Osamu Matsuzaki

Collecting Duct (Bellini Duct) Renal Cell Carcinoma: A Nationwide Survey in Japan

PURPOSE Collecting duct carcinoma, a rare type of renal cell carcinoma, remains poorly understood. To analyze the nature of collecting duct carcinoma a retrospective survey was performed in Japan. MATERIALS AND METHODS This survey was done from August 2001 to April 2003. A total of 281 institutions throughout Japan were requested to document all cases of collecting duct carcinoma. All pertinent clinical information was compiled, including patient age, sex, mode of presentation, evaluation modality, preoperative laboratory data, surgery type, macroscopic and microscopic findings, and survival data. Two urological pathologists reviewed microscopic slides of all tumor specimens to confirm collecting duct carcinoma. RESULTS Two pathologists confirmed collecting duct carcinoma in 81 of the 120 cases documented as collecting duct carcinoma. Mean patient age was 58.2 years and males comprised 71.6% of all patients. The mode of presentation was classified as symptomatic in 65.4% of cases, incidental in 24.7% and not available in 9.9%. Regional lymph node metastasis was histologically detected in 44.2% of patients who underwent lymph node dissection, while 32.1% of the population had distant metastasis at presentation. Although postoperative adjuvant therapy against metastasis or recurrence was performed in 25 patients, no obvious responses were identified except in 1 with lung metastases, who showed a partial response to combined gemcitabine and carboplatin therapy. At a median followup of 15 months 1, 3, 5 and 10-year disease specific survival was 69.0%, 45.3%, 34.3% and 13.7%, respectively. CONCLUSIONS We report what is to our knowledge the largest known series of collecting duct carcinoma. Since advanced or recurrent collecting duct carcinoma is resistant to standard treatment modalities, new treatment strategies are needed for advanced collecting duct carcinoma.

Histopathologic studies of basal cell adenoma of the parotid gland

Five‐hundred‐thirty‐one cases of primary epithelial tumors of the parotid gland were examined. The incidence of basal cell adenomas was 7.5% (40 cases). The tumors could be classified histologically into these subtypes: basal cell (21/40; 52.5%); tubular, (13/40; 32.5%); trabecular (4/40; 10.0%); and papillary (2/40; 5.0%). The pattern of classic basal cell adenoma predominated in the basal‐cell type but was also seen in varying degrees in the latter three types with a reciprocal transition. Accordingly, it could be suggested that tubular, trabecular, and papillary types are variants of basal cell adenoma. The higher incidence of basal cell adenomas in our survey could be accounted for by this categorization. Histologically, basal cell adenomas presented various features: (1) cystic formation (26/40; 65.0%), being most frequently seen in tubular and trabecular types; (2) adenoid cystic pattern (4/40; 10.0%); (3) elastosis in the stromal tissues (2/40; 5.0%). Basal cell adenomas were clinicopathologically compared with 291 cases of pleomorphic adenomas. Basal cell adenomas were seen more often in female patients, (60.0%), as were pleomorphic adenomas (68.4%). They were observed more frequently in patients over 50 years of age and the average was ten years higher than for pleomorphic adenoma. The tumor size tended to be smaller (below 2 cm at the greatest diameter) than pleomorphic adenomas.

Histopathologic studies on carcinoma in pleomorphic adenoma of the parotid gland

Five‐hundred‐eighteen cases of primary epithelial tumors of the parotid gland were examined. The incidence of carcinomas in pleomorphic adenoma was 9.3% (48 cases). In addition to cellular atypism, the following histological findings were thought to be important criteria for the diagnosis of carcinomas: (1) capsular invasion, (2) infiltration into adjacent organs, (3) proliferation of atypical cells within fibrous tissues and chondroid matrix in the area of pleomorphic adenoma, (4) vascular involvement, and (5) mitotic figures. Pleomorphic adenomas (282 cases) were found predominantly in females (70.8%), at the age of 30 to 49 (48.2%), whereas carcinomas in pleomorphic adenoma were more often found in males (70.8%) and at the ages over 50 (43.8%). Histologic types were composed mostly of undifferentiated carcinoma (56.2%) and adenocarcinoma (37.5%). The prognosis of the carcinomas, especially the undifferentiated type, was generally poor; about 45% of the cases either experienced recurrence or died within five years. Electron microscopy on this undifferentiated carcinoma revealed characteristic filamentous structure in the carcinoma cells, resembling that observed in myoepithelial cells. It was assumed that the undifferentiated carcinoma cells were of myoepithelial origin.

