The application and diagnostic utility of immunocytochemistry on direct smears in the diagnosis of pulmonary adenocarcinoma and squamous cell carcinoma
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.Diagnostic Cytopathology (Impact Factor: 1.12). 11/2012; 40(11):949-55. DOI: 10.1002/dc.21680
The importance of subclassifying pulmonary nonsmall cell carcinoma (NSCLC) in cytologic material is becoming increasingly paramount. Occasionally, cell blocks traditionally used for ancillary studies are sparsely cellular or acellular. Hence, we investigated the diagnostic utility of immunocytochemistry for Napsin-A, TTF-1, and p63 on direct smears of NSCLC. Immunohistochemistry for Napsin-A was initially tested on a tissue microarray (TMA) composed of pulmonary adenocarcinoma. Subsequently, in 25 cases, immunocytochemistry for Napsin-A, TTF-1, and p63 was performed on cytologic direct smears. Smears were prepared from tumor cells scraped from lung resection specimens (n = 10), endobronchial ultrasound-guided transbronchial fine-needle aspirates (n = 13), and pelleted cell material from pleural effusions (n = 2). Immunohistochemistry utilizing the TMA revealed Napsin-A positivity in 73% of pulmonary ADCs. Next, immunocytochemistry on direct cytologic smears demonstrated a Napsin-A(+)/TTF-1(+) immunophenotype in 15 of 18 adenocarcinomas; p63 was completely negative (n = 12) or only focally positive (n = 3) in these 15 adenocarcinomas. The remaining three adenocarcinomas were negative for all three markers. All six squamous cell carcinomas were Napsin-A(-)/TTF-1(-) and diffusely p63(+). In conclusion, direct smears represent a feasible and robust source of cellular material for immunocytochemical studies to diagnose pulmonary ADC and SQC. Our method allows the cytologist to confirm on site that material for diagnostic immunocytochemistry is present thereby serving as a safeguard in instances where the cell block is of insufficient cellularity. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
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ABSTRACT: Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) may diagnose suspected lung cancer. Determination of non-small cell lung cancer (NSCLC) subtype may guide therapy in select patients. Small-volume biopsies may be subject to significant interobserver variability in subtype determination. Three pathologists independently reviewed specimens from 60 patients who underwent EBUS-TBNA for diagnosis/staging of suspected/known NSCLC. Smear, haematoxylin and eosin (H&E) and immunohistochemistry (IHC) specimens were reviewed without reference to other specimen types obtained from the same patient. Final diagnoses, and degree of confidence in the diagnosis, were recorded for each specimen. Almost perfect agreement was seen for distinguishing between small cell lung cancer and NSCLC for all specimen types. Agreement in determination of NSCLC subtype for smear, H&E and IHC specimens was slight (κ=0.095, 95% CI -0.164-0.355), fair (κ=0.278, 95% CI 0.075-0.481) and moderate (κ=0.564, 95% CI 0.338-0.740), respectively. Perfect agreement was seen when all three observers were confident of diagnoses made on IHC specimens. Interobserver agreement in interpretation of EBUS-TBNA specimens is moderate for determination of NSCLC subtype. Agreement is highest following examination of IHC specimens. Clinicians should be aware of the degree of pathologist confidence in the tissue diagnosis prior to commencement of subtype-specific therapy for NSCLC.European Respiratory Journal 02/2012; 40(3):699-705. DOI:10.1183/09031936.00109711 · 7.64 Impact Factor
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ABSTRACT: Background: With the introduction of new treatment modalities and guidelines, it is important to subclassify primary pulmonary non-small cell carcinoma (NSCCA). Subsequent treatment and testing is dependent on accurate subclassification. Endobronchial ultrasound fine-needle aspiration (EBUS FNA) is used for primary evaluation and diagnosis, and can provide a cell block for ancillary testing. Methods: EBUS FNA cases from primary pulmonary NSCCA with an immunohistochemical (IHC) panel performed on a cell block with concomitant surgical pathology biopsy were analyzed. Cell block preparations underwent an IHC panel including monoclonal antibodies for napsin A (nap-A), thyroid transcription factor (TTF-1), p63, and cytokeratin 5/6 (CK5/6). Results: A total of 81 cases from 81 patients were identified. Of these, 69 cases (85%) were provided a specific diagnosis of adenocarcinoma (ADCA) or squamous cell carcinoma (SCCA) on the EBUS FNA. In 12 cases (15%), a diagnosis of NSCCA, not otherwise specified was provided. For specific subclassifications, there were 35 ADCA cases, 34 SCCA cases, and 12 NSCCA, not otherwise specified cases. For ADCA, nap-A showed granular cytoplasmic staining and TTF-1 nuclear staining. For SCCA, CK5/6 showed cytoplasmic staining and p63 nuclear staining. Surgical pathology concomitant material was present in 29 of 81 cases with 18 correlations and 11 noncorrelations. Conclusions: With new treatment guidelines for patients with primary pulmonary NSCCA, specific diagnosis is increasingly important. EBUS FNA with cell block provided a specific subclassification of NSCCA in 85% of cases when used in conjunction with a specific IHC panel including nap-A, TTF-1, CK5/6, and p63.Cancer Cytopathology 03/2013; 121(3). DOI:10.1002/cncy.21222 · 3.35 Impact Factor
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ABSTRACT: Our aim was to determine whether or not non-small-cell lung cancer is squamous cell carcinoma (SQCC); even in small samples, it is essential in view of the side effects attendant on new therapeutics. Lung adenocarcinoma (ADC) with the EML4-ALK fusion gene has been described as demonstrating mucinous cribriform/acinar growth and signet-ring cells, sometimes partially simulating SQCC. We investigated the relation among morphology, anaplastic lymphoma kinase (ALK) rearrangement, and immunophenotype in 321 ADCs by tissue microarray using SQCC markers cytokeratin (CK)5/6, CK14, desmocollin-3, desmoglein-3, p40, p63 versus ADC markers thyroid transcription factor (TTF)-1 and napsin A. Unlike 312 ALK-negative ADCs, 9 ALK-positive cases were negative for 4 SQCC markers. Only 1 ALK-positive ADC showing assertive morphology was positive for CK5/6 and p63 as well as for TTF-1 and napsin A. Coexpression of TTF-1/p40 was not observed, unlike that of TTF-1/p63 reported previously. There was no statistically significant difference between ALK-negative and ALK-positive ADC by immunohistochemical profiling.International Journal of Surgical Pathology 06/2013; 21(5). DOI:10.1177/1066896913489345 · 0.95 Impact Factor
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