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Anetodermic Primary Cutaneous B-Cell Lymphoma:  A Unique Clinicopathological Presentation of Lymphoma Possibly Associated With Antiphospholipid Antibodies FREE

Emmilia Hodak, MD; Hana Feuerman, MD; Aviv Barzilai, MD; Michael David, MD; Lorenzo Cerroni, MD; Meora Feinmesser, MD
[+] Author Affiliations

Author Affiliations: Department of Dermatology (Drs Hodak, Feuerman, and David) and Institute of Pathology (Dr Feinmesser), Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; Department of Dermatology, Sheba Medical Center, Tel Hashomer, Israel (Dr Barzilai); Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (Drs Hodak, Feuerman, Barzilai, David, and Feinmesser); and Department of Dermatology, University of Graz, Graz, Austria (Dr Cerroni).


Arch Dermatol. 2010;146(2):175-182. doi:10.1001/archdermatol.2009.340.
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Background  Primary cutaneous B-cell lymphoma manifested by anetoderma has been reported in 7 cases. In all, the secondary anetoderma developed in lesions of marginal-zone lymphoma or posttransplant lymphoproliferative disorder resembling marginal-zone lymphoma. The mechanisms underlying the destruction of elastic tissue in anetoderma are unclear. However, there is growing evidence linking primary anetoderma with a wide range of immunologic abnormalities, the most common being the presence of antiphospholipid antibodies.

Observations  We analyzed data from 5 patients (3 male, 2 female) with clinical and histopathological features of anetodermic primary cutaneous B-cell lymphoma. Three had marginal-zone lymphoma and 2 had follicle-center cell lymphoma. In all, secondary anetoderma developed in self-regressing nodules/plaques of the lymphoma. Two patients also had lesions clinically and histopathologically compatible with primary anetoderma. Associated immunologic diseases were systemic lupus erythematosus–like disease and rheumatoid arthritis (1 patient each; not in patients with primary anetoderma). Antiphospholipid antibodies were found in 4 patients.

Conclusions  Anetodermic primary cutaneous B-cell lymphoma is a rare and unique clinicopathological manifestation not only of marginal-zone lymphoma, as previously described, but also of follicle-center cell lymphoma. This type of secondary anetoderma, like primary anetoderma, might be associated with immunologic disorders, particularly antiphospholipid antibodies.

Figures in this Article

Anetoderma, derived from the Greek word anetos, meaning slack, is a rare elastolytic disorder characterized by a limited area of slack skin associated with loss of substance on palpation and a histologic finding of loss of elastic tissue. It is classically divided into 2 forms. Primary, or idiopathic, anetoderma develops in clinically normal skin or following a nonspecific inflammatory process. Secondary anetoderma arises at the site of certain well-defined skin diseases, such as cutaneous infections, inflammatory disorders, and tumors.1

The etiopathogenesis of anetoderma is unclear. Several studies suggested that the destruction of the elastic tissue is mediated by the release of elastase, metalloproteinases, cytokines, or still-undefined substances by the inflammatory or tumoral cells.14 A growing body of evidence in recent years has linked primary anetoderma to a wide range of immunologic abnormalities, the most common being the presence of antiphospholipid antibodies (aPLs).57

In 1993, Jubert et al8 described a patient in whom primary cutaneous B-cell lymphoma (PCBCL) manifested as infiltrated plaques as well as anetodermic lesions.8 Since then, reports of an additional 6 cases of anetodermic manifestation of PCBCL have been published.912

To shed further light on the characteristics of this rare presentation, we analyzed data from a series of 5 patients with anetodermic PCBCL with emphasis on the clinicopathological findings, associated diseases, and autoimmune laboratory findings. The pertinent literature is reviewed as well.

The study group consisted of 5 patients with a diagnosis of PCBCL and anetoderma who were followed up at the Department of Dermatology of Rabin Medical Center from 1994 to 2008. Primary cutaneous B-cell lymphoma was defined as cutaneous lymphoma without nodal and/or visceral involvement.13 The diagnosis of anetoderma was based on the typical clinical features combined with histologic findings of partial or complete loss of elastic tissue in the dermis. The staging procedure included physical examination; standard blood tests; computed tomography of the chest, abdomen, and pelvis (and, in some patients, also the neck); and bone marrow biopsy. Punch and/or incisional skin biopsy specimens were obtained from typical lesions of lymphoma, typical lesions of anetoderma, and lesions clinically demonstrating the coexistence of both processes, on an as-needed, case-by-case basis. Biopsy specimens were fixed in 10% formalin, embedded in paraffin, and stained with hematoxylin-eosin and Verhoef–van Gieson elastic stain. Immunohistochemical studies were carried out on the paraffin-embedded sections with an avidin-biotin complex immunoperoxidase technique (ABC Vectastain Kit; Vector Laboratories Inc, Burlingame, California) with the use of a panel of monoclonal antibodies that included CD20, CD3, LCA, Bcl-2, CD68, and CD79a (Dako A/S, Glostrup, Denmark); Bcl-6 and CD21 (Ventana, Tucson, Arizona); CD10 (Novocastra, Newcastle Upon Tyne, England); Ki67 (Lab Vision, Fremont California); LN-1 (BioGenex, San Ramon, California); MUM-1 (Diagnostic BioSystems, Pleasanton, California); and κ and λ light chains (Pierce-Endogen, Rockford, Illinois). DNA extracted from paraffin-embedded or frozen tissue was analyzed by polymerase chain reaction (PCR) to determine the gene rearrangement of the immunoglobulin heavy chain, as previously described.14

Additional investigations at the time of diagnosis of anetodermic PCBCL included serologic testing for Borrelia burgdorferi and tests for aPLs, including anticardiolipin antibodies (IgG, IgM, and IgA) and anti–β2-glycoprotein 1 (IgG, IgM, and IgA). Lupus anticoagulant, VDRL test, Treponema pallidum hemagglutination, prothrombin time, and partial thromboplastin time were measured when indicated. Other tests performed in each patient included immunoelectrophoresis, determination of antinuclear antibody, and tests for antithyroid, antiparietal, and anti–smooth muscle antibodies. One patient underwent PCR analysis for the detection B burgdorferi in skin lesions. The local Helsinki Committee approved the study.

