Large Cell Transformation Of Mycosis Fungoides Research Articles

TBI/Ratg-Based Conditioning for Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in 11 Cases of Chemotherapy-Resistant Advanced-Stage Peripheral T-Cell Lymphoma

Objectives: To evaluate the clinical outcomes and safety of haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT)with total body irradiation (TBI)/rabbit Anti-thymocyte globulin (rATG) based conditioning regimen in chemotherapy-resistant advanced-stage peripheral T-cell lymphoma (PTCL). Methods: From September 2019 to December 2022, eleven chemotherapy-resistant advanced-stage PTCL patients who underwent haplo-HSCT were enrolled in our study. All of them received TBI/rATG-based conditioning regimen in our centers. Results: ①Among 11 patients, there were 6 males and 5 females with a median age of 40(range：22~58) years old. Six cases of them are peripheral T-cell lymphoma not otherwise specified (PTCL NOS), 3 cases are angioimmunoblastic T-cell lymphoma (AITL), 1 case is large-cell transformation of mycosis fungoides (MF-LCT), and 1 case is T-cell large granular lymphocytic leukemia(T-LGLL). The Lugano stage was III or IV in all cases, and 8 patients had B symptoms. The median number of previous chemotherapy exposure before transplantation was 4 (range: 2~10) lines and the disease status before transplantation was progressive diseases (PD) in all cases. The median time from diagnosis to transplantation was 17(range：6~36) months.②The conditioning regimen consisted of TBI 2Gy d-8, 4Gy from day-7 to -6, rATG 2.5 mg/kg/d day-5 to -2, etoposide 15mg/kg/d day-5 to -4, cyclophosphamide (CTX) 50mg/kg/d, day-3 to -2. The patients with central nervous system involvement received a regimen of thiotepa 5 mg/kg/d， from day -5 to -4 instead of CTX and etoposide, and add 2.0 g/m2 of cytarabine twice a day, from day -3 to day -2 into the conditioning.③All patients were successfully engrafted. Only one patient developed Grade III-IV acute graft-vs-host disease (aGvHD). Among the 8 survivors, 4 cases developed chronic graft-vs-host disease (cGvHD).④After transplantation, CR was obtained in 9 patients. ⑤Regimen related toxicities: all were non-fatal. Hematopoietic suppression occurred in all patients after conditioning. Three patients had diarrhea and four had mucositis and three had elevated transaminase/bilirubin levels. Seven patients had infections.⑥The 1-year cumulative non-relapse mortality (NRM) and 1-year cumulative incidence of relapse (CIR) was 22.5±14.0% and 20.2±12.7%, respectively. The 1-year overall survival (OS) and 1-year disease-free survival (DFS) was 72.7±13.4% and 63.6±14.5%, respectively Conclusions: TBIand rATG based conditioning regimen is effective and safe for haplo-HSCT in chemotherapy-resistant advanced-stage PTCL.

Efficacy and safety of TBI+rATG-based conditioning regimen for haploidentical allogeneic hematopoietic stem cell transplantation in 11 cases of chemotherapy-resistant advanced peripheral T-cell lymphoma

