Cutaneous B-Cell Lymphoma and Lymphedema

[patoco]

Cutaneous B-Cell Lymphoma and Lymphedema - Is There A Connection

Our Home Page: Lymphedema People

http://www.lymphedemapeople.com

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Primary cutaneous B-cell lymphoma of the leg in a chronic lymphedematous extremity.

Torres-Paoli D, Sanchez JL.

Department of Dermatology, University of Puerto Rico, School of Medicine, San Juan 00936-5067, USA.

This is a case report of a woman who had chronic lymphedema on one leg and who developed a primary cutaneous large B-cell lymphoma of the leg at that site. She received radiotherapy and did not show any systemic involvement thereafter. Other neoplasms may appear in a clinical setting of chronic lymphedema, namely, lymphangiosarcoma (Stewart-Treves), melanoma, and metastatic carcinoma. There are four other reports in the English literature of cutaneous lymphoma arising in an extremity with chronic lymphedema.

Publication Types:
Case Reports
Review
Review of Reported Cases

MeSH Terms:
Aged
Aged, 80 and over
Chronic Disease
Combined Modality Therapy
Female
Humans
Leg
Lymphedema/complications*
Lymphedema/pathology
Lymphedema/therapy
Lymphoma, B-Cell/etiology*
Lymphoma, B-Cell/pathology
Lymphoma, B-Cell/therapy
Lymphoma, Large-Cell/etiology*
Lymphoma, Large-Cell/pathology
Skin Neoplasms/etiology*
Skin Neoplasms/pathology
Skin Neoplasms/therapy

PMID: 10871070 [PubMed - indexed for MEDLINE]

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

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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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Primary cutaneous large B-cell lymphoma: the relation between morphology, clinical presentation, immunohistochemical markers, and survival.

Fernandez-Vazquez A, Rodriguez-Peralto JL, Martinez MA, Platon EM, Algara P, Camacho FI, Lopez-Rios F, Zarco C, Sanchez-Yus E, Fresno MF, Barthe L, Aliaga A, Fraga M, Forteza J, Oliva H, Piris MA.

Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas, Madrid, Spain.

The histogenesis, morphology, immunophenotype, and clinical behavior of cutaneous large B-cell lymphomas (CLBCL) are largely a matter of controversy. We performed an investigation to determine whether CLBCL have features that differentiate them from other large B-cell lymphomas and whether CLBCL is itself a heterogeneous group. To this end, we reviewed the main characteristics of a series of 32 cases of LBCL found in the skin. We reviewed the clinical findings and paraffin sections of the tumors from these 32 patients. The immunohistochemical study performed included p53, MIB1, Bcl2, Bcl6, and CD10 markers. We carried out statistical analysis of these data (univariate and multivariate), seeking an association between the features of the tumors and clinical outcome, as defined by failure-free survival time. Only one patient died as a consequence of the lymphoma. Nevertheless, the accumulated probability of survival without failure at 48 months was 0.46. The number, type, and localization of the lesions were not associated with variations in either survival or failure-free survival. The expression of p53 was negative in this group of CLBCL, whereas Bcl-2 expression or localization in the lower leg did not relate to any other significant feature. Histologic examination of the cases disclosed three different groups: Grade III follicular lymphomas (FLs), monomorphous large B-cell lymphomas (LBCL type I), and LBCL with an admixed component of small B-lymphocytes (LBCL type II). Grade III FL (11 cases) tended to be found in the head and neck and showed CD10 expression in a majority of cases. A higher probability of lymph node relapses was associated with cases located in the head and neck and with CD10+ tumors. Cutaneous large B-cell lymphomas are indolent tumors, but follow an insidious course. Our data support the interpretation that CLBCL is a heterogeneous condition; comprises some LBCL derived from CD10+ germinal center cells which manifests more frequently as tumors in the head and neck region, with an increased probability of relapse in lymph nodes [1] and has some distinctive morphologic features. The existence of a component of small B-cells within the other CLBCL could lend support to the theory that some of these tumors, more than arise de novo, may have originated in preexistent small B-cell lymphomas, but no firm evidence of this is provided in this study.

PMID: 11224600 [PubMed - indexed for MEDLINE]

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

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Cutaneous B-cell lymphoma: pathological spectrum and clinical outcome in 51 consecutive patients.