CLINICAL AND LABORATORY FINDINGS

The study group consisted of 3 male and 2 female patients with a mean age of 55 years at diagnosis of PCBCL (range, 39-70 years) (Table 1). In all cases, the eruption at onset was characterized by asymptomatic nodules or infiltrated plaques. Some of the nodules and plaques regressed to anetodermic lesions over time (6 months to 8 years).

Table Graphic Jump LocationTable 1 Clinical Presentation of Patients With Anetodermic Primary Cutaneous B-Cell Lymphoma

Evaluation at presentation yielded multifocal asymmetric nodular disease in 3 patients (patients 1-3) and a single infiltrated plaque in 2 patients (patients 4 and 5). Anetodermic skin was observed at the sites of the partially or completely disappearing preexistent erythematous nodules or plaques.

Three patients (patients 1, 4, and 5) were diagnosed as having primary cutaneous marginal-zone B-cell lymphoma (PCMZL); 1 of them presented with multifocal lesions. The other 2 patients (patients 2 and 3) were diagnosed as having multifocal primary cutaneous follicle-center cell lymphoma (PCFCL), including 1 (patient 3) with diffuse large-type lymphoma. All 5 patients had histopathological findings of anetoderma that developed secondary to the self-regressing lesions (Figure 1 and Figure 2).

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Figure 1

Multifocal presentation of anetodermic primary cutaneous marginal-zone B-cell lymphoma in patient 1. A, Several erythematous nodules located over the back and buttocks, some of which are embedded in circumscribed areas of slack skin. B, Close-up view of the left buttock showing 2 erythematous nodules with wrinkled overlying skin, surrounded by an area of slack skin.

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Figure 2

Anetodermic primary cutaneous follicle-center cell lymphoma in patient 3. Erythematous tumor located over the left frontoparietal scalp and soft hanging nodule with wrinkled overlying skin, representing partially regressing tumor on the left eyebrow (arrow).

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Further examination disclosed that, in 2 patients (patients 1 and 4), asymptomatic anetodermic skin lesions had appeared years before the typical nodular erythematous eruption, without any precedent inflammatory phase. Patient 1 had multiple oval skin-colored protrusions measuring 1 to 3 cm in diameter, located symmetrically on the sides of the back and extensor aspects of both arms. The lesions had wrinkled overlying skin and a feeling of tissue loss on palpation (Figure 3). The lesions in patient 4 were located symmetrically on the lower part of the back. The clinical appearance in conjunction with the histopathological findings was compatible with primary anetoderma.

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Figure 3

Lesions characteristic of primary anetoderma in patient 1. Small oval skin-colored monomorphic outpouching flaccid lesions are seen on the left upper part of the back and over the extensor aspect of the left arm near the axilla.

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Associated autoimmune diseases were diagnosed in 2 patients (patients 2 and 3) (Table 2). Patient 3 was known to have a systemic lupus erythematosus–like disease manifested by polyarthralgia, a sustained elevated erythrocyte sedimentation rate, and high titers of antinuclear antibody before diagnosis of the lymphoma. In patient 2, a form of rheumatoid arthritis developed during the course of follow-up of the lymphoma, characterized by fatigue, fever, morning stiffness accompanied by seronegative symmetric polyarthritis of the proximal interphalangeal and metacarpophalangeal joints, and evidence of synovitis of the wrist joints.

Table Graphic Jump LocationTable 2. Laboratory Abnormalities, Treatment, and Follow-up of Patients With Anetodermic Primary Cutaneous B-Cell Lymphoma

A deliberate laboratory investigation at the diagnosis of PCBCL disclosed the presence of aPLs in 4 of the 5 patients, but without lupus anticoagulant or prolonged partial thromboplastin time. None of the patients had a history of a thromboembolic event. We failed to detect any of the other autoantibodies tested, except for an abnormal titer of antinuclear antibody in patient 3. Results of serologic testing for B burgdorferi were negative in all 3 patients tested (patients 1-3). Patient 1 was tested for this spirochete by PCR, and the findings were negative in both the erythematous nodule and the lesion of primary anetoderma. Patients 1, 2, 3, and 5 were tested for the presence of Epstein-Barr virus (EBV) infection in the lymphoma biopsy specimens by means of EBV-encoded RNA in situ hybridization; the findings were negative in all of these cases.

Two of the patients with localized PCMZL (patients 4 and 5) were treated with electron beam radiation, and 1 patient with multifocal PCFCL (patient 3) was treated by her hematologist with the CHOP regimen (cyclophosphamide, doxorubicin hydrochloride/hydroxydoxorubicin, vincristine sulfate, and prednisone). All 3 had a complete response. Two patients (patients 1 and 2) refused therapy. Both showed a relapsing course on follow-up, with regression of some of the nodules, leaving secondary anetoderma (Figure 4). Patient 2 was in a sustained remission for the last 3 years of follow-up. It is noteworthy that in patient 1 the lesions diagnosed as primary anetoderma remained stable throughout follow-up, whereas patient 4 showed outpouching of atrophic lesions with wrinkled overlying skin, located on the popliteal fossa and on the previously affected shin. Repeated biopsy specimens yielded a diagnosis of primary anetoderma.

