Aplastic anemia secondary to dual cancer immunotherapies a physician nightmare: case report and literature review.

BACKGROUND: Treatment with immune checkpoint inhibitors has revolutionized cancer treatment over the past several years. Despite their clinical benefits, a wide range of immune-mediated toxicities can be observed including hematological toxicities. Although, the majority can easily be managed, immune-mediated adverse events rarely can be severe and difficult to approach. Herein, we are reporting a case of very severe aplastic anemia secondary to ipilimumab (I) and nivolumab (N) treatment that failed various treatment including intensive immune suppressive therapy. CASE PRESENTATION: We described a case of a 45-year old white male, heavy smoker presented to the clinic complaining of left flank pain. He was found to have a metastatic renal cell carcinoma for which he was treated with dual immunotherapy and later complicated by severe immune related adverse events. The patient later died after failing intensive immune suppressive therapy. CONCLUSION: Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with variant malignancies. Yet, lethal adverse events can occur in rare cases. It is our duty, as physicians, to remain alert and cautious.

Inflammatory Myofibroblastic Tumor of the Liver Mimicking Metastasis on 18F-FDG PET/CT.

A 62-year-old woman with history of stage III endometrial cancer was found to have a small enhancing liver lesion on follow-up abdominal CT and MRI, suspicious for metastasis. Subsequent F-FDG PET/CT was performed, demonstrating intense uptake within the liver lesion, consistent with metastasis. Subsequently, laparoscopic wedge liver lesion resection was performed. Histopathologic examination confirmed the diagnosis of inflammatory myofibroblastic tumor (IMT) with predominant inflammatory cells. Although solitary liver IMTs are rare occurrences with imaging features overlapping with malignancy, IMT should be considered in the differential diagnosis of suspicious liver lesions, especially when the pattern of spread is unusual.

Radiology residents from learners to teachers: A multi-centric study.

PURPOSE: The teaching role of radiology residents has seldom been evaluated, and little is known about how teaching skills of radiology residents evolve throughout their training in the absence of formal teaching guidance. Our objective is to identify residents' characteristics correlating with better teaching and compare teaching characteristics of junior and senior residents. METHOD: All seven medical schools in Lebanon were involved in this multi-centric study. A self-assessment questionnaire was sent to sixty-nine radiology residents and filled anonymously. Fifty-seven (83 %) responses were received and represent the study population. Data analysis was based on factors correlating with overall teaching effectiveness. A comparison of senior and junior residents' responses was also performed. RESULTS: Overall teaching effectiveness correlated with better knowledge, technical skills, clinical judgment, communication skills, identification and correction of learning problems, and importantly providing and receiving feedback. Senior residents rated themselves significantly better than juniors in "knowledge related to radiology" and in "technical skills" but not in "overall teaching effectiveness". Seniors did not agree on the statement "medical students make my clinical responsibilities easier". Although not reaching statistical significance, seniors showed a trend towards improving teaching skills. CONCLUSIONS: Overall teaching effectiveness is correlated with the adoption of proper skills and techniques. Despite the lack of formal teaching guidance, senior radiology residents are improving their techniques as teachers but still face difficulties in several domains.

Unique Presentation and Management Approach of Pleural Solitary Fibrous Tumor.

Solitary fibrous tumor (SFT) of the pleura is an uncommon tumor that is often discovered incidentally on a routine chest X-ray. We report a case of a young female with a large, sessile, hypervascularized SFT of the pleura presenting with cardiopulmonary shock to a rural hospital with limited therapeutic interventions. We propose, in this case report, a unique multidisciplinary approach for the management of such a critical patient and the safe resection of the tumor.

Comparison of hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging and positron emission tomography/computed tomography for evaluation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1.

