Lymphoma

The lymphatic system is a part of immune system consisting of red bone marrow, thymus, a network of lymphatic vessels, and other structures/organs like lymph nodes and spleen that are made up of lymphatic tissue (a specialized reticular tissue containing many lymphocytes or white blood cells [WBCs], which destroy the pathogens and filter out other harmful substances). The lymph (a clear liquid consisting of lymphocytes) flow through the lymphatic vessels and lymph nodes under the influence of skeletal muscle contractions and respiratory movements and finally enters the superior vena cava. The lymphatic system imparts immunity, helps in draining the interstitial fluid, and transports dietary lipids. The lymphatic system mainly consists of 2 types of lymphocytes – T-cells and B-cells. 

NHL is a group of different lymphoid neoplasms with variable characteristics. Most NHLs, about 80-85%, arise from the B-cells while about 15% arise from T-cells or natural killer (NK) cells. NHL may start in any part of the lymphatic system including lymph nodes, spleen, bone marrow, thymus, and gastrointestinal tract. HL mainly arise from the B-cells. HL may start in any part of the lymphatic system, but it usually starts in lymph nodes in the neck, under the arms, and in the chest.

What are the Types of Hodgkin’s Lymphoma?

According to WHO classification, HL can be divided into following 2 main types:

Classic Hodgkin lymphoma (CHL)

This is the most common type of HL that comprises about 95% of all HL cases in the western countries. The characteristic feature of CHL is the presence of Reed-Sternberg cells (abnormal B-cells) in a background of in?ammatory and accessory cells such as eosinophils, neutrophils, histiocytes, plasma cells, and fibroblasts. The Reed-Sternberg cells of CHL usually express CD30, CD15, and variably CD20 surface markers. CHL is further divided into following 4 subtypes:

• Nodular sclerosis Hodgkin lymphoma (NSCHL)
• Mixed cellularity Hodgkin lymphoma (MCCHL)
• Lymphocyte-rich Hodgkin lymphoma
• Lymphocyte-depleted Hodgkin lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)

This is a relatively less common type of HL comprising about 5% of all cases of HL. The characteristic feature of NLPHL is the presence of “popcorn” or lymphocyte-predominant (LP) cells, the variant of Reed-Sternberg cells. The LP cells usually express CD45, CD20, and rarely CD30 surface markers. The NLPHL is inherently slow growing compared to HL and is treated slightly differently than HL.

What are the types of Non-Hodgkin’s Lymphoma?

NHL can be broadly classified into the following 2 categories:

Indolent lymphomas

Lymphoma cancer doctor in Gurgaon: This is a category of slow-growing lymphomas. Most of the NHLs in this category do not require treatment right away, but patients with these lymphomas can be closely monitored until the appearance of bothering symptoms. Sometimes, these lymphomas progress to aggressive lymphoma type after their diagnosis, which generally indicates poor disease prognosis. Following are some example of NHLs which fit into this category:

Follicular lymphoma (FL)

This B-cells lymphoma is the second most common NHL diagnosed in the US and comprises about 20% of all new NHL cases. Involvement of multiple lymph nodes throughout the body along with bone marrow is commonly observed. FL cells in most patients possess t(14;18) translocation causing deregulated of BCL-2 gene and certain characteristic cell surface proteins (CD20+, CD10+, CD3–, CD5–).

Lymphoplasmacytic lymphoma (LPL)/ Waldenström’s macroglobulinemia (WM)

Lymphoma cancer specialist in Gurgaon: LPL is a rare, indolent, B-cell lymphoma that accounts for about 1% of all NHL cases. Clinically the disease resembles small lymphocytic lymphoma and multiple myeloma. LPL cells are usually small and mainly present in the lymph nodes, spleen, and bone marrow. LPL that is associated with a monoclonal serum paraprotein of IgM type it is known as WM. WM cells mainly build-up in bone marrow causing a decreased number of other blood cells. The LPL cells generally possess activating mutations in MYD88 gene and express IgM, CD19 and CD20 surface antigens and lack CD10 or CD23.

