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Purpose/objective: Local treatment options for patients with in-field non-small cell lung cancer (NSCLC) recurrence following conventionally fractionated external beam radiation therapy (CF-EBRT) are limited. Stereotactic body radiation therapy (SBRT) is a promising modality to achieve reasonable local control, although toxicity remains a concern., Materials/methods: Patients previously treated with high-dose CF-EBRT (≥59.4 Gy, ≤3 Gy/fraction) for non-metastatic NSCLC who underwent salvage SBRT for localized ultra-central in-field recurrence were included in this analysis. Ultra-central recurrences were defined as those abutting the trachea, mainstem bronchus, or esophagus and included both parenchymal and nodal recurrences. The Kaplan-Meier method was used to estimate local control and overall survival. Durable local control was defined as ≥12 months. Toxicity was scored per the CTC-AE v4.0., Results: Twenty patients were treated with five-fraction robotic SBRT for ultra-central in-field recurrence following CF-EBRT. Fifty percent of recurrences were adenocarcinoma, while 35% of tumors were classified as squamous cell carcinoma. The median interval between the end of CF-EBRT and SBRT was 23.3 months (range: 2.6 - 93.6 months). The median CF-EBRT dose was 63 Gy (range: 59.4 - 75 Gy), the median SBRT dose was 35 Gy (range: 25 - 45 Gy), and the median total equivalent dose in 2 Gy fractions (EQD2) was 116 Gy (range: 91.3 - 136.7 Gy). At a median follow-up of 12 months for all patients and 37.5 months in surviving patients, the majority of patients (90%) have died. High-dose SBRT was associated with improved local control (p < .01), and the one-year overall survival and local control were 77.8% and 66.7% respectively in this sub-group. No late esophageal toxicity was noted, although a patient who received an SBRT dose of 45 Gy (total EQD2: 129.7 Gy) experienced grade 5 hemoptysis 35 months following treatment., Conclusions: Although the overall prognosis for patients with in-field ultra-central NSCLC recurrences following CF-EBRT remains grim, five-fraction SBRT was well tolerated with an acceptable toxicity profile. Dose escalation above 35 Gy may offer improved local control, however caution is warranted when treating high-risk recurrences with aggressive regimens.

Background and Purpose: Radiotherapy of central lung tumors carries a higher risk of treatment-related toxicity and local failure. In the era of aggressive oligometastic management the exploration of the proper dose-fractionation for metastatic central lung tumors is essential., Materials and Methods: Patients diagnosed with high-risk metastatic lesions of the central pulmonary tree comprised this single-institutional retrospective analysis. "High-risk" central pulmonary lesions were defined as those with abutment and/or invasion of the mainstem bronchus. All patients were treated using the CyberKnife SBRT system in 5 fractions to a total dose of 35 or 40 Gy., Results: Twenty patients were treated from 2008 to 2011 at Georgetown University Hospital. At a median follow up of 19 months, 1-year Kaplan-Meier local control and overall survival was 70 and 75 %, respectively. Late grade 2 or higher atelectasis was the most common treatment-related toxicity and was significantly associated with maximum dose to the mainstem bronchus. Gross endobronchial involvement was associated with significantly lower overall survival., Conclusions: Five-fraction SBRT to a total dose of 35 or 40 Gy appears to be a safe and effective management strategy for high-risk central pulmonary metastatic lesions, though care should be taken to limit the maximum point dose to the mainstem bronchus.