Sah A, Barrans SL, Parapia LA, Jack AS, Owen RG.

HMDS, Leeds General Infirmary, Leeds, United Kingdom. anitasah@doctors.org.uk

The clinical behavior and optimal treatment of patients presenting with skin infiltration by B-cell lymphoma have not been established. To clarify this we assessed the clinical and laboratory features of 51 patients presenting with cutaneous infiltration by B-cell lymphoma. Follow-up data was available for 46 patients with a median age of 68 years (range 16-89 years) and a median follow-up of 32.5 months (range 5-123 months). Thirty-three of 51 (65%) patients had diffuse large B-cell lymphoma (DLBCL), and 15/51 (29%) had marginal zone lymphoma (MZL). The remaining 3 patients had follicular lymphoma, CLL, and post-transplant lymphoproliferative disease. Of the 33 patients with DLBCL, follow-up was available in 29; 24/29 (83%) had primary cutaneous disease, which was unifocal in 17/24 (71%). Following treatment, 8/24 (33%) of the primary cases relapsed. Of the 8 who relapsed, 7 had received local forms of treatment only. Follow-up data was available in 14/15 patients with MZL. 11/14 (79%) had primary cutaneous disease, which was unifocal in 8 (73%). Following treatment, 4 of these cases relapsed (36%); all had received local therapy only. It is evident from this study that a significant proportion ( reverse similar 20%) of patients who present with cutaneous infiltration by B-cell lymphoma have systemic disease. Staging is therefore mandatory in these patients. Approximately 1/3 patients with primary cutaneous DLBCL or MZL ultimately relapse, and relapse rates appear higher in those patients receiving local therapy only. Systemic or combined modality therapy may therefore be the most appropriate treatment at presentation. This should be assessed prospectively in randomized trials. Copyright 2004 Wiley-Liss, Inc.

PMID: 15054808 [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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American Cancer Society

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The Cancer Council Australia

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ACOR.ORG - Association of Cancer Online Resources

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The Cancer Information Network

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Cancer Prevention Resource Guide - Medical Transcription.net

ttp://www.medicaltranscription.net/reso ... rce-guide/

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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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Good Information on B-Cell Lymphomas:

Lymphoma, B-Cell
Last Updated: January 10, 2005 Rate this Article
Email to a Colleague

Synonyms and related keywords: non-Hodgkin lymphoma, NHL, lymph node, lymphoid tissue, indolent lymphomas, aggressive lymphomas, Burkitt lymphoma, B-cell neoplasms, T/NK-cell neoplasms, Hodgkin lymphoma, Hodgkin's lymphoma, B-cell chronic lymphocytic leukemia, CLL, B-cell CLL, B-cell small lymphocytic lymphoma, lymphoblastic lymphomas, T-cell acute lymphocytic leukemias, diffuse large B-cell lymphoma, follicular lymphoma, follicular large cell lymphoma, mantle cell NHL, small lymphocytic lymphoma, splenic marginal zone lymphoma, extranodal B-cell lymphoma of mucosa-associated lymphoid tissue, MALT, mediastinal diffuse large B-cell lymphoma, indolent NHL, lymphoproliferative malignancy, lymphoproliferative disease, Revised European-American Lymphoma Classification, REAL Classification, immunocytoma, mycosis fungoides, Sézary syndrome, lymphadenopathy, Waldeyer ring, bcl-2 apoptotic inhibitor oncogene

http://www.emedicine.com/med/topic1358.htm

and also at:

Up To Date Patient Information

Lymhoma

http://patients.uptodate.com/topic.asp? ... homa/18381

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For information about Lymphedema

http://www.lymphedemapeople.com/thesite ... hedema.htm

For Information about Lymphedema Complications

http://www.lymphedemapeople.com/thesite ... ations.htm

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Primary cutaneous B-cell lymphoma (low-grade, non large cell).

Dermatol Online J. 2007 Jan

Moore MM, Kovich OI, Brown LH.
New York University Department of Dermatology, USA.