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Figure 4.

Nodular lesion on the abdomen of patient 1 (A); after several months, the nodule showed spontaneous partial regression (B), leaving combined features of lymphoma and secondary anetoderma.

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LIGHT MICROSCOPIC AND IMMUNOHISTOCHEMICAL FINDINGS

Table 3 shows the histopathological findings of the different lesions observed in our patients with anetodermic PCBCL. The spectrum of lesions included nodular lesion of lymphoma, partially regressing nodular lesion, completely regressing lesion, and primary anetoderma.

Table Graphic Jump LocationTable 3. Histopathological, Immunohistochemical, and Genotypic Findings in Patients With Anetodermic Primary Cutaneous B-Cell Lymphoma

Three patients presented with erythematous nodular lesions without clinical evidence of regression as well as with lesions showing partial regression (patients 1-3). However, 2 patients presented with nodular lesions that were already partially regressing (patients 4 and 5). In 3 patients (patients 2-4), we detected nodular lesions that had regressed completely. In those cases, we also documented the histopathological findings. Two patients (patients 1 and 4) also exhibited lesions of what seemed to be primary anetoderma.

Three patients had hematoxylin-eosin and immunohistochemical findings of PCMZL: 2 with typical findings (patients 1 and 5) and 1 with findings of immunocytoma, currently classified as part of PCMZL (patient 4).

The histopathological findings of the lymphoma and the anetoderma secondary to the partially regressing lymphoma of patient 1 are shown in Figure 5 and Figure 6.

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Figure 5

Histopathological findings of a nodule on the abdomen of patient 1 showing features of primary cutaneous marginal-zone B-cell lymphoma. Heavy diffuse and nodular lymphocytic infiltrates are seen in the dermis (hematoxylin-eosin, original magnification ×20). Inset, Higher-power view showing aggregates of monocytoid B lymphocytes and plasma cells (hematoxylin-eosin, original magnification ×200).

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Figure 6

Histopathological findings of a partially regressing nodule on the abdomen of patient 1 showing anetoderma secondary to lymphoma. A, Residual perivascular and interstitial lymphocytic infiltrates in the dermis (hematoxylin-eosin, original magnification ×40) B, CD20 immunopositivity of the infiltrates (original magnification ×40). C, Elastic stain demonstrating a marked reduction in elastic fibers (original magnification ×100).

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Two patients had diagnostic findings of PCFCL (patients 2 and 3), one of which was diffuse large type. The histopathological findings of the lymphoma and the anetoderma secondary to the partially regressing lymphoma of patient 2 are shown in Figure 7 and Figure 8.

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Figure 7

Histopathological findings of a representative nodule in patient 2 showing features of primary cutaneous follicle-center cell lymphoma. A, Diffuse and dense infiltrates are seen involving the dermis and are separated from the epidermis by a grenz zone (hematoxylin-eosin, original magnification ×40). B, Higher-power view. The infiltrate is composed of small and large cells, many with cleaved nuclei (hematoxylin-eosin, original magnification ×200). Inset, BCl-6 immunopositivity in the small and large atypical cells (original magnification ×400).

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Figure 8

Histopathological findings of a partially regressing nodule in patient 2 showing features of anetoderma secondary to lymphoma. A, Residual perivascular and interstitial lymphocytic infiltrates in the dermis (hematoxylin-eosin, original magnification ×40). B, Elastic stain demonstrating a marked reduction in the elastic tissue (original magnification ×40).

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The association between hematologic malignant neoplasms and cutaneous elastolysis, although rare, is well recognized. The literature includes descriptions of granulomatous slack skin,15 anetodermic mycosis fungoides (a recently described unusual variant of mycosis fungoides),16 acquired cutis laxa in association with multiple myeloma,17 heavy-chain deposition disease,18 and cutaneous angiocentric T-cell lymphoma.19

In the present study, we evaluated 5 cases of PCBCL with a unique clinicopathologic presentation, for which we suggest the term anetodermic PCBCL. Our review of the literature yielded 7 similar cases, which are summarized in Table 4. The patients were diagnosed as having PCMZL, plasmocytoma without underlying multiple myeloma or immunocytoma (the latter two are currently classified as PCMZL13), or posttransplant lymphoproliferative disorder in the skin resembling PCMZL. In all, the elastolytic skin lesions were a manifestation of the cutaneous lymphoma, which showed spontaneous partial regression in the form of anetoderma. The authors of a report of 2 cases9 specifically classified the anetoderma as secondary. In the other case reports, the authors did not use this term, but the available data indicate that they also represented secondary anetoderma, namely, anetoderma that arises at the site of a well-defined skin disease—specifically, in these cases, regressing lymphomatous infiltrates. In addition, colocalization of elastolysis and lymphoproliferative disorder was reported in 1 patient with benign cutaneous lymphoid hyperplasia and secondary anetoderma20 and another with localized acquired cutis laxa and primary cutaneous lymphoplasmocytoid lymphoma (immunocytoma).21

Table Graphic Jump LocationTable 4. Summary of Reported Cases of Primary Cutaneous B-Cell Lymphoma With Anetoderma

