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Background Diagnostic evaluation of thyroid nodules by FNA is used in the clinical management triage based on the knowledge of the rate of malignancy of each diagnostic category. The Bethesda System for Reporting Thyroid Cytopathology was published in 2007 by the National Cancer Institute (NCI). Using this classification, we studied our institution's experience in the pediatric population calculating the rate of malignancy for each diagnostic category, comparing our findings to our general patient population and that of the literature. Methods 13,312 thyroid FNAs were performed at our institution between 1998 and 2010. 282 cases were from patients under 19 years of age. We reviewed and reclassified these cases using the new NCI categories, and pursued cytology-surgical follow-up. Results Of the 282 FNA cases, 20.92% (59) were classified as unsatisfactory (U), 48.22, % (136) benign (B), 2.12% (6) Atypia of undetermined significance (AUS), 14.18% (40) suspicious for follicular neoplasm (FN), 2.12% (6) suspicious for malignancy (SM) and 12.41% (35) positive for malignancy (P). The U-category was further classified into nondiagnostic (ND) 12.41% (35) and cysts (C) 8.51% (24). Seventy-four children had surgical follow-up. The rates of histologically confirmed malignancy were 10% in U (1/10), 0% in B (0/17), 50% in AUS (2/4), 39% in FN (7/18), 100% in SM (4/4) and 100% in P (24/24) categories respectively. Among the U category, malignancy rate was 0% for the ND category and 25% for the C category. Conclusions To our knowledge, this is the first study to apply the NCI categories to the pediatric population. The rate of malignancy in the U category was only seen in the specimens with cystic component. AUS and FN categories had a higher malignancy rate (50 and 39% respectively) as compared with that of the general population (15 and 30% respectively). Given that the rates of malignancy are higher for cysts and AUS, the literature recommendation to “follow-up and repeat” may not apply to the pediatric population. Surgery may be reasonable in these categories instead. Diagn. Cytopathol. 2015;43:598-604. © 2015 Wiley Periodicals, Inc.

The Accreditation Council for Graduate Medical Education (ACGME) is responsible for oversight of pathology residency and fellowship organizations in the United States. Residents must have successfully completed their training in an ACGME-accredited or Royal College of Physicians and Surgeons of Canada-accredited residency to be eligible to take the American Board of Pathology (ABP) examinations. For subspecialties like cytopathology, only ACGME-accredited fellowships are accepted. The ACGME is undergoing major restructuring with a shift to continuous accreditation and outcomes assessment, the “Next Accreditation System” (NAS). With the NAS, site visits will be extended to 10 years for those individual pathology and fellowship programs that are performing well. The episodic “biopsy” model for accredited programs will be replaced by annual data collection, and program information forms will be replaced by self-studies. Each ACGME review committee will monitor the program data and trends and will determine whether the program needs to submit additional data or take action. The annual data will include resident and faculty surveys, case log information, scholarly activity, and educational milestones data. The Milestones project is the keystone of the NAS, requiring discernible developmental stages in attaining proficiency at established times during training. The educational milestones are based on the six ACGME competencies, planned in a systematically progressive framework. Milestones for the pathology resident are now posted in draft form on the ACGME website, and those for cytopathology fellows are in draft form but not published at this time. Each milestone is arranged in numbered levels, with level 1 representing most fellows at the beginning of training, level 4 representing the graduating fellow target, and level 5 being aspirational or representative of a cytopathologist in practice several years. The fellow interpretive and diagnostic knowledge milestones at level 4 will most likely be worded to state that fellows accurately diagnose most cytology samples. The ACGME revised program requirements for cytopathology that are effective July 1, 2013 specifically state that cytopathology fellows must demonstrate diagnostic proficiency and that they must demonstrate competence in the application of additional diagnostic adjuncts, including molecular testing. Fellows must evaluate at least

BACKGROUND: Atypia of undetermined significance is a controversial category in thyroid fine-needle aspiration (FNA), not only for its questioned clinical utility, but also for its very existence as an expression of uncertainty. The current study was performed to investigate the potential impact of eliminating this category on the sensitivity and specificity for detecting thyroid neoplasms by FNA. METHODS: Forty cases originally diagnosed as atypia of undetermined significance with histologic follow-up were selected for the present study. These cases were reinterpreted blindly by 2 experienced reviewers, who eliminated atypia of undetermined significance as a diagnostic possibility and reclassified these cases as either benign, follicular neoplasm, suspicious for malignancy, or malignant. Twenty-six cases of atypia of undetermined significance were randomly selected and reevaluated 6 months later to study intraobserver variation. RESULTS: After eliminating the atypia of undetermined significance category, the sensitivity for detecting papillary thyroid carcinoma (PTC) was reduced from 100% to 27% (P = .04). In those atypia of undetermined significance cases that were reclassified as benign, 37% had PTC. In those reclassified as follicular neoplasm or suspicious for malignancy, 38% were histologically proven to be benign lesions. Unanimous interobserver and intraobserver agreement was observed in only 60% of cases. CONCLUSIONS: Eliminating the diagnosis of atypia of undetermined significance substantially decreases the sensitivity of thyroid FNAs and increases both false-positive and false-negative rates. In addition, it increases interobserver and intraobserver variability. Therefore, the atypia of undetermined significance category should not be eliminated; but we advocate minimizing its use. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

