High-Frequency US for BK Polyomavirus-associated Nephropathy after Kidney Transplant.

Background BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of chronic renal allograft dysfunction. However, US features indicative of BKPyVAN have not been fully evaluated. Purpose To assess the value of high-frequency US for the diagnosis of BKPyVAN in kidney transplant recipients. Materials and Methods In this prospective cohort study, participants who tested positive for BK viruria after kidney transplant from September 2019 to January 2021 were evaluated with high-frequency US 1 day before biopsy. Clinical characteristics and US features were compared between participants with and without BKPyVAN. Significant predictors associated with BKPyVAN were determined using logistic regression analyses. The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic performance. Results A total of 105 participants who underwent kidney transplant (mean age, 38 years ± 11 [SD]; 63 men) were evaluated; 45 participants were diagnosed with BKPyVAN. Multivariable analysis demonstrated that eccentric hydronephrosis and subcapsular hypoechoic areas were independent factors for BKPyVAN. The AUC for predicting BKPyVAN according to subcapsular hypoechoic areas was 0.66 (95% CI: 0.55, 0.77), with a specificity of 92% (55 of 60 participants). The AUC of combined US (eccentric hydronephrosis plus subcapsular hypoechoic area) and clinical (urine BKPyV DNA load [BKPyV-DNA] plus BK viremia) features was 0.90, with a specificity of 92% (55 of 60 participants). Parenchymal hyperechoic and subcapsular hypoechoic areas were independent factors for differentiating BKPyVAN from transplant rejection. The pooled specificity of subcapsular hypoechoic areas was 96% (21 of 22 participants), with an AUC of 0.67 (95% CI: 0.54, 0.80). For the combination of US (parenchymal echogenicity plus subcapsular hypoechoic area) and clinical (urine BKPyV-DNA plus time since transplant) features, the AUC reached 0.92 and specificity was 82% (18 of 22 participants). Conclusion High-frequency US characteristics are valuable for diagnosing BK polyomavirus-associated nephropathy (BKPyVAN) and distinguishing BKPyVAN from rejection in kidney transplant recipients. © RSNA, 2022 Online supplemental material is available for this article.

Imaging of Merkel Cell Carcinoma: What Imaging Experts Should Know.

Merkel cell carcinoma (MCC) is a rare and aggressive cutaneous neuroendocrine tumor with a higher mortality rate than melanoma. Approximately 40% of MCC patients have nodal or distant metastasis at initial presentation, and one-third of patients will develop distant metastatic disease over their clinical course. Although MCC is rare, its incidence has been steadily increasing. Furthermore, the immunogenicity of MCC and its diagnostic and therapeutic application have made MCC one of the most rapidly developing topics in dermatology and oncology. Owing to the aggressive and complex nature of MCC, a multidisciplinary approach is necessary for management of this tumor, including dermatologists, surgeons, radiation oncologists, medical oncologists, pathologists, radiologists, and nuclear medicine physicians. Imaging plays a crucial role in diagnosis, planning for surgery or radiation therapy, and assessment of treatment response and surveillance. However, MCC is still not well recognized among radiologists and nuclear medicine physicians, likely owing to its rarity. The purpose of this review is to raise awareness of MCC among imaging experts by describing the epidemiology, pathophysiology, and clinical features of MCC and current clinical management with a focus on the role of imaging. The authors highlight imaging findings characteristic of MCC, as well as the clinical significance of CT, MRI, sentinel lymph node mapping, fluorine 18 fluorodeoxyglucose PET/CT, and other nuclear medicine studies such as bone scintigraphy and somatostatin receptor scintigraphy. ©RSNA, 2019.

HIV-related Malignancies and Mimics: Imaging Findings and Management.