In line with the literature, 3 of our 5 patients had anetodermic PCMZL. The other 2 constitute the first reported cases of anetodermic PCFCL, to our knowledge. This diagnosis is unexpected given the rarity of self-regression in PCFCL. Multifocality is also a rare occurrence in PCFCL, with a rate of 8% (of 101 patients) reported in a recent Dutch series.22 Because 1 of these patients (patient 2) refused therapy, we were able to observe the natural course of his malignant neoplasm. We found that it was typified by chronic relapse/self-regression during a period of many years. This finding suggests that anetodermic PCFCL may have different biological characteristics from classic PCFCL. By contrast, a multifocal presentation is not rare in PCMZL, and it was observed in most of the previously described patients with anetodermic PCBCL.810,12 According to the Dutch Cutaneous Lymphoma Working Group, multifocality occurs in 44% to 72% of cases,22,23 and sometimes the skin lesions resolve spontaneously.13

Interestingly, 2 of our patients, both with PCMZL, also had skin lesions with clinical and histopathological characteristics of primary anetoderma. It is unlikely that a preceding lymphoma at the sites of the anetoderma was overlooked owing to the symmetric distribution of monomorphic anetodermic skin lesions and the absence of inflammatory or tumoral infiltrates on biopsy study. Furthermore, in 1 of these patients (patient 4) during follow-up we were able to detect the appearance of new anetodermic lesions that showed typical clinical and histopathological findings of primary anetoderma.

Primary anetoderma in conjunction with anetodermic PCBCL has not been previously described, to our knowledge.812 However, in 1 case,12 the available data were not sufficient to reach a definite conclusion regarding the nature of the additional anetodermic lesions that appeared in conjunction with the anetodermic lymphoma lesion.

Prompted by earlier reports of an association of primary anetoderma with autoimmune disorders,1 followed by studies in the 1990s2427 and a later one from our center5 that focused specifically on aPLs, we conducted a thorough investigation of autoantibodies in all of our patients. Four of them, including the 2 with primary anetoderma, were found to have aPLs without evidence of antiphospholipid syndrome. Lymphoproliferative malignant neoplasms have been reported to be related to the generation of aPLs,28 although this seems to occur rarely in PCBCL (our unpublished data, 2007). Therefore, we postulate that immunologic mechanisms, possibly mediated by aPLs, may be involved not only in primary anetoderma but also in anetodermic PCBCL. Likewise, there are other rare examples of an association of secondary anetoderma with increased aPLs in patients with human immunodeficiency virus/infection.29 Anetoderma, mostly secondary to resolving lesions, has been described in other infections such as borreliosis,30 which also might be associated with aPLs.31Borrelia burgdorferi has been isolated from the DNA of patients with PCBCL, specifically PCMZL.32 In our 3 patients who underwent serologic testing, 2 with PCFCL and 1 with PCMZL, no evidence of Bburgdorferi infection was found. Lesions from the latter patient were also tested by PCR. Nevertheless, the infection cannot be definitively ruled out.33

An immunologic nature of anetodermic PCPBL was further suggested by the various autoimmune diseases diagnosed in 2 of our 5 patients and in 3 of the 7 previously described patients.810 These include primary Sjögren syndrome (1 patient), rheumatoid arthritis (2 patients), urticarial vasculitis (1 patient), and systemic lupus erythematosus–like disease (1 patient). This observation is in keeping with the known higher risk of non-Hodgkin lymphoma among patients with such chronic inflammatory diseases.34 Sjögren syndrome was found to be associated with PCMZL in extranodal locations including the skin, as well as in the nodes.35 Primary Sjögren syndrome has also been reported in association with primary anetoderma.36

Studies have shown that aPLs may be detected in a significant proportion of patients with primary Sjögren syndrome or rheumatoid arthritis.37,38 However, data on the aPL status are lacking in the previous reports.8,36 Two additional patients were renal transplant recipients who had posttransplant lymphoproliferative disorder associated with EBV infection.10,11 Although the cause of the renal disease was not provided in these reports, EBV infection has been found to be associated with aPLs.31

How aPLs affect the elastic fibers remains to be clarified. It has been suggested that aPLs bind directly to the elastic fibers because of the presence of an antigenic epitope that is phospholipid related, possibly apolipoprotein H.39

Salmon et al40 demonstrated that activation of complement is a central mechanism in aPL-induced pregnancy loss in a murine model of antiphospholipid syndrome, and they suggested that this mechanism might be involved in the tissue injury in systemic lupus erythematosus. Because C3 deposits on remaining elastic fibers have been detected in primary anetoderma, we have previously suggested that the same mechanism might play a role in the destruction of elastic tissue in patients with aPLs who have primary and/or secondary anetoderma.6

Others have hypothesized that the elastolytic process may be induced by local inflammatory factors directly secondary to the lymphoma or reactive infiltrates.9 Cytokines, and particularly interleukin 6, the central plasma growth factor involved in the final maturation of activated B cells into immunoglobulin-producing cells, might serve as mediators of this process.20 Findings that myeloma cells in culture could produce aspartic acid proteases41 suggest that these elastolytic enzymes might play a role in the development of anetoderma in cutaneous lymphoproliferative nodules and plaques rich in plasma cells. Alternatively, given that elastases are also produced by macrophages, polymorphonuclear leukocytes, and fibroblasts, elastolysis may be effected by these other inflammatory cells associated with the neoplastic ones.10 Finally, it is plausible that combined inflammatory and immunologic mechanisms are involved in the pathogenesis of anetodermic PCBCL.

