The utility of endobronchial ultrasound-guided transbronchial needle aspiration biopsy in the diagnosis of mediastinal lymphoproliferative disorders

BACKGROUND:

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) biopsy is routinely used to stage lung cancer; however, its usefulness in diagnosing lymphoproliferative disorders has not been well established. In this retrospective study, we determined the utility of EBUS‐TBNA in evaluating mediastinal lymphadenopathy in patients with suspected lymphoproliferative disorders.

METHODS:

The authors searched the pathology database at their institution to identify all patients who had undergone EBUS‐TBNA biopsy for possible lymphoproliferative disorders. The cytologic diagnoses were correlated with concurrent and subsequent biopsy findings and clinical follow‐up data.

RESULTS:

Of 886 lymph nodes evaluated by EBUS‐TBNA biopsy, 91 nodes from 33 patients (23 men and 10 women) were eligible. Fourteen patients had a history of lymphoma. Adequate material for diagnosis was obtained in 31 of 34 procedures (1 patient had 2 procedures). The cytologic diagnoses of the 31 adequate procedures included 19 with benign disease (8 reactive lymph nodes and 11 granulomatous inflammation), 8 with lymphoma (2 large B‐cell, 2 small lymphocytic, 2 Hodgkin, 1 mantle cell, and 1 T‐cell lymphoblastic), 2 with cells suspicious for Hodgkin lymphoma, and 2 cases with atypical cells.

CONCLUSIONS:

EBUS‐TBNA proved to be useful for evaluating mediastinal lymphadenopathy in patients with suspected lymphoproliferative disorders. Its use may decrease the need for invasive diagnostic procedures. Immediate assessment is valuable in these cases because of the need to triage material for immunophenotyping or other studies to determine optimal and clinically meaningful diagnoses. Cancer (Cancer Cytopathol) 2011. © 2011 American Cancer Society     

The role of fluorescence in situ hybridization and polymerase chain reaction in the diagnosis and classification of lymphoproliferative disorders on fine‐needle aspiration

BACKGROUND:

Fine‐needle aspiration (FNA) has been used in the evaluation of lymphadenopathy for a long time and is highly reliable in the identification of metastatic malignancies. However, the role of FNA in the assessment of new lymphoproliferative disorders continues to be a subject of debate. The objective of the current study was to evaluate the role of molecular cytogenetic studies in FNA diagnoses of lymphoproliferative disorders.

METHODS:

A retrospective, computer‐based search for lymph node FNAs from 2006 to 2007 was performed. Cases with either fluorescence in situ hybridization (FISH) and/or polymerase chain reaction (PCR) studies were subjected to further analysis.

RESULTS:

In total, 243 lymph node FNAs were performed during the period, including 104 that were positive/suspicious for metastatic malignancies, 16 that were positive/suspicious for lymphomas, 15 that demonstrated atypical lymphoid proliferation, 73 that were reactive, 14 that were deemed granulomas, and 21 that were determined to be nondiagnostic. Molecular analysis included combined FISH/PCR in 4 cases, FISH only in 7 cases, and PCR only in 4 cases. By using multiplex PCR, 6 cases with atypical/negative flow cytometry results were diagnosed as 4 B‐cell lymphomas, 1 T‐cell lymphoma, and 1 reactive lymph node; and 4 cases that had atypical T cells determined by flow cytometry were diagnosed as reactive. One CD10‐negative follicular lymphoma and 2 cases with suspicious flow cytometry results were positive for t(14;18)(q32;q21) by FISH. Forty‐five cases had follow‐up histology with 3 false‐negative findings and no false‐positive results.

CONCLUSIONS:

In this study, multiplex PCR studies for immunoglobulin heavy‐chain or T‐cell receptor gene rearrangements were useful for demonstrating clonality, and FISH studies were able to detect translocations or gene rearrangements that allowed for the subclassification of B‐cell non‐Hodgkin lymphomas. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Cytologic,flow cytometry,and molecular assessment of lymphoid infiltrate in fine‐needle cytology samples of Hashimoto thyroiditis

BACKGROUND:

The thyroidal lymphoid infiltrate (TLI) in Hashimoto thyroiditis (HT) represents the substrate from which thyroid lymphoma may arise. The objective of the current study was to classify the TLI in HT by comparing the cytologic features with flow cytometry (FC) data and evaluating the κ/λ light chain ratio and its molecular assessment.

