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1
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Goodlad JR. Updated Classification of Cutaneous Lymphoma. Adv Anat Pathol 2025; 32:239-255. [PMID: 40066774 DOI: 10.1097/pap.0000000000000487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
The International Consensus Classification (ICC) of myeloid and lymphoid neoplasms follows the precedent set in the Revised European-American lymphoma classification for modern lymphoma classifications by defining specific diseases on the basis of all the available morphologic, immunophenotypic, genetic, and clinical findings. Primary cutaneous lymphomas exhibit a broad range of clinical behavior ranging from lesions which spontaneously regress to those which run an aggressive, often fatal course. Accurate separation of entities is therefore essential for prognostication and to ensure appropriate treatment is administered. However, despite marked differences in clinical course, many subtypes of primary cutaneous lymphoma exhibit remarkably similar, often overlapping, and sometimes indistinguishable pathologic features. While molecular analysis has furthered our understanding of some of these disease entities, it does not yet facilitate robust distinction. Thus, clinical correlation retains a central role in both the diagnosis and classification of primary cutaneous lymphoma. This review aims to draw attention to problem areas in differential diagnosis and hopefully offer some practical suggestions for resolving difficult cases. It will also highlight recent advances in the field and discuss how they reinforce the current classification system and how they might impact of future classifications and treatment strategies.
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Affiliation(s)
- John R Goodlad
- Department of Pathology, NHS Greater Glasgow and Clyde, Glasgow, Scotland
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2
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Zhang Y, Yescas JA, Tefft K, Ng S, Qiu K, Wang EB, Akhtar S, Walker A, Welborn M, Zaiac M, Guitart J, Qureshi AM, Kim YH, Khodadoust MS, Issa NT, Choi J. Addiction of primary cutaneous γδ T cell lymphomas to JAK/STAT signaling. J Clin Invest 2025; 135:e180417. [PMID: 40231467 PMCID: PMC11996904 DOI: 10.1172/jci180417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/16/2025] Open
Affiliation(s)
- Yue Zhang
- Department of Dermatology, Northwestern University, Chicago, Illinois, USA
- Department of Dermatology, Indiana University, Indianapolis, Indiana, USA
| | - Julia A. Yescas
- Department of Dermatology, Northwestern University, Chicago, Illinois, USA
| | - Kristy Tefft
- Department of Dermatology, Northwestern University, Chicago, Illinois, USA
| | - Spencer Ng
- Department of Dermatology, Northwestern University, Chicago, Illinois, USA
- Division of Dermatology, Department of Medicine, and Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Kevin Qiu
- Department of Dermatology, Northwestern University, Chicago, Illinois, USA
| | - Erica B. Wang
- Department of Dermatology, Stanford University, Palo Alto, California, USA
| | - Shifa Akhtar
- Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA
| | - Addie Walker
- Department of Dermatology, University of Florida, Gainesville, Florida, USA
| | - Macartney Welborn
- Department of Dermatology, University of Florida, Gainesville, Florida, USA
| | - Martin Zaiac
- Department of Dermatology, Florida International University, Miami, Florida, USA
| | - Joan Guitart
- Department of Dermatology, Northwestern University, Chicago, Illinois, USA
| | | | - Youn H. Kim
- Department of Dermatology, Stanford University, Palo Alto, California, USA
| | - Michael S. Khodadoust
- Department of Dermatology, Stanford University, Palo Alto, California, USA
- Division of Oncology, Stanford Medicine, Stanford, California, USA
| | - Naiem T. Issa
- Department of Dermatology, Cleveland Clinic, Cleveland, OH, USA
| | - Jaehyuk Choi
- Department of Dermatology, Northwestern University, Chicago, Illinois, USA
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3
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Erem AS, Kempf W, Mitteldorf C, Pulitzer M, Torres-Cabala CA, Pileri S, Pinilla SMR, Feldman AL, Gru AA. Primary Cutaneous Anaplastic Large Cell Lymphoma With TCR-γδ Expression: A Case Series of Eleven Patients of a Rare Immunophenotypic Variant. J Cutan Pathol 2025. [PMID: 40202044 DOI: 10.1111/cup.14809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2024] [Revised: 03/04/2025] [Accepted: 03/22/2025] [Indexed: 04/10/2025]
Abstract
BACKGROUND Primary cutaneous anaplastic large cell lymphoma (pcALCL) and lymphomatoid papulosis (LyP) are indolent CD30-positive lymphoproliferative disorders that rarely express TCR-γδ. However, primary cutaneous gamma-delta T-cell lymphoma (pcGDTCL), characterized by TCR-γδ expression on neoplastic cells, is a rare, aggressive cutaneous T-cell lymphoma with a poor prognosis. Accurate differentiation is essential due to distinct clinical behavior and treatment. METHODS We identified 11 TCR-γδ-positive pcALCL cases from internal and consultation files, verified by two cutaneous lymphoma experts, with clinicopathologic data recorded. RESULTS The median age was 68 years (range 38-95). Most cases presented as a single dermal lesion on the upper extremities. All were ALK-negative, CD30-positive (> 90% tumor cells), TCR-βF1-negative, and diffusely TCR-γδ-positive. CD4-/CD8- (54.5%) and CD4+/CD8- (45.5%) immunophenotypes were observed. CD2 (63.6%) and CD3 (54.5%) were the most common T-cell antigens. Ulceration, inflammation (both 45.5%), and necrosis (36.4%) were frequent. Angiotropism, angiocentricity, and myxoid stroma appeared in one case; epidermotropism in two. Four of ten tested were DUSP22-rearranged, and TP63 was negative in all eight tested. CONCLUSIONS Most ALK-negative TCR-γδ-positive pcALCL were CD4-/CD8-, followed by CD4+/CD8-. DUSP22 rearrangement occurred in 40% of cases, similar to reports in typical pcALCL. Its prognosis and the role of DUSP22 are yet to be clarified.
