Cutaneous T-cell lymphoma and Lymphedema

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Cutaneous T-cell lymphoma and Lymphedema

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Our Home Page: Lymphedema People

http://www.lymphedemapeople.com/

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Cutaneous T-cell lymphoma and Lymphedema

There is increasing evidence that patients with long standing lymphedema may be susceptible to various forms of lymphoma.

This will generally involve the skin (cutaneous) and often presents as a brown plaque and/or lesions. Because this is classified as an indolent (slow growing)lymphoma, a patient may have it for years without realizing it is a malignancy or without having significant problems.

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What is cutaneous T-cell lymphoma?

Cutaneous T-cell lymphoma is a disease in which certain cells of the lymph system (called T-lymphocytes) become cancer (malignant) and affect the skin. Lymphocytes are infection-fighting white blood cells that are made in the bone marrow and by other organs of the lymph system. T-cells are special lymphocytes that help the body's immune system kill bacteria and other harmful things in the body.

The lymph system is part of the immune system and is made up of thin tubes that branch, like blood vessels, into all parts of the body, including the skin. Lymph vessels carry lymph, a colorless, watery fluid that contains lymphocytes. Along the network of vessels are groups of small, bean-shaped organs called lymph nodes. Clusters of lymph nodes are found in the underarm, pelvis, neck, and abdomen. The spleen (an organ in the upper abdomen that makes lymphocytes and filters old blood cells from the blood), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat) are also part of the lymph system.

There are several types of lymphoma. The most common types of lymphoma are called Hodgkin's disease and non-Hodgkin's lymphoma. These types of lymphoma usually start in the lymph nodes and the spleen. See the patient information summaries on adult or childhood non-Hodgkin's lymphoma or adult or childhood Hodgkin's disease for treatment of these cancers.

Cutaneous T-cell lymphoma usually develops slowly over many years. In the early stages, the skin may itch, and dry, dark patches may develop on the skin. As the disease gets worse, tumors may form on the skin, a condition called mycosis fungoides. As more and more of the skin becomes involved, the skin may become infected. The disease can spread to lymph nodes or to other organs in the body, such as the spleen, lungs, or liver. When large numbers of the tumor cells are found in the blood, the condition is called the Sezary syndrome.

If there are symptoms of cutaneous lymphoma, a doctor may remove a growth from the skin and look at it under a microscope. This is called a biopsy.

The chance of recovery (prognosis) and choice of treatment depend on the stage of the cancer (whether it is just in the skin or has spread to other places in the body) and the patient's general state of health.

There are several other types of cancer that start in the skin. The most common are basal cell cancer and squamous cell cancer, which are covered in the PDQ patient information summary on skin cancer. Another type of skin cancer called melanoma is covered in the patient information summary on melanoma. Kaposi's sarcoma, a rare type of cancer that occurs most commonly in patients with the Acquired Immunodeficiency Syndrome (AIDS), also affects the skin. See the PDQ patient information summary on Kaposi's sarcoma for treatment of this cancer. Cancers that start in other parts of the body may also spread (metastasize) to the skin.

Stages of cutaneous T-cell lymphoma

Once cutaneous T-cell lymphoma is found, more tests will be done to find out if cancer cells have spread to other parts of the body. This is called staging. A doctor needs to know the stage of the disease to plan treatment. The following stages are used for cutaneous T-cell lymphoma:

Stage I

The cancer only affects parts of the skin, which has red, dry, scaly patches, but no tumors. The lymph nodes are not larger than normal.

Stage II

Either of the following may be true:

The skin has red, dry, scaly patches, but no tumors. Lymph nodes are larger than normal, but do not contain cancer cells.
There are tumors on the skin. The lymph nodes are either normal or are larger than normal, but do not contain cancer cells.

Stage III

Nearly all of the skin is red, dry, and scaly. The lymph nodes are either normal or are larger than normal, but do not contain cancer cells.

Stage IV

The skin is involved, in addition to either of the following:

Cancer cells are found in the lymph nodes.
Cancer has spread to other organs, such as the liver or lung.

Recurrent

Recurrent disease means that the cancer has come back after it has been treated. It may come back where it started or in another part of the body

From: National Cancer Institute - PDQ

For the complete article, including treatment information, please see the link below.

http://www.meds.com/pdq/tcell_pat.html

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Symptoms & Complications of Lymphoma

Lymphomation.org

http://www.lymphomation.org/symptoms.htm

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Cutaneous T-cell Lymphoma

eMedicine

http://www.emedicine.com/med/topic3486.htm

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Cutaneous T cell lymphoma

Cancerbacup - UK

http://www.cancerbackup.org.uk/Cancerty ... eousT-cell

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Cutaneous T cell lymphoma

Lymphoma Information Network

http://www.lymphomainfo.net/nhl/types/ctcl-mf.html

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Cutaneous T cell lymphoma

DermNet NZ

http://dermnetnz.org/dermal-infiltrativ ... phoma.html

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Non-Hodgkin's lymphoma of the skin associated with chronic limb lymphoedema.

Tatnall FM, Mann BS.

Cutaneous non-Hodgkin's lymphoma developed within a leg affected by chronic lymphoedema. The lymphoedema had followed radiotherapy to bony metastases from a carcinoma of the prostate. Eighteen months after the development of the cutaneous tumours, extracutaneous involvement by the lymphoma became apparent. This is the second report of a non-Hodgkin's lymphoma appearing within a lymphoedematous limb. The possible reasons for such an unusual localization are discussed. Our case report illustrates that cutaneous tumours other than lymphangiosarcomas may localize to a lymphoedematous limb and clinically simulate the Stewart-Treves syndrome.

Publication Types:
Case Reports

PMID: 4096886 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/quer ... query_hl=6

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Squamous cell carcinoma in chronic lymphedema: case report and review of the literature.

Furukawa H, Yamamoto Y, Minakawa H, Sugihara T.

Department of Plastic and Reconstructive Surgery, Hokkaido University, School of Medicine, Sapporo, Japan. furufuru@beach.ocn.ne.jp

BACKGROUND: Squamous cell carcinoma (SCC) arising in chronic lymphedema is rare; only nine cases have been reported. OBJECTIVE: To present the evolution of SCC in chronic lymphedema. METHODS: Case report and literature review. RESULTS: The tumor was treated by wide excision and covered by a skin graft. CONCLUSION: In most of the other reported SCC cases in lymphedema, there are additional factors for carcinogenesis. There is no additional carcinogenic factor except for chronic lymphedema in our case. This strongly supports that lymphedema itself is one of the carcinogenic factors for not only angiosarcoma but also SCC.

Publication Types:
Case Reports
Review
Review of Reported Cases

PMID: 12410682 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/quer ... query_hl=6

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Chronic lymphoedema and angiosarcoma.

Azurdia RM, Guerin DM, Verbov JL.

Department of Dermatology, The Royal Liverpool University Hospital NHS Trust, UK.

Angiosarcoma has frequently been described arising within chronic lymphoedema of the upper limb following mastectomy and radiotherapy for carcinoma of the breast. We report a case of angiosarcoma arising in a lymphoedematous leg that had been subjected to radiotherapy 20 years previously for Hodgkin's disease. The diagnosis was expedited once the patient noticed the development of bleeding nodules. Prognosis of angiosarcoma is poor with treatment options being wide-excision surgery, palliative radiotherapy or chemotherapy. Unusual bruised areas or bleeding nodules developing within chronic lymphoedematous limbs should be biopsied to exclude the diagnosis.

