Cutaneous Follicular Lymphoma Research Articles

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Non-healing skin lesions in the right mammary region Although almost all dermatological conditions are visible, some patients wait a long time to consult a dermatologist. Nevertheless, an early diagnosis is important for the treatment and prognosis in case of cutaneous cancers. A 39-year-old man with skin lesions on his right chest, present for 3 years and slowly growing over time, consulted the dermatologist. The anatomopathological examination showed a diffuse-type primary cutaneous follicular B-cell non-Hodgkin lymphoma. Staging revealed a primary cutaneous lymphoma. After deliberation in a multidisciplinary oncologic consultation, radiotherapy was started. Cutaneous lymphomas are often difficult to diagnose because of their non-specific and variable clinical presentation. Skin biopsies should be performed when patients present with atypical cutaneous lesions. In case of cutaneous B-cell lymphomas, early diagnosis is important to detect and treat an underlying systemic or aggressive B-cell lymphoma. A multidisciplinary management team including dermatologists, pathologists, hematologists and radiation oncologists is necessary.

Panel Sequencing of Primary Cutaneous B-Cell Lymphoma.

Primary cutaneous follicular B-cell lymphoma (PCFBCL) represents an indolent subtype of Non-Hodgkin's lymphomas, being clinically characterized by slowly growing tumors of the skin and common cutaneous relapses, while only exhibiting a low propensity for systemic dissemination or fatal outcome. Up to now, only few studies have investigated underlying molecular alterations of PCFBCL with respect to somatic mutations. Our aim was to gain deeper insight into the pathogenesis of PCFBCL and to delineate discriminatory molecular features of this lymphoma subtype. We performed hybridization-based panel sequencing of 40 lymphoma-associated genes of 10 cases of well-characterized PCFBCL. In addition, we included two further ambiguous cases of atypical B-cell-rich lymphoid infiltrate/B-cell lymphoma of the skin for which definite subtype attribution had not been possible by routine investigations. In 10 out of 12 analyzed cases, we identified genetic alterations within 15 of the selected 40 target genes. The most frequently detected alterations in PCFBCL affected the TNFRSF14, CREBBP, STAT6 and TP53 genes. Our analysis unrevealed novel mutations of the BCL2 gene in PCFBCL. All patients exhibited an indolent clinical course. Both the included arbitrary cases of atypical B-cell-rich cutaneous infiltrates showed somatic mutations within the FAS gene. As these mutations have previously been designated as subtype-specific recurrent alterations in primary cutaneous marginal zone lymphoma (PCMZL), we finally favored the diagnosis of PCMZL in these two cases based on these molecular findings. To conclude, our molecular data support that PCFBCL shows distinct somatic mutations which may aid to differentiate PCFBCL from pseudo-lymphoma as well as from other indolent and aggressive cutaneous B-cell lymphomas. While the detected genetic alterations of PCFBCL did not turn out to harbor any prognostic value in our cohort, our molecular data may add adjunctive discriminatory features for diagnostic purposes on a molecular level.

Abstract 4129: Descriptors of primary cutaneous follicular helper T-cell lymphoma (PCFHTCL): Analysis of a pooled database of a rare entity

Abstract Introduction: Primary Cutaneous Follicular Helper T-cell Lymphoma (PCFHTCL) is a rare cutaneous T-cell lymphoma that was recently described. PCFHTCL is comprised of small to medium lymphocytes that express CD4, CD19, Bcl6, PD1, ICOS, CXCR5, and CXCL13. While it tends to have mostly an indolent course, occasionally PCFHTCL may display a more aggressive pattern. We conducted this analysis to explore the key clinicopathologic characteristics of this rare and little-known entity. Methods: In order to study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 57 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival and disease-free survival. Results: A total of 57 patients with confirmed PCFHTCL were identified. The median age was 57 years with a peak incidence between ages 53 and 64. There was a male predominance with an M:F ratio of 1.25. PCFHTCL commonly involved the head (54%), followed by the torso (24%) and limbs (12%). Sixteen percent of the lesions were solitary and mostly involved the head. The most common pattern was nodular/tumorous. Histologically, PCFHTCL involved mainly the dermis with occasional focal epidermotropism (27%), folliculotropism (43%), syringotropism (7%), and subcutaneous extension (14%). Extracutaneous involvement comprised lymph nodes (11%), bone marrow (4%), and the peripheral blood (2%). The median duration of symptoms prior to diagnosis was 5 months. The six-year disease-free survival is around 85%. Surgical resection alone resulted in durable remission in 40% of the cases. Recurrent disease was successfully salvaged with re-resection, radiation, and chemotherapy. While solitary lesions tended to have a better disease-free survival, it did not reach statistical significance. Conclusions: This study represents the largest cohort of this rare cutaneous T-cell entity. It describes the demographic and clinical patterns of disease presentation and provides a detailed update on the clinicopathologic features PCFHTCL. Citation Format: Philip A. Haddad, Dalia Hammoud, Kevin Gallagher. Descriptors of primary cutaneous follicular helper T-cell lymphoma (PCFHTCL): Analysis of a pooled database of a rare entity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4129.

