Akira Hirayama

Glomangiosarcoma in a glomus tumor. An immunohistochemical and ultrastructural study

An extremely rare case of glomangiosarcoma (GS) occurring in a glomus tumor (GT) was evaluated ultrastructurally and histochemically. A man 65 years of age who was suffering from back pain underwent resection of a deep cutaneous nodule. Cells of a solid type GT showed numerous subplasmalenimal pinocytotic vesicles, thin filaments with scattered dense bodies, and thick external lamina, but negative desmin staining and a lack of glycogen. Similar findings also were observed in the GS, but were less obvious. The GS compressed the surrounding GT, exhibited many mitotic figures, prominent nucleoli, elongated nuclei and cytoplasm, and reacted more strongly to vimentin staining than the GT. The GT contained S‐100 protein‐positive Schwann cells, a few substance P‐positive nerve fibers, and moderate numbers of infiltrating mast cells. None of these findings were observed in the GS. Results were consistent with the view that GS was transformed possibly from the GT, and that the good prognosis for GS may be due to its small size that may be related to the preexistence of a pain‐causing GT.

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 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.

Primary adrenocortical micronodular dysplasia : enzyme histochemical and ultrastructural studies of two cases with a review of the literature

The adrenal glands from two patients with primary adrenocortical micronodular dysplasia (PAMD) were studied (no. 1, a 23-year-old man with cardiac myxomas and sarcoidosis; no. 2, a 16-year-old girl). The PAMD cells showed intense activity of 3 beta-hydroxysteroid dehydrogenase (3 beta DH), succinate DH, glucose-6-phosphate DH, alkaline phosphatase (AlPase), and other DHs and lysosomal hydrolases, giving a characteristic staining pattern. The staining patterns correlated well with ultrastructural findings. The larger adrenals (no. 1: 16.6 g) were associated with larger black nodules and internodular cortex (INC) with fairly well-retained enzyme activities, and contained cell clusters and single cells with intense AlPase activity with the appearance of PAMD nodules in the buds. The smaller adrenals (no. 2: 5.4 g) were associated with smaller black/yellow nodules, and had INC with weaker enzyme activity. Analysis of descriptions of INC in 25 previously reported cases revealed that the larger adrenals (more than 10 g) had less atrophic INC than the smaller ones. The characteristic enzyme pattern in PAMD cells explains the paradox that PAMD adrenals smaller than normal can cause Cushings syndrome, and may be useful for investigating neoplastic and non-neoplastic counterparts in other adrenal lesions. The relationship between PAMD cells and INC is not simply one of autonomy versus atrophy, and both cell types may be stimulated by a certain common trophic factor. Thus, PAMD belongs to the category of hyperplasia.

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.

IgG‐KAPPA‐PRODUCING PRIMARY PLASMACYTOMA OF THE THYROID GLAND WITH PREOPERATIVE SERUM M PROTEIN

A case of primary plasmacytoma of the thyroid gland which occurred in a 63‐year‐old woman is reported. Histologic and ultramicroscopic examination revealed that the excised thyroid tumor was plasmacytoma superimposed on lymphocytic thyroiditis. Immunohistological study showed that the tumor cells produced intracytoplasmic immunoglobulin (IgG‐kappa). Electropho‐retic and immunoelectrophoretic studies disclosed the presence of monoclonal immunoglobulin (IgG‐kappa) in samples of the patients serum which had been obtained preoperatively. After completion of irradiation therapy to the neck following tumor removal, the serum monoclonal immunoglobulin disappeared. The patient is currently alive and well without any evidence of the tumor three years after surgery.

So-called sclerosing hemangioma of the lung with nuclear inclusion bodies. Immunohistochemical study of a case.

A so‐called sclerosing hemangioma of the lung was removed from a 45‐year‐old woman after a follow‐up of 15 years. In addition to the histology of solid, hemorrhagic, papillary and sclerosing patterns, two types of various‐sized, irregularly shaped spaces were found to be lined by either small cells with a high N/C ratio (LI cells) or large, eosinophilic or foamy cells (L2 cells). These spaces (LI and L2 spaces) were often alternately arranged. Clusters of LI cells or L2 cells were also observed in solid‐pattern areas with or without lumen formation. Eosinophilic nuclear inclusion bodies (NIB) were exclusively found among L2 cells. L2 cells as well as NIB‐containing cells showed an immunohistochemical reactivity similar to that of type II pneumocytes (i.e., positive cytokeratin, epithelial membrane antigen (EMA), surfactant apoprotein, alpha‐1‐antitrypsin and nonspecific cross‐reacting antigen). LI cells were immunohistochemically similar to solidly growing cells (S cells) which showed positive EMA, alpha‐1‐antitrypsin and vimentin. These results are consistent with the view that NIB are a good marker for type II pneumocytes in so‐called sclerosing hemangioma, and that the two characteristic types of spaces were formed in different ways, thus favoring the theory that S cells are an immature form of type II pneumocytes. ACTA PATHOL JPN 38: 873‐881, 1988.

Augmented enkephalin-immunoreactivity in adrenaline-producing phaeochromocytomas

Immunohistochemical studies for methionine- and leucine-enkephalin were performed on 26 phaeochromocytomas to elucidate the patho-physiological roles of enkephalins. Positive reactions were seen in all phaeochromocytomas with varying intensities. The location of methionine- and leucine-enkephalin agreed fairly well with each other. Stronger immunostaining was obtained in phaeochromocytomas secreting both adrenalin and noradrenalin than in those secreting predominantly noradrenalin. Paroxysmal hypertension was frequently observed in patients with adrenalin-secreting phaeochromocytomas, especially those with marked enkephalin positivity. Urinary excretion of metanephrine was significantly correlated with enkephalin positivity. These findings show that all phaeochromocytomas retain the ability to produce enkephalins of the adreno-medullary or extra-medullary chromaffin tissues from which they derive. Augmented enkephalin-immunoreactivity in adrenalin-producing phaeochromocytomas may be interpreted as reflecting a close association of enkephalins with adrenalin under physiological conditions.