T cell/histiocyte-rich large B-cell lymphoma
| T-cell/histiocyte-rich large B-cell lymphoma | |
|---|---|
| Other names | THRLBCL |
| Specialty | Hematology, Oncology, |
| Differential diagnosis | Variant form of nodular lymphocyte predominant Hodgkin lymphoma |
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a malignancy of
THRLBCL commonly afflicts middle-aged individuals but has been diagnosed in rare pediatric cases.
Many studies have found that THRLBCL can overlap with the variant form of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). That is, some cases of variant NLPHL, which is a relatively indolent malignancy, share with THRLBCL similar disease presentations, histologies (i.e. microscopic appearances), genetic abnormalities, and apparent etiologies.[4] Indeed, NLPHL can, in rare cases, progress into THRLBCL.[2] Comapared to THRLBCL, however, these variant NLPHL cases are less aggressive, are more responsive to treatment, and have a better prognosis.[4] Thus, THRLBCL and NLPHL may be biologically related diseases that represent opposite ends of a severity spectrum.[5]
Presentation
T-cell/histiocyte-rich large B-cell lymphoma most commonly afflicts middle-aged (i.e. 49–57 years old) individuals but has been diagnosed in persons aged 4
Pathogenesis
Due to its rarity, the causes of THRLBCL have not been well studied and consequently remained unclear. The malignant B-cells in the disease commonly have mutations in several genes such as:[2]
- JUNB which codes for JunB, a protein that regulates cell growth and survival and is highly expressed in other lymphocyte malignancies;[10]
- tumor suppressor) which codes for dual specificity protein phosphatase 2, a protein that regulates several components of the ERK/MAPK signaling pathway that controls cell proliferation;[11]
- SGK1 which codes for serine/threonine-protein kinase, a protein that regulates several signaling pathways that control cell proliferation and survival;[12]
- and
- CREBBP, a gene that is commonly mutated in other DLBCL subtypes as well as other lymphomas and codes for the transcription coregulator, CREB-binding protein.[14]
The neoplastic cells in this disease also show gains on the short arm of chromosome 2 at position 16.1 which affect the
The neoplastic B-cells in THRLBCL infiltrations are dominated by high numbers of histiocytes and dendritic cells. Studies suggest that the latter cells help to create a microenvironment that is tolerant or promotes tumor growth and spread to other sites.[4]
Diagnosis
The diagnosis of THRLBCL, particularly as it pertains to differentiating it from DLBCL and other lymphomas, depends on examining involved tissues obtained by biopsy or operation for their
Differential diagnosis
While the histological features of THRLBCL are distinctly different that those found in other DLBCL subtypes, they can closely resemble, and be mistaken for, those found in the variant form of nodular lymphocyte predominant Hodgkin lymphoma.[4] Some important histological features that favor the diagnosis of THRLBCL over NLPHL include the presence of:
- <10% neoplastic B-cells;
- CD163-expressing histiocytes (cases of THRLBCL in which histiocytes are absent appear to take a less aggressive course than cases in which these cells are present);
- a diffuse rather than nodular cell infiltration pattern with any nodular infiltrates present in THRLBCL containing follicular dendritic cells;
- CD57-expressing T-cells;
- cells strongly expressing the BAT3/BAG6 ubiquitin domain-containing protein;[3] and
- few or no small lymphocytes, variant Hodgkin Reed-Sternberg cells.[8]
Treatment
Patients diagnosed with THRLBCL have been treated with