Reliability of a computational platform as a surrogate for manually interpreted immunohistochemical markers in breast tumor tissue microarrays

BackgroundPathologist and computational assessments have been used to evaluate immunohistochemistry (IHC) in epidemiologic studies. We compared Definiens Tissue Studio® to pathologist scores for 17 markers measured in breast tumor tissue microarrays (TMAs) [AR, CD20, CD4, CD8, CD163, EPRS, ER, FASN, H3K27, IGF1R, IR, Ki67, phospho-mTOR, PR, PTEN, RXR, and VDR].Methods5 914 Nurses’ Health Study participants, diagnosed 1976–2006 (NHS) and 1989–2006 (NHS-II), were included. IHC was conducted by the Dana-Farber/Harvard Cancer Center Specialized Histopathology Laboratory. The percent of cells staining positive was assessed by breast pathologists. Definiens output was used to calculate a weighted average of percent of cells staining positive across TMA cores for each marker. Correlations between pathologist and computational scores were evaluated with Spearman correlation coefficients. Receiver-operator characteristic curves were constructed, using pathologist scores as comparison.ResultsSpearman correlations between pathologist and Definiens assessments ranged from weak (RXR, rho=-0.05; CD163, rho = 0.10) to strong (Ki67, rho = 0.79; pmTOR, rho = 0.77). The area under the curve was >0.70 for all markers except RXR.ConclusionOur data indicate that computational assessments exhibit variable correlations with interpretations made by an expert pathologist, depending on the marker evaluated. This study provides evidence supporting the use of computational platforms for IHC evaluation in large-scale epidemiologic studies, with the caveat that pilot studies are necessary to investigate agreement with expert assessments. In sum, computational platforms may provide greater efficiency and facilitate high-throughput epidemiologic analyses.     

Telecytologic diagnosis of breast fine needle aspiration biopsies. Intraobserver concordance

OBJECTIVE: To determine the intraobserver concordance between telecytologic and glass slide diagnosis of breast fine needle aspirates. STUDY DESIGN: Twenty-five cases, originally received in consultation, were each examined by three cytopathologists. An average of seven compressed digital images per case were presented, together with a brief clinical history, using the http protocol and an internet browser. RESULTS: Agreement between the telecytologic and glass slide diagnosis ranged from 80% to 96%. Nevertheless, two cases that had been unequivocally diagnosed as malignant based upon video images were considered to be benign by the same pathologist when reviewing the glass slides. Both diagnostic confidence and self-concordance were higher for one pathologist having significant previous video microscopy experience. CONCLUSION: Although intraobserver concordance between telecytologic and glass slide diagnoses of breast fine needle aspirates is high, refinement of existing criteria for diagnosis of malignancy, taking account of the particular limitations associated with telecytologic diagnosis, may be prudent prior to widespread use of telecytology for fine needle aspiration evaluation.     

Development of multigene expression signature maps at the protein level from digitized immunohistochemistry slides

Molecular classification of diseases based on multigene expression signatures is increasingly used for diagnosis, prognosis, and prediction of response to therapy. Immunohistochemistry (IHC) is an optimal method for validating expression signatures obtained using high-throughput genomics techniques since IHC allows a pathologist to examine gene expression at the protein level within the context of histologically interpretable tissue sections. Additionally, validated IHC assays may be readily implemented as clinical tests since IHC is performed on routinely processed clinical tissue samples. However, methods have not been available for automated n-gene expression profiling at the protein level using IHC data. We have developed methods to compute expression level maps (signature maps) of multiple genes from IHC data digitized on a commercial whole slide imaging system. Areas of cancer for these expression level maps are defined by a pathologist on adjacent, co-registered H&E slides, allowing assessment of IHC statistics and heterogeneity within the diseased tissue. This novel way of representing multiple IHC assays as signature maps will allow the development of n-gene expression profiling databases in three dimensions throughout virtual whole organ reconstructions.     

