Equivocal diagnoses in breast aspiration biopsy cytology: sources of uncertainty and the role of "atypical/indeterminate" terminology.

In 1996, a National Cancer Institute committee recommended four categories as uniform terminology for breast fine-needle aspirations (FNAs): benign, malignant, suspicious/probably malignant, and atypical/indeterminate. The latter is a controversial category. This study evaluates the usefulness of the atypical/indeterminate term, and examines sources of diagnostic equivocation in breast FNA. Eight hundred and twenty-two consecutive breast FNAs were previously classified as benign, malignant, suspicious, or unsatisfactory. Two hundred and thirteen (25.9%) cases had surgical follow-up and were classified as true positive (TP), false positive (FP), true negative (TN), false negative (FN), true suspicious (TS), or false suspicious (FS). Slides from FN, FP, TS, and FS were reviewed for interpretative error, poor clarity or preservation, obscuring material, sampling error, or insufficient malignant criteria. Cases were also evaluated as to whether classification as "atypical/indeterminate" would have improved patient care. There were 21/822 (2.6%) FN, 37/822 (4.5%) TS + FS, and 0 FP diagnoses. Seventy percent of suspicious diagnoses showed cancer on follow-up. The majority of FN and suspicious cases were due to sampling problems and insufficient criteria of malignancy. None were deemed more appropriately classified as "atypical/indeterminate" All required surgical confirmation for treatment. All equivocal breast diagnoses are due to similar problems. Splitting them into "suspicious/probably malignant" and "atypical/indeterminate" would not lower the biopsy rate. A simpler three-part terminology of benign, malignant, and suspicious/equivocal, without qualification of the latter favoring benign or malignant, would provide more effective communication and appropriate follow-up. Diagn. Cytopathol. 1999;21:217-222.     

Correlation of thyroid nodule fine-needle aspiration cytology with corresponding histology at Mayo Clinic, 2001-2007: an institutional experience of 1,945 cases

Following the National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference, the thyroid fine‐needle aspiration biopsy (FNAB) practice at Mayo Clinic, Rochester, Minnesota, conducted retrospective analyses correlating cytologic and histologic evaluations of thyroid nodules. Cytologic and histologic reports were retrieved for patients with thyroid nodules who underwent thyroid FNAB between January 2001 and December 2007, with subsequent surgical thyroid resection. Cases were classified by major cytologic and histologic diagnosis and specific diagnostic subcategories. Of 1,945 FNAB cytologic results, 180 (9.3%) were nondiagnostic; 512 (26.3%) were negative for malignancy; 27 (1.4%) were atypical; 729 (37.5%) were suspicious for malignancy; and 497 (25.6%) were positive for malignancy. Histology was benign in 1,179 (60.6%) and malignant in 766 (39.4%). For thyroid malignancy as the disease outcome, at cytologic thresholds of atypical, suspicious, and positive, overall sensitivity of thyroid FNAB was 94.5%, 94.1%, and 65.0%, respectively, and specificity was 46.0%, 48.3%, and 98.5%, respectively. Positive predictive value for all malignancies was 97.0%, and negative predictive value was 92.0%. When separated by specific malignant outcomes, diagnoses of papillary carcinoma, medullary carcinoma, and lymphoma had specificity of suspicious FNAB diagnoses ranging from 90.5% to 99.6%; positive predictive value ranged from 87.5% to 91.4%. For follicular or Hürthle carcinoma, suspicious FNAB diagnoses had a specificity of 52.5% and a positive predictive value of 5.9%. Sensitivity of indeterminate FNAB diagnoses ranged from 72.7% to 95.3%. For follicular or Hürthle pattern malignancies, indeterminate cytologic diagnoses should be interpreted with caution by the clinician considering surgical management. Diagn. Cytopathol. 2012;40:E27–E32. © 2010 Wiley Periodicals, Inc.     

