Malignant teratoma of the thyroid: A difficult diagnosis by fine-needle aspiration.

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 utility of cellient cell blocks in low-cellularity thyroid fine needle aspiration biopsies.

BACKGROUND: Low cellularity can be problematic in thyroid fine needle aspiration (FNA) biopsies. The Cellient cell block (CB) system has been reported to improve cell recovery compared to traditional methods. Therefore, we studied the utility of Cellient CBs in the evaluation of thyroid FNAs, with an emphasis on low-cellularity specimens. METHODS: ThinPrep slides were prepared from thyroid FNAs submitted in Cytolyt. After assessment using TBSRTC criteria, Cellient CBs were requested on samples with residual FNA material and an initial cytologic impression of non-diagnostic, AUS/FLUS, and on apparently benign samples with marginally adequate cellularity. The contribution of the CB findings to the final diagnosis was assessed. RESULTS: 965 cases of paired ThinPrep and CB sections were examined. Overall, the cell block findings resulted in a change of the initial ThinPrep impression in 15% (n = 148) of cases. The vast majority of these changed cases were initially inadequate for interpretation, and specifically, 31% (n = 123) of the non-diagnostic ThinPrep samples became diagnostic with a CB. The cell block findings contributed to a change in diagnosis in 8% (n = 23) of AUS/FLUS cases, and in less than 1% of low-cellularity benign samples. CONCLUSION: 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.

Public-academic partnerships: the University of Hawai'i Rural Health Collaboration: partnerships to provide adult telepsychiatry services.

To address the twofold problem of mental health disparities and limited access to health resources in rural areas, the University of Hawai'i Rural Health Collaboration aims to increase access to behavioral health services to rural areas across the state, primarily via telepsychiatry. The authors highlight lessons learned in regard to forging a university-community partnership, specifically community engagement for patient referral, the shift toward integrated services and away from a specialty clinic model, the importance of community diversity and contextual relevance, and ethical research and practice with indigenous communities.

Conformational changes in Sindbis virions resulting from exposure to low pH and interactions with cells suggest that cell penetration may occur at the cell surface in the absence of membrane fusion.

Alphaviruses have the ability to induce cell-cell fusion after exposure to acid pH. This observation has served as an article of proof that these membrane-containing viruses infect cells by fusion of the virus membrane with a host cell membrane upon exposure to acid pH after incorporation into a cell endosome. We have investigated the requirements for the induction of virus-mediated, low pH-induced cell-cell fusion and cell-virus fusion. We have correlated the pH requirements for this process to structural changes they produce in the virus by electron cryo-microscopy. We found that exposure to acid pH was required to establish conditions for membrane fusion but that membrane fusion did not occur until return to neutral pH. Electron cryo-microscopy revealed dramatic changes in the structure of the virion as it was moved to acid pH and then returned to neutral pH. None of these treatments resulted in the disassembly of the virus protein icosahedral shell that is a requisite for the process of virus membrane-cell membrane fusion. The appearance of a prominent protruding structure upon exposure to acid pH and its disappearance upon return to neutral pH suggested that the production of a "pore"-like structure at the fivefold axis may facilitate cell penetration as has been proposed for polio (J. Virol. 74 (2000) 1342) and human rhino virus (Mol. Cell 10 (2002) 317). This transient structural change also provided an explanation for how membrane fusion occurs after return to neutral pH. Examination of virus-cell complexes at neutral pH supported the contention that infection occurs at the cell surface at neutral pH by the production of a virus structure that breaches the plasma membrane bilayer. These data suggest an alternative route of infection for Sindbis virus that occurs by a process that does not involve membrane fusion and does not require disassembly of the virus protein shell.

Deletions in the transmembrane domain of a sindbis virus glycoprotein alter virus infectivity, stability, and host range.

The alphaviruses are composed of two icosahedral protein shells, one nested within the other. A membrane bilayer derived from the host cell is sandwiched between the protein shells. The protein shells are attached to one another by protein domains which extend one of the proteins of the outer shell through the membrane bilayer to attach to the inner shell. We have examined the interaction of the membrane-spanning domain of one of the membrane glycoproteins with the membrane bilayer and with other virus proteins in an attempt to understand the role this domain plays in virus assembly and function. Through incremental deletions, we have reduced the length of a virus membrane protein transmembrane domain from its normal 26 amino acids to 8 amino acids. We examined the effect of these deletions on the assembly and function of virus particles. We found that progressive truncations in the transmembrane domain profoundly affected production of infectious virus in a cyclic fashion. We also found that membrane composition effects protein-protein and protein-membrane interactions during virus assembly.

Morphological variants of Sindbis virus produced by a mutation in the capsid protein.

Sindbis virus is a complex aggregate of RNA, protein and lipid. The virus is organized as two nested T = 4 icosahedral protein shells between which is sandwiched a lipid bilayer. The virus RNA resides within the inner protein shell. The inner protein shell is attached to the outer protein shell through contacts to proteins in the outer shell, which penetrate the lipid bilayer. The data presented in the following manuscript show that mutations in the capsid protein can result in the assembly of the virus structural proteins into icosahedra of different triangulation numbers. The triangulation numbers calculated, for these morphological variants, follow the sequence T = 4, 9, 16, 25 and 36. All fall into the class P = 1 of icosadeltahedra as was predicted by. The data support their hypothesis that families of icosahedra would be developed by altering the distance between the points of insertion of the five-fold axis. This capsid protein defect also results in the incorporation of much of the capsid protein, into large cytoplasmic aggregates of protein and RNA. These observations support models suggesting that the geometry of a pre-formed nucleocapsid organizes the assembly of the virus membrane proteins into a structure of identical configuration and argues against models suggesting that assembly of the membrane glycoproteins directs the assembly of the nucleocapsid.