CARMIL2 Immunodeficiency with Epstein Barr Virus Associated Smooth Muscle Tumor (EBV-SMT). Report of a Case with Comprehensive Review of Literature.

Background: Primary immunodeficiency (PID) having defects related to lymphocyte cytotoxic pathway or T-cell dysfunction are well known for developing opportunistic infections and Epstein-Barr virus (EBV)-associated diseases. CARMIL2 deficiency is a recently described combined immunodeficiency (CID) disorder characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, susceptibility to various infections and Epstein Barr Virus smooth muscle tumor (EBV-SMT). Case report: We report a homozygous CARMIL2 pathogenic variant presenting with recurrent infections and EBV associated smooth muscle tumor (SMT) in a child. Conclusion: The present study reports that EBV SMT may occur in a child with CARMIL2 deficiency.

18F-FDG PET/CT imaging of multiple intrahepatic Epstein-Barr virus-associated smooth muscle tumors in a pediatric patient after heart transplantation.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is an exceedingly rare neoplastic disease with a predisposition in immune-compromised individuals, especially in patients with prior transplantation, human immunodeficiency virus infection, or congenital immunodeficiency. Here, we present imaging findings of EBV-SMT in multiphasic contrast-enhanced computed tomography (CT) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT in a two-and-a-half-year-old boy with prior heart transplantation.

Long-term follow-up of post renal transplantation Epstein-Barr virus-associated smooth muscle tumors: Report of two cases and review of the literature.

Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) following solid organ transplantation are very rare slow growing neoplasms. Most tumors present with non-specific symptoms mainly related to tumor location. Post-transplant EBV-associated small muscle tumors have been reported in various anatomical locations. The tumors have a predilection to unusual sites for SMTs and tend to be multifocal. The histologic appearance of these tumors generally does not predict their clinical behavior. Surgery and reduction in immunosuppression are the main stays of management. We herein report two cases of post renal transplant EBV-associated SMTs with over 6 years of follow-up. A 33-year-old male patient presented with hepatic lesions and a 49-year-old female patient presented with multiple mesenteric and gluteal lesions. The tumors were diagnosed 6 and 10 years after renal transplantation, respectively. Surgical resection and reduction/discontinuation of immunosuppression were successful in delaying progression of the disease; however, in both cases, the allografts failed during the course of management.

Epstein-Barr Virus-Associated Smooth Muscle Tumor and Its Correlation With CD4 Levels in a Patient With HIV Infection.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare tumor found in immunocompromised patients, and its treatment is not well-established. A role for antiretroviral therapy in human immunodeficiency virus (HIV)-related EBV-SMT has been proposed; however, the relevance of tumor size, CD4 levels, and immune reconstitution inflammatory syndrome (IRIS) has not been previously reported. We present the first case, to our knowledge, of a tumor that shrank in association with elevated CD4 counts. IRIS occurred in this case following antiretroviral therapy. This finding highlights the importance of the immune response in HIV-related EBV-SMT.

Adoptive Cell Transfer of Allogeneic Epstein-Barr Virus-Specific T Lymphocytes for Treatment of Refractory EBV-Associated Posttransplant Smooth Muscle Tumors: A Case Report.

Posttransplant smooth muscle tumors (PTSMTs) are rare Epstein-Barr virus (EBV)-associated neoplasms, mostly occurring after solid organ transplantation. Current therapeutic strategies include surgery and reduction of immunosuppressive medication. We describe for the first time a novel treatment approach for PTSMT by adoptive cell transfer (ACT) of EBV-specific T cells to a 20-year-old patient with a medical history of cardiac transplantation, posttransplant lymphoproliferative disease, and multilocular PTSMT. During ACT, mild cytokine release syndrome occurred, while no unexpected safety signals were recorded. We observed in vivo expansion of EBV-specific T cells and reduction of EBV viremia. Best response was stable disease after 4 months with reduction of EBV viremia and normalization of lactate dehydrogenase levels. ACT with EBV-specific T cells may be a safe and efficacious therapeutic option for PTSMT that warrants further exploration.

Epstein-Barr virus associated hepatic smooth muscle tumor in a patient with acquired immunodeficiency syndrome: A case report.

