Kazuhito Matsumoto

Increased in situ expression of nitric oxide synthase in human colorectal cancer

Abstract There is growing evidence that nitric oxide (NO) has an important role in tumor growth. However, information on the expression of NO synthase (NOS) in colorectal cancers is scanty. We therefore investigated the distribution and expression of NOS in human colorectal cancers. The expression of three types of NOS, inducible (iNOS), endothelial (eNOS) and neuronal (nNOS), was examined by immunohistochemistry in 25 cases of colorectal cancer. The expression of iNOS was also investigated at the mRNA level using the reverse transcriptase polymerase chain reaction (RT-PCR) in 6 cases. Correlations were made between iNOS expression and the histopathological findings. Immunoreactive iNOS was detected in the tumor cells in 22 cases (88%) with diffuse cytoplasmic reactions. Expression of iNOS-mRNA detected by RT-PCR in three tumor tissues was over five-fold that in normal mucosa. Intensified immunoreactivity of iNOS was associated with vascular invasion. iNOS expression did not correlate with pathological staging, tumor size, lymph node metastasis, p53 expression or tumor vessel density. Immunoreactive eNOS stained more strongly in the endothelial cells of microvessels within and around the tumor than in the areas remote from the tumor. There is enhanced expression of iNOS and eNOS in human colorectal cancers, which may correlate with tumor growth and vascular invasion.

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.

Pancreatic malignant fibrous histiocytoma, inflammatory myofibroblastic tumor, and inflammatory pseudotumor related to autoimmune pancreatitis: characterization and differential diagnosis

Malignant fibrous histiocytoma (MFH) and inflammatory myofibroblastic tumor (IMT) are uncommon primary non-epithelial cell tumors of the pancreas. In addition, there are inflammatory pseudotumors (IPT) that may arise in the course of autoimmune pancreatitis (AIP). In the English language literature, only 24 cases of IMT and nine cases of MFH in the pancreas have been reported to date. We investigated three individual spindle cell tumors of the pancreas that were identified as MFH, IMT, and IPT, respectively, using immunohistochemical and molecular analysis. Both the MFH and the IMT, but not the IPT, showed nuclear p53 expression and mutations of the p53 gene. The MFH and the IMT also had higher mitotic and Ki-67 (MIB-1) indexes than the IPT. The IPT was found to be a tumor-like case of AIP. Many IgG4-positive plasma cells, which are considered to be a feature of AIP, were found in all three tumors. It is concluded that in this series of spindle cell tumors of the pancreas, apart from immunohistochemical features, the demonstration of p53 mutations may be helpful in distinguishing true neoplastic tumors from pseudotumors such as IPTs arising in the context of AIP.

Immunohistochemical detection of carcinoma in radical prostatectomy specimens following hormone therapy.

Following hormone therapy, residual carcinoma is frequently difficult to identify on HE‐stained prostatectomy specimens. The aim of the present study was therefore to investigate whole‐mounted specimens obtained by radical prostatectomy from patients who had undergone hormone therapy. Formalin‐fixed and paraffin‐embedded specimens were immunostained with prostate secretory cell markers including prostate‐specific antigen (PSA), P504S (α‐methylacyl‐coenzyme A racemase, AMACR), P501S (prostein), and prostate‐specific membrane antigen (PSMA). Residual carcinoma was detected in 250 histological slides of 42 patients in a total of 497 slides from 45 patients. In five of 250 slides (2%), carcinoma was not able to be recognized on HE‐stained slides, but was found on the immunohistochemistry slides. PSMA had reacted positively beyond a moderate degree in carcinoma from all patients. PSA was positive for carcinoma in most of the patients, while negative or minimal staining was observed in a small number of patients. Carcinoma was positively reactive with P504S and P501S in most of the patients, but was negatively reactive in a few. The Gleason score for a pretreatment needle biopsy correlated with P504S staining of the prostatectomy specimens. P504S and P501S had limited ability to identify degenerated carcinoma. PSMA was the most useful marker to identify carcinoma after hormone therapy.

Malignant glomus tumor in the branchial muscle of a 16-year-old girl.

Malignant glomus tumor is an extremely rare neoplasm and its histological features are not well characterized. We report a 16‐year‐old female patient with a malignant glomus tumor. The patient was admitted to our hospital presenting with a mass in the right upper arm that she had noticed for the previous 6 months. Computed tomography and magnetic resonance imaging revealed an expanded mass involving the surrounding tissues. At surgery, an ill‐defined and expanded mass was found, 5 × 4 × 3 cm in size, in the right branchial muscle. The tumor was extirpated, along with neighboring muscle tissues. Histologically, tumor cells were round to short‐spindle shaped, forming solid sheets admixed with vessels of varying size. Their nuclei were uniformly oval to round, and their cytoplasms were slightly eosinophilic. The growth pattern of the tumor cells resembled that of glomus tumor, but mitotic figures were frequent (as high as 10 per 10 high‐power fields). Immunohistochemically, the tumor cells were positive for vimentin and muscle actin, but negative for desmin. There were no areas typical of benign glomus tumor or sarcomatous change. These findings led us to a diagnosis of primary malignant glomus tumor arising de novo. There has been no recurrence or metastasis for 21 months after wide excision.

