Cancer Ribbon Colors, Meanings, and Months
Exploring The Distinct Characteristics Of Nodular Lymphocyte ...
This review offers an in-depth exploration of Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL), highlighting its distinct characteristics across various domains such as epidemiology, clinical presentation, histopathology, immunophenotype, genetic findings, and challenges in differential diagnosis.
Epidemiology and clinical presentationNLPHL is a relatively rare subtype of Hodgkin lymphoma, comprising approximately 10% of all Hodgkin lymphoma cases. It predominantly affects males, with a higher incidence observed in those aged 30 to 50 years. Unlike classical Hodgkin lymphoma, NLPHL often presents with localized lymphadenopathy rather than systemic symptoms, which are rare unless the disease is in an advanced stage. The most commonly involved sites include the cervical, axillary, and inguinal lymph nodes, with mediastinal and extranodal presentations being less frequent. The disease generally follows an indolent course, but in approximately 5-10% of cases, it can transform into diffuse large B-cell lymphoma (DLBCL), which has a more aggressive clinical course.
Histopathologic characteristicsNLPHL is characterized histologically by a nodular growth pattern, often involving pre-existing reactive follicles. The hallmark cells of NLPHL are the lymphocyte-predominant (LP) cells, also known as "popcorn cells" due to their distinctive multilobated nuclei. These cells are typically surrounded by a background of small lymphocytes and histiocytes. A notable feature in NLPHL is the presence of progressive transformation of germinal centers (PTGC), which can be observed in the surrounding non-involved lymphoid tissue. However, PTGC is not considered a direct precursor to NLPHL, and its presence does not necessarily increase the risk of developing the disease.
ImmunophenotypeThe immunophenotypic profile of NLPHL is distinct, with LP cells expressing B-cell markers such as CD20, CD79a, Pax5, and Bcl-6. Notably, these cells lack expression of CD10 and MUM-1/IRF4, which are commonly found in other types of lymphoma. The LP cells show strong expression of transcription factors Oct-2 and Bob1, which are crucial for immunoglobulin transcription. Furthermore, LP cells in NLPHL are generally negative for Epstein-Barr virus (EBV), distinguishing them from certain subtypes of classical Hodgkin lymphoma where EBV is frequently detected. An intriguing aspect of NLPHL is the presence of T-follicular helper (TFH) cells, which form rosettes around the LP cells and may play a role in the pathogenesis of the disease.
Genetic findingsGenetic studies of NLPHL reveal that the LP cells carry functional immunoglobulin rearrangements and exhibit a high load of somatic hypermutations, indicative of their origin from germinal center B-cells. Mutations in genes such as PAX5, PIM1, RHOH, and MYC have been identified, alongside aberrations in SGK1, DUSP2, and JUNB. These genetic features highlight the complexity of NLPHL and suggest a close relationship with T-cell/histiocyte-rich large B-cell lymphoma (THRLBL), another type of lymphoma that shares some histologic and immunophenotypic similarities with NLPHL.
Differential diagnosisThe differential diagnosis of NLPHL is challenging due to its overlapping features with other lymphomas, particularly THRLBL and lymphocyte-rich classical Hodgkin lymphoma (LRCHL). While NLPHL and THRLBL share several genetic and immunophenotypic characteristics, they differ in clinical presentation and histopathologic features. THRLBL often presents with more widespread disease and systemic symptoms, whereas NLPHL typically remains localized with an indolent course. Histologically, NLPHL can be distinguished from LRCHL by its nodular growth pattern and the presence of LP cells. In contrast, LRCHL is characterized by regressed germinal centers and a distinct mantle zone, which are not features of NLPHL.
ConclusionsThe review underscores the importance of recognizing the diverse histopathologic and immunophenotypic features of NLPHL for accurate diagnosis and treatment. The close relationship between NLPHL and other lymphomas, such as THRLBL, necessitates careful consideration in differential diagnosis to avoid misclassification. Understanding the unique characteristics of NLPHL, including its epidemiology, clinical presentation, and genetic underpinnings, is crucial for developing effective therapeutic strategies and improving patient outcomes.
