Histological evidence supports low anesthetic bladder capacity as a marker of a bladder-centric disease subtype in interstitial cystitis/bladder pain syndrome.

INTRODUCTION AND HYPOTHESIS: Low anesthetic bladder capacity has been shown to be a biomarker for bladder-centric interstitial cystitis/bladder pain syndrome (IC/BPS). The goal of this study was to determine if histopathological evidence from bladder biopsies supports anesthetic bladder capacity (BC) as a marker to distinguish a bladder-centric IC/BPS subtype. METHODS: From a review of our large IC/BPS cohort of patients undergoing hydrodistention, we identified a total of 41 patients with low BC (≤ 400 ml); an additional 41 consecutive patients with BC > 400 ml were selected as the comparator group. The original bladder mucosal biopsy pathology slides were re-reviewed by a single pathologist (blinded to patient information) using a standardized grading scale developed for this study. RESULTS: Histologically, the low BC subjects exhibited higher levels of acute inflammation (p = 0.0299), chronic inflammation (p = 0.0139), and erosion on microscopy (p = 0.0155); however, there was no significant difference in mast cell count between groups (p = 0.4431). There was no significant gender difference between the groups; female patients were the majority in both groups (low BC: 94.12%, non-low BC: 100%; p = 0.1246). Individuals in the low BC group were older (p < 0.0001), had a higher incidence of Hunner's lesions on cystoscopy (p < 0.0001), and had significantly higher scores, i.e., more bother symptoms, on two IC/BPS questionnaires (ICPI, p = 0.0154; ICSI, p = 0.0005). CONCLUSIONS: IC/BPS patients with low anesthetic bladder capacity have histological evidence of significantly more acute and chronic inflammation compared with patients with a non-low bladder capacity. These data provide additional evidence to support low bladder capacity as a marker of a distinct bladder-centric IC/BPS phenotype.

Giant pericardial lymphangioma--imaging, surgical, and pathologic correlations.

Pericardial lymphangiomas are extremely rare benign tumors of lymphatic origin that are usually diagnosed in children. These tumors are often asymptomatic but can cause symptoms secondary to mass effect. We report a case of a giant pericardial lymphangioma that was incidentally discovered in a 58-year-old woman and present imaging, surgical, and pathologic correlations.

Feasibility of lung cancer RNA acquisition from a single transbronchial or transthoracic needle pass (FASTT trial).

INTRODUCTION: RNA isolation from tumor tissue is used for biomarker analyses and validation. Limited diagnostic material from small volume biopsies combined with an increasing demand for standard histologic, molecular characterization, and next generation sequencing applications often leads to limited material for research. We sought to evaluate small volume sampling of lung cancer tissue collected from a single needle pass during a diagnostic procedure and determine if it can provide RNA of acceptable quantity and quality. METHODS: We enrolled 140 patients with probable primary bronchogenic carcinoma and collected RNA from a dedicated FNA aspiration. Total RNA (ηg), RNA integrity number (RIN), and %Mass in base pairs were evaluated from each patient sample. A customized nanoString nCounter® 95-gene panel was used to profile the expression patterns of feature NSCLC genes. We compared gene expression patterns that distinguish lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) in our cohort with a corresponding Cancer Genome Atlas (TCGA) NSCLC datasets. RESULTS: Of the 149 patients consented. RNA-extraction was performed in 101 eligible patients. A satisfactory total RNA mass and RIN was quantified for all samples with a similar distribution among cellular subtypes. Mean %-Mass over 300 base pairs was noted for all specimens and 96% of samples met criteria to perform genetic evaluation with our commercialized gene expression assay. The FNA-derived transcriptomic results showed excellent consistency with the TCGA counterparts, and the differential expression pattern of LUAD vs LUSC subtypes were highly similar. DISCUSSION: In this study, RNA retrieval from a single-pass FNA regardless of procedural approach showed equivalence and suitability for gene expression assessments. RNA extraction from small volume samples has the potential to provide valuable material for genetic profiling.

Fine needle aspiration biopsy diagnosis of primary clear cell chondrosarcoma: A case report.

Clear cell chondrosarcoma is a rare chondrosarcoma variant often involving the long bone epiphyses of young to middle aged adults. We report herein a case involving the left femoral head in a 25-year-old female with a 3-month history of worsening left hip pain. Radiographs revealed a complex, multifocal and lytic lesion centered in the left proximal femoral epiphysis with involvement of the femoral neck. Computed tomography-guided fine needle aspiration biopsy with concomitant core needle biopsy was performed, and a diagnosis of clear cell chondrosarcoma was rendered. Cytologic smears revealed aggregates of matrix material accompanied by a population of mostly uniform spindled to epithelioid and histiocytoid cells, rarely accompanied by osteoclast-type giant cells. The patient underwent surgical resection with -total hip replacement, and subsequent pathologic examination confirmed the initial needle biopsy diagnosis. There has been no evidence of local recurrence or distant metastases with 3-years follow-up. To our knowledge, this is the first reported example of a primary clear cell chondrosarcoma initially evaluated by fine needle aspiration biopsy.

Nafcillin-Induced Allergic Eosinophilic Cholestatic Hepatitis.

