Toshiro Kawai

MEN1 gene mutations in sporadic neuroendocrine tumors of foregut derivation

Foregut‐derived neuroendocrine (NE) tumors occur sporadically or in association with multiple endocrine neoplasia type 1 (MEN1) syndrome. Thirty‐nine sporadic NE tumors of foregut derivation (six thymic, 21 bronchial, three gastric, and nine pancreatic tumors) as well as two hindgut‐derived rectal carcinoids for somatic MEN1 gene mutation were analyzed by direct sequencing analysis. Five tumors showed mutations: nonsense mutations (Q393X and R98X) in thymic and pancreatic NE tumors, respectively, a 4 b.p. deletion (357del4) in a gastric NE carcinoma, and missense mutations (D172Y and S178Y) in pancreatic NE tumors. No mutation was identified in pulmonary or rectal NE tumors. In a patient with a pancreatic NE tumor (D172Y), the corresponding germline DNA showed the same mutation, suggesting that sporadic MEN1 syndrome was masked in this case. Somatic MEN1 gene mutations and deletions may play a crucial role in the tumorigenesis of a subset of foregut‐derived NE tumors. Sporadic MEN1 syndrome may occur as a sporadic NE tumor of the pancreas.

Mucinous cystadenoma of the testis

A 35‐year‐old man complained of a painless enlargement of the right testis. Imaging diagnostic procedures demonstrated a multiloculated cystic tumor, 9 cm in maximal diameter, in the right testis with hydrocele. Orchidectomy specimen showed that the tumor was confined within the testis and separated from the epididymis. The locules of the tumor were lined by single‐layered columnar epithelium, intermingled with MUC2 immunopositive goblet and chromogranin‐A immunopositive neuroendocrine cells, exhibiting intestinal differentiation. No ciliated cell, teratomatous element or intratubular germ cell neoplasia were seen. Channels of rete testis were compressed peripherally by the tumor but there was no connection with the tumor locules. The tumor was diagnosed as mucinous cystadenoma of the testis. This seems to be the first published case of benign mucinous cystadenoma occurring within the testis. This intratesticular tumor with intestinal differentiation may represent a benign monodermal teratoma.

CRYSTALLINE STRUCTURES IN HUMAN PANCREATIC BETA CELL ADENOMA

An electron microscopic observation on a pancreatic tumor removed from a 34‐year‐old woman revealed the fine structural morphology of a functional beta cell adenoma. Characteristic PAS positive crystalline structures were frequently observed in the cytoplasm of the tumor cells. They were not bounded by a membrane and had a rectangular or irregular hexagonal shape. Highly regular patterns were seen as such as lattice or honeycomb and parallel ripple structures. They are similar to the Reinkes crystal or crystalline structures reported in human hepatocytes suffering from several different diseases and considered as a protein‐carbohydrate complex. Occasionally, small paracrystalline structures appeared to indicate an immature type of these structures in the opaque fine fibrillar mass. Crystalline or paracrystalline structures were not detected in the normal pancreatic tissue removed with the tumor from the patient.

Pleomorphic carcinoma of the pancreas with massive lymphocytic stromal infiltration and long-term survival after resection

SummaryBackground. Pleomorphic carcinoma of the pancreas is a rare tumor with an extremely poor prognosis. The mean survival time is reported to be approx 3 mo.Clinical and Histological Findings. A 56-yr-old Japanese man presenting with general fatigue, loss of weight, and high fever was found to have a large hypervascular mass in the body of the pancreas with regional lymph node metastases. Laboratory investigation revealed leukocytosis, elevated erythrocyte sedimentation rate (ESR), and high serum C-reactive protein (CRP). In addition to distal pancreatectomy, splenectomy and lymph node dissection were performed. Histology showed the presence of pleomorphic large cells with bizarre mono- or multinuclei, growing in sarcomatoid pattern without mutual cohesiveness. Another noticeable finding was massive lymphocytic infiltration of the stroma of the neoplasm. Immunohistochemically, the infiltrating lymphocytes consisted of cytotoxic type of T cells. In addition, in situ hybridization for Epstein-Barr virus-encoded RNA (EBAR-1) was not seen in the tumor cells or in lymphocytes. After surgery the patient did not undergo chemotherapy or radiotherapy. He has been well without recurrence for 8 yr.Conclusion. We report a case of pleomorphic carcinoma, possibly lymphoepithelioma-like carcinoma, of the pancreas with massive lymphocytic stromal infiltration and long-term survival after resection. Cytokine responses and cellular immunoreactivity may have contributed to a long-term survival, which is unusual in the common type of pleomorphic carcinoma of the pancreas.