Marginal zone lymphoma (MZL)

These B-cell lymphomas make-up about 5% to 10% of all cases of NHL in the US. Common subtypes include extranodal MZL (or mucosa-associated lymphoid tissue [MALT] lymphoma, Nodal MZL, and Splenic MZL. MALT lymphoma is the most common MZL subtype that generally affects gastrointestinal tract (especially the stomach), parotid, salivary glands, skin, eyes, breast, lung, ovary, prostate, and other head and neck regions. The MALT lymphoma affecting stomach are generally associated with infection by Helicobacter pylori and its treating generally resolve lymphoma. Many other pathogens such as Chlamydia psittaci, Campylobacter jejuni, Borrelia burgdorferi, and hepatitis C virus (HCV) have been linked to the development of MZLs. Nodal MZL is a rare subtype commonly affecting older females and is generally associated with peripheral lymphadenopathy. Splenic MZL is another rare type commonly affecting older males. Enlarged spleen, low blood cell count, and bone marrow involvement are observed in almost all cases of splenic MZL. MZL cells in most patients possess t(11;18) translocation causing the formation of API2-MALT1 (a chimeric fusion gene) and certain characteristic cell surface proteins (CD5–, CD10–, CD20+, and cyclin D1–).

Mycosis Fungoides (MF) and Sézary Syndrome (SS)

MF and SS are types of cutaneous T-cell lymphomas (CTCLs) characterized by the presence of abnormal mature T-cells primarily invading skin which may spread to lymph nodes, blood, and other organs. MF is the most common, indolent lymphoma accounting for about 50% to 70% of all CTCLs and SS is rare, aggressive lymphoma accounting for about 1% to 3% of all CTCLs. Clinical skin manifestation of MF includes patches, plaques, cutaneous tumors, ulcers, and erythroderma (diffuse erythema involving more than 80% of the skin surface with or without scaling) while SS causes erythroderma with extensive skin involvement and diffuse exfoliation. SS is characterized by the presence of >/=1,000 Sézary cells/mm^3 of blood. MF and SS cells generally possess a high CD4/CD8 ratio with CD2+, CD3+, CD5+, CCR4+, TCR-beta+, and CD45RO+ and absence of T-cell markers, CD7 and CD26.

Aggressive Lymphomas

This is a category that includes relatively fast growing and rapidly-spreading NHLs. These lymphomas generally require immediate treatment upon diagnosis. Following are some example of NHLs which fit into this category:

Diffuse large B-cell lymphoma (DLBCL)

As the name indicates, it arises from the B-cells (that looks large immature cells under the microscope), and it is the most common type of NHL in the US constituting about 30% of all newly diagnosed NHLs. DLBCL commonly affect deep-sited lymph nodes in the chest and abdomen. DLBCL cells generally possess BCL-6 and BCL-2 gene rearrangements and certain characteristic cell surface proteins (CD20+, CD45+, and CD3–). Based on gene expression profiling (GEP), DLBCL can be divided into 2 subtypes, germinal center B-cell (GCB) subtype and non-GCB subtype. The GCB subtype generally has a better prognosis compared to non-GCB subtype. Some lymphomas have characteristics intermediate between DLBCL and classical Hodgkin lymphoma (cHL) and known as grey zone lymphomas.

Burkitt lymphoma (BL)

These B-cell lymphomas make-up about 1% to 2% of all cases of NHL in the US. This is a common childhood lymphoma but a rare malignancy in adults. Medical literature describes three variants of BL: endemic, sporadic, and immunodeficiency-associated BL. The endemic BL is observed in equatorial African children with most cases linked to Epstein-Barr virus (EBV) infection. Sporadic BL is generally observed in the US and other western countries with about 30% cases liked to EBV infection. Immunodeficiency-associated BL is generally observed in immunocompromised people and commonly linked to HIV infection. The BL cells generally possess translocation and deregulation of MYC gene on chromosome 8 with and certain characteristic cell surface proteins (CD10+, CD20+, CD19+, CD22+, CD3–, CD10–, CD5–, TdT–, and Ki67+).