Macrophage-rich reaction in lymph nodes as a mimic of metastatic renal cell carcinoma on fine needle aspiration. A case report

BACKGROUND: Renal cell carcinomas have a high metastatic potential. Many of them are occult at initial presentation and mimic a primary neoplasm of the metastatic site. However, not all lymph node enlargements in a patient with a history of renal cell carcinoma are due to metastasis. Foamy macrophages can mimic metastatic renal cell carcinoma cells. CASE: A 60-year-old male with a known diagnosis of renal cell carcinoma of clear cell type developed enlarged neck nodes 44 months after the diagnosis. These were aspirated to yield cystic fluid that, on smears, showed numerous clear cells with low nuclear grade. Immunohistochemical stains revealed these cells to be foamy macrophages (CD68 immunoreactive) and not metastatic renal cell carcinoma, as had been suspected on initial examination of Diff-Quik and Papanicolaou-stained smears. CONCLUSION: Immunohistochemistry is a valuable adjunct in avoiding a false diagnosis of metastatic carcinoma in macrophage-rich nodal reactions in patients with a history of renal cell carcinoma.     

Fine needle aspiration cytology of neuroblastoma, including peripheral neuroectodermal tumor, with immunocytochemical and ultrastructural confirmation

Eleven fine needle aspiration (FNA) biopsies were performed on seven children with neuroblastoma, including one patient with a congenital neuroblastoma and another with a peripheral neuroblastoma of the thoracopulmonary region. FNA cytology made the primary diagnosis of neuroblastoma in four of the seven cases. The other biopsies documented local recurrences and metastases to liver, lymph nodes, orbit and breast. The cytologic features included varying numbers of small primitive cells with scanty cytoplasm, poorly to well-formed pseudorosettes, cell processes, a fibrillary matrix and multinucleated ganglion cells. Five of the seven patients had electron microscopic (EM) examination of the FNA specimen, which in all cases confirmed the diagnosis. Batteries of immunoperoxidase stains were performed on all 11 aspirates with variable results. Staining for neuron-specific enolase was positive in four of the five neoplasms tested, although strongly positive in only three of the cases. Staining for neurofilament markers was positive in only two of five tumors. Studies for cytokeratin markers (AE1/3), low-molecular-weight cytokeratin (35BH11), hematopoietic markers (T29/33), immunoglobulin light chains and myoglobin were negative. One case was positive for vimentin. This study attests to the value of FNA cytology in suggesting a correct diagnosis of either primary, recurrent or metastatic neuroblastoma in children. Selective use of immunoperoxidase stains and EM on the aspirates may be of value.     

Histopathological diagnosis of mycoses

Infectious diseases emerge as a cause of pathology in our patients. Among the possible etiologies, mycoses have shown a considerable increase in the two last decades. In general, the clinical features of fungal diseases are not very distinctive. The morphology and the clinical aspects of the fungi serve as a protocol for their correct identification. Clinicians, microbiologists and pathologists are essential for the diagnosis. The pathologist using a simple and fast methodology can diagnose some types of mycosis, but they do not only identify the causal agent, but also the kind of injury that produces, the inflammatory response and the affected organ or organs. Moreover, they can classify the mycosis as superficial, cutaneous, subcutaneous, deep and systemic depending on the location. The present review paper describes study guidelines for the pathologist faced with a fungal infection and new technical advances that are established in pathology laboratories for a more precise identification of the mycoses.     

Realities of diagnosing Helicobacter pylori infection in clinical practice: a case for non-invasive indirect methodologies.

