What do you know about different lymphomas?

Hello everyone.

I am again here with a new exciting blog. But before anything, I want to ask a question.

What is your favourite Blink 182 song? Mine are- Adam’s song and Always.

You might be wondering what am I asking out of the blue.

Well, the thing is. I have recently got to know about Mark Hoppus’s condition, who is the bassist of the band Blink 182. He has been diagnosed with lymphoma. It’s a deadly disease. Hence all of his fans are in shock.

That’s why! Today, we will learn about Lymphoma. We will find out the questions:

  • What is lymphoma?
  • How many types there are?
  • What are their symptoms?

Well then, let’s get going.

What is Lymphoma?

Lymphoma is a tumor of lymphatic system that arise from lymph nodes. Though, it can also be extranodal(outside lymph nodes) involving liver, skin or lungs etc.

Question for you: Q1. Do you know which is the biggest lymph node in the body?

A: It is spleen, a secondary lymphoid organ. Secondary lymphoid organs also includes peyer’s patches in small intestine(part of Mucosal associated lymphoid tissue/MALT) and tonsils(on your throat’s back) etc. These organs provide platform for lymphocytes to get in contact with antigens as these organs filter and traps them.

About: A1. Lymphocytes- A type of WBC that includes Natural killer(NK) cells, B cells and T cells.

Lymphoma is further divided into 2 types i.e. Hodgkin lymphoma(HL) and non-hodgkin lymphoma(NHL).

Before looking into each one separately, we should know common things between them. And that is, both show B symptoms. What is it you ask? These refers to unexplained fever, loss of weight(>10% of body weight) within 6 months and night sweats.

Now let’s continue on discussion. First about HL, then we will jump into NHL which our rockstar has been diagnosed with.

Hodgkin lymphoma-

  • This spreads from node to node via lymphatic vessels(see A3).( vs NHL, where it also spreads through blood, hence gets into extranodal tissues.)
  • Has better prognosis.
  • Epidemiology: Mostly occurs in young-adult(15 to 30 years old) and >55 years old i.e. bimodal age distribution. Whereas NHL can occurs either in children or adults.
  • Characterized by Reed-Sternberg(RS) cells.

About: A2. RS cells- These are giant tumor cells that are binucleated or multinucleated. These are also referred to as ‘Owl eyes‘. They are normally originated from B cell but unlike them, their cell markers(proteins or carbohydrates that are attached to cellular membrane and specifically expressed by specific cells for intercellular signalling) are CD15 and CD30 where B cell markers are CD19 or those cells that are in the line of CD20s.

A3. Lymphatic vessels- Or lymph vessels. Carries lymph. It is a clear fluid which is formed by fluid drained from cells and tissues. It contains WBCs (lymphocytes mainly) that kill bacteria and carries proteins, fats from intestine.

HL subtypes-

  1. Nodular sclerosis(NSCHL)- Most common HL. More common in females than in males unlike other HL. Curable but challenging.
  2. Mixed cellularity(MCCHL)- 2nd most common. Seen in males more that are immunosuppressed. Eg, patients of AIDS. Almost same prognosis as NSCHL.
  3. Lymphocyte rich(LRCHL)- 3rd most common. Best prognosis.
  4. Lymphocyte depleted(LDCHL)- Least common among all classical HL.  Twice common in men than in women. Also seen in immunocompromisd patients. Poor prognosis.

NHL types: These are divided into neoplasms of T and B cells.

T cell neoplasms: Adult T-cell lymphoma and Mycosis fungoides.

Before jumping ahead, first we should know about Human T-cell lymphotropic virus(HTLV).

HTLV:

  • These are retroviruses that are grouped HTLV-1 to 4.
  • Transmitted primarily by sexual contacts or mother to child, also by blood transfusion and by contaminated needles.

Here, we will talk mainly about HTLV-1.

  • This group is mainly endemic to Japan, South Africa and Caribbean.
  • It causes 2 distinct diseases i.e. demyelinating disease known as by HTLV-1 Associated Myelopathy(HAM)/Tropical Spastic Paralysis(TSP) and Adult T-cell lymphoma-leukemia(ATL).