Publication Types:
Case Reports

PMID: 10457127 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/quer ... query_hl=6

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Non-Hodgkin's lymphoma of the skin associated with chronic limb lymphoedema.

Tatnall FM, Mann BS.

Cutaneous non-Hodgkin's lymphoma developed within a leg affected by chronic lymphoedema. The lymphoedema had followed radiotherapy to bony metastases from a carcinoma of the prostate. Eighteen months after the development of the cutaneous tumours, extracutaneous involvement by the lymphoma became apparent. This is the second report of a non-Hodgkin's lymphoma appearing within a lymphoedematous limb. The possible reasons for such an unusual localization are discussed. Our case report illustrates that cutaneous tumours other than lymphangiosarcomas may localize to a lymphoedematous limb and clinically simulate the Stewart-Treves syndrome.

Publication Types:
Case Reports

MeSH Terms:
Aged
Bone Neoplasms/radiotherapy
Bone Neoplasms/secondary
Chronic Disease
Humans
Leg
Lymphedema/complications*
Lymphedema/etiology
Lymphoma/complications*
Lymphoma/pathology
Male
Radiotherapy/adverse effects
Skin Neoplasms/complications*

PMID: 4096886 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Citation

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SQUAMOUS-CELL CARCINOMA ON LONG LASTING LYMPHOEDEMA.

ECHENIQUE-ELIZONDO, Miguel, MD, FACS

ELORZA, José, L. MD

Correspondence:

Echenique-Elizondo, M., MD,FACS.

Associated Professor of Surgery. Basque Country University. School of Medicine.

P. Dr. Begiristain, 105

20010 San Sebastián. Spain

Phone. +34-943017319

E-mail. gepecelm@sc.ehu.es

Key Words

Chronic

Lymphoedema

Squamous-cell

Although lymphangiosarcoma (1)is a well recognized complication of chronic lymphoedema, squamous cell carcinoma has only been reported on seven previous occasions in a recent review (2). Multiple epithelial tumor on a single limb has also been recorded (3).

Case report:

A 63 years old white male living in a rural area and complaining of congenital non previously treated lymphoedema was admitted with the aspect seen in Lymphoedema (4)may be primary or secondary to the presence of other disease and/or to the consequences of surgery. Primary lymphoedema may be congenital – Milroy´s disease – or may occur at any phase of life but it most commonly appears at puberty. Secondary lymphoedema is encountered more often. The most prevalent worldwide cause of lymphoedema is filariasis, which is particularly common in south-east Asia and Africa. In Western countries postsurgical lymphoedema of the extremity prevails. Complications of chronic limb lymphoedema include recurrent cellulitis and lymphangiosarcoma.

Although lymphangiosarcoma is a well recognized complication of chronic lymphoedema, squamous cell carcinoma has only been reported on seven previous occasions in a recent review. Multiple epithelial tumor on a single limb has been recorded. Other neplasms such as primary cutaneous B-cell lymphoma has also been registered (5) . Lymphangiosarcoma is an aggressive, malignant vascular tumor following long-lasting chronic lymphedema. Today, due to changes in the operative techniques of breast cancer, less chronic lymphoedema is seen with only a scant number of lymphangiosarcoma patients in our work place. The true incidence of lymphangiosarcoma after post-mastectomy lymphoedema remains controversial and may we underdiagnosed. One of the large reviews on the subject done between 1954 and 1983, 7620 patients were treated for breast carcinoma at Institut Gustave Roussy (France) (6). Of these patients, 6919 were followed for at least 1 year. Out of these, 11 presented with sarcomas thought to be induced by irradiation, 2 of which were Steward-Treves Syndrome, and 9 of which were sarcomas within the irradiated fields. The sites of these sarcomas were: parietal wall, 1 case; second costal cartilage, 1 case; infraclavicular region, 1 case; supraclavicular region, 2 cases; internal third of the clavicle, 2 cases; axillary region 2 cases; and the internal side of the upper arm (Stewart-Treves syndrome), 2 cases. The cumulative incidence of sarcoma following irradiation of breast cancer was 0.2% (0.09-0.47) at 10 years. The standardized incidence ratio (SIR) of sarcoma (observed n# of cases (Obs)/expected n# of cases (Exp) computed from the Danish Cancer Registry for the same period was 1.81 (CI 0.91-3.23). This is significantly higher than one, with a p = 0.03 (One Tailed Exact Test). The mean annual excess (Obs-Exp)/100.000 person-years at risk during the same period/(100,000) was 9.92. This study suggests that patients treated by radiation for breast cancer have a risk of subsequent sarcomas that is higher than the general population.

However in the current of epidermoid carcinoma arising on long lasting lymphoedema case there is not experience large enough in treatment and follow-up because we are dealing with a few isolated clinical reports and no large series registered exists to set the appropriate management. Treatment options include radical ablative surgery, radiation therapy, and chemotherapy. Early recognition and radical ablative surgery must be considered on the changes arising on chronic long lasting lymphoedema.

References.

1.- Heitmann C, Ingianni G. Stewart-Treves syndrome: lymphangiosarcoma following mastectomy.

Ann Plast Surg. 2000.44(1).72-75

2.- Lister RK, Black MM, Calonje E, Burnand KG.

Squamous cell carcinoma arising in chronic lymphoedema.

Br J Dermatol. 1997 Mar;136(3):384-7.

3.- Dandurand M, Bernard F, Barneon G, Guilhou E, Guillot B, Guilhou JJ.Multiple spinocellular carcinomas on chronic lymphedema. Association with vitiligo.

Ann Dermatol Venereol. 1990;117(12):953-6.

4.- Szuba A, Rockson SG.

Lymphedema: classification, diagnosis and therapy.

Vasc Med. 1998;3(2):145-56.

5.- Torres-Paoli D, Sanchez JL. Primary cutaneous B-cell lymphoma of the leg in a chronic lymphedematous extremity.

Am J Dermatopathol. 2000 Jun;22(3):257-60.

6.- Taghian A, de Vathaire F, Terrier P, Le M, Auquier A, Mouriesse H, Grimaud E, Sarrazin D, Tubiana M.Long-term risk of sarcoma following radiation treatment for breast cancer.

Int J Radiat Oncol Biol Phys. 1991 Jul;21(2):361-7.

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A case of peripheral T-cell lymphoma unspecified involving subcutaneous tissue.

Futagami A, Aoki M, Kawana S.

Department of Dermatology, Nippon Medical School, Main Hospital, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, Japan. aya-f@nms.ac.jp

A 36-year-old man presented with a 3-year-old red-brown plaque with subcutaneous nodules on his left thigh. Although a similar lesion was observed on his right thigh 3 years earlier, it spontaneously disappeared 1 year later. However, the lesion on the left thigh was growing larger. Histologically, the lesion showed a diffuse and dense infiltration of atypical lymphocytes extending from the superficial dermis to the subcutaneous tissue. Severe lobular panniculitis, composed of small- and medium-sized atypical lymphocytes and large normal histiocytes, was observed in the subcutaneous adipose tissue. Immunohistochemical studies revealed a post-thymic T-cell phenotype. A genetic analysis demonstrated a rearrangement of the T-cell receptor chain gene. The left skin lesion also gradually disappeared after skin biopsy without therapy, and he continues to be in remission.