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Affiliation(s)
- Anna Sarah Erem
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Werner Kempf
- Kempf Und Pfaltz Histologische Diagnostik, University of Zurich, Department of Dermatology, Zurich, Switzerland
| | - Christina Mitteldorf
- Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, Germany
| | - Melissa Pulitzer
- Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, New York, USA
| | - Carlos A Torres-Cabala
- Department of Pathology & Dermatology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Stefano Pileri
- Department of Pathology, Hematopathology Division, European Institute of Oncology IRCCS, Milan, Italy
| | | | - Andrew L Feldman
- Mayo Clinic, Laboratory Medicine and Pathology, Rochester, Minnesota, USA
| | - Alejandro A Gru
- New York Presbyterian Hospital, Vagelos College of Physician and Surgeons of Columbia University, New York, New York, USA
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4
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Stuver R, Horwitz SM. Through thick and thin: confronting the aggressive cutaneous T-cell lymphomas. HEMATOLOGY. AMERICAN SOCIETY OF HEMATOLOGY. EDUCATION PROGRAM 2024; 2024:62-68. [PMID: 39644025 PMCID: PMC11665522 DOI: 10.1182/hematology.2024000529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/09/2024]
Abstract
The cutaneous T-cell lymphomas (CTCLs) comprise a diverse set of diseases with equally diverse presentations ranging from asymptomatic solitary lesions to highly aggressive diseases with propensity for visceral spread. The more aggressive CTCLs, which herein we consider as certain cases of advanced-stage mycosis fungoides/Sézary syndrome (MF/SS), primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (PCAETCL), and primary cutaneous gamma delta T-cell lymphoma (PCGDTCL), require systemic therapy. Over the last 5 years, treatment options for MF/SS have expanded with biological insights leading to new therapeutic options and increasingly unique management strategies. An enhanced appreciation of the compartmental efficacy of these agents (skin, blood, lymph nodes, visceral organs) is incorporated in current management strategies in MF/SS. In addition, approaches that combine modalities in attempts to increase depth and durability of responses across multiple compartments are being trialed. In contrast to MF/SS, PCAETCL and PCGDTCL remain diseases with few prospective studies to guide treatment. However, recent genomic insights on these diseases, such as the presence of JAK2 fusions in PCAETCL and cell of origin findings in PCGDTCL, have created options for new biomarker-driven strategies.
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Affiliation(s)
- Robert Stuver
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Steven M Horwitz
- Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
- Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY
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5
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Azimpouran M, Bui CM, Balzer B, Kitahara S. Rapidly Progressive Primary Cutaneous Gamma Delta T-Cell Lymphoma With FYN Gene Alteration. Am J Dermatopathol 2024; 46:e120-e123. [PMID: 39412302 DOI: 10.1097/dad.0000000000002856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2024]
Abstract
ABSTRACT Primary cutaneous gamma delta T-cell lymphoma (PCGDTCL) is a rare type of non-Hodgkin lymphoma accounting for <1% of primary cutaneous T-cell lymphomas. The exact cause of PCGDTCL is not known, however, it is thought that chronic antigen exposure in the skin may lead to immune dysregulation at the site, resulting in abnormal proliferation of mature, post-thymic cytotoxic gamma delta T cells. Mutations are the most common genetic alteration seen in PCGDTCL, while structural abnormalities such as gene fusions are not common. We report a case of PCGDTCL with atypical immunophenotypic features, including expression of CD5 with lack of cytotoxic marker expression, and a structural alteration leading to FYN deletion at exon 8. Recently, it was described that a deletion of the area between FYN exon 8 and TRAF3IP2 intron 2 results in a novel FYN::TRAF3IP2 fusion in peripheral T-cell lymphoma, not otherwise specified. We describe our patient's clinical course, differential diagnosis, and potential implications of FYN deletion on disease pathogenesis. To our knowledge, this is the first report of an FYN structural alteration to be described in PCGDTCL.
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Affiliation(s)
- Mahzad Azimpouran
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA
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6
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Fisher CM, Capen SF, Bandino JP, Holmes AR, Lee CM. Prominent tissue hemophagocytic lymphohistiocytosis obscuring primary cutaneous gamma/delta (γδ) T-cell lymphoma. J Cutan Pathol 2024; 51:959-963. [PMID: 39295229 DOI: 10.1111/cup.14718] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 08/14/2024] [Accepted: 09/01/2024] [Indexed: 09/21/2024]
Abstract
Primary cutaneous gamma/delta (γδ) T-cell lymphoma (PCGDTCL) is a rare, aggressive malignant neoplasm of γδ T lymphocytes arising within the skin and subcutis. We present a challenging case of PCGDTCL diagnosed in a 35-year-old male soldier who presented with constitutional symptoms, pancytopenia, hemophagocytic lymphohistiocytosis (HLH), disseminated lymphadenopathy, and cutaneous lesions on his extremities and back following a deployment to Iraq and Syria. Histopathologic evaluation of an excisional biopsy showed that PCGDTCL can be focal, localized to the subcutaneous adipose tissue, and obscured by predominant HLH in the surrounding tissues. Pathologists should recognize that the diagnosis of PCGDTCL may be confounded by florid HLH and require multiple biopsies and a comprehensive immunohistochemical panel.
