Role of whole body MRI in paraneoplastic/autoimmune syndromes: An MRPET study to standardize protocols, pattern interpretation, and establish yield of MRI.

Imaging a case of autoimmune encephalitis (AIE) can be challenging as the underlying tumor may be occult. The aim of this retrospective case-based study is to evaluate role of whole-body MRI/Positron emission tomography (PET) in workup of AIE. Standardizing the whole-body MRI/PET protocol, Cross modality yield with serology and magnetic resonance/PET (MR/PET) and finally highlight the advantage of hybrid MR/PET. We present the retrospective review data from January 2016 to December 2019 referred for whole body MR/PET with suspected AIE/Paraneoplastic syndrome, per consensus criteria, treated at a single tertiary center. Analysis is done group wise based on referral being for oncological, immunological or neuropsychiatric condition. Detailed results with sensitivity and specificity are presented in tabular format with case-based review in our series for protocols and advantages of MR/PET. Among total of 600 MR/PET cases, 227 were suspected of AIE/paraneoplastic syndrome and were referred for whole body imaging. Distribution of Group 1 Known oncology group (n = 10), Group 2 Non oncological systemic illness group (n = 174) and group 3 the primary neuropsychiatric illness (n = 43) with Group 2 being largest. The gender distribution was similar and mean age was 42 years. Seronegative cases (n = 130) were greater than seropositive cases (n = 97). Seropositivity was in the following order Autoimmune > Paraneoplastic > Myositis panel. Whole body MRPET yielded occult malignancy in 9% and imaging abnormality in 88% of cases. Whole body MR/PET has an important role in workup of AIE. Selection of the appropriate protocol is important, especially when history and physical examination are nonspecific.

Imaging characteristics of phosphaturic mesenchymal tumors.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome associated with phosphaturic mesenchymal tumors (PMTs). Localization of the causative tumor in these cases is an arduous task since the culprit lesions are usually small, slow-growing, and can be located almost anywhere from head to toe. PURPOSE: To describe the morphological characteristics of histologically proven PMTs on various radiological modalities. MATERIAL AND METHODS: After institutional ethical approval, this retrospective study analyzed 20 cases with a histopathological evidence of PMT. Various imaging characteristics of the tumors on available computed tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated. Descriptive statistical analyses were conducted. RESULTS: The tumors were located in diverse locations: lower extremities (n = 10); head and neck (n = 5); vertebral column (n = 3); pelvis (n = 1); and upper extremities (n = 1). Bone lesions seen on CT had variable morphology: sclerotic (n = 3/8, 37.5%); lytic (n = 3/8, 37.5%), and both lytic and sclerotic (n = 2/8, 25%) with presence of narrow zone of transition in all cases (n = 8/8) and amorphous internal matrix calcifications in 25% of cases (n = 2/8). Of the tumors, 68.4% (n = 13/19) were hypointense on T1 and all of them showed hyperintense signal on T2-weighted and STIR images (n = 19/19) and contrast enhancement (n = 16/16). Of the tumors, 66.7% (n = 6/9) showed restricted diffusion. DOTANOC PET/CT showed tumor uptake in all cases (n = 8/8). CONCLUSION: PMTs may have variable and non-specific tumor appearances on various imaging modalities. However, in an appropriate clinical scenario and a background of suggestive biochemical work-up, the radiologist should keep a high index of suspicion.

Paraneoplastic Syndromes from Head to Toe: Pathophysiology, Imaging Features, and Workup.

Patients often have symptoms due to the mass effect of a neoplasm on surrounding tissues or the development of distant metastases. However, some patients may present with clinical symptoms that are not attributable to direct tumor invasion. In particular, certain tumors may release substances such as hormones or cytokines or trigger an immune cross-reactivity between malignant and normal body cells, resulting in characteristic clinical features that are broadly referred to as paraneoplastic syndromes (PNSs). Recent advances in medicine have improved the understanding of the pathogenesis of PNSs and enhanced their diagnosis and treatment. It is estimated that 8% of patients with cancer develop a PNS. Diverse organ systems may be involved, most notably the neurologic, musculoskeletal, endocrinologic, dermatologic, gastrointestinal, and cardiovascular systems. Knowledge of various PNSs is necessary, as these syndromes may precede tumor development, complicate the patient's clinical presentation, indicate tumor prognosis, or be mistaken for metastatic spread. Radiologists should be familiar with the clinical presentations of common PNSs and the selection of appropriate imaging examinations. Many of these PNSs have imaging features that can assist with arriving at the correct diagnosis. Therefore, the key radiographic findings associated with these PNSs and the diagnostic pitfalls that can be encountered during imaging are important, as their detection can facilitate early identification of the underlying tumor, reveal early recurrence, and enable monitoring of the patient's response to therapy. © RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Paraneoplastic musculoskeletal disorders: review and update for radiologists.

