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.

The Bethesda System thyroid diagnostic categories in the African-American population in conjunction with surgical pathology follow-up.

BACKGROUND: It has been reported that African-Americans (AA) have a higher prevalence of overall malignancy compared to Caucasians, in the United States, yet the incidence of thyroid malignancy is half. The aim of this study is to assess the rate of malignant versus benign thyroid disease in AA from an urban-based hospital with an academic setting. Our study analyzed the AA population with respect to fine needle aspiration (FNA) of thyroid lesions, in correlation with final surgical pathology. This is the first study of its kind to our knowledge. DESIGN: We retrospectively reviewed thyroid FNA cytology between January 2005 and February 2011. Consecutive FNA specimens with corresponding follow-up surgical pathology were included. The patients were categorized as African- American (AA) and Non-African-American (NAA), which included Caucasians (C), Hispanics (H), and Others (O). The FNA results were classified using the latest edition of The Bethesda System for Reporting Thyroid Cytopathology (TBS-Thy) and the follow-up surgical pathology was used for the final categorization. RESULTS: We studied 258 cases: 144 AA (56%) and 114 NAA [43 C (17%), 3 H (1%), and 68 O (28%)]. The average age for AA was 51 years (range 20 - 88) and for NAA was 53 years (range 25 - 86). There were more females than males in the AA versus the NAA group (85 vs. 75%). The incidence of thyroid lesions in the FNA specimens was similar between these two populations. The distribution of benign versus malignant diagnosis on follow-up surgical pathology was examined across TBS-Thy class. CONCLUSION: Our data suggest that distribution of benign versus malignant lesions in the thyroid FNA of AA versus NAA, with follow-up surgical pathology, is comparable for TBS-Thy classes, non-diagnostic (I), benign (II), suspicious for malignancy (V), and malignant (VI) in AA versus NAA.

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.

Transgenic overexpression of a stable Plasminogen Activator Inhibitor-1 variant.

INTRODUCTION: Plasminogen Activator Inhibitor-1 (PAI-1) is a member of the Serine Protease Inhibitor (SERPIN) gene family and a key regulator of fibrinolysis. PAI-1 is unique among SERPINs in its spontaneous transition to a latent, inactive state, with a half-life of approximately 2 hours under physiologic conditions. The biologic importance of the PAI-1 transition to latency is unknown. This study aimed to engineer transgenic overexpression of a stable murine PAI-1 variant to examine the physiologic effects in vivo from delayed transition of PAI-1 to latency. MATERIALS AND METHODS: Ten independent transgenic lines were generated with expression of a stable PAI-1 variant driven by the hybrid CMV/chicken beta-actin promoter. RESULTS: Plasma PAI-1 levels in the transgenic founders ranged from 3.1+/-0.1 ng/mL to 1268.8+/-717.0 ng/mL. Quantitative PCR analysis in 3 transgenic lines demonstrated elevated PAI-1 mRNA in multiple tissues, with the highest increases observed in liver, brain, heart, and kidney. The fold-increase in PAI-1 mRNA over wild-type ranged from 2-fold to >2000-fold. Immunohistochemistry showed increased PAI-1 in liver, kidney, heart, spleen, and lung. Histologic examination of transgenic mice showed no evidence of thrombosis. The two founders with the highest plasma PAI-1 levels failed to produce any transgenic offspring that survived to weaning, although genotyping of expired pups revealed successful transmission of the transgene. CONCLUSION: These results suggest that high expression of a stable variant of PAI-1 may be lethal in mice, while more moderate expression is generally well tolerated and produces no apparent thrombosis.

Differential expression of galectin-3, CK19, HBME1, and Ret oncoprotein in the diagnosis of thyroid neoplasms by fine needle aspiration biopsy.