Renal Fine Needle Aspiration Cytology (FNAC) has gained popularity due to increasing options in management of renal lesions such as energy ablation and active surveillance. The diagnostic yield of renal FNAC varies between 40-90%. We hypothesized that adequate and diagnostic FNA samples would be associated with higher number of needle passes and higher number of slides examined.The pathology database at our institution was retrospectively searched for renal FNACs performed between 1995 and 2005. Patient gender, side, indication, cytological diagnosis, final histological diagnosis when available, number of needle passes performed, number of slides examined, and adequacy of the FNAC sample as determined by Diff Quik staining by the cytotechnologist (CS) were recorded. Chi square test was performed for statistical analysis.Out of 377 renal biopsies performed, 259 were core biopsies for medical renal disease, and 118 were FNACs for renal lesions, including 16 for indeterminate complex renal cysts and 102 for solid renal masses. Indeterminate renal cysts were excluded from the study. Out of 102 FNACs for solid renal masses, 22 were inadequate with 13 (59%) being non-diagnostic; and 80 FNACs were adequate with 3 (4%) being non-diagnostic. The number of needle passes was not significantly different between non-diagnostic and diagnostic samples (2.5 vs 3.2); and between inadequate and adequate samples (3.4 vs 3.0). Similarly, the number of slides examined was not significantly different between non-diagnostic and diagnostic samples (9.5 vs 10.9); and between inadequate and adequate samples (11.3 vs 10.6). Diff Quik adequate samples had significantly higher diagnostic yields when compared to Diff Quik inadequate samples (965 vs 41%; p0.01).The number of needle passes and microscopic slides examined did not correlate with sample adequacy or diagnostic yield of renal FNAC. Sample adequacy as determined by Diff Quik staining correlated with diagnostic FNAC. Despite the retrospective nature of this study, a cytotechnologist should be present during the FNA procedure to ensure adequate samples have been obtained to increase the diagnostic yield of renal FNAC.

BACKGROUND. The Papanicolaou Society of Cytopathology recently proposed 6 diagnostic categories for the classification of thyroid fine-needle aspiration (FNA) cytology. Using these categories, the experience with FNA from 2 institutions was studied with emphasis on cytologic-histologic correlation, source of errors, and clinical management. METHODS. Patient cytology data were retrieved by a retrospective search of thyroid FNA in the institutional databases. Cytologic diagnoses were classified as unsatisfactory, benign, atypical cellular lesion (ACL), follicular neoplasm (FN), suspicious for malignancy, and positive for malignancy. Samples with a histologic discrepancy were re-evaluated, and clinical follow-up information was recorded. RESULTS. Of of 4703 FNA samples, 10.4% were classified as unsatisfactory, 64.6% were classified as benign, 3.2% were classified as ACL, 11.6% were classified as FN, 2.6% were classified as suspicious, and 7.6% were classified as malignant. Five hundred twelve patients had at least 1 repeat FNA, mainly for results in the unsatisfactory and ACL categories. One thousand fifty-two patients had surgical follow-up, including 14.9% of patients with unsatisfactory FNA results, 9.8% of patients with benign results, 40.6% of patients with ACL results, 63.1% of patients with FN results, 86.1% of patients with suspicious results, and 79.3% of patients with malignant results. The rates for histologically confirmed malignancy in these categories were 10.9%, 7.3%, 13.5%, 32.2%, 64.7%, and 98.6%, respectively. The cytologic-histologic diagnostic discrepancy rate was 15.3%. Sources of errors included diagnoses on inadequate specimens, sample errors, and overlapping cytologic features between hyperplastic nodules and follicular adenoma. The sensitivity and specificity of thyroid FNA for the diagnosis of malignancy were 94% and 98.5%, respectively. CONCLUSIONS. The current results indicated that FNA provides an accurate diagnosis of thyroid malignancy. The 6 diagnostic categories were beneficial for triaging patients for either clinical follow-up or surgical management. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.

Background Pulmonary adiaspiromycosis is a common disease of many species of wild rodents and occasionally of humans, caused by the inhalation of spores of the fungus Chrysosporium parvum var crescens (Emmonsia crescens). Case A 74-year-old female with pulmonary adiaspiromycosis was diagnosed by radiologically guided lung fine needle aspiration (FNA). The specimen showed intracellular and extracellular 100-300 microm conidia with a distinct thick, trilaminar wall, which was positive for Gomori-methenamine silver and periodic acid-Schiff stain. The background consisted of a granulomatous process. Conclusion FNA is an effective method of diagnosing pulmonary adiaspiromycosis, and pathologists need to be aware of the characteristic features of this unusual opportunistic fungal infection.