Objective: To evaluate the clinical outcomes and safety of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using a conditioning regimen based on total body irradiation (TBI) and rabbit anti-human thymocyte globulin (rATG) in the management of chemotherapy-resistant advanced peripheral T-cell lymphoma (PTCL) . Methods: Clinical data of 11 patients with chemotherapy-resistant advanced PTCL who underwent haplo-HSCT with a TBI+rATG-based conditioning regimen at the Department of Hematology, Shanghai Liquan Hospital and Shanghai Zhaxin Integrated Traditional Chinese and Western Medicine Hospital, from September 2019 to December 2022 were retrospectively analyzed. Results: ①Among the 11 patients (six males and five females), with a median age of 40 years (range: 22-58 years), there were six cases of PTCL, not otherwise specified (PTCL-NOS), three cases of angioimmunoblastic T-cell lymphoma (AITL), one case of large-cell transformation of mycosis fungoides (MF-LCT), and one case of T-cell large granular lymphocytic leukemia (T-LGLL). According to the Lugano staging system, all patients were in stage Ⅲ or Ⅳ, and eight patients had B symptoms. Before transplantation, the median number of prior lines of chemotherapy was 4 (range: 2-10), and all patients had progressive disease (PD). The median time from diagnosis to transplantation was 17 months (range: 6-36 months). ②The conditioning regimen consisted of a TBI dose of 10 Gy, administered at 2 Gy on day -8 and 4 Gy from day -7 to day -6, rATG was administered at a daily dose of 2.5 mg/kg from day -5 to day -2. Etoposide (VP-16) was given at a dose of 15 mg/kg/d from day -5 to day -4, while cyclophosphamide (CTX) was administered at a dose of 50 mg/kg/d from day -3 to day -2. In patients with central nervous system involvement, etoposide and cyclophosphamide were replaced with thiotepa (TT) at a dose of 5 mg/kg/d from day -5 to day -4. Additionally, cytarabine (Ara-C) was added at a dose of 2.0 g/m(2) twice a day from day -3 to day -2 into the conditioning. ③Successful engraftment was achieved in all patients, with a median time to neutrophil engraftment of 14.5 d (range: 11-16 d) and a median time to platelet engraftment of 13 days (range: 8-18 days). Acute graft-versus-host disease (aGVHD) occurred in one patient (grade Ⅰ-Ⅱ), and another patient experienced grade Ⅲ-Ⅳ aGVHD. Among the eight survivors, four developed chronic GVHD (cGVHD). ④Post-transplantation, nine patients achieved complete response (CR). ⑤Hematopoietic suppression occurred in all patients after conditioning, with three experiencing diarrhea, four developing mucositis, three exhibiting elevated transaminase/bilirubin levels, and seven developing infectious complications. These non-hematologic adverse events were effectively managed. ⑥At one year post-transplantation, the non-relapse mortality (NRM) was (22.5±14.0) %, the cumulative incidence of relapse (CIR) was (20.2±12.7) %, and overall survival (OS) rate was (72.7±13.4) %, and disease-free survival (DFS) rate was (63.6±14.5) % . Conclusion: TBI+rATG-based conditioning regimen for haplo-HSCT is an effective and safe treatment approach for patients with chemotherapy-resistant advanced PTCL.

Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides.

Simple SummaryTransformed mycosis fungoides (LCT-MF) is a histopathological marker of poor prognosis and associated with worse survival. We compared miRNA and mRNA expression profiles of LCT-MF with classic MF and found a distinct miRNA regulatory network modulated immunosuppressive tumor microenvironment in LCT-MF. Our findings provide novel insights and therapeutic targets for LCT-MF.Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20–50% of advanced MF and is generally associated with poor response and dismal prognosis. Although different mechanisms have been proposed to explain the pathogenesis, little is known about the role of microRNAs (miRs) in transcriptional regulation of LCT-MF. Here, we investigated the miR and mRNA expression profile in lesional skin samples of patients with LCT-MF and non-LCT MF using RNA-seq analysis. We found miR-146a and miR-21 to be significantly upregulated, and miR-708 the most significantly downregulated miR in LCT-MF. Integration of miR and mRNA expression profiles revealed the miR-regulated networks in LCT-MF. Ingenuity pathway analysis (IPA) demonstrated the involvement of genes for ICOS-ICOSL, PD1-PDL1, NF-κB, E2F transcription, and molecular mechanisms of cancer signaling pathways. Quantitative real time (qRT)-PCR results of target genes were consistent with the RNA-seq data. We further identified the immunosuppressive tumor microenvironment (TME) in LCT-MF. Moreover, our data indicated that miR-146a, -21 and -708 are associated with the immunosuppressive TME in LCT-MF. Collectively, our results suggest that the key LCT-MF associated miRs and their regulated networks may provide insights into its pathogenesis and identify promising targets for novel therapeutic strategies.