A 71-year-old female with no history of liver disease or antibiotic allergy developed jaundice with elevated liver enzymes and eosinophilia following treatment with nafcillin for septic arthritis. Further workup demonstrated hepatocellular dysfunction and liver biopsy showed expansion of portal tracts by lymphocytes and eosinophils consistent with a hypersensitivity reaction. Nafcillin and related antibiotics were withdrawn, and her symptoms resolved 3 months later. We searched PubMed using terms of "nafcillin cholestasis" and "nafcillin hepatitis", and a review of the literature showed other reports of nafcillin-induced hepatitis and cholestasis. Avoidance and on occasion the guarded use of glucocorticoids can lead to recovery from the insult. This case report shows that while rare, nafcillin can cause cholestatic hepatitis through a likely eosinophil-mediated hypersensitivity reaction. Further studies are needed to elucidate the mechanism of this reaction.

Changes in cardiac myocyte morphology alter the properties of voltage-gated ion channels.

OBJECTIVE: The goal of this study was to determine if the properties of the transient outward potassium (I(to)), TTX-resistant sodium (I(Na)) and L-type calcium (I(Ca)) currents are altered during changes in cardiac cell shape. METHODS: Ventricular myocytes were isolated from 3- to 4-day-old neonatal rats and cultured on either non-aligned or aligned collagen thin gels. In contrast to the flat, stellar-shaped myocytes obtained when the cells are plated on non-aligned collagen gels, myocytes plated on aligned gels display an elongated, rod-like shape. Ion channel expression was measured using the whole-cell arrangement of the patch clamp technique and Western blot analysis. RESULTS: Peak values for I(to), I(Na) and I(Ca) were 9+/-1, 71+/-13 and 7+/-1 pA/pF, respectively, in the flat cells, and increased to 21+/-2, 190+/-26 and 13+/-1 pA/pF, respectively, in the aligned cells. Application of forskolin (2 microM) and 3-isobutyl-1-methylxanthine (100 microM) resulted in a 101+/-18% increase in I(Ca) in the flat cells, but increased the current by only 43+/-9% in the aligned cells. Internal dialysis of the myocytes with cAMP strongly increased the peak I(Ca) in the flat cells, but caused no significant change in the aligned cells. While both basal and forskolin-stimulated levels of cAMP were the same in the two cell morphologies, the expression of the calcium channel alpha(1C) subunit was increased in the aligned cells. CONCLUSIONS: The expression and regulatory properties of voltage-gated calcium channels are modified during changes in neonatal rat myocyte shape.

Mucoepidermoid carcinoma of the thyroid with concomitant papillary carcinoma: comparison of findings on fine-needle aspiration biopsy and histology.

We report two cases of mucoepidermoid carcinoma (MEC) of the thyroid gland coexisting with, and possibly arising in, papillary thyroid carcinoma (PTC). In the first case, CT-guided fine-needle aspiration (FNA) was performed on a paratracheal mass representing extrathyroidal invasion of a right thyroid lobe tumor. The aspirate showed papillary fronds and cells in honeycombed arrangements with fine chromatin, enlarged nuclei, nuclear grooves, and intranuclear inclusions in a background of mucus and blood; a diagnosis of PTC was rendered initially. However, examination of histologic sections of the mass showed nests of malignant squamous cells with interspersed mucous cells and extracellular mucin, concordant with MEC, as well as PTC. A retrospective review of the FNA specimen identified MEC. In the second case, ultrasound-guided FNA was performed on a right thyroid lobe nodule. The aspirate contained two populations of epithelial cells: larger cells showing foci of both squamous and glandular differentiation that were interpreted as MEC and smaller follicular cells with nuclear changes characteristic of PTC; both were addressed in the diagnostic report. Primary MEC of the thyroid is a rare neoplasm typically exhibiting indolent clinical behavior, although our first case demonstrated extensive local invasion. It is thought to arise from squamous metaplasia associated with PTC, Hashimoto thyroiditis, or other inflammatory or neoplastic processes. In thyroid FNAs, the presence of neoplastic mucous cells and extracellular mucin plus malignant squamous cells is diagnostic of MEC. As MEC is thought to arise in PTC, the finding of the latter in these aspiration specimens is not unexpected.

Cushing's syndrome and nocardiosis associated with a pulmonary carcinoid tumor: report of a case and review of the literature.

Ectopic hormone production is an uncommon complication of neoplastic lung disease. Rarely, patients may present with signs and symptoms of systemic endocrine dysfunction related to a hormone-secreting tumor. Bronchopulmonary carcinoids are the most common neoplasm implicated in ectopic ACTH-dependent Cushing's syndrome. Persistent hypercortisolism, such as that which occurs in Cushing's syndrome, causes immunosuppression and makes patients vulnerable to opportunistic infections. We present a case of a 42-year-old woman diagnosed with ACTH-dependent Cushing's syndrome which was originally thought to stem from a pituitary lesion as interpreted on magnetic resonance imaging. Her symptoms persisted after undergoing hypophysectomy, and further work-up involving a fine needle aspiration of the left lung revealed an ACTH-producing carcinoid tumor. Before treatment could be administered, the patient developed several new suspicious nodules in the left lung that were shown by fine needle aspiration to be infectious in nature. A Gram stain revealed numerous Gram positive branching organisms, and culture of the specimen grew Nocardia asteroides. Her pulmonary infection was treated with antibiotics and she underwent successful ablation of the carcinoid tumor.