Thyroid fine-needle aspiration (FNA) is a standard procedure for the clinical triage of thyroid nodules. The diagnosis of an adequately sampled thyroid FNA is generally grouped into three categories: benign, malignant, and indeterminate. The latter group usually includes follicular neoplasm, follicular lesion, and sometimes a more specific diagnosis such as Hurthle cell neoplasm or follicular lesion/neoplasm with Hurthle cell change. Whether a FNA diagnosis of Hurthle cell lesion/neoplasm (HLN) denotes a worse clinical outcome than follicular lesion/neoplasm (FLN) remains controversial. A cohort of 303 thyroid FNA cases with follow-up thyroidectomy in our institutes was identified, with the follow-up excision diagnosis compared to the FNA diagnosis in order to address this issue. Of this cohort, 87 cases had an FNA diagnosis of HLN while 216 cases had a diagnosis of FLN. Upon excision, the FNA diagnosis of HLN group had 14 cases of goiter/nodular hyperplasia (16%), 46 cases of adenoma (12 follicular adenoma (14%) and 34 cases of Hurthle cell adenoma (39%)), and 27 cases of carcinoma (31%, 12 papillary carcinoma and 15 Hurthle cell carcinoma). The FLN group had 74 cases of goiter/nodular hyperplasia (34.3%), 8 cases of Hashimoto thyroiditis (3.7%), 73 cases of follicular adenoma (33.8%), one case of granular cell tumor, and 60 cases of carcinoma (27.8%, 46 papillary carcinoma, 12 follicular carcinoma, and 1 Hurthle cell carcinoma and 1 parathyroid carcinoma) upon excision. There is no significant difference in predicting cancer between the two cytology diagnosis groups (HLN versus FLN, 31% versus 27.8%, P = 0.5771). When sorting all the cases by the surgical diagnosis, while comparable for age at diagnosis, the cancer group having the higher proportion of male patients than the non-cancer group (28.7% versus 16.7%, P = 0.0259). Hurthle cell carcinoma patients are typically older than patients with other cancer diagnoses (59 versus 44, P = 0.0077). Our results suggest that an FNA diagnosis of HLN does not predict more malignancy than FLN. Males and older patients with a HLN FNA diagnosis carry a higher risk of Hurthle cell carcinoma upon thyroidectomy.

Langerhan’s cell histiocytosis (LCH) results from the proliferation of immunophenotypically and functionally immature, morphologically rounded Langerhan’s cells along with eosinophils, macrophages, lymphocytes, and, commonly, multinucleated giant cells. Here we report a case in a 6-year-old boy of differential diagnoses including dermatopathic lymphadenitis (DL), parasitic infection, Kimura’s disease, hypersensitivity reactions, cat-scratch disease, sinus histiocytosis with massive lymphadenopathy (SHML), hyperplasic lymph nodes, and lymphoma.

Objective To analyze the potential sources of diagnostic errors and overall accuracy rate of the fine needle aspiration biopsy (FNAB) diagnosis of cystic salivary gland neoplasms. Study design A 10-year (1993-2002) retrospective review of the cytopathology slides from the Division of Cytopathology, Department of Pathology, Long Island Jewish Medical Center, New Hyde Park, New York, identified a total of 97 consecutive salivary gland FNAB cases that microscopically were interpreted as representing cystic lesions. Of these, 21 cases had histologic follow-up at our institution. Results A correct diagnosis was rendered by FNAB in 15 of 21 (72%) cases. This included 9 Warthin's tumors, 2 mucoepidermoid carcinomas, 2 simple cysts, 1 cystadenoma and 1 abscess. Clinically insignificant discrepancies were identified in 3 of 21 (14%) FNABs. Clinically significant misdiagnoses were identified in a further 3 of 21 (14%) cases. Conclusion A systematic approach to the diagnosis of cystic salivary gland lesions by FNAB can result in a correct diagnosis in > 70% of cases. Careful attention should be directed at identifying the extracellular fluid components present (mucoid vs. watery proteinaceous) as well as the predominant cellular component (e.g., lymphocytes, histiocytes, epithelial cells and oncocytes). It is important to recognize, however, that occasionally epithelial cells may not be detected on FNAB of cystic salivary gland lesions, as a result of either cellular dilution by cystfluid or inadequate sampling. Regardless, with all FNABs tentatively diagnosed as a mucinous cystic lesion, the referring clinician should be informed that a low grade mucoepidermoid carcinoma cannot be ruled out.

BACKGROUND: Malignant rhabdoid tumor (MRT) of the kidney is a rare and aggressive neoplasm with a controversial histogenesis. Although their immunohistochemistry may be diverse, the rhabdoid phenotype and mutations of the INI1 gene are consistently exhibited by MRTs regardless of their location. CASE: MRT recurred in the contralateral kidney in a 12-month-old child within 6 months after the initial histologic diagnosis, nephrectomy and autologous stem cell transplant. The presence of widespread metastases at the time of the recurrence precluded any further chemical and surgical diagnostic or therapeutic intervention. CONCLUSION: To the best of our knowledge, only a few cases describing the cytologic diagnosis of MRT of the kidney in a child have been reported. This case illustrates the usefulness of cytologic diagnosis in an MRT recurrence.

To evaluate the combination of fine-needle aspiration (FNA) and flow cytometric immunophenotyping (FCI) in the diagnosis of lymphadenopathy in children, we reviewed a total of 71 FNA specimens from pediatric patients with persistent lymphadenopathy. Two cases were deemed inadequate. In the remaining 69 cases, 54 (78%) were diagnosed as benign lesions, 9 (13%) as Hodgkin's lymphoma, 4 (6%) as non-Hodgkin's lymphoma or leukemic infiltrate, and 2 as metastatic tumors. Of the 69 cases, 25 cases (38%) were diagnosed based on cytomorphology alone, 30 (43%) by combined cytomorphology and FCI, and 19 (28%) by surgical biopsy. In conclusion, FNA is an easy, safe, and reliable procedure in the diagnosis of lymphadenopathy in children. In difficult cases, FCI can be used to exclude non-Hodgkin's lymphomas.

This article discusses the paraganglion system and extra-adrenal paragangliomas. In particular, the clinicopathologic, immunohistochemical, and ultrastructural features of paragangliomas and neuroendocrine neoplasms of the larynx are presented with a discussion of the differential diagnosis.