Background: Achieving durable local control while limiting normal tissue toxicity with definitive radiation therapy in the management of high-risk brain metastases remains a radiobiological challenge. The objective of this study was to examine the local control and toxicity of a 5-fraction stereotactic radiosurgical approach for treatment of patients with inoperable single high-risk NSCLC brain metastases., Methods: This retrospective analysis examines 20 patients who were deemed to have "high-risk" brain metastases. High-risk tumors were defined as those with a maximum diameter greater than 2 cm and/or those located within an eloquent cortex. Patients were evaluated by a neurosurgeon prior to treatment and determined to be inoperable due to tumor or patient characteristics. Patients were treated using the CyberKnife® SRS system in 5 fractions to a total dose of 30 Gy, 35 Gy, or 40 Gy., Results: Twenty patients with a median age of 65.5 years were treated from April 2010 to August 2014 in 5 fractions to a median total dose of 35 Gy. At a median follow up of 11.3 months local tumor control was observed in 18 of 20 metastases (90 %). Both local failures were observed in patients receiving a lower dose of 30 Gy. Median pre-treatment dexamethasone dose was 10 mg/day and median post-treatment nadir dose was 0 mg/day. Salvage intracranial therapy was required in 45 % of patients. Symptomatic radionecrosis was observed in 4 of 20 patients (20 %), two of which were treated to 40 Gy and the remainder to 35 Gy. Kaplan-Meier 1-year, 2-year, and median survival were calculated to be 45 %, 20 %, and 13.2 months, respectively., Conclusions: Five-fraction SRS to a total dose of 35 Gy appears to be a safe and effective management strategy for single high-risk NSCLC brain metastases, while a total dose of 40 Gy leads to an excess risk of neurotoxicity.

Adult Wilms' tumor (WT) is a rare entity with less than 300 cases reported to date in the medical literature. Histologic and cytologic features of adult WT of the kidney are similar to findings in pediatric WT. While the lungs are noted to be the most frequent site of metastatic disease in the pediatric population, the incidence of lung metastases remains unknown for adult WT. A search revealed 38 cases of adult WT with lung metastases published to date in the English literature. Amongst these cases only two have utilized cytology of the lung lesions as a means to arrive at a final diagnosis. We report a case of adult WT metastatic to the lung that was initially diagnosed using endobronchial ultrasound-guided fine needle aspiration biopsy. The aim is to compare the current cytologic and immunohistochemical findings with those cases previously published, to outline the cytologic features of adult WT metastatic to the lung, and to emphasize the significance of cytologic diagnosis in the work-up of adult WT., (© 2013 Wiley Periodicals, Inc.)

Objective: Endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) cytology and EBUS-miniforceps biopsy (MFB) have emerged as less invasive tools for evaluating mediastinal lymph nodes and pulmonary lesions. The aim of this study is to compare the diagnostic yields of EBUS-FNA cytology to EBUS-MFB., Study Design: A retrospective cohort study was performed by reviewing the database at our institution between December 12, 2010, and August 10, 2012. A total of 476 consecutive cases were identified. Of these, 227 patients had concurrent FNA and MFB taken during the procedure. The results and diagnostic yields of both techniques are calculated., Results: Of the 476 cases, the mean age was 62 ± 14 years with 53% being males. In 453 of the total cases, the less invasive FNA technique alone produced enough diagnostic cytology material negating the need for concurrent MFB. Of these FNA cases, 280 were diagnosed as malignant neoplasms. The diagnostic yield of EBUS-FNA cytology was comparable to EBUS-MFB (95% FNA and 94% MFB). There were discordant diagnoses between cytology and histology in 19 of the 227 (∼8.4%) cases., Conclusions: EBUS-FNA cytology is a more efficacious diagnostic modality compared to EBUS-MFB.