In conclusion, anetodermic PCBCL is a unique clinicopathological manifestation of low-grade B-cell lymphoma. It is a rare variant of PCMZL, as has already been described, and can also be a manifestation of PCFCL. Therefore, PCFCL should be added to the list of diseases causing secondary anetoderma. Primary cutaneous B-cell lymphoma is also sometimes associated with primary anetoderma. The cause of this peculiar clinicopathological manifestation is still unknown. However, our study results and review of the literature suggest that immunological mechanisms, possibly mediated by aPLs, may be involved in at least some cases of anetoderma secondary to PCBCL, as in primary anetoderma. Further studies are needed before a definite conclusion can be reached.

Correspondence: Emmilia Hodak, MD, Department of Dermatology, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel 49100 (hodake@post.tau.ac.il).

Accepted for Publication: September 9, 2009.

Author Contributions: Dr Hodak had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hodak. Acquisition of data: Hodak, Feuerman, Barzilai, Cerroni, and Feinmesser. Analysis and interpretation of data: Hodak, Feuerman, David, Barzilai, and Feinmesser. Drafting of the manuscript: Hodak. Critical revision of the manuscript for important intellectual content: Feuerman, Barzilai, David, and Cerroni.

Financial Disclosure: None reported.

Venencie  PYWinkelmann  RKMoore  BA Anetoderma: clinical findings, associations, and long-term follow-up evaluations. Arch Dermatol 1984;120 (8) 1032- 1039
PubMed
Werb  ZBanda  MJMcKerrow  JHSandhaus  RA Elastases and elastin degradation. J Invest Dermatol 1982;79 ((suppl 1)) 154s- 159s
PubMed
Werth  VPIvanov  IENussenzweig  V Decay-accelerating factor in human skin is associated with elastic fibers. J Invest Dermatol 1988;91 (5) 511- 516
PubMed
Venencie  PYBonnefoy  AGogly  B  et al.  Increased expression of gelatinases A and B by skin explants from patients with anetoderma. Br J Dermatol 1997;137 (4) 517- 525
PubMed
Hodak  EFeuerman  HMolad  YMonselise  YDavid  M Primary anetoderma: a cutaneous sign of antiphospholipid antibodies. Lupus 2003;12 (7) 564- 568
PubMed
Hodak  EDavid  M Primary anetoderma and antiphospholipid antibodies: review of the literature. Clin Rev Allergy Immunol 2007;32 (2) 162- 166
PubMed
Weinstein  SPiette  W Cutaneous manifestations of antiphospholipid antibody syndrome. Hematol Oncol Clin North Am 2008;22 (1) 67- 77, vi
PubMed
Jubert  CCosnes  AClerici  T  et al.  Sjögren's syndrome and cutaneous B cell lymphoma revealed by anetoderma. Arthritis Rheum 1993;36 (1) 133- 134
PubMed
Child  FJWoollons  APrice  MLCalonje  ERussell-Jones  R Multiple cutaneous immunocytoma with secondary anetoderma. Br J Dermatol 2000;143 (1) 165- 170
PubMed
Kasper  RCWood  GSNihal  MLeBoit  PE Anetoderma arising in cutaneous B-cell lymphoproliferative disease. Am J Dermatopathol 2001;23 (2) 124- 132
PubMed
Garcìa-Dura  EGarcia-Mellado  VMassare  EEsquivias  J Presentación cutánea anetodérmica de un trastorno linfoproliferativo postrasplante. Actas Dermosifiliogr 2003;94 (4) 243- 246
Segurado  MAGuerra-Tapia  AZarco  CIsarria  MJRodriguez  JL Anetoderma secondary to cutaneous B-cell lymphoma. Clin Exp Dermatol 2006;31 (1) 130- 131
PubMed
Willemze  RJaffe  ESBurg  G  et al.  WHO-EORTC classification for cutaneous lymphomas. Blood 2005;105 (10) 3768- 3785
PubMed
Zuckerman  EZuckerman  TSahar  D  et al.  Bcl-2 and immunoglobulin gene rearrangement in patients with hepatitis C virus infections. Br J Haematol 2001;112 (2) 364- 369
PubMed
Kempf  WOstheeren-Michaelis  SPaulli  M  et al. Cutaneous Lymphoma Histopathology Task Force Group of the European Organization for Research and Treatment of Cancer, Granulomatous mycosis fungoides and granulomatous slack skin: a multicenter study of the Cutaneous Lymphoma Histopathology Task Force Group of the European Organization for Research and Treatment of Cancer (EORTC). Arch Dermatol 2008;144 (12) 1609- 1617
PubMed
Requena  LGonzález-Guerra  EAngulo  JDeVore  AESangueza  OP Anetodermic mycosis fungoides: a new clinicopathological variant of mycosis fungoides. Br J Dermatol 2008;158 (1) 157- 162
