Antenatal dexamethasone treatment leads to changes in gene expression in a murine late placenta.

Antenatal steroids like dexamethasone (DEX) are used to augment fetal lung maturity and there is a major concern that they impair fetal growth. If delivery is delayed after using antenatal DEX, placental function and hence fetal growth may be compromised even further. To investigate the effects of DEX on placental function, we treated 9 pregnant C57/BL6 mice with DEX and 9 pregnant mice were injected with saline to serve as controls. Placental gene expression was studied using microarrays in 3 pairs and other 6 pairs were used to confirm microarray results by semi-quantitative RT-PCR, real-time PCR, in situ hybridization, western blot analysis and Oligo ApopTaq assay. DEX-treated placentas were hydropic, friable, pale, and weighed less (80.0+/-15.1mg compared to 85.6.8+/-7.6mg, p=0.05) (n=62 placentas). Fetal weight was significantly reduced after DEX use (940+/-32mg compared to 1162+/-79mg, p=0.001) (n=62 fetuses). There was >99% similarity within and between the three gene chip data sets. DEX led to down-regulation of 1212 genes and up-regulation of 1382 genes. RT-PCR studies showed that DEX caused a decrease in expression of genes involved in cell division such as cyclins A2, B1, D2, cdk 2, cdk 4 and M-phase protein kinase along with growth-promoting genes such as EGF-R, BMP4 and IGFBP3. Oligo ApopTaq assay and western blot studies showed that DEX-treatment increased apoptosis of trophoblast cells. DEX-treatment led to up-regulation of aquaporin 5 and tryptophan hydroxylase genes as confirmed by real-time PCR, and in situ hybridization studies. Thus antenatal DEX treatment led to a reduction in placental and fetal weight, and this effect was associated with a decreased expression of several growth-promoting genes and increased apoptosis of trophoblast cells.

Recurrent, progressive giant cell hepatitis in two consecutive liver allografts in a middle-aged woman.

In this report, we present a 41-year-old woman who developed rapidly progressive "giant cell hepatitis" that lead to end-stage liver disease. She underwent a successful liver transplantation in 1989. However, the giant cell hepatitis recurred in the allograft, resulting in cirrhosis within 4 years. She underwent a second liver transplantation in 1993. After 2 years of a relatively stable course, she again developed cirrhosis and was awaiting liver transplantation at the time of this report. The histopathologic features in the two allografts were identical to her original disease. Despite extensive investigations, no etiology for her liver disease could be found.

Dysembryoplastic neuroepithelial tumor-like neoplasm of the septum pellucidum: a lesion often misdiagnosed as glioma: report of 10 cases.

The authors report a series of 10 low-grade neoplasms arising in the midline anteriorly in the region of the septum pellucidum with many of the histologic features of dysembryoplastic neuroepithelial tumor (DNT). The patients (five female, five male) ranged in age from 6 to 35 years (mean age, 21.5 years). The most common presenting symptoms were headache, nausea and vomiting, and visual disturbances. Radiographically, the tumors extended into the lateral ventricles from the septal region and obstructed the foramen of Monro. Varying degrees of hydrocephalus were present. The lesions were lobular, well-delineated, hypointense to brain on T1-weighted magnetic resonance imaging, and hyperintense on T2-weighted images. They were uniformly nonenhancing or showed only minimal peripheral enhancement. The tumors, in aggregate, had the histologic features of DNT. These included a mucin-rich background, oligodendrocyte-like cells, "floating neurons," and a "specific glioneuronal element." Seven patients underwent gross total resection and two underwent subtotal resection. No patients received adjuvant chemotherapy or radiotherapy. On follow-up (n = 6; median, 14 months), all tumors had either not recurred or were radiologically stable. On the basis of both neuroimaging and histopathology, DNT-like lesions should be considered in the differential diagnosis of midline intraventricular tumors in children and young adults. Distinction from more aggressive neoplasms is essential because these tumors appear to behave in a benign fashion.

HMB-45 immunohistochemical staining of sentinel lymph nodes: a specific method for enhancing detection of micrometastases in patients with melanoma.

Despite the profound therapeutic and prognostic implications of nodal metastases in patients with melanoma, there is no consensus strategy for the optimal detection of metastases in sentinel lymph node biopsies. Traditional microscopic examination may be too crude to detect scattered, individual tumor cells. Conversely, molecular genetic techniques are prone to false-positive results. The authors evaluated the ability of HMB-45 immunohistochemistry to enhance detection of melanoma cells in histologically negative sentinel lymph nodes. Ninety-six sentinel lymph nodes, collected over a 25-month period from 66 consecutive patients with melanoma, were processed routinely and sectioned serially. Slides 1, 3, and 5 were stained with hematoxylin and eosin. HMB-45 staining was performed on an intervening slide in histologically negative nodes. To assess the background incidence of HMB-45-positive cells in lymph nodes draining the skin, the authors stained 244 cervical and axillary lymph nodes from patients without melanoma. Metastases were apparent microscopically in 12 (18%) of the 66 patients with melanoma. Of the remaining 54 patients, four patients (7%) had lymph nodes harboring individual, scattered HMB-45-positive cells. Benign nevocellular aggregates were present in four of the 96 sentinel lymph nodes (4% nodal incidence), but they were HMB-45-negative. The authors did not observe a single HMB-45-positive cell in the 244 lymph nodes from patients without melanoma. Immunohistochemistry appears to represent a specific means of enhancing tumor detection in sentinel lymph nodes from patients with melanoma.

Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy.

The diagnosis of prostate cancer on needle biopsy is based on a constellation of histologic features. There are, however, three histologic findings that are diagnostic of prostate carcinoma: perineural invasion (PNI), mucinous fibroplasia, and glomerulations. We prospectively identified core needle biopsies during a 5-month period in which one of these three entities was the key diagnostic feature of carcinoma within the biopsy specimen. Of 1480 consult cases reviewed, the following were key features to the diagnosis of very limited carcinoma: PNI (n = 9; 0.6%), mucinous fibroplasia (n = 2; 0.1%), and glomerulations (n = 0). To assess the incidence of PNI as the key feature, we also analyzed reports from Dianon during a 1-year period. Of approximately 16,300 Dianon needle biopsies with cancer, 12(0.07%) cases had PNI as the key diagnostic feature. Six of these 12 cases were also consult cases. Of the total of 15 cases with PNI, cancer was limited with 11 of the cases showing involvement of only one nerve. The median number of glands per nerve was five (range, 1-15). In addition to PNI, malignant cytologic features included amphophilic cytoplasm in 11 of 11 assessable cases and nuclear enlargement and hyperchromasia in 11 of 15 cases. Other malignant features were limited. Twelve cases showed rare to no visible nucleoli. Two cases had eosinophilic intraluminal debris. Blue mucin, crystalloids, and mitoses were absent in all cases. Nine of the 15 cases of PNI and the two cases of mucinous fibroplasia were verified as carcinoma with immunohistochemistry using high molecular weight cytokeratin. In rare cases, PNI is virtually the sole finding necessary to establish the diagnosis of carcinoma on needle biopsy. Although mucinous fibroplasia and glomerulations are also considered diagnostic of carcinoma, their occurrence alone without more conventional forms of carcinoma is even more rare.

Metastatic meningioma in fine-needle aspiration (FNA) of the lung: cytomorphologic finding.

Pulmonary metastasis of intracranial meningioma is rare. We present the cytomorphologic features of such a tumor in a 71 yr-old woman who was found to have multiple lung nodules 13 years following the resection of an atypical intracranial meningioma. Cytomorphologic features were quite distinct and included hypercellularity with large syncytial groups of monomorphic cells with epithelioid morphologic features, often in perivascular arrangements. Occasional intranuclear cytoplasmic inclusions as well as binucleated cells with wispy cytoplasmic extensions were also noted. Immunoperoxidase studies showed focal positivity for epithelial membrane antigen. The differential diagnosis includes primary or metastatic adenocarcinoma, malignant mesothelioma, and melanoma.

Infantile myofibromatosis.

Infantile myofibromatosis is a mesenchymal tumor most commonly seen in infancy. The tumors have a variable appearance on CT/MR and often simulate a more aggressive neoplasm. This report describes CT/MR findings in cases of infantile myofibromatosis with pathologic correlation. Discussion into the success of imaging in suggesting the correct diagnosis is also addressed.

Prospective hospital-based survey of attitudes of Southern women toward surgical treatment of breast cancer.

BACKGROUND: Breast-conserving surgery is equivalent to total mastectomy in the treatment of breast cancer. The Southern part of the United States has a low rate of breast conservation. METHODS: We surveyed 300 women: 100 hospital personnel, 100 cancer clinic patients, and 100 non-cancer clinic patients. The women were asked about their attitudes toward breast cancer, surgery preferences, and factors that might influence their decisions. RESULTS: One hundred eighty-nine chose mastectomy as the best operation, 106 women chose lumpectomy, and five women were undecided. There was no difference in mean age, racial distribution, education level, income level, percentage of women who considered themselves Southern women, concerns about breast cancer, recent mammograms, previous breast surgery, previous breast cancer treatment, or acquaintances with breast cancer between the mastectomy and the lumpectomy groups. Women interested in saving the breast were more likely to pick lumpectomy (35 vs. 84%, p = 0.001). A fear of cancer recurrence played a role in the decision (88 vs. 40%, p = 0.001). Fear of radiation therapy (76 vs. 57%, p = 0.002) and of the side effects (80 vs. 63%, p = 0.005) was a significant factor. CONCLUSIONS: The choice of surgery for breast cancer is an individual process between a woman and her surgeon. Attitudes and fears regarding cancer recurrence and radiation therapy may make women select mastectomy over lumpectomy.