Benefits of a combined approach to sampling of renal neoplasms as demonstrated in a series of 351 cases.

Percutaneous radiofrequency ablation is increasingly used for curative treatment of primary cancers of the kidney. We reviewed our experience of percutaneous sampling performed under computed tomographic guidance with fine needle aspiration biopsy (FNAB) and core biopsy (CB), and we report on the complementary roles of these 2 techniques in a series of 351 consecutive patients undergoing radiofrequency ablation for renal neoplasms. Both FNAB and CB were obtained in 290 cases, of which 156 patients (54%) were positive for neoplasm in both specimens, and 27 (9%) were negative for tumor in both specimens. In 58 (20%) patients, the FNABs were positive, but the CBs were negative, and the reverse occurred in 11 patients (4%). When suspicious interpretations by FNAB and CB are included as positives in the calculations, both their complementary nature and the relative higher diagnostic yield of FNAB persisted. In 25 cases with FNABs positive for neoplasm, the CB allowed a more specific tumor classification. The 19 cases of FNAB which were read as negative/benign had corresponding CBs that were also negative/benign in 13 cases; yet, 6 were diagnostic of renal cell carcinoma not otherwise specified (1 case), renal cell carcinoma clear cell/conventional (4 cases), and non-Hodgkin lymphoma (1 case). These and additional findings illustrate the complementary value of the combination of the 2 biopsy methods for a reliable pretherapy morphologic confirmation of specific renal neoplasms. FNAB has relatively greater sensitivity and utility for on-site evaluation, whereas CB provides an additional sample for more specific subclassification and additional studies.

Developing selection criteria for prostate-sparing cystectomy: a review of cystoprostatectomy specimens.

OBJECTIVES: To determine risk factors for prostate pathology, which may serve as guidelines for identifying patients who may be inappropriate for prostate-sparing cystectomy for treatment of transitional cell cancer of the bladder. METHODS: After obtaining Institutional Review Board approval, we reviewed the clinical and pathologic data from consecutive men treated with radical cystoprostatectomy (RCP) between January 2003 and September 2008. We reviewed the RCP pathology for prostatic involvement by transitional cell carcinoma (PI-TCC) as well as presence of prostate cancer (PCa). Univariate analysis was used to test for association of clinical parameters with prostatic involvement in RCP specimens. RESULTS: A total of 96 patients with a median age of 67 (interquartile range: 47, 79) underwent RCP between January 2003 and September 2008. PI-TCC was present in 24 patients (25%) of which 6 (25%) had carcinoma in situ (CIS) only and 18 (75%) had stromal invasion. We identified PCa in 40 patients (42%). CIS (odds ratio, 3.2, P = .018) and tumor situated at or below the trigone (odds ratio, 3.3, P = .046) at the pre-RCP transurethral bladder tumor resection were associated with PI-TCC. CONCLUSIONS: PI-TCC and PCa are common findings at RCP. The location of the bladder tumor situated at or below the trigone and the presence of CIS at transurethral bladder tumor resection is associated with increased risk for PI-TCC and should be considered at least relative contraindications for prostate-sparing cystectomy. A thorough investigation for PCa should be conducted for all possible candidates.

Increased vacuolar Na(+)/H(+) exchange activity in Salicornia bigelovii Torr. in response to NaCl.

Shoots of the halophyte Salicornia bigelovii are larger and more succulent when grown in highly saline environments. This increased growth and water uptake has been correlated with a large and specific cellular accumulation of sodium. In glycophytes, sensitivity to salt has been associated with an inability to remove sodium ions effectively from the cytoplasm in order to protect salt-sensitive metabolic processes. Therefore, in Salicornia bigelovii efficient vacuolar sequestration of sodium may be part of the mechanism underlying salt tolerance. The ability to compartmentalize sodium may result from a stimulation of the proton pumps that provide the driving force for increased sodium transport into the vacuole via a Na(+)/H(+) exchanger. In current studies, increased vacuolar pyrophosphatase activity (hydrolysis of inorganic pyrophosphate and proton translocation) and protein accumulation were observed in Salicornia bigelovii grown in high concentrations of NaCl. Based on sodium-induced dissipation of a pyrophosphate-dependent pH gradient in vacuolar membrane vesicles, a Na(+)/H(+) exchange activity was identified and characterized. This activity is sodium concentration-dependent, specific for sodium and lithium, sensitive to methyl-isobutyl amiloride, and independent of an electrical potential. Vacuolar Na(+)/H(+) exchange activity varied as a function of plant growth in salt. The affinity of the transporter for Na(+) is almost three times higher in plants grown in high levels of salt (K(m)=3.8 and 11.5 mM for plants grown in high and low salt, respectively) suggesting a role for exchange activity in the salt adaptation of Salicornia bigelovii.