Primary adenocarcinoma of the rectovaginal septum arising in pregnancy in the absence of endometriosis.

A case of primary adenocarcinoma of the rectovaginal septum (PARVS) is reported with clinical and pathological findings. A 37-year-old Caucasian woman with a history of sterility and small posterior leiomyoma, a few months after a cesarean section, was admitted because of vaginal spotting, abdominal pain and constipation. Her previous history did not reveal exposure to diethylstil bestrol (DES). Pelvic computed tomography showed a heterogeneous pelvic mass in the Douglas pouch, measuring 9 cm in diameter, located in the rectovaginal septum, involving the rectal and vaginal wall. Histological examination of neoplastic tissue revealed solid sheet structures, occasional tubular lumen, extensive necrotic areas and clear cells. The neoplastic elements showed immunoreactivity for Mullerian markers (cytokeratin 7, CA-125 and vimentin). Because, the present case of PARVS cannot be due to DES exposure, the clear appearance of the neoplastic elements could represent only one differentiation of Mullerian rests. Moreover, because no foci of endometriosis were identified in several sections of the neoplasm, uterine and cervical wall, and tissues nearby the neoplasm could represent a rare subtype of PARVS arising in the absence of endometriosis.

Patients with advanced stage breast carcinoma immunoreactive to biotinylated Herceptin are most likely to benefit from trastuzumab-based therapy: an hypothesis-generating study.

BACKGROUND: Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry. We previously showed that BiotHER immunoreactivity is highly correlated with HER2 amplification and indicated that it could be associated with better clinical outcome in advanced breast cancer patients receiving trastuzumab. PATIENTS AND METHODS: Tumor specimens and clinical information from 234 patients who received trastuzumab-based treatments were collected from 10 institutions. HER2 amplification and BiotHER immunoreactivity were assessed centrally. The effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer. The pathologic reviews of the assays were blinded to patient outcomes. RESULTS: BiotHER was positive in 109/194 (56%) HER2-amplified breast cancers and in one not amplified tumor. RRs were 74% [95% (confidence interval) CI 64%-81%] and 47% (95% CI 36%-58%) in BiotHER-positive and -negative tumors, respectively (P < 0.001). BiotHER immunoreactivity was independently associated with increased probability of tumor response (odds ratio 3.848; 95% CI 1.952-7.582), with reduced risk of disease progression [hazard ratio (HR) 0.438; 95% CI 0.303-0.633] and with reduced risk of death (HR 0.566; 95% CI 0.368-0.870) by multivariate analysis. CONCLUSION: The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers.

Cytotoxic and antiproliferative activity of the single agent epirubicin versus epirubicin plus tamoxifen as primary chemotherapy in human breast cancer: a single-institution phase III trial.

This study was designed to address whether simultaneous primary chemo-hormonal therapy provides additional activity compared with chemotherapy alone in breast cancer patients with operable or locally advanced disease. Between January 1997 and January 2002, 211 consecutive patients with T2-4, N0-1, M0 breast cancer were randomized to receive either epirubicin alone (EPI) or epirubicin plus tamoxifen (EPI-TAM). Ki67 expression was evaluated immunohistochemically in tumor specimens obtained before chemotherapy by incision biopsy and at definitive surgery. Tumor shrinkage of >50% was obtained in 76% of patients randomized in the EPI arm and 81.9% of patients randomized in the EPI-TAM arm (not significant). The corresponding rates of clinical and pathological complete response were 20.2 and 21.9% (not significant), and 4.8 and 6.7% (not significant), respectively. Pathologically complete response was more frequently observed in estrogen receptor (ER)-negative (ER-) tumors (P=0.04) and correlated with elevated baseline Ki67 expression (P<0.01). Both EPI and EPI-TAM treatments resulted in a significant reduction in Ki67 expression, either in overall patients (P=0.000) or in patients with ER+ breast cancer (P=0.000). The reduction in Ki67 immunostaining in the EPI-TAM arm was greater than in the EPI arm, leading to a lower Ki67 expression at post-operative residual histology (P=0.0041). The addition of tamoxifen to epirubicin chemotherapy did not improve the response rate but led to a significantly higher reduction in the Ki67 expression. Baseline elevated Ki67 expression and the ER- status were both associated with a greater chance of obtaining a pathological complete response at residual histology.

p53 but not bcl-2 immunostaining is predictive of poor clinical complete response to primary chemotherapy in breast cancer patients.