HAM/TSP- In this, destruction of neuronal myelin sheath occurs, making it challenging to conduct signals through the damaged area. Here, it happens in spinal cord(SC), causing paraperesis, difficulty in moving your legs and weakness.

About: A4. Retrovirus- Virus that uses RNA as genetic material. After infecting cell, by reverse transcriptase enzyme it makes its own DNA that incorporates into host cell’s DNA and directs it to form viral DNA particles.

A5. Myelin sheath- Covering of nerves that is made of lipids and proteins. Form by Schwann cells in Peripheral Nervous System(PNS, consisting nerves) and by Oligodendrocytes in Central Nervous System(CNS, consisting brain and spinal cord). Provides insulation i.e. electrical impulses can’t travel continuously through the axon, a part of neuron. Impulses jump between nodes of ranvier(myelin sheath gaps) making conduction faster. This conduction is called Saltatory conduction.           

Now, let’s move onto T-cell neoplasms.

  • Adult T-cell lymphoma-leukemia(ATL):
    • Rare and aggressive T cell lymphoma, found in blood(leukemia), lymph nodes(lymphoma) or/and skin.
    • Caused by HTLV-1(by IntraVenous drug abuse).
    • Aggressive and poor prognosis.
    • Epidemiology- Endemic to Japan, Caribbean, South America and some parts of Africa.
    • Adults(around 60 years old) are presented with cutaneous lesions(ulcer and rash) and hypercalcemia (calcium is increased in blood because of bone resorption by osteoclasts).
  • Mycosis fungoides:
    • Rare but more common than ATL.
    • Indolent and chronic disease of skin and plaques i.e. cutaneous T-cell lymphoma.
    • Identified by sezary cells(A6) and pautrier microabscess(A7).
    • May progress to sezary syndrome(T-cell leukemia), when sezary cells also appear in blood i.e. diffused system involvement.

About: A6. Sezary cells- Cancerous T-cells( atypical  CD4+) with cerebriform nuclei when occurs in blood called as sezary cells.

A7. Pautrier Microabscess- Intraepidermal atypical CD4+ cells aggregate.

B-cell neoplasms(these are more common than T-cell neoplasms): Types:

  • Diffuse large B-cell lymphoma(DLBCL):
    • Most common type of NHL in adults.
    • Epidemiology: Occurs in adults(usually around 60 years old) more than in children.
    • There is mutation in BCL-2(chromosome 18q21) and BCL-6(chromosome 3q27) gene.
    • BCL-2 protein, located on outer mitochondrial membrane, prevents apoptosis of B-cell(induced by BAX gene/protein as they bind mitochondrial membrane inducing release of cyt C causing apoptosis) during their normal growth and development.
    • BCL-6 protein is a transcriptional repressor, hence regulates B-cell growth.

To know more about BCL-2 and BCL-6, you can see this article.

This is the one, Mark hoppus has been diagnosed with. He is in stage IV. We will walk into more details now.

DLBCL Stage I- Only one region(lymph node or any lymphoid structure) is involved.

Stage II- Two or more lymph nodes or structures are involved on the same side of body.

Stage III- Both sides are affected.

Stage IV- Extranodal structures are involved like liver, lungs or bone marrow.

Treatment: Commonly used treatment is chemotherapy(drugs inhibiting cancer cell growth), that can be used along radiotherapy( high energy radiation like X-rays to kill cancer cells) and immunotherapy(immune system fights cancer cells).

As chemotherapy is main treatment for DLBCL, we will talk more about it.

  • The regimen for chemotherapy is CHOP i.e. Cyclophosphamide, Hydroxydaunorubicin, Vincristine, Prednisone.
  • But generally, it is called R-CHOP where R is Rituximab(monoclonal antibody(A8) actually an immunotherapy).
  • For early stage, patients are exposed for 3 to 6 cycles after every 3 weeks.
  • For advanced stage, 6 to 8 cycles are needed every 3 weeks.

About: A8. Monoclonal Antibody- These are proteins that copy our immune system to kill target cells. Here, rituximab targets B-cells by inducing numerous means, like complement dependent and antibody dependent cell mediated cytotoxicity. It complements chemotherapy by making more cancer cells sensitive to drugs. Note: Rituximab is contraindicated in heart problems as it produces arrhythmic symptoms and angina(chest pain).

