Primary Cutaneous Follicle Center Lymphoma Research Articles

Concomitant 1p36 deletion and TNFRSF14 mutations in primary cutaneous follicle center lymphoma frequently expressing high levels of EZH2 protein.

Primary cutaneous follicle center lymphoma (PCFCL) is an indolent variant of follicular lymphoma (FL) with limited information available on the genetic background of the disease. The genetic hallmark of nodal FL, the t(14;18) translocation, affecting the BCL2 gene, is rare in PCFCL. Loss of 1p36, the most common secondary chromosomal abnormality in nodal FL, has been recently reported in 16.7% of PCFCL cases. In order to further characterize PCFCL, 21 cases were analyzed using interphase fluorescence in situ hybridization with BCL2 break apart and 1p36/1q25 dual color probes. Sanger sequencing was used to investigate TNFRSF14 and EZH2 mutations and immunohistochemistry to assess BCL2, EZH2 protein expressions.1p36 deletion occurred in 22% (5/21), BCL2 gene break in 10% (2/20) of the PCFCL cases. Mutations of the candidate tumor suppressor gene of the 1p36 region, TNFRSF14 mutations were detected in 4/17 (23.5%) cases with 2 cases presenting with concurrent 1p36 deletion. EZH2 hotspot mutations at Y641, A682, and A692 were not found. High EZH2 protein expression associated with a BCL2 negative phenotype was observed in 43% (9/21) of the cases. BCL2 gene break or 1p36 deletion did not impact the prognosis; however, they showed association with advanced stages at diagnosis (p = 0.016) and a tendency with shorter event free survival (p = 0.052).In conclusion, 1p36 deletion co-occurs with acquired TNFRSF14 mutations, suggesting a role of this tumor suppressor gene in the development of a subgroup of PCFCL. High EZH2 protein expression associated with BCL2 negative phenotype is common and might represent an ideal therapeutic target.

Dermoscopy of the Month: Dermoscopy of Primary Cutaneous B-Cell Lymphoma

Abstract Primary cutaneous B- cell lymphomas (PCBLs) are B-cell malignant neoplasms that originate in the skin, and have no extracutaneous manifestations of disease at the time of diagnosis. PCBLs are classified into three main types: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL- LT). Dermoscopic characterization of PCBLs has been limited and dermoscopy may help to augment the clinical recognition of PCBLs with the most common dermoscopic findings of salmon colored areas and serpentine vessels. Recognition of dermoscopic features of primary cutaneous B- cell lymphomas can improve the early diagnosis of these tumors and their proper management.

Outcomes of radiation therapy of indolent cutaneous B-cell lymphomas and literature review.

Primary cutaneous B-cell lymphomas represent approximately 25% of primary cutaneous lymphomas. Follicular centre cell lymphomas (PCFCL) and marginal zone lymphomas (PCMZL) are the two histological subtypes that present an indolent evolution. Radiotherapy is one of the recommended treatment options with few series reported. This study aimed to evaluate radiotherapy outcomes in term of overall survival (OS) and disease-free survival (DFS) for patients suffering from a PCMZL or PCFCL, to search for predictive factors of recurrence, and to evaluate chronic and aesthetics adverse events and patient's satisfaction. Patients treated with contact low energy radiotherapy for a PMZCL or PCFCL from April 2009 to June 2017 in Saint Louis hospital were retrospectively analysed. Total dose ranged from 18 to 30 Gy. Objective response (OR) rates, DFS and OS as patterns of recurrence according to radiation fields were analysed. Univariate analysis of DFS has been performed according to clinical and biological parameters. Acute toxicity, long-term adverse events and satisfaction were collected via individualized questionnaires. Forty-six patients were included. Median follow-up was 43.5 months. OR was achieved for 100% of cases. Recurrence occurred in 39% of cases. Median DFS was 44 months. Three-year DFS and 5-year DFS were 56% and 51%, respectively. OS at 3 and 5 year was 100%. Only sex was significantly associated with DFS. Acute AEs occurred in 48% of cases without grade 3 and 4. 55% reported some moderate aesthetic sequelae for long-term AEs. 97% were satisfied with treatment. This study confirms the good risk-benefit of radiotherapy for the treatment of primary cutaneous indolent B-cell lymphomas due to the high response rate and a long DFS. No significant factor for recurrence was identified, except female sex. Long-term aesthetic evaluation was good or excellent for most of the patients.

