Ultrasound for monitoring different stages of post-transplant lymphoproliferative disorder in a transplanted kidney: A case report and review of the literature.

RATIONALE: Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized, but uncommon complication in patients with kidney transplantation, which poses challenges in diagnosis and poor prognosis due to its low incidence and nonspecific clinical manifestations. As a routine follow-up examination method for kidney transplant patients, ultrasound (US) plays a significant role in the diagnosis of PTLD. Therefore, it is critical to evaluate the ultrasonic characteristics of PTLD in transplanted kidney patients for early detection and diagnosis. PATIENT CONCERNS: A 59-year-old female patient was unexpectedly found with a mass in the hilum of the transplanted kidney 12th month after transplantation, which gradually grew up in the following 4 months. The latest US examination found hydronephrosis. Contrast-enhanced ultrasound (CEUS) demonstrated a hypo-enhancement pattern in arterial and parenchymal phases and showed a new irregular area lacking perceivable intensification within the mass, which was considered necrosis. Meanwhile, the patient developed an acute increase in serum creatinine from 122 to 195 µmol/L. DIAGNOSIS: A US-guided biopsy was conducted with the final pathological diagnosis of PTLD (polymorphic). INTERVENTIONS: After receiving 3 times of rituximab and symptomatic treatment, blood creatinine returned to normal but the mass was still progressing in the patient. Therefore, the treatment approach was modified to immune-chemotherapy. OUTCOMES: The patient was in a stable condition to date. LESSONS: PTLD is a rare complication in a transplanted kidney. US and CEUS are the preferred imaging methods in renal transplant patients due to their good repeatability and no nephrotoxicity. This case demonstrates that continuous dynamic monitoring by using US and CEUS has significant value in the detection and diagnosis of PTLD in a transplanted kidney, suggesting early clinical intervention to avoid further progression.

FDG-Avid But Pentixafor-Negative in EBV-Associated T-Cell Lymphoproliferative Disorders.

ABSTRACT: An 18-year-old woman with intermittent fever, pancytopenia, abnormal liver function, and enlarged lymph nodes and hepatosplenomegaly was clinically suspected as hemophagocytic lymphohistiocytosis. 18 F-FDG PET/CT showed increased metabolism in multiple lymph nodes, which were highly suggestive of lymphoma. No increased CXCR4 expression in lymph nodes was demonstrated on 68 Ga-pentixafor PET/CT. Subsequent right neck lymph node biopsy pathology revealed EBV-associated lymphoproliferative disorders. Our case shows that 68 Ga-pentixafor PET/CT may have potential value in differentiating EBV-associated lymphoproliferative disorders from lymphomas.

Hepatic Superscan in Methotrexate-Associated Lymphoproliferative Disorder.

ABSTRACT: A 60-year-old man on methotrexate for treatment of adult-onset Still disease presented with acute onset of fever, pancytopenia, and deranged liver function. Besides FDG-avid lesions in spleen and skeleton, his 18 F-FDG PET/CT study showed diffuse and intense uptake in the liver with significantly suppressed heart and brain activity (reminiscent of a hepatic superscan). Subsequent biopsy confirmed the diagnosis of methotrexate-associated lymphoproliferative disorder.

Slowly Expanding 18 F-FDG PET-Positive Irregular Opacities in the Lung Due to Diffuse Lymphoid Hyperplasia Preceding Rheumatoid Arthritis.

ABSTRACT: Pulmonary diffuse lymphoid hyperplasia (DLH), a nonneoplastic lymphoproliferative disorder (LPD), is extremely rare, and no PET/CT findings have been reported for pulmonary DLH. We observed slowly expanding irregular opacities with 18 F-FDG accumulation (SUV max , 3.64) in the right lower lobe of a 51-year-old asymptomatic man. The patient underwent video-assisted thoracoscopic biopsy on suspicion of malignant lesions. Histologically, no neoplastic cells were present, and the lesion was consistent with DLH. Six months later, the patient developed rheumatoid arthritis. DLH should be considered in the differentiation of PET-positive irregular opacities, even in the absence of known immune abnormalities.

The value of 18 F-FDG PET/CT quantitative indexes in the diagnosis of nondestructive posttransplant lymphoproliferative disorders after pediatric liver transplantation.

BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious complication after pediatric liver transplantation (pLT), which may lead to death. 18 F-FDG PET/CT is rarely considered in PTLD after pLT and lacks clear diagnostic guidelines, especially in the differential diagnosis of nondestructive PTLD. The aim of this study was to find a quantifiable 18 F-FDG PET/CT index to identify nondestructive PTLD after pLT. METHODS: This retrospective study collected the data of patients who underwent pLT, postoperative lymph node biopsy, and 18 F-FDG PET/CT at Tianjin First Central Hospital from January 2014 to December 2021. Quantitative indexes were established using lymph node morphology and the maximum standardized uptake value (SUVmax). RESULTS: A total of 83 patients met the inclusion criteria and were included in this retrospective study. To distinguish between PTLD-negative cases and nondestructive PTLD cases, according to the receiver operating characteristic curve, (the shortest diameter of the lymph node at the biopsy site [SDL]/the longest diameter of the lymph node at the biopsy site [LDL])*(SUVmax at the biopsy site [SUVmaxBio]/SUVmax of the tonsils [SUVmaxTon]) had the maximum area under the curve (0.923; 95% confidence interval: 0.834-1.000), and the cutoff value was 0.264 according to the maximum value of Youden's index. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 93.6%, 94.7%, 97.8%, 85.7%, and 93.9%, respectively. CONCLUSIONS: (SDL/LDL)*(SUVmaxBio/SUVmaxTon) has good sensitivity, specificity, positive predictive and negative predictive values, and accuracy, and can be used as a good quantitative index for the diagnosis of nondestructive PTLD.

Complete Recovery After Immunosuppressive Treatment Change in a Patient With Posttransplant Lymphoproliferative Disorder.

Posttransplant lymphoproliferative diseases are a rare but important cause of morbidity and mortality secondary to immunosuppression after solid-organ or bone marrow transplant. Generally, posttransplant lymphoproliferative diseases develop in the first 2 years after transplant, when immunosuppressive therapy is the most intense. Change or reduction in immunosup - pressive treatment is an option for treatment of posttransplant lymphoproliferative diseases. We evaluated the treatment of a patient with posttransplant lymphoproliferative disease after liver transplant. A 64-year-old man underwent liver transplant from a living donor (the patient's son) in 2011 to treat hepatocellular cancer secondary to chronic hepatitis B. Tacrolimus and mycophenolate mofetil were used for immunosuppression through 9 years after liver transplant. In the abdominal computed tomography performed in response to abdominal pain during follow-up in March 2019, multiple solid lesions were observed. A liver biopsy revealed posttransplant lymphoproliferative disease with diffuse large B-cell lymphoma. Fluorine-18 positron emission tomography/computed tomography imaging of the patient showed no pathology in favor of primary lymphoproliferative disease. Mycophenolate mofetil and tacrolimus treatment was changed to everolimus. In the follow-up dynamic magnetic resonance imaging examination that was performed at 3 months after treatment change, we observed that the lesion at liver segment 6 had regressed to 30 mm and several lesions with similar features were observed in the right lobe of the liver. Additional liver biopsy results were compatible with complete remission. The patient's clinical symptoms had fully regressed at 18 months after the diagnosis of PTLD, at the time of this writing. Ongoing radiological and clinical follow-up has shown complete remission. Change from calcineurin treatment to treatment with an inhibitor of the mechanistic target of rapamycin may be an essential and new option for treatment of posttransplant lymphoproliferative disease after liver transplant.

Magnetic resonance imaging of methotrexate-related lymphoproliferative disorder with a chief complaint of oral symptoms.

OBJECTIVES: To determine the magnetic resonance imaging (MRI) features of methotrexate-related lymphoproliferative disorder (MTX-LPD) in the oral cavity of a patient with a chief complaint of oral symptoms. METHODS: We included six patients who visited our hospital between November 2014 and November 2019, histopathologically diagnosed with MTX-LPD. All images were examined using 3 T MRI and reviewed by two radiologists. RESULTS: Masses were detected in five cases; all masses demonstrated signal hypointensity and homogeneous signal hyperintensity on T1- and T2-weighted images with fat suppression. Homogeneous enhancement with fat suppression was evident on post-contrast T1-weighted imaging. We performed dynamic contrast-enhanced MRI in three cases and observed early enhancement with a low washout ratio pattern in all cases. Four patients underwent diffusion-weighted MRI and revealed low mean apparent diffusion coefficient (ADC) of 0.57 (range 0.5-0.65) × 10-3 mm2/s. CONCLUSIONS: We reported on the imaging characteristics of six rare cases of MTX-LPD in the oral cavity. Homogeneous hyperintensity on fat-suppressed T2-weighted images and low ADC values are possible features of MTX-LPD. Moreover, MTX-LPD can be differentiated from other carcinomas in the oral cavity.

