Customize your JAMA Network experience by selecting one or more topics from the list below.
Author Affiliations: Departments of Dermatology (Dr Barzilai) and Pathology (Drs Barzilai and Tabibian-Keissar) and Hematology Institute (Dr Amarilgio), Sheba Medical Center, Tel-Hashomer, Israel; Departments of Dermatology (Drs Feuerman, David, and Hodak) and Pathology (Drs Feinmesser and Halpern), Beilinson Hospital, Rabin Medical Center, Petach-Tikva, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel (Drs Barzilai, Feuerman, David, Feinmesser, Halpern, and Hodak); Department of Pathology, Kaplan Medical Center, Rehovot, Israel (Drs Barzilai and Feldberg); and Department of Biomedical Sciences and Human Oncology, Dermatologic Clinic (Dr Quaglino) and Laboratory of Cutaneous Pathology (Dr Tomasini), University of Turin, Turin, Italy.
Background Unlike T-cell neoplasms, B-cell lymphoproliferative disorders have a limited clinical spectrum of skin involvement. Cutaneous B-cell neoplasms mimicking rosacea or rhinophyma are rare.
Observations We described 12 patients with B-cell lymphoproliferative neoplasms presenting with a facial eruption clinically mimicking rosacea or rhinophyma. Eleven patients were women; ages ranged from 36 to 81 years. The clinical presentation included small papules on the nose and cheeks and around the eyes mimicking granulomatous rosacea; nodules on the nose, cheeks, chin, or forehead mimicking phymatous rosacea; or a combination of both. Three patients had preexisting erythematotelangiectatic rosacea and 1 had rhinophyma. Based on a clinicopathologic correlation and B-cell clonality analysis, the diagnosis was primary cutaneous follicular center B-cell lymphoma in 4 cases, primary cutaneous marginal zone lymphoma in 6, and skin involvement of chronic lymphocytic leukemia in 2. All patients had an indolent course as expected for their disease.
Conclusions Cutaneous involvement of B-cell neoplasms may mimic granulomatous rosacea or rhinophyma. This unusual clinical presentation is more common in women and appears in the setting of preexisting rosacea or as a new eruption. Proliferative B-cell disorders should be added to the differential diagnosis of symmetric papular or papulonodular eruptions of the face.
B-cell neoplasms can involve the skin as a primary cutaneous lymphoma or as a secondary process, including specific infiltrates of nodal or extranodal lymphoma or leukemia.1 When involving the skin, both B-cell neoplasms, lymphoma and leukemia, have a distinct clinical appearance, presenting as isolated, grouped, or multiple erythematous to violaceous papules, plaques, or nodules, usually in an asymmetric distribution. B-cell lymphoproliferative diseases simulating rosacea are extremely rare.2-8 In this report, we describe 12 patients who presented with rosacea or rhinophymalike lesions and discuss various aspects of this rare clinical manifestation of low-grade B-cell lymphoma/leukemia involving the face.
We performed a retrospective case analysis of 12 patients with cutaneous B-cell neoplasms who were referred to our tertiary dermatology clinics from January 1, 1996, through December 31, 2010, for a persistent facial rash. The differential diagnoses included rosacea and rhinophyma. We retrieved clinical history, clinical findings, laboratory results, and follow-up data from the medical files and reviewed the biopsy specimens. Final diagnosis was made according to the criteria of the World Health Organization or the European Organization for Research and Treatment of Cancer.1 The study was approved by the local ethics committees.
The patients' clinical data and final diagnoses are described in Table 1. The study group included 11 women and 1 man with a mean age of 57 (range, 36-81) years. The time elapsed from the initial presentation to the final diagnosis varied from a few months to 10 years (mean time, 23 months). The distinguishing features of the clinical presentation included nonpustular granulomatous rosacea-like lesions and rhinophyma/phymatous plaques (Table 1, Figure 1, and Figure 2). Four patients (patients 1-3 and 10) had a history of preexisting rosacea manifesting as erythematotelangiectatic rosacea (in 3 patients) and rhinophyma (in 1 patient) (Figure 3). Two of these patients developed rhinophymalike lymphoma on the nose. Half the patients were treated for rosacea with topical or systemic antibiotics or both, without any benefit (Table 1).
Figure 1. Erythematous (granulomatous rosacea-like) papules on the right cheek in a patient with primary cutaneous follicular center B-cell lymphoma (patient 1).
Figure 2. Rhinophymalike lesion in a patient with primary cutaneous marginal zone lymphoma (patient 11).
Figure 3. Papular/granulomatous rosacea-like lesions on the background of preexisting erythematotelangiectatic rosacea. Small erythematous papules that were determined to be primary cutaneous marginal zone lymphoma were found on erythema and telangiectasia (patient 3). This patient had papules on both cheeks and also on the submental areas.