BACKGROUND: The current, arbitrarily defined gold standard for the diagnosis of H. pylori infection requires histologic examination of two specially stained antral biopsy specimens. However, routine histology is potentially limited in general clinical practice by both sampling and observer error. The current study was designed to examine the diagnostic performance of invasive and non-invasive H. pylori detection methods that would likely be available in general clinical practice. METHODS: The diagnostic performance of rotating clinical pathology faculty using thiazine staining was compared with that of an expert gastrointestinal pathologist in 38 patients. In situ hybridization stains of adjacent biopsy cuts were also examined by the expert pathologist for further comparison. Receiver operator characteristic (ROC) analysis was performed to evaluate whether the diagnostic performance of the expert pathologist differed depending upon the histologic method employed. A similar analysis was made to evaluate the diagnostic performance of pathology trainees relative to the expert. In the absence of an established invasive gold standard, non-invasive testing methods (rapid serum antibodies, formal Elisa antibodies and carbon-14 urea breath testing) were evaluated in 74 patients by comparison with a gold standard defined using a combination of diagnostic tests. RESULTS: Using either rapid urease testing of biopsy specimens or urea breath testing as the gold standard for comparison, the diagnostic performance of the rotating clinical pathology faculty was inferior to that of the expert gastrointestinal pathologist especially with regard to specificity (e.g., 69 percent for the former versus 88 percent, with the latter relative to rapid urease testing). Although interpretation of in situ hybridization staining by the expert appeared to have an even higher specificity, ROC analysis failed to show a difference. The mean ROC areas for thiazine and in situ hybridization staining for trainee pathologists relative to the expert were 0.88 and 0.94, respectively. In untreated patients, urea breath testing had a sensitivity and specificity of 100 percent as compared with thiazine staining with a sensitivity of 83 percent and a specificity of 97 percent. Post-therapy, breath testing had a sensitivity of 100 percent but a specificity of only 86 percent as compared with invasive testing with a sensitivity and specificity of 100 percent. Rapid serum antibody testing and formal Elisa antibody testing agreed in 93 percent of cases (Kappa 0.78) with the rapid test being correct in three of the four disagreements. CONCLUSIONS: The current study illustrates a number of realities regarding H. pylori diagnosis. There is no diagnostic gold standard in general clinical practice. Accurate interpretation of specially stained slides is a learned activity with a tendency towards overdiagnosis early on. Urea breath testing is likely to be the diagnostic method of choice for untreated patients in general clinical practice although antibody testing is almost as accurate. Rapid antibody tests are at least as accurate as formal Elisa antibody tests. Urea breath testing is useful for confirming cure after therapy, but false-positive results may occur in some patients.     

Renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. A case report

BACKGROUND: Renal cell carcinoma is an unpredictable tumor that can recur many years after the original diagnosis and metastasize to uncommon sites, including the thyroid gland. Differential diagnosis from primary thyroid tumor is often difficult both clinically and pathologically. We report a case of metastatic renal cell carcinoma in follicular adenoma of the thyroid gland. CASE: A 48-year-old woman presented with a 3-cm-diameter, palpable mass in the left lobe of the thyroid gland. The patient's history included removal of a left renal mass, which was conventional renal cell carcinoma. Fine needle aspiration cytology smears contained a few small clusters of polygonal cells with abundant, clear cytoplasm and irregular, hyperchromatic nuclei as well as bland-looking thyroid follicle cells and stromal cells. A papillary or follicular growth pattern was not detected. A cell block made from the aspirated sample was composed mainly of clear cells. By immunohistochemical stains, the clear cells were completely negative for TTF-1, thyroglobulin, calcitonin and inhibin while equivocally staining for cytokeratin, CD10 and galectin-3. The histologic diagnosis was renal cell carcinoma metastatic to follicular adenoma of the thyroid gland. CONCLUSION: Renal cell carcinoma metastatic to the thyroid may masquerade as a primary thyroid neoplasm. A history of prior nephrectomy, the presence of unremarkable thyroid follicle cells, the absence of a papillary or follicular growth pattern and immunohistochemical study can help differentiating metastatic renal cell carcinoma from a primary thyroid lesion with clear cell change.     