BACKGROUND: Fine needle aspiration biopsy (FNAB) is a common and excellent procedure for the evaluation of thyroid lesions that require surgical resection. At times, the FNAB diagnosis can be difficult, particularly of follicular-patterned lesions. Previous studies have shown that some immunohistochemical (IHC) markers may be helpful in establishing more accurate diagnosis. In this study, our goal was to evaluate four of the recently investigated markers in differentiating benign from malignant thyroid nodules on FNABs. MATERIALS AND METHODS: We performed IHC staining of galectin-3, Ret oncoprotein (Ret), HBME-1, and cytokeratin 19 (CK19), on cell block sections of thyroid FNAB cases that had corresponding surgical resections. They included 44 benign lesions (37 hyperplastic or cellular nodules, HN; and 7 follicular adenomas, FA) and 27 malignant tumors (6 follicular carcinoma, FC; 19 classic papillary carcinoma, PTC; and 2 follicular variant of papillary carcinoma, FVPC). The stains were done according to the standard avidin-biotin-peroxidase method. RESULTS: Statistical analysis showed that immunoexpression was significantly higher in the malignant group for all four markers. The sensitivity for positive expression for all benign lesions versus malignant tumors was as follows: 10/44 (22.7%) versus 25/27 (92.6%) for galectin-3; 14/44 (31.8%) versus 23/27 (85%) for Ret; 12/44 (27.3%) versus 24/27 (88.8%) for HBME-1; and 13/44 (29.5%) versus 23/27 (85%) for CK19. The sensitivity and specificity was highest for galectin-3 (92.6% and 77.3%, respectively) followed by HMBE-1 (88.9% and 72.7%, respectively). When combining the markers' expressions, the panel of galectin-3 + HBME-1 showed the highest sensitivity and specificity (90.7% and 75%, respectively), but this was, however, lower than galectin-3 alone (92.3% and 77.3%, respectively). CONCLUSION: We conclude that galectin-3 is the best single marker in differentiating benign from malignant thyroid lesions with the highest sensitivity and specificity. The galectin-3 + HBME-1 was the best combination for distinguishing benign from malignant lesions. Because they were the best two independent and combined markers, we recommend the use of the galectin-3 + HBME-1 panel to enhance the diagnostic accuracy of follicular-patterned thyroid lesions on FNABs.

Accuracy and added value of triage beyond segregating potentially neoplastic effusions in immediate wet preparation.

OBJECTIVE: To sudy the accuracy and value of immediate wet preparation (WP) procedure on effusion and washing cytologic specimens. STUDY DESIGN: Two hundred specimens were identified over 3 months in our cytology laboratory, including 102 pleural effusion, 59 peritoneal effusion, 28 pelvic washing and 11 pericardial fluid specimens. WP slides were prepared, stained with toluidine blue (TB) and .. evaluated. Findings were reported as negative, suspicious or positive for malignant cells. For negative specimens, the remaining prepared slides were stained together. For suspicious or positive interpretation, slides were stained separately. Accuracy and additional benefits from this immediate triage step were studied. RESULTS: Interpretation ofslides resulted in 152 negative, 34 positive and 14 suspicious for malignancy. Analysis for additional values resulted in immediate interpretation relayed to clinicians, additional fluid centrifuged for adequate sediment in samples with scant cellularity, selection of bloody specimens for acid washing procedures, selection of cases to optimize cell block preparation when pivotal histologic evaluation or immunohistochemistry was anticipated and selection of cases for potentially needed ancillary studies. Accuracy, sensitivity, specificity and positive and negative predictive values were high. CONCLUSION: WP using the TB is accurate, sensitive and highly specific and has considerable value beyond segregating potential neoplastic cases.

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.

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.

Fine needle aspiration outcomes of masses detected by positron emission tomography: correlation with standard uptake value.

OBJECTIVES: To characterize the cytopathologic outcome of lesions detected on positron emission tomography (PET) scan. STUDY DESIGN: Cases with fine needle aspiration (FNA) performed because of a PET-positive lesion over an 18-month period were reviewed. Correlation with the standard uptake value (SUV) (using 2.5 as a cutoff value) was carried out. RESULTS: A total of 112 FNAs were found, of which 83 had adequate tissue for evaluation and available corresponding SUVs to be included in the final study. Fisher's exact test was carried out for correlation between FNA diagnosis and SUV Sixty-one (73.5%) lesions had an SUV > or = 2.5, 53 (87%) ofwhich were malignant and 8 (13%) benign on cytology. Twenty-two (26.5%) lesions had an SUV < 2.5, of which 12 (54.5%) showed benign and 10 (45.5%) showed malignant cytology. The overall sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of SUV were 84%, 60%, 87%, 56% and 78%, respectively. CONCLUSION: Our data show that FNA procedures performed for PET-positive lesions have high PPV, but low NPV. Therefore interpretation of PET SUV values < 2.5 as benign should be made with extreme caution.

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.

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.

A proposal for a new and more practical grading scheme for pancreatic ductal adenocarcinoma.