Preoperative chemotherapy administered to breast cancer (BC) patients is a model for studying in vivo the interaction between cytotoxic treatment and clinical and biological parameters. Apoptosis induced by anticancer agents is a mechanism of treatment activity; therefore, overexpression of genes inhibiting the apoptotic pathway could produce drug resistant tumors. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 gene and the mutant p53, have been evaluated to assess whether they may play a role in modulating response of BC to primary chemotherapy. From August 1990 to January 1997, 143 patients bearing T(2-4)N(0-1)M0 primary BC were submitted to two different chemotherapeutic regimens before surgery. The first 64 received the cyclophosphamide, methotrexate, 5-fluorouracil (CMF) regimen (on days 1 and 8 and every 28 days thereafter) associated with tamoxifen (30 mg daily) in case of estrogen receptor (ER)-positive BC, and the remaining 79 were submitted to single agent epirubicin (120 mg/m2 every 21 days). The expression of p53, bcl-2, Ki67, ER, progesterone receptor, c-erbB2, and the multidrug resistance P-glycoprotein (gp-170) was evaluated in BC specimens obtained at diagnosis by incision biopsy and at postchemotherapy surgery. At the end of chemotherapy administration (median, 3 cycles; range, 2-6), the clinical complete response (cCR) rate was superimposable in the patient subgroups with bcl-2-positive or -negative primary tumors; conversely, p53 expression, at a cutoff of 10% positive cells, was significantly associated with a lower cCR rate (9.4 versus 27.0%; P < 0.04). p53 was a significant predictor for poor cCR in the subset submitted to epirubicin (3.6 versus 25.5%; P < 0.02; in patients with p53+ and p53- BC, respectively); by contrast, only a trend toward lower cCR has been observed in patients with p53+ tumors receiving CMF +/- tamoxifen with respect to p53- ones. The distribution of cCR according to the gp-170-positive or -negative tumors was 8 versus 22% in patients submitted to epirubicin and 29 versus 30% in those receiving CMF +/- tamoxifen, respectively. In a multivariate regression analysis, after adjusting for treatment administered (epirubicin versus CMF +/- tamoxifen), menopausal status, tumor and node status, histology grade, ER, progesterone receptor, c-erbB2, Ki67, bcl-2, and gp-170 expression, the p53 status maintained an independent predictive role for cCR. Most of the tumors undergoing change in percentage of p53 expression after both treatments originally harbored mutant protein, and only four BC specimens that were p53 negative before chemotherapy became positive afterward. These data confirm in vivo the concept that the responsiveness of tumors to chemotherapy in part derives from the capability of BC cells to undergo apoptosis. The role of mutated p53 in preventing response is more evident in patients submitted to epirubicin, and this may be caused by the up-regulation of multidrug resistance gene expression by p53 inactivation. p53 is a stable phenotype and is not inducible by at least three or four chemotherapy cycles.

Cytotoxic and antiproliferative activity of the CMF regimen administered in association with tamoxifen as primary chemotherapy in breast cancer patients.

