Anaplastic Large T-cell Lymphoma Research Articles

Primary cutaneous aspergillosis due to Aspergillus flavus in a neutropenic patient

Summary Cutaneous aspergillosis is a rare disease that generally affects immunosuppressed patients. We report a case of primary cutaneous aspergillosis developed at the site of cervical lymphadenectomy in a 32-year-old man with underlying anaplastic large T-cell lymphoma. The lymphadenectomy was performed to confirm relapse of the malignancy. Wound infection developed during the second week of post-chemotherapy neutropenia. Histopathologic examination of a skin biopsy specimen showed abundant hyphae, cultures yielded Aspergillus flavus and galactomannan antigenemia was positive. Treatment consisted of combination of voriconazole and surgical debridement. Patient died of multiorgan failure caused by bacterial sepsis without secondary dissemination of the Aspergillus infection. Conclusion Aspergillus infection should always be considered in the differential diagnosis of wound infections, especially in neutropenic patients.

Treatment Algorithms for Mature T-Cell and Natural Killer-Cell Neoplasms

Mature T-cell and natural killer (NK)-cell lymphomas are rare neoplasms, differing geographically in frequencies. T-cell lymphomas are more common in Asia than in western countries, and NK-cell lymphomas occur almost exclusively in Asia and South America. The rarity of these lymphomas means that treatment algorithms of T-cell and NK-cell lymphomas have not been well established. Angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma and peripheral T-cell lymphoma, not otherwise specified, are the more commonly encountered T-cell lymphomas. Treatment with anthracycline-based regimens designed for aggressive B-cell lymphomas gives unsatisfactory results. Cutaneous T-cell lymphomas may remain indolent, but outcome is poor for advanced diseases. Novel therapies, including monoclonal antibodies, nucleoside analogs, histone deacetylase inhibitors and small molecules targeting cellular signaling pathways, are being explored alone or in combination with chemotherapy. High-dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is recommended for high-risk cases. NK-cell lymphomas exhibit the multidrug resistance phenotype due to P-glycoprotein expression, so that anthracycline-based regimens are ineffective. Non-multidrug resistance-dependent regimens and L-asparaginase-based protocols have been shown to be highly active. Autologous HSCT is not routinely performed. The role of allogeneic HSCT is being examined.

Anaplastic Large T-Cell Lymphoma and Breast Implants

Anecdotal reports and one case-control study suggested an association, without evidence of causation, between breast implants and anaplastic lymphoma kinase-negative anaplastic large T-cell lymphoma (ALCL), a rare non-Hodgkin's lymphoma. This review summarizes the published evidence, including case reports and epidemiologic studies. A PubMed search limited to English language articles was conducted using the search terms "breast implant" and "lymphoma," "primary T-cell breast lymphoma," or "breast implant and ALCL" to identify all published cases of breast-associated ALCL. A total of 18 publications were retrieved describing 27 cases of ALCL in breast implant recipients. Breast-associated ALCL occurred in women with and without implants. Approximately 78 percent of cases (21 of 27) were CD30 anaplastic lymphoma kinase-negative, with an indolent clinical course. Both saline- and silicone-filled devices were identified; however, implant style and surface texture were largely unreported. The tumor stage at diagnosis was I in 16 of 27, II or higher in seven of 27, or unreported in four of 27. No prospective epidemiologic study has linked implants and ALCL; however, a single case-control study in Dutch women reported increased odds of association between ALCL and implants, and an estimated frequency of one in 1 million women with and without breast implants. An association, without evidence of causation, was reported between breast implants and ALCL. Further study is required to confirm this association. Breast-associated ALCL occurred rarely in women with and without breast implants and had a primarily indolent clinical course, which may provoke a revision of the World Health Organization nomenclature for lymphoma; however, aggressive clinical behavior was also reported. The cases of ALCL were not confined to a specific type of implant. Risk, V.

Kutane Manifestation eines nodalen, großzellig-anaplastischen, CD30-positiven, ALK-negativen T-Zell-Non-Hodgkin-Lymphoms

CD30-positive anaplastic large T-cell lymphomas are either primary cutaneous T-cell lymphomas or primary systemic T-cell lymphomas. Primary cutaneous CD30-positive anaplastic large T-cell lymphomas are usually ALK-negative whereas systemic CD30-positive T-cell lymphomas are more often ALK-positive (60 – 80 %). We present a rare case of a 67 year old patient with a systemic CD30-positive ALK-negative T-cell lymphoma and secondary cutaneous manifestation. This form of a CD30-positive anaplastic large T-cell lymphoma has a bad prognosis and must be treated more aggressively than a primary cutaneous form of CD30-positive ALK-negative anaplastic large T-cell lymphoma.