PMID: 16019520 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Abstract

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PubMed Links Page on Cutaneous T Cell Lymphomas

http://www.ncbi.nlm.nih.gov/entrez/quer ... d=16019520

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Cancer Resources and Information:

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Cancer Topics - National Cancer Institute

http://www.nci.nih.gov/cancertopics

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American Cancer Society

http://www.cancer.org/docroot/home/index.asp

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Canadian Cancer Society

http://www.cancer.ca/ccs/internet/niw_s ... %2C00.html

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CancerBACUP - UK / Europe

http://www.cancerbacup.org.uk/Home

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The Cancer Council Australia

http://www.cancer.org.au/

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ACOR.ORG - Association of Cancer Online Resources

http://www.acor.org/

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Your Body After Cancer Treatment

http://www.nci.nih.gov/cancertopics/lif ... ment/page5

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Cancer - Medline Plus Information and Links Page

http://www.nlm.nih.gov/medlineplus/cancer.html

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Cancer Information on the Internet

http://www.hackley.org/medical_services ... _links.htm

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Cancer Resource Center

http://patient.cancerconsultants.com/li ... x?id=32333

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Cancer Lynx

http://www.cancerlynx.com/

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The Cancer Information Network

http://www.cancerlinksusa.com/

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Cancer Information & Support International

http://www.cancer-info.com/

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Arm and Leg Swelling After Cancer

With the advent of better and more effective cancer treatments, the survival rate for all cancers has risen dramatically. With this progress, a new and often misunderstood and misdiagnosed complication has arisen.

Many cancer survivors , having overcome cancer, find themselves with sudden and often unexplained swelling, usually of the arms or of the legs.

This swelling occurs because of one of several factors.

First, the swelling begins after lymph nodes have been removed for cancer biopsies.

Second, the swelling may start as a result of radiation damage to either the lymph nodes and/or the lymph system.

Due to either the removal of lymph nodes or damage to the lymph system, your body is no longer able to rid itself of excess fluids. The fluids collect in the limbs effected and swelling beings.

This swelling is called lymphedema. The swelling that occurs is permanent, and while it is not curable it is treatable.

Permanent Leg or Arm Swelling

****In the situation of any permanent leg swelling whether the cause is known or unknown, the diagnoses of lymphedema must be considered****

There are several groups of people who experience leg or arm swelling from known causes, but it doesn't go away or unknown causes where the swelling can actually get worse as time goes by.

Group One

This group includes those who have had the injuries, infections, insect bites, trauma to the leg, surgeries or reaction to a medication. When this swelling does not go away, and becomes permanent it is called secondary lymphedema.

Group Two

Another extremely large group that experiences permanent leg or arm swelling are cancer patients, people who are morbidly obese, or those with the condition called lepedema. What causes the swelling to remain permanent is that the lymph system has been so damaged that it can no longer operate normally in removing the body's waste fluid.

In cancer patients this is the result of either removal of the lymph nodes for cancer biopsy, radiation damage to the lymph system, or damage from tumor/cancer surgeries.

This is also referred to as secondary lymphedema.

Group Three

Group three consists of people who have leg or arm swelling from seemingly unknown reasons. There may be no injury, no cancer, no trauma, but for some reason the leg simply is swollen all the time.

The swelling may start at birth, it may begin at puberty, or may begin in the 3rd, 4th or even 5th decade of life or sometimes later.

This type of leg or arm swelling is called primary lymphedema. It can be caused by a genetic defect, malformation or damage to the lymph system while in the womb or at birth or be part of another birth condition that also effects the lymph system.

This is an extremely serious medical condition that must be diagnosed early, and treated quickly so as to avoid painful, debilitating and even life threatening complications. Treatment should NOT include the use of diuretics.

What is Lymphedema?

Lymphedema is defined simply as an accumulation of excessive protein rich fluid in the tissues of the leg. The accumulation of fluid causes the permanent swelling caused by a defective lymph system.

A conservative estimate is that there may be 1-2 million people in the United States with some form of primary lymphedema and two to three million with secondary lymphedema.

What are the symptoms of Lymphedema?

If you are an at risk person for arm lymphedema there are early warning signs you should be aware of. If you experience any or several of these symptoms, you should immediately make your physician aware of them.

1.) Unexplained aching, hurting or pain in the arm

2.) Experiencing "fleeting lymphedema." This is where the limb may swell, even slightly, then return to normal. This may be a precursor to full blown arm lymphedema.

3.) Localized swelling of any area. Sometimes lymphedema may start as swelling in one area, for example the hand, or between the elbow and hand. This is an indication of early lymphatic malfunction.

4.) Any arm inflammation, redness or infection.

5.) You may experience a feeling of tightness, heaviness or weakness of the arm.

How is Lymphedema Treated?

The preferred treatment today is decongestive therapy. The forms of therapy are complete decongestive therapy (CDT) or manual decongestive therapy (MDT), there are variances, but most involve these two type of treatment.

It is a form of massage therapy where the leg is very gently massaged to actually move the fluid out of the leg and into an area where the lymph system still functions normally.

With these massage treatments, swelling is reduced and then the patient is fitted with a pre-measured custom pressure garment to keep the swelling down and/or is taught to use compression wraps to maintain the leg size.

What are some of the complications of lymphedema?

1. Infections such as cellulitis, lymphangitis, erysipelas. This is due not only to the large accumulation of fluid, but it is well documented that lymphodemous limbs are localized immuno-deficient.

2. Draining wounds that leak lymphorrea which is very caustic to surrounding skin tissue and acts as a port of entry for infections.

3. Increased pain as a result of the compression of nerves usually caused by the development of fibrosis and increased build up of fluids.

4. Loss of Function due to the swelling and limb changes.

5. Depression - Psychological coping as a result of the disfigurement and debilitating effect of lymphedema.

6. Deep venous thrombosis again as a result of the pressure of the swelling and fibrosis against the vascular system. Also, can happen as a result of cellulitis, lymphangitis and infections.

7. Sepsis, Gangrene are possibilities as a result of the infections.

8. Possible amputation of the limb.

9. Pleural effusions may result if the lymphatics in the abdomen or chest are to overwhelmed to clear the lung cavity of fluids.

10. Skin complications such as splitting, plaques, susceptibility to fungus and bacterial infections.

11. Chronic localized inflammations.

Can lymphedema be cured?

No, at the present time there is no cure for lymphedema. But it can be treated and managed and most of the complications can be avoided. Life with lymphedema can still be active and full, with proper treatment, patient education, and patient life style adaptation.

For extensive information on lymphedema, please visit our home page:

Lymphedema People

http://www.lymphedemapeople.com

(c) Copyright 2005 by Pat O'Connor and Lymphedema People. Use of this information for educational purpose is encouraged and permitted. It must be available free and without charge and not used for financial renumeration or gain. Please include an acknowledgement to the author and a link to Lymphedema People.

