Spindle-cell lesions of the mediastinum: Diagnosis by fine-needle aspiration biopsy

Spindle cells seen in fine-needle aspiration biopsy (FNAB) of the mediastinal lesions can be a component of a wide variety of benign and malignant conditions. Few of these conditions, however, are described in the FNA cytopathology literature. This review discusses the cytopathologic features, differential diagnoses, and potential pitfalls of a variety of lesions with a significant component of spindle cells encountered in mediastinal FNAB. The cytopathology files from four institutions were searched for cases of mediastinal FNAB containing a spindle-cell component that was a key or predominant cytologic feature of the diagnostic specimen. The cytomorphologic features of these cases were analyzed, and their differential features are discussed. Of 196 mediastinal FNABs, 22 (11%) were lesions with significant spindle-cell component: granulomatous inflammation (four); benign nerve sheath tumor (four); thymic cyst (two); spindle-cell thymoma (two); large-cell non-Hodgkin's lymphoma with sclerosis (two); nodular sclerosing Hodgkin's disease (two); liposarcoma (two); spindle-cell squamous carcinoma possibly arising in a teratoma (one); unspecified high-grade sarcoma (one); spindle-cell malignant melanoma (one); and nonspecific fibrous tissue (one). The cytologic features of each lesion were analyzed as an aid for accurate classification. These findings were correlated with radiologic and clinical information when available. The value of ancillary studies performed on aspirated material in selected cases was also reviewed. FNA of mediastinal lesions with significant spindle-cell morphology represents an infrequent and heterogeneous group of entities that may pose significant diagnostic challenges. This review presents the salient cytopathologic features of various spindle-cell lesions of the mediastinum with particular emphasis on differential diagnosis and pitfalls. The pathologist must use caution when interpreting these lesions and ancillary studies may be of significant value in selected cases. Diagn. Cytopathol. 1997;17:167–176. © 1997 Wiley-Liss, Inc.     

Utility of glypican‐3 and survivin in differentiating hepatocellular carcinoma from benign and preneoplastic hepatic lesions and metastatic carcinomas in liver fine‐needle aspiration biopsies

Glypican‐3 (GPC‐3), a membrane‐anchored heparin sulfate proteoglycan, has been shown to be expressed in ～80% of hepatocellular carcinoma (HCC) but not in benign hepatic lesions. Survivin, a novel inhibitor of apoptosis, and a prognostic marker, has also been expressed in HCC. We evaluated these two immunomarkers (GPC‐3 and survivin) in differentiating HCC from benign and preneoplastic hepatic lesions and metastatic carcinomas, comparing them to HepPar‐1 (hepatocyte paraffin‐1) in liver fine‐needle aspiration biopsies (FNAB). Immunohistochemistry for GPC‐3, survivin and HepPar‐1 was performed on 92 FNAB including HCC, hepatic cirrhosis, focal nodular hyperplasia (FNH), hepatic adenoma, dysplastic hepatic nodules and metastatic carcinomas. Immunostaining was scored as positive, if ≥10% of tumor cells stained. GPC‐3 is immunoexpressed in 56.8% of HCC, but not in benign and preneoplastic hepatic lesions, or metastatic carcinomas; whereas survivin is expressed in HCC (86.4%), benign hepatic lesions (85.7%), dysplastic hepatic nodules (100%) and metastatic carcinomas (94.3%). HepPar‐1 is immunoexpressed in HCC (72.7%), benign hepatic lesions (100%), dysplastic nodules (100%) and metastatic carcinomas (2.9%). The sensitivity and specificity of GPC‐3, survivin and HepPar‐1 for detection of HCC are 56.8 and 100%, 86.4 and 6.3%, 72.7 and 70.8%, respectively. GPC‐3 is a reliable and more specific immunohistochemical marker than survivin for the diagnosis of HCC in FNAB. HepPar‐1, although a more sensitive marker than GPC‐3, has a lower specificity for detection of HCC. Our data supports the potentially significant diagnostic utility of GPC‐3 in FNABs in differentiating primary malignant from benign and preneoplastic liver lesions, and metastatic carcinomas. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Endoscopic ultrasound-guided fine-needle aspiration of lymph nodes: the Hennepin County Medical Center experience

Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) allows for the sampling and diagnosis of lesions of the gastrointestinal system and adjacent tissues. It has also proved helpful with the sampling of lymphadenopathy both for the staging of malignancy and for the diagnosis of lymphadenopathy of other causes. We review our experience with EUS-guided FNA of lymph nodes. The cytology files were searched at Hennepin County Medical Center (HCMC) for all cases of lymph nodes sampled by EUS. Clinical history, biopsy site, diagnosis, and follow-up information (including ancillary testing) were reviewed. Between January 1, 2000 and December 5, 2002, 217 lymph nodes from 185 different patients were sampled by EUS at HCMC. Biopsy sites included 62 mediastinal, 9 paraesophageal, and 146 intra-abdominal lymph nodes. Diagnoses were as follows: metastatic non-small cell carcinoma (n = 69); benign, reactive lymph node (n = 76); granulomatous lymphadenopathy (n = 18); malignant lymphoma (n = 7); atypical-suspicious for malignancy (n = 5); metastatic small cell carcinoma (n = 2); necrotic debris (n = 4), and foreign material (n = 1); 35 cases were nondiagnostic (16.1%) in 22 of 185 patients (11.9%). Ancillary tests including flow cytometry, cytogenetics, and cultures were performed. EUS-guided FNA of mediastinal and intra-abdominal lymph nodes provides diagnostic material from which ancillary testing may be performed.     

The cytology of pediatric masses: a differential diagnostic approach.

In the United States, fine-needle aspiration biopsy (FNAB) and other cytodiagnostic methods have been underutilized in the evaluation of masses in the pediatric age group. Cytopathologists and cytotechnologists are therefore relatively unfamiliar with the cellular features of lesions that occur in children. On the basis of the cytologic findings from 64 pediatric cases, including 56 FNABs and 8 intra-operative imprints, a differential diagnostic approach to lesions in this age group is presented. The majority of cases can be placed into 1 of 5 cytomorphologic categories: (1) round-cell pattern, (2) mixed inflammatory pattern, (3) spindle-cell pattern, (4) epithelial pattern, and (5) cystic pattern. Once a cytomorphologic category is determined, evaluation for unique cellular features, special studies, and clinical correlation allows a specific diagnosis to be made in most cases. Pitfalls in pediatric cytopathology are illustrated by discussion of the following cases: a renal Burkitt's lymphoma mimicking a Wilms' tumor, a traumatic neuroma masquerading as a recurrent malignant schwannoma, Langerhans-cell histiocytosis resembling granulomatous inflammation, and a cystic granuloma that mimicked a branchial cleft cyst. Consideration of these problems and use of the recommended diagnostic approach will aid in interpretation in this difficult area.     

Telecytology of fine-needle aspiration biopsies of the pancreas: a study of well-differentiated adenocarcinoma and chronic pancreatitis with atypical epithelial repair changes

Four experienced cytopathologists provided consultations using telecytology and routine microscopy. Twenty-seven fine-needle aspiration biopsies (FNABs) from patients with chronic pancreatitis with atypical epithelial repair changes (n = 9) and pancreatic low-grade adenocarcinomas (LG-AC) (n = 18) were studied. False-positive and false-negative diagnostic rates were 19.4% and 12.5% by microscopy and 11.1% and 2.8% by telecytology. Comparisons of agreements between the correct diagnoses and consultations rendered by the two methods and among the diagnoses rendered on the same cases by the two modalities yielded kappa coefficients ranging from 0.444-1.000. Telecytology yielded slightly better kappa coefficients than microscopy. This method, which to our knowledge has not been previously applied to pancreatic FNAB, provides a potentially useful consultative tool for the interpretation of these difficult specimens. The diagnosis of FNAB from patients with chronic pancreatitis and LG-AC is difficult even for experienced consultants, as underscored by the considerable intraobserver and interobserver variability encountered in this study.     

