Drug-induced Sarcoid-like Reaction Presenting as Fascitis.

Maximizing FDG-PET/CT Utility in Staging of Follicular Lymphoma (FL): The Role of Spleen Involvement and Bone Standardized Uptake Values

Predicting early clinical failure in patients with untreated follicular lymphoma (FL) is important but difficult. This study aimed to determine the incidence and patterns of extranodal (EN) and spleen disease using PET/CT, and assess their utility in predicting early clinical failure. PET/CT images from 613 cases of untreated FL (2003-2016) were reviewed. The location and number of EN sites, patterns of bone involvement, and splenic involvement were recorded. Outcomes were assessed using event-free survival (EFS), overall survival (OS), and early clinical failure at 24 months (EFS24). So, 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. The presence of ≥2 EN sites, spleen, bone or soft tissue involvement all predicted failure to achieve EFS24. Presence of ≥2 EN sites and bone involvement pattern were also predictive of OS in a univariate analysis. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (HR 1.49 (1.11-2.00), P = .007; HR 1.71 (1.10-2.65), P = .017; and HR 1.67 (1.06-2.62), P = .026, respectively). When the multivariate analysis was performed using PRIMA-PI factors (marrow and B2M), the number of EN sites was an independent prognostic factor for inferior OS (HR 2.28; P = .05). Baseline PET/CT identifies EN involvement in nearly half of patients with untreated FL. The presence of ≥2 EN sites, bone, soft tissue, or splenic involvement predicts early clinical failure. These results, when combined with other factors, may better identify high-risk patients and guide therapy.

Standard bone marrow biopsy (BMB) and bone involvement with follicular lymphoma (FL) on positron emission tomography (PET)/computed tomography (CT) both predict early clinical failure in FL. The key clinical question is whether PET/CT findings can obviate the need for BMB. The goal of this study was to determine the value of PET/CT in determining bone involvement in FL, using posterior iliac crest BMB as the gold standard. A total of 548 patients with newly diagnosed grade 1-3A FL were included. The presence, pattern, and location of bone involvement, spleen involvement, and standardized uptake values (SUVs) in the L3 vertebral body were recorded for all patients and compared with the BMB report. Excluding patients with focal bone lesions on PET/CT, the sensitivity and specificity of PET/CT in detecting bone or marrow involvement, compared with BMB, were 53% and 88%, respectively. The sensitivity and specificity of spleen involvement on PET/CT in predicting a positive BMB were 55% and 86%, respectively. An L3 SUVmax of less than 2.0 resulted in a negative predictive value (NPV) of 96% for marrow involvement on BMB; an L3 SUVmean below 1.4 resulted in an NPV of 100%. In newly diagnosed FL, PET/CT-detected bone and splenic involvement is highly specific for a positive BMB, and very low SUV values (<2.0 SUVmax and < 1.4 SUVmean ) in the lumbar spine have a high NPV for a negative BMB. Routine BMB may be obviated in these patients. BMB remains necessary to definitively exclude bone marrow involvement in a large majority of patients with a negative PET. Predicting early clinical failure in follicular lymphoma (FL) is important but difficult. Bone marrow involvement by FL is associated with early clinical failure, and determining this involvement is a key component of the initial staging. This study highlights that in certain patients, positron emission tomography/computed tomography is sufficient in determining bone or marrow involvement, without the need for a confirmatory bone marrow biopsy (BMB). An algorithm is provided based on these findings to help clinicians determine which patients would benefit from BMB and when it can be avoided.

Background:Predicting early clinical failure in patients with untreated follicular lymphoma (FL) is important but difficult. Lymphoma involvement of extranodal (EN) sites is better detected by FDG‐PET/CT than CT alone, but PET parameters are not part of the usual predictive indices.Aims:We aimed to determine the incidence and patterns of EN and spleen disease, and learn if they were useful in predicting early clinical failure.Methods:PET/CT images from 613 cases of newly diagnosed FL between 2003 – 2016 were retrospectively reviewed for EN and spleen involvement. The location, number, and pattern of EN sites, as well as splenic involvement, were recorded. Associations with outcomes were assessed using event‐free survival (EFS), overall survival (OS), and early clinical failure at 24 months (EFS24).Results:49% (301/613) of patients had PET/CT‐detected EN involvement, and 28% (171/613) had spleen involvement. Presence of ≥2 EN sites, spleen, bone or soft tissue involvement all predicted failure to achieve EFS24. These factors, as well as pattern of bone involvement by imaging, were predictors of EFS on univariate analysis; presence of ≥2 EN sites and bone involvement pattern were also predictive of OS. In a multivariate analysis with FLIPI‐2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (Table 1). When the multivariate analysis was performed using PRIMA‐PI factors (marrow and B2 M), the presence of ≥2 EN sites was an adverse independent prognostic factor for OS (HR 2.28; 95% CI 1.01–5.18; p = 0.05).Table 1: Extranodal and spleen involvement by PET/CT as predictors of event‐free survival Summary/Conclusion:Baseline PET/CT identifies EN and spleen sites of disease that can predict early clinical failure in FL. These results, when combined with other factors, may better identify high‐risk patients and guide appropriate therapy.imageimage