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[patoco]

Cutaneous lymphomas

Semin Radiat Oncol. 2007 Jul

Smith BD, Wilson LD.
United States Air Force, Wilford Hall Medical Center, Lackland AFB, TX.

Address reprint requests to Lynn D. Wilson, MD, MPH, Department of Therapeutic Radiology, Yale University School of Medicine, HRT 132, 333 Cedar Street, New Haven, CT 06520.

The skin is the most common site of extranodal non-Hodgkin lymphoma, with a yearly incidence approaching 1 per 100,000 individuals in the United States. Skin lymphomas are classified broadly into cutaneous T-cell lymphoma (CTCL) and cutaneous B-cell lymphoma (CBCL). Within these broad categories, multiple unique pathologic entities exist with a wide array of natural histories and treatment options. Radiotherapy plays an important role in the curative treatment of localized CTCL and CBCL and may be used to palliate cutaneous and visceral symptoms associated with advanced disease. This review highlights the role of radiotherapy in the multidisciplinary management of cutaneous lymphoma.

http://www.semradonc.com/article/PIIS10 ... 4/abstract

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Cutaneous lymphomas

Rev Prat. 2007 Mar

Bachelez H.
Service de dermatologie 1 et unité Inserm U697, hôpital Saint-Louis, 75475 Paris. herve.bachelez@sls.aphp.fr

Cutaneous lymphoma is a heterogenous entity regarding clinical and pathological features, evolutive profiles and prognosis, molecular abnormalities and response to therapy. Recent classification is based on these specificities, giving a major concern to the prognostic implications of these different entities. While treatment is effective and prognosis is favorable in low grade forms, recent therapeutic innovations relying on the use of biological tools are likely to improve the prognosis of the most severe ones, as it is the case for anti-CD20 monoclonal antibodies (rituximab) in disseminated cutaneous B-cell lymphomas, and anti-CD52 monoclonal antibody (alemtuzumab) in refractory forms of cutaneous T-cell lymphoma. The deciphering of key molecular mechanisms underlying these malignancies should open new therapeutic perspectives in a close future.

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

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Cutaneous T-cell lymphoma: molecular and cytogenetic findings

Oncology (Williston Park). 2007 Feb

Sterry W.
Department of Dermatology, and Allergy, Charité University Medicine, Berlin, Germany. wolfram.sterry@charite.de

Chromosomal changes have been identified early in the disease process in cutaneous T-cell lymphoma (CTCL): both losses and gains of chromatin have been found on several chromosomes. The extent of chromosomal aberrations increases with disease stage and in more aggressive subtypes of the disorder. Changes in specific genes, such as NAV3, have been characterized in patients with CTCL, and may produce a proliferation advantage for affected cells. In addition, the expression of some genes can discriminate between controls and patients with CTCL. Therefore, the over- or underexpression of certain genes may be of diagnostic and pathogenic relevance in this disease, and may allow the development of selective treatments.

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

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The pathology of cutaneous T-cell lymphoma

Oncology (Williston Park). 2007 Feb

Robson A.
Department of Dermatopathology, St. John's Institute of Dermatology, London, United Kingdom. alistair.robson@gstt.nhs.uk

The diagnosis of cutaneous T-cell lymphoma (CTCL) requires accurate histopathology, including immunocytochemistry, as well as careful clinical appraisal and analysis for T-cell clonality. This paper reviews the key histologic features of mycosis fungoides (MF) and its variants, and of lymphomatoid papulosis (LyP). Mycosis fungoides is an epidermotropic CTCL that evolves through distinct disease stages of patch, plaque, and tumor, often leading to transformation in the final stages. Disease staging is made clinically, and diagnosis may be difficult during the early stages because several common dermatologic conditions share features with MF. Therefore, clinical appraisal plus the presence of characteristic histopathologic features are needed to ensure accurate diagnosis. Clinical information is particularly important in the diagnosis of LyP, as the disease appears malignant histologically, but has a benign clinical course. Several other T-cell lymphomas were defined in a recent classification of these cutaneous lymphomas, and some key features of these disorders are also briefly reviewed.

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

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Chemokine Receptor Expression by Leukemic T Cells of Cutaneous T-Cell Lymphoma: Clinical and Histopathological Correlations.

J Invest Dermatol. 2007 Jun

Capriotti E, Vonderheid EC, Thoburn CJ, Bright EC, Hess AD.
1Department of Dermatology, University of Rome, “Tor Vergata”, Rome, Italy.

Correspondence: Dr Eric C. Vonderheid, 550 N. Broadway, Suite 1002, Baltimore, Maryland 21205, USA. E-mail: evonder1@jhmi.edu

Studies performed in the laboratory of Dr Hess, Baltimore, MD USA.

Abbreviations: CLA, cutaneous lymphocyte antigen; CTCL, cutaneous T-cell lymphoma; FC, flow cytometry; HEV, high endothelial venule; MF, mycosis fungoides; SS, Sézary syndrome

Chemokine receptors expressed by normal and neoplastic lymphocytes provide an important mechanism for cells to traffic into the skin and skin-associated lymph nodes. The goal of this study was to correlate chemokine receptor and CD62L expression by circulating neoplastic T cells with the clinical and pathological findings of the leukemic phase of cutaneous T-cell lymphoma, primarily Sézary syndrome (SS). Chemokine receptor mRNA transcripts were found in the majority of leukemic cells for CCR1, CCR4, CCR7, CCR10, CXCR3, and CD62L and in 20-50% of the samples for CXCR5. In patients with SS, relatively high expression levels of CCR7 and CCR10 by circulating neoplastic T cells correlated with epidermotropism, CXCR5 expression correlated with density of the dermal infiltrate, and CD62L correlated with extent of lymphadenopathy. Of note, CXCR5 expression and a dense dermal infiltrate correlated with a poor prognosis. The chemokine receptor profile supports the concept that neoplastic T cells are central memory T cells, and that CCR10 and CD62L play a fundamental role respectively in epidermotropism and lymphadenopathy that is observed in SS.Journal of Investigative Dermatology advance online publication, 28 June 2007; doi:10.1038/sj.jid.5700916.

http://www.nature.com/jid/journal/vaop/ ... 476419E95D

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ECP versus PUVA for the Treatment of Cutaneous T-Cell Lymphoma

Skin Therapy Lett. 2007 May

Geskin L.
Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA.

Key Words: ECP, PUVA, Extracorporeal Photopheresis, CTCL, Cutaneous T-cell Lymphoma, Psorlen + UVA Therapy

Extracorporeal photopheresis (ECP) and psoralen plus ultraviolet A therapy (PUVA) are widely accepted types of photochemotherapy used for the treatment of cutaneous T-cell lymphomas (CTCL). PUVA and ECP utilize a photosensitizing agent, that can be taken orally (PUVA) or added to the concentrated sample of white blood cells extracorporeally (ECP) prior to UVA exposure. Both therapies have been shown to be safe and effective for the treatment of CTCL. As a monotherapy, PUVA is preferentially used for treatment of patients at earlier stages with skin involvement alone (T1 and T2). ECP is usually used for patients with erythrodermic skin involvement (T4) in advanced stages (Stage III and IVA) with peripheral blood involvement as in Sézary syndrome (SzS). Use of ECP in earlier stages is controversial and is currently under investigation. Both PUVA and ECP are rarely used as monotherapy, though long-term remissions after PUVA monotherapy for early disease have been reported. CTCL is a rare disease and randomized prospective clinical trials are difficult. The best efficacy data derived from prospective case studies and meta-analysis are reviewed here.

