Magda Esebua

Impact of the Reclassification of the Non-Invasive Follicular Variant of Papillary Carcinoma as Benign on the Malignancy Risk of the Bethesda System for Reporting Thyroid Cytopathology: A Meta-Analysis Study

Objectives: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established diagnostic categories for cytologic specimens of the thyroid. Each category was associated with an estimated risk of malignancy. Recently, the non-invasive follicular variant of papillary thyroid carcinoma has been reclassified as benign. This reclassification may alter the malignancy risk of TBSRTC diagnostic categories. Study Design: A literature search was made for all studies investigating the effect of reclassification of some non-invasive follicular variant papillary thyroid carcinomas as benign on the malignancy risk associated with TBSRTC categories. The authors calculated the malignancy risk for TBSRTC categories in a series of 315 thyroid aspirates when the non-invasive follicular variant of papillary thyroid carcinoma was considered benign. A meta-analysis of malignancy risk data for the 3 published studies and the current study was performed. Results: The meta-analysis showed that the malignancy risk was reduced for all TBSRTC categories except the “non-diagnostic” category. The reduction in malignancy risk was greatest in the categories “suspicious for malignancy” and “atypia/follicular lesion of undetermined significance.” Conclusion: A meta-analysis of all pertinent studies demonstrated that re-categorization of the non-invasive follicular variant of papillary thyroid carcinoma as benign reduces the malignancy risk in the majority of TBSRTC categories.

Accuracy and Reproducibility of Nuclear/Cytoplasmic Ratio Assessments in Urinary Cytology Specimens.

Evaluation of the nuclear to cytoplasmic ratio is commonly used for assessment of the presence of malignancy and for grading and typing of malignant neoplasms. Despite its widespread usage, little information exists regarding the accuracy and reproducibility of non‐automated assessment.

Interobserver reproducibility for HER2/neu immunohistochemistry: A comparison of reproducibility for the HercepTest™ and the 4B5 antibody clone

BACKGROUND IHC results for HER2/neu vary with replicate testing using the same antibody clone and when alternate clones are utilized. A number of factors appear to be responsible for this variability, including fixation times, equipment utilized and training and experience of staff. A number of studies have documented interobserver variability for a single antibody clone but few have evaluated reproducibility between antibody clones and which clones demonstrate the highest degree of interobserver reproducibility. DESIGN We studied a series of 93 cases stained by both the HercepTest™ and the 4B5 clone for interobserver reproducibility. Formalin-fixed, paraffin-embedded sections were stained by the immunohistochemical technique using the manufactures directions for both the HercepTest™ and the 4B5 clone. FISH testing was performed on formalin-fixed paraffin embedded sections according to the PathVysion HER-2 DNA probe kit instructions. RESULTS Absolute agreement rate for Hercep was 85%. Absolute agreement for 4B5 was 69%. This difference was statistically significant (p<0.0001). The chance-corrected agreement (weighted kappa) for the HercepTest™ was 79% and 71% for 4B5 (p<0.0001). Absolute agreement between antibody clones was 58% with the chance corrected agreement being 51%. Absolute agreement of 4B5 with FISH was significantly greater than that of the HercepTest™ (54% vs 35%). CONCLUSION Agreement between evaluators was greater with the HercepTest. However, agreement with FISH results was superior for the 4B5 clone. Interobserver agreement was less than the 95% agreement threshold recommended by the ASCO/CAP guidelines for development of a new testing method for HER2 evaluation.

Episodic painful parotid swelling caused by sialodochitis with eosinophilic inflammation: a new entity.

Management of recurring parotid gland swelling is challenging because it presents in such a wide variety of disorders in all age groups. Chronic parotitis occurs mostly in middle age and is characterized by episodes of swelling, discomfort, and inflammation separated by variable periods in which the glands seem normal. Characteristically, an episode crescendos over one to three days and persists for several days, which is the time sequence for an acute infectious disease. However, some episodes last only hours and others span weeks. Most authors have clumped cases together in their series, but numerous entities undoubtedly exist within the clumps. We present a case of chronic parotitis that is unique in clinical and histologic features. A 34-year-old woman complained of gradually worsening episodic parotitis of two years duration unresponsive to antibiotics or systemic steroids. These almost-daily episodes were rapid in onset and resolution, over six to 12 hours, with symptoms of severe pain, parotid swelling, tenderness, and occasional angioedema of her cheek and eyelid. Either gland might be involved, but generally the attacks were unilateral and most frequently involved the right parotid gland. Massage of the gland expressed thick mucus from Stensen’s duct, which was swollen, firm, and exquisitely tender during the attacks. Between the episodes physical examination was essentially normal. The severity and frequency of these attacks were unresponsive to antibiotics, antihistamines, and a steroid burst. A prolonged course of steroids was tried as well, without improvement. Work-up for the known causes of parotitis was negative. A CT scan showed the parotid glands to be symmetrically hyperdense, mildly enlarged, and without calculi. Sialography showed a dilated Stensen’s duct with areas of constriction. Cytologic examination of the mucus expressed from the gland showed numerous squamous and glandular cells without atypia. SS-A and SS-B were negative; rheumatoid factor was less than 15; erythrocyte sedimentation rate was

Cytologic separation of branchial cleft cyst from metastatic cystic squamous cell carcinoma: A multivariate analysis of nineteen cytomorphologic features

The separation of branchial cleft cysts from metastatic cystic squamous cell carcinomas in adults can be clinically and cytologically challenging. Diagnostic accuracy for separation is reported to be as low as 75% prompting some authors to recommend frozen section evaluation of suspected branchial cleft cysts before resection. We evaluated 19 cytologic features to determine which were useful in this distinction.