The histological and immunophenotypical features of the cases and the results of molecular studies are described in Table 2. Four cases revealed superficial and deep nodular aggregates of centrocytes and centroblasts, features of follicular-center cell lymphoma (Figure 4). Six cases showed superficial and deep nodular aggregates of small irregular B lymphocytes, some with a monocytoid or plasmacytoid appearance and residual fragmented germinal centers, features of marginal cell lymphoma (Figure 5). Two cases had diffuse dermal infiltrates of mostly small regular B cells (Figure 6), consistent with skin involvement by chronic lymphocytic leukemia (CLL). Furthermore, in patient 4, results of an IgH rearrangement study showed an identical clone in the blood and skin (Figure 6), establishing the diagnosis of leukemia cutis. Demodex folliculorum was not present in any of the biopsy specimens.
Figure 4. Histological features of primary cutaneous follicular center B-cell lymphoma (patient 8). A, Superficial and deep nodular aggregates show irregular lymphoid germinal center–like areas (hematoxylin-eosin, original magnification ×20). B and C, The areas are composed of small and large B lymphocytes (hematoxylin-eosin [B] and CD20 [C], original magnification ×400).
Figure 5. Histological features of primary cutaneous marginal zone lymphoma (patient 3). A, Superficial and deep nodular aggregates are seen (hematoxylin-eosin, original magnification ×20). B and C, The aggregates show distended marginal zones of monocytoid B cells (hematoxylin-eosin [B] and CD20 [C], original magnification ×200). C, The residual germinal center reveals positive staining for CD20 and negative staining for bcl-2. D, The marginal B cells are positive for bcl-2 (original magnification ×200).
Figure 6. Leukemia cutis of chronic lymphocytic leukemia mimicking phymatous rosacea (patient 4). A, Erythematous plaques and nodules on the nose, cheeks, and chin. B, Diffuse lymphocytic infiltrate involving the dermis (hematoxylin-eosin, original magnification ×40). C, The infiltrate is composed of small round lymphocytes and larger cells (prolymphocytes and paraimmunoblasts) (hematoxylin-eosin, original magnification ×400). D, Results of the IgH study show identical clones (dark filled peaks marked by arrows at 125 kilobase) in the skin biopsy specimen (top) and in the peripheral blood (bottom). The y-axes show peak intensity, measured in arbitrary units; the x-axes show DNA fragment size, measured in kilobases.
Based on a full workup including clinicopathologic correlation and analysis of B-cell clonality, the diagnosis retained was primary cutaneous follicular center B-cell lymphoma in 4 of 12 cases (33%), primary cutaneous marginal zone lymphoma in 6 (50%), and skin involvement of CLL in 2 (17%) (Table 2). All the patients had an indolent course as expected for their disease. Initial therapy, which included radiotherapy and/or excisions for 8 patients with primary cutaneous B-cell lymphoma (PCBCL), led to complete remission. However, in patients 3 and 8, new lesions developed at sites not previously treated. Intralesional or potent topical corticosteroids applied to these small lesions led to complete remission. The cutaneous lesions of CLL resolved completely after a course of prednisone and chlorambucil therapy in patient 4 and rituximab and radiotherapy in patient 10. Two patients had only received the diagnosis at the time of this report, and follow-up was not available.
B-cell lymphoproliferative diseases clinically mimicking rosacea are extremely rare and have been previously reported in only 7 cases detailed in Table 3. The findings of the present case series of 12 patients with B-cell lymphoproliferative diseases simulating granulomatous rosacea, rhinophyma, or both are comparable to those reports. Likewise, most of our patients were women. However, our patients were somewhat younger than those described in the previous reports (mean age, 57 vs 76 years), making the initial diagnosis of rosacea more plausible. Clinically, all our patients presented with phymatous lesions (mostly rhinophyma), granulomatous rosacea-like lesions, or both. In contrast, all previously described patients who had PCBCL had phymatous lesions.3-7 Three patients described herein and 1 described previously6 had preexisting rosacea presenting as facial flushing, erythema, and telangiectasia. Therefore, the development of papules or rhinophyma in these patients was considered part of the preexisting rosacea. Two patients described in the literature also had pustules,2,8 and both of them had CLL. In one of those patients, earlier biopsy findings showed polymorphonuclear leukocytes, which probably represented preexisting rosacea.2 In the other patient, histological features of the pustules were not described. Thus, pustules might have formed secondary to occlusion of the folliculosebaceous unit by the leukemic infiltrate.8 In contrast, none of the patients described herein had a pustular eruption.
