Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.

BACKGROUND: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown. METHODS: We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments. RESULTS: This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation. CONCLUSION: Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.

Erdheim-Chester Disease Due to a Novel Internal Duplication of NRAS: Response to Targeted Therapy with Cobimetinib.

Histiocytoses encompass a group of exceptionally rare disorders characterized by the abnormal infiltration of tissues by histocytes. Among these, Erdheim-Chester disease (ECD) stands out as a multisystem histiocytosis that typically affects bones and various other tissues. Historically, the treatment of ECD has been challenging. However, recent breakthroughs in our understanding, particularly the discovery of somatic mutations in the RAS-MAPK pathway, have opened new opportunities for targeted therapy in a significant subset of patients with ECD and other histiocytoses. In this report, we present the case of a patient with ECD harboring a previously unidentified microduplication in the NRAS gene in a small fraction of skin cells. This discovery played a pivotal role in tailoring an effective therapeutic approach involving kinase inhibitors downstream of NRAS. This case underscores the crucial role of deep sequencing of tissue samples in ECD, enabling the delivery of personalized targeted therapy to patients.

Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Giant Left Pectoral Muscle Plasmacytoma and Multiple Myeloma Case.

Extramedullary plasmacytoma is an unusual manifestation in multiple myeloma (MM). It can present as a solitary bone lesion and/or soft-tissue mass. Plasmacytoma can be presented at any location, but it is more common in the head and neck, usually without systemic involvement. The presence of plasmacytoma in MM is a predictor of rapidly progressive disease. The value of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (PET-FDG) is increasing, in the diagnosis, detection of occult lesions, and therapeutic monitoring. We describe a patient with rapidly-progressive, refractory, left pectoral muscle plasmacytoma and MM. A PET-FDG guided the therapy and allowed to identify the presence of disease relapse.

Effect of positive carbon-11-choline PET/CT results in the therapeutic management of prostate cancer biochemical relapse.

OBJECTIVE: Carbon-11-(C)-choline PET/computed tomography (CT) has shown good results in re-staging of prostate cancer (PCa) with raised serum levels of prostate-specific antigen. Our aim was to evaluate the effect of positive C-choline PET/CT results in the therapeutic management of patients with PCa with biochemical relapse (BR) after curative intention treatment. PATIENTS AND METHODS: A total of 112 patients with PCa BR and positive C-choline PET/CT were retrospectively evaluated. PET/CT was acquired 20 min after intravenous administration of 555-740 MBq of C-choline. The therapeutic management after C-choline PET/CT was obtained from the clinical records. The minimum follow-up time was 18 months. RESULTS: In 80 (71.4%) of 112 patients, C-choline PET/CT showed local recurrence of PCa; in 17 (15.2%) patients, distant recurrence; and in 15 (13.4%) patients, local plus distant recurrence. A second malignancy was detected in five (4.5%) patients. The planned therapeutic management was changed as per positive C-choline PET/CT result in 74 (66.1%) patients and were treated as follows: 31 (27.7%) patients with HT, combined with other treatments in eight (7.1%), 17 (15.2%) with BT, 13 (11.6%) with external beam radiotherapy, one (0.9%) with RP, and four (3.6%) with chemotherapy. Treatment approach was not modified in 37 (33%) patients. No data was available from one (0.9%) patient. CONCLUSION: Positive C-choline PET/CT result had an important effect in the therapeutic management of patients with PCa and BR, leading to a change in the planned approach in two (66.1%) out of three patients. In addition, in 4.5% of the patients, the C-choline PET/CT allowed the detection of a second malignancy.

Value of the visual and semiquantitative analysis of carbon-11-methionine PET/CT in brain tumors' recurrence versus post-therapeutic changes.

To compare the visual and semiquantitative analysis of carbon-11-methionine (C-MET) PET/computed tomography (CT) images in patients with primary brain tumors and suspected recurrence, persistence, or necrotic post-therapeutic changes. A total of 41 consecutive C-MET-PET/CT scans on 35 (21 men, mean age 44.1±16.6 years) patients were requested for MRI suspicion of recurrent or persistent primary tumor after therapy. The C-MET PET/CT were obtained 20 min after an intravenous injection of 555-740 MBq (15-20 mCi) of C-MET. Both visual and semiquantitative evaluations were performed comparing C-MET uptake between suspicious areas and different lesion/normal-to-background ratios. The final diagnosis was established by histological examination in 12 cases and clinical and MRI follow-up in 29 cases. Visual analyses were positive in 27 (63.4%) and negative in 14 (36.6%) of the C-MET PET/CT. The sensitivity was 83.9%, specificity was 90.0%, positive predictive value was 96.3%, negative predictive value was 64.3% and accuracy was 71.4%. For the semiquantitative analysis, all the lesion/normal-to-background ratios could differentiate between tumor and nontumor (P<0.001), the lesion/contralateral parenchyma (L/CP) maximum standardized uptake value (SUVmax) being the index with the highest area under de curve (0.938). Applying an L/CP SUVmax index of 1.21, the sensitivity was 89.3%, specificity was 90.0%, positive predictive value was 96.1%, negative predictive value was 75%, and accuracy was 82.9%. C-MET-PET/CT was a useful technique to differentiate post-therapeutic changes from tumor presence in treated patients with brain neoplasm in whom cerebral MRI is nonconclusive, showing a high diagnostic performance. Our results showed only slight differences between visual analysis methods and the L/CP SUVmax ratio, the best of the semiquantitative methods.

