'Atypical' and 'suspicious' diagnoses in breast aspiration cytology

BACKGROUND: In 1996, the National Cancer Institute (NCI) recommended five categories for the diagnosis of breast aspiration cytology: benign, atypical, suspicious, malignant, and unsatisfactory. The authors evaluated the usefulness of separating inconclusive diagnoses into the aforementioned atypical and suspicious categories. The current study examined the correlation between cytologic and histologic findings made in breast aspiration cytology specimens that were categorized in accordance with these NCI guidelines. METHODS: From 1992 to 2000, 7727 breast aspirations were performed at the University of Miami/Jackson Memorial Medical Center (Miami, FL). Aspirates were classified using criteria similar to the NCI recommendations. Four hundred eighty-nine aspirates (6%) were classified as being cytologically 'atypical' or 'suspicious'. Of those, 225 'atypical' aspirates and 162 'suspicious' aspirates had available histologic follow-up data and were included in the study. RESULTS: Among the 'atypical' aspirates, 118 (52%) yielded malignant findings on histologic evaluation. Infiltrating ductal carcinoma (n = 87; 74%) was the most common malignant diagnosis, followed by infiltrating lobular carcinoma (n = 12; 10%). Among 'suspicious' aspirates, 135 (83%) yielded malignant findings on histologic analysis. The most common benign diagnosis in both 'atypical' and 'suspicious' aspirates was proliferative fibrocystic changes with or without atypia, followed by fibroadenoma. CONCLUSIONS: Most aspirates that yielded suspicious findings on cytologic examination proved to be malignant, as did > 50% of aspirates that yielded atypical findings. Infiltrating lobular carcinoma commonly was underdiagnosed as being atypical on cytologic examination. Benign lesions with atypical or suspicious cytologic diagnoses included certain cases of atypical ductal hyperplasia. The authors concluded that the distinction between the atypical and suspicious categories, as recommended by the NCI, is not warranted. Therefore, they suggest the use of a single term, such as 'equivocal', to describe inconclusive diagnoses on breast fine-needle aspiration cytology.     

Absence of BRAF gene mutations differentiates spitz nevi from malignant melanoma

BACKGROUND: Distinction of Spitz nevus from malignant melanoma is sometimes difficult on the basis of conventional histology. A high rate of BRAF gene mutations in malignant melanomas (66%) and nevi (82%) has recently been reported. MATERIALS AND METHODS: We screened a series of 20 Spitz nevi for BRAF mutations in exons 11 and 15 by denaturing gradient gel electrophoresis (DGGE). RESULTS: BRAF mutations could not be identified in Spitz nevi. CONCLUSION: Our results show that mutations within the BRAF gene are useful markers for the differential diagnosis between Spitz nevus and malignant melanoma.     

Experimental rat models of types 1 and 2 diabetes differ in sympathetic neuroaxonal dystrophy

Dysfunction of the autonomic nervous system is a recognized complication of diabetes, ranging in severity from relatively minor sweating and pupillomotor abnormality to debilitating interference with cardiovascular, genitourinary, and alimentary dysfunction. Neuroaxonal dystrophy (NAD), a distinctive distal axonopathy involving terminal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in man and several insulinopenic experimental rodent models. Although the pathogenesis of diabetic sympathetic NAD is unknown, recent studies have suggested that loss of the neurotrophic effects of insulin and/or insulin-like growth factor-I (IGF-I) on sympathetic neurons rather than hyperglycemia per se, may be critical to its development. Therefore, in our current investigation we have compared the sympathetic neuropathology developing after 8 months of diabetes in the streptozotocin (STZ)-induced diabetic rat and BB/ Wor rat, both models of hypoinsulinemic type 1 diabetes, with the BBZDR/Wor rat, a hyperglycemic and hyperinsulinemic type 2 diabetes model. Both STZ- and BB/Wor-diabetic rats reproducibly developed NAD in nerve terminals in the prevertebral superior mesenteric sympathetic ganglia (SMG) and ileal mesenteric nerves. The BBZDR/Wor-diabetic rat, in comparison, failed to develop superior mesenteric ganglionic NAD in excess of that of age-matched controls. Similarly, NAD which developed in axons of ileal mesenteric nerves of BBZDR/Wor rats was substantially less frequent than in BB/Wor- and STZ-rats. These data, considered in the light of the results of previous experiments, argue that hyperglycemia alone is not sufficient to produce sympathetic ganglionic NAD, but rather that it may be the diabetes-induced superimposed loss of trophic support, likely of IGF-I, insulin, or C-peptide, that ultimately causes NAD.     