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Affiliation(s)
- Craig M Fisher
- Department of Dermatology, Wilford Hall Ambulatory Surgical Center, JBSA Lackland, Texas, USA
| | - Steven F Capen
- Department of Pathology and Area Laboratory Services, Brooke Army Medical Center, JBSA-Fort Sam Houston, Texas, USA
| | - Justin P Bandino
- Department of Dermatology, Wilford Hall Ambulatory Surgical Center, JBSA Lackland, Texas, USA
| | - Allen R Holmes
- Department of Pathology and Area Laboratory Services, Brooke Army Medical Center, JBSA-Fort Sam Houston, Texas, USA
| | - Christine M Lee
- Department of Pathology and Area Laboratory Services, Brooke Army Medical Center, JBSA-Fort Sam Houston, Texas, USA
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7
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Swallow MA, Micevic G, Zhou A, Carlson KR, Foss FM, Girardi M. Clinical and Histologic Variants of CD8+ Cutaneous T-Cell Lymphomas. Cancers (Basel) 2024; 16:3087. [PMID: 39272944 PMCID: PMC11394026 DOI: 10.3390/cancers16173087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/28/2024] [Accepted: 09/03/2024] [Indexed: 09/15/2024] Open
Abstract
Although the vast majority of CTCL subtypes are of the CD4+ T-helper cell differentiation phenotype, there is a spectrum of CD8+ variants that manifest wide-ranging clinical, histologic, and phenotypic features that inform the classification of the disease. CD8, like CD4, and cytotoxic molecules (including TIA and granzyme) are readily detectable via IHC staining of tissue and, when expressed on the phenotypically abnormal T-cell population, can help distinguish specific CTCL subtypes. Nonetheless, given that the histopathologic differential for CD8+ lymphoproliferative disorders and lymphomas may range from very indolent lymphomatoid papulosis (LyP) to aggressive entities like CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (AECTCL), CD8 and/or cytotoxic molecule expression alone is insufficient for diagnosis and is not in itself an indicator of prognosis. We present a review of CTCL subtypes that can demonstrate CD8 positivity: CD8+ mycosis fungoides (MF), LyP type D, subcutaneous panniculitis-like T-cell lymphoma (SPTCL), primary cutaneous gamma/delta T-cell lymphoma (PCGDTL), CD8+ AECTCL, and acral CD8+ T-cell lymphoproliferative disorder (acral CD8+ TCLPD). These diseases may have different clinical manifestations and distinctive treatment algorithms. Due to the rare nature of these diseases, it is imperative to integrate clinical, histologic, and immunohistochemical findings to determine an accurate diagnosis and an appropriate treatment plan.
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Affiliation(s)
| | - Goran Micevic
- Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA; (G.M.); (A.Z.); (K.R.C.)
| | - Amanda Zhou
- Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA; (G.M.); (A.Z.); (K.R.C.)
| | - Kacie R. Carlson
- Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA; (G.M.); (A.Z.); (K.R.C.)
| | - Francine M. Foss
- Hematology and Stem Cell Transplantation, Yale School of Medicine, New Haven, CT 06510, USA;
| | - Michael Girardi
- Department of Dermatology, Yale School of Medicine, New Haven, CT 06510, USA; (G.M.); (A.Z.); (K.R.C.)
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8
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Rogers A, MacGillivary ML, Hull PR, Selegean S, Cerroni L. A prominent cutaneous eruption as a harbinger for aggressive systemic disease: Gamma-delta T-cell lymphoma. JAAD Case Rep 2024; 51:10-13. [PMID: 39345283 PMCID: PMC11437391 DOI: 10.1016/j.jdcr.2024.06.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/01/2024] Open
Affiliation(s)
- Alexandra Rogers
- Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Michael L. MacGillivary
- Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Peter R. Hull
- Division of Clinical Dermatology and Cutaneous Science, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Sorin Selegean
- Department of Pathology and Laboratory Medicine, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada
| | - Lorenzo Cerroni
- Department of Dermatology, Medical University of Graz, Graz, Austria
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9
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Nielsen PR, Schejbel L, Josefsson PL, Skov L, Nielsen SL. Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation. Open Life Sci 2024; 19:20220925. [PMID: 39091627 PMCID: PMC11292030 DOI: 10.1515/biol-2022-0925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 06/12/2024] [Accepted: 06/19/2024] [Indexed: 08/04/2024] Open
Abstract
Mycosis fungoides is the most frequent subtype of primary cutaneous T-cell lymphomas. The diagnosis is based on a thorough clinic-pathologic correlation, which can, especially in early-stage disease, be challenging due to similarities with several benign skin disorders such as psoriasis and atopic dermatitis. Here, we present a case of an 81-year-old man with a 20-year-long medical history of skin problems treated as psoriasis with limited effect. Since December 2021, the patient experienced worsening of his skin symptoms with rapidly growing tumors and widespread patches and plaques. Positron emission tomography/computed tomography evaluation revealed markedly metabolic activity related to the skin tumors and increased FDG uptake in several retroperitoneal lymph nodes. Histological assessment of skin biopsies demonstrated a highly proliferative T-cell lymphoma with a γ/δ+ and CD8+ cytotoxic phenotype. The morphology of the tumor cells appeared blastic with an abnormal immunephenotype CD3+, CD2-, CD5dim, CD4-, CD8+, CD56-, and CD30-. Next-generation sequencing detected a likely pathogenic SOCS1 mutation with an allele frequency of 72% as well as a STAT3 variant of unknown significance. This case highlights the diagnostic complexity of an indolent skin lymphoma evolving into an aggressive cytotoxic lymphoma.
