Diagnostic pitfalls in fine-needle aspiration cytology of temporomandibular chondroblastoma: report of two cases.

Chondroblastoma is a benign bone neoplasm, which usually presents in the epiphysis of long bones, but can occur in unusual locations. This report describes the clinical, radiologic, and cytologic features on FNA of two chondroblastomas of the temporomandibular region that were only recognized by histopathologic study. This emphasizes the diagnostic pitfalls of this entity and expands the cytologic differential diagnosis of tumors of the parotid region.

Fine-needle aspiration biopsy of nonpalpable breast lesions in a multicenter clinical trial: results from the radiologic diagnostic oncology group V.

PURPOSE: To determine the diagnostic accuracy of ultrasonographically (US) and stereotactically guided fine-needle aspiration biopsy (FNAB) in the diagnosis of nonpalpable breast lesions. MATERIALS AND METHODS: At 18 institutions, 442 women who underwent 22-25-gauge imaging-guided FNAB were enrolled. Definitive surgical, core-needle biopsy, and/or follow-up information was available for 423 (95.7%) of these women. The reference standard was established from additional clinical and imaging information for an additional six (1.4%) women who did not undergo further histopathologic evaluation. The FNAB protocol was standardized at all institutions, and all specimens were reread by one of two expert cytopathologists. RESULTS: When insufficient samples were included in the analysis and classified as positive, the sensitivity and specificity of FNAB were 85%-88% and 55.6%-90.5%, respectively; accuracy ranged from 62.2% to 89.2%. The diagnostic accuracy of FNAB was significantly better for detection of masses than for detection of calcifications (67.3% vs. 53.8%, P =.006) and with US guidance than with stereotactic guidance (77.2% vs. 58.9%; P =.002). CONCLUSION: FNAB of nonpalpable breast lesions has limited value given the high insufficient sample rate and greater diagnostic accuracy of other interventions, including core-needle biopsy and needle-localized open surgical biopsy.

Soft tissue aspiration cytopathology of malignant lymphoma and leukemia.

BACKGROUND: Malignant lymphoma (ML) and leukemia infrequently involve soft tissue and, to the authors' knowledge few reports exist regarding the role of fine-needle aspiration biopsy (FNAB) in their diagnosis. In the current study, the authors report their experience with FNAB in patients with soft tissue ML and leukemia. METHODS: All cases of ML, leukemia, or atypical lymphoid cells from soft tissue aspirates were reviewed. Masses from lymph node-rich sites, those adjacent to enlarged lymph nodes, or those associated with cutaneous lesions were excluded. RESULTS: Twenty-one patients (male:female ratio of 1:1) who ranged in age from 10 months to 87 years (mean age, 51 years) were studied. Seven patients had superficial masses and 14 patients had deep soft tissue masses. Sites included the extremities (10 patients), trunk (8 patients), and head (3 patients). Cytologic diagnoses were ML (large cell [11 patients] and Hodgkin [1 patient]), acute leukemia (lymphoblastic [3 patients] and myelogenous [2 patients]), and atypical lymphoid cells (4 patients). Eight aspirates represented the initial diagnosis of ML, three were recurrent ML, four were recurrent leukemia, one was initial leukemia, and one ML aspirate was obtained concurrently with core needle biopsy. Four aspirates were diagnosed as atypical lymphoid cells. Three subsequently were diagnosed as ML and one aspirate was diagnosed as acute leukemia. All ML were of large B-cell type. One case of atypical lymphoid cells was found to be a mantle cell lymphoma. The leukemia cases were T-cell (two cases), pre-B-cell (two cases), and myelogenous (two cases). Immunophenotyping confirmed the cytology by flow cytometry (five cases), cytospin (three cases), and cell block (four cases). Immunophenotyping of eight cases was performed on tissue samples. In one case a cytopathologic diagnosis of ML reversed a prior tissue core biopsy diagnosis of liposarcoma. The specificity and sensitivity rates for a definitive diagnosis of ML or leukemia were 100% and 82%, respectively. CONCLUSIONS: In the majority of cases, it is possible to determine a specific diagnosis and subtype of soft tissue ML or leukemia using FNAB. Cancer (Cancer Cytopathol)

Competency assessment and proficiency testing.