METHODS:

Fine?needle aspiration cytology (FNAC) was performed in 34 patients with HT with nodular or diffuse palpable enlargement of the gland. Two or 3 passes were performed to prepare traditional smears, FC, and immunophenotyping, and RNAlater suspensions for molecular assessment. FC was performed using the following antibodies: CD3, CD5, CD4, CD8, CD10, CD19, and κ and λ light chains. In 4 cases, high molecular weight DNA was extracted and used for polymerase chain reaction (PCR) to amplify the variable diversity joining region of the heavy chain immunoglobulin (Ig) genes (IgH). Statistical analysis was performed to evaluate possible associations between clinical ultrasound presentation, cytologic pattern, and TLI phenotype. Light chain expression was evaluated as the percentage of the expressing cells (≤20% and >20%) and as the κ/λ ratio.

RESULTS:

Smears were classified as “lymphocytic,” “lymph node‐like,” or “mixed.” FC demonstrated T cells (CD3 positive [+], CD5+) in all cases, and T cells and B cell (CD19+, CD10+/‐) lymphocytes in 22 cases. Light chains were expressed in 30 cases (in <20% of the gated cells in 13 cases and in >20% of the gated cells in 17 cases). Five cases demonstrated small κ/λ ratio imbalances and PCR analysis demonstrated diffuse bands in the gel and Gaussian curves at the heteroduplex. Statistical analysis indicated significant associations between the “lymphocytic” pattern and T‐cell phenotype and between the “lymph node‐like” pattern and B‐cell phenotype. A significant association also was observed between light chain restriction and low light chain expression (P < .005).

CONCLUSIONS:

The cytologic pattern of TLI in HT is quite representative of the clinical presentation and phenotypic cell type. Small light chain imbalances are not sustained by heavy chain Ig gene (IgH) rearrangements. FNA coupled with FC may contribute to making the distinction between florid TLI and non‐Hodgkin lymphoma. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Comparative evaluation of flow‐cytometric immunophenotyping and immunocytochemistry in the categorization of malignant small round cell tumors in fine‐needle aspiration cytologic specimens

BACKGROUND.

The precise diagnosis of malignant small round cell tumors (MSRCTs) in fine‐needle aspiration (FNA) cytology is a challenge that requires ancillary investigations. In this study, the authors evaluated the applicability of flow‐cytometric immunophenotyping (FCI) and compared it with immunocytochemistry (ICC) for the accurate categorization of MSRCTs.

METHODS.

In total, 37 consecutive MSRCTs that had been diagnosed with FNA cytology were analyzed by ICC and FCI using a panel of antibodies against desmin, vimentin, CD99/major histocompatibility class I‐related antigen 2, neuron‐specific enolase, and pancytokeratin. The final diagnoses included Ewing sarcoma (n = 17), rhabdomyosarcoma (n = 6; 4 embryonal and 2 alveolar subtypes), neuroblastoma (n = 10), desmoplastic small round cell tumor (n = 2), and retinoblastoma (n = 2).

RESULTS.

Accurate categorization was possible in 67.5% of cases by ICC and in 64.8% of cases by FCI. Concordant immunophenotyping results with either technique were obtained in 21 cases (59.4%). Low cellularity of the sample and negativity for all markers tested were some limitations to both techniques when applied on fine‐needle aspirates. However, using a combination of both techniques, 86.4% (32 of 37 cases) MSRCTs were typed accurately.

CONCLUSIONS.