A 43-year-old man presented with erythematous, indurated plaques on the scalp in the setting of a 16-year history of recurrent cutaneous tumors of the head and trunk. Clinical and histopathologic findings were consistent with a diagnosis of primary cutaneous B-cell lymphoma. Laboratory data and computed tomography imaging of the chest, abdomen, and pelvis failed to show an associated systemic lymphoma. Primary cutaneous B-cell lymphomas are a heterogenous group of lymphomas that primarily involve the skin but have variable clinical, histopathologic, and immunologic phenotypes. Successful treatment for most localized subtypes consists of surgical excision and radiation therapy. Rituximab, a chimeric monoclonal antibody that binds the B-cell-specific antigen CD20, has shown promise in treating a number of primary cutaneous B-cell lymphomas.

PMID: 17511941 [PubMed - in process]

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

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The expression of CD23 and CD40 in primary cutaneous B-cell lymphomas

J Cutan Pathol. 2007 Jun

Magro C.
Department of Pathology, Weill Medical College of Medicine, NY 10021, USA. cym2003@med.cornell.edu

BACKGROUND: CD23 expression in normal B lymphocytes is limited to autoreactive B cells, naïve B cells and mature B cells manifesting an activated phenotype. As a marker of hematologic dyscrasia/malignancy, expression of CD23 is associated with small lymphocytic lymphoma/chronic lymphocytic leukemia. An absence of CD23 expression within small lymphocytes is typically seen in marginal zone lymphoma and mantle cell lymphoma. Positive CD23 expression amidst neoplastic cells in primary cutaneous B-cell lymphoma is not a reported phenomenon. METHODS: This paper reports nine patients with cutaneous B-cell lymphoma manifesting CD23 expression.

RESULTS: In seven of the nine cases CD23 expression was observed in the setting of recurrent disease, being present in both large and small lymphocytes. CD23 expression paralleled staining for CD40 in all but one case.

CONCLUSIONS: A potential mechanism of CD23 upregulation may involve the anti-apoptotic nuclear kappa beta CD40-CD40 ligand pathway. Neoplastic B cells manifesting CD23 expression could have a survival advantage, predisposing to recurrent disease and or oncogenic events permissive to disease progression.

http://www.blackwell-synergy.com/doi/ab ... 06.00653.x

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Primary cutaneous large B-cell lymphoma in chronic venous leg ulcer

Ann Dermatol Venereol. 2007 Apr

Cendras J, Sparsa A, Bedane C, Delage M, Touati M, Bonnetblanc JM.
Service de Dermatologie, CHU Dupuytren, Limoges Cedex.

BACKGROUND: Large B-cell lymphoma of the leg in elderly subjects, of intermediate prognosis according to the new EORTC classification, may present as nodular or ulcerated forms. There has been relatively little study of the various etiological hypotheses advanced, including venous insufficiency. We report the case of an elderly man with chronic leg ulcer, recently undergoing modification, in which microscopy revealed large B-cell lymphoma (CD20-).

PATIENTS AND METHODS: A 78 year-old man presented chronic ulcer of the right leg of mixed origin with severe venous insufficiency and arteritis. In the previous 2 months, 2 nodules appeared in the centre of the ulcer. Histological examination of a skin biopsy revealed the presence of large B-cell lymphoma and immunohistochemical analysis showed positive anti-CD79a+, CD20- antibody labeling of cells. Staging studies showed only locoregional invasion. Because of the positive CD20- labeling, ZEM chemotherapy (idarubicine, cyclophosphamide, prednisolone) was given, resulting in disappearance of the nodules after four months and preliminary epidermal healing of the ulcer. Several months later, severe infectious complications necessitated amputation. Examination of the excised sample showed no residual tumor.

DISCUSSION: Many causal links have been proposed between large B-cell lymphoma of the leg and aetiologies such as infectious agents, Koebner phenomenon and chronic lymphedema, as well as various other vascular factors. A number of hypotheses were proposed in the present case. It may have been leg ulcer cutaneous B-cell lymphoma, or, more likely, development of lymphoma on a chronic mixed ulcer, with the respective roles of vascular disease, local immunosuppression and antigenic stimulation subject to debate.

http://www.masson.fr/masson/portal/book ... Locations=

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Bcl-2 expression in rituximab refractory cutaneous B-cell lymphoma

Wobser M, Voigt H, Eggert AO, Houben R, Kauczok CS, Bröcker EB, Becker JC.
Department of Dermatology, University of Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg, Germany.

