Primary Cutaneous Follicle Center Research Articles

Primary Cutaneous Follicle Center B-cell Lymphoma at the Site of a Resolved Herpes Zoster Eruption.

Primary Cutaneous Follicle Center B-cell Lymphoma at the Site of a Resolved Herpes Zoster Eruption.

Investigating Factors Predictive of Large Cell Transformation and Outcomes From Low Grade Lymphomas

<h3>Purpose/Objective(s)</h3> Relapses of low grade (indolent) lymphomas typically remain low grade, but there is a 1-3% annual risk of transformation to large B-cell lymphoma. Predictive factors at time of initial lymphoma diagnosis and clinical outcomes after transformation remain poorly characterized. In this study we aim to characterize clinical and positron emission tomography (PET) features of a cohort with transformed disease. <h3>Materials/Methods</h3> We performed a retrospective review of patients diagnosed with large cell transformation from initial low-grade lymphoma. Patients who did not experience transformation during follow up were referenced as a control. Standardized uptake unit (SUV) parameters from initial staging or low-grade disease follow up diagnostic PET scans were analyzed. Statistical analyses included t-test and Fisher's exact test for significance (SS) using alpha level of 0.05. Statistical analysis was performed using Python (version 3). <h3>Results</h3> We identified 50 patients with a mean age at initial diagnosis of 53 years (range: 16-73). The most common lymphoma types were follicular lymphoma (FL) in 40 (80%) patients, marginal zone (MZL) in 4 (8%), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) in 3 (6%), 2 (4%) with Waldenstrom's (WM) and one (2%) with primary cutaneous follicle center (PCFCL). Initial lymphoma (non-WM) stages were 23% stage I, 8% stage II, 36% stage III and 33% stage IV. Mean time to transformation was 105 months (range: 5-373). Predominant transformed histology was diffuse large B-cell lymphoma (DLBCL) in 42 (84%) patients. Stage at transformation was 30% stage I-II and 70% stage III-IV. Median follow up from time of transformation was 52 months (range: 2-207). 1-year OS from transformation was 85%. 21 (42%) patients had PET-CT scans 7 months to 13 years prior to transformation with mean SUV-max of 12.2 (range: 3.8-30.0). Compared to 21 (1:1) non-transformed control patients with PET scans, a significant difference was found between the mean SUV-max values of 12.2 vs 6.3 (<i>P</i> < 0.001). Further, as an exploratory analysis, we generated a prognostic scoring model for post-transformation outcomes directly proportional to SUV-max squared and inverse to the time to transformation (in months). Among the 21 patients with pre-transformation PET imaging, the 17 who were alive at last follow up had a mean score of 2.4 vs. 64.2 among the 4 patients who died (<i>P</i> = 0.005). <h3>Conclusion</h3> We demonstrate the utility of PET-CT to identify patients with low grade lymphoma at high risk of transformation to large cell lymphoma. Specifically, we observe an increased risk of poor outcomes with increasing SUV-max and shorter time to transformation. If validated, our study may serve to risk stratify patients initially diagnosed with low grade lymphoma.

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.

Dermoscopic characterization of cutaneous lymphomas: a pilot survey.

While substantial dermoscopic analysis of melanocytic lesions has been performed, dermoscopic characterization of cutaneous lymphoid proliferations has been limited. Cutaneous lymphoma, particularly early mycosis fungoides (MF) and its variants, is often challenging to clinically and pathologically distinguish from inflammatory processes of the skin. This study aimed to survey the dermoscopic findings of cutaneous lymphomas and to discern whether any patterns might potentially serve as specific signatures. Fifteen patients with an established diagnosis of cutaneous lymphoma were prospectively recruited and seen in the university multidisciplinary cutaneous lymphoma program with MF, an MF- variant, CD30-positive lymphoproliferative disorder, or cutaneous B-cell lymphomas and were included in our study. Dermoscopic findings, histologic features, clinical characteristics, and demographic data were analyzed. Patch stage MF was characterized by interconnected white structureless patches encircling small fine linear vessels, yielding an overall trabeculated to fenestrated pattern under dermoscopy. Corresponding histopathologic findings for these patterns included epidermotropism, atypical pleomorphic cells, and lichenoid infiltrates. Folliculotropic mycosis fungoides (FMF) was characterized by folliculocentric erosions surrounded by dotted and fine linear vessels, loss of terminal follicles, comedo-like openings, and interconnected regular-appearing structureless patches. Corresponding histopathologic findings in these FMF cases were typical of FMF. Notably, these changes were not appreciated in lymphomatoid papulosis. Primary cutaneous follicle center B cell lymphoma showed crystalline structures and vascular pseudopods. Cutaneous lymphomas appear to demonstrate characteristic dermoscopic patterns, reflective of the specific lymphoma type and its corresponding histopathology, which have not been seen in inflammatory skin conditions, such as psoriasis and eczematous dermatitis.

Clonal Evolution in a Primary Cutaneous Follicle Center B Cell Lymphoma Revealed by Single Cell Analysis in Sequential Biopsies

B cell neoplasias descending from germinal center cells harbor the hallmark of intraclonal diversity resulting from ongoing mutation in the variable parts of their immunoglobulin-encoding genes. To characterize a primary cutaneous follicle center B cell lymphoma in more detail, we analyzed the respective V H and V L genes in single cells mobilized from four sequential biopsies, three taken from the skin and one obtained after internal dissemination from a retrobulbar infiltrate. The lymphoma cells were found to contain V5-51/D6-12/JH5b (heavy chain) and A27/Jkappa2 (light chain) gene rearrangements detected on both the genomic and the transcriptional level. To provide an accurate mutation analysis, the specific V H gene counterpart (V5-5lUK) was cloned from the patient’s germline. Analyzing 226 single cells, we found: (i) complete nucleotide identity when V H and V L genes of lymphoma cells from one particular biopsy were compared among each other; (ii) intraclonal diversity due to ongoing mutation comparing the sequences obtained from sequential biopsies; (iii) both V H and V L genes to be highly mutated. Deducing from the sequence data, we propose a scenario of the clonal evolution of the B cell tumor in this patient. From the molecular-biological point of view, this primary cutaneous follicle center B cell lymphoma shows the features of a germinal center cell lymphoma. To draw this conclusion from single cell PCR data, however, a sample of sequential biopsies had to be analyzed.