Leg Type Research Articles

Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type: A Narrative Review

Primary cutaneous lymphomas are rare manifestations of extranodal lymphomas. Comprising the majority of cutaneous lymphoma cases with neoplastic B-cell origins, three main subtypes exist. In general, grossly and microscopically these subtypes are similar. However, these are three distinct variants with diverse clinicopathologic, cytogenetic, molecular, and prognostic features. Primary cutaneous diffuse large B-cell lymphoma, leg type is an exceedingly rare and aggressive variant of primary cutaneous B-cell lymphomas. Thus, increased clinical awareness is needed to differentiate between the three subtypes because earlier identification not only leads to the appropriate treatment, but also improved survival. Here, characteristic features of the three predominant variants of primary cutaneous B-cell lymphomas are presented while remaining focused on the most aggressive subtype- primary cutaneous diffuse large B-cell lymphoma, leg type.

Primary cutaneous diffuse large B-cell lymphoma, leg type – case report and literature review

Primary cutaneous diffuse large B-cell lymphoma, leg type – case report and literature review

Diagnosis and Treatment of Primary Cutaneous B-Cell Lymphomas: State of the Art and Perspectives.

Primary cutaneous B-cell lymphomas are rare entities that develop primarily in the skin. They constitute a heterogeneous group that represents around a quarter of primary cutaneous lymphomas. The 2018 update of the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification differentiates primary cutaneous marginal zone lymphoma and primary cutaneous follicle center lymphoma with an indolent course from primary cutaneous diffuse large B-cell lymphoma, leg type with an aggressive behavior. The broad spectrum of clinical presentations and the disease course marked by frequent relapses are diagnostic and therapeutic challenges. The classification of these diseases has been refined in recent years, which allows to better define their immunopathogenesis and specific management. In the present article, we review the main clinico-biological characteristics and the current therapeutic options of these three main subsets. Based on the recent therapeutic advances in nodal B-cell lymphomas, we focus on the development of novel treatment options applicable to primary cutaneous B-cell lymphomas, including targeted therapies, combination treatments and immunotherapeutic approaches, and cover basic, translational and clinical aspects aiming to improve the treatment of cutaneous B-cell lymphomas.

Primary Cutaneous B-Cell Lymphomas: An Update.

Primary cutaneous B-cell lymphomas (PCBCLs) comprise a group of extranodal B-cell non-Hodgkin lymphomas B-cell derived, which primarily involve the skin without evidence of extracutaneous disease at the time of diagnosis. They include ~25% of all cutaneous lymphomas and are classified in three major subgroups (World Health Organization (WHO) 2017): primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-center cell lymphoma (PCFCL), and diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). This classification also includes some less common entities such as intravascular large B-cell lymphoma. Recently, WHO-EORTC added Epstein–Barr virus positive (EBV+) mucocutaneous ulcer, as a new provisional distinct entity, to cutaneous B-cell lymphomas. PCBCLs are classically characterized by patches, plaques, or nodules showing great variability for color, shape, and location. Diagnosis requires histological examination with immunohistochemical staining. In general, therapeutic options depend on the exact histological and immunohistochemical classification, disease presentation, and risk assessment. PCMZL and PCFCL are considered indolent lymphomas with a good prognosis and are associated with 5-year disease-specific survival ≥ 95%. In contrast, PCDLBCL, LT is considered an aggressive lymphoma with a survival rate in 5 years of lower than 60%. Patients with a solitary lesion or limited lesions in a single anatomical site require different treatments as compared to patients with generalized lesions or refractory disease or extracutaneous involvement. Therapeutic choice includes observation, local, or systemic therapy based on histology and disease extension. Patient management is multidisciplinary, including dermatologists, pathologists, hemato-oncologists, and radiation oncologists.

