Follicle Center Cell Lymphoma Research Articles

Composite Lymphoma Comprising of BCL2 Rearrangement Negative, CD23 Positive Follicle Center Cell Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report

Abstract Introduction/Objective BCL2 rearrangement negative, CD23-positive follicle center cell lymphoma (BCL2 neg CD23 pos FCL) is a rare, recently described provisional entity in International Consensus Classification (2022). It has a predominantly diffuse growth pattern and often involves inguinal region. The molecular profile includes a high frequency of STAT6 and CREBBP co-mutation as well as 1q gain and a recurrent 1p36 loss/TNFRS14 abnormalities. We describe a composite tumor comprising of a rare entity BCL2 neg CD23 pos FCL and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). To the best of our knowledge this is the first reported case description of this co-occurrence. Methods/Case Report A 59 y/o woman presented with right cervical and axillary lymphadenopathy (upto 1.6 cm). Sections showed partial effacement of nodal architecture by interfollicular and diffuse proliferation of atypical lymphoid cells. The interfollicular areas were comprised of a monotonous population of small lymphocytes. Immunohistochemical stains performed showed that the interfollicular CD20+ PAX5+ atypical lymphoid cells coexpressed CD5, CD23, BCL2 and LEF1 and were negative for CD10, BCL6, CD3, and SOX11, with MIB1 of 5-10%. Based on these, a diagnosis of CLL/SLL was made. Admixed with the CLL/SLL, a second neoplastic B-cell component that distorted nodal architecture was also identified. It composed of a diffuse proliferation of intermediate sized lymphoid cells with a centrocytic/centroblastic morphology. This smaller population of small to intermediate sized B cells expressed CD10, BCL6, and CD23 with a MIB1 proliferation index of ~30%. This population was CD5 and BCL2 negative. CD21 showed residual follicular dendritic cell meshworks. SOX11 and BCL1 were negative. Therefore, a diagnosis of BCL2 neg CD23 pos FCL was made. Flow cytometry showed two distinct populations of monotypic B-cells, one CD5-positive and the other CD10-positive. FISH studies were negative for BCL2 and BCL6 rearrangements as well as del1p36. Cytogenetics was positive for trisomy 12, supporting CLL/SLL. Next Generation Sequencing showed Tier 1 / 2 mutations in STAT6, TNFRSF14, CREBBP, and FOXO1, supporting BCL2 neg CD23 pos FCL. Hence, this represents a unique case of composite CLL/SLL and BCL2 neg CD23 pos FCL. B cell gene rearrangement showed 2 distinct clones confirming 2 separate B cell lymphomas. Results (if a Case Study enter NA) NA Conclusion Here, we describe a composite CLL/SLL and BCL2 rearrangement negative, CD23 positive, FCL never previously described in literature.

ABCL-310 Primary Cutaneous Follicle Center Cell Lymphoma, Follicular Type, With High Ki-67 Index Arising on the Forehead

ABCL-310 Primary Cutaneous Follicle Center Cell Lymphoma, Follicular Type, With High Ki-67 Index Arising on the Forehead

Primary Cutaneous Follicle Center Cell Lymphoma, Follicular Type, With High Ki-67 Index Arising on the Forehead

Primary Cutaneous Follicle Center Cell Lymphoma, Follicular Type, With High Ki-67 Index Arising on the Forehead

New Insights into Macular Type of Primary Cutaneous B-Cell Lymphoma: Extension of the Clinical and Histopathological Patterns

Background: Primary cutaneous B-cell lymphoma (PCBCL) classically presents with papules, plaques, and nodules/tumors. Previous reports of PCBCL manifesting with macular lesions are scarce and focused on primary cutaneous follicle-center cell lymphoma (PCFCL). Objectives: The objective of this study was to report our experience with PCBCL presenting with erythematous macules. Methods: Patients with low-grade PCBCL manifesting with erythematous patches, diagnosed and managed between January 2000 through December 2019 at 2 tertiary cutaneous-lymphoma outpatient clinics, were included. Clinical data were retrospectively collected, and biopsy specimens of the macules, and if present of the typical nodular/tumoral lesions, were reviewed. Results: There were 14 patients, aged 16–67 years, 8 had PCFCL and 6 marginal zone lymphoma (PCMZL). All had 1–15 cm erythematous macules, mimicking: interstitial granuloma annulare/vascular tumors/early-stage folliculotropic mycosis fungoides, or presenting with figurate erythema or livedo reticularis-like/net-like pattern. In 3 patients, macules were the presenting lesions, in 2 as the sole manifestation, whereas in 12 patients, typical PCBCL lesions were observed during disease course. The macules showed in all, superficial and deep perivascular infiltrates, and in most, periadnexal infiltrates. Micronodules were observed in 11 specimens, with nodular infiltrates also observed in 4. B cells comprised the majority of the lymphocytes in only 4. Seven of 11 cases tested showed immunoglobulin heavy chain monoclonality. Conclusions: PCMZL and PCFCL may manifest with erythematous macules. Physicians should be aware of this unusual manifestation of low-grade PCBCL, which may represent a clinicopathological diagnostic pitfall.