Full Text Article

http://www.skintherapyletter.com/2007/12.5/1.html

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Trithiocarbonates-Exploration of a new head group for HDAC inhibitors

Bioorg Med Chem Lett. 2007 Jun

Dehmel F, Ciossek T, Maier T, Weinbrenner S, Schmidt B, Zoche M, Beckers T.
Altana Pharma AG, a Member of the Nycomed Group, Byk-Gulden-Strasse 2, D-78467, Germany.

Inhibition of histone deacetylases class I/II enzymes is a new, promising approach for cancer therapy. In the present study, we disclose a new structural class of HDAC inhibitors with the trithiocarbonate motif. A clear structure-activity-relationship was obtained for the cap-linker motif and the putative Zn(2+) complexing head group. Selected analogs display potent inhibition of HDAC enzymatic activity and a cellular potency comparable to that of suberoylanilide hydroxamic acid (SAHA), recently approved for treatment of patients with advanced cutaneous T-cell lymphoma.

http://www.sciencedirect.com/science?_o ... 02f8f3521d

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Vorinostat: a new oral histone deacetylase inhibitor approved for cutaneous T-cell lymphoma.

Madeleine Duvic‌1 & Jenny Vu‌
1University of Texas MD Anderson Cancer Center, Department of Dermatology, 1515 Holcombe Boulevard, Houston, TX 77030, USA. mduvic@mdanderson.org

Keywords: cutaneous T-cell lymphoma, histone deacetylase inhibitors, mycosis fungoides, Sézary syndrome, suberoylanilide hydroxamic acid, vorinostatv

Epigenetic regulation of gene transcription by small-molecule inhibitors of histone deacetylases (HDACs) is a novel cancer therapy. Vorinostat (suberoylanilide hydroxamic acid) is the first FDA-approved HDAC inhibitor for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL). Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in Phase I development. In two Phase II trials, vorinostat 400 mg/day was safe and effective with an overall response rate of 24 – 30% in refractory advanced patients with CTCL including large cell transformation and Sézary syndrome. The common side effects of vorinostat, which are similar in all studies, include gastrointestinal symptoms, fatigue and thrombocytopenia and the most common serious event was thrombosis.

Full Text Article Available

http://www.expertopin.com/doi/abs/10.15 ... .16.7.1111

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Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma.

J Clin Oncol. 2007 Jun 18

Olsen EA, Kim YH, Kuzel TM, Pacheco TR, Foss FM, Parker S, Frankel SR, Chen C, Ricker JL, Marie Arduino J, Duvic M.
Duke University, Durham, NC; Stanford University, Stanford, CA; Northwestern University, Chicago, IL; University of Colorado Health Sciences Center at Fitzsimons, Aurora, CO; Tufts-New England Medical Center, Boston, MA; Emory University, Atlanta, GA; Merck Research Laboratories, Upper Gwynedd, PA; and the M.D. Anderson Cancer Center, Houston, TX.

PURPOSE: To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes.

PATIENTS AND METHODS: Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief (>/= 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated.

RESULTS: Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be >/= 185 days (34+ to 441+). Median TTP was 4.9 months overall, and >/= 9.8 months for stage IIB or higher responders.

Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE.

CONCLUSION: Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.

http://jco.ascopubs.org/cgi/content/abs ... .10.2434v1

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Low-dose intermittent alemtuzumab in the treatment of Sézary syndrome: clinical and immunologic findings in 14 patients.

Haematologica. 2007 Jun

Bernengo MG, Quaglino P, Comessatti A, Ortoncelli M, Novelli M, Lisa F, Fierro MT.
Department of Biomedical Sciences and Human Oncology, Section of Dermatology, 1st Dermatologic Division, University of Turin, Turin, Italy. mariagrazia.bernengo@unito.it

BACKGROUND AND OBJECTIVES: Alemtuzumab may be effective in Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma, but is associated with severe hematologic toxicity and infections. This study investigated whether low-dose subcutaneous alemtuzumab can induce hematologic, immunologic, and clinical responses similar to those obtained with the standard regimen, but with less toxicity.

DESIGN AND METHODS: Fourteen SS patients were enrolled: 11 had relapsed/refractory disease and three had untreated SS with high counts of circulating Sézary cells (SC). Four received 3 mg alemtuzumab on day 1, 10 mg on day 3, then 15 mg on alternating days; circulating SC were evaluated after the fourth 15 mg dose and treatment was interrupted in the presence of counts <1,000/mm (3). A reduced dosage (3 mg on day 1, then 10 mg on alternating days) was administered to the remaining patients, with SC counted before every injection, until a reduction to values of <1,000/mm (3).

RESULTS: The median SC count decreased by 95.5%. Overall, 12/14 patients (85.7%) achieved a clinical response, with three complete responses (21.4%). After a median follow-up of 16 months, the median time-to-treatment failure is 12 months. Infectious complications occurred in 28.6% of patients, all included in the group treated with 15 mg. No patient in the group treated with 10 mg developed hematologic toxicity or infections. An early recovery of circulating NK, B and CD3+CD8+ cells occurred after the first cycle.

INTERPRETATION AND CONCLUSIONS: Subcutaneous alemtuzumab at very low doses (10 mg maximum per administration), given for a short period based on SC levels, has a good toxicity profile, high response rate and causes durable remissions in SS patients with high tumor burden in the peripheral blood.

PMID: 17550851 [PubMed - indexed for MEDLINE]

Search=17550851&ordinalpos=17&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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The effect of psoralen plus ultraviolet A in vitro in HUT-78 enhances by 5-aminolevulinic acid.

Photodermatol Photoimmunol Photomed. 2007 Apr-Jun

Akita Y, Watanabe D, Yanagishita T, Kuhara T, Kawamura C, Masuda Y, Kawada M, Nakaseko H, Tamada Y, Matsumoto Y.
Department of Dermatology, Aichi Medical University School of Medicine, Nagakute, Japan. 106039@gk.amu.aichi-med-u.ac.jp

BACKGROUND: Sezary syndrome and mycosis fungoides are forms of cutaneous T-cell lymphoma, and in the early stage of these diseases psoralen plus ultraviolet A (PUVA) is one of the treatments of choice. Photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) is an effective, non-invasive, and safe treatment for most superficial skin cancers. In order to obtain greater efficacy of PUVA, we investigated the synergistic anti-tumor effects of ALA-PDT and PUVA using 8-methoxypsoralen (8-MOP) and a UVA lamp.

METHODS: The in vitro effects of PUVA and ALA-PDT and their combination in HUT-78 cell line from human SS were determined by MTT assay.

RESULTS: In our results, cell proliferation compared with controls was inhibited to 53.2% with UVA alone, 52.3% with 1 microM 8-MOP, 43.8% with 100 microM ALA, and 19.2% with combined 8-MOP and ALA.

CONCLUSION: Combined use of ALA and PUVA using 8-MOP and UVA lamps, which are widespread in Japan, had a strong anti-tumor effect in vitro. Combined treatment with ALA-PDT and PUVA using a UVA lamp appears to have a strong treatment effect.

