Immunosuppressed patients are susceptible to a variety of neoplasms, whether the immunodeficiency is due to genetic disorders, AIDS, or immunosuppressive therapy for organ transplantation. Lymphoma and cutaneous malignancies are the most commonly reported neoplasms. PTSMT is also a rare entity in this field. This was first expressed by Pritzker et al. in 1970, and in 1995 Lee et al. noticed the role of the EBV in tumorigenesis (1, 2, 3). Conventionally, the condition has been more frequent in AIDS patients, and a small number of cases have been solid organ transplant recipients (3). The vast majority of PTSMTs appear after kidney transplantation (60%), and the liver is the most common location in both the pediatric and the adult patients. Lungs, lymph nodes, adrenal gland, spleen, heart, kidney, and less often, the central nervous system may also be involved (5, 6). The precise incidence is not known, but they are reported to arise in less than 1% of the immunodeficient population. The average time it takes for this tumor to appear following an organ transplantation is 4 years (6, 7, 8).
The pathogenesis of EBV-SMT is not well recognized. EBV is a DNA herpes virus with a potential to immortalize infected cells. It has traditionally been related to the pathogenesis of Burkitt lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and other B-cell lymphomas in immunodeficient patients (6, 9, 10). Since EBV-PTSMT can be developed in various organs, some authors hypothesized that SMT may originate from smooth muscle cells of the blood vessel wall. Immunosuppression may permit an abnormal pass of EBV into smooth muscle cells, which could direct to a latent infection and consequent neoplasm formation altered by cytogenetic incidences (11, 12).
Greater than 50% of patients with EBV-SMT present with multiple tumors, and this multifocal involvement appears to be the result of multiple infectious events rather than metastases from a single neoplastic site. EBV-SMTs are often slow-growing and invading only locally. Despite the common multifocal presentation of EBV-SMTs, they are not often fatal (9, 13, 14).
Smooth muscle tumors have a wide range of clinical behavior and pathologic features. The lesions can be broadly classified into those with obvious malignant signs of leiomyosarcoma, and ‘borderline’ cases with little pleomorphism, cellular crowding, and mitotic activity with ‘uncertain biological potential’. Intratumoral T lymphocytes may also be identified. (1, 3, 5). The most reliable methods for detection of EBV within cancer cells are demonstration of EBV RNA by in situ hybridization (ISH) and PCR (2, 3).
Although serology confirms previous EBV infection, it has little bearing on diagnosis, recurrence monitoring, or disease burden (9).
Surgical excision with negative margins, especially in unifocal lesions, is frequently curative(5, 9, 15). Reducing immunosuppressive medication may allow EBV-specific cytotoxic T-cell responses to proliferate, but the risk of graft rejection must also be considered. Incorporating antiviral medicine that reduce EBV viral load and cyclosporine by sirolimus (as an oncogenesis inhibitor) improve disease control and may lead to better outcomes. Antiviral therapy, chemotherapy, and radiotherapy have not been demonstrated to be effective in all cases, but they may be useful in patients with unresectable neoplasms (5, 9).
Krenzlin et al. recently discovered that mouse CMV can be reactivated in perivascular, intratumoral pericytes of glioblastoma, as well as its involvement in tumor promotion (16). Human CMV has also been identified as a cancer-causing virus by demonstrating its presence in > 90% of common tumor types such as breast cancer, while being absent in surrounding normal tissue. Having invaded many cell types in tumor tissues, CMV can cause all the ten proposed hallmarks of cancer. This virus exhibits cellular tumor-promoting and immune-evasive methods, hijacks proangiogenic and anti-apoptotic systems and promotes immunosuppressive effects in the tumor micro-environment(17–19).
Using recent detection methods (ISH, PCR, electron microscopy, DNA and RNA sequencing, immunostaining of tissue specimens, and flow cytometry) some research groups have discovered a high prevalence of CMV in breast, colon, and prostate cancer, rhabdomyosarcoma, hepatocellular cancer, salivary gland tumors, neuroblastoma and brain tumors (medulloblastoma and glioblastoma (GBM)(20–26).
Our case was a post-liver transplant patient with consequent colon polyposis, liver and lung lesions, which histologically were compatible with EBV-associated smooth muscle tumor. Despite the fact that he was not checked for EBV infection during post-transplantation follow-up, he had recurrent and resistant systemic CMV infection. Generally, according to previous investigations, CMV infection should also be considered as a stimulator for smooth muscle proliferation besides EBV infection.