Cervical Health in Systemic Lupus Erythematosus.

Objective: A health disparity exists for African American (AA) women with systemic lupus erythematosus (SLE) who have increased prevalence of human papilloma virus (HPV) infection and cervical neoplasia. We used a self-sampling brush to obtain cervical cells to assess cytology, HPV infection, and vaginal cytokine production in AA women with SLE. Methods: Thirty AA women with SLE ages 18-50 years consented to participate. Clinical information was obtained by review of records and patient interviews, and surveys administered to assess cervical health history, knowledge of HPV, and satisfaction with the self-sampling brush. Vaginal samples were analyzed for cytology, HPV DNA and RNA, and vaginal cytokine RNA. Results: Our cohort (mean 36.9, ±9.4 years) had moderate/severe SLE and were on immunosuppressives. The majority had history of abnormal pap smears (63%) with prevalent risk factors for HPV infection: multiple sex partners (9.5 ± 7), not vaccinated for HPV (83.3%), smoking (26.7%), and not using condoms (73.3%). Most were aware of HPV causing cervical cancer (70%) but were unaware of other HPV-related diseases. Most preferred self-sampling over traditional pap smear (80%). Abnormal cytology was detected in 13.3%. HPV DNA was detected in 70%, with half showing multiple types, and all showing active infection (+RNA). HPV-infected samples demonstrated RNA expression of multiple cytokines with no specific/ consistent pattern. Conclusion: Our high-risk cohort lacked knowledge about HPV-related diseases and were not employing strategies to reduce their risk with vaccination and condoms. This study highlights the need for cervical health education, increased monitoring, and intervention in these high-risk women.

Dedifferentiated endometrial carcinoma: an ongoing diagnostic dilemma.

Tumours of uterine corpus are the most common gynaecological malignancies. The clinicopathological features of most of these tumours are well understood; however, dedifferentiated endometrial carcinoma still requires a lot of research to establish adequate management guidelines. The entity was first described in 2006 and is an aggressive tumour with poor prognosis. We present two cases of this tumour with a literature review, emphasising morphologic and immunohistochemical features that may help in the differential diagnosis.

Factors predicting nodal metastasis in endometrial cancer.

PURPOSE: Evaluation of lymph node (LN) metastases in endometrial carcinoma (EC) is an important prognostic factor and a required element of cancer staging. The purpose of this study is to analyze what factors might predict the likelihood of nodal involvement in EC. METHODS: A retrospective search of our institutional database for hysterectomies with associated LN dissection in women with EC revealed 207 cases between 2005 and 2012. Cases with primary EC, irrespective of histologic subtype, including carcinosarcomas were included in the study, but pure sarcomas were excluded. We evaluated various factors including tumor size (TS; ≤2.0 cm and >2.0 cm), depth of myometrial invasion (DMI; absent, ≤50 %, >50 %), positive pelvic cytology (PPC), cervical stromal invasion (CSI), and lymph-vascular invasion (LVI), to determine which factors correlated with the presence of LN metastasis. RESULTS: Of the 207 (age = 62.29 ± 10.9, mean ± SD) cases of EC with LN dissection in our study group, 34 (16.42 %) had positive LNs. On univariate analysis, we found that TS (p = 0.04), tumor grade (Grade I and II versus grade III, p < 0.0001), DMI (p < 0.0001), CSI (p < 0.0001), LVI (p < 0.0001), and PPC (p = 0.001) showed statistically significant correlation with LN metastasis. However, on multivariate analysis, only DMI (p = 0.002) and LVI (p = 0.004) independently showed statistically significant correlation with LN metastasis. In addition, 18 (8.7 %) grade I and II (well/moderately differentiated) tumors with TS ≤2.0 cm and <50 % DMI showed no LN metastasis, LVI, CSI, or PPC. CONCLUSION: We concluded that DMI and LVI were independent factors predictive of LN metastasis.

Preoperative fine needle aspiration of axillary lymph nodes in breast cancer: clinical utility, diagnostic accuracy and potential pitfalls.

