Luteinized thecoma associated with sclerosing peritonitis--conservative surgical approach followed by corticosteroid and GnRH agonist treatment--a case report.

BACKGROUND: Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare tumor that has no standard definitive treatment regimen. CASE: A 25 year-old patient diagnosed with luteinized thecoma and sclerosing peritonitis in the omentum. The patient received high dose corticosteroids (IV Hydrocortisone 500 mg/d) and GnRH agonist (IM Leuprolide 3.75 mg) in order to achieve ovarian suppression and relief of the clinical peritonitis. She was re-admitted two weeks later due to bowel obstruction which was treated conservatively. The steroid regimen was continued by oral intake for 5 weeks with complete remission of the peritonitis related symptoms. The bilateral enlarged ovarian tumor-like solid was the prominent finding in consecutive ultrasound exams with no decrease in size despite of the above mentioned protocol. Thus, the patient was re-operated for exploration and biopsies of the ovary and the pathology report showed no evidence of remnant disease in the ovary, or in the peritoneum. Completing follow-up of 15 months since the last operation, the patient is asymptomatic. She conceived spontaneously and currently is in her 24th week of a normal pregnancy. CONCLUSION: This is the first case report in the English literature of a successful medical conservative treatment of a young patient with luteinized thecoma associated with sclerosing peritonitis that led to complete relief of the symptoms and allowed fertility preservation.

The Ki67+ proliferation index correlates with increased cellular retinol-binding protein-1 and the coordinated loss of plakophilin-1 and desmoplakin during progression of cervical squamous lesions.

AIMS: To investigate the modulation of cellular retinol-binding protein (CRBP)-1 and the desmosomal plaque proteins plakophilin (PKP)-1 and desmoplakin (DP) in correlation with the Ki67+ proliferation index (PI) during the progression of cervical squamous intraepithelial lesions (SIL) to squamous cell carcinoma (SCC). METHODS: Using in situ imaging by brightfield and confocal laser scanning microscopy, the expression of CRBP-1 protein and transcripts, PKP-1, DP and the Ki67 PI were analysed in 38 low-grade (L) SIL, 56 high-grade (H) SIL, 49 SCC, 30 control cervices and 10 human papillomavirus-positive condylomatous lesions. RESULTS: CRBP-1+ cells increased from 11.4% in the normal cervix to 80.3% in LSILs, 92.3% in HSILs and slightly decreased to 78.3% in invasive SCCs (P = 0.0001) in close association with the Ki67 PI (r =0.41; P < 0.0001). PKP-1+ and DP+ cells were correlated (0.32; P < 0.0001) and decreased from normal (81% versus 92.3%) to LSIL (53.1% versus 85.3%), to HSIL (46.4% versus 67.5%) and SCC (35.1% versus 35.9%). The Ki67+ PI was inversely correlated with DP (-0.20, P = 0.0014) and PKP-1 (-0.19, P = 0.015). Condylomata retained low CRBP-1 and high expression of PKP-1 and DP. CONCLUSIONS: The gain of CRBP-1 and the loss of desmosomal proteins occur early in cervical carcinogenesis.

Cellular retinol-binding protein-1 expression in endometrial stromal cells: physiopathological and diagnostic implications.