Discussion: Managing Late Periprosthetic Fluid Collections (Seroma) in Patients with Breast Implants: A Consensus Panel Recommendation and Review of the Literature

The recent attention to an extremely rare form of lymphoma known as Anaplastic Large T-Cell Lymphoma (ALCL) has spurred great interest in defining the etiology of this highly unusual malignancy and its potential association with breast implants. Because of the rarity of this disease, data regarding its characteristics can only be gleaned from case reports in the literature and from sporadic unpublished cases from plastic surgeons. Given that the data are too sparse to guide treatment, the Food and Drug Administration has coordinated a registry in order to collect cases prospectively in an effort to better understand this disease. Until better data are available, patients and physicians are seeking guidance from experts. It is generally believed that ALCL associated with breast implants has a more benign course and can be treated effectively by draining the seroma and removing the breast implants.1,2 The literature suggests that most women with ALCL who had their breast implants removed can be disease free and do not require more intensive therapy such as chemotherapy or radiation therapy. However, given the uncertainty of this unique disease, the recommendations are based on empiric observations rather than robust epidemiology studies.

Primary anaplastic large-cell lymphoma associated with breast implants

Primary T-cell anaplastic large-cell lymphoma (ALCL) of the breast is a rare entity, which has been reported in association with breast implants. In a retrospective analysis of the City of Hope pathology database, we uncovered nine such patients, eight of whom had breast implants proximal to primary ALCL. The diagnosis of ALCL in the implant capsule occurred at a median of 7 years (range 5–30) following implant surgery, and median patient age was 45.5 years (range 32–62). Malignancy was effusion-associated in two cases and tissue-associated in six. Seven patients were negative for anaplastic large-cell kinase (ALK) and one patient was positive. Treatment and follow-up data were available for four patients, all tissue-associated cases: two patients were lost to follow-up after failing to mobilize stem cells and two patients were in remission, 6 years and 7.5 years post-autologous transplant. These cases represent 24% of reported primary ALCL cases associated with breast implants. Our review of these cases and the literature suggest that (1) there is a strong skew in primary breast lymphomas associated with implant capsules toward T-cell, ALCL ALK−, and (2) the disease course for tissue-associated cases is not always indolent, with four patients requiring multiple treatment regimens.

Successful treatment of recurrent malignancy-associated hemophagocytic lymphohistiocytosis with a modified HLH-94 immunochemotherapy and allogeneic stem cell transplantation

Acquired hemophagocytic lymphohistiocytosis (HLH) triggered by a known or still to be recognized malignancy is a life-threatening hyperinflammatory syndrome due to massive cytokine release from activated lymphocytes and macrophages. Malignancy-associated HLH (M-HLH) often impedes adequate treatment of malignancy and has the worst outcome compared with any other form of HLH. The incidence of M-HLH is unknown, and there are no published treatment recommendations addressed to this HLH form. Here, we report the case of a young woman with recurrent ALK1-positive anaplastic large T-cell lymphoma and M-HLH successfully treated with a modified HLH-94 protocol, allogeneic stem cell transplantation (alloSCT) and donor lymphocyte infusion (DLI). More than 3 years after DLI, the patient is alive, in complete remission from her malignancy and HLH-free, although suffering from extensive chronic graft-versus-host disease. AlloSCT and, if needed, DLI performed to consolidate remission of malignancy and HLH may have a curative impact on both entities. We propose that when discussing possible treatment options for patients with M-HLH, alloSCT should be considered in eligible individuals.

Presence of B‐cell clones in T‐cell lymphoma

The presence of B-cell clones in 76 cases with peripheral T-cell lymphoma (PTCL) and precursor T-lymphoblastic lymphoma (T-LBL) and its correlation with Epstein-Barr virus (EBV) was studied. DNA was extracted from paraffin sections and/or fresh-frozen samples and then used for clonality analysis using a modified BIOMED-2 polymerase chain reaction (PCR)-based method. T- and B-cell clones were detected in 59 (77.6%) and 14 (18.4%) of 76 patients, respectively: 90% and 30% of cases with PTCL, not otherwise specified, 76.4% and 17.6% of cases with angioimmunoblastic T-cell lymphoma, 77% and 7.6% of cases with adult T-cell lymphoma, 50% and 0% of cases with anaplastic large T-cell lymphoma, 62.5% and 12.5% of cases with T-LBL, and 50% and 0% of cases with intestinal T-cell lymphoma, respectively. Histological and immunohistochemical analyses revealed the presence of large B cells in lesional tissues, which were occasionally monoclonal. The presence of B-cell clones was highly associated with EBV positivity, as revealed by in situ hybridization. In two cases that were evaluated by serial histological and molecular examination, EBV-positive cells persisted in one and disappeared in the other. These findings suggest a role for EBV in the evolution of B-cell clones in T-cell lymphomas.