Progression of prostate cancer to neuroendocrine cell tumor.

Abstract Background: The progression to endocrine therapy‐resistant prostate cancer is partly due to clonal change to neuroendocrine cell tumor. To elucidate this pathologic process, the clinical courses of four cases of neuroendocrine cell tumor that were found at autopsy are reported.

Histopathologic studies of undifferentiated carcinoma of the parotid gland.

Five‐hundred‐fifty‐five primary epithelial tumors of parotid gland origin were examined. Eighteen cases could be defined undifferentiated carcinomas, constituting 3.2% of the total number or 10.2% of 176 malignant tumors. The undifferentiated carcinomas could be divided on the basis of the cell size into two types: (1) Small‐cell type (12/18; 66.7%); the tumor cells were as large as, or slightly larger than lymphocytes. The cytoplasm was scanty with dark chromatin. Mitotic figures were numerous. The tumor cells in the periphery of the cell clusters exhibited a palisading arrangement. Electron microscopy revealed that these cells were rich in tonofilaments and connected by desmosomes. (2) Large‐cell type (6/18; 33.3%); the carcinoma cells were roughly twice as large as those of the small‐cell carcinoma. The tumor cells were spheroidal or spindle in shape with rich and clear cytoplasm. Many of the tumorcell clusters showed macroalveolar structures, suggesting the possibility that this type occurred as a variant of poorly differentiated adenocarcinoma or epidermoid carcinoma. Clinicopathologically, there was no sex difference in the total number of the undifferentiated carcinomas, but the large‐cell carcinomas were frequently encountered in females (83.3%). As to the age distribution, the carcinomas were found frequently in middle‐aged patients from 30–49 years (66.7%). Many of the tumors were 2–4.9 cm at their greatest diameter (55.6%). Tumor mass less than 1.9 cm could not be found.

THE IMPACT OF A 4 CM. CUTOFF POINT FOR STRATIFICATION OF T1N0M0 RENAL CELL CARCINOMA AFTER RADICAL NEPHRECTOMY

PURPOSE The 1997 TNM classification defines T1 tumors as those smaller than 7 cm. Recently, a cutoff point of 4 cm. has been proposed to create a subclass of T1 tumors. We evaluated the validity of this cutoff point by assessing the pathological findings and prognoses of patients with T1N0M0 renal cell carcinoma following radical nephrectomy. MATERIALS AND METHODS We reviewed the hospital charts of 333 patients with T1N0M0 tumors, followed as long as 282 months (median 63) after radical nephrectomy. The validity of tumor size cutoff point for predicting survival outcome was tested in relation to other prognostic factors, including patient age, tumor position, nuclear grade, tumor histopathology and degree of microscopic venous invasion. RESULTS During followup 32 patients (9.6%) had tumor recurrence and 21 (6.3%) died of renal cell carcinoma. A 5 cm. cutoff point maximized the differences in cancer specific survival rates and a 4 cm. cutoff point maximized the differences in disease-free survival rates. Tumor size was directly related to microscopic venous invasion and nuclear grade, which are significant prognostic factors, and a 4 cm. cutoff point enhanced these relationships. CONCLUSIONS Tumor size is an important prognostic factor for patients with T1N0M0 renal cell carcinoma. A cutoff point of 4 cm. is practical for dividing the T1N0M0 classification into T1a and T1b subclasses.

A histopathologic study of benign and malignant lymphoepithelial lesions of the parotid gland.