Rapidly enlarging, painful plexiform neurofibromas (PN) in neurofibromatosis type 1 (NF1) patients are at higher risk for harboring a malignant peripheral nerve sheath tumor (MPNST). Fludeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has been used to support more invasive diagnostic and therapeutic interventions. However, PET/CT imparts an untoward radiation hazard to this population with tumor suppressor gene impairment. The use of FDG PET coupled with magnetic resonance imaging (MRI) rather than CT is a safer alternative but its relative diagnostic sensitivity requires verification. Ten patients (6 females, 4 males, mean age 27 years, range 8-54) with NF1 and progressive PN were accrued from our institutional NF Clinic. Indications for PET scanning included increasing pain and/or progressive disability associated with an enlarging PN on serial MRIs. Following a clinically indicated whole-body FDG PET/CT, a contemporaneous PET/MRI was obtained using residual FDG activity with an average time interval of 3-4 h FDG-avid lesions were assessed for both maximum standardized uptake value (SUVmax) from PET/CT and SUVmax from PET/MR and correlation was made between the two parameters. 26 FDG avid lesions were detected on both PET/CT and PET/MR with an accuracy of 100%. SUVmax values ranged from 1.4-10.8 for PET/CT and from 0.2-5.9 for PET/MRI. SUVmax values from both modalities demonstrated positive correlation (r = 0.45, P < 0.001). PET/MRI radiation dose was significantly lower (53.35% ± 14.37% [P = 0.006]). In conclusion, PET/MRI is a feasible alternative to PET/CT in patients with NF1 when screening for the potential occurrence of MPNST. Reduction in radiation exposure approaches 50% compared to PET/CT.

Visual detection of regional brain hypometabolism in cognitively impaired patients is independent of positron emission tomography-magnetic resonance attenuation correction method.

Fluorodeoxyglucose (FDG) positron emission tomography-magnetic resonance (PET/MR) is useful for the evaluation of cognitively-impaired patients. This study aims to assess two different attenuation correction (AC) methods (Dixon-MR and atlas-based) versus index-standard computed tomography (CT) AC for the visual interpretation of regional hypometabolism in patients with cognitive impairment. Two board-certified nuclear medicine physicians blindly scored brain region FDG hypometabolism as normal versus hypometabolic using two-dimensional (2D) and 3D FDG PET/MR images generated by MIM software. Regions were quantitatively assessed as normal versus mildly, moderately, or severely hypometabolic. Hypometabolism scores obtained using the different methods of AC were compared, and interreader, as well as intra-reader agreement, was assessed. Regional hypometabolism versus normal metabolism was correctly classified in 16 patients on atlas-based and Dixon-based AC map PET reconstructions (vs. CT reference AC) for 94% (90%-96% confidence interval [CI]) and 93% (89%-96% CI) of scored regions, respectively. The averaged sensitivity/specificity for detection of any regional hypometabolism was 95%/94% (P = 0.669) and 90%/91% (P = 0.937) for atlas-based and Dixon-based AC maps. Interreader agreement for detection of regional hypometabolism was high, with similar outcome assessments when using atlas- and Dixon-corrected PET data in 93% (Κ =0.82) and 93% (Κ =0.84) of regions, respectively. Intrareader agreement for detection of regional hypometabolism was high, with concordant outcome assessments when using atlas- and Dixon-corrected data in 93%/92% (Κ =0.79) and 92/93% (Κ =0.78). Despite the quantitative advantages of atlas-based AC in brain PET/MR, routine clinical Dixon AC yields comparable visual ratings of regional hypometabolism in the evaluation of cognitively impaired patients undergoing brain PET/MR and is similar in performance to CT-based AC. Therefore, Dixon AC is acceptable for the routine clinical evaluation of dementia syndromes.

Ipilimumab-Induced Organizing Pneumonia on 18F-FDG PET/CT in a Patient With Malignant Melanoma.

A 60-year-old woman with history of vaginal malignant melanoma and inguinal nodal metastases underwent F-FDG PET/CT for restaging following ipilimumab (Yervoy) immunotherapy, a Food and Drug Administration-approved human monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4. PET/CT demonstrated mildly FDG-avid multifocal enlarging bilateral lung opacities. Within each lung lesion, there was circumferential uptake localizing to a high-attenuation rim with a photopenic ground-glass center on CT, consistent with "reversed halo sign." Patient was asymptomatic at the time of imaging. Ipilimumab was discontinued, and 3-month follow-up PET/CT revealed spontaneous complete resolution of the lung lesions, supporting the diagnosis of ipilimumab-induced organizing pneumonia.

