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Lichen planus pemphigoides is a rare bullous disorder with bullae arising from papules of lichen planus and from normal-appearing skin. Oral cavity-limited lichen planus pemphigoides has never been reported. This report presents a 47-year-old woman who had oral mucous membrane pemphigoid with lichen planus. This lesion is not known among existing clinical diagnoses. When considering the heterogeneous nature of lichen planus pemphigoides, this case may be classified as a variant of lichen planus pemphigoides.

BACKGROUND: Adenocarcinoma arising in the rectovaginal septum is exceedingly rare and is difficult to diagnose by pathologic examination prior to surgery because of the anatomic position of the tumor. CASE: A 42-year-old woman presumed to have adenocarcinoma of the rectovaginal septum underwent fine needle aspiration for diagnosis. Although a previously performed biopsy from the posterior vaginal fornix was unsuccessful, fine needle aspiration cytology via the posterior vaginal wall detected adenocarcinoma cells. The cell clusters were composed of cells with enlarged and hyperchromatic nuclei. The nuclei themselves demonstrated round and/or irregular morphologic patterns, with high nuclear/cytoplasmic ratios, and often contained an enlarged, round nucleolus and sometimes multiple ones in a single nucleus. Anisonucleosis was severe, and the chromatin patterns ranged from coarse to finely granular. The cytoplasm was narrow and lightly stained. Following fine needle aspiration, the patient underwent posterior exenteration on the basis of the cytologic diagnosis. CONCLUSION: Fine needle aspiration cytology was useful in establishing the preoperative diagnosis of adenocarcinoma of the rectovaginal septum, and curative exenterative surgery could be then performed. To our knowledge, this is the first report of fine needle aspiration cytology of adenocarcinoma at this location.

With respect to the immunohistochemical expression of TS, 18 cases of triple cancers were studied and all included gastric cancer. Of the gastric cancers, 3 were synchronous and the others were metachronous against 1 or 2 other cancers. The histological stages of gastric cancer ranged from stage I to IV, and included 9, 5, 2 and 2 cases in the ascending order of stage, respectively. Overall expression of TS was 38.9% in gastric cancers. Chronologically, the rates were 12.5%, 37.5% and 50.0% in preceded, simultaneous and followed gastric cancers, respectively. TS was detectable in 76.0% of other cancers examined, of which colorectal cancer composed one third. Among 10 cases in which TS was examined in each triple cancer site, 2 had 3 cancers with TS(+), 5 had 2 cancers with TS(+) and 3 had 1 cancer with TS(+) and none had TS(-) in all. Prognosis was poorer for the group with positive TS in more than 2 cancer sites than in less TS positivity. Therefore, it was considered that the prognosis of the triple cancer patients could be more predicted by combining TS positivity of each cancer.

In a previous paper, we suggested that tamoxifen (TAM)-mediated endometrial carcinogenesis may not involve estrogenic pathways because of random estrogen receptor positivity among endometrial carcinomas with and without TAM treatment for breast cancer. DNA adduct formation (reported in rat liver and human endometrium) was considered to be a more plausible mechanism for TAM-mediated carcinogenesis. To examine the reported correlation between DNA adduct formation and p53, the present study examined p53 expression in the endometrial carcinomas reported in the previous study. Seven endometrial adenocarcinomas associated with long-term TAM treatment for breast carcinoma and 4 carcinomas without TAM treatment but with history of breast carcinoma were immunohistochemically investigated for nuclear p53 expression. The bcl-2 product was also examined. Diffuse and intense nuclear reactivity for p53 protein was present in only one TAM-related case. Essentially, no differences were observed in the bcl-2 staining patterns of TAM-treated and -untreated patients with cancer. Thus, p53 overexpression in endometrial carcinomas occurring in patients with breast cancer seems to be not specific for TAM-treated patients, and, if DNA adduct formation has any role in this type of endometrial carcinogenesis, it may not be related preferentially to p53 gene alteration. Further studies are needed to understand the precise mechanism(s) of the endometrial carcinogenesis.

The contribution of cell proliferation and apoptosis to growth patterns in endometrial adenocarcinoma were investigated. Immunohistochemical staining was carried out by an antibody for Ki-67 proliferative antigen, Ley apoptotic antigen, and oncogene products bcl-2 and p53. Forty cases of endometrial adenocarcinoma were classified as exophytic, endophytic, and mixed exo- and endophytic in light of their vertical growth pattern, and, in each case, the carcinomatous area was divided into three layers by its vertical axis. In all but one case, no zonal distribution of the antigen expression was observed. In one case, an exophytic tumor, Ki-67 expression was intense in the surface layer and Ley expression in the deep layer was also intense, suggesting a correlation between macroscopic growth pattern and cellular growth and apoptotic potential. However, in general, zonal distribution of cell proliferation and apoptosis could not explain the growth morphology of endometrial adenocarcinoma of the uterus and it was suggested that factor(s) other than cell proliferation and apoptosis determine macroscopic growth patterns.

