Artificial sweeteners and bladder cancer in Manchester, U.K., and Nagoya, Japan.

We have evaluated the relation between cancer of the lower urinary tract ("bladder cancer") and the use of artificial sweeteners, by means of case-control studies in Manchester, U.K., and Nagoya, Japan, areas where extensive use occurred 30-40 years ago. In each area, a broadly based series of cases (555 in Manchester, 293 in Nagoya) was interviewed and a series of controls (735 in Manchester, 589 in Nagoya) chosen from the general population. A history of use of sugar substitutes primarily saccharin, was not associated with an elevated risk of bladder cancer in either study area. Risk of bladder cancer did not increase regularly with frequency or duration of use of sugar substitutes. Data on dietetic beverages were not obtained in Nagoya. This exposure was not associated with a greater risk of bladder cancer in Manchester. The results of this study suggest that use of artificial sweeteners confers little or no risk of bladder cancer.     

Prognostic significance of histologic grading compared with subclassification of papillary thyroid carcinoma

BACKGROUND: Papillary thyroid carcinomas represent a diversity of morphologic subtypes and variants, but to the authors' knowledge the prognostic significance of subclassification is not clear. Therefore, the authors compared the value of histologic classification with a combined assessment of histologic key features such as marked nuclear atypia, tumor necrosis, and vascular invasion (i.e., histologic grade). METHODS: One hundred twenty-eight surgically treated patients with papillary carcinoma > 10 mm were studied. The tumors were subclassified and individual histologic features were examined and compared in univariate and multivariate survival analyses. RESULTS: Of all the cases, 55% were of the usual type, whereas 27% showed complex histologic features with different components present and 18% represented specific subtypes. Tall cell differentiation showed an increased frequency of tumor necrosis and vascular invasion, and tumors with solid areas had an increased occurrence of mitotic figures and vascular invasion. Patients with tall cell tumors tended to have reduced survival (P = 0.074), and two patients with columnar cell features died of the disease. When combined, the group of patients with all tumor subtypes had significantly reduced survival when compared with the remainder of patients (P = 0.034), although the difference was only minor. Histologic grade was highly significant (P = 0.0001) in survival analysis, together with mitotic frequency (P = 0.028), S-phase (P = 0.015), and G(2)M-phase fractions (P = 0.040). In multivariate analysis, tumor dimension (P = 0.019) and histologic grade (P = 0. 008) showed significant and independent prognostic importance, whereas subclassification was not found to be significant. CONCLUSIONS: Subclassification of papillary thyroid carcinomas had only a minor prognostic impact, whereas histologic grade was a strong and independent prognostic marker. The authors recommend that all papillary carcinomas be given a histologic grade based on a combined examination of nuclear atypia, tumor necrosis, and vascular invasion. [See editorial on pages 1766-68, this issue.] Copyright 2000 American Cancer Society.     

Gastric cancer heterogeneity

This study was carried out on 222 samples from 37 gastric carcinomas to assess the incidence of multiple stem lines in primary tumors and metastasis as reflected by multiple DNA stem lines and their relationship to epidermal growth factor (EGF) receptor expression, histologic grade, tumor size, and degree of wall infiltration. Fifteen primary tumors (40.5%) were homogeneously diploid/peridiploid whereas 22 (59.5%) were aneuploid. In the lymph node metastasis, seven patients (29.2%) had an homogeneous diploid/peridiploid pattern in all metastatic lymph nodes. On the other hand, 17 (70.8%) had at least one aneuploid peak in the lymph node metastasis. DNA content heterogeneity was seen in 12 (33%) of primary tumors whereas 14 (66.6%) of 21 patients had multiple cell clones in the metastasis. Therefore, 12 patients had a metastatic clone which was not observed in the primary tumor. DNA content heterogeneity was seen even in tumors with submucosal invasion suggesting that this phenomenon is also present at earlier stages. No correlation between the histologic grade and the DNA distribution was observed. Furthermore, histologic heterogeneity was independent of DNA content heterogeneity. The EGF receptor expression was observed in six of the 23 patients in whom this analysis was done. The EGF receptor expression was constant in all samples which were studied and even samples with a different DNA content and histologic grade were stables for the EGF receptor expression.     