Background: Endobronchial ultrasound guided (EBUS) fine-needle aspiration (FNA) biopsy has become widely used to evaluate patients with thoracic abnormalities. Rapid on-site evaluation (ROSE) can provide the bronchoscopist with immediate evaluation findings during the procedure. This study examines EBUS FNA biopsy procedures with and without ROSE, and investigates the impact of ROSE service on the EBUS procedure and laboratory resource utilization., Methods: The cytopathology database at Washington University Medical Center, St. Louis, Missouri, was searched for EBUS FNA biopsy cases before and after introduction of ROSE service, and a matched cohort was collected. Reports were reviewed and pertinent data was collected, such as sites biopsied, ROSE performance, slide smears, cell blocks, and diagnostic categories. Statistical analysis of the results was performed., Results: A matched case-controlled EBUS FNA cohort of 340 patients (680 total) for each category of non-ROSE and ROSE service were identified. There was a 33% reduction in the number of sites biopsied with ROSE. A total of 68% of patients with ROSE had just one biopsy site compared to only 36% of non-ROSE patients. There was a 30% decrease in total slides (mean, 5.27 slides) after the introduction of ROSE. All of these improvements were statistically significant., Conclusions: EBUS FNA biopsy ROSE service benefits patients by contributing to significantly fewer biopsies and improved utilization of health care resources. ROSE service results in substantially fewer total slides, which has a significant impact on the cytopathology laboratory work effort. The use of ROSE for EBUS FNA biopsy provides significant improvements in patient care and laboratory resource utilization., (© 2013 American Cancer Society.)

Pulmonary neuroendocrine tumors (PNET) are histologically subclassified into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). The criteria for subclassification in cytological specimens are not well defined. In this study, we reviewed histologically confirmed 18 TC, 8 AC, 10 LCNEC, and 10 SCLC cytologic specimens from 45 patients. The following features were reviewed: small clusters, geographic sheets, trabecular structures, pseudo-rosettes, single cells, doublets, triplets or short cords, papillary-like structures, capillary vasculatures, necrosis, smear background, cell size, cell pleomorphism, amount of cytoplasm, plasmacytoid cells, spindle cells, nuclear atypia, molding, palisading and smearing, chromatin textures, nucleoli, and mitotic figure count. Based on our results, geographic clusters and necrosis were often seen in LCNEC and SCLC; while AC only showed scattered single cell necrosis. TC and AC commonly exhibited trabecular structures. Papillary-like structures and capillary vasculature were only present in TC, AC, and LCNEC. Cells forming doublets, triplets, and short cords were more commonly seen in SCLC and rarely seen in other entities. Plasmacytoid and spindle cells were only seen in TC and AC. Nuclear smearing was not identified in TC, rare in AC, focally present in LCNEC and obvious in SCLC. Mitotic figures were nearly absent in TC, ≤5/10 HPF in AT, and ≥10/10 HPF in SCLC. LCNEC showed a wide span of mitotic count ranging between 2 and 16/10 HPF. In this study, we propose a set of cytological features that are essential for subclassification of PNETs in cytologic specimens., (Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.)

Background: With the introduction of new treatment modalities and guidelines, it is important to subclassify primary pulmonary non-small cell carcinoma (NSCCA). Subsequent treatment and testing is dependent on accurate subclassification. Endobronchial ultrasound fine-needle aspiration (EBUS FNA) is used for primary evaluation and diagnosis, and can provide a cell block for ancillary testing., Methods: EBUS FNA cases from primary pulmonary NSCCA with an immunohistochemical (IHC) panel performed on a cell block with concomitant surgical pathology biopsy were analyzed. Cell block preparations underwent an IHC panel including monoclonal antibodies for napsin A (nap-A), thyroid transcription factor (TTF-1), p63, and cytokeratin 5/6 (CK5/6)., Results: A total of 81 cases from 81 patients were identified. Of these, 69 cases (85%) were provided a specific diagnosis of adenocarcinoma (ADCA) or squamous cell carcinoma (SCCA) on the EBUS FNA. In 12 cases (15%), a diagnosis of NSCCA, not otherwise specified was provided. For specific subclassifications, there were 35 ADCA cases, 34 SCCA cases, and 12 NSCCA, not otherwise specified cases. For ADCA, nap-A showed granular cytoplasmic staining and TTF-1 nuclear staining. For SCCA, CK5/6 showed cytoplasmic staining and p63 nuclear staining. Surgical pathology concomitant material was present in 29 of 81 cases with 18 correlations and 11 noncorrelations., Conclusions: With new treatment guidelines for patients with primary pulmonary NSCCA, specific diagnosis is increasingly important. EBUS FNA with cell block provided a specific subclassification of NSCCA in 85% of cases when used in conjunction with a specific IHC panel including nap-A, TTF-1, CK5/6, and p63., (Copyright © 2012 American Cancer Society.)

