Hitoshi Yasoshima

Primary hepatic carcinoid tumor

A case of primary carcinoid tumor arising in the liver of a 69 year old woman with no endocrine symptoms is reported. Histopathologically, the tumor was diagnosed initially as a hepatocellular carcinoma in the biopsy specimen, and was shown subsequently to be a carcinoid tumor, demonstrating diffuse positive staining with Grimelius method. Mucin stained with periodic acid‐Schiff (PAS), alcian‐blue, and mucicar‐mine, and was shown partially in the glandular structures. Immunohistochemically, most of the tumor cells stained positively for chromogranin‐A, epithelial membrane antigen (EMA) and neuron specific enolase (NSE). Ultrastructural examination revealed electron‐dense core granules, measuring 40‐120 nm in diameter in some of the tumor cells. Intensive and careful searches pre‐ and post‐operatively revealed no other primary source of tumor other than the liver. The patient was reported well with no symptoms 31/2 years after the operation.

Increased expression of c‐erbB‐3 protein and proliferating cell nuclear antigen during development of verrucous carcinoma of the oral mucosa

The roles of c‐erbB‐3 gene and protein in the pathogenesis, progression, and outcome of oral carcinoma remain unknown. To determine whether c‐erbB‐3 expression could serve as an indicator of progression from premalignant to malignant transformation and of prognoses in patients with oral carcinoma, the authors examined the relation between the expression of c‐erbB‐3 protein and cell proliferation activity during the development of oral verrucous carcinoma (VC).

Testicular seminoma with human chorionic gonadotropin production

Testicular seminoma with elevated serum human chorionic gonadotropin level (hCG‐positive seminoma) is regarded as more malignant than marker‐negative seminoma, although Its prognosis is still unclear. To clarify the malignant potential of seminoma with hCG production, the serum levels of the beta subunit of hCG (β‐hCG) and lactic acid dehydrogenase (LDH) were examined in 35 and 40 patients, respectively, and the Immunohistochemical expression of β‐hCG examined in 45 tumors. The elevation of the LDH serum level correlated to the Invasive status, metestatic status and poor outcome, while that of the serum β‐hCG level correlated only to the metastatic status. Immunohistochemical expression of β‐hCG was observed in syncytiotrophoblastic giant cells in 11 tumors and a few mononuclear seminoma cells In 36 tumors. Expression was not associated with the malignancy potential, except where the expression In mononuclear cells Inversely correlated to the invasive status. These results suggest that most seminomas produce a slight amount of hCG; that an elevated hCG serum level Indicates the pressnce of metastatic tumors and mainly reflects an increase in tumor volume but not in cellular malignancy potential; and that the LDH serum level, rather than hCG, is more useful as a prognostic indicator for patients with seminoma.

Increased expression of cyclooxygenase‐2 in human salivary gland tumors

We examined the immunohistochemical localization of cyclooxygenase (COX)‐2 in human salivary gland tumors. Thirty salivary gland adenomas (SGA), 40 salivary gland carcinomas (SGC) and 15 normal salivary glands (NSG) were studied. NSG showed restricted COX‐2 staining only in the epithelial cells of salivary ducts. In contrast, COX‐2 protein was detected in 27 cases of SGA (90%), except for three myoepitheliomas, and in all cases of SGC (100%) at various intensities and in various fashions. Thirteen SGA (43%) and 36 SGC (90%) cases showed strong COX‐2 staining predominantly in tumor cells containing ductal components, as did serous and mucous acinic components of acinic cell carcinomas, mucoepidermoid carcinomas and mucinous carcinomas. These findings may suggest that COX‐2 in salivary gland tumors is expressed in tumor cells derived from pluripotential ductal epithelium that can histologically develop into either serous or mucinous acinar cells.

CONTRIBUTION OF CELL PROLIFERATIVE ACTIVITY TO MALIGNANCY POTENTIAL IN TESTICULAR SEMINOMA

Testicular anaplastic seminoma, which has a high mitotic activtiy, is regarded aa more malignant than typical seminoma, although its prognosis is still unclear. To determine whether seminoma with relativety greater malignancy potential can be ldentified based on the cell proliferative activity, the mitotic rate (MR; mitotic count per high‐power field), mitotic Index (MI; mitotic count per 1000 cells), Ki‐67 labeling Index (K1–67 LI; the percentage of positive cells) and prolifereting cell nuclear antigen LI (PCNA LI; the percentage of positive cells) were histologically examined In 44 patients. The MI, Kl‐67 LI and PCNA LI In patients with metastatlc disease were signmeantly higher than those in patients without metastatic disease, and the MI In patients with fatal disease was signmcantly higher than those in patients cured of the disease. However, these distributions of the MI, K1–67 LI and PCNA LI values overiapped for both pairs of groups. There were no significant differences in the YR. These results suggest that the cell proliferatbe activity makes a small contribution to the malignancy potential in testicular seminoma, with the activity being not necessarily indicative of metastasis and prognosis.

Candida parapsilosis endocarditis that emerged 2 years after abdominal surgery.

A 22-year-old man was hospitalized after 3 months of persistent fever and malaise. He had undergone abdominal surgery 24 months before admission. Echocardiography demonstrated two mobile pedunculated masses in the right ventricle. Multiple blood cultures were positive for Candida parapsilosis. After 4 weeks of miconazole treatment, the two masses were excised via a right atriotomy incision and the transtricuspid value approach. Histological examination revealed that they were fungal vegetation. Antifungal agents were continued for 1 year after surgery. The patient has remained well with no further symptoms for 3 years. This case suggests the necessity for careful evaluation of past history to avoid diagnostic delay in fungal endocarditis.