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Affiliation(s)
- Pia Rude Nielsen
- Department of Pathology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 73, Staircase 7, floor 4 (L5), 2730 Herlev, Copenhagen, Denmark
| | - Lone Schejbel
- Department of Pathology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
| | - Pär Lars Josefsson
- Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Lone Skov
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Signe Ledou Nielsen
- Department of Pathology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark
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10
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Lee ML, Lim PN, Colgan J, Goodlad JR. Subcutaneous panniculitis-like T-cell lymphoma and lupus erythematosus profundus: a diagnostic dilemma. BMJ Case Rep 2024; 17:e255592. [PMID: 38925673 DOI: 10.1136/bcr-2023-255592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/28/2024] Open
Abstract
A white Caucasian woman in her 30s presented with an indurated lesion on her right upper arm. Panniculitis was clinically suspected. Antinuclear antibody testing was positive but incisional biopsy showed subcutaneous panniculitis-like T-cell lymphoma (SPTCL), although with some unusual features more in keeping with lupus. Initial treatment was with oral prednisolone and radiotherapy but with only partial response. A second biopsy was taken from an area of presumed residual disease. This displayed histological features that were much more typical of lupus erythematosus profundus (LEP) but with tiny foci suggesting concomitant microscopic areas of SPTCL. Immunofluorescence for IgM was positive. This case highlights the rare occurrence of a patient with overlapping clinical and pathological features of SCPTL and LEP. It emphasises the need for close clinicopathological correlation in the workup of patients with suspected panniculitis and the importance of careful pathological examination for features of both diseases.
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11
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Adams PE, Ehyayee V, Ahmed A. A Case of CD4 + T-Cell Lymphoma With Gamma-Delta Phenotype, Incidentally Manifesting in a Wound Debridement Sample. Am J Dermatopathol 2024; 46:383-385. [PMID: 38574061 DOI: 10.1097/dad.0000000000002695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
ABSTRACT We report an 85-year-old male patient with a medical history significant for psoriasis who presented with a thigh wound that expanded slowly over the course of 9 months. The patient was previously treated with amputation of hand digits for osteomyelitis. Histologic examination of the tissue sample revealed a broad ulceration with large areas of necrosis extending into the subcutis. The edge of the specimen also revealed a nodular lymphoid infiltrate in the subcutaneous adipose tissue composed of atypical cells. These cells were only positive for CD3, CD4, and T-cell receptor (TCR) delta stains . The Ki-67 proliferation index of tumor cells was about 70%. The tumor cells were negative for CD30, CD8, CD56, TCR BF1, granzyme, TIA1, CD123, and Epstein-Barr encoding region (EBER)-ish stains. A diagnosis of gamma-delta T-cell lymphoma was made. Further imaging showed regional lymphadenopathy. The patient was started on mini-CHOP and filgrastim; however, the patient died within 1 month after the diagnosis. This is an interesting case of gamma-delta T-cell lymphoma that was incidentally diagnosed on a chronic wound. In addition, it showed a CD4 + , CD8 - phenotype that is exceedingly rare for T-cell lymphomas with gamma-delta phenotype.
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Affiliation(s)
| | - Vida Ehyayee
- Department of Pathology, Rush University Medical Center, Chicago, IL
| | - Aadil Ahmed
- Dermatopathology Section, Illinois Dermatology Institute, Park Ridge, IL; and
- Department of Pathology, Loyola Stritch School of Medicine, Maywood, IL 60153
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12
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Alberti-Violetti S, Berti E. Update on primary cutaneous T-cell lymphomas rare subtypes. Dermatol Reports 2024; 16:9961. [PMID: 39295878 PMCID: PMC11406209 DOI: 10.4081/dr.2024.9961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 02/15/2024] [Indexed: 09/21/2024] Open
Abstract
Rare subtypes of cutaneous T-cell lymphomas (CTCL) include four entities, primary cutaneous γδ T-cell lymphoma, primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, and primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders, primary cutaneous acral CD8+ T-cell lymphoma, which were previously considered provisional and are now included in the new 5th World Health Organization classification of hematolymphoid tumors as distinct entities. An updated summary of the clinical, histological, and genomic characteristics of these uncommon CTCL subtypes is given in this review, with a focus on the growing body of knowledge regarding their classification and possible treatment strategies.