Cytologic-histologic correlation of nongynecologic cytopathology cases: separation of determinate from indeterminate cytologic diagnoses for analysis and monitoring of laboratory performance

Much of the literature on the quality-assurance aspect of cytologic-histologic correlation (CHC) has focused on gynecologic cytology. For nongynecologic cytopathology, the process is complicated by the use of determinate (positive for malignant cells, negative for malignant cells) and indeterminate (atypical, suspicious, or follicular lesion) diagnostic categories. Here, we illustrate our routine methodology for analyzing CHC data on nongynecologic cytopathology cases by separating determinate from indeterminate cases. A focused list of determinate and indeterminate cytopathology cases with surgical pathology correlation is generated each week. The determinate cases are ascertained as true positive (TP), true negative (TN), false positive (FP), or false negative (TN). The discrepant cases (FP and FN) are investigated to determine the cause (sampling, interpretation, or screening). For indeterminate cases, the surgical pathology outcome (benign, malignant) and suitability of the cytopathology category utilized are reviewed. For the focused period of 4 mo, sensitivity was 70% and specificity was 100%. The most common reason for false-negative diagnoses was a sampling problem in the cytologic specimen; there were no false-positive diagnoses. Malignant outcomes for follicular lesion, atypical, and suspicious diagnoses were 29%, 40%, and 76%, respectively. Data derived from regularly performed CHC are useful in reviewing the diagnostic performance of the laboratory.     

Fine-needle aspiration cytology of unusual germ cell tumors of the mediastinum: atypical seminoma and parietal yolk sac tumor

To assess the efficacy of fine-needle aspiration biopsy (FNAB) of axillary lymph nodes (ALN), we retrospectively analyzed 140 FNAB of ALN at Memorial Sloan-Kettering Cancer Center, examining technique and cytologic-histologic correlation. Of the 140 FNAB, 124 were performed by the conventional method and 16 by ultrasound guidance (USG). The diagnoses included: unsatisfactory, 20; negative, 38; positive, 72; suspicious, 6; and indeterminate, 4. Positive diagnoses included: carcinoma, 44.4%; melanoma, 43.0%; lymphoma, 5.6%; sarcoma, 5.6%; and mesothelioma, 1.4%; one of which was false-positive, attributed to misinterpretation. All indeterminate and most false-negative cases were due to lymphoproliferative conditions. The sensitivity and specificity of FNAB of ALN were 94.7% and 97.1% and the adequacy rate was 85.7%. The sensitivity, specificity, and adequacy rates of USG FNAB were 100%. Our study shows that FNAB of ALN is an excellent method for diagnosing reactive conditions as well as neoplasms.     

Cytology and immunophenotyping of low- and intermediate-grade B-cell non-Hodgkin's lymphomas with a predominant small-cell component: a study of 56 cases

Diagnosis of non-Hodgkin's lymphomas based on cytologic evaluation of fine-needle aspirates and body cavity fluids has gained increasing acceptance. However, the accurate diagnosis and classification of low- and intermediate-grade B-cell lymphomas with a predominant small-cell population still present a diagnostic challenge. In this study, we reviewed the cytology and immunophenotype of 56 cases of low- and intermediate-grade non-Hodgkin's B-cell lymphomas composed of predominantly small cells, with histologic correlation in all cases. These cases consisted of 23 small lymphocytic lymphomas (SLL), 15 follicular center lymphomas (FCL), grade I (small cell predominant), 8 lymphoplasmacytoid lymphomas (LPL), 6 mantle-cell lymphomas (MCL), and 4 marginal zone lymphomas (MZL) including mucosa-associated lymphoid tissue (MALT) lymphoma. Histologic comparison was available in all cases. A cytologic diagnosis of malignant lymphoma was made in 46 (82%) cases. Based on cytomorphology and immunophenotyping of cytologic material, 39 (85%) cases were correctly classified using the Revised European and American Lymphoma classification. In 7 (11%) cases, which included 3 FCLs, 2 MALT lymphomas, and 2 SLLs, the findings were atypical but not diagnostic of lymphoma. There were 3 (5%) false-negative cases. They were 2 SLLs and a FCL. Immunophenotyping done in 4 "atypical" cases was noncontributory. No marker studies were done in the remaining "atypical" case and all false-negative cases. We conclude that cytology, when used in conjunction with immunophenotyping, can accurately diagnose and in most instances subclassify low- and intermediate-grade B-cell non-Hodgkin's lymphoma with a predominant small-cell population.     