Successful experience in treating primary cutaneous anaplastic large cell lymphoma occuring with common lesions of the skin and lung tissue

The aim of the study is to present a successful case in treating primary cutaneous anaplastic large cell lymphoma (PCALCL) occurring with common lesions of the skin and lung tissue.Materials and methods. For the verification of the diagnosis in a patient with three types of skin elements (spot, thin plaque with and without ulceration), differential diagnosis was performed between ulcerative pyoderma gangrenosum, PCALCL, large-cell transformation of mycosis fungoides, and secondary skin lesions under the nodal ALK-negtaive ALCL. A complex of studies, including histological, immunohisto - chemical, cytogenetic studies of skin tumor biopsy, allowed the verification of the PCALCL diagnosis. For the treatment of the patient, intensive induction chemotherapy was used followed by high-dose consolidation and autologous transplantation of hematopoietic stem cells.Results. The selected treatment tactics allowed a long-term complete remission of the disease to be achieved in a patient from the poor prognosis group.Conclusion. An algorithm for the differential diagnosis and tactics of treating is presented for a patient with primary anaplastic large cell lymphoma with a widespread skin lesion and extradermal foci.

Altered microRNA expression in folliculotropic and transformed mycosis fungoides.

Mycosis fungoides (MF) is a common, indolent primary cutaneous T-cell lymphoma (CTCL), with rare, more aggressive variants, such as folliculotropic MF (FMF). A minority of the MF cases may undergo large cell transformation (T-MF) associated with poor prognosis. A selection of microRNAs (miRs) contribute to the pathogenesis and progression of classic MF, and may also be useful in differential diagnostics. However, the molecular background of FMF and the mechanisms involved in large cell transformation are obscure. We analyzed the expression of 11 miRs in 9 FMF and 7 T-MF cases. Three miRs, including miR-93-5p, miR-181a and miR-34a were significantly upregulated in both FMF and T-MF. FMF also showed overexpression of miR-155 and miR-223, while miR-181b and miR-326 were overexpressed in T-MF cases compared to controls. These results by identifying a number of differentially expressed microRNAs add further insight into the molecular pathogenesis of folliculotropic MF and large cell transformation of MF.

P11.08 * CENTRAL NERVOUS SYSTEM LYMPHOMA IN A PATIENT WITH MYCOSIS FUNGOIDES

Mycosis fungoides (MF), the most common malignant T-cell lymphoma of the skin with an annual incidence of 4.2 cases per million in the United States, usually evolves slowly over many years. Extracutaneous manifestations of MF are observed in 50-75% of cases, typically occurring in patients with advanced infiltration of other organs. The incidence of central nervous system (CNS) involvement in MF was reported to be 14% in autopsy series and less than 1.6% in clinical cohorts particularly in patients with large-cell transformation of MF. A 67-year-old woman was diagnosed with plaque stage MF in 1990 after having developed disseminated, well demarcated, erythematous macules and plaques on the trunk. The patient reported that psoriasiform skin lesions had been present over the past 35 years. Treatment consisted of topical corticosteroids, systemic psoralen plus ultraviolet A, acitretin and interferon, resulting in a complete remission since 2007, without further treatment. In April 2013, the patient presented with a 2-month history of cognitive deficits and bifrontal headache, followed by rapidly decreasing visual acuity with central and peripheral visual field defects. Magnetic resonance imaging (MRI) showed thickening of the optic chiasm and both optic nerves with homogeneous contrast medium enhancement and space-occupying effect on the hypothalamus. Cerebrospinal fluid (CSF) analysis revealed lymphocytic pleocytosis of 107 cells/µl, no lymphoma cells were detected, CSF protein was elevated (116 mg/dl), glucose and lactate were normal. A subsequent brain biopsy confirmed the diagnosis of a diffuse large-cell lymphoma of the B-cell type. Despite preoperatively started dexamethasone treatment the patient experienced severe visual loss. Following 4 cycles of chemotherapy containing high-dose methotrexate and cytarabine according to the IELSG protocol and 2 cycles of methotrexate monotherapy from May until October 2013, clinical examination showed marked visual improvement, consistent with almost complete resolution of the MRI abnormalities. Due to pituitary gland insufficiency the patient needs further hormone replacement therapy. This case illustrates the importance of considering CNS lymphoma in the context of MF, even after long-term remission of the disease limited to the skin. To the best of our knowledge, this is the first description of a primary CNS B-cell lymphoma secondary to MF.