Rheumatic paraneoplastic syndromes are rare syndromes that occur at distant sites from the underlying tumor and may involve the bones, joints, fasciae, muscles, or vessels. In the absence of a known tumor, early recognition of a rheumatic syndrome as paraneoplastic permits dedicated work-up for, and potentially early treatment of an occult malignancy. Although there is a continuously growing list of paraneoplastic rheumatic disorders, not all of these disorders have a well-established association with a neoplastic process. The goals of this article are to review the clinical characteristics, diagnostic work-up, and imaging findings of well-documented rheumatic paraneoplastic disorders.

Whole-body computed tomography as first-line imaging procedure to exclude cancer in patients with neurological suspicion of paraneoplastic syndromes: shall clinical practice adhere to recommendations?

INTRODUCTION: To assess the efficacy of whole-body computed tomography (WB-CT) as imaging procedure to exclude cancer in patients with neurological symptoms and signs at clinical onset. METHODS: A retrospective observational study was designed to identify consecutive WB-CT requested by the Neurology Unit with a suspicion of an underlying tumor potentially linked to a paraneoplastic neurological syndrome (PNS) between January 2019 and February 2022. The following data were collected: diagnosis at admission and at discharge, the presence of onconeural antibodies, the scans dose length product (DLP), the estimated effective dose (ED), the total estimated time requested; the PNS-Care-Score was retrospectively calculated only in subjects with available antibodies. RESULTS: The total number of patients included was 158. In 13/158 (positive group) a malignant or locally aggressive neoplasm was found while in 145/158 no malignant lesions were found on the WB-CT. Among the positive group, in 7/13 onconeural antibodies were diagnosed, resulting negative in all cases and the most frequent tumor was lung cancer (30.8%). PNS-Care-Score was of 6-7 in 2/7 (probable PNS) and in no case the PNS-Care-Score was ≥8 (definite PNS). The mean DLP for all the scans was 2798 ± 952 mGy cm (average estimated ED of 42 ± 14 mSv). The total estimated time requested for all scans was 11,060 min. CONCLUSION: If a PNS is suspected, we encourage the prescription of unenhanced chest CT and/or abdomen/testis/female pelvis ultrasound and/or mammography based on clinical picture. The WB-CT using a single portal phase would be appropriate as a second-line technique while magnetic resonance imaging might be indicated for the exclusion of nervous system diseases. IMPLICATIONS FOR PRACTICE: Our suggestion results in saving in terms of radiation exposure, financial resources and time.

Tumour-induced osteomalacia: a rare cause of chronic pain and weakness.

Tumor-induced osteomalacia is a rare and often misdiagnosed condition that presents with progressively worsening unexplained chronic pain and proximal muscle weakness. The osteomalacia leads to multiple stress fractures which do not heal properly, leading to progressive disability. It is caused by chronic hypophosphatemia due to inappropriate urinary phosphate wasting. This is due to a typically benign mesenchymal tumor that over-secretes a phospaturic hormone. Neurologists need to appreciate the relevance of chronic hypophosphatemia in people with chronic unexplained pain, as timely diagnosis and treatment of tumour-induced osteomalacia can be curative.

Phosphaturic Mesenchymal Tumor.

Phosphaturic mesenchymal tumors (PMTs) are neoplasms associated with tumor-induced osteomalacia. Patients typically present with pathologic fractures in the setting of chronic hypophosphatemic hyperphosphaturic osteomalacia, as well as gradual muscle weakness, bone pain, and difficulty walking. Because of their rarity and nonspecific symptomatology, phosphaturic mesenchymal tumors often go undiagnosed for years. Even when discovered on imaging, the tumors can be diagnostically challenging for radiologists. Phosphaturic mesenchymal tumors often tend to be small and can be located nearly anywhere in the body, and, therefore, can mimic many other tumors. This case highlights the imaging and pathologic markers of a phosphaturic mesenchymal tumor, often found in a patient with tumor-induced osteomalacia.

Thoracoabdominal computed tomography neoplasia detection in patients with paraneoplastic pemphigus: the importance of collaboration between specialists.