Seventy six consecutive patients with T2-4, N0-1, M0 primary breast cancer (BC) received a median of 3 cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Tamoxifen was concomitantly administered in patients with estrogen receptor positive (ER+) BC. Ki67 antigen was evaluated immunohistochemically in tumor specimens obtained before chemotherapy and at mastectomy. At post chemotherapy evaluation, tumor shrinkage greater than 50% was obtained in 60 patients (78.9%), 21 of them being complete responders (27.6%). As a whole, primary chemotherapy significantly decreased the number of Ki67 positive cells. More than 50% decrease in Ki67 expression was observed in 78.9% of patients attaining a clinical complete response (CR), in 44.7% of patients with partial remission (PR) and in 50.0% of non-responders, while an increase (>25%) in Ki67 expression was found in 5.3%, 18.4% and 18.7% of patients with CR, PR and non-response, respectively. Both CR and PR rates were superimposable in patients with ER+ and ER- primary BC, while the reduction in Ki67 expression was mainly found in ER+ cases. Patients with increased Ki67 expression from baseline, at the end of primary chemotherapy, had a shorter disease-free interval (70 months) with respect to patients with no change (88+ months) or decrease (87+ months), p<0. 05. To conclude, the activity of CMF + tamoxifen in primary BC does not seem superior to that expected administering CMF alone. The reduction in Ki67 expression, as a whole, correlated with clinical CR, but some individual discrepancies between tumor shrinkage and Ki67 pattern have been observed. The Ki67 reduction mainly confined to the ER+ primary BC suggests that tumor response in this subset may be linked to the reduction in proliferation activity, whereas other mechanisms such as apoptosis might be responsible for the tumor shrinkage in ER- tumors. Since the increase in proliferation activity after primary chemotherapy was associated with a greater recurrence rate and lower disease free interval, irrespective of tumor response, changes in proliferation activity after primary chemotherapy may represent a potentially available parameter that, in addition to the tumor response, can discriminate patients who would benefit from the cytotoxic treatment from patients who would not.

Eosinophil-tumor cell interaction in advanced gastric carcinoma: an electron microscopic approach.

BACKGROUND: Tumor-associated tissue eosinophils have been observed in human tumors and experimental tumor models, but their function is poorly understood. MATERIALS AND METHODS: One case of intestinal-type adenocarcinoma of the stomach, mainly infiltrated by eosinophils, is studied by light and electron microscopy, focusing on the relationships between eosinophils and tumor cells and on the nature of tumor cell death. RESULTS: Using light microscopy, eosinophils, single or in clusters, were present both in the stroma and within neoplastic glands. With electron microscopy, tumor cells in intimate contact with eosinophils revealed changes consistent with autophagic cell death such as chromatin condensation in small masses into the nucleus, dilation of the nuclear envelope, and numerous cytoplasmic vacuoles. The adenocarcinoma cells, not contacted by neutrophils, remained morphologically well preserved. CONCLUSIONS: Our ultrastructural study suggests the hypothesis of a direct relationship between eosinophil infiltration and induction of autophagic cell death in gastric adenocarcinoma cells.

Effect of neoadjuvant chemotherapy on Ki67 labelling index, c-erbB-2 expression and steroid hormone receptor status in human breast tumours.

The administration of neoadjuvant chemotherapy to breast cancer (BC) patients with operable disease allowed studies aimed of exploring the interaction between cytotoxic treatment and tumour biology in vivo. 99 patients with T2-4, NO-1, M0 primary BC received a median of 3 cycles of either CMF regimen (cyclophosphamide, methotrexate, 5-fluorouracil) or single agent epirubicin. Endocrine therapy was also concomitantly administered in the first 45 patients with estrogen receptor positive (ER+) BC. 92 ended the treatment plan. Ki67 labelling index, estrogen receptor (ER), progesterone receptor (PgR), and c-erbB-2 oncoprotein expression were evaluated immunohistochemically in tumour biopsies obtained before and after chemotherapy. At post-chemotherapy evaluation, tumour shrinkage greater than 50% was obtained in 71 patients (79.7%), 27 of them being complete responders (30.3%). The median Ki67 labelling index, which was 13% in the first biopsy, decreased to 4.5% (p < 0.001) upon mastectomy. No significant differences were observed in steroid hormone receptor and c-erbB-2 expression before and after neoadjuvant treatment. In conclusion, neoadjuvant chemotherapy, whether associated or not to endocrine therapy, leads to a significant decrease in BC proliferation without any appreciable impact on c-erbB-2 and steroid hormone receptor expression.

[Hepatocellular carcinoma. Significance of the association with cirrhosis, alcohol consumption and the hepatitis B virus (serum markers and tissue antigens)]. / Carcinoma epatocellulare. Importanza dell'associazione con cirrosi, consumo di alcol e virus epatitico B (marcatori sierici e antigeni tissutali).

