Primary Cutaneous Diffuse Large B-cell Research Articles

Abstract 3833: Primary cutaneous diffuse large B-cell lymphoma-leg type and clinicopathologic determinants of survival: Analysis of a pooled database

Abstract Background: Primary Cutaneous Diffuse Large B-cell Lymphoma-Leg Type (PCDLBCL-LT) is a rare but non-indolent subtype of B-cell lymphoma. While most PCDLBCL-LT starts over the lower extremities, some cases may present at other cutaneous sites. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this disease. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 122 cases that fit the diagnostic criteria for PCDLBCL-LT. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results: A total of 122 patients with confirmed PCDLBCL-LT were identified. The median age was 76. There was a male preponderance with M:F of 2.4. Seventy-three percent involved the extremities. The median duration of symptoms before diagnosis was 3.5 months. Involvement of lymph nodes, bone marrow, bone, and CNS occurred in 11%, 3%, 4%, and 3%, respectively. Constitutional symptoms were reported in 5%. The median OS and DFS of the whole group were 39 and 32 months, respectively. Patients younger than 70 had better median DFS (NR vs. 24 months, p=0.02) with a non-significant better median OS. Lymphadenopathy (45 vs. 18 months, p=0.006) and stage T3 compared to T1/T2 (16 vs 41 months, p=0.006) were associated with worse OS. Sex, constitutional symptoms, IHC phenotype, extra-lymphatic/extra-cutaneous organ involvement, and histologic cutaneous patterns did not impact OS. Compared to no treatment, chemotherapy, XRT+/-surgery, and stem cell transplant had numerically better OS without reaching statistical significance (5 vs. 39 vs. 41 vs. NR months, p=0.15). Patients who attained CR as their best response also had a superior median OS compared to responses less than CR and none (61 vs. 23 vs. 11 months, p<0.0001). Conclusion: This study presents updated clinicopathologic data from a large, pooled cohort of patients with PCDLBCL-LT. It identifies age, lymph node involvement, T stage, type of therapy, and quality of response to treatment as critical determinants of OS. Citation Format: Philip A. Haddad, Millicent Amankwah. Primary cutaneous diffuse large B-cell lymphoma-leg type and clinicopathologic determinants of survival: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3833.

A Descriptive Study of 103 Primary Cutaneous B-Cell Lymphomas: Clinical and Pathological Characteristics and Treatment from the Spanish Lymphoma Oncology Group (GOTEL).

Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40-65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed.

Primary cutaneous diffuse large B-cell lymphoma NOS with short-term relapse

Primary cutaneous B-cell lymphomas are a unique, heterogeneous group of lymphoproliferative dis¬orders without evidence of extra-cutaneous manifestations. Primary cutaneous diffuse large B-cell lymphomas (PCDLBCLs) are aggressive neoplasms with poor prognosis. The infiltrate in some cases could involve the underlying subcutaneous tissues, but rarely reported. Accurate diagnosis is man¬datory as these patients respond well to systemic anthracycline-based chemotherapy (R-CHOP). In this article, we report a case of PCDLBCL/NOS that presented with skin manifestations and was diagnosed based on clinical features, pathology, and immunohistochemical staining. The patients were treated with systemic chemotherapy, CHOP-R, and responded well and the PET scan showed no evidence of residual disease after the 5th cycle. After 3 months of follow-up, the patient succumbed to his disease involving almost all his skin.

New Perspectives for Patients with Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg-Type

New Perspectives for Patients with Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg-Type

Characteristics of Primary Cutaneous Lymphoma in Italy: A Tertiary Care, Single-Center Study.

Data on primary cutaneous lymphomas (PCLs) patients in the Italian population are limited, and, despite the existence of several treatment options, the management of those patients remains challenging. Our study aimed to investigate the clinical and therapeutic features of PCL patients in a referral center in Italy. We conducted a retrospective study on 100 consecutive PCL patients between January 2017 and December 2022. The mean (SD) age of our cohort was 70.33 (14.14) years. Cutaneous T-cell lymphomas (CTCLs) represented 65% of all cases; the majority were mycosis fungoides (42%), followed by cases of Sezary syndrome (10%) and primary cutaneous anaplastic large cell lymphoma (4%). Cutaneous B-cell lymphomas (CBCLs) accounted for 35 % of PCLs, with 15 cases of primary cutaneous follicle center lymphoma, 10 cases of primary cutaneous diffuse large B-cell lymphoma leg type, and 9 cases of marginal zone B-cell lymphoma. A higher frequency of pruritus (p = 0.008) and higher peripheral blood levels of beta-2 microglobulin (p ≤ 0.001) and lactate dehydrogenase (p = 0.025) were found in CTCLs compared to those of CBCLs. Considering all therapeutic lines performed, treatments were extremely heterogeneous and skin-directed therapies represented the most frequently used approach. Our study confirms the distribution of PCL subtypes formerly reported in the literature and highlights the utility of real-life data in treatments to improve the current management of PCL patients.

