Rhabdomyosarcoma with epithelioid morphology: A challenging cytologic diagnosis in a pleural effusion.

Rhabdomyosarcomas (RMS) are rare malignant skeletal muscle tumors that present more commonly in pediatric populations. The WHO currently classifies RMS into four types, embryonal, alveolar, pleomorphic, and spindle cell/sclerosing variants. Epithelioid rhabdomyosarcoma (EpiRMS) is another rare, recently described subtype of RMS presenting in older patients with a male predominance and has a rapidly progressive clinical course with frequent metastases. EpiRMS closely mimics poorly differentiated carcinoma or melanoma, demonstrating discohesive large epithelioid cells with abundant eosinophilic cytoplasm, frequent glassy cytoplasmic inclusions, large vesicular nuclei, and prominent nucleoli. We present a case of metastatic rhabdomyosarcoma with features reminiscent of EpiRMS presenting as a pleural effusion, closely followed by an inguinal lymph node biopsy. The malignant cells in the pleural fluid were diffusely positive for desmin, negative for MyoD1, myogenin, S100 and SOX10, and retained INI-1 expression. Subsequent lymph node biopsy demonstrated identical malignant epithelioid cells that were positive for desmin, myoD1 and myogenin, and a cytological diagnosis of "metastatic rhabdomyosarcoma, favor epithelioid rhabdomyosarcoma" was given considering the concurrent lymph node biopsy morphology and immunoprofile. A diagnosis of rhabdomyosarcoma, though rare and challenging, should not be overlooked when considering malignant cells with an epithelioid morphology in cytology specimens.

Mycophenolate Mofetil and Pulmonary Fibrosis After Kidney Transplantation: A Case Report.

BACKGROUND Mycophenolate mofetil (MMF) induced lung disease has been described in only a few isolated reports. We report a case of fatal respiratory failure associated with MMF after kidney transplantation. CASE REPORT A 50-year-old Hispanic male with a history of end-stage renal disease secondary to hypertension underwent deceased donor kidney transplantation. His preoperative evaluations were normal except for a chest x-ray which showed bilateral interstitial opacities. Tacrolimus and MMF were started on the day of surgery. His postoperative course was uneventful and he was discharged on postoperative day 5. One month later, he presented with shortness of breath and a cough with blood-tinged sputum. His respiratory condition deteriorated rapidly, requiring intubation. Chest computer tomography (CT) demonstrated patchy ground-glass opacities with interlobular septal thickening. Comprehensive pulmonary, cardiac, infectious, and immunological evaluations were all negative. Open lung biopsy revealed extensive pulmonary fibrosis with no evidence of infection. He temporarily improved after discontinuation of tacrolimus and MMF, however, on resuming MMF his respiratory status deteriorated again and he subsequently died from hypoxic respiratory failure. CONCLUSIONS An awareness of pulmonary lung disease due to MMF is important to prevent adverse outcomes after organ transplantation. MMF must be used with utmost care in recipients with underlying lung disease as their pulmonary condition might make them more susceptible to any harmful effects of MMF.

Double slide viewing as a cytology quality improvement initiative.

Few studies have measured the effect of pre-sign out double viewing of cytology cases as a means to decrease error. Three Agency for Healthcare Research and Quality-funded project sites performed pre-sign out double viewing of 431 pulmonary cytology cases. Two-step or more differences in diagnosis were arbitrated as interpretive errors, and the effect of double viewing was measured by comparing the frequency of cytologic-histologic correlation-detected errors in the previous 2 years with the double-viewing period. The number of interpretive errors detected by double viewing for the 3 institutions was 2.7%, 0% and 1.9%, respectively. Double viewing did not lower the frequency of cytologic-histologic correlation false-negative errors. We conclude that double viewing detects errors in up to 1 of every 37 cases and that biases in the double-viewing process limit error detection.

Use of a new method in reaching consensus on the cause of cytologic-histologic correlation discrepancy.

Pathologists exhibit very poor agreement in adjudicating the cause of cytologic-histologic correlation discrepancies, which contributes to problems in designing interventions to reduce discrepancy frequency. In this observational study, we developed a visual method of adjudicating discrepancy cause, termed the No-Blame Box method, which consisted of initially assessing specimen interpretability by separately evaluating specimen quality and the presence of tumor. Five pathologists blindly adjudicated the cause of discrepancy in pulmonary specimens from 40 patients. The kappa statistic of all pathologist pairs in adjudicating discrepancy cause using the No-Blame Box method ranged from 0.400 to 0.796, indicating acceptable to excellent agreement. Pathologists ranged in their assessment of specimen interpretability from 13% to 20%, and in no case did all 5 pathologists concur that a specimen was interpretable. Most discrepancies resulted from pathologists diagnosing noninterpretable samples. Pathologists who used the No-Blame Box showed significant agreement in the adjudication of discrepancy cause.