The role of dermatoscopy and reflectance confocal microscopy in the assessment of relapsing secondary cutaneous follicular B-cell lymphoma

A 72-year-old man presented with several infiltrated painless patches and nodules (5-15 mm) on his scalp, without lymphadenopathy. The patient reported that he previously had similar erythematous-to-purple lesions and had been treated with a 2-week course of topical steroid, reporting a partial response (Fig 1).

26892 Secondary cutaneous follicular center lymphoma presenting after use of topical fluorouracil for actinic keratosis

26892 Secondary cutaneous follicular center lymphoma presenting after use of topical fluorouracil for actinic keratosis

Primary cutaneous indolent B-cell lymphomas – a retrospective multicenter analysis and a review of literature

Introduction: Primary cutaneous indolent B-cell lymphomas (PCBCLs) are not well characterized due to their rarity and indolent character. Methods: We retrospectively reviewed the data from 52 patients with primary cutaneous follicular lymphoma (PCFL) (n = 26), marginal zone lymphoma (PCMZL) (n = 25) or undefined PCBCL (n = 1) treated in 10 hematology centers in 1999–2019. Results: Patients characteristics and diagnostic approach: In almost half of the patients, pruritus or pain were present at diagnosis. The lesions were predominantly located on the head and trunk. The disease was present in a form of solitary infiltration or disseminated lesions with a similar frequency. Treatment details and outcomes: Surgery, radiotherapy, rituximab alone or combined with chemotherapy were applied as first-line treatment in 33%, 25%, 21% and 21% of patients, with complete response (CR) achieved by 94%, 83%, 50% and 70% of patients, respectively (p = 0.28). The median duration of response (DoR) was 65 months (95%CI 35–155). Survival: After the median follow-up time of 46 months (range: 3–225), the estimated 5-year overall survival (OS) and progression-free survival (PFS) were 93% and 54%, respectively. Discussion: Clinical presentation was largely consistent with the literature data, however, we observed some differences, including higher predilection to affect upper extremities (25%) and more frequent multifocal appearance in PCFCL (64%) and unifocal in PCMZL (70%). A high proportion of patients with indolent PCBCL achieved CR after the first-line therapy (77%), regardless of treatment mode. We did not find any impact of clinical features on treatment outcomes. Conclusions: All treatment modalities resulted in a high overall response rate. Surgery and/or radiotherapy are the optimal therapeutic options for patients with localized disease. The decision to treat systemically should rather be limited to the generalized form of the disease. High response rate, long duration of remission and excellent long-term survival confirm the truly indolent character of PCFCL and PCMZL.

The Mutational Landscape and Immune Microenvironment of Primary Intestinal Follicular Lymphoma (PIFL)