Spontaneous Regression of Primary Cutaneous Diffuse Large B-Cell Lymphoma on Sequential FDG PET.

Primary cutaneous diffuse large B-cell lymphoma, leg type is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities. We present a case of an elderly woman with pathology diagnosis of primary cutaneous diffuse large B-cell lymphoma, leg type with spontaneous regression without systematic therapy documented by sequential FDG PET scans and clinical follow-up.

CD20 Negative Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type with Rapidly Progressing Skin Lesions

A 95-year-old man came with violaceous nodular skin lesions of the left shin. The lesions were not painful or pruritic but progressed rapidly over the 3 months. Fever, night sweats, weight loss, and other systemic symptoms were absent. Shave biopsy of the lesion revealed the cells negative for CD20 but positive for BCL2, BCL6, FOX-P1, and CD10. PET/CT showed high uptake in the left leg and a sizeable hypermetabolic lymph node in the left pelvis. The patient was started on rituximab treatment as a single agent. This report highlights some of the diagnostic and treatment difficulties in CD20 negative lymphomas and the importance of a multidisciplinary approach in those cases.

O-124 - Liquid biopsy assessment in primary cutaneous diffuse large B-Cell lymphoma- leg type

O-124 - Liquid biopsy assessment in primary cutaneous diffuse large B-Cell lymphoma- leg type

44603 Primary cutaneous diffuse large B-cell lymphoma, leg type with spontaneous regression: report of 2 cases

44603 Primary cutaneous diffuse large B-cell lymphoma, leg type with spontaneous regression: report of 2 cases

O-125 - Detection of circulating tumor DNA in liquid biopsies of patients with primary cutaneous diffuse large B-cell lymphoma, leg type

O-125 - Detection of circulating tumor DNA in liquid biopsies of patients with primary cutaneous diffuse large B-cell lymphoma, leg type

F-18 FDG PET/CT in staging and response assessment of primary cutaneous diffuse large B-cell lymphoma (leg type)

Primary cutaneous Diffuse Large B-Cell Lymphoma-leg type (PCDLBCL-LT) is a rare subtype of cutaneous lymphomas, with high frequency of extra-cutaneous relapse and poor prognosis. We report a case of 70-year-old lady who was diagnosed with PCDLBCL-LT on biopsy and underwent a baseline F-18 FDG PET/CT, followed by interim and post-treatment PET/CTs. With this case report, we highlight the findings of F-18 FDG PET/CT in the staging of this cutaneous lymphoma, and also emphasize on its role in the response assessment.

[Clinical characteristics and efficacy analysis of 11 patients with primary cutaneous diffuse large B-cell lymphoma, leg type].

[Clinical characteristics and efficacy analysis of 11 patients with primary cutaneous diffuse large B-cell lymphoma, leg type].

Orbital Involvement by Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type.

Orbital Involvement by Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type.

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.

CD30 expression in cutaneous B-cell lymphomas.

CD30 expression has been infrequently described in cutaneous B-cell lymphomas (CBCLs). We examined CD30 expression in reactive lymphoid hyperplasia (RLH) and CBCL and correlated expression with clinicopathologic features. CD30 was examined in 82 CBCL patients and 10 RLH patients that had been evaluated in our cutaneous lymphoma clinics. The CBCL patients included: primary cutaneous follicle center lymphoma (PCFCL), Grade 1/2 systemic/nodal follicular lymphoma (SFL); primary cutaneous marginal zone lymphoma/lymphoproliferative disorder (PCMZL/LPD); systemic marginal zone lymphoma (SMZL); primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT); and extracutaneous/systemic diffuse large B-cell lymphoma (eDLBCL). We scored CD30 expression for intensity and extent and related CD30 expression to age at first diagnosis, sex, site of biopsy, clinical appearance, extracutaneous involvement, multiple cutaneous lesions, B-symptoms, lymphadenopathy, positive positron emission tomography/computed tomography (PET/CT), elevated lactate dehydrogenase (LDH), and positive bone marrow biopsy. CD30 expression was identified in 35% of CBCL, ranging from few, weak, scattered cells to strong and diffuse expression. It was most common in PCFCL and was not expressed in PCDLBCL-LT. Rare PCFCL expressed strong, diffuse CD30. Some cases of PCMZL/LPD, SMZL, FL, and RLH showed scattered, strongly positive cells. CD30 expression in CBCL was associated with favorable clinical features: younger age, negative PET/CT, and an LDH within normal limits. CD30 may be expressed in CBCL, possibly causing diagnostic confusion. CD30 expression was most commonly identified in PCFCL and is associated with favorable clinical features. In cases with strong and diffuse expression, CD30 could be a therapeutic target.