Objective: Specific subclassification of pulmonary non-small cell carcinoma (NSCCA) is clinically necessary, and the aim of this study is to examine the utilization of p40 (ΔNp63) in fine-needle aspiration (FNA) biopsy for lung NSCCA., Study Design: Database files of the Washington University Medical Center were searched. Patients who underwent endobronchial ultrasound and CT FNA of a primary lung neoplasia were selected and immunohistochemistry (IHC) was performed. A panel of markers was utilized, including p40, p63, cytokeratin (CK) 5/6, thyroid transcription factor, and napsin., Results: One hundred patients were identified and comprised 38 squamous cell carcinomas (SCCA), 46 adenocarcinomas (AdCA), and 16 NSCCA. For SCCA, p40 was positive in 34/38 cases (89%) and negative in 4/38 cases (11%); p63 was positive in 33/38 cases (87%) and negative in 5/38 cases (13%); CK5/6 was positive in 38/38 cases. For AdCA cases, p40 was negative, p63 was positive in 2 cases (5%) and CK5/6 was negative in 43/46 cases (92%)., Conclusion: For NSCCA, p40 had 89% sensitivity and 100% specificity compared to p63 with 86% sensitivity and 96% specificity and CK5/6 with 100% sensitivity and 96% specificity. In the evaluation of FNA biopsy for pulmonary NSCCA, p40 is a useful IHC marker for neoplastic subclassification, with better specificity in comparison to p63.

Objective: To report clinical efficacy and toxicity of fractionated CyberKnife radiosurgery for the treatment of hilar lung tumors., Methods: Patients presenting with primary and metastatic hilar lung tumors, treated using the CyberKnife system with Synchrony fiducial tracking technology, were retrospectively reviewed. Hilar location was defined as abutting or invading a mainstem bronchus. Fiducial markers were implanted by conventional bronchoscopy within or adjacent to tumors to serve as targeting references. A prescribed dose of 30 to 40 Gy to the gross tumor volume (GTV) was delivered in 5 fractions. Clinical examination and PET/CT imaging were performed at 3 to 6-month follow-up intervals., Results: Twenty patients were accrued over a 4 year period. Three had primary hilar lung tumors and 17 had hilar lung metastases. The median GTV was 73 cc (range 23-324 cc). The median dose to the GTV was 35 Gy (range, 30 - 40 Gy), delivered in 5 fractions over 5 to 8 days (median, 6 days). The resulting mean maximum point doses delivered to the esophagus and mainstem bronchus were 25 Gy (range, 11 - 39 Gy) and 42 Gy (range, 30 - 49 Gy), respectively. Of the 17 evaluable patients with 3 - 6 month follow-up, 4 patients had a partial response and 13 patients had stable disease. AAT t a median follow-up of 10 months, the 1-year Kaplan-Meier local control and overall survival estimates were 63% and 54%, respectively. Toxicities included one patient experiencing grade II radiation esophagitis and one patient experiencing grade III radiation pneumonitis. One patient with gross endobronchial tumor within the mainstem bronchus developed a bronchial fistula and died after receiving a maximum bronchus dose of 49 Gy., Conclusion: CyberKnife radiosurgery is an effective palliative treatment option for hilar lung tumors, but local control is poor at one year. Maximum point doses to critical structures may be used as a guide for limiting toxicities. Preliminary results suggest that dose escalation alone is unlikely to enhance the therapeutic ratio of hilar lung tumors and novel approaches, such as further defining the patient population or employing the use of radiation sensitizers, should be investigated.