The risk of developing malignancy is higher in patients with human immunodeficiency virus (HIV) infection than in non-HIV-infected patients. Several factors including immunosuppression, viral coinfection, and high-risk lifestyle choices lead to higher rates of cancer in the HIV-infected population. A subset of HIV-related malignancies are considered to be acquired immunodeficiency syndrome (AIDS)-defining malignancies, as their presence confirms the diagnosis of AIDS in an HIV-infected patient. The introduction of highly active antiretroviral therapy (HAART) has led to a significant drop in the rate of AIDS-defining malignancies, including Kaposi sarcoma, non-Hodgkin lymphoma, and invasive cervical carcinoma. However, non-AIDS-defining malignancies (eg, Hodgkin lymphoma, lung cancer, hepatocellular carcinoma, and head and neck cancers) now account for an increasing number of cancer cases diagnosed in HIV-infected patients. Although the number has decreased, AIDS-defining malignancies account for 15%-19% of all deaths in HIV-infected patients in the post-HAART era. Most HIV-related malignancies in HIV-infected patients manifest at an earlier age with a more aggressive course than that of non-HIV-related malignancies. Understanding common HIV-related malignancies and their specific imaging features is crucial for making an accurate and early diagnosis, which impacts management. Owing to the weakened immune system of HIV-infected patients, other entities such as various infections, particularly opportunistic infections, are prevalent in these patients. These processes can have confounding clinical and imaging manifestations that mimic malignancy. This article reviews the most common AIDS-defining and non-AIDS-defining malignancies, the role of imaging in their diagnosis, and the imaging mimics of malignancies in HIV-infected patients. ©RSNA, 2018.

Unusual cause of fever, vision loss and super refractory status epilepticus in association with simian virus 40 (SV40).

We present a case of a 23-year-old man with history of fever followed by painless complete vision loss, with subsequent new-onset refractory status epilepticus (NORSE). He initially developed bilateral retinitis. A few days later, he started having focal seizures, and subsequently developed super-refractory status epilepticus, requiring anaesthetic agents. MRI brain revealed multifocal cortical and subcortical hyperintensities in occipital and temporoparietal regions without contrast enhancement. MRI repeated a month later showed new lesions with non-visualisation of some previous lesions. Finally, a brain biopsy was done which revealed presence of lymphocytic infiltrate with SV40 inclusions in oligodendrocyte. We propose the affliction of an atypical virus affecting the retina and brain grey and white matter, presenting with NORSE in our patient. Future similar cases and isolation of the virus may help in establishing the conclusive diagnosis.

18 F-FDG PET/CT vs. human papillomavirus, p16 and Epstein-Barr virus detection in cervical metastatic lymph nodes for identifying primary tumors.

Squamous cell carcinoma of unknown primary of the head and neck (SCCUP) is a heterogeneous disease entity that requires careful examination to locate the occult primary. We examined the diagnostic value of expression of biomarkers, such as human papillomavirus (HPV), p16 and Epstein-Barr virus (EBV), in metastatic lymph nodes vs. 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT). We prospectively enrolled 54 consecutive SCCUP patients who received HPV, p16 and EBV analyses of lymph node fine-needle aspirates and 18 F-FDG PET/CT scans and subsequently underwent examinations and biopsies under general anesthesia to detect primary tumors. The diagnostic performance of the biomarkers and 18 F-FDG PET/CT were compared by using receiver operating characteristics (ROC) curve analyses with histopathological results for identification of primary tumors. Primary tumors were identified in 28 (51.9%) of 54 patients: the palatine tonsil in 24, base of the tongue in 1, nasopharynx in 2, and hypopharynx in 1. The sensitivity of p16 (85.7%) and accuracy of HPV (85.2%) were higher than those (42.9% and 68.5%) of 18 F-FDG PET/CT (p < 0.05). The area under the ROC curve of HPV was higher than that of 18 F-FDG PET/CT (0.857 vs. 0.666, p = 0.007). The disease-free survival rates were higher in the patients with primary tumor detection or p16 nodal immunopositivity than in the other patients (p < 0.05). The results showed that HPV and p16 detection in metastatic lymph nodes can help locate hidden primary tumors, guide definitive treatment and predict patient survival.