Keywords: cutaneous B-cell lymphoma (CBCL); rituximab; RKIP; bcl-2

Rituximab has been established as an effective and safe therapy for cutaneous B-cell lymphoma (CBCL). Different survival pathways, that is the Raf/MEK/Erk- or the p38MAPK cascade, have been suggested as downstream mediators of rituximab and may be involved in treatment failure.

Biopsies from four patients, suffering from different subtypes of CBCL, which were obtained at various time points of relapse during or after therapy with 375 mg rituximab per m2 of body surface area, were analysed for the expression of CD20, CD3, Ki-67, Raf-kinase inhibitory protein (RKIP) and bcl-2 by immunohistochemistry. No CD20-loss variants, that is the suggested main tumour escape mechanism to rituximab therapy, were observed in any specimen of relapsing CBCL. Notably, the expression of proapoptotic RKIP remained increased in these tumour samples.

This was concomitated by a constant to slightly reduced proliferation status as demonstrated by Ki-67 staining. However, relapsing CBCL exhibited a strong upregulation of the antiapoptotic molecule bcl-2 in comparison to pretherapeutic levels. The immunohistochemical analyses of this case series of rituximab refractory CBCL suggest that upregulation of bcl-2 may play a major role in therapy resistance.

http://www.nature.com/bjc/journal/v96/n ... FA24CDD728

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Primary cutaneous lymphoma: local control and survival in patients treated with radiotherapy.

Anticancer Res. 2007 Jan-Feb

De Sanctis V, Osti MF, Berardi F, Ardito F, Valeriani M, Martelli M, Enrici RM.
Radiotherapy Oncology, Department of Radiology, Università di Roma La Sapienza, Roma, Italy. vitaliana.desanctis@uniroma1.it

BACKGROUND: The treatment of primary cutaneous lymphoma is still ongoing and the role of radiotherapy, as exclusive or combined modality, is not yet clear.

MATERIALS AND METHODS: From 1994 to June 2004, 29 patients with cutaneous B-cell lymphoma and 9 patients with cutaneous T-cell lymphoma were treated by radiotherapy (median dose of 3900 cGy, range 600-4600 cGy). Eight patients had previously received chemotherapy.

RESULTS: The complete response rate was 94.7% with progressive disease in two patients (5%). Sixteen (42.1%) patients relapsed, with the relapse occurring only in the skin site as single episode (9 patients) and more than two episodes (7 patients). The 5-year overall survival and event-free survival were 94% and 53%, respectively.

CONCLUSION: Radiotherapy offers a substantial local control of primary cutaneous lymphoma, both as exclusive or combined approach. The patients with wide-spread or multiple lesions, usually candidates for radiotherapy and chemotherapy, are amenable to radiotherapy alone.

PMID: 17348448 [PubMed - indexed for MEDLINE]

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

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High frequency of primary cutaneous lymphomas associated with lymphoproliferative disorders of different lineage

Ann Hematol. 2007 Jul

Hallermann C, Kaune Kjell M, Tiemann M, Kunze E, Griesinger F, Mitteldorf C, Bertsch HP, Neumann C.
Department of Dermatology, University of Goettingen, Goettingen, Germany.

Keywords: Cutaneous T-cell lymphoma, Hairy cell leukemia, Sézary syndrome

In patients suffering from primary cutaneous lymphomas, secondary malignancies of various origin may develop. However, the frequency of a second neoplasm deriving from another lymphoid lineage is still unclear and may be underestimated. We screened all our patients with primary cutaneous lymphomas from a 4-year recruitment period for a coexisting secondary lymphoproliferative disorder. The cohort comprised of a total of 82 patients with primary cutaneous lymphomas, 62 with primary cutaneous T-cell lymphoma (CTCL), 18 with primary cutaneous B-cell lymphomas, and two with CD4+/CD56+ hematodermic neoplasm/blastic lymphomas. Seven patients (8.5%) were identified with a coexisting lymphoma of a different lymphoid lineage. Four patients with Sézary syndrome (SS) suffered from systemic B-cell lymphoma. Two of these developed SS after chemotherapy of their B-cell lymphoma. The other three patients with various types of skin lymphomas (SS, Mycosis fungoides [MF], primary cutaneous marginal zone lymphoma) developed Hodgkin's disease (hairy cell leukemia). Our data indicate that patients with primary cutaneous lymphomas have an elevated risk for the development of a secondary lymphoproliferative disorder even without previous chemotherapy. Possible explanations for this association include a genetic predisposition, alterations in early progenitor cells, underlying viral infections, and/or stimulation of a B-cell clone by the malignant helper T cells of the primary CTCL and vice versa

http://www.springerlink.com/content/r53m651262687650/

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New prognostic relevant factors in primary cutaneous diffuse large B-cell lymphomas.

