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Pagetoid Reticulosis

Last updated Dec. 14, 2018

Approved by: Maulik P. Purohit MD, MPH

Pagetoid Reticulosis is a variant of Mycosis Fungoides, which is a cutaneous T-cell non-Hodgkin’s lymphoma. It is usually present as a single, slow-growing patch or plaque on the arm or leg.


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

  • Localized Epidermotropic Reticulosis
  • Mycosis Fungoides Palmaris et Plantaris
  • Worringer-Kolopp Disease

What is Pagetoid Reticulosis? (Definition/Background Information)

  • Pagetoid Reticulosis is a variant of Mycosis Fungoides, which is a cutaneous T-cell non-Hodgkin’s lymphoma. It is usually present as a single, slow-growing patch or plaque on the arm or leg
  • Pagetoid Reticulosis is a rare form of primary cutaneous non-Hodgkin lymphoma, which means that it is a lymphoma that originates in the skin. In rare cases, Pagetoid Reticulosis may later involve additional parts of the body including the lymph nodes and bone marrow. This is known as systemic Pagetoid Reticulosis
  • The condition can lead to the formation of skin lesions (papules and plaques) that may ulcerate and cause secondary infections. Widespread symptoms, such as weight loss, fatigue, anemia, fever, and night sweats, can also be present when other body regions are affected
  • Pagetoid Reticulosis is typically diagnosed with a biopsy of the affected skin or with a biopsy of the swollen lymph nodes or affected organ. Other diagnostic methods may be used to examine the extent of the condition and its severity
  • The treatment is dependent upon the stage of Pagetoid Reticulosis. It may be skin-directed treatment (such as the use of topical medications, phototherapy, or local radiation therapy), or in rare instances, systemic therapy (through a combination of chemotherapy, radiation therapy, and surgery) when other organs are involved
  • The prognosis is dependent on many factors including the progression of the condition, response to treatment, and health status of the individual. Generally, the prognosis is good with appropriate, early treatment

General information on lymphoma and lymphocytes:

  • Lymphoma is a type of cancer stemming from uncontrollable division of lymphocytes (type of white blood cells). There are two types of lymphomas:
    • Hodgkin lymphoma
    • Non-Hodgkin lymphoma
  • Lymphocytes are the primary white blood cells located in the lymph, which is the fluid of the lymphatic system; just as blood is the fluid of the circulatory system
  • Lymphocytes are produced in bone marrow, and can mature into either B-cells or T-cells. T-cells mature in the thymus; Pagetoid Reticulosis arises from cancerous T-cells
  • Lymph results from filtration of blood as it moves to and from tissues. Lymph is colorless because it contains no 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 fight infections and irregularities within the cells (cell-mediated immunity). They fight viruses and cancerous cells
    • B-lymphocytes or B cells: They generate antibodies that are bodily defense proteins, which target foreign invaders outside the cells (humoral immunity). They combat bacterial cells, cell fragments, and other immunogenic elements
    • Natural killer cells or NK cells: They perform various functions related to both cell-mediated and humoral immunity. They also search for cancer cells, a process called immune surveillance

Who gets Pagetoid Reticulosis? (Age and Sex Distribution)

  • Pagetoid Reticulosis a rare condition that generally affects adults in the age group 30-70 years
  • Both males and females can be affected, though it is more common in males
  • All races and ethnic groups can be affected

What are the Risk Factors for Pagetoid Reticulosis? (Predisposing Factors)

Numerous studies have indicated the subsequent risk factors for Pagetoid Reticulosis:

  • Cigarette smoking for 40 years or more
  • Skin conditions such as eczema
  • Family history of multiple myeloma
  • Individuals in occupations such as painting, carpentry, farming, and pottery and ceramics
  • Viral infections

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 Pagetoid Reticulosis? (Etiology)

Lymphocytes are a type of white blood cells that are responsible for providing immunity in the human body. B-cells and T-cells are the two different types of lymphocytes. When under certain circumstances, when the lymphocytes grow and reproduce abnormally, it leads to a condition called as lymphoma, which is a common type of cancer. There are 2 types of lymphoma:

  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma

The cause for this type of non-Hodgkin lymphoma is unknown. Pagetoid Reticulosis may be triggered by a viral infection. It is thought to be a localized form of Mycoses Fungoides. Also, there may be certain genetic defects, such as translocation, which is a juxtaposition of regions of the chromosomes. This may result in: 

  • Change in regulatory features of certain cancer-causing genes called as oncogenes, which can lead to amplified production of their mRNA (overexpression), thus increasing their protein levels
  • Exchange of protein coding regions of gene, giving rise to new proteins that can encourage the inappropriate growth of cells

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

Note:

  • Pagetoid Reticulosis is not contagious and is not transmitted from one individual to another. One cannot contract the condition through close physical interaction with the affected individual
  • Some researchers believe that it is not a subtype of Mycosis Fungoides, and may be a separate entity in itself

What are the Signs and Symptoms of Pagetoid Reticulosis?