Hist-O-08 - Macular type of primary cutaneous B-cell lymphoma: extension of the clinical and histopathological patterns

<h3>Importance:</h3> Primary cutaneous B-cell lymphoma (PCBCL) classically presents with papules, plaques, nodules/ tumors. Previous reports of PCBCL manifesting with macular lesions are scarce, and focused on primary cutaneous follicle-center cell lymphoma (PCFCL), with limited data on its clinicopathological correlation. <h3>Objective:</h3> To report our experience with PCBCL presenting with erythematous macules. <h3>Design:</h3> Retrospective cohort. <h3>Setting:</h3> Two tertiary cutaneous-lymphoma outpatient clinics. <h3>Participants:</h3> Fourteen patients with low-grade PCBCL manifesting with erythematous patches, diagnosed and managed between January 2000 and December 2019. <h3>Intervention:</h3> Clinical data were collected from the medical files. Biopsy specimens of the macules, and if present of the typical nodular/tumoral lesions, were reviewed. <h3>Main outcome measures:</h3> Characterizing the macular lesions of low-grade PCBCL. <h3>Results:</h3> There were 14 patients, aged 16–67 years, 8 had PCFCL and 6 had primary cutaneous marginal zone lymphoma (PCMZL). All had erythematous macules, measuring 1–15 cm, which mimicked: figurate erythema, interstitial granuloma annulare, livedo reticularis, vascular tumors, and in 7 patients showed also follicular accentuation, thus simulated early-stage folliculotropic mycosis fungoides. In 3 patients macules were the presenting lesions, in 2 as the sole manifestation, whereas in 12 patients typical PCBCL lesions were observed during the disease course. On histopathology, the macular lesions showed in all superficial and deep perivascular infiltrates and in all but 1 also periadnexal lymphoid infiltrates. Microdules were observed in 11 biopsy specimens, in only 4 of them nodular infiltrates were also observed B-cells comprised the majority of the lymphocytes in only 4 patients, while in the remaining 10, B and T-cells were either equally distributed or T-cells outnumbered B. Polymerase-based analysis of a patch showed immunoglobulin heavy chain monoclonality in 7 of 11 cases tested. <h3>Conclusions and relevance:</h3> PCMZL and not only PCFCL, as previously reported, may manifest with erythematous macules, rarely as the sole presentation, and more often in conjunction with typical lesions. Histopathologically, the macules are characterized by distinct perivascular-periadnexal and micronodule pattern, and in most of the cases without the nodule formation classically observed in such lymphomas. Physicians should be aware of this unique variant representing a pitfall in the clinical and histopathologic diagnosis of low-grade PCBCL.

Teledentistry in the management of a non‐Hodgkin's lymphoma manifesting as a gingival swelling: A case report

Oral cavity lymphomas constitute only 3% of all lymphomas in the general population but are the third most common oral malignancy. A 67-year-old female with a history of osteoporosis, Graves' disease and non-Hodgkin's lymphoma was referred to the Department of Dental Specialties with a chief complaint of persistent soft tissue swelling facial to the maxillary incisors of possible non-odontogenic origin. To expedite care, the patient was first seen via teledentistry and subsequently appointed for an in-person evaluation and treatment. Examination revealed 1-3mm probing depths and a firm, non-tender, non-fluctuant mass in the facial soft tissues approximating teeth nos. 7-10. Biopsy of the affected area was performed. A diagnosis of recurrent follicle center cell lymphoma, a form of non-Hodgkin's lymphoma, was rendered. The patient was subsequently referred to the Oncology and Hematology team, followed for 6weeks and remained symptom-free. This case underlies the importance of teledentistry to expedite care and manage patient expectations. Additionally, it also underscores the importance of microscopic examination of tissue samples from oral lesions that appear non-odontogenic in nature and reinforces the role of dentistry in uncovering the oral-systemic link.

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.