AIMS: Cellular retinol-binding protein-1 (CRBP-1) contributes to the maintenance of the differentiated state of the endometrium through retinol bioavailability regulation. The aim was to analyse CRBP-1 expression in endometrial stromal cells at eutopic and ectopic sites in different physiopathological conditions. METHODS AND RESULTS: Antibodies to CRBP-1, CD10 and alpha-smooth muscle actin were applied to proliferative (n = 10), secretory (n = 9) and atrophic (n = 7) endometrium, decidua (n = 4), adenomyosis (n = 5), endometriosis (n = 10), endometrial polyps (n = 9), simple endometrial hyperplasia (n = 6), well-differentiated endometrioid carcinoma (n = 6) and submucosal leiomyomas (n = 5). In some cases, Western blotting and reverse transcription-polymerase chain reaction were also applied. CRBP-1 was expressed by eutopic and ectopic endometrial stromal cells more markedly during the late secretory phase and in decidua of pregnancy. CRBP-1 expression was low in the stroma of atrophic endometrium and absent in myometrium, leiomyomas and cervical stroma. CD10 immunoreactivity was weak in atrophic endometrium and in decidua. CONCLUSIONS: CRBP-1 expression characterizes endometrial stromal cells at eutopic and ectopic sites and appears to be more specific than CD10. The level of CRBP-1 varies in intensity according to hormonal variations, reaching its maximum in predecidua and decidua. Thus, immunodetection of CRBP-1 may help to elucidate the physiopathological changes which occur in endometrial stroma and can also be applied as an adjuvant stromal marker.

Calcifying fibrous pseudotumor of mesentery presenting with acute peritonitis: case report with immunohistochemical study and review of literature.

Calcifying fibrous pseudotumor (CFP) is a benign soft tissue lesion composed of thick collagen bundles, scattered fibroblasts, and psammomatous and dystrophic calcifications, located most commonly in the extremities and trunk of children and young adults. The present case in a 36-year-old woman is to the best of our knowledge the first report of a large CFP confined to the mesentery, which, because of torsion, led to acute peritonitis and emergency laparotomy. The typical histologic features were accompanied by a prominent myofibroblastic proliferation along with inflammatory response at the periphery of the lesion. The spindle cells of the lesion were positive for vimentin and focally for CD34 and smooth-muscle actin. Review of the literature and discussion of differential diagnosis in this report focuses on abdominal CFP and other intraabdominal soft tissue lesions, some of which may be precursors of CFP. Int J Surg Pathol 9(3):249-253, 2001

Alpha-smooth muscle actin-positive myofibroblasts in endometrial stroma are not a reliable criterion for the diagnosis of well differentiated endometrioid adenocarcinoma in small tissue samples.

Although a desmoplastic stromal reaction in well-differentiated endometrioid adenocarcinoma is considered a major criterion in the differential diagnosis with atypical hyperplasia, this histologic feature has not met with universal approval. Since alpha-smooth muscle (alpha-SM) actin positive myofibroblasts characterize the desmoplastic stromal response in a variety of neoplasms, the present study was undertaken in order to establish whether these cells are also prominent in the stroma of endometrioid carcinoma and if present could be used as a valid criterion in the differential diagnosis between benign and malignant lesions. The present study of 100 endometrial samples showed focal desmoplastic stromal reaction with alpha-SM actin positive myofibroblasts in 30% of small samples and in 50% of hysterectomy specimens with endometrioid carcinoma. In normal endometrium and in benign lesions lacking a desmoplastic reaction, focal stromal alpha-SM actin positivity was a very common finding. Stromal alpha-SM actin-positive cells were also frequently seen in nondesmoplastic stroma of endometrioid carcinoma. Thus the common presence of alpha-SM actin-positive myofibroblasts in normal endometrial stroma and in benign and malignant lesions precludes its usefulness in the diagnosis of well differentiated endometrioid adenocarcinoma, especially in small tissue samples.

Brenner tumors but not transitional cell carcinomas of the ovary show urothelial differentiation: immunohistochemical staining of urothelial markers, including cytokeratins and uroplakins.

