Keiichi Honma

Lymph Node Metastasis In Small Peripheral Adenocarcinoma Of The Lung

OBJECTIVE Our aim in this study is to clarify the clinical and pathologic features of small peripheral adenocarcinoma of the lung with special emphasis on intraoperative identification of lymph node metastasis. PATIENTS AND METHODS Between 1980 and 1996, 157 patients underwent lobectomy and complete hilar/mediastinal lymphadenectomy for small (1.1 to 2.0 cm in diameter) peripheral adenocarcinoma of the lung. The intraoperative assessment, the distribution of metastatic lymph nodes, and the association between the tumors histopathologic characteristics and lymph node metastasis were retrospectively investigated in this study. RESULTS Postoperative examination revealed lymph node metastasis in 27 (17%) patients. Lymph node metastases were not noticed during the operation in 19 of these 27 patients. Metastases were localized in single lymph nodes in 10 patients; the metastases were distributed over a segmental, a lobar, an interlobar, and a mediastinal lymph node. The prevalence of lymph node metastasis was as follows: Of 92 patients with well-differentiated adenocarcinoma, seven (8%) had lymph node metastases; of the 65 patients with other types of tumors, 20 (31%) had lymph node metastases. Of 120 patients without pleural involvement, 13 (11%) had lymph node metastases; of the 37 with pleural involvement, 14 (38%) had lymph node metastases. Five-year survivals were estimated at 91% +/- 6% (mean +/- 95% confidence interval) for 130 patients with N0 tumor and 30% +/- 22% for 27 patients with N1 or N2 tumor. CONCLUSIONS Intraoperative assessment is not reliable for identifying lymph node metastasis. Lobectomy and complete hilar/ mediastinal lymphadenectomy are necessary to determine N stage rigidly. Histologic degree of differentiation and pleural involvement are significantly associated with lymph node metastasis.

Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach.

Fatty acid synthase is highly expressed in carcinoma, adenoma and in regenerative epithelium and intestinal metaplasia of the stomach

Expression of heart-type fatty acid-binding protein in human gastric carcinoma and its association with tumor aggressiveness, metastasis and poor prognosis.

Objective: Fatty acid-binding proteins (FABPs) are involved in lipid metabolism by intracellular transport of long-chain fatty acids. Heart-type (H-) FABP has been reported to inhibit cell growth and induce cell differentiation, but to our knowledge the significance of H-FABP expression in human gastric carcinoma has not been elucidated. The aim of the current study was to examine the expression of H-FABP and its relation to clinicopathologic parameters and fatty acid synthase (FAS) status of gastric carcinoma, since gastric cancer shows increased expression of FAS. Methods: Immunohistochemistry with anti-H-FABP antibody was performed in 669 gastric carcinomas and 60 tubular adenomas of the stomach. H-FABP-positive and H-FABP-negative carcinomas were analyzed for their clinicopathologic characteristics and FAS status. Results: None of the adenomas expressed H-FABP, whereas 127 of 669 carcinomas (19.0%) were positive for the protein. H-FABP positivity was associated with the depth of invasion (p < 0.0001), vascular invasion (p < 0.0001), lymph node metastasis (p < 0.0001), hepatic metastasis (p = 0.0011), stage of the carcinoma (p < 0.0001) and FAS status of the carcinoma (p = 0.0476). A higher survival rate was noted in H-FABP-negative cases compared with H-FABP-positive cases (p = 0.0004). Conclusions: A subset of human gastric carcinoma expresses H-FABP and its expression is associated with FAS status, disease progression, tumor aggressiveness and poor patient survival.

