Cutaneous Anaplastic Large T-cell Lymphoma Research Articles

Primary cutaneous anaplastic large T-cell lymphoma: From a lesion peculiar to its diagnosis

The authors present a clinical case of a 42-year-old woman presented to the Emergency Department for a non-pruritic skin lesion in the left lower limb with a few months of evolution.

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas.

In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

Cutaneous anaplastic large T-cell lymphoma in a cat - case report

Cutaneous anaplastic large T-cell lymphoma in a cat - case report

CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA CD30+ IN ITS EXTENSIVE FORM: ABOUT A CASE

Primary cutaneous anaplastic large T-cell lymphoma CD30+ is a rare cutaneous lymphoma, which belongs to the group of cutaneous T-cell lymphoproliferations CD30+. It is characterized by an excellent prognosis and the treatment is therefore not very aggressive. However, its histological and molecular characteristics have many similarities with lymphoproliferative diseases whose prognosis is completely different. For this reason, it is important to study the patient from the anamnestic and clinical point of view in order to reach a correct diagnosis.

Dermoscopy of Primary Cutaneous Anaplastic Lymphoma Kinase Negative Large T-Cell Lymphoma.

Dermoscopy of Primary Cutaneous Anaplastic Lymphoma Kinase Negative Large T-Cell Lymphoma.

Lack of PRAME Expression in Cutaneous T-Cell Lymphomas.

Cutaneous T-cell lymphomas (CTCLs) are rare tumors with no established markers that can reliably distinguish between benign and malignant lesions. Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is found in many solid and hematologic malignancies. PRAME overexpression typically portends a poor prognosis and lower chemotherapeutic response. To date, no studies have established a role for PRAME in CTCL. An analysis was performed on 47 cases definitively diagnosed as CTCL: 25 cases of mycosis fungoides, 2 of Sezary syndrome, 5 of CD30+ lymphoproliferative disorder, 7 of primary cutaneous anaplastic large T-cell lymphoma, 3 of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, 1 of subcutaneous panniculitis-like T-cell lymphoma, and 4 of angiocentric T-cell lymphoma. PRAME immunohistochemistry was completely negative in all cases. PRAME expression was not found in any CTCL subtypes, suggesting that the pathogenesis of CTCL is not mediated by PRAME. Further study is required to identify biomarkers that might aid in the diagnosis and prognostication of CTCLs.

Recurrent Oncogenic JAK and STAT Alterations in Cutaneous CD30-Positive Lymphoproliferative Disorders

The group of cutaneous CD30-positive lymphoproliferative disorders (LPD) comprises two different entities, namely lymphomatoid papulosis (LyP) and cutaneous anaplastic large T-cell lymphoma (cALCL). LyP constitutes a benign lymphoproliferation with spontaneously regressing papules, whereas cALCL presents with solitary or multiple skin tumors with a low propensity to disseminate. To elucidate the hitherto largely unknown molecular pathogenesis of these entities, we performed comprehensive next-generation sequencing in a well-characterized cohort of 12 patients. Considering the low tumor cell content of LyP, we applied targeted sequencing technologies with a hybrid capture-based DNA library preparation approach and for the identification of fusion transcripts an anchored multiplex PCR enrichment kit. As the major finding, we detected, in 50% of LPD, genetic events that implied a constitutively activated Janus kinase-signal transducer and activator of transcription signaling (JAK-STAT) pathway in these entities. The identified molecular aberrations comprised either pathogenic STAT mutations or oncogenic fusion transcripts comprising effector domains of JAK. With respect to LyP, we report to our knowledge such previously unreported genetic aberrations in this specific entity. The detection of these convergent aberrations within the JAK-STAT signaling pathway deciphers common potential driving mechanisms of lymphomagenesis within LPD being shared between LyP and cALCL. Moreover, the presence of these oncogenic alterations paves the way to develop novel personalized treatment strategies.

Comparative Analysis of Cytokines of Tumor Cell Lines, Malignant and Benign Effusions Around Breast Implants.

