Primary Cutaneous Marginal Zone B-cell Research Articles

Paediatric cutaneous lymphomas including rare subtypes: A 40-year experience at a tertiary referral centre.

Primary cutaneous lymphomas are neoplasms of the immune system with a distinct tropism for the skin and an absence of extracutaneous manifestations at the time of diagnosis. Studies focusing on cutaneous lymphomas in children and adolescents remain scarce and often do not encompass the rare subtypes. To address this knowledge gap by describing the clinical, histological and molecular characteristics of a large group of paediatric patients affected by primary cutaneous lymphoma. We also provided the Paediatric Primary Cutaneous Lymphoma Atlas that illustrates the clinicopathological spectrum of observed presentations, in the hope of supporting other physicians in the diagnostic process. Retrospective chart review of paediatric patients diagnosed with primary cutaneous lymphomas between 1980 and 2022 at the Paediatric Dermatology Unit of Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan. A total of 101 patients (58 males, 43 females) met the inclusion criteria. The most common subtypes were lymphomatoid papulosis (n = 48) and mycosis fungoides (n = 31). These were followed by primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders (n = 7), primary cutaneous anaplastic large-cell lymphomas (n = 5), primary cutaneous marginal zone B-cell lymphomas (n = 3), primary cutaneous follicle centre lymphomas (n = 2), subcutaneous panniculitis-like T-cell lymphomas (n = 2), primary cutaneous peripheral T-cell lymphoma not otherwise specified (n = 1), primary cutaneous precursor B-lymphoblastic lymphoma (n = 1) and Sézary syndrome (n = 1). Clinical follow-up data covering a median of 70.8 months (range 1-324) were available for 74 patients, of whom three died due to cutaneous lymphoma. Our findings shed light on the peculiar aspects and long-term outcomes of paediatric cutaneous lymphomas, particularly emphasizing their distinctive features in comparison to their adult counterparts and exploring the less common subtypes. Further larger-scale studies are warranted to better characterize these entities and to achieve a more rapid and accurate diagnosis.

Classifications of cutaneous lymphomas and lymphoproliferative disorders: An update from the EORTC cutaneous lymphoma histopathology group.

The classification of primary cutaneous lymphomas and lymphoproliferative disorders (LPD) is continuously evolving by integrating novel clinical, pathological and molecular data. Recently two new classifications for haematological malignancies including entities of cutaneous lymphomas were proposed: the 5th edition of the WHO classification of haematolymphoid tumours and the International Consensus Classification (ICC) of mature lymphoid neoplasms. This article provides an overview of the changes introduced in these two classifications compared to the previous WHO classification. The main changes shared by both classifications include the downgrading of CD8+ acral T-cell lymphoma to CD8+ acral T-cell LPD, and the recognition of entities that were previously categorized as provisional and have now been designated as definite types including primary cutaneous small or medium CD4+ T-cell LPD, primary cutaneous gamma/delta T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, Epstein-Barr virus-positive mucocutaneous ulcer. Both classifications consider primary cutaneous marginal zone B-cell clonal neoplasm as an indolent disease but use a different terminology: primary cutaneous marginal zone lymphoma (WHO) and primary cutaneous marginal zone LPD (ICC). The 5th WHO classification further introduces and provides essential and desirable diagnostic criteria for each disease type and includes chapters on reactive B- or T-cell rich lymphoid proliferations formerly referred as cutaneous pseudolymphomas, as well as histiocyte and CD8 T-cell rich LPD in patients with inborn error of immunity. As already emphasized in previous lymphoma classifications, the importance of integrating clinical, histological, phenotypic and molecular features remains the crucial conceptual base for defining cutaneous (and extracutaneous) lymphomas.

Clinical Remission of Primary Cutaneous Marginal Zone B-Cell Lymphoma in a Patient With Crohn's Disease After Helicobacter pylori Quadruple Therapy and Vedolizumab.

Clinical Remission of Primary Cutaneous Marginal Zone B-Cell Lymphoma in a Patient With Crohn's Disease After Helicobacter pylori Quadruple Therapy and Vedolizumab.

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.

106 The lymphoid follicle in pseudolymphoma, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma may activate the differentiation of B-cells and class-switching reaction as tertiary lymphoid structures

106 The lymphoid follicle in pseudolymphoma, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma may activate the differentiation of B-cells and class-switching reaction as tertiary lymphoid structures

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.

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.

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.

Pediatric Cutaneous Hematologic Disorders: Cutaneous Lymphoma and Leukemia Cutis-Experience of a Tertiary-Care Pediatric Institution and Review of the Literature.

