Tsunehisa Kaku

Adenosarcoma of the uterus : a gynecologic oncology group clinicopathologic study of 31 cases

SummaryWe report on the clinical and pathologic findings in 31 cases of adenosarcoma of the uterus subjected to hysterectomy and staging laparotomy. Nine of 30 patients (30%) have had recurrent tumor and six of 30 (20%) have already died of tumor in a relatively short follow-up period (mean, 38.3 months). Seventeen of 31 cases were diagnosed as adenosarcoma with sarcomatous overgrowth (SO). Ten of these 17 with SO contained focal or extensive rhabdomyosarcoma. In six cases, extrauterine spread was identified as follows (two patients had two sites each): vaginal involvement (two cases), pelvic lymph node metastases (two), positive peritoneal cytologic findings (two), parametrial invasion (one), and ovarian metastasis (one). Extrauterine spread (stage III) (p < 0.001) and myometrial invasion (p = 0.04) were associated with higher rates of recurrence. The presence of lymphatic and/or vascular invasion, SO, and rhabdomyosarcomatous differentiation also indicated poor prognosis but did not attain statistical significance. Based on this experience, staging laparotomy including peritoneal cytology is suggested in cases of clinical stages I and II adenosarcoma. The differential diagnosis of these tumors is also discussed.

Clinicopathological characteristics of mucinous adenocarcinoma of the ovary

OBJECTIVE We conducted the present study to clarify the clinicopathological characteristics of mucinous adenocarcinoma. METHODS Two hundred twenty-five patients were diagnosed with mucinous adenocarcinoma at individual institutes and underwent primary treatment between 1998 and 2003. Of these patients, 189 patients who could undergo central pathological review were enrolled in this study. Of 189 patients undergoing central pathological review, 64 patients (33.9%) were diagnosed with mucinous invasive adenocarcinoma, 45 mucinous intraepithelial carcinoma, and 42 mucinous tumor of borderline malignancy. Twenty-five patients were diagnosed with other histological subtypes, including 8 endometrioid adenocarcinoma, 5 clear cell carcinoma, 3 serous adenocarcinoma, and 4 mixed type. There were 13 cases of metastatic mucinous adenocarcinoma, including 7 pseudomyxoma peritonei. Four hundred thirty-three patients with serous adenocarcinoma were used as controls. RESULTS Forty-five patients with mucinous invasive carcinoma were in FIGO I-II stages and 19 in III-IV stages. There was no difference in the outcome between mucinous invasive adenocarcinoma and serous adenocarcinoma in I-II stage patients and III-IV stage patients with optimal operation. In contrast, patients with mucinous invasive adenocarcinoma receiving suboptimal operation showed a significantly worse prognosis (survival rate: 27.8% vs. 61.5%). The response rate to chemotherapy for mucinous invasive adenocarcinoma was significantly lower than for serous adenocarcinoma (12.5% vs. 67.7%). CONCLUSIONS The diagnosis of mucinous invasive adenocarcinoma was difficult. Since patients with mucinous invasive adenocarcinoma had a lower response to chemotherapy, aggressive cytoreductive surgery was an effective treatment to improve the prognosis for advanced stage patients. A new chemotherapeutic regimen should be established for mucinous adenocarcinoma of the ovary.

Is lobular endocervical glandular hyperplasia a cancerous precursor of minimal deviation adenocarcinoma?: a comparative molecular-genetic and immunohistochemical study.

Although lobular endocervical glandular hyperplasia (LEGH) was originally described as a distinct hyperplastic glandular lesion of the uterine cervix, recent studies have raised a question that LEGH may be a cancerous precursor of minimal deviation adenocarcinoma (MDA) and other mucinous adenocarcinomas (MACs) of the uterine cervix. In the present study, we studied LEGH, MDA, and MAC by using molecular-genetic and immunohistochemical methods for chromosomal imbalance, microsatellite instability, human papillomavirus (HPV) infection, and gastric pyloric-type mucin secretion to clarify their relationship. Comparative genomic hybridization revealed recurrent chromosomal imbalances, that is, gains of chromosome 3q and a loss of 1p, which were common to MDA and MAC, in 3 of 14 LEGHs analyzed (21%). LEGHs with chromosomal imbalances showed a degree of cellular atypia in the hyperplastic glandular epithelium. Dual-color fluorescence in situ hybridization confirmed a gain of chromosome 3 fragment in these cervical glandular lesions. HPV in situ hybridization revealed that high-risk HPV (types 16 and 18) was positive in over 80% of MACs, but negative in all LEGHs and MDAs examined. Microsatellite instability was rarely detected in these cervical glandular lesions. Our present study results demonstrated a molecular-genetic link between LEGH and cervical mucinous glandular malignancies including MDA and MAC, and are thought to support the hypothesis that a proportion of LEGHs are cancerous precursors of MDA and/or MAC.