Competency assessment is an ongoing, continuous process of monitoring individuals' abilities to perform their specific job functions. A variety of methods are useful in monitoring cytology competency, including rescreening studies, descriptive monitors (abnormality rates), discrepancy rates, workload patterns, competency-based educational programs and programs using unknown slide challenges. The goal of proficiency testing (PT) is to ascertain and assess the ability of individuals beyond the particular items or challenges presented. However, cytology PT faces many challenges for implementation as it cannot duplicate normal working conditions, and there is often no gold standard to define the truth. PT is just one measure of performance and should be considered in conjunction with other quality assessment monitors. There is no consensus on the value or validity of a large-scale regulatory PT program. Any regulatory PT program should be field tested prior to implementation, and the grading system should be scientifically defensible. Scoring of performance on PT should occur in a timely fashion, and there should be an opportunity for educational feedback. The ultimate aim of both competency assessment and PT is to positively affect laboratory procedures and improve the cervical cancer screening process.

Aspiration cytopathology of epithelioid angiosarcoma.

BACKGROUND: Epithelioid angiosarcoma (EA) is an uncommon neoplasm readily mistaken for carcinoma. In contrast to the histopathology of this tumor, the cytopathology as obtained using fine-needle aspiration (FNA) biopsy has rarely been described. METHODS: Three patients with histologically and immunohistochemically proven EA each underwent FNA using standard technique before surgical resection. RESULTS: Aspirate smears were obtained from 3 males (ages 47, 63, and 15 years) each of whom presented with a solitary palpable soft tissue mass, 1 from the left calf and 2 from the right popliteal region. No patient had a history of malignancy or had been exposed to prior radiation therapy. Smears were relatively hypocellular due to the dilutional effects of abundant blood. Cells were scattered on slides primarily in a single cell dissociated pattern; small aggregates were present in a fraction of the slides. Malignant cells generally monotonous in size and averaging three to four times the dimension of a mature lymphocyte had a rounded so-called epithelioid configuration. Cells possessed primarily rounded, single nuclei often eccentrically placed, with some anisokaryosis, and smooth nuclear borders. Binucleated cells with mirror-image nuclei were much less frequent, and cells with three or four nuclei were even more scarce. Cells contained large single nucleoli or more often multiple misshapen smaller nucleoli. Cytoplasm was abundant and finely granular in virtually all cells. In some, the cytoplasm acquired a central spheric density thus producing a "rhabdoid" appearance that was only seen with air-dried Diff-Quik (Fisher Scientific, Biochemical Sciences, Inc., Swedesboro, NJ) stained smears. Mitoses were readily found. Immunostaining of the cell block in one case permitted a specific diagnosis of EA before subsequent surgical excision. CONCLUSIONS: Epithelioid angiosarcoma may display a rhabdoid morphology in FNA biopsy smears, and this cytopathology can closely mimic that of nonsmall carcinoma, malignant melanoma, and other epithelioid types of soft tissue tumors. Immunophenotyping is essential for definitive diagnosis. Cancer (Cancer Cytopathol)

Cytologic findings from a nipple discharge in an infant with premature telarche.

Premature telarche is a condition of isolated unilateral or bilateral breast development without additional signs of sexual maturation in girls primarily under 2 yr of age presumably occurring as a response to hormonal stimulation by estrogens. Prior reports concerning pathologic findings in premature telarche have been scarce. We report the cytologic findings from a nipple discharge in a 10-mo-old girl with unilateral breast enlargement due to premature telarche. The discharge showed an increased number of clusters of breast ductal epithelium, with a few in a papillary configuration. There was a moderate degree of nuclear irregularity in the epithelial cells, but no significant nuclear overlapping. No atypical single cells were present, and a rare myoepithelial cell was noted. These cytologic findings are in accord with a prior study describing the histology in three cases of premature telarche.

Interobserver variability in the classification of proliferative breast lesions by fine-needle aspiration: results of the Papanicolaou Society of Cytopathology Study.

