Follicle Center Lymphoma Research Articles

A case of primary cutaneous follicle center lymphoma that recurred 5 years after the first diagnosis as pseudolymphoma

37歳，男性。2016年11月右前額部に紅色結節を生じた。病理では，真皮全層に小型リンパ球の密な浸潤がみられT細胞，B細胞は混在していた。偽リンパ腫と診断，ステロイド局注にて消退した。2021年8月より前額部の紅色結節再発。皮膚生検にて表皮から皮下脂肪織にかけて大型の異型細胞を混じる密な細胞浸潤がみられた。免疫グロブリンH鎖遺伝子再構成あり。免疫染色にて，CD20（＋）CD79a（＋）bcl－6（＋）bcl－2（－）MUM－1（－）で原発性皮膚濾胞中心リンパ腫（PCFCL）と診断。PETCT検査にて明らかな転移等認めず，ステロイド局注・放射線治療行い紅色結節は消退した。PCFCLは予後良好な皮膚原発のB細胞性リンパ腫であり，しばしば偽リンパ腫との鑑別が困難で，診断に難渋することがある。初回の組織学的所見が異型性に乏しく治療反応性が良好であっても慎重に経過を観察することが望ましい。

Clinical Outcomes and CNS Relapse Risk in Patients with Primary Cutaneous DLBCL, Leg Type Treated in the Rituximab Era: Long-Term Follow-up of a Single-Center Experience

Clinical Outcomes and CNS Relapse Risk in Patients with Primary Cutaneous DLBCL, Leg Type Treated in the Rituximab Era: Long-Term Follow-up of a Single-Center Experience

Epi-O-08 - Primary cutaneous B-cell lymphomas in children and adolescents: a SEER population-based study

<h3>Background:</h3> The incidence of primary cutaneous B-cell lymphomas (PCBCL) in the pediatric population is unknown, and the information on pediatric PCBCL has mostly been gathered from individual case reports or series from single centers. <h3>Objective:</h3> To assess the incidence of PCBCL in the pediatric population (<20 years) compared with adult patients (≥20 years) and delineate its demographic and clinicopathologic characteristics. <h3>Methods:</h3> This was a population-based, retrospective cohort study of patients in 18 cancer registries in the United States diagnosed between 2000 to 2016 through the Surveillance, Epidemiology, and End Results (SEER) program. Age-adjusted incidence rates were calculated for PCBCL in pediatric and adult populations. Demographic, clinical, and pathological characteristics were compared between the two groups. <h3>Results:</h3> 5,128 adult and 48 pediatric PCBCL cases were included. The median age at diagnosis in the pediatric group was 16.5 years. The major histologic subtypes of pediatric cases were marginal zone lymphoma (77.1%), diffuse large B-cell lymphoma (12.5%) and follicle center lymphoma (10.4%), which significantly differed from the distribution in the adult group (p<0.001) where subtypes were equally distributed. The age-adjusted pediatric PCBCL incidence rate (per 1,000,000 person‐years) was 0.12 (95% CI 0.09-0.16) and incidence in the adult population was approximately 40-fold higher (IRR 41.4, 95% CI 31.2-56.2, P<0.001). All 48 pediatric cases were alive during a median follow-up time of 48 months. <h3>Conclusions:</h3> Pediatric PCBCL is a rare and indolent disease, which affects mostly adolescents of both sexes. Clinical presentation is similar to adults, but marginal zone subtype is significantly over-represented.