Primary cutaneous B-cell lymphomas- clinical and histopathologic features, differential diagnosis, and treatment.

Cutaneous B-cell lymphomas (CBCLs) are a heterogeneous group of diseases that can have variable presentations, prognoses, and treatments. The proper identification of a CBCL hinges on proper histopathologic and clinical evaluation. Comprising 25% to 30% of the primary cutaneous lymphomas, incident cases of CBCL are rare. Given the variable natural history of the CBCL, proper classification is critical so that patients are treated appropriately. CBCLs can be divided into 2 main groups: indolent and aggressive. Indolent CBCLs include primary cutaneous follicle center lymphoma and primary cutaneous marginal zone lymphoma. These subtypes usually do not affect a patient's lifespan but can lead to substantial symptomatology, prompting the need for treatment. The aggressive subtypes of CBCL include diffuse large B-cell lymphoma leg type and intravascular large B-cell lymphoma. These are treated as systemic lymphomas, and their prognoses are not as good. In this article, we discuss the clinical features, differential diagnoses, histopathologic features, and treatment options for each of the 4 types of CBCL. The proper categorization of these diseases can allow physicians to properly treat a patient with CBCL, including the avoidance of unnecessary therapy.

Primary cutaneous B-cell lymphoma: A single-center 5-year experience.

Skin is the second most common site for extranodal non-Hodgkin's lymphoma (NHL). Most primary cutaneous NHLs are of T-cell origin (70%). Primary cutaneous B-cell lymphoma (PCBCL) is a rare entity. Patients diagnosed with PCBCL between January 2012 and July 2017 at our center were retrospectively analyzed. Eight patients of PCBCL were diagnosed. Three patients (37.5%) were males while 5 patients (62.5%) were females. The median age at diagnosis was 45 years (range, 18-60 years). Scalp was the most common site of involvement (50% of the patients). Diffuse large B-cell lymphoma (DLBCL) was the most common histology (63%), with leg-type DLBCL diagnosed in 1 patient. Two patients had primary cutaneous follicle center lymphoma, whereas the remaining 1 patient had precursor B-lymphoblastic lymphoma. All 5 DLBCL cases were treated with CHOP chemotherapy, and rituximab was given to 3 patients. Of the primary cutaneous follicle center lymphomas, 1 patient with stage II disease was treated with CHOP and is alive without recurrence for the past 5 years, whereas the other patient is on observation alone. The patient with precursor B-lymphoblastic lymphoma was started on MCP-841 protocol; however, the patient did not complete the treatment and died after 11 months. PCBCL is a heterogeneous group of diseases and dividing them into subtypes, based on morphology and immunophenotype, has therapeutic implications.

SKIN B-CELL LYMPHOMAS: 20 YEARS EXPERIENCE IN OBSERVATION AND TREATMENT

Authors observed 18 patients with cutaneous B-cell lymphomas (B-CLS): primary cutaneous follicle center lymphoma (PCFCL) (44,45%), primary diffuse large B-cell lymphoma (B-CLL) (44,45%), cutaneous marginal zone B-cell lymphoma (CMZL) (11,1%). Features of cutaneous marginal zone B-cell lymphoma are: appearance of multiple spots; identification of diagnosis in stages T2aN0M0; treatment - excision or laser destruction; frequent recurrence do not affect prognosis. Features of primary cutaneous follicle center lymphoma are: appearance of single node; identification of diagnosis in stages T1aN0M0 and T2aN0M0; treatment - excision, can be also combined with radiotherapy. Features of primary diffuse B-CLL are: appearance of multiple spots; identification of diagnosis in stages T3bN0M0, T1aN1M0 and T2bN2M0; disease is aggressive; treatment is a local radiotherapy, interferon alpha intralesional, chemotherapy according to schemes CHOP, COP and R-CHOP, photodynamic therapy is possible.