OBJECTIVE: This study evaluates the diagnostic accuracy of axillary lymph node fine needle aspiration (FNA) cytology in breast cancer and correlates it with clinical parameters/outcomes. STUDY DESIGN: A total of 91 females underwent FNA of axillary lymph nodes at our institution from January 2007 to February 2013. The cases were classified as 'positive', 'negative for malignancy' and 'nondiagnostic'. RESULTS: Forty-six cases (50.5%) had a histologic follow-up (4.4 ± 3.1 months); of these, 22 (47.8%) were true positive, 7 (15.2%) were true negative, 2 (4.3%) were false negative, 5 (11%) were false positive and 10 (21.7%) were nondiagnostic. However, cytological review of all false positive and false negative cases confirmed the presence or absence of tumor, respectively. All false positive cases had undergone preoperative neoadjuvant chemotherapy, with no residual tumor present, and a treatment effect identified only histologically. Meanwhile, the 2 false negative cases involved micrometastasis (≤ 1.5 mm). Thus, if we exclude these false positive cases (complete responders), then the sensitivity, specificity, positive predictive value and negative predictive value were 91.7, 100, 100 and 77.8%, respectively. All preoperative FNA-positive axillary lymph nodes were spared from sentinel lymph node biopsy except for 3 of 27 (11.1%). CONCLUSION: We suggest that axillary lymph node FNA is a highly sensitive technique with a low false negative rate (4.3%) and a diagnostic accuracy of 93.5%.

Cervical cytology with a diagnosis of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H): a follow-up study with corresponding histology and significance of predicting dysplasia by human papillomavirus (HPV) DNA testing.

OBJECTIVES: To evaluate the clinical significance of "atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion" ASC-H by comparing the original cytologic findings with follow-up tissue biopsies, and its association with high-risk HPV. METHODS: A total of 235,518 ThinPrep Pap tests were performed at our institution from January 2008 through December 2010, but only 727 (0.3%) of these cases were diagnosed as ASC-H. RESULTS: Of the 309 cases diagnosed as ASC-H on cytology for which follow-up histologic material was available, 120 (38.8%) were definitively diagnosed as high-grade dysplasia (CIN 2/3) and 75 (24.2%) showed features of low-grade dysplasia (CIN 1). We observed that the incidence of dysplasia in patients less than 30 years of age was 73.4% (113/154) and 48.3% (14/29) in patients greater than 49 years of age (p = 0.001). There were 71 cases for which high-risk HPV DNA testing was conducted. HPV DNA was found to be positive in 41 of the dysplastic cases (CIN 1 = 18 cases and CIN 2/3 = 23) and negative in six of the dysplastic cases (CIN1 = 2 and CIN2/3 = 4). CONCLUSION: We conclude that cases diagnosed as ASC-H should be followed-up with caution as they are strongly associated with dysplasia of any grade (63.1%), especially high-grade dysplasia (38.8%). Reflex HPV DNA testing is an important predictor of dysplasia with a positive predictive value of 87.2% in our study.

Metastatic renal cell carcinoma to the pancreas: diagnostic significance of fine-needle aspiration cytology.

BACKGROUND: Renal cell carcinoma rarely metastasizes to the pancreas. Diagnosing a neoplasm that is metastatic to the pancreas by fine-needle aspiration (FNA) cytology is often challenging. A detailed clinical history may prove to be beneficial. CASE REPORTS: A total of 729 pancreatic FNAs were performed from January 2005 through August 2012 at our institution. Among these, we found 3 patients with a prior history of a malignant renal neoplasm who presented with a pancreatic mass: 2 in the tail and 1 in the head. Radiographically, they ranged in size from 2.5 to 7.0 cm. Microscopic evaluation of cytologic material obtained during endoscopic ultrasound-guided FNA (EUS-FNA) revealed cohesive clusters of atypical cells with clear cytoplasm and prominent nucleoli surrounded by a thin capillary network. The neoplastic cells were immunoreactive with CD10 (cases 2 and 3). A diagnosis of metastatic clear cell renal cell carcinoma was rendered for each case based on the morphologic features and immunohistochemical staining pattern of the neoplastic cells. Histologic comparison with the available slides of the corresponding primary renal neoplasm confirmed the diagnosis. CONCLUSION: We conclude that EUS-FNA of pancreatic masses is an important, effective, and accurate diagnostic modality for early diagnosis of both primary and metastatic neoplasms of the pancreas.

Prognosis and reproducibility of new and existing binary grading systems for endometrial carcinoma compared to FIGO grading in hysterectomy specimens.