Rate of detection of lymph node metastasis is correlated with the depth of submucosal invasion in early stage gastric carcinoma.

BACKGROUND: Gastric carcinoma invading the submucosa is often accompanied by lymph node metastasis. However, the relation between the depth of submucosal invasion and the status of metastasis has not been investigated. The objective of this study was to clarify the relation between lymph node status and the histologic features of gastric carcinoma invading the submucosa. METHODS: The histopathology of 118 patients who underwent gastrectomy and lymph node dissection for gastric carcinoma invading the submucosa was examined. These pT1 tumors with invasion of the submucosa were confirmed by histologic examination of the resected specimens. Tumor size, depth of submucosal invasion, histologic type, and macroscopic type were investigated in association with presence or absence of and anatomic level of lymph node metastasis. RESULTS: Among the 118 patients, 16 (14%) had lymph node metastasis, and the status of metastasis significantly correlated with tumor size and depth of submucosal invasion. The frequency of metastasis to perigastric lymph nodes and extragastric lymph nodes was 0% and 0% for < or =1-cm tumors, 5% and 1% for 1- to 4-cm tumors, and 46% and 15% for >4-cm tumors, respectively. There was no lymph from a node metastasis in tumors with less than 300 microm of submucosal invasion. The frequency of lymph node metastasis for tumors with 300-1000 microm and >1000 microm of submucosal invasion were 19% and 14%, respectively. CONCLUSIONS: Tumor size and depth of submucosal invasion serve as simple and useful indicators of lymph node metastasis in early stage gastric carcinoma. Optimal lymph node dissection levels are as follows: 1) local resection (D0) for lesions < or =1 cm, 2) limited lymph node dissection (D1) for 1- to 4-cm lesions, and 3) radical lymph node dissection (D2) for lesions >4 cm. When submucosal invasion of a locally resected tumor is more than 300 microm, additional gastrectomy and lymph node dissection are necessary.     

Some international differences in histology and survival in breast cancer

Survival rates for patients with breast cancer have been reported to be higher in Japan than in the United States. It has also been reported that histologic features associated with more favorable survival are more frequent in Tokyo than in the United States. In this report data are presented on the question of whether differences in breast cancer histology could account for the differences in survival rate between Tokyo and two western areas–Boston, USA, and Glamorgan, Wales. Intraductal carcinoma was found to be most frequent in Tokyo and least frequent in Boston, but survival differences between the two cities were found when non-invasive cases were excluded. Low (relatively malignant) nuclear grade was observed most often in Glamorgan; there was little difference in frequency of this characteristic between Boston and Tokyo. Since nuclear-grade specific survival ratios were highest in Tokyo, this histologic feature also does not account for the better survival experience of Japanese patients. Tumors of medullary histologic type and those with high degrees of lymphoid infiltration were most frequent in Japan and least frequent in Boston. However, the relationships of histologic type and lymphoid infiltrate to survival were not consistent in the three areas, and the higher survival ratio of the Japanese patients could not be related to these characteristics.     

Correlation of DNA ploidy and clinical outcome in early gastric carcinomas

The nuclear DNA content was measured in 120 early gastric carcinomas and the results correlated with histologic findings and S-phase fractions measured by in vivo bromodeoxyuridine (BrdU) labeling. Forty-six cases (38%) were diploid and 74 cases were aneuploid. In aneuploid tumors, incidence of submucosal invasion, vascular invasion, and lymph node involvement were significantly higher than that in diploid tumors. In addition, the S-phase fractions in aneuploid tumors were significantly higher than those in diploid tumors. There was no recurrence in diploid tumors; whereas 21% of cases with aneuploid tumors recurred. These results indicate that DNA content may be a prognostic factor in early gastric carcinoma.     