Cutaneous hematologic malignancies are rare in children, and the literature about them is still sparse. The purpose of our study was to report our experience with pediatric cases of cutaneous hematologic disorders and describe their clinical and histological features. Data were retrospectively collected from the histopathologic database of the CHU Sainte-Justine, University of Montreal, Montreal, Canada. All patients up to 18 years of age with a diagnosis of a primary cutaneous lymphoma (including lymphomatoid papulosis), secondary cutaneous lymphoma or cutaneous manifestations of leukemia, followed from 1980 to 2019 at our center were reviewed. Thirty-six patients were included. Age at presentation ranged from birth to 18 years of age (mean 7.83 ± 5.16; median 7.0). Ten different hematologic disorders were identified according to the WHO-EORTC classifications: lymphomatoid papulosis (10 cases), mycosis fungoides (6 cases), anaplastic large cell lymphoma (4 cases), pre-B acute lymphoid leukemia (5 cases), primary cutaneous marginal zone B-cell lymphoma (4 cases), primary cutaneous CD4+medium T-cell lymphoproliferative disorder (1 case), extranodal NK/T-cell lymphoma (1 case), hydroa vacciniforme-like lymphoproliferative disorder (1 case), B-cell lymphoblastic lymphoma (1 case) and acute myeloid leukemia (3 cases). The most common subtype of cutaneous hematologic disease in our single institution study was lymphomatoid papulosis (type A and type C), followed by mycosis fungoides. Recognition of this large clinical and histological spectrum by dermatologists is important because diagnosis is often established by biopsy of skin lesions, even in secondary cutaneous cases. Moreover, the clinicopathological correlation is of utmost importance for the final diagnosis of those pathologies.

Asymptomatic, reddish-brown papules and plaques in an elderly Japanese woman

Asymptomatic, reddish-brown papules and plaques in an elderly Japanese woman

Primary cutaneous lymphomas in children: A prospective study from the Spanish Academy of Dermatology and Venereology (AEDV) Primary Cutaneous Lymphoma Registry.

Primary cutaneous lymphomas are rare in pediatric patients. The clinical and histopathological manifestations may differ from those in adults. Due to their low frequency and the insidious clinical picture, the diagnosis is usually delayed. The Spanish Primary Cutaneous Lymphoma Registry was initiated in 2016 as a multicenter registry that would allow better insight into the epidemiological, clinical, histopathological, and treatment response characteristics of patients with primary cutaneous lymphomas. We conducted a prospective observational cohort study of primary cutaneous lymphomas in pediatric patients participating in the Spanish Academy of Dermatology and Venereology (AEDV) Primary Cutaneous Lymphoma Registry. At the time of the analysis, 10 patients under 18years of age out of 799 all-age cases (1.25%) had been included in the registry (7 males, 3 females). The mean age at diagnosis was 9.7years (SD: 4.8). Seven (70%) had mycosis fungoides, 2 of them had the folliculotropic variant; and 3 (30%) had primary cutaneous marginal zone B-cell lymphoma. Primary cutaneous lymphomas are extremely rare in pediatric patients and usually have a good prognosis. Therefore, a high level of suspicion is necessary for the diagnosis. We suggest management by experienced physicians and follow-up into adulthood.

Follicular T-Helper Cells in Marginal Zone Lymphoma: Evidence of an Organoid Immune Response.

Primary cutaneous marginal zone B-cell lymphoma (MZL) follows an indolent clinical course. Histopathologically, there is a polymorphous infiltrate that includes small lymphocyte-like and centrocyte-like B cells and plasma cells usually with a substantial T-cell fraction. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, in which the signature cells have a follicular T-helper (TFH) phenotype and are admixed with numerous B cells. Thus, both present histologies of combined B-cell and T-cell infiltrates and represent differential diagnoses. The presence of TFH in MZL has yet to be elucidated. Forty-one biopsies from 40 cases of MZL and 7 cases of lymphoid hyperplasia cutis (LCH) were stained with antibodies to follicular T-helper cells, including Bcl-6, PD-1, ICOS, and CD10, as part of their diagnostic workup, were reviewed, and the stained slides were evaluated semiquantitively. Five reactive lymph nodes were also evaluated as controls. All cases of MZL and LCH contained TFH, albeit usually in low proportions. There were repeated differences in levels of expression between TFH markers, with PD1 and Bcl-6 being the most prevalent. The pattern of involvement in MZL and LCH closely mirrored that observed in the reactive lymph nodes. MZL includes TFH cells, similar to reactive lymph nodes, and a complexity of cell types. This provides evidence of an organoid immune response challenging its simple categorization as a malignancy.

Dermoscopic and trichoscopic features of primary cutaneous lymphomas - systematic review.

