Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes.

BACKGROUND: Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early. METHODS: Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass. RESULTS: Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P<0.05), while a six miRNA profile subset distinguished presurgical plasma from benign and ovarian cancer patients. There were also significant differences in miRNA profiles in presurgical plasma from women diagnosed with ovarian cancer who had short overall survival when compared to women with long overall survival (P<0.05). CONCLUSION: Our preliminary data support the utility of circulating plasma miRNAs to distinguish women with ovarian cancer from those with a benign mass and identify women likely to benefit from currently available treatment for serous epithelial ovarian cancer from those who may not.

Asymptomatic expectoration of surgical staples complicating lung volume reduction surgery.

Lung volume reduction surgery (LVRS) has recently been introduced as a palliative treatment for patients with severe emphysema. The most common postoperative complication is persistent air leak requiring prolonged tube thoracostomy. We describe a unique case of a patient with severe emphysema who underwent LVRS and presented, about a year later, with the repeated expectoration of surgical staples.

Mixed columnar cell and tall cell variant of papillary carcinoma of thyroid: a case report and review of the literature.

Columnar cell and tall cell carcinomas are newly described variants of papillary thyroid carcinoma associated with aggressive clinical behaviour. Although several cases of tall cell and columnar cell variants have been reported, only a single detailed case report of a mixed tall cell and columnar cell variant has been described in the English-language literature. We report another such composite tumour with predominant columna cell features in an elderly female. The tumour showed extrathyroidal extension with intraluminal superior thyroid vein invasion and lymph node metastasis. DNA ploidy analysis showed a diploid DNA content with no increase of S-phase fraction. Immunohistochemistry showed focal positivity for p53 and Ki-67 at the infiltrating margins of the tumour and diffuse positivity for proliferating cell nuclear antigen. The adverse clinical course warrants aggressive treatment and careful follow-up.

Primary synovial sarcoma of the kidney: a case report with literature review.

We describe a case of primary renal synovial sarcoma (SS) in a 48-year-old man. The patient presented with hematuria and was found to have a large tumor in his left kidney on computed tomography scan. Histology revealed a highly cellular spindle cell neoplasm with minimal pleomorphism. The major differential diagnoses included leiomyosarcoma, hemangiopericytoma, and SS. The presence of focal areas with a biphasic pattern, uniformly positive immunostain for bcl-2, focally positive immunostains for epithelial membrane antigen and cytokeratin, and negative immunostains for CD-34, smooth muscle actin and S-100 established the diagnosis. This was subsequently confirmed by molecular testing for t(X;18) translocation. Since the existence of primary SS in the kidney was first suggested in 1999, to the best of our knowledge a total of 19 cases including the present case have been reported to date. Although primary renal SS is rare, these findings indicate that it should be included in the differential diagnosis of spindle cell tumors of the kidney.

Primary salivary gland amyloidosis causing sicca syndrome.

Sicca syndrome (SS), consisting of xerostomia and xerophthalmia, may be caused by various disease processes. We present a unique case of SS secondary to primary amyloidosis. Amyloidosis is a rare but definite cause of SS and should be included in the differential diagnosis of any patient who presents with sicca symptoms. A literature review comparing amyloidotic patients with SS and patients with amyloidosis only demonstrates that both of these groups of patients present similarly with regard to symptoms. However, the majority of patients with SS present with sicca symptoms initially in addition to symptoms of amyloidosis. These SS patients also present with proteinuria and negative serology test results. Therefore, patients presenting with sicca symptoms, proteinuria, and negative serologic findings should be suspect for amyloidosis. The importance of distinguishing the diagnosis of Sjögren's syndrome from SS in these patients cannot be overemphasized. There is a significantly higher incidence of developing a lymphoma in Sjögren's syndrome patients. This has important implications for the head and neck surgeon treating these patients.

Polymorphous low-grade adenocarcinoma: flow cytometric, p53, and PCNA analysis.

Polymorphous low-grade adenocarcinoma of minor salivary glands (terminal duct carcinoma, lobular carcinoma) was first defined more than a decade ago. A 17% recurrence rate and a 9% metastasis rate have been reported. Fifteen formalin-fixed, paraffin-embedded archival cases were analyzed. Ploidy and proliferative activity were evaluated with flow cytometric analysis. Demonstration of an abnormal p53 gene product and proliferative cell nuclear antigen analyses were also performed with routine immunohistochemical procedures. The purpose of this investigation was to evaluate these parameters and determine if a correlation existed. Flow cytometry was performed on 10 cases; 3 showed an aneuploid cell line (mean, S-phase diploid tumor cells 5.9%; S-phase aneuploid 26.7%). Products of a mutation of the p53 tumor suppressor gene have been noted to accumulate in salivary gland tumors, both benign and malignant. Qualitative assessment revealed p53 positive staining in 4 of 15 tumors; positive cells comprised 5% to 10% of the tumor. The percentage of tumor cells positive for proliferative cell nuclear antigen staining ranged from 0.5% to 70%. There was no correlation between proliferative activity as determined by proliferative cell nuclear antigen when compared with results of flow cytometric analysis except for one case that exhibited p53 staining, a 26% proliferative cell nuclear antigen fraction, and a distinct aneuploid cell line.

Scrape cytology of meningioangiomatosis: a report of two cases with diagnostic cytologic features.

