Purpose: CD40 ligand (CD40L, CD154) plays a central role in immunoregulation and also directly modulates epithelial cell growth and differentiation. We previously showed that the CD40 receptor is commonly expressed in primary breast cancer tissues. In this proof-of-principle study, we examined the breast cancer growth^regulatory activities of an oncolytic adenoviral construct carrying the CD40L transgene (AdEHCD40L). Experimental Design: In vitro and in vivo evaluations were carried out on AdEHCD40L to validate selective viral replication and CD40L transgene activity in hypoxia inducing factor-1a and estrogen receptor^expressing human breast cancer cells. Results: AdEHCD40L inhibited the in vitro growth of CD40 + human breast cancer lines (T-47D, MDA-MB-231, and BT-20) by up to 80% at a low multiplicity of infection of1. Incorporation of the CD40L transgene reduced the effective dose needed to achieve 50% growth inhibition (ED 50 ) by f10-fold. In contrast, viral and transgene expression of AdEHCD40L, as well its cytotoxicity, was markedly attenuated in nonmalignant cells. Intratumoral injections with AdEHCD40L reduced preexisting MDA-MB-231xenograft growth in severe combined immunodeficient mice by >99%and was significantly more effective (P < 0.003) than parental virus AdEH (69%) or the recombinant CD40L protein (49%).This enhanced antitumor activity correlated with cell cycle blockade and increased apoptosis in AdEHCD40L-infected tumor cells. Conclusions: These novel findings, together with the previously known immune-activating features of CD40L, support the potential applicability of AdEHCD40L for experimental treatment of human breast cancer.

Pharyngoesophageal diverticula (PED) of the Zenker's and Killian-Jamieson types arise in close proximity to the thyroid gland, and may rarely be confused with a thyroid nodule on ultrasonography. In this brief report, we detail the cytologic, clinical, and radiologic findings of three PED that were thought to be thyroid nodules, and were subjected to fine-needle aspiration (FNA). The patients were females with an age range of 51-64 years. All three patients had multiple thyroid nodules, and two patients reported symptoms attributable to the diverticulum. Nodule sizes ranged from 1.0 to 2.7 cm, and either the right or left thyroid lobe could be involved. Microcalcifications were present by ultrasonography in all three cases. FNA of these thyroid nodule mimics showed squamous cells with granular or amorphous debris, bacterial and/or fungal colonies, inflammation, and food particles. These cytologic features, particularly the presence of vegetable or meat fragments, are characteristic, and have also been reported in the few previous reports of PED. The presence of a diverticulum was confirmed with imaging studies in all our patients. Although a rare occurrence, the inadvertent FNA of a PED masquerading as a thyroid nodule is important to recognize, as a recommendation for appropriate radiologic studies could potentially avoid inappropriate therapy for thyroid disease.

Primary thyroid teratomas are rare, usually benign, and typically occur in children. We report the unusual occurrence of a malignant thyroid teratoma in a young man. Initial ultrasound and CT studies revealed an 8.5 heterogeneous mass involving the entire right thyroid lobe causing tracheal compression and deviation. Fine‐needle aspiration (FNA) revealed malignant cells with possible neuroendocrine features. Similar findings have been previously reported, with an occasional interpretation as possible medullary thyroid carcinoma. In no report, as with our case, has the correct diagnosis been suggested with FNA. The surgical specimen contained abundant primitive neuroepithelium with a very minor component of mature ectodermal tissue in one area. Like this case, an abundance of immature neuroepithelium has been reported in essentially all previous reports of primary malignant thyroid teratoma, sometimes creating a challenge to find another type of germ cell tissue. Array comparative genomic hybridization studies in this case revealed a markedly complex karyotype including gain of chromosome 12 and loss of 17p. Amplification of MYCN, EWSR1 rearrangement and isochromosome 12p were not identified, providing no evidence for neuroblastoma or Ewing sarcoma/peripheral neuroectodermal tumor, both of which have also rarely been reported as primary thyroid tumors. With the use of cisplatinum‐based chemotherapy combined with radiation, survival times have increased dramatically. Our patient is now disease free and back to his normal activities after relatively short follow‐up. Although rare, it is important to be aware that teratomas may present as a thyroid nodule. Recognition by FNA is challenging, and requires multiple modalities for full identification.

The use of CBs in low-cellularity thyroid FNAs has not been well described. In this study, we found that the contribution of CBs in this setting varied by TBSRTC category. Specifically, the samples that benefited most were initially non-diagnostic specimens and select cases of AUS/FLUS, while low-cellularity benign samples gained very little additional information. Diagn. Cytopathol. 2016;44:737-741. © 2016 Wiley Periodicals, Inc.

63-year-old Hispanic woman with prior systemic hypertension was well until 39 days before death when she fainted in her kitchen and was hospitalized. An electrocardiogram and telemetry monitoring disclosed sinus bradycardia (50 beats per minute) with first-degree atrioventricular block, left bundle branch block, frequent atrial and ventricular premature complexes, and sinus pauses up to 8 seconds. An echocardiogram showed mitral regurgitation (2+/4+) and an ejection fraction of 60%. An angiogram disclosed normal coronary arteries. e left ventricular and aortic pressures were normal. During her 3 days in the hospital, she had recurrent sinus pauses with associated syncope, and a permanent atrioventricular sequential pacemaker was implanted. ereafter, she felt well and was active until 22 days before she died, when exertional dyspnea appeared and progressed, prompting rehospitalization 20 days before death. Her blood pressure was 120/75 mm Hg, her paced heart rate was 80 beats per minute, and her temperature was normal. A grade 2/6 apical systolic ejection murmur and a third heart sound were audible. She had diffuse pulmonary rales and decreased breath sounds at both lung bases. A chest radiograph showed pulmonary vascular congestion, cardiomegaly, and bilateral pulmonary effusions. An electrocardiogram disclosed atrioventricular sequentially paced rhythm with no ST-T changes. Her serum troponin I level was 6.6 ng/mL, and her creatine phosphokinase level was 189 U/L with an MB fraction of 39 ng/mL. Her brain natriuretic peptide level was 2570 ng/L, and her white blood cell count was 10.7 × 10 3 /mm 3. An echocardiogram showed severe global hypokinesis with an ejection fraction of 35%. Over the subsequent 19 days in the hospital, the patient's status progressively deteriorated, requiring intravenous inotropic support, mechanical ventilation, and continuous veno-venous hemodialysis. She also developed hemodynamically unstable