FCI is applicable on FNA material and complements ICC in accurate the typing of MSRCTs. This is particularly useful in advanced‐stage disease, when neoadjuvant chemotherapy may be instituted promptly. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Classifying B‐cell non‐Hodgkin lymphoma by using MIB‐1 proliferative index in fine‐needle aspirates

BACKGROUND:

MIB‐1 proliferation index (PI) has proven helpful for diagnosis and prognosis in non‐Hodgkin lymphomas (NHLs). However, validated cutoff values for use in fine‐needle aspiration (FNA) samples are not available. We investigated MIB‐1 immunocytochemistry as an ancillary technique for stratifying NHL and attempted to establish PI cutpoints in cytologic samples.

METHODS:

B‐cell NHL FNA cases with available cytospins (CS) MIB‐1 immunocytochemistry results were included. Demographic, molecular, immunophenotyping and MIB‐1 PI data were collected from cytologic reports. Cases were subtyped according to the current World Health Organization classification and separated into indolent, aggressive, and highly aggressive groups. Statistical analysis was performed with pairwise Wilcoxon rank sum test and linear discriminant analysis to suggest appropriate PI cutpoints.

RESULTS:

Ninety‐one NHL cases were subdivided in 56 (61.5%) indolent, 30 (33%) aggressive, and 5 (5.5%) highly aggressive lymphomas. The 3 groups had significantly different MIB‐1 PIs from each other. Cutpoints were established for separating indolent (<38%), aggressive (≥38% to ≤80.1%) and highly aggressive (>80.1%). The groups were adequately predicted in 76 cases (83.5%) using the cutpoints and 15 cases showed discrepant PIs.

CONCLUSIONS:

MIB‐1 immunohistochemistry on CS can help to stratify B‐cell NHL and showed a significant increase in PI with tumor aggressiveness. Six misclassified cases had PIs close to the cutpoints. Discrepant MIB‐1 PIs were related to dilution of positive cells by non‐neoplastic lymphocytes and to the overlapping continuum of features between diffuse large B‐cell lymphoma and Burkitt lymphoma. Validation of our approach in an unrelated, prospective dataset is required. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.     

Accuracy and sensitivity of computed tomography‐guided percutaneous needle biopsy of pulmonary hilar lymph nodes

BACKGROUND:

Because of their proximity to the pulmonary artery or vein, hilar lymph nodes are routinely biopsied with endobronchial or endoscopic ultrasonography (EUS)‐guided fine‐needle aspiration biopsy (FNAB). Computed tomography (CT)‐guided percutaneous needle biopsy (PNB) allows the operator to acquire a larger core needle biopsy (CNB) when initial samples are inconclusive, when the suspected disease is not optimally diagnosed with FNAB, or when biomarkers are required. The purpose of this study was to retrospectively evaluate the sensitivity and accuracy of CT‐guided PNB in patients with hilar adenopathy.

METHODS:

The authors identified 80 patients who underwent 81 CT‐guided PNBs of pulmonary hilar lesions from October 2002 through December 2006 and retrospectively reviewed their medical and imaging records. The PNB sensitivity and accuracy were calculated in each case, and each case was reviewed for complications, including pneumothorax and subsequent thoracostomy tube insertion.

RESULTS:

PNB included FNAB and CNB in 81 (100%) and 14 (17%) procedures, respectively. Data on 69 PNB specimens (67 FNAB specimens and 13 CNB specimens) were available for statistical analysis. Overall, PNB had a sensitivity of 91.4% (95% confidence interval [CI], 81.0%‐97.1%) and an accuracy rate of 92.8% (95% CI, 83.9%‐97.1%). Pneumothoraxes occurred in 39 patients (48%), 26 (32%) of whom required thoracostomy tube insertion.

CONCLUSIONS:

CT‐guided PNB of pulmonary hilar lesions has high sensitivity and accuracy and represents a viable alternative for endobronchial ultrasound‐ or EUS‐guided FNAB when larger biopsy samples are required for diagnosis or biomarker analysis. However, the procedure can result in high rates of pneumothorax. Cancer 2010. © 2010 American Cancer Society.     

Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2‐positive breast cancer

BACKGROUND:

The axillary pathologic complete response rate (pCR) and the effect of axillary pCR on disease‐free survival (DFS) was determined in patients with HER2‐positive breast cancer and biopsy‐proven axillary lymph node metastases who were receiving concurrent trastuzumab and neoadjuvant chemotherapy. The use of neoadjuvant chemotherapy is reported to result in pCR in the breast and axilla in up to 25% of patients. Patients achieving a pCR have improved DFS and overall survival. To the authors' knowledge, the rate of eradication of biopsy‐proven axillary lymph node metastases with trastuzumab‐containing neoadjuvant chemotherapy regimens has not been previously reported.

METHODS:

Records were reviewed of 109 consecutive patients with HER2‐positive breast cancer and axillary metastases confirmed by ultrasound‐guided fine‐needle aspiration biopsy who received trastuzumab‐containing neoadjuvant chemotherapy followed by breast surgery with complete axillary lymph node dissection. Survival was evaluated by the Kaplan‐Meier method. Clinicopathologic factors and DFS were compared between patients with and without axillary pCR.

RESULTS:

Eighty‐one patients (74%) achieved a pCR in the axilla. Axillary pCR was not associated with age, estrogen receptor status, grade, tumor size, initial N classification, or median number of lymph nodes removed. More patients with an axillary pCR also achieved a pCR in the breast (78% vs 25%; P < .001). At a median follow‐up of 29.1 months, DFS was significantly greater in the axillary pCR group (P = .02).

CONCLUSIONS:

Trastuzumab‐containing neoadjuvant chemotherapy appears to be effective in eradicating axillary lymph node metastases in the majority of patients treated. Patients who achieve an axillary pCR are reported to have improved DFS. The success of pCR with concurrent trastuzumab and chemotherapy in eradicating lymph node metastases has implications for surgical management of the axilla in these patients. Cancer 2010. © 2010 American Cancer Society.     

Fluorescence in situ hybridization studies on direct smears

BACKGROUND:

In the fine‐needle aspiration biopsy (FNAB) diagnosis of B‐cell non‐Hodgkin lymphomas (B‐NHL), the role of flow cytometry (FC) can be limited because of nondiagnostic findings. Fluorescence in situ hybridization (FISH) studies, similar to FC, can be helpful in establishing clonality and in subclassifying the lymphoma. The aim of the current study was to determine whether FISH studies performed on unstained direct smears improved the ability to diagnose and/or subclassify B‐NHL on FNAB.

METHODS:

A total of 181 cases of B‐NHL diagnosed by FNAB were retrieved. The cytomorphology, ancillary study results, clinical information, and available pathologic follow‐up were reviewed.

RESULTS:

Of the 181 cases, FISH studies were performed in 106 cases (59%). The indications for FISH studies were for subclassification (59 cases; 56%) and nondiagnostic or unavailable FC results (47 cases; 44%). Of the 59 cases submitted for subclassification, 23 cases (39%) were successfully subclassified. The 47 cases with nondiagnostic or unavailable FC results included cases in which FC demonstrated a surface immunoglobulin‐negative population (19 cases; 40%), had insufficient cellularity (18 cases; 38%), yielded negative results (6 cases; 13%), or had no specimen submitted (4 cases; 9%). In this group, 26 cases (55%) demonstrated an immunoglobulin heavy‐chain gene rearrangement and/or chromosomal translocation.

CONCLUSIONS:

The results of the current study illustrate that FISH studies performed on unstained direct smears play a complementary role to FC in establishing the diagnosis and/or subclassification of B‐NHL. Thus, the preparation of unstained smears at the time of FNAB can be helpful for potential FISH studies. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

The evolving role of axillary lymph node fine-needle aspiration in the management of carcinoma of the breast

BACKGROUND:

Image‐guided fine‐needle aspiration (FNA) studies of axillary lymph nodes (LN) to evaluate breast carcinoma have shown high specificity but variable sensitivity. The purposes of this study were to evaluate the performance of axillary LN FNA depending on clinicoradiologic findings and to document how treatment varied according to FNA results.

METHODS:

The study cohort consisted of consecutive axillary LN FNA cases over a 4‐year period, in which subsequent treatment was known. Clinicoradiologic assessment was classified as “low suspicion” or “high suspicion” and cytopathologic findings as “positive,” “negative,” or “indeterminate”. The test performance for each, using surgical pathology outcome as the “gold standard,” was calculated. The impact of axillary LN FNA on subsequent management decisions was analyzed.