Role of fine-needle aspiration cytology in breast lymphoma

Lymphomas of the breast are rare and may mimic carcinoma clinically. We investigated the ability of fine-needle aspiration (FNA) biopsy combined with adjunctive flow cytometry (FC), immunofluorescence microscopy (IFM), and immunocytochemistry (ICH) to diagnose and eventually subclassify lymphomas of the breast according to the Revised European American Lymphoma/World Health Organization classification. We retrieved 21 breast aspirates from 19 patients with a cytologic diagnosis of lymphoma or plasmacytoma over a 10-year period (1992-2002), excluding 98 benign intramammary lymph nodes and 1 atypical lymphohistiocytic proliferation (Rosai Dorfman disease). FC was performed in 15/21 aspirates, IFM in 1/21, ICH in 3/21. Histologic follow-up (HF) was obtained for 10 patients, most of them with primary lymphoma. For the remaining nine patients without HF, flow cytometric analysis, comparative morphology, or remission after chemotherapy regimens supported the cytologic diagnosis. Of 19 patients, 11 patients had a secondary lymphoma (SL) and 8 patients had a primary lymphoma (PL). FNA and FC/IFM/ICH classified 7/8 PLs as B-cell lymphomas and 1/8 PLs as plasmacytoma. However, FNA could only subclassify 3 of 8 PLs. FNA and/or FC subclassified accurately 10/11 SLs. All cases were accurately immunophenotyped as B-, T-cell non-Hodgkin's lymphomas or plasmacytoma. World Health Organization classification was achieved in 3/8 PLs (42%) and 10/11 SLs (91%; P = 0.04). Subclassification (which has an impact on long-term management and prognosis) was significantly better in SL, when a previous histologic diagnosis had already been made, when compared to PL, of which 5/8 cases (62.5%) could not be accurately classified.     

Diagnostic accuracy of image-guided percutaneous fine needle aspiration biopsy of the mediastinum

Interpreting a fine needle aspiration biopsy (FNAB) from the mediastinum is challenging as this location may harbor many lesions, including primary and metastatic tumors. Image-guided transthoracic (percutaneous) FNAB is less invasive than mediastinoscopy or endoscopic-guided FNAB. The aim of this study was to determine the diagnostic accuracy of FNAB performed percutaneously for evaluating mediastinal lesions.A retrospective study of 157 consecutive CT-guided transthoracic FNAB of the mediastinum was performed (1988-2004). Direct smears (N = 145; average 13 slides/case), ThinPrep slides (N = 25), and adequate cell blocks (N = 131) were prepared from procured cytologic material. When needed, ancillary studies included immunocytochemistry (N = 53) and flow cytometry (N = 8). Subsequent histologic tissue diagnoses available for 68 cases were also reviewed.Patients were of average age 57 yr (range 1-88 yr), including 75 males and 82 females. A definitive diagnosis was rendered in 128 (82%) cases. Primary neoplasms (N = 38) included 24 lymphomas (6 Hodgkin and 18 non-Hodgkin), 7 thymomas, 1 thymic carcinoma, and 6 peripheral nerve sheath tumors. Metastases (N = 72) were mainly carcinomas (N = 71) and 1 melanoma. There were 4 non-neoplastic lesions (1 granulomatous process; 2 bronchogenic and 1 pericardial cyst), 1 case of undifferentiated malignant large cell neoplasm, 13 cases negative for malignancy, and 29 (18%) that were indeterminate, due largely to insufficient cellularity. Subsequent histologic diagnoses were concordant with FNAB diagnoses in 53/68 cases (78%). Nine FNAB were inadequate/nondiagnostic. There were 6 discordant cases, including 5 FNAB that were of adequate cellularity but interpreted as negative for malignant cells (on subsequent histology 2 turned out to be Hodgkin lymphoma, 2 carcinomas, and 1 diffuse large cell lymphoma), and 1 diagnosed as thymoma that on histologic evaluation was a thymic large cell lymphoma.Adequate diagnostic cytologic material was obtained by image-guided percutaneous FNAB of mediastinal lesions in 82% of our cases. Sufficient material was available to make cell blocks and perform ancillary studies when necessary. These data also show a high proportion of agreement (78%) between FNAB and subsequent histologic diagnoses for a wide variety of mediastinal lesions. The majority of discordant cases were primarily interpretive, with a final cytologic diagnosis negative for malignancy. Only one problematic case misdiagnosed on FNAB as thymoma was found on subsequent surgical excision to be a thymic large B cell lymphoma. Cases with nondefinitive FNAB diagnoses were largely due to sampling error and/or insufficient cellularity. Therefore, percutaneous FNAB of the mediastinum is a diagnostically helpful, minimally invasive procedure that can be performed in patients of all ages as part of the evaluation of a mediastinal mass lesion.     

