Primary Cutaneous Marginal Zone B-cell Lymphoma Research Articles

Clinician's perspective on the diagnosis of primary cutaneous B-cell lymphoma

Primary cutaneous B-cell lymphomas (PCBCLs) account for 25% of all cutaneous lymphomas: the main subtypes within this group are primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone B-cell lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). Biopsy with histological examination and immunohistochemistry is the gold standard for the diagnosis of PCBCLs. A clinically oriented approach to PCBCLs classifies these entities according to their clinical behavior into indolent or intermediate to aggressive subtypes. While PCFCL and PCMZL are indolent diseases, PCDLBCL, LT has an aggressive course spreading to extracutaneous sites in approximately 45% of cases. Therefore, instrumental staging for extracutaneous disease is not performed following a diagnosis of PCMZL and PCFCL, while it is recommended for PCDLBCL, LT. Finally, dermatoscopy, under the guide of a strong clinical suspicion, may provide a novel diagnostic tool to enhance the clinical recognition of different subtypes of PCBCL.

32514 Primary cutaneous marginal zone B-cell lymphoma involution with anetoderma

A 57-year-old gentleman presented with an 8-year history of rash on his trunk and limbs. He initially presented with small erythematous patches, which became plaque-like, violaceous, and resolved over months to years with atrophy. The initial clinical impression was of a cutaneous lymphoma or a lupus-like process. A biopsy showed a leucocytoclastic vasculitis with eosinophils with no epidermotropism or basal exocytosis, and loss of elastic fibres in the upper to mid dermis confirming anetoderma in the resolved sites. Immunostaining demonstrated scattered CD3+ T-cells showing a mix of CD4 and CD8 subtypes. CD20 was negative. Few macrophages were CD60+. T-cell gene rearrangement testing was inconclusive. A mildly positive anticardiolipin antibody (10.7, range 0-10) was noted. An inflammatory anetoderma secondary to antiphospholipid syndrome was suspected. Aspirin and warfarin therapy trial showed no benefit. As his rash was stable, he was discharged, but presented 3 years later with a significant flare. On examination he had raised, violaceous and indurated plaques across his trunk. Anetoderma was noted where the rash had resolved. A skin biopsy showed an atypical lymphoid infiltrate consisting of prominent lymphoplasmacytoid cells with lambda-light-chain restriction consistent with a primary cutaneous marginal zone B cell lymphoma (PCMZL). PCMZL is a form of cutaneous B-cell lymphoma which follows an indolent course. Patients may have solitary skin lesions or present with multiple papulonodular lesions, as in our case. Involution of lesions of PCMZL with secondary anetoderma has been previously described. We present this case of PCMZL involuting with anetoderma to highlight this rare presentation.

32514 Primary cutaneous marginal zone B-cell lymphoma involution with anetoderma

A 57-year-old man presented with an 8-year history of rash on his trunk and limbs. He initially presented with small erythematous patches, which became plaque-like, violaceous, and resolved over months to years with atrophy. The initial clinical impression was of a cutaneous lymphoma or a lupus-like process. A biopsy showed a leucocytoclastic vasculitis with eosinophils with no epidermotropism or basal exocytosis, and loss of elastic fibres in the upper to mid dermis confirming anetoderma in the resolved sites. Immunostaining demonstrated scattered CD3+ T-cells showing a mix of CD4 and CD8 subtypes. CD20 was negative. Few macrophages were CD60+. T-cell gene rearrangement testing was inconclusive. A mildly positive anticardiolipin antibody (10.7, range 0-10) was noted. An inflammatory anetoderma secondary to antiphospholipid syndrome was suspected. Aspirin and warfarin therapy trial showed no benefit. As his rash was stable, he was discharged, but presented 3 years later with a significant flare. On examination he had raised, violaceous and indurated plaques across his trunk. Anetoderma was noted where the rash had resolved. A skin biopsy showed an atypical lymphoid infiltrate consisting of prominent lymphoplasmacytoid cells with lambda-light-chain restriction consistent with a primary cutaneous marginal zone B-cell lymphoma (PCMZL). PCMZL is a form of cutaneous B-cell lymphoma which follows an indolent course. Patients may have solitary skin lesions or present with multiple papulonodular lesions, as in our case. Involution of lesions of PCMZL with secondary anetoderma has been previously described. We present this case of PCMZL involuting with anetoderma to highlight this rare presentation.