Skin Recurrence of Transformed Mycosis Fungoides Postumbilical Cord Blood Transplant despite Complete Donor Chimerism.

Background. Allogeneic stem cell transplant is the treatment of choice for systemic cutaneous T-cell lymphoma (CTCL) which provides graft-versus-lymphoma effect. Herein we discuss a case of recurrence of CTCL skin lesions after cord blood transplant in a patient who continued to have 100% donor chimerism in bone marrow. Case Presentation. A 48-year-old female with history of mycosis fungoides (MF) presented with biopsy proven large cell transformation of MF. PET scan revealed multiple adenopathy in abdomen and chest suspicious for lymphoma and skin biopsy showed large cell transformation. She was treated with multiple cycles of chemotherapy. Posttherapy PET scan showed resolution of lymphadenopathy. Later she underwent ablative preparative regimen followed by single cord blood transplant. Bone marrow chimerism studies at day +60 after transplant showed 100% donor cells without presence of lymphoma. However 5 months after transplant she had recurrence of MF with the same genotype as prior skin lesion. Bone marrow chimerism study continued to show 100% donor cells. Conclusion. A differential graft-versus-lymphoma effect in our case prevented lymphoma recurrence systemically but failed to do so in skin. We hypothesize that this response may be due to presence of other factors in the bone marrow and lymph node microenvironments preventing recurrence in these sites.

Allogeneic stem cell transplantation for advanced cutaneous T-cell lymphomas: a study from the French Society of Bone Marrow Transplantation and French Study Group on Cutaneous Lymphomas

The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38-0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41-0.77) and progression-free survival 31% (95%CI: 0.19-0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1-0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3-6.2; P=0.01) but also transplant-related mortality (HR=10(-7), 95%CI: 4.10(-8)-2.10(-7); P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides.

The expression of CXCR3 and CD30 in mycosis fungoides.

The clinical progression of mycosis fungoides (MF) often correlates with microscopic large cell transformation (LCT). It is reported that CD30 expression in the LCT of MF is associated with an absence of CXCR3 expression. This study investigates a large number of patients diagnosed with MF to determine the correlation between expression of CXCR3 and CD30 in additional sections. The study included archival skin specimens from 101 patients with MF. We analyzed these specimens by immunohistochemistry for expressions of CXCR3 and CD30. The biopsy specimens showed microscopic features of low grade MF (LG-MF) in 80 cases and transformed MF (T-MF) in 21 cases. Tumor lymphocytes expressed CXCR3 in 61 out of 80 cases (76.3%) of LG-MF and in 10 out of 21 cases (47.6%) of T-MF. CD30 positivity (CD30+) was seen in 16 of 80 cases (20%) of LG-MF and 12 of 21 cases (57.1%) of T-MF. The tumor cells in 8 of the 12 CD30+ T-MF cases showed scattered expression of CXCR3. CXCR3 expression was associated with epidermotropic T cell tumors but was greatly absent in dermal ones. Scattered or diffuse CD30 expression in T-MF was not associated with an absence of CXCR3 expression.

