Camille Laurent

Double‐positive CD4/CD8 mycosis fungoides: a rarely reported immunohistochemical profile

Mycosis fungoides (MF) represents the most common epidermotropic cutaneous T‐cell lymphoma (CTCL), and tumor cells typically express a mature T‐helper memory phenotype. A minority of MF patients display an unusual phenotype, which may be either CD4(−)/CD8(+) or double negative. Herein, we report a case of biopsy‐proven MF in a 31‐year‐old woman who presented with infiltrated plaques involving photoprotected areas of the skin. Immunohistochemical study combined with confocal microscopy revealed co‐expression of CD4 and CD8 in a subset of atypical T lymphocytes. To our knowledge, this is the second report of a CD4/CD8 dual‐positive MF.

Characterization of bone marrow lymphoid infiltrates after immunochemotherapy for follicular lymphoma.

We studied the distribution of lymphoid cells in the bone marrow of 10 follicular lymphoma (FL) cases in complete response after immunochemotherapy but with nodular lymphoid infiltrates mimicking persistent lymphoma nodules. Immunohistochemical analysis showed that most of these cells displayed a T-cell phenotype with important proportions of regulatory T cells (CD3+/CD4+/FOXP3+) and mast cells. These populations were also present before treatment. Whereas no CD20+ cells were observed, immature B cells (CD79a+/terminal deoxynucleotidyl transferase+/CD20-) were detected. These cells were scarce before immunochemotherapy, suggesting that immunochemotherapy enabled their expansion. Fluorescence in situ hybridization and quantitative polymerase chain reaction failed to detect residual lymphoma cells in 5 cases with the t(14;18) translocation. Our study describes 2 important features in bone marrow in FL following immunochemotherapy. It is probable that the accumulation of regulatory T cells has some role in the control of FL. The expansion of nonmalignant B cells reflects the regeneration of B-cell lineage following immunochemotherapy.

Unusual concomitant rearrangements of Cyclin D1 and MYC genes in blastoid variant of mantle cell lymphoma: Case report and review of literature.

We report herein a case of blastoid variant mantle cell lymphoma (MCL) with both aberrant phenotype and unusual genetics. Unexpectedly, lymphoma cells were CD5(-) and CD10(+). Standard karyotype and FISH techniques showed that tumor cells carried two distinct translocations which had not been reported together in a same tumor. The first translocation juxtaposed the immunoglobulin lambda light chain locus with CCND1 locus, leading to Cyclin D1 overexpression. The second translocation revealed MYC rearrangement with a non-immunoglobulin gene partner located on the short arm of chromosome 4. The interpretation of the case on tissue sections alone could have been challenging. Indeed, the lack of CD5 and expression of CD10 associated with MYC rearrangement detected on interphasic nuclei could support the diagnosis of diffuse large B-cell lymphoma or Burkitt lymphoma. This distinction is also especially important as these lymphoma subtypes require specific treatment.

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

Indolent non‐hodgkin lymphomas (iNHL) are a rare cause of monoclonal immunoglobulin deposits‐related glomerulopathy (mIgGN). In patients with iNHL‐related mIgGN, whether treatment should include either single or a combination of drug(s) to target the malignant clone and renal inflammation remains elusive. In this retrospective study, we report a cohort of 14 patients with iNHL‐related mIgGN (cryoglobulinemic glomerulonephritis [n = 5], membranous nephropathy [n = 3], membranoproliferative glomerulonephritis [n = 3], AL or AL/AH amyloidosis [n = 2], and Light Chain Deposits Disease [n = 1]) and who received a treatment combining rituximab, cyclophosphamide, and dexamethasone (RCD). After a mean follow‐up of 18 ± 4 months, nine patients (63%) had complete haematological response. Renal response was observed in 12 of the 14 patients (86%; complete response: n = 9; partial: n = 3). Estimated glomerular filtration rate increased from 47 ± 7 to 63 ± 8 mL/min/1.73 m2, and proteinuria decreased from 6.5 ± 0.7 to 1.4 ± 0.8 g/24 hr at one year. Following hematological relapse, renal relapse occurred in two patients suggesting sustained clonal eradication offers the best renal protection. Tolerance of RCD was good and the most frequent adverse event was pneumonia (3/14, 21%). RCD is a promising regimen for patients with iNHL and mIgGN, irrespective of glomerular pathologic pattern. Whether steroids can be avoided or minimized remains to be addressed. Am. J. Hematol. 89:969–973, 2014.

High frequency of Epstein-Barr virus–infected lymphocytes in pilonidal cysts

Circulating memory B cells are considered as the main reservoir for Epstein-Barr virus. Several studies identified the presence of Epstein-Barr virus-infected B cells in the lesions of Crohn disease and ulcerative colitis suggesting that colon mucosa with chronic inflammation could be a potential site of Epstein-Barr virus replication. However, whether skin could be also an Epstein-Barr virus reservoir has not yet been investigated. We used pilonidal cysts as a model of skin chronic inflammation, and we found in 20 (55.6%) of 36 cases variable amounts of Epstein-Barr virus-infected cells as assessed by in situ hybridization using Epstein-Barr virus-encoded RNA probe and immunostainings. Most (95%) of the Epstein-Barr virus-positive cells were of B-cell phenotype, whereas scattered cells were double stained with Epstein-Barr virus-encoded RNA probes and T-cell markers. Epstein-Barr virus-encoded RNA+ cell density correlated with the intensity of inflammation. This density was similar to that observed in chronic diverticulitis but higher when compared with appendicitis, suggesting that chronic rather than acute inflammation facilitates the recruitment of Epstein-Barr virus-infected cells in diseased tissues. Altogether, these data suggest that, in immunocompetent patients, skin inflammatory lesions contain Epstein-Barr virus-infected cells exhibiting latency type I. Moreover, skin-like gastrointestinal mucosa is a potential site of Epstein-Barr virus replication and spreading. Our results may explain the pathogenesis of the Epstein-Barr virus-positive mucocutaneous ulcer.

Bendamustine plus rituximab for indolent B-cell lymphoma of renal significance

Treatment of indolent B‐cell non‐Hodgkin lymphomas (iNHL) of renal significance is challenging given the need for deep and prolonged hematological response to restore and control renal function overtime, yet to be balanced with the risk of adverse drug‐related events. This prospective single‐center study included 20 patients with iNHL of renal significance (tubulointerstitial presentation [n = 8], glomerulopathy with or without monoclonal Ig deposits [n = 12]) who received a steroid‐sparing regimen of rituximab plus bendamustine (BR), with either no or <1 month of steroid intake (as a first line therapy in 80%). Seventeen patients (85%) achieved a complete (CHR, n = 12) or a partial (PHR, n = 5) hematological response. Nine out of the 12 patients (75%) with iNHL‐related glomerulopathy had a complete (CRR) or a partial (PRR) renal response. Among the six patients with glomerulopathy and CHR, five had a CRR (83%) compared to 1/6 (17%) that did not reach CHR. eGFR increased from 38 to 58 mL/min/1.73 m2, and returned to baseline in five patients. Among the eight patients with a tubulointerstitial presentation, six (75%) had a renal response (5 CRR), and eGFR increased from 29 to 48 mL/min/1.73 m2. One patient with a PHR had a renal relapse. Mortality rate was 10% at 12 months. The BR regimen was well tolerated overall. Thus, despite severe renal disease at presentation, a relapsing iNHL in 20% of patients and several comorbidities, the BR regimen was efficient and safe in our series. It should be further assessed as a first line therapy for patients with iNHL of renal significance.