Ultrasound findings of BK polyomavirus-associated nephropathy in renal transplant patients.

BK polyomavirus (BKV) is an emerging pathogen in immunocompromised patients. BKV infection occurs in 1-9 % of renal transplants and causes chronic nephropathy or graft loss. Diagnosis of BKV-associated nephropathy (BKVAN) is based on detection of viruria then viremia and at least a tubule-interstitial nephritis at renal biopsy. This paper describes the ultrasound and color Doppler (US-CD) features of BKVAN. Seventeen patients affected by BKVAN were studied using a linear bandwidth 7-12 MHz probe. Ultrasound showed a widespread streak-like pattern with alternating normal echoic and hypoechoic streaks with irregular edges from the papilla to the cortex. Renal biopsy performed in hypoechoic areas highlighted the typical viral inclusions in tubular epithelial cells. Our experience suggests a possible role for US-CD in the non-invasive diagnosis of BKVAN when combined with blood and urine screening tests. US-CD must be performed with a high-frequency linear probe to highlight the streak-like pattern of the renal parenchyma.

BK polyomavirus encephalitis in a patient with thrombotic microangiopathy after an allogeneic hematopoietic stem cell transplant.

To date, only one case of BK polyomavirus (BKPyV) encephalitis combined with transplant-associated thrombotic microangiopathy has been reported in an hematopoietic stem cell transplantation (HCT) recipient. We report the case of an HCT recipient who developed thrombotic microangiopathy and subsequent BKPyV encephalitis. She died despite treatment with cidofovir, ciprofloxacin, and intravenous immunoglobulin without improvement in mental status. Early suspicion of BKPyV encephalitis in an HCT recipient presenting with altered mental status and hemorrhagic cystitis is important.

BK Nephritis and Venous Thrombosis in Renal Transplant Recipient Detected by 111In Leukocyte Imaging.

Three months after deceased donor kidney transplant, a patient who presented with proteinuric renal dysfunction and fever of undetermined origin was found to have BK viruria by quantitative polymerase chain reaction analysis. An ¹¹¹In leukocyte scan showed increased renal transplant uptake consistent with nephritis and linear uptake in the knee. Venous duplex ultrasound revealed acute occlusive thrombosis in the superficial right lesser saphenous vein in the area of increased radiolabeled leukocyte uptake. This ¹¹¹In leukocyte scan performed for fever of undetermined origin demonstrated findings of BK nephritis in a renal transplant patient and associated acute venous thrombosis related to leukocyte colonization.

Imaging virus-associated cancer.

Cancer remains an important and growing health problem. Researchers have made great progress in defining genetic and molecular alterations that contribute to cancer formation and progression. Molecular imaging can identify appropriate patients for targeted cancer therapy and may detect early biochemical changes in tumors during therapy, some of which may have important prognostic implications. Progress in this field continues largely due to a union between molecular genetics and advanced imaging technology. This review details uses of molecular-genetic imaging in the context of tumor-associated viruses. Under certain conditions, and particularly during pharmacologic stimulation, gammaherpesviruses will express genes that enable imaging and therapy in vivo. The techniques discussed are readily translatable to the clinic.

Oncogenic viruses in AIDS: mechanisms of disease and intrathoracic manifestations.

OBJECTIVE: The objective of this article is to introduce the reader to the thoracic manifestations of neoplasms that are related to common oncogenic viruses in HIV-infected patients. We review the pathologic basis of the infections and illustrate the imaging features of their thoracic manifestations. CONCLUSION: The intrathoracic manifestations of oncogenic viral infection in AIDS patients are protean. Understanding their epidemiologic, pathologic, and imaging features is crucial to diagnosing and managing these often-treatable conditions.

Intranasal verrucous carcinoma: relationship to inverting papilloma and human papillomavirus.

