Subcutaneous panniculitis-like T-cell lymphoma: Morphological, immunophenotypical and clonality assessment in six cats.

BACKGROUND: Primary cutaneous lymphoma represents 0.2%-3% of all feline lymphomas, with nonepitheliotropic lymphomas being the most common. In humans and dogs, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a primary nonepitheliotropic lymphoma with a T-cell phenotype developing in the subcutis and often mimicking inflammation. OBJECTIVE: The aim of this report is to describe pathological, phenotypical and clonal features of SPTCL in cats. ANIMALS: Six cats with SPTCL were included in this study. MATERIALS AND METHODS: Skin biopsies were formalin-fixed, routinely processed and stained. Histological and immunohistochemical investigation for anti-CD18, CD204, CD79a, CD20, CD3, FeLVp27and FeLVgp70 and clonality assessment were performed. RESULTS: Four male and two female domestic shorthair cats, mean age 11.2 years, developed SPTCL in the abdominal (three), inguinal (two) and thoracic (one) regions. Variably pleomorphic neoplastic lymphoid cells were present in the panniculus in percentages, expanding the septa (six of six) and extending into fat lobules in one of six cats. Tumours were associated with elevated numbers of neutrophils (five of six), lesser macrophages (six of six) and variable necrosis (six of six). Neoplastic cells expressed CD3+ (six of six), with clonal T-cell receptor rearrangement detected in five of six cats. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first description of SPTCL in cats. Lesions can be confused with panniculitis, leading to delay in diagnosis and therapy. Awareness of this neoplastic disease is relevant to avoid misdiagnoses and to gain greater knowledge about the disease in cats.

Primary cutaneous gamma-delta T-cell lymphoma masquerading as leukemia cutis in a patient recently diagnosed with small lymphocytic lymphoma: Clues to the diagnosis.

A 54-year-old man recently diagnosed with small lymphocytic lymphoma (SLL) had waxing and waning, indurated, erythematous plaques on his legs, with leukopenia and anemia disproportionate to the SLL burden in his marrow and pelvic lymph nodes. Punch biopsy of a plaque performed to evaluate for leukemia cutis revealed a lymphocytic lobular-panniculitis-like infiltrate resembling lupus panniculitis, but a preponderance of CD8+/Ki-67+ T-cells surrounding adipocytes raised concern for subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Additional immunohistochemistry (IHC) studies showed that the adipotropic T-cells expressed TCR-gamma, supporting the rare, unexpected diagnosis of Primary cutaneous gamma-delta T-cell lymphoma (PCGDTCL). The patient subsequently met diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). PCGDTCL is an aggressive, HLH-associated lymphoma requiring different management than SPTCL and SLL. This case illustrates how PCGDTCL can co-exist with B-cell lymphoma and resemble panniculitis on biopsies. PCGDTCL and SPTCL should enter the differential diagnosis whenever patients present with the constellation of lobular panniculitis and unexplained cytopenias. In the present case, close clinicopathologic correlation and judicious use of IHC on a small sample allowed for a prompt diagnosis.

Ruxolitinib as adjunctive therapy for secondary hemophagocytic lymphohistiocytosis: A case series.

INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a cytokine storm syndrome associated with mortality rates of up to 88%. Standard therapy with high-dose glucocorticoids and etoposide used in adults is extrapolated from pediatric trials, with significant toxicity in older patients and those with poor performance status. The JAK1/2 inhibitor ruxolitinib has recently gained attention as a treatment option for HLH due to its broad cytokine-modulating abilities and safety profile. Herein we report our center's experience using ruxolitinib in the treatment of adult-onset secondary HLH. CASE SERIES: We report four patients with profound secondary HLH provoked by diverse triggers, including invasive pulmonary aspergillosis on background systemic lupus erythematosus, disseminated tuberculosis, and T-cell lymphoma treated with ruxolitinib as monotherapy or combination therapy in upfront and salvage settings. RESULTS: All four patients had rapid, sustained improvement in clinical status, inflammatory markers, and hematological cell counts followed by durable remission. Three patients developed manageable infectious complications postruxolitinib. CONCLUSIONS: This series demonstrates the effective use of JAK inhibition with ruxolitinib to control pathological immune activation in critically ill patients with secondary HLH and otherwise limited therapeutic options. JAK inhibition is also an area of urgent investigation for the treatment of cytokine storm associated with COVID-19.