Recognizing large-cell transformation of mycosis fungoides

Although patients with mycosis fungoides (MF) typically experience an indolent disease course, a minority undergo a process of large-cell transformation (LCT), which often heralds more aggressive disease and shortened survival. Regrettably, most dermatologists are unfamiliar with LCT, and even fewer understand how to recognize it clinically. Because a diagnosis of LCT typically triggers more aggressive therapy and/or referral to cutaneous T-cell lymphoma (CTCL) centers, it is paramount for clinicians to be able to recognize suspect lesions visually. LCT is diagnosed histologically; however, diagnostic biopsy is performed only if transformed lesions are suspected clinically. Because the literature provides little information on what clinical features should lead to suspicion of LCT, we sought to identify and categorize the presentations of LCT to aid in its recognition. We identified 14 patients with biopsy-proven LCT confirmed by a board-certified dermatopathologist experienced with this diagnosis. The clinical presentations of LCT, timing of its evolution, and treatment regimens were evaluated by chart and photograph review. We devised 3 categories that clinically represent LCT: (1) LCT occurring as a new, solitary nodule within a classic MF patch or plaque, (2) LCT occurring as abrupt onset of multiple scattered papules and/or nodules without spontaneous resolution, and (3) LCT occurring within new or enlarging tumors. A larger number of reviewed cases might reveal additional clinical presentations of LCT. Dermatologists may use our categories of clinical indicators to recognize and diagnose LCT earlier, allowing implementation of more aggressive treatment regimens when appropriate.

The expression of MUM1 in cutaneous T-cell lymphoproliferative disorders

MUM1 is a member of the interferon regulatory factor family of transcription factors. It is normally expressed in plasma cells, late B cells, and activated T cells, and has been described in several B-cell malignancies. Although its expression has been reported in some T-cell neoplasms, the full range and character of expression have not been explored. We studied 58 cases of T-cell lymphoproliferative lesions, including systemic and cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis (LyP), mycosis fungoides (MF), MF with large cell transformation, and Sézary syndrome (SS). Nearly all cutaneous (5/5) and systemic anaplastic large cell lymphomas (4/5) were positive for MUM1, mainly in the large cell population. Similarly, 12 of 16 types A and C LyP showed MUM1 reactivity in greater than 50% of the large cells. Focal MUM1 staining was seen in 3 type B LyP, mostly in reactive lymphoid cells. All 9 MF with large cell transformation expressed MUM1 in large cells, where it paralleled CD30 expression. In comparison, most MF (11/12) were MUM1 negative. Interestingly, all SS cases (8/8) were MUM1 positive, 3 of which demonstrated diffuse staining. There was a significant difference in MUM1 expression between MF and SS groups as well as between MF and large cell transformation of MF groups (P < .001 for both). In summary, MUM1 is not helpful in separating different types of CD30-positive lymphoproliferative disorders. Potentially, MUM1 could serve as an adjunct marker for SS and/or large cell transformation of MF.

Evaluation of New Tumors in the Setting of Stage I/IIA Mycosis Fungoides

Although mycosis fungoides is usually a slowly progressive indolent lymphoma, new cutaneous tumors might signal an aggressive phase of the disease. In order to provide appropriate therapeutic management when such tumors arise, it is important to make a correct diagnosis, which requires a bridge between clinical and histopathologic evaluations of the tumors. In this article, we describe 4 patients with preexisting diagnoses of mycosis fungoides, each of whom developed a distinct, new skin tumor. These tumors represented the following: mycosis fungoides without transformation, large-cell transformation of mycosis fungoides, lymphomatoid papulosis–associated CD30+ lymphoproliferative disorder arising in a patient with mycosis fungoides, and a primary cutaneous CD30+ lymphoproliferative disorder arising in a patient with mycosis fungoides. Each new and histologically distinct tumor was identified and treated according to a diagnosis concluded by careful clinicopathologic correlation, allowing for the selection of appropriate treatment in each case.

Conjugal transformed mycosis fungoides: The unknown role of viral infection and environmental exposures in the development of cutaneous T-cell lymphoma

The etiology of mycosis fungoides (MF) is uncertain, although infectious agents and other environmental exposures have been implicated. We describe what appears to be the first case in which both a husband and his wife were diagnosed with large-cell transformation of MF. After 10 years of having stage I MF, the wife developed tumors that showed sheets of large transformed cells with dysplastic nuclei on skin biopsies, leading to a diagnosis of transformed MF. Her husband was diagnosed 14 months later with transformed MF following a biopsy of his right arm and leg after a 15-year history of presumed psoriasis. The fact that this rare occurrence happened in a couple who had been married for more than 25 years points to a common environmental exposure. Future studies should aim to clarify the potential role of infectious agents, such as human T-lymphotropic virus I and II, cytomegalovirus, Epstein-Barr virus, and other environmental exposures, in the development of MF.

