Epstein-Barr Virus-associated Leiomyomatosis and Posttransplant Lymphoproliferative Disorder in a Child with Severe Combined Immunodeficiency: Case Report and Review of the Literature

Abstract

The occurrence of smooth muscle neoplasms and lymphoproliferative disorders in immunocompromised patients is well recognized. We report the case of an 8-year-old girl with adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) status post-bone marrow transplant (BMT), in whom Epstein-Barr virus (EBV) was detected in innumerable leiomyomas involving the gallbladder (leiomyomatosis), and multifocal leiomyomas in liver, spleen, pancreas, intestinal tract, and lung. The leiomyomas of the gallbladder, liver, spleen, and lung were asymptomatic, while those located in the colon became clinically manifest by recurrent lower intestinal hemorrhage. The patient also developed extensive EBV-associated polymorphic lymphoproliferative disorder (PTLD) in nodal and extranodal sites. In addition, there were pulmonary and gastric adenovirus and small and large intestine cryptosporidum infections. Our case appears to be the first example of leiomyomatosis of the gallbladder coexisting with multifocal leiomyomas of the liver, spleen, pancreas, intestinal tract, and lung, as well as EBV-derived lymphoproliferative disorder in a young girl with ADA-deficient SCID. Awareness of the pattern of involvement and of the coexistence of benign leiomyomatous proliferations with lymphoproliferative disorder is of value when gallbladder, pancreatic, biliary tree, lung, and intestinal lesions become clinically manifest in these patients. The demonstration of EBV infection in both leiomyomata and the PTLD suggests a common pathogenesis that may have therapeutic and prognostic implications.

Molecular and Clinicopathological Analysis of Epstein-Barr Virus–Associated Posttransplant Smooth Muscle Tumors

“…Monomorphic or polymorphic PTLD preceded PTSMT manifestation in 18% of patients (4,5,28,29,33,37,40,41). As could be expected from the known risk profiles of PTLD (1), most of these patients were children and the PTLD manifested significantly earlier than the PTSMT.…”

“…It could be expected that most PTSMT which did not manifest in the graft are likely to be of recipient origin. Remarkably, the main site of tumor manifestation was the liver and the transplant liver (2,(5)(6)(7)10,11,15,(17)(18)(19)(20)(21)24,25,(27)(28)(29)(30)(31)(33)(34)(35)(36)38,41). Other solid grafts were less frequently affected; kidney transplants in particular rarely developed PTSMT, although kidneys were the most frequently transplanted organ in all patients with subsequent PTSMT (2,4,(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

“…Polymorphic or monomorphic high grade B-cell PTLD manifestation occurred in a subgroup of patients with PTSMT (n = 12/68, 18%) (4,5,28,29,33,37,40,41). Except for one adult case (37), all of these patients were children (n = 11/12, 92%).…”

“…The femaleto-male ratio was 1:1.2 (no statistical significance) (2-41). The majority of PTSMT developed after kidney transplantation (n = 38/68, 60%) (2,4,6,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) and the site of tumor manifestation was mainly the liver/transplant liver (n = 38/68, 56%) (2,(5)(6)(7)10,11,15,(17)(18)(19)(20)(21)24,25,(27)(28)(29)(30)(31)(33)(34)(35)(36)38,41). PTSMT occurred in a total of 11 transplant Liver (n = 10/68, 15%) Heart (n = 9/68, 13%) Lung (n = 4/68, 6%) Heart + lung (n = 1/68, 2%) Bone marrow (n = 3/68, 4%)…”

Epstein-Barr Virus-Associated Smooth Muscle Tumours after Transplantation, Infection with Human Immunodeficiency Virus and Congenital Immunodeficiency Syndromes

“…immunodeficiencies predisposing to severe EBV-associated complications like X-linked lymphoproliferative disease or CD27 deficiency do not seem to have an impact on CI-SMT development [6,7,8,9,10,11]. Furthermore, some patients with congenital immunodeficiency syndromes have undergone bone marrow transplantation and have then developed EBV-positive SMT (overlap between PTSMT and CI-SMT) [2,12,13]. …”