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Affiliation(s)
- Silvia Alberti-Violetti
- Dermatology Unit, IRCCS Ca'Granda - Ospedale Maggiore Policlinico, Milan
- Department of Pathophysiology and Transplantation, University of Milan
| | - Emilio Berti
- Inter-Hospital Pathology Division, IRCCS Multimedica, Milan, Italy
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13
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Cheng J, Toner K, Habeshian K, Cardis M, Cowen EW, Bollard CM, Wistinghausen B, Kirkorian AY. Pediatric cutaneous T-cell neoplasm and mimics with gamma-delta expression: Not always aggressive. Pediatr Blood Cancer 2024; 71:e30837. [PMID: 38177069 DOI: 10.1002/pbc.30837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 12/06/2023] [Accepted: 12/18/2023] [Indexed: 01/06/2024]
Abstract
Pediatric cutaneous T-cell lymphoma with γδ immunophenotype is extremely rare. Only a few cases of γδ T-cell neoplasm have been reported in the literature, and therefore little is known whether γδ T-cell neoplasms in children are distinct from their adult counterparts with respect to the clinicopathological presentation, behavior, and prognosis. In this study, we demonstrate three unique pediatric cutaneous T-cell neoplasm and mimics with increased γδ T cells. All cases showed an indolent clinical course.
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Affiliation(s)
- Jinjun Cheng
- Department of Pathology and Laboratory Medicine, Children's National Hospital, Washington, District of Columbia, USA
- Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia, USA
- George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
| | - Keri Toner
- Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia, USA
- George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
- Center for Cancer and Blood Disorders, Children's National Hospital, Washington, District of Columbia, USA
| | - Kaiane Habeshian
- George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
- Division of Dermatology, Children's National Hospital, Washington, District of Columbia, USA
| | - Michael Cardis
- Department of Dermatology, Medstar-Georgetown University School of Medicine, Washington, District of Columbia, USA
| | - Edward W Cowen
- Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, Maryland, USA
| | - Catherine M Bollard
- Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia, USA
- George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
- Center for Cancer and Blood Disorders, Children's National Hospital, Washington, District of Columbia, USA
| | - Birte Wistinghausen
- Center for Cancer and Immunology Research, Children's National Hospital, Washington, District of Columbia, USA
- George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
- Center for Cancer and Blood Disorders, Children's National Hospital, Washington, District of Columbia, USA
| | - A Yasmine Kirkorian
- George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
- Division of Dermatology, Children's National Hospital, Washington, District of Columbia, USA
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14
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Torre-Gomar FJ, Gimeno-Castillo J, Sagasta-Lacalle A, Arrue-Michelena I. Primary Cutaneous Gamma/Delta T-cell Lymphoma Simulating Lupus Erythematosus Panniculitis: What do we know about this aggressive mimicker? Sultan Qaboos Univ Med J 2024; 24:141-142. [PMID: 38434474 PMCID: PMC10906768 DOI: 10.18295/squmj.2.2024.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 12/13/2023] [Accepted: 12/19/2023] [Indexed: 03/05/2024] Open
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15
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Sudo M, Fujimoto K. Diffusive mediator feedbacks control the health-to-disease transition of skin inflammation. PLoS Comput Biol 2024; 20:e1011693. [PMID: 38236792 PMCID: PMC10796066 DOI: 10.1371/journal.pcbi.1011693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 11/16/2023] [Indexed: 01/22/2024] Open
Abstract
The spatiotemporal dynamics of inflammation provide vital insights into the understanding of skin inflammation. Skin inflammation primarily depends on the regulatory feedback between pro- and anti-inflammatory mediators. Healthy skin exhibits fading erythema. In contrast, diseased skin exhibits expanding erythema with diverse patterns, which are clinically classified into five types: circular, annular, arcuate, gyrate, and polycyclic. Inflammatory diseases with expanding erythema are speculated to result from the overproduction of pro-inflammatory mediators. However, the mechanism by which feedback selectively drives the transition from a healthy fading erythema to each of the five types of diseased expanding erythema remains unclear. This study theoretically elucidates the imbalanced production between pro- and anti-inflammatory mediators and prospective treatment strategies for each expanding pattern. Our literature survey showed that eleven diseases exhibit some of the five expanding erythema, thereby suggesting a common spatiotemporal regulation underlying different patterns and diseases. Accordingly, a reaction-diffusion model incorporating mediator feedback reproduced the five observed types of diseased expanding and healthy fading patterns. Importantly, the fading pattern transitioned to the arcuate, gyrate, and polycyclic patterns when the productions of anti-inflammatory and pro-inflammatory mediators were lower and higher, respectively than in the healthy condition. Further depletion of anti-inflammatory mediators caused a circular pattern, whereas further overproduction of pro-inflammatory mediators caused an annular pattern. Mechanistically, the bistability due to stabilization of the diseased state exhibits circular and annular patterns, whereas the excitability exhibits the gyrate, polycyclic, arcuate, and fading patterns as the threshold of pro-inflammatory mediator concentration relative to the healthy state increases. These dynamic regulations of diffusive mediator feedback provide effective treatment strategies for mediator production wherein skins recover from each expanding pattern toward a fading pattern. Thus, these strategies can estimate disease severity and risk based on erythema patterns, paving the way for developing noninvasive and personalized treatments for inflammatory skin diseases.