INTRODUCTION: Epstein-Barr virus (EBV) associated smooth muscle tumors (SMTs) usually present under the condition of immunosuppression, including congenital immunodeficiency syndrome-SMT, post-transplantation-SMT and HIV-SMT. HIV-SMTs are most likely to invade the central nervous system, followed by the liver, lungs, and other locations. Many laboratory techniques, including serological techniques, polymerase chain reaction and immunohistochemistry (IHC), are employed to determine the aetiologies of these tumours. With respect to therapy, surgical resection is the main treatment. In patients with immunodeficiency, improving immune status is significant for defending against other viruses. We describe a case of the primary focus of SMT in the liver of HIV-positive patient without any metastasis. PATIENT CONCERNS: A young male HIV-positive patient complained of fever and abdominal pain for 2 months. DIAGNOSIS: IHC of liver tissue confirmed the finding: EBV-related smooth muscle tumor. INTERVENTIONS: Given the patient's general condition, he was not a suitable candidate for surgical resection. He was given antibiotics, antifungal agents and EBV-directed agents to control infection as well as highly active antiretroviral therapy to enhance the immunity. OUTCOMES: The patient's symptoms improved. He was discharged. CONCLUSIONS: In conclusion, EBV-related HIV-SMTs is a rare neoplasm found in the liver among immunodeficient patients. This case highlights that a variety of examinations such as IHC for smooth muscle markers (smooth muscle actin and desmin) and EBER, as well as polymerase chain reaction for EBV DNA should be done when diagnoses are ambiguous.

Pseudo-Meigs' syndrome caused by uterine smooth muscle tumor of uncertain malignant potential with low vascular endothelial growth factor expression.

Smooth muscle tumor of uncertain malignant potential (STUMP) presenting as pseudo-Meigs' syndrome with low vascular endothelial growth factor (VEGF) expression has not been reported in previous literature. Here, we report a case of uterine STUMP associated with ascites and pleural effusion, which was resolved completely after hysterectomy. A 47-year-old woman presented to the clinic with a complaint of progressive abdominal distension for several months. A large movable, painless pelvic mass located upward above the umbilical level was palpated. Sonography and computed tomography showed a hypervascular solid pelvic mass measuring 20 x 17 x 15 cm in size associated with ascites and right pleural effusion. Laparotomy revealed a large uterine mass with ascites in the abdomen. Total hysterectomy and left-side salpingo-oophorectomy were performed. The final pathologic report revealed a STUMP tumor with low expression of VEGF by immunohistochemistry. A follow-up chest X-ray revealed that the pleural effusion was resolved completely 1 week postoperatively. The patient is doing well without recurrence in the following 2 years. Uterine STUMP tumor may cause pseudo-Meigs' syndrome. However, the ascites or the pleural effusion may not be induced by VEGF, known as vascular permeability factor, in our case.

Synchronous Epstein-Barr virus-associated skull base and adrenal smooth-muscle tumors in an 8-year-old girl with recent Epstein-Barr virus infection.

Epstein-Barr virus-associated smooth-muscle tumors are rare tumors seen in immunocompromised patients. Most cases occur in the context of AIDS and organ transplantation, and very rarely in the setting of congenital immunodeficiency, with only 5 case reports of the latter published so far in the literature. The authors report the case of a previously healthy 8-year-old girl with headaches and precocious puberty who was found to have a large skull base lesion. There was a synchronous left adrenal lesion. She underwent resection of the skull base lesion and a left adrenalectomy. Thorough evaluation for immunodeficiency was negative for a known congenital immunodeficiency syndrome. She had a short course of intravenous immunoglobulin and has had no recurrence of disease or new lesions in the 17 months since presentation. Continued surveillance for the development of opportunistic infections and new or recurrent lesions is warranted in this case. Repeat surgery for surgically accessible tumors or chemoradiation would be recommended for any additional lesions.

Early post-transplant smooth muscle neoplasia of the colon presenting as diminutive polyps: a case complicating post-transplant lymphoproliferative disorder.