Dermoid cysts of the oral cavity are rare. When they do occur, the most common site is the floor of the mouth. Intralingual dermoid cysts are even more rare, and until now, there were only 15 such reports in the English-language literature. In this article, we describe two additional cases. Magnetic resonance imaging is extremely helpful in establishing a differential diagnosis. Surgical excision is recommended to correct deglutition and speech problems. Its rarity notwithstanding, dermoid cyst should be considered in the differential diagnosis of tongue masses in the younger population.

BACKGROUND: Primary pulmonary artery sarcomas (PPASs) are uncommon neoplasms with a poor prognosis. They often present with symptoms of pulmonary thromboembolus. They may be locally aggressive and give rise to embolic pulmonary metastases. Extrathoracic metastases are uncommon. They are usually diagnosed late in the course of the disease or at autopsy. Radiographic studies alone are insufficient to definitively diagnose PPAS. CASE: A 68-year-old female presented with symptoms consistent with pulmonary thromboemboli. Computed tomography of the chest with intravenous contrast revealed an intraluminal filling defect involving the left main pulmonary artery. Despite anticoagulation therapy, the symptoms persisted. Four months after the initial presentation, the patient developed multiple nodules in the left lung. Fine needle aspiration (FNA) of one of the nodules showed loosely cohesive clusters of pleomorphic and spindle-shaped malignant cells and isolated ones. These cells were embedded in extracellular, metachromatic material. They were vimentin positive and keratin negative. There was no evidence of extrapulmonary disease. A diagnosis of metastatic pulmonary artery sarcoma was made and confirmed on histology. Three weeks following the pneumonectomy, the patient died of postoperative complications. CONCLUSION: Patients with PPAS often present with symptoms of atypical or nonresolving pulmonary thromboemboli. The interval between presentation and definitive diagnosis is usually delayed and probably affects the prognosis. The timely use of FNA techniques could result in an earlier diagnosis, possibly improving outcome.

BACKGROUND: We report the first case of a composite tumor (tall cell and columnar cell variants) of papillary thyroid carcinoma (PTC) diagnosed by fine needle aspiration. It is important to differentiate these uncommon aggressive variants from the usual indolent papillary carcinomas. CASE: Fine needle aspiration cytology was obtained from a rare composite tumor of tall cell and columnar cell variants of papillary thyroid carcinoma. The smears showed a cellular aspirate with scattered single tumor cells and several tissue fragments arranged in a papillary pattern. The tumor cells had abundant nuclear grooves and intranuclear pseudoinclusions. Several of the fragments showed columnar cells with nuclear pseudostratification, and a few clusters displayed tall columnar cells with basal nuclei and abundant cytoplasm. A rare cluster exhibited composite features of tall cell and columnar cell variants. CONCLUSION: Columnar cell and tall cell variants of PTC manifest aggressive clinical behavior. The differential diagnosis of columnar cell variant includes medullary carcinoma of thyroid and metastatic adenocarcinoma. Immunohistochemical stains for calcitonin and thyroglobulin play an important role in difficult cases. The tall cell variant needs to be differentiated from Hurthle cell papillary neoplasm of thyroid, which displays prominent nucleoli and lacks the characteristic nuclear features of PTC. The preoperative diagnosis of these aggressive variants is important in planning the most appropriate type of treatment.

Follicular cervicitis is usually easily identifiable on Papanicolaou (Pap) tests; however, historically, follicular cervicitis is reported to lead to false-positive diagnoses of epithelial cell abnormalities.To assess participant responses in the College of American Pathologists (CAP) Pap educational program (CAP-PAP) to determine the accuracy and false-positive rate of follicular cervicitis cases. Design.-We performed a retrospective review of 4914 participant responses for gynecologic cytology challenges with the reference diagnosis of follicular cervicitis during 11 years (2000-2010) from CAP-PAP. Reference diagnosis category, false-positive rates by participant type (laboratory, cytotechnologist, pathologist), and preparation type (conventional smears, ThinPrep) were analyzed.Of the total 4914 general category responses, 4368 (88.9%) were benign while 546 (11.1%) responses were epithelial cell abnormalities (false positives). Of benign responses, only 2026 (46.4%) were an exact match to follicular cervicitis. Adenocarcinoma and high-grade squamous intraepithelial lesion were the most common diagnoses chosen as a false-positive interpretation (42.3% and 20.1%, respectively). Participant type was significantly associated with false-positive interpretations (laboratory: 19.2%; cytotechnologist: 11.1%; pathologist: 7.9%; P.001). ThinPrep was also significantly associated with false-positive results as compared to conventional smears (12.2% versus 3.6%; P.001).In an interlaboratory comparison educational program, follicular cervicitis is difficult to interpret accurately and represents an important cause of false-positive responses. Follicular cervicitis may mimic adenocarcinoma or high-grade squamous intraepithelial lesion, particularly in liquid-based preparations. The diagnostic difficulty most likely arises from the lymphocytes being less conspicuous in the background as well as their tendency to aggregate in ThinPrep as compared to conventional smears.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl adducts from DNA and may be important in tumor resistance to alkylation chemotherapy. MGMT was visualized in human cells and tumor tissues with monoclonal antibodies against MGMT and immunofluorescence microscopy, and fluorescent signals were quantified by digital image analysis. MGMT was found both in the cytoplasm and the nucleus, and in either locale the protein reacts with alkylated DNA bases and becomes inactivated and lost from the cell. Cell lines in culture and xenografts showed a broad normal distribution of nuclear MGMT levels, but human brain tumors often showed a skewed distribution, with a significant fraction of cells with high levels of MGMT. O(6)-Benzylguanine, a suicide substrate inactivator for MGMT activity, reduced MGMT in human cells and in a mouse xenograft to levels undetectable by antibody assay 1 h post-treatment. In melanoma specimens taken from a patient 3 h post-treatment with temozolomide, MGMT levels were reduced by 70%. This quantitative immunofluorescence assay can be used to monitor MGMT and it depletion in human tumors to improve the use of alkylating agents in cancer chemotherapy.