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

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Aminosuberoyl hydroxamic acids (ASHAs): A potent new class of HDAC inhibitors.

Bioorg Med Chem Lett. 2007 Jul


Belvedere S, Witter DJ, Yan J, Secrist JP, Richon V, Miller TA.
Merck Research Laboratories, Departments of Drug Design & Optimization and Cancer & Biology Therapeutics, 33 Avenue Louis Pasteur, Boston, MA 02115, USA.

Histone deacetylase (HDAC) inhibitors that target Class I and Class II HDACs are currently in advanced clinical trials for the treatment of cancer. Vorinostat (Zolinzatrade mark, SAHA) is a hydroxamic acid approved for the treatment of patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. As part of an on-going effort to better understand the nature of the HDAC enzyme/inhibitor interaction and design highly effective HDAC inhibitors, we herein report the design, synthesis and HDAC inhibitory activity of a vorinostat-derived series of substrate-based HDAC inhibitors.

http://www.sciencedirect.com/science?_o ... a4ac0546ac

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The therapeutic uses of chromatin-modifying agents.

Expert Opin Ther Targets. 2007 Jun

Mai A.
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università di Roma La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy. antonello.mai@uniroma1.it

Keywords: cancer, chromatin remodelling, epigenetics, histone acetyltransferase, histone deacetylase, histone methyltransferase

In contrast to genetic aberrations, epigenetic aberrations can be reversed by the use of histone acetyltransferase (HAT), histone deacetylase (HDAC), SIRT, or histone methyltransferase (HMT) inhibitors. A well-known HDACi, suberoylanilide hydroxamic acid, has been recently approved for the treatment of cutaneous T cell lymphoma, and a number of HDACi are in clinical trials as anticancer drugs. In addition, HDACi could be useful in antimalarial and antifungal therapies and can reactivate the HIV-1 expression in latent cellular reservoirs, thus suggesting the use in a combination therapy with highly active antiretroviral therapy. HDACi have also been reported to have anti-inflammatory effects through inhibition of cytokines and key transcription factors, and to ameliorate the phenotypes in animal models of neurological disorders. HDACi can also reactivate the gamma-globin gene for the treatment of beta-thalassaemia, and recently were shown to relieve morphological and functional effects of muscular dystrophia. Dysfunction of HAT enzymes is also often associated with several diseases, including cancer; thus, the HATi can represent new chemical entities for the development of new drugs. Only a few HMTi have been described to date, but these small molecules could be a useful scaffold to discovering new highly active and enzyme-selective compounds to develop as therapeutics.

http://www.expertopin.com/doi/abs/10.15 ... 2.11.6.835

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Systemic monotherapy vs combination therapy for CTCL: rationale and future strategies.

Oncology (Williston Park). 2007 Feb

Duvic M.
Department of Dermatology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. mduvic@mdanderson.org

There are few approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. For patients with early-stage disease, the oral retinoids can be combined with other therapies, such as psoralen plus ultraviolet A or interferon alpha, to improve response rates. Combined-modality therapy with oral retinoids, combined chemotherapy, electron-beam therapy, and topical mustargen has also proved effective. For the treatment of advanced-stage disease, the targeted therapy denileukin diftitox (Ontak) provides a nonimmunosuppressive alternative to conventional chemotherapy or radiation therapy. Of the conventional chemotherapies that have been tested in CTCL, gemcitabine (Gemzar) has demonstrated good efficacy in producing responses, particularly in patients with tumors. This agent can be used in combination with a maintenance therapy of bexarotene (Targretin) to manage the plaques and patches of mycosis fungoides. Several other targeted therapies are now also in testing, for example, alemtuzumab (CamPath), HuMax-CD4, several histone deacetylase inhibitors, and the transition-state inhibitor forodesine. These drugs, in combination with currently used therapies, may increase the number and combinations of therapies available for the treatment of this chronic condition to optimize long-lasting responses in CTCL.

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

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Optimal combination with PUVA: rationale and clinical trial update

Oncology (Williston Park). 2007 Feb

Stadler R.
Department of Dermatology, Medical Centre Minden, Germany. hautklinik@klinikum-minden.de

Cutaneous T-cell lymphoma (CTCL) is relatively benign in its early stages, but survival rates decrease dramatically as the disease progresses. As no curative therapies are currently available, the goal of therapy is preventing or delaying progression from early disease stages while minimizing long-term toxicity. No single agent, including psoralen plus ultraviolet A (PUVA), can control disease progression fully, so combination therapy is needed to improve response rates. In addition, low-dose combination therapy may improve treatment safety and tolerability. A combination of PUVA and interferon (IFN) alpha in early disease has been shown to be effective and well tolerated. Likewise, small studies of PUVA and bexarotene (Targretin) indicate good efficacy for this combination. Reduced doses of these combinations may also be effective as maintenance therapies following complete remission. Other treatment combinations shown to be effective in early disease stages include bexarotene with IFNalpha and bexarotene with denileukin diftitox (Ontak). In advanced stages of CTCL, liposomal-encapsulated doxorubicin or extracorporeal photopheresis may be combined with bexarotene or IFNalpha.

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

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Systemic monotherapy vs combination therapy for CTCL: rationale and future strategies.

Oncology (Williston Park). 2007 Feb

Duvic M.
Department of Dermatology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, USA. mduvic@mdanderson.org

There are few approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. For patients with early-stage disease, the oral retinoids can be combined with other therapies, such as psoralen plus ultraviolet A or interferon alpha, to improve response rates. Combined-modality therapy with oral retinoids, combined chemotherapy, electron-beam therapy, and topical mustargen has also proved effective. For the treatment of advanced-stage disease, the targeted therapy denileukin diftitox (Ontak) provides a nonimmunosuppressive alternative to conventional chemotherapy or radiation therapy. Of the conventional chemotherapies that have been tested in CTCL, gemcitabine (Gemzar) has demonstrated good efficacy in producing responses, particularly in patients with tumors. This agent can be used in combination with a maintenance therapy of bexarotene (Targretin) to manage the plaques and patches of mycosis fungoides. Several other targeted therapies are now also in testing, for example, alemtuzumab (CamPath), HuMax-CD4, several histone deacetylase inhibitors, and the transition-state inhibitor forodesine. These drugs, in combination with currently used therapies, may increase the number and combinations of therapies available for the treatment of this chronic condition to optimize long-lasting responses in CTCL.

http://www.ncbi.nlm.nih.gov/sites/entre ... stractPlus

[patoco]

Subcutaneous Panniculitic T-cell lymphoma

Med J Malaysia. 2006 Dec

Ng TG, Ayadurai K, Gangaram HB, Hussein SH.
Department of Dermatology, Hospital Kuala Lumpur, Jalan Pahang, 50586 Kuala Lumpur.