Cutaneous lymphomas : Clinical presentation- diagnosis- treatment

Cutaneous lymphomas comprise different subgroups with distinct biological behavior. Mycosis fungoides, the most common cutaneous lymphoma, presents with patches, plaques, tumors and erythroderma. Therapeutic options depend on stage and comprise local skin-directed treatment in early stages, while later stages and Sézary syndrome require systemic therapies including bexarotene, interferon or brentuximab vedotin. While the rare CD4-positive lymphoproliferation and acral CD8-positive lymphoma present with an invariably indolent course, cutaneous peripheral T‑cell lymphomas exhibit an aggressive clinical behavior. Among the subgroup of cutaneous B‑cell lymphomas, primary cutaneous marginal zone lymphoma and follicle center cell lymphoma belong to indolent entities with almost unrestricted overall survival, whereas cutaneous large B‑cell lymphoma presents with asignificant risk of systemic dissemination and is associated with high lethality.

Cutaneous lymphomas : Clinical presentation- diagnosis- treatment

Cutaneous lymphomas comprise different subgroups with distinct biological behavior. Mycosis fungoides, the most common cutaneous lymphoma, presents with patches, plaques, tumors and erythroderma. Therapeutic options depend on stage and comprise local skin-directed treatment in early stages, while later stages and Sézary syndrome require systemic therapies including bexarotene, interferon or brentuximab vedotin. While the rare CD4-positive lymphoproliferation and acral CD8-positive lymphoma present with an invariably indolent course, cutaneous peripheral T‑cell lymphomas exhibit an aggressive clinical behavior. Among the subgroup of cutaneous B‑cell lymphomas, primary cutaneous marginal zone lymphoma and follicle center cell lymphoma belong to indolent entities with almost unrestricted overall survival, whereas cutaneous large B‑cell lymphoma presents with asignificant risk of systemic dissemination and is associated with high lethality.

Primary cutaneous follicle center cell lymphoma: a case report and literatures review

Primary cutaneous follicle center cell lymphoma: a case report and literatures review

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.

B-cell cutaneous lymphoid hyperplasia: report of two cases and histopathologic differentiation of cutaneous B-cell lymphoma

B-cell cutaneous lymphoid hyperplasia (B-cell pseudolymphoma) represents a heterogeneous group of benign reactivelymphoproliferative diseases caused by polyclonal B-cell rich lymphocytic infiltrates, simulating the appearance of acutaneous B-cell lymphopma clinically and/or histologically. A histopathologic differentiation of cutaneous lymphoidhyperplasia with follicular growth pattern from follicle center cell lymphoma is important. However, the differentiationbetween cutaneous lymphoid hyperplasia and cutaneous lymphoma is somewhat difficult and close long-term follow-upmay be necessary. Herein, we present two cases of B-cell cutaneous lymphoid hyperplasia with a clinico-pathologicreview of the literature.

Immunocytochemical p63 expression discriminates between primary cutaneous follicle centre cell and diffuse large B cell lymphoma‐leg type, and is of the TAp63 isoform

The p63 gene shares structural and functional homologies with the p53 family of transcriptional activators, but differs in exhibiting a consistent expression pattern in normal tissues. Although p63 is rarely mutated in malignancy studies of primary human tumours and cell lines suggest that p63 may promote tumour development. In non-Hodgkin's nodal lymphoma, TAp63 expression in follicular lymphoma (54%) and diffuse large B cell lymphoma (34%) has been described and correlated with the proliferative index. In this study, we analysed a series of primary cutaneous B cell lymphomas for immunohistochemical expression of p63. Thirty cases of diffuse large B cell lymphoma leg type (pcDLBCLL) and 34 cases of follicle centre cell lymphoma (pcFCCL) were stained using a generic antibody to p63, and a subset of these with an antibody specific for delta-Np63 isoform. The results indicate a significant difference between pcDLBCLL (21 of 30) and pcFCCL (four of 34) in p63 expression (P=0.000); expression correlated strongly with the proliferation rate as assessed by Ki-67 (P=0.015). None of the p63((+)) cases tested expressed the delta-Np63 isoform, suggesting that expression is of the TAp63 isoform. Functional studies are required to clarify the significance of p63 overexpression in primary cutaneous B cell lymphoma.