Bio-O1-02 - Deciphering discrepancies in cutaneous lymphomas genetics

In several instances, our group has reported opposite findings to others when analyzing the genetic features of primary cutaneous T-cell or B-cell lymphomas (CTCL or CBCL). This was especially the case for the absence of NAV3 rearrangements in CTCL, the low rate of BCL2 or MYC rearrangement in primary cutaneous follicle center lymphomas (CFCL) or primary cutaneous large B-cell lymphomas, leg-type (CLBCL, LT), respectively. Here, we review bias accounting for such discrepancies. Primary cutaneous lymphoma usually present with characteristic clinical and pathological features which serve as universal criteria for initial diagnosis and treatment. When required, extensive staging including CT scan, blood analysis and for some groups bone marrow staging, is mandatory to eliminate a secondary CTCL or CBCL. Early spreading may change the initial diagnosis and a long-term follow-up is also necessary to determine the risk for extracutaneous involvement. Non-uniform inclusion criteria and follow-up time may contribute to discrepancies, especially for studies claiming for a high rate of BCL2 rearrangement in CBCL. Most CBCL or CTCL usually display an indolent course except for aggressive subtypes arising de novo such as Sézary syndrome (SS), tumor or transformed mycosis fungoides (T-MF) or CLBCL-LT. Borderline cases between indolent and aggressive cutaneous lymphomas exist and may be called for example as leukemic CTCL or CBCL, not-otherwise specified (NOS) leading to heterogeneous terminology between centers. Moreover, aggressive CL are rare occurring mainly in adults or elderly that limits therapeutic options and comparison of small groups in retrospective series. The distribution of diagnosis between the three main primary CBCL including marginal-zone lymphoma (MZL), CFCL and CLBCL, LT has considerably evolved and its heterogeneity between centers may also hamper uniform findings. Our proposal to classify large CBCL according to germinal center or non-germinal center origin has so far not been validated by others while in systemic lymphomas genomic profiling appears mandatory to identify patients with impaired prognosis. In the most frequent cutaneous lymphomas, no highly recurrent genetic mutation is commonly used for diagnosis purpose. Some genetic lesion such as CCND1 rearrangement in mantle cell lymphoma can serve a positive criteria of secondary skin involvement. Alternatively, exceptional primary anaplastic large cell lymphoma (ALCL) bear ALK rearrangement preventing to use such criteria as a hallmark of secondary skin ALCL. BCL2 rearrangement in primary CFCL contributes to identify patients at risk for extracutaneous spreading. Most reports found negative data for NAV3 rearrangement in CTCL that may not be a primary oncogenic driver but a secondary event. Interestingly, MYC rearrangement or double-hits may have a low impact on prognosis in CBCL while they are usually associated with impaired prognosis in systemic or nodal lymphomas. Alternatively, some highly recurrent mutation such as those of MYD88 in CLBCL, LT should be routinely assessed. While clinical presentation will remain a basis for CL diagnosis and treatment, it is now time to integrate molecular profiling in research studies or clinical trials to standardize diagnosis and to identify patients which will exhibit therapeutic resistance to conventional first-line treatment.

Bio-O2-09 - Clues for disease progression at time of diagnosis in patients with primary cutaneous follicle center lymphoma

Bio-O2-09 - Clues for disease progression at time of diagnosis in patients with primary cutaneous follicle center lymphoma

Epi-P-02 - Epidemiology of primary cutaneous lymphomas in Greece: a 12-year retrospective study