Subcutaneous panniculitic T-cell lymphoma (SPTL) is a rare variant of cutaneous T-cell lymphoma where lymphoma cells infiltrate preferentially into subcutaneous tissue. Five cases of SPTL were seen during the period from 2001-2004 at the Department of Dermatology, Hospital Kuala Lumpur. All five presented with multiple subcutaneous nodules on the face, trunk and limbs of one week to six months duration with associated fever and loss of weight. Physical examination showed multiple tender, erythematous indurated plaques and subcutaneous nodules on their face, trunk and limbs. One patient also presented with unhealing ulcerated nodules. Two patients had hepatosplenomegaly and one hepatomegaly. Two patients had pancytopaenia while the other three had leucopaenia. One patient had deranged liver function. Out of the five patients, three had bone marrow examination with haemophaegocytosis in two and one hypocellular marrow. Skin biopsy of all patients showed infiltration with atypical lymphoid cells in the upper dermis and subcutaneous fat. These neoplastic cells showed positivity for CD3 and CD30 in three patients with CD8, TIA-1 and LCA (Leucocyte common antigen) being positive in one patient. One patient treated with prednisolone and subcutaneous Roferon 3Mu three times a week since 2001 was in remission. Two patients who were planned for chemotherapy had deteriorated rapidly and succumbed to septicaemia from pancytopaenia. Subcutaneous panniculitic T-cell lymphoma has been reported to show two distinct clinical presentations. The first is characterized by an indolent course with good prognosis and the second with rapid clinical deterioration, haemophaegocytosis and death. Both presentations were seen in our five patients seem to demonstrate these two subtypes of SPTL.

PMID: 17623960 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/sites/entre ... d_RVDocSum

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Subcutaneous panniculitis-like T-cell lymphoma with hemophagocytic syndrome successfully treated with cyclosporin A.

Skinmed. 2006 Jul-Aug

Al Zolibani AA, Al Robaee AA, Qureshi MG, Al Nosian H.
College of Medicine, Qassim University, Buraidah, Saudi Arabia azolibani@yahoo.com

A 17-year-old girl previously in good health presented with a 2-month history of recurrent, high-grade fever; general fatigue; anorexia; a 10-kg weight loss; and multiple, painful, reddish skin lesions on the lower abdomen. Some lesions were ulcerated, with an oily yellowish brown discharge. A systemic review was unremarkable other than bleeding from the nose. Her medical and family histories were unremarkable. On examination, the patient was pale, jaundiced, and febrile (temperature of 39 degrees C). She had enlarged lymph nodes in the axillary and inguinal areas. There was moderate hepatosplenomegaly. Local skin examination revealed multiple erythematous, tender, and firm subcutaneous nodules of variable size (1-2 cm) on the lower abdomen. Some nodules were ulcerated, with oily yellowish brown discharge and overlying ecchymosis (Figures 1 and 2). Mucous membranes were free of lesions. Laboratory investigations showed pancytopenia, an elevated erythrocyte sedimentation rate (>80 mm/h), normal renal function tests, abnormal hepatic function tests (alanine aminotransferase 172 U/L, aspartate aminotransferase 229 U/L, alkaline phosphatase 725 U/L, and total bilirubin 100 mmol/L [normal range 0-18 mmol/L]), conjugated bilirubin 45 mmol/L (normal range 0-5 mmol/L), and high triglycerides 855 mg/dL (normal range 20-200 mg/dL). Prolonged prothrombin time, 26 seconds (normal range 13-16 seconds); prolonged activated partial thromboplastin time, 61 seconds (normal range 26-38 seconds); positive disseminated intravascular coagulation studies evidenced by low fibrinogen, 74 mg/dL (normal range 160-350 mg/dL); and positive fibrinogen degradation products were also noted. Throat, midstream urine, and blood culture results were negative. Serologic tests for syphilis, HIV, and hepatitis B and C viruses were negative. Epstein-Barr virus and cytomegalovirus serologic values revealed evidence of past infection. Tuberculin and Coombs tests were negative. The alpha1-antitrypsin level was normal. Antinuclear and anti-smith antibodies, rheumatoid factor, and cryoglobulins were negative. CT showed enlarged lymph nodes in the axillary and inguinal areas, bilateral small pleural effusion, moderate hepatosplenomegaly, severe fatty infiltration of the liver, and thickening of lower abdominal subcutaneous tissue. A liver biopsy showed steatohepatitis. Bone marrow aspirate and trephine were normal. A deep punch biopsy of a nodule from the right lower abdomen revealed lobular panniculitis with atypical lymphocytes and large macrophages with cytophagocytosis ("beanbag" cells) (Figures 3 and 4). Immunohistochemistry showed that these atypical cells were positive for CD3, CD8, granzyme B, and perforin, and negative for CD56. T-cell gene rearrangement studies on skin lesions revealed a monoclonal T-cell receptor (gamma-chain) gene rearrangement, supporting the diagnosis of subcutaneous panniculitis-like T-cell lymphoma. On presentation, the initial treatment included 6 U of fresh frozen plasma, 2 U of packed red blood cells, and 2 g IV fibrinogen for 3 consecutive days. The patient was started on prednisolone 60 mg orally once daily and cyclosporine A 5 mg/kg/d orally in two divided doses. The fever and other systemic symptoms and skin lesions resolved within 2 weeks after the treatment. The prednisolone dose was tapered gradually, and a maintenance dose of cyclosporine A was continued. The patient's condition remained in remission at 12-month follow-up; there was no evidence of clinical relapse.

PMID: 16855414 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/sites/entre ... stractPlus

[patoco]

Adult T-cell leukemia/lymphoma in an adolescent presenting with skin lesions.

Pediatr Dermatol. 2008 May-Jun

Lucas CT, Gillis KJ, Ness JM, Hammers YA, Crawford DF, Kelly DR, Theos A.
Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Adult T-cell leukemia/lymphoma is a T-cell malignancy caused by the human T-cell lymphotropic virus-I. Adult T-cell leukemia/lymphoma is primarily a disease of adults due to the long latency period between initial infection and development of leukemia. We present a case of acute adult T-cell leukemia/lymphoma in an adolescent. Skin lesions had appeared 3 years earlier and were the initial sign of human T-cell lymphotropic virus-I infection and T-cell malignancy. Her disease failed to respond to both intensive chemotherapy and antiviral therapy. Cutaneous lesions are sometimes the initial sign of adult T-cell leukemia/lymphoma and early recognition is imperative.

Blackwell Synergy

http://www3.interscience.wiley.com/jour ... 04902/home

Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma.

Leuk Lymphoma. 2008 Jun

Capriotti E, Vonderheid EC, Thoburn CJ, Wasik MA, Bahler DW, Hess AD.
Department of Dermatology, University of Rome, "Tor Vergata", Italy.

Keywords: Lymphoma; Szary syndrome; T-plastin; FoxP3; Mic-B; CD28; regulatory T-cell

Peripheral blood cells from 28 patients with leukemic cutaneous T-cell lymphoma including 25 patients with Sezary syndrome were evaluated for expression of regulatory T-cell-associated markers (FoxP3, CD25, CTLA-4, neurophilin-1), T-cell activation markers (CD28 and its ligands B7.1 and B7.2) and NK cell-associated markers (NKG2D and its ligands Mic-A and Mic-B) using real-time quantitative polymerase chain reaction. T-plastin served as a positive genetic marker, and its expression correlated to blood tumor burden. More than 90% of samples had transcripts for CD28 and Mic-B, but less than 30% of samples expressed FoxP3, CTLA-4 and CD25. Expression of Mic-B by neoplastic cells could provide another mechanism to inhibit anti-tumor immune responses. FoxP3 expression correlated with a poor prognosis. Although the underlying mechanisms accounting for this correlation remain unclear, the expression of the Foxp3 and CTLA-4 regulatory elements indicates that a subset of leukemic cases displays a regulatory T-cell phenotype.