Metachronous soft-tissue masses in children and young adults with cancer: correlation of histology and aspiration cytology

We describe a series of 28 fine needle aspiration biopsies (FNAB) of soft tissue from 22 patients. Four patients had two separate FNABs, and one had three aspiration procedures. The patient population was limited to children and young adults (age range, 2 months to 29 years; mean, 16 years) who were known to have diverse forms of cancer, and who subsequently developed a mass in the peripheral soft tissues (including breast). The interval between the time of diagnosis of the primary malignant neoplasm and FNAB ranged from 1 day to 17 years (mean, 39 months). All FNAB diagnoses were confirmed by subsequent surgical open biopsy or clinical follow-up greater than 1 year. No complications occurred from the procedure. The cytomorphology is presented in selected cases and correlated with the patient's original tissue histopathology. Twenty aspirates were diagnosed as cytologically malignant, one as suspicious for malignancy. Seven were considered benign. None were unsatisfactory. One false-positive and no false-negative cytologic diagnoses were obtained. The overall accuracy of FNAB diagnoses was 96%, while sensitivity was 100% and specificity 88%. Sites of aspiration included soft tissues of the head and neck (seven cases), trunk (eight cases), breast (four cases), and extremities (nine cases). Malignant cytologic diagnoses included sarcoma (thirteen), seminoma (two), lymphoma/leukemia (two), melanoma (one), undifferentiated neoplasm (one), and neuroblastoma (one). Electron microscopy of aspirated cells was used to confirm the diagnosis in two cases. Fine needle aspiration biopsy of soft tissue masses from children and young adults with cancer demonstrates a high diagnostic accuracy, and its use is justified in this population.     

Flow cytometry immunophenotyping of fine-needle aspiration specimens: utility in the diagnosis and classification of non-Hodgkin lymphomas

Barrena S, Almeida J, García‐Macias M D C, López A, Rasillo A, Sayagués J M, Rivas R A, Gutiérrez M L, Ciudad J, Flores T, Balanzategui A, Caballero M D & Orfao A
(2011) Histopathology  58 , 906–918
Flow cytometry immunophenotyping of fine‐needle aspiration specimens: utility in the diagnosis and classification of non‐Hodgkin lymphomas Aims: To establish the utility of flow cytometry (FCM) for screening and diagnosis of B cell non‐Hodgkin lymphoma (B‐NHL) from lymphoid tissue samples obtained by fine‐needle aspiration (FNA). Methods and results: We compared prospectively FCM versus cytology/histology analysis of FNA samples for the diagnostic screening and further World Health Organization (WHO) subclassification of B‐NHL. FCM and cytology showed a high degree of agreement (93%); however, diagnosis of reactive processes (RP), B‐NHL and T‐NHL by FCM showed higher sensitivity than cytology (92–100% versus 64–94%, respectively), without false positive NHL cases. The antibody combination used did not allow a positive diagnosis of Hodgkin lymphoma as distinct from a RP. A high concordance rate was found between FCM and histopathology (74%) in subtyping B‐NHL. In this regard, mantle‐cell lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma showed the highest degree of agreement (100% concordant rates). In turn, FCM showed higher sensitivity/specificity in classifying follicular lymphoma (FL) and large B cell lymphomas, while the opposite occurred for marginal‐zone and lymphoplasmacytic lymphomas. Conclusions: FCM enhances the diagnostic ability of FNA cytology, playing a crucial role in a rapid and accurate differential diagnosis between RP, B‐NHL and T‐NHL. In addition, immunophenotyping of FNA samples contributes to a more precise subclassification of B‐NHL when combined with histopathology and genetic/molecular data.     