<h3>Introduction:</h3> Primary cutaneous lymphomas (PCL) encompass a heterogeneous group of cutaneous T cell (CTCL) and B cell (CBCL) lymphomas. The scarcity of these clinical entities makes the epidemiological study quite challenging. To date, a few studies of PCL have been conducted in the USA, Europe and Asia. We present epidemiological data of PCL in Greece based on a twelve-year retrospective study. <h3>Methods:</h3> Our study is based on histology reports from the major haemopathology referral centre in Athens, Greece from 2009 to 2020. Clinical data including the type of lymphoma, date of first diagnosis, age at diagnosis and gender were collected and processed. The patients' classification is according to the 2018 update of WHO-EORTC classification for PCL. <h3>Results:</h3> In total, 1171 new cases with PCL have been registered from the 1st of January 2009 to the 31st of December 2020, consisting of 715 males and 456 females, with a male/female ratio of 1.6. The vast majority was CTCL accounting for 83.2% (n=975) of PCL, followed by CBCL with 196 new cases comprising 16.7% of PCL. The male:female ratio was 1.8 for CTCL and 0.9 for CBCL. Mycosis fungoides (MF) was the most common cutaneous lymphoma accounting for 82.3% of CTCL and 68.6% of all PCL (n=803). Classic MF (n=553, 69%) was the most frequent subtype among MF patients followed by folliculotropic MF (n=138, 17.2%). One hundred and twelve patients with MF were presented with atypical forms of the disease. A male predominance was observed among MF patients with 526 newly diagnosed MF in men and 277 in women and a ratio male/female of 1.9. In contrast to the literature, a decreased number of primary cutaneous CD30+ lymphoproliferative disorders was noticed comprising 8.4% of PCL and 10% of CTCL. The most frequent CBCL was the primary cutaneous follicle centre lymphoma (pcFCBCL). Ninety-five new pcFCBCL cases were recorded accounting for 48.4% of CBCL and 8.1% of PCL. The marginal zone lymphoma (pcMZBCL) was the second most common CBCL with 86 new cases representing 43.8% and 7.3% of CBCL and PCL, respectively. <h3>Discussion:</h3> In the present study, an increasing trend for PCL was observed through the years. This increase may reflect the improvements in the detection and classification of these lymphomas in conjunction with an increase of the underlying causative agents. It is noteworthy that in 2020, during the COVID-19 era, there was a downward trend in new PCL diagnoses, mainly those of MF, whilst the diagnoses of CBCL were steady. While the COVID-19 pandemic may be held responsible for this, other reasons may be implicated and it needs further monitoring over the next few years. This report will empower the comparison with epidemiological data of PCL from other countries and the observation of the diagnostic trend contributing to the investigation of pathogenesis of the disease and novel therapies in the near future.

Hist-O-07 - Classification of primary cutaneous large B-cell lymphomas according to cell of origin is clinically relevant