InformaWorld

http://www.informaworld.com/smpp/conten ... 0802064917

Folliculotropic mycosis fungoides: an aggressive variant of cutaneous T-cell lymphoma.

Arch Dermatol. 2008 Jun

Gerami P, Rosen S, Kuzel T, Boone SL, Guitart J.
Department of Dermatology, Northwestern University Feinberg School of Medicine, and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois, USA.

OBJECTIVES: To study the clinical features, therapeutic responses, and outcomes in patients with folliculotropic mycosis fungoides (FMF) and to compare our single-center experience of 43 patients with the findings from the Dutch Cutaneous Lymphoma Group.

SETTING: A single-center experience from the Northwestern University Multidisciplinary Cutaneous Lymphoma Group.

PATIENTS: Forty-three patients with FMF were included in the study and compared with 43 age- and stage-matched patients with classic epidermotropic mycosis fungoides (MF) with similar follow-up time. RESULTS: Folliculotropic mycosis fungoides showed distinct clinical features, with 37 patients having facial involvement (86%) and only 6 having lesions limited to the torso (14%). The morphologic spectrum of lesions is broad and includes erythematous papules and plaques with follicular prominence with or without alopecia; comedonal, acneiform, and cystic lesions; alopecic patches with or without scarring; and nodular and prurigolike lesions. Sixty-five percent of patients had alopecia, which in 71% of cases involved the face. Severe pruritus was seen in 68% of patients. In general, patients responded poorly to skin-directed therapy and in almost all cases required systemic agents to induce even a partial remission, including patients with early-stage disease. Overall survival was poor. Patients with early-stage disease (< or =IIA) had a 10-year survival of 82%, which took a steep drop off to 41% by 15 years. Patients with late-stage disease (> or =IIB) had an outcome similar to those patients in the control group with conventional epidermotropic MF of a similar stage.

CONCLUSIONS: The morphologic spectrum of clinical presentation for FMF is broad and distinct from those in conventional MF. This is at least partially attributed to the ability of FMF to simulate a variety of inflammatory conditions afflicting the follicular unit. The disease course is aggressive, and many patients, including those with early disease, show a poor outcome particularly between 10 and 15 years after the initial onset of disease. Response to skin-directed therapy is poor even in early-stage disease, and our best results were seen with psoralen plus UV-A (PUVA) therapy with oral bexarotene or PUVA with interferon alfa. These findings corroborate those of the Dutch Cutaneous Lymphoma Group and further validate the classification of FMF as a distinct entity.

Archiveds of Dermatology

http://archderm.ama-assn.org/cgi/content/full/144/6/738

Clinical and in vitro resistance to bexarotene in adult T cell leukemia: loss of RXR-alpha receptor.

Blood. 2008 Jun 16.

Lin JH, Kim EJ, Bansal A, Seykora J, Richardson SK, Cha XY, Zafar S, Nasta S, Wysocka M, Benoit B, Rook AH, Fakharzadeh SS.
Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, United States.

The oral rexinoid, bexarotene (Targretin), is widely used for treatment of cutaneous T-cell lymphomas (CTCL). We recently reported the first case of adult T-cell Leukemia/Lymphoma (ATLL) that rapidly responded to combination therapy of bexarotene and interferon (IFN)-alpha2b with complete clinical response.(1) We demonstrated that bexarotene induced apoptosis of the patient's malignant peripheral blood T-cells in vitro. However, our patient developed skin and nodal relapse 180 days after starting treatment. We now demonstrate that his peripheral blood malignant T-cells became resistant to bexarotene-induced apoptosis. We investigated potential mechanisms that may cause aberrations in the RXR receptor subunits, RXR-alpha and RXR-beta, to account for these findings. Sequence analysis did not reveal acquisition of mutations in the genes encoding RXR-alpha and RXR-beta by resistant cells. We assessed RXR-alpha and RXR-betaexpression by Western blot analysis and found that resistant cells had significantly decreased RXR-alpha expression compared to pre-therapy bexarotene-sensitive cells. Our findings indicate that reduced expression of the RXR-alpha receptor subunit may represent a mechanism for resistance to bexarotene in T-cell malignancies.

Blood

http://bloodjournal.hematologylibrary.o ... 3-141424v1

Transformation of cutaneous gamma/delta T-cell lymphoma following 15 years of indolent behavior.

J Cutan Pathol. 2008 Jun 9

Hosler GA, Liégeois N, Anhalt GJ, Moresi JM.
Department of Dermatology, Johns Hopkins University, Baltimore, MD, USA.

Subcutaneous gamma/delta (gamma/delta) T-cell lymphoma is a rare lymphoma, characterized by its unique immunophenotype and clinical course. It has been shown to behave more aggressively than its counterpart bearing the alpha/beta receptor and has recently been removed from the subcutaneous panniculitis-like T-cell lymphoma category for this very reason. We present a case of a patient with a 15-year running diagnosis of panniculitis. Following these years of indolent behavior, the disease began an aggressive clinical course and she was diagnosed with gamma/delta T-cell lymphoma. Molecular analysis identified a T-cell clone, which through retrospective analysis, was also shown to be present in the patient's original biopsy material. We present this case as a rare example of initial indolent behavior in a lymphoma typically considered very aggressive.

http://www3.interscience.wiley.com/jour ... 7/abstract

[patoco]

Emerging drugs in cutaneous T cell lymphoma.

Expert Opin Emerg Drugs. 2008 Jun

Mestel DS, Assaf C, Steinhoff M, Beyer M, Moebs M, Sterry W.
Charité Universitaetsmedizin Berlin, Skin Cancer Center, Department of Dermatology and Allergy, Charitéplatz 1, DE-10117 Berlin, Germany.

Key Words: alemtuzumab; belinostat; bexarotene; bortezomib; CTCL; denileukin diftitox; forodesine; gemcitabine;
histone; deacetylase inhibitors; mycosis fungoides; panobinostat; pegylated liposomal doxorubicin; proteasome inhibitors;
romidepsin; Sézary syndrome; vorinostat; zanolimumab

BACKGROUND: Mycosis fungoides (MF) represents the most common type of primary cutaneous T cell-lymphomas (CTCL), which are characterized by a clonally proliferation of malignant CD4+ lymphocytes in the skin.

OBJECTIVE: Skin-directed treatment regimens, like phototherapy and corticosteroids, are commonly used in early stages; systemic treatments and chemotherapies are used in advanced stages. Because conventional treatments usually end in a transient remission without curative results, there is a high need for new therapeutic strategies with acceptable side effects.

METHODS: Literature and reference research was done by using the data bank PubMed, and updates of ongoing studies were taken out of ASCO and ASH annual meeting abstracts.

RESULTS/CONCLUSIONS: This article gives an overview of the various medications in current use, with emphasis on emerging drugs with novel therapeutic targets.

Expert Opinion

http://www.expertopin.com/doi/abs/10.15 ... 4.13.2.345