Can Cutaneous Low-Grade B-cell Lymphoma Transform Into Primary Cutaneous Diffuse Large B-cell Lymphoma? An Immunohistochemical Study of 82 cases

Low-grade B-cell lymphomas of the skin, especially, primary cutaneous follicle center cell lymphoma has several distinctive features when compared with nodal/systemic follicular lymphomas, as they are frequently negative for bcl-2 and CD10, and only fewer than 25% of the cases show a bcl-2 rearrangement. The risk of transformation of a cutaneous low-grade B-cell lymphoma, such as primary cutaneous follicle center cell lymphoma, to primary cutaneous diffuse large B-cell lymphomas (PCDLBCL) has not been clearly delineated in the literature. Transformation of systemic/nodal follicular lymphoma into aggressive DLBCL is associated with rapid disease progression, refractoriness to treatment, and poor prognosis. The authors studied 82 cases of primary cutaneous DLBCL using antibodies for follicular dendritic cells (FDCs), CD21, and CD35 to detect networks of FDCs that could possibly indicate transformation of preexisting low-grade B-cell lymphoma to PCDLBCL. All cases were classified as PCDLBCL using strict histologic and immunophenotypic criteria. Fifty-three cases were classified as primary cutaneous DLBCL of "leg type," and 29 cases were classified as primary cutaneous DLBCL, "NOS" category. Immunohistochemical studies were performed in all 82 cases; in 15 cases, a CD21/CD35+ network of FDCs was noted within the tumor, indicating the presence of remnants of residual germinal centers, suggesting the possibility of a transformed low-grade B-cell lymphoma. In summary, the authors' findings seem to indicate that some cases of primary cutaneous DLBCL may result from transformation of a low-grade B-cell lymphoma. Further studies are necessary to evaluate the significance of their findings by using ancillary techniques including genetic analysis.

Cutaneous Double-Hit B-Cell Lymphoma

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell 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 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

Chromosomal anomalies in primary cutaneous follicle center cell lymphoma do not portend a poor prognosis

The t(14;18)(q32;q21) chromosomal translocation is found in the majority of nodal follicular lymphomas but only rarely in primary cutaneous follicle center cell lymphomas (PCFCL). Recent studies have postulated that the translocation is more prevalent in PCFCL than previously described and that it might be a molecular prognostic marker. The purpose of our study was to analyze cases of PCFCL for the presence of a t(14;18) translocation using fluorescence in situ hybridization to detect balanced translocations involving either the BCL2 or MALT1 loci and to correlate the results with growth pattern, immunophenotype, and clinical outcome. In all, 57 patients with PCFCL were extracted from our cutaneous lymphoma database. Retrospective analysis of clinical parameters including lesion type, location, diagnostic stage, lactate dehydrogenase, initial treatment, relapse rate, and survival was performed. In all, 57 patients with PCFCL were included in this study. We detected 1 BCL2 chromosomal amplification, 4 translocations of BCL2, and 1 IGH/MALT1 translocation. This was a case series retrospective study. PCFCL has an excellent 5-year overall survival (100% disease-specific survival). Chromosomal abnormalities of either BCL2 or MALT1 were detected in 10% of cases but do not correlate with a specific immune pathology or clinical outcome.

CD30 expression in cutaneous B-cell and post-transplant peripheral T-cell lymphoma: report of 2 cases

CD30 expression is the hallmark of the cutaneous CD30+ lymphoproliferative disorders, lymphomatoid papulosis and anaplastic large cell lymphoma. We report CD30 expression in cutaneous follicle center cell lymphoma and in cutaneous post-transplant peripheral T-cell lymphoma. Histopathologists should be aware of CD30 expression in cutaneous lymphomas outside the realm of so-called CD30+ lymphoproliferative disorders to avoid diagnostic errors and improper medical treatment.

Primary cutaneous B-cell lymphoma in Nottinghamshire U.K.: prognosis of subtypes defined in the WHO-EORTC classification

Primary cutaneous B-cell lymphomas (PCBCL), with the exception of large B-cell lymphoma of leg type and intravascular large B-cell lymphoma, are associated with an excellent prognosis. These lymphomas have become much better understood in recent years leading to the publication in 2005 of the World Health Organization-European Organisation for Research and Treatment of Cancer classification. To determine the relative frequency of occurrence of subtypes of PCBCL in a defined population, and the survival of patients with these subtypes. During the period 1987-2009, 61 consecutive patients with PCBCL were identified from the Nottingham Lymphoma Registry (population 1·1 million). After histological review, the number of patients with each subtype was as follows: marginal zone, 18; follicle centre, 14; diffuse large B cell, leg type, 16; diffuse large B cell, other sites, 12; and intravascular large B cell, one. The 5- and 10-year lymphoma-specific survival for patients with marginal zone lymphoma was 100%. The only patient with intravascular large B-cell lymphoma died from widespread disease in spite of chemotherapy. The 4-year lymphoma-specific survival for follicle centre cell lymphoma was 90%. Patients with the other subtypes had the following 5-year lymphoma-specific survival rates: diffuse large B cell, leg type, 61% and diffuse large B cell, other, 40%. The median age at diagnosis for patients with diffuse large B-cell lymphoma, leg type was 82 years and as a consequence the 5-year overall survival was only 15%. There was a 3·4-fold increase in the incidence of PCBCL from the period 1987-1997 to the period 1998-2009. PCBCL is a rare disease (incidence around three per million population per year). It is, in our view, essential that it is diagnosed by a pathologist with an interest in cutaneous lymphoma and that the very different prognosis of the individual subtypes is appreciated by the treating clinician.