RESULTS:

Of the 163 cases, axillary FNA was positive in 94 of 163 (58%), negative in 55 of 163 (34%), and atypical/nondiagnostic in 14 of 163 (8%). A clinicoradiologic assessment of “high suspicion” had a positive predictive value (PPV) of 88%, whereas a “low suspicion” assessment had a negative predictive value (NPV) of only 68%. In contrast, the PPV and NPV of axillary LN FNA were 98.7% and 81.8%, respectively. Whereas all of the FNA‐nonpositive cases were managed surgically, surgery was deferred in 26 of 94 of the FNA‐positive cases, including 11 cases of neoadjuvant treatment. Most of the remaining (65 of 68) FNA‐positive patients were spared sentinel lymph node biopsy.

CONCLUSIONS:

Image‐guided LN FNA is highly sensitive and specific for lymph node involvement by breast carcinoma and plays a role both in sparing sentinel lymph node biopsy and in triaging cases for systemic therapy. Cancer (Cancer Cytopathol) 2011. © 2011 American Cancer Society.     

MicroRNA expression profiling is a potential diagnostic tool for thyroid cancer

BACKGROUND:

Approximately 30% of fine‐needle aspiration (FNA) biopsies of thyroid nodules are indeterminate or nondiagnostic. Recent studies suggest microRNA (miRNA, miR) is differentially expressed in malignant tumors and may have a role in carcinogenesis, including thyroid cancer. The authors therefore tested the hypothesis that miRNA expression analysis would identify putative markers that could distinguish benign from malignant thyroid neoplasms that are often indeterminate on FNA biopsy.

METHODS:

A miRNA array was used to identify differentially expressed genes (5‐fold higher or lower) in pooled normal, malignant, and benign thyroid tissue samples. Real‐time quantitative polymerase chain reaction was used to confirm miRNA array expression data in 104 tissue samples (7 normal thyroid, 14 hyperplastic nodule, 12 follicular variant of papillary thyroid cancer, 8 papillary thyroid cancer, 15 follicular adenoma, 12 follicular carcinoma, 12 Hurthle cell adenoma, 20 Hurthle cell carcinoma, and 4 anaplastic carcinoma cases), and 125 indeterminate clinical FNA samples. The diagnostic accuracy of differentially expressed genes was determined by analyzing receiver operating characteristics.

RESULTS:

Ten miRNAs showed >5‐fold expression difference between benign and malignant thyroid neoplasms on miRNA array analysis. Four of the 10 miRNAs were validated to be significantly differentially expressed between benign and malignant thyroid neoplasms by quantitative polymerase chain reaction (P < .002): miR‐100, miR‐125b, miR‐138, and miR‐768‐3p were overexpressed in malignant samples of follicular origin (P < .001), and in Hurthle cell carcinoma samples alone (P < .01). Only miR‐125b was significantly overexpressed in follicular carcinoma samples (P < .05). The accuracy for distinguishing benign from malignant thyroid neoplasms was 79% overall, 98% for Hurthle cell neoplasms, and 71% for follicular neoplasms. The miR‐138 was overexpressed in the FNA samples (P = .04) that were malignant on final pathology with an accuracy of 75%.

CONCLUSIONS:

MicroRNA expression differs for normal, benign, and malignant thyroid tissue. Expression analysis of differentially expressed miRNA could help distinguish benign from malignant thyroid neoplasms that are indeterminate on thyroid FNA biopsy. Cancer 2011. © 2011 American Cancer Society.     

Cytopathologic diagnoses of fine‐needle aspirations from endoscopic ultrasound of the mediastinum

BACKGROUND.

Endoscopic ultrasound‐guided fine‐needle aspiration biopsy through the esophagus (EUS‐FNA) or the bronchial tree (endobronchial ultrasound guided transbronchial needle aspiration [EBUS‐TBNA]) may be used to obtain specimens from mediastinal structures. The accuracy of this procedure has been well documented. However, no studies have studied the reproducibility of the pathologic assessment of the aspirated material.