A 44-year-old woman, 3 years post-transplant for pulmonary sarcoidosis, developed abdominal pain and diarrhea 13 months subsequent to an eradicated diffuse large B-cell-type, post-transplant lymphoproliferative disorder (PTLD) of the cecal region. Endoscopic examination identified multiple pale tan 5-to-9 mm rubbery nodules of the transverse and right colon in an otherwise unremarkable mucosa. Histology was characterized by bland smooth muscle proliferations, focally pushing into the mucosa. Immunohistochemistry (IHC), in situ hybridization (ISH), and polymerase chain reaction (PCR) of the sampled nodules confirmed Epstein-Barr virus (EBV) infection of neoplastic cells. To our knowledge, this is the first reported case of EBV-related post-transplant lymphoproliferative and smooth muscle neoplasms (PTSN) having distinct tropism for the colon. Endoscopic features of early PTSN, which in this case presented as diminutive polypoid lesions, have not been described previously.

Smooth muscle tumour of uncertain malignant potential (SMTUMP) in the nasal cavity: an incidental finding.

Sino-nasal smooth muscle tumours of uncertain malignant potential (SMTUMP) are very rare neoplasms of mesenchymal origin with features in between a benign leiomyoma and a leiomyosarcoma. We report a rare case of SMTUMP in a 44-year-old woman, who presented with vague symptoms of pharyngitis. Nasal endoscopy revealed a smooth mass in left nasal cavity. Contrast-enhanced CT and MRI scans showed features likely to be inverted papilloma or olfactory neuroblastoma or meningioma. Excision was planned and intraoperatively, frozen section revealed a probable spindle cell lesion. Final histopathological report following immunohistochemistry (IHC) & immunofluoresence (IF) confirmed it to be a SMTUMP. This patient underwent complete resection via endoscopic KTP laser assisted, anterior skull base surgery with no recurrence on follow-up.

A slow progressor HIV-infected boy developing quadriplegia with evidence of Epstein-Barr virus associated smooth muscle tumour of the cervical spinal cord.

The authors report a case of slowly progressive HIV in an 11-year-old boy whose initial presenting AIDS-defining symptom was progressive quadriplegia with complete cord compression and pathological confirmation of Epstein-Barr virus associated smooth muscle tumour. Despite tumour removal, quadriplegia persisted as did ventilator dependence.

Multiple smooth muscle tumors arising in deep soft tissue of lower limbs with uterine leiomyomas.

A 40-year-old woman had multiple smooth muscle tumors in the left inguinal region, the bilateral thighs, the omentum, the peritoneum, and the right infundibulum pelvic ligament associated with uterine leiomyomas. She had a history of uterine leiomyomas, which were resected 13 years ago. Histopathologic evaluation revealed tumor masses composed of smooth muscle cells with relatively low cellularity, which were consistent with a diagnosis of leiomyoma. Tumor necrosis and nuclear atypia were absent. Mitotic figures were very scarce (less than 1 mitotic figure per 10 high-power fields). Immunohistochemical evaluation revealed a positive reaction of the tumor cells to muscle markers, estrogen receptors, and progesterone receptors. No pulmonary lesion was found. Similar instances of uterine leiomyomas with histologically benign extrauterine smooth muscle tumors have been reported. This curious condition has been referred to as "benign metastasizing leiomyoma," in which most of the reported cases involve the lungs. The distribution of extrauterine tumors in our case is very unusual and may be the first case with multiple leiomyomas in deep soft tissue of the limbs. Consideration was given to the concept that these may be of multifocal origin, rather than metastases.

Brain involvement in multicentric Epstein-Barr virus-associated smooth muscle tumours in a child after kidney transplantation.

Epstein-Barr virus (EBV)-associated smooth muscle tumours (SMT) have been reported in young patients with induced immunosuppression associated with organ transplantation, acquired immunodeficiency syndrome or congenital immunodeficiencies. EBV-associated SMT are frequently multicentric or multifocal and often occur in unusual locations. We are reporting a case of EBV-associated multicentric SMT that occurred after kidney transplantation in a 2-year-old boy with a history of oligomeganephrony. Headaches and left VIth cranial nerve paralysis led to the discovery of a brain tumour 3 years after transplantation. There were multiple pulmonary, hepatic and splenic nodules and enlarged mesenteric lymph nodes. Histological examination revealed multicentric SMT of uncertain malignant potential. Further investigations using in situ hybridisation demonstrated EBV early RNAs in the nucleus of most tumour cells. The immunosuppressive therapy was reduced, and the child was treated with chemotherapy, but died 2 months later, due to neurological complications.