Erythema Nodosum-Like Panniculitis as a False-Positive 18F-FDG PET/CT in Advanced Melanoma Treated With Dabrafenib and Trametinib.

We present a 35-year-old woman with left axillary mass. Histopathological analysis revealed metastatic infiltration for BRAF-mutant melanoma. F-FDG PET/CT showed bilateral axillary lymphadenopathy as well as bone and subcutaneous metastases. Dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) combined therapy was started with a complete metabolic response established by 2 consecutive PET/CT scans. A follow-up PET/CT showed FDG uptake in several subcutaneous nodules in both distal legs, suggesting metastases. Painless cutaneous lesions were observed on physical examination, and biopsy revealed erythema nodosum-like panniculitis.

The Role of PET/CT Molecular Imaging in the Diagnosis of Recurrence and Surveillance of Patients Treated for Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide and its prognosis remains poor. Molecular imaging with 18F-FDG PET/CT can metabolically characterize the nature of lesions as benign or malignant, allowing a better staging at the diagnosis of this kind of patient. This advantage can also be applied in the re-staging due to the suspicion of recurrent disease. Many patients have a recurrence of the disease, including surgically treated patients. In the current context, with new personalized oncological treatments, the surveillance for recurrence and its accurate diagnosis are crucial to improve their survival. In this paper, we revise the current knowledge about the clinical and molecular factors related to the recurrent disease. In the context of new, promising, available personalized treatments, the role of molecular imaging with PET/CT and 18F-FDG and non-18F-FDG radiotracers in the follow-up of NSCLC-treated patients is especially attractive and interesting.

11C-Choline and 18F-FDG PET/CT in the Detection of Occult Prostate Cancer in the Context of a Paraneoplastic Syndrome.

In a 73-year-old man, an occult neoplasm was suspected after 2 consecutive deep venous thrombosis, the latter under anticoagulant therapy and previous axonopathy. After normal CT and MRI findings, a requested (18)F-FDG PET/CT showed a focal uptake in the prostate. Because FDG uptake in the prostate is infrequent, a (11)C-choline PET/CT was indicated revealing a focal uptake in the same location. No other abnormalities were detected in the rest of the body. A guided biopsy by ultrasonography was performed revealing a prostate carcinoma and inflammation in both prostatic lobes.

Diagnosis of mantle-cell lymphoma relapse by 18F-FDG PET/CT after water gastric distention.

Proper gastric distention with oral contrast agents is a well-recognized CT technique for imaging of the stomach. We present the basal and after water ingestion F-FDG PET/CT images that show abnormal focal FDG uptake in a clinically unsuspected gastric relapse of mantle-cell lymphoma. The patient had achieved complete remission after chemoradiotherapy and autologous stem-cell transplantation 3 years before. The images obtained after the distention of the stomach with water were crucial to confirm the presence of an FDG-avid lesion in the antrum and to distinguish between physiological and pathological radiotracer uptake. Histological analysis confirmed mantle-cell lymphoma infiltration.

Diagnosis of recurrence and assessment of post-recurrence survival in patients with extracranial non-small cell lung cancer evaluated by 18F-FDG PET/CT.

UNLABELLED: The accurate diagnosis of recurrence of non small cell lung cancer (NSCLC) is crucial for the appropriate management of patients with suspicion of recurrence (SOR). We evaluated prospectively in the clinical setting the contribution of FDG PET/CT in patients with SOR of NSCLC in terms of sensitivity, specificity, impact on therapy and on survival. METHODS: Of the 55 patients included in the study, recurrence was confirmed in 37 but, follow up data for survival evaluation was available in 34. There were 59 SOR in the 55 patients and in 41 recurrence was confirmed. 53 of the 59 suspicions, had a contrast enhanced CT. All patients had a FDG PET/CT scan after iv injection of 8 MBq/kg of F18-FDG. RESULTS: Of the 59 SOR, FDG PET/CT was positive in all 41 in which recurrence was confirmed (100% sensitivity) and, it was negative in 15 of the 18 in which it was ruled out (specificity 83%). In 27 SOR with inconclusive CT, FDG PET/CT showed 100% sensitivity (18/18) and 78% specificity (7/9). FDG PET/CT had an impact on treatment in 42 of the 59 SOR. In all 34 patients, FDG PET/CT diagnosed recurrence and overall survival at 20 months and 5 years was 44% and 11%, respectively. When the extent of recurrence assessed by FDG PET/CT was considered, survival at 20 months and at 5 years of patients with loco-regional recurrence was 77% and 28% and in patients with distant recurrence 14% and 0% (p < 0.001). CONCLUSION: Despite the small number of patients, our study demonstrates that FDG PET/CT is highly accurate for the detection of NSCLC recurrence. Therefore it has a great impact on the therapy regimen and on survival depending on the extent of the recurrent disease, survival being better for patients with local recurrence. By differentiating local from distant recurrence, it allows the selection of patients who, could potentially benefit from new therapies. The results also suggest that there are grounds to include FDG PET/CT in the guidelines for surveillance for NSCLC.