Controversy exists about whether thyroid fine-needle aspirates (FNAs) should be processed with conventional smears or liquid-based preparations (LBPs).To compare the performance of conventional smears to LBPs for thyroid FNA slides circulated in the College of American Pathologists Interlaboratory Comparison Program in Non-Gynecologic Cytology.Participant responses for thyroid FNA slides were compared with the reference diagnosis at the level of 3 general diagnostic categories: negative, suspicious (which included only follicular and Hürthle cell neoplasm), and malignant. For specific reference diagnoses of benign/goiter and papillary thyroid carcinoma, the participants' specific diagnoses were analyzed and poorly performing slides were rereviewed.The 47, 076 thyroid FNA slide responses, between 2001 and 2009, included 44, 478 responses (94%) for conventional smears and 2598 responses (6%) for LBPs. For the general reference category negative, participant responses were discrepant in 14.9% of conventional smears compared with 5.9% for LBPs (P.001). The specific reference diagnosis of benign/goiter was misdiagnosed as a follicular neoplasm in 7.8% of conventional smears, compared with 1.3% of LBP. For the general reference category of malignant, participant responses were discrepant in 7.3% of conventional smears compared with 14.7% of LBPs (P.001). The specific reference diagnosis of papillary thyroid carcinoma was misdiagnosed as benign/goiter in 7.2% of LBPs, compared with 4.8% of conventional smears (p.001).LBPs performed worse than conventional smears for cases with a reference diagnosis of papillary thyroid carcinoma. However, LBPs performed better than conventional smears for cases with a benign reference diagnosis. Specific features in thyroid FNAs that may improve the diagnostic accuracy of LBPs and conventional smears are described.

A testis biopsy is used to assess quantitatively testicular spermatogenesis in infertile patients. Recently, several reports have used less invasive, percutaneous methods to obtain testis tissue. Percutaneous testis biopsies and touch imprints, immediately followed by open testis biopsies, were performed on 24 testes (19 patients) to ascertain whether they could provide the same histological information as an open biopsy. The technique of percutaneous testis biopsy using a core biopsy system is described. Comparisons of the percutaneous and open biopsy histological diagnoses revealed a 95 percent correlation. The percutaneous method using 1 pass through the testis failed to provide adequate tissue in 2 of 24 patients. Touch imprints obtained by the percutaneous method also provided a 95 percent correlation compared with the open method (2 of 24 touch imprints were lost during processing and, thus, were not evaluated). Percutaneous testis biopsies and touch imprints provide adequate tissue for hist...

Interinstitutional consultation in pathology has shown to improve patient safety by detecting interpretive errors that may significantly impact clinical management. We conducted a study of 922 cases of thyroid FNAC slides, referred to our institution over a 2-year period, to assess the magnitude of discrepancies and determine the clinical impact of second opinion. Disagreements were categorized as none, minor or major, the latter two defined as one- or two-step deviations respectively on the NCI diagnostic categories scale. There were 122 disagreements (13%), including 44 major and 78 minor. Seventy-five patients underwent a change in management based on second opinion, in conjunction with clinical and radiologic findings (age, size of nodule, family history, ultrasonographic appearance, and solitary versus multiple nodules). The second opinion was supported on follow-up in 57% of major discrepancies, and the initial diagnosis was concurrent with the surgical diagnosis in 7% cases. The remainder (36%) of major discrepancy cases did not undergo surgery, precluding tissue confirmation. Critics have alleged increased costs due to interinstitutional consultations. However, cost avoidance from lost wages, potential surgical complications, and litigation is not easily quantified. Using a simplified calculation to objectively measure the costs associated with changed diagnoses, we estimate that second opinion of these 922 cases resulted in potential cost saving of $940,166 based on current Medicare reimbursement codes. Our study indicates the need for a quality-control program of outside thyroid FNA slides, especially in "high discrepancy categories" as discussed in the article.

(1993). O6-Methylguanine-DNA Methyltransferase in Human Normal and Malignant Lung Tissues. Cancer Investigation: Vol. 11, No. 3, pp. 258-263.

Synovial sarcoma (SS) of the head and neck region are rare, accounting for less than 10% of all head and neck soft tissue sarcomas. A limited number of SS have been reported in the parapharyngeal space and these reports have all been based on histological examination of resection material. The diagnosis of monophasic SS on cytology is extremely difficult. We report the first case where a SS was correctly diagnosed on a fine needle aspirate by cytology with the assistance of immunocytochemistry and fluorescence in situ hybridization. We will emphasize the importance of ancillary techniques, such as immunocytochemistry and cytogenetic/molecular pathology, in avoiding diagnostic pitfalls and correctly diagnosing monophasic SS on cytologic material. We will propose an algorithmic approach to accurately diagnose parapharyngeal spindle cell neoplasms with the use of appropriate ancillary studies in conjunction to morphological features.

