Lymphomas In The Bone

Introduction

It is defined as a classification of blood cancer which affects the lymphatic system of the human body, the vital part of the immune system whose mechanism involves the production and transportation of WBC around the body. It also involves in the result of removal of waste products from individuals.¹ 

Rarity and significance of primary lymphoma of bone (PLB)

Primary Lymphoma of bone was earlier termed a reticulum cell sarcoma.³ Primary lymphoma of the bone is very uncommon. It represents a mere 5% of primary bone tumours and makes up around 3-15% of all non-Hodgkin's lymphoma that occurs outside of the lymph nodes. Those cancer cells who produce in the different parts of the body and metastasize towards the bone are very common than the cancer cell who induce in the bone. 

Patients who are diagnosed with primary lymphoma of bone can be found in the stage where more than one bone has been damaged. The initial indication of primary lymphoma of bone as a diagnosis was proposed by Oberling in 1928. However, it was in 1939 that Parker and Jackson confirmed this condition as a distinct entity, reporting a total of 17 cases.

These lesions can happen in any part of the body however it has been often observed in bones with red bone marrow, Such as Flat bones – found in the pelvis, spine and ribs and Long bones – found in the femur and humerus. This disease can happen at any age but most of the time it is diagnosed in people whose age is above 30 years and also found more in Men than Women.²

Symptoms and diagnostic methods

Symptoms of lymphoma can be differentiated as per the type of the lymphoma and located at which part of the body. Below is the list of the most common symptoms however, it does not mean that these define as lymphoma.

The common symptoms are:

• Swollen lymph nodes, typically known as swollen glands under the area such as armpits
• Fatigue
• sudden weight loss
• itching
• temperature
• abdominal pain etc⁴

There are different types of diagnostic tests for lymphomas. They are Blood tests, PET AND CT scans, MRI scans, ultrasound scans and X-rays, Biopsy, Bone Marrow Biopsy, and Lumbar Puncture. 

Types of lymphomas in the bone

Non-hodgkin lymphoma

Non-Hodgkin lymphoma is a form of blood cancer that impacts lymphocytes, a type of white blood cell crucial for the immune system's functioning. Their types depend upon the cells that are treated and how the cancer functions.⁵ Non-Hodgkin lymphoma encompasses all lymphomas that lack Reed-Sternberg cells, which are specific and large abnormal cells observed exclusively in the blood samples of individuals with Hodgkin lymphoma.¹ 

The particular sub-types of non-Hodgkin Lymphoma are: 

• Diffuse large B cell lymphoma
• Follicular lymphoma
• Burkitt lymphoma
• Waldenstrom macroglobulinaemia

Symptoms of non – hodgkin lymphoma

One prevalent indication of non-Hodgkin lymphoma is the presence of lumps, which are enlarged lymph nodes. These painless swellings can occur in various parts of the body such as the neck, collarbone, armpit, groin, and other regions.

In certain cases, swollen lymph nodes can exert pressure on organs, resulting in chest pain, coughing, difficulty breathing, or discomfort in the abdominal region. Some of the other symptoms are fever, undefined weight loss and night sweating.⁵

Hodgkin lymphoma

It is an uncommon cancer which evolves in the lymphatic system made up of networks of vessels and glands that are distributed throughout the body.⁸ While Hodgkin lymphoma can occur in children of any age, it is more frequently observed in older teenagers and young adults. In the United Kingdom, approximately 70 children aged 0-14 years, 120 young individuals aged 15-19 years, and 180 young individuals aged 20-24 years are diagnosed with Hodgkin lymphoma each year.⁹

Two main types of Hodgkin Lymphoma are

• Classical Hodgkin Lymphoma, which infects 95% of the populations
• Lymphocyte Predominant Hodgkin Lymphoma (LPHL), which is rare and found to only infected to 5% of the population

LPHL is found to proliferate slowly compare to classical Hodgkin Lymphoma and does not require in-depth treatment. Younger people are found to have a single swollen gland or multiple swollen glands in a particular area like the neck. Sometimes it takes month to develop and present before proceeding to further biopsy and therapies.⁹ 

Primary vs. secondary bone lymphomas

Primary bone lymphomas

It refers to the lymphoma which affects the skeletal tissue of the body. Nevertheless, skeletal tissues are reacted because of the non-Hodgkin’s lymphoma, it is rarely observed for the primary and exclusive involvement of the skeletal system. PBL is believed to occur in approximately 3-7% of all primary bone tumours and in less than 2% of all lymphomas in adults. 