Ganglion Cyst on 131I Whole-Body Scintigraphy.

Interpretation of iodine I whole-body scintigraphy can be challenging, as there are many nonpathologic findings that may present with increased radiotracer uptake. Radiotracer uptake has been reported in the literature involving the salivary glands, thymus, renal cysts, skin contamination, and other benign etiologies. We present the case of an incidental right wrist ganglion cyst demonstrating persistent increased uptake on I whole-body scintigraphy.

Prospective Pilot Study to Evaluate the Incremental Value of PET Information in Patients With Bladder Cancer Undergoing 18F-FDG Simultaneous PET/MRI.

PURPOSE: The aim of this study was to conduct a prospective pilot study comparing the diagnostic performance of MRI alone and F-FDG simultaneous PET/MRI using a diuresis protocol in bladder cancer patients. METHODS: Twenty-two bladder cancer patients underwent F-FDG PET/MRI, using intravenous furosemide and oral hydration for bladder clearance. A radiologist scored probability of tumor in 3 locations (urinary bladder, pelvic lymph nodes, nonnodal pelvis) using 1- to 3-point scale (1 = negative, 2 = equivocal, 3 = definite tumor). A nuclear medicine physician reviewed fused PET/MRI images, after which scores were reassigned based on combined findings. Follow-up pathologic and imaging data served as reference. Performances of MRI alone and PET/MRI were compared. RESULTS: Of these patients, 82%, 38%, and 18% were positive for bladder, pelvic nodal, and nonnodal pelvic tumor, respectively. At a score of 3, PET/MRI exhibited greater accuracy for detection of bladder tumor (86% vs 77%), metastatic pelvic lymph nodes (95% vs 76%), and nonnodal pelvic malignancy (100% vs 91%). In the bladder, PET changed the level of suspicion in 36% of patients (50% increased suspicion, 50% decreased suspicion), with 75% of these changes deemed correct based on reference standard. For pelvic lymph nodes, PET changed suspicion in 52% (36% increase, 64% decrease), with 95% of changes deemed correct. For nonnodal pelvis, PET changed suspicion in 9% (100% increase), with 100% deemed correct. CONCLUSIONS: Additional PET information helped to appropriately determine level of suspicion in multiple anatomic sites for otherwise equivocal findings on MRI alone. Although requiring larger studies, findings suggest a possible role for simultaneous PET/MRI to assist bladder cancer management.

Squamous cell carcinoma of the rectum: a consequence of immunosuppression resulting from inhibiting tumour necrosis factor (TNF)?

Treatment with tumour necrosis factor (TNF) antagonists may lead to enhanced susceptibility to certain malignancies. In particular, an association is seen emerging between TNF antagonists and development of squamous cell carcinomas (SCCs) of the skin (in association with psoriasis), the oral cavity, and in the anogenital areas (possibly related to prior human papilloma virus infection). We present here a case of a 53-year old woman with a history of severe rheumatoid arthritis (RA), most recently treated with the TNF antagonist etanercept plus methotrexate, presented to our service after several months of increasing left pelvis and buttock pain. Evaluation with a computerised tomography (CT)-directed biopsy of a pelvic side wall mass revealed a metastatic SCC. On a fluorodeoxyglucose (FDG) positron-emission tomography (PET) an additional area of uptake was identified in the left posterior rectum corresponding to a 1 cm nodule palpable on digital exam. Colonoscopic biopsy revealed a basaloid SCC of the rectum as the likely primary site. Immunosuppression following TNF antagonist therapy may have given arise to this unrestrained neoplastic growth. It thereby underscores the need for an initial baseline study of risk factors and identification of patients who are at higher risk for development of a malignancy, in order to achieve a diagnosis at an early stage.

Comparison of Whole-Body (18)F FDG PET/MR Imaging and Whole-Body (18)F FDG PET/CT in Terms of Lesion Detection and Radiation Dose in Patients with Breast Cancer.