Liver-Type Fatty Acid-Binding Protein Is Highly Expressed in Intestinal Metaplasia and in a Subset of Carcinomas of the Stomach without Association with the Fatty Acid Synthase Status in the Carcinoma

Objective: To investigate the relation of liver-type fatty-acid-binding protein (L-FABP) expression to the clinicopathological characteristics or the fatty acid synthase status of gastric cancers. Methods: L-FABP expression was examined immunohistochemically in 667 gastric cancers, 60 gastric adenomas, and non-neoplastic epithelium contiguous with cancer tissue including normal foveolae, intestinal metaplasia, regenerative epithelium, and gastric glands. Results: L-FABP was positive in 38% (high in 9% and low in 29%) of gastric cancers. It occurred preferentially in papillary carcinomas, female cases, and in patients under 50 years. In gastric cancers, L-FABP expression had no intimate correlation with the FAS status, and it showed no relationship with prognosis and cancer progression as indicated by venous and lymphatic permeation, and nodal or hepatic metastasis. Gastric tubular adenomas mainly revealed low (22%) expression of L-FABP while intestinal metaplasia showed the most frequent (>95%) and intense L-FABP expression. Normal foveolae and gastric glands showed no or less L-FABP expression. Conclusions: L-FABP is highly and intensely expressed in metaplasia and in a subset of gastric adenocarcinomas, without association with progression, prognosis and fatty acid synthase status of the carcinoma.

DIFFUSE PANBRONCHIOLITIS WITH MULTIPLE TUMORLETS

An autopsy case of diffuse panbronchiolitis with incidentally observed multiple tumorlets was reported. Quantitative study revealed the distribution and number of single Kultschitzky cell and its cluster. These cells were more frequently observed in the present case than in 20 control cases, and moreover, they tended to occur more frequently in the pulmonary segment in which tumorlets were found and there was an apparent transition of them into tumorlets. Immunohistochemically, gastrin‐releasing peptide, calcitonin, and serotonin were demonstrable in the cells which consisted of both tumorlets and Kultschitzky cell clusters. It is suggested that the Kultschitzky cell is a precursor cell of the tumorlet and that tumorlet is benign, being hyperplastic in nature.

KIT expression in normal and neoplastic renal tissues : Immunohistochemical and molecular genetic analysis

Renal chromophobe cell carcinomas (ChCC) and oncocytomas express KIT. This character seems to reflect their common histogenesis from distal nephrons. In the normal kidney, however, the expression and localization of KIT are unclear. KIT expression in angiomyolipoma and congenital mesoblastic nephroma (CMN), is still controversial. c‐kit mutations are reportedly rare in ChCC, but there is little information in other renal neoplasms, and no reported data on mutations of platelet‐derived growth factor receptor (PDGFR). In order to address these issues the authors examined five ChCC, five oncocytomas, seven papillary cell carcinomas, two collecting duct carcinomas, 12 angiomyolipomas, and three CMN, as well as 10 normal renal tissues. In the normal kidney KIT was specifically expressed in the distal nephrons. Nine of 12 (75%) angiomyolipomas contained scattered KIT‐positive cells, whereas all three CMN were completely negative for KIT. The presence of KIT‐positive cells in angiomyolipomas was likely to correspond to that of melanocytic marker‐positive cells, which mainly showed epithelioid morphology. Polymerase chain reaction‐single‐strand conformation polymorphism showed no evidence of mutations of c‐kit or PDGFR in any of the tumors examined.

Immunohistochemical localization of endothelin‐1, endothelin‐3 and endothelin receptors in human pheochromocytoma and paraganglioma