Secondary bone lymphomas

It refers to the lymphoma which affects the bones and represents the nodal diseases which occur within 6 months or the duration of the 6 months after having the initial diagnosis. The involvement of bones can be present through the direct spread of nodal disease or hematogenous metastases. Particularly, the spine of the axial skeleton seems to be more affected with respect to the appendicular skeleton. 

Common subtypes of lymphomas affecting the bone

Diffuse large B cell lymphoma

DLBCL is a type of Non-Hodgkin Lymphoma typically it is a cancer of the Lymphatic system. This disease develops when the body produces a large number of abnormal B lymphocytes. When an individual is diagnosed with lymphoma, it has been observed that the treatments should be started as soon as possible as DLBCL produces spontaneously.⁷

Follicular lymphoma

It is the second most common form of Non – Hodgkin Lymphoma, which develops when the WBC undergo abnormal growth which results in an increasing number of cells and producing clusters which are commonly called as follicles inside the lymph nodes. These follicles react into painless swellings and are located in the lymph glands such as the neck, armpits and groin.⁶

Burkitt lymphoma

It is an uncommon type of rapidly growing NHL. It evolves when B-cells show abnormalities in their functions. Mostly the causes of this disease are unknown, but sometimes it shows the expression which causes the glandular fever virus called Epstein Bar virus. However, it does not always cause the development of lymphomas.¹²

Mantle Cell Lymphoma

It is a less common and aggressive in nature type of NHL produce from cells originating in the mantle zone, which define as the outer ring of smaller lymphocytes surrounded by the core of a lymphatic module.¹³

Lymphoblastic lymphoma

It is an NHL which specifically targets the immature lymphocytes, commonly called lymphoblasts which are the important cells of the immune system. This type of disease mostly affects children. Further, it has been observed that 35% of cases of NHL are observed in children than in adults.¹⁴

Marginal zone lymphoma

It is also the type of cancer which affects the lymphatic system of the body made up of network of the lymphnodes, organs and other structure that builds the part of the immune system. It works similarly like the transportation of blood done by the blood vessels, lymphatic system involves in the transportation of the lymph which is fluid in nature that fight against the diseases cell.¹⁵

Etiology and risk factors

Risk factors and predispositions

The exact source for this disease is still not defined but some of the factors which stimulate increasing the chances of getting lymphoma are¹⁶

• Relationship with someone having diagnosed with lymphoma
• Encounter with chemicals like benzene
• Paget’s disease disturbed the process of bone recycling
• AIDS or Viral infection
• Individuals over 60 yrs old

Causes of lymphoma

In numerous cases of gastric, MALT lymphoma is triggered by a bacterial infection called Helicobacter Pylori. Mostly, the bacteria is responsible for stomach ulcers and indigestion however, it can be effectively managed. Individuals suffering from this bacterial infection do not possess lymphoma but people who are diagnosed with MALT lymphoma can have this bacterial infection. By treating this infection, they tend to cure the lymphomas and this makes the one of the reasons for causing lymphoma with bacterial infection.

Another reason causing lymphoma is BIA-ALCL – breast implant-associated anaplastic large cell lymphoma, which occurs as a result of having textured breast implants and eventually concluded as a lymphoma instead of breast cancer. Developing BIA-ALCL is higher for people having implants with a rough, textured surface in comparison to smooth implants. 