Primary Cutaneous B-Cell Lymphoma: An Update on Pathologic and Molecular Features

Primary cutaneous B-cell lymphomas (PCBCLs) account for 25% of all primary cutaneous lymphomas. Three major types are currently recognized by the WHO classification: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL) (both considered indolent lymphomas) and primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT), which is, instead, a very aggressive disease. Nowadays, the PCBCL’s category also includes some rare entities such as intravascular B-cell lymphoma (IVBL) and the EBV+ mucocutaneous ulcer (EBVMCU). Furthermore, controversies still exist concerning the category of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), because some cases may present with clinical and histological features between PCFCL and PCDLBCL-LT. Therefore, some authors proposed introducing another category called PCDLBCL, not otherwise specified (NOS). Regardless, PCBCLs exhibit distinct features and differ in prognosis and treatment from their nodal/systemic counterparts. Therefore, clinicopathologic analysis is a key diagnostic element in the work-up of these lymphomas.

Erythematous, telangiectatic nodule within the melomental fold

Erythematous, telangiectatic nodule within the melomental fold

Primary cutaneous marginal zone lymphoma

We report the case of a histologically confirmed primary cutaneous marginal zone B-cell lymphoma (PCMZL), which was treated by surgical excision. PCMZL is the second-most common type of primary cutaneous lymphoma, including cells of the marginal zone, lymphoplasmacytic cells, and plasma cells. Treatment options include surgery, radiotherapy, topical therapy, corticosteroids, chemotherapy, rituximab, and antibiotics. After treatment, local recurrence may occur but metastasis is extremely rare. Tumor prognosis shows an indolent course with a 5-year disease-free survival rate approaching 97%–99%. We present the case of a woman aged 69 who was diagnosed with PCMZL for a pruritic, erythematous lesion with an undefined border on the upper left leg.

Primary Cutaneous Diffuse Large B-Cell Lymphoma – a Case Report

Abstract In 2005, the World Health Organization - European Organization for Research and Treatment of Cancer (WHOEORTC) classified cutaneous B-cell lymphomas into 4 categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), and primary cutaneous diffuse large B-cell lymphoma, other (PCDLBCL-O). The absence of evident extra-cutaneous disease is a necessary condition for the diagnosis of primary cutaneous B-cell lymphomas, because they have a completely different clinical behavior and prognosis from their nodal counterparts. PCDLBCL-O basically represents a morphological variation, lacking the typical features of PCDLBCLLT, neither confirming the definition of PCFCCL, but on the clinical ground, its behavior seems at least to partially overlap the indolent course of PCFCCL. In fact, the present WHO lymphoma classification from 2008 overcame the previous WHO-EORTC classification, including at least a part of PCDLBCL-O within the spectrum of PCFCCL. However, owing to the rarity and heterogeneity of the PCDLBCL-O, the precise clinicopathological characteristics have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Nevertheless, dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatment. We present a case of a 46-year-old Caucasian male with one large round-shaped tumor and a few scattered nodules localized on the back. The histopathological features of the lesion corresponded to PCDLBCL-O. The patient follow-up showed that he was disease-free three months after surgical excision of the lesions and adjuvant local radiotherapy. No additional therapy was introduced, including chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisolone (R-CHOP).

Paediatric primary cutaneous marginal zone B-cell lymphoma: does it differ from its adult counterpart?