Fine needle aspiration biopsy of three cases of squamous cell carcinoma presenting as a thyroid mass: cytological findings and differential diagnosis

M. Rosa and K. Toronczyk Fine needle aspiration biopsy of three cases of squamous cell carcinoma presenting as a thyroid mass: cytological findings and differential diagnosis Objective: Primary squamous cell carcinomas of the thyroid gland are extremely rare, comprising about 1% of thyroid malignancies. Although squamous cell carcinomas are readily identified as such on aspiration cytology in the majority of cases, the differentiation of primary versus metastatic tumour might not always be easy. Herein, we report three cases of squamous cell carcinomas involving the thyroid gland. Methods: Fine needle aspiration cytology (FNAC) was performed in three patients with a thyroid mass using standard guidelines. Smears were stained with Diff‐Quik and Papanicolaou stains. Results: Two patients were male and one was female, aged 59, 45 and 35 years, respectively. In all three patients a thyroid mass was present. FNAC smears in all cases showed cytological features of squamous cell carcinoma including keratinization and necrosis. After clinical and cytological correlation, one case appeared to be primary, one case metastatic, and in the third case no additional clinical information or biopsy follow‐up was available for further characterization. Conclusions: Because primary squamous cell carcinoma of the thyroid is a rare finding, metastatic squamous cell carcinoma should always be excluded first. Metastatic disease usually presents in the setting of widespread malignancy, therefore a dedicated clinical and radiological investigation is necessary in these cases. In both clinical scenarios the patient’s prognosis is poor.     

Mucinous adenocarcinoma of the ovary metastatic to the eye: report of a case with diagnosis by fine needle aspiration biopsy

BACKGROUND: Metastatic malignancy involving the ocular uveal tract is rare. Approximately one-third of patients will present without a known primary site. This is the ninth reported clinically detected case of ovarian carcinoma metastatic to the eye, the second with mucinous differentiation and the first in which the diagnosis was established by fine needle aspiration (FNA). CASE: A woman developed ovarian mucinous adenocarcinoma metastatic to the choroid layer of the eye. CONCLUSION: FNA is useful in diagnosing lesions of the eye and orbit, including diagnosis of rare metastatic lesions.     

The value of lymph node imprint cytodiagnosis: an assessment of interobserver agreement and diagnostic accuracy

The value of lymph node imprint cytodiagnosis: an assessment of interobserver agreement and diagnostic accuracy
The aim of this study was to assess the reliability of cytodiagnosis of lymph node imprints without fixed tissue sections. One hundred randomly selected archival cases were used in the study. These air‐dried May–Grünwald–Giemsa imprint slides were assessed independently and blind by three pathologists. Cases were assigned to one of four diagnostic categories: reactive changes, non‐Hodgkin's lymphoma (NHL), Hodgkin's disease (HD) and secondary malignancy. Each broad diagnosis was compared with the 'correct' reviewed histological diagnosis to calculate interobserver agreement and diagnostic accuracy. The overall κ score (+0.59) was indicative of moderate agreement. The mean pathologist diagnostic accuracy was 78%, with complete agreement with the histological diagnosis in 61% of cases. The main diagnostic difficulties were in the distinction between reactive changes and NHL and distinguishing NHL from HD. Further diagnostic classification, e.g. typing of lymphomas and subclassification of Hodgkin's disease, was not found to be reliable using the imprints alone. With these limitations in mind, pathologists should be able to use lymph node imprints for cytodiagnosis in selected cases. The study also emphasized the utility of imprints as a corollary to the histology and as a tool for cytology training and continuing education.     

