Oncocytic Follicular Cell-Derived Thyroid Tumors With Papillary Growth Pattern: A Clinicopathologic Study of 32 Cases.

CONTEXT.­: Oncocytic thyroid tumors displaying a papillary growth pattern are rare and may cause diagnostic problems. OBJECTIVE.­: To examine the clinicopathologic features of a series of 32 follicular cell-derived tumors composed of cells with oncocytic cytoplasm and displaying papillary architecture. DESIGN.­: Thirty-two cases were collected and studied to assess clinicopathologic features, including immunohistochemical and molecular testing for BRAF V600E. RESULTS.­: The patients were 26 women and 6 men, aged 17 to 77 years. The nodules ranged from 0.3 to 6.0 cm. Eighteen cases showed features of oncocytic hyperplastic nodules and were identified against a background of thyroid follicular nodular disease; 4 cases showed features of oncocytic follicular adenoma; and 10 cases corresponded to carcinomas with oncocytic and papillary features. Nuclear features of papillary thyroid carcinoma were absent or exceedingly rare. All cases were negative for HBME-1 and cytokeratin 19 (CK19) and wild type for BRAF V600E. Follow-up in 25 patients showed that all patients with hyperplastic nodules and oncocytic follicular adenomas were alive and well and free of disease from 7 to 20 years. One patient with oncocytic follicular carcinoma showed metastases and died of tumor at 16 months; 2 patients with carcinoma had metastases and recurrence at 6 and 7 years; and 5 patients with invasive tumors were free of disease from 5 to 10 years. CONCLUSIONS.­: Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma.

Differentiation of intracranial Rosai-Dorfman histiocytosis from meningioma using MR perfusion.

Intracranial Rosai-Dorfman disease may be indistinguishable from meningioma. This distinction is essential, as they are treated very differently. We present two cases where perfusion imaging helped make this distinction, allowing one to be treated successfully without craniotomy. Perfusion imaging may be a powerful adjunct in cases where RDD mimics meningioma.

Histopathology of Pituitary Lesions.

This article reviews the histopathology and classification of neoplasms that arise from the adenohypophysis (anterior pituitary), the neurohypophysis (posterior pituitary) as well as other common miscellaneous lesions that arise within or secondarily involve the pituitary gland.

Metastatic Pleomorphic Lobular Carcinoma of the Breast to the Hypothalamus Presenting as a Primary Pituitary Lesion Presenting 17 Years Later-Report of a Case and Review of the Literature.

Carcinomas metastatic to the brain are common, however, metastatic disease to the hypothalamic- pituitary region is uncommon and account for less than 3.6% of all resected malignant pituitary tumors. Most metastatic disease in that region derives from a lung or breast primary, with both ductal and lobular carcinoma reported. We report what we believe is the first case of pleomorphic lobular carcinoma metastatic to the hypothalamus. This case is also reaffirms that late metastasis from breast cancer should be considered in the differential diagnosis. It is important for the clinician to consider the clinical history of breast cancer, even when remote, in the differential diagnosis.

Genotype phenotype analysis in a family carrying truncating mutations in the titin gene.

We report a family carrying a previously described truncating mutation, NM_001267550.2(TTN):c.107889del p.(Lys35963Asnfs*9) in exon 364, and a novel truncating mutation, NM_001267550.1:c.100704C > A p.(Tyr33568*) in exon 358 in the titin gene. The c.107889del mutation, which was maternally transmitted, has been previously described in patients from the Iberian Peninsula. The mother was of Peruvian descent suggesting a potential European ancestral origin of this mutation. In this family, a daughter, who is a compound heterozygote carrying both these mutations, developed a peripartum cardiomyopathy during her second pregnancy. Subsequently, she was diagnosed with a myopathy following electromyography testing and a muscle biopsy which showed fiber type disproportion. Her brother, who carries only the paternally inherited c.100704C > A mutation, developed a cardiomyopathy following a suspected viral illness. Their father, who transmitted this mutation, has no evidence of a cardiomyopathy. We hypothesize that the c.100704C > A mutation confers susceptibility to the development of cardiomyopathy which may be brought on by cardiovascular stress. Our study of this family expands the genotype and phenotype spectrum of disorders that can be associated with mutations in the titin gene.

A Case of Reversible Infantile Respiratory Chain Deficiency Presenting With Hypotonia, Hyperammonemia, and Failure to Thrive.

Reversible infantile respiratory chain deficiency, previously termed reversible infantile cytochrome c oxidase (COX) deficiency myopathy, is a rare mitochondrial disorder that is characterized by severe hypotonia and generalized muscle weakness in infancy that is associated with lactic acidosis. Affected infants will spontaneously recover, if they survive the first months of life. Here, we present the case of a 4-week-old girl who initially presented with hyperammonemia, hypotonia, and failure to thrive, for which she was referred for genetic evaluation. After several tests, a distinct genetic syndrome could not be identified and she continued to deteriorate. A muscle biopsy was performed and demonstrated severe mitochondrial myopathy with abundant COX-negative fibers. Ultrastructural abnormalities of the mitochondria, diagnostic of mitochondrial myopathy, were identified on electron microscopy. Molecular studies revealed the classic homoplasmic disease causing mutation, m.14674 T>C in the MT-TE gene, associated with reversible COX deficiency. Although hyperammonemia is an unusual presentation for mitochondrial myopathies, specifically reversible infantile respiratory chain deficiency, it should be included in the list of possible presenting symptoms for this condition.

Post-Traumatic Pituitary Tumor Apoplexy After Closed Head Injury: Case Report and Review of the Literature.

