Highly aggressive B cell malignancy, small non-cleaved-cell lymphoma.
Derived from the mature germinal center B cell.
Among fastest growing malignancies.
Less than 2000 cases annually.
Accounts for 20-30% of pediatric lymphomas but only approximately 1% of adult non-Hodgkin lymphomasin the United States for an estimated 1480 cases annually.
There are three major variants: endemic, occurring it Equatorial Africa, sporadic, occurring worldwide, and immunodeficiency associated, occurring in patients with HIV infections.
The clinical presentation is often dramatic and associated with tumor doubling times of 24 to 48 hours.
Tumor proliferation and growth is advanced by means of the phosphatidyllonisitide 3-kinase pathway and cyclin-dependent kinases.
About 10% of patients with c-myc gene translocation seen in diffuse large b CELL LYMPHOMA.
Must be distinguished from diffuse large B cell lymphoma since it requires high intensity treatment.
Prophylactic intrathecal chemotherapy or chemotherapy that crosses the blood brain barrier is needed because of the high risk of involvement of the CNS.
Diagnosis based on morphologic, immunophenotyping and cytogenetic studies.
Morphologically BL tumors show complete effacement of the normal lymph node architecture, with monotonous appearing B cells.
Originates from germinal center B cells.
B cells are small to intermediate in size and have round, basophilic nuclei and coarse chromatin.
Frequent mitoses may be present and tumor cells may have small vacuoles, and the proliferation growth rate fractions approach 100%.
Characteristically there is a “starry sky“ appearance produced by intermittent benign histicytes the that have ingested apoptic debris.
Characteristic t(8;14) translocation.
Increased expression of c-myc target gene, decreased expression of major histocompatibility complex class I and nuclear factor κB target genes and expression of germinal center B cell genes.
Includes endemic and sporadic types associated with immunodeficiency and immunosuppression.
Occurs mostly in pediatric patients and infrequently in adults in the absence of HIV infection or posttransplant setting.
HIV increases risk by 10 fold.
Young patients with sporadic disease have a favorable outcome with short-term intense chemotherapy, whereas adults patients and those with immunodeficiency related disease have inferior outcomes.
Of the three clinical variants, endemic BL is the most common worldwide with incidence in equatorial Africa of 3-6 children per hundred thousand.
Endemic BL accounts for 30-50% of cases of childhood cancer in this region, with a 2 to 1 male predominance and median age of presentation of 4-7 years.
The incidence of endemic BL is highest in areas with a high prevalence of Plasmodium falciparum malaria and early exposure to Epstein-Barr virus, such as Equatorial Africa, Brazil, and Papua New Guinea.
Virtually all cases of endemic BL are positive for EBV, and a high serologic titer of EBV is associated with an increased risk of BL.
Children with endemic BL present with rapidly growing jaw or periorbital region masses, and extranodal sites including the ileum, cecum, gonads, kidney, and breasts.
In endemic BL the bone marrow is involved in fewer cases than other variants initially, but is often a complication of disease relapse.
CNS involvement is also uncommon at diagnosis in the endemic variant.
Sporadic BL occurs in immunocompetent patients outside of endemic regions.
Sporadic BL is found primarily in orth Africa and western Europe, and accounts for 30 to 50% of pediatric non-Hodgkin lymphomas but only 1 to 2% of adult lymphomas.
Sporadic BL in adults has a slight male predilection, the median age of diagnosis between 30-40 years with bimodal peaks at 10 and 75 years of age.
In contrast to endemic BL, only 40% of cases of sporadic BL are positive for EBV.
In sporadic BL the abdominal region is frequently involved, particularly the ileocecal region.
Sporadic BL patients may present with abdominal pain, nausea, vomiting, and can imitate small bowel obstruction or acute appendicitis prompting surgical attention.
Bone marrow involvement is more common in sporadic BL than in endemic BL, and some cases are categorized as leukemia with extensive involvement of blasts in the bone marrow.
CNS involvement is present at diagnosis in 10 to 20% cases of sporadic BL.
Immunodeficient-associated BL is most commonly in patients infected with HIV, although cases can occur after solid organ or stem cell transplant.
Immunodeficiency-associated BL is the variiant that is seen in approximately 20% of cases in the US annually.
This process can occur even in well-controlled HIV and the incidence has not significantly declined despite the widespread use of highly active anti-retroviral therapy.
HIV-associated BL typically has nodal involvement but ihas a high frequency of dissemination to extra nodal sides, including the CNS, bone marrow, breast, gonads, and adrenal glands. Y Treated with intensive chemotherapy, plus agents that penetrate the blood brain barrier because the tumor tend to spread to the CNS.
Highly sensitive to chemotherapy and can be cured with highly intensive combination treatment regimens that include agents that penetrate the CNS, along with intensive supportive care.
The anti-CD20 monoclonal antibody rituximab further improves survival when added to standard chemotherapy.