PubMed
Gupta  AHelm  TN Acquired cutis laxa associated with multiple myeloma. Cutis 2002;69 (2) 114- 118
PubMed
Harrington  CRBeswick  TCSusa  JSPandya  AG Acquired cutis laxa associated with heavy chain deposition disease. J Am Acad Dermatol 2008;59 (5) ((suppl)) S99- S101
PubMed
Chartier  SFaucher  LTousignant  JRochette  L Acquired cutis laxa associated with cutaneous angiocentric T-cell lymphoma. Int J Dermatol 1997;36 (10) 772- 776
PubMed
Jubert  CCosnes  AWechsler  JAndre  PRevuz  JBagot  M Anetoderma may reveal cutaneous plasmocytoma and benign cutaneous lymphoid hyperplasia. Arch Dermatol 1995;131 (3) 365- 366
PubMed
Machet  MCMachet  LVaillant  L  et al.  Acquired localized cutis laxa due to cutaneous lymphoplasmacytoid lymphoma. Arch Dermatol 1995;131 (1) 110- 111
PubMed
Hoefnagel  JJVermeer  MHJansen  PM  et al.  Primary cutaneous marginal zone B-cell lymphoma: clinical and therapeutic features in 50 cases. Arch Dermatol 2005;141 (9) 1139- 1145
PubMed
Senff  NJHoefnagel  JJNeelis  KJVermeer  MHNoordijk  EMWillemze  RDutch Cutaneous Lymphoma Group, Results of radiotherapy in 153 primary cutaneous B cell lymphomas classified according to the WHO-EORTC classification. Arch Dermatol 2007;143 (12) 1520- 1526
PubMed
Hodak  EShamai-Lubovitz  ODavid  MHazaz  BLahav  MSandbank  M Primary anetoderma associated with a wide spectrum of autoimmune abnormalities. J Am Acad Dermatol 1991;25 (2, pt 2) 415- 418
PubMed
Hodak  EShamai-Lubovitz  ODavid  M  et al.  Immunologic abnormalities associated with primary anetoderma. Arch Dermatol 1992;128 (6) 799- 803
PubMed
Stephansson  EANiemi  KM Antiphospholipid antibodies and anetoderma: are they associated? Dermatology 1995;191 (3) 204- 209
PubMed
Sparsa  APiette  JCWechsler  BAmoura  ZFrances  C Anetoderma and its prothrombotic abnormalities. J Am Acad Dermatol 2003;49 (6) 1008- 1012
PubMed
Pusterla  SPrevitali  SMarziali  S  et al.  Antiphospholipid antibodies in lymphoma: prevalence and clinical significance. Hematol J 2004;5 (4) 341- 346
PubMed
Lindstrom  JSmith  KJSkelton  HG  et al. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR), Increased anticardiolipin antibodies associated with the development of anetoderma in HIV-1 disease. Int J Dermatol 1995;34 (6) 408- 415
PubMed
James  WDedBerger  TGedElston  DMed Andrews' Diseases of the Skin. 10th ed. Philadelphia, PA WB Saunders2006;- 292, 516
Asherson  RACervera  R Antiphospholipid antibodies and infections. Ann Rheum Dis 2003;62 (5) 388- 393
PubMed
Cerroni  LZochling  NPutz  BKerl  H Infection by Borrelia burgdorferi and cutaneous B cell lymphoma. J Cutan Pathol 1997;24 (8) 457- 461
PubMed
Eisendle  KGrabner  TKutzner  HZelger  B Possible role of Borrelia burgdorferi sensu lato infection in lichen sclerosus. Arch Dermatol 2008;144 (5) 591- 598
PubMed
Hansen  ALipsky  PEDorner  T B cell lymphoproliferation in chronic inflammatory rheumatic diseases. Nat Clin Pract Rheumatol 2007;3 (10) 561- 569
PubMed
Royer  BCazals-Hatem  DSibilia  J  et al.  Lymphomas in patients with Sjögren's syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses. Blood 1997;90 (2) 766- 775
PubMed
Herrero-González  JEMateu  C Herrero Primary anetoderma associated with primary Sjögren's syndrome. Lupus 2002;11 (2) 124- 126
PubMed
Ramos-Casals  MNardi  NBrito-Zeron  P  et al.  Atypical autoantibodies in patients with primary Sjögren syndrome: clinical characteristics and follow-up of 82 cases. Semin Arthritis Rheum 2006;35 (5) 312- 321
PubMed
Szekanecz  ZKoch  AE Vascular involvement in rheumatic diseases: “vascular rheumatology.” Arthritis Res Ther 2008;10 (5) 224
PubMed10.1186/ar2515
Romaní  JPérez  FLlobet  MPlanagumá  MPujol  RM Anetoderma associated with antiphospholipid antibodies: case report and review of the literature. J Eur Acad Dermatol Venereol 2001;15 (2) 175- 178
PubMed
Salmon  JEGirardi  GHolers  VM Activation of complement mediates antiphospholipid antibody-induced pregnancy loss. Lupus 2003;12 (7) 535- 538
PubMed
Spens  EHäggström  L Protease activity in protein-free NS0 myeloma cell cultures. In Vitro Cell Dev Biol Anim 2005;41 (10) 330- 336
PubMed