The signs and symptoms of Pagetoid Reticulosis mostly involve the skin and these include:

  • The presence of a (usually) single plaque or patch; rarely, these may be many in numbers
  • The lesion usually occur as well-circumscribed patches and plaques
  • The patch may be reddish in color and have a scaly appearance
  • The lesions are slow-growing in nature and generally indolent (may be termed as low-grade malignancy)
  • The most common location for Pagetoid Reticulosis is the arm or leg
  • But as they grow they can ulcerate and spread to other parts of the body

Note:

  • The presence of a solitary skin lesion on the arm or leg in Pagetoid Reticulosis during middle-age is called Woringer-Kolopp Disease. Apart from the skin, other organs or body systems are not affected
  • An aggressively developing form of Pagetoid Reticulosis is called Ketron-Goodman Disease, which presents generalized symptoms and diffuse skin involvement

In rare cases, if other organs are involved, the following general signs and symptoms may be seen, which include:

  • Unintentional weight loss; changes in appetite
  • Fatigue and weakness, headache
  • High temperatures and excessive night sweats (may be recurrent)
  • Anemia (low red blood cell count)
  • Low lymphocyte count, established by a blood test
  • Recurrent infections
  • Trouble breathing
  • Low blood pressure
  • Back pain
  • Swelling of the legs
  • Abdominal pain and swelling; constipation
  • Frequent urination

Very rarely, Pagetoid Reticulosis can affect other parts of the body. The signs and symptoms are dependent upon the specific organ or area involved, which may include:

  • Non-painful swelling of lymph nodes in the neck, armpits, or groin
  • There may be associated autoimmune disorders, which can cause joint and muscle pain, heat intolerance, recurrent rashes, abdominal pain, and a general feeling of malaise
  • If the brain is involved, then the following neurological symptoms may be present:
    • Confusion
    • Tinnitus (ringing in the ears)
    • Hearing and visual impairment
  • If the gastrointestinal (GI) tract is involved, then the following GI tract symptoms may be present:
    • Ulcers
    • Diarrhea
    • Inflammation
    • GI bleeding
  • Liver and spleen enlargement
  • Joint inflammation and fluid accumulation (edema) can occur, if the joints are affected

How is Pagetoid Reticulosis Diagnosed?

Pagetoid Reticulosis diagnosis is typically performed by obtaining skin biopsy samples from the affected region and examining them under a microscope to detect the cancerous cells. In rare cases, for systemic diseases, other methods may be used to diagnose Pagetoid Reticulosis, and these include:

  • A thorough physical examination and a complete medical history, which is very important
  • 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
  • Skin 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
  • If the lymphoma involves the lymph nodes then, 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
  • 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
  • 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 the condition and also to detect residual levels of disease after treatment. This tool can help in diagnosing relapse and can determine if restarting treatment is necessary
  • 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
  • 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: 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 Pagetoid Reticulosis?

Rarely, complications of Pagetoid Reticulosis due to the participation of other organs are observed. The complications may include the following:

  • Spread of the condition from the lymph nodes to other areas of the body
  • Loss of function of the organ/area in which cancer has spread
  • A weakened immune system (or immunosuppression), which can become more severe throughout treatment. As a result of this, individuals are more vulnerable to infections and have an increased risk of developing serious complications from such infections
  • If the condition spreads to the brain and central nervous system, it can give rise to:
    • Inflammation of the meninges or brain (that can be lethal)
    • Headache
    • Changes in vision
    • Facial numbness
  • If the abdomen is affected, it can cause intestinal obstruction that results in urine outflow obstruction and kidney damage
  • Occasionally, Pagetoid Reticulosis can convert into a more destructive form of lymphoma

The complications related to chemotherapy used in treating the condition may include the following:

  • Side effects such as dizziness, vomiting, appetite loss, mouth ulcers, and hair loss
  • By damaging healthy cells, the individual is more vulnerable to subsequent 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

The treatment measures can also give rise to secondary cancers such as skin cancer.

How is Pagetoid Reticulosis Treated?