Primary cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome. Part II: Prognosis and management.

Primary cutaneous T-cell lymphomas (CTCLs) other than mycosis fungoides (MF) and Sézary syndrome (SS) encompass a heterogenous group of non-Hodgkin lymphomas with variable clinical courses, prognoses, and management approaches. Given the morphologic and histologic overlap among the CTCL subtypes and other T-cell lymphomas with cutaneous manifestations, thorough evaluation with clinicopathologic correlation and exclusion of systemic involvement are essential prior to initiating therapy. Staging and treatment recommendations vary, depending on the subtype, clinical behavior, and treatment response. Generally, for subtypes in which staging is recommended, Ann Arbor or tumor, node, metastasis staging specific to CTCL other than MF or SS are used. For many subtypes, there is no standard treatment to date. Available recommended treatments range widely, from no active or minimal intervention with skin-directed therapy to aggressive systemic therapies that include multi-agent chemotherapy with consideration for hematopoietic stem cell transplant. Emerging targeted therapies, such as brentuximab, a chimeric antibody targeting CD30, show promise in altering the disease course of non-MF/SS CTCLs.

Primary cutaneous T-cell lymphomas other than mycosis fungoides and Sézary syndrome. Part I: Clinical and histologic features and diagnosis.

Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous disease at initial presentation. CTCLs other than mycosis fungoides and Sézary syndrome (SS) account for approximately one third of CTCLs and encompass a heterogenous group of non-Hodgkin lymphomas, ranging from indolent lymphoproliferative disorders to aggressive malignancies with a poor prognosis. The spectrum of CTCLs continues to broaden as new provisional entities are classified. Given the morphologic and histologic overlap among CTCLs and other diagnoses, a thorough clinical history, physical evaluation, and clinicopathologic correlation are essential in the work up and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than mycosis fungoides and SS.

Unraveling subcutaneous panniculitis-like T-cell lymphoma: An association between subcutaneous panniculitis-like T-cell lymphoma, autoimmune lymphoproliferative syndrome, and familial hemophagocytic lymphohistiocytosis.

Germline HAVCR2 mutations, recently identified in a large subset of patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). Discovery of this heritable HLH/SPTCL diathesis has expanded our understanding of a rare and molecularly heterogeneous lymphoma. Furthermore, patients with SPTCL have excellent survival unless they develop HLH. Therefore, through compiling data on SPTCL-related conditions that predispose patients to HLH, we are better able to predict which patients with SPTCL have the greatest risk of mortality. We present the first case of SPTCL with concomitant HLH and autoimmune lymphoproliferative syndrome (ALPS) in a patient who was subsequently diagnosed with familial HLH (F-HLH) attributable to a germline STXBP2 splice-site mutation. She had wild-type HAVCR2. Reports including ours show how SPTCL can evolve in the setting of an exaggerated host inflammatory response attributable to a variety of unusual underlying etiologies.

Subcutaneous panniculitis-like T cell lymphoma presented as erythema nodosum: A case report.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is an extremely rare subtype of primary cutaneous T cell lymphomas mimicking panniculitis. Clinically, patients are usually presented with subcutaneous nodules, which usually leads to initial misdiagnosis as a benign cutaneous condition. Here, we report a 40-year-old female who presented with subcutaneous erythematous nodules on her extremities with fever. On the basis of the clinical presentations, histopathological features and immunohistochemical findings, a diagnosis of SPTCL was made. The patient was treated with the injection of recombinant human interferon α-1b (30 µg) every other day for 3 months. The lesions gradually regressed. No new erythema nodules reappeared during the 10-month follow-up.

Intrapleural infections in patients with subcutaneous panniculitis-like T-cell lymphoma are susceptible to hemophagocytic lymphohistiocytosis.