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) has rarely been reported in patients younger than 20 years. To report our experience with PCMZL in the paediatric/adolescent age group. Medical records of patients diagnosed with PCMZL before age 20 years and managed at two cutaneous lymphoma clinics in the U.S.A. and Israel from 1992 to 2015 were reviewed. The study group included 11 patients (six girls; median age 16 years, range 6-19·5); 10 had generalized/multifocal (T3) and one had regional/localized (T2) disease. Lesions were located on the limbs in all patients and the trunk in six; two had facial lesions. Staging in all but one was based on whole-body computed tomography or positron emission tomography. Initial management in most patients included nonradiation modalities: one patient with localized disease received intralesional steroids; six patients with multifocal disease received the following: topical/intralesional steroids (n = 3); excision (n = 2); 'watch and wait' (n = 1). No extracutaneous progression was noted during a median follow-up of 5·5 years (mean 7·5, range 0·5-14). At present, five patients are in complete remission. Based on our data (largest series in the literature with the longest follow-up), the clinicopathological presentation and course of PCMZL in the paediatric/adolescent age group are similar to those in adults. Given the indolent course and the long life expectancy of these young patients, the cumulative risk of imaging studies and the age-related potential toxicity of treatment, especially radiation, should be taken into consideration.

Recent advances in primary cutaneous B-cell lymphomas

In the last decade, there has been considerable debate regarding the classification and terminology of the group of primary cutaneous B-cell lymphomas (CBCLs). With the introduction of the WHO-EORTC classification for cutaneous lymphomas, three main types of CBCLs are recognized: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL) and primary cutaneous large B-cell lymphoma, leg type (PCLBCL, LT). Epidemiological studies performed on different patient cohorts showed that the CBCL entities described in the WHO-EORTC classification and the 4th WHO classification of tumours of haematopoietic and lymphoid tissues are reproducible worldwide and are clinically relevant, thereby illustrating the clinical usefulness of the WHO-EORTC classification. Furthermore, collaborative studies between the ISCL and EORTC lymphoma group resulted in recommended staging procedures and consensus treatment recommendations for different CBCL subtypes. The advances in the classification, staging procedures and treatment of CBCLs have led to a major improvement in clinical care. The progress in CBCL classification enables molecular studies on well defined groups of patients and facilitates comparison of treatment results between different centres. Recent studies found that intralesional/intravenous rituximab has a therapeutic value in PCFCL and PCMZL with widespread cutaneous lesions and suggest that therapies targeting the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway could be helpful in DLBCL, LT.

Is Bone Marrow Biopsy Always Indicated in Patients With Primary Cutaneous Marginal Zone B-Cell Lymphoma?

Bone marrow involvement at the time of diagnosis is uncommon in patients with primary cutaneous marginal zone B-cell lymphoma (PCMZL). Moreover, in these patients such involvement is rarely found in isolation on diagnosis. Typically the few patients with PCMZL who have early bone marrow involvement also present secondary nodal or visceral involvement, which is detected by other staging studies (usually computed tomography). In recent years, this has given rise to some debate about whether a bone marrow biopsy should be routinely performed in patients diagnosed with PCMZL in view of the good prognosis and low incidence of bone marrow infiltration and/or extracutaneous involvement in this type of lymphoma.

¿Está siempre indicada la biopsia de médula ósea en los pacientes con linfoma primario cutáneo de células B de la zona marginal?

Bone marrow involvement at the time of diagnosis is uncommon in patients with primary cutaneous marginal zone B-cell lymphoma (PCMZL). Moreover, in these patients such involvement is rarely found in isolation on diagnosis. Typically the few patients with PCMZL who have early bone marrow involvement also present secondary nodal or visceral involvement, which is detected by other staging studies (usually computed tomography). In recent years, this has given rise to some debate about whether a bone marrow biopsy should be routinely performed in patients diagnosed with PCMZL in view of the good prognosis and low incidence of bone marrow infiltration and/or extracutaneous involvement in this type of lymphoma.