Low hospital mortality in patients with acute interstitial pneumonia.

STUDY OBJECTIVES: To compare the presenting features and outcome of patients with acute interstitial pneumonia (AIP) with other patients with diffuse alveolar damage (DAD) and with historical control subjects. DESIGN: Retrospective chart review. SETTING: A large, urban, teaching hospital. INTERVENTIONS: Patients were classified into idiopathic (AIP group) and secondary causes of DAD (ARDS group) according to available clinical and microbiology data. AIP and ARDS cases were compared, and ARDS cases were analyzed for long-term outcome. MEASUREMENTS AND RESULTS: Twenty patients with pathologic diagnosis of DAD were identified. Four cases were excluded; eight cases of ARDS due to known etiologies were identified. These etiologies included pneumonia and sepsis (n = 6), cocaine use (n = 1), and carmustine chemotherapy (n = 1). Eight cases of AIP were found. When compared with the ARDS group, patients in the AIP group had a longer time from the onset of symptoms until hospital admission (16.8 +/- 15.7 days vs 2.2 +/- 1.0 days, p = 0.0015) and a shorter time from hospital admission to open-lung biopsy (8.3 +/- 3.0 days vs 15.5 +/- 9.5 days, p = 0.02) [mean +/- SD]. Seven of eight patients with AIP and four of eight patients with ARDS survived to hospital discharge (p = not significant). The 12.5% mortality rate for patients with AIP reported in this series was significantly lower than the previously reported cumulative rate of 69.5% (p = 0.0025). Follow-up in five AIP survivors for a mean of 7.6 +/- 3.5 years (range, 3 to 11 years) showed all to be without shortness of breath or relapse despite mild residual fibrosis on chest radiograph and mild-to-moderate restriction on pulmonary function tests (mean total lung capacity, 68.5 +/- 6.2% predicted). CONCLUSIONS: Our data support a favorable hospital and long-term outcome for patients with AIP, with no evidence of recurrence or progression to chronic interstitial lung disease.

Wound healing in the paranasal sinuses after Coblation, Part II: evaluation for endoscopic sinus surgery using a sheep model.

BACKGROUND: A previous study on wound healing with a rabbit model showed thermal injury to sinus mucosa with complete respiratory re-epithelialization by postoperative day (POD) 29. This study was designed to further understand the pattern of injury using the bipolar radiofrequency plasma process used by the Coblator and evaluate postprocedure healing. METHODS: Based on experience with our rabbit model, three sheep underwent endoscopic sinus surgery. Coblation was applied to inferior turbinate mucosa in three areas for 2, 4, or 6 seconds. After resection of the contralateral middle turbinate and ethmoidectomy, Coblation was applied to the lateral wall or lamina papyracea for 2 seconds. The ethmoid and turbinate specimens were resected en bloc during necropsy immediately for the first sheep and on POD 14 for the others. RESULTS: Coblation resulted in immediate loss of surface respiratory epithelium and thermal-type injury to the underlying seromucinous glands. On POD 14, the Coblation site showed re-epithelialization with respiratory epithelium. The underlying seromucinous glands were replaced by mild fibrosis. A small, well-defined zone of injury was shown. Longer use did not result in a deeper injury. Rather, the depth of injury was dependent on the type of submucosal tissue present. Underlying bone was associated with reactive, regenerative changes. No histological changes were shown in the orbit. CONCLUSION: The effects of Coblation on sheep mucosa show a similar injury and healing pattern to that shown on rabbit mucosa. Based on this work and the previous rabbit study, the Coblator may be an additional tool for use in endoscopic sinus surgery.

Racial differences in sarcoidosis granuloma density.

STUDY OBJECTIVES: While sarcoidosis generally inflicts a greater morbidity on African-American compared with Caucasian patients, no studies have examined whether racial differences exist in the intensity of the histologic hallmark of sarcoidosis, noncaseating granulomas. DESIGN AND SETTING: The study was conducted as a retrospective case series in a tertiary referral center. PATIENTS: The study included 187 patients with histopathologic confirmation of sarcoidosis by trans- and/or endobronchial biopsy between July 1991 and December 2001. MEASUREMENTS AND RESULTS: Granuloma density was the average number of granulomas per biopsy piece on the slide with the most intense granulomatous inflammation at fourfold magnification. Overall, African-American patients had a twofold greater median granuloma density than Caucasians (p = 0.005). In a negative binomial multivariate model, radiographic pattern had the strongest association with granuloma density, with Scadding stage II and III patients having adjusted granuloma densities of 60% (p = 0.005) and 105% (p = 0.0001) higher than stage I patients. In the specific-tissue types, radiographic stage-adjusted granuloma densities in African-American patients were 49% greater in bronchial tissue (p = 0.03), but only a 27% greater in alveolar tissue (p = 0.51). CONCLUSIONS: A greater granuloma density in bronchiolar lung tissue of African-American sarcoidosis patients may explain racial differences in diagnostic yield by lung biopsy and disease severity at diagnosis. This association persists even after controlling for Scadding radiographic stage, a measure of disease severity strongly associated with granuloma density.

