- Constitute 2% to 3% of NHL and occur predominantly in females (female:male ~= 2:1) and young adults; three-fourths of cases are less than 35 years old.
- Weeks to several months of chest pain (73%), cough (60%), dyspnea (46%), and superior vena cava obstruction (30%-57%).
- Over two-thirds of patients have large masses (>10 cm).
- Local extension of the mass into the pericardium, chest wall, or lung is common, whereas distant involvement of peripheral nodes, marrow, or CNS is infrequent.
Vascular involvement by the tumor was the only finding on CT that was independently associated with a higher likelihood of PMBL rather than Hodgkin lymphoma or T cell lymphoblastic lymphoma- Patients with involvement of the bone marrow or distant lymph nodes likely have systemic lymphoma with secondary mediastinal involvement, rather than PMBCL.
- Unusual extranodal sites of involvement include kidney, ovaries, and adrenal glands.
- The stage of disease is I or II in 80% of patients at diagnosis, and the IPI has not correlated well with prognosis.
- Poor prognostic factors in PMBCL have been the presence of pleural or pericardial effusion, multiple (≥2) extranodal sites of disease, bulk (≥10 cm), and high LDH (>3× normal).
- The immunophenotype of PMBCL can be confirmed by histochemistry or flow cytometry. The tumor cells express B cell-associated antigens (CD19, CD20, CD22, CD79a) and CD45, and are negative for CD5 and CD10.
- Staining for pan-B cell markers, such as CD20 and CD79a, is sufficient to establish the diagnosis in many cases; additional stains for CD30, nuclear Rel, and TRAF-1 can be helpful in cases with atypical features.
- Unlike most B cell tumors (but like classical Hodgkin lymphoma Reed-Sternberg cells), the tumors typically do not express immunoglobulins.
- A molecular signature with similarities to classical HL, perhaps reflected in the shared clinical and pathologic features and dysregulation of c-REL/NFkB pathways.
- Gains in chromosome
9p24 or 2p15 have been recognized in up to 75% and 50% of patients, respectively.
- BCL2 and BCL6 gene rearrangements rarely occur, whereas overexpression of the
MAL gene is common.
- Programmed death ligands 1 and 2 are also in the 9p region and are rearranged in 20% of PMBCL, making them susceptible to
PD1 inhibition similar to HL.
- Dose-adjusted R-EPOCH would be preferred for patients who wish to avoid RT, such as young (age <30 years) females with disease requiring irradiation of the breast tissue.
- Optimal first-line therapy is more controversial than other subtypes of NHL; however, treatment regimens include (in order of preference):
- Dose-adjusted EPOCH-R ([etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin] + rituximab) x 6 cycles.
- For persistent focal disease, RT can be added.
- RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) x 6 cycles + RT.
- RCHOP x 4 cycles followed by ICE (ifosfamide, carboplatin, etoposide) ± rituximab x 3 cycles ± RT (category 2B).
- Role of RT in first-line therapy is controversial. If PET/CT scan was negative at the end of treatment and initial disease was non-bulky, observation may be considered.
- Residual mediastinal masses are common. PET/CT scan is essential post-treatment. Biopsy of PET/CT scan positive mass is recommended if additional systemic treatment is contemplated.
- Relapsed/refractory therapy