Primary cutaneous large B-cell lymphomas (PCLBCL) correspond to either PCLBCL, leg type (PCLBCL, LT) or to primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC). Patients with PCFCL, LC are mostly treated by local approaches such as radiotherapy or when multiple lesions by rituximab only. Alternatively, PCLBCL, LT have an aggressive course, requiring a combination of rituximab and polychemotherapy as first line therapy. The combination of clinico-pathological criteria according to WHO-EORTC guidelines permit to classify most cases but those with discordant findings may fall in a not otherwise specified (PLBCL, NOS) category without therapeutic guidelines. Moreover, the expected rate of the NOS diagnosis may vary between centers. We used an already well-characterized retrospective series with long-term follow-up data to evaluate the cell of origin classification of PCLBCL as either germinal center (GC)-type or non-germinal center (NGC)-type using either an immunohistochemical profiling or a reverse transcriptase multiplex ligation assay (RT-MLPA). This cohort contained 21 PCFCL, LC cases, 27 PCLBCL, LT cases and 7 PCLBCL, NOS cases for which the review of clinical data, morphology and immunophenotype could not achieve categorization. The Hans algorithm classified 21 PCFCL, LC cases as GC-type and 27 PCLBCL, LT as NGC-type. Accordingly, the RT-MLPA analysis classified 21 PCFCL, LC cases as GC-type and 25 out of 27 PCLBCL, LT as NGC-type with two undetermined or non-contributive cases containing less than 20% tumoral cells. A concordant profiling between the two techniques permitted to reclassify 4 of the 7 PCLBCL, NOS into either PCFCL, LC (n=2) or PCLBCL, LT (n=2). RT-MLPA profiling was also concordant with lymphopanel mutational analysis providing an integrative categorization of PCLBCL especially in 6 out of 7 NOS cases categorized as PCFCL, LC (n=3) or PCLBCL, LT (n=3). A single case with a discordant profiling remained as NOS and presented with leg involvement, a GC RT-MLPA profile, no mutation and a complete remission. Survival analyses confirmed the clinical relevance of the cell of origin and molecular classifications of PCLBCL reducing the NOS diagnosis to only one case. Primary cutaneous large B-cell lymphomas (PCLBCL) correspond to either PCLBCL, leg type (PCLBCL, LT) or to primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC). Patients with PCFCL, LC are mostly treated by local approaches such as radiotherapy or when multiple lesions by rituximab only. Alternatively, PCLBCL, LT have an aggressive course, requiring a combination of rituximab and polychemotherapy as first line therapy. The combination of clinico-pathological criteria according to WHO-EORTC guidelines permit to classify most cases but those with discordant findings may fall in a not otherwise specified (PLBCL, NOS) category without therapeutic guidelines. Moreover, the expected rate of the NOS diagnosis may vary between centers. We used an already well-characterized retrospective series with long-term follow-up data to evaluate the cell of origin classification of PCLBCL as either germinal center (GC)-type or non-germinal center (NGC)-type using either an immunohistochemical profiling or a reverse transcriptase multiplex ligation assay (RT-MLPA). This cohort contained 21 PCFCL, LC cases, 27 PCLBCL, LT cases and 7 PCLBCL, NOS cases for which the review of clinical data, morphology and immunophenotype could not achieve categorization. The Hans algorithm classified 21 PCFCL, LC cases as GC-type and 27 PCLBCL, LT as NGC-type. Accordingly, the RT-MLPA analysis classified 21 PCFCL, LC cases as GC-type and 25 out of 27 PCLBCL, LT as NGC-type with two undetermined or non-contributive cases containing less than 20% tumoral cells. A concordant profiling between the two techniques permitted to reclassify 4 of the 7 PCLBCL, NOS into either PCFCL, LC (n=2) or PCLBCL, LT (n=2). RT-MLPA profiling was also concordant with lymphopanel mutational analysis providing an integrative categorization of PCLBCL especially in 6 out of 7 NOS cases categorized as PCFCL, LC (n=3) or PCLBCL, LT (n=3). A single case with a discordant profiling remained as NOS and presented with leg involvement, a GC RT-MLPA profile, no mutation and a complete remission. Survival analyses confirmed the clinical relevance of the cell of origin and molecular classifications of PCLBCL reducing the NOS diagnosis to only one case.

Epi-P-08 - A retrospective study on diagnostics and treatment outcomes of primary cutaneous B-cell lymphomas

<h3>Background:</h3> Primary cutaneous B-cell lymphomas (PCBCLs) are a group of commonly indolent diseases that comprises primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT). PCBCLs affect mainly adults but also children. Treatment is watchful waiting, excision, radiotherapy, rituximab, and systemic chemotherapy in case of extracutaneous spread disease. The disease is rare and there is a huge need of studies on clinical features and treatment outcomes. <h3>Aim:</h3> The aim of the study was to present demographics, clinical features and treatment outcomes of patients with PCBCLs in West Sweden. <h3>Methods:</h3> This is a descriptive, register-based, single center retrospective study of patients diagnosed with PCBCLs at Department of Dermatology and Venerology at Sahlgrenska University Hospital between 2002-2021. Data regarding demographics, clinical characteristics, pathological- and medical examination findings, comorbidities, staging according to TNM-system and treatment response were collected from patients' medical records and the hospital-based skin lymphoma register. <h3>Results:</h3> Nine patients with PCBCLs were identified and included in the study. Mean age at diagnosis was 53.8±14.5 years for patients with PCFCL (n=5) and 49.2±28.1 for PCMZL (n=4), respectively. Skin presentations of PCFCL were in form of papules, plaques and tumors (40%) preferably distributed on the head (60%) and trunk (40%). Papules (75%) on upper extremity (50%) were the most common manifestation in PCMZL. In most cases the histopathological diagnosis was set after the first pathological anatomical diagnosis but for PCFCL it required two or three biopsies before the diagnosis was confirmed. Monoclonality was identified in 20–25% in PCFCL and PCMZL. Lactate dehydrogenase was increased at any time in PCFCL 40% and PCMZL 25%. All the patients with PCFCL were tested for borreliosis and all were negative. One of two PCMZL patients was tested positive for borreliosis. Enlarged lymph node was found in 20% of the patients with PCFCL, all had done a CT. Radiotherapy, excision, topical/intralesional corticosteroids, chemotherapy and rituximab were used to treat PCBCLs. PCMZL had complete remission when treated with chemotherapy, radiotherapy and with excision. The treatments were commonly used as monotherapy or in a combination over time. The study population had a wide range of different comorbidities including cardiovascular diseases, hypothyroidism, rheumatic arthritis and dermatological diseases including malignant melanoma, basal cell carcinoma and herpes zoster. <h3>Conclusion:</h3> This study contributes to increased knowledge on demographics, clinical features, diagnostics, and treatment response of PCBCLs. The results of the study can be used in future research and adds some new knowledge about these unusual diseases in clinical practice.