Cytologic analyses of spindle-cell lesions of the thorax and retroperitoneum

Thoracic and retroperitoneal spindle-cell lesions represent a diagnostic challenge in the evaluation of fine-needle aspiration (FNA) specimens. The challenge is due to the morphologic similarities and wide variety of different entities with spindle-cell morphology in these two sites. The purpose of this study was to identify criteria helpful in the classification and differential diagnosis of spindle-cell lesions in these two locations. A set of cytologic features was analyzed in 57 thoracic or retroperitoneal spindle-cell lesions. Our results show that pleomorphism and abundant single cells were parameters associated with high-grade tumors in univariate and multivariate analysis, while coarse chromatin pattern was significant only in a univariate analysis. The combination of absence of pleomorphism, rare single cells, tight cluster arrangement, fine chromatin pattern, and absence of macronucleoli was seen only in benign cases. Assessment of background material was helpful in the differential diagnosis and classification. Necrosis was only found in high-grade cases.     

Diagnostic role of fine-needle aspiration of bone lesions in patients with a previous history of malignancy

At the present time fine-needle aspiration (FNA) is considered a routine diagnostic procedure in evaluating neoplastic vs. nonneoplastic lesions in many organs, with high sensitivity and specificity. The purpose of this study was to assess the utility of FNA in areas of diagnostic difficulty and its limitations in evaluating bone lesions in patients with a previous history of malignancy. From 1989 to 2000, 249 CT-guided FNAs of bone lesion were performed at our institutions; 187/249 (75.1%) patients had a previous history of malignancy. Aspirated material was air-dried for Diff-Quik stain or fixed in ethanol for Papanicolaou staining. Subsequent surgical tissue was available in 69/187 (36.9%) of the cases. There were 114 males and 73 females, ages 14-86 yr (mean, 64 yr). The primary tumor site was lung 49, genitourinary 46, breast 31, gastrointestinal 28, hematopoietic 26, soft tissue/skin 5, and thyroid 2. There were 125 FNAs of the vertebral spine, 19 from the pelvis, 11 from the ribs, 9 from the sternum, 5 from the femur, and 18 from miscellaneous bone sites. Out of 187, 166 (88.7%) were malignant aspirates confirming the patients' primary malignancies. The most common malignancy encountered was adenocarcinoma, 126/187 (67.4%). Surgical tissue was available for review in 69 patients and the results were in agreement with the FNAs diagnosis in all cases. Nine out of 187 (4.8%) cases were diagnosed as marrow elements on cytological material. These patients have been followed for 1-9 yr and have failed to reveal signs or symptoms of clinical recurrence. Three out of 187 (1.6%) cases showed osteomyelitis. Nine out of 187 (4.8%) were unsatisfactory specimens, with biopsy follow-up available in four cases, showing three metastatic tumors and one case of osteomyelitis. FNA of metastatic bone lesions is a major step in pretreatment diagnosis. On satisfactory specimens, the cytological diagnosis viewed in the clinical-radiological context proves to be similar to surgical diagnosis. FNA is an excellent technique with a high accuracy rate in assessing metastatic bone lesions.     

Expression and clinicopathologic significance of glypican 3 in hepatocellular carcinoma

Glypican 3 (GPC3) is a glycosylphosphatidylinositol-anchored membrane protein and plays an important role in regulation of cell growth, differentiation, and migration. The aims of this study were to investigate the expression of GPC3 in human liver, biliary tract, and pancreatic tumors and to evaluate its diagnostic role in differentiating hepatocellular carcinoma (HCC) from other hepatic mimickers. Immunohistochemistry was performed on a large collection of surgically resected samples from 941 primary liver tumors, 50 metastatic adenocarcinomas, and 30 normal livers as well as primary adenocarcinomas of the pancreas (n = 17), gallbladder (n = 30), and extrahepatic bile duct (n = 20). The relationship of GPC3 expression and clinicopathologic features in patients with HCC was determined. We found that 516 (52%) of the 991 liver neoplastic tissue samples demonstrated positive staining for GPC3. A high incidence of GPC3 expression (492/757; 65%) was observed in HCC, whereas intrahepatic cholangiocarcinomas, adenocarcinomas, and benign liver lesions displayed rare positive cases. There were significant correlations between GPC3 expression and clinicopathologic characteristics, including histologic grade (P < .001), intrahepatic metastasis (P = .007), and positive serum hepatitis B surface antigen (P = .042), in patients with HCC. In conclusion, our results confirm the high expression of GPC3 in HCC and suggest its potential diagnostic value as a clinical marker for this disease.     