Twenty‐three cases of benign and malignant lymphoepithelial lesions without Sjögrens syndrome were examined: 21 were classical benign lymphoepithelial lesions, and were mostly found in males older than 50 years of age. The other two cases were identified as undifferentiated carcinoma arising from benign lymphoepithelial lesion (8.7%; 2/23). Histologically, this carcinoma is characterized by the formation of cell nests of variable size and by marked lymphoplasmacytic infiltrations into the stromal tissue. In immunofluorescence, an increase of plasma cells containing IgA and IgG was noted in the marginal areas of carcinoma cell clusters. Electron microscopy disclosed that the carcinoma was composed of poorly differentiated cells with occasional squamous differentiation. No dysplastic characteristics were found in the infiltrating lymphocytic components. These two cases of carcinoma were found in middle‐aged females.

Histopathologic studies of benign infantile hemangioendothelioma of the parotid gland

Five hundred and eighty‐four cases of primary parotid gland tumors and tumor‐like conditions were examined. Primary benign hemangiomas of the parotid gland were relatively rare, comprising 29 cases (4.9%) of 584 tumors. These could be divided into either cavernous hemangioma or so‐called benign hemangioendothelioma. In our series, the incidence of the latter was 1.5% (nine cases), or 31.0% of the total number of hemangiomas. The so‐called benign hemangioendotheliomas were found in patients under the age of 12 months, during the infantile period, and occurred predominantly in females and on the right side. Histologically, this tumor showed a uniform growth pattern so that each lobular portion exhibited a strikingly identieal appearance. The vascular lumina of the tumor were lined by flattened endothelial cells that were occasionally mixed with some plump cells showing mild atypism. Electron microscopy revealed that the tumor consisted of two distinct components, one being definite endothelial cells lining the vascular channels and the other pericytes located outside of the endothelium embracing the vascular channels. The tumor cells can be interchangeable with one auother. It seems that this tumor is derived from the intralobular vascular system of the parotid gland. This tumor is benign in nature and found atmost exclusively during the infantile period. Hence, from the clinicopathologic aspect, „benign infantile hemangioendothelioma”︁ seems to be a more suitably descriptive term than simply „benign hemangioendothelioma.”︁.

Serum immunosuppressive acidic protein as a tumor marker for renal cell carcinoma

Since there are no reliable tumor markers in renal cell carcinoma, the present study was undertaken to evaluate immunosuppressive acidic protein (IAP) in patients with this tumor. Serum IAP levels were measured in 143 consecutive patients before and/or after nephrectomy by turbidimetric immunoassay. IAP levels had increased according to tumor diameter. Positivity rates of IAP were noticed as 45%, 75%, and 100% for patients with stage I/II, stage III, and stage IV diseases, respectively. Three-year survival rates also correlated with IAP: 96%, 81%, and 44% in preoperative levels below 500, of 501-1,000, and of more than 1,001 micrograms/ml, respectively. Serum IAP levels decreased within 3 months after the operation and increased with recurrence. These results suggest that serum IAP may serve as a tumor marker in patients with renal cell carcinoma.

Changes on distribution of CD4+/CD45RA- and CD8+/CD11- cells in tumor-infiltrating lymphocytes of renal cell carcinoma associated with tumor progression

To study the distribution of subsets of T cells in renal cell carcinoma, peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were analyzed in 43 untreated patients using two-color flow cytometry. An increase in the relative number of CD4+/CD45RA-, CD8+/CD11- and HLA-DR+/CD3+ cells was shown in TIL when compared with PBL. When the influence of various tumor factors on subsets of TIL was examined, a decrease in CD4, CD4+/CD45RA- and CD16+/CD57- cells and an increase in CD8+ and CD8+/CD11- cells was observed along with the aggravation of tumor stage and grade. In TIL of stage III/IV and grade III/IV disease, most patients showed an increase in CD8+/CD11- associated with a decrease in CD4+/CD45RA- cells, or the reverse, resulting in changes of the CD4+/CD45RA- to CD8+/CD11- ratio. The prognosis for these patients was poor, suggesting that changes in the ratio were a sign of the impairment of local immune status associated with disease progression.