Single-cell RNA sequencing profiling in a patient with discordant primary cutaneous B-cell and T-cell lymphoma reveals micromilieu-driven immune skewing.

Primary cutaneous lymphomas comprise a heterogeneous group of B-cell and T-cell malignancies which often show an indolent course, but can progress to aggressive disease in a subset of patients. Diagnosis is often delayed owing to clinical and histopathological similarities with benign inflammatory conditions. Especially during early disease, cancer cells are present at relatively low percentages compared with the inflammatory infiltrate, an interplay that is currently only insufficiently understood. To improve diagnostics and perform molecular characterization of a complex type of primary cutaneous lymphoma. Single-cell RNA sequencing (scRNA-seq) was performed and combined with T-cell and B-cell receptor sequencing. We were able to diagnose a patient with concurrent mycosis fungoides (MF) and primary cutaneous follicle centre lymphoma (PCFCL), appearing in mutually exclusive skin lesions. Profiling of tumour cells and the tissue microenvironment revealed a type-2 immune skewing in MF, most likely guided by the expanded clone that also harboured upregulation of numerous pro-oncogenic genes. By contrast, PCFCL lesions exhibited a more type-1 immune phenotype, consistent with its indolent behaviour. These data not only illustrate the diagnostic potential of scRNA-seq, but also allow the characterization of specific clonal populations that shape the unique tissue microenvironment in clinically distinct types of lymphoma skin lesions.

Assessing the diagnosis of “primary cutaneous mantle cell lymphoma”: A systematic review and population-based analysis

To the Editor: Primary cutaneous B-cell lymphomas include 3 malignancies in the World Health Organization-European Organisation for Research and Treatment of Cancer (WHO-EORTC) 2018 classification system: mucosa-associated lymphoid tissue/marginal zone lymphoma, follicle center lymphoma, and diffuse large B-cell lymphoma. 1 Swerdlow S.H. Campo E. Pileri S.A. et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127: 2375-2390 Crossref PubMed Scopus (3553) Google Scholar In the literature, there are occasional reports of an additional candidate for primary cutaneous status: “primary cutaneous mantle cell lymphoma” (MCL). In this report, we perform a systematic review and meta-analysis to assess whether “primary cutaneous MCL” should be a candidate for addition to classification systems. Secondary cutaneous involvement of MCL is a well-acknowledged phenomenon. 2 Gru A.A. Hurley M.Y. Salavaggione A.L. et al. Cutaneous mantle cell lymphoma: a clinicopathologic review of 10 cases. J Cutan Pathol. 2016; 43: 1112-1120https://doi.org/10.1111/cup.12802 Crossref PubMed Scopus (7) Google Scholar

Primary Cutaneous B-Cell Lymphomas in Children and Adolescents: A SEER Population-Based Study

