A Proposal for Separation of Nuclear Atypia and Architectural Atypia in Bethesda Category III (AUS/FLUS) Based on Differing Rates of Thyroid Malignancy.

Objectives: Bethesda category III (atypia of undetermined significance/follicular lesion of undetermined significance) includes sparsely cellular specimens with nuclear atypia (3N) and/or architectural atypia (3A). This study investigates whether the two types of atypia have different rates of malignancy (ROMs). Methods: Cytologic and histologic diagnoses of resected thyroid nodules were recorded. ROM was calculated for all Bethesda categories and for 3N and 3A subcategories. Possible noninvasive follicular thyroid neoplasms with papillary-like nuclear features were reviewed and removed from malignancies, and ROM was recalculated. Results: A total of 1,396 nodules were included. ROM of 3N (33.3%-26.0%) was higher than 3A (7.7%-5.0%) (P < .0001) and was similar to suspicious for follicular neoplasm (25.0%-20.3%) (P = .3). ROM of 3A approached benign (2.4%-1.5%) (P = .02). Conclusions: Strong consideration should be given to separating 3N (nuclear atypia with higher risk for papillary thyroid carcinoma) from 3A (architectural atypia with higher chance of being benign) to convey different ROMs.

Autoimmune gastrointestinal dysmotility due to small cell lung cancer.

The diagnosis of autoimmune gastrointestinal dysmotility requires a high level of clinical suspicion when standard work-up is unrevealing. We report the case of a 56-year-old male patient with history of tobacco use and a subacute presentation of weight loss, vomiting and cerebellar ataxia. The discovery of paraneoplastic type 1 antineuronal nuclear antibodies and neuronal acetylcholine receptor antibodies led to further directed imaging and diagnostic studies in spite of prior negative chest imaging. Bronchoscopy with endobronchial ultrasound was used to confirm a diagnosis of small cell lung cancer and paraneoplastic syndrome as the cause of the presenting upper gastrointestinal symptoms.

Thyroid Nodule Size at Ultrasound as a Predictor of Malignancy and Final Pathologic Size.

BACKGROUND: Thyroid-related mortality has remained constant despite the increasing incidence of thyroid carcinoma. Most thyroid nodules are benign; therefore, ultrasound and fine needle aspiration (FNA) are integral in cancer screening. We hypothesize that increased nodule size at ultrasound does not predict malignancy and correlation between nodule size at ultrasound and pathologic exam is good. METHODS: Resected thyroids with preoperative ultrasounds were identified. Nodule size at ultrasound, FNA diagnosis by Bethesda category, size at pathologic examination, and final histologic diagnosis were recorded. Nodule characteristics at ultrasound and FNA diagnoses were correlated with gross characteristics and histologic diagnoses. Nodules for which correlation could not be established were excluded. RESULTS: Of 1003 nodules from 659 patients, 26% were malignant. Nodules <2 cm had the highest malignancy rate (∼30%). Risk was similar (∼20%) for nodules ≥2 cm. Of the 548 subject to FNA, 38% were malignant. Decreasing malignancy rates were observed with increasing size (57% for nodules <1 cm to 20% for nodules >6 cm). At ultrasound size cutoffs of 2, 3, 4, and 5 cm, smaller nodules had higher malignancy rates than larger nodules. Of the 455 not subject to FNA, 11% were malignant. Ultrasound size alone is a poor predictor of malignancy, but a relatively good predictor of final pathologic size (R2 = 0.748), with less correlation at larger sizes. In nodules subject to FNA, false negative diagnoses were highest (6-8%) in nodules 3-6 cm, mostly due to encapsulated follicular variant of papillary carcinoma. CONCLUSIONS: Thyroid nodule size is inversely related to malignancy risk, as larger nodules have lower malignancy rates. However, the relationship of size to malignancy varies by FNA status. All nodules (regardless of FNA status) demonstrate a risk trough at ≥2 cm. Nodules subject to FNA show step-wise decline in malignancy rates by size, demonstrating that size alone should not be considered as an independent risk factor. Size at ultrasound shows relatively good correlation with final pathologic size. False negative rates are low in this series. Lesions with the appropriate constellation of clinical and radiographic findings should undergo FNA regardless of size. Both size and FNA diagnosis should influence the clinical decision-making process.

Heart and Neural Crest Derivatives Expressed Transcript 2 (HAND2): a novel biomarker for the identification of atypical hyperplasia and Type I endometrial carcinoma.

Progesterone inhibits the proliferative growth effects of estrogen in the endometrium and prevents the development of endometrial hyperplasia and Type I adenocarcinoma. The exact mechanism of this action is unknown. The progesterone-induced helix-loop-helix transcription factor Heart and Neural Crest Derivatives Expressed 2 (Hand2) was recently shown to suppress production of growth factors in the endometrium. In Hand2 knockout mice, continuous proliferation of the endometrium was observed. In this study, archival paraffin-embedded tissue from 56 hysterectomy specimens was examined by immunohistochemistry for the expression and localization of Hand2, estrogen receptor (ER), progesterone receptor (PR), and Ki-67. Diagnoses included disordered proliferative endometrium, simple and complex hyperplasia with or without atypia, and endometrioid adenocarcinoma. Hand2 expression is localized to endometrial stromal nuclei. In benign endometrium, Hand2 expression was moderate to strong (10/11; 91%), with weak Hand2 expression in only 1 case (1/11; 9%). Similar Hand2 expression patterns were observed in disordered proliferative endometrium and simple hyperplasia without atypia, with moderate to strong expression in 91% of cases (10/11) and weak expression in 9% of cases (1/11). In contrast, simple and complex hyperplasia with atypia exhibited moderate to strong Hand2 expression in 8% of cases (1/12) and a loss of expression or weak expression in 92% of cases (11/12). In endometrioid adenocarcinomas, Hand2 expression was absent in all cases (22/22). Hand2 is expressed in the stroma of benign endometrium, but expression is significantly reduced or lost in atypical hyperplasia and endometrioid carcinoma. Thus, the absence of Hand2 expression may be a useful biomarker for atypical hyperplasia and endometrioid carcinoma.