Primary mediastinal B-cell lymphoma

Primary mediastinal B-cell lymphoma, abbreviated PMBL or PMBCL, is a rare type of lymphoma that forms in the mediastinum (the space in between the lungs) and predominantly affects young adults.^[1][2][3]

Primary mediastinal large B-cell lymphoma
Micrograph of a primary mediastinal large B-cell lymphoma. H&E stain.
Specialty	Hematology and oncology

While it had previously been considered a subtype of diffuse large B-cell lymphoma;,^[4] the World Health Organization no longer classifies it as such, based on distinct clinicopathologic and molecular features.^[5]

Pathophysiology

PMLBCL arises from a putative thymic peripheral B cell.^[6][7] It has several distinctive biological features.^[6] Molecular analysis shows that PMLBCL is distinct from other types of diffuse large B-cell lymphomas (DLBCL).^[7] MAL gene expression is seen in 70%, unlike other diffuse large B-cell lymphomas.^[8]: 370 Gene expression profiling shows considerable variance from other DLBCLs and similarity to Hodgkin disease.^{[9]: 290–293}

PMLBCL is CD20 positive, expresses pan-B markers including CD79a, and has clonal immunoglobulin gene rearrangements and mRNA but paradoxically does not express cytoplasmic or cell surface immunoglobulin.^[8]: 370

Clinically, PMLBCL is unusual in several respects. Despite 80% PMLBCL being stage I or II, the presenting anterior mediastinal mass is often over 10 cm and is locally invasive of lung, chest wall, pleura, and pericardium.^[6] At initial presentation, PMLBCL is usually confined to mediastinum, but its bulk, rather than additional adenopathy, can sometimes be palpated at the low neck.^[6] Increased LDH is seen in approximately 75%,^{[8]: 370 [6]} but unlike other large cell lymphomas, no increase in beta-2 microglobulin is seen even when bulky^[8]: 370 which may relate to defective major histocompatibility complex expression.^[8]: 370

Diagnosis

Diagnosis requires a biopsy, so that the exact type of tissue can be determined by examination under a microscope. PMBCL is a distinct type of lymphoma that shares some features with both diffuse large B-cell lymphoma, and nodular sclerosing Hodgkin lymphoma (NSHL).^[10] Tumors that are even more closely related to NSHL than typical for PMBCL are called gray zone lymphoma.^[10]

Treatment

Multiagent chemotherapy is recommended, but the preferred regimen is controversial, as is consolidative radiotherapy.^{[6][11][12][13]}

Treatment commonly begins with either R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or DA-EPOCH-R (dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab).^[14] Other, more intense, regimens may be more effective.^[10] PD-1 and PD-L1 inhibitors can be used.^[3]

Radiation therapy may be added, especially if chemotherapy does not seem sufficient on its own.^[14] Radiation may cause other health problems later, such as breast cancer, and there is some debate about the best approach to it.^[10][3]

FDG-PET scanning is not as useful for predicting treatment success in PMBCL as it is in other lymphomas.^[10][3]

Prognosis

Most people with PMBCL are successfully treated and survive for many years. However, if the initial treatment is unsuccessful, or if it returns, the long-term prognosis is worse.^[14] Relapses generally appear within 12 to 18 months after the completion of treatment.^[10]

Epidemiology

This lymphoma is most commonly seen in women between the age of 20 and 40.^[10]

See also

• Diffuse large B-cell lymphoma
• Hodgkin lymphoma