What are the other Names for this Condition? (Also known as/Synonyms)

• Lennert’s Lymphoma
• Lymphoepithelioid Lymphoma
• Lymphoepithelioid Variant of Peripheral T-Cell Lymphoma

What is Lennert Lymphoma? (Definition/Background Information)

• Lennert Lymphoma is a rare type of non-Hodgkin lymphoma that is a variant of peripheral T-cell lymphoma. It is also known as Lymphoepithelioid Lymphoma
• The peripheral T-cell lymphoma (or PTCL) is a type of nodal or soft tissue lymphoma, which are generally restricted to lymph nodes and do not enter the bloodstream until later stages of the disease
• In many cases, Lennert Lymphoma may be confused with classical Hodgkin lymphoma, and hence, special studies such as immunohistochemical stains and molecular studies may be necessary to arrive at a diagnosis. A diagnosis of Lennert Lymphoma is typically made based upon the histological features (i.e., how the lymphoma appears under a microscope when examined by a pathologist)
• Lennert Lymphoma typically affects the lymph nodes of the body. It can later involve or spread to other parts of the body. The general signs and symptoms of the condition may include high fever, weight loss, fatigue, and anemia. Bone marrow involvement is commonly seen with Lennert Lymphoma
• Chemotherapy using a combination of drugs forms part of the treatment measures due to systemic (whole body) involvement of the cancer. The treatment of Lennert Lymphoma also depends upon the stage of the condition and the organs involved
• The prognosis depends on many factors including the stage of lymphoma, progression of the condition, response to treatment, and overall health of the individual. In general, the prognosis of Lennert Lymphoma is poor despite treatment

General information on lymphoma and lymphocytes:

• Lymphoma is a type of cancer stemming from uncontrollably dividing lymphocytes (type of white blood cells). There are two types of lymphomas:
  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma
• Lymphocytes are the main white blood cells found in the lymph, which is the fluid of the lymphatic system; just as blood is the fluid of the circulatory system
• Lymphocytes are made in bone marrow, and can develop into either B-cells or T-cells. Lennert Lymphoma arises from cancerous T-cells
• Lymph results from filtration of blood as it travels to and from tissues. Lymph is colorless because it lacks red blood cells; instead, it contains lymphocytes. It is central to the immune system
• There are 3 different kinds of lymphocytes:
  • T-lymphocytes or T cells: They help combat infections and abnormalities within the cells (cell-mediated immunity). They fight viruses and cancerous cells
  • B-lymphocytes or B cells: They produce antibodies that are bodily defense proteins, which target foreign invaders outside the cells (humoral immunity). They fight bacterial cells, cell fragments, and other immunogenic elements
  • Natural killer cells or NK cells: They perform diverse functions related to both cell-mediated and humoral immunity. They also scout for cancer cells, a process called immune surveillance

Who gets Lennert Lymphoma? (Age and Sex Distribution)

• Lennert Lymphoma is a rare condition that typically affects older individuals
• Adults in the 20-90 years age range are at risk; the median age of diagnosis is 60 years
• Both males and females are likely to develop the condition
• All racial and ethnic groups may be affected and no specific preference to any race or ethnicity is seen

What are the Risk Factors for Lennert Lymphoma? (Predisposing Factors)

The risk factors associated with Lennert Lymphoma may include:

• Epstein-Barr virus infection
• Exposure to chemicals, such as pesticides and fertilizers, as well as smoking and diet, has been suggested as links to other forms of non-Hodgkin lymphoma.

The International Prognostic Index, for aggressive non-Hodgkin Lymphoma, lists a few factors that determine the overall risk:

• Age over 60 years
• Elevated level of serum lactate dehydrogenase - LDH (a type of enzyme)
• Performance status, i.e. the overall health condition of the individual, which could range from being fully active (low risk) to being completely disabled (very high risk) 
• Individual, who have already suffered from lymphoma, or other types of blood cancers, may have a relapse or a recurrence
• Presence of an immunodeficiency syndrome, like AIDS, is a high risk factor
• Those infected with Epstein-Barr virus

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Lennert Lymphoma? (Etiology)

• The exact cause of Lennert Lymphoma is not completely known or understood
• It may be caused by certain genetic defects, such as translocation, which is a juxtaposition of regions of chromosomes that may result in:
  • Change of regulatory elements of certain cancer-causing genes called as oncogenes, which can lead to increased production of their mRNA (overexpression), thus increasing their protein levels
  • Exchange of protein coding regions of gene, giving rise to new proteins that can stimulate the inappropriate growth of cells

It is believed that the abnormal development of lymphocytes gives rise to cancerous cells leading to the formation of this condition. Nevertheless, how this occurs and the factors that cause it remain under investigation.