Hypoglycemia in four dogs with smooth muscle tumors.

Tumor-associated hypoglycemia has been reported in dogs with pancreatic beta-cell tumors, hepatic tumors, and, rarely, with other neoplasms. This article describes 4 dogs with marked hypoglycemia associated with smooth muscle tumors (jejunal leiomyoma, gastric leiomyoma and leiomyosarcoma, and splenic leiomyosarcoma). Presenting clinical signs included grand mal seizures, lethargy, weakness, ataxia, and, in 1 dog, polyuria/polydipsia. The serum insulin concentration was low in 1 dog and normal in the other dog evaluated. Immunohistochemical staining for insulin was negative in the 4 tumors; the 3 tumors arising from the stomach and jejunum stained diffusely positive for glucagon. Blood glucose concentrations rapidly returned to normal after complete surgical resection of the tumors, and clinical signs associated with hypoglycemia resolved. Long-term follow-up available in 3 of the 4 dogs found no recurrence of clinical signs related to hypoglycemia at 15, 31, and 38 months after surgery, respectively.

Smooth muscle tumour of the pharynx: a rare tumour presenting with globus pharyngeus symptoms.

A rare case of a smooth muscle tumour in the pharynx is reported, together with histopathological findings. The patient's psychiatric background and recurrent complaint of a sensation of a lump in the throat all pointed to a psychogenic aetiology, and diagnosis was delayed. The importance of mirror or endoscopic examination of the pharynx is stressed in patients with globus pharyngeus symptoms.

Meckel's diverticulum-rare complications and review of the literature.

Meckel's diverticulum is the most common congenital anomaly of the gastro-intestinal tract. It arises as a result of incomplete dissolution of the vitello-intestinal duct. Approximately 4% of patients with Meckel's diverticula develop complications, most commonly obstruction, gastro-intestinal bleeding and inflammation. We describe three unusual presentations of Meckel's diverticulum-perforation due to ingested foreign body, a smooth muscle neoplasm simulating an ovarian tumour, and a Littre's hernia.

Epstein-Barr virus-associated adrenal smooth muscle tumors and disseminated diffuse large B-cell lymphoma in a child with common variable immunodeficiency: a case report and review of the literature.

This article reports the clinical and the histological features in a 7-year-old girl affected by common variable immunodeficiency (CVID) who developed multiple Epstein-Barr virus-associated tumors, represented by bilateral adrenal smooth muscle tumors (EBV-SMT) and multifocal diffuse large B-cell lymphoma. The EBV-SMTs showed features compatible with a benign or at least a low-malignant potential neoplasm. A peculiar feature observed in both EBV-SMTs was the occurrence of numerous lymphocytes intermingled with the spindle cells, which consisted of CD3+ CD5+ T-cells, with a predominant cytotoxic CD8+ component. Interestingly, EBV status differed in the neoplasms, since the EBV-SMTs were negative for LMP1 and positive for EBER, whereas the B-cell lymphoma expressed both EBV markers. Furthermore, EBV-LMP1 deletion was positive only in the EBV-SMTs, thus indicating that these tumors were the consequence of 2 distinct, EBV-dependent transformations. Similarly, lymphocyte clonality assay also showed different clonal bands in different sites (skin and nasal cavity), suggesting the development of intratumoral mutations. Finally, the authors review all 127 previously reported EBV-SMT, with discussion of their clinical and pathological features.

Epstein-Barr virus-associated smooth muscle tumors in AIDS patients: a largest case (series).

This study aimed to determine the outcomes of Epstein-Barr virus (EBV)-associated smooth muscle tumors (SMTs) in AIDS patients at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, treated from 2001-2011. Of the 17 patients, there were five men with a median CD4 count of 26 cells/µL. Eight and nine patients had single and multiple sites, respectively. The most common site was the cranial epidura (58.8%). All patients had EBV within the tumor. Seven patients underwent surgery. The median follow-up was one year. The mortality rate was 41.2%. All patients with undetectable HIV viremia survived. This is the largest case series regarding EBV-associated SMTs in AIDS patients with a long follow-up period.