Sarcoidosis presenting as transient ischemic attack status.

We report a patient who experienced multiple transient ischemic attacks (TIAs) over a 3-month period as the presenting clinical manifestation of sarcoidosis. This previously healthy 27-year-old man was admitted due to several daily episodes of usually left hemiparesis and dysarthria lasting between 15 seconds and 3 minutes. He did not respond to aggressive antithrombotic treatment. Extensive investigations were negative except for a computed tomography body scan showing several small right hilar lymphoadenopathies, which were confirmed by abnormal 67-gallium scintigraphy and 18F-fluorodeoxyglucose positron emission tomography uptakes. The TIA episodes disappeared after the initiation of prednisone therapy. The lymphadenopathy specimens were biopsied via mediastinoscopy, and histological study revealed noncaseating epithelioid granulomatous inflammation consistent with sarcoidosis. Sarcoidosis should be considered in the differential diagnosis of stroke of unknown origin in any young patient, even in the absence of other clinical or laboratory features of sarcoidosis.

Early planar and early SPECT Tc-99m sestamibi imaging: can it replace the dual-phase technique for the localization of parathyroid adenomas by omitting the delayed phase?

PURPOSE: To evaluate whether an early protocol (EP) (early planar and early SPECT) with Tc-99m sestamibi could demonstrate the delayed image of the established dual-phase scintigraphy unnecessary without any decrease in sensitivity for the localization of parathyroid adenomas. MATERIALS AND METHODS: A study was carried out in 80 consecutive patients with primary hyperparathyroidism (65 women; mean age, 61.8±14.2 years). Final diagnosis by surgery was possible in 79 patients and confirmed parathyroid adenoma in 76 patients, 1 hyperplasic gland in 1 patient, 2 hyperplasic glands in 1 patient, and differentiated thyroid carcinoma in another patient. Ten minutes after intravenous injection of 740 MBq (20 mCi) of Tc-99m sestamibi, a planar image followed by a SPECT and a 2 to 3 hours delayed planar image were acquired. Two sets of images were evaluated, one without (EP) and the other with the delayed image (dual-phase protocol [DPP]). An abnormality rating of 0 to 4 was given to each set and was compared with the final diagnosis. RESULTS: When any focal uptake, no matter the intensity, was considered positive, that is setting the threshold in the abnormality rating 1, 71 of the 76 adenomas were correctly localized by DPP and EP (sensitivity: 93.4%). CONCLUSIONS: The delayed planar image could be omitted without any loss in sensitivity for the localization of parathyroid adenomas, and therefore EP could replace DPP.

Hepatorenal polycystic disease and fever: diagnostic contribution of gallium citrate Ga 67 scan and fluorine F 18 FDG-PET/CT.

A cyst infection was suspected in a patient who was on haemodialysis for renal failure secondary to hepatorenal polycystic disease with persistent fever and pain in right hypochondrium despite antibiotherapy. Radiologic exams (ultrasonography, computed tomography [CT]), however, did not show signs of infection. For surgical removal of the infected cyst, a precise location was required. This report shows how functional imaging, gallium citrate Ga 67 scan, and fluorine F 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed which cyst was infected; however, the fused image provided by PET/CT showed the precise, required location. The infected cyst was located on the right kidney. A week later, after nephrectomy, all symptoms disappeared.

Diagnosis of common iliac artery thrombosis and renal artery thrombosis in a kidney transplant by radionuclide renography.

In a 58-year-old woman, the external iliac artery was accidentally dissected during the arterial anastomosis of a kidney transplant. An immediate CT angiogram showed an almost total occlusion of the common iliac artery. After the transplantation, radionuclide renography with Tc-99m MAG3 showed no flow across the right common iliac artery and no graft vascularization. Sequential images showed a photopenic area corresponding to the renal graft. These findings were interpreted as common iliac artery thrombosis and renal artery thrombosis associated with renal graft infarct. Excision of the transplant and iliofemoral bypass were performed. Pathologic examination of the graft showed massive acute renal infarct and renal artery thrombosis.