METHODS.

A total of 102 slides from EUS‐FNA or EBUS‐TBNA were assessed 2 times by 4 pathologists who classified each slide to 1 of 5 diagnostic categories and judged if the aspirate came from a lymph node. Between the 2 rounds the criteria to be used in the assessment of the slides were reviewed in a limited education session. The 4 observers had at least 15 years of pathology experience, but their experience in EUS‐FNA and/or EBUS‐TBNA varied from almost none to more than 10 years. The kappa statistic was applied for the analysis of reproducibility.

RESULTS.

The reproducibility of the diagnoses in the first round was good to excellent (kappa, 0.52–0.89). The teaching session led to a significant improvement of the reproducibility between the least and the most experienced observers (kappa ranges of 0.52–0.55 in the first round improved to 0.65–0.71 in the second round).

CONCLUSIONS.

The reproducibility of the diagnosis on EBUS‐TBNA and EUS‐FNA is excellent among pathologists experienced with these types of samples. Pathologists who are generally experienced but have little experience with EBUS‐TBNA and EUS‐FNA show a steep learning curve. From a pathologic point of view, EBUS‐TBNA and EUS‐FNA are feasible, but only experienced pathologists should do the assessments. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.     

Cytomorphologic examination of anaplastic large cell lymphoma by fine‐needle aspiration cytology

BACKGROUND.

The cytomorphology of anaplastic large cell lymphoma (ALCL) is distinctive yet variable. To the authors' knowledge, to date only small case series have described the cytologic findings noted in patients with ALCL. The current series is the largest case series presented to date to retrospectively review the cytomorpholgic findings noted in patients with ALCL, with specific attention paid to those with anaplastic lymphoma kinase (ALK)‐negative ALCL.

METHODS.

Over a 13‐year period, the available Diff‐Quik cytology smears and surgical excision specimens taken from patients with ALCL were evaluated. Different clinical and morphologic parameters were evaluated, including ALK status.

RESULTS.

A total of 37 cases were retrieved and evaluated, 19 of which had both cytology and surgical pathology specimens available for review. ALK‐negative ALCL cytology smears were found to have a high number of anaplastic cells compared with ALK‐positive cases. The hallmark cells in the ALK‐negative cases were not classic.

CONCLUSIONS.

ALCL can be diagnosed accurately by fine‐needle aspiration cytology (FNAC) alone when aided by immunocytochemistry in ALK‐positive cases. Ancillary studies should be anticipated such that material for cell block preparation and molecular studies is taken at the time of FNAC. The results of the current study demonstrate the varied FNAC morphology of ALCL. The presence of severe pleomorphism and anaplasia was found to correlate with ALK‐negative status. Cancer (Cancer Cytopathol( 2007. © 2007 American Cancer Society.     

Cystic pancreatic endocrine tumors

BACKGROUND:

Cystic pancreatic endocrine tumors (PETs) are rare neoplasms with a preoperative diagnostic challenge. The aim of this study was to evaluate the preoperative diagnostic strategy for these tumors and to assess the clinical and pathologic characteristics.

METHODS:

Six cases of cystic PET were retrospectively enrolled. Endoscopic ultrasound‐guided fine‐needle aspiration biopsy (EUS‐FNAB) was performed in 4 cases. All cytomorphologic data from conventional smears, ThinPrep preparations, and cell block preparations were reported in detail.

RESULTS:

There were 3 male and 3 female patients with a mean age of 52.3 years. Tumor size ranged from 10 mm to 60 mm (mean, 29.8 mm). EUS‐FNAB contributed to an accurate diagnosis in all cases. Cytologically, loosely cohesive aggregates and single cells were predominant. Cells were small and typically plasmacytoid, with occasional cytoplasmic vacuolization. Nuclei were round or oval, uniform, with finely and evenly distributed chromatin. Immunocytochemistry confirmed the endocrine differentiation. Histologic findings were typical for endocrine proliferation. All tumors were well differentiated.