7554 Background: Predicting early clinical failure in patients with untreated FL is important but difficult. Lymphoma involvement of EN sites is better detected by FDG-PET/CT than CT alone, but PET parameters are not part of the usual predictive indices. We aimed to determine the incidence and patterns of spleen and EN disease using PET/CT, and learn if they are useful in predicting early clinical failure. Methods: PET/CT images from 613 cases of newly diagnosed FL between 2003 – 2016 were retrospectively reviewed. The location, pattern, and number of EN sites, as well as splenic involvement, were recorded. Associations with outcomes were assessed using event-free survival (EFS) and overall survival (OS). Results: 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. Presence of ≥2 EN sites, spleen, bone, or soft tissue involvement, as well as a multifocal on diffuse pattern of bone involvement by imaging, were univariate predictors of EFS; presence of ≥2 EN sites and bone involvement pattern were also predictive of OS. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (Table). When the multivariate analysis was performed using PRIMA-PI factors, the presence of ≥2 EN sites was an adverse independent prognostic factor for OS (HR 2.28; 95% CI 1.01-5.18; p=0.05). Conclusions: Baseline PET/CT identifies EN and spleen sites of disease that can predict early clinical failure of FL. These results may be useful to better identify high-risk patients and guide appropriate therapy. [Table: see text]

e20068 Background: FL grade 3B (FL3B) is an aggressive subtype of FL with a distinct morphologic, cytogenetic and immunohistochemical profile that is associated with higher mortality compared to other subtypes of FL. FL3B is a rare disease, and data regarding its prognostication beyond grading is lacking. Recent data suggests that spleen and extranodal (EN) involvement on PET/CT predict early clinical failure in FL grades 1-3A[1]. We aimed to determine the incidence of spleen and EN involvement on PET/CT in FL3B, and whether these can predict EFS. Methods: Patients with untreated FL3B diagnosed between 2003-2016, with available pre-treatment PET/CT, were identified using the Mayo Clinic Lymphoma Database and the University of Iowa/Mayo Clinic Lymphoma SPORE database. 27 patients were included in this analysis. All but two patients received treatment with immunochemotherapy. Associations with outcomes were assessed using EFS, defined as disease progression, relapse, transformation, or death. Results: 11/27 (40.7%) of patients had EN involvement on PET/CT. The most common EN site was bone, in 8/27 (29.5%) of patients. Soft tissue involvement was present in 4/27 (14.8%) of patients. Liver, brain, and endometrial involvement were each noted once. 11/27 (40.7%) of patients had spleen involvement on PET/CT. Presence of bone involvement as detected on PET/CT was associated with lower EFS (p = 0.02). EN involvement was associated with a trend toward a lower EFS but statistical significance was not reached likely secondary to low numbers in this cohort. Results in the table are compared to results obtained from our analysis in patients with FL grade 1-3A[1]. Conclusions: Bone involvement on pre-treatment PET/CT in FL3B was associated with early clinical failure in this small cohort of 27 patients. EN involvement at diagnosis may also be associated with poorer outcomes. These findings are similar to our analysis of a large (n = 613) cohort of patients with FL grade 1-3A. These findings may aid in the prognostication of patients with newly diagnosed FL3B, to guide therapy in select higher risk patients. [Table: see text]

Does staging computered tomography change management in thick malignant melanoma?