Source:
Journal reference:
Ding, Y., & Jaffe, E. S. (2024). Histopathologic Features and Differential Diagnosis in Challenging Cases of Nodular Lymphocyte Predominant B-cell Lymphoma/Nodular Lymphocyte Predominant Hodgkin Lymphoma. Journal of Clinical and Translational Pathology. Doi.Org/10.14218/jctp.2024.00015.
Shades Of Gray Between Large B-cell Lymphomas And Hodgkin ... - Nature
CHL is characterized by the presence of characteristic large neoplastic cells: mononuclear Hodgkin cells and binucleated or multinucleated Reed–Sternberg cells (HRS cells) in a background of variable numbers of lymphocytes, histiocytes, eosinophils and plasma cells (Figures 1a–f).3 Diagnostic Reed–Sternberg (RS) cells are large cells with bilobed, double or multiple nuclei, with a large, eosinophilic, inclusion-like nucleolus in at least two lobes or nuclei. The neoplastic cells typically lack conventional markers of the B-cell differentiation program (Figure 2), including pan-B-cell markers such as CD19, CD20, CD79a, and immunoglobulin heavy and light chains, but express the B-cell antigen Pax5 (usually more weakly than normal small B cells). Oct2 and/or Bob1 may be expressed, but both are not typically strongly positive. Some cases have weak and variable expression of CD20. They are typically IRF4/Mum1+ but CD138−. In addition, they express a marker not typically associated with normal B cells, CD15, and the activation marker, CD30. The background inflammatory cells typically include T cells and variable numbers of B cells; the latter may form follicular aggregates with which the neoplastic cells may be associated—a variant known as LRCHL. Immunoglobulin genes (IGH) rearranged and highly mutated. Conventional cytogenetics shows frequent aneuploidy and polyploidy but no consistent recurring abnormalities. CGH has shown gains of 2p, 9p and 12q and amplification of 4p16, 4q23–24 and 9p23–24.3 There is activation of the NFkB, AP-1 and JAK/STAT pathways in HRS cells, with expression of TRAF and nuclear REL.3 Recently, translocations of the major histocompatibility complex (MHC) class II transactivator CIITA have been reported in 15% of the cases of CHL.4
Figure 1Morphological features of classical Hodgkin lymphoma (CHL) (hematoxylin and eosin stain). (a) Nodular sclerosis CHL (NSCHL) is characterized by cellular nodules surrounded by fibrous bands. (b) The infiltrate contains lacunar variants of Reed–Sternberg (RS) cells, with lobulated nuclei and abundant pale cytoplasm, in a background of lymphocytes and variable numbers of histiocytes and eosinophils. (c) Mixed cellularity CHL (MCCHL) is characterized by classical RS cells and mononuclear variants in a background of lymphocytes, histiocytes and eosinophils. (d) Lymphocyte-rich CHL (LRCHL) has a nodular pattern, with meshworks of follicular dendritic cell (FDC) and sometimes remnants of regressed germinal centers. (e) Classical RS cells and variants are located within the follicles, mantle zones and interfollicular regions in a background of lymphocytes and histiocytes. (f) Lymphocyte-depleted CHL (LDCHL) has a diffuse pattern with variable amounts of sclerosis and often bizarre RS cell variants.
Figure 2Immunophenotype of classical Hodgkin lymphoma. (a) Lymphocyte-rich classical Hodgkin lymphoma (LRCHL) has Reed–Sternberg (RS) cells that are CD15+. (b) The RS cells also express CD30. (c) The RS cells are CD20− in a background of CD20+ small B lymphocytes.
Variants of CHL are defined both by the morphology of the neoplastic cells and the characteristics of the background infiltrate, and include nodular sclerosis (NSCHL),5 mixed cellularity (MCCHL),6 lymphocyte-rich (LRCHL)7 and lymphocyte-depleted (LDCHL)8 types. Particularly in the NSCHL and LDCHL subtypes, large numbers of neoplastic cells may be present and give rise to a differential diagnosis of LBCL.