Primary cutaneous B-cell lymphoma: narrative review of the literature

Primary cutaneous B-cell lymphomas comprehend a group of lymphoproliferative disorders characterized by being monoclonal proliferations of B-cell primarily involving the skin. Despite being recognized as autonomous and distinct clinico-pathologic entities since the late 80s, their classification is still an ongoing matter of debate. At the moment, WHO classification recognizes three disorders: primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma and primary cutaneous diffuse large b-cell lymphoma (leg type). Primary cutaneous diffuse large b-cell lymphoma (other) has been used to define rare cases which show histologically an infiltrate with diffuse pattern composed by large b-cell, but not fitting with criteria for follicle center lymphoma nor for primary cutaneous diffuse large b-cell lymphoma (leg type). Aim of this review was to briefly describe all recognized and provisional entities included in the primary cutaneous b-cell lymphomas and to discuss recent acquisitions that may influence their future classifications.

Linfoma cutáneo primario de células B centrofolicular: un desafío diagnóstico

El linfoma cutáneo primario de células B (LCPCB) centrofolicular corresponde a una proliferación neoplásica infrecuente e indolente de células del centro germinal confinadas a la piel. Se reporta y revisa un caso de LCPCB centrofolicular.Paciente femenino de 76 años, con antecedentes de hipertensión arterial y resistencia a la insulina. Consultó por aumento de volumen frontal de dos años de evolución. Al examen físico destacaba un nódulo único en región frontal derecha. La ecografía de partes blandas fue compatible con quiste epidérmico. La histopatología demostró en dermis profunda, tejido adiposo subcutáneo y tejido muscular estriado una proliferación linfoide sólida dispuesta en patrón nodular y difuso. A la inmunohistoquímica (IHQ), los linfocitos fueron CD20 y BCL-6 positivo, con un Ki-67 de 60% y BCL-2, CD3, CD5 y CD10 negativo. El estudio de diseminación tumoral resultó negativo. El LCPCB centrofolicular concentra el 60% de todos los LCPCB. Se presenta en promedio a los 51 años. Se ha descrito asociación con Borrelia burgdorferi, VIH, virus hepatitis C y virus Epstein-Barr. Clínicamente corresponde a un nódulo eritematoso y asintomático, localizado preferentemente en cabeza, cuello y tronco. La IHQ es fundamental para diferenciarlo de otros tipos de LCPCB. Habitualmente, el tratamiento es con radioterapia o cirugía escisional. La supervivencia es de un 95% a 5 años. Se presenta este caso dado que el LCPCB centrofolicular corresponde a un tumor cutáneo infrecuente, con múltiples diagnósticos diferenciales, que requiere de un alto índice de sospecha para lograr un diagnóstico y tratamiento oportuno.

Composite Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia and Follicular Lymphoma: A Clinicopathological Study of Six Cases.

Composite small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and follicular lymphoma (FL) is extremely rare, and only 13 cases have been reported previously. We identified 6 cases of composite SLL/CLL and FL in our database and studied their clinical, histologic, immunophenotypic, and cytogenetic features. A literature review of the existing cases was also conducted. The patients included 4 males and 2 females, with a median age of 72 years. Four patients presented with lymphadenopathy and 2 with extranodal diseases. Lymphocytosis was seen in 2 cases. Serum lactate dehydrogenase levels were within normal range in all but one case. There were 2 histologic patterns: SLL/CLL predominant pattern (type I) and FL predominant or mixed pattern (type II). The type I pattern was exclusively associated with in situ follicular neoplasia (ISFN). The SLL/CLL showed typical morphology and immunophenotype in all the cases. The FL component included low grade (n = 3), ISFN (n = 2), and primary cutaneous FL (n = 1). Four cases had staging bone marrow biopsies including 3 cases with involvement by SLL/CLL and 1 case with involvement by SLL/CLL and FL. Four patients received treatments, one was under clinical surveillance, and one had no available information. All patients were alive after a median follow-up of 22 months. This is the largest case serial of composite SLL/CLL and FL. The CL affects elderly individuals, presents with advanced clinical stage, and appears to have a relatively indolent clinical course.