Perineural spread of basal cell carcinomas treated with Mohs micrographic surgery

BACKGROUND: Perineural spread is a well-documented feature of cutaneous tumors and may portend a more aggressive course. The incidence of perineural invasion in basal cell carcinoma (BCC) is reportedly 1%. The authors sought to determine whether perineural spread occurs more commonly than previously thought. METHODS: The authors prospectively evaluated 434 patients with BCC treated with Mohs surgery, assessing the presence or absence of perineural inflammation and invasion in tumors requiring more than one stage of surgery. They also documented the demographic features, clinical characteristics, histologic subtype, and operative data in each case. RESULTS: Seventy-eight BCCs required more than one stage of Mohs surgery. Perineural inflammation, perineural tumor invasion, or both were present in 29 of the 78 tumors (37%), or 6.7% of all 434 prospectively evaluated cases. Twenty-one of the 78 tumors (26.9%) exhibited perineural inflammation, 3 (3.8%) demonstrated perineural invasion, and 5 (6.4%) exhibited both. Tumors with perineural invasion required 5.3 surgical stages on average for clearance, in contrast to tumors without perineural invasion, which required 2.2 stages. Tumors with perineural inflammation, inflammation plus tumor invasion, and invasion alone were, respectively, 138%, 149%, and 194% greater in area preoperatively than tumors without perineural involvement, and their mean defect areas after Mohs surgery were, respectively, 151%, 121%, and 605% larger than those of tumors without perineural involvement. CONCLUSIONS: The incidence of perineural invasion among cases of BCC appears higher than previously recognized. Tumor aggressiveness appears to correlate with the presence of perineural invasion. Surgery with horizontal frozen-section margin control enables easy detection of perineural involvement and should therefore be strongly considered for the treatment of high risk BCC patients.     

Expression of pepsinogen II in gastric cancer. Its relationship to local invasion and lymph node metastases

We have determined the prevalence of pepsinogen II (PG II) immunoreactive cells in a large series of early and advanced gastric cancers and relationships among PG II-positivity, tumor histologic type, extent of gastric wall invasion, and presence of lymph node metastases. Of the 316 cancers evaluated, 150 (47%) expressed PG II. The prevalence by histologic type was 55% in 146 glandular tumors, 43% in 83 diffuse tumors, 16% in 25 mucoid tumors, and 51% in 59 mixed-type cancers. Two parietal cell cancers and one undifferentiated cancer were PG II-negative. In glandular and diffuse cancers, but not mucoid and mixed tumors, both the extent of gastric wall invasion and incidence of lymph node metastases were associated positively with PG II expression by the primary tumor. In particular, PG II-reactive cells were found significantly more often in advanced than in early diffuse cancers (P less than 0.05) and significantly more often in submucosal early cancers than in intramucosal early cancers (P less than 0.01). The prevalence of PG II expression also was higher significantly in metastatic cancers than in nonmetastatic cancers. This was true for advanced gastric cancers as a whole (P less than 0.01), advanced glandular-type cancer alone (P less than 0.01), advanced glandular- and diffuse- type cancers together (P less than 0.001), and early diffuse-type cancer (P less than 0.05). Only four (3%) of 145 cancers evaluated for pepsinogen I (PG I) were positive, and each also was positive for PG II. The results suggest that the expression of PG II by glandular and diffuse types of gastric cancer may be a marker of increased malignancy.     

Defining Morphologic Features of Invasion in Pulmonary Nonmucinous Adenocarcinoma With Lepidic Growth: A Proposal by the International Association for the Study of Lung Cancer Pathology Committee

IntroductionSince the eight edition of the Union for International Cancer Control and American Joint Committee on Cancer TNM classification system, the primary tumor pT stage is determined on the basis of presence and size of the invasive components. The aim of this study was to identify histologic features in tumors with lepidic growth pattern which may be used to establish criteria for distinguishing invasive from noninvasive areas.MethodsA Delphi approach was used with two rounds of blinded anonymized analysis of resected nonmucinous lung adenocarcinoma cases with presumed invasive and noninvasive components, followed by one round of reviewer de-anonymized and unblinded review of cases with known outcomes. A digital pathology platform was used for measuring total tumor size and invasive tumor size.ResultsThe mean coefficient of variation for measuring total tumor size and tumor invasive size was 6.9% (range: 1.7%–22.3%) and 54% (range: 14.7%–155%), respectively, with substantial variations in interpretation of the size and location of invasion among pathologists. Following the presentation of the results and further discussion among members at large of the International Association for the Study of Lung Cancer Pathology Committee, extensive epithelial proliferation (EEP) in areas of collapsed lepidic growth pattern is recognized as a feature likely to be associated with invasive growth. The EEP is characterized by multilayered luminal epithelial cell growth, usually with high-grade cytologic features in several alveolar spaces.ConclusionsCollapsed alveoli and transition zones with EEP were identified by the Delphi process as morphologic features that were a source of interobserver variability. Definition criteria for collapse and EEP are proposed to improve reproducibility of invasion measurement.     