Figures

Place holder to copy figure label and caption
Figure 1

Multifocal presentation of anetodermic primary cutaneous marginal-zone B-cell lymphoma in patient 1. A, Several erythematous nodules located over the back and buttocks, some of which are embedded in circumscribed areas of slack skin. B, Close-up view of the left buttock showing 2 erythematous nodules with wrinkled overlying skin, surrounded by an area of slack skin.

Graphic Jump Location
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Figure 2

Anetodermic primary cutaneous follicle-center cell lymphoma in patient 3. Erythematous tumor located over the left frontoparietal scalp and soft hanging nodule with wrinkled overlying skin, representing partially regressing tumor on the left eyebrow (arrow).

Graphic Jump Location
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Figure 3

Lesions characteristic of primary anetoderma in patient 1. Small oval skin-colored monomorphic outpouching flaccid lesions are seen on the left upper part of the back and over the extensor aspect of the left arm near the axilla.

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Figure 4.

Nodular lesion on the abdomen of patient 1 (A); after several months, the nodule showed spontaneous partial regression (B), leaving combined features of lymphoma and secondary anetoderma.

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Figure 5

Histopathological findings of a nodule on the abdomen of patient 1 showing features of primary cutaneous marginal-zone B-cell lymphoma. Heavy diffuse and nodular lymphocytic infiltrates are seen in the dermis (hematoxylin-eosin, original magnification ×20). Inset, Higher-power view showing aggregates of monocytoid B lymphocytes and plasma cells (hematoxylin-eosin, original magnification ×200).

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Figure 6

Histopathological findings of a partially regressing nodule on the abdomen of patient 1 showing anetoderma secondary to lymphoma. A, Residual perivascular and interstitial lymphocytic infiltrates in the dermis (hematoxylin-eosin, original magnification ×40) B, CD20 immunopositivity of the infiltrates (original magnification ×40). C, Elastic stain demonstrating a marked reduction in elastic fibers (original magnification ×100).

Graphic Jump Location
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Figure 7

Histopathological findings of a representative nodule in patient 2 showing features of primary cutaneous follicle-center cell lymphoma. A, Diffuse and dense infiltrates are seen involving the dermis and are separated from the epidermis by a grenz zone (hematoxylin-eosin, original magnification ×40). B, Higher-power view. The infiltrate is composed of small and large cells, many with cleaved nuclei (hematoxylin-eosin, original magnification ×200). Inset, BCl-6 immunopositivity in the small and large atypical cells (original magnification ×400).

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Figure 8

Histopathological findings of a partially regressing nodule in patient 2 showing features of anetoderma secondary to lymphoma. A, Residual perivascular and interstitial lymphocytic infiltrates in the dermis (hematoxylin-eosin, original magnification ×40). B, Elastic stain demonstrating a marked reduction in the elastic tissue (original magnification ×40).

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Tables

Table Graphic Jump LocationTable 1 Clinical Presentation of Patients With Anetodermic Primary Cutaneous B-Cell Lymphoma
Table Graphic Jump LocationTable 2. Laboratory Abnormalities, Treatment, and Follow-up of Patients With Anetodermic Primary Cutaneous B-Cell Lymphoma
Table Graphic Jump LocationTable 3. Histopathological, Immunohistochemical, and Genotypic Findings in Patients With Anetodermic Primary Cutaneous B-Cell Lymphoma
Table Graphic Jump LocationTable 4. Summary of Reported Cases of Primary Cutaneous B-Cell Lymphoma With Anetoderma