J Am Acad Dermatol. 2007 Apr

Hallermann C, Niermann C, Fischer RJ, Schulze HJ.
Department of Dermatology, Institute for Tumors of the Skin, Munster, Germany. christian.hallermann@fachklinik-hornheide.de

Abbreviations used: ABC, activated B cell, DSS, disease-specific survival, EORTC, European Organization for Research and Treatment of Cancer, GC, germinal center, LBCL, large B-cell lymphoma, LBCL-L, large B-cell lymphoma, leg type, LFCL, follicle center lymphoma, OS, overall survival, PCDLBCL, primary cutaneous diffuse large B-cell lymphoma, WHO, World Health Organization

BACKGROUND: There is a growing body of literature that has enhanced our understanding of the biology of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) including in the context of gene profiling studies. Recent studies have demonstrated an activated proliferation profile associated with leg type lymphoma including overexpression of proto-oncogenes PIM1, PIM2, and cMYC, and the transcription factors MUM1 and OCT2. Although gene profiling is very useful in understanding the molecular basis of diffuse large B-cell lymphoma (LBCL), it is not practical from a routine diagnostic perspective.

In this regard, the purpose of the study was to further define an armamentarium of easily applied immunohistochemical stains to accurately prognosticate PCDLBCL.

METHODS: In all, 35 patients with PCDLBCL, 14 of follicle center and 21 of leg type, were analyzed using antibodies against CD5, CD138, BCL2, BCL6, OCT2, MUM1, FOXP1, and cMYC. Findings were correlated with clinical data. RESULTS: All cases stained negative for CD5 and CD138. Both subtypes differed in distinct staining patterns for BCL6, BCL2, OCT2, MUM1, and FOXP1. Staining for BCL2, OCT2, and/or MUM1 was associated with poor, and BCL6 with a favorable prognosis. Expression of cMYC was irrespective of prognosis or subtype, whereas ulceration or primary manifestation on the leg or multiple lesions was indicative for worse prognosis.

LIMITATIONS: Case number was a limitation. CONCLUSION: Discriminating PCDLBCL supports the validity of the World Health Organization/European Organization for Research and Treatment of Cancer classification. To identify risk factors in patients with PCDLBCL we recommend thorough evaluation of clinical presentation and exploratory staining pattern for BCL2, BCL6, MUM1 and OCT2.

http://www.eblue.org/article/PIIS019096 ... 7/abstract

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Cutaneous sarcomatoid B-cell lymphoma

Am J Dermatopathol. 2007 Feb

Ries S, Barr R, LeBoit P, McCalmont T, Waldman J.
Department of Pathology, Memorial Medical Center of Long Beach, Long Beach, CA, USA. sries@memorialcare.org

A rare case of a spindle cell (sarcomatoid) B-cell lymphoma is described. The patient, a 48-year-old male, presented with a several month history of an enlarging lesion on the scalp. Although there have been a few recent reports of cutaneous sarcomatoid lymphomas, this case is especially unusual because it presented as a scarlike plaque rather than a tumor and microscopically exhibited a prominent myxoid matrix. Given these features, the lesion was initially interpreted as an atypical fibromucinosis.

The differential diagnosis included fibromucinous lesion consistent with variant of lichen myxedematosus, spindle cell carcinoma, spindle cell melanoma, atypical fibroxanthoma, and atypical smooth muscle tumors.

Initial immunoperoxidase studies demonstrated negative staining for CD68, factor XIIIa, CD57, cytokeratin(AE1/AE3), S100, EMA, and vimentin, essentially ruling out the previously mentioned neoplasms. Subsequently, strong positive staining for LCA(CD45RB) and CD20 was demonstrated characteristic of a B-cell lymphoma.

