of surgical samples (video-assisted thoracoscopy or open lung thoracotomy).

Immunohistochemical analysis is mandatory in diagnosing all types of pulmonary lymphomas. The neoplastic lymphocytes are characterized in fact by distinct molecular profles that can be easily demonstrated on routine paraffn sections, and can be utilized to distinguish pulmonary MALT lymphoma from reactive processes and also other lymphomas. The analysis of immunoglobulin light chains (kappa and lambda) can occasionally provide evidence of clonal expansion, especially in cases with increased secretory differentiation­ . Neoplastic marginal-zone cells can be characterized by either positive markers (e.g., the abnormally expressed CD43 antigen) or by the absence of a variety of relevant markers, including those expressed by follicular lymphoma (CD10+, Bcl6+), mantle cell lymphoma (cyclin D1 nuclear expression), chronic lymphocytic leukemia (CD5+, CD23+) [2].

Flow cytometry can provide relevant information by revealing the presence of clonal B cell populations characterized by immunoglobulin light chain restriction, as well as illustrating an antigenic profle compatible with the diagnosis.

PCR molecular genetic analysis can provide information regarding the presence of clonal lymphocyte population by investigating rearrangements of either immunoglobulin or T cell receptor genes. This analysis can be performed, due to its extraordinary sensitivity, on very small amount of tissue, but the possible occurrence of false-negative and false-­ positive results must be taken into account.

Staging procedures to evaluate the extension of the disease will include a complete physical examination of the patient, laboratory tests such as beta2 microglobulinemia, LDH, lymphocytic total count, lymphocyte subsets analysis, serology for HIV, Cytomegalovirus, and Epstein–Barr viruses infection, thoracic, abdominal and pelvic CT scan, bone marrow biopsy. CT-PET provides morphologic and metabolic information increasing the diagnostic accuracy in the initial staging, and in the subsequent follow-up of lymphomas, although in low-grade lymphomas PET might result negative or vice versa it could be positive in lung in ammatory lesions (drug related lung injury, infections, etc.). Different studies have documented that an extensive staging in patients with nongastrointestinal MALT lymphoma might be useful as a multiorgan involvement occurs at the beginning in 30% of patients [55] with dissemination to lymph nodes (18%) bone marrow (7%) and for lung a simultaneous specifc gastric localization o gastric relapse in 14% of patients [56].

Treatment

The knowledge of biology and pathogenetic mechanisms leading to lymphoid neoplastic proliferation is greatly

expanded in recent years [57]. This improvement of comprehension has been mirrored in a more detailed classifcation [2] and in more effective treatments. For localized indolent low-grade lymphomas (MALT lymphoma) a conservative approach, mainly in elderly, is advised. Surgery or radiotherapy may be indicated when only a nodule is detected. Treatment with chemotherapy and rituximab is however indicated in the large majority of cases [58]. Traditional chemotherapic regimens are reported in Table 39.3. New drugs or the different use of already known drugs [immune check point inhibitors such as pembrolizumab and nivolumab, tiroxine kinase inhibitors such as ibrutinib and acalabrutinib, the antibody-drug conjugates polatuzumab vedotin and pinatuzumab vedotin, duvelisib, a frst-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, PI3K-inhibitors such as copanlisib, brentuximab vedotin, and bendamustine], radioimmunotherapy and more experience in allogeneic stem cells transplant represent consolidated treatment approaches in more aggressive tumors [59]. In PTLD the modulation of immunosuppression is also an important therapeutic step.

Table 39.3  Chemotherapeutic regimens and doses

Adapted by Cecil Internal Medicine. Goldman L, Schafer AI (Eds). Goldman-Cecil Internal Medicine, Elsevier 2019

aR-EPOCH (Rituximab, Etoposide phosphate, Prednisone, Vincristine sulphate,Cyclophosphamide, and Doxorubicin hydrochloride)