Yoshimasa Kamata

Role of Multiple Cerebral Microthrombosis in Symptomatic Cerebral Vasospasm: With a Case Report

In our studies of the pathogenesis of cerebral vasospasm, we have been emphasizing that microthrombosis may play an important role in the induction of cerebral ischemic symptoms or cerebral infarction. In this report, multiple microthrombi are demonstrated histologically to be a major cause of cerebral infarction in the autopsied brain of a 63-year-old woman who died from typical cerebral vasospasm that occurred after the rupture of an anterior communicating artery aneurysm. We discuss the significance of thrombus formation and subarachnoid perivascular acidosis in vasospasm.

Relationship between postoperative recurrence and expression of cyclin E, p27, and Ki-67 in non-small cell lung cancer without lymph node metastases

Abstract.Background: Cyclin E and p27 play pivotal roles in cancer development and progression. We investigated whether the prognosis in cases of non-small cell lung cancer without lymph node metastases that underwent complete resection could be associated with tissue expression of cyclin E, p27, and Ki-67. Methods: Tumors from 62 patients at least 5 years after surgery were assessed by immunohistochemistry for expression of cyclin E, p27, and Ki-67. Disease-free survival (DFS) after surgery was used to evaluate disease prognosis. We also investigated the relationship between expression of these factors and postoperative recurrence. Results: In non-small cell lung cancer, p27-negative expression and pT factor were significantly unfavorable prognostic factors in multivariate analysis. The DFS rate in cyclin E-positive expression was significantly lower than in cyclin E-negative expression. Similarly, p27-negative expression and high Ki-67 expression correlated with a shortened DFS rate. In combinations of expression of cyclin E and p27, the cyclin E-negative/p27-positive group had a significantly higher DFS rate than did the other groups. According to histological type, there were correlations between the risk of postoperative recurrence and expression of these three biological factors, especially in adenocarcinoma. Conclusion: By analyzing the expression of cyclin E, p27, and Ki-67 of tumor cells, it was possible to extract the patient group for whom closer follow-up and postoperative treatment is necessary to improve survival rate.

ELECTRON MICROSCOPICAL STUDY ON THE TUMOR OF VON RECKLINGHAUSEN'S NEUROFIBROMATOSIS

Five cases of von Recklinghausens neurofibromatosis were examined electron‐microscopically. The tumors were composed of Schwann cells, myelinated and non‐myelinated axons, fibroblasts, collagenous fibers, endothelial cells and mast cells. From our observation, the Schwann cells as well as the fibroblasts were capable of producing collagenous fibers. This observation was strengthened by the following findings: (a) collagenous fibers were just adjacent to Schwann cell surface, occasionally showing a banded structure; (b) the vesicular elements similar to those of the fibroblasts were observed within the cytoplasm of Schwann cells. Each Schwann cell was invariably surrounded by a basement membrane, and in the area of the collagenous fibers formed, the basement membrane became a hazy homogeneous substance extending irregularly into the connective tissue space. The membrane bounded vesicular elements appeared to discharge their content into the extracellular space after fusion with the cell membrane, and here the basement membrane as well as the cell membrane became obscure and looked homogenous. The tumors of von Recklinghausens neurofibromatosis were basically composed of both Schwann cells and fibroblasts. The name “neurofibroma” seemed suitable for these types of tumors.

Small adenocarcinoma of the lung: prognostic significance of central fibrosis chiefly because of its association with angiogenesis and lymphangiogenesis.

To clarify the reason why central fibrosis (CF) is an important histological prognostic factor in small adenocarcinoma (SA) of the lung, tumor tissues from 50 patients with SA ≤2 cm in diameter were investigated using immunohistochemical and in situ hybridization analysis for factors relating to extracellular matrix and vessels. CF was observed in 33/50 cases (66%). In adenocarcinoma areas, positive activity was observed with both primary antibodies and probes for matrix metalloproteinase‐2 (MMP‐2) in 11/50 patients (22%), membrane‐type 1 matrix metalloproteinase (MT1‐MMP) in 39/50 patients (78%) and tissue inhibitor of metalloproteinase‐2 (TIMP‐2) in 49/50 patients (98%). In CF areas, the positive activity of fibroblastic cells was seen for only TIMP‐2 in 32/33 patients (97%). In CF areas, both CD34‐positive (blood and lymphatic) vessels and D2‐40‐positive lymphatic vessels were semiquantitatively increased in 16/33 patients (48.5%) by immunohistochemistry. Tumors with increased vessel density were associated with statistically lower disease‐free survival curves compared with tumors without increased vessels. Lymphatic vessels in some CF showed intravasation by carcinoma cells. In conclusion, CF could be an important histological prognostic factor in SA chiefly because of its association with angiogenesis and lymphangiogenesis.

Adenoma of the Nipple in an Adolescent

We recently treated a 14-year-old girl with a clinically and histologically diagnosed with adenoma of the nipple. Enucleation of a mass preserving the nipple was successfully performed. Adenoma of the nipple is a rare disease which is often mistaken clinically for Paget’s disease. About 200 cases of the tumors have been reported worldwide so far. The most common symptom is erosion of the nipple and nipple discharge. Our case had erosion of the nipple but no discharge. Adenoma of the nipple is a benign lesion which can be successfully treated by a simple surgery.