Introduction: Follicular lymphoma (FL) comprises a heterogeneous group of diseases. Typical FL (TFL) most commonly presents with advanced stage (AS), has a variable clinical course, and is incurable. A small subset of TFL cases present with limited stage (LS) disease, and may be cured with radiotherapy. Primary cutaneous follicular lymphoma and pediatric-type follicular lymphoma (PTFL) are non-typical FL subtypes with localized presentation and invariably benign behavior. In contrast to ASTFL, these subtypes lack BCL2 -rearrangements. We recently discovered that, in contrast to typical FLs, the majority of PTFL cases are driven by mutations activating the MAP kinase pathway and lack mutations in epigenetic modifier genes (Louissaint, Blood 2016; Schmidt, Blood 2017).Primary intestinal FL (PIFL) is another non-typical variant of FL, characterized by its distinctive restriction to the intestine (most commonly the duodenum). Despite this striking behavior, PIFL is indistinguishable from ASTFL and LSTFL by routine histology and immunohistochemistry (IHC) alone, and has a remarkably low tendency to progress or disseminate. The cell-intrinsic alterations (e.g. mutations) and cell-extrinsic factors (microenvironment) underlying the distinctive clinical behavior of PIFL are unknown.Patients and Methods: A total of 38 PIFL cases were available through the Kiel Lymph Node Registry and the Dana-Farber Cancer Institute (DFCI) / Massachusetts General Hospital (MGH), with clinical follow-up for 19 cases. We excluded cases of intestinal FL with evidence of mesenteric lymph node involvement or extra-intestinal manifestation. A total of 17 LSTFL cases were available from DFCI / MGH. We used 241 ASTFL cases from our previous study (Pastore, Lancet Oncology 2015) as a reference cohort.The targeted mutational landscape was determined by customized hybrid-capture targeted sequencing of 104 genes. In addition, we performed whole-exome-sequencing (WES) on 11 PIFL. The FL immune microenvironment was assessed on 8 PIFL and 7 LSTFL cases, respectively, by digital multiplexed gene expression profiling using the nCounter PanCancer Immune Profiling Panel (NanoString).Results: PIFL patients had a median age of 57 years (range 22-84) and a male-to-female ratio of 2:3. Most cases were restricted to the duodenum (22/38, 58%). BCL2 -rearrangements and BCL2 expression by IHC was detected in 91% (20/23) and 95% (32/33) of evaluable cases, respectively. The 10-year overall survival was 100% (median follow-up of 9.1 years), and significantly superior to LSTFL and ASFL (p <0.01, respectively).31/38 PIFL (82%) and all LSTFL (100%) cases were successfully sequenced. The mutation frequencies of the majority of recurrently mutated genes were not different between PIFL, LSTFL and ASTFL (Figure A), including CREBBP (65% vs 76% vs 70%), TNFRSF14 / HVEM (35% vs 35% vs 35%), and EZH2 (16% vs 29% vs 23%), respectively.However, the mutation frequency of the histone lysine methyltransferase KMT2D was lower in PIFL (45%, p=0.35) and LSTFL (24%, p=0.001) compared to ASTFL (77%). Approximately one-half of KMT2D- mutated ASTFL harbored multiple, potentially biallelic mutations in this gene (86/185, 47%). In contrast, biallelic mutations were present in only 12% of LSTFL (p=0.06) and 0% of PIFL (p <0.0001; Figure B).WES of 11 PIFL identified novel gene mutations in EEF1A1 and FLG in 2 cases, respectively. Furthermore, 4 cases harbored mutations in HVCN1 ,which have recently been associated with favorable clinical course (Krysiak, Blood 2017).Profiling of the immune microenvironment revealed significant differences between PIFL and LSTFL. Chemokines and cytokines including CCL21, TNFSF15, CCL11, CXCL1, CXCL6 and CCL20 were strongly enriched among the top differentially expressed genes (p=0.03). Unsupervised, hierarchical clustering by expression levels of 147 chemokines and cytokines clearly separated PIFL and LSTFL into two distinct groups (Figure C).Summary: The mutational landscape of PIFL is highly related to typical FL, both LSTFL and ASTFL. However, the lower frequency of biallelic mutations in KMT2D in PIFL and LSTFL indicates an increasing selection pressure for complete KMT2D loss during the development of, or the progression to advanced-stage FL. The highly dissimilar immune microenvironment of PIFL implies biological and clinical relevance. [Display omitted] DisclosuresDreyling:Janssen: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Sandoz: Consultancy; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; MorphoSys AG: Consultancy; Mundipharma: Consultancy, Research Funding.

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.

Asymptomatic pink nodules on a 28-year-old patient

Asymptomatic pink nodules on a 28-year-old patient

Aggressive cutaneous follicular lymphoma in a 18F-FDG PET/CT study

Aggressive cutaneous follicular lymphoma in a 18F-FDG PET/CT study

Outcomes of Follicular Lymphoma Patients Treated with Frontline Bendamustine and Rituximab: Impact of Histologic Grade and Early Progression on Overall Survival

Outcomes of Follicular Lymphoma Patients Treated with Frontline Bendamustine and Rituximab: Impact of Histologic Grade and Early Progression on Overall Survival

Primary cutaneous follicular center B-cell lymphoma with spontaneous regression in a Hispanic woman

Primary cutaneous follicular center B-cell lymphoma with spontaneous regression in a Hispanic woman

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.