Hepatocellular carcinoma complicating autoimmune hepatitis without either hepatitis C viral infection or corticosteroid therapy.

She was readmitted to our hospital in June 2000 because of hematemesis. Endoscopic examination demonstrated rupture of esophageal varix, and sclerotherapy was performed. She was also readmitted in June 2001, for the same reason, and blood transfusion was performed. Serum α-fetoprotein was elevated to 62.3ng/ ml, and serum total bilirubin level also gradually became elevated. She died of liver failure in August 2001. Autopsy demonstrated a hepatoma, measuring 7cm in diameter, in the cirrhotic liver. The tumor was recognized as HCC (Fig. 1). Histology of the nontumorous area showed macronodular cirrhosis with interface hepatitis (Fig. 2). There was a small amount of liver cell rosetting (Fig. 3) and plasmacytic infiltration. Neither hepatitis B virus DNA nor HCV RNA was detected in extraction from paraffin-embedded liver tissue by real-time polymerase chain reaction (PCR) or reverse transcriptase-PCR assay.1 Watanabe et al. described the natural course of a patient with HCV-seronegative AIH who had not received corticosteroid therapy, but had developed HCC, and suggested that the development had been related to the cirrhosis itself rather than to corticosteroid therapy.4 The present patient had not received corticosteroid therapy either and also had cirrhosis, but did not demonstrate HCV RNA in either serum or liver tissue. Therefore, our case further suggests that HCC can occur even in patients with serum and tissue HCV-negative AIH without corticosteroid therapy, and screening for HCC should be performed in patients with AIH complicating cirrhosis, regardless of the results of serum HCV detection. The development of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH) is a rare event.1 Hepatitis C virus (HCV) is a carcinogen, and its detection in liver tissue has been reported in two of four HCV RNA-seronegative patients with HCC complicating AIH.1 Corticosteroid has been used in patients with AIH; however, this therapy is regarded as a risk for the development of HCC.2 Herein, we report a woman with HCC complicating HCV-tissue-negative AIH without corticosteroid therapy. An 89-year-old woman was admitted to our hospital in July 1999 because of tarry stool. Endoscopic examination demonstrated hemorrhagic gastritis and esophageal varices without plug. Computed tomography scans showed a mass measuring 4cm in diameter in a cirrhotic liver, suggesting HCC. Laboratory data are shown in Table 1. There was no evidence of any viral hepatitis infection, and she had no history of either a blood transfusion or of drinking liquor. There was no history of using known or suspected hepatotoxic drugs, and she had no remarkable past medical history, except for mild diabetes beginning 3 years earlier. We scored the AIH as 16 in this patient, using a scoring system for the diagnosis of AIH (definite AIH, 15).3 Her family history was not contributory, except that one of her six children, a daughter, has Behçet’s syndrome. The patient was 140cm in height and weighed 51kg. There was foot and face edema, but no ascites and no struma. Thyroid function suggested autoimmune thyroiditis (Table 1). Corticosteroid therapy was not performed because of her advanced age, hemorrhagic gastritis, diabetes, HCC, and absence of severe hepatitis. She was treated with a proton pump inhibitor for the gastritis, and discharged.

Benign mesenchymoma of the cheekReport of a case and review of the literature

Benign mesenchymoma is a soft tissue neoplasm that contains 2 or more differentiated mesenchymal components in addition to fibrous tissue. A rare case of benign mesenchymoma of the cheek in a 6-year-old boy is presented. The literature pertaining to mesenchymoma in the head and neck region is reviewed and discussed.

Endovascular papillary angioendothelioma (Dabska tumor) in an elderly woman

A patient with endovascular papillary angioendothelioma with a low grade of malignancy showing papillary proliferation of endothellold cells Is presented. The patient, an 83‐year‐old woman, underwent resection of a tumor of the neck. At operation a 9×7 cm cystic tumor containing yellow transparent liquid with clots was found In the subcutaneous tissue. Histological studies showed endotheliold cells with spindle‐shaped nuclei proliferated in layers around the fibrovascular cores, which showed the characteristic appearance of papillary proliferation. These cells were Immunohlstochemlcally positive for CD31, CD34 and factor VIII‐related antigen. Based on these observations, the tumor was considered to be an endovascular papillary angioendothelioma (Dabska tumor). Dabska tumor Is a vascular tumor with a low grade of malignancy and usually occurs in infants and young children. About 13 cases of Dabska tumor have been reported. The occurrence of a Dabska tumor In an aged patient is considered to be rare.

Immunohistochemical analysis of the nm23 gene products in testicular seminoma.

The nm23 gem, has been ldenwied as a metastasis suppressor gene. To clam the role of nm23 as a metastasis sup pressor gene In testicular seminoma, the expression of the nm23‐Hl and ‐H2 proteins (human nucleoside‐dlphosphate kinase‐A and ‐B) was Immunohistochemically examined in 43 patients. Thirty‐six (84%) and 21 (49%) of the 43 primary tumors were posithre for the nm23‐H1 and ‐H2 proteins, respecthrely. There was no significant difference in either nmH1 or ‐H2 expression between the 24 primary non‐invashre tumors and the 19 primary invasive tumors, or between the 31 primary tumors without metastasis and the 12 primary tumors with metastasls. In all, and 5 of 6 meta‐static tumors, the expression of nm23H1 and ‐H2 proteins was obsenred, respectively, and the expression was not decreased in the metestetlc tumors, compared to the primary tumors. In conclusion, the lmmunohistochemlcal expression of both the nm23‐Hl and ‐H2 gene products is not associated with the metastatic status or the invasive status of testicular seminoma, and it Is unlikely to be a useful non‐metastatic Indicator for testicular seminoma. Further studies are needed to elucidate the biological role of nm23.