Purpose To compare fluorine 18 ((18)F) fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and magnetic resonance (MR) imaging with (18)F FDG combined PET and computed tomography (CT) in terms of organ-specific metastatic lesion detection and radiation dose in patients with breast cancer. Materials and Methods From July 2012 to October 2013, this institutional review board-approved HIPAA-compliant prospective study included 51 patients with breast cancer (50 women; mean age, 56 years; range, 32-76 years; one man; aged 70 years) who completed PET/MR imaging with diffusion-weighted and contrast material-enhanced sequences after unenhanced PET/CT. Written informed consent for study participation was obtained. Two independent readers for each modality recorded site and number of lesions. Imaging and clinical follow-up, with consensus in two cases, served as the reference standard. Results There were 242 distant metastatic lesions in 30 patients, 18 breast cancers in 17 patients, and 19 positive axillary nodes in eight patients. On a per-patient basis, PET/MR imaging with diffusion-weighted and contrast-enhanced sequences depicted distant (30 of 30 [100%] for readers 1 and 2) and axillary (eight of eight [100%] for reader 1, seven of eight [88%] for reader 2) metastatic disease at rates similar to those of unenhanced PET/CT (distant metastatic disease: 28 of 29 [96%] for readers 3 and 4, P = .50; axillary metastatic disease: seven of eight [88%] for readers 3 and 4, P > .99) and outperformed PET/CT in the detection of breast cancer (17 of 17 [100%] for readers 1 and 2 vs 11 of 17 [65%] for reader 3 and 10 of 17 [59%] for reader 4; P < .001). PET/MR imaging showed increased sensitivity for liver (40 of 40 [100%] for reader 1 and 32 of 40 [80%] for reader 2 vs 30 of 40 [75%] for reader 3 and 28 of 40 [70%] for reader 4; P < .001) and bone (105 of 107 [98%] for reader 1 and 102 of 107 [95%] for reader 2 vs 106 of 107 [99%] for reader 3 and 93 of 107 [87%] for reader 4; P = .012) metastases and revealed brain metastases in five of 51 (10%) patients. PET/CT trended toward increased sensitivity for lung metastases (20 of 23 [87%] for reader 1 and 17 of 23 [74%] for reader 2 vs 23 of 23 [100%] for reader 3 and 22 of 23 [96%] for reader 4; P = .065). Dose reduction averaged 50% (P < .001). Conclusion In patients with breast cancer, PET/MR imaging may yield better sensitivity for liver and possibly bone metastases but not for pulmonary metastases, as compared with that attained with PET/CT, at about half the radiation dose. (©) RSNA, 2016 Online supplemental material is available for this article.

Standardized Uptake Values from PET/MRI in Metastatic Breast Cancer: An Organ-based Comparison With PET/CT.

Quantitative standardized uptake values (SUVs) from fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are commonly used to evaluate the extent of disease and response to treatment in breast cancer patients. Recently, PET/magnetic resonance imaging (MRI) has been shown to qualitatively detect metastases from various primary cancers with similar sensitivity to PET/CT. However, quantitative validation of PET/MRI requires assessing the reliability of SUVs from MR attenuation correction (MRAC) relative to CT attenuation correction (CTAC). The purpose of this retrospective study was to assess the utility of PET/MRI-derived SUVs in breast cancer patients by testing the hypothesis that SUVs derived from MRAC correlate well with those from CTAC. Between August 2012 and May 2013, 35 breast cancer patients (age 37-78 years, 1 man) underwent clinical 18F-FDG PET/CT followed by PET/MRI. One hundred seventy metastases were seen in 21 of 35 patients; metastases to bone in 16 patients, to liver in seven patients, and to nonaxillary lymph nodes in eight patients were sufficient for statistical analysis on an organ-specific per patient basis. SUVs in the most FDG-avid metastasis per organ per patient from PET/CT and PET/MRI were measured and compared using Pearson's correlations. Correlations between CTAC- and MRAC-derived SUVmax and SUVmean in 31 metastases to bone, liver, and nonaxillary lymph nodes were strong overall (ρ = 0.80, 0.81). SUVmax and SUVmean correlations were also strong on an organ-specific basis in 16 bone metastases (ρ = 0.76, 0.74), seven liver metastases (ρ = 0.85, 0.83), and eight nonaxillary lymph node metastases (ρ = 0.95, 0.91). These strong organ-specific correlations between SUVs from PET/CT and PET/MRI in breast cancer metastases support the use of SUVs from PET/MRI for quantitation of 18F-FDG activity.