Diagnostic value of STMN1, LMO2, HGAL, AID expression and 1p36 chromosomal abnormalities in primary cutaneous B cell lymphomas.

Distinction between primary cutaneous follicular lymphoma (PCFL) and primary cutaneous marginal zone lymphoma (PCMZL) is challenging, as clear-cut immunophenotypical and cytogenetic criteria to segregate both entities are lacking. To characterize PCFL and PCMZL more clearly and to define criteria helpful for the differential diagnosis, we compared expression of immunohistochemical markers [LIM-only transcription factor 2 (LMO2), human germinal centre-associated lymphoma (HGAL), stathmin 1 (STMN1), activation-induced cytidine deaminase (AID), myeloid cell nuclear differentiation antigen (MNDA)] and the presence of cytogenetic abnormalities described previously in nodal follicular lymphoma [B cell lymphoma 2 (BCL2) and BCL6 breaks, 1p36 chromosomal region deletion (del 1p36)] in a series of 48 cutaneous follicular and marginal zone lymphomas [cutaneous follicular lymphoma (CFL) and cutaneous marginal zone lymphoma (CMZL)]. Immunostaining for STMN1, LMO2, HGAL and AID allowed the distinction between CFL and CMZL, and STMN1 was the most sensitive marker (100% CFL, 0% CMZL). LMO2, HGAL and AID were positive in 93.2%, 82.1% and 86.2% CFL (all CMZL-negative). MNDA was expressed in both entities without significant difference (10.3% CFL, 30.8% CMZL, P = 0.18). BCL2, BCL6 breaks and the del 1p36 were present in 16.7%, 10.7% and 18.5% CFL and no CMZL. Finally, three and 29 CFL were reclassified as secondary cutaneous follicular lymphomas (SCFL) and PCFL without significant differences concerning phenotypical and cytogenetic features. BCL2, BCL6 breaks and the del 1p36 were present in 11.1%, 8% and 16.7% PCFL and did not impact the prognosis. LMO2, HGAL, STMN1 and AID, but not MNDA, are discriminant for the recognition between CFL and CMZL. BCL2, BCL6 rearrangements and the del 1p36 have a role in the pathogenesis of PCFL, the latest being the most common alteration.

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).

Age as a potential new prognostic indicator in primary cutaneous B-cell lymphoma (PCBCL).

e19034 Background: PCBCL is a group of rare lymphoproliferative disorders, with an estimated annual incidence of 2.5 per 1,000,000 persons. Indolent subtypes include Primary Cutaneous Marginal Zone Lymphoma (PCMZL) and Primary Cutaneous Follicular Center Lymphoma (PCFCL). Primary Cutaneous Diffuse Large B-cell Lymphoma (PCDLBCL) is an aggressive subtype with a fatality rate of 50%. The Cutaneous Lymphoma International Prognostic Index (CLIPI) can risk-stratify indolent subtypes, but age is not considered. Here we present our single-institutional analysis of clinicopathologic features and outcomes of patients with PCBCL. Methods: This is a retrospective study of patients evaluated at Moffitt Cancer Center between 01/1990 and 12/2016. Patients were identified using our PCBCL database and diagnosis was verified by independent hematopathologists and dermatopathologists. Staging was determined by ISCL/EORTC criteria. Demographics, subtype, stage, disease course, and CLIPI scores were collected. Continuous and categorical values were tested using Kruskal-Wallis ANOVA method and Fisher’s Exact Test, respectively. Kaplan-Meier curves were produced to determine PFS. Results: We identified 37 patients who met diagnostic criteria for PCBCL (35% PCFCL, 40.5% PCMZL, 13.5% PCDLBCL, and 11% indolent, unspecified). Male:female ratio was 2.4:1. 51% of patients were ≥ 60 years old (yo), and 49% were < 60 yo. 54% had stage T1 disease, 27% T2, and 19% T3. Median PFS for patients <60 was 1.1 years, but was not reached for those ≥60. Mean follow-up time was 2.6 years for all patients. Log-rank test showed a statistically significant difference in PFS between the two age groups (p=0.01). PFS for stage of indolent subtypes showed marginal significance (p <0.06). CLIPI for indolent subtypes did not show a significant difference in PFS. Conclusions: We found that age is a highly statistically significant prognostic parameter in PCBCL, as patients ≥ 60 yo had a longer PFS compared to younger patients, even after adjusting for stage and CLIPI. These results are promising for age as a possible prognostic indicator for PCBCL, but validation is needed with a larger sample size.