This is a retrospective study of 48 patients who underwent EBUS-TBNA procedure between the periods January 2008 to September 2009 at Long Island Jewish Medical Center. The study was undertaken with the following objectives: First, to define practical and useful on-site adequacy criteria for EBUS-TBNA samples; Second, to understand the diagnostic pitfalls associated with accurate interpretation of EBUS-TBNA samples. EBUS-TBNA procedure was able to diagnose 24/48 (50%) patients with malignancy, 1/48 (2%) suspicious for malignancy, 9/48 (19%) with granulomatous process, and 9/48 (19%) negative for disease. Only five cases (10%) could not be diagnosed with this procedure. Based on our experience, any smear with presence of > 5 low power fields (×100) with ≥ 100 lymphocytes in each and containing < 2 groups of bronchial cells/low power field (×100) can be considered adequate for evaluation. Also, the presence of germinal center fragments renders a smear adequate for evaluation, irrespective of the above mentioned criteria. Adequacy criteria are to be applied only to the smears not showing any identifiable pathology such as malignancy or granuloma. An understanding of diagnostic pitfalls associated with accurate interpretation of EBUS-TBNA samples is essential to avoid false-positive and false-negative diagnosis. To conclude, an effective communication between the clinician and cytologist, an algorithmic approach to diagnosis, and the on-site adequacy criteria proposed in this study can markedly improve the diagnostic yield of the procedure.

OBJECTIVES To determine the aetiology of non-diagnostic renal fine-needle aspiration cytologies (FNACs) in a contemporary series. PATIENTS AND METHODS We retrospectively reviewed our institutional database of renal FNACs performed between 1995 and 2005. There were 118 patients with renal lesions that underwent FNAC. Indications for FNAC were indeterminate complex renal cysts, significant medical comorbidities, previous history of malignancy, multiple bilateral renal lesions, and suspected metastatic disease. A cytotechnologist was present during the FNA procedure to perform Diff-Quik staining and ensure an adequate sample of cells were obtained. Except for seven (six open, one ultrasound-guided), all of the FNACs were performed with CT guidance. RESULTS The median (range) number of passes for each FNAC session was 2.7 (1–6). Of the 16 FNACs performed for indeterminate complex renal cysts, nine (56%) were adequate with the cytodiagnosis of benign cysts. Of the seven inadequate specimens, three had benign cysts and another three were non-diagnostic due to acellularity. Therefore, the technical failure rate was 19% (3/16) for indeterminate complex renal cysts. The last patient had a cytodiagnosis of benign cyst and the final histological diagnosis of renal cell carcinoma (RCC; papilllary, grade III). Therefore, this represents a sampling error (false negative rate) of 0.8% (1/118). For the 102 solid renal masses, 22 (22%) had inadequate specimen by Diff-Quik staining. The technical failure rate (inability to obtain sufficient epithelial cells) was 16% (16). In 18 patients, immunocytochemistry (ICC) was used to differentiate primary renal parenchymal tumours from others such as transitional cell carcinoma (TCC), lymphoproliferative, colon, and lung. There were two FNACs with misdiagnosis (2%), where ICC was not used. In both, the cytodiagnosis was TCC and the final histological diagnosis was RCC in one and atypical urothelium in another. CONCLUSIONS Non-diagnostic renal FNACs can be attributed to misdiagnosis (2%), sampling error (0.8%) and technical failure (16%).

We report on the fine-needle aspiration cytological findings of a metastatic granulosa-cell tumor of the ovary to bone. The patient had undergone resection of a primary ovarian granulosa-cell tumor 15 yr prior to her last admission. Recently she injured her right hip, sustained after a fall. CT examination revealed hypodense lesions involving the posterior body and the right pedicle of the L1 vertebra. The aspirate from the bone yielded a highly cellular smear, composed of round to oval cells with scanty cytoplasm. Many of the cells revealed the presence of nuclear grooves. In areas, the cells were arranged in clusters resembling Call-Exner bodies. The rarity of skeletal metastases from granulosa-cell tumors can cause diagnostic difficulty in diagnosing this entity. Accurate clinical data, radiological findings, and cytological features are important in arriving at the correct diagnosis.

A 3-month-old male with a chief complaint of episodic choking with feeds and a hoarse cry is presented. Left eye ptosis and asymmetric soft palate elevation were detected on physical examination. Fiberoptic examination showed a left vocal fold paresis and pooling of secretions in the pyriform sinuses. MRI demonstrated an ill-defined lesion at the left jugular foramen extending into the left carotid sheath. A fine needle biopsy revealed spindle shaped cells consistent with fibromatosis. The histopathology of fibromatosis and the differential diagnosis of jugular foramen masses in children will be described. To our knowledge, this represents the earliest reported case of fibromatosis in the jugular foramen.