Histopathologic findings predicting lymph node metastasis and prognosis of patients with superficial esophageal carcinoma: analysis of 240 surgically resected tumors

BACKGROUND: If it were possible to elucidate the histopathologic findings predicting lymph node metastasis and prognosis in superficial squamous cell carcinoma of the esophagus (SSCCE), they could be used as markers to identify patients who do not require additional surgical resection after endoscopic mucosal resection (EMR). METHODS: Two hundred forty surgically resected SSCCEs were examined histopathologically. Histopathologic factors including vertical tumor invasion depth in the submucosal layer (VTIDsm), degree of nuclear atypia (low, one point; high, two points), growth pattern (expansive, one point; infiltrative, two points), and histologic grade (calculated by adding the latter two scores to obtain Grade 1, two points; Grade 2, three points; and Grade 3, four points) were evaluated to investigate the associations among these factors, lymph node metastasis, and prognosis. RESULTS: No lymph node metastasis was found in 54 patients with carcinoma limited to the lamina propria. Their 5-year survival rate was 100%. Multivariate analysis of 186 carcinomas invading beyond the lamina propria showed that lymphatic permeation correlated with lymph node metastasis (P<0.0001) and the presence of lymph node metastasis and a high histologic grade were independent factors indicating a poor prognosis (P = 0.0061 and 0.023, respectively). In 53 patients whose tumors had invaded the lamina muscularis or slightly invaded the submucosa (VTIDsm <500 microm), no lymph node metastasis was found in the lymphatic permeation negative and blood vessel permeation negative patients with VTIDsm values <200 microm and histologic Grades 1 or 2. CONCLUSIONS: Lymphatic permeation is a good predictor of lymph node metastasis in patients with SSCCE. Lymph node metastasis and the histologic grade are independent prognostic factors. Vessel permeation, VTIDsm, and histologic grade were found to be important factors for identifying patients who did not require additional surgical treatment after EMR.     

Low grade fibromyxoid sarcoma: fine-needle aspiration cytology with histologic, cytogenetic, immunohistochemical, and ultrastructural correlation

BACKGROUND: Although the histologic features of the recently described low grade fibromyxoid sarcoma are well established, to the authors' knowledge there are no reports in the literature describing the cytologic features of this tumor by fine-needle aspiration. Recognition of this lesion is important because of its indolent but metastasizing nature. METHODS: The authors retrospectively reviewed their surgical pathology files for cases of low grade fibromyxoid sarcoma with a preoperative fine-needle aspiration biopsy (FNAB); three such cases were found. Immunohistochemical studies were performed in all three tumors, ultrastructural examination was performed in two tumors, and fresh tissue for cytogenetic analysis was obtained in one tumor. RESULTS: All FNABs showed similar features. The aspirates were relatively hypocellular with an abundant myxoid background; the neoplastic cells contained oval to spindle shaped nuclei with minimal pleomorphism. No capillaries or areas of fibrous tissue were identified. Cytogenetic study of one case revealed no chromosomal abnormalities. The histologic findings were characteristic for this lesion. By immunohistochemistry the tumor cells showed diffuse and strong reactivity for vimentin only; at the ultrastructural level the neoplastic spindle cells had characteristics of fibroblasts. CONCLUSIONS: The cytologic features of low grade fibromyxoid sarcoma are not specific enough for a definitive diagnosis based on FNAB alone; however, correlating the cytologic and clinical findings can narrow the range of diagnosis. The differential diagnosis includes other myxoid lesions, in particular superficial or intramuscular myxoma and myxofibrosarcoma. In addition, the immunohistochemical and ultrastructural findings support a fibroblastic origin for this neoplasm.     