Multiple myeloma and cutaneous anaplastic large T-cell lymphoma in the same patient: Is there a causal relation?

Synchronous occurrence of lymphomatous proliferations of B and T lineage in the same patient is a very rare event and still poorly understood. All the cases reported in the English language literature are described as single case reports. We report a case of 49-year-old man, with 2-year history of multiple myeloma, presented with a raised, erythematous and ulcerated nodule in the anterior aspect of his right thigh. Histologic examination of biopsy specimen showed a dense dermic infiltrate made of large balastic cells displaying anaplastic morphology with no epidermotropism. Immunohistochemical study showed that tumor cells stained positive with CD30, EMA and CD4, and negative for CD3, CD8, CD5, CD20, CD79a, CD138 and anaplastic lymphoma kinase 1 (ALK or Ki-1).

Extrinsic apoptotic pathways: A new potential "Target" for more sufficient therapy in a case of cutaneous anaplastic large CD30+ ALK-T--cell lymphoma

The primary cutaneous T-cell lymphomas (CTCL) represent a clonal T-lymphocyte proliferation infiltrating the skin. CD30+T-cell lymphomas present clinically as nodules with a diameter between 1 and 15 cm, mostly in elderly patients. The role of the CD30 molecule in patients suffering from T-cell lymphomas is not completely clear yet. The signal transduction pathway which includes CD30 seems to play a key role in tumor progression. In certain forms of T-cellular lymphomas, the interaction between CD30/CD30-ligand is able to provoke apoptosis of the “tumor lymphocytes”. The modern conceptions of the pathogenesis of T-cell lymphomas include disorders in the pathways involved in programmed cellular death and disregulation in the expression of certain of its regulatory molecules. We are presenting an unusual case of a female patient with a primary cutaneous form of CD30+/ALK− anaplastic large T-cell lymphoma. Upon the introduction of systemic PUVA, (psoralen plus ultraviolet light radiation) combined with beam therapy, a complete remission could be noticed. Eight months later, we observed a local recurrence, which was overcome by CHOP chemotherapy (Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vincristin (Oncovin®), Predniso(lo)n). Six months later, new cutaneous lesions had been noticed again. A new therapeutic hope for the patients with anaplastic large CTCL is actually based on the influence of the activity of the different apoptotic pathways. Death ligands, including tumor necrosis factor (TNF)-α, CD95L/FasL, and TRAIL, mediate also some important safeguard mechanisms against tumor growth in patients with CD30+ cutaneous anaplastic large T-cell lymphomas and critically contribute to lymphocyte homeostasis.

A Case of an Unusually Aggressive Cutaneous Anaplastic Large T-Cell Lymphoma in an HIV Patient Treated with CHOP

Anaplastic large cell lymphoma (ALCL) is the second most common malignancy of T-cell phenotype. This case report describes an unusual rapidly progressing cutaneous anaplastic large T-cell lymphoma in an HIV patient. Our patient is a twenty-year-old African American male with perinatally acquired HIV who presented with a 2 × 2 centimeter necrotic lesion in the right 1st toe; however, 2-3 weeks later multiple smaller lesions appeared on the anterior aspect of the right foot, ankle, and thigh. Biopsy showed cells strongly positive for CD3 and CD30 and negative for CD56 and the ALK gene product. CT of the chest, abdomen, and pelvis was negative for extracutaneous involvement favoring cutaneous ALCL. Patient was treated with 6 cycles of CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) chemotherapy and went into complete remission. Due to the aggressive course that this malignancy follows in HIV patients we suggest prompt treatment with systemic therapy.