BackgroundAlthough primary cutaneous B-cell lymphomas (PCBCL) comprise 25% of all cutaneous lymphomas, their incidence in the pediatric population is unknown, and the information on pediatric PCBCL has mostly been gathered from individual case reports or series from single centers. Patients and MethodsThis was a population-based, retrospective cohort study of patients in 18 cancer registries in the United States diagnosed between 2000 to 2016 through the Surveillance, Epidemiology, and End Results (SEER) program. Age-adjusted incidence rates were calculated for PCBCL in pediatric (<20 years) and adult (≥20 years) populations. Demographic, clinical, and pathological characteristics of PCBCL were compared between the two groups. ResultsA total of 48 pediatric and 5128 adult PCBCL cases were included. Median age at diagnosis was 16.5 years and 65 years in the two groups, respectively. The major histologic subtypes of pediatric cases were marginal zone lymphoma (77.1%), followed by diffuse large B-cell lymphoma (12.5%) and follicle center lymphoma (10.4%), which were equally distributed in adults. The age-adjusted pediatric PCBCL incidence rate (per 1,000,000 person‐years) was 0.12 (95% CI 0.09-0.16). The incidence in the adult population was approximately 40-fold higher than the one observed in the pediatric group (IRR 41.4, 95% CI 31.2-56.2). All 48 pediatric cases were alive during a median follow-up time of 48 months. ConclusionsPediatric PCBCL is a very rare disease affecting mostly adolescents of both sexes. The major histologic subtype is marginal zone lymphoma, and the prognosis is favorable.

Analysis of clonality in cutaneous B-cell lymphoma and B-cell pseudolymphoma using skin flow cytometry: Comparison of immunophenotyping and gene rearrangement studies.

To identify clonal neoplastic cells in skin affected by B-cell lymphoma using skin flow cytometry (FCM) techniques, we investigated light-chain restriction using skin FCM with clonality assessed by polymerase chain reaction and light-chain restriction by in situ hybridization (ISH). We retrospectively analyzed 16 cases of B-cell lymphoma with cutaneous involvement: primary cutaneous diffuse large B-cell lymphoma, leg type (pcDLBCL-LT) (n=7), DLBCL-not otherwise specified (DLBCL-NOS) (n=6), primary cutaneous follicle center lymphoma (pcFCL) (n=1), and follicular lymphoma (n=2), as well as cutaneous B-cell pseudolymphoma (n=9). Results of skin FCM light-chain restriction analyses were compared with immunoglobulin H (IgH) gene rearrangement and κ/λ ISH findings. Skin FCM detected light-chain restriction in 11 of 14 B-cell lymphoma patients but none of the B-cell pseudolymphoma patients. The sensitivity of skin FCM for distinguishing B-cell lymphoma and B-cell pseudolymphoma was 79%, and the specificity was 100%. Eleven of 13 B-cell lymphoma patients exhibited gene rearrangement (sensitivity 85%), whereas six of seven pseudolymphoma patients were negative (specificity 86%). ISH was positive in three of 16 B-cell lymphoma cases (sensitivity 19%) but none of the B-cell pseudolymphoma cases (specificity 100%). ISH sensitivity was 29% for pcDLBCL-LT, 17% for DLBCL-NOS, and 0% for pcFCL and follicular lymphoma. Skin FCM therefore appears to be more sensitive than ISH in detecting light-chain restriction in DLBCL and follicular lymphoma, and as sensitive as IgH gene rearrangement analysis in detecting clonality. Skin FCM is thus a promising diagnostic tool for identifying monoclonal neoplastic B-cell populations.