To determine whether Brenner tumors and transitional cell carcinomas (TCCs) of the ovary are urothelial in type, the immunoprofiles of 14 Brenner tumors, including three malignant examples, and eight ovarian TCCs were compared with those of Walthard nests, urothelium, 12 urinary bladder TCCs and 17 ovarian adenocarcinomas (serous, endometrioid, mucinous, and undifferentiated type). The immunohistochemical stains used included those for cytokeratins CKs 5/6, CK7, CK8, CK13, and CK20, vimentin, CA125, and the specific urothelial differentiation marker uroplakin III. CK7 and CK8 were broadly expressed in most tumors of ovary and bladder examined, while vimentin was focally present in some ovarian TCCs and adenocarcinomas. As in normal and neoplastic bladder urothelium, urothelial markers, including uroplakin III, CK13, and CK20, were detected in the epithelial nests of Brenner tumors. Brenner tumor cells also expressed uroplakins Ia and II. CA125 was observed focally in some Brenner tumors. In contrast, TCCs of the ovary and Walthard nests lacked uroplakins and were essentially negative for CK20 and CK13 but quite strongly expressed CA125. This immunophenotype closely resembled that found in ovarian adenocarcinomas. Thus, it appears that the only true urothelial-type ovarian neoplasm is the Brenner tumor, whereas ovarian TCC most likely represents a poorly differentiated adenocarcinoma with a morphologic transitional cell pattern. These results may explain the controversies as expressed in the recent literature concerning TCC of the ovary and establish its place among the ovarian adenocarcinomas of müllerian type.

Nuclear localization of beta-catenin and plakoglobin in primary and metastatic human colonic carcinomas, colonic adenomas, and normal colon.

Beta-catenin is a cytoskeleton-associated signaling molecule shown to be elevated in various carcinomas but mostly in colon cancer owing to its impaired degradation. In contrast, its close homologue plakoglobin was shown to suppress the tumorigenicity of certain tumor cells. In the present study, we have used a semiquantitative immunohistochemical approach to evaluate the extent of nuclear localization of beta-catenin in human colonic adenocarcinomas and adenomas and compared it to the distribution of plakoglobin in the same tissues. We show that beta-catenin accumulates in the nuclei of the epithelium of primary and metastatic colonic adenocarcinoma as well as in colonic adenomas. In contrast, nuclear plakoglobin levels in these tissues were low, even compared to those found in epithelial cells of normal colon. These results support the view that the increase in beta-catenin levels in colon cancer cells occurs early in the tumorigenic process, leading to its nuclear localization, not only in invasive adenocarcinoma, but also in colonic adenoma with mild dysplasia.

Cadherin expression in glandular tumors of the cervix.

BACKGROUND: The cadherins are homotypic adhesion proteins that are important in cell sorting during organogenesis. Classic cadherins include several different types that show tissue specific expression. Specific tissue expression of cadherins often is preserved in neoplastic transformation, and cadherin phenotype can be used to differentiate morphologically similar but histogenetically distinct tumors. METHODS: The authors examined by using immunohistochemistry in paraffin sections the expression of E- (epithelial) and P- (placental) cadherin in 39 patients with glandular tumors of the cervix, including invasive adenocarcinoma, villoglandular adenocarcinoma, adenocarcinoma in situ (AIS), and adenoma malignum. RESULTS: In all cases, E-cadherin was expressed in both normal and malignant glands without appreciable differences. P-cadherin, normally confined to basal epithelial cells and not observed in benign glands, was aberrantly expressed in neoplastic glands in 27 cases, including 96%(23 of 24 cases) of invasive cancers, 40% (2 of 5) of villoglandular carcinomas, 25% (2 of 8) of AIS, and 0% (0 of 2) of adenoma malignum. CONCLUSIONS: The authors' results show that E-cadherin is uniformly expressed in glandular tumors of the cervix with no evidence of decreased expression in these tumors. In addition, P-cadherin is aberrantly expressed in most adenocarcinomas and appears to be preferentially expressed in invasive rather than in situ lesions. Thus, aberrant expression of P-cadherin may be a useful marker of invasive or aggressive clinical behavior in glandular lesions of the cervix.

The effect of interferon-gamma and tumor necrosis factor-alpha on the expression of ICAM-1 and HLA-DR molecules on cells of a human germ cell neoplasm and their susceptibility to lysis by lymphokine-activated killer cells.