Primary mediastinal large B-cell lymphoma (PMBL)

This is a subtype of DLBCL that generally affect young adults and starts in the mediastinum (the middle chest region behind the breastbone). It is usually associated with troubled breathing (as the growing tumor presses on trachea), swelling in face and arms (as the growing tumor presses on superior vena cava), pericardial and pleural effusions. PMBL cells usually possess cell surface antigens (CD19+, CD20+, CD22+, CD21–, IRF4/MUM1+ and CD23+).

Mantle cell lymphoma (MCL)

These B-cell lymphomas constitutes about 5% to 6% of all new cases of NHLs. MCLs are inherently aggressive, which are usually diagnosed at an advanced stage. MCL cells are small to medium-sized and consist of relatively less cytoplasm with an irregular nucleus. MCL cells are generally found in expanded mantle region of lymph nodes and show diffuse arrangement. MCL cells generally harbor t(11;14) translocation leading to cyclin D1 overexpression and possess certain characteristic cell surface proteins (CD20+, CD5+, CD10–, and CD3–).

Post-transplantation lymphoproliferative disorder (PTLD)

Lymphoma cancer surgeon in Gurgaon: PTLDs are a group of heterogeneous lymphomas that occur after solid organ transplantation (SOT) or allogeneic stem cell transplantation. Most of them arise from B-cells and have been linked with EBV infection. Following are four major subtypes of PTLD: early lesions, monomorphic PTLD, polymorphic PTLD, and classical Hodgkin lymphoma (cHL) type PTLD. Early lesion PTLD generally develops within the first year of transplantation. Monomorphic PTLD is the most common subtype and corresponds to an aggressive B-cell lymphoma, e.g. DLBCL. Polymorphic PTLD generally affects children and can consist of either monoclonal or polyclonal lymphoma cells. The cHL type PTLD is rare subtype and mostly associated with EBV infection.

AIDS-Related NHLs

These are a group of lymphomas that affect individuals with AIDS. These mainly include systemic lymphoma (accounting for about 70% to 90%) and primary CNS lymphoma (PCNSL). Systemic lymphoma occurs mainly as BL or DLBCL. Plasmablastic lymphoma (PBL) and primary effusion lymphoma (PEL) are other lymphoma types that commonly affect HIV-infected individuals who are concomitantly infected with EBV and/or human herpesvirus 8 (HHV8). PBL mostly involves the jaw and oral cavity while PEL mostly involves pleural, pericardial, and abdominal cavities.

Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)

This is a group of aggressive subtypes of T-cell lymphomas that accounts for about 6% of all NHLs. PTCL-NOS generally affect lymph nodes but may be present as an extranodal manifestation involving the liver, bone marrow, GI tract, and skin.  PTCL-NOS cells are generally mature T-cells that harbor t(7;14), t(11;14), inv(14), and t(14;14) translocation leading to TCR gene rearrangement and a majority of cases possess certain characteristic cell surface proteins (CD4+ and CD8–).

Angioimmunoblastic T-cell lymphoma (AITL)

It is the second most common peripheral T-cell lymphoma that accounts for about 4% of all NHLs. AITL is generally associated with generalized lymphadenopathy, hepatomegaly or splenomegaly, eosinophilia, hypergammaglobulinemia, B symptoms, skin rash, and autoimmune disorder like polyarthritis, thyroid dysfunction, and hemolytic anemia. AITL cells are generally surrounded by EBV-infected B-cells and may progress to secondary B-cell lymphoma such as DLBCL. AITL cells express common T-cell surface antigens and are usually CD4+ with about 50% of cases featuring ten-eleven translocation 2 (TET2). 