Value of fine needle aspiration cell blocks in the diagnosis and classification of lymphoma

Fine needle aspiration biopsy (FNAB) is a simple yet accurate diagnostic procedure. However, the role of FNAB in lymphoma diagnosis and classification remains controversial. This study aimed to evaluate the value of FNAB cell blocks in the diagnosis and classification of lymphoma using our patented aspirator in a pencil-grip operation manner and a simplified cell block preparation method. We retrospectively reviewed 177 cases of lymph node and extranodal lymphoproliferative disorders that were diagnosed with cytomorphology, morphology, and immunohistochemistry of cell blocks. Of these, 83 were primary lymphoma; 14 were recurrent lymphoma; 8 were suspected as lymphoma, and 72 were benign reactive hyperplasia (BRH). Our analysis indicated 99.0% sensitivity, 95.9% specificity, 97.1% positive predictive value, and 98.6% negative predictive value in discriminating among primary/recurrent lymphoma and BRH. The diagnostic accuracy for sub-classification of lymphoma was 86.6% (84/97), with 77.8% (7/9) for classical Hodgkin’s lymphoma and 87.5% (77/88) for non-Hodgkin’s lymphoma. Our results implicated cell blocks as a reliable and useful adjunct to FNAB for the diagnosis and classification of lymphoma. Cytomorphology, morphology, and immunohistochemical studies of cell blocks offered very high accuracy in the diagnosis of lymphoma and allowed further sub-classification in many cases. Thus, patients with a definitive diagnosis and classification might avoid invasive and expensive surgical biopsy procedures.     

Role of repeat fine-needle aspiration biopsy (FNAB) in the management of thyroid nodules

The purpose of the present study was to determine the role of repeat fine-needle aspiration biopsy (FNAB) in the evaluation of thyroid nodules initially classified as "nondiagnostic" due to limited cellularity or as "indeterminate for neoplasm." We reviewed a cohort of 431 patients (352 females, 79 males; average age 50 yr); 237 patients were classified as "nondiagnostic" due to limited cellularity and 194 as "indeterminate for neoplasm" over a 3-yr period (1999-2002). Repeat FNAB under ultrasound guidance was performed in 226 patients (226/431, 52%); surgical pathology results were available in 101 patients. Repeat FNAB diagnoses were: benign 70 (31%), follicular/Hürthle cell neoplasm 62 (27%), suspicious for papillary carcinoma 25 (12%), malignant 17 (7%), and nondiagnostic 52 (23%) cases. Surgical follow-up was available in 101 (45%) patients; malignancy was identified in 50 (49%) patients. The malignancy rate was 51% and 48% in cases in which initial FNAB was nondiagnostic and indeterminate for neoplasm, respectively. There were no false-positives and all malignant cases undergoing surgery were found to be malignant. This study demonstrates that repeat FNAB is warranted in patients with thyroid nodules diagnosed on initial FNAB as nondiagnostic and indeterminate for neoplasm since it can yield a definitive diagnosis in the majority of cases with an overall malignancy rate of 49%.     

A Bethesda‐like system for breast cytopathology: A retrospective assessment two decades on

Fine‐needle aspiration biopsy (FNAB) has been used for many decades in the investigation of breast lesions. Originally, cases were signed out using the categories benign and malignant. The benign category contained specimens showing fibrocystic change as well as benign neoplasms such as fibroadenoma. The malignant category contained carcinomas, lymphomas, and phyllodes tumors with specific diagnoses often given in place of the term malignant. Categorization was less clear when the cytopathologists could not definitively separate benign from malignant. This led to the use of terms, such as atypical, suspicious for malignancy, and atypical suspicious with variable definitions and utilization among cytopathologists. In 1997, a uniform approach to breast FNAB was proposed with well‐defined diagnostic categories and criteria. This system foreshadowed the recent International Academy of Cytology Standardized Reporting System for Breast Fine‐Needle Aspiration Biopsy. These two systems are compared and contrasted.     