Outcome of small lung nodules missed on hybrid PET/MRI in patients with primary malignancy.

PURPOSE: To assess outcomes of lung nodules missed on simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI) compared to the reference standard PET and computed tomography (PET/CT) in patients with primary malignancy. MATERIALS AND METHODS: In all, 208 patients with primary malignancy undergoing clinically indicated (18F) fluorodeoxyglucose (FDG) PET/CT followed by PET/MRI were independently reviewed by two readers. Upon review of the thoracic station on PET/MRI and PET/CT, 89 non-FDG avid small lung nodules in 43 patients were detected (by reader 1) only on the CT component of the PET/CT but were not identified on PET/MRI. Overall, 84 of these 89 nodules were examined on follow-up imaging with PET/CT or chest CT. The remaining five nodules had no follow-up imaging but had remote imaging available for comparison. RESULTS: Among the 84 nodules with follow-up, three nodules (3%) in one patient progressed, 10 (12%) nodules partially/completely resolved, whereas 71 nodules (85%) remained stable. The five nodules without follow-up were all stable since prior imaging of over 21 months. CONCLUSION: The vast majority (97%) of small non-FDG avid lung nodules missed on PET/MRI either resolved or remained stable on follow-up, suggestive of benignity. PET/MRI remains a viable alternative imaging modality in oncology patients, despite its low sensitivity in detecting small lung nodules.

Does Fluorodeoxyglucose Positron Emission Tomography With Computed Tomography Facilitate Treatment of Medication-Related Osteonecrosis of the Jaw?

PURPOSE: There is considerable controversy over the treatment of medication-related osteonecrosis of the jaw (MRONJ) and growing interest and debate related to the timing, type, technique, and goals of surgical intervention. The specific aim was to evaluate the predictive value of fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) on healing outcomes in patients undergoing surgery for MRONJ of the mandible. MATERIALS AND METHODS: A retrospective cohort study of 31 patients with 33 MRONJ lesions of the mandible who had undergone surgery using FDG PET-CT was conducted. Data were collected on FDG uptake patterns, healing, follow-up, demographics, lesion characteristics, antiresorptive therapy, and adjunctive therapy. Panoramic and/or periapical radiographs were used to identify non-restorable teeth and PET-CT images were used to identify sequestra and FDG uptake. Above the mandibular canal, surgery consisted of marginal resection and/or debridement of clinically involved bone and exposure of clinically uninvolved bone identified by FDG uptake. Below the mandibular canal, mobile segments of bony sequestra were removed, but areas of clinically uninvolved bone with FDG uptake were not. Patients who did not heal underwent segmental resection and reconstruction with rigid fixation and a local or regional soft tissue flap or free fibular flap. The primary predictor variable was the FDG uptake pattern for each patient. The outcome variable was postoperative healing defined by mucosal closure without signs of infection or exposed bone at the time of evaluation. RESULTS: Two risk groups were identified based on FDG uptake pattern. The low-risk group, type A, included 22 patients with activity limited to the alveolus, torus, and/or basal bone superior to the mandibular canal. The high-risk group, type B, included 11 patients with type A FDG activity with extension inferior to the mandibular canal. Treatment of type A MRONJ lesions was more successful than treatment of type B MRONJ lesions (100 vs 27%; P < .001). Seven of the type B failures were successfully retreated by segmental resection and reconstruction (1 patient refused further treatment). CONCLUSION: These results showed that low-risk FDG PET-CT findings predicted successful healing with surgery above the mandibular canal. In contrast, high-risk FDG findings were associated with a greater than 50% risk of failure for treatment that extended below the mandibular canal. Although these failures suggest that FDG uptake indicates infected tissue, further research is needed to identify which high-risk patients are most likely to benefit from a conservative treatment protocol.

Imaging and evaluation of patients with high-risk prostate cancer.

