Jining Feng

Combination of MUC5ac and WT‐1 immunohistochemistry is useful in distinguishing pancreatic ductal carcinoma from ovarian serous carcinoma in effusion cytology

Malignant ascites may be the first presentation of an unsuspected cancer. Pancreas and ovary are among the organs that are usually evaluated as a source of primary. The purpose of this study is to investigate a panel of immunohistochemical stains to help differentiate pancreatic from ovarian carcinoma. We evaluated the immunohistochemical staining of eight commercially available antibodies MUC1, MUC2, MUC5ac, Wilms tumor susceptibility gene 1 (WT1), cytokeratin 7 (CK7), CK20, CA125, and CA19.9 in 25 effusion specimens with evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9 pancreatic adenocarcinomas, and 2 unknown primaries. Primary ovarian serous carcinomas were positive for WT‐1 (100%), CK7 (93%), CK20 (43%), CA125 (100%), CA19.9 (50%), MUC1 (100%), MUC2 (0%), and MUC5ac (0%). Primary pancreatic carcinomas were positive for MUC5ac (100%), MUC1 (100%), CA19.9 (100%), CK7 (78%), CK20 (22%), CA125 (89%), WT‐1 (0%), and MUC 2 (0%). The combination of MUC5ac positivity/WT‐1 negativity was seen in 100% of pancreatic carcinoma, whereas MUC5ac negativity/WT‐1 positivity in 100% of ovarian serous carcinoma. It appears that the combination of MUC5ac and WT‐1 stains is useful in distinguishing pancreatic ductal from ovarian serous carcinoma in body fluid cytology. Diagn. Cytopathol. 2010.

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.

Dual color multiplex TTF-1 + Napsin A and p63 + CK5 immunostaining for subcategorizing of poorly differentiated pulmonary non-small carcinomas into adenocarcinoma and squamous cell carcinoma in fine needle aspiration specimens

Background: The distinction of lung adenocarcinoma (ADC) from squamous cell carcinoma (SCC) has important therapeutic implications. Napsin A is a recently developed marker, which has shown high specificity for lung tissue in the surgical pathology specimens. In this study, we have evaluated whether the use of a panel of novel multiplex cocktails of TTF-1 + Napsin A and p63 + CK5 for dual color immunostaining will improve the diagnostic accuracy of lung adenocarcinoma and squamous cell carcinoma in fine needle aspiration (FNA) specimens, usually with relatively scant microfragments of diagnostic material. Materials and Methods: Formalin-fixed, paraffin-embedded, adequately cellular FNA cell blocks with a confirmed diagnosis of either ADC (n = 22), SCC (n = 20) or poorly differentiated carcinoma (PDC; n = 7), from a total of 49 consecutive cases, were studied. All these cases had subsequently confirmed diagnosis in biopsies or resection specimens. The sections were immunostained with two color methods of TTF-1 + Napsin A and p63 + CK5 multiplex cocktails. The presence of one or more unequivocal individual tumor cells with convincing brown nuclear TTF-1 and red cytoplasmic Napsin A staining, and cells with brown nuclear p63 and membranous / cytoplasmic CK5 staining were interpreted as ‘positive’. Results: All 20 FNA cell blocks from SCC cases were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A. The sensitivity and specificity of the dual immunoexpressions of p63 + CK5 for SCC of lung FNAs were both 100%. All 22 ADC cases were positive with dual stain of TTF-1 + Napsin A and negative for dual stain of p63 + CK5. On follow-up of the surgical pathology specimens, 22 cases were confirmed as ADC. The sensitivity of the dual immunoexpression of TTF-1 + Napsin A for ADC of lung FNAs was 100% and the specificity was also 100%. Of the seven PDC cases, five cases that were positive for dual stain p63 + CK5 and negative for dual stain TTF-1 + Napsin A could be categorized as SCC. Two of the seven (2 / 7) PDC cases were positive for dual stain TTF-1 + Napsin A and negative for dual stain p63 + CK5, consistent with ADC. Conclusions: Simultaneous coordinate or individual immunostaining for Napsin A / TTF-1 in ADC and p63 / CK5 in SCC demonstrated high sensitivity and specificity. The panel with multiplex Napsin A / TTF-1 and p63 / CK5 dual color immunostains could specifically subcategorize PDC into ADC and SCC in lung FNA specimens. Multiplex dual color Napsin A / TTF-1 and p63 / CK5 immunostaining is especially recommended for evaluation of FNA specimens with relatively scant cellularity.

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.

Vacuolated cell pattern of pancreatobiliary adenocarcinoma: a clinicopathological analysis of 24 cases of a poorly recognized distinctive morphologic variant important in the differential diagnosis