Objective: To report serial 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) tumor response following CyberKnife radiosurgery for stage IA non-small cell lung cancer (NSCLC)., Methods: Patients with biopsy-proven inoperable stage IA NSCLC were enrolled into this IRB-approved study. Targeting was based on 3-5 gold fiducial markers implanted in or near tumors. Gross tumor volumes (GTVs) were contoured using lung windows; margins were expanded by 5 mm to establish the planning treatment volumes (PTVs). Doses ranged from 42-60 Gy in 3 equal fractions. 18F-FDG PET/CT was performed prior to and at 3-6-month, 9-15 months and 18-24 months following treatment. The tumor maximum standardized uptake value (SUV(max)) was recorded for each time point., Results: Twenty patients with an average maximum tumor diameter of 2.2 cm were treated over a 3-year period. A mean dose of 51 Gy was delivered to the PTV in 3 to 11 days (mean, 7 days). The 30-Gy isodose contour extended an average of 2 cm from the GTV. At a median follow-up of 43 months, the 2-year Kaplan-Meier overall survival estimate was 90% and the local control estimate was 95%. Mean tumor SUV(max) before treatment was 6.2 (range, 2.0 to 10.7). During early follow-up the mean tumor SUV(max) remained at 2.3 (range, 1.0 to 5.7), despite transient elevations in individual tumor SUV(max) levels attributed to peritumoral radiation-induced pneumonitis visible on CT imaging. At 18-24 months the mean tumor SUV(max) for controlled tumors was 2.0, with a narrow range of values (range, 1.5 to 2.8). A single local failure was confirmed at 24 months in a patient with an elevated tumor SUV(max) of 8.4., Conclusion: Local control and survival following CyberKnife radiosurgery for stage IA NSCLC is exceptional. Early transient increases in tumor SUV(max) are likely related to radiation-induced pneumonitis. Tumor SUV(max) values return to background levels at 18-24 months, enhancing 18F-FDG PET/CT detection of local failure. The value of 18F-FDG PET/CT imaging for surveillance following lung SBRT deserves further study.

Objective: Curative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC), but radical radiosurgery may be effective., Methods: Inoperable patients with small peripheral clinical stage I NSCLC were enrolled in this study. Three-to-five fiducial markers were implanted in or near tumors under CT guidance. Gross tumor volumes (GTVs) were contoured using lung windows. The GTV margin was expanded by 5 mm to establish the planning treatment volume (PTV). A dose of 42-60 Gy was delivered to the PTV in 3 equal fractions in less than 2 weeks using the CyberKnife radiosurgery system. The 30-Gy isodose contour extended at least 1 cm from the GTV. Physical examination, CT imaging and pulmonary function testing were completed at 6 months intervals for three years following treatment., Results: Twenty patients with an average maximum tumor diameter of 2.2 cm (range, 1.1 - 3.5 cm) and a mean FEV1 of 1.08 liters (range, 0.53 - 1.71 L) were treated. Pneumothorax requiring tube thoracostomy occurred following CT-guided fiducial placement in 25% of the patients. All patients completed treatment with few acute side effects and no procedure-related mortality. Transient chest wall discomfort developed in 8 of the 12 patients with lesions within 5 mm of the pleura. The mean percentage of the total lung volume receiving a minimum of 15 Gy was 7.3% (range, 2.4% to 11.3%). One patient who received concurrent gefitinib developed short-lived, grade III radiation pneumonitis. The mean percent predicted DLCO decreased by 9% and 11% at 6 and 12 months, respectively. There were no local failures, regional lymph node recurrences or distant metastases. With a median follow-up of 25 months for the surviving patients, Kaplan-Meier overall survival estimate at 2 years was 87%, with deaths due to COPD progression., Conclusion: Radical CyberKnife radiosurgery is a well-tolerated treatment option for inoperable patients with small, peripheral stage I NSCLC. Effective doses and adequate margins are likely to have contributed to the optimal early local control seen in this study.