Cytopathologic analysis of paraspinal masses: a study of 59 cases with clinicoradiologic correlation

Paraspinal masses (PSM) are uncommon and present a wide spectrum of differential diagnoses on fine-needle aspiration (FNA). We analyzed 59 cases of PSM on FNA in a 15-yr period, in the context of clinicoradiologic correlation. Radiologic findings, clinical data, and tissue biopsies were reviewed. Patients were 14-83 yr of age (mean 54.7) with a M:F ratio of 1.36:1. Of the 59 cases, 39 (66%) were deemed diagnostic. Of these, 8 (21%) revealed nonneoplastic lesions and 31 (79%) yielded neoplasms: 2 (6%) benign and 29 (94%) malignant. Of the malignant cases, 22 (76%) were metastatic tumors from various sites, while 7 (24%) were cancers from local spread, which included non-Hodgkin's lymphoma (NHL, 5) and myeloma (2). Benign neoplasms were nerve sheath tumors. Metastatic tumors consisted of adenocarcinoma, 9; squamous-cell carcinoma, 3; renal-cell carcinoma, 1; and non-small-cell carcinoma/not otherwise specified (NOS), 9. Twenty-four (41%) cases received further studies: immunoperoxidase (IPOX) alone, 17 (71%); special stains for microorganisms, 2 (8%); IPOX/other special stains, 4 (17%); and flow cytometry analysis, 1 (4%). Eight (14%) cases received follow-up biopsies. Half of these biopsies added information to previously "nondiagnostic" FNAs. Of the previously "diagnostic" FNAs, tissue biopsy yielded no additional information. Cytopathologic diagnoses were consistent with the pre-FNA radiology analyses in 13 (39%) cases. In instances of radiologic and cytopathologic discrepancy (4 cases, 12%), diagnoses made by FNA reversed the initial radiologic impression of neoplasm to infection, and vice versa. PSMs are rare lesions (0.26% of total FNAs done in 15 yr at our institution). The most common lesion encountered is metastatic adenocarcinoma, followed by NHL. Ancillary studies are helpful in difficult cases. In cases of radiologic/cytopathologic discrepancy, FNA diagnoses are more accurate and decisive for patient management. The sensitivity and specificity of a PSM FNA are 88% and 75% respectively.     

Utilization of fine-needle aspiration biopsy in the diagnosis of metastatic tumors to the pancreas

There is relatively little information concerning the use of fine-needle aspiration biopsy (FNAB) to diagnose a mass in the pancreas that is secondary to metastatic tumor. This study reviews the incidence and types of neoplasms which metastasize to the pancreas and assesses the contribution FNAB can make in their diagnosis. of 117 radiologically guided FNABs of the pancreas, 11% (n = 13) showed metastatic malignancy. Nine patients had a previous history of malignancy while four patients presented with a pancreatic mass and were subsequently found to have widespread malignant disease. the majority of metastatic lesions were epithelial (77%, n = 10). Patient outcomes were generally poor (mean survival 2.8 mo). Metastases to the pancreas occur from a variety of primary sites and should be considered in patients with a pancreatic mass and a history of prior malignancy. FNAB is useful in diagnosing these metastases and this is clinically important because of their poor prognosis.     

Utility of CD10 and RCCma in the diagnosis of metastatic conventional renal-cell adenocarcinoma by fine-needle aspiration biopsy

The cytologic diagnosis of primary conventional renal-cell adenocarcinoma (cRCC) is usually straightforward; however, metastatic cRCC must be distinguished from a variety of neoplasms with clear-cell features. CD10, a cell membrane-associated neutral endopeptidase, and renal-cell carcinoma marker (RCCma), an antibody against human proximal tubular brush border antigen, have recently been shown to be useful in the diagnosis of cRCC. We compared CD10 and RCCma in cell block material from fine-needle aspiration biopsies (FNABs) to assess their utility in the diagnosis of metastatic cRCC, in cytologic specimens. Seven primary and sixteen metastatic cRCCs were immunostained with CD10 and RCCma. The immunoreactivity results were compared with those of a variety of neoplasms originating from other sites such as the liver, lungs, breast, and the gastrointestinal tract. The sensitivity and specificity of CD10 for cRCC were 100% and 59%, respectively. The sensitivity and specificity of RCCma for cRCC were 35% and 100%, respectively. We conclude that CD10 has limited value in confirming the diagnosis of cRCC because of its low specificity. RCCma, when positive, is highly specific for cRCC, but its low sensitivity hinders its diagnostic usefulness.     