This study evaluates the applicability of the published cytologic criteria in the categorization of proliferative breast lesions by assessing the diagnostic accuracy and interobserver reproducibility of a panel of experts. Twelve breast fine-needle aspiration (FNA) specimens of biopsy-proven nonproliferative breast lesion (NPL) (1 case), proliferative lesions without atypia (PL) (7 cases), proliferative lesion with atypia (PLA) (1 case), and low-nuclear grade ductal carcinoma in situ (DCIS) (3 cases) were selected. Six FNAs were Papanicolaou (PAP) and 6 were Diff-Quik-stained (DQ). Six expert cytopathologists classified the smears using a summary of published criteria as a guideline. All 6 participants rendered the same cytologic diagnosis in 2/12 (16%) cases. The agreement among the 6 raters was low (Kappa = 0.35). Cytohistologic correlation was achieved in 26/72 (36%) FNA diagnoses. The correlation of the PAP-stained cases was better than the DQ: 17/36 (47%) PAP and 9/36 (25%) DQ correlated. Improving the correlation was achieved by amalgamation of NPL and PL into "low risk" and PLA and DCIS into "high risk" categories: 47/72 (65%) FNA diagnoses then correlated with histology [29/36 (81%) PAP and 18/36 (50%) DQ]. We conclude that the cytologic criteria of proliferative breast lesions need to be further defined and assessed. Consideration should be given to minimizing the number of diagnostic categories and adopting a terminology that has a direct effect on patient management.

Rate of insufficient samples for fine-needle aspiration for nonpalpable breast lesions in a multicenter clinical trial: The Radiologic Diagnostic Oncology Group 5 Study. The RDOG5 investigators.

BACKGROUND: Radiologic Diagnostic Oncology Group 5 is a multicenter clinical trial designed to evaluate fine-needle aspiration (FNA) of nonpalpable breast lesions performed by multiple operators using the same protocol. METHODS: Four hundred and nineteen women with mammographically detected nonpalpable breast lesions were enrolled on the trial at 18 institutions. Group A institutions randomized women to stereotactically guided FNA (SFNA) followed by stereotactically guided core needle biopsy (SCNB), or SCNB only. Group B institutions randomized women to SFNA and SCNB, SCNB, or ultrasonographically guided FNA followed by ultrasonographically guided core needle biopsy (USCNB), or USCNB only. A total of 377 women were eligible for analysis. RESULTS: FNA yielded 128 insufficient samples for the 377 patients (33.95%; 95% confidence interval, 29.2-38.7%). The rate of insufficient samples varied by type of lesion with calcified lesions associated with a significantly higher rate of insufficient sampling than masses (P < 0.001). The radiologist's level of suspicion of the lesion was not a statistically significant predictor of insufficient samples for mass lesions, but was a predictor for calcified lesions. For the 336 lesions for which histologic information was available, insufficient samples occurred in significantly more benign than malignant lesions. CONCLUSIONS: The high rate of insufficient samples for FNA of nonpalpable breast lesions in this multicenter trial makes its use impractical in this setting. Because of this factor, the study was terminated early.

ASCUS and AGUS criteria. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses. CONSENSUS POSITION: Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category. Regardless of the term utilized, an equivocal diagnosis should be qualified in some manner to indicate that the diagnosis defines a patient at increased risk of a lesion, particularly for those cases which raise concern about a possible high grade lesion. Qualification of an equivocal diagnosis can also be accomplished by appending laboratory statistics of the likelihood of various clinical outcomes or recommendations for patient follow-up. In contrast to favoring a reactive process versus squamous intraepithelial lesion (SIL), a more rationale approach to qualification of atypical squamous cells of undetermined significance may be to separate cases equivocal for low grade SIL from those suspicious for high grade SIL. With regard to glandular lesions, the conference participants expressed unanimous support for the separation of adenocarcinoma in situ (AIS) from atypical endocervical cells of undetermined significance when sufficient criteria are present. However, the diagnosis of a precursor lesion to AIS, endocervical glandular dysplasia, was controversial. The majority of conference participants discourage the use of such terms as mild glandular dysplasia and low grade glandular dysplasia for cytologic diagnoses. ONGOING ISSUES: Conference participants agreed that a term reflecting diagnostic uncertainty is necessary to communicate findings that are equivocal. However, participants could not agree on the wording of such a term. Opinions differed as to: (1) use of atypical, abnormal or morphologic changes to describe cell changes, (2) whether the diagnosis should indicate a squamous or glandular origin of the cells in question when this determination can be made, and (3) the value of defining morphologic criteria for such a diagnosis. The debate over terminology, as well as morphologic criteria, is ongoing, and the readership is invited to communicate opinions to Acta Cytologica. Management of women with equivocal diagnoses varies widely from locale to locale and may differ based on how the equivocal diagnosis is qualified. Findings insufficient for the diagnosis of a high grade lesion may warrant more aggressive follow-up than cases equivocal for a low grade lesion. Where sensitivity of detection of lesions is of paramount importance, follow-up will generally consist of more frequent cytology screening or colposcopy and biopsy. However, in some countries it is considered unethical to have a high percentage of false positive diagnoses, which result in overtreatment and an unnecessary burden for women participating in cervical screening. Future studies may provide a morphologic, or perhaps molecular, basis for distinguishing true precursors of neoplasia from minor lesions of no significant clinical import; this would allow a more coherent and rational approach to diagnosis and management of women with equivocal cytologic findings.