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Affiliation(s)
- Maki Sudo
- Department of Biological Sciences, Osaka University, Machikaneyama-cho, Toyonaka, Japan
- Program of Mathematical and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, Kagamiyama, Higashi-Hiroshima, Japan
| | - Koichi Fujimoto
- Department of Biological Sciences, Osaka University, Machikaneyama-cho, Toyonaka, Japan
- Program of Mathematical and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, Kagamiyama, Higashi-Hiroshima, Japan
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16
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Ashok Kumar P, Sivapiragasam A, Wang D, Huang D, Gentile T. Descriptive Analysis and Factors Influencing Survival in Patients With Primary Cutaneous Gamma-Delta T Cell Lymphoma. A Retrospective National Cancer Database Study. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2023; 23:897-904. [PMID: 37690902 DOI: 10.1016/j.clml.2023.08.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 08/16/2023] [Accepted: 08/18/2023] [Indexed: 09/12/2023]
Abstract
BACKGROUND Gamma delta T cells gives rise to a rare malignancy called Primary cutaneous Gamma-Delta T cell lymphoma (PCGDTCL). METHODS From the National Cancer Database (NCDB), 110 (0.015%) patients with PCGDTCL were identified. RESULTS Males aged >60 years were the commonest cohort. Caucasian race was the most common (Caucasian: 79.09%, African American:16.36%). Most patients were diagnosed at stage 1 (52.33%), followed by stage 4 (30.23%). On analyzing income categories, <$48,000 group had 48.15% stage 4 (13/27) and 40.74% (11/27) stage 1. Overall survival (OS) of the study group at 3 years by Kaplan-Meier (KM) analysis was 46.6%. African American race (37.5%), income of <$48,000 (27.6%) and government insurance (38.8%) had lower survival rates in KM analysis. In the adjusted hazard ratio (HR) analysis, only age <=40 years compared to >60 years (0.165 [0.036, 0.768], P= .0217) reached significance. Although the group that did not receive any chemotherapy or radiation seemed to have a better survival by KM analysis at 74.3% at 3 years, significance was not seen in the adjusted HR estimates and majority of the patients in this group were stage 1. This group may have received topical treatments which may have not been captured in NCDB. Adjusted analysis also revealed chemoradiation to have a lower mortality risk compared to chemotherapy alone (0.229 [0.079, 0.670], P = .0071), suggesting that aggressive strategies may be required for management when needed. CONCLUSION Socioeconomic disparities significantly impact access to healthcare and are of particular importance in rare lymphomas.
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Affiliation(s)
- Prashanth Ashok Kumar
- Division of Hematology-Oncology, Upstate Cancer Center, Upstate University Hospital, Syracuse, NY.
| | - Abirami Sivapiragasam
- Division of Hematology-Oncology, Upstate Cancer Center, Upstate University Hospital, Syracuse, NY
| | - Dongliang Wang
- Department of Public Health and Preventive Medicine, Upstate University Hospital, Syracuse, NY
| | - Danning Huang
- Department of Public Health and Preventive Medicine, Upstate University Hospital, Syracuse, NY
| | - Teresa Gentile
- Division of Hematology-Oncology, Upstate Cancer Center, Upstate University Hospital, Syracuse, NY
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17
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Bhansali RS, Barta SK. SOHO State of the Art Updates and Next Questions | Challenging Cases in Rare T-Cell Lymphomas. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2023; 23:642-650. [PMID: 37302955 PMCID: PMC10524462 DOI: 10.1016/j.clml.2023.05.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 05/19/2023] [Indexed: 06/13/2023]
Abstract
Mature T- and NK-cell neoplasms (MTNKN) collectively represent a rare disorder, representing less than 15% of all non-Hodgkin lymphoma (NHL) cases and qualifying for orphan disease designation by the U.S. Food and Drug Administration (FDA). These consist of 9 families in the fifth revised WHO classification of lymphoid neoplasms, which are made up of over 30 disease subtypes, underscoring the heterogeneity of clinical features, molecular biology, and genetics across this disease group. Moreover, the 5 most common subtypes (peripheral T-cell lymphoma, not otherwise specified; nodal TFH cell lymphoma, angioimmunoblastic type; extranodal NK-cell/T-cell lymphoma; adult T-cell leukemia/lymphoma; and ALK-positive or -negative anaplastic large cell lymphoma) comprise over 75% of MTNKN cases, so other subtypes are exceedingly rare in the context of all NHL diagnoses and consequently often lack consensus on best practices in diagnosis and management. In this review, we discuss the following entities-enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), hepatosplenic T-cell lymphoma (HSTCL), subcutaneous panniculitis-like T-cell lymphoma (SPTCL), and primary cutaneous ɣδ T-cell lymphoma (PCGD-TCL) - with an emphasis on clinical and diagnostic features and options for management.
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Affiliation(s)
- Rahul S Bhansali
- Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Stefan K Barta
- Department of Medicine, Division of Hematology and Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA.