The diagnostic utility of CK5/6 and p63 in fine-needle aspiration of the breast lesions diagnosed as proliferative fibrocystic lesion

Fine-needle aspiration (FNA) biopsy (FNAB) in the preoperative assessment of breast lesions has shown diagnostic limitations with false-positive and false-negative diagnoses. We investigated the diagnostic value of cytokeratin 5/6 (CK5/6) and p63 in a series of breast FNABs, diagnosed as proliferative breast lesions with or without atypia, to see whether these ancillary studies enhance the ability to make an accurate diagnosis by FNAB. Sixty-four breast FNABs were retrieved between January 2000 and December 2005 and included in the study as follows: 29/64 (45%) cases as proliferative with atypia and 35/64 (55%) without atypia. We also included 10 cases of fibroadenoma. All cases had histological follow-up available for correlation. Immunostaining for CK5/6 and p63 was performed on the cell block material in all cases. The percentage of staining cells in the specimen was graded as 0 (0-10%), 1 (11-25%), 2 (26-50%), and 3 (>50%). There were 9/29 (31%) cases in the atypical group that were found to be malignant on resection, compared with 6/35 (17%) in the cases without atypia. In histologically proven malignant cases, CK5/6 was negative in 11/15 (73%) or showed 1+ stain in 2/15 (13%) cases. In benign breast lesions, CK5/6 stained more than 25% of cell proliferation in 44/49 (90%). p63 showed characteristic staining for single naked bipolar nuclei in the background of the specimen (not appreciated by CK5/6) in all fibroadenoma cases. In conclusion, CK5/6 may enhance the ability to differentiate between benign and malignant epithelial proliferations in breast FNABs. In fibroepithelial lesions, p63 may be more useful than CK5/6.     

Frozen section discrepancy in the evaluation of nonneoplastic central nervous system samples

Frozen section (FS) for intraoperative evaluation of central nervous system (CNS) lesions provides the neurosurgeon with a rapid preliminary pathologic diagnosis. Diagnosis of nonneoplastic lesions is particularly challenging in this venue. To highlight common diagnostic pitfalls, we sought to identify discrepancies between FS and final diagnoses among nonneoplastic CNS samples via a retrospective review of 303 FS cases encountered from 1997 to 2006. Thirty-nine (12.9%) discrepant diagnoses were identified, of which 27 were clinically suspected tumors. Final diagnoses in the discrepant group included the following: inflammatory lesions (n = 8, 20.5%), malformation of cortical development-cortical dysplasia (n = 5, 12.8%), gliosis (n = 5, 12.8%), vascular malformations (n = 5, 12.8%), demyelination/progressive multifocal leukoencephalopathy (n = 3, 7.7%), infarct (n = 3, 7.7%), hemorrhage/blood clot (n = 3, 7.7%), and no pathologic changes (n = 3, 7.7%). The remaining 4 (10.2%) discrepant cases involved one case each of amyloid angiopathy, nonspecific vasculopathy, vasculitis, and meningioangiomatosis. Nonneoplastic lesions are often more challenging than neoplastic lesions at FS, particularly because they are less commonly sampled for FS and, therefore, less familiar to pathologists.     

Cytology of low-grade endocrine neoplasms involving liver: a series of 24 specimens, including 4 with hepatoid or glandular features

Low-grade endocrine neoplasms (LGENs) involving the liver usually show typical endocrine features. Occasionally these tumors display cytologic characteristics that mimic hepatocellular carcinoma (HCC) or adenocarcinoma (ACA). Twenty-four liver FNABs from 22 patients were reviewed. Twenty specimens showed cytologic characteristics typical of LGENs, including small to medium-sized cells with salt-and-pepper or granular chromatin, moderate to high N/C ratios, and inconspicuous or absent nucleoli. Plasmacytoid cells were observed in 19 cases. Immunocytochemical stains (ICCs) confirmed endocrine differentiation in 9 cases. 4 FNABs were comprised of larger tumor cells that displayed cytologic features that overlapped with HCC or ACA, including transgressing or wrapping endothelium, moderate to abundant cytoplasm, and conspicuous nucleoli. LGENs involving the liver typically demonstrate characteristic cytologic features. Cases comprised of larger cells with abundant cytoplasm, conspicuous nucleoli, and transgressing or wrapping endothelium may pose diagnostic difficulties. ICCs and plasmacytoid morphology are beneficial in classifying the endocrine origin of these tumors.     