What is new about primary cutaneous B cell lymphomas.

Primary cutaneous B-cell lymphomas (CBCL) are a heterogeneous group of B-cell lymphomas without evidence of extracutaneous disease at the time of diagnosis. The 2022 World Health Organization classification of mature lymphoid neoplasms differentiates the indolent primary cutaneous marginal zone lymphoproliferative disorder, primary cutaneous follicle center lymphoma and Epstein-Barr virus-positive mucocutaneous ulcer, from the more aggressive primary cutaneous diffuse large B-cell lymphoma, leg-type and intravascular large B-cell lymphoma. The new updates in the 2022 classification are based on recent scientific advances in the understanding and characterization of these entities. This article aims to review the main clinical, cellular and molecular features of the five CBCL subsets along with their management and treatment. The exponentially growing evidence for new treatment options for systemic B-cell lymphomas raises expectations for the field of CBCL as well. However, specific prospective high quality research on CBCL is still crucial to further define their management and update international guidelines.

Cutaneous B-cell lymphomas: 2023 update on diagnosis, risk-stratification, and management.

Approximately one-fourth of primary cutaneous lymphomas are B-cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). Diagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B-cell lymphomas from systemic B-cell lymphomas with secondary skin involvement. Disease histopathology remains the most important prognostic determinant in primary cutaneous B-cell lymphomas. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5-year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis. PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single-agent rituximab may be employed for patients with more widespread skin involvement, multiagent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.

1421 Primary cutaneous diffuse large B-cell lymphoma–leg type masquerading as a mucocele

1421 Primary cutaneous diffuse large B-cell lymphoma–leg type masquerading as a mucocele

Unilateral lower extremity lymphedema as a first symptom of primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT)

Unilateral lower extremity lymphedema as a first symptom of primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT)

Clinicopathological, cytogenetic, and molecular profiles of primary cutaneous diffuse large B-cell lymphomas

We analyzed the clinicopathological, cytogenetic, and molecular features of 18 primary cutaneous diffuse large B-cell lymphomas (PCDLBCLs)and 15 DLBCLs secondarily localized to the skin (SCDLBCLs), highlighting biological similarities and differences between the 2 groups. PCDLBCLs were subclassified after histopathological review as PCDLBCL-leg type (PCDLBCL-LT, 10 cases) and the PCDLBCL-not otherwise specified (PCDLBCL-NOS, 8 cases). Immunohistochemistry for Hans' algorithm markers, BCL2, and MYC was performed. The molecular study included the determination of the cell of origin (COO) by Lymph2Cx assay on NanoString platform, FISH analysis of IgH, BCL2, BCL6, and MYC genes, as well as the mutation analysis of MYD88 gene. In immunohistochemistry analysis, BCL2 and MYC hyperexpression was more frequent in LT than in NOS cases and, according to Hans' algorithm, PCDLBCL-LTs were mostly of the non-GC type (8/10), whereas in PCDLBCL-NOS, the GC type prevailed (6/8). The determination of COO using Lymph2Cx supported and further confirmed these results. In FISH analysis, all but one LT cases versus 5 of 8 PCDLBCL-NOS showed at least one gene rearrangement among IgH, BCL2, MYC, or BCL6. In addition, MYD88 mutations were more frequently present in LT than in NOS subtypes. Interestingly, MYD88-mutated patients were older, with a non-GC phenotype and had worse OS, compared to MYD88 WT cases. Overall, SCDLBCL did not show, at the genetic and expression level, different profiles than PCDLBCL, even if they bear a significantly worse prognosis. At survival analysis, the most important prognostic factors in patients with PCDLBCL were age and MYD88 mutation, whereas relapse and high Ki-67 expression were relevant in patients with SCDLBCL. Our study comprehensively analyzed the clinicopathological and molecular features of PCDLBCL-LT, PCDLBCL-NOS, and SCDLBCL, underlining the differences among them and the importance of properly identifying these entities at the time of diagnosis.