Primary Cutaneous MZL with Amyloid Deposition, Initially Misdiagnosed as Amyloidosis Mimics Primary Dural MZL upon Dural Dissemination

Primary cutaneous marginal zone B-cell lymphoma (MZL) is considered a cutaneous counterpart of extranodal MZL of mucosa-associated lymphoid tissue and an indolent lymphoma. Amyloid deposition in this tumor is very rare. We report here a case of primary cutaneous MZL with massive amyloid deposition. The tumor disseminated to the dura and mimicked primary dural MZL. The patient had a four year history of the recurrence cutaneous lesions with a misdiagnosis of amyloidosis. The correct diagnosis was made after the metastatic dural lesion was confirmed by radiology, pathology and molecular biology approaches. It is of crucial importance for differential diagnosis to avoid misdiagnosis and the patients are indeed required long-term regular examinations and treatment because of the possibility of recurrence or dissemination.

Splenic Marginal Zone B-Cell Lymphoma with Epidermotropic Skin Involvement

Marginal zone B-cell lymphoma (MZL) is subclassified into extranodal MZL of mucosa-associated lymphoid tissue (including cutaneous lymphomas), splenic MZL, and nodal MZL. We report the case of a 68-year-old man with erythematous-violaceous plaques and nodules. Skin biopsy showed an epidermotropic lymphocytic infiltration and cytology and immunohistochemistry were consistent with MZL. The workup revealed disease in the peripheral blood and bone marrow and massive splenomegaly. Splenectomy confirmed the diagnosis of splenic MZL and led to resolution of the skin lesions. Cutaneous recurrence was treated successfully with chemotherapy and rituximab but caused fatal hepatitis due to hepatitis B virus reactivation. Skin involvement by splenic MZL is uncommon; this form of the disease can present epidermotropism, a very rare finding in primary cutaneous MZL. Treatment consists of splenectomy, which may be associated with chemotherapy and/or rituximab; this treatment may lead to reactivation of latent hepatitis B infection and screening for hepatitis should therefore be performed prior to starting therapy.

Linfoma B esplénico de la zona marginal con afectación cutánea epidermotropa

Marginal zone B-cell lymphoma (MZL) is subclassified into extranodal MZL of mucosa-associated lymphoid tissue (including cutaneous lymphomas), splenic MZL, and nodal MZL. We report the case of a 68-year-old man with erythematous-violaceous plaques and nodules. Skin biopsy showed an epidermotropic lymphocytic infiltration and cytology and immunohistochemistry were consistent with MZL. The workup revealed disease in the peripheral blood and bone marrow and massive splenomegaly. Splenectomy confirmed the diagnosis of splenic MZL and led to resolution of the skin lesions. Cutaneous recurrence was treated successfully with chemotherapy and rituximab but caused fatal hepatitis due to hepatitis B virus reactivation. Skin involvement by splenic MZL is uncommon; this form of the disease can present epidermotropism, a very rare finding in primary cutaneous MZL. Treatment consists of splenectomy, which may be associated with chemotherapy and/or rituximab; this treatment may lead to reactivation of latent hepatitis B infection and screening for hepatitis should therefore be performed prior to starting therapy.

Primary cutaneous marginal zone B-cell lymphoma with anetoderma: spontaneous involution plus de novo clonal expansion

We describe a rare case of primary cutaneous marginal zone B-cell lymphoma (PCMZL) in a 33-year-old male affected by hepatitis B virus (HBV)-related chronic active hepatitis. The patient presented with multiple cutaneous papulonodular lesions characterized by polymorphic immunomorphology, with inverse pattern of immunoglobulin light chain restriction in two different lesions, coupled with mucin deposition and anetoderma in a third lesion. The involution of lesions of PCMZL with secondary anetoderma has been previously described, but this has not been reported in the context of multiple lesions showing differing immunoglobulin light chain restriction. We speculate that these findings may be secondary to a variable interaction between a chronic antigenic stimulus (i.e. HBV) and its specific immune response.