The patient underwent local radiotherapy with complete resolution. Although all variants of cutaneous sarcomatoid B-cell lymphomas are rare, it is imperative to consider them in the differential diagnosis of otherwise difficult to categorize spindle cell proliferations. This includes neoplasms and, based on the current case, fibromucinoses as well.

http://www.amjdermatopathology.com/pt/r ... 29!8091!-1

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Reclassification of 300 primary cutaneous B-Cell lymphomas according to the new WHO-EORTC classification for cutaneous lymphomas: comparison with previous classifications and identification of prognostic markers

J Clin Oncol. 2007 Apr

Senff NJ, Hoefnagel JJ, Jansen PM, Vermeer MH, van Baarlen J, Blokx WA, Canninga-van Dijk MR, Geerts ML, Hebeda KM, Kluin PM, Lam KH, Meijer CJ, Willemze R.
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands. N.J.Senff@LUMC.nl

PURPOSE: In the new WHO-European Organisation for Research and Treatment of Cancer (WHO-EORTC) classification for cutaneous lymphomas three major groups of primary cutaneous B-cell lymphoma (CBCL) are distinguished: primary cutaneous marginal zone B-cell lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) with a good prognosis, and primary cutaneous large B-cell lymphoma, leg type (PCLBCL-LT), with an intermediate-level prognosis. This study aimed to assess the clinical significance of the new classification compared with previous classification schemes (EORTC 1997; WHO 2001) and to define prognostic factors within the newly defined categories.

PATIENTS AND METHODS: In the present study clinical data and histologic sections of 300 patients with CBCL, formerly classified according to the EORTC classification, were reviewed and reclassified according to the WHO and the new WHO-EORTC classification schemes. RESULTS: After reclassification, the study comprised 71 patients with PCMZL, 171 patients with PCFCL, and 58 patients with PCLBCL-LT, showing 5-year disease-specific survivals of 98%, 95%, and 50%, respectively. When compared with the EORTC and WHO schemes, 5.3% and 36.3% of patients with CBCL were reclassified into another prognostic category. Multivariate analysis of PCFCL revealed localization on the leg and expression of FOXP1 as independent parameters associated with a poor prognosis. Expression of Bcl-2 or MUM-1 had no significant effect on survival in this group. In PCLBCL-LT, no independent prognostic parameters were found.

CONCLUSION: These results emphasize the clinical significance of the WHO-EORTC classification, but suggest that within the group of PCFCL, distinction should be made between lymphomas presenting on the legs and lymphomas presenting at other sites.

http://jco.ascopubs.org/cgi/content/abstract/25/12/1581

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Three coexisting lymphomas in one patient: genetically related or only a coincidence?

J Clin Pathol. 2006 Dec

Steinhoff M, Assaf C, Anagnostopoulos I, Geilen CC, Stein H, Hummel M.
Department of Dermatology and Allergy, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany. matthias.steinhoff@charite.de

Abbreviations: ALPS, autoimmune lymphoproliferative syndrome; APAAP, alkaline phosphatase anti-alkaline-phosphatase; cHL, classic Hodgkin’s lymphoma; EBV, Epstein–Barr virus; HRS, Hodgkin’s and Reed–Sternberg; IgH, immunoglobulin H; MZBL, marginal zone B cell lymphoma; TCL, T cell lymphoma; TCR, T cell antigen receptor

The simultaneous manifestation of different lymphomas in the same patient or even in the same tissue, defined as composite lymphoma, is very rare. The exceptional case of a patient who, presented with simultaneous manifestation of three different lymphomas after 30 years of successful treatment of a nodal T cell lymphoma is reported here.

The three lymphomas were: (1) primary cutaneous marginal zone B cell lymphoma (MZBL); (2) nodal Epstein-Barr virus (EBV)-associated classic Hodgkin's lymphoma (cHL) of the B cell type; and (3) peripheral T cell lymphoma coexisting in the skin and cervical lymph node.

Immunohistochemical and molecular analyses showed different clonal origins of EBV-negative cutaneous MZBL and EBV-positive B cell cHL and, in addition, the presence of the same clonal T cell population in the skin and lymph node. The simultaneous occurrence of three different, clonally unrelated lymphomas in one patient at the same time has not been reported yet.

http://jcp.bmj.com/cgi/content/abstract/59/12/1312

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Pat O'Connor
Lymphedema People
http://www.lymphedemapeople.com

[patoco]

De novo CD5-positive diffuse large B-cell lymphoma of the skin arising in chronic limb lymphedema.