Extranodal diffuse large B cell lymphoma of cutaneous follicle centre lymphoma type: a study of 24 patients with non‐cutaneous primary limited stage extranodal diffuse large B cell lymphoma in support of a new concept

Follicle centre cell lymphoma of small cell type showing either a follicular or diffuse growth pattern similar to cutaneous follicle centre lymphoma (cFCL) has been recognized in extranodal non-cutaneous sites. Our aim was (i) to investigate whether diffuse large B cell lymphoma (DLBCL) of cFCL type could be identified in extranodal non-cutaneous sites and (ii) whether clinical characteristics similar to primary cFCL could be recognized. Of 24 extranodal non-cutaneous DLBCLs, nine (38%) had large centrocytoid morphology and 15 (62%) were either 'centrocytoid and centroblastic' or 'centroblastic and immunoblastic'. Six centrocytoid cases were Irf-4 negative, Bcl-6 positive and at most weakly CD10- or Bcl-2-positive by immunohistochemistry, consistent with DLBCL of cFCL type. All patients with cFCL type were stage IE and were significantly younger than other patients. Recurrences occurred in two patients and were exclusively extranodal. Our results suggest that DLBCL of cFCL type can be identified in extranodal non-cutaneous sites and shows clinical characteristics similar to genuine cFCL. We propose to expand the concept of cFCL to encompass large cell lymphomas in extranodal sites.

The Histomorphologic Spectrum of Primary Cutaneous Diffuse Large B-Cell Lymphoma: A Study of 79 Cases

Primary cutaneous large B-cell lymphomas (PCLBCL) have historically been a matter of debate in the literature. The 2005 World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification scheme segregated cutaneous B-cell lymphomas into 3 groups: primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicle center cell lymphoma, and primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), "leg type" (PCDLBCL-LT). Additionally, the WHO-EORTC classification scheme utilized the term PCLBCL "other" not otherwise specified (NOS) type for rare cases of PCLBCL not belonging to either the "leg type" or the primary cutaneous follicle center cell lymphoma group. In this study, we retrospectively assessed the histomorphologic features of 79 cases of PCDLBCLs, including those of "leg type" and "other" NOS type, to further categorize the histologic spectrum of these unusual cutaneous neoplasms. The histologic diagnosis of PCLBCL usually poses little diagnostic difficulty; however, some cases may adopt unusual or unfamiliar appearances mimicking other lymphoproliferative disorders or other malignant neoplasms. Seventy-nine cases, occurring in 37 men and 42 women, aged 34-94 years, were analyzed. Fifty-three cases were classified as "leg type" and 26 cases were classified as "other" NOS type using the WHO-EORTC classification. Of the 53 cases classified as "leg type," 33 were women and 20 were men; of the 26 cases of "other" NOS type, 9 were women and 17 were men. In the "leg type" category, 31 cases were located on the lower extremities, 5 cases on the face, 5 cases on the arm, 3 cases on the chest, 2 cases on the shoulder, 2 cases on the back, 1 case on the trunk, 1 case on the buttock, 1 case on the supraclavicular area, 1 case on the head, and 1 case on the flank. Of the "other" NOS type category, 8 cases were located on the face, 5 cases on the shoulder, 3 cases on the head, 2 cases on the abdomen, 2 cases on the chest, 1 case on the trunk, 1 on the vulva, 1 on the axilla, 1 on the back, 1 on the neck, and 1 on the hip. Most cases assessed showed the classic morphologic appearance of PCDLBCL, but cases mimicking Burkitt lymphoma (starry-sky pattern), natural killer-cell (NK) lymphoma, mycosis fungoides (epidermotropism), low-grade B-cell lymphomas, epithelial malignancies, and Merkel cell carcinoma were encountered in this series. The high frequency of these rare histologic patterns can be explained by a bias associated with consultation practice. Careful histologic examination and immunohistochemical stains were used to establish the correct diagnosis. The differential diagnosis of PCDLBCL is broad and difficult to define histologically. Knowledge of these rare histologic variants is necessary to avoid misinterpretation of these cases as nonlymphoid malignancies.