Molecular insights into the pathogenesis of follicular lymphoma

: Follicular lymphoma (FL) represents a group of B-cell neoplasms derived from germinal center (GC) B cells. A better understanding of the pathogenic mechanisms of FL is important for developing innovative therapies. The most common form of FL is primarily nodal and associated with the t(14;18). Recent advances obtained via genomic profiling have provided unprecedented insights into the pathogenesis of FL. Conventional FL evolves through multiple independent or convergent genetic pathways. The classical pathogenesis of t(14;18)-positive FL is a multi-stage and multi-hit process escalating along accumulation of genetic and epigenetic alterations, which starts from FL-like B cells, through premalignant lesions, into full-blown malignancy. Early precursor lesions have been recognized in the form of FL-like B cells in normal peripheral blood, and both in-situ follicular neoplasia (ISFN) and duodenal-type FL. In comparison, t(14;18)-negative FL is much more heterogeneous at the molecular level, and the underlying mechanisms are less well understood. Some variants of FL, while lacking upregulation of BCL2, share a common mutational profile with conventional FL, including mutations in epigenetic modifiers. These cases also show some clinical overlap with BCL2-positive FL, including mainly nodal involvement. Other forms of FL show more profound differences, both clinically and biologically. These emerge more clearly as separate entities and include FL, grade 3B, testicular FL (TFL), pediatric-type FL (PTFL), and primary cutaneous follicle center lymphoma (PCFCL). Mutations in epigenetic regulators and 1p36/TNFRSF14 abnormalities are highly recurrent and are seen across different subtypes of FL. Genetic profiling has offered important new insights, and will continue to impact the diagnostic approach, with changes in future classification schemes.

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

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

Clinical and Histological Spectrum of Primary Cutaneous B-Cell Lymphoma in an Ethnically-Diverse Group of Patients: A Case Series

Primary cutaneous lymphomas, which are diagnosed with only skin involvement, can be of B or T cell origin. Due to their varied origin as well as their diverse presentations, these groups have been divided further into more descriptive and representative groups. The subtypes are primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B cell lymphoma, leg type (PCDLBCL-LT) and intravascular large B-cell lymphoma. Here, we present the cases of three ethnically diverse patients with distinct clinical and histological forms of cutaneous B cell lymphoma.

Genomic landscape of cutaneous follicular lymphomas reveals 2 subgroups with clinically predictive molecular features

AbstractPrimary cutaneous follicle center lymphomas (PCFCLs) are indolent B-cell lymphomas that predominantly remain skin restricted and manageable with skin-directed therapy. Conversely, secondary cutaneous involvement by usual systemic follicular lymphoma (secondary cutaneous follicular lymphoma [SCFL]) has a worse prognosis and often necessitates systemic therapy. Unfortunately, no histopathologic or genetic features reliably differentiate PCFCL from SCFL at diagnosis. Imaging may miss low-burden internal disease in some cases of SCFLs, leading to misclassification as PCFCL. Whereas usual systemic FL is well characterized genetically, the genomic landscapes of PCFCL and SCFL are unknown. Herein, we analyzed clinicopathologic and immunophenotypic data from 30 cases of PCFCL and 10 of SCFL and performed whole-exome sequencing on 18 specimens of PCFCL and 6 of SCFL. During a median follow-up of 7 years, 26 (87%) of the PCFCLs remained skin restricted. In the remaining 4 cases, systemic disease developed within 3 years of diagnosis. Although the SCFLs universally expressed BCL2 and had BCL2 rearrangements, 73% of the PCFCLs lacked BCL2 expression, and only 8% of skin-restricted PCFCLs had BCL2 rearrangements. SCFLs showed low proliferation fractions, whereas 75% of PCFCLs had proliferation fractions >30%. Of the SCFLs, 67% had characteristic loss-of-function CREBBP or KMT2D mutations vs none in skin-restricted PCFCL. Both SCFL and skin-restricted PCFCL showed frequent TNFRSF14 loss-of-function mutations and copy number loss at chromosome 1p36. These data together establish PCFCL as a unique entity with biological features distinct from usual systemic FL and SCFL. We propose 3 criteria based on BCL2 rearrangement, chromatin-modifying gene mutations (CREBBP, KMT2D, EZH2, and EP300), and proliferation index to classify cutaneous FL specimens based on the likelihood of concurrent or future systemic spread.