The treatment is determined by the stage and location of the tumor. There are 2 main treatment procedures for Pagetoid Reticulosis and these include the following:

  • Skin-directed therapy
  • In very rare cases, systemic therapy is used

Skin-directed therapies are used (and often in combination) when the tumor is predominantly confined to the skin. This may include the following treatment measures:

  • Sunlight therapy (or exposure to ultraviolet light)
  • Use of topical steroids and chemotherapy
  • Systemic chemotherapy
  • Radiation therapy to affected (local) skin area
  • Other systemic treatment measures, such as the use of interferons, retinoids, etc.
  • Biological therapy

Systemic therapy is generally used for advanced stage tumors. A combination of treatment methods may be effectively used to treat the condition, which may include the following:

  • Chemotherapy: This approach uses a combination of drugs to destroy the cancerous cells and can be used in patients of all stages of Pagetoid Reticulosis
    • There can be serious side effects including fatigue, nausea, hair loss, anemia, high probability of infection, and drug-specific reactions
    • Many T-cell lymphomas can be resistant to chemotherapy. It can also injure healthy cells
    • Chemotherapy can be administered as a pill, liquid, shot, or intravenously

Note: Men and women in child-bearing age would greatly benefit from counseling regarding fertility issues. Some chemotherapy agents can cause infertility in both men and women. There can be permanent damage to the testicles and ovaries, harming their ability to produce sperms or ova. In men, sperm banking can be considered before initiating therapy. In women, in many cases, due to urgency of starting chemotherapy, it is often difficult to perform ovum banking. However, if there is sufficient time prior to chemotherapy, ovum banking may be performed. The healthcare provider may help assess the risk-benefit analysis, depending upon each individual’s specific circumstances.

  • Radiation: Radiation therapy uses 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 often used in combination with chemotherapy
    • The radiation may be administered by a machine placed outside the body, or by placing a radioactive material inside the body
    • Some side effects of radiation therapy include nausea, vomiting, fatigue, pain, risk of cancer later in life, and risk of heart disease
    • Radiation can damage healthy cells in addition to cancer cells, causing further problems
  • Surgery: After initial biopsies to diagnose Pagetoid Reticulosis, surgery is a rare treatment option since lymphomas are systemic and might have already spread to more than one lymph node in a majority of patients. Under such circumstances, removing all of the affected lymph nodes would be exceedingly difficult
  • Supportive treatment: Steroids, blood transfusions, anti-nausea medications, and antibiotics may be used as supportive therapy. In combination with other treatment methods, these can help fight the symptoms of immunodeficiency
  • In order to inhibit infections because the immune system is weakened by Pagetoid Reticulosis or by its treatment, the patient is contained in an isolated ward and treated with suitable antibiotics

Your healthcare provider will determine the best course of treatment depending on your individual circumstances. Also, follow-up care with regular screening and check-ups are important post-treatment.

How can Pagetoid Reticulosis be Prevented?

Currently, the cause of Pagetoid Reticulosis is unknown. Hence, there are no known methods to prevent tumor occurrence. Removing the variable risk factors may help in preventing the condition. The following factors may be considered:

  • Avoid or stop smoking
  • Undertaking appropriate and rapid treatment for skin conditions, such as eczema, or viral infections
  • Using suitable protective apparel (face masks, hand gloves, protective clothing) and adhering to proper safety practices, especially if you are a painter, carpenter, farmer, or working in the ceramics industry
  • Healthy diet and exercise, as well as avoidance of unnecessary exposure to chemicals, may help lessen the risk of cancer
  • In order to avoid a relapse, or to be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures instigated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations are required. Often, several years of active vigilance are critical and necessary.

What is the Prognosis of Pagetoid Reticulosis? (Outcomes/Resolutions)

  • The prognosis of Pagetoid Reticulosis depends upon a set of numerous 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 later-stage tumors, such as tumors with metastasis, the prognosis is poor
    • Health status of the individual: Individuals with excellent health overall have a better prognosis compared to those with poor health
    • Age of the individual: Older individuals usually experience a poorer prognosis than younger individuals
    • The size of the tumor: Individuals with smaller tumors cope better than those with larger tumors
    • Individuals with bulky disease have a worse prognosis
    • Involvement of vital organs may complicate the condition
    • The surgical respectability of the tumor (meaning, if the tumor can be removed entirely) is a rare option
    • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have a worse prognosis than tumors that do not reappear
    • Response to treatment: Tumors that respond to treatment have an improved prognosis compared to tumors that do not respond to treatment
    • Progression of the condition makes the result worse (progressive Pagetoid Reticulosis)
  • An early diagnosis and prompt treatment of the tumor generally results in better outcomes than a late diagnosis and deferred treatment
  • The combination chemotherapy drugs used may have some serious side effects such as cardio-toxicity). This primarily impacts 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 related to short survival

Additional and Relevant Useful Information for Pagetoid Reticulosis:

  • There are many variants of Mycosis Fungoides and they include the following:
    • Pagetoid Reticulosis
    • Syringotropic Mycosis Fungoides
    • Folliculotropic Mycosis Fungoides
    • Granulomatous Mycosis Fungoides
  • T-cell lymphomas are less common than B-cell lymphomas
  • Treatment for Pagetoid Reticulosis can cause physical and emotional distress; supportive care and encouragement can help positively and bring a measure of relief to patients

The following article link will help you understand leukemia and lymphoma (blood cancer):

http://www.dovemed.com/diseases-conditions/leukemia-and-lymphoma/

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Feb. 21, 2016
Last updated: Dec. 14, 2018