FDG-PET/CT imaging parameters for predicting spontaneous regression of methotrexate-associated lymphoproliferative disorder in patients with rheumatoid arthritis.

In this study, we investigated the usefulness of FDG-PET/CT for predicting spontaneous regression in methotrexate-associated lymphoproliferative disorder (MTX-LPD). Twenty patients with rheumatoid arthritis who were diagnosed with MTX-LPD were enrolled in the study. These patients were divided into those who showed spontaneous regression (SR group: ten patients) and those who received chemotherapy after discontinuation of MTX (CTx group: ten patients). Between-group differences in potential biomarkers were compared, including clinical markers at the onset of LPD [serum LDH and interleukin 2 receptor (sIL-2R)], change in absolute number of peripheral lymphocytes (ΔALC) over follow-up, and the FDG-PET/CT-derived parameters of maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), sum of the metabolic tumor volume (MTVsum), and sum of total lesion glycolysis (TLGsum). The levels of sIL-2R, MTVsum, and TLGsum were significantly lower in the SR group than in the CTx group. In addition, ΔALC was higher in the SR group. In conclusion, MTV and TLG values measured by FDG-PET/CT may be suitable for use as predictors of SR in patients with MTX-LPD.

Solitary Central Nervous System Relapse of Posttransplant Lymphoproliferative Disorder on 18 F-FDG PET/CT.

ABSTRACT: A 41-year-old woman received stem cell transplant due to acute myeloid leukemia. Six months after the stem cell transplant, the patient experienced monomorphic PTLD (posttransplant lymphoproliferative disorder) and underwent chemotherapy. Postchemotherapy PET/CT did not show any abnormal 18 F-FDG accumulation in the scanned body, including brain. Four months later, she presented with nausea and vomiting. Brain MRI showed a lesion in the right temporal lobe. In addition to the abnormal 18 F-FDG accumulation in the brain, no other abnormal foci were noted in the torso PET/CT. Biopsy pathology confirmed the diagnosis of monomorphic PTLD.

Prognosis Prediction Using Magnetic Resonance Spectroscopy and Oligoclonal Bands in Central Nervous System Methotrexate-associated Lymphoproliferative Disorder.

Central nervous system methotrexate-associated lymphoproliferative disorder (CNS-MTX-LPD) is rare, but its spontaneous regression has been observed in some patients after withdrawal of agents. We herein report three cases of primary CNS-MTX-LPD that received oral MTX for rheumatoid arthritis. Epstein-Barr virus and oligoclonal bands (OCBs) were positive, while proton magnetic resonance spectroscopy (1H-MRS) showed an elevated lipid peak and slightly elevated choline/N-acetylaspartate ratio in common. After MTX withdrawal, brain lesions showed spontaneous regression in all cases. Our patient's 1H-MRS findings and OCBs may reflect a non-monoclonal lymphoproliferative histology as benign-type lesions in CNS-MTX-LPD.

Pulmonary lymphoproliferative disorders in children: a practical review.

Pulmonary lymphoproliferative disorders represent an uncommon spectrum of proliferation of lymphoid tissue in the lung parenchyma ranging from benign hyperplasia to malignancy. They tend to occur in certain clinical situations and have typical imaging features that together can be used by the radiologist to suggest these entities as part of the differential diagnosis. We review key clinical, histopathological and computed tomography features of pulmonary lymphoproliferative disorders in children including follicular bronchiolitis, lymphoid interstitial pneumonia, granulomatous-lymphocytic interstitial lung disease, lymphoma and post-transplant lymphoproliferative disorder to familiarize the pediatric radiologist with this group of disorders.

[Primary central nervous system post-transplant lymphoproliferative disorder with few specific abnormal findings observed on MRI and in the cerebrospinal fluid].