More than 700 women have developed an anaplastic large T cell lymphoma (ALCL) surrounding textured surface breast implants, termed breast implant-associated ALCL (BIA-ALCL). Most patients with BIA-ALCL present with an accumulation of fluid (delayed seroma) around the implant. However, benign seromas without malignant cells complicating scar contracture, implant rupture, trauma, infection, and other causes are more common. For proper patient management and to avoid unnecessary surgery, a simple diagnostic test to identify malignant seromas is desirable. The aim of this study was to develop an ancillary test for the diagnosis of malignant seromas and to gain insight into the nature of the malignant cells and their microenvironment. We employed an immunologic assay on only 50 µL of aspirated seroma fluid. The assay measures 13 cytokines simultaneously by flow cytometry. To establish a baseline for clinical studies we measured cytokines secreted by BIA-ALCL and cutaneous ALCL lines. Our study of cell line culture supernatants, and 8 malignant compared with 9 benign seromas indicates that interleukin 9 (IL-9), IL-10, IL-13, IL-22, and/or interferon γ concentrations >1000 pg/mL distinguish malignant seromas from benign seromas. IL-6, known to be a driver of malignant cells, is also elevated in benign seromas and does not distinguish them from malignant seromas. The cytokine assay introduced in this study can be used together with levels of soluble CD30 to identify malignant seromas. Validation of these findings in a larger prospective patient cohort is warranted. The unique pattern of cytokine expression in malignant effusions surrounding breast implants gives further insight into the pathogenesis and cells of origin of BIA-ALCL.

Cutaneous Anaplastic Large T-Cell Lymphoma with Invasion of the Central Nervous System: A Case Report.

Anaplastic large T-cell lymphoma (ALCL) encompasses different clinical entities that can be aggressive or localized. Scalp anaplastic lymphoma kinase (ALK)-negative ALCL is considered a localized lymphoma, and usually extends to the regional lymph nodes; intracranial invasion is rare. A 74-year-old woman was diagnosed with scalp ALK-negative ALCL, but did not exhibit invasion of the lymph nodes. Computed tomography and magnetic resonance imaging revealed intracranial masses with bony erosions. We treated the patient using CHOP chemotherapy and achieved short-term regression of the scalp and intracranial lesions. However, the patients ultimately died of pneumonia during the pancytopenic period. Therefore, caution must be exercised when treating scalp ALK-negative ALCL with intracranial invasion.

A Case of an Unusually Aggressive Cutaneous Anaplastic Large T-Cell Lymphoma in a Young Patient

Primary Cutaneous Anaplastic Large‑cell Lymphoma (PC‑ALCL) is the second most common cutaneous T‑cell Lym‑ phoma. PCALCL is composed of large cells with an anaplastic, pleomorphic, or immunoblastic cytomorphology, and expression of the CD30 antigen by the majority (>75%) of tumor cells .Wehere by report a case of unusually aggressive PC‑ALCL in a young adult.

Primary cutaneous CD30(+) lymphoproliferative disorders.

Primary cutaneous CD30(+) lymphoproliferative disorders are the second most common group of cutaneous T-cell lymphomas (CTCL) and include lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large T-cell lymphoma (cALCL). Both disease entities share overlapping clinical, histopathological, and molecular features, thus representing a spectrum of cutaneous CD30(+) lymphoproliferative disorders. LyP may be distinguished from cALCL by clinicopathological correlation. In some patients, both diseases may coexist at initial diagnosis or develop over the course of the disease. Mycosis fungoides (MF), the most common CTCL, is not considered a primary cutaneous CD30(+) lymphoproliferative disorder, but may occur in some LyP patients. In addition, LyP-like lesions may develop in MF patients. However, this is frequently a manifestation of MF rather than a representation of two different disease entities. Caution also has to be taken in the setting of transformed MF with lesions expressing CD30, as they may be mistaken for either LyP or cALCL, resulting in an inadequate therapeutic approach.