INTRODUCTION: Paraneoplastic pemphigus (PNP) is an autoimmune disorder that is almost always linked to an underlying neoplasia. General radiologists are usually not aware of what kind of neoplasia can be associated with PNP. Therefore, this study evaluates the effect of a dermatology lecture on radiologists' neoplasia diagnosis performance. METHODS: Two radiologists evaluated thoracoabdominal computed tomography (CT) examination images of 43 patients with PNP in separate reading sessions blinded to each other's assessments. Six months after the first CT image evaluation session, the two radiologists attended a lecture by two dermatologists about PNP, and 6 months later the two radiologists assessed the same CT examinations again. RESULTS: Statistical analysis showed statistically significant differences in CT sensitivity between the first and the second round of image evaluation for both radiologists (reader 1: p = 0.0313; reader 2: p = 0.0156). CONCLUSIONS: This is the first study to evaluate the effectiveness of a dermatology lecture on diagnostic performance. It is very important for radiologists to be familiar with the particular neoplasms that can be associated with PNP because this can have a direct clinical impact on diagnostic performance.

Bilateral Hypertrophic Olivary Degeneration as a Paraneoplastic Syndrome of a Poorly Differentiated Carcinoma of the Upper Gastrointestinal Tract: A Case Report and Literature Review.

INTRODUCTION: Hypertrophic olivary degeneration (HOD) is a unique form of trans-synaptic neuronal degeneration within the dentato-rubro-olivary pathway which is manifested by the enlargement and hyperintensities of the inferior olivary nucleus in the brain magnetic resonance imaging. CASE REPORT: We report a 53-year-old man admitted to our emergency department with a history of progressive ataxia and vertigo for 6 months before admission. Neurological examination revealed cerebellar dysfunction, and the brain magnetic resonance imaging showed bilateral HOD without an identifiable causative lesion within the brain or abnormal meningeal enhancement. Cerebrospinal fluid analysis showed mild lymphocytic pleocytosis, elevated protein, and negative cytology. Malignancy and paraneoplastic workup exhibited marked elevation of carbohydrate antigen 19-9 level and para-aortic lymphadenopathy. A histologic examination demonstrated the infiltration of lymph nodes by a malignant, poorly differentiated carcinomatous tumor that arises from the upper gastrointestinal tract. Considering the primary site of the tumor and HOD as a paraneoplastic effect of carcinoma, a FOLFIRINOX regimen, intravenous immunoglobulin, and pulse methylprednisolone were started. A follow-up imaging after 3 months depicted a significant resolution of HOD but the neurological status only mildly improved. The patient developed liver and adrenal metastasis over the following 6 months, culminating in his death. CONCLUSION: This study strengthens a relationship between HOD and malignancy as a paraneoplastic syndrome and provides a new incentive for further researches to confirm this association.

Bone Impairment in a Large Cohort of Chinese Patients With Tumor-Induced Osteomalacia Assessed by HR-pQCT and TBS.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density (aBMD) in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral (distal radius and tibia) and axial (lumbar spine) skeleton using high-resolution peripheral quantitative computed tomography (HR-pQCT) and trabecular bone score (TBS) and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry (DXA) or HR-pQCT scans were enrolled. Compared with age-, sex-, and body mass index (BMI)-matched healthy controls, TIO patients (n = 113) had lower volumetric BMD, damaged microstructure, and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS (<1.35) was higher than that with low L1 to L4 aBMD Z-score (Z ≤ -2) (43.9% versus 89.6%, p < 0.001). Higher intact fibroblast growth factor 23 (iFGF23), intact parathyroid hormone (iPTH), alkaline phosphatase, and ß-isomerized C-terminal telopeptide of type I collagen (ß-CTx) levels, more severe mobility impairment, and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection. © 2021 American Society for Bone and Mineral Research (ASBMR).

Radiotherapy for a rare phosphaturic mesenchymal tumor in the middle ear presenting with oncogenic osteomalacia: A case report.

RATIONALE: Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm causing oncogenic osteomalacia. Surgery remains the definitive treatment for PMT, and radiotherapy is seldom employed. However, surgery for PMT involving the head and neck is often difficult due to the local invasion and complicated anatomy. We report the first case of PMT, which was successfully treated with the combination of radiotherapy and supplementation of activated vitamin D. PATIENT CONCERNS: A 55-year-old woman suffered from pain in the hip and bilateral femur. Serum phosphate and calcium decreased to abnormal levels. Serum alkaline phosphatase and fibroblast growth factor 23 increased to abnormal levels. The hearing loss of the right ear had continued and a middle ear tumor was revealed. DIAGNOSES: Subsequent biopsy provided the diagnosis of PMT that caused oncogenic osteomalacia. These clinical and pathological characteristics were consistent with and provided the final diagnosis of benign PMT. INTERVENTIONS: Surgery of the PMT was difficult and the patient underwent radiotherapy. The prescribed dose was 36 Gy in 10 fractions. Simultaneously, the patient started supplementation of 1,25-dihydroxyvitamin D3 (1-2 µg/day) and continued for 2 years. OUTCOMES: Near-complete resolution of the symptoms was achieved and abnormal laboratory values recovered. At 5 years of follow-up, the irradiated tumor showed no regrowth. Severe hearing loss of the right ear was not observed. LESSONS: Radiotherapy was effective for the PMT and could be an important treatment option for inoperable cases.