Linfoma Cutâneo Primário de Grandes Células B, Tipo Perna: Relato de Caso com Apresentação Rara

Linfomas cutâneos primários são definidos como um grupo heterogéneo de neoplasias malignas linfoproliferativas que acometem a pele, sem evidência de envolvimento extracutâneo no momento do diagnóstico. O subgrupo “linfoma cutâneo primário de grandes células B, tipo perna (PCLBCL, LT)” geralmente acomete um ou ambos membros inferiores, porém 10% - 15% dos casos apresentam lesões em outros locais. Apresenta-se um caso raro de PCLBCL, LT com lesão nodular na região cervical posterior, enfatizando sua apresentação atípica. Considerando o crescimento rápido da lesão e o alto índice proliferativo, é importante conhecer todas as possíveis apresentações clínicas para assim realizar o diagnóstico precoce e instituir o tratamento efetivo.

Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type.

Primary Cutaneous Diffuse Large B-cell Lymphoma, Leg Type.

18FDG PET/CT in Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type

An 86-year-old woman was referred for a rare but aggressive subtype of primary cutaneous lymphoma of the right lower limb: diffuse large B-cell lymphoma leg type. Initial evaluation by whole-body F-FDG PET/CT showed intense hypermetabolic activity of multiple cutaneous and subcutaneous nodules of the distal third of the right leg. Follow-up evaluations by F-FDG PET/CT showed complete response after 4 and 8 cycles of appropriate rituximab combination with polychemotherapy. Although no specific recommendations are available, our case stresses the major role of F-FDG PET/CT for initial extension and treatment response evaluation in clinical practice of primary cutaneous diffuse large B-cell lymphoma leg type.

A New Metamorphic Parallel Leg Mechanism with Reconfigurable Moving Platform

This paper proposes the concept of full configuration state of metamorphic mechanism. Based on the concept, the configuration synthesis principle of metamorphic parallel mechanism is put forward. Firstly, a metamorphic parallel mechanism in full configuration state is synthesized, and then full configuration state evolves into a specific configuration state by increasing constraints or decreasing degrees of freedom. A reconfigurable moving platform based on the triple symmetric Bricard spatial closed-loop mechanism with a single degree of freedom is proposed. Based on this, a new method for switching motion configuration states of the metamorphic parallel mechanism is constructed. According to the configuration synthesis principle presented above, a novel metamorphic parallel mechanism that can switch between three- and four-degree-of-freedom is synthesized, and then the triple symmetric Bricard spatial closed-loop mechanism is used as the reconfigurable moving platform (that is, the reconfigurable foot of a walking robot) of the metamorphic mechanism, and thus, a novel metamorphic parallel leg mechanism is created. The screw theory is used to verify the degrees of freedom of the new type of metamorphic parallel leg. The proposed metamorphic parallel leg mechanism is expected to improve flexibility and adaptability of walking robots in unstructured environment.

Response of hybrid III and Mil-Lx ATD legs to explosively driven vehicle floor loading

Results are reported of small-scale explosive experiments with Hybrid III and Mil-Lx anthropomorphic test device (ATD) legs. The legs were subject to loadings from deforming metallic plates, driven by explosive loadings to replicate the movement of the floor of a protected vehicle subject to a land-mine strike. The forces measured by the legs are reported and compared between the two different leg types. The benefits of protective measures, including false-floors and commercially available footpads, are compared for their ability to reduce the forces measured in each leg type. It is concluded that the two leg types respond differently to different protective measures and hence cannot be used interchangeably.