BACKGROUND: The current International Federation of Gynecology and Obstetrics (FIGO) grade in endometrial carcinomas requires the evaluation of histologic features with proven prognostic value but with questionable reproducibility. This study tests the prognostic power and reproducibility of a new binary grading system. STUDY DESIGN: Specimens from 254 hysterectomies were graded according to the new 3- and 2-tiered FIGO grading systems described by Alkushi et al. The selected morphologic parameters for the new grading system included the presence of predominant solid or papillary architecture pattern, severe nuclear atypia, tumor necrosis, and vascular invasion. The Cox proportional hazards and κ statistics were used for comparisons. RESULTS: On multivariate analysis, and looking at all tumor cell types, the 4 tested grading systems were independent predictors of survival, with the 3-tiered FIGO grading system being the most predictive (P = 0.005). In the subset of endometrioid tumors, the 3- and 2-tiered FIGO grading systems and the new grading system retained their statistical significance as predictors of survival (P = 0.004, P = 0.03, and P = 0.007, respectively), whereas the grading system of Alkushi et al did not (P = 0.1). In nonendometrioid tumors, the new grading system proved to be the best predictor of survival, reaching near statistical significance (P = 0.06). The new grading system had acceptable intraobserver and interobserver reproducibility assessment (κ = 0.87 and κ = 0.45, respectively). CONCLUSION: The 3-tiered FIGO grading system retained its superior prognostic power. However, available binary grading systems remain an attractive option by being highly reproducible and by eliminating the clinical ambiguity of intermediate grades of disease.

Ovarian malignant mixed mullerian tumor with primitive neuroectodermal differentiation: case report with review of the literature.

Ovarian malignant mixed mullarian tumor (OMMMT) is a rare and aggressive tumor of the female genital tract, occurring mainly in elderly women. Stage of disease is the most important predictor for survival with no prognostic effect, yet, of heterologous elements. Rare case reports described the peculiar presence of primitive neuroectodermal tissue among other heterologous elements in these tumors. Attractive designations, such as teratoid carcinosarcoma, were set by some authors to describe this subset of lesions, where it was considered a primary neuroectodermal tumor capable of multilineage differentiation. We here report a case of OMMMT in an elderly woman with focal primitive neuroectodermal differentiation as the sole heterologous element, and review the controversy on this topic in the literature.

Pancreatic solid-pseudopapillary neoplasm: report of a case in an elderly man with cytologic-histologic correlation.

BACKGROUND: Solid-pseudopapillary neoplasms of the pancreas are rare and unusual tumors, occurring mostly in young women. Their cytologicfeatures are well described in textbooks; however, published reports still show some cytologic findings overlapping with pancreatic endocrine neoplasms and demonstrate the important diagnostic role of endoscopic ultrasound-guided fine needle aspiration. CASE: A case of solid-pseudopapillary neoplasm of the pancreas occurred in a 61-year-old man; on cytology it was initially diagnosed as pancreatic endo crine neoplasm. The resection specimen in addition to immunohistochemical stains gave away the diagnosis. CONCLUSION: Endoscopic ultrasound-guided fine needle aspiration remains a valid, minimally invasive procedure in pancreatic cytology. Tumor cells grouped around fibrovascular cores are the most reproducible cytologic finding in these tumors. Immunostains can play an important role when cell block material is available.

Fast drying of Fine Needle Aspiration slides using a hand held fan: impact on turn around time and staining quality.

To analyze the impact of using a hand held fan to speed the air-drying process during immediate adequacy evaluation of Fine Needle Aspirations. The effect on turn around time and staining quality is evaluated. Two mirror image air-dried smears for each pass were prepared. One was subjected to a small hand-held fan with a fan diameter of 7 cm held an average distance of 3 to 5 cm from the slide. The other smear was left to dry without a fan. A total of 93 consecutive pairs were evaluated over a 2-month duration. The average time needed for air-drying using the fan was 73 seconds (range 10-300 seconds, standard error 6.986), while it was 200 seconds (range 15-645 seconds, standard error 17.799) for those without fan. This difference was statistically significant (p < 0.001). Smears were then evaluated for single cells, cell clusters and background material and no appreciable difference in stain quality was noted between the 2 groups. The use of a small hand-held fan for air-drying shortened the drying time for FNA adequacy by an average of 127 seconds (63% time reduction) for each pass. The quality of staining was comparable. Using a fan is highly recommended.

Histopathologic and cytopathologic diagnostic discrepancies in head and neck region: pitfalls, causes, and preventive strategies.