There is no uniformly applied grading system for pancreatic ductal adenocarcinoma (DA). The scheme advocated by the WHO is essentially that of Kloppel et al, and is based on the "highest grade" focus. Although it is precise with good prognostic value, it is unfortunately not widely applied, largely because of the lack of recognition and partly because of its complex nature (interpretation of multiple parameters). Furthermore, it is fundamentally different from the one used in Japan, which evaluates the overall pattern. To establish a more widely applicable, practical, and clinically relevant grading system, a scheme similar to Gleason's scoring system was developed and tested on 112 cases of resected pancreatic DA and was compared with the WHO system. In the grading system devised, patterns (P) of infiltration were classified as follows: P1, well-defined glands with easily discernible contours; P2, fused or poorly formed glands with ill-defined contours; P3, nonglandular patterns. A score was then obtained by the summation of the predominant and the secondary patterns. Scores < or =3 (at least some well-formed glands and no nonglandular pattern) was graded as G1, 4 as G2, and > or =5 (at least some nonglandular patterns and no well-formed glandular pattern) as G3. Seventy-three percent of the cases displayed mixed patterns, with disparate patterns (P1 with P3) in 13%, confirming the high degree of heterogeneity of DA. There was a significant correlation between grade and survival, better than the correlation between survival and either the major or minor patterns evaluated separately. The median survival for G1, G2, and G3 were 22, 14, and 8 months; 1-year survival 68%, 44%, and 33%; 2-year was 67%, 11%, and 0%; and 3-year was 23%, 4%, and 0%, respectively (P = 0.0019). In a multivariate analysis, correlating survival with grade, tumor size, and lymph node status, the grade was the strongest independent predictor of survival. Odds ratio of dying of disease were 3.56 (P < 0.0001) in G3 versus G1, 1.79 (P = 0.058) in G2 versus G1, and 1.98 (P = 0.03) in G3 versus G2. Compared with this, the same odds ratio were 1.17 (P = 0.01) in tumors >2 cm versus < or =2 cm and 1.78 (P = 0.01) in cases with positive versus negative lymph nodes. The WHO grading scheme was not found to have as good a correlation with survival in this study, with WHO grade 2 showing a better survival than 1. The reproducibility of both the proposed grading system and that of WHO were found to be moderately good (with kappa values of 0.43 and 0.44, respectively), when 32 slides of DA were graded by four independent observers. The grading scheme for pancreatobiliary adenocarcinoma proposed here is highly applicable because it is practical and readily adoptable. It reflects biologic characteristics of ductal carcinoma (prominent tubule formation and tumor heterogeneity). Most importantly, it is clinically relevant with good prognostic value. Lastly, it is also applicable for use in research, by utilizing "patterns," even in small specimens like microarrays or biopsies.

Molecular subtypes of ductal carcinoma in situ in African American and Caucasian American women: distribution and correlation with pathological features and outcome.

BACKGROUND: Molecular subtypes of breast cancer have been extensively studied in invasive carcinoma. They were shown to have a different distribution within the various ethnic populations. Few studies have applied the same classification to Ductal Carcinoma in Situ (DCIS). We report the distribution of the molecular breast cancer subtypes in DCIS between African American (AA) and Caucasian American (CA) women, their association with pathological features and outcome. MATERIALS AND METHODS: Tissue microarrays were constructed from paraffin blocks of 94 DCIS cases (67 AA and 27 CA) selected from a cohort of AA and CA patients diagnosed with DCIS between 1996 and 2000; mean age at diagnosis was 61±12 for the AA and 58±11 years for the CA group. TMA blocks were labeled with antibodies for ER, PR, HER2, Ki-67, and CK5/6. The cases were subtyped as Luminal A (ER+ and/or PR+; HER2-), Luminal B (ER+ and/or PR+; HER2+), HER2+ (ER-, PR-; HER2+), basal-like (BL) (ER-, PR-, HER2-; CK5/6+) or unclassified triple negative (UTN) (ER-, PR-, HER2-, CK5/6-). Information on grade, size and follow-up were obtained. RESULTS: (1) Most DCIS cases were Luminal A, comprising 80% of the DCIS cases in AA and 92.6% in CA patients. (2) HER2+, BL and UTN DCIS subtypes were not seen in the CA population, and formed 9% of the DCIS cases in the AA population; these cases were all high grade. (3) In the cases with recurrence (8 AA and 1 CA patients), DCIS was Luminal A in 6 AA and 1 CA and Luminal B in 2 AA patients. CONCLUSION: The distribution of the molecular subtypes of DCIS did not show a significant difference between the two ethnic groups in our study. In addition, the risk of recurrence might not be higher in the non-luminal subtypes than in Luminal A and B.

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, Wilm's 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.

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.

Choroidal metastasis from an occult primary diagnosed by fine-needle aspiration: a case report.

Choroidal masses are rarely the first presentation without the primary tumor being discovered. We described fine needle aspiration biopsy (FNAB) of a choroidal mass for diagnosis and determining the primary site. The patient, a 50-year-old Caucasian male without significant past medical history, presented with visual disturbances and headaches. Intraoperative ocular FNA was performed which was sparsely cellular showing a few loosely cohesive sheets and singly arranged epithelial cells with moderate amount cytoplasm, round large nuclei and prominent nucleoli. Immunohistochemical stainings on the cell block material showed positive staining of cytokeratin and negative staining of melanoma markers. The diagnosis of metastatic adenocarcinoma was rendered. During clinical follow up studies, the patient was found to have a PET positive lung nodule and multiple visceral metastasis.