Phosphaturic mesenchymal tumors: radiological aspects and suggested imaging pathway.

Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal neoplasms of soft tissue or bone origin that can give rise to a challenge in diagnostic imaging. These tumors are frequently associated with tumor-induced osteomalacia, also called oncogenic osteomalacia, which is a rare paraneoplastic syndrome characterized by ectopic secretion of fibroblast growth factor 23, a hormone that regulates serum phosphate level. PMTs show polymorphic features on both radiological findings and histological examination, causing problems in diagnosis owing to their similarity with other mesenchymal tumors. Thus, this paper aims to describe radiological aspects of PMTs and suggest an imaging pathway for accurate diagnosis throughout the evidence from the literature review.

Clinical challenges and management of primary renal epithelioid angiomyolipoma of duplex kidney with paraneoplastic syndrome.

Giant renal epithelioid angiomyolipoma of a duplex kidney has rarely been reported, especially in patients with paraneoplastic syndrome. The present report describes a 33-year-old man of Miao nationality who presented with a 6-month history of intermittent dull pain in the left upper abdomen that occurred after eating. Ultrasonography, intravenous pyelography, and computed tomography revealed a mass lesion localized in the left kidney and connected to the left renal artery. Radical nephrectomy was successfully performed, and the postoperative histopathological examination verified the lesion as epithelioid angiomyolipoma. Inpatient treatment for paraneoplastic syndrome was also performed. The present case is discussed in the context of the patient's clinical presentation and imaging findings, drawing attention to the challenges and management of this condition to assist clinicians in practice.

Thymic Carcinoma With Multiple Paraneoplastic Disorders.

Thymic neoplasms are rare and may run an indolent course. Among them, thymic epithelial carcinoma is exceptional as it may be presented with extensive local invasion and distant metastases. There is a wide spectrum of autoimmune/paraneoplastic syndromes associated with thymic tumors including autoimmune diseases, some of which may precede the diagnosis of thymoma. This article describes a 37-year-old woman with metastatic malignant thymoma and a combination of manifestations from different organs. Vitiligo, Raynaud's phenomenon and anti-centromere antibodies were preceded while eosinophilia, interstitial lung disease, rash, thickening of the skin and asymptomatic cryoglobulinemia were diagnosed concomitantly with the neoplasm. We have reviewed the literature and found only twenty case reports with a cluster of three or more autoimmune/paraneoplastic syndromes in the same patient but none with this unique constellation of disorders. The diversity of thymoma's clinical presentation and laboratory/histological features may cause diagnostic dilemmas and therapeutic challenges.

Neoplastic Meningitis and Paraneoplastic Syndromes.

Neoplastic meningitis (NM) and paraneoplastic syndromes (PNSs) are a rare group of disorders present in patients with cancer. Clinical diagnosis of these conditions is challenging, and imaging and laboratory analysis play a significant role in diagnosing. Diagnosis of NM largely depends on documenting circulating tumor cells in the cerebrospinal fluid (CSF) and/or leptomeningeal and nodular enhancement on contrast-enhanced MR imaging of the brain or axial spine. PNSs encompass a variety of symptoms or syndromes. Paraneoplastic neuronal disorder diagnosis requires a multidimensional approach, high clinical suspicion, CSF and serum examination, and imaging. Neuroimaging is an integral part in the evaluation.