What are the Signs and Symptoms of Lennert Lymphoma?

The signs and symptoms of Lennert Lymphoma may include:

• Non-painful swelling of lymph nodes; the lymph nodes all over the body may be involved
• Fatigue
• Fever, high temperatures
• Excessive night sweats
• Weight loss, loss of appetite
• Anemia (low red blood cell count)
• 10% cases have skin involvement
• In many, bone marrow involvement is seen

Lennert Lymphoma is a systemic condition affecting various organs of the body. In such cases, specific signs and symptoms of the lymphoma involving the different organs or body systems may be manifested.

How is Lennert Lymphoma Diagnosed?

It often takes multiple tests and procedures to diagnose a lymphoma. It is important that the specific type of lymphoma be diagnosed correctly, in order to accommodate a proper treatment plan. The diagnosis of Lennert’s Lymphoma involves:

• A physical examination by a doctor can help determine, if symptoms like lymph node swelling, are likely caused by an infection, or if there is a risk of lymphoma
• Blood tests that may include:
  • Complete blood cell count (CBC) blood test
  • Absolute lymphocyte count on peripheral blood
  • Liver function blood test (LFT)
  • Lactate dehydrogenase (LDH) blood test
• Since the lymphoma involves the lymph nodes, biopsies of enlarged lymph nodes are taken and examined in a lab to determine if the cells are malignant or benign. The biopsies may be performed under general or local anesthesia. Normally, the entire lymph node is removed to help determine the subtype of lymphoma
• Tissue biopsy from the affected area:
  • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis
• Radiological imaging may be performed to determine the extent of lymphoma in the body including:
  • X-ray of the affected region
  • Ultrasound scan of the affected region
  • Computerized tomography (CT) scan of the affected region
  • Vascular radiological studies
  • Whole body bone scan
  • Whole body CT-PET scans to determine how far the lymphoma has spread, by checking the size and metabolic rate (a reflection of uncontrolled growth) of lymph nodes, throughout the body. This can also help determine, if the cancer has spread to other organ systems
  • Brain MRIs are used if neurological symptoms are present, which can help determine if the cancer has spread to the brain, or to tissues that cover the brain
• T-cell receptor gene rearrangement
• Bone marrow aspiration and biopsy is performed and sent to a laboratory for a pathological examination, to determine if the bone marrow is involved. Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, histochemical stains, molecular testing, and very rarely electron microscopic studies. However, a bone marrow biopsy is not needed in the early stages of the condition
• Flow cytometry to identify cells as they flow through an instrument, called a flow cytometer. Flow cytometry measures the number and percentage of cells in a blood sample, and cell characteristics such as size, shape, and the presence of biomarkers on the cell surface. This method helps to sub-classify leukemias and also to detect residual levels of disease after treatment. This tool can help in diagnosing relapse and restart treatment as needed
• Fluorescence in situ hybridization (FISH): It is a test performed on the blood or bone marrow cells to detect chromosome changes (cytogenetic analysis) in blood cancer cells. The test helps in identifying genetic abnormalities that may not be evident with an examination of cells under a microscope
• Immunophenotyping to identify a specific type of cell in a sample, which can help determine the best treatment course to be followed
• Polymerase chain reaction (PCR): It is used to measure the presence of certain biomarkers in blood or bone marrow cells. The test is ultrasensitive and detects extremely low amounts of biomarkers remaining in blood, which can be missed by cytogenetic methods, such as FISH, karyotype, or flow cytometry. PCR allows a more sensitive follow-up of patients in remission and can help determine whether additional treatment is necessary
• GI endoscopy: It may be performed to assess the extent of tumor spread
• Multigated acquisition (MUGA) scan or echocardiography to identify cardiotoxicity as a result of chemotherapy
• Lumbar puncture to determine if the brain is involved
• In addition, the cerebrospinal spinal fluid (CSF) may be collected by inserting a needle in the spine and subjected to microscopic, flow cytometric, PCR, and biochemical analysis, to diagnose central nervous system (CNS) involvement, if any
• Exploratory laparoscopy (diagnostic laparoscopy) may be required, if gastrointestinal symptoms are present. In this procedure, the abdomen is examined using a minimally-invasive technique, and a tissue biopsy and tissue for culture obtained. Minimally-invasive approaches help decrease complications and the length of stay at the hospital. A diagnostic laparoscopy is also helpful in staging of the tumor. Nevertheless, this procedure is not very much used

Note:

• In this lymphoma, in addition to the malignant lymphocytes, there are abundant epithelioid histiocytes present in the background. Epithelioid histiocytes are a type of inflammatory cells
• Differential diagnoses, to eliminate other tumor types are often considered, before arriving at a definitive diagnosis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Lennert Lymphoma?