Dermoscopy and trichoscopy are non-invasive methods used as auxiliary tools in diagnostics of different dermatoses. To date, no systematic review concerning the utility of dermoscopy and trichoscopy in the diagnostics of primary cutaneous lymphomas has been published. The aim of this study was to summarize the current state of knowledge on this topic based on systematic search of PubMed database and related references published before 8th of August 2020. Besides dermoscopic features, type of dermoscope, polarization mode, magnification, number of cases and histopathological correlation were analysed. A total of 34 records were included into the final analysis, evaluating 141 patients diagnosed with primary cutaneous T-cell lymphomas and 70 patients with primary cutaneous B-cell lymphomas. Most of the analysed records evaluated dermoscopic features (n=206); trichoscopy was analysed in only 5 cases. Structures most commonly observed in classical mycosis fungoides (n=108) were fine short linear vessels/linear vessels, spermatozoa-like vessels and orange-yellow patchy areas. In folliculotropic mycosis fungoides (n=12), most frequently observed were comedonal lesions/comedo openings/central keratotic plugs and white halo around hair follicles/perifollicular accentuation. Primary cutaneous marginal zone B-cell lymphoma (n=42) and primary cutaneous follicle centre lymphoma (n=20) most commonly presented with salmon-coloured background and fine short/linear irregular/serpentine vessels. For other PCL, with less than 10 cases reported in the analysed records, details have been provided in the article. Most observations analysed in this systematic review rely on findings from case reports/case series (with the level of evidence V) and lack a control group. A few studies provided information concerning technical aspects of dermoscopic/trichoscopic examination. The role of dermoscopy/trichoscopy in diagnostics of cutaneous lymphomas requires further studies, especially in entities where dermoscopic features have been described in only single or a few cases. However, it seems that this practical, accessory tool in future may provide additional clues during clinical assessment.

A case report of primary cutaneous marginal zone B-cell lymphoma with mastocytosis

A 53-year-old man presented with asymptomatic, dusky reddish nodules on his trunk, which had persisted for 7 years. Histological findings showed nodular to diffuse dermal infiltration of lymphocytes with irregular nuclei, eosinophils, plasma cells, and mast cells. CD20 revealed patch positivity. Periphery of lymphoid follicles showed BCL-2 positivity and BCL-6 positivity focally at the center. CD30 and toluidine blue staining showed positivity, and several mast cells were confirmed. The immunoglobulin heavy chain gene rearrangement result showed B-cell monoclonality. The patient’s condition was diagnosed as cutaneous marginal zone B-cell lymphoma, plasmacytoid type with mastocytosis. Primary cutaneous marginal zone B-cell lymphoma is an indolent lymphoma with a tendency for local recurrence. In the specimen obtained from our patient, multiple mast cells were observed. Primary cutaneous marginal zone B-cell lymphoma with prominent mastocytosis is rare and there are a few reported cases. Therefore, this case is worth reporting for its rarity and for the purpose of reminding mastocytosis in primary cutaneous marginal zone B-cell lymphoma.

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.

Helicobacter pylori and skin disorders: a comprehensive review of the available literature.

Helicobacter pylori is a Gram-negative bacterium identified for the first time about 30 years ago and commonly considered as the main pathogenic factor of gastritis and peptic ulcer. Since then, it was found to be associated with several gastrointestinal and extra-gastrointestinal diseases. Helicobacter pylori is also associated with many skin disorders including, but not limited to, chronic urticaria, rosacea, lichen planus, atopic dermatitis, psoriasis, pemphigus vulgaris, vitiligo, primary cutaneous MALT-type lymphoma, sublamina densa-type linear IgA bullous dermatosis, primary cutaneous marginal zone B-cell lymphomas and cutaneous T-cell pseudolymphoma. Literature up to September 2020 shows that clear evidence exists only for some of the mentioned associations, while in the majority of cases, data appear contrasting. The aim of this review is to summarize the available studies on the topic and draw possible conclusions. Further clinical and laboratory studies are needed to assess the real plausibility and relevance of these associations, as well as the possible role of Helicobacter pylori with the underlying pathogenic mechanisms.

伴显著浆细胞分化的原发性边缘区B细胞淋巴瘤一例

伴显著浆细胞分化的原发性边缘区B细胞淋巴瘤一例

Adnexotropism as a Histopathological Clue for the Diagnosis of Primary Cutaneous CD4+ Small/Medium-Sized T-Cell Lymphoproliferative Disorder.