Analysis and Design of Test Bench for a Hexapod Robot

This article presents the design of a test bench focused on the control of the legs of a hexapod robot, which allows studying the characteristics of the robot and obtaining some primary behaviors, whether mechanical, electrical or programming. In this way, a test bench structure is proposed to validate the control, performance and identification systems according to the efforts exerted by each of the components of the hexapod and also obtain a detailed view of their performance in structured environments and unstructured in order to correct its possible limitations so that in its implementation it can have coherence in response to the tasks that are posed. The results show the development of the test bench in which different types of legs were implemented which were considered the study of the mathematical model of direct kinematics and the selection of materials. For this reason, it is obtained that the best leg was the carbon fiber, since it has a very high safety coefficient, and it is very difficult for a fracture to occur when implementing it in the prototype, it is also chosen for its weight in comparison to other materials, since its characteristics have a lower structure density and high elasticity, it supports more axial loads than the other legs, even when subjected to intensive work. Finally, it is validated that the robot's performance in locomotion actions, basing this validation on the interpretation of the parameters captured by an optical sensor arranged for this task that generates the monitoring of movements in a controlled environment free of obstacles.

Diffuse large B-cell lymphoma, leg type: A case report

Diffuse large B-cell lymphoma, leg type: A case report

Transformation from Indolent Primary Cutaneous Marginal Zone Lymphoma to Aggressive Primary Cutaneous Diffuse Large B-Cell Lymphoma: A Rare Case and Review of the Literature

Introduction Primary cutaneous B-cell lymphomas (PCBCLs) arise within the skin without evidence of extracutaneous involvement at the time of diagnosis. The incidence of PCBCL is rare, and PCBCLs are less common than primary cutaneous T-cell lymphomas. There are three subgroups of PCBCL: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle-cell lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). The 5-year survival rates of the former two subtypes exceed 90%, whereas PCDLBCL-LT is approximately 50% (Wilcox 2015). We describe a rare case of indolent PCMZL transforming into the more aggressive PCDLBCL-LT as well as a review of literature and case series. Case A 62-year-old man with history of PCMZL refractory to external beam radiation and rituximab chemotherapy presented with a two-month history of an enlarging rash and three nodules on his left leg. On physical exam, two violaceous, infiltrative plaques with distinct borders were present on the left leg, resembling his past PCMZL. Three new lesions were described as deep-seated 2 cm erythematous nodules (Fig 1). Histologic review of the new nodules revealed a diffuse, dermal-based atypical lymphoid infiltrate extending from the papillary dermis into the subcutis. The atypical lymphoid cells contained mostly round nuclei, vesicular chromatin, and prominent nucleoli consistent with an immunoblastic and centroblastic morphology (Fig 2). They expressed B-cell markers such as CD79a and CD19, and were negative for CD20 most likely due to prior treatment with rituximab. Immunohistochemistry demonstrated positivity for Bcl-2 and MUM1. Discussion Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare and aggressive B-cell lymphoma. This subtype is positive for CD20 and CD79, negative for CD5 and CD10, and strongly positive for Bcl-2 and MUM1. It has the gene expression profile of the ABC subtype. A nodule on the lower leg is an ominous sign given this subtype's predilection for lower extremities. This subtype affects the elderly as opposed to the indolent subtypes that arise in middle age (Willemze 2005). Prognosticating PCDLBCL-LT is challenging, as survival rates vary from 40 to 70% (Willemze 2005). Additionally, the aggressive nature of PCDLBCL-LT confers use of more aggressive, systemic chemotherapy regimens. Rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (R-CHOP) chemotherapy followed by external beam irradiation is recommended, though no large prospective clinical trials have been performed to date. If lesions remain refractory to R-CHOP, the treatment goal should be redirected to treat as a refractory systemic diffuse large B-cell lymphoma which may require bone marrow transplant or targeted agents with known activity in the ABC subtype such as lenalidomide or ibrutinib. Transformation from PCMZL to PCDLBCL-LT is a rare event and has only been described in 2 case series (Table 1). In our review of the prior cases, the age group was heterogenous ranging from 29 years-old to 80 years-old. There was no consensus treatment, however, the majority of patients did receive at least CHOP-based regimen. Survival ranged from 24 months to 180 months, showing the heterogeneity of the disease process. In our patient, he underwent R-CHOP but progressed and then received salvage R-ICE with CR. He then underwent bone marrow transplantation but unfortunately had recurrence 36 days post-transplantation, proven PCDLBCL-LT, and he died 161 days following his allogeneic transplant. Conclusion Although PCMZL and PCFCL frequently recur despite treatment, transformation to PCDLBCL-LT is unusual. To date, transformation from PCMZL to PCDLBCL-LT has been described rarely in the literature (Table 1). PCMZL is indolent and is treated with external beam radiation therapy or surgical excision with excellent prognosis, the aggressive PCDLBCL-LT subtype has a poor outcome and requires systemic chemotherapy. Because of the vast difference in prognosis and treatment between PCMZL and PCDLBCL-LT, early recognition and exhaustive work-up is beneficial to the patient. Considering this transformation is both rare and diagnostically challenging, clinicians should have heightened concern for new nodular lesions in the setting of recurrent indolent primary cutaneous B-cell lymphomas. Disclosures Yazbeck: Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Primary Cutaneous Diffuse Large B Cell Lymphoma -Leg Type in United States: Epidemiology and Survival Outcome