BACKGROUND: Meningioangiomatosis is a rare, probably hamartomatous condition characterized by nonneoplastic intracortical proliferation of meningothelial cells, capillaries and fibroblasts. The lesion may mimic a tumor both clinically and radiologically. We present two cases of the entity, including its cytologic features. CASES: A 71-year-old man presented with an eight-month history of headache, change in vision, loss of depth perception and unsteady gait. Magnetic resonance imaging (MRI) revealed an infiltrative lesion of the left occipital lobe, diffuse in nature. Cytologic smears prepared at the time of intraoperative consultation showed numerous thin-walled capillaries together with bland spindle cells. Occasional large cells with prominent nucleoli were also present. Frozen section confirmed the presence of linear, small capillaries surrounded by fibroblasts and meningothelial cells, consistent with meningioangiomatosis. The second case was a 3-year-old girl who presented with a one-day history of seizure, vomiting, fever and perioral cyanosis. MRI revealed an enhancing lesion in a temporal lobe of the cerebrum. The patient underwent excision of the lesion. Intraoperative cytology showed numerous meningothelial whorls together with neurons and occasional capillaries. Both patients were well, one after three months and the other after six. CONCLUSION: Meningioangiomatosis is a lesion characterized by linear capillaries, meningothelial cells and neurons, some exhibiting nuclear atypia. The combination can lead to an erroneous diagnosis of more common conditions, such as meningioma (with intracortical extension) and anaplastic astrocytoma. Contrary to these more sinister diagnoses, meningioangiomatosis is a completely benign, presumably hamartomatous entity.

Fine needle aspiration cytology of mixed tall and columnar cell papillary carcinoma of the thyroid. A case report.

BACKGROUND: We report the first case of a composite tumor (tall cell and columnar cell variants) of papillary thyroid carcinoma (PTC) diagnosed by fine needle aspiration. It is important to differentiate these uncommon aggressive variants from the usual indolent papillary carcinomas. CASE: Fine needle aspiration cytology was obtained from a rare composite tumor of tall cell and columnar cell variants of papillary thyroid carcinoma. The smears showed a cellular aspirate with scattered single tumor cells and several tissue fragments arranged in a papillary pattern. The tumor cells had abundant nuclear grooves and intranuclear pseudoinclusions. Several of the fragments showed columnar cells with nuclear pseudostratification, and a few clusters displayed tall columnar cells with basal nuclei and abundant cytoplasm. A rare cluster exhibited composite features of tall cell and columnar cell variants. CONCLUSION: Columnar cell and tall cell variants of PTC manifest aggressive clinical behavior. The differential diagnosis of columnar cell variant includes medullary carcinoma of thyroid and metastatic adenocarcinoma. Immunohistochemical stains for calcitonin and thyroglobulin play an important role in difficult cases. The tall cell variant needs to be differentiated from Hürthle cell papillary neoplasm of thyroid, which displays prominent nucleoli and lacks the characteristic nuclear features of PTC. The preoperative diagnosis of these aggressive variants' is important in planning the most appropriate type of treatment.

Correlation of proliferative index (PCNA reactivity and Ki-67 reactivity) in primary breast carcinoma with hormone status, lymph node status, and disease-free survival.

The proliferative activity in 42 cases of breast cancer were assessed immunohistochemically using antibodies to proliferating cell nuclear antigen (PCNA) and Ki-67. These indices were correlated with the steroid receptor status, pathologic stage, and disease-free survival. There was a strong direct correlation between the two proliferation indices (r = .902, P < 0.001, Kendall's rank correlation). There was a weak correlation between the hormone receptor status and proliferation indices that was not significant when statistically tested. The cases were stratified into PCNA low proliferative index (PI) group (< 4.5% positive cells) and PCNA high PI group (> 4.5% positive cells). In the low PI group, five of 18 (28%) patients were node-positive in contrast to eight of 14 (58%) patients in the high PI group. After a follow-up period of 42-60 months, 14 of 19 (74%) patients in the low PI group were disease-free compared to 10 of 17 (53%) patients in the high PI group. The PCNA and Ki-67 proliferative indices appear to be of great prognostic value and may help identify a subset of breast cancer patients who should be given adjuvant therapy.

Merkel cell carcinoma arising in the oral mucosa.

This is the first reported case of a Merkel cell carcinoma arising in the oral mucosa. The tumor occurred in a 53-year-old white man, and it originated in the right mucobuccal fold. The Merkel cell origin was confirmed by electron microscopic and immunohistochemical studies.

Interferon-alpha generation in mice responding to challenge with UV-inactivated herpes simplex virus.

In humans with advanced human immunodeficiency virus (HIV) infection, an interferon-alpha (IFN-alpha) response by a specialized blood mononuclear cell to herpes simplex virus (HSV) in vitro is associated with resistance to opportunistic infections. A cell type of unknown lineage, designated the natural IFN-producing cell (NIPC), has been identified preliminarily as the source of these IFNs and may have a role in other host defense functions. Earlier studies suggested the existence of analogous HSV-responsive cell populations in mice. The role specifically of IFN-alpha in the murine system, however, has not been characterized. Using IFN bioassay and neutralization with antisera against Type I IFNs and IFN-beta, we have defined the types and sources of IFNs produced by mice in response to in vivo and in vitro challenge with UV-inactivated HSV. After intraperitoneal inoculation with HSV, BALB/c and C57Bl/6 strains produced characteristically different levels of serum IFNs that appeared principally to be IFN-alpha. The response of mononuclear cells from these mice differed from that of the intact mouse. Isolated cells from bone marrow and spleen released detectable IFNs much later than did whole animals, and the IFNs produced by marrow, spleen, and peritoneal cells were usually neutralized by the anti-IFN-beta. Only bone marrow cells produced detectable amounts of IFN-alpha. Both intact mice and their cells became refractory to restimulation with similar kinetics.