Wound healing in the rabbit paranasal sinuses after Coblation: evaluation for use in endoscopic sinus surgery.

BACKGROUND: Bipolar radiofrequency can be used surgically to excise and cauterize tissue simultaneously. It has potential for use in endoscopic sinus surgery (ESS). This study was performed to determine the extent and pattern of injury in the paranasal sinuses with bipolar radiofrequency and evaluate wound healing. METHODS: Eight rabbits underwent Coblation of maxillary sinus mucosa with biopsy immediately, on postoperative day (POD) 3, 7, 14, or 29. Maxillary mucosa was exposed through the nasal dorsum, and a Coblator PROciseXP wand used on a power setting of 7 for 2 seconds. Three of the rabbits also had Coblation of ethmoid mucosa over the lamina papyracea, after extending the maxillary ostomy, with biopsy immediately. RESULTS: Coblation resulted in immediate loss of surface respiratory epithelium and thermal-type injury to the underlying seromucinous glands. On POD 3, the site showed reepithelialization with squamous metaplastic epithelium. The seromucinous glands underwent coagulative necrosis. At POD 7, there was partial replacement of overlying epithelium by respiratory epithelium. The underlying seromucinous glands were lost and replaced by fibroblastic proliferation, with less fibrosis than the mechanically created ostomy site. The underlying bone had reactive, regenerative changes. On PODs 14 and 29, there was further regeneration of respiratory epithelium. Fibrosis was mild. Coblation resulted in gross violation of the bony wall in one maxillary sinus. There were no histological changes in the orbit. CONCLUSION: Rabbit paranasal sinus mucosa heals appropriately after Coblation injury.

The "Big Dog" effect: variability assessing the causes of error in diagnoses of patients with lung cancer.

PURPOSE: The frequency of diagnostic error in patients who have a lung mass and a pathology specimen is as high as 15%. This study examined the role of inter-pathologist agreement in identifying the cause of error in these patients. METHODS: Pathologists from six institutions reviewed the slides of 40 patients who had a pulmonary specimen false-negative diagnosis. The initial assessment of error cause arose from cytologic-histologic correlation slide review of discrepant diagnostic samples in patients who had both a bronchial brushing cytologic and surgical specimen. The cause of error was attributed either to clinical sampling (diagnostic material obtained in one but not the other sample) or interpretation (pathologist failed to identify the salient diagnostic features). The pairwise kappa (kappa) statistic was used to calculate interobserver agreement between the review and original diagnoses and between the separate review diagnoses. RESULTS: The pairwise kappa statistic ranged widely from -0.154 to 1.0, and the pairwise kappa statistic of the slides from one institution was undetermined because that institutional pathologist never made the assessment that error was secondary to interpretation. Agreement for observers within the same institution was better than agreement between observers from different institutions. CONCLUSION: Pathologists exhibit poor agreement in determining the cause of error for pulmonary specimens sent for cancer diagnosis. We developed a psychosocial hypothesis (the "Big Dog" Effect) that partially explains biases in error assessment. This lack of agreement precludes confident targeting of these errors for quality improvement interventions with prospects of success across a variety of institutions.

Developmental lung anomalies in the adult: radiologic-pathologic correlation.

Encountering a developmental lung anomaly in the adult can be a challenge, as the abnormality may be mistaken for something more sinister. The common anomalies encountered are classified into three broad categories: bronchopulmonary (lung bud) anomalies, vascular anomalies, and combined lung and vascular anomalies. The imaging features of these developmental anomalies at conventional radiography, ventilation-perfusion lung nuclear scanning, angiography, computed tomography, and magnetic resonance imaging are useful in differential diagnosis of thoracic lesions. Lung bud anomalies include agenesis, congenital bronchial atresia, congenital lobar emphysema, congenital cystic adenomatoid malformation, pulmonary bronchogenic cysts, tracheal or pig bronchus, and accessory cardiac bronchus. Vascular anomalies include interruption or absence of a main pulmonary artery, anomalous origin of the left pulmonary artery from the right, anomalous pulmonary venous drainage (partial or complete), and pulmonary arteriovenous malformation. Combined lung and vascular anomalies include the hypogenetic lung (scimitar) syndrome and bronchopulmonary sequestration, both intralobar and extralobar.