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18
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Murray DW, Fagan KK, Timmermann PC, Grider DJ. Erythematous Patches and Plaques: What to Make of a Rash that Looks like Pepperoni Pizza? Am J Dermatopathol 2023; 45:427-428. [PMID: 37191374 DOI: 10.1097/dad.0000000000002425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/17/2023]
Affiliation(s)
| | - Kiley K Fagan
- Section of Dermatology, Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA
| | - Paul C Timmermann
- Section of Dermatology, Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA
| | - Douglas J Grider
- Virginia Tech Carilion School of Medicine, Roanoke, VA
- Section of Dermatology, Department of Internal Medicine, Virginia Tech Carilion School of Medicine, Roanoke, VA
- Department of Basic Science Education, Virginia Tech Carilion School of Medicine, Roanoke, VA; and
- Dominion Pathology Associates, Roanoke, VA
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19
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Aggressive Cutaneous Lymphomas and Their Mimics. Surg Pathol Clin 2023; 16:361-383. [PMID: 37149363 DOI: 10.1016/j.path.2023.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023]
Abstract
Cutaneous lymphomas encompass a heterogeneous group of neoplasms with a wide spectrum of clinical presentations, histopathologic features, and prognosis. Because there are overlapping pathologic features among indolent and aggressive forms and with systemic lymphomas that involve the skin, clinicopathologic correlation is essential. Herein, the clinical and histopathologic features of aggressive cutaneous B- and T-cell lymphomas are reviewed. Indolent cutaneous lymphomas/lymphoproliferative disorders, systemic lymphomas, and reactive processes that may mimic these entities are also discussed. This article highlights distinctive clinical and histopathologic features, increases awareness of rare entities, and presents new and evolving developments in the field.
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20
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Onkarappa Mangala Y, Onukogu ID, Breen CM, Colvin GA. Primary Cutaneous Gamma-Delta T-cell Lymphoma: A Case Report and Review of Literature. Cureus 2023; 15:e35442. [PMID: 36994286 PMCID: PMC10042491 DOI: 10.7759/cureus.35442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2023] [Indexed: 02/27/2023] Open
Abstract
Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a rare type of lymphoma, representing less than 1% of all cutaneous T-cell lymphomas. It is typically aggressive and chemotherapy-refractory. Hence, most institutions tend to employ intensive chemotherapy followed by stem cell transplantation although there is no standard of care established. We report a case of PCGD-TCL and discuss the challenges associated with the diagnosis and management of PCGD-TCL.
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21
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Singh R, Alejos D, Rankins C, Devitt KA, Conant JL, Adrianzen-Herrera D. Isolated Bone Marrow Gamma-Delta T-Cell Lymphoma: Another Challenge to the WHO Lymphoid Neoplasm Classification. Leuk Res Rep 2023; 19:100363. [PMID: 37006952 PMCID: PMC10050643 DOI: 10.1016/j.lrr.2023.100363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 01/10/2023] [Accepted: 01/27/2023] [Indexed: 01/30/2023] Open
Affiliation(s)
- Rohit Singh
- Department of Medicine, Division of Hematology and Oncology, Larner College of Medicine at the University of Vermont, Burlington VT, United States of America
| | - David Alejos
- Department of Medicine, Division of Hematology and Oncology, Larner College of Medicine at the University of Vermont, Burlington VT, United States of America
| | - Casey Rankins
- Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington VT, United States of America
| | - Katherine A. Devitt
- Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington VT, United States of America
| | - Joanna L. Conant
- Department of Pathology & Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington VT, United States of America
| | - Diego Adrianzen-Herrera
- Department of Medicine, Division of Hematology and Oncology, Larner College of Medicine at the University of Vermont, Burlington VT, United States of America
- Corresponding author at: Larner College of Medicine at the University of Vermont 89 Beaumont Avenue, Given Building E-214, Burlington, VT 05405.
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22
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Goodlad JR, Cerroni L, Swerdlow SH. Recent advances in cutaneous lymphoma-implications for current and future classifications. Virchows Arch 2023; 482:281-298. [PMID: 36278991 PMCID: PMC9852132 DOI: 10.1007/s00428-022-03421-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/27/2022] [Accepted: 09/27/2022] [Indexed: 01/24/2023]
Abstract
The Revised European-American Classification of mature lymphoid neoplasms published in 1994 and the 2001, 2008 and 2016 WHO classifications that followed, were the product of international collaboration and consensus amongst haematopathologists, geneticists, molecular scientists and clinicians. Primary cutaneous lymphomas were fully incorporated into this process following the publication of the WHO-EORTC classification of cutaneous lymphomas in 2005. The definition, diagnostic criteria and recommended studies for primary cutaneous lymphoma continue to be refined. The 2022 International Consensus Classification represents the most recent update and an overview of all the main entities presenting primarily in the skin, together with the major changes in classification, are summarized herein. Primary cutaneous marginal zone lymphoma is segregated from other extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT lymphoma) and downgraded to a lymphoproliferative disorder in line with its markedly indolent behaviour. In addition, two subtypes are recognised, based largely but not exclusively on whether they are heavy chain class-switched or IgM positive. Similarly, in keeping with a trend to greater conservatism, primary cutaneous acral CD8 positive T cell lymphoma is now also classified as a lymphoproliferative disorder. In addition, significant new insights into the biology of primary cutaneous lymphoma have also recently been forthcoming and will be presented. These studies have enhanced our knowledge of genetic, epigenetic and transcriptional changes in this group of diseases. They not only identify potential targets for novel therapies, but also raise as yet unanswered questions as to how we categorise cutaneous lymphomas, particularly with respect to relationships with similar lymphomas at extracutaneous sites.