The possible complications from Lennert Lymphoma include:

• Involvement of local and distant organs: It can spread from the lymph nodes to other parts of the body, resulting in the loss of function of the organ/area to which the cancer has spread
• Recurrence of the lymphoma

There may be complications related to chemotherapy used in treating the condition, which may include:

• Side effects such as dizziness, vomiting, appetite loss, mouth ulcers, and hair loss
• By damaging healthy cells, the individual is more open or vulnerable to secondary infections
• The treatment can also cause infertility in men and women. Hence, measures to protect the individual’s fertility must be considered, before starting chemotherapy
• Tumor lysis syndrome: This can occur due to chemotherapy treatment and can result in kidney failure, if not recognized promptly

How is Lennert Lymphoma Treated?

Once a definitive diagnosis of Lennert Lymphoma has been made, staging is used to describe how far the cancer has spread. The stage can describe:

• How many lymph nodes are affected
• Their locations in the body
• And, if other organs are being affected

Staging is important because different treatment regimens are necessary, depending on the progression of the lymphoma.

• Stage 1: Only one group of lymph nodes in one location is affected
• Stage 2: Lymph nodes in multiple locations that are all above or below the diaphragm are affected
• Stage 3: Lymph nodes in multiple locations, both above and below the diaphragm are affected
• Stage 4:  Lymph nodes located throughout the body, the bone marrow, and other organs are affected

A combination of treatments is used to most effectively treat this cancer. The aggressiveness of the treatment is determined by the disease stage.

Surgery: After initial biopsies to diagnose the condition, surgery is a very uncommon treatment option, because lymphomas are systemic and have already spread to more than one lymph node in most patients. Removing all affected lymph nodes would be extremely difficult.

Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used for patients, at all stages of Lennert Lymphoma.

• Commonly, the drug combination CHOP is used first, which includes doxorubicin, vincristine, cyclophosphamide, and prednisolone
• There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
• Many T-cell lymphomas can be resistant to chemotherapy. It can also damage healthy cells
• Chemotherapy can be administered as a pill, liquid, shot, or intravenously

Radiation: Radiation therapy is the use of high-energy radiation waves, to kill cancer cells by destroying their DNA.

• This treatment modality is generally used for early stage lymphomas. It is most commonly used in combination with chemotherapy
• The radiation may be administered by a machine placed outside the body, or by putting a radioactive material inside the body
• The side effects of radiation therapy include nausea, vomiting, fatigue, pain, risk of cancer later in life, and a risk of heart disease
• Radiation can damage healthy cells in addition to cancer cells, causing further complications

Stem cell support: In combination with chemotherapy, blood stem cells can be taken from a patient before treatment and administered to them, later during the treatment, in order to help restore blood cells killed by chemotherapy. This treatment can have severe side effects; hence, it is not administered to all patients.

Clinical trials: There are some new treatment options, currently on clinical trials that can be considered for some patients, depending on their risk factors.

How can Lennert Lymphoma be Prevented?

• Currently, there are no definitive ways to prevent Lennert Lymphoma
• However, healthy diet and exercise, as well as avoidance of unnecessary exposure to chemicals, may help decrease its risk
• Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory for those who have already endured the tumor, due to its metastasizing potential and possibility of recurrence. Often several years of active vigilance is necessary

What is the Prognosis of Lennert Lymphoma? (Outcomes/Resolutions)

• Lennert Lymphoma is an aggressive form of T-cell lymphoma with a generally poor prognosis
• The tumors do not respond well to chemotherapy and the average survival period following diagnosis is 16 months
• Besides, studies have indicated that almost 70% of the cases are diagnosed at stages 3 and 4 (higher or advanced stages). This can make the prognosis even worse
• Typically, the prognosis depends upon a set of several factors, which include:
  • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
  • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
  • Individuals with bulky disease have a poorer prognosis
  • Involvement of vital organs may complicate the condition
  • The surgical respectability of the tumor (meaning, if the tumor can be removed completely) - it is a rare option
  • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
  • Progression of the condition makes the outcome worse (progressive Lennert Lymphoma)
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor
• Progression to bone marrow failure is usually associated with short survival; most cases of Lennert Lymphoma are associated with bone marrow involvement

Additional and Relevant Useful Information for Lennert Lymphoma:

Initially, Lennert Lymphomas were thought to be a special type of Hodgkin lymphoma; however, research has now shown that it is a type of non-Hodgkin lymphoma.