BACKGROUND: Clinicians commonly utilize fine needle aspiration biopsy (FNAB) for the primary investigation of head and neck masses. Correlation of these results with the surgical resection diagnosis is an essential part of quality control and assurance programs in all cytology laboratories. METHODS: Of 610 cases, 20 (3.3%) had corresponding surgical resections performed within 3 months of the FNAB, with a discrepant diagnosis identified through a search that involved all FNABs performed on the head and neck region, excluding the thyroid gland, at Wayne State University between 1999 and 2004. Sites of discrepant samples included the parotid or submandibular gland (n = 5), lymph nodes (n = 8), and paratracheal/paraesophageal neck masses (n = 7). RESULTS: The reasons of false-negative FNABs included sampling errors (n = 3), insufficient material for an adequate interpretation (n = 5), lack of triage necessary for ancillary studies (n = 4), and interpretation errors (n = 6). There were 2 false-positive FNABs, both reported as mucoepidermoid carcinoma and showed chronic sialadenitis in one and lymphoepithelial cyst in the other. CONCLUSIONS: FNAB is an effective tool for the diagnosis and triage of patients with head and neck masses that can be further improved with an onsite immediate adequacy evaluation and triage performed by a pathologist.

[Cutaneous lupus profundus]. / Le lupus cutané profond.

The objective of this studies is to review clinical and laboratory features of lupus panniculitis. The authors report 3 cases of lupus profundus from a group of 70 lupus erythematosus. In both cases the lupus panniculitis presented as subcutaneous infiltrated and indurated nodules. The diagnosis was confirmed on clinical, histological and therapeutic data. The evolution is slow and is characterised by regression of the inflammatory lesions with treatment by antimalarial drugs. The lupus panniculitis has generally a favorable prognosis.

Early oxidative stress in the diabetic kidney: effect of DL-alpha-lipoic acid.

Oxidative stress is implicated in the pathogenesis of diabetic nephropathy. The attempts to identify early markers of diabetes-induced renal oxidative injury resulted in contradictory findings. We characterized early oxidative stress in renal cortex of diabetic rats, and evaluated whether it can be prevented by the potent antioxidant, DL-alpha-lipoic acid. The experiments were performed on control rats and streptozotocin-diabetic rats treated with/without DL-alpha-lipoic acid (100 mg/kg i.p., for 3 weeks from induction of diabetes). Malondialdehyde plus 4-hydroxyalkenal concentration was increased in diabetic rats vs. controls (p <.01) and this increase was partially prevented by DL-alpha-lipoic acid. F(2) isoprostane concentrations (measured by GCMS) expressed per either mg protein or arachidonic acid content were not different in control and diabetic rats but were decreased several-fold with DL-alpha-lipoic acid treatment. Both GSH and ascorbate (AA) levels were decreased and GSSG/GSH and dehydroascorbate/AA ratios increased in diabetic rats vs. controls (p <.01 for all comparisons), and these changes were completely or partially (AA) prevented by DL-alpha-lipoic acid. Superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione transferase, and NADH oxidase, but not catalase, were upregulated in diabetic rats vs. controls, and these activities, except glutathione peroxidase, were decreased by DL-alpha-lipoic acid. In conclusion, enhanced oxidative stress is present in rat renal cortex in early diabetes, and is prevented by DL-alpha-lipoic acid.

An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense.

Aldose reductase inhibitors (ARIs) prevent peripheral nerve dysfunction and morphological abnormalities in diabetic animal models. However, some experimental intervention studies and clinical trials of ARIs on diabetic neuropathy appeared disappointing because of either 1) their inadequate design and, in particular, insufficient correction of the sorbitol pathway activity or 2) the inability to reverse established functional and metabolic deficits of diabetic neuropathy by AR inhibition in general. We evaluated whether diabetes-induced changes in nerve function, metabolism, and antioxidative defense are corrected by the dose of ARI (sorbinil, 65 mg/kg/d in the diet), resulting in complete inhibition of increased sorbitol pathway activity. The groups included control rats and streptozotocin-diabetic rats treated with/without ARI for 2 weeks after 4 weeks of untreated diabetes. ARI treatment corrected diabetes-induced nerve functional changes; that is, decrease in endoneurial nutritive blood flow, motor and sensory nerve conduction velocities, and metabolic abnormalities (i.e., mitochondrial and cytosolic NAD+/NADH redox imbalances and energy deficiency). ARI restored nerve concentrations of two major non-enzymatic antioxidants, reduced glutathione (GSH) and ascorbate, and completely arrested diabetes-induced lipid peroxidation. In conclusion, treatment with adequate doses of ARIs (that is, doses that completely inhibit increased sorbitol pathway activity) is an effective approach for reversal of, at least, early diabetic neuropathy.