Immunohistochemical characteristics of undifferentiated carcinomas of the ovary were examined using formalin-fixed, paraffin-embedded tissues with an avidin-biotin staining approach. Eight cases were collected from the pathology files of our Institute from a total of 214 recorded malignant ovarian tumors. For immunostaining, antibodies reacting with epithelial membrane antigen (EMA), pankeratin, vimentin, CA 125, CA 19-9, carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), alpha-1-antitrypsin (AT), epidermal growth factor receptor (EGFR), c-erbB-2, bcl-2 and p53 proteins were used. All the cases examined were positive for EMA and pankeratin, specific markers for epithelial tumors, negative for the non-epithelial tumor marker, vimentin, and also positive for EGFR. Interestingly, only one case was positive for CA 125, despite it being one of the commonest reported indicators of ovarian cancer. CA 19-9 was positive in 7 cases, CEA in 5, AFP in 2, AT in 6 and c-erbB-2 protein in 4. Two cases were positive for p53 protein, and in 1 of these positive staining for bcl-2 was also observed. These results indicate that the epithelial nature is well preserved in undifferentiated ovarian carcinomas, although consistently positive reactions were not observed within the cases for some antigens. They further clearly show that a negative signal for CA 125 can not be considered to exclude the possibility of a primary ovarian tumor.

A case of poorly differentiated adenocarcinoma of the stomach with unique histological features is reported: in addition to characteristic adenocarcinoma cells, a large number of tumor cells contained bright eosinophilic and argentaffin granules in their cytoplasm. On routine histologic examination, the latter cells closely resembled the endocrine cells present in the normal human gastrointestinal tract, although the granules were distributed throughout the cytoplasm and did not show any polarity, which is usually subnuclear in normal endocrine cells. Immunohistochemical studies demonstrated positive staining for lysozyme, CEA, gastrin and HCG. Electron microscopic examination revealed cytoplasmic neurosecretory granules, and some tumor cells were found to contain both secretory granules and mucinous material within the same cytoplasm. These neoplastic endocrine cells presumably originated from primitive digestive system elements capable of differentiating towards both endocrine and mucus-secreting varieties.

Anomalies, vol 2. New York, NY, Oxford University Press, 1993 3. Gorlin RJ, Cohen MM Jr, Hennekam R, et al: Syndromes of the Head and Neck (ed 3). New York, NY, Oxford University Press, 1990 4. Wigglesworth JS, Singer DB (eds): Textbook of Fetal and Perinatal Pathology (ed 2). Malden, MA, Blackwell Science, 1998 5. Clarke L, Hepworth WB, Carey JC, et al: Chondrodystrophic mice with coincidental agnathia. Teratology 38:565, 1988

Background. The immunohistochemical expression of thymidylate synthase (TS) and thymidine phosphorylase (TP) was examined in a comparative study of the recurrence rates and prognoses of patients with advanced gastric cancer at the same stage. Methods. We examined the resected specimens of 67 patients with stage IIIB gastric cancer (pT3, pN2, M0) under 70 years of age who had undergone curative gastrectomy followed by adjuvant chemotherapy with 5-fluoropyrimidines. Paraffin sections of the resected specimens were stained with human anti-TS polyclonal and anti-TP monoclonal antibodies by the avidin-biotin-peroxidase complex (ABC) method. Results. The overall expression of TS and TP was 45.4% and 43.4%, respectively. The postoperative survival curve for the TS-positive group was significantly depressed compared with that for the TS-negative group ( P = 0.0480). The survival curves for TP-positive and TP-negative groups did not show any difference. In regard to the combination of TS and TP expression, the best survival curve was obtained for the TS(−)/TP(+) group, followed by those for the TS(−)/TP(−), TS(+)/TP(−), and TS(+)/TP(+) groups in descending order. With regard to the recurrence site, there was no significant difference in peritoneal recurrence in relation to positivity for TS or TP. Lymph node recurrence, however, was significantly higher in the TS-positive and TP-positive groups, with P -values being 0.0466 and 0.0058, respectively, versus the corresponding negative groups. The incidence of hepatic recurrence was higher in the TP-positive group than in the TP-negative group ( P = 0.0910). As for the total doses of 5-fluoropyrimidines given, more favorable survival curves were obtained for the high dose of negative TS and TP groups, but no significant differences were observed in their positivities. Conclusion. The expressions of TS and TP showed different characteristics in overall survival and recurrence rate or site. They should be used for predicting prognosis in comprehension on their properties.

Cytopathological characteristics of undifferentiated carcinoma of the ovary were examined and reviewed. Seven cases of undifferentiated carcinoma were encountered among 202 malignant ovarian neoplasms in the Saitama Cancer Center. Histologically, two cases contained a minor component of usual Mullerian carcinoma and five others were purely of solid architecture without differentiation. Nevertheless, six cases, four of which were totally undifferentiated histologically, showed cytological features characteristic of adenocarcinoma. the results indicate that even carcinomas histologically diagnosed as undifferentiated may have cytological features of glandular differentiation, which may be Mullerian in origin. © Wiley-Liss, Inc.