OBJECTIVES: To establish the incidence, appearance, behavior, and appropriate treatment of intranasal verrucous carcinoma and determine its relationship to inverting papilloma and human papillomavirus (HPV). STUDY DESIGN: Retrospective review of all cases of intranasal verrucous carcinoma seen at the Mayo Clinic from 1960 through May 1996. METHODS: Retrospective chart review and data collection for age, sex, smoking history, location, association with inverting papilloma, treatment, recurrence, and follow-up. Polymerase chain reaction (PCR) testing for the presence of HPV DNA was performed on all specimens. RESULTS: Of the 13 patients identified, most presented with nasal obstruction (10) or a noticeable intranasal lesion (8). The maxillary sinus was the extranasal site most often involved. Five patients had verrucous cancer develop in an inverting papilloma, and one had squamous cell carcinoma with the verrucous component (a hybrid tumor). All but one patient underwent surgery as initial treatment; only one patient had preoperative radiation therapy. Surgical procedures ranged from local excision to a craniofacial resection. Follow-up ranged from 2 months to 32 years (mean, 6.5 y). Four patients had a single recurrence and two tumors recurred a second time. No metastases developed and no one died from the tumor. In seven patients (10 specimens), DNA was successfully amplified for PCR testing, and no HPV DNA was detected. CONCLUSIONS: When verrucous tumors are discovered early, they can be treated effectively with wide local excision. In some cases, a more extensive procedure may be required. A possible role for HPV in the etiology of these tumors was not found.

Epstein-Barr-virus-associated lymphoproliferative disease of the lung: CT and histologic findings.

PURPOSE: To assess the computed tomographic (CT) and histologic findings of intrathoracic lymphoproliferative disease (LPD) associated with the Epstein-Barr virus (EBV). MATERIALS AND METHODS: The authors retrospectively reviewed the CT scans of the chest and the pathologic specimens obtained in 24 patients with histologically proved intrathoracic LPD and with positive serologic findings or immunohistochemical staining for EBV. Five patients had acquired immunodeficiency syndrome (AIDS); one had common variable immune deficiency; and 18 were receiving immunosuppressive therapy for heart, lung, or heart-lung (n =15) or bone marrow (n = 2) transplantation and vasculitis (n = 1). RESULTS: Final diagnoses included malignant lymphoma (n = 15), polyclonal LPD (n = 8), and hyperplasia of bronchus-associated lymphoid tissue (n = 1). CT findings included multiple nodules (n = 21), lymphadenopathy (n = 9), areas of groundglass opacification (n = 8), septal thickening (n = 7), consolidation (n = 5), pleural effusion (n = 4), and solitary endobronchial lesion (n = 2). The nodules were 2-4 cm in diameter, involved mainly the middle and lower lung zones, and frequently had a predominantly peribronchovascular (n = 15) or subpleural (n = 14) distribution. CONCLUSION: EBV-associated LPD may range from benign lymphoid hyperplasia to high-grade lymphoma. The most common CT manifestation consists of multiple nodules, frequently in a predominantly peribronchovascular or subpleural distribution.

Case report: hypoechoic submucosal nodules: a sign of Epstein-Barr virus-associated early gastric cancer.

The Epstein-Barr virus (EBV) has been reported to be detectable in about 10% of gastric carcinomas. We performed a comparative study of endosonographic findings of EBV-positive and -negative early gastric carcinomas. Epstein-Barr virus was detected in 11.8% (four of 34) of endosonographically observed early gastric carcinoma lesions. Endoscopic ultrasonography (EUS) revealed a hypoechoic mass in the third layer, which reflected submucosal nodules, in 75% (three of four) of EBV-associated lesions. Endoscopically, in 66.7% (two of three) of EBV-associated carcinomas, the depressed lesion was surrounded by a raised margin covered with normal mucosa and was similar to a submucosal tumour (P < 0.05). Histologically, all three cases of EBV-associated lesions with submucosal tumour invasion had submucosal nodules of carcinoma with lymphoid stroma and 75% (three of four) were located in the gastric body. The ratio of maximal thickness to width of EBV-associated lesions was significantly larger than that of EBV-negative lesions, and this tendency was marked in lesions with submucosal tumour invasion (P < 0.05). This study indicated that EUS and endoscopy are of great use for the determination of EBV association with early gastric carcinoma.