  • Burkitt lymphoma:
    • Epidemiology: Endemic to Africa. Adolescents or young adults.
    • Forms mandible mass.
    • Involving t(8;14)- translocation of c-myc(on chromosome 8, see A9) and heavy-chain of Ig(14).
    • Associated with Epstein-Barr virus(EBV). It impedes apoptosis in B-cells.
    • Identified by ‘Starry sky’ appearance. It is distributed tangible body macrophages (Mphage contain apoptic debris of tumor cells).

About: A9. Myc gene- Family of regulatory genes that code for transcription factors. It has 3 genes i.e. c-myc, i-myc and n-myc.

  • Mantle cell lymphoma(MCL):
    • Epidemiology: Adults. More in males.
    • Poor prognosis, aggressive.
    • t(11;14)– translocation of cyclin D1(chromosome 11, see A10) and Heavy Chain Ig(chromosome 14).

About: A10. Cyclin D1- Regulates cell cycle transition from G1 phase to S phase with cyclin dependent kinases(CDK4 and CDK6). After mutation, overexpression occurs causing rapid growth. Cyclin D1 is a useful marker of MCL.

  • Marginal zone lymphoma(MZL):
    • Epidemiology: Adults.
    • Seen in patients with chronic conditions like Sjogren syndrome(see A11) and MALT lymphoma(see A12).
    • Associated with t(11;18) of apoptosis inhibitor gene on chromosome 11 and MALT1 gene on chromosome 18. However, MALT lymphoma(see A12) is rarely involved with such translocation.

About: A11. Sjogren syndrome- Most common symptoms- Dry eyes and mouth.

  • Autoimmune disorder where body’s immune attacks the body itself.
  • First mucous membranes in lacrimal(tear) gland and salivary gland are affected, then joints and organs like kidney, liver or lungs are targeted.
  • Treatment- Can’t be cured fully. Only underlying symptoms can be improved.

A12. MALT lymphoma- Most common symptoms- Long lasting indigestion and abdominal pain.

  • Indolent and most common type of MZL.
  • MALT lymphoma is associated with Heliobacter pylori(gram negative bacteria in stomach mainly causing ulcer and gastritis) and Hashimoto thyroiditis (autoimmune disease destroying thyroid gland, leads to underactive thyroid gland causing hypothyroidism. Sometimes it causes hyperthyroidism because of leaking of thyroid hormones).
  • Treatment- Almost same treatment as for other cancers like using radiotherapy, chemotherapy. Antibiotics are used if associated with H pylori.
  • Follicular lymphoma:
    • Epidemiology: Adults, principally in their 60s.
    • Accounts around ¼ of all NHL.
    • Highly associated with translocation of gene of heavy chain of Ig(14) and BCL-2(18) i.e. t(14;18).
    • Painless lymphadenopathy in nodes which are close to body surface(neck, groin and armpits). Actually it is a non-specific as it is also seen in other lymphoma.
  • Primary CNS lymphoma:
    • Epidemilogy: Rare, primarily in immunocompromised adults.
    • Caused by EBV virus in AIDS patients. T-cells in these patients are less likely to counter EBV.
    • Neurological symptoms like confusion, seizures, headaches, memory loss etc.
    • Single nodular enhancing lesion(A13) is seen on MRI.

About: A13. Ring enhancing lesion- By using radiocontrast medium(drugs that enhance the distinctness of internal structures in imaging techniques), a peculiar lesion is seen, indicating brain tumor, metastasis and infections by HIV or toxoplasmosis.

Question for you: Q2. Who is the primary host of toxoplasma gondii?

A: Cats are primary host of Toxoplasma gondii, where they excrete their oocysts in the environment. From there, during cleaning cat litter, one can get infected or oocysts enter into other animal which is consumed by humans later without cooking properly.

All these lymphomas, whether Hodgkin or not, are treated with chemotherapy mainly, which could be or could be not followed by radiation or immunotherapy.

Hope, you have found many things interesting and have gotten your some questions cleared. For your curiosity, Mark Hoppus’s chemotherapy is going well enough. Recent news are informing about improvement in his condition. Which is a great news! But as I mentioned, there is a long journey ahead of him.

If you have any query, you can ask me anytime by commenting below. Later.

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