Patients with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) are prone to the development of hemophagocytic lymphohistiocytosis (HLH). It is not known whether small infections in SPTCL patients can trigger the development of HLH. The clinical data were collected from 21 SPTCL patients admitted to our hospital from January 2006 to October 2019. Among 21 cases of SPTCL, six cases had HLH as the first manifestation (SPTCL/HLH), seven cases had intrathoracic infection (ITI), five cases were SPTCL/HLH, 13 cases had no ITI or HLH (SPTCL/no HLH). Two patients with SPTCL/noHLH healed spontaneously. We found that 28.6% of the SPTCL patients had HLH as the first presentation. ITI may cooperate with SPTCL to trigger HLH and a small number of SPTCL/noHLH can fully recover without treatment.

Subcutaneous panniculitis-like T-cell lymphoma in a 14-year-old female homozygous for HAVCR2 mutation.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma preferentially involving subcutis. A link between patients with SPTCL and HAVCR2 mutations has recently been discovered. We present a 14-year-old girl of Chinese heritage who was diagnosed with SPTCL in the context of homozygous HAVCR2 status for c.245A>G p. (Tyr82Cys) and achieved complete remission after treatment with cyclosporin and steroids. Dermatologists should be aware of the diagnostic, management and familial genetic counselling utility of HAVCR2 for investigating and managing patients with SPTCL.

TIM-3 deficiency presenting with two clonally unrelated episodes of mesenteric and subcutaneous panniculitis-like T-cell lymphoma and hemophagocytic lymphohistiocytosis.

This report offers novel clinical and diagnostic aspects of the association between germline mutations in HAVCR2 and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). The patient presented with panniculitis-like T-cell lymphoma involving mesenteric fatty tissue associated with hemophagocytic lymphohistiocytosis (HLH). Five years later, he developed a clonally unrelated SPTCL and underwent hematopoietic stem cell transplantation. Retrospectively, he was found to carry germline mutations in HAVCR2 associated with reduced T-cell immunoglobulin mucin-3 (TIM-3) expression. We show that mesenteric fatty tissue localization of SPTCL can be the presenting manifestation of TIM-3 deficiency, that this condition predisposes to recurrent lymphoma, and that flow cytometry is a possible screening tool.

The epidemiology of subcutaneous panniculitis-like alpha-beta T-cell lymphoma in New Zealand.

BACKGROUND/OBJECTIVES: Subcutaneous panniculitis-like alpha-beta T-cell lymphoma is a rare disease, which comprises less than 1% of all non-Hodgkin lymphoma. The epidemiology of this disorder has not been established in New Zealand, particularly the ethnic variation. METHODS: A retrospective study was conducted from 2005 to 2017 in South Auckland, New Zealand. Patients with histopathologically confirmed subcutaneous panniculitis-like alpha-beta T-cell lymphoma, according to the WHO-EORTC classification, were included. Cases were identified from multiple data sources to ensure the study population was completely surveyed. Census data were used as the denominator. RESULTS: Ten cases were identified. Five were men and five women. The median age at diagnosis was of 38.5 years (range 17-73 years). Nine were Maori/Pacific, and one was European. The ethnic relative risk of subcutaneous panniculitis-like alpha-beta T-cell lymphoma in Maori/Pacific versus European was 11.1 (95% Cl 1.83-246.1, P = 0.005). CONCLUSION: Maori and Pacific have a higher relative risk of subcutaneous panniculitis-like alpha-beta T-cell lymphoma compared to non-Maori/Pacific.

Utility of CD123 immunohistochemistry in differentiating lupus erythematosus from cutaneous T cell lymphoma.