CONCLUSIONS:

Cystic PET is an unusual finding that presents diagnostic challenges for both endoscopists and cytologists. EUS‐FNAB with the Thinprep preparation technique and cell block material were found to be helpful in improving diagnostic accuracy. Immunocytochemical staining with endocrine markers confirmed the diagnosis. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

Endoscopic ultrasound-guided paracentesis of ascitic fluid: a morphologic study with ultrasonographic correlation

BACKGROUND:

Endoscopic ultrasound (EUS)‐guided fine needle aspiration (FNA) has been widely used for the diagnosis of primary and metastatic gastrointestinal (GI) and non‐GI malignancies. Few studies have been published to evaluate the accuracy and the cytologic features of EUS‐guided paracentesis in the diagnosis and staging of malignant neoplasms.

METHODS:

All EUS‐guided paracenteses of ascitic fluid performed at the University of California Irvine Medical Center (UCIMC) from January 2003 to February 2006 were retrospectively retrieved. Corresponding EUS findings, cytology and histology slides, and follow‐up information were reviewed.

RESULTS:

One hundred one (101) cases were found. Two smears were submitted in 11 cases because of the scanty amount of fluid aspirated. In the remaining cases, 5 mL or less of fluid were aspirated in 56 patients, and, of 9 who had prior computed tomography (CT), ascitic fluid was not seen in 6. The cytologic diagnoses were as follows: 17 were positive for adenocarcinoma, 1 positive for metastatic small‐cell carcinoma of the lung, 1 positive for diffuse large‐cell lymphoma, 3 suspicious for adenocarcinoma, 1 suspicious for plasmacytoma, 4 atypical epithelial cells, and 74 negative. Cell block was available in 80 cases and immunohistochemical stains were performed in 71 cases to confirm the diagnosis. Six patients had peritoneal biopsy. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were 80%, 100%, 100%, 95%, and 96%, respectively.

CONCLUSIONS:

EUS‐guided paracentesis is a valuable aid in the cytologic diagnosis of malignant ascites. It is particularly useful when no abnormality is identified by CT. Cancer (Cancer Cytopathol) 2010;. © 2010 American Cancer Society.     

A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome

BackgroundThe prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome.Patients and methodsThis study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other.ResultsMedian follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II–IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P = 0.016). Overall survival at 3 years was 41% for all patients.ConclusionAllogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies.     

Cytologic features of extragonadal germ cell tumors

BACKGROUND.

The objective of the current study was to evaluate and describe the cytologic features of extragonadal germ cell tumors (GCTs), both primary and metastasis from gonadal sites, in fine‐needle aspiration cytology.

METHODS.

Aspirates from 88 extragonadal GCTs were retrieved with their clinical features and cytologic smears. The smears were assessed for cellularity, cell patterns, and cytologic features, which were summarized. Histopathology was available in 47 cases, and cytohistologic correlation was done in all such cases.

RESULTS.

Of 88 cases, 57 with adequate cytologic material were analyzed. Each type of GCT, except for embryonal carcinoma, had characteristic morphologic features. Seminomas had dyscohesive tumor cells with well defined, vacuolated cytoplasm; prominent nucleolus; and background lymphocytes. ‘Tigroid’ background was noted in only a minority of cases. Yolk sac tumors revealed papillary fragments of tumor cells with metachromatic basement membrane‐like material in the fragments. Mixed germ cell tumors were difficult to diagnose except for cases in which more than 1 type of GCT was observed on cytologic smears. In 37% of cases with mixed GCT, only 1 component was observed on cytology.

CONCLUSIONS.

Fine‐needle aspiration cytology can reliably offer a diagnosis of GCT at extragonadal sites, even in rare locations and in patients in whom metastatic tumor may be the first clinical presentation. Immature teratoma and mixed GCTs pose a significant problem in cytology because of sampling error on needle aspiration. At extragonadal sites, the list of differential diagnoses is wider than that for gonadal GCTs. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Breast implant-associated, ALK-negative, T-cell, anaplastic, large-cell lymphoma: establishment and characterization of a model cell line (TLBR-1) for this newly emerging clinical entity

BACKGROUND:

Primary lymphomas of the breast are very rare (0.2‐1.5% of breast malignancies) and the vast majority (95%) are of B‐cell origin. Recently, 40 cases of clinically indolent anaplastic large‐cell kinase (ALK)‐negative, T‐cell, anaplastic, non‐Hodgkin lymphomas (T‐ALCL) have been reported worldwide.