Interpreting microbiopsies in cervical smears. A cytohistologic approach

OBJECTIVE: To assess interobserver variation in the diagnosis of thick tissue specimens (microbiopsies) in cytology smears and histologic sections taken from them, to evaluate the applicability of MIB-1 in histologic sections from microbiopsies and to evaluate whether processing microbiopsies in inconclusive smears has additional diagnostic value. STUDY DESIGN: Cytologic smears were selected in which there were diagnostic disagreements between pathologists and cytologists and microbiopsies were present. Interobserver variation among three pathologists and three cytologists in the diagnosis of these microbiopsies was investigated. The smears were processed for histologic sections, and interobserver variation between pathologist diagnoses were analyzed. An additional histologic slide stained for MIB-1 was used for consensus diagnosis. The consensus diagnosis was compared with available follow-up and its sensitivity and specificity determined. The value of applying the microbiopsy technique in slides diagnosed as inadequate or atypical squamous cells of undetermined significance (ASCUS) was analysed. RESULTS: From a series of 62,334 cervical smears, 49 with microbiopsies were selected. It was possible to derive histologic slides from 38 cases. Interobserver variability in the diagnosis of microbiopsies and histologic sections from them was moderate--kappa = .44 (SE = .06) and kappa = .44 (SE = .09), respectively. In the consensus meeting for all cases, a conclusive diagnosis was reached. The Pearson correlation coefficient between the consensus diagnosis and MIB-1 staining was r = .62. The sensitivity of the consensus diagnosis for the follow-up diagnosis was 71% and the specificity 60%. Diagnosis on approximately 50% of slides diagnosed as inadequate or ASCUS could be made. CONCLUSION: The histotechnical workup of microbiopsies is not difficult; however, their diagnosis can be a problem. Adequate diagnostic criteria are not available. Aided by MIB-1 staining, histologic sections from microbiopsies can be diagnosed, and the diagnoses correlated with follow-up in most cases. Processing of microbiopsies in smears with an inconclusive cytologic diagnosis or a diagnosis of ASCUS allowed correct diagnosis in 50% of cases in this study.     

Fine needle aspiration of the prostate gland in the community hospital. A predictive value analysis

Fine needle aspiration cytology of the prostate gland has not been widely accepted into the clinical armamentarium of most urologists, even though its benefits are well recognized. This sluggish acceptance is most likely due to a cautious reluctance on the part of the general pathologist in the community hospital to evaluate these specimens and to uncertainty on the part of the urologist on how to interpret the pathologist's impressions should the pathologist attempt to evaluate the specimens. This article offers a predictive value analysis of the data obtained from four general pathologists after reviewing 50 fine needle aspirations of the prostate.     

High-risk HPV DNA detection rate in patients with atypical squamous cells and its relationship to the atypical squamous cell: squamous intraepithelial lesion ratio

OBJECTIVE: To determine if there is any relationship between the atypical squamous cell (ASC):squamous intraepithelial lesion (SIL) ratio and high-risk HPV DNA detection rate. STUDY DESIGN: Data on the frequency of various cytologic diagnoses for each pathologist were retrieved from 2002 to 2003. ASC:SIL ratio for each pathologist was calculated. In addition, data related to high-risk HPV detection rate was obtained during the study period. HPV DNA testing was performed using HC II (Digene, Gaithersburg, Maryland U.S.A). Cases with insufficient quantity were excluded. RESULTS: Five pathologists, with experience ranging from 2 to 15 years, reviewed Pap tests during the study period. For the entire laboratory, the ASC:SIL ratio was 2.0, and the high-risk HPV DNA detection rate in ASC specimens was 31%. For individual pathologists, ASC:SIL ratio ranged from 1.2 to 4.0 and high-risk HPV DNA detection rate from 31% to 38%. No significant correlation was noted between the ASC:SIL ratio and high-risk HP DNA detection rate. CONCLUSION: Our ASC:SIL ratios (except for 1 pathologist) and high-risk HPV DNA detection rates were within an acceptable range. We did not observe any association between ASC:SIL ratio and high-risk HPV detection rate.     

Fine needle aspiration cytology of primitive neuroectodermal tumors. A report of these cases.