An Aggressive Primary Cutaneous Follicle Center Lymphoma With c-MYC Translocation and CDKN2A (9p21) Deletion: A Case Report and Review of the Literature

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 1 female patient 85 years of age with an aggressive form of primary cutaneous B-cell lymphoma manifesting in multiple firm erythematous indurated solid nodules 1-2 cm each symmetrically on the face periorbitally and on the upper extremities bilaterally. The tumor was a de novo presentation of this aggressive form of lymphoma. The disease demonstrated an aggressive course with only transient improvement of skin lesions after chemotherapy. Punch biopsy taken from a left arm skin lesion showed a diffuse and nodular large cell lymphocytic infiltrate in the 15-20 μm range exhibiting round to oval nuclei and prominent eosinophilic nucleoli. Phenotypically, the tumor cells were CD10, Bcl-2, Bcl-6, and CD43 positive with a residuum of a follicular dendritic cell network revealed by CD21 staining. There was c-MYC rearrangement and CDKN2A deletion in this sample. The importance in reporting this case is to emphasize that in the context of primary cutaneous B-cell lymphoma, the 9p21 deletion while characteristic of the leg-type lymphoma is not a unique signature of the leg-type lymphoma and is not exclusionary to lymphomas falling under the designation of follicle center lymphoma. As with the leg-type lymphoma, however, this cytogenetic abnormality is a critical determinant to a more aggressive clinical course.

Transformation of primary cutaneous follicle centre lymphoma into primary cutaneous diffuse large B-cell lymphoma of other type.

Transformation of primary cutaneous follicle centre lymphoma into primary cutaneous diffuse large B-cell lymphoma of other type.

A Case of Diffuse Large B-cell Lymphoma Transformed from Follicular Center Cell Lymphoma in a Dog

A Case of Diffuse Large B-cell Lymphoma Transformed from Follicular Center Cell Lymphoma in a Dog

The B-Cell Receptor of Primary Cutaneous Follicle Center Lymphoma: Implications for Pathogenesis