A Phase I Dose-Escalation Trial of Oral Clofarabine for Relapsed/Refractory Non-Hodgkin Lymphoma

AbstractAbstract 1775 Background:Clofarabine is a second-generation purine analogue currently FDA-approved for intravenous use for relapsed/refractory pediatric ALL. Purine analogues demonstrate significant clinical activity in non-Hodgkin lymphomas (NHL), though clofarabine offers potential pharmacologic advantages over existing agents. Clofarabine is a more efficient substrate for deoxycytidine kinase, more completely inhibits ribonucleotide reductase and DNA polymerase α, and demonstrates improved activity in cells that are non-dividing or have a low proliferation rate. This phase I trial is the first evaluation of an oral formulation of clofarabine in relapsed or refractory non-Hodgkin lymphoma. Patients and Methods:The primary objective was to determine the maximum tolerated dose (MTD) and define dose-limiting toxicities (DLT). Efficacy was a secondary objective. Patients (pts) were eligible if they had relapsed or refractory B-cell or T-cell NHL without prior stem cell transplant. All pts were required to have adequate organ function and performance status ≤2 as well as absence of both CNS involvement and HIV infection. No routine infectious prophylaxis was given. Patients were treated at 4 dose levels (1mg, 2mg, 4mg and ultimately 3mg) with oral clofarabine administered once daily on days 1–21 of a 28 day cycle for up to 6 cycles. Three to 6 pts were treated at each dose level in a traditional 3+3 design. Response assessment occurred after cycles 2 and 6. DLT was assessed during cycle 1 and was defined as Grade 4 neutropenia or thrombocytopenia occurring for ≥5 days, any grade 3–4 non-hematologic toxicity, and grade 2 non-hematologic toxicity that did not recover prior to the subsequent cycle of therapy. Results:Twenty-one pts were enrolled on the dose-escalation phase of the study. The median age was 63 years (range 51–85). The median number of prior regimens was 2 (range 1–7). Histologies included follicular lymphomas (FL; 5 pts), small lymphocytic lymphomas (SLL; 5 pts), diffuse large B-cell lymphomas (DLBCL; 4 pts), marginal zone lymphomas (MZL; 4 pts), mantle cell lymphomas (MCL. 2 pts) and lymphoplasmacytic lymphoma (LPL; 1 pt). Median number of cycles administered was 5.5. No DLTs were observed at the 1mg or 2mg dose levels. Three pts were accrued at 4mg with 1 patient experiencing DLT of persistent grade 3 thrombocytopenia and grade 4 neutropenia. No additional DLTs occurred in the cohort, but the majority of pts required late dose reductions due to grade 3–4 hematologic toxicity. The dose was therefore de-escalated to 3mg and 6 additional pts were accrued. No DLTs were observed at the 3mg dose level with a median of 6 cycles administered (range 5–6); 3mg was declared the recommended phase 2 dose. Grade 3–4 hematologic toxicity included neutropenia (7 pts), thrombocytopenia (4 pts), and anemia (2 pts). Grade 1–2 non-hematologic toxicities were uncommon, and included fatigue, diarrhea, cough, and dizziness. There were no grade 3–4 non-hematologic toxicities. Seventeen pts completed one cycle of therapy and were evaluable for response. Radiographic disease reduction was observed in 11 of 17 pts (65%). The overall response rate (ORR) was 35% (6 of 17), all partial responses (PR). Responders included FL (2 pts), MZL (2 pts), SLL and LPL (1 pt ea.). ORR among low grade histologies (FL, MZL, SLL) was 43% in this phase 1 trial. Seven pts had stable disease, including 5 pts with reduction in tumor size that did not reach threshold for PR. Of the 4 pts with progressive disease, 2 had DLBCL, 1 had MCL and 1 had FL with biopsy following relapse identifying ALK-negative anaplastic large T-cell lymphoma. Of the 4 pts not evaluable for response, 1 pt died of progressive DLBCL during cycle 1 on dose level 1 and was replaced, 1 pt was the DLT pt on the 4mg dose level and was removed due to prolonged cytopenias, and 2 pts withdrew consent (1pt at 4mg, 1pt at 3mg), and were replaced. The 3mg dose level has been expanded in a 10-patient dose-expansion cohort limited to low-grade NHL and MCL. Conclusions:Oral clofarabine demonstrates encouraging tolerability and efficacy in relapsed B-cell NHL, particularly in low-grade histologies, warranting further investigation. Disclosures:Abramson:Genzyme: Consultancy. Off Label Use: Clofarabine is not FDA approved for NHL.

Anaplastic large-cell lymphoma with atypical chromosomal translocation t(2;5) and hypophyseal tumor

Anaplastic large T-cell lymphoma (ALCL) is frequently associated with the t(2;5)(p23;q35). Here, we report a case of ALCL with an atypical translocation of t(2;5)(p24;q13) and other complex translocations. This complex abnormal karyotype may result in chemotherapy resistance and a poor outcome. Interestingly, a hypophyseal tumor was detected simultaneously by magnetic resonance imaging in this case. We think it is probable that the tumor in the hypophysis might be associated with the ALCL.