A case of hibernoma arising in the scapular region.

背景:褐色脂肪腫は褐色脂肪組織に由来するまれな腫瘍で, 臨床病理学的, 電顕的には多数の研究がなされているが, 細胞所見に関する報告はきわめてまれである.症例:63歳女性. 左肩甲部腫脹を主訴に当院を受診, 腫瘍部の穿刺捺印細胞診にて褐色細胞腫が疑われ腫瘍切除が施行された. 皮下脂肪組織内に大きさ8×8×3cm, 境界明瞭な黄褐色の腫瘍を認めた. 捺印細胞診では大型類円形ないし多辺形の細胞が集塊状に出現, 毛細血管の介在も認めた. 構成細胞は微細穎粒状胞体を有するもの, 多空胞状胞体を有するもの, 単空胞状の胞体を有し脂肪細胞に類似するもの, の3種類で, ときおり胞体に色素穎粒が観察された. いずれもN/C比は小さく核は小型類円形, 核縁は平滑で1個の核小体を有していた. 組織学的には典型的な褐色脂肪腫の所見を示し, ズダンIII染色陽性, 一部の細胞の胞体にはリポフスチン穎粒が認められた. 電顕的には腫瘍細胞胞体に豊富なミトコンドリアと種々の程度の脂肪空胞を認めた.結論:本腫瘍は異型性の乏しい3種類の細胞から構成され, しばしば胞体にリポフスチン穎粒を認めることから, それらの特徴が細胞学的診断にも有用と考えられた.

A case of primary malignant lymphoma of the uterine corpus detected by cervical smear.

背景:子宮体部原発の悪性リンパ腫はきわめてまれな腫瘍であるが, 今回子宮癌検診で発見された1例を経験したので報告する.症例:57歳女性.子宮癌検診の頸部擦過細胞診にて悪性リンパ腫が疑われ, 子宮内膜生検でBcell typeの非ポジキンリンパ腫と診断された.全身検索にて, 子宮体部以外に病変はみられず, 子宮体部原発悪性リンパ腫 (Ann-Arbor分類Stage IE) の診断のもとに, 準広範子宮全摘術と, 術後化学療法5クールが施行された.結論:今回のわれわれの症例は子宮体部原発にもかかわらず, 検診時の子宮頸部擦過細胞診にて発見された.その理由として腫瘍が子宮内腔に突出しており, 表面が壊死性で, 腫瘍細胞が剥離しやすかったことが考えられる.腫瘍細胞は弱拡大でリンパ球の集簇のようにみえたが, 核はやや大きく, 核形の不整が著明で, 悪性リンパ腫の診断は比較的容易であった.

REACTIVITY OF ANTIBODY YU-311 IN FORMALIN-FIXED, PARAFFIN-EMBEDDED SPECIMENS OF NORMAL ORGANS, NON-HEMATOPOIETIC TUMORS, AND MAST CELL TUMORS

YU‐311 Is a monoclonal antibody that reacts with a human leukemia cell line resistant for cytoslne arabinoside and that Identifies a 92 kDa membrane protein. The reactivity of YU‐311 in normal organs, various non‐hematopoietic tumors and in mast cell tumors In formalin‐flxed, paraffinembedded specimens was examined using immunohlstochemlcal methods. in normal organs, YU‐311 reacted with fundic glands of the stomach, the Intercalated duct of the pancreas, the distal portion and the loop of Henle of renal tubules and tlssue mast cells. Benign neoplasms of various organs showed no immunoreactlon with YU‐311, except for mast cell tumors. Some types of malignant neoplasms were occasionally positive against YU‐311, suggesting neoplasms arising from or differentiating along normal YU‐311‐positive counterparts. Some other types of malignancies were rarely positive for YU‐311, although their normal counterparts showed no immunoreactlvity with YU‐311. None of the non‐epitheilal tumors reacted with YU‐311, except for one case of malignant melanoma. in contrast, normal tissue mast cells and their related tumors, such as urtlcarla pigmentosa or solitary mastocytoma, were constantly positive for YU‐311. None of the non‐hematopoietlc human tumor cell lines examined in the present study was reactlve with YU‐311. These findlngs indicate that YU‐311 is a good marker of some types of tumors and mast cell tumors and that an aberrant expression of YU‐311 rarely occurs.