AIMS: Histopathological overlap between lupus erythematosus and certain types of cutaneous T cell lymphoma (CTCL) is well documented. CD123+ plasmacytoid dendritic cells (PDCs) are typically increased in lupus erythematosus, but have not been well studied in CTCL. We aimed to compare CD123 immunostaining and histopathological features in these conditions. METHODS AND RESULTS: Skin biopsies of cutaneous lupus erythematosus (CLE, n = 18), lupus erythematosus panniculitis (LEP, n = 17), mycosis fungoides (MF, n = 25) and subcutaneous panniculitis-like T cell lymphoma (SPTCL, n = 9) were retrospectively reviewed and immunostained with CD123. Percentage, distribution and clustering of CD123+ cells were compared between CLE and MF and between LEP and SPTCL using χ2 and two-tailed t-tests. A higher percentage of CD123+ cells was observed in CLE than MF (P < 0.01), more frequently comprising ≥20% of the entire infiltrate (P < 0.01) and forming clusters (P < 0.01). Similarly, LEP showed a higher percentage of CD123+ cells than SPTCL (P = 0.01), more frequently comprising ≥20% of the infiltrate (P = 0.04) and forming clusters (P = 0.01). Basal vacuolar change or dyskeratosis was observed in all CLE cases and in 48% cases of MF cases (P = 0.05). Plasma cells were readily identified in 76% cases of LEP but in none of the SPTCL cases (P = 0.01). Adipocyte rimming by lymphocytes, hyaline fat necrosis and fibrinoid/grungy necrosis did not significantly differ between LEP and SPTCL. Dermal mucin also failed to distinguish between groups. CONCLUSIONS: CD123 immunostaining is helpful in differentiating CLE from MF and LEP from SPTCL, but should be interpreted in conjunction with clinicopathological features and other ancillary studies to ensure accurate diagnosis.

Rare T-Cell Subtypes.

There are a number of rare T-cell lymphoma subtypes that may be encountered in clinical practice. In recent years, improved immunohistochemical techniques and molecular tumor profiling have permitted refinement of some of the diagnostic categories in this group, as well as the recognition of distinct conditions not previously well elucidated. In this chapter, we cover the diagnostic and clinical features of some of the more common of these conditions, including subcutaneous panniculitis-like T-cell lymphoma, cutaneous gamma-delta T-cell lymphoma, enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma, CD4-positive small/medium T-cell lymphoproliferative disorder, and acral CD8-positive T-cell lymphoma. Given the rarity of these conditions, optimal treatments approaches are not always well established, not least as data from large-scale clinical trials are lacking. In this chapter, we aim to provide a summation of current thinking around best treatment, as well as highlighting some controversies in the management of these diagnoses.

Clinicopathologic, immunophenotypic, and molecular analysis of subcutaneous panniculitis-like T-cell lymphoma: A retrospective study in a tertiary care center.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTL) as strictly defined by World Health Organization-European Organization for Research and Treatment of Cancer classification is a rare cytotoxic α/ß T-cell lymphoma, characterized by primary involvement of subcutaneous tissue mimicking panniculitis. OBJECTIVES: To describe the clinicopathologic, immunophenotypic, and molecular features of SPTL. METHODS: A 10-year retrospective study of 18 patients diagnosed with SPTL was thoroughly reviewed according to clinicopathology, immunophenotype, and T-cell receptor (TCR) gene rearrangement. RESULTS: Of the 18 patients, 16 patients were definitely diagnosed with SPTL. The median age was 26 years (ranged 14-53 years) with female predominance. Most patients presented with prolonged fever and subcutaneous nodules and/or plaques, usually located on lower extremities. 37.5% of patients had hemophagocytic syndrome. The main histopathology was lobular panniculitis with rimming of atypical lymphocytes highlighted by CD3+, CD8+, Beta-F1+, granzyme B+, and Ki-67 (50%-90%). Monoclonal TCR gene rearrangement was found in 50% of patients and upper extremities involvement indicated a poor prognosis. CONCLUSION: The correlation between clinicopathologic and immunophenotypic study is the most helpful method to give a precise diagnosis of SPTL. Rimming of CD8+ atypical lymphocytes highlighted by high Ki-67 index is highly specific for the diagnosis of SPTL.

[Concurrent subcutaneous panniculitis-like T-cell lymphoma and myelodysplastic syndrome with fibrosis].