BACKGROUND: Head trauma is a rare inciting factor of pituitary apoplexy (PA); however, there is a clear temporal relationship between trauma and apoplexy, and this is the first reported case of PA after an assault. CASE DESCRIPTION: We present a rare case of a 63-year-old man who developed PA after sustaining a closed head injury from assault with a metal pole. The patient had a known pituitary tumor for which he had previously declined surgical resection. On initial computed tomography scan, there was no traumatic intracerebral hemorrhage or subarachnoid hemorrhage. There was sellar expansion but no obvious sellar hemorrhage. Within 48 hours of admission, the patient was presumed septic after developing altered mental status, fevers, hypotension, and tachycardia. Magnetic resonance imaging of the brain with and without gadolinium revealed a poorly enhancing, necrotic, and hemorrhagic pituitary mass, consistent with pituitary tumor apoplexy. After administration of intravenous glucocorticoids, the patient underwent emergent endoscopic transsphenoidal resection of the pituitary tumor apoplexy. Postoperatively, the patient had neurologic improvement with stable vision. CONCLUSIONS: Early and accurate diagnosis is important to allow for timely neurosurgical intervention. Symptoms of fever, hypotension, and tachycardia in a patient with a known sellar mass should raise the suspicion of hypocortisolemia from pituitary tumor apoplexy.

Novel Mutation in Anoctamin 5 Gene Causing Limb-Girdle Muscular Dystrophy 2L.

We report a 49-year-old man who presented with a history of asymmetric weakness. His neurological examination and electromyogram testing suggested the presence of a myopathy. A muscle biopsy confirmed the presence of a myopathy with several lobulated, whorled and ring fibers, and it showed no evidence of inflammation. Genetic testing of more than 50 genes known to cause myopathy was performed and demonstrates the presence of the common founder mutation in ANO5 gene c.191dupA, which he inherited from his unaffected father. In addition, he inherited a novel mutation, c.1063C>T (p.L355F) in exon 11 of ANO5 gene from his unaffected mother. The founder mutation is a known pathogenic variant and, based on our protein modeling analysis, the novel c.1063C>T (p.L355F) variant is likely pathogenic. This indicates that he is a compound heterozygote, providing strong support for the diagnosis of limb-girdle muscular dystrophy 2L.

An in vivo model of double-unit cord blood transplantation that correlates with clinical engraftment.

Double-unit cord blood transplantation (DCBT) appears to enhance engraftment despite sustained hematopoiesis usually being derived from a single unit. To investigate DCBT biology, in vitro and murine models were established using cells from 39 patient grafts. Mononuclear cells (MNCs) and CD34(+) cells from each unit alone and in DCB combination were assessed for colony-forming cell and cobblestone area-forming cell potential, and multilineage engraftment in NOD/SCID/IL2R-γ(null) mice. In DCB assays, the contribution of each unit was measured by quantitative short tandem repeat region analysis. There was no correlation between colony-forming cell (n = 10) or cobblestone area-forming cell (n = 9) numbers and clinical engraftment, and both units contributed to DCB cocultures. In MNC transplantations in NOD/SCID/IL2R-γ(null) mice, each unit engrafted alone, but MNC DCBT demonstrated single-unit dominance that correlated with clinical engraftment in 18 of 21 cases (86%, P < .001). In contrast, unit dominance and clinical correlation were lost with CD34(+) DCBT (n = 11). However, add-back of CD34(-) to CD34(+) cells (n = 20) restored single-unit dominance with the dominant unit correlating not with clinical engraftment but also with the origin of the CD34(-) cells in all experiments. Thus, unit dominance is an in vivo phenomenon probably associated with a graft-versus-graft immune interaction mediated by CD34(-) cells.

Astrovirus encephalitis in boy with X-linked agammaglobulinemia.

Encephalitis is a major cause of death worldwide. Although >100 pathogens have been identified as causative agents, the pathogen is not determined for up to 75% of cases. This diagnostic failure impedes effective treatment and underscores the need for better tools and new approaches for detecting novel pathogens or determining new manifestations of known pathogens. Although astroviruses are commonly associated with gastroenteritis, they have not been associated with central nervous system disease. Using unbiased pyrosequencing, we detected an astrovirus as the causative agent for encephalitis in a 15-year-old boy with agammaglobulinemia; several laboratories had failed to identify the agent. Our findings expand the spectrum of causative agents associated with encephalitis and highlight unbiased molecular technology as a valuable tool for differential diagnosis of unexplained disease.

Further genetic evidence for a panic disorder syndrome mapping to chromosome 13q.

Substantial evidence supports that there is a genetic component to panic disorder (PD). Until recently, attempts at localizing genes for PD by using standard phenotypic data have not proven successful. Previous work suggests that a potential subtype of PD called the panic syndrome exists, and it is characterized by a number of medical conditions, most notably bladder/renal disorders. In the current study, a genome scan with 384 microsatellite markers was performed on 587 individuals in 60 multiplex pedigrees segregating PD and bladder/kidney conditions. Using both single-locus and multipoint analytic methods, we found significant linkage on chromosome 22 (maximum heterogeneity logarithm of odds score = 4.11 at D22S445) and on chromosome 13q (heterogeneity logarithm of odds score = 3.57 at D13S793) under a dominant-genetic model and a broad phenotypic definition. Multipoint analyses did not support the observation on chromosome 22. The chromosome 13 findings were corroborated by multipoint findings, and extend our previous findings from 19 of the 60 families. Several other regions showed elevated scores by using when one analytic method was used, but not the other. These results suggest that there are genes on chromosome 13q, and possibly on chromosome 22 as well, that influence the susceptibility toward a pleiotropic syndrome that includes PD, bladder problems, severe headaches, mitral valve prolapse, and thyroid conditions.