Adrenoceptor mechanisms underlying imipramine-induced memory deficits in rats

The post-training administration of tricyclic antidepressant imipramine impairs memory consolidation in the passive avoidance task. The present study investigated the effects of intrahippocampal (i.h.) injection of adrenoceptor agents on imipramine-induced (2-8 microg/rat) amnesia. The administration of the alpha1-adrenoceptor agonist phenylephrine (0.05 microg/rat) and the alpha1-adrenceptor antagonist prazosin (0.5 microg/rat) did not alter the effect of imipramine. The lower doses of phenylephrine (0.005 and 0.015 microg/rat) impaired, while the higher dose of the drug (0.025 and 0.05 microg/rat) improved retention. The effect of phenylephrine was not altered by prazosin (0.5 and 1 microg/rat) pretreatment, although prazosin alone decreased retention latencies. The alpha2-adrenoceptor antagonist yohimbine (0.5 and 1 microg/rat) decreased the response induced by imipramine. However, the alpha2-adrenoceptor agonist clonidine (0.08 microg/rat) did not alter the effect of the drug. Clonidine (0.15 and 0.3 microg/rat) by itself decreased, while yohimbine (1 and 2 microg/rat) increased retention latencies. Yohimbine pretreatment attenuated the effect of clonidine. It is concluded that alpha2-adrenoceptor mechanism(s) may be involved in imipramine-induced impairment of memory.     

Production and characterization of monoclonal antibodies with specificity for human HLA-G isoforms

Production of monoclonal antibodies to HLA-G, a nonpolymorphic antigen of non-classical HLA class I, is of basic and clinical importance. In the present study, monoclonal antibodies were prepared which recognize different membrane bound and soluble isoforms of HLA-G, following immunization of BALB/c mice with a synthetic peptide. Use of this peptide (23 residues), which is present in the alpha1 domain of HLA-G, was previously demonstrated to provide antibodies useful for recognition of HLA-G isoforms in human placenta. Antibody-producing hybridomas were screened by an indirect one-step ELISA method. A clone designated 5E6H7, secreted antibodies useful in immunostaining studies involving both surface HLA-G of placental tissues and soluble forms of this antigen in human sera. In addition, unreactivity of this antibody with human lymphocytes and sections of normal human skin was observed by immunofluorescence microscopy, thus demonstrating its specificity for HLA-G.     

Vascular Pattern and Spectral Parameters of Power Doppler Ultrasound as Predictors of Malignancy Risk in Thyroid Nodules

Introduction: Determination whether spectral Doppler ultrasound parameters, including resistance index (RI) and pulsatility index (PI), or vascular pattern can be used to distinguish malignant from benign thyroid nodules. Materials and Methods: We prospectively examined 85 thyroid nodules in patients undergoing surgery. The flow pattern seen via power Doppler examination was ranked for each nodule on a scale of 0 to 4 as follows: absent, perinodular alone, mixed with perinodular prominency, mixed with intranodular prominency, and exclusively intranodular, respectively. For each nodule, the RI and PI values were recorded as the average of the recordings obtained. Pathological examination were used as a proof of final diagnosis to categorize all nodules as benign or malignant. Results: The malignant nodules had a mean RI of 0.72 ± 0.13. These values were significantly higher than those associated with benign nodules (0.60 ± 0.08) (P = .000). Malignant nodules had a mean PI of 1.15 ± 0.33 that were also significantly different from those associated with benign nodules (0.91 ± 0.19) (P = .000). Shifting to intranodular vascularization had a significant correlation with malignancy (P = .001). Conclusion: Spectral parameter and vascular pattern are useful to distinguish malignant from benign thyroid nodules, especially for those with suspicious or undetermined fine‐needle aspiration biopsy.     

Extending the capabilities of a laboratory computer system through cooperative processing

The concept of cooperative processing within the context of a hospital or laboratory computer systems environment is introduced. Two examples that produce graphical display of laboratory data are described to illustrate cooperative processing's ability to enhance a system's functionality without placing significant additional burden on system resources.