Endothelln (ET) and its receptor system have been shown to exert varlous biological effects on dlfferent types of cells In addition to their well‐known vasoconstrictor activity. Recently ET‐1, ET‐3 and the ET3 receptor have been shown to play an Important role In the development of neural crest‐derived cells and, in this context, pheochromocytomas have been reported to harbor ET‐1. Endothelin‐3 or ET receptor subtypes, however, have not been examined in pheochromocytoma and paraganglioma so far. In the present study the Immunohistochemical localization of ET‐1/big ET‐1, ET‐3/big ET‐3 and the ETA and ETB receptors were lnvestigated to clarify the biological characteristics of these two tumors using 32 pheochromocytomas and 11 extra‐adrenal paragangliomas. Endothelin‐lhig ET‐1 was detected in 19 pheochromocytomas (59%) and eight paragangliomas (72%), while ET‐3hIg ET‐3 was detected in 10 pheochromocytomas (31%) and three paragangllomas (27%). The ETA receptor was found in 21 pheochromocytomas (66%) and In eight paragangllomas (73%), whlle the ETB receptor was found in 25 pheochromocytomas (78%) and In eight paragangllomas (73%). Normal adrenomedullary cells lacked each antigen examined. Endothelin‐immunoreactive tumor cells were dlstrlbuted focally or In a manner scattered, whlle receptor‐immunostained tumor cells were distributed wlth a focal pattern for the ETa receptor and wlth a focal or diffuse pattern for the ETB receptor. Endothelln and its receptor coexlsted In the same tumor in 21 of 28 ET‐posltive pheochromocytomas and in eight of 10 ET‐positlve paragangliomas. In additlon, seven pheochromocytomas and two paragangllomas revealed posltivlty of the receptor(s) irrespective of the absence of ET‐immunoreactlvlty. In concluslon, ET and Its receptor are frequently and concomitantly expressed in the pheochromocytoma and paraganglloma. From the highly frequent expression of this system or the receptor(s), ET‐receptor‐mediated slgnal transduction of these tumors concernlng growth and/or cell survival Is expected, although definite blological slgniflcance of thls llgand‐receptor system in these tumors awaits further Investigation.

Surgical results for centrally-located early stage lung cancer

BACKGROUND With the increasing use of mass screening programs for lung cancer, and especially the use of sputum cytology, the incidence of roentgenographically occult lung cancer has been increasing. These occult cancers comprise mainly histologically centrally-located early stage lung cancers. This study examined the clinicopathologic characteristics and surgical results of centrally-located early stage lung cancer. RESULTS From 1980 to 1998, there were 98 patients and 99 lesions of centrally-located early stage lung cancer resected. A total of 64 patients were detected by mass screening. Histologic examination revealed that 96 lesions were squamous cell carcinoma, and in these patients, there were 10 lesions of carcinoma in situ. The 5-year survival rate was 81.4% in all patients, and 88.9% in carcinoma in situ patients. In the postoperative follow-up period, a second lung cancer occurred in 13 patients. CONCLUSIONS The surgical results for centrally-located early lung cancer were good. However, sometimes these cancers are accompanied by a second centrally-located primary lung cancer, so it is necessary to follow-up with sputum cytology to allow early detection of additional centrally-located lung cancer.

Epithelioid Malignant Schwannoma

A case of epithelioid malignant schwannoma (EMS) is reported. The tumor arose in the left radial nerve at the axillary fossa of a 65‐year old male. A few months after resection of the primary axillary tumor, several intrapulmonary metastases appeared. Microscopically, the primary tumor showed highly cellular areas of polygonal or rounded cells, resembling lymphoma or melanoma, while the metastatic tumors revealed cord formation or rows, resembling carcinoma. Immunohistochemical studies showed that some of these tumor cells contained S‐100 protein. Ultrastructurally, these tumor cells revealed delicate cytoplasmic projections, which contained bundles of microfilaments. However, the tumor cells did not have melanosomes. Varying amounts of basal lamina material surrounded the tumor cells. From the above features, we obtained a correct diagnosis of EMS. Acta Pathol. Jpn. 32: 195∼202, 1989.

Vascular tumor in the mediastinum

Mediastinal venous hemangioma is a very rare neoplasm. Here, we describe our experience in treating a patient demonstrating such a tumor. The patient, a 23-year-old man, was admitted to our hospital because of a mediastinal cyst. A biopsy of the cystic wall was performed by Video-Assisted-Thoracic-Surgery, in April 1999. Clear serous fluid was found in the cyst, and it was thus incorrectly diagnosed to be a thymic cyst. The cyst continued to increase in size, and the patient began to show an increased temperature after being discharged. A resection of the tumor was performed in June 1999. The cyst was filled with bloody fluid and, according to the pathological analysis, was diagnosed to be a mediastinal venous hemangioma.