Assessment of a cutaneous anaplastic large T-cell lymphoma by real-time tissue elastography

Assessment of a cutaneous anaplastic large T-cell lymphoma by real-time tissue elastography

Aggressive Variant of Primary Cutaneous Anaplastic Large T-Cell Lymphoma

Primary cutaneous anaplastic large cell lymphoma (ALCL) represents less than 2% of all T-cell lymphomas and usually manifests as a solitary cutaneous lesion generally in older males. It is an indolent disorder with a survival rate of 90% at 10 years, and rarely shows extracutaneous dissemination. The FDG avidity of the lesions of cutaneous ALCL is the lowest reported among T-cell lymphoma subtypes. However, the available positron emission tomography (PET) literature has not taken account of a subtype of primary cutaneous ALCL that presents with extensive limb disease, has a much more aggressive course, and responds poorly to conventional therapy. We report serial F-18 FDG PET/CT imaging of a 72-year-old man with this aggressive subtype of primary cutaneous ALCL. This case demonstrates that despite the low reported sensitivity of FDG PET/CT in cutaneous ALCL, PET/CT may in fact play a vital role in identifying patients with the more aggressive extensive limb disease subtype, and help guide therapeutic decisions toward much better outcomes than currently achieved.

CD8-Positive Primary Cutaneous Anaplastic Large T-Cell Lymphoma (PCALCL): Case Report and Review of This Unusual Variant of PCALCL

Primary cutaneous anaplastic large T-cell lymphoma (PCALCL) is a well-defined CD30-positive lymphoproliferative disorder with relatively good prognosis and response to treatment. We describe a case of PCALCL expressing CD8. The patient is a 57-year-old man that clinically presented with an ulcerated nodule in his left middle finger. Histopathologic sections showed an ulcerated epidermis with a diffuse lymphocytic infiltrate in the superficial dermis with focal epidermotropism. The large cohesive atypical cells were admixed with a reactive infiltrate composed of neutrophils, eosinophils, and small lymphocytes. Immunohistochemical studies showed the tumor cells to be strongly positive for CD8, CD30, and TIA-1, focally positive for CD3, and negative for CD4, CD20, CD56, Anaplastic Lymphoma Kinase (ALK-1), and HSV. Epstein-Barr virus by in situ hybridization was negative. The diagnosis of a CD8+ PCALCL was confirmed. There is limited precedent literature regarding CD8-positive PCALCL and this case falls within the clinical and histopathologic spectrum of CD30+ lymphoproliferative disorders. CD8/CD30 coexpression is rare in PCALCL and may have important clinical and prognostic implications. To the best of our knowledge there are only 4 previously reported cases describing similar findings.

Cutaneous presentation of post‐renal transplant lymphoproliferative disorder: a series of four cases

We report detailed histological and molecular characteristics of four post transplant lymphoproliferative disorders (PTLD) presenting in the skin of renal transplant patients, and their clinical outcome. Three had B-cell lymphomas (cases 1-3), and one had a T-cell lymphoma (case 4). All B-cell lymphomas showed Epstein-Barr virus (EBV) by immunohistochemistry (IHC) or in situ hybridization (ISH). Cases 1 and 2 were large cell lymphomas, and case 3 a plasmacytoma. Case 1 showed light chain restriction and heavy chain gene rearrangement by polymerase chain reaction (PCR). The patient was then diagnosed with an abdominal lymphoma and died of sepsis. Case 2 had no recoverable DNA. Case 3 had a plasmacytoma that showed monoclonal light chain restriction on IHC and an oligoclonal heavy chain rearrangement by PCR. In cases 2 and 3, the lesions regressed following reduction of immunosuppression, and died 1.5 and 8 years later from unrelated medical causes. Case 4 was a CD 30+ anaplastic large T-cell lymphoma with no EBV detected by IHC, ISH and PCR, and died of heart failure 2 years later. Cutaneous manifestations of PTLD are rare, show wide array of clinical and pathological features, and generally have a favorable prognosis. EBV appears to be associated only with B-cell cutaneous lymphomas.