Histologic examination of two cases of cystosarcoma phylloaes with pulmonary metastases

BACKGROUND: Cystosarcoma phyllodes (CP) is a rare neoplasm of the breast. Many studies of the histology of CP have been reported. However, few reports have included an evaluation of the histologic appearance of pulmonary metastases, or the change in histologic grade as a function of time in patients with recurrent tumors. METHODS: We treated two patients with pulmonary metastases, CP from 1973 to 1995. One patient died of respiratory failure. The other underwent six operations for CP. We evaluated the histologic characteristics of these metastases and changes in the histologic grade of recurrent tumors. RESULTS: The primary lesions in these two cases were typical high-grade malignant tumors. Case 1 had multiple pulmonary metastases and histologic findings indicated typical malignant CP. Case 2 had a solitary pulmonary metastasis and histologic findings showed low-grade malignant CP, which could be resected. The first patient died of respiratory failure ten months after surgery. The second had no further pulmonary metastases although she had frequent local recurrences, and the histologic features of these tumors became progressively worse. CONCLUSION: We suggest that patients with malignant CP be followed closely and that when pulmonary metastases are detected, they should be resected if possible, because pulmonary metastatic tumors may represent lower-grade malignant CP.     

Multivariate analysis for clinical prognostic factors in 163 patients with soft tissue sarcoma

Clinical and histologic findings in 163 patients with localized soft tissue sarcoma (STS) in the extremities and trunk were reviewed. There were 91 male patients and 72 female patients ranging in age from 2 to 84 years (median, 46 years). The histologic status of the tumors was as follows: low grade, 29 cases; intermediate grade, 52 cases; and high grade, 82 cases. The primary tumors were treated by intralesional excision (two cases), marginal (88), wide local (52), or amputation (21). Subsequent adjuvant therapy was given to 61 patients; 17 had radiotherapy (RT), 27 had chemotherapy (CH), and 17 had combined RT and CH. The overall survival (P less than 0.1) and disease-free survival (P less than 0.001) were better in the group that received multimodal treatment (radical surgery and adjuvant chemotherapy with or without radiotherapy) than in the group treated only by surgery. This suggests the favorable role of adjuvant therapy. The univariate and the Cox multivariate analysis for prognosis revealed that sex, tumor-related symptoms, tumor size, tumor depth, and histologic grade were the significant factors. Among the treatment schemes, adjuvant chemotherapy was the only one that affected survival, especially for the intermediate-grade tumors. Initial surgical treatment (marginal versus wide local excision) significantly contributed to the local control of the primary tumors.     

A clinico-pathological study involving a consecutive series of 75 primary liver carcinomas with resection

Seventy-five consecutive primary liver cancers that had a hepatic resection have been examined clinicopathologically. Eighteen were HBsAg+ cases (mean age: 50.9 yr) and 57 were HBsAg- cases (mean age 60.1 yr). HBsAg was not detected in the livers of the 57 HBsAg- cases, though it was found in the noncancerous parts of 16 of these cases and in the cancerous parts of 3 of the 18 HBsAg+ cases. A histologic, comparative study between the HBsAg+ and HBsAg+ cases showed no significant morphologic differences, except for somewhat frequent portal invasions in the former. From the viewpoint of prognosis, the ominous signs seem to be a positivity of serum HBsAg, large tumors, the presence of a portal and/or hepatic venous invasion, the presence of intra-and/or extrahepatic implants, and a high Edmondson's grade.     

Prognostic significance of tumor grade in clinical trials of adjuvant therapy for breast cancer with axillary lymph node metastasis