Sclerosing stromal tumor of the ovary: a clinicopathologic, immunohistochemical, ultrastructural, and cytogenetic analysis with special reference to its vasculature.

Sclerosing stromal tumor (SST) is a rare ovarian neoplasm occurring predominantly in young women and is histologically characterized by cellular heterogeneity, prominent vasculature, and a pseudolobular appearance composed of cellular and hypocellular areas. In the current study, three cases of SST were ultrastructurally examined and the tumors were found to be composed of several kinds of cells, i.e., luteinized thecalike cells, spindle-shaped fibroblastic cells, and primitive mesenchymal cells. These findings thus supported the ovarian stromal origin of SST. Twelve cases of SST also were analyzed immunohistochemically and demonstrated an expression of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in the luteinized thecalike cells and its receptor, fms-like tyrosine kinase 1 (flt-1), in capillary to medium-sized blood vessels. Reverse transcription-polymerase chain reaction (RT-PCR) also showed an expression of VPF/VEGF messenger RNA in SSTs. Accordingly, the characteristic vasculature and edema of SSTs were considered to be associated with the expression of VPF/VEGF. In addition, a fluorescence in situ hybridization (FISH) analysis also showed cells with three copy number of chromosome 12 in 13-21% of all examined SST cells, which suggested the presence of chromosome 12 trisomy in SSTs as well as in other ovarian stromal tumors.

Microscopic ovarian metastasis of the uterine cervical cancer

Six hundred forty-seven cases of carcinoma of the uterine cervix with FIGO stages Ib or more were initially treated with hysterectomy at Kyushu University Hospital from 1973 to 1987. In these, 597 cases could be pathologically reviewed for ovarian metastasis. In these 597 cases, 335 were stage Ib, 71 IIa, 185 IIb, and 6 IIIb. Only 3 (0.5%) of 597 showed ovarian metastasis. All 3 cases were stage IIb. None of stage Ib cancer cases had ovarian metastasis. One (0.19%) of 524 squamous cell carcinomas metastasized to the ovary, whereas 2 (5.5%) of 36 pure adenocarcinomas revealed ovarian metastasis. Interestingly, all ovarian metastatic lesions were microscopic in size and found in the ovarian hilus. As for the primary lesion, all cases with ovarian metastasis showed deep myometrial invasion, corpus invasion, and lymphatic permeation. Two cases showed pelvic lymph node metastases and positive peritoneal washing cytology. From the results of our study, it can be said that it is fairly safe to preserve the ovary at the time of radical operation in squamous cell carcinoma of the uterine cervix, but it may not be safe to preserve the ovary in pure adenocarcinoma of the uterine cervix.

Prognostic factors in ovarian carcinosarcoma: a clinicopathological and immunohistochemical analysis of 23 cases.

Carcinosarcoma of the ovary is a rare, highly aggressive neoplasm comprising histologically of both epithelial and mesenchymal components. The aim of this study was to evaluate the clinicopathological prognostic factors in ovarian carcinosarcoma, including the immunohistochemical expression of p53 protein and Ki67.

Expression of angiogenesis factors in monolayer culture, multicellular spheroid and in vivo transplanted tumor by human ovarian cancer cell lines.

We examined the expression of four angiogenesis factors (vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), platelet-derived endothelial cell growth factor (PD-ECGF) and basic fibroblast growth factor (bFGF)) in five human ovarian cancer cell lines by Northern blot analysis and immunohistochemical staining. The cancer cells were grown as a subconfluent monolayer culture, a multicellular aggregate (spheroid) in a three-dimensional culture, and a nude mouse-transplanted subcutaneous tumor in order to simulate the cellular conditions of ovarian cancers in peritonitis carcinomatosa, i.e. floating single tumor cells, multicellular aggregates and peritoneally implanted tumors. In each cell line, the expression of VEGF was detected in a monolayer culture and obviously enhanced in a three-dimensional culture. IL-8 was expressed in two of five cultured cell lines, but neither PD-ECGF nor bFGF was detected. Each cell line-derived transplanted tumor expressed immunohistochemical products of the four angiogenesis factors examined. These observations were confirmed by surgical specimens and suggested that ovarian cancer cells expressed different kinds and/or doses of angiogenesis factors depending on the form of the changed tumor cells during peritoneal implant formation.