A 60-year-old woman, who had a kidney transplant 16 years ago, was admitted to our hospital owing to cognitive decline and gait disturbances. She developed ataxia, consciousness disturbances, and myoclonus, and died two years after the onset of symptoms. No specific findings were observed on MRI or in the cerebrospinal fluid and blood analyses. The patient was diagnosed with post-transplant lymphoproliferative disorder (PTLD) based on the results of the autopsy. Pathological findings revealed proliferating monoclonal B cells in the perivascular space that was confined to the central nervous system. PTLD is a serious complication of transplantation. Furthermore, PTLD of the central nervous system usually presents as nodular lesions on MRI. When neurological symptoms appear after transplantation, it is necessary to consider PTLD as a differential diagnosis even if abnormal findings cannot be pointed out on MRI.

Methotrexate-Associated Lymphoproliferative Disorders Mimicking Granulomatosis With Polyangiitis: A Radiological Diagnostic Challenge.

Methotrexate-associated lymphoproliferative disorders (MTX-LPD) frequently involve the extranodal organs throughout the body. Among the extranodal occurrences of MTX-LPD, pulmonary involvement is most frequent. In contrast, there are only a few reports of MTX-LPD in the nasal cavity or paranasal sinuses. Moreover, there are no previous reports of MTX-LPD mimicking granulomatosis with polyangiitis (GPA) in imaging examinations. We describe a case of a 53-year-old woman with MTX-LPD mimicking GPA in the nasal cavity and lungs. She complained of left nasal obstruction and discharge, general fatigue, and continual fever for 2 months. The patient had been diagnosed with rheumatoid arthritis and received methotrexate (MTX) for over 10 years. Contrast-enhanced computed tomography revealed unenhanced masses in the nasal cavity and multiple masses with cavitary changes in the bilateral lungs, suggesting GPA. However, histological examination of the nasal lesion and a history of MTX treatment indicated a diffuse large B-cell lymphoma type MTX-LPD. Two weeks after MTX withdrawal, prominent improvements in both lesions were observed. Complete regression of the nasal lesion was observed 3 months after discontinuation of MTX. Thus, MTX-LPD may mimic GPA in imaging examinations.

Posttransplant Lymphoproliferative Disorder Status Post-Solid Organ Transplant Presenting to the Emergency Department: Single Institute Experience.

OBJECTIVE: The objective of this study was to evaluate the clinical, laboratory, imaging, and pathology findings associated with emergency department presentations of posttransplant lymphoproliferative disorder (PTLD) after solid organ transplant (SOT). METHODS: Fifteen patients presenting to a single tertiary care center between 2004 and 2019 with PTLD after SOT were identified from a pathology database. Twelve patients presenting through the emergency department were included in the study. Demographic, clinical, imaging, pathology, treatment, and outcome data were reviewed. RESULTS: Among this 12 patient cohort (7 men; mean age, 44.2 years), transplant history included 4 combined kidney/pancreas, 4 kidney, 2 liver, 1 cardiac, and 1 lung. Mean time from transplant to diagnosis was 7.6 years. Posttransplant lymphoproliferative disorder was identified on initial computed tomography scans in 10 of 12 patients. The most common sites for PTLD development were the gastrointestinal tract (4/12) and liver (3/12). Outcomes included resolution of PTLD in 9 of 12 patients, with 3 patients dying within 6 months of diagnosis. CONCLUSIONS: Posttransplant lymphoproliferative disorder is a serious consequence of solid organ transplantation that can present in various locations and with varied symptomatology in the emergency setting. Other posttransplant complications may present similarly including chronic rejection and infection. Posttransplant lymphoproliferative disorder should be considered in SOT patients presenting with worsening abdominal pain or constitutional symptoms, even with normal laboratory workup.

Methotrexate-associated lymphoproliferative disorder of the thoracic spine in a patient with rheumatoid arthritis receiving methotrexate: a case report.

Methotrexate-associated lymphoproliferative disorder is recognized as a lymphoma that occurs following methotrexate administration. The lesion of the spine is extremely rare, and only one case of lesion in the lumbar spine has been reported so far. Here, we present a case of methotrexate-associated lymphoproliferative disorder of the thoracic spine in a 54-year-old woman with rheumatoid arthritis. The lesion formed an extra-skeletal tumor mass from lateral to the vertebral body to the paravertebral muscle extending posterior to the epidural space without bone destruction. Magnetic resonance imaging showed low signal intensities on both T1- and T2-weighted images and high signal intensity with short-tau inversion recovery. These radiological findings were similar to those for primary spinal lymphoma. The lesion rapidly paralyzed the patient, forcing her to be treated with posterior spinal decompression. The lesion could not be resected because it adhered to the dura. Following the histopathological diagnosis as methotrexate-associated lymphoproliferative disorder, methotrexate administration was terminated. The remaining mass lesion showed complete regression within 6 months. Methotrexate-associated lymphoproliferative disorder, which could be cured by the discontinuation of methotrexate, should be considered a differential diagnosis in spinal lesion cases showing lymphoma-like appearance with methotrexate treatment to avoid unnecessary treatments.