Introduction & Objectives: Primary Cutaneous Follicle Center Lymphoma (PCFCL) is a very indolent mature B-cell lymphoma that shares germinal center (GC) morphology with follicular lymphoma (FL) but lacks the characteristic t(14;18). Unlike FL, immunohistochemistry fails to detect expression of BCL2, CD10, and immunoglobulin in PCFCL. We investigated the B-cell receptor (BCR) to gain insight into the immunobiology of PCFCL.Materials & Methods: Whole Genome Sequencing (WGS) and RNAseq were performed on five PCFCL biopsies. Full-length heavy and light chain BCR transcripts were amplified by unbiased ARTISAN PCR (Koning et al., BJH 2016). More than 2000 sequences per BCR transcript were sequenced as full-length single molecules on the PacBio next-generation sequencing platform.Results: In addition to various minor translocations and deletions, WGSidentified a t(14;22) that resulted in juxtaposition of IGH and IGLL5 in one PCFCL case. No PCFCL case carried a t(14;18). Despite the absence of detectable surface Ig by immunohistochemistry, ARTISAN PCR and RNAseq-based de novo BCR assembly independently demonstrated expression of functional VDJ and VJ genes with heavily mutated V regions (VDJ: 7,1-16,0%; VJ: 4,6-11,1%) in all cases. Lack of intraclonal sequence variation indicated absence of ongoing somatic hypermutation (SHM). The t(14;22)-carrying PCFCL expressed an inconspicuous IgM. BCR of all remaining four PCFCL carried sequence motifs for N-linked glycosylation in antigen-binding regions that were apparently acquired by SHM. Three cases had undergone class switch recombination to IgG. The remaining case expressed IgM with extensive mutations. An L265P mutation in MYD88 was identified in one case, and two cases carried amplifications in chromosome 2 involving the proto-oncogene REL.Conclusions: GC morphology, extensive SHM, and class switch recombination indicate a shared origin of GC B cells for both PCFCL and FL. Clonal BCR sequences and previously identified copy number alterations prove that PCFCL represents a neoplastic clonal expansion. However, lack of ongoing SHM indicates that the immune follicles of PCFCL are not fully functional germinal centers. Since ongoing SHM is thought to contribute to lymphomagenesis by targeting non-BCR loci, absence of both ongoing SHM and the t(14;18) may explain the relatively benign clinical course of PCFCL compared to FL. As previously described for FL, continuous BCR stimulation through glycosylation-mediated binding of lectins on resident cells of the follicular microenvironment may cause clonal expansion of PCFCL cells and could play a decisive role in maintaining the follicular microarchitecture in both FL and PCFCL. In comparison to this BCR glycosylation, acquired somatic alterations in oncogenes that recurrently involved in other types of indolent B-cell lymphomas may constitute secondary driver events. Further comparisons to define the extent of malignant transformation between PCFCL, FL, and other B-lymphomas are warranted. DisclosuresVermeer:Innate Pharma: Other: Investigator in a clinical trial.

Primary cutaneous B-cell lymphomas with large cell predominance–primary cutaneous follicle center lymphoma, diffuse large B-cell lymphoma, leg type and intravascular large B-cell lymphoma

In this review, we present clinical features and detailed histopathologic, immunologic, and molecular information regarding primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type which together represent two of the three most common types of primary cutaneous B-cell lymphoma recognized in the current WHO classification system.1,2 Overall, B-cell lymphomas represent 19-27% of primary cutaneous lymphomas in most large European and American studies3-6 and together, primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type account for approximately 2/3 to ¾ of these cases.5,7-11 Both subtypes can contain a high content of large B-lymphocytes, although most cases of primary cutaneous follicle center lymphomas exhibit a range in cell size and cytology. Intravascular large B-cell lymphoma, a less commonly-encountered EBV-negative primary cutaneous B-cell lymphoma composed of large cells, will be more briefly discussed in this report as well.

Evaluation of the Role of Radiological Imaging and Bone Marrow Biopsy in Staging of Cutaneous B-Cell Lymphoma

