Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a slow-growing

CD20 B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase ( CD45R+, CD117+) and progressively increasing in concentration until maturity. In humans CD20 is encoded by the ''MS4A1'' gene. This gene ...

positive form of

Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition w ...

, a cancer of the immune system's

B cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted o ...

. NLPHL is an uncommon sub-type of Hodgkin lymphoma, making up 5-10% of Hodgkin lymphomas. It is distinguished from classic Hodgkin lymphoma by the presence of CD20 positive lymphocyte predominant cells, also known as popcorn cells due to their polylobated nuclei, which look like popcorn. There are small but clear differences in prognosis between the various forms. Lymphocyte predominant HL is an uncommon subtype composed of vague nodules of numerous reactive lymphocytes admixed with large popcorn-shaped RSC. Unlike classic RSC, the non-classic popcorn-shaped RS cells of NLPHL are

CD15 Sialyl LewisX (sLeX), also known as cluster of differentiation 15s (CD15s) or stage-specific embryonic antigen 1 (SSEA-1), is a tetrasaccharide carbohydrate which is usually attached to O- glycans on the surface of cells. It is known to play a vi ...

and

CD30 CD30, also known as TNFRSF8 ( TNF receptor superfamily member 8), is a cell membrane protein of the tumor necrosis factor receptor family and a tumor marker. Function This receptor is expressed by activated, but not by resting, T and B cel ...

negative while positive for the B cell marker

. The anti-CD20 monoclonal antibody

Rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in non-geriatric pa ...

has been used in lymphocyte predominant Hodgkin lymphoma with encouraging results. BCL6 gene rearrangements have been frequently observed.

Signs and symptoms

B symptoms B symptoms are a set of symptoms, namely fever, night sweats, and unintentional weight loss, that can be associated with both Hodgkin lymphoma and non-Hodgkin lymphoma. These symptoms are not specific to lymphomas, especially each one considere ...

are uncommon.

Diagnosis

The characteristics of NLPHL differ from classical Hodgkin lymphoma (cHL). Lymphocyte predominant (LP) ("popcorn") cells are present embedded in nodules consisting of B cells and other reactive cells (mainly reactive T cells). Reed-Sternberg and Hodgkin (RSH) cells are rarely seen, and immunohistochemistry shows a different pattern on the malignant cells; RSH cells typically express CD15 and CD30, whereas LP cells lack expression of these markers, but express B cell markers like CD20, CD22, and CD79a and also express the common leukocyte antigen CD45, which is uncommon on RSH cells. The LP cells have scant cytoplasm and one folded or multilobated nuclei with prominent, mostly basophilic nucleoli. Expert pathology review of multiple morphologic and immunophenotypic features including the use of immunohistochemistry is essential. Tumors generally located in the peripheral lymph nodes, which can be detected via

PET scan Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...

and CT scan. Ann Arbor staging is used to classify tumors and symptoms. Stage IV disease is very rare.

Sex

There is a male predominance of NLPHL diagnosis.

Early detection

Diagnosis usually occurs at an early stage of disease progression.

Management

A treatment guide provided by NCCN Guidelines for Patients is available, while the NCCN Clinical Practice Guidelines in Oncology provides a reference for clinicians. Any proposed therapeutic strategy must have minimal acute and long-term toxicities.

Watchful waiting

Watchful waiting Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed. Related terms include ''expe ...

(watch and wait) is defined as a period of observation of at least 3 months without any treatment.

Surgical excision

Surgical lymph node excision may be carried out at the time of diagnosis in certain cases such in children diagnosed at an early stage of progression. One study found sustained complete remission in half of the cases with a watch-and-wait strategy after surgical lymph node excision at the time of diagnosis.

Radiation therapy

Studies indicate that

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...

(radio therapy) may reduce the risk of progression in adults. In one study, stage I-II patients treated with radiation therapy showed 10-year cause-specific survival of 98%, and the rate of developing radiotherapy-related second malignancies was not increased by the treatment (1% after 10 years). A study published in 2013 on large group of patients with early-stage NLPHL indicated support for using limited-field radiation therapy as the sole treatment of early-stage disease. In a study of 1,162 NLPHL patients from the Surveillance, Epidemiology and End Results (SEER) cancer registry program, radiation therapy improved overall survival and disease specific survival.

Immunotherapy

An example

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

for use in

immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

has specific use in treatment of NLPHL as it is a chimeric monoclonal antibody against the protein CD20. Studies indicate Rituximab offers potential in relapsed or refractory patients, and also in front-line treatment especially in advanced stages. Because of a tendency for relapse, maintenance treatment such as every 6 months for 2 years is suggested. Rituximab has been shown to improve patient outcomes after histological transformation.

Chemotherapy

Possible options such as

anthracycline Anthracyclines are a class of drugs used in cancer chemotherapy that are extracted from ''Streptomyces'' bacterium. These compounds are used to treat many cancers, including leukemias, lymphomas, breast, stomach, uterine, ovarian, bladder canc ...

-containing regimens include

ABVD ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, replacing the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs: * Adriamycin (also known as doxorubicin/hydroxydaunorubicin, ...

BEACOPP BEACOPP is a chemotherapy regimen for treatment of Hodgkin lymphoma developed by the German Hodgkin Study Group used for patients in Stages > II or early (IA or IB) with unfavorable risk factors. Patients typically receive treatment in cycles of 21 ...

and CHOP. Results of a trial with COPP/ABV in children suggested positive results with chemotherapy alone are possible without the need for radiation therapy. Optimal chemotherapy is a topic for debate, for example there is evidence of support for treatment with R-CHOP instead of

, results showing high rates (40%) of relapse after 10 years since ABVD chemotherapy. BEACOPP has higher reported toxicity risk.

Combined treatment

One study reported combined

(radio therapy) and antibody

. R-CHOP optionally followed by radiation therapy is recommended in newly diagnosed late stage disease, while for early stage disease radio therapy alone (stage IA without risk factors) or a brief ABVD-based chemotherapy followed by radiation therapy (early stages other than stage IA without risk factors) was advised.

Prognosis

Prognosis is favourable in comparison with classic HL despite a tendency for disease recurrence requiring long term followup. Relapse can occur at a comparatively late stage in comparison to classic HL. There is limited information regarding the outcome for patients with advanced-stage progression.

Ethnicity

One study in the United States has suggested improved overall survival in response to chemotherapy for African Americans.

Histological transformation

Histologic transformation to diffuse large B-cell lymphoma (DLBCL) can occur in up to 12% of cases. After transformation, neoplastic cells carry monoclonal immunoglobulin gene rearrangements. Histological transformation may lead to poor prognosis and therefore repeat biopsy is required at relapse. One study found a transformation rate of 7.6%, and suggested that prior exposure to chemotherapy and a presentation with splenic involvement were associated with increased risks of transformation.

References

External links

{{Hematological malignancy histology Hodgkin lymphoma