Objective Both increased production of reactive oxygen and nitrogen intermediates (RONI) and reduced levels of complement may play a role in the increased apoptosis and reduced clearance of apoptotic cells in systemic lupus erythematosus (SLE). The objective of this study was to evaluate both processes in a parallel, prospective, longitudinal manner. Methods Sixty‐seven SLE patients were evaluated during multiple visits, and 31 healthy control subjects were evaluated once or twice. Clinical and laboratory features of SLE disease activity were determined, and blood was collected for measurement of serum nitrate plus nitrite (NOx) levels and for isolation of peripheral blood mononuclear cells (PBMCs). PBMCs were cultured with a nitric oxide (NO) donor and SLE or control plasma, with or without heat inactivation, cobra venom factor (CVF), or lipopolysaccharide plus interferon‐γ treatment. Cells were analyzed for apoptotic index (AI), cellular subsets, and RONI production. Results The PBMC AI was associated with SLE and was inversely associated with complement levels over time. Changes in the AI with addition of a NO donor was longitudinally associated with serum NOx levels, and stimulation of SLE PBMCs led to parallel increases in RONI production and apoptosis. Addition of SLE plasma resulted in a greater PBMC AI, an effect that was increased with heat inactivation and was corrected with CVF treatment. Conclusion These data suggest that the greater AI observed in SLE PBMCs relates to increased PBMC RONI production and reduced complement levels. The longitudinal nature of these parallel associations within individuals suggests that these processes are dynamic and additive.

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.

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.

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.

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.