Background: Primary monophasic spindle synovial sarcoma can occur in areas with no apparent relation to synovial structures. The diagnosis can be challenging because of the ability to mimic other spindle cell neoplasms. Within the lung, these neoplasms are rare and cytologic descriptions are limited., Case: A 58-year-old woman was diagnosed with colonic adenocarcinoma; chest computed tomography (CT) revealed a 5-cm solitary pulmonary mass, and CT-guided fine needle aspiration was performed. Aspirate smears were cellular, with large, loosely cohesive complex tissue fragments that showed dense spindled cells with numerous single stripped spindle cells. Spindle cells were bland and monomorphic, with minimal cellular variation. There was no anaplasia or specific mesenchymal differentiation. Immunohistochemical stains on the cell block were positive for vimentin and bcl-2. A diagnosis of spindle cell neoplasm was rendered; it was believed to be a second neoplasm unrelated to the colonic adenocarcinoma. The main diagnostic consideration was synovial sarcoma. On resection, the neoplasm demonstrated t(x:1 8) chromosomal translocation by fluorescence in situ hybridization., Conclusion: In a spindled cell neoplasm arising as a single peripheral pulmonary nodule, monophacir spindle synorvial sarcoma should be considered in the differential diagnosis; detection of the t(x;18) chromosomal translocation can confirm the diagnosis.

Background: Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors., Methods: Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3-5) were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45-60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months., Results: Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease., Conclusion: Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.

Purpose: This study examined the complication rates associated with percutaneous fiducial placement for the purpose of stereotactic body radiation therapy of primary and metastatic lung neoplasms., Patients and Methods: This is a retrospective review of computed tomography (CT) scans and follow-up chest radiographs of 48 consecutive patients who underwent CT-guided percutaneous fiducial placement. The effect of age, sex, number of fiducials placed, and performance of a concomitant biopsy on the complication rates were assessed., Results: Of 48 patients with a total of 221 fiducials placed, 16 (33%) had a procedure-related pneumothorax. There was no significant difference in pneumothorax rate based on age (P = 0.16), sex (P > 0.99), and number of fiducials placed (P = 0.21). Overall, 6 of 48 patients (12.5%) required a thoracostomy tube. Performance of a concomitant core needle biopsy at the time of fiducial placement was associated with pneumothorax rates of 64% compared with 26% without biopsies (P = 0.03). Postprocedural CT demonstrated hemorrhage in 9 patients (19%). Two patients had hemoptysis; one required admission. Patients' age, sex, number of fiducials placed, and performance of concomitant biopsy had no statistically significant implications on parenchymal hemorrhage incidence., Conclusion: Approximately one third of the patients develop a pneumothorax during CT-guided fiducial placement. Most are asymptomatic and do not require a thoracostomy. A concurrent biopsy at the time of fiducial placement is associated with an increased risk of pneumothorax. Hemorrhage occurs but is usually clinically insignificant.

Background: Pulmonary epithelioid hemangioendothelioma (PEH) is a rare, low grade, malignant vascular tumor that typically presents with multiple pulmonary nodules in young women. This report details the cytopathologic and pathologic findings in an unusual case presenting in an older male with a pleural effusion, dominant nodule and multiple bilateral infiltrates., Case: A 62-year-old, male nonsmoker was referred due to increasing dyspnea. Chest radiography revealed a pleural effusion and nodular infiltrate in the right upper lobe of the bronchus. Thoracocentesis and thoracoscopy were performed, with a pleural drain inserted. Bronchoscopy revealed a right upper lobe bronchus occluded by a greyish, necrotic mass. Various cytopathologic sampling techniques, including fine needle aspiration biopsy, as well as traditional histopathologic biopsies were performed. Cytologic specimens showed loosely cohesive, epithelioid cells that were binucleated and multinucleated. Chromatin was granular, with scattered, small, multiple nucleoli with occasional, variably sized cytoplasmic vacuoles. The patient's condition deteriorated, and he died 3 weeks after admission., Conclusion: Pulmonary epithelioid hemangioendotheliomas are unusual neoplasms with a epithelioid, discohesive cellular appearance. It can mimic other, more commonly seen pulmonary neoplasms. Careful attention to cytomorphologic features and application of ancillary studies assist in making the diagnosis.