Recurrent Intestinal Perforation After Cessation of Immunosuppression in Posttransplant Lymphoproliferative Disease in Pediatric Liver Transplant Recipient.

Posttransplant lymphoproliferative disease (PTLD) is the most common malignant complication after solid organ transplantation. Gastrointestinal involvement as the presentation in early PTLD can occur in 25-30% of pediatric liver transplant recipients and can be the only system involved in 20%. Recurrent gastrointestinal perforation due to resolution of PTLD is an extremely rare complication. We report a 13-month-old male child diagnosed with PTLD, treatment of which lead to recurrent intestinal perforations. The child presented with gastrointestinal bleed 5 months after living donor liver transplantation for biliary atresia. Evaluation was suggestive of PTLD and biopsy confirmed diffuse large B-cell lymphoma. Positron emission tomography scan showed diffuse involvement of small intestine and ileum. Tacrolimus was withdrawn abruptly following diagnosis of PTLD as there was associated renal impairment. Child developed six episodes of small intestinal perforations over 3 weeks which required multiple laparotomies with closure of perforation and/or small bowel resection. Complete remission was achieved six months after diagnosis with cessation of immunosuppression alone and child is alive at 48 months follow-up without any recurrence. To avoid bowel perforation and complications related to tumor necrosis, immunosuppression reduction in PTLD should be gradual while carefully monitoring Epstein-Barr virus levels, tumor response, graft function, and general health status of the patient.

18F-FDG PET/CT for Evaluation of Post-Transplant Lymphoproliferative Disorder (PTLD).

Post-transplant lymphoproliferative disorders (PTLD) are a spectrum of heterogeneous lymphoproliferative conditions that are serious and possibly fatal complications after solid organ or allogenic hematopoietic stem cell transplantation. Most PTLD are attributed to Epstein-Barr virus reactivation in B-cells in the setting of immunosuppression after transplantation. Early diagnosis, accurate staging, and timely treatment are of vital importance to reduce morbidity and mortality. Given the often nonspecific clinical presentation and disease heterogeneity of PTLD, tissue biopsy and histopathological analysis are essential to establish diagnosis and most importantly, determine the subtype of PTLD, which guides treatment options. Advanced imaging modalities such as 18F-FDG PET/CT have played an increasingly important role and have shown high sensitivity and specificity in detection, staging, and assessing treatment response in multiple clinical studies over the last two decades. However, larger multicenter prospective validation is still needed to further establish the clinical utility of PET imaging in the management of PTLD. Significantly, new hybrid imaging modalities such as PET/MR may help reduce radiation exposure, which is especially important in pediatric transplant patients.

Application of contrast-enhanced ultrasound in the diagnosis of post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation: A case report.

INTRODUCTION: Post-transplant lymphoproliferative disease (PTLD) is a series of proliferative diseases of the lymphatic system. Among patients receiving hematopoietic stem cell transplantation (HSCT), PTLD is a prevalent complication that severely affects rates of survival. Ultrasound plays an essential role in the early diagnosis of PTLD. Contrast-enhanced ultrasonography (CEUS) and CEUS-guided biopsy are critical procedures for tumor diagnosis. PATIENT CONCERNS: Herein, we report the case of a 40-year-old male patient with acute lymphoblastic leukemia who received HSCT more than 1 year ago. Sonography revealed a small hypoechoic nodule in the liver four months after HSCT. Eight months after HSCT, larger and more nodules were observed via ultrasound; CT was used to identify the lesions. DIAGNOSES: CEUS and CEUS-guided biopsy were performed, and the pathological diagnosis was PTLD. INTERVENTIONS: The final clinical diagnosis was PTLD, and cyclophosphamide, epirubicin, and dexamethasone were administered as chemotherapy. OUTCOMES: The patient was discharged after his condition improved. CONCLUSION: Ultrasound can be used to effectively detect lesions of PTLD early after HSCT. Furthermore, CEUS and CEUS-guided biopsy were effective for early confirmatory diagnoses of PTLD after HSCT.