**3. Diagnosis**

#### **3.1. Definition: anatomopathology**

PTLDs, as their name suggests, are lymphoid proliferations occurring after solid or hematopoietic organ transplantation and are authentic entities recognized in the WHO classification [5], presented in **Table 2**. We will retain some peculiarities to this classification:



**Table 2.** WHO classification for PTLD.

**2. Epidemiology**

184 Heart Transplantation

EBV is almost always found [4].

**3.1. Definition: anatomopathology**

• Monomorphic lesions are clonal.

• Early lesions are almost always EBV positive.

**3. Diagnosis**

of the cases.

It is usual in the literature to estimate between 3 and 5% the risk of a cardiac-transplanted patient developing a PTLD [1]; however, these figures are old and vary depending on immunosuppression and duration of patients' lives, fortunately improved in the last 10 years. The largest study on the epidemiology of PTLD [2] involved 175,732 organ transplants between 1987 and 2008, including 10% of heart transplants. Pulmonary cancers represent the most frequent cancers (386/100,000/years) just in front of the NHL (283/100,000/years) but the standardized incidence ratio (SIR) of the NHL is very clearly superior to that of all the other cancers. **Table 1** presents the incidence and the SIR of the main cancers according to the transplanted organ. The risk of PTLD persists as long as immunosuppression is used, that is, until death for cardiac transplant patients; it is maximum the first year after transplantation, with an SIR greater than 10, but

remains stable thereafter, with a SIR between 3 and 10 for a follow-up of up to 15 years.

Heart 283/7.79 386/2.67 13.8/1.02 90.1/2.90 Kidney 141/6.05 115/1.46 10.7/1.08 126/6.66 Liver 217/7.77 178/1.95 495/44 39.9/1.80 Lung 532/18.73 626/6.13 17/2.04 34/1.49

**Transplanted organ Cancer: incidence (100,000/years)/SIR**

EBV, initially described as always associated with PTLDs, is actually only half of the time. Almost always found in children, most often on the occasion of a primary infection, and in early forms (before the first year after transplantation), it has become rare in the late forms, the most common situation of our days [3]. In cerebral PTLDs, representing 10% of PTLDs,

**Table 1.** Incidence and SIR of the main cancers developed after transplantation depending on the transplanted organ.

**NHL Lung cancer Liver cancer Kidney cancer**

PTLDs, as their name suggests, are lymphoid proliferations occurring after solid or hematopoietic organ transplantation and are authentic entities recognized in the WHO classification

• Polymorphic lesions (infiltration by cells of different types) are polyclonal in almost half

[5], presented in **Table 2**. We will retain some peculiarities to this classification:

#### **3.2. Diagnosis and extension assessment**

The presentation of PTLDs is not unambiguous and the signs are not specific. In early forms, an alteration of the general status with fever is often present. In the other forms, the clinical signs depend on the tumoral localizations; for this reason, the digestive localizations are frequent and can be a source of digestive disorders, pain, even perforation, or necrosis (**Figure 1**).

**Figure 1.** Gut necrosis due to a PTLD.

PTLDs are preceded by an increase in EBV load or a simple positivity in the case of primary infections [8]. The most classic attitude is to reduce immunosuppression, where possible [9–11]. As the EBV reservoir is the B lymphocyte, rituximab has also been used successfully in this setting, especially after allografts of hematopoietic stem cells [12]. Much less available and usable only in the context of protocols, anti EBV T lymphocytes, either autologous (taken from the patient and stimulated ex vivo) [13, 14], or allogeneic (from healthy donor lymphocyte banks) [15], have been used effectively in case of EBV reactivation. Specifically developed in cardiac-transplant patients, a treatment algorithm has been validated on nearly 300 patients whose immunosuppression was identical [16]; it is based initially on the serological status before transplant and then on the EVL carried out at each follow-up visit, for at least 1 year. The algorithm is described in **Figure 3**. In summary, immunosuppression is reduced as soon as the EVL is positive if the recipient was seronegative, since it is then

**Figure 3.** Algorithm for preemptive treatment of PTLD after heart transplantation, depending on serological status and

EBV viral load.

copies/ml in other case.

Post-Heart Transplantation Lymphoproliferations http://dx.doi.org/10.5772/intechopen.76042 187

a primary EBV infection, that is, when the EVL is greater than 105

**Figure 2.** Cerebral PTLD, MRI in T1 with gadolinium.

Paraclinically, the EBV viral load (EVL) is essential, and a high rate is in favor of an EBV-positive PTLD; it is also a good marker of response during treatment. Imaging, CT scanning, or especially PET-CT scan are diagnostic [6] and allow an adequate extension assessment. The appearance of tumors and nodes is similar to that of lymphomas of immunocompetent patients. In the particular case of cerebral PTLD, the lesions are necrotic, in the form of a cockade, identical to toxoplasmic lesions, as in patients with HIV (**Figure 2**). MRI spectrometry can point to PTLD rather than infection. In the absence of contraindication, a lumbar puncture is necessary; it must include a cytology with anti-CD20 labeling on a slide, a phenotyping, a search for B clonality, and an EBV viral load. If lumbar puncture is found in lymphoma cells, cerebral biopsy is not necessary.