Subgrouping and grading of soft-tissue sarcomas by fine-needle aspiration cytology: a histopathologic correlation study

To evaluate the accuracy and reproducibility of subgrouping and grading soft-tissue sarcomas by fine-needle aspiration biopsy (FNAB), a blind review was conducted of 84 FNAB specimens from 77 malignant and 7 benign soft-tissue lesions. Cytomorphologic subgroups included 31 spindle-cell, 24 pleomorphic, 11 myxoid, 7 epithelioid/polygonal, 3 small round cell, and 8 nondiagnostic cases. Malignancies included one lymphoma and 41 primary, 15 recurrent, and 20 metastatic soft-tissue sarcomas. Adequacy was defined as a majority of slides with at least 5 clusters of 10 unobscured cells. Five originally false-negative cases were considered nondiagnostic on review. Sarcoma was recognized in 59 of 64 adequate cases (92%) with available histology; however, the specific histopathologic subtype was identified in only 9 cases (14%). Benign myxoid and spindle-cell lesions were difficult to separate from low-grade sarcomas in 4 cases, and a B-cell lymphoma with sclerosis mimicked a low-grade myxoid sarcoma. The assigned cytologic grade accurately reflected the histologic grade in 90% of sarcomas when segregated into high and low grades. Pleomorphic, small round cell, and epithelioid/polygonal subgroups corresponded to high-grade sarcomas in all cases with only minor noncorrelations. Major grading noncorrelations occurred in 50% of myxoid and 9% of spindle-cell sarcomas. Therefore, attention should be given to specimen adequacy, and caution should be exercised when attempting to grade myxoid and spindle-cell sarcomas by FNAB.     

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.     

Fine-needle aspiration biopsy of liver masses: diagnostic value and reproducibility of cytological criteria.

There are many helpful cytological criteria for the diagnosis of liver fine-needle aspiration biopsies (FNABs), but none of them are pathognomonic of primary or metastatic tumors. We analyzed the diagnostic value and reproducibility of 28 cytological parameters in FNABs from 140 hepatic masses, including 29 benign lesions, 49 hepatocellular carcinomas (HCCs), and 62 metastatic tumors, encompassing 48 adenocarcinomas (ACAs). Five different observers evaluated each sample, and the interobserver and intraobserver agreement was studied. Multivariable analysis showed that the criteria more closely associated with malignancy were irregular nuclear contour, three-dimensional cell groups, and atypical naked nuclei. Capillaries separating tumor cells and granular cytoplasm were strongly associated with HCCs, while eccentrically placed nuclei and necrosis were most commonly seen in ACAs and in metastatic tumors. The intraobserver and interobserver agreement was excellent for the final cytological diagnosis, and there was fair to very good interobserver agreement for 22 of the 28 criteria studied. Architectural features were less reproducible than pure cytological criteria. Intraobserver variability was not influenced by the years of experience in the field. A precise and strict definition of terminology rendered a better reproducibility of the cytological criteria.     

Granulomatous myositis. Clinicopathologic study of 12 cases.