A 66-year-old male presented with fever and erythema at our hospital, and leukoerythroblastosis, anemia, thrombocytopenia, and multiple low-density lesions in the moderately enlarged spleen were detected. Skin tissue revealed CD8+ T cells with the expression of cytotoxic molecule markers involving fat lobules, and subcutaneous panniculitis T-cell lymphoma (SPTCL) was diagnosed. The bone marrow displayed no infiltration of lymphoid tumor cells, but hyperplasia of granulocytes and megakaryocytes with grade 2 stromal fibrosis. In addition, the bone marrow exhibited diffuse 18F-fluorodeoxyglucose (FDG) accumulation on FDG positron-emission tomography/computed tomography (FDG-PET/CT). Although chemotherapy improved SPTCL, the patient died from leukocytosis with leukoerythroblastosis. We obtained negative results for the JAK2 V617F mutation, and CD34+ cells were elevated in the bone marrow compared with the levels at initial examination. The final diagnosis was concurrent myelodysplastic syndrome (MDS) with fibrosis and SPTCL. This report highlights that it is essential to consider MDS or other myeloproliferative neoplasms (MPN) as possible complications when malignant lymphoma complicates myelofibrosis in the absence of bone marrow infiltration of lymphoma cells. Perhaps, the assessment of clonal markers of MPN and FDG accumulation patterns in the bone marrow by FDG-PET/CT could enable differentiation.

[Clinical Comparative Analysis of Lupus Panniculitis and Subcutaneous Panniculitis-like T-cell Lymphoma].

OBJECTIVE: To explore the similarities and differences in clinical pathological features and gene rearrangement of lupus erythematosus profundus(LEP) and subcutaneous panniculitis-like T-cell lymphoma(SPTL). METHODS: We compared the clinical presentations, histopathology, immunophenotypical features and T-cell receptor (TCR) gene rearrangement findings of 9 cases of LEP and SPTL. RESULTS: For clinical features, most patients of LEP occurred on head and face without systemic symptoms. LEP patients responded well to hydroxycholorquine treatment with good prognosis. Most patients of SPTL tended to lower extremities involvement and accompanied with systemic symptoms, the patients with disseminated lesions or hemophagocytic syndrome(HPS) showed poorer prognosis. For histopathology, LEP patients showed dense inflammatory infiltrate in the dermis consisting predominantly of lymphocytes with less numbers of plasma cells. However, the dermis was spared in SPTL, and rimming of adipocytes and erythrophagocytosis was observed in SPTL. Lymphocytes of LEP expressing CD4+/CD8+, as well as clusters of CD20+. CD138-positive cells and scatter of CD123-positive cells were also observed in LEP. Tumor cells of SPTL were CD4-/CD8+, ßF1+, CD138- and CD123-. The expression of TIA-1 or GrB was more favor in SPTL. Monoclonal T-cell receptor-γ gene rearrangement was found in 89% of SPTL patients while negative for LEP. CONCLUSION: Base on different clinical and pathological features, it is easy to distinguish LEP from SPTL. However, a minority of lesions in LEP localize at subcutaneous tissue, which may turn to immunophenotypical and TCR gene rearrangement test for diagnosis.

Subcutaneous panniculitis-like T-cell lymphoma: Clinical features, therapeutic approach, and outcome in a case series of 16 patients.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma of mature cytotoxic T cells. Initially, patients with SPTCL were treated with doxorubicin-based polychemotherapy. OBJECTIVE: To analyze clinical, biologic, immunophenotypical, molecular, imaging, treatment, and outcome data reflecting the current state of knowledge. METHODS: A retrospective multicenter study of 16 patients with SPTCL that was diagnosed between 1996 and 2016. RESULTS: The female-to-male ratio was 1.7. The median age at diagnosis was 46.5 years. Patients presented with multiple nodular or plaque-like lesions preferentially affecting the legs and/or trunk. Histopathology typically showed a lobular panniculitis with individual adipocytes surrounded by atypical lymphocytes, usually with a CD3+, CD4-, CD8+, CD56-, TIA1 cytotoxic granule associated RNA binding protein 1-positive phenotype and high proliferation rate. SPTCL was associated with autoimmune diseases in 25% of patients, and with the development of hemophagocytic syndrome in 18% of patients. Oral steroids alone or in combination with low-dose methotrexate or cyclosporine A were the most common initial treatment, achieving a complete response in 85% of the treated patients. The median follow-up time was 14 months. The 5-year disease-specific survival rate was 85.7%. LIMITATIONS: This was a retrospective study. CONCLUSIONS: SPTCL has an excellent prognosis. Immunosuppressive agents can be considered for first-line treatment.