In a consecutive series of 35 cases of HCC, 21 (60%) had a habitual alcoholic intake of greater than 80 g/die and 26 (74.2%) were positive for at least one HBV serum marker. At tissue level, HBsAg was positive in non-tumoral tissue in 8 cases (22.9%) and HBcAg in 6 cases (17.1%) in non-neoplastic tissue and in 3 cases (8.6%) in neoplastic tissue with focal type positivity. The positivity of HBsAg presented at cytoplasmatic level and that of HBcAg almost exclusively at nuclear level. The comparatively low expression of HBV antigens at tissue level can be explained by the integration of viral DNA in the host genome which probably took place in many of these cases. Cirrhosis was associated with HCC in 23 cases (65.7%). In 9 (25.7%) cirrhosis was macronodular, in 4 (11.4%) micronodular and in 10 (28.6%) it was mixed. 18 cases (51.4%) presented an association of significant alcoholic consumption and positivity of at least one HBV marker. In 19 cases (54.3%), cirrhosis was associated with positivity of at least one HBV marker. Finally, in 14 cases (40%) there was an association of cirrhosis, alcohol and positivity of at least one HBV marker. These results suggest a multifactorial aetiology of HCC in our geographic area, identifying the factors in question in cirrhosis of the liver, independently of its aetiology (through the hyperplastic-regenerative process that characterises it) in HBV and in alcohol (with direct and independent pathogenetic mechanisms known only in part, or mediated by cirrhosis of which HBV and alcohol represent the two main aetiological agents). In cases in which more than one of the aetiological factors considered was observed, it is legitimate to admit a cocarcinogenic perhaps synergistic hypothesis of this cancer.

Nd: YAG laser treatment of vesical leiomyosarcoma.

The first in the literature of bladder leiomyosarcoma, treated by transurethral resection followed by laser irradiation, in a 75-year-old woman is reported. At 22 months follow-up the patient is well and has no evidence of metastasis.

[Light-chain deposition disease. Presentation of a case]. / Malattia da depositi di catene leggere (lcdd). Presentazione di un caso.

A case of 66-years-old woman with mild renal failure due to deposition of K light chains on glomerular nodules, is reported. Monoclonal K light chains were found by immunofixation in serum and concentrated urine. Bone marrow examination showed a moderate increase of plasma cells, all stained for K light chains. Amyloid was not identified. No chemotherapy was started. Despite this, in the 15-months follow-up, renal function was preserved; no signs of myeloma, nor of extrarenal involvement were found. Careful follow-up is emphasized. The reason why light chains form amyloidoses or nodular deposits, like diabetic glomerulosclerosis of Kimmelstiel-Wilson, is briefly discussed, together with the differential diagnosis from other nephropathies.

[Mixed ovarian germinal neoplasia: adult embryonal carcinoma and dysgerminoma with trophoblasts]. / Neoplasia germinale ovarica complessa: carcinoma embrionale adulto e disgerminoma con trofoblasto.

Malignant mixed germ cell tumor of the ovary: embryonal carcinoma and dysgerminoma with trophoblastic cells. A case of ovarian neoplasia in a 19-years-old woman is described showing mixed germ cell tumor patterns. The main component is a solid embryonal carcinoma with mainly syncytial-like, highly anaplastic cells, displaying diffuse CK-immunoreactivities and scattered PLAP-positive cells. Many CK- and beta-HCG-positive syncytiotrophoblastic and intermediate trophoblastic cells are present. A second component is a dysgerminoma with lymphoid stroma and diffuse PLAP-cytomembrane immunoreactivities: rare cells, to be identified as intermediate trophoblast cells, are CK- and strongly beta-HCG-positive. Many syncytiotrophoblastic cells with a brisk CK- and beta-HCG-positivities are also noted. The embryonal carcinoma component is metastasized to the controlateral ovary, uterus and omentum. A complete immunohistochemical analysis is recommended to properly diagnose germ cell neoplasias of the ovary both for descriptive and prognostic-therapeutic purposes. The very rare presence in the same ovarian tumor of mixed patterns as adult embryonal carcinoma and dysgerminoma with trophoblastic cells, is stressed.