The ICAM-1 molecule plays a role in the interaction of NK cells with a variety of tumor cells, including carcinoma, melanoma and glioblastoma cells. In the present study, we analyzed the effect of IFN-gamma and TNF-alpha on both the expression of HLA-DR and ICAM-1 molecules on HGCN (Germa-2), and on their susceptibility to lysis by LAK cells. Our results show that 1,000 U/ml IFN-gamma induced a substantial increase in the expression of both ICAM-1 molecules and HLA-DR on the cell surface, while the effect of TNF-alpha on the expression of these molecules was substantially less prominent. When Germa-2 cells, previously exposed to 1,000 U/ml IFN-gamma, were employed as target cells in a 4-hour 51Cr release assay, a statistically significant increase in the lysis by LAK cells was noted. These results show that in the presence of IFN-gamma, Germa-2 tumor cells undergo modulation which affects both the expression of ICAM-1 and HLA-DR molecules as well as their susceptibility to lysis by LAK cells.

Primary angiosarcoma of the ovary: a clinicopathologic, immunohistochemical and electronmicroscopic study.

The present report of a 25 year old woman with a primary ovarian angiosarcoma is supplemented by histochemical and ultrastructural studies and reviews the literature of this extremely rare neoplasm. Since this ovarian tumor, especially in young women, may constitute a diagnostic pitfall, problems relating to differential diagnosis are emphasized. Although the origin of this neoplasm appears to occur most likely from the rich ovarian vasculature, other less conventional histogenetic theories such as a possible origin in mixed mullerian tumor, in teratoma or in other ovarian germ cell tumors have also been proposed and are considered in this paper.

Clinical-pathological study of uterine leiomyomas with high mitotic activity.

OBJECTIVE: To evaluate clinical-pathological aspects of mitotically active leiomyomas. STUDY DESIGN: Twenty patients with smooth muscle tumors of the uterus, with 5-9 mitotic figures per 10 high power fields and without atypia or necrosis were studied. The clinical and pathological characteristics of these tumors were reviewed and analyzed. RESULTS: Patients' ages ranged from 33 to 63 years (mean 42.5 years). The size of the tumors ranged from 1.5 to 9.5 cm (mean 5.4 cm). On gross examination all tumors appeared as typical leiomyomas. Treatment included hysterectomy in 16 patients and myomectomy in four. Follow-up periods ranged from 1.5 to 11 years (mean 6.8 years). None of the patients developed a recurrent tumor. CONCLUSION: The benign clinical behavior of such tumors supports their current designation as mitotically active leiomyomas, thus deleting the previous misnomer 'smooth muscle tumors of uncertain malignant potential'. Myomectomy is an appropriate treatment, particularly in young patients interested in reproduction.

Expression of the adherens junction protein vinculin in human basal and squamous cell tumors: relationship to invasiveness and metastatic potential.

The acquisition of an invasive or metastatic phenotype in malignant neoplasms is often correlated with reduced cellular adhesiveness. We investigated the expression of the adhesion-associated cytoplasmic protein, vinculin, in normal and neoplastic human squamous epithelia, as well as in metastases of squamous cell carcinomas, and correlated the results with invasiveness and metastatic potential. Tissue samples from various tumors were examined, including basal cell carcinomas (BCC), keratoacanthomas, and squamous cell carcinomas (SCC). In addition, lymph node metastases from nine of the SCC were tested in this study. Our results indicate that most BCC, keratoacanthomas, and in situ SCC display strong positive staining for vinculin. The level of immunolabeling for vinculin and its pattern of distribution in the low malignant, nonmetastasizing lesions was similar to those observed in normal squamous epithelia. In contrast, in SCC, which are invasive and possess metastatic potential, as well as in their metastases, vinculin labeling was negative or poor, irrespective of their degree of differentiation. In conclusion, poor vinculin labeling in tumors of squamous epithelial origin examined here appears to be related to the metastatic potential of the tumor. Vinculin immunostaining of primary tumors originating in stratified squamous epithelia may thus be of value in helping to determine the metastatic potential of these neoplasms.