Researchers identify the reason as being an inflammatory reaction to the implant. After the implantation, it usually takes 8 to 10 years, although it can occur sooner or later. Mostly, people with breast implants do not fall for BIA-ALCL. However, the population developing BIA-ALCL has been observed with the condition of breast implants. In many instances, the removal of the breast implants effectively cures the lymphoma. Consequently, breast implants are not just a risk factor but a causative factor in this regard.⁴

Diagnostic methods and procedures

• Medical History and Examination – The GP will examine patient's medical history which includes symptoms or other risk factors and perform some tests to investigate the signs of lymphoma
• Imaging test – it helps to visualise the bone and identify the abnormal activities of cell that suggest the signs of lymphoma
• CT scan – it can establish detailed information of the cross-sectional images of bone which leads to the detection of lymphoma-related irregularities
• MRI – magnetic resonance imaging – It helps to produce detailed images of the bones and surrounding tissues with the help of strong magnets and radio waves
• PET – Positron Emission Tomography – It involves the use of injection of a radioactive tracer that explains the particular area with active lymphoma cells in the bones
• Biopsy – it serves as the definite diagnostic procedure. It works by extracting the sample of bone tissue to examine under a microscope. It can involve multiple methods such as
  • Core Needle Biopsy – Needle is used to extract a small tissue of the bone for testing
  • Surgical Biopsy – It involves the removal of a large piece of bone tissue for analysis

Treatment approaches

Multidisciplinary treatment approach

Treatment for lymphomas is generally based on the factors such as types of lymphomas, their location and the growing stages.

Active monitoring treatment – end up having regular checkups and GP will monitor the health to observe the lymphoma effects on the health. This is the watch and wait treatment where treatment can only be done under the difficult symptoms affecting the patients. 

Chemotherapy regimens

Chemotherapy – The mechanism of chemotherapy is to destroy the cancerous lymphoma cells. Most of the time, chemotherapy is used as a treatment because lymphomas can be easily killed by cytotoxic drugs. These drugs help in preventing lymphoma which help to cure the patients.

Chemotherapy can been given orally, through an injection into a vein called intravenous chemotherapy, intrathecally meaning injected on the surface of brain or spinal cord. 

Role of radiation therapy

Radiotherapy – This treatment involves the use of radiation to prevent the spread of cancerous cells. It has been divided into two types of treatment:

• Curative treatment- This means completely eliminating lymphomas from the body. It usually works at the early stage of diseases
• Palliative treatment – which means regulating the symptoms for the betterment of life which helps in reducing the pain and gives relief from the complications in the day to day activities
• Local disease control – Radiotherapy is more effective when it is treated in a particular location such as lymph nodes or other regions of the bones
• Combined treatment approach – Radiotherapy can also be used with other therapies like immunotherapy or chemotherapy to get the appropriate outcomes. However, multiple approaches are often used at the advanced stage of lymphomas 

Potential role of surgery

Surgery is rarely used to treat lymphoma diseases because other therapies such as chemotherapy and immunotherapy or radiotherapy, are much more effective and feasible. 

However, the important role of surgery is when an individual needs to remove the lymph node for testing as well as to prevent diseases from a particular organ such as the stomach or the small bowel. It also plays an important role in the removal of the spleen in a splenic marginal zone lymphoma, which is an uncommon disease.⁷

Long-term effects and complications

Some side effects of the lymphoma treatments are⁷

• Bowel problems – These problems can lead to in diarrhoea, constipation and flatulence
• Chemo brain – It triggers changes in the thinking process such as memory loss, and concentration or involve the brain the complex thinking process. For instance, taking time to react to things
• Dry sore and itchy skin – It creates skin problems like eczema or psoriasis
• Peripheral Neuropathy – It can damage the peripheral nervous system

Summary

Lymphoma of the bone is a type of cancer that affects the cells of the bones and target the lymphatic system. It is subdivided into two types, Non-Hodgkin and Hodgkin lymphoma and is mostly observed in adults than in children. 

There are some of the common symptoms which include fever, weight loss, temperature fractures, swellings and nausea. There are different types of therapies which are used to cure the diseases like immunotherapy, chemotherapy and Radiotherapy. 

Mostly, chemotherapy is used to treat the disease. Apart from having multiple therapies, there are also some side effects of the therapies, such as memory loss, skin problems, spinal issues and many more. To handle the treatment, follow-ups and regular observations are necessary. Further, steps should be taken to manage treated-related side effects.