Inflammatory Myofibroblastic Tumor Driven by Novel NUMA1-ALK Fusion Responds to ALK Inhibition.

Inflammatory myofibroblastic tumors (IMTs) are soft tissue neoplasms with rare metastatic potential. Approximately half of IMTs are positive for an ALK rearrangement, and ALK inhibitors have been used successfully in the treatment of IMTs with a variety of ALK fusions. This report describes a 21-year-old woman with an aggressive, metastatic IMT with a novel NUMA1-ALK fusion that showed a dramatic response to the ALK inhibitors crizotinib and alectinib. To our knowledge, this report provides the first published description of an IMT with a NUMA1-ALK fusion. The patient's aggressive IMT responded favorably to crizotinib and alectinib, suggesting that ALK inhibitors may be effective in IMT with NUMA1-ALK fusions. We review published reports of ALK-driven IMTs that have received ALK inhibitor therapy and suggest characteristics that may be associated with favorable response to treatment. We also discuss the strengths and limitations of immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing in the diagnosis and management of IMTs.

Rapid motor learning in the translational vestibulo-ocular reflex.

Motor learning was induced in the translational vestibulo-ocular reflex (TVOR) when monkeys were repeatedly subjected to a brief (0.5 sec) head translation while they tried to maintain binocular fixation on a visual target for juice rewards. If the target was world-fixed, the initial eye speed of the TVOR gradually increased; if the target was head-fixed, the initial eye speed of the TVOR gradually decreased. The rate of learning acquisition was very rapid, with a time constant of approximately 100 trials, which was equivalent to <1 min of accumulated stimulation. These learned changes were consolidated over >or=1 d without any reinforcement, indicating induction of long-term synaptic plasticity. Although the learning generalized to targets with different viewing distances and to head translations with different accelerations, it was highly specific for the particular combination of head motion and evoked eye movement associated with the training. For example, it was specific to the modality of the stimulus (translation vs rotation) and the direction of the evoked eye movement in the training. Furthermore, when one eye was aligned with the heading direction so that it remained motionless during training, learning was not expressed in this eye, but only in the other nonaligned eye. These specificities show that the learning sites are neither in the sensory nor the motor limb of the reflex but in the sensory-motor transformation stage of the reflex. The dependence of the learning on both head motion and evoked eye movement suggests that Hebbian learning may be one of the underlying cellular mechanisms.

Thymoma and parathyroid adenoma: false-positive imaging and intriguing laboratory test results.

IMPORTANCE: Parathyroid hormone (PTH)-secreting thymomas are an exceedingly rare entity. A PTH-secreting thymoma was discovered in the workup of a patient with primary hyperparathyroidism. A concomitant parathyroid adenoma was removed from the same patient. We present the intriguing clinical course and review the literature on this rare entity. In addition, we discuss the use of scanning with technetium Tc 99m sestamibi, the PTH assay, and cervical ultrasonography in the workup of a parathyroid adenoma. OBSERVATIONS: Scanning with technetium Tc 99m sestamibi demonstrated false-positive uptake of the mediastinal thymoma and false-negative uptake of the true cervical parathyroid adenoma. After removal of the thymoma, the parathyroid adenoma demonstrated appropriate uptake on a follow-up scan. After removal of the parathyroid adenoma, the hyperparathyroidism was cured. CONCLUSIONS AND RELEVANCE: Given the extremely rare incidence of a PTH-secreting thymoma with a concurrent parathyroid adenoma, we do not recommend alterations in the diagnostic algorithm for primary hyperparathyroidism. However, in this case, the need for 2 separate operations may have been avoided by obtaining an ultrasonogram to further explore the findings on the technetium Tc 99m sestamibi scan. We recommend that both studies be considered in unclear cases of primary hyperparathyroidism.

Revisiting the Marrow Metabolic Changes after Chemotherapy in Lymphoma: A Step towards Personalized Care.

Purpose. The aims were to correlate individual marrow metabolic changes after chemotherapy with bone marrow biopsy (BMBx) for its potential value of personalized care in lymphoma. Methods. 26 patients (mean age, 58 ± 15 y; 13 female, 13 male) with follicular lymphoma or diffuse large B-cell lymphoma, referred to FDG-PET/CT imaging, who had BMBx from unilateral or bilateral iliac crest(s) before chemotherapy, were studied retrospectively. The maximal standardized uptake value (SUV) was measured from BMBx site over the same area on both initial staging and first available restaging FDG-PET/CT scan. Results. 35 BMBx sites in 26 patients were evaluated. 12 of 35 sites were BMBx positive with interval decrease in SUV in 11 of 12 sites (92%). The remaining 23 of 35 sites were BMBx negative with interval increase in SUV in 21 of 23 sites (91%). The correlation between SUV change over the BMBx site before and after chemotherapy and BMBx result was significant (P < 0.0001). Conclusions. This preliminary result demonstrates a strong correlation between marrow metabolic changes (as determined by FDG PET) after chemotherapy and bone marrow involvement proven by biopsy. This may provide a retrospective means of personalized management of marrow involvement in deciding whether to deliver more extended therapy or closer followup of lymphoma patients.

Fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography predicts extrahepatic metastatic potential of colorectal metastasis: a practical guide for yttrium-90 microsphere liver-directed therapy.

The objective of this retrospective study was to assess the likelihood of extrahepatic metastases based on tumor metabolic load index (TMLI) for patients with colorectal liver metastases to determine the potential intermediate endpoint of yttrium-90 (Y-90) microsphere liver-directed therapy. Forty-eight (48) patients with colorectal metastatic cancer of the liver who were referred for Y-90 microsphere therapy and F-18 fluoro-2-deoxy-D-glucose positron emission tomography (PET) imaging were included. All patients had baseline computed tomography, hepatic angiography, and planning intra-arterial technetium-99m macro-aggregated albumin scans. Pretreatment PET images were analyzed by visual inspection of extrahepatic metastases and by computer quantification of total liver tumor metabolism. For each patient, regions of interest were drawn along the liver edge to measure total liver standard uptake value on axial images, covering the entire span of the liver. The total liver standard uptake value was then converted by logarithm in equivalent volumes of liver mass to obtain TMLI for comparison. A Levene test for equality of variances and t-tests were used for comparing pretreatment TMLIs of patients with or without extrahepatic metastasis. Discriminant and receiver operating characteristic (ROC) analyses were used to obtain a cutoff value with highest specificity in predicting negative extrahepatic metastasis. There were 21 and 27 patients identified as negative and positive for extrahepatic metastasis, respectively. The TMLI of the group with negative extrahepatic metastasis was significantly lower than that with positive extrahepatic metastasis (10.22 + 0.32 versus 10.74 + 0.57, p < 0.0005). The cutoff TMLI with 100% specificity was found to be 10.65. There was a significant difference in liver tumor load with respect to the presence or absence of an extrahepatic metastatic tumor as evaluated objectively with PET. This leads to the identification of TMLI threshold, below which extrahepatic metastases are unlikely and thus may provide guidance for Y-90 therapy.

Correlating metabolic activity with cellular proliferation in follicular lymphomas.

PURPOSE: The aim of this study was to correlate metabolic behavior of follicular lymphoma with proliferative index (Ki67). MATERIALS AND METHODS: Pre-treatment 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography-computed tomography scans of 23 patients with pathologic diagnosis of follicular lymphoma were retrospectively analyzed together with Ki67. The maximal standardized uptake value (SUV) was measured and corrected to glucose level of 100 mg/dl over the biopsy region (BxSUV100) and at the highest tumor activity of the body (BmSUV100). RESULTS: BxSUV100 was significantly correlated with Ki67 (p = 0.037). There was an increasing trend of metabolic activity across the pathologic grades of follicular lymphomas. BmSUV100 and BxSUV100 were also significantly different (p < 0.0005), suggesting potential pitfalls of sampling error by histology. CONCLUSION: The increasing trend of metabolic activity across follicular lymphoma grades correlates with cellular proliferation. The metabolic information from positron emission tomography-computed tomography may offer another useful parameter in the management of follicular lymphomas.

Exceptionally low metabolic activity in aggressive peripheral T-cell lymphoma.

PURPOSE: To investigate metabolic behavior of aggressive peripheral T-cell (PTC) lymphoma compared with other aggressive T-cell (OTC) nonHodgkin's lymphomas (NHLs) and the various grades (1, 2, 3) of follicular B-cell (FC) NHL as a reference cell type for indolent to aggressive behavior. MATERIALS AND METHODS: Pretreatment 2-deoxy-2-[¹8F] fluoro-d-glucose positron emission tomography-computed tomography scans of 33 patients with pathologic diagnosis of aggressive T-cell NHL and FC (FC1 = 6, FC2 = 8, FC3 = 9, PTC = 6, OTC = 4) were analyzed. The maximal standardized uptake value (SUV) was measured over biopsy region (BxSUV) and the highest tumor activity of the body (BmSUV). RESULTS: There were significant differences in both BxSUV (P = 0.036) and BmSUV (P = 0.026) among these five groups with significantly lower metabolic activity in PTC compared with other aggressive NHL (FC3, OTC). BmSUV in PTC was significantly lower than that in OTC (8.2 ± 2.5 vs. 22.3 ± 7.0, P = 0.029) and was similar to that of FC1 (9.4 ± 1.9) and FC2 (9.7 ± 1.4) but lower than that of FC3 (14.6 ± 2.7). Similar findings were noted in BxSUV between PTC and OTC (6.7 ± 2.5 vs. 20.4 ± 7.2, P = 0.035). CONCLUSION: Although 2-deoxy-2-[¹8F]fluoro-d-glucose positron emission tomography has been found to reflect metabolic activity for the aggressiveness of B-cell NHL, PTC has an exceptionally low metabolic activity, similar to that of low-grade B-cell FC1 and FC2.