Primitive neuroectodermal tumor (PNET) is a small round cell malignancy arising in soft tissue and bone, predominantly in older children and adolescents. We report the cytomorphologic features and findings of ancillary studies of eight fine needle aspiration (FNA) biopsies from three patients (7-year-old male, 12-year-old female, 9-year-old female). Two of the biopsies suggested the initial diagnosis of PNET of the chest wall, while the remaining six documented recurrent or metastatic disease. In one of these cases the primary diagnosis made by FNA biopsy enabled the pediatric oncologists to give specific therapy for the unresectable tumor and achieve remission. Local recurrences included the chest wall (two cases), pleura (one case) and pericardium (one case), while metastatic disease involved the supraclavicular lymph node and breast. All the cases consisted of small malignant cells with a high nuclear/cytoplasmic ratio and hyperchromatic nuclei without prominent nucleoli. Homer Wright rosettes were seen in only two of the aspirates, and neuropil and ganglion cells were not present. Ancillary studies, including electron microscopy (two cases), immunocytochemistry (four aspirates from two cases) and cytogenetics (11/22 translocation, one case) performed on the aspirated material were aids in making a specific diagnosis and excluded other small round cell tumors of childhood, such as malignant lymphoma, rhabdomyosarcoma and Ewing's sarcoma. The differential diagnosis between PNET and neuroblastoma can be difficult on the basis of an FNA biopsy alone, although light microscopic morphologic differences exist. Clinical features (e.g., age, primary site, metastatic patterns), catecholamine levels, electron microscopy and cytogenetics are necessary in establishing the correct diagnosis.     

Diagnosis of malignant mesothelioma by fine needle aspiration of a cervical lymph node. A case report

BACKGROUND: Clinically documented distant metastases are rare in mesothelioma and tend to occur late in the course of the disease, well after the diagnosis has been made. In this instance, diagnosis was not made until a metastatic deposit was identified microscopically in the enlarged lymph node. CASE: A 65-year-old male with no definite history of occupational asbestos exposure presented with chest pain, pleural effusion and supraclavicular lymphadenopathy. Cytologic examination of material obtained by fine needle aspiration from his cervical lymph node revealed malignant mesothelioma. This was confirmed on histology. CONCLUSION: This was a particularly rare presentation and, as far as we are aware, was the first case in which mesothelioma was diagnosed by fine needle aspiration of a cervical lymph node. It serves to remind the pathologist that when confronted with a lymph node involved by tumor, the possibility of mesothelioma should be included in the differential diagnosis. The case also demonstrates the usefulness of fine needle aspiration in the diagnosis of metastatic tumor.     

Appraisal of the World Health Organization classification of lung tumours.

The 1967 World Health Organization (WHO) classification of the histologic types of lung tumours has been examined in relation to 303 tumours of patients admitted to a national trial of the treatment of lung cancer. In 63 instances (20%) there was disagreement between the diagnoses of the local pathologist and the reference pathologist. The slides for these 63 tumours were reviewed by two other pathologists, and the slides for 60 tumours for which there was agreement between the local and reference pathologists were reviewed by one of the other pathologists. The main disagreement was in the diagnosis of epidermoid (squamous) tumours. It is apparent that many pathologists do not adhere to the strict criterion of the presence of keratinization or intercellular prickles or both for the diagnosis of epidermoid carcinoma. In addition, there was substantial variation in the use of subtypes within the WHO classification. Use of the revised classification proposed by the WHO would have removed a small amount of the variation from these findings but would not have affected the main discrepancy. Stricter attention to the definition of types is required for a uniform approach to the histologic classification of lung tumours.     

Cytologic diagnosis of mastocytosis by fine needle aspiration biopsy: a case report