Testis specific Y-like 5: gene expression, methylation and implications for drug sensitivity in prostate carcinoma

BackgroundTSPYL5, a putative tumor suppressor gene, belongs to the nucleosome assembly protein family. The chromosomal location of the TSPYL5 gene is 8Q22.1, and its exact role in prostate cancer etiology remains unclear. Further TSPYL5 gene and protein expression in prostate carcinoma cells and diseased tissues including its susceptibility for epigenetic silencing is unknown. Also, not known is the variation in TSPYL5 protein expression with regards to progression of prostatic carcinoma and its possible role in drug sensitivity.MethodsTSPYL5, DNMT-1 and DNMT-B gene expression in DU145, LNCaP and RWPE-1 cells and prostate tumor tissues was analyzed by qRT-PCR and RT-PCR. Demethylation experiments were done by treating DU145 and LNCaP cells with 5-aza-2′-deoxycytidine in vitro. Methylation analysis of TSPYL5 gene was performed by methylation specific PCR and pyrosequencing. TSPYL5 protein expression in benign and diseased prostate tumor tissues was performed by immunohistochemistry and in the cells by Western blotting.ResultsTSPYL5 was differentially expressed in non-tumorigenic prostate epithelial cells (RWPE-1), androgen independent (DU145), dependent (LNCaP) prostate carcinoma cells and tissues. Methylation-specific PCR and pyrosequencing analysis identified an inverse relationship between DNA methylation and expression leading to the silencing of TSPYL5 gene. Treatment of prostate carcinoma cells in which TSPYL5 was absent or low (DU145 and LNCaP) with the demethylating agent 5-aza-2′-deoxycytidine upregulated its expression in these cells. Immunohistochemical studies clearly identified TSPYL5 protein in benign tissue and in tumors with Gleason score (GS) of 6 and 7. TSPYL5 protein levels were very low in tumors of GS ≥ 8. TSPYL5 overexpression in LNCaP cells increased the cell sensitivity to chemotherapy drugs such as docetaxel and paclitaxel, as measured by the cellular viability. Furthermore, the cells also exhibited reduced CDKN1A expression with only marginal reduction in pAKT.ConclusionsDecrease in TSPYL5 protein in advanced tumors might possibly function as an indicator of prostate tumor progression. Its absence due to methylation-induced silencing can lead to reduced drug sensitivity in prostate carcinoma.

Interobserver reproducibility and agreement with original diagnosis in the categories “atypical” and “suspicious for malignancy” for bile and pancreatic duct brushings

The Papanicolaou Society of Cytopathology has developed a set of guidelines which include a diagnostic scheme with the categories “atypical” and “suspicious for malignancy.” These intermediate categories may help stratify risk of malignancy for samples obtained from the bile and pancreatic ducts. However, the reproducibility of these intermediate categories is currently unknown.

Risk stratification using cytomorphologic features in endoscopic ultrasonographic-guided fine-needle aspiration diagnosis of pancreatic ductal adenocarcinoma.

Endoscopic ultrasonographic‐guided fine‐needle aspiration (EUS‐FNA) is the procedure of choice for the investigation of pancreatic lesions. It shows good sensitivity and excellent specificity. Diagnostic criteria have been published but not statistically validated for the diagnosis of malignancy and stratification of risk for malignancy.

Cytotechnologist screening of fine-needle aspiration specimens: impact on turnaround time and diagnostic accuracy.

Fine‐needle aspiration (FNA) is widely utilized due to its short turnaround time (TAT), diagnostic accuracy, and low cost. Controversy exists as to what role cytotechnologists should play in evaluation of FNAs. Some authorities believe all FNAs should be screened by cytotechnologists while others believe that cytotechnologist review is unnecessary.

A Novel del(20q) in Aggressive Nodal Marginal Zone Lymphoma.

This is a case report of a previously undescribed 20q chromosomal deletion (del(20q)) in marginal zone lymphoma (MZL). A 54-year-old Caucasian male presented with an enlarging neck mass and multiple violaceous skin nodules over his chest. Biopsy of the neck mass and cervical lymph nodes revealed MZL. Cytogenetic evaluation of both lymph node and bone marrow tissue revealed del(20q). This was an unexpected finding, as del(20q) is associated with myelodysplastic syndromes and myeloproliferative neoplasms and rarely seen in diffuse large B-cell lymphoma, follicular lymphoma, and T-cell lymphoma, but has not previously been described in MZL. We describe the case presentation and histologic findings and discuss the significance of this novel finding.