Background: Primary cutaneous diffuse large B cell lymphoma-leg type (DLBCL-LT) is relatively uncommon lymphoma accounting for about 1 to 3 % of all cutaneous lymphoma and about 10-20% of primary cutaneous B cell lymphomas. There is data for survival outcomes in primary cutaneous B cell lymphoma in general population after introduction of rituximab but little is known about outcomes in DLBCL-LT patients in general population. The available data on survival in DLBCL-LT are from small case series and single institution studies. We conducted this study to evaluate the survival outcome in patients with PCDLBCL-LT after introduction of rituximab. Methods: We utilized SEER 18 database to select adult (18+ years) patients diagnosed from 2004 to 2014 with ICD-3-0 code of 9680/3 (diffuse large B cell lymphoma, not otherwise specified)with localized stage by summary stage 2000 with skin as the primary site of disease to identify patient with DLBCL-LT. Patients were divided into various cohorts based on age (<65 versus 65+ years), sex, race (Caucasians, African American and Others) and median household income of county of residence (< $50,00 versus ≥ $50,000). We utilized SEER*stat to calculate age adjusted incidence rate using 2000 US standard population. Kaplan Meyer curve was utilized to calculate 5-year overall survival. Cox proportional hazard model was used for multivariate analysis of factor associated with survival. Result: A total of 485 patients were identified with DLBCL-LT as the only or first primary cancer case. The median age at diagnosis was 70 years. Its incidence was found to be about 0.09 case per 100,000 population with incidence in males being about 1.6 times that of females. Majority of patient included in our study were males (52 %), older (59.4%), and Caucasians (85.6%). 5-year overall survival was found to be 59%. Older patients were found to have significantly worse 5-year overall survival compared to younger patients with HR of 7.9 with 95% CI of 4.9 to 12.7. There was no disparity in cancer outcome based on race, sex or median income of the county of residence. When we compared the outcome of patients diagnosed in earlier 5 years to later 6 years of the study period, the survival curves almost overlapped suggesting that there has been little if any improvement in outcome in recent years. Conclusion: Our study showed that about 60% of patients with DLBCL-LT live for 5 years in real world setting which is comparable to the outcome reported by other studies on outcome in primary cutaneous B cell lymphoma. Even though this is disease of elderly, as the median age at diagnosis is 70 years, the outcome in older population was found to be significantly worse compared to younger patients. Given this is relatively uncommon disease, we recommend large registry-based studies to try to improve outcome in these patient population. Disclosures No relevant conflicts of interest to declare.