References

Venencie  PYWinkelmann  RKMoore  BA Anetoderma: clinical findings, associations, and long-term follow-up evaluations. Arch Dermatol 1984;120 (8) 1032- 1039
PubMed
Werb  ZBanda  MJMcKerrow  JHSandhaus  RA Elastases and elastin degradation. J Invest Dermatol 1982;79 ((suppl 1)) 154s- 159s
PubMed
Werth  VPIvanov  IENussenzweig  V Decay-accelerating factor in human skin is associated with elastic fibers. J Invest Dermatol 1988;91 (5) 511- 516
PubMed
Venencie  PYBonnefoy  AGogly  B  et al.  Increased expression of gelatinases A and B by skin explants from patients with anetoderma. Br J Dermatol 1997;137 (4) 517- 525
PubMed
Hodak  EFeuerman  HMolad  YMonselise  YDavid  M Primary anetoderma: a cutaneous sign of antiphospholipid antibodies. Lupus 2003;12 (7) 564- 568
PubMed
Hodak  EDavid  M Primary anetoderma and antiphospholipid antibodies: review of the literature. Clin Rev Allergy Immunol 2007;32 (2) 162- 166
PubMed
Weinstein  SPiette  W Cutaneous manifestations of antiphospholipid antibody syndrome. Hematol Oncol Clin North Am 2008;22 (1) 67- 77, vi
PubMed
Jubert  CCosnes  AClerici  T  et al.  Sjögren's syndrome and cutaneous B cell lymphoma revealed by anetoderma. Arthritis Rheum 1993;36 (1) 133- 134
PubMed
Child  FJWoollons  APrice  MLCalonje  ERussell-Jones  R Multiple cutaneous immunocytoma with secondary anetoderma. Br J Dermatol 2000;143 (1) 165- 170
PubMed
Kasper  RCWood  GSNihal  MLeBoit  PE Anetoderma arising in cutaneous B-cell lymphoproliferative disease. Am J Dermatopathol 2001;23 (2) 124- 132
PubMed
Garcìa-Dura  EGarcia-Mellado  VMassare  EEsquivias  J Presentación cutánea anetodérmica de un trastorno linfoproliferativo postrasplante. Actas Dermosifiliogr 2003;94 (4) 243- 246
Segurado  MAGuerra-Tapia  AZarco  CIsarria  MJRodriguez  JL Anetoderma secondary to cutaneous B-cell lymphoma. Clin Exp Dermatol 2006;31 (1) 130- 131
PubMed
Willemze  RJaffe  ESBurg  G  et al.  WHO-EORTC classification for cutaneous lymphomas. Blood 2005;105 (10) 3768- 3785
PubMed
Zuckerman  EZuckerman  TSahar  D  et al.  Bcl-2 and immunoglobulin gene rearrangement in patients with hepatitis C virus infections. Br J Haematol 2001;112 (2) 364- 369
PubMed
Kempf  WOstheeren-Michaelis  SPaulli  M  et al. Cutaneous Lymphoma Histopathology Task Force Group of the European Organization for Research and Treatment of Cancer, Granulomatous mycosis fungoides and granulomatous slack skin: a multicenter study of the Cutaneous Lymphoma Histopathology Task Force Group of the European Organization for Research and Treatment of Cancer (EORTC). Arch Dermatol 2008;144 (12) 1609- 1617
PubMed
Requena  LGonzález-Guerra  EAngulo  JDeVore  AESangueza  OP Anetodermic mycosis fungoides: a new clinicopathological variant of mycosis fungoides. Br J Dermatol 2008;158 (1) 157- 162
PubMed
Gupta  AHelm  TN Acquired cutis laxa associated with multiple myeloma. Cutis 2002;69 (2) 114- 118
PubMed
Harrington  CRBeswick  TCSusa  JSPandya  AG Acquired cutis laxa associated with heavy chain deposition disease. J Am Acad Dermatol 2008;59 (5) ((suppl)) S99- S101
PubMed
Chartier  SFaucher  LTousignant  JRochette  L Acquired cutis laxa associated with cutaneous angiocentric T-cell lymphoma. Int J Dermatol 1997;36 (10) 772- 776
PubMed
Jubert  CCosnes  AWechsler  JAndre  PRevuz  JBagot  M Anetoderma may reveal cutaneous plasmocytoma and benign cutaneous lymphoid hyperplasia. Arch Dermatol 1995;131 (3) 365- 366
PubMed
Machet  MCMachet  LVaillant  L  et al.  Acquired localized cutis laxa due to cutaneous lymphoplasmacytoid lymphoma. Arch Dermatol 1995;131 (1) 110- 111
PubMed
Hoefnagel  JJVermeer  MHJansen  PM  et al.  Primary cutaneous marginal zone B-cell lymphoma: clinical and therapeutic features in 50 cases. Arch Dermatol 2005;141 (9) 1139- 1145
PubMed
Senff  NJHoefnagel  JJNeelis  KJVermeer  MHNoordijk  EMWillemze  RDutch Cutaneous Lymphoma Group, Results of radiotherapy in 153 primary cutaneous B cell lymphomas classified according to the WHO-EORTC classification. Arch Dermatol 2007;143 (12) 1520- 1526
PubMed
Hodak  EShamai-Lubovitz  ODavid  MHazaz  BLahav  MSandbank  M Primary anetoderma associated with a wide spectrum of autoimmune abnormalities. J Am Acad Dermatol 1991;25 (2, pt 2) 415- 418
PubMed
Hodak  EShamai-Lubovitz  ODavid  M  et al.  Immunologic abnormalities associated with primary anetoderma. Arch Dermatol 1992;128 (6) 799- 803
PubMed
Stephansson  EANiemi  KM Antiphospholipid antibodies and anetoderma: are they associated? Dermatology 1995;191 (3) 204- 209
PubMed
Sparsa  APiette  JCWechsler  BAmoura  ZFrances  C Anetoderma and its prothrombotic abnormalities. J Am Acad Dermatol 2003;49 (6) 1008- 1012
PubMed
Pusterla  SPrevitali  SMarziali  S  et al.  Antiphospholipid antibodies in lymphoma: prevalence and clinical significance. Hematol J 2004;5 (4) 341- 346
PubMed
Lindstrom  JSmith  KJSkelton  HG  et al. Military Medical Consortium for the Advancement of Retroviral Research (MMCARR), Increased anticardiolipin antibodies associated with the development of anetoderma in HIV-1 disease. Int J Dermatol 1995;34 (6) 408- 415
PubMed
James  WDedBerger  TGedElston  DMed Andrews' Diseases of the Skin. 10th ed. Philadelphia, PA WB Saunders2006;- 292, 516
Asherson  RACervera  R Antiphospholipid antibodies and infections. Ann Rheum Dis 2003;62 (5) 388- 393
PubMed
Cerroni  LZochling  NPutz  BKerl  H Infection by Borrelia burgdorferi and cutaneous B cell lymphoma. J Cutan Pathol 1997;24 (8) 457- 461
PubMed
Eisendle  KGrabner  TKutzner  HZelger  B Possible role of Borrelia burgdorferi sensu lato infection in lichen sclerosus. Arch Dermatol 2008;144 (5) 591- 598
PubMed
Hansen  ALipsky  PEDorner  T B cell lymphoproliferation in chronic inflammatory rheumatic diseases. Nat Clin Pract Rheumatol 2007;3 (10) 561- 569
PubMed
Royer  BCazals-Hatem  DSibilia  J  et al.  Lymphomas in patients with Sjögren's syndrome are marginal zone B-cell neoplasms, arise in diverse extranodal and nodal sites, and are not associated with viruses. Blood 1997;90 (2) 766- 775
PubMed
Herrero-González  JEMateu  C Herrero Primary anetoderma associated with primary Sjögren's syndrome. Lupus 2002;11 (2) 124- 126
PubMed
Ramos-Casals  MNardi  NBrito-Zeron  P  et al.  Atypical autoantibodies in patients with primary Sjögren syndrome: clinical characteristics and follow-up of 82 cases. Semin Arthritis Rheum 2006;35 (5) 312- 321
PubMed
Szekanecz  ZKoch  AE Vascular involvement in rheumatic diseases: “vascular rheumatology.” Arthritis Res Ther 2008;10 (5) 224
PubMed10.1186/ar2515
Romaní  JPérez  FLlobet  MPlanagumá  MPujol  RM Anetoderma associated with antiphospholipid antibodies: case report and review of the literature. J Eur Acad Dermatol Venereol 2001;15 (2) 175- 178
PubMed
Salmon  JEGirardi  GHolers  VM Activation of complement mediates antiphospholipid antibody-induced pregnancy loss. Lupus 2003;12 (7) 535- 538
PubMed
Spens  EHäggström  L Protease activity in protein-free NS0 myeloma cell cultures. In Vitro Cell Dev Biol Anim 2005;41 (10) 330- 336
PubMed

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