Granulomatous inflammation is infrequently encountered in skeletal muscle biopsy material. Of 2,985 muscle biopsy specimens reviewed over 12 years, 12 (0.4%) with granulomatous inflammation were identified. The patients included 9 women who ranged in age from 24 to 76 years (mean 50.3 years). The most common clinical findings included decreased strength or weakness in the extremities (n = 8), muscle pain (n = 5), and weight loss (n = 3). All muscles exhibited nonnecrotizing granulomas; an associated vasculitic process was identified in 2. Endomysial chronic inflammation consisting primarily of lymphocytes and plasma cells was present in 10 muscles, and perivascular chronic inflammation in 8. Degenerating muscle fibers were noted in 10 cases, and regenerating fibers in 11. Evidence of neurogenic atrophy was seen in 8 muscles. Increased endomysial fibrosis was observed in 5 muscles, and type II muscle fiber atrophy in 5 muscles. Stains for acid-fast bacilli and Gomori methenamine silver stain were performed in all but 2 cases and failed to demonstrate organisms. In 3 cases, concomitant sural nerve biopsies were performed, and granulomas were identified in 2 of those cases. Clinicopathologic diagnoses included sarcoidosis (n = 6), vasculitis (n = 2), and granulomatous myositis not otherwise specified (n = 2). In 2 cases, there was insufficient clinical information or follow-up data to determine a cause. In conclusion, granulomatous myositis is infrequently found in muscle biopsy specimens (0.5% of all biopsies in this series); most muscles demonstrate evidence of chronic endomysial or perivascular inflammation accompanied by muscle fiber degeneration and regeneration; and the most common cause for granulomatous myositis was sarcoidosis in this series.     

Comparison of cytological results obtained by repeated US‐guided fine‐needle aspiration biopsies of thyroid nodules: Focus on the rate of malignancy and diagnostic concordance

The debate still continues on the repeated fine‐needle aspiration biopsies (FNABs) for thyroid nodule in clinical practice. In this study, we determined the rate of cytological change to malignancy and the diagnostic concordance of repeated FNABs when the same nodules were targeted under US‐guidance. We retrospectively reviewed data for 187 thyroid nodules (173: twice, 14: three times) from 160 patients who underwent repeated US‐guided FNABs, which were performed by one skilful radiologist targeting for the same nodules at a mean interval of 7.5 months. Their initial cytological findings were compared with second or third results and histopathologic follow‐up. The initial FNABs findings of 187 nodules were unsatisfactory, benign, and indeterminate in 56, 52, and 79 cases, respectively. The rate of a second cytological diagnosis changed to malignancy was significantly higher in the unsatisfactory aspirates (10.7%; 6/56), when compared with those of the benign (0.0%; 0/52) or of indeterminate aspirates (3.8%; 3/79) (P = 0.022). However, there was no change to malignancy at third cytological findings of all 14 nodules. After the second US‐guided FNABs, 30.8% (16/52) of the initially diagnosed as benign aspirates were reclassified as indeterminate, while 26.6% (21/79) of the initially diagnosed as indeterminate were reclassified as benign. In conclusion, to identify malignancies, repeated US‐guided FNABs are recommended for thyroid nodules initially classified as unsatisfactory aspirates. However, although US‐guidance is applied, a discrepancy might be unavoidable in the cytological interpretation of the nodules classified as benign or as indeterminate aspirates because of overlapping cytological criteria. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Fine-needle aspiration of spindle cell and mesenchymal lesions of the salivary glands

Fine-needle aspiration (FNA) biopsy can accurately diagnose epithelial lesions of the salivary gland. Its role in the evaluation of salivary gland lesions containing a significant spindle cell component is less clear. We describe the cytologic features of 25 spindle cell lesions of the salivary gland and discuss the differential diagnosis and potential diagnostic pitfalls. Twenty-five aspiration smears (3.0%) containing a significant spindle cell or mesenchymal component were identified out of 844 salivary gland FNAs performed over a 5-year period. These aspiration smears were from 25 patients. The smears were classified into three categories: 1) reactive or inflammatory conditions, including one granulation tissue and four granulomatous sialoadenitis; 2) benign neoplasms, including one schwannoma, one fibromatosis, four lipomas, and nine pleomorphic adenomas; 3) malignant neoplasms, including one recurrent malignant fibrous histiocytoma (MFH), two metastatic melanomas, and two metastatic osteosarcomas. There was one false-negative biopsy. The metastatic desmoplastic malignant melanoma was initially interpreted as a reactive lymph node with fibrosis. A specific diagnosis was rendered in 21 (84%) cases. The schwannoma was diagnosed cytologically as benign spindle cell lesion, not otherwise specified (NOS), fibromatosis as an atypical cellular proliferation, and MFH as poorly differentiated malignant neoplasm. Salivary gland lesions with a significant spindle cell component are rarely encountered on FNA and constitute a heterogeneous group. A specific diagnosis can be rendered in the majority of cases by correlating clinical and cytologic findings.