Jumping and Grasping: Universal Locking Mechanisms in Insect Legs

AbstractThickened femora of insects are correlated to enlarged muscle masses and serve two basic purposes: jumping/kicking and grasping/holding. Modifications on the ventral femoral wall and the tibial flexor tendon that are possibly involved in catch mechanisms have been described in multiple insect taxa with both jumping and grasping legs. Our comparative study aims to explore the functional and structural similarities of these modification in jumping and grasping leg types from Coleoptera, Hymenoptera, Diptera, and Orthoptera with the combination of cutting edge, noninvasive imaging methods, and classical dissections techniques. Our data indicate that locking mechanisms are present in the jumping and grasping legs of insects. We describe three femoro-tibial lock types based on the location of the interacting sclerites relative to the site of origin of the tibial flexor tendon. All of the three types can be found in jumping insect legs, whereas only one type is present in grasping legs. The locking mechanism might aid in keeping the femoro-tibial joint in a flexed position for an extended period of time. Our data indicate that morphologically similar modifications in the femoro-tibial joint are involved in energy-saving mechanisms both in jumping and grasping legs in insects.

Navigating the cutaneous B-cell lymphomas: avoiding the rocky shoals.

In recent years great progress has been made in understanding the classification of lymphomas. The integration of morphologic, clinical, immunophenotypic, and molecular features provides a rational basis for defining disease entities and has led to worldwide consensus. Hematopathologists and dermatopathologists have worked together to define those lymphomas that are present most commonly in the skin. Some cutaneous lymphomas have distinctive features and differ from their nodal counterparts. This is most evident in the delineation of primary cutaneous follicle center lymphoma and primary cutaneous marginal zone lymphoma. Both are very indolent, with low risk to spread beyond the skin. Primary cutaneous marginal zone lymphoma shows evidence of immunoglobulin class switching, as distinct from involvement by other extranodal marginal zone lymphomas of MALT type, which may involve the skin secondarily. Some have suggested that primary cutaneous marginal zone lymphoma may be considered a benign clonal expansion, probably driven by antigen. Many cutaneous lymphomas share biological and clinical features with their systemic counterparts. For example, primary cutaneous large B-cell lymphoma, leg type, exhibits a similar gene expression and molecular profile as diffuse large B-cell lymphoma of the activated B-cell type, especially for those cases arising in other extranodal sites. In addition, Epstein-Barr virus plays a role in many cutaneous lesions including mucocutaneous ulcer, plasmablastic lymphoma, and even some cases of marginal zone lymphoma. These EBV-driven conditions may present primarily in the skin, but also involve other mainly extranodal sites. Thus, it is evident that some cutaneous and systemic lymphomas are driven by common pathogenetic mechanisms, necessitating an integrated approach for the classification of lymphoma in all sites.

Rituximab, lenalidomide and pembrolizumab in refractory primary cutaneous diffuse large B‐cell lymphoma, leg type

Rituximab, lenalidomide and pembrolizumab in refractory primary cutaneous diffuse large B‐cell lymphoma, leg type

Treatment of diaphyseal fractures of tibia with intramedullary interlocking nail

<p class="abstract"><strong>Background:</strong> The tibia, or shinbone, is the most commonly fractured long bone in the body. A tibial shaft fracture occurs along the length of the bone, below the knee and above the ankle. It typically takes a major force to cause this type of broken leg. Motor vehicle collisions, for example, are a common cause of tibial shaft fractures. In many tibia fractures, the smaller bone in the lower leg (fibula) is broken as well. The objective was to study fracture healing and union rates with closed intra-medullary interlocking nailing.</p><p class="abstract"><strong>Methods:</strong> Patients of both sexes belonging to adult age group presenting with fracture tibia to Orthopedic Department, Vydehi Institute of Medical Sciences, of are admitted from January 2015 to December 2015.<strong></strong></p><p class="abstract"><strong>Results:</strong> In the present study maximum number of patients belongs to 18 to 27 years age group (18 cases) followed by 28 to 37 years age group (15 cases), maximum number of patients sustained tibia fracture due to RTA (38 cases) followed by fall (12 cases), maximum number of patients sustained simple tibia fracture (32 cases), followed by type 2 compound tibia fracture (13 cases) and 36 patients had excellent functional results and 8 patients had good functional outcome, while only 4 patients had fair functional outcome.</p><p class="abstract"><strong>Conclusions:</strong> IM rods are secured within the bone by screws both above and below the fracture. The metal screws and the rod can be removed if they cause problems, but can also be left in place for life. Tibial rodding provides excellent fixation and alignment of the bones.</p>