Long-term Therapeutic Success of Intravenous Rituximab in 26 Patients with Indolent Primary Cutaneous B-cell Lymphoma.

Systemic monotherapy with rituximab is a well-known treatment approach for primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone lymphoma. Both have excellent prognosis despite high relapse rates. To investigate the long-term effectiveness and clinical outcome of intravenous rituximab at a dose of 375 mg/m2 once weekly, data for 26 patients (17 primary cutaneous follicle centre lymphoma and 9 primary cutaneous marginal zone lymphoma) were analysed retrospectively. Complete remissions occurred in 20 (77%) and partial remissions in 6 patients (23%), demonstrating an overall response rate of 100%. The relapse rate was 52.9% in primary cutaneous follicle centre lymphoma and 88.9% in primary cutaneous marginal zone lymphoma. Ongoing complete remissions after therapy with rituximab were observed in 9 patients (34.6%) with a median progression-free survival of 161 months (13.4 years). These results confirm that intravenous rituximab is an effective and well-tolerated treatment with durable responses in a relevant percentage of patients at a median follow-up of 148 months (12.3 years).

Cutaneous Lymphomas — Part II: Other Cutaneous Lymphomas

Primary cutaneous T-cell lymphomas other than mycosis fungoides, Sézary syndrome, and lymphoproliferative CD30+ disorders are few, accounting for less than 5% of all cutaneous lymphomas. A cytotoxic phenotype is characteristic of these tumors, and their clinical behavior is usually aggressive. Patients often present with extracutaneous symptoms or develop them shortly after diagnosis. Management is usually multidisciplinary, and intensive systemic therapy and bone marrow transplantation should be considered. Cutaneous B-cell lymphomas account for approximately 30% of primary cutaneous lymphomas. They make up a heterogeneous group of tumors that have different clinical and pathological features. Clinical course also varies. Presenting as papules, nodules, or tumors of variable reddish–violaceous coloring, the lesions may be solitary or multiple and occasionally form clusters. There may also be generalized lesions, present at multiple sites on the trunk, head, or extremities. Three well-defined groups of primary cutaneous lymphoma have been reported: follicle center lymphoma; marginal zone lymphoma, which follows an indolent course; and a diffuse large B-cell lymphoma, leg type, which follows an aggressive course.

18057 Primary cutaneous follicle center lymphoma: Does location matter? A clinical and histologic comparison between scalp involvement versus other sites

Background: Primary cutaneous follicle center lymphoma (PCFCL) is a rare cutaneous lymphoma which commonly presents on the scalp and torso. Limited data is available on location dependent clinical course and histopathologic features.

Primary cutaneous follicle center lymphoma of the breast: Management of an exceedingly rare malignancy.

Primary cutaneous follicle center lymphoma (PCFCL) is defined as a low-grade B-cell non- Hodgkins lymphoma, which primarily occurs and remains confined to the skin, without evidence of extracutaneous or systemic involvement at the time of diagnosis. PCFCL affecting the breast skin is an exceedingly rare entity with only two cases reported in the English literature. We present a case of PCFCL affecting the periareolar breast skin and review the relevant literature. Our patient was a 64-year-old female who presented with an erythematous plaque in the periareolar region of the left breast. The diagnosis of PCFCL was confirmed by a biopsy performed with a seven-month delay, as the tumor had been initially misdiagnosed as a benign lesion. The patient was successfully treated with local radiation therapy. PCFCL is an indolent lymphoma associated with an excellent prognosis. For localized lesions, skin-directed therapies mainly consisting of radiation therapy or complete surgical excision are curative therapeutic approaches, while systemic chemotherapy should be reserved for patients with extensive disease. This case highlights the need to consider PCFCL as an important differential diagnosis in patients presenting with non-resolving erythematous breast skin lesions. A timely biopsy should be obtained to avoid delays in the initiation of appropriate treatment.