Epstein-Barr virus-associated post-transplant lympho-proliferative disease of donor origin in liver transplant recipients.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disease, a potential complication of solid organ transplantation, occurs in about 3% of orthotopic liver transplant recipients. We report the genetic and virological characterization of two cases of post-transplant lymphoproliferative disease that occurred early (4 and 6 months) after orthotopic liver transplant as large-cell non-Hodgkin's lymphomas located at the hepatic hilum. METHODS: Lymphomatous tissues were analyzed for clonality and presence of Epstein-Barr virus (EBV) sequences by Southern blot, polymerase chain reaction, and in situ hybridization techniques. RESULTS: The tumors in both cases were sustained by a clonal proliferation of B lymphocytes containing type A EBV DNA. Moreover, in situ hybridization with a digoxigenin-labeled EBV-specific probe evidenced a strong nuclear signal in most of the neoplastic cells. DNA microsatellite analysis at three different loci detected alleles of donor origin in both tumor samples, suggesting that the neoplastic B cells were of donor origin. CONCLUSIONS: EBV-infected donor B lymphocytes might be responsible for intragraft post-transplant lymphoproliferative disease in orthotopic liver transplant recipients. As 20 to 30% of post-transplant lymphomas involve the graft itself, donor-derived post-transplant lymphoproliferative disease might be more frequent than presently appreciated. Prospective studies are needed to assess its real incidence and identify possible risk factors.

Spontaneous retropharyngeal haematoma attributable to Epstein-Barr virus infection.

Life-threatening sequelae of Epstein-Barr virus infection are uncommon but may present as: local pharyngeal manifestations, splenic rupture, neurological and haematological disorders and altered hepatic function. We present a case of retropharyngeal haematoma with posterior hypopharyngeal wall necrosis, thrombocytopenia and altered clotting function as a result of Epstein-Barr virus infection. A review of the literature on retropharyngeal haematoma reveals this to be the only recorded case which can be directly attributed to Epstein-Barr virus infection.

Tc-99m HMPAO brain SPECT findings in pediatric viral encephalitis.

Two children were diagnosed with viral encephalitis, due to Epstein-Barr virus infection in one case and to herpes simplex virus infection in the other. Tc-99m HMPAO brain SPECT was arranged to detect changes in regional cerebral blood flow (rCBF) secondary to viral encephalitis. During the acute episode, Tc-99m HMPAO brain SPECT showed that the two cases had increased rCBF. After the acute episode, follow-up brain SPECT was arranged 6 months later. The rCBF in one case was restored to normal on the second brain SPECT, and that in the other case was decreased. The child with normal rCBF in the follow-up brain SPECT had better learning ability and intelligence than the other child with decreased rCBF.

Evaluation of the sensitivity of cervicography in a consecutive colposcopic series.

Cervicography was performed in 606 women referred for colposcopy. Cervigrams were blindly reviewed by two independent readers. The positivity rate at cervicography was high (operator A = 50%, B = 58.8%). The sensitivity for papillomavirus infection (HPV)/cervical intraepithelial neoplasia I (CIN I) (n = 141) was 79.4% for operator A and 80.8% for operator B. The sensitivity for CIN II or more severe lesions (n = 22) was 95.2% and 90.5% for operators A and B, respectively. The positive predictive value for HPV/CIN I or CIN II, or more severe lesions was 36.9% and 6.9% for operator A and 32.1% and 5.3% for operator B, respectively. Interobserver variability was acceptable (kappa = 0.62). Cervicography suspected 27 HPV/CIN I, 1 CIN II and 1 CIN III which showed no cytologic abnormalities. This study confirms that cervicography has a good sensitivity for cervical lesions, but it is based on a selected series, not representative of a screening condition. The combination of cervicography and cytology in screening is presently under evaluation in a prospective study of screened women.