Audit of tumour histopathology reviewed by a regional oncology centre.

AIMS--To analyse the diagnostic differences in reporting tumour histopathology between a district general hospital and a regional oncology centre. METHODS--Tumour histopathology reports (n = 227) extracted from Bolton General Hospital files between 1988 and 1992 were compared with the corresponding Christie Hospital (oncology centre) reports, the same material having been seen at both hospitals. RESULTS--Diagnostic agreement existed in 77% of all cases. The incidence of major discrepancies was 8.37%. Of the diagnoses, 19 (36%) cases involved major discrepancies and 34 (64%) cases minor discrepancies. Most discrepancies occurred in the lymphoma group and involved subclassification of Hodgkin''s and non-Hodgkin''s lymphoma. Ki1 anaplastic large cell lymphoma and T cell rich B cell lymphoma were problematic diagnoses. The correct grading of follicle centre cell lymphomas using the Kiel classification was another problem area. In 19 cases certain aspects of immunohistochemistry produced discrepancies. In one case an incorrect diagnosis was made at the oncology centre and in another both centres gave an incorrect diagnosis. CONCLUSIONS--Areas of diagnostic difficulty mainly involve the subclassification of lymphomas. Review of tumour pathology by experts is recommended, at least in certain categories, to ensure correct diagnosis and uniformity in subclassification of tumours.     

Diagnosis of lymphoma,leukemia, and metastatic tumor involvement of the cerebrospinal fluid by cytology and immunocytochemistry

Fifty-five cerebrospinal fluid (CSF) specimens from 42 patients with suspected meningeal tumor involvement were reviewed. Cytology in conjunction with immunocytochemistry identified 26 CSF specimens as malignant. There were fifteen cases of lymphoma, four cases of leukemia, two cases of carcinoma, and two cases of melanoma. A monoclonal light chain expression was demonstrated in nine out of eleven B cell lymphomas. the three T-cell lymphomas all expressed pan T markers (CD 3) and two the T-helper antigen (CD 4). One patient had meningeal involvement of a true histiocytic lymphoma which was indentified by its large atypical cells which were positive for α-1-anti-trypsin and muramidase. in four patients with a primary diagnosis of acute lymphoblastic leukemia, CSF involvement was confirmed by the demonstration of blasts with CD 10 (cALLA) or light chain restriction. Epithelial or melanocytic markers were demonstrated on the tumor cells in CSF from the remaining four patients. In 29 CSF specimens a diagnosis of reactive lymphocytosis was made using cytomorphology which mostly was characterized by macrophages mixed with small mature lymphoid cells. Immunologic evaluation showed that these mature cells were CD 10 negative T-cells and only few specimens contained polyclonal B-cells. the subsequent clinical course of these patients showed no evidence of CNS malignancy. It is concluded that cytology should be used in conjunction with immunocytochemistry to accurately evaluate CSF specimens from patients with possible malignant meningitis.     

An investigation into false‐negative transthoracic fine needle aspiration and core biopsy specimens