PF509 MOLECULAR ANALYSIS OF PRIMARY CUTANEOUS DIFFUSE LARGE B‐CELL LYMPHOMA LEG TYPE AT DIAGNOSIS AND RELAPSE – IMPLICATIONS FOR TARGETED THERAPIES

Background:Primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL‐LT) is an aggressive cutaneous lymphoma with a 5‐year disease‐specific survival (DSS) of ∼55%. In the past decades, survival hardly improved. Currently, no routine classifiers are available to predict patients at risk for relapsed/refractory disease and to adjust treatment strategies accordingly.Aims:To improve disease classification and risk stratification, we aimed to identify the clinical relevance of advanced molecular profiling in PCDLBCL‐LT.Methods:Using targeted NGS with a 52 B‐cell lymphoma‐related gene panel and stepwise ‘triple FISH’ (MYC/BCL2/BCL6), we investigated skin biopsies of 54 PCDLBCL‐LT patients, at diagnosis (n = 49) and at relapse (n = 20). Sequential analysis was available in 15 cases. Patients were diagnosed in the Leiden University Medical Center, the Netherlands, or the University Hospital Leuven, Belgium, between 2000 and 2019. The obtained profiles were correlated with the clinical characteristics and survival outcomes.Results:The cohort consisted of 54 patients, 27 (50%) females, with a median age at diagnosis of 78 (range 47–92) years. Median follow‐up duration was 81 (range 1–172) months. Additional clinical characteristics are presented in Figure 1. The 5‐year overall survival (OS) was 42% and the DSS 55%. At diagnosis (Figure 1A), highly frequent mutations were seen in MYD88 (69%) and CD79B (51%), both resulting in constitutive activation of the NF‐κB pathway. Other commonly mutated genes were PIM1 (29%), MYC (14%), BTG1 (12%), and TBL1XR1 (10%). MYC rearrangements were present in 26%, including one double hit (BCL6). At relapse (Figure 1B), common mutations were seen in MYD88 (75%), CD79B (55%), PIM1 (35%), MYC (15%), BTG1 (20%), and TBL1XR1 (20%), and MYC was rearranged in 39%. Sequential analysis showed newly obtained mutations in MYC and CD79B (n = 1), PIM1 (n = 2), and PRDM1 (n = 1), and rearrangements in MYC (n = 1) and a double hit in BCL6 (n = 1). In addition, circulating tumor DNA (ctDNA) was detected with digital droplet PCR in 3 of 4 patients harbouring MYD88 L265P, corresponding to the clinical disease status. Female gender and MYC rearrangements, especially in combination with a MYC mutation, showed an inferior OS (gender: p = 0.001, HR 3.88, 95% CI 1.61–9.36; MYC: p = 0.029, HR 1.80, 95% CI 1.06–3.06) and DSS (gender: p = 0.004, HR 6.96, 95% CI 1.97–24.61; MYC: p = 0.004, HR 2.76 95% CI 1.52–5.01) in univariate analysis (Figure 1C‐D). Multivariate analysis demonstrated independent prognostic significance of gender in OS (gender: p = 0.003, HR 4.16, 95% CI 1.63–10.61; MYC: p = 0.137) and both in DSS (gender: p = 0.006, HR 6.04, 95% CI 1.68–21.67; MYC: p = 0.008, HR 3.86, 95% CI 1.42–10.51).Summary/Conclusion:Our data corroborate the importance of the NF‐κB pathway as the major driver of lymphomagenesis in PCDLBCL‐LT, both at diagnosis (82%) and at relapse (90%). Secondly, MYC is commonly involved (26%) and associated with inferior survival. In addition, females had an independently adverse survival compared with males. The molecular profile of primary and relapsed disease largely overlaps without recurrently acquired alterations, suggesting that relapses may result from suboptimal initial therapy. The detection of ctDNA identifies liquid biopsy as a potentially new tool of monitoring treatment response and detecting minimally residual disease. Altogether, these results underline the need for precision medicine in PCDLBCL‐LT patients, with the NF‐κB pathway and MYC as the central targets for novel therapeutic approaches.image

