GATA3 as a valuable marker to distinguish clear cell papillary renal cell carcinomas from morphologic mimics

Publication date: Available online 11 July 2017
Source:Human Pathology
Author(s): Jose G. Mantilla, Tatjana Antic, Maria Tretiakova
Clear cell papillary renal cell carcinoma (CCPRCC) is a low-grade, indolent neoplasm, with no reported cases of death from disease or metastasis. These lesions can show clinical, morphologic and immunophenotypic overlap with several aggressive forms of renal cell carcinoma (RCC), including clear cell (CCRCC), translocation RCC and papillary RCC (PRCC) with cytoplasmic clearing. Given the difference in behavior, it is important to reliably separate these entities.We retrospectively reviewed 47 tumors from 45 patients with morphologic features of CCPRCC. All cases were stained against CK7, CAIX and GATA3. Cases inconsistent with CCPRCC were reclassified. Additionally, we stained tissue microarrays with 103 typical CCRCC and 62 PRCC, each in triplicate. 25 cases were morphologically and immunophenotypically consistent with CCPRCC; all of them showed diffuse CK7 expression and cup-like reactivity with CAIX. Of these, 19 (76%) showed strong nuclear reactivity for GATA3. Although some non-CCPRCC neoplasms showed at least partial CK7/CAIX co-expression, none were immunopositive for GATA3. All background normal kidneys studied showed GATA3 expression in the distal tubules, collecting ducts and retention cysts of the distal nephron. On follow-up, none of the patients with CCPRCC had recurrences or metastasis. Sensitivity and specificity for GATA3 staining in the diagnosis of CCPRCC were 76% and 100%, with positive and negative predictive values of 100% and 74%.In conclusion, GATA3 is specific and sensitive for CCPRCC, and can be used for accurate distinction from its main mimickers. Co-expression of GATA3 and CK7 in most CCPRCC provides evidence of their origin from distal nephron.



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Inflammatory myofibroblastic tumors of the lung carrying a chimeric A2M–ALK gene: report of two infantile cases and review of the differential diagnosis of infantile pulmonary lesions

Publication date: Available online 11 July 2017
Source:Human Pathology
Author(s): Mio Tanaka, Kenichi Kohashi, Kei Kushitani, Misa Yoshida, Sho Kurihara, Masumi Kawashima, Yuka Ueda, Ryota Souzaki, Yoshiaki Kinoshita, Yoshinao Oda, Yukio Takeshima, Eiso Hiyama, Tomoaki Taguchi, Yukichi Tanaka
We report two infantile cases of pulmonary tumor carrying a chimeric A2M–ALK gene. A2M–ALK is a newly identified anaplastic lymphoma kinase (ALK)-related chimeric gene from a tumor diagnosed as fetal lung interstitial tumor (FLIT). FLIT is a recently recognized infantile pulmonary lesion defined as a mass-like lesion that morphologically resembles the fetal lung. Grossly, FLIT characteristically appears as a well-circumscribed spongy mass, whereas the tumors in these patients were solid and firm. Histologically, the tumors showed intrapulmonary lesions composed of densely proliferating polygonal or spindle-shaped mesenchymal cells with diffuse and dense infiltrations of inflammatory cells, forming microcystic or micropapillary structures lined by TTF1-positive pneumocytes, favoring IMT rather than FLIT. The proliferating cells were immunoreactive for ALK, and A2M–ALK was identified in both tumors with reverse transcription (RT)–PCR. The dense infiltration of inflammatory cells, immunoreactivity for ALK, and the identification of an ALK-related chimeric gene suggested a diagnosis of inflammatory myofibroblastic tumor. Histologically, most reported FLIT show sparse inflammatory infiltrates and a relatively low density of interstitial cells in the septa, although prominent infiltration of inflammatory cells and high cellularity of interstitial cells are seen in some FLITs. The present cases suggest that ALK rearrangements, including the chimeric A2M–ALK gene, may be present in these infantile pulmonary lesions, especially those with inflammatory cell infiltration. We propose that these infantile pulmonary lesions containing a chimeric A2M–ALK gene, be categorized as a specific type of IMT that develops exclusively in neonates and infants.