To the Editor: Primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder (PCSM-TCLPD) is considered as a World Health Organization provisional entity, histopathologically characterized by diffuse or nodular infiltrates of small- to medium-sized pleomorphic T lymphocytes with CD3+/CD4+/CD8−/CD30− phenotype, sometimes admixed with less than a 30% of large pleomorphic cells. Recognition of this disorder requires differential with other neoplastic and inflammatory disorders in the skin, including primary cutaneous marginal zone B-cell lymphoma, insect bite inflammatory reaction, mycosis fungoides, and T cell helper follicular primary cutaneous T-cell lymphoma, a neoplastic condition that may present similarities but portends a worse prognosis We have recently reviewed all the biopsies of lymphomas in our hospital from January 2010 to January 2018 to select 33 cases with clinical or histopathological diagnosis of PCSM-TCLPD diagnosed in our department. We applied the diagnostic criteria described within the last updated World Health Organization classification of hematological malignancies.1,2 Our patients clinically correspond to 16 women and 10 men with a mean age of 55.1 years (range 29–86) and with no other epidemiological features showing differences with the previously described.FIGURE 1.: A, Panoramic view of a PCSM-TCLPD with nodular infiltrates showing a rounded interface with the subcutaneous fat, (B) atypical lymphocytes surrounding and partially destructing the hair follicle, (C) infiltration by the tumoral cells in the eccrine ducts, and (D) infiltration of the piloerector muscle by the same medium-sized atypical lymphocytes.FIGURE 2.: A, Eccrine ducts that show areas with partial destruction and (B–D) different fields showing the eccrine ducts infiltration by the tumoral cells. Double immunohistochemistry LEF1 (peroxidase)/E-cadherin (alkaline phosphatase).The more striking histopathological feature, to our eyes, was a distribution showing nodules mostly located in the dermis, which tends to embrace the adnexal structures and presenting in the deeper areas a rounded pushing interface (Fig. 1A). Moreover in a lymphoma where finding epidermotropism is an exclusion criterion, was striking to find infiltration by the tumoral cells in the eccrine ducts as well as in the hair follicle in all the cases (Figs. 1B–D). This finding, adnexotropism, was first described by Beltraminelly and cols,3 and it is also observed in the larger series, although these articles have not highlighted this finding enough.3,4 In our experience, this adnexotropism is very characteristic, and the finding of an atypical lymphocytic infiltrate with these features and with scarce or lacking epidermotropism should raise the suspicion of PCSM-TCLPD. It was also striking to find infiltration by the tumoral cells in the epithelium of the eccrine ducts involving both the superficial epithelium and the basal layer that also are hyperplastic. The gland presented a multilobulated contour due to the hyperplasia of both components. In all the cases, the affected eccrine ducts showed areas with partial destruction. It was also quite characteristic to find an infiltration of the piloerector muscle by the same atypical cells.5 In these lesions is also quite frequent to find scarce nonclustered CD30-positive cells, in less than 10% of the tumoral lymphocytes and some B-cell lymphocytes. PD1 staining showed clusters of cells in all the studied cases as previously described (Fig. 2). Is important to how that syringotropism does not equal malignancy, it may be observed in several different dermatoses.6 In conclusion, precise diagnosis of PCSM-TCLPD is still a challenge, but a multilobulated nodular infiltrate of slightly atypical lymphoid cells infiltrating hyperplastic eccrine ducts that is presence of siringotropism is a useful marker that, in the appropriate context, may facilitate its recognition of PCSM-TCLPD. In this context, an immunohistochemical panel including T-cell markers, PD1, and CD30 will confirm the correct diagnosis.

Primary cutaneous marginal zone b-cell lymphoma: Case report

Primary cutaneous marginal zone B-cell lymphoma is a very rare, indolent entity, classified in in the category of extranodal marginal zone B cell lymphoma, and which presents 2% of all cutaneous lymphomas. It is an entity with several clinical characteristics and evolutionary, and especially histological, sometimes common with other neighboring entities, and posing above all the problem of positive and differential diagnosis. We expose a case of PCMZL with a particular presentation and difficulty of diagnosis over several years, insisting us through our observation on the necessity of repeating the anatomopathological examination with Immunohistochemistry to be able to make the diagnosis. The treatment is not codified, the therapeutic modalities proposed by the experts are many and varied.

Complete resolution of primary cutaneous marginal zone B-cell lymphoma on the cheek of a 7-year-old boy with intralesional triamcinolone and tincture of time.

A 7-year-old healthy boy presented with an asymptomatic smooth, firm red plaque on the cheek. Histopathology, immunostaining, molecular testing and imaging confirmed a diagnosis of a primary cutaneous marginal zone B-cell lymphoma. The lesion was treated with intralesional triamcinolone, with complete clinical resolution achieved within one year. Intralesional steroid injection is an effective first-line modality for the treatment of patients with limited disease in cosmetically sensitive areas.