Mutations of the B-Cell Receptor Pathway Confer Chemoresistance in Primary Cutaneous Diffuse Large B-Cell Lymphoma Leg Type

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) preferentially involves the lower limb in elderly subjects. A combination of polychemotherapy and rituximab has improved prognosis. However, about 50% of patients will experience progression or relapse without any predictive biologic marker of therapeutic response. The mutational profile of PCLBCL-LT has highlighted mutations contributing to constitutive NF-κB and B-cell receptor (BCR) signaling pathways but has not demonstrated clinical utility. Therefore, the mutational status of 32 patients with PCLBCL-LT (14 patients with complete durable response and 18 patients with relapsing or refractory disease) was determined with a dedicated lymphopanel. Tumor pairs at diagnosis and relapse or progression were analyzed in 14 relapsing or refractory patients. Patients with PCLBCL-LT harboring one mutation that targets one of the BCR signaling genes, CD79A/B or CARD11, displayed a reduced progression-free survival and specific survival (median 18 months, P= 0.002 and 51 months, P= 0.03, respectively, whereas median duration in the wild-type group was not reached) and were associated with therapeutic resistance (P= 0.0006). Longitudinal analyses revealed that MYD88 and CD79B were the earliest and among the most mutated genes. Our data suggest that evaluating BCR mutations in patients with PCLBCL-LT may help to predict first-line therapeutic response and to select targeted therapies.

Primary cutaneous large B-cell lymphomas: relevance of the 2017 World Health Organization classification: clinicopathological and molecular analyses of 64 cases.

We applied the 2017 World Health Organization (WHO) classification criteria to categorise a series of 64 primary cutaneous large B-cell lymphomas (PCLBCLs), containing a majority (≥80%) of large cells and a proliferative rate of ≥40%, raising the problem of the differential diagnosis between PCLBCL, leg type (PCLBCL-LT) and primary cutaneous follicle centre lymphoma, large cell (PCFCL-LC). The aims were to determine the reproducibility and prognostic relevance of the 2017 WHO criteria. Morphology and phenotype identified 32 PCLBCLs-LT and 25 PCFCLs-LC; seven cases (11%) remained unclassified. Morphology was less reproducible than immunophenotype. Pertinent markers for the differential diagnosis were MUM1, FOXP1, CD10, and IgM. bcl-2 and bcl-6 were expressed by both PCFCLs-LC and PCLBCLs-LT at substantial levels. Neither Ki67 expression nor p63 expression was of diagnostic value. MYD88 was found to be mutated only in PCLBCLs-LT (n = 22, 69%). According to Hans/Hans modified algorithms, 23 of 25 PCFCLs-LC had germinal centre (GC) status, and the 32 PCLBCLs-LT had non-GC status. Overall survival was poorer for PCLBCLs-LT than PCFCLs-LC (P = 0.0002). Non-GC cases had poorer overall survival than GC cases (P = 0.0007). In PCLBCLs-LT, MYC expression was associated with cutaneous relapses (P = 0.014). When GC/non-GC status was applied to unclassified cases, only a single case remained discordant. Our results support the 2017 WHO classification criteria for PCLBCL diagnosis. The Hans modified algorithm using CD10 and MUM1 distinguished PCFCLs-LC from PCLBCLs-LT with optimal diagnostic value without requiring bcl-6 immunolabelling (poorly reproducible). Rare unclassified cases may constitute a provisionally heterogeneous subgroup for which GC/non-GC status (relevant for prognosis) may guide therapeutic decisions.