Composite cutaneous lymphoma of diffuse large B-cell lymphoma-leg type and subcutaneous panniculitis-like T-cell lymphoma.

Composite lymphoma (CL) is a rare disease defined by the occurrence of two distinct lymphomas within a single tissue at the same time. We present the case of an 89-year-old male with a clinical history of immunoglobulin M monoclonal gammopathy of undetermined significance. The patient presented cutaneous eruption of nodules on the right bottom and arm. An excisional biopsy revealed cutaneous infiltration composed of two components. The first one consisted of large B-cells with CD20+/MUM1+/BCL2+ phenotype whereas the second one involved the subcutaneous fat in a panniculitic manner, and was CD3+/CD8+/granzyme B+/TCRßF1+. The final diagnosis was CL of primary cutaneous large B-cell lymphoma-leg type (PCLBCL-leg type) and subcutaneous panniculitis-like T-cell lymphoma (SPTCL). We report and characterize for the first time coexistent PCLBCL-leg type and SPTCL in a patient.

Subcutaneous Panniculitis-Like T-cell Lymphoma in Dogs: Morphologic and Immunohistochemical Classification.

Canine nonepitheliotropic cutaneous T-cell lymphomas (NECTCL) are poorly characterized. In humans, a number of distinct subtypes of NECTCL have been recognized, including subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Five dogs with subcutaneous T-cell lymphomas histologically similar to SPTCL in humans are herein described. The mean age was 8.5 years (5.5 to 12 years). No breed or sex predilection was identified in this small cohort. Two dogs presented with an acute onset of multiple skin masses and 3 dogs had solitary masses with subsequent development of multiple smaller masses within 0.5 to 2 months post-diagnosis without treatment. Locations, when specified, included shoulder, neck, and ventral abdomen. Two dogs were euthanized following diagnosis and one dog treated with chemotherapy (CCNU) survived 7 months post-diagnosis. Histologically, all cases were characterized by proliferations of either small to intermediate or large sized, CD3-positive T cells that infiltrated the subcutis in a lace-like pattern and frequently rimmed adipocytes. No epitheliotropism was observed, neoplastic cells were often karyorrhectic, and there were regions of extensive necrosis. Heavy infiltrates of histiocytes with prominent phagocytosis masked the lymphoid neoplastic cell population in some sections. A clonal T-cell receptor gamma gene rearrangement was found in 4 of the 5 cases. While SPTCLs typically have a less aggressive clinical course in humans, their biological behavior in dogs remains to be determined. In summary, SPTCL may represent a distinct entity in dogs and needs to be accurately diagnosed to better determine clinical behavior.

Immunohistochemistry reveals an increased proportion of MYC-positive cells in subcutaneous panniculitis-like T-cell lymphoma compared with lupus panniculitis.

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a malignant primary cutaneous T-cell lymphoma that shares significant clinical, histopathologic and immunophenotypic overlap with lupus erythematosus panniculitis (LEP). METHODS: We performed immunohistochemistry for the MYC oncoprotein on 23 cases of SPTCL (1 CD8 negative) and 12 cases of LEP to evaluate if there are quantitative or qualitative differences in protein expression of this marker in these entities. RESULTS: In SPTCL cases, the percentage of all cells that were c-Myc positive ranged from 0.8% to 16%, with a mean of 5.0% and a median of 4.4%. In contrast, in the LEP cases, the percentage of c-Myc-positive cells in the cases ranged from 0.34% to 3.7%, averaged 1.4% and the median was 0.8%. The difference between the means of these 2 diagnostic categories was statistically significant. Fluorescence in situ hybridization performed on 4 cases of SPTCL with a relatively high level of MYC immunohistochemical staining, however, failed to demonstrate evidence of MYC rearrangement or amplification. CONCLUSIONS: Our work demonstrates that MYC expression levels differ between these 2 histologic mimics and suggests that this important oncoprotein may play a role in the pathogenesis of SPTCL.