Anaplastic large cell lymphoma (ALCL)

It is the third most common peripheral T-cell lymphoma accounting for about 2% of all NHLs. Following 3 are main subtypes of ALCL: ALK-positive systemic ALCL, ALK-1 negative systemic ALCL, and primary cutaneous ALCL. The ALK-positive subtype is most commonly reported and is usually associated with t(2;5) translocation leading to overexpression of the ALK-1 protein. ALK-positive subtype mostly reported in children and young adults. ALK+/- systemic ALCL is generally an aggressive lymphoma that affects lymph nodes or extranodal sites while primary cutaneous ALCL can be indolent with the disease in most cases restricted to the skin and cancer cells not showing the ALK rearrangement. One relatively different subtype of ALCL, breast implant-associated ALCL (BIA-ALCL) has been reported in patients with the textured-surface implant. Most patients have localized disease with breast enlargement, periprosthetic effusion, rash, lymphadenopathy, tumor mass, and skin ulceration. Almost all ALCL cells possess CD30 surface antigen (CD30+).

Enteropathy-associated T-cell lymphoma (EATL)

It is a rare type of T-cell lymphoma accounting for less than 1% of NHLs. EATL usually affect small intestine’s intraepithelial T-cells and commonly associated with Celiac disease (an autoimmune disease related to gluten-diet in which immune cells start attacking intestinal lining). Children who have been diagnosed and appropriately treated for celiac disease do not develop EATL. This is common in old age individuals especially men. EATL cells usually possess CD3 and CD103 cell surface antigens with intestinal lymphocytes possessing integrin.

Adult T-cell leukemia/lymphoma (ATLL)

ATLL is almost always associated with human T-cell lymphotropic virus type I (HTLV-1) infection and thus reported in geographical regions where this virus is endemic, for example, southern Japan, the Caribbean basin, western Africa, the Southeastern United States and northeast Iran. A long latency period is generally observed between the HTLV-1 infection and ATLL development. ATLL can affect the lymph nodes, spleen, liver, bone marrow, skin, and other organs. Following four subtypes of ATLL have been reported: Smoldering (indolent subtype with >/=5% abnormal T-cells in the blood); Chronic (indolent subtype with lymphocytosis and chances of disease progression to acute form); Acute (aggressive subtype with leukemic manifestations); and Lymphoma (less aggressive than acute with lymphoid manifestations). ATLL cells usually possess characteristic cell surface antigen (CD4+, CD2+, CD3+, CD5+, CD25+, CD7–).

Extranodal NK-/T-cell lymphoma (ENKL)

It a rare type of NHL that generally affect the upper respiratory tract with the extranodal presentation. It mostly involves NK-cells and virtually all cases are associated with EBV-infection. Clinical features include nasal obstruction, nasal bleeding, mucosal ulceration of the site, vascular invasion, and tissue necrosis. Common extranasal sites affected by ENKL include the skin, testis, intestine, lungs, and eyes, which are associated with poor prognosis. ENKL cells generally possess typical cell surface antigen (CD2+, surface CD3–/cytoplasmic CD3+, CD43+, CD56+, CD20–, CD4–, CD5–) with overexpression of p53 and/or TP53 mutations.

How do I know if I am at risk for Lymphoma? What are the causes of Lymphoma?

Different types of lymphoma generally have different risk factors along with some common factors that can predispose their development. Following is the list of such risk factors:

Age

Most NHL types are common among old-age individuals with an exception of a few types more common among youngsters.

Gender

Most NHL types are common in males compared to females with an exception of a few types more common in females.

Race and ethnicity

NHLs are most commonly reported in Caucasians compared to African Americans and Asian Americans, in the US.

Exposure to Radiation

Individuals with a history of exposure to radiation, for example, survivors of atomic bomb explosions and nuclear reactor accidents remain at high risk of developing NHLs.

Exposure to certain chemicals

Chronic exposure to certain chemicals like benzene, arsenic, chlorophenols, lead, vinyl chloride, asbestos, insecticides, and herbicides have been reported to elevate the risk of developing certain types of NHL. 

Geographical location

Some NHL types are restricted to certain geographical locations, for example, endemic Burkitt lymphoma (BL) that is usually observed in equatorial African children and Adult T-cell leukemia/lymphoma (ATLL) that is generally observed in southern Japan, the Caribbean basin, western Africa, the Southeastern United States and northeast Iran.

