Mohamed El Hag, MD and Michael Nalesnik, MD
Immunodeficient individuals in general are prone to various infections, including viral. In the setting of acquired or congenital immunodeficiency, certain viruses are associated with specific tumors such as HHV8 associated Kaposi sarcoma and EBV-associated post-transplant lymphoproliferative diseases (PTLD) (Hussein, Rath, Ludewig, Kreipe, & Jonigk, 2014). A rare and lesser known entity is immunodeficiency associated smooth muscle tumors. In 1970 Pritzker et al described a smooth muscle tumor of the bowel metastatic to the liver in an immunosuppressed patient, later on Chadwick et al associated smooth muscle tumors with AIDS in three children (Chadwick, 1990; Pritzker, Huang, & Marshall, 1970). In 1995 the association between EBV and smooth muscle tumors was described in immunosuppressed patients following organ transplantation and in children with AIDS (Lee et al., 1995; McClain et al., 1995).
EBV- Associated Smooth Muscle Tumors occur in different sites and with different forms of immunodeficiency. They can be divided into separate groups based on cause of immunodeficiency:
Here we describe a post-transplant EBV associated smooth muscle tumor and provide a succinct review of this entity.
The patient is a teenager boy with a history of congenital anomalies involving the heart and gut who underwent orthotopic heart transplantation two years ago. Tacrolimus and prednisolone were given for immunosuppression. 18 months post transplantation he underwent exploratory laparotomy for lysis of adhesions and gut derotation and he was found to have a liver lesion. Contrast CT scan showed a rim-enhancing lesion that was stable in subsequent scans. Blood workup showed: EBV: 71,000 copies/ml, HIV: negative, CMV: negative. The lesion was biopsied and subsequently resected.
On gross examination the liver lobe weighed about 430 grams and showed a tan-brown smooth surface. On sectioning, multiple white, whorled, and well-demarcated nodules were identified, ranging in size from 0.5 to 3.7 cm. Nodules were present in the subcapsular area. Margins of resection were free of tumor.
Microscopic examination showed multiple well-demarcated nodules that were cuffed and infiltrated by lymphocytes (Figs. 1A, 1B). Nodules consisted of spindle cell proliferations arranged in short fascicles with swirling around small blood vessels (Figs. 2A, 2B). Nodules exhibited areas of hyalinized stroma, hypocellularity and necrosis. Lesional cells were spindled with blunt-ended cigar shaped nuclei, little pleomorphism and rare mitotic figures (<1 per 10 HPF). There were prominent intra-tumoral infiltrating lymphocytes consisting mostly of T-cells highlighted by a CD3 stain (Figs. 3A).
Immunohistochemistry and in-situ hybridization
A panel of immunohistochemical stains showed the following: Actin: positive (Fig. 4A), Desmin: positive, Ki-67 proliferation index: 20%, CD3: highlights predominance of T-lymphocytes within the tumor and the cuff, CD20: occasional positive cells, C-Kit: negative, DOG-1: negative, ERG: negative, EBER: diffusely positive in tumor cells (Fig. 4B).
Cytogenetics analysis showed interstitial deletion of the long arm of chromosome 2.