PBL is characterized by its predilection of involving the oral cavity of HIV-positive individuals as originally described [
1]. Following the first report, a number of cases have been reported in extraoral sites, in HIV-positive cases. The most commonly affected sites are the gastrointestinal tract, lymph nodes, and skin [
3,
11‐
14]. A similar pattern is seen in patients with HIV-negative PBL, with the oral cavity and gastrointestinal tract being the most commonly involved sites [
15]. The frequency of oral involvement is higher in HIV-positive (58%) than in HIV-negative patients (16%) [
16]. Other less common extraoral sites include the central nervous system [
17,
18], paranasal sinuses [
18,
19], lungs [
19‐
21], liver [
21], and testes [
12,
22]. Bone marrow involvement has been reported at 30% in both HIV-positive and HIV-negative patients [
16]. PBL has also been documented to arise from longstanding sacrococcygeal cysts in HIV-positive persons [
4]. In a literature review of 228 patients with PBL, 157 patients (69%) were HIV-positive and 71 (31%) were HIV-negative [
16]; among HIV-negative patients, 33% of the patients had some form of immunosuppression, most often solid organ transplantation or steroid therapy [
23]. The remainder of the HIV-negative patients were apparently immunocompetent. In a recent case series from Korea, none of the patients reported showed evidence of immunosuppression [
24]. In this rare case, our patient had no evidence of HIV or HHV-8 infections, and he was apparently healthy. We can postulate that PBL developed years before, probably when he had his cycles of chemotherapy for his polycythemia. The size of the mediastinal mass (9.7 × 8 × 5.7 cm) could confirm this hypothesis. In such a case, an accurate histological evaluation of the endothoracic mass is crucial to establish the optimal medical treatment, in particular when a morbid surgery is the alternative [
20]. Excisional biopsy should be the gold standard; however, when the site of the disease is difficult to access, as in this case, core needle biopsy and FNAB may be performed in conjunction with appropriate ancillary techniques for the diagnosis and differential diagnosis. In fact, the histopathological features are frequently ambiguous, thus rendering the correct diagnosis quite difficult. This neoplasm may be confused with the plasmablastic type of plasma cell myeloma; however, the absence of serum monoclonal protein and lack of significant bone marrow involvement may argue against this diagnosis [
1]. In addition, PBL is almost entirely composed of blasts with numerous mitotic figures. These features are not typical for plasma cell myeloma. The plasma cell markers VS38c, CD38, multiple myeloma oncogene-1 (MUM1), and CD138 (syndecan-1) seem to be almost universally expressed [
3,
9,
25]. PBL is characterized by a high proliferation index reflected by Ki67 expression, usually > 80%. Immunophenotypically, the neoplastic cells lacked B cell-associated antigens (CD20, CD45RA, and CD79a). T cell-associated antigens (CD3 and CD45RO) as well as leukocyte common antigen (CD45) were also absent. The neoplastic cells expressed plasma cell-associated antigens CD138 and VS38c. Transthoracic FNAB allowed making the right diagnosis thus saving the patient uncomfortable, more invasive, procedures, like in other similar cases [
20]. Both biopsies, mediastinal and cutaneous, were performed under local anesthesia, and our patient was allowed to start his chemotherapy promptly. An aggressive medical therapy resolved, just after the first cycle and without invasive surgery, our patient’s superior vena cava syndrome (cutaneous rash, right palpebral ptosis, dyspnoea, cough) [
26].
PBL is a therapeutic challenge with a clinical course characterized by a high rate of relapse and death. The prognosis is generally poor, with most patients dying within 2 years from initial presentation, and long-term survivors are very few. Patients carrying the MYC/IgH gene rearrangement have been shown to have a very poor median overall survivor of only 3 months.
A standard therapy has not yet been established. Treatment usually consists of chemotherapy with or without consolidation radiation and hematopoietic stem cell transplantation [
27]. Various chemotherapy regimens including cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), R-CHOP, and cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) are also possible options [
10,
28]. Patients with PBL who were not treated with chemotherapy invariably died with a median survival of 3 months [
16]. Due to disappointing response and survival rates, the National Comprehensive Cancer Network (NCCN) guidelines recommend against CHOP in favor of more intensive regimens, such as intravenous EPOCH, cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD), or CODOX-M/IVAC [
10]. One of the newest therapeutic options for PBL is bortezomib, which is a proteasome inhibitor and a cornerstone in myeloma and relapsed or refractory mantle cell lymphoma therapy [
29]. Some studies have reported that the proteasome inhibitor bortezomib alone or in combination with chemotherapy may have an antitumor effect in PBL or overcoming the typical chemoresistance of this disease. For the same reason, the use of lenalidomide has been reported in PBL [
30]. In the presented case, the EPOCH scheme brought the best outcome, with a rapid response, a prompt resolution of compression symptoms and a final complete recovery.