METHODS:

A tumor biopsy specimen from a patient in this series was obtained for characterization. By using a human stromal feeder layer and IL‐2, a novel cell line, TLBR‐1, was established from this biopsy and investigated by using cytogenetics and various biomolecular methods.

RESULTS:

Immunoperoxidase staining of the tumor biopsy showed a CD30/CD8/CD4 coexpressing T‐cell population that was epithelial membrane antigen (EMA)⁺ and perforin⁺. Multiplex polymerase chain reaction (PCR) of TCRγ genes showed monoclonality that suggested a T‐cell origin, yet pan‐T markers CD2/5/7, anaplastic large‐cell kinase (ALK)‐1, pancytokeratins, CD20, CD56, and Epstein‐Barr virus (EBV) by in situ hybridization (ISH) were negative. TLBR‐1 is IL‐2 dependent, has a relatively long doubling time (55 hours), and displays different cellular shapes in culture. Cytogenetic analysis of tumor and TLBR‐1 cells confirmed a highly anaplastic cell population with a modal number of 47 chromosomes lacking t(2;5). PCR screens for EBV and human T‐lymphotropic virus types 1 and 2 (HTLV‐1/2) were negative. Fluorescence‐activated cell‐sorting (FACS) analysis showed strong positivity for CD4/8, CD30, CD71, and CD26 expression, and antigen presentation (HLA‐DR⁺CD80⁺CD86⁺), IL‐2 signaling (CD25⁺CD122⁺), and NK (CD56⁺) markers, and Western blots demonstrated strong Notch1 expression. Severe combined immunodeficiency (SCID) mouse TLBR‐1 heterotransplants recapitulated the histology and marker characteristics of the original tumor.

CONCLUSIONS:

TLBR‐1, a novel ALK‐negative, T‐cell, anaplastic, large‐cell lymphoma, closely resembles the original biopsy and represents an important tool for studying this newly recognized disease entity. Cancer 2011. © 2010 American Cancer Society.     

Cytology of desmoplastic small round‐cell tumor

BACKGROUND.

Desmoplastic small round‐cell tumor (DSRCT) is an aggressive malignancy of young adults, which is amenable to fine‐needle aspiration biopsy (FNAB). As this entity is increasingly recognized and biopsied, cytopathologists are compelled to become familiar with the range of cytologic features of DSRCT. In addition, postchemotherapy tumors may be sampled to confirm disease recurrence before planning additional therapy. This study was designed to compare prechemotherapy and postchemotherapy cytomorphology of DSRCT and to evaluate for distinct chemotherapy‐induced changes.

METHODS.

The authors searched their respective institutional databases for all DSRCT cases with an associated FNAB. FNAB slides, immunocytochemistry, and cytogenetic results were reviewed.

RESULTS.

Six aspirates from 5 patients were identified, 3 of which were postchemotherapy. The postchemotherapy cases demonstrated cytologic findings not typically described in DSRCTs, including prominent and conspicuous nucleoli, discohesive single‐cell architecture, and slightly larger cell size.

CONCLUSIONS.

Cytomorphologic variability was prominent in prechemotherapy cases, and no case could be classified as DSRCT on cytology alone; immunohistochemistry was necessary for definitive diagnosis. Chemotherapy increased the spectrum of cytologic features. The most notable difference between the 2 groups was a predominantly discohesive single‐cell pattern with conspicuous nucleoli in the postchemotherapy group, instead of the clustering pattern of medium‐sized cells with inconspicuous nucleoli typically attributed to de novo cases reported in the literature. Cancer (Cancer Cytopathol) 2006 © 2006 American Cancer Society.