Background: Primary cutaneous B-cell lymphoma (PCBCL) refers to B-lymphocyte derived lymphoma that develops in the skin without any extracutaneous involvement at the time of diagnosis. Primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous large B-cell lymphoma (PCLBCL) are the three major entities of PCBCL under the World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification of cutaneous lymphomas. Current guidelines recommend obtaining staging Positron emission tomography/computed tomography (PET/CT) scan or CT scan for all PCBCL, and bone marrow biopsy for at least PCLBCL-leg type variant. However, evidence supporting these recommendations, especially radiological imaging, is lacking.Methods: Data including demographics, white blood cell (WBC) count at diagnosis, lactate dehydrogenase (LDH) at diagnosis, and results of staging CT-scan, PET/CT-scan, single-photon emission computed tomography scan (SPECT-scan), and bone marrow biopsy were collected through chart review on all patients seen at Roswell Park Cancer Institute between 2001-2016 who presented with a skin lesion and had a biopsy diagnostic of B-cell lymphoma. Patients without any radiological imaging at diagnosis and those diagnosed of diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL), or follicular lymphoma (FL) prior to cutaneous manifestation were excluded.Results: 67 patients met criteria for this study of whom 97% were Caucasian and 60% were male. Cutaneous biopsies noted follicle center cell histology (16 patients; 24%), marginal zone histology (32 patients; 48%), or large B-cell histology (19 patients; 29%). Staging CT-scan, functional imaging (PET/CT-scan or SPECT-scan), and bone marrow biopsy were performed for 59 (88%), 48 (72%), and 36 (54%) patients respectively (distribution across B-cell lymphomas shown in Figure 1). Radiological imaging studies were over-interpreted in 13 patients. Radiological imaging upstaged diagnosis in 13 patients (8 DLBCL, 3 MZL, 2 FL) while bone marrow biopsy alone upstaged diagnosis in only 1 patient (DLBCL). Together, work-up upstaged diagnosis in patients with cutaneous high-grade lymphoma (large B-cell lymphoma) significantly more than it did for cutaneous low-grade lymphoma (follicle center cell and marginal zone lymphoma) histology (47% vs. 10%; p=0.0018). Presence of B-symptoms correlated with systemic disease (0 patients with PCBCL vs. 4 patients with systemic disease; p=0.0013). However, age (p=0.059), gender (p=0.5418), WBC (p=0.6676), and LDH (p=0.1736) had no correlation with systemic disease.Conclusion: Our single center retrospective analysis showed that staging work-up including radiological imaging (CT-scan or functional imaging like PET/CT-scan) and bone marrow biopsy upstaged the diagnosis in a small minority (10%) of low-grade cutaneous B-cell lymphomas. However, nearly half (47%) of those with cutaneous large B-cell lymphoma histology were found to have systemic disease upon staging. Given the aggressive disease course of large B-cell lymphomas, staging through radiological imaging and bone marrow biopsy should be pursued as currently recommended. However, for low-grade B-cell lymphomas, where even observation is a reasonable management option in selected stage IV patients, staging radiological imaging and bone marrow biopsies could be avoided unless dictated by clinical judgment. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Cutaneous B-cell lymphomas - pathogenesis, diagnostic workup, and therapy.

Cutaneous B-cell lymphomas (CBCLs) comprise a group of mature lymphoproliferative B-cell disorders that primarily affect the skin. Characterized by great biological and clinical variability among its various subtypes, CBCLs fundamentally differ from primary nodal or systemic B-cell lymphomas. Given their uncomplicated course and excellent prognosis, lymphoma classifications rank primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous follicle center lymphoma (PCFCL) as indolent CBCLs. By contrast, diffuse large B-cell lymphoma, leg type (DLBCL-LT) in particular, represent more aggressive lymphoma variants associated with a poorer prognosis. Therapeutic decisions and diagnostic procedures are based on the exact histological and immunohistochemical classification as well as the exclusion of systemic involvement and thus differentiation from nodal and systemic lymphomas. In this context, the diagnostic workup should also include molecular biology methods. Primary therapeutic options for indolent CBCL lesions include surgery and radiation therapy, as well as systemic treatment with rituximab (anti-CD20 antibody) in case of dissemination. More aggressive CBCLs usually require a combination of rituximab and polychemotherapy, primarily the CHOP regimen or modifications thereof. Given that the pathogenesis and biology of CBCLs has not been conclusively elucidated, and given the limited therapeutic armamentarium available, there is great need for comprehensive research, especially with respect to DLBCL-LT.

Primary cutaneous B‐cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers

Categorization of primary cutaneous B‐cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL‐LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus‐based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL‐LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL‐NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and MUM1, and a “double hit score” upon positivity for BCL2 and MYC. PCDLBCL‐NOS had a clinical presentation more similar to PCFCCL, whereas the histology was more consistent with the picture of a diffuse large B‐cell lymphoma, as predominantly composed of centroblasts but with intermixed a reactive infiltrate of small lymphocytes. Its behavior was intermediate between the other two forms, particularly when considering only cases with a “non‐germinal B‐cell” profile, whereas “germinal center” cases resembled PCFCCL. Our data confirmed the aggressive behavior of PCDLBC‐LT, which often coexpressed MYC and BCL2. The impact of single factors on 5‐year survival was documented, particularly histogenetic profile in PCDLBCL and BCL2 translocation in PCFCCL. Our study confirms that a further group—PCDLBCL‐NOS—exists, which can be recognized through a careful combination of histopathologic criteria coupled with adequate clinical information.