The value of molecular diagnostics in primary cutaneous B-cell lymphomas in the context of clinical findings, histology, and immunohistochemistry

Primary cutaneous B-cell lymphoma (PCBCL) is classified into 3 major subtypes: primary cutaneous follicle center lymphoma (PCFCL); primary cutaneous marginal zone B-cell lymphoma (PCMZL); and primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT). Diagnosis of PCBCL is mainly based on clinical and (immuno)-histochemical grounds. We investigated the diagnostic value of the BIOMED-2 Concerted Action BMH4 CT98-3936 protocol in PCBCL. We analyzed with the BIOMED-2 Concerted Action BMH4 CT98-3936 protocol skin specimens from patients with well-defined clinical and (immuno)-histologic PCBCL (n = 18) in comparison with benign lymphocytic infiltrates (n = 9). For molecular staging we also investigated 13 extracutaneous samples from 6 patients with PCLBCL, LT. Each sample was investigated at least twice. Monoclonality was detected in all of 5 PCFCL; 5 of 6 PCMZL; all of 6 PCLBCL, LT; and 2 of 9 benign lymphocytic infiltrates. In 5 of 6 patients with PCLBCL, LT, a clone corresponding to the clone detected in the skin was detected in 3 of 5 bone-marrow, 4 of 5 blood, and 1 of 3 lymph node specimens. DNA amplification using tubes A and B of IgH was not possible in PCFCL/PCMZL, benign lymphocytic infiltrates, and extracutaneous specimens of PCLBCL, LT, even after repeated analysis up to 11 times. Pseudomonoclonality was identified by repeated analyses in one case of PCMZL and in one case of benign lymphocytic infiltrate. A multicentric, randomized, blinded study is necessary to confirm our results. Molecular diagnosis supports the clinical and (immuno)-histologic diagnosis in PCBCL. In PCLBCL, LT, molecular staging may be useful. Tubes C through E of IgH and Igκ analyses seem to be superior to tubes A and B of IgH. Each sample should be analyzed at least twice to assess the possibility of pseudomonoclonality.

Pediatric primary cutaneous marginal zone B-cell lymphoma treated with intralesional rituximab

Auteur(s) : Min Young Park1, Hyun Joo Jung2, Jun Eun Park2, You Chan Kim1 1Department of Dermatology 2Department of Pediatrics, Ajou University School of Medicine, 5 Wonchon-Dong, Yeongtong-Gu, Suwon 443-721, South Korea Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is an indolent lymphoma which is extremely rare in children. Recently, intralesional therapy with anti-CD20 monoclonal antibodies (rituximab) has shown favorable results for the treatment [...]

Primary cutaneous marginal zone B-cell lymphoma with amyloid deposition: report of two cases with review of literature