Altered mental status (AMS) is a common presentation in the emergency department (ED). A previous study revealed 78% electroencephalogram (EEG) abnormalities, including nonconvulsive seizure (NCS; 5%), in ED patients with AMS. The objective of this study was to assess the impact of EEG on clinical management and outcomes of ED patients with AMS. This was a randomized controlled trial at two urban teaching hospitals. Adult patients (≥18 years old) with AMS were included. Excluded patients had immediately correctable AMS (e.g., hypoglycemia) or were admitted before enrollment. Patients were randomized to routine care (control) or routine care plus EEG (intervention). Research assistants used a scalp electrode set with a miniature, wireless EEG device (microEEG) to record standard 30-minute EEGs at presentation, and results were reported to the ED attending physician by an off-site epileptologist within 30 minutes. Primary outcomes included changes in ED management (differential diagnosis, diagnostic work-up, and treatment plan from enrollment to disposition) as determined by surveying the treating physicians. Secondary outcomes were length of ED and hospital stay, intensive care unit (ICU) requirement, and in-hospital mortality. A total of 149 patients were enrolled (76 control and 73 intervention). Patients in the two groups were comparable at baseline. EEG in the intervention group revealed abnormal findings in 93% (95% confidence interval [CI] = 85% to 97%), including NCS in 5% (95% CI = 2% to 13%). Using microEEG was associated with change in diagnostic work-up in 49% (95% CI = 38% to 60%) of cases and therapeutic plan in 42% (95% CI = 31% to 53%) of cases immediately after the release of EEG results. Changes in probabilities of differential diagnoses and the secondary outcomes were not statistically significant between the groups. An EEG can be obtained in the ED with minimal resources and can affect clinical management of AMS patients.

We have evaluated the effect of dehydroepiandrosterone (DHEA) replacement therapy in 60- to 70-year-old women (n = 15) who received a single daily percutaneous application of a 10% DHEA cream for 12 months. While anthropometric measurements showed no change in body weight, we observed a 9.8% decrease in subcutaneous skinfold thickness at 12 months (P < 0.05). This was confirmed by measurements of midthigh fat and muscle areas by computed tomography where a 3.8% decrease (P < 0.05) in femoral fat and a 3.5% increase (P < 0.05) in femoral muscular areas were observed at 12 months. There was no significant change in abdominal fat measurements but the waist-to-hip ratio was only 0.83 at the onset of treatment. These changes in body fat and muscular mass were associated with a 11% decrease (P < 0.05) in fasting plasma glucose and a 17% decrease (P < 0.05) in fasting insulin levels. Treatment with DHEA had no adverse effect on the lipid or lipoprotein profile. In fact, an overall trend towards a decrease in total cholesterol and its lipoprotein fractions was observed. Plasma triglycerides were not affected. Plasma high-density lipoprotein (HDL) cholesterol decreased by 8% but the ratio HDL/cholesterol was unchanged by DHEA treatment because of a parallel decrease in total cholesterol. The index of sebum secretion showed a 73% increase (P < 0.05) during the 12 months of DHEA therapy followed by a return to pretreatment values 3 months after cessation of therapy. At the same time, sex hormone-binding globulin levels decreased (P < 0.05) during treatment and returned to pretreatment values 3 months after the end of therapy. Serum gonadotropins were not changed by DHEA treatment. Although not significant, we observed a tendency towards an elevation in serum GH levels. Values of serum IGF-I remained unchanged while plasma IGF-binding protein-3 levels significantly decreased (P < 0.05) during treatment and returned to pretreatment values after cessation of DHEA therapy. The present data clearly indicate the beneficial effects of DHEA therapy in postmenopausal women through its transformation into androgens and/or estrogens in specific intracrine tissues without any significant side effects.

BackgroundImmune checkpoint inhibition has dramatically transformed the treatment of malignant melanoma. With increasing use, their unique spectrum of immune-mediated toxicity has become apparent.Case presentationWe describe a case of sequential immune-related adverse events (irAEs) in a patient with metastatic melanoma treated with single-agent anti-programmed cell death-1 (PD-1) therapy, pembrolizumab. Although numerous cases of irAEs have been reported, sequential multi-organ involvement, including progressive atopic dermatitis, vitiligo, autoimmune nephritis, autoimmune hepatitis, and autoimmune encephalitis after cessation of therapy, has not been previously documented.ConclusionsImmunosuppression resulted in clinical remission of each irAE, highlighting the importance of vigilance for autoimmune complications in patients treated with checkpoint inhibition, even after immunotherapy cessation.