The pathologic distinction of small cell from non-small cell-lung carcinoma is of considerable therapeutic significance. In particular, the ability to distinguish poorly differentiated non-small-cell lung cancer from small-cell lung carcinoma (SCLC) is at times difficult based upon morphology alone; available immunohistochemical markers such as neuroendocrine markers are of limited utility. We have demonstrated the role of p63 and thyroid transcription factor-1 (TTF-1) in the differential diagnosis of poorly differentiated squamous-cell carcinoma (PDSCC) versus SCLC, mostly in biopsy samples (Wu et al., American Journal of Clinical Pathology 2003;119:696-702). Here, we examine further the utility of this panel in cytologic cell-block samples of lung cancers including both primary and metastatic cancers of pulmonary origin, and cases of nonpulmonary cancers metastatic to lung in which differential diagnoses included a lung primary.Four-micron thick sections of 30 alcohol-fixed paraffin-embedded cell blocks from 14 lung FNAs, 6 liver FNAs, 3 bronchial washings, 1 subcarinal lymph node FNA, 1 iliac lymph node FNA, 1 pelvic mass FNA, 1 neck lymph node FNA, 1 adrenal FNA, and 1 pleural effusion were deparaffinized and stained with monoclonal antibodies reactive to p63 (1:800, Santa Cruz Biotechnology) and TTF-1 (1:50, Dako). Slides were stained for p63 using a streptavidin-biotin kit (BioGenex) and diaminobenzidine as chromagen, and counterstained with hematoxylin. Slides were stained for TTF-1 using a Dako Autostainer. Thirty cases were examined, including 8 primary SCLCs, 8 extra-pulmonary metastases of lung SCLCs, 4 PDSCCs and 4 primary pulmonary adenocarcinomas, and 6 nonpulmonary adenocarcinomas metastatic to lung or other sites. Fifteen out of 16 (94%) SCLC cases were p63-/TTF-1+, ranging in intensity from focal-weak to diffuse-strong; 1/16 SCLCs from a bronchial washing was p63-/TTF-1- but synaptophysin was positive. All 4 primary lung adenocarcinoma cases were p63-/TTF-1+; contrasting with nonpulmonary adenocarcinomas that were all p63-/TTF-1-. All 4 PDSCC cases were p63+/TTF-1-. The panel of p63 and TTF-1 appears to be useful in the diagnostic evaluation of cytologic cell-block samples of pulmonary malignancy.

Malignant rhabdoid tumor (MRT) of the kidney is a rare and aggressive neoplasm with a controversial histogenesis. Although their immunohistochemistry may be diverse, the rhabdoid phenotype and mutations of the INI1 gene are consistently exhibited by MRTs regardless of their location.MRT recurred in the contralateral kidney in a 12-month-old child within 6 months after the initial histologic diagnosis, nephrectomy and autologous stem cell transplant. The presence of widespread metastases at the time of the recurrence precluded any further chemical and surgical diagnostic or therapeutic intervention.To the best of our knowledge, only a few cases describing the cytologic diagnosis of MRT of the kidney in a child have been reported. This case illustrates the usefulness of cytologic diagnosis in an MRT recurrence.

Acinar cell carcinomas (ACCs) are uncommon malignant tumors of the exocrine pancreas, constituting 1% to 2% of all nonendocrine pancreatic neoplasms. Cases of acinar cell carcinoma developing in heterotopic pancreatic tissue are extremely rare. To the best of our knowledge, no cases of primary ACC developing in the stomach have been reported in the literature. We report the first case of a primary ACC arising in the stomach in an 86-year-old female who presented with a 5-cm gastric submucosal mass with superficial ulceration and a history of anemia. The neoplasm exhibited typical acinar morphology. Immunohistochemical studies demonstrated strong positive reactivity for antitrypsin and antichymotrypsin, and electron microscopy confirmed the presence of zymogen granules. A complete metastatic workup failed to identify any primary pancreatic tumor or other nonpancreatic tumor.

The objective of this study was to determine the presence of oestrogen and/or progesterone receptors in laryngeal pyogenic granulomas and the impact of these receptors on recurrence of pyogenic granulomas. Twenty-two consecutive patients who underwent microlaryngoscopy and removal of pyogenic granulomas were studied retrospectively. The indications for surgery were airway compromise, failure of medical therapy and suspicion of malignancy. Twelve of these patients' granulomas were analysed for oestrogen and progesterone receptors. Charts were analysed for age, sex, location of the lesion, history of trauma, intubation or gastroesophageal reflux disease (GORD), airway symptoms and recurrence. Oestrogen/progesterone receptors were analysed following deparaffinization of specimens and immunostaining with prediluted anti-oestrogen receptor monoclonal antibody and anti-progesterone receptor monoclonal antibody. No sample expressed oestrogen or progesterone receptors. There were too few recurrences to detect if lack of these receptors played any role in determining outcome in this group. Most of the patients had a history of GORD, intubation or laryngeal surgery. There were 12 recurrences in four patients. All of the recurrences improved on prolonged courses of omeprazole. Pyogenic granulomas do not possess oestrogen or progesterone receptors and are unlikely to respond to hormonal therapy. Patients who have, or are being operated on for, laryngeal pyogenic granulomas should be placed on proton pump inhibitors to decrease the likelihood of recurrence.

To describe a case of papillary carcinoma of the thyroid that mimicked a diffuse toxic goiter.We present a detailed case report, review related cases in the literature, and discuss the possible role of autoantibodies in promoting the growth of papillary thyroid tumor.A 28-year-old woman had a 6-month history of weight loss, palpitations, increased anxiety, and enlargement of her thyroid gland. Laboratory studies confirmed the presence of hyperthyroidism. A 1-cm nodule was identified at the left upper pole of the thyroid. Fine-needle aspiration biopsy of this nodule revealed papillary carcinoma of the thyroid. Total thyroidectomy and a modified radical neck dissection were performed. Microscopic examination showed that the entire gland was replaced by a papillary carcinoma with a predominantly follicular pattern of growth. Of 44 lymph nodes tested, 31 were positive for metastatic papillary thyroid carcinoma. The presence of thyroid antibodies may have had a role in the aggressiveness of the patient's disease.To our knowledge, this is the first published report of a papillary thyroid cancer with manifestations resembling Graves' disease.