PAX5-positive T-cell anaplastic large cell lymphomas associated with extra copies of the PAX5 gene locus

Cell lineage is the major criterion by which lymphomas are classified. Immunohistochemistry has greatly facilitated lymphoma diagnosis by detecting expression of lineage-associated antigens. However, loss or aberrant expression of these antigens may present diagnostic challenges. Anaplastic large cell lymphoma is a T-cell lymphoma that shows morphologic and phenotypic overlap with classical Hodgkin's lymphoma, which is a tumor of B-cell derivation. Staining for the B-cell transcription factor, paired box 5 (PAX5), has been suggested to be helpful in this differential, as it is positive in most classical Hodgkin's lymphomas, but absent in anaplastic large cell lymphomas. In this study we report four systemic T-cell anaplastic large cell lymphomas that were positive for PAX5 by immunohistochemistry, with weak staining intensity similar to that observed in classical Hodgkin's lymphoma. All diagnoses were confirmed by a combination of morphologic, phenotypic, and molecular criteria. Three cases were anaplastic lymphoma kinase (ALK) negative and one was ALK positive. PAX5 immunohistochemistry was negative in 198 additional peripheral T-cell lymphomas, including 66 anaplastic large cell lymphomas. Unexpectedly, although PAX5 translocations were absent, all evaluable PAX5-positive anaplastic large cell lymphomas showed extra copies of the PAX5 gene locus by fluorescence in situ hybridization (FISH). In contrast, only 4% of PAX5-negative peripheral T-cell lymphomas had extra copies of PAX5. We conclude that aberrant expression of PAX5 occurs rarely in T-cell anaplastic large cell lymphomas, and may be associated with extra copies of the PAX5 gene. PAX5-positive lymphomas with morphologic features overlapping different lymphoma types should be evaluated with an extensive immunohistochemical panel and/or molecular studies to avoid diagnostic errors that could lead to inappropriate treatment. As PAX5 overexpression causes T-cell neoplasms in experimental models, PAX5 may have contributed to lymphomagenesis in our cases.

Primary ALK-positive Anaplastic Large Cell Lymphoma of the Breast: A Case Report and Review of the Literature

Non-Hodgkin lymphomas of the breast are uncommon, which represent less than 1% of all breast malignancies and predominantly are of B-cell origin. In this report, a rare case of anaplastic lymphoma kinase (ALK)-positive anaplastic large T-cell lymphoma in the breast of a 16-year-old female without breast implant is described. The patient presented with a 3-month history of progressive right breast swelling and erythema. Clinically, inflammatory breast carcinoma was highly suspected. A tru-cut needle biopsy of the right breast demonstrated infiltration of tumoral cells around the breast lobules and soft tissue and also in angiolymphatic spaces. The immunohistochemical profile showed positivity for CD30 and ALK and confirmed the diagnosis of ALK-positive anaplastic large T-cell lymphoma of the breast. Anaplastic large T-cell lymphoma of the breast is rare, and can clinically mimic inflammatory breast carcinoma in adolescence.

Cutaneous Anaplastic Large Cell Lymphoma and Peripheral T-Cell Lymphoma NOS Show Distinct Chromosomal Alterations and Differential Expression of Chemokine Receptors and Apoptosis Regulators

Primary cutaneous anaplastic large cell lymphoma (C-ALCL) has an indolent clinical course and favorable prognosis. On the contrary, primary cutaneous peripheral T-cell lymphoma not otherwise specified (PTL-NOS) shows aggressive clinical behavior. To identify genomic events relevant in the pathogenesis of these cutaneous T-cell lymphomas (CTCLs), we carried out array-based comparative genomic hybridization (CGH) analysis. Simultaneously, gene expression profiling was conducted to gain insight into gene expression programs associated with the different clinical behavior of these CTCLs. C-ALCL was characterized by gains on chromosome 7q and 17q and losses on 6q and 13q. PTL-NOS similarly showed gains on 7q and 17q, but was distinguished by gains on chromosome 8 and loss of a focal overlapping region on 9p21. We identified minimal common regions harboring candidate oncogenes and tumor suppressor genes in C-ALCL and PTL-NOS. Genes with a role in lymphocyte chemotaxis, apoptosis, and proliferation were overrepresented among genes differentially expressed between these lymphomas. C-ALCL showed higher expression of the skin-homing chemokine receptor genes CCR10 and CCR8, which may explain the lower tendency to disseminate to extracutaneous sites. Furthermore, C-ALCL and PTL-NOS showed aberrant expression of distinct genes implicated in apoptosis and proliferation, such as IRF4/MUM1 and PRKCQ, which may account for differences in clinical aggressiveness.