Medicolegal affairs. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

ISSUES: Increasing litigation over alleged false negative cervical cytologic (CC) smears threatens the viability of this test for cervical cancer detection. The problem appears to be largely American but is beginning to appear in some other countries. In the vast majority of cases there is either a settlement or jury verdict for the plaintiff based largely on the testimony of expert witnesses. Cases are judged on an individual basis without significant consideration of the general performance of the CC smear in laboratories operating in compliance with a wide array of laboratory regulations and with documented and comprehensive quality control practices in place. It is acknowledged that there are problem laboratories and cytology practitioners. There is an emerging issue of automated preparation and screening devices and issues of informed patient consent. CONSENSUS POSITION: Cytology professionals have done an extraordinary and commendable job of educating the public about the benefits of the CC smear. We have been less successful and conscientious about explaining and defining the limitations of the CC test. There is a need for public and professional education as to the benefits and limitations of the CC smear for cervical cancer detection. The process suggested is to work with women's groups, public health agencies, government agencies, and state and national legislatures and to coordinate professional committees working on liability issues. Contextual information could be included with the CC smear report to indicate that a negative report confers a low probability of developing cervical cancer. It is suggested that appropriate language and a menu of statements be developed. Increased efforts should be directed to physician education with respect to informed consent concerning the benefits and limitations of CC smear testing and the application of new technology to improve smear accuracy. The process should include development of appropriate statements on the use of alternative technology. The profession should develop "process guidelines" for review of CC smears in the context of possible litigation, including standardized methods for blind slide review of smears that reduce or eliminate context and outcome bias. It is suggested that review panels be anonymous, that the process be standardized and that there be limitations on liability for participating organizations. Professional cytopathology and pathology societies should formulate acceptable guidelines for expert witnesses. The standards should be applicable to both defendant and plaintiff experts. All materials to the extent practical, including consultant opinions, should be available for peer review. Professional cytopathology and pathology societies should monitor expert testimony for objectivity and scientific accuracy. ONGOING ISSUES: For the near future, litigation will continue to focus on false negative CC smears on a case-by-case basis. Laboratories and individuals can reduce the risk of malpractice liability by directing their attention to proactive quality control and quality assurance methods. In the final analysis, consumer education about the benefits and limitations of the test is key to limiting malpractice claims. To stem the tide of continued medicolegal challenges to the integrity of cytology practice, the cytology community has now focused its efforts on developing and utilizing standards that convey to patients, attorneys and cytologists the contemporary status of and reasonable expectations for the practice of cytology. Guidelines such as those for uniform reporting terminology and clinical management of cervical abnormalities form the basis of cytology practice standards on which legal standards of practice can be based. Consensus conference reports, clinical management trials and scientifically valid studies of false negative rates that analyze the type, frequency and cause of missed cases represent sounder methods of establishing defensible

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.

Fine-needle aspiration cytopathology of malignant fibrous histiocytoma.