Granulocytic sarcoma is an uncommon extramedullary, solid tumor of myeloid cells. Only rarely has this entity been diagnosed by fine-needle aspiration (FNA) cytology. This report encompasses the cytologic findings of FNAs from seven patients with granulocytic sarcomas, including four male and three female patients with a mean age of 52 years (range, 12 to 77 years). The aspirates were obtained from skin or subcutaneous tissue (four cases), testis (one case), posterior ileum (one case), lymph node (one case), and abdominal washing (one case). Morphology of the aspirates varied from well-differentiated to poorly differentiated cells showing little or no evidence of myeloid differentiation. Thorough search for evidence of myeloid differentiation and a high index of suspicion of granulocytic sarcoma are of paramount importance. In three cases, flow cytometric and immunocytochemical studies were applied to the FNA materials to confirm the myeloid lineage of the cells and the diagnosis. In the other four cases more than one site was involved by the tumor; once the diagnosis of granulocytic sarcoma was established with a biopsy, the FNA sufficed to confirm the diagnosis at another location. This study demonstrates that FNA cytology in conjunction with appropriate immunophenotyping can provide an accurate diagnosis of granulocytic sarcoma. Fine-needle aspiration can reduce the need for surgical intervention when combined with immunophenotypic studies and when additional anatomic sites are involved.

About 11,600 cases of laryngeal cancer were reported in the United States in 1995, accounting for 1% of all reported cancers. Fewer than 1% of laryngeal cancers are sarcomas, osteosarcoma being the rarest type. Twelve cases of laryngeal osteosarcoma have been cited in the literature. A 47-year-old man presented with hoarseness following a benign vocal polypectomy. The entire larynx appeared swollen, although both vocal folds moved well. Biopsies did not reveal pathologic tissue. Computed tomographic imaging revealed a destructive, expansile lesion of the thyroid cartilage. A computed tomography-guided biopsy of this cartilage revealed a high-grade sarcoma. Laryngeal osteosarcoma was diagnosed following total laryngectomy. Laryngeal osteosarcoma is a highly malignant neoplasm with early hematogenous spread. Survival statistics for peripheral osteosarcoma are poor. Limited experience reveals that a combination of surgery and radiotherapy with adjuvant chemotherapy can offer some palliation. The literature and published cases of laryngeal osteosarcoma are reviewed.

Pathology, University of Washington,Seattle, WashingtonIntroduction: Urothelial cancer is on the rise. The relatively longersurvival is attributed to timely diagnosis and effective clinical manage-ment. The role of urinary cytology is central in the continued surveillanceand cannot be over-emphasized. In literature urine cytology has a muchhigher sensitivity and specificity for high grade urothelial carcinomaapproaching 75%-98%, when compared to 8.5 to 50% for low-gradelesions.The objective of our study was to review and benchmark the accuracy ofurine cytology and risk of malignancy (predicted probability) for every urinecytology diagnostic category.Materials and Methods: A laboratory information system search (Cernerand Meditech) retrieved 443 GU biopsies along with their preceding 920urine cytologies from January 2008 to January 2011. Statistical analysiswas performed using the cytology specimen within 6 months and closestto biopsy date and more than 6 months and farthest from the biopsy date.Cytology diagnostic categories included negative for malignant cells(NMC) (N Z 183), reactive cellular change (RCC) (N Z 15), atypical(A) (N Z 77), suspicious(S) (N Z 38) and positive (P) (N Z 61). NMCand RCC were classified as negative. All other categories wereconsidered positive. Logistic regression was used to model malignancyas a function of urine cytology diagnostic category within 6 months frombiopsy.Results: The overall sensitivity and specificity of urine cytology was 62.8%and 74.2% respectively (Table 1). Sensitivity for high grade lesions wasgreater (71.6%) than that for low grade (46.3%). Sensitivity for both highgrade and low grade lesions was similar before and after 6 months but spec-ificity declined after 6 months (Table 3). The risk of malignancy was highfor positive, suspicious and atypical categories at 0.82, 0.82 and 0.7 respec-tively (Table 2).

An important component of high-dose chemotherapy/autologous bone marrow support regimens for adjuvant treatment of breast cancer is carmustine. Preclinical studies have shown that the level of the DNA repair protein O6-methylguanine-DNA methyltransferase is correlated with the resistance of cultured human tumor cells to this drug, but little is known about transferase levels of breast tissue in vivo. We measured the DNA repair activity in 80 tissue samples from 65 patients, including normal, abnormal, benign, and malignant specimens. Wide interindividual variations was observed and average transferase levels were similar in normal and benign tissue. However, transferase levels were significantly elevated in stage I-IV disease. In addition, the frequency of samples with no detectable transferase was greatly reduced in this malignant group, and transferase was positively correlated with the presence of positive nodes, a marker for disease progression. In contrast, transferase levels were not correlated with age or estrogen receptor status, and the levels in normal tissue did not vary between patients with benign or malignant disease. These results suggest that this DNA repair activity may be increased in breast cancer relative to normal tissue and encourage further study of the predictive value of transferase measurements in high-dose chemotherapy/autologous bone marrow transplant for breast cancer.