A case of early-stage primary malignant melanoma of the esophagus

From the First Department of Internal Medicine, the First Department of Surgery, and Central Pathology, Hirosaki University School of Medicine, Hirosaki, Japan. Reprint requests: Shinsaku Fukuda, MD, First Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, 0368562 Aomori, Japan. Copyright

Study on the Ultrastructure and Acetylcholinesterase Activity in Von Recklinghausen′s Neurofibromatosis

The cutaneous nodules obtained from seven patients with von Reckling‐hausens neurofibromatosis were investigated by electron microscopy, and ultrastructural localization of acetylcholinesterase activity was demonstrated in the nerve fibers of this tumor for the first time using Karnovskys thiocholine method. The enzymatic activity was mainly found in unmyelinated fibers, exactly associated with their axonal membranes, the interspace between the apposing axonal and Schwann cell membrane, and some different mesaxons, which indicated their cholinergic nature. Almost all myelinated fibers and some unmyelinated fibers did not possess the activity. The relationship between axon and Schwann cell was quite similar to that of normal peripheral nervous system, but two striking alterations of the nerves existed: One is the dissociation of unmyelinated fibers, and the other is the degenerative changes of the axon and the myelin sheath. As the evidence of schwannian proliferation, onion bulb formations and collagen pockets were observed. Some signs of fibroblastic proliferation were also found.

PRIMARY MESENCHYMAL CHONDROSARCOMA OF THE LUNG : A CASE REPORT WITH IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL STUDIES

A case of primary pulmonary mesenchymal chondrosar‐coma is reported. The tumor occurred first in the lower lobe of the right lung of a Japanese female aged 45. Three years after the first operation it metastasized to the upper lobe of the left lung. The tumors were highly cellular and composed of undifferentiated mesenchymal cells and inter spersed islands of well‐differentiated cartilaginous tissue. lmmunohistochemistry failed to detect S‐ 100 and vimentin in the undifferentiated cells. In contrast, Leu‐ 7 and blood coagulation factor Xllla were positive in these cells. Electron microscopically, undifferentiated mesenchymal cells had narrow cytoplasm with sparsity of organelles, but no intermediate‐sized filaments were detected. In the transitional areas between undifferentiated cells and cartilaginous components, thin intracytoplasmic filaments were sometimes observed in the tumor cells. The differ entiation toward cartilaginous cells of undifferentiated mesenchymal cells was suggested by immunohisto chemistry and electron microscopy. This is the first case of mesenchymal chondrosarcoma occurring in the lung with long‐ term follow‐ up. Acta Pathol Jpn 42: 364–371, 1992.

A Multihormonal Pituitary Adenoma with Growth Hormone and Adrenocorticotropic Hormone Production, Causing Acromegaly and Cushing Disease

Pituitary adenoma with growth hormone (GH) and corticotropin (ACTH) production causing apparent acromegaly and Cushing disease is extremely rare. A 45-year-old woman had a pituitary macroadenoma and severe insulin resistance. Physical examination showed a fully developed acromegaly associated with mild Cushingoid features. Serum GH, insulin-like growth factor-I, ACTH, and cortisol levels were all elevated. Hormonal loading tests resulted in GH levels increasing paradoxically in response to thyrotropin-releasing hormone (TRH), but not corticotropin-releasing hormone (CRH). A similar unexpected increase in ACTH and cortisol levels occurred in response to TRH and GH-releasing hormone. After trans-sphenoidal resection of the pituitary macroadenoma immunohistochemistry revealed the presence of either diffuse but faintly GH-positive cells or sparse but distinct ACTH-stained cells. A marked amelioration of insulin resistance was observed postoperatively. The elevated ACTH and cortisol levels should therefore be investigated by CRH and dexamethasone suppression tests for the coexistence of Cushing disease to exclude the possibility of underlying ACTH-producing tumors.

An unusual heterotopia of pyloric glands of the stomach with inverted downgrowth.

A rarely reported, large heterotopia of gastric glands in the submucosal layer of the stomach is observed in a 79 year old Japanese man with early gastric cancer. Histologically, it consists of marked hyperplasia of benign foveolar‐type epithelia and tubular glands which instead of growing upwards grow downwards into the submucosa. Immunohistochemically, many gastrin‐positive G cells are observed within it, indicating the existence of independent pyloric‐type glands from the surrounding mucosa with intestinal metaplasia. Muscle actin‐positive fascicles, derived from the muscularis mucosae, are demonstrated to branch into it and to encapsulate it. This result suggests that the present lesion may not represent a truly submucosal ectopic location, but an inverted downgrowth of the mucosa into the submucosa, thus resembling an inverted polyp of the colon. An awareness of this unique lesion is important in order that it not be mistaken for a submucosal extension of the primary adenocarcinoma.