Amyloid deposition is rare. If there was a great amount of amyloid depositions in the skin tissue, it would be considered to be amyloid deposition disease at first, and then primary cutaneous marginal zone B-cell lymphoma (PCMZL). This study was to analyze the diagnosis and differential diagnosis of two cases of PCMZL with amyloid deposition. Clinicopathologic characteristics and follow-up of two cases of PCMZL were analyzed. Immunohistochemical staining was performed by EnVision method using antibodies LCA, CD19, CD20, CD79a, CD3, CD7, MUM1, kappa, lambda, Ki-67. IgH and TCRgamma gene rearrangement was detected by polymerase chain reactive (PCR). Case 1, a 71-year-old Chinese male, had a subcutaneous mass on the right elbow that was initially diagnosed with "amyloidosis" in 2004. Three years after the initial diagnosis, he developed recurrences on the right para-auxillary that was still diagnosed with "probably amyloidosis". Four years after the first diagnosis, the patient presented a lesion on the right para-auxillary with a diameter of 2 cm and a lesion on the temporal-parietal dural with a size of 6.0 cmx3.0 cmx3.0 cm. Case 2, a 68-year-old Chinese male, had a subcutaneous mass next to back of the left ear with a size of 9.0 cmx5.0 cm, and he underwent a operation one year previously because of subcutaneous mass in the same site. Microscopically, the tumors of both cases were located in dermis and subcutaneous, tumor cells were medium size with a nodular or diffuse distribution, and some of tumor cells were plasmacytoid/plasma cells. Morphologically, the temporal-parietal dural lesion was similar to subcutaneous lesion and infiltrated into cranial (case 1). Juxtaposed the tumor cells of two cases, there were the large amyloid deposits of amorphous hyaline material and concentrically laminated hyaline spherules in case 1, while cord-like amyloid deposits in case 2. Reactive lymphoid follicles with germinal centers and foreign body giant cells in the stroma were found surrounding the amyloid deposits. Congo red staining showed positive of amyloid deposition in tumor tissues of both cases. Immunohistochemical staining revealed that LCA, CD19, CD20, CD79a and MUM1 expressions were positive in tumor cells, and Ki-67 expression was about 8%-10%. IgL restricted expression as kappa positive while lambda negative was found in both cases. PCR results showed monoclone gene rearrangement of IgH gene in both cases. Our findings suggest that amyloid deposition rarely present in both primary and metastatic tumors in PCMZL, and its diagnosis should be considered to avoid misdiagnosis. The patients with PCMZL should undergo regular examinations and chemotherapy as well as a long-term follow-up since it is apt to recur or relapse.

Symmetrical primary cutaneous marginal zone lymphoma associated with rheumatoid arthritis

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is an indolent low grade B cell lymphoma of the skin, with lack of extracutaneous involvement at the time of diagnosis. Herein we report the case of a patient with rheumatoid arthritis (RA) who developed symmetrical PCMZL lesions on both ear lobes. Lesions occurring symmetrically on ear lobes are more specific for cutaneous lymphoid hyperplasia (CLH) and this kind of symmetrical localization hasn't been reported for PCMZL before. PCMZL is considered to arise from a background of reactive lymphoid hyperplasia and this case point out the concept of CLH and PCMZL spectrum. Association of marginal zone lymphoma with rheumatoid arthritis and resolution of lesions together with the resolution of symptoms due to rheumatoid arthritis after rituximab therapy is another interesting point for this case. To the best of our knowledge PCMZL associated with RA has not been reported previously.

CD123-positive Plasmacytoid Dendritic Cells in Primary Cutaneous Marginal Zone B-cell Lymphoma

The histogenesis of primary cutaneous marginal zone B-cell lymphoma (PCMZL) has not yet been clarified. Plasma-cytoid dendritic cells (PDC) play a crucial role in the initiation of immune responses and activation of T-cells and B-cells. We analyzed the presence of PDC by immunohistochemistry in various forms of primary cutaneous B-cell lymphomas and in B-cell pseudolymphomas. Clusters of CD123+PDC were observed in all PCMZL (23 of 23 cases; 100%) and in two-thirds of cutaneous B-cell pseudolymphomas (14 of 22; 64%), but only in a minority of primary cutaneous follicle center lymphoma (4 of 31; 13%) and not in primary cutaneous diffuse large B-cell lymphoma, leg type. CD123+ PDC clusters were found in close proximity to monoclonal plasma cells and T-cells and were already present at high numbers in early lesions and initial recurrences of PCMZL. In conclusion, the detection of larger clusters of PDC in PCMZL provides a useful adjunctive diagnostic marker and suggests a pathogenetically relevant role of these cells in PCMZL. Furthermore, the occurrence of PDC could explain the high number of T-cells typically found in PCMZL. We propose considering PCMZL as a unique and potentially antigen-driven neoplasm with PDC, T-cells, and B-cells as the constitutive tumor components.