The prognostic significance of histologic tumor grade has been evaluated in 1537 women entered into the Ludwig Trials I-IV of adjuvant therapy for node-positive breast cancer. Tumor grade was determined on histologic review of primary tumor sections by two central review pathologists using a modification of the Bloom and Richardson grading system. The 5-year overall survival rates (+/- SE) were: Grade 1, 86% +/- 2; Grade 2, 70% +/- 2; and Grade 3, 57% +/- 2 (P less than 0.0001). This survival difference was seen in both premenopausal (P less than 0.0001) and postmenopausal (P less than 0.0001) women. Significant differences in disease-free survival (DFS) by tumor grade were also observed (P less than 0.0001). The tumor grade determined by the 75 contributing local clinic pathologists was also highly significant for predicting DFS and overall survival. Tumor grade remained a statistically significant prognostic factor for DFS (P less than 0.0001) and overall survival (P less than 0.0001) in multivariate analyses controlling for nodal status, tumor size, estrogen receptor status, menopausal status, age, peritumoral vessel invasion, and treatment assigned. In postmenopausal patients for whom adjuvant treatment was compared with no adjuvant therapy, the prognostic significance of tumor grade was modified by the effect of treatment. The presence of vessel invasion by primary tumor cells was a stronger predictor of early recurrence than was increasing tumor grade in postmenopausal patients who received no adjuvant therapy. The higher failure rates for patients with high-grade tumors was due to a larger number of failures in regional and visceral sites. Tumor grade can be determined by any pathologist and allows for selection of a subpopulation of breast cancer patients at high risk for early mortality.     

Is invasive lobular carcinoma different from invasive ductal carcinoma?

AIMS: The purpose of this study is to determine whether the histopathologic features and outcome in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are different, and whether the histologic type is a prognostic factor for outcome. METHODS: A retrospective cohort study was conducted in consecutive 510 stage I/II breast carcinoma patients who underwent modified radical mastectomy. The features of 65 patients with ILC were compared with those of 445 patients with IDC. In patients with median follow-up period of 44 months, univariate and multivariate prognostic factor analyses for cancer-specific death and relapse were carried out. RESULTS: The median ages in patients with ILC and those with IDC were 52 and 41 (P=0.04). Tumor size, estrogen receptor positive expression and nodal positivity were not significantly different between the histologic types. Patients with ILC had more frequently (81.5%) low grade tumors and less lymphatic vascular invasion (9.3%) in primary tumor than those with IDC (P<0.05). Whereas the rates of 5-year overall survival were 94% in ILC and 90% in IDC, the rates of 5-year event-free survival were 71 and 67%, respectively (P=NS). Multivariate analyses in all patients demonstrated that tumor size, pathologic lymph node status and age at diagnosis were the most important prognostic factors for overall and event-free survival. Histologic type was not statistically significant for both outcomes. CONCLUSIONS: Although patients with ILC had older age, low grade tumor and less lymphatic vascular invasion, they had no survival advantage comparing with their counterparts. Histologic type was not an independent prognostic factor for outcome.     

Breast carcinoma in pregnant women: assessment of clinicopathologic and immunohistochemical features

BACKGROUND: Breast carcinoma is one of the most common carcinomas in pregnant women. The incidence of breast carcinoma may increase in the future because of the trend toward delayed childbearing and increased screening. However, very few contemporary studies have attempted to identify the combined histopathologic and immunohistochemical features of breast carcinoma in these patients. METHODS: The authors evaluated 39 patients with breast carcinoma occurring coincident with pregnancy. This was comprised of a critical histologic review and immunohistochemical evaluation to determine the status of prognostic and predictive markers including estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, Ki-67, and p53. RESULTS: The mean age at presentation was 33 years (range, 24-44 years). Densities and/or masses were noted on mammograms in 14 of 16 patients with available radiographic information. The primary tumors were a mean of 4.5 cm in greatest dimension (range, 0.1-13.5 cm). Two of the 39 patients had clinical (American Joint Committee on Cancer) Stage I disease, 19 patients had Stage II disease, 16 had Stage III disease, and 2 patients had Stage IV disease at the time of presentation. Histologically, high-grade invasive ductal carcinomas were found in 32 of 38 patients. The primary tumor was not available for review in one patient. A predominantly solid pattern of growth was observed in nine patients. Lymphovascular invasion was identified in 61% of cases. Ductal carcinoma in situ was identified in 72% of tumors and was high grade in all cases. Of the 25 patients tested, ER positivity was found in 7 patients, PR positivity was found in 6 patients, HER-2/neu positivity was found in 7 patients, and p53 positivity was found in 12 patients. The proliferation rate as shown by Ki-67 staining was high in 60% of the cases. Follow-up information was available for 35 patients and the mean follow-up period was 43 months (range, 2-163 months). Distant metastasis occurred in seven patients. The mean time to disease recurrence was 20.4 months (range, 10-33 months). Of 35 patients, 4 have died, 22 were alive with no evidence of disease, and 9 were alive with disease at the last follow-up. The remaining four patients died of unknown causes. CONCLUSIONS: Pregnant women with breast carcinomas generally present with advanced-stage disease and the tumors have poor histologic and prognostic features. The findings from the follow-up indicated that these tumors do not follow a very aggressive clinical course as was proposed in earlier reports. Breast carcinomas occurring during pregnancy share many histologic and prognostic similarities with breast carcinoma occurring in other young women.     