BackgroundDespite lithium being the most efficacious treatment for bipolar disorder, its use has been decreasing at least in part due to concerns about its potential to cause significant nephrotoxicity. Whilst the ability of lithium to cause nephrogenic diabetes insipidus is well established, its ability to cause chronic kidney disease is a much more vexing issue, with various studies suggesting both positive and negative causality. Despite these differences, the weight of evidence suggests that lithium has the potential to cause end stage kidney disease, albeit over a prolonged period.MethodsA search strategy for this review was developed to identify appropriate studies, sourced from the electronic databases EMBASE, PubMed (NLM) and MEDLINE. Search terms included lithium with the AND operator to combine with nephrotoxicity or nephropathy or chronic kidney disease or nephrogenic diabetes insipidus or renal and pathophysiology.ResultsThe risks for the development of lithium induced nephropathy are less well defined but appear to include the length of duration of therapy as well as increasing age, as well as episodes of over dosage/elevated lithium levels. Whilst guidelines exist for the routine monitoring of lithium levels and renal function, it remains unclear when nephrological evaluation should occur, as well as when cessation of lithium therapy is appropriate balancing the significant attendant mental health risks as well as the potential for progression to occur despite cessation of therapy against the risks and morbidity of bipolar disorder itself.ConclusionThis paper will elucidate on the current evidence pertaining to the topic of the clinical management of lithium induced nephrotoxicity and provide a guide for clinicians who are faced with the long-term management of these patients.

Oral cancers have a tendency to invade the surrounding bone structures, and this has a direct influence on the treatment management and on outcomes. The objective of this study was to correlate the clinical parameters (location, clinical presentation and TNM staging) of oral malignant tumors that can be associated with a potential of bone invasion and determine the accuracy of clinical examination to predict bone involvement, using computed tomography (CT). Twenty five patients, with oral malignant tumors were submitted to clinical and CT examinations. CT was considered the standard parameter to evaluate the presence of bone involvement. Clinical assessment of location, presentation form and TNM staging of the tumors were then compared to the CT findings in predicting bone involvement. Bone involvement was observed in 68% of the cases. It was predicted that tumors located in the retromolar trigone and hard palate, with a clinical aspect of infiltrative ulcer or nodule and classified in stage IV had a high potential to cause bone involvement. The clinical examination assessment of these tumors showed to be a valuable tool to predict bone invasion, with high sensitivity (82%) and specificity (87.5%), based on the results found in the CT images. No statistical significance was found between the CT and clinical examinations regarding bone involvement. The identification of some clinical parameters such as location, clinical presentation, and TNM stage, associated with a detailed clinical examination, was considered a valuable tool for the assessment of bone destruction by oral malignant tumors.

A 65-year-old male presented with headaches and painless episodes of unilateral vision loss. He had a history of renal cell carcinoma, in remission following surgery and immunotherapy with ipilimumab and nivolumab, discontinued 2 years and 3 months before presentation, respectively. MRI revealed an optic nerve sheath mass and perineuritis. After 1 month of corticosteroid therapy, there was a robust clinical and radiographic response, which relapsed dramatically following cessation. An optic nerve sheath biopsy showed chronic mild inflammation, and extensive work-up for alternative etiologies of orbital inflammation was negative. Following a prolonged taper of corticosteroids, he demonstrated complete response. In the setting of ocular immune privilege, ophthalmic immune-related adverse events (irAE) are rare, although multifarious. While on-treatment irAE are well-characterized, posttreatment irAE have become increasingly recognized across multiple organ systems. We report a case of a delayed-onset inflammatory optic nerve sheath mass and perineuritis after cessation of immunotherapy.

BackgroundImmune checkpoint inhibitors (ICI) are a new class of therapy used to treat many advanced malignancies. There is increased recognition of rare and severe neurological immune-related adverse events(irAEs) related to...

Although epithelial malignancies can have bone metastases, involvement of small bones is exceedingly rare, representing either first manifestation of an occult carcinoma or late disseminated disease. Small bone metastases may mimic primary skeletal diseases leading to misdiagnosis and delayed treatment. We report three cases of metastatic epithelial malignancies diagnosed by computed tomography (CT)-guided fine-needle aspiration (FNA) biopsy in two patients with lytic calcaneal lesions and a patellar lesion in a third patient; all with histologic confirmation. Case 1, a 63-year-old female, presented with heel pain. FNA and tissue biopsy of the calcaneus revealed a clear cell malignancy consistent with a renal primary. Follow-up abdominal CT scan revealed a renal lesion consistent with renal cell carcinoma. Case 2, a 37-yr-old male with squamous cell carcinoma of the esophagus, presented with foot pain. FNA and tissue biopsy of the calcaneous revealed metastatic squamous cell carcinoma. Case 3, a 52-yr-old male with a history of squamous cell carcinoma of floor of mouth, presented with knee pain and swelling. FNA and tissue biopsy of the patella revealed metastastic squamous cell carcinoma. To the best of our knowledge, this is the first complete FNA cytology report with histologic confirmation of unusual small bone metastases of the feet and patella from epithelial malignancies and shows the value of FNA cytology in establishing a correct diagnosis, and excluding primary skeletal diseases.