Distinctive clinical features include the typical presentation of NSCHL in the mediastinum in young adults, with frequent occurrence in females; presentation of MCCHL and LDCHL with advanced disease, splenic and/or bone marrow involvement, and association with immunodeficiency, particularly human immunodeficiency virus (HIV) infection, as well as EBV positivity.
Nodular Sclerosis CHLNSCHL is characterized by collagen bands that surround at least one nodule, and HRS cells including some with 'lacunar' type morphology—a multilobated nucleus, small nucleoli, and abundant, pale cytoplasm, which retracts in formalin-fixed sections, producing an empty space or lacuna (Figures 1a and b). The background contains lymphocytes, histiocytes, eosinophils and plasma cells.5 Necrosis may be prominent. Histiocytes may form sarcoidal or necrotizing granulomas. In the so-called syncytial variant, there are large sheets of RS cell variants. NS can be stratified according to the number of neoplastic cells or the characteristics of the background infiltrate (proportion of eosinophils) either of which may predict prognosis. However, these grading schemes are not currently used to determine therapy.5 EBV positivity is uncommon (∼20%).
NSCHL is the most common subtype of HL in developed countries (60–80% in most series). It is most common in adolescents and young adults, but can occur at any age; affected females equal or exceed males. The mediastinum and other supradiaphragmatic sites are commonly involved.
Mixed Cellularity CHLIn MCCHL, the infiltrate is diffuse or vaguely nodular, without band-forming sclerosis, although fine interstitial fibrosis may be present. RS cells are of the classic, diagnostic type and are usually easily identified (Figure 1c). Many mononuclear variants are usually also present. The infiltrate typically contains lymphocytes, epithelioid histiocytes, eosinophils and plasma cells. EBV positivity is seen in about 75% of the cases.5
MCCHL comprises 15–30% of HL cases in most series; it may be seen at any age (median age of 40 years), and lacks the early adult peak of NSCHL. Involvement of the mediastinum is less common, and abdominal lymph node and splenic involvement are more common.
Lymphocyte-Rich CHLSome cases of CHL have a background infiltrate that consists predominantly of lymphocytes, with rare or no eosinophils (Figures 1d and e). The term LRCHL was proposed for these cases in the REAL classification and was adopted by the WHO.7 Most cases of LRCHL have a nodular pattern, with meshworks of follicular dendritic cell (FDC) and remnants of regressed germinal centers; RS cells and variants are located within the mantle zones and interfollicular regions, mimicking NLPHL. However, NLPHL rarely has a distinct germinal center remnant within the nodules.
Immunophenotyping (Figure 2a–c) is essential to distinguish LRCHL from NLPHL, as in LRCHL the RS cells should have a classical (CD20− CD15+ CD30+ IRF4/Mum1+) immunophenotype in contrast to the NLPHL, which is typically CD20+ CD15− CD30− IRF4/Mum1−, although exceptions occur. The immunophenotype of the B-cell nodules may be very similar in both entities, including the presence of T cells expressing CD57 and CD279 associated with the RS cells.9 In one study, the B-cell expression program (Oct2, Bob1) was more often preserved in LRCHL compared with other CHL subtypes, and had infrequent expression of REL compared with other CHL but comparable expression of TRAF1, suggesting that LRCHL may be a distinct entity from either CHL or NLPHL.10
LRCHL comprises about 5% of the cases of HL.11 The clinical features at presentation similar to those of NLPHL: similar to NLPHL, patients have early stage disease, lack bulky disease or B-symptoms, lack mediastinal disease and have a predominance of males, and a median age higher than that for NSCHL. The prognosis appears to be slightly better than that of other subtypes of CHL, and similar to that of NLPHL, although with fewer late relapses.7, 11
Lymphocyte-Depleted CHLLDCHL is characterized by RS cells, and bizarre 'sarcomatous' variants, and relatively few inflammatory cells. In some cases there is a diffuse hypocellular infiltrate, with diffuse fibrosis and necrosis (Figure 1f); in other cases, sheets of RS cells and variants may occur ('reticular' variant or 'Hodgkin sarcoma').8 Before the availability of immunophenotyping studies, many cases diagnosed as LCHL were LBCL or T-cell lymphomas, often of the anaplastic large cell type.