BACKGROUND: Mastocytosis is an abnormal proliferation of mast cells and their subsequent accumulation in various organs. Diagnosis of mast cell disease relies on proper identification of abnormal mast cells. CASE: A 55-year-old man presented with a history of fever for several months, associated with night sweats, involuntary 20lb weight loss, progressive fatigue, weakness, worsening abdominal distention, shortness of breath, and diffuse lymphadenopathy. Physical examination and computed tomography (CT) showed hepatosplenomegaly, massive ascites, and generalized lymphadenopathy. Bone marrow biopsy with immunohistochemistry (ICH) studies revealed mastocytosis. CT-guided fine needle aspiration biopsy (FNAB) of the retroperitoneal lymphadenopathy was performed. The smears were cellular for a mixed population of mature plasma cells, eosinophils, left-shifted granular and lymphoid cells, and abundant abnormal mast cells. The mast cells had round to oval lobulated nuclei, some of which were binucleated or eccentrically located, with coarse, evenly distributed chromatin. Abundant pale cytoplasm contained numerous metachromatic granules. IHC studies and flow cytometry confirmed the cytologic diagnosis of mastocytosis. CONCLUSION: This case highlights the cytologic features of mastocytosis in FNA specimens. IHC stains and flow cytometry are helpful to confirm the cytologic diagnosis. To the best of our knowledge, this is the second case that describes the cytologic characteristics of mastocytosis.     

2010 Reviewers for Biotechnic & Histochemistry

Pancreatic cancer is characterized by aggressive growth and resistance to treatment. Identification of unique biomarkers for diagnosis and prognosis is important for treatment of this disease. We investigated the expression patterns of mucin 1 (MUC1), mucin 2 (MUC2) and cytokeratin 17 (CK17) in both normal tissues and metastatic adenocarcinomas using immunohistochemistry (IHC). We have shown that MUC1 (pan-epithelial membrane mucin), MUC2 (intestinal-type secretory mucin) and CK17 can be used as a panel of markers to distinguish collectively pancreatobiliary carcinoma from other primary site carcinomas. Tumors originating in the pancreatobiliary system showed an expression pattern of MUC1 (+), MUC2 (?) and CK17 (+). By contrast, tumors arising from the colorectal region were MUC1 (?), MUC2 (+) and CK17 (?), while tumors originating from non-pancreatobiliary system tissue expressed a MUC1 (+), MUC2 (?) and CK17 (?) profile. More importantly, the MUC1 (+), MUC2 (?) and CK17 (+) result showed greater sensitivity than CA19-9 by IHC, which is the currently accepted and widely used pancreatic tumor marker for diagnosing pancreatic cancer. Thirteen of 51 cases (25%) of pancreatobiliary adenocarcinomas with the pattern MUC1 (+), MUC2 (?) and CK17 (+) showed no immunoreactivity for CA19-9, while 34/51 (67%) cases having MUC1 (+), MUC2 (?) and CK17 (+) were correlated with positive CA19-9 staining. Our data support using an antibody panel of MUC1, MUC2 and CK17 to enhance current methods for pancreatic cancer diagnosis by identifying specifically the primary tissue of origin.     

Immunocytochemistry and fluorescence in situ hybridization in HER-2/neu status in cell block preparations

OBJECTIVE: Recent studies have validated the use of cytologic materials to determine HER-2/neu status. Good concordance has been shown between results obtained by immunocytochemistry (ICC), immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) on cytologic and surgical specimens. However, the utility of cytologic cell block material in determining HER-2/neu status has not been reported and is the subject of this study. STUDY DESIGN: HER-2/neu status was determined in 25 cases of primary or metastatic breast carcinoma by IHC and FISH. All cases were formalin-fixed, paraffin-embedded (FPPE) cell block preparations. ICC was performed using monoclonal antibodies TAB250 (Zymed) and CB11 (Novacastra Laboratories). FISH analysis was performed using the PathVysion HER-2 probe kit (Vysis, Inc.). Results of ICC and FISH were compared in each case. RESULTS: Of 25 cases studied, 17 showed no protein overexpression or amplification. Five cases showed protein overexpression and amplification. The remaining 3 cases showed 2+ staining intensity by ICC in 10, 20, and 50% of carcinoma cells, respectively, and all demonstrated lack of amplification. CONCLUSION: Immunocytochemistry performed on FFPE cell block material is a reliable method for determining HER-2/neu status in cytologic specimens. We recommend routine preparation of FFPE cell block material in instances of suspected primary of metastatic breast carcinoma.