Pancreatic ductal adenocarcinoma (PDCA) is characterized by well-defined tubular units in the vast majority of the cases; however, variations in this theme do occur. It is important to recognize the morphologic spectrum of PDCA to avoid misdiagnosis especially in small specimens and also in metastatic foci. Here, we document a morphologic variant of PDCA that is characterized by a distinctive pattern of infiltrating cribriform nests in a distinctive “microcystic” or “secretory” pattern. Twenty-four cases of PDCA have been identified in a review of 505 cases diagnosed with PDCA. Histologically, this pattern was characterized by infiltrating nests of tumor cells with large vacuoles and “signet-ring” like appearance imparting a cribriform growth pattern. The vacuoles were one to five cells in size, often merging to form multilocular spaces separated by a thin rim of cell membrane. Many of these spaces contained CA19.9 positive granular secretory material. The nuclei were often pushed to the periphery and compressed in a pattern resembling adipocytes, although the nuclei were often densely hyperchromatic and displayed significant atypia. Especially in biopsies from the peripancreatic fat and peritoneum, these neoplastic cells had been misdiagnosed as degenerating adipocytes, and in the lymph nodes, they had been misinterpreted as lipogranulomas. Clinical findings of the patients were similar to that of conventional PDCA, except higher incidence of history of smoking (83% vs. 60%; p = 0.034). In conclusion, vacuolated cell adenocarcinoma is a distinct morphologic variant of PDCA, and the presence of this peculiar pattern in a metastatic site, although not specific, should raise the suspicion of a PDCA.

Significance of high-risk human papillomavirus DNA-positive atypical squamous cells of undetermined significance pap smears in perimenopausal and postmenopausal women

OBJECTIVE To determine the risk of high-grade squamous intraepithelial lesion (HSIL)/cervical intraepithelial neoplasia (CIN) 2 or 3 in perimenopausal and postmenopausal women with high-risk human papillomavirus (HPV) DNA-positive atypical squamous cells of undetermined significance (ASCUS) on Pap tests. STUDY DESIGN A total of 752 perimenopausal and postmenopausal women (patients 45 years) with an ASCUS interpretation on ThinPrep Pap tests were identified in 2002 and 2003. High risk HPVDNA was detected in 191 (25.4%) women. The follow-up results in these 136 women were compared with those of women <45 years. RESULTS Of the 136 perimenopausal and postmenopausal women, 64.7% became negative on cytology or biopsy and 30.9% revealed persistent low-grade SIL (LSIL)/CIN 1. Furthermore, 5 women (3.68%) were diagnosed with HSIL/CIN 2 or 3, and 1 patient had squamous cell carcinoma (0.74%). The rate of HSIL/CIN 2 or 3 or worse detected in perimenopausal and postmenopausal women was significant lower than 10.6% in women <45 years (p = 0.028). CONCLUSION Our study showed that perimenopausal and postmenopausal women with high-risk HPV positivity and an ASCUS interpretation have a significantly lower risk of HSIL/CIN 2 or 3 detected. Nonetheless, the risk of a significant finding on workup, including invasive carcinoma, indicates the need for colposcopic evaluation of these women.

Frequency and Rationale of Fine Needle Aspiration Biopsy Conversion to Core Biopsy as a Result of Onsite Evaluation

OBJECTIVE To measure the frequency and analyze the rationale and potential diagnostic benefits of converting the fine needle aspiration (FNA) procedure to core biopsy. STUDY DESIGN The frequency of conversion to core biopsy was calculated over 13 months. Analysis of these cases was conducted in regard to the appropriateness for conversion and whether the core biopsy provided additional specific diagnostic information. RESULTS During this period, the onsite triaging pathologist recommended FNA conversion to core biopsy in 31 of 821 procedures (3.7%). In 3 instances, the core biopsy could not be performed. The rationale for conversion in the remaining 28 cases (3.4%) included either scant aspirated material in 9 cases (32%) or an anticipated need for additional histologic material to further characterize the lesion in the other 19 (68%). In 27 cases (96%), the rationale for conversion was considered to be appropriate, and in 3 of these (11%) the core provided a change in diagnosis. Additional useful diagnostic information was identified in 12 cases (44%). CONCLUSION Conversion to core biopsy during FNA is infrequent but justified in most cases. Appropriate utilization of this approach is helpful and may be cost effective.

Outcomes of Women with Atypical Squamous Cells of Undetermined Significance and High-Risk Human Papillomavirus DNA

OBJECTIVE To study the risk of high-grade squamous intraepithelial lesion (HSIL) and cervical intraepithelial neoplasia (CIN) 2 or 3 in women with human papillomavirus (HPV)-positive atypical squamous cells of undetermined significance (ASCUS) cytology over a 2-year period using the 2001 Bethesda System and ThinPrep Paps. STUDY DESIGN In 2002, 846 patients with ThinPrep cervical cytology having an ASCUS interpretation and positive for high-risk HPV DNA were identified. A cohort of 514 (60.8%) patients with follow-up by repeat cytology, cervical biopsy or both was included in the study. Patient age was 12-81 years, with a median of 25 years. RESULTS There were 291 women (56.6%) with negative status by cytology, HPV testing or biopsy with a median interval of 8.5 months, and an additional 174 patients (33.9%) had persistent ASCUS, positive HPV DNA or low-grade SIL/CIN 1. Finally, 49 patients (9.5%) had CIN 2 or 3, with a median interval of 8.5 months. CONCLUSION Our study suggests that HSIL or CIN 2 or 3 will be detected in 1 in 10 women with HPV-positive index ASCUS cervical cytology at initial colposcopy or within a 2-year follow-up period.

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.

Fine needle aspiration of head and neck masses in the operating room: accuracy and potential benefits.

Fine needle aspiration (FNA) in the operating room is a convenient optional diagnostic approach. Our objective of this study was to evaluate the accuracy and study the potential benefits of fine needle aspiration in the operating room.