In order to investigate the role of blood platelets in regenerative proliferation of hepatocytes in vivo, partial hepatectomy was carried out under conditions of severe thrombocytopenia achieved by X‐irradiation and the time‐dependent degree of hepatocyte regeneration was measured as labeling index (LI) after (3)H‐thymidine injection. LI values reached a maximum 36 h after hepatectomy performed 7 days subsequent to a whole‐body irradiation of 7.5 Gy, although the maximum rate was found to be only about one‐third of that found in unirradiated control rats. At this time point, the number of peripheral blood platelets was decreased to about 2% of that of unirradiated controls and bone marrow megakaryocytes were virtually undetectable. A decrease of LI, similar to that found for the whole‐body irradiation in degree, was also observed after local irradiation of the liver with the same dose but without an apparent decrease in platelets. When whole‐body irradiation was performed with the liver shielded, under which conditions the numbers of blood platelets decreased to about 8% of the control levels, almost no decrease in LI was found. The results thus suggest that the observed inhibition of hepatocyte regeneration was directly due to liver irradiation and that depletion of blood platelets itself does not interfere with the regeneration process, providing evidence against a dominant role of the platelets in the regeneration as proposed by other authors.

The responses of B16 melanoma in C57BL mice to cytotoxic agents, cyclophosphamide, doxorubicin, and dactinomycin, were studied by different methods both in vivo and in vitro. Either treated tumors were allowed to grow in vivo or cells were isolated and cultured in vitro afterwards. The tumor cells were also treated in vitro and assayed in vitro. For cyclophosphamide, a fairly good correlation was found among the dose responses measured: the tumor growth delay, incidence of giant cells, decrease in mitotic index, clonogenic cell survival of tumor cells treated in vivo and the survival of cells treated in vitro. For doxorubicin and dactinomycin, on the other hand, the tumor growth delay was not marked, the appearance of giant cells and decrease in mitotic index were minimal, and almost no decrease was found in the clonogenic cell survival for tumor treated in vivo, although the cells responded well to in vitro exposure. The results indicate substantial differences in the expression of damage according to the conditions of tumor cell growth and assay after treatment with different agents.

Human melanoma, HMV-I, multicellular spheroids were irradiated and cure was determined by the absence of cellular outgrowth. Their cellular radiosensitivity was measured by the colony-forming ability of cells dispersed from the spheroid. Analysis of radiocurability of spheroids in terms of their cellular radiosensitivity predicted three necessary conditions: a linearity of dose versus the double-minus logarithm of curability; constancy of a critical cell number; and constancy of cellular radiosensitivity. These conditions were found to exist in the observed data for each of three size classes of spheroids. Analysis suggests that cellular radiosensitivity in multicellular spheroids with diameters of 250 and 400 microns was different from that of monolayers, and that the increase of spheroid-control doses was found to be a function of cellular radiosensitivity, total cell number per spheroid and a critical cell number. The critical cell number increased from 0.8 in a 150 microns spheroid to 4 in a 250 microns spheroid and to 57 in 400 microns spheroid. This number is a unique characteristic of multicellular systems and is one important factor in determining their radiocurability. X-ray-induced growth delay of spheroid size was increased with increasing dose. At high doses a sharp increase in delay time was seen, sometimes accompanying fragmentation of spheroids at late postirradiation times. The clonogenic activity of these fragments may serve as a model of exfoliation, the first step of radiation-induced metastasis.

The dynamics of lymphoid cell subpopulations in bronchoalveolar lavage fluid (BALF) and the systemic lymphoid organs of mice after intravenous injection of B16 melanoma cells were examined with a fluorescence-activated cell sorter. The lymphoid cell subpopulations of BALF and mediastinal lymph nodes showed significant changes in numbers and proportions, while those of other lymphoid organs including inguinal lymph nodes, thymus and spleen, showed little change. In week 1, the cells with a Thy-1.2+, Lyt-1+, L3T4-, Lyt-2- phenotype and asialo-Gm1+ cells in BALF significantly increased and L3T4+ cells slightly increased in number. By week 3, the numbers of Lyt-2+ cells in BALF markedly increased in number (by about 90 times) compared with controls. The number of Thy-1.2+ cells in mediastinal lymph nodes also increased significantly by week 3. Mice that had been pretreated with an immunosuppressive dose of cyclophosphamide were also inoculated intravenously with B16 melanoma cells. In these mice, a significantly increased number of pleural tumors developed and the number of Thy-1.2+ cells in BALF was markedly reduced from week 1 to 3. The results indicate that L3T4 and Lyt-2 double negative T-cells and natural killer (NK) cells may be generated and/or mobilized to the lung in an early phase of experimental metastasis of B16 melanoma cells and that at a later stage, when multiple metastases develop, T-cells with a Lyt-2+ phenotype markedly increase, probably as an expression of a host reaction against proliferating metastatic tumor cells.