Association between RCAS1 expression and clinical outcome in uterine endometrial cancer

RCAS1, which acts as a ligand for a putative receptor on immune cells such as peripheral lymphocytes and natural killer cells, is strongly expressed in human cancers. RCAS1 can induce these cells to undergo apoptotic cell death, which suggests that RCAS1 expression may prohibit the stromal reaction occurring in a tumour. To clarify the clinical significance of RCAS1 expression in uterine endometrial cancer, we analysed the association between RCAS1 expression and clinicopathologic variables by statistical methods. With the use of immunohistochemical techniques, we performed a retrospective study of RCAS1 expression in resected tumour tissue from 147 patients with uterine endometrial cancer. We evaluated the statistical correlation between RCAS1 expression and clinicopathologic variables. RCAS1 was expressed in 106 of 147 patients with uterine endometrial cancer ; 30 of these 147 patients showed RCAS1 overexpression. Overexpression of RCAS1 was significantly correlated with age at surgery, stage, extent of myometrial invasion, and positive peritoneal cytologic results. Multivariate analysis revealed that RCAS1 expression and metastasis were clinically significant prognostic factors for the overall survival. These findings indicated that analysis for RCAS1 expression can provide crucial information about the clinical behaviour of uterine endometrial cancer, which may be valuable for the management of patients with this disease.

Early adenocarcinoma of the uterine cervix—Its histologic and immunohistologic study

Eight cases of early adenocarcinoma selected from 101 adenocarcinomas of the uterine cervix were studied to establish the criteria of early adenocarcinoma. Lesions of these 8 cases were small in size. In 7 of 8 cases, these tumors originated in the area of the squamocolumnar junction (SCJ). Tumor cells consisted of two types of atypical columnar cells, i.e., tall columnar cells with enlarged and deeply eosinophilic cytoplasm and clear cells with enlarged and clear vacuoles. Tall columnar cells showed weak or negative reaction to high iron diamine (HID) stain and negative to Alcian blue (AB) stain. Clear cells showed negative reaction to HID stain and positive to AB stain. Although normal endocervical columnar cells showed markedly positive reaction to HID stain and negative reaction to AB stain, invasive adenocarcinoma cells showed similar reaction to early adenocarcinoma cells. From this study, it is surmised that early adenocarcinoma of the uterine cervix originates in the area of the SCJ and consists of tall cells in all cases and clear cells in 4 of 8 cases, and that HID-AB stain is useful in differentiating early adenocarcinoma cells from normal endocervical columnar cells.

Clinical management of atypical polypoid adenomyoma of the uterus. A clinicopathological review of 29 cases.

OBJECTIVE The clinical management of atypical polypoid adenomyoma (APAM) of the uterus remains to be established. We collected APAM cases, reviewed the clinicopathological features, and discussed the clinical management. METHODS Twenty-nine patients with APAM were identified by searching the tumor registry of the Japan Clinical Oncology Group (JCOG). Clinical information and histological specimens were obtained from 13 institutional members of the JCOG, and a central pathological review was performed. RESULTS The mean age of the patients was 38 years (range, 22-58). Squamous metaplasia was present in 19 cases (65.5%), and well-differentiated endometrioid adenocarcinoma coexisted in 5 cases (17.2%). Primary treatment consisted of dilatation and curettage in 9 patients (31.0%), vaginal resection in 2 patients (6.9%), hysteroscopic transcervical resection (TCR) using hysteroscopy in 10 patients (34.5%), and hysterectomy in 8 patients (27.6%). There were recurrences in 5 (23.8%) of the 21 cases in which fertility was preserved, and the recurrent rate was 10% (1/10) in patients those were treated with TCR and 36.4% (4/11) in those the other treatment options were selected. All patients were alive after primary treatment (a mean follow-up period was 39.6 months; range, 1-202). CONCLUSION The clinical outcome of APAM is benign. However, differential diagnosis should be performed because of its histological similarity to invasive endometrial carcinoma and the possibility of coexistence with other endometrial neoplasms. TCR is a recommended diagnostic and treatment option for patients who desire to preserve fertility.