Transthoracic fine needle aspiration (TFNA)/core needle biopsy (CNB) under computed tomography (CT) guidance has proved useful in the assessment of pulmonary nodules. We sought to determine the TFNA false‐negative (FN) rate at our institution and identify potential causes of FN diagnoses. Medical records were reviewed from 1,043 consecutive patients who underwent CT‐guided TFNA with or without CNB of lung nodules over a 5‐year time period (2003–2007). Thirty‐seven FN cases of “negative” TFNA/CNB with malignant outcome were identified with 36 cases available for review, of which 35 had a corresponding CNB. Cases were reviewed independently (blinded to original diagnosis) by three pathologists with 15 age‐ and sex‐matched positive and negative controls. Diagnosis (i.e., nondiagnostic, negative or positive for malignancy, atypical or suspicious) and qualitative assessments were recorded. Consensus diagnosis was suspicious or positive in 10 (28%) of 36 TFNA cases and suspicious in 1 (3%) of 35 CNB cases, indicating potential interpretive errors. Of the 11 interpretive errors (including both suspicious and positive cases), 8 were adenocarcinomas, 1 squamous cell carcinoma, 1 metastatic renal cell carcinoma, and 1 lymphoma. The remaining 25 FN cases (69.4%) were considered sampling errors and consisted of 7 adenocarcinomas, 3 nonsmall cell carcinomas, 3 lymphomas, 2 squamous cell carcinomas, and 2 renal cell carcinomas. Interpretive and sampling error cases were more likely to abut the pleura, while histopathologically, they tended to be necrotic and air‐dried. The overall FN rate in this patient cohort is 3.5% (1.1% interpretive and 2.4% sampling errors). Diagn. Cytopathol. 2014;42:1063–1068;. © 2014 Wiley Periodicals, Inc.     

Renal lymphoma. The diagnostic and therapeutic roles of fine-needle aspiration

This study focused on 19 patients with renal lymphoma (RL) from whom 20 initial (1 patient with fine-needle aspiration [FNA] specimens of masses in both kidneys) and 1 repeated FNA specimen were obtained. Of the 19 patients, 10 had secondary RL, 8 primary RL, and 1 transplant RL. The FNA samples were studied by smears (all cases), tissues (11), phenotyping by immunostaining (13) or flow cytometry (4), and gene rearrangement (3). The final diagnoses included 1 T-cell lymphoma and 18 B-cell lymphomas. Of the 20 original specimens, 14 were reported as positive for lymphoma, 3 suggestive of lymphoma, 1 positive for transitional cell carcinoma, and 2 unsatisfactory. The follow-up specimen showed reactive changes. Tissue correlation, available in 11 cases, confirmed a positive cytodiagnosis (7), provided a final diagnosis in the cytologically inconclusive cases (3), or revised the misdiagnosis of transitional cell carcinoma from smears (1). The phenotyping elucidated the B vs T lineage of the lymphoma in all tested cases, confirmed the positive cytodiagnosis in 10 cases, confirmed the reactive cytodiagnosis in 1 case, and helped achieve a conclusive diagnosis in 2 cases suggestive of lymphoma. Gene rearrangement studies showed light chain restriction in the 2 tested cases. FNA has an essential role in treatment planning for RL. Although FNA usually is diagnostically conclusive, a high index of suspicion and awareness of atypical or misleading cytomorphologic features are important for a correct interpretation, especially for primary RL. Ancillary testing is essential for the diagnosis in problematic cases and lays the foundation for the differential diagnosis.     

Reliability of fine-needle aspiration biopsy in the initial diagnosis of soft-tissue lesions

We retrospectively reviewed fine-needle aspiration biopsy (FNAB) specimens of 301 soft tissue lesions of the extremities and trunk. Final diagnoses were 137 benign and 86 malignant neoplasms and 78 nonneoplastic lesions. Of the 301 FNAB samples, 279 (93%) were adequate for cytologic diagnosis. The adequate FNAB specimens were initially grouped into three broad categories: benign (197 cases), malignant (57 cases), and suspicious for malignancy (25 cases). Sensitivity and specificity for diagnosis of a malignant lesion were 92% and 97%, respectively. The specimens were cytomorphologically classified into nine categories: small round (14 cases), spindle cell (77 cases), epithelioid/polygonal (16 cases), pleomorphic (29 cases), myxoid (19 cases), lipomatous (37 cases), epithelial (23 cases), inflammatory lesions (28 cases), and others (36 cases). Specific FNAB diagnoses were correct in 151 of 279 cases (54%) in combination with clinical and radiologic findings. FNAB is a valuable technique for the primary diagnosis of soft-tissue lesions.     