Extracutaneous Tumour Mass Following Bexarotene and Interferon Therapy of Primary Cutaneous CD30+ Large Cell Lymphoma

) no prior or concurrent lymphomatoid papulosis (LyP), mycosis fungoides (MF), or other type of cutaneous lymphoma or extracutaneous localization at presentation (1, 2).Lesions of primary cu-taneous CD30+ ALCL tend to be large nodules, tumours, or subcutaneous masses that often ulcerate. Primary cu-taneous CD30+ lymphoproliferative disorders, including CD30+ ALCL, LyP and borderline cases, represent a clinical and histological continuum. In contrast to primary systemic and secondary CD30+ ALCL (e.g. large-cell transformation of MF), the primary cutaneous variant is characterized by an indolent clinical course with 5- and 10-year survival rates exceeding 95% and disseminated or extracutaneous disease in less than 10% (1). There is no uniform therapeutic approach for CD30+ ALCL, but most patients receive combinations of surgery, local radiation and/or chemotherapy (2, 3). Bexarotene, a retinoid X-receptor (RXR)-selective reti-noid, has recently been approved by the Food and Drug Administration (FDA) for cutaneous T-cell lymphoma including refractory MF and Sezary syndrome (4). There are only anecdotal reports on the treatment of CD30+ ALCL with bexarotene (5, 6). We describe here a patient with a predominantly inter-triginous manifestation of primary cutaneous ALCL, who rapidly developed extracutaneous tumour mass following bexarotene and interferon-α (IFN-α).CASE REPORTA 41-year-old Caucasian woman was referred to our hospital with a 10-month history of progressive cuta-neous tumours located mainly in the intertriginous areas such as the axillae, submammary region and inguinal folds (Fig. 1). Apart from slight pruritus she felt other-wise healthy, and had no concomitant diseases except obesity. Several skin biopsies showed mainly dermal and in part subcutaneous infiltration of atypical large lymphoid cells with pleomorphic nuclei and prominent nucleoli. Immunophenotyping revealed that these cells were strongly positive for CD30, CD4 and CD3, and negative for CD20 and CD56. A complete work-out, including clinical and bone marrow examinations, sonography and computerized tomography (CT), showed no evidence for systemic disease. A diagnosis of primary cutaneous CD30+ ACLC was made. Surgi-cal treatment was not considered because of the number of skin lesions. Hence, local radiotherapy with a total dose of 40 Gy given as 20 daily 2-Gy fractions was performed, resulting in a marked decrease of tumour load. However, she experienced new lesions shortly after finishing radiotherapy, and therefore monthly cycles of extracorporeal photophoresis (ECP) in combination with 3×4.5 MIU/week IFN-α-2b were initiated. After a stable outcome for 9 months, new lesions appeared, so bexarotene was added at a dosage of 300 mg/m

Expression pattern of T-cell–associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma

AbstractChemokine receptors mediate the migration of lymphocytes through the binding of soluble ligands, and their expression is differentially regulated in lymphocyte subsets. The pattern of chemokine receptor expression in T-cell non-Hodgkin lymphoma has not been previously studied. Using a panel of mouse monoclonal antibodies, we studied the immunohistochemical expression of the Th1-associated chemokine receptor CXCR3 in 141 patients with T-cell lymphoma, and we studied the receptors CCR4 and CCR5 and some of their ligands in a subset of these tumors. Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic lymphoma (15 of 18 patients), angiocentric lymphoma (3 of 3 patients), histiocyte-rich tumors (4 of 5 patients), and unspecified T-cell lymphomas (17 of 39 patients). CXCR3 expression was seen in only 1 of 15 patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. In contrast, all ALK-positive tumors showed diffuse reactivity for the Th2-associated receptor CCR4 (5 of 5 patients). CCR4 expression was also a consistent feature of the large-cell transformation of mycosis fungoides. CCR5 expression showed no consistent association with any T-cell tumor type. The chemokines Mig (CXCR3 ligand), TARC (CCR4 ligand), and MCP-2 (CCR5 ligand) were detected in intratumoral blood vessels and histiocytes. Mig was also coexpressed by a subset of CXCR3-positive tumor cells in 6 of 20 lymphomas. MCP-2 was highly expressed in stromal cells in 3 patients with nodal involvement by cutaneous T-cell lymphoma. As with normal T-cell subsets, we demonstrated that there is frequent differential expression of chemokine receptors in T-cell tumors, which may explain, in part, the distinctive patterns of spread in different tumor subtypes.

Expression pattern of T-cell–associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma

Chemokine receptors mediate the migration of lymphocytes through the binding of soluble ligands, and their expression is differentially regulated in lymphocyte subsets. The pattern of chemokine receptor expression in T-cell non-Hodgkin lymphoma has not been previously studied. Using a panel of mouse monoclonal antibodies, we studied the immunohistochemical expression of the Th1-associated chemokine receptor CXCR3 in 141 patients with T-cell lymphoma, and we studied the receptors CCR4 and CCR5 and some of their ligands in a subset of these tumors. Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic lymphoma (15 of 18 patients), angiocentric lymphoma (3 of 3 patients), histiocyte-rich tumors (4 of 5 patients), and unspecified T-cell lymphomas (17 of 39 patients). CXCR3 expression was seen in only 1 of 15 patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. In contrast, all ALK-positive tumors showed diffuse reactivity for the Th2-associated receptor CCR4 (5 of 5 patients). CCR4 expression was also a consistent feature of the large-cell transformation of mycosis fungoides. CCR5 expression showed no consistent association with any T-cell tumor type. The chemokines Mig (CXCR3 ligand), TARC (CCR4 ligand), and MCP-2 (CCR5 ligand) were detected in intratumoral blood vessels and histiocytes. Mig was also coexpressed by a subset of CXCR3-positive tumor cells in 6 of 20 lymphomas. MCP-2 was highly expressed in stromal cells in 3 patients with nodal involvement by cutaneous T-cell lymphoma. As with normal T-cell subsets, we demonstrated that there is frequent differential expression of chemokine receptors in T-cell tumors, which may explain, in part, the distinctive patterns of spread in different tumor subtypes.

Clinical evidence of transfer of contact dermatitis to mycosis fungoides

MUM1 is a member of the interferon regulatory factor family of transcription factors. It is normally expressed in plasma cells, late B cells, and activated T cells, and has been described in several B-cell malignancies. Although its expression has been reported in some T-cell neoplasms, the full range and character of expression have not been explored. We studied 58 cases of T-cell lymphoproliferative lesions, including systemic and cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis (LyP), mycosis fungoides (MF), MF with large cell transformation, and Sézary syndrome (SS). Nearly all cutaneous (5/5) and systemic anaplastic large cell lymphomas (4/5) were positive for MUM1, mainly in the large cell population. Similarly, 12 of 16 types A and C LyP showed MUM1 reactivity in greater than 50% of the large cells. Focal MUM1 staining was seen in 3 type B LyP, mostly in reactive lymphoid cells. All 9 MF with large cell transformation expressed MUM1 in large cells, where it paralleled CD30 expression. In comparison, most MF (11/12) were MUM1 negative. Interestingly, all SS cases (8/8) were MUM1 positive, 3 of which demonstrated diffuse staining. There was a significant difference in MUM1 expression between MF and SS groups as well as between MF and large cell transformation of MF groups (P < .001 for both). In summary, MUM1 is not helpful in separating different types of CD30-positive lymphoproliferative disorders. Potentially, MUM1 could serve as an adjunct marker for SS and/or large cell transformation of MF.