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 &lt; 60 yo. 54% had stage T1 disease, 27% T2, and 19% T3. Median PFS for patients &lt;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 &lt;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.

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.

Primary cutaneous follicular B-cell lymphoma with marginal zone differentiation: A case discussion

Primary cutaneous follicular B-cell lymphoma with marginal zone differentiation: A case discussion

Primary Cutaneous Follicle Center Lymphoma and Its Molecular Landscape

Primary cutaneous B-cell lymphomas are non-Hodgkin lymphomas of skin without evidence of extracutaneous disease or within 6 months of diagnosis. Primary cutaneous follicle center lymphoma (PCFCL) — neoplastic proliferation of follicular centrocytes or centroblasts affecting the head or trunk of middle-aged adults — is one such lymphoma. Detection of BCL-2 protein, which correlates with BCL2 translocation, is commonly used to differentiate PCFCL from secondary cutaneous follicular lymphoma (SCFL). …

Are there any Dermoscopic Signs of Primary Cutaneous Follicular Center B-cell Lymphoma?

Cutaneous follicular center B-cell lymphoma is an indolent tumor that arise on head or neck. Histology by immunotyping with monoclonal antibodies in frozen or paraffin - embedded tissue is necessary for diagnosis. The tumor is usually treated by surgery or radiotherapy, although other treatments may be used such as interferon-α, chemotherapy, and biological agents. We report the case of a 70-year-old woman C, having a son followed in our department for Primary cutaneous follicular center B-Cell lymphoma who consulted for erythematous tumour in the temporal region that exhibit special features in dermoscopy and who was diagnosed with cutaneous follicular center B-cell lymphoma after biopsy, laboratory tests, thoracic-abdominal-pelvic computed tomography and abdominal ultrasound. These observation provide a first indication that early stage PCFCCL exhibits a characteristic dermoscopic pattern which is different. Prospective studies with long term follow-up are needed to determine the value of these dermoscopic.

Primary Cutaneous Follicle Center Lymphomas Expressing BCL2 Protein Frequently Harbor BCL2 Gene Break and May Present 1p36 Deletion: A Study of 20 Cases.

The classification of cutaneous follicular lymphoma (CFL) into primary cutaneous follicle center lymphoma (PCFCL) or secondary cutaneous follicular lymphoma (SCFL) is challenging. SCFL is suspected when tumor cells express BCL2 protein, reflecting a BCL2 translocation. However, BCL2 expression is difficult to assess in CFLs because of numerous BCL2+ reactive T cells. To investigate these issues and to further characterize PCFCL, we studied a series of 25 CFLs without any extracutaneous disease at diagnosis, selected on the basis of BCL2 protein expression using 2 BCL2 antibodies (clones 124 and E17) and BOB1/BCL2 double immunostaining. All cases were studied using interphase fluorescence in situ hybridization with BCL2, BCL6, IGH, IGK, IGL breakapart, IGH-BCL2 fusion, and 1p36/1q25 dual-color probes. Nineteen CFLs were BCL2 positive, and 6 were negative. After a medium follow-up of 24 (6 to 96) months, 5 cases were reclassified as SCFL and were excluded from a part of our analyses. Among BCL2+ PCFCLs, 60% (9/15) demonstrated a BCL2 break. BCL2-break-positive cases had a tendency to occur in the head and neck and showed the classical phenotype of nodal follicular lymphoma (CD10+, BCL6+, BCL2+, STMN+) compared with BCL2-break-negative PCFCLs. Del 1p36 was observed in 1 PCFCL. No significant clinical differences were observed between BCL2+ or BCL2- PCFCL. In conclusion, we show that a subset of PCFCLs harbor similar genetic alterations, as observed in nodal follicular lymphomas, including BCL2 breaks and 1p36 deletion. As BCL2 protein expression is usually associated with the presence of a BCL2 translocation, fluorescence in situ hybridization should be performed to confirm this hypothesis.