BACKGROUND: Most pathologists generally accept malignant fibrous histiocytoma (MFH) as the most common soft tissue sarcoma in adults. This study examines the authors' aspiration cytopathology experience with this tumor, describes its cytomorphology, and determines the reliability of such a diagnosis by fine-needle aspiration biopsy (FNAB). METHODS: The authors' files were reviewed for cases diagnosed as MFH by FNAB, and for surgical pathology cases of MFH previously aspirated but not diagnosed as such by cytology. RESULTS: Fifty-two cases of MFH (by FNAB or histology) were recovered from the combined files; 42 aspirates had tissue confirmation. Patient age ranged from 15-88 years (mean, 63 years); the male:female ratio was 1.2. Thirty aspirates were from primary tumors, and 12 were from recurrences or metastases. From the 29 aspirates diagnosed as MFH, 24 (83%) were determined to be MFH on subsequent surgical excision. Four of the remaining cases were other sarcoma subtypes, and there was one organizing thrombus (false-positive). The remaining 13 aspirates were identified as unqualified sarcoma (11 cases) or a different sarcoma subtype (2 cases). Eleven of these were histologically diagnosed as MFH, and 2 as other sarcomas. No single cytologic feature or combination of features distinguished MFH. Patterns ranged from single cells to large storiform fragments. Spindled, plasmacytoid, and pleomorphic cell shapes were found; pleomorphic cells were often multinucleated. All cases of MFH had malignant nuclear morphology. Diagnostic pitfalls included low cellularity, obscuring blood and inflammation, and inadequate clinical and/or radiologic information. CONCLUSIONS: The diagnostic role of FNAB in soft tissue lesions remains controversial. FNAB is important in the initial triage of patients with soft tissue tumors, and is particularly accurate for confirming recurrent or metastatic disease. Although making an initial diagnosis of sarcoma by FNAB is reliable, specific subtyping of them as MFH is more problematic.

Diagnostic pitfalls in fine-needle aspiration biopsy of the mediastinum.

A retrospective review of 189 fine-needle aspiration (FNA) biopsies of the mediastinum from four university medical centers was performed. Review of Diff-Quick- and Papanicolaou-stained direct smears was performed from a series of 189 FNA biopsies along with surgical pathology correlation obtained in 42% of the cases. There were 28 (14.8%) nondiagnostic or unsatisfactory for diagnosis cases. Of the satisfactory FNA specimens with histologic correlation, 12 cases (6%) were discordant. These errors primarily involve subclassification of small-cell malignancies involving the mediastinum, including a misdiagnosis of small-cell carcinoma for lymphoma. Large-cell lesions that were problematic included the accurate diagnosis of Hodgkin's lymphoma including the separation from non-Hodgkin's lymphoma. Large-cell lymphoma with sclerosis was misinterpreted in two cases due to distortion of cells by the mesenchymal tissue and sparsely cellular smears. In two cases classification of primary germ-cell tumors and separation from metastatic carcinoma was a problem. In general, FNA of the mediastinum is an accurate procedure, but can be challenging in a minority of cases due to sparse cellularity of the lesions and accurate classification of a variety of neoplasms that occur in this region. These 12 discordant cases serve as the basis of our report.

Primary lymphoma of the endometrium. A report of two cases diagnosed on cervicovaginal smears.

BACKGROUND: Primary lymphomas of the endometrium are extremely rare. Diagnosis is difficult, especially when the neoplasm is originally evaluated on a cervicovaginal smear. When lymphomas involve the endometrium, the cervix is three times more likely to be the primary site rather than the endometrium. Two of the symptoms of primary lymphoma of the endometrium are abnormal vaginal bleeding and an abdominal or pelvic mass. CASES: Case 1 was a 36-year-old, obese, black female with an abdominal mass and recent onset of ascites. The second case was a 31-year-old, obese, black female with a history of menometrorrhagia. The cytologic findings in both cases revealed an individual cell population, high nuclear/cytoplasmic ratio, small nucleoli and coarsely granular chromatin with some chromatin clearing. Endometrial currettings showed a histologic pattern of malignant non-Hodgkin's lymphoma, diffuse, large cell type. Immunoperoxidase staining was positive for leukocyte common antigen. CONCLUSION: Two cases of lymphoma of the endometrium were diagnosed first by a cervical cytologic smear, supported by a positive body cavity fluid in one case and histology in both. The differential diagnoses included various inflammatory lesions, small cell carcinoma, endometrial stromal sarcoma and granulocytic sarcoma.