LDCHL comprises <1% of CHL in recent reports.11, 12 It is seen more commonly in HIV+ individuals, and in resource-poor settings than in otherwise healthy, affluent persons. Patients present more commonly with advanced disease at diagnosis and B symptoms than with other subtypes. Response to treatment, progression-free and overall survival are reported to be significantly worse than for other subtypes, but may be improved with very aggressive treatment regimens.11, 12
Understanding Hodgkin Lymphoma -- Diagnosis And Treatment
Lymphoma is a type of cancer that begins in infection-fighting cells of the immune system, called lymphocytes. These cells are in the lymph nodes, spleen, thymus, bone marrow, and other parts of the body. When you have lymphoma, lymphocytes change and grow out of control.
Lymphoma is very treatable, and the outlook can vary depending on the type and stage of the illness. Understand the basics of lymphoma, the differences between Hodgkin and non-Hodgkin lymphoma, and why some people may be more susceptible to this type of cancer. Your doctor can help you find the right treatment for your type and stage of the illness.
Lymphoma is different from leukemia. Each of these cancers starts in a different type of cell.
Lymphoma is also not the same as lymphedema, a collection of fluid that forms in body tissues when the lymph system is damaged or blocked.
Lymphoma begins in cells called lymphocytes, which fight off infection. (Photo Credit: Science Photo Library/Getty Images)
There are two main types of lymphoma:
Non-Hodgkin lymphoma
Non-Hodgkin lymphoma (NHL) makes up about 90% of lymphoma diagnoses. This form of the disease has two categories: B-cell lymphomas and T-cell lymphomas. B-cell lymphomas affect 80% of people with non-Hodgkin lymphoma. There are different subtypes of B-cell and T-cell lymphomas, some of which are more aggressive and need treatment right away, usually chemotherapy. More slow-growing (indolent) types of NHL may not require immediate treatment. Instead, doctors take a watch-and-wait approach.
B-cell lymphomas include:
T-cell lymphomas include:
Cutaneous T-cell lymphoma is a rare skin-related form of the condition that usually requires only ointments applied to the skin for treatment.
Hodgkin lymphoma
If you've formed mutant cells called Reed-Sternberg cells, your doctor will diagnose you with Hodgkin lymphoma. There are two main types: classical and nodular lymphocyte predominant. Cancer treatments such as chemotherapy can cure many people with this type of lymphoma. And if it comes back, chemo combined with stem cell transplants works well to wipe out the disease.
Doctors aren't entirely sure why lymphoma develops, but it starts with changes in the DNA of lymphocytes. Normally, DNA in cells carries instructions that control how fast cells grow and multiply and when they should die. But in lymphoma, the DNA in lymphocytes changes.
These changes cause the cells to behave abnormally — they grow uncontrollably and live longer than they should. This uncontrolled growth leads to too many abnormal lymphocytes, especially in areas such as the lymph nodes, spleen, and liver, causing these organs to enlarge.
You may have a higher chance of lymphoma if you:
Warning signs of lymphoma include:
Local symptoms of lymphoma
Systemic symptoms of lymphoma
Many of these symptoms can also be warning signs of other illnesses. See your doctor to find out for sure if you have lymphoma.
Are there any early warning signs of lymphoma?
Many times, the first symptom of lymphoma is painless swelling of lymph nodes in your neck, groin, or underarm.
Before you have any tests, your doctor will do a physical exam, including a check for swollen lymph nodes. This symptom doesn't mean you have cancer. Most of the time, an infection -- unrelated to cancer -- causes swollen lymph nodes. They'll also ask about your family's medical history and symptoms.
You might get a lymph node biopsy to check for cancer cells. For this test, a doctor will remove all or part of a lymph node or use a needle to take a small amount of tissue from the affected node.