ALPHA‐FETOPROTEIN PRODUCING RHABDOMYOSARCOMA OF THE ADULT LIVER

An autopsy case of a rare primary tumor in a 76‐year‐old man is described. The tumor is histologically comprised of rhabdomyoblasts massively infiltrating without any epithelial elements referable to be as hepatoma. There was no evidence that regarded the hepatic tumor as metastatic secondary tumor in histological examination of other organs. Furthermore, interesting was the production of alpha‐fetoprotein from the tumor cells that was detected by immunofluorescent antibody technique. Review of the literature on primary liver rhabdomyosarcomas or adult hepatoblastomas shows no similar case. ACTA PATH. JAP. 29: 485–491, 1979.

Malignant mesenchymoma of the heart

A case of a rare primary cardiac tumor in a 46‐year‐old woman is described. The tumor arose from the left atrium and was histologically composed of multiple mesenchymal elements of fibrosarcoma, rhabdomyosarcoma, chondrosarcoma, myxosarcoma, and liposarcoma. Metastasis of this tumor occurred in the left femur, lung, and hilar lymph nodes after the second heart operation. Histogenesis of malignant mesenchyoma was considered with a survey of the literature.

Absence of initiating activity by quercetin in the rat liver

Initiating activity of quercetin was tested in rats which were treated with partial hepatectomy and given a liver cancer promoter, phenobarbital. A few intestinal neoplasms were seen but without significant difference in incidence from those in the quercetin-untreated group. Moreover, neither neoplastic nor preneoplastic liver changes were detected in quercetin-treated groups. With hepatocyte primary culture/DNA repair test, quercetin did not produce genotoxicity. The results show that quercetin has no initiating or genotoxic activities in the rat liver.

Effect of storage on carcinogenic activity of bracken fern.

Effect of storage on carcinogenic activity of bracken fern was examined with inbred strain ACI rats of both sexes. The experiment was broken down into 3 groupings: Group I received a diet containing fresh dry bracken powder: Group II received a diet which contained the same dry bracken powder used in Group I but preserved for 1 year at 4 degrees C (Group II-C) or room temperature (Group II-R); Group III received the diet containing bracken powder preserved for 2 years at 4 degrees C (Group III-C) or room temperature (Group III-R). Three control groups corresponding to Groups I, II and III were fed a normal basal diet. Significant differences in incidence of ileal tumors were observed between Group I and both groups of Group III and latent period of intestinal tumors in Group II or III was longer than that of Group I. The results indicate a decreased carcinogenic activity of bracken fern by preservation.

A case of endometrial adenocarcinoma with microglandular hyperplasia-like pattern.

今回われわれは, 子宮内膜に発生したmicroglandular adenocarcinomaの1例を経験したので報告する.症例は65歳女性, 不正性器出血を主訴とし受診した.超音波検査にて内膜増殖症が疑われ内膜細胞診, 組織診が施行された.その細胞像は, 小型でやや大小不同を示す微小腺管構造が特徴的で, 粘液貯留により嚢胞状に拡張した腺管内には好中球がみられ, 一部で集籏し微小膿瘍状を呈した.腺管周囲の重積性の構成細胞は円形核, 細顆粒状のクロマチン, 明瞭な核小体をもち核問距離は不均等であった.細胞内粘液による核圧排像やシート状配列にみられた豊富な細胞質から, 高分化な粘液性腺癌と診断された.生検組織診でも, 頸部に発生するmicroglandular hyperplasiaに類似した組織像であったが, 内膜から得られた検体であること, 細胞異型がみられることから診断確定のため子宮内膜全面掻爬が行われた.その組織像もほとんど生検と同様であったが, 一部に類内膜腺癌の組織像が得られ, microglandular adenocarcinomaと診断, 子宮が摘出された.手術標本では, 腫瘍の大部分はrnicrogladularな構造を有する乳頭状増殖であったが, 深部の腫瘍は定型的な類内膜腺癌 (G1) で, 子宮筋層に浸潤していた.

A case of oxyphilic cell adenoma of the thyroid associated with intranuclear cytoplasmic inclusions and grooves.

We report a case of oxyphilic cell adenoma of the thyroid gland in a 79-year-old female. Fine needle aspiration cytology revealed isolated or sheetly-arranged tumor cells which had abundant eosinophilic granular cytoplasm. Eccentric nuclei showed intranuclear cytoplasmic inclusions and grooves. Histologically, a follicular adenoma, oxyphilic cell type was well-encapsulated and did not show vascular invasion or metastasis.