Infection

Risk of developing certain types of NHL is higher in individuals who have a history of infection with associated viruses or other pathogens. Following are some examples: 

• Epstein-Barr virus (EBV) infection is generally associated with the incidence of Burkitt lymphoma (BL) in African children, Angioimmunoblastic T-cell lymphoma (AITL), Extranodal NK-/T-cell lymphoma (ENKL), and post-transplantation lymphoproliferative disorder (PTLD). In conjunction with HIV, EBV infection may lead to the development of Plasmablastic lymphoma (PBL) and primary effusion lymphoma (PEL).
• Human T-cell lymphotropic virus (HTLV-1) infection has been linked with the development of Adult T-cell leukemia/lymphoma (ATLL) commonly observed in Japan and Caribbean region.
• Human herpesvirus 8 (HHV-8) infection increases the risk of PEL.
• HIV infection is usually associated with the development of primary CNS lymphoma (PCNSL), BL, and diffuse large B-cell lymphoma (DLBCL).
• Hepatitis C virus is usually associated with Lymphoplasmacytic lymphoma (LPL)/ Waldenström’s macroglobulinemia (WM) and splenic marginal zone lymphoma (MZL).
• Helicobacter pylori infection has been reported to cause mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach.
• Chlamydophila psittaci infection may result into MALT lymphoma in the tissues around the eye.
• Campylobacter jejuni infection may cause MALT lymphoma of the small intestine.
• Borrelia burgdorferi infection has been reported to be associated with the development of extranodal MZLs.

Weakened immune system

Individuals with a weak immune system that may be due to HIV infection, auto-immune disease, or medicines used to suppress the immune system in patients who have undergone an organ transplant are considered at higher risk of developing certain types of NHL, for example, PTLD, AIDS-Related NHLs, and DLBCL. Certain inherited immunodeficiency syndromes such as Wiskott-Aldrich syndrome, Chédiak-Higashi syndrome, X-linked lymphoproliferative syndrome, ataxia telangiectasia, and common variable immunodeficiency syndrome have been linked to increased incidences of aggressive lymphomas.

Family History

Individual with a history of NHL, HL, or chronic lymphocytic leukemia (CLL) in first-degree relatives (such as a parent or sibling) are considered to be at increased risk of developing NHL. The risk is particularly very high in individuals who have an identical twin who got the disease at a younger age.

Breast implants

Patients who had have breast implants with the textured surface are considered at an increased risk of developing breast implant-associated anaplastic large cell lymphoma (BIA-ALCL).

Body weight and diet have also been reported to play a role in the development of a few types of NHL. Obese people and individuals who consume fat-rich diet are generally at higher risk of developing some types of NHL.

What are the Symptoms and Signs of Lymphoma? How do I know if I have Lymphoma or not?

Following are some common signs and symptoms of lymphoma, which may help in early diagnosis if attended appropriately:

• Painless swelling of lymph nodes especially those in the neck, under the arm, or in the groin. Often these lymph nodes appear as a lump under the skin which gets bigger over time.
• Enlarged spleen and/or liver
• B Symptoms: Unexplained weight loss, Fever (>38 degree Celsius), and night sweats occur in many patients with NHL
• Fatigue and weakness attributable to anemia, other anemia-related symptoms may include shortness of breath and dizziness
• Loss of appetite
• Cough or chest pain mainly due to swollen lymph nodes in the chest pressing on the trachea
• Swelling in abdomen
• Headache, weakness in body parts, confusion, mood change, and seizures may appear when lymphoma affects the brain.
• Itching and other skin involvement signs may be visible in some NHL types mainly involving skin 

Besides above listed common symptoms, few other systems may appear depending upon the type of lymphoma and site of disease.

What is the Treatment for Lymphoma? Where can I get the best treatment for Lymphoma in Gurgaon?

Oncoexperts is a cancer clinic in Gurgaon for treatment for lymphoma from our team of cancer experts that include medical oncologists and radiation oncologists who are experts in treating all types of lymphoma.