Dargent JL, Lespagnard L, Feoli F, Debusscher L, Greuse M, Bron D.
Department of Pathology, CHU Saint-Pierre and Institut Jules Bordet, Brussels, Belgium. jean.dargent@bordet.be

Keywords: Skin; lymphedema; diffuse large B-cell lymphoma; CD5

We report the case of a 79-year-old woman with a longstanding lymphedema of the right arm who developed a skin lymphoma involving the right wrist area. Microscopically, the lesion was composed of numerous centroblasts infiltrating both the dermis and the subcutaneous tissue. Phenotypic investigations showed expression of CD20, CD79a, and bcl-2 protein by neoplastic cells. In addition, these cells were CD5 positive. No expression of anaplastic large cell lymphoma kinase (ALK), CD10, CD23, CD30, CD43, bcl-6, cyclin D1, p53 or p16INK4a could be seen. Polymerase chain reaction (PCR) analysis demonstrated a clonal rearrangement of the genes coding for the kappa light chain of the immunoglobulin (Ig). No rearrangement of the genes coding for the Ig heavy chain, t(14;18) or t(11;14) chromosome translocations, or Epstein-Barr virus (EBV) genomic sequences could be found. The tumor was classified as stage IE and was first cured by complete surgical excision. Nineteen months later, a recurrence was noted in the right elbow area. This study further illustrates that lymphoma of the skin may complicate chronic limb lymphedema. Like most of the previously reported cases, this neoplasm belonged to the category of diffuse large B-cell lymphoma. However, it showed CD5 expression as a singular feature.

http://www.informaworld.com/smpp/conten ... 0500051208

[patoco]

Primary cutaneous B-cell lymphomas - Clinicopathological, prognostic and therapeutic characterisation of 54 cases according to the WHO-EORTC classification and the ISCL/EORTC TNM classification system for primary cutaneous lymphomas other than mycosis fungoides and Sezary syndrome.

Leuk Lymphoma. 2008 Jun

Golling P, Cozzio A, Dummer R, French L, Kempf W.
Department of Dermatology, Cutaneous Lymphoma Study Group, University Hospital, Zurich, Switzerland.

Keywords: Cutaneous; lymphoma; B cell; staging; therapy

Clinical, prognostic and therapeutic features of 54 primary cutaneous marginal zone B-cell lymphoma (pcMZL), follicle centre lymphoma (pcFCL) and diffuse large B-cell lymphoma, leg type (pcDLBL) were analysed applying the WHO-EORTC classification for cutaneous lymphomas and the new TNM staging scheme of the International Society of Cutaneous Lymphomas. Solitary (T1) or regionally clustered (T2) tumors were observed in pcMZL and pcFCL. Disseminated tumors (T3 stage) were found in 26% of patients with pcMZL and in one patient with pcDLBL. A complete remission was achieved in 41% of the patients. Three of 7 patients (43%) with pcDLBL died due to lymphoma.

The new TNM staging system is easily applicable for disease documentation, but our relatively small number of patients in each T stage does not allow the assessment of its prognostic value. Surgical excision or radiotherapy is highly effective in pcMZL and pcFCL.

InformaWorld

http://www.informaworld.com/smpp/conten ... 0802064925

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European Organization for Research and Treatment of Cancer (EORTC) and International Society for Cutaneous Lymphoma (ISCL) consensus recommendations for the management of cutaneous B-cell lymphomas.

Blood. 2008 Jun 20

Senff NJ, Noordijk EM, Kim YH, Bagot M, Berti E, Cerroni L, Dummer R, Duvic M, Hoppe RT, Pimpinelli N, Rosen ST, Vermeer MH, Whittaker S, Willemze R.
Dept. of Dermatology, Leiden University Medical Center, Leiden, Netherlands.

Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20-25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) consensus classification for cutaneous lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms was introduced.

However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centres, which may be due to the fact that consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the three main groups of CBCL.

Since no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state of the art management as currently practised in major cutaneous lymphoma centres. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL.

http://bloodjournal.hematologylibrary.o ... 4-152850v1