Morphological evidence of neutrophil-tumor cell phagocytosis (cannibalism) in human gastric adenocarcinomas.

The phenomenon of neutrophil-tumor cell emperipolesis or phagocytosis has been documented by light microscopy in various human carcinomas, but little is known about the cellular pathological processes and the morphological changes involved. In an attempt to clarify the nature of this phenomenon, the authors' ultrastructural studies on the relationships among neutrophils and tumor cells in human gastric carcinomas are reviewed and analyzed. At the electron microscopy level, apoptotic neutrophils were found within vacuoles of adenocarcinoma cells in 2 cases. They showed either early apoptotic morphology with perinuclear chromatin aggregation but cytoplasm integrity or late apoptotic morphology with uniform, collapsed nucleus and tightly packed cytoplasmic granules. A light microscopy review of 200 cases of resected gastric carcinomas identified 22 cases (11%) that were characterized by neutrophil-tumor cell phagocytosis (cannibalism). TUNEL staining confirmed the presence of apoptotic neutrophils within the cytoplasm of the tumor cells. This study provides light and electron microscopic evidence of apoptotic neutrophils phagocytosed by gastric adenocarcinoma cells. The morphological features of neutrophil-tumor cell phagocytosis (cannibalism) would suggest a particular mechanism of tumor-immune escape in human gastric carcinoma.

Clinicopathological features of early gastric cancer in younger versus older patients in a high incidence area of northern Italy.

AIMS: The relationship between the clinicopathological features of early gastric cancer and age were analysed in a retrospective study of 168 patients. METHODS: 168 patients, residents of the Region of Cremona, who had undergone surgery in the period 1978 to 1990 for early gastric cancer, were divided into two groups by age and compared. Group I (n = 89) consisted of patients less than 65 years of age and Group II (n = 79) of patients between 66 and 85 years of age. RESULTS: There were no significant differences between the two groups with respect to the sex ratio, tumour size, depth of tumour invasion, and 5-year survival rate. Group I patients showed more lymph node involvement (p < 0.01), cancer of the diffuse histological type (p < 0.01), and cancers located in the gastric body (p < 0.05). Conversely, Group II exhibited more cancers of the protruded (p < 0.05) and intestinal histological type (p < 0.01), and more adenomatous residue (p < 0.01). CONCLUSIONS: Our findings suggest that early gastric cancer may present differently in different age groups; persons 65 years of age and older are more likely to have early gastric cancer of the slow-growing type than middle-aged patients.

Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer.

The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen + tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage >50% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (P<0.01 and <0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l(-1) onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, P<0.05) and 13.0 g/dl(-1) (81.0 vs 57.6%, P<0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels

Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer.

The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage of >50% occurred in 72.4% of patients. Ki67 expression significantly decreased after chemotherapy; the reduction correlated with tumour response in both univariate (P < 0.005) and multivariate analysis (P = 0.02). p53, bcl-2, steroid hormone receptor and c-erbB2 immunostaining were scarcely affected. Baseline bcl2 (P = 0.04) and c-erbB2 (P = 0.02) were directly and inversely associated with the reduction in Ki67 immunostaining, respectively. Baseline p53 expression (P < 0.01) was directly related with Ki67 expression at residual tumour, whereas oestrogen receptor expression (P < 0.001) was inversely related. Ki67 at residual tumour was a better predictor for relapse-free survival (RFS) than baseline Ki67. Clinical response (P < 0.03), but not reduction in Ki67, was a significant independent predictor for disease recurrence. Chemotherapy was found to induce tumour shrinkage and to reduce the number of cells in the cell cycle, but its effect on tumour biology/aggressiveness was minimal. Reduction in Ki67 immunostaining correlated with clinical response but failed to be related to RFS. Ki67 expression at surgery rather than at baseline appears to be a better predictor for disease relapse.