Following is the brief description of various treatment types employed for lymphoma:

Chemotherapy

Chemotherapy is the mainstay of treatment for lymphoma. Chemotherapy means treatment with anti-cancer drugs that kill or decrease the growth of rapidly-growing cancer cells. Chemotherapy may be employed in combination with immunotherapy or radiation therapy for the management of lymphoma. Certain standard combination regimen involving multiple drugs are used for the treatment, for example, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), ABVD (Adriamycin, Bleomycin, Vinblastine, and Dacarbazine), and Stanford V (Adriamycin, Mechlorethamine, Vincristine, Vinblastine, Bleomycin, Etoposide, Prednisone). 

Radiation Therapy

Radiation therapy (or radiotherapy) uses high-energy x-rays or other high-energy radiations which are directed to the affected area to kill cancer cells. Radiotherapy is generally employed for the treatment of lymphoma, especially in case of disease limited to a part of the body. Involved-site radiation therapy (ISRT) may also be employed to treat a certain types of lymphoma, in which the radiation is targeted only at the affected lymph node(s). An external beam radiation therapy can sometimes be employed (along with high-dose chemotherapy) before SCT. 

Immunotherapy/Monoclonal Antibodies

Monoclonal antibodies are man-made antibodies which can be directed to certain protein characteristic of cancer cells. For the treatment of NHL, Rituximab (that targets CD20 protein on many types of NHL cells) is generally employed. These drugs help immune cells to destroy the cancer cells. Rituximab is generally employed for the treatment of NHL in combination with chemotherapy. For the treatment of HL, Brentuximab Vedotin (that targets CD30 protein on HL cells) and Rituximab (that targets CD20 protein on the HL/NLPHL cells) are generally employed. These drugs help immune cells to destroy the cancer cells. Brentuximab Vedotin is generally employed for the treatment of advanced-stage HL in combination with chemotherapy or to treat a refractory disease that is not responding to chemotherapy and radiation therapy.

Stem Cell Transplant (SCT)

SCT can be considered for some patients with lymphoma who are the good candidate for the same (younger patients in good health) and are not responding or have achieved a complete response to chemoimmunotherapy and/or radiotherapy. 

Following are major types of SCT techniques used for the treatment of NHL:

Autologous SCT

In this technique, the patient’s own stem cells are first collected from the healthy bone marrow tissue or peripheral blood (preferred nowadays). Then, the patient receives high-dose chemotherapy with or without radiation therapy to kill all the lymphoma cells. The collected stem cells are re-administered to the patient which slowly replenish the blood cells in the patient body.

Allogeneic SCT

In this technique, healthy stem cells to be administered to the patient after high dose chemotherapy are obtained from another person known as the donor. It is very important that donor is a close blood relative (preferably a sibling) so that donor cells (HLA type) closely match with the patient’s cell types.

Supportive Care

 Lymphoma treatment in gurgaon: Supportive care is a very important component of NHL therapy and may include management of infectious complications, use of myeloid growth factors or blood product transfusions, and management of tumor lysis syndrome. Re-activation of certain viral infections and new bacterial infections are common among NHL patients receiving treatment. Anti-viral and antibiotic treatment both prophylactic or with curative intent is generally employed in such cases. Additionally, patients may frequently require transfusion of blood products or growth factor treatment to maintain an appropriate count of normal blood cells. Treatment with chemotherapy and other anti-cancer agents causes NHL cells to die abruptly which trash their intracellular contents in the blood that may lead to tumor lysis syndrome characterized by sudden metabolic changes, loss of muscle control, cardiac arrhythmias, acute renal failure, seizures, and even death if not managed appropriately. The management of TLS mainly involve proper hydration and controlling hyperuricemia using allopurinol or rasburicase as first-line treatment.

Where can I find the best specialists for Lymphoma treatment in Gurgaon?

Dr. Sunny Garg is a renowned Medical Oncologist in Gurgaon with an experience of more than 10 years of treating lymphoma patients. He has treated lymphoma patients with Chemotherapy, Targeted Therapy and Personalized Cancer Treatment. He is currently practicing at Sanar International Hospital, Golf Course Road, Gurgaon.

Call Or WhatsApp +91 9686813020 For Appointment.