Utility of 18F-AlF-NOTA-Octreotide PET/CT in the Localization of Tumor-Induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a paraneoplastic disorder, usually caused by benign mesenchymal tumors that produce high levels of fibroblast growth factor 23. The only curative therapy is resection of the causative tumors. OBJECTIVE: This research was conducted to evaluate the efficacy of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT) in detecting TIO and its impact on patient management. METHODS: Retrospective analysis was conducted of 17 patients with hypophosphatemic osteomalacia suspected to be TIO. A  18F-OC PET/CT study was performed in all 17 patients to localize the tumor and 68Ga-DOTATATE PET/CT was performed in 4 out of 17 patients; both studies were performed within 1 week of each other. Both studies were interpreted blindly without the knowledge of other imaging findings. The image findings were compared with the results of histopathological examinations and clinical follow-ups. RESULTS: The 18F-OC PET/CT scans were positive in 14 patients. Furthermore, 4 of 14 patients were scanned with both 18F-OC and 68Ga-DOTATATE PET/CT. Both studies were able to localize the tumor in all 4 patients. In total, 14 patients had surgery to remove the lesions. Postsurgical pathological examination confirmed causative tumors in these patients, whose symptoms diminished promptly. Serum phosphate levels normalized, confirming the diagnosis of TIO. 18F-OC PET/CT sensitivity, specificity, and accuracy were 87.5%, 100%, and 88.2% respectively. 18F-OC PET/CT findings affected patient management in 88.2% of cases. CONCLUSION: 18F-OC PET/CT scan is useful in the detection of tumors causing TIO. Further studies with larger patient populations are needed to validate the result.

Comparison of 18 F-FDG PET/CT and 68 Ga-DOTATATE PET/CT in the Targeted Imaging of Culprit Tumors Causing Osteomalacia.

OBJECTIVE: To assess and compare the performance of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18 F-FDG-PET/ CT) and gallium-68-labeled tetraazacyclododecanetetraacetic acid-DPhe1-Tyr3-octreotate (68 Ga- DOTATATE) PET/CT in the targeted imaging of culprit tumors causing osteomalacia. METHODS: This was a clinical retrospective analysis. We analyzed 13 patients (five men, eight women; mean age, 49 years; range, 19-55 years) with suspicion of tumor-induced osteomalacia (TIO) between March 2017 and October 2019. All patients underwent two functional imaging methods to locate the culprittumors. Studies were performed on a PET/CT scanner. The injection doses of 18 F- FDG and 68 Ga-DOTATATE were 0.5mCi/kg and approximately 5.0mCi, respectively. In the two scans, the whole body was captured from head to toe 45 to 60 min after intravenous tracer injection. 68 Ga-DOTATATE PET/CT and 18 F-FDG PET/CT imaging results locate culprit tumors according to the following criteria: (i) abnormal foci uptake concentration was observed locally, and the uptake level was higher than the background level of the right lobe of the liver; (ii) combined CT showed or did not have obvious abnormal density changes; and (iii) non-specific ingestion lesions due to fracture, arthritis, necrosis of femoral head are excluded. Compared with the results of pathological examination and clinical follow-up, the sensitivity, specificity and accuracy of 68 Ga-DOTATATE PET/CT imaging and 18 F-FDG PET/CT imaging for TIO were analyzed. RESULTS: All patients had symptoms of osteomalacia and hypophosphatemia. The lag time (symptoms to PET diagnosis) ranged from 2 to 12 years. There were eight cases of TIO patients and five cases of non-TIO patients confirmed by surgery, pathology and follow-up. Among the eight TIO patients, there were six cases (75.0%) of PMTs, one case (12.5%) of giant cell tumor, one case (12.5%) of hemangiopericutoma. Most (n = 6, 75.0%) of the confirmed tumors in our patient population were in the lower extremities, followed by craniofacial regions (n = 1, 12.5%), and torso (n = 1, 12.5%), respectively. Among the five non-TIO patients, there were two cases of Fanconi syndrome, one case of rickets, and two cases of sporadic osteomalacia hypophosphorus. The culprit tumors could be located either in the bone (n = 5, 62.5%) or the soft tissue (n = 3, 37.5%). 18 F-FDG PET/CT was able to localize the tumor in six (6/13, 46.1%) patients. 68 Ga-DOTATATE PET/CT detected tumor in 8 (83.3%) of 13 patients. The sensitivity of 68 Ga-DOTATATE PET/CT imaging and 18 F-FDG PET/CT imaging in the evaluation of TIO in our patient population were 100% (8/8) vs 75% (6/8). The specificity of the two different methods was 80% (4/5). The overall accuracy was 92.3% (12/13) vs 76.9% (10/13). CONCLUSIONS: 68 Ga-DOTATATE PET/CT is very effective in assessing hypophosphatemia patients with TIO typical symptoms compared with 18 F-FDG. Therefore, in clinically suspected cases of hypophosphatemic osteomalacia, 68 Ga-DOTATATE PET/CT should be preferred as an imaging modality investigation to avoid delay in the treatment of this disease.