Primary gastric lymphomas. A clinicopathologic study of 58 cases with long-term follow-up and literature review

A large series of primary gastric lymphomas with long-term follow-up (average, 12.8 years) is reported. A number of factors known to affect nodal lymphoma were examined. Five- and ten-year survival rates were 57 and 46%, respectively. Statistically significant favorable prognostic variables were smaller tumor size (less than or equal to 7 cm), superficial mural invasion (submucosal only), and pathologic Stage I disease; these variables were intimately interrelated. A favorable influence on survival was discerned concerning histologic type and nodular histology, although still below statistical significance. No significant relation to survival was observed concerning clinical weight loss or palpable mass, vascular invasion, mode of therapy, or histologic subtypes of "histocytic" lymphoma. Of patients who succumbed to disease, 75% did so within two years (average, 1.8 years); however, later recurrence and death may occur. An argument for resection of localized disease is presented. Mitotic index and nuclear diameter were of diagnostic importance, and associated lesions such as pseudolymphomas are discussed in relation to pathogenesis. Histologic variation within tumors suggested visualization of clonal development in non-Hodgkin's lymphomas.     

Leiomyosarcoma of the external soft tissues. A clinicopathologic, immunohistochemical, and electron microscopic study

This clinicopathologic study concerns 25 cases of leiomyosarcoma of the external soft tissues, including an immunohistochemical survey of 19 cases and an electron microscopic examination of six. There was a female preponderance in a ratio of 16:9. The most common site of tumors was the thigh (nine cases), followed by the knee (five cases). Three tumors were located in the dermis, 9 were confined down to the subcutis, 2 involved the deep fascia, and 11 involved the skeletal muscle. Superficially located tumors were smaller than deeply located ones. According to the predominant histologic features, the tumors were classified into well (6), moderately (14), and poorly (5) differentiated. In addition to the classical microscopic features, dedifferentiated areas resembling malignant fibrous histiocytoma were noted in three primary tumors and one recurrent tumor. In six tumors, the anatomical location and histologic features were highly suggestive of leiomyosarcoma arising in the venous wall. Many tumor cells immunoreactive for actin were seen in 13 and for desmin in 9 of the 19 cases. Four tumors contained a few tumor giant cells positive for alpha-1-antichymotrypsin. Ultrastructurally, the tumors were characterized by smooth muscle tumor cells showing a spectrum of differentiation of varying degrees. In two cases, histiocyte-like tumor cells were detected. The most reliable prognostic parameter was the depth of the initial tumors; all patients with a leiomyosarcoma confined down to the subcutis are living, most of them more than 5 years after excision, whereas seven of the nine patients with a tumor involving the muscle have died within 5 years after excision.     

Thyroid carcinoma: a clinical and pathologic study of 125 cases.

Retrospective clinicopathological study of 125 thyroid carcinoma cases followed for 9 to 19 years was performed. Case selection for unfavorable histologic type and advanced disease was observed for referred cases. All medullary and anaplastic tumors were in patients over age 40; younger patients all had papillary and follicular carcinoma. Actuarial survival rates showed favorable outcome from papillary carcinoma followed by follicular and medullary or anaplastic tumors. Within the papillary carcinoma group, older age and male sex adversely affected survival; the former appeared related to clinical stage at presentation. Clinically palpable papillary carcinomas that were poorly circumscribed or showed vascular invasion were associated with poorer survival than tumors without these features. For papillary carcinomas under 1.5 cm, soft tissue invasion, vascular invasion, and occult lymph node metastases did not effect disease free survival. Two deaths from thyroid cancer were observed in this group, however, in patients who presented initially and with distant metastases. The biology of these small lesions is briefly discussed.