Approximately 15% of men with newly diagnosed prostate cancer have high-risk disease. Imaging is critically important for the diagnosis and staging of these patients, and also for the selection of management. While established prostate cancer staging guidelines have increased the appropriate use of imaging, underuse for high-risk prostate cancer remains substantial. Several factors affect the utility of initial diagnostic imaging, including the variable definition of high-risk prostate cancer, variable guideline recommendations, poor accuracy of existing imaging tests, and the difficulty in validating imaging findings. Conventional imaging modalities, including CT and radionuclide bone scan, have been employed for local and metastatic staging, but their performance characteristics have generally been poor. Emerging modalities including multiparametricMRI, positron emission tomography (PET)-CT, and PET-MRI have shown increased diagnostic accuracy and could improve accuracy in staging patients with high-risk prostate cancer.

Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome.

Although animal studies have shown that the immunomodulator ipilimumab causes inflammation of the myocardium, clinically significant myocarditis has been observed only infrequently. We report a case of suspected acute coronary syndrome without a culprit lesion on cardiac angiography and takotsubo cardiomyopathy (TC)-like appearance on echocardiography in a patient with metastatic melanoma who received four standard doses of ipilimumab. Apical ballooning, hyperdynamic basal wall motion, systolic anterior motion of the mitral valve, and associated severe left ventricular outflow tract obstruction were present. Restaging with positron emission tomography-computed tomography done soon after discharge incidentally revealed increased fludeoxyglucose uptake in the apex. This case illustrates that a TC-like syndrome might be caused by autoimmune myocarditis after ipilimumab treatment although this was not biopsy-confirmed. Post-marketing surveillance should capture cardiac events occurring in patients treated with ipilimumab to better document and clarify a relationship to the drug, and biopsies should be considered. Physicians utilizing this novel agent should be aware of the potential for immune-related adverse events.

A complication of tracheobronchopathia osteochondroplastica presenting as acute hypercapnic respiratory failure.

BACKGROUND: Tracheobronchopathia osteochondroplastica is a rare benign and often indolent disease. We report the first case of tracheobronchopathia osteochondroplastica (TBO) presenting as acute hypercarbic respiratory failure due to superimposed subglottic submucosal abscess. CASE REPORT: A 27-year-old man presented to the emergency department in respiratory distress that required mechanical ventilation for acute hypercarbic respiratory failure. Upon extubation the next day, stridor was elicited with ambulation. Spirometry revealed fixed upper airway obstruction. Neck imaging showed a 2.8 × 2.0 × 4.0 cm partially calcified subglottic mass with cystic and solid component obstructing 75% of the airway. Surgical exploration revealed purulent drainage upon elevation of the thyroid isthmus and an anterolateral cricoid wall defect in communication with a subglottic submucosal cavity. Microbiology was negative for bacteria or fungi. Pathology showed chondro-osseous metaplasia compatible with tracheobronchopathia osteochondroplastica (TBO). The patient received a course of antibiotics and prophylactic tracheostomy. Since tracheostomy removal 3 days later, the patient remains asymptomatic. CONCLUSIONS: Tracheobronchopathia osteochondroplastica is a rare disease with usually benign clinical course and incidental diagnosis. It may present as acute hypercarbic respiratory failure when subglottic infection is superimposed.

Ipilimumab-induced hepatitis on 18F-FDG PET/CT in a patient with malignant melanoma.

A 78-year-old man with metastatic malignant melanoma underwent a restaging 18F-FDG PET/CT after initiation of ipilimumab therapy, a Food and Drug Administration-approved human monoclonal antibody targeting CTLA-4. PET/CT demonstrated intense FDG uptake fusing to poorly circumscribed hypodensities throughout the liver. Patient was experiencing high-grade fever, chills, and generalized fatigue at the time of imaging, as well as mildly elevated liver function tests. Patient was subsequently treated with corticosteroids for suspected ipilimumab-induced hepatitis, and the patient rapidly improved clinically. Follow-up PET/CT 2 months later revealed complete resolution of abnormal FDG uptake in the liver, confirming the diagnosis of ipilimumab-induced hepatitis.