Endometrial pathology.

The current literature on endometrial neoplasia deals with proliferative lesions such as endometrial proliferation in early pregnancy, atypical polypoid adenomyofibromata and their possible relationship to carcinoma, and histological grading of endometrial cancer with emphasis on nuclear grading and subtypes of endometrial cancer including the newly described intestinal and hepatoid types. Recent publications dealing with p53 protein, genetic studies, and nucleolar organizer regions are of interest but have provided no striking new insight into endometrial neoplasia. Angiogenesis has appeared for the first time in the literature in connection with endometrial neoplasia. Tamoxifen continues to occupy an important place in the literature, and endometrial adenosarcoma has been identified recently as one of the myriad of lesions which patients treated with tamoxifen are prone to develop.

Metastasizing placental site trophoblastic tumor: immunohistochemical and DNA analysis. 2 case reports and a review of the literature.

Placental-site trophoblastic tumor (PSTT) is a rare form of gestational trophoblastic neoplasia. The clinical behaviour of PSTT is usually benign, but sometimes it can be highly malignant with late recurrence and metastasis. We describe two cases of PSTT with pulmonary metastasis in patients aged 35 and 29 years respectively. The mitotic rate was elevated to 9 and 13 mitotic figures per 10 high-power fields respectively. Immunohistochemical staining showed a predominance of human placental lactogen (hPL) positive cells when compared with human chorionic gonadotropin (hCG) reactive cells in one case, and a reverse pattern in the other one. DNA measurement in one case showed an aneuploid tumor with a tetraploid DNA peak. The clinical behaviour of PSTT remains unpredictable, and there are no reliable means of predicting clinical outcome.

Phenotypic modulation of fibroblasts in massive ovarian edema: an immunohistochemical study of three cases.

An immunohistochemical study of three cases of massive ovarian edema revealed coexpression of vimentin, total actins, alpha-smooth muscle actin, desmin and low molecular weight cytokeratins in the stromal spindle cells composing the edematous ovarian tissue. In addition these stromal cells expressed smooth muscle myosin which is a marker for terminal smooth muscle differentiation. This remarkable fibroblastic cell plasticity in massive ovarian edema may represent yet another example of fibroblastic modulations occurring under the influence of microenvironmental stress factors.

Diagnosis and management of malignant germ cell ovarian tumors in young females.

Germ cell tumors (GCT) compose most of the preadolescent malignant ovarian tumors; dysgerminoma being the most common (48%), followed by endodermal sinus tumor, immature teratoma, mixed GCT and embryonal carcinoma. The percentage of malignant epithelial ovarian tumors rises with increasing age, while that of the GCT tumors declines. Of all tumor markers discussed, only AFP and hCG are being routinely monitored. Their most effective use is in monitoring response to therapy and detecting recurrences early. The current therapeutic regimens are presented, among them bleomycin, etoposide and platinol (BEP) and other new regimens; their influence on the patients' fertility is discussed. Further improvement in the prognosis of these young patients will hopefully follow development of new surgical and chemotherapeutic approaches.

Metastatic breast carcinoma manifesting as postmenopausal uterine bleeding in a patient on tamoxifen therapy.

A rare case of breast carcinoma metastasizing to the endometrial and endocervical mucosa during tamoxifen treatment is presented. Routine histologic evaluation has been supplemented by immunohistochemical staining for intermediate filaments. Although the association of tamoxifen therapy for breast carcinoma with the development of endometrial carcinoma is well known, this is, to the best of our knowledge, the first report of metastatic breast carcinoma to the uterus of a patient on tamoxifen therapy.

Adrenal cortical adenoma with extensive fat cell metaplasia.

This report describes a large adrenal cortical tumor with a significant component of mature adipose tissue in a 40 year old woman. No bone marrow elements were identified in multiple sections. This lesion, representing most likely an adrenal cortical adenoma with extensive fat cell metaplasia, has not been previously reported and must be differentiated from adrenal myelolipoma.