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A novel sclerosing atypical lipomatous tumor/well-differentiated liposarcoma in a 7-year-old girl: Report of a case with molecular confirmation

Publication date: Available online 11 July 2017
Source:Human Pathology
Author(s): Ran Peng, Huijiao Chen, Xuantao Yang, Xianliang Zhang, Zhang Zhang, Xin He, Hongying Zhang
Atypical lipomatous tumor/well-differentiated liposarcoma/dedifferentiated liposarcoma (ALT/WDL/DDL) is a common type of liposarcoma in late adulthood. However, pediatric ALT/WDL/DDL is extremely rare, and only 3 cases have been described in children younger than 10years of age. Notably, none of these cases harbored MDM2 gene amplification. Here, we reported a sclerosing ALT/WDL in a 7-year-old Chinese girl. Histologically, in most areas, the neoplastic cells were embedded within the collagenous background and typical lipogenic areas were inconspicuous throughout the sclerotic areas. Additionally, scattered small foci of atypical osseous/chondrous elements were identified. Notably, a small typical lipoma-like ALT/WDL area was detected in the periphery of the mass. Immunohistochemically, all the neoplastic components demonstrated positivity for MDM2, CDK4, and p16. Fluorescence in situ hybridization revealed MDM2 gene amplification in all the tumor components. To the best of our knowledge, this is the first example of MDM2-amplified ALT/WDL in this age group.



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Using anatomical landmark to avoid phrenic nerve injury during balloon-based procedures in atrial fibrillation patients

Abstract

Purpose

Atrial fibrillation (AF) is an arrhythmia which affects as many as 2.7 million Americans. AF should be treated, because it can lead to a four-to-fivefold increased risk of experiencing a stroke. The American College of Cardiology/American Heart Association guidelines for the treatment of drug refractory and symptomatic paroxysmal AF denote catheter ablation as the standard of care. The newest ablation treatment, cryoballoon, uses a cold balloon tip. The biggest risk factor associated with the cryoballoon ablation is phrenic nerve injury (PNI). The purpose of this study is to measure relevant distances from specific landmarks to the right phrenic nerve (RPN) to create a safe zone for physicians.

Methods

Using 30 cadaveric specimens, we measured laterally from the right superior pulmonary vein orifice (RSPV) to the RPN at the level of the sixth thoracic vertebra and laterally from the lateral border of the sixth thoracic vertebral body (T6) to the RPN. The depth and width of the left atrium (LA) were also measured to establish a cross-sectional area of the LA. The cross-sectional area of the LA was then correlated with the averaged measurements to see if the area of the LA could be a predictor of the location of the RPN.

Results

The average distance from the RPN–RSPV was 9.6 mm (range 4.3–18.8 mm). The average RPN-T6 distance was 30.6 mm (range 13.7–49.9 mm). There was a non-significant trend that suggests as the size of the LA increases, the measured distances also increased.

Conclusion

Using the lateral border of the sixth thoracic vertebra as a landmark, which can be viewed under fluoroscopy during the procedure, physicians can triangulate the distance to the RSPV and determine the approximate position of the RPN. Furthermore, physicians can perform a preoperative echocardiogram to determine the size of the LA to assist in determining the position of the RPN with the hopes of avoiding injury to the RPN.

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Periaortitis induced by epirubicin and cyclophosphamide for a patient with advanced breast cancer

