes show a variable amount of reaction products from intense deposition to a complete absence of product indicating hydrolysis of TG by lysosomal enzymes. There is no reaction product in rough endoplasmic reticulum or Golgi apparatus in spite of positive reaction product in the subapical vesicles. These subapical vesicles are composed of both endocytotic and exocytotic vesicles.

IMMUNOELECTRON MICROSCOPIC LOCALIZATION OF THYROGLOBULIN IN HUMAN FOLLICULAR ADENOMA

An electron microscopic immunohistochemical localization of thyroglobulin (TG) using PAP methods has been made in 15 cases of cold follicular adenoma. All cases of follicular adenoma showed organ specific functions such as synthesis, storage, reabsorption, and hydrolysis of thyroglobulin except for an area composed of follicular cells with trabecular arrangement. Immuno‐reaction product for TG was precisely demonstrated in follicular lumina, subapical vesicles and reabsorbed colloid droplets. The reaction product observed in the follicular lumen was clearly demarcated from the cytoplasm of the follicular cells by the apical plasma membrane. The subapical vesicles ranging approximately from 50 mμ to 300 mμ in diameter were rarely observed in follicular adenoma and some of them fused with the reabsorbed colloid droplets. The reabsorbed colloid droplets usually had the intense reaction product and hydrolyzed colloid droplets had a vacuole containing floccular low electron dense materials. There is no reaction product in rough endoplasmic reticulum and Golgi complexes.

An immuno-electron microscopic study on intracellular localization of thyroglobulin (TG) in the thyroid gland in Grave's disease.

Intracellular localization of thyroglobulin (TG) using a pre‐embedding diffusion technique and an indirect localization sequence has been made in human thyroid obtained from 20 patients with treated Graves disease. Both antibodies, anti‐human TG‐rabbit IgG F(ab′)2 and anti‐rabbit IgG F(ab′)2‐goat IgG F(ab′)2 fragments easily penetrated the cytoplasm of follicular cells which were dissociated by RPMI‐1640 solution containing collagenase, dispase, and deoxyribonuclease. With light microscopic observation of semithin sections positive immuno‐reaction for TG was demonstrated as fine granular deposits in the cytoplasm of the dissociated cells. In electron microscopic studies, intracellular antigen was well circumscribed within certain cell organelles in all cases with the positive immuno‐reaction for TG being observed in perinuclear space, rough endoplasmic reticulum, Golgi complexes, secretory granules, and reabsorbed colloid droplets. Content of positive immuno‐reaction product differed somewhat from one case to another and from one follicle to another even in the same case. There was no immuno‐reaction product in nuclei, mitochondria, lysosomes, and lipofuscin‐like granules. ACTA PATHOL. JPN. 35 : 591–603, 1985.

Endocytosis of human thyroglobulin (TG) in adenomatous goiter studied by an immuno-electron microscopic procedure.

Five cases of adenomatous goiter have been studied by an electron microscope using an immuno‐reaction for thyroglobulin (TG) and focusing on the mechanism of endocytosis. Positive stain for TG was demonstrated in follicular lumina, large reabsorbed colloid droplets and small subapical vesicles. Endocytotic vesicles ranging from 320 nm to 1600 nm in diameter were observed in the cytoplasm as pits in the apical plasma membrane. Some of them showed direct connection with the positive stain for TG in the follicular lumen and the others were completely ingested in the cytoplasm. With statistic analysis, a majority of the vesicles showing the positive stain for TG in the cytoplasm distributed in the range of 200 nm to 1200 nm in diameter with the peak in 300 nm to 399 nm and was situated within an extent of the diameter measured from the endocytotic vesicles. Engulfment of colloid by pseudopods and fusion of the reabsorbed colloid droplets were encountered as extremely rare findings and appeared to play no major role for formation of large colloid droplets in adenomatous goiter.