You might also have one of these tests to help diagnose, stage, or manage lymphoma:
Bone marrow aspiration or biopsy. Your doctor uses a needle to remove fluid or tissue from your bone marrow -- the spongy part inside the bone where your body makes blood cells -- to look for lymphoma cells.
Chest X-ray. This test uses low doses of radiation to make images of the inside of your chest.
MRI. A technician uses powerful magnets and radio waves to take pictures of organs and structures inside your body.
PET scan. This imaging test uses a radioactive substance to look for cancer cells in your body.
Molecular test. This test is used to find changes to genes, proteins, and other substances in cancer cells to help your doctor figure out which type of lymphoma you have.
Blood tests. These check the number of certain cells, levels of other substances, or evidence of infection in your blood.
If your diagnosis is positive for lymphoma, here are some questions to consider asking your doctor:
The treatment you get depends on your type of lymphoma and its stage.
Treating non-Hodgkin lymphoma
The main treatments for non-Hodgkin lymphoma are:
Treating Hodgkin lymphoma
The main treatments for Hodgkin lymphoma are:
If these treatments don't work, you might have a stem cell transplant. First, you'll get very high doses of chemotherapy. This treatment kills cancer cells but also destroys stem cells in your bone marrow that make new blood cells. After chemotherapy, you will get a transplant of stem cells to replace the ones that were destroyed.
Your doctor can do two types of stem cell transplants:
Can lymphoma go away without treatment?
Some types of lymphoma can go away without treatment, but it depends on the type of lymphoma and the person who has it:
Follicular lymphoma. This type of lymphoma can go away without treatment, especially if it's not causing health problems beyond swollen lymph nodes. It often grows slowly and responds well to treatment, but it's hard to cure and can come back after treatment.
Low-grade lymphoma. This type of lymphoma grows so slowly that patients can live for many years without symptoms, and some may never need treatment.
Intermediate-grade lymphoma. This type of lymphoma gets worse quickly without treatment, but treatment can cause remission in many cases.
Hodgkin lymphoma and high-grade non-Hodgkin lymphoma. These types of lymphoma can often go into complete remission and may not need further treatment.
Lymphoma treatment can cause side effects. Talk to your medical team about ways to ease any symptoms you have.
Also, ask your doctor about changes to your diet and exercise that can help you feel better during your treatment. Ask a dietitian for help if you're not sure what types of food to eat. Exercises such as walking or swimming can ease fatigue and help you feel better during treatments such as chemotherapy and radiation. You might also try alternative therapies such as relaxation, biofeedback, or guided imagery to help ease pain.
Treatments have improved a lot, and many people do very well after treatment. Your doctor will talk to you about a survivorship care plan. Your outlook depends on:
You can get support from people who have gone through this kind of illness. Contact the Leukemia & Lymphoma Society or Lymphoma Research Foundation to learn more.
It's also crucial to keep your loved ones close — they can offer both emotional and practical support, such as helping around the house when you're in the hospital. Also, find someone you can openly talk to about your feelings and worries, whether it's a friend, family member, or a professional such as a counselor or social worker.
Lymphoma is a cancer stemming from lymphocytes, the infection-fighting cells within your immune system. It appears in two forms: non-Hodgkin lymphoma (which is more common) and Hodgkin lymphoma. Lymphoma's causes remain mostly unknown, but risk factors include age, gender, a compromised immune system, infection, and exposure to certain chemicals.
Symptoms such as swollen glands, weight loss, fever, and night sweats could suggest lymphoma. Treatment varies by type and stage of lymphoma but may include chemotherapy, radiation, immunotherapy, targeted therapy, and potentially stem cell transplants.
What is the survival rate for lymphoma?
Overall, the 5-year survival rate for non-Hodgkins lymphoma is 74%, but this varies based on the type and stage of your cancer.
How long can you live with lymphoma without knowing?
Some types of lymphoma grow so slowly that you can live for years without knowing you have the disease.
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