Type D Lymphomatoid Papulosis: An uncommon Variant. A case report and review of the literature

Lymphomatoid papulosis (LyP) is an indolent form of primary cutaneous T-cell lymphoma, currently classified together with primary cutaneous anaplastic large T-cell lymphoma within the spectrum of CD30-positive lymphoproliferative disorders. It is characterized by presenting as a clinically benign but histopathological malignant disease. Clinical features consist in recurrent waxing and waning red papules. Histopathologically, there are 4 variants recognized, Type A or Hystiocitic type, being the most frecuent of all, Type B or Mycosis fungoides-like, Type C or Anaplastic large-cell lymphoma-like and Type D, the most recently described and uncommon variant with features similar to Cutaneous Aggressive CD8-Positive Cytotoxic T-Cell Lymphoma. We present a case of a 22-year-old female with multiple papules and nodules in trunk and limbs that after histopathological and immunochemical examination was compatible with Type D LyP. It is important to report this case, as a perfect example of an uncommon variant of LyP, with emphasis in its typical clinical, histopathological and inmunohistochemical findings and review of the literature.

Phenotypic Variability in Primary Cutaneous Anaplastic Large T-cell Lymphoma

Primary cutaneous anaplastic large T-cell lymphoma (pcALCL) is a well-defined entity characterized by neoplastic cells expressing CD30, CD2, CD3, CD4, and CD5. Cases with different phenotype have been reported, including variable loss of CD2, CD3, and CD5, and expression of cytotoxic phenotype (CD8⁺) and/or of cytotoxic proteins. Aberrant phenotypes represent a diagnostic pitfall and may be the cause of misdiagnoses. We reviewed 35 cases of pcALCL (M:F = 19:16; mean age, 50.8 years; range, 14-92 years), to better characterize the immunophenotypic spectrum of the disease. Twelve cases (34%) had a T-helper phenotype (CD4⁺/CD8⁻), and TIA-1 was positive in 5 of 8 stained cases. Six cases (18%) had a T-cytotoxic phenotype (CD4⁻/CD8⁺) and were also positive for TIA-1. Positivity for both CD4 and CD8 was observed in 7 cases (20%), 4 of which were stained for TIA-1 and found to be positive, whereas both CD4 and CD8 were negative in 9 cases (26%, only 1/8 tested cases being TIA-1 positive). CD2 was positive in 21 of 27 tested cases (78%), CD3 in 21 of 34 cases (62%), and CD5 in 15 of 31 cases (48%). Interestingly, 11 cases (31%) showed a profoundly aberrant phenotype lacking simultaneously several T-cell markers. Our data allow a better characterization of pcALCL with aberrant phenotypes, showing the remarkable variability in expression of different markers.

Lymphomatoid Papulosis Type D or an Aggressive Epidermotropic CD8+ Cytotoxic T-cell Lymphoma?

Lymphomatoid papulosis (LyP) is defined as a chronic, recurrent, self-healing eruption of papules and small nodules, characterised by a waxing and waning course, and by histological features of a CD30+ cutaneous T-cell lymphoma CTCL. Classically, 3 histologic subtypes of LyP are recognised: Type A (histiocytic), type B (MFlike) and type C (anaplastic like CTCL) (1). Together with primary cutaneous anaplastic large Tcell lymphoma, LyP is classified as a part of the primary cutaneous CD30+ lymphoproliferative disorders in the WHO-EORTC classification of cutaneous lymphomas (2). Recently, a new histologic LyP variant termed type D, simulating an aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, but with the typical clinical presentation and indolent course of LyP, has been described (3–5). We describe a new case of this variant, of which diagnosis is particularly challenging and emphasises the importance of cross-disciplinary collaboration.