This unique clinical presentation of B-cell neoplasm involving the skin and simulating rosacea led to a diagnosis delay that ranged from months to years. Half the patients in the present series (6 of 12) and most of the patients described in the literature (6 of 7)2-7 had been initially treated with topical or systemic antibiotics for at least a few months without any benefit before a biopsy specimen was obtained. Thus, rosacea and rhinophyma should be added to the list of the unusual manifestations of B-cell neoplasms simulating other skin diseases (Table 4). The clinical differential diagnosis of these lesions does not include only rosacea. For the papular/granulomatous rosacea-like lesions, the differential diagnosis would include mostly adnexal tumors, such as basal cell carcinoma, trichoepithelioma, or sebaceous hyperplasia, and cutaneous sarcoidosis. For the phymatous lesions, granulomatous diseases (infectious or noninfectious) and T-cell lymphoma should be considered.
Fifteen of the 19 total patients (10 in the present series and 5 in previously reported cases) had PCBCL, with the marginal zone lymphoma being the most common (10 of 19 patients, including 1 with immunocytoma, currently considered a type of marginal zone lymphoma) followed by follicular center cell lymphoma (5 of 19 patients). In 4 patients, the skin infiltrative lesions represented leukemia cutis of CLL. In general, primary cutaneous marginal zone lymphoma is uncommonly located on the face.1 One may therefore speculate that chronic antigenic stimulation caused by a resident organism such as D folliculorum leads to the development of the lymphoma similar to the relation between Helicobacter pylori and gastric lymphoma.19 Although we did not observe Demodex organisms in any of the biopsy specimens, such a mechanism is plausible because it would account for the lymphoma development and the clinical presentation.20 Alternatively, similar to descriptions of leukemic infiltrates of CLL localized to the sites of herpes zoster,14,15 the lymphomatous/leukemic infiltrates localized to the face may represent the isomorphic phenomenon on the sites of a preexisting rosacea/rhinophyma.
In all 19 reported cases, the diagnosis was based on histological and immunophenotypical characteristics, supported in most of the cases by genotypic findings. Demonstration of a monotypic plasma cell population or IgH gene rearrangement is crucial for the diagnosis of primary cutaneous marginal zone lymphoma in this setting because some cases of rosacea may show dense lymphohistoplasmacytic infiltrate.21 It is also essential to show the identical clone of B cells in the skin infiltrate and in the blood in cases of CLL, especially if the findings for CD5 are negative (as in patient 4) or when a concomitant B-cell lymphoma has to be excluded.
The PCBCLs were treated with excision or radiotherapy, as indicated for low-grade PCBCL.22 In contrast, skin infiltrates of CLL in which most of the cells are small are related to a favorable prognosis and do not require specific therapy.23 However, in cases in which they pose an aesthetic problem, such as those described in the present series, radiotherapy and even systemic therapy may be indicated. For small papules and nodules that continue to appear, topical corticosteroids may be the treatment of choice for early lesions. This modality may be more practical and accepted from the cosmetic point of view, probably without affecting the course of the disease. Nevertheless, further studies are needed to validate this approach, particularly in cases of follicular center B-cell lymphoma.
In summary, cutaneous involvement by B-cell neoplasms may mimic rosacea or rhinophyma. This unusual clinical presentation is more common in women and appears in the setting of preexisting rosacea or as a new eruption. A B-cell proliferative disorder presenting in the skin should be added to the long list of diseases affecting the face manifested by rhinophyma or papulonodular rosacea-like eruptions.
Correspondence: Aviv Barzilai, MD, MSc, Department of Dermatology, Sheba Medical Center, 52621 Tel-Hashomer, Israel (firstname.lastname@example.org).
Accepted for Publication: December 29, 2012.
Published Online: April 16, 2012. doi:10.1001/archdermatol.2011.3575
Author Contributions: Drs Barzilai, Feuerman, Quaglino, and Hodak had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Barzilai, Feuerman, and Hodak. Acquisition of data: Barzilai, Feuerman, Quaglino, and Hodak. Analysis and interpretation of data: Barzilai, Feuerman, Quaglino, David, Feinmesser, Halpern, Feldberg, Tomasini, Tabibian-Keissar, Amarilgio, and Hodak. Drafting of the manuscript: Barzilai. Critical revision of the manuscript for important intellectual content: Barzilai, Feuerman, Quaglino, David, and Hodak. Administrative, technical, and material support: Feinmesser, Tabibian-Keissar, and Amarilgio. Study supervision: Barzilai and Hodak.
Financial Disclosure: None reported.
Barzilai A, Feuerman H, Quaglino P, et al. Cutaneous B-Cell Neoplasms Mimicking Granulomatous Rosacea or Rhinophyma. Arch Dermatol. 2012;148(7):824–831. doi:10.1001/archdermatol.2011.3575
Coronavirus Resource Center