Abstract

Aortitis is an extremely rare condition, and it may mimic febrile neutropenia during cancer chemotherapy. A 55-year-old female diagnosed with T2N1M1 stage IV breast carcinoma received chemotherapy with EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m² every 3 weeks). At the eleventh day after the first administration of EC, she developed a high-grade fever of 38 °C and stomatitis. We started the intravenous administration of antibiotics at hospitalization, because the laboratory data showed normal white blood cell values 3800/μl but a severe inflammatory reaction (CRP 25.13 mg/dl). The fever and high CRP value continued, and the WBC rose to 14,500/μl at 20th day. However, her condition was stable. On the 25th day after the administration of EC, she complained of back pain, so we performed computed tomography (CT) again and observed thickening of the rind surrounding the descending aorta and bilateral pleural effusion, indicating acute periaortitis. We performed examinations concerning vasculitis and connective tissue disease, but the values were all within normal ranges showing no relationship with other diseases. We stopped the administration of antibiotics on the 20th day, and while we did not administer corticosteroids, however, the fever was resolved and her WBC decreased. She was discharged on day 33, and the other chemotherapy was restarted with pertuzumab, trastuzumab and docetaxel. The patient has remained well without inflammatory reactions. CT at 90 days after EC therapy showed the resolution of the thickened rind of the descending aorta and no aneurysmic changes.

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Inter- and intraindividual variability of the pupillary unrest index

Abstract

Objective

The recording of slow pupillary oscillations in complete darkness is a promising approach for objective evaluation of daytime sleepiness at the physiological level. The aim of the present study was to analyze the magnitude of between- and within-subject variation of the pupillary unrest index (PUI) in a sample of healthy individuals.

Materials and methods

The present data were collected within the framework of a mobile phone study on possible effects of radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Pupillary behavior was monitored in 30 young healthy male volunteers (age 18–30 years) on ten non-consecutive experimental days at 11:00 a.m. and 04:00 p.m., using infrared video pupillography (compact integrated pupillograph, CIP). Since RF-EMF had no impact on the PUI, data were pooled for the present analysis.

Results

Mixed-model analyses of variance (ANOVAs) showed that the PUI was subject to higher interindividual variation as compared to intraindividual variation at both times of measurement. This resulted in intraclass correlation coefficients pointing to a substantial stability of these interindividual differences. A comparison of the PUI results with currently used cutoff values revealed that more than 50% of recordings from young, healthy, non-sleep-disturbed males showed values beyond the “normal” range.

Conclusion

The significant interindividual variability implies that the PUI is not only a state marker. Evaluations of such measurements should therefore consider the PUI as a possible trait marker to ensure comparability and correct interpretation.

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The effects of estradiol valerate and remifemin on liver lipid metabolism

Publication date: Available online 11 July 2017
Source:Acta Histochemica
Author(s): Biao Jin, Wenjuan Wang, Wenpei Bai, Jing Zhang, Ke Wang, Lihua Qin
To investigate the lipid metabolism dysregulation in the liver of ovariectomized (OVX) rats and effects of estradiol valerate (E) and remifemin (ICR) thereon, forty female Sprague-Dawley rats were randomly divided into sham-operated (SHAM), OVX, OVX+E, and OVX+ICR group. After 4 weeks’ E or ICR treatment, serum estrogen, cholesterol, and triglyceride levels; lipid droplets in hepatocytes; hepatocyte morphology; and the expression of estrogen receptor α (ERα), liver X receptor (LXR), and sterol regulatory element binding proteins (SREBPs) in the liver of the rats were assessed. OVX rats had significantly decreased serum estrogen levels, which significantly increased after treatment with E but not with ICR. Serum triglyceride levels and the amount of lipid droplets in hepatocytes increased after ovariectomy, and significantly decreased after E treatment. In addition, ICR treatment markedly increased serum triglyceride levels and lipid droplet size. No significant differences in the serum cholesterol levels were observed among the four groups. After ovariectomy, hepatocyte mitochondria became hypertrophic and misformed, which were reversed with E or ICR treatment. ICR-treated rats also showed endoplasmic reticulum disorganization. After ovariectomy, ERα and LXR levels significantly decreased while SREBP expression increased. E treatment increased ERα and LXR levels while ICR treatment only increased LXR expression. E treatment decreased SREBP-1c levels, whereas SREBP-1c levels increased with ICR treatment. Treatment with E significantly reversed the ovariectomy-induced dysregulation of hepatocyte lipid metabolism, which was, however, exacerbated with ICR treatment. The effects of E and ICR on hepatocyte lipid metabolism may involve the regulation of LXR and SREBP-1c.



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