Cutaneous Intravascular Anaplastic Large T-Cell Lymphoma

Intravascular lymphoma (IVL) is a rare subtype of extranodal lymphoma. In the 2008 WHO classification of tumors of the hematopoietic and lymphoid tissues intravascular large B-cell lymphoma is included as a distinct entity. IVL of T-cell type is not included as a diagnostic category and is only mentioned in passing by Nakamura et al. as "a different entity" in their discussion of intravascular large B-cell lymphoma. T-cell IVL is rare, the majority of cases being of natural killer/T-cell phenotype. Exceptionally rare is primary cutaneous intravascular anaplastic large T-cell lymphoma. We present such a case in an otherwise well 39-year-old female having disease limited to the skin established after detailed staging investigations. This is only the third such case described in the literature. We report the clinicopathological features of this case and also review previously documented cases of cutaneous intravascular anaplastic large cell lymphoma.

Human herpesvirus 8‐associated lymphoma mimicking cutaneous anaplastic large T‐cell lymphoma in a patient with human immunodeficiency virus infection

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.

A Case of ALK+ Anaplastic Large T Cell Lymphoma (ALCL) with Lymphomatous Meningitis

Abstract 5226 Background:Anaplastic large T cell lymphoma may present with indolent cutaneous T cell infiltration, progressing to more aggressive skin disease and systemic involvement. In adults lymphomatous meningitis is very rare complication. Case Report:A 62 year old Jamaican woman had been diagnosed with biopsy proven psoriasis when 42 years of age. Ustekinumab had been initiated without effect two months prior to her presentation to us. A new cutaneous nodule on her left neck was then found, shave biopsy of which revealed psoriasiform dermatitis with epidermotropism, suspicious for early patch stage mycosis fungoides. The lesion was CD30+, suggestive of ALCL and was positive for ALK. Positron emission tomography revealed an SUV of 6.0 in the neck mass, but lymph nodes in all regions had an SUV of <2.3. Axillary lymph node biopsy, bone marrow biopsy and flow cytometry were negative. Local electron beam radiation was administered to the left supraclavicular space with complete resolution of the cutaneous nodule. About 2 months following completion of radiation therapy she noted anorexia, 30 lb weight loss, night sweats and left hip pain. Physical examination revealed a sick woman, with whole body scaling red-brown macules and plaques. CBC was normal except for Hb of 10 g/dl, platelets 453,000/dl. Hepatic and renal function studies were normal. ESR was 84 mm/hr, lactic dehydrogenase 670 IU (reference range 300–600 IU) and calcium 15.1 mg/dl. HTLV1, HIV, hepatitis panel and anti-nuclear antibody serologies were negative. Computer automated tomography of the pelvis demonstrated 6×2×8 cm soft tissue mass on the sacrum invading left sacro-iliac joint and ilium. Biopsy revealed ALCL, positive for CD43, CD2dim, CD7dim, CD30, and nuclear and cytoplasmic ALK1, while negative for CD43, 3, 4, 5, 8, 19,20, 34, 138, PAX5, AE1/AE3, Cam5, S100 and TdT. The mass was irradiated with alleviation of pain, but cutaneous nodules progressively appeared and continuous fever developed with negative blood cultures. There was increasing confusion, blurred vision and bilateral abducens paralysis. Magnetic resonance imaging of the head and spine revealed dural enhancement and multiple extra- and intercranial interosseous masses, one of which involved the posterior sella turcica. Cyclophosphamide, doxorubicin, vincristine and prednisone were initiated; lumbar puncture was refused. Within 2 days after treatment initiation the cutaneous nodules disappeared, fever subsided, the left abducens palsy resolved completely while the right improved. Conclusion:Our patient's long standing indolent skin disease abruptly progressed to cutaneous and systemic ALCL, with evidence of lymphomatous meningitis. The response of her abducens palsies and other CNS findings to systemic chemotherapy alone suggests that her meningeal involvement may have arisen from that of adjacent bones. Involvement of CNS in ALK positive systemic anaplastic large cell lymphoma is rare and reported in mainly pediatric cases. Disclosures:No relevant conflicts of interest to declare.

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).

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.

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