Immunohistochemical detection of EGFR, fibrillin-2, P-cadherin and AP2β as biomarkers for rhabdomyosarcoma diagnostics

Aims:  Subclassification of rhabdomyosarcoma (RMS) has clinical relevance, as the two major subclasses embryonal (ERMS) and alveolar (ARMS) rhabdomyosarcoma differ greatly in terms of aggressiveness and prognosis. However, histological analysis is not always sufficient for an unequivocal subclassification of RMS. Furthermore, clinical presentation of ARMS has been reported to mimic other tumour types, specifically lymphoma. The aim was to determine the role of four biomarkers in the diagnosis of rhabdomyosarcoma.
Methods and results:  Recently, we identified four potential biomarkers to subclassify RMS with high sensitivity and specificity. These included epidermal growth factor receptor (EGFR) and fibrillin-2 as markers for ERMS, and AP2β and P-cadherin as markers for translocation-positive ARMS. Here, we further validate the potential of these four markers in a second, independent patient cohort by immunohistochemistry on 80 sections of RMS biopsy specimens as well as a tissue microarray representing 18 different additional tumour types, including seven lymphomas. The combination of EGFR and fibrillin-2 was able to detect ERMS with a specificity of 76% and sensitivity of 90%. The combination of AP2β and P-cadherin detected ARMS with a specificity of 97% and sensitivity of 90%, data very similar to our previous study. Furthermore, all lymphomas were clearly negative for AP2β and P-cadherin.
Conclusions:  These four biomarkers are suitable for clinical implementation in the future diagnosis of RMS.     

The cell block for body cavity fluids: do the results justify the cost?

We reviewed retrospectively reports on cytologic smears and cell blocks from body cavity fluids received in our department over a 12-mo period. In order to evaluate the usefulness of the two modalities independently, all available slides were studied with the reviewers blinded to the original diagnoses, history, and appearances on corresponding cytology/cell block. Of 524 cytology samples, 283 had cell blocks, of which 263 were available for comparative cytologic and histologic review. Twenty-four cases based on the original reports and 22 cases in the review had diagnoses with major discrepancies between the cell block and cytology. On original reports, cytology favored malignancy in 21 cases in which the cell block was benign, with one false suspicious cytology. In three cases, the cell block was suspicious/positive (two false suspicious cell blocks), but cytology was negative/atypical. In the review diagnoses, there were also 21 cases of suspicious/positive cytology (one false suspicious cytology) and negative/atypical cell blocks. In only one case did the cell block favor malignancy when cytology was benign (a false suspicious cell block). Review of Medicare data indicated that the physician's fee charged for these 283 cell blocks would range from about $7,000 to $28,000 to detect one additional malignancy. We conclude that the routine use of cell blocks is not a cost-effective method of detecting malignancy in body cavity fluids. We advise that samples be refrigerated or be kept fixed. If immunoperoxidase studies are desired following cytologic evaluation, they may be performed subsequently on fresh smears or a cell block.     

Use of fine-needle aspiration biopsy in the evaluation of splenic lesions in a cancer center

Fine-needle aspiration biopsy (FNAB) of the spleen was performed on 50 patients, of whom 40 had had a previous diagnosis of malignancy (23 lymphoproliferative disorders, 13 carcinomas, 3 melanomas, and 1 sarcoma). The cytologic diagnoses included 22 cases positive for malignancy (10 lymphomas, 9 metastatic carcinomas, 2 metastatic melanomas, and 1 sarcoma), 18 cases negative for malignancy, 4 cases suspicious for malignancy, and 6 nondiagnostic specimens. No major complications were associated with the FNAB procedure; however, one patient did develop a pneumothorax that resolved spontaneously. Subsequent splenectomy was performed in 10 of the 50 cases. There were no false-positive diagnoses, and only one false-negative diagnosis, which was attributed to sampling error. The aspirate, showing only benign splenic parenchyma, was from a patient with splenomegaly and no previous diagnosis; subsequent splenectomy showed acute myelogenous leukemia. In our study, FNAB proved to be a safe and valuable diagnostic tool for evaluating splenic lesions in oncologic patients. Diagn. Cytopathol. 16:312–316, 1997. © 1997 Wiley-Liss, Inc.