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Affiliation(s)
- JR Goodlad
- Department of Pathology, NHS Greater Glasgow and Clyde, Level 3 Laboratory Medicine Building Queen Elizabeth University Hospital, 1345 Govan Rd, Glasgow, G51 4TF UK
| | - L Cerroni
- Department of Dermatology, Medical University of Graz, Graz, Austria
| | - SH Swerdlow
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA USA
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23
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Hobayan CG, Chung CG. Indolent cutaneous lymphoma with gamma/delta expression after COVID-19 vaccination. JAAD Case Rep 2022; 32:74-76. [PMID: 36530557 PMCID: PMC9746077 DOI: 10.1016/j.jdcr.2022.12.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/06/2022] [Accepted: 12/07/2022] [Indexed: 12/15/2022] Open
Affiliation(s)
| | - Catherine G. Chung
- Department of Pathology, The Ohio State University, Columbus, Ohio
- Department of Dermatology, The Ohio State University, Columbus, Ohio
- Correspondence to: Catherine G. Chung, MD, Departments of Pathology and Dermatology, The Ohio State University Wexner Medical Center, 2050 Kenny Rd MMT930, Columbus, OH 43221
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24
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Ayesh Haj Yousef MH, Al-Khatib SM, Khasawneh RA, Rahabneh L. Subcutaneous panniculitis-like T-cell lymphoma: an unusual cause of right thigh hypertrophy. BMJ Case Rep 2022; 15:e253469. [PMID: 36460313 PMCID: PMC9723879 DOI: 10.1136/bcr-2022-253469] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2022] [Indexed: 12/04/2022] Open
Abstract
A man in his mid-20s presented with a painless swelling over his right thigh, which had been progressively increasing over 3 years. He underwent an excisional biopsy for the same, which showed reactive lymphadenopathy. Since the last year and a half, he developed a lower abdominal wall swelling with mild redness over it. In addition, over the last few months before presentation to haematology outpatient clinic, he experienced bouts of fever, night sweats, anorexia, weight loss and right inguinal lymphadenopathy. On examination, splenomegaly was identified. In view of the patients' symptoms, he underwent a positron emission tomography scan, which showed hypermetabolic activity in the subcutaneous tissue sparing the lymph nodes and spleen. A deep skin punch biopsy taken from his right thigh was consistent with the diagnosis of subcutaneous panniculitis-like T-cell lymphoma αβ T-cell phenotype. The patient was treated successfully with oral steroids and on routine follow-up, he is in remission for 5 years.
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Affiliation(s)
| | - Sohaib M Al-Khatib
- Deapertment of Pathology and Microbiology, Jordan University of Science and Technology, Irbid, Jordan
| | - Ruba A Khasawneh
- Department of Diagnostic Radiology and Nuclear Medicine, Jordan University of Science and Technology, Irbid, Jordan
| | - Laith Rahabneh
- Department of Medicine, Jordan University of Science and Technology, Irbid, Jordan
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25
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Muhsen IN, El Fakih R, Hamadani M, Lazarus HM, Kharfan-Dabaja MA, Aljurf M. Clinical, Diagnostic and Prognostic Characteristics of Primary Cutaneous Gamma Delta T-cell Lymphomas. Clin Hematol Int 2022; 4:1-10. [PMID: 35950208 PMCID: PMC9358781 DOI: 10.1007/s44228-022-00011-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 12/26/2021] [Indexed: 12/04/2022] Open
Abstract
Primary cutaneous γδ T-cell lymphoma (PCGDTL) is a rare subtype of non-Hodgkin lymphoma (NHL) that arises from T-cells with γδ T-cell receptors. The exact incidence of PCGDTL is unknown, as it is usually lumped with other cutaneous lymphomas, which are also uncommon. It is one of the peripheral T-cell lymphoma (PTCL) subtypes which is known to have a dismal prognosis due to poor response and the paucity of available therapies. Despite the rarity and uncertainties of PCGDTL, a number of studies over the past decade were published about the pathologic, diagnostic, cytogenetic and clinical features of this disease. These diagnostic advances will open the doors to explore new therapeutics for this rare entity, specifically targeted and immune therapies. In this review, we highlight these advances, summarize the contemporary treatment approaches, and shed the light on future potential therapeutic targets.
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Affiliation(s)
| | - Riad El Fakih
- Oncology Center, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh, 11211 Saudi Arabia
| | - Mehdi Hamadani
- BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI USA
| | - Hillard M. Lazarus
- Division of Hematology and Oncology, Case Western Reserve University, Cleveland, OH USA
| | - Mohamed A. Kharfan-Dabaja
- Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapies Program, Mayo Clinic, Jacksonville, FL USA
| | - Mahmoud Aljurf
- Oncology Center, King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh, 11211 Saudi Arabia
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26
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Galadari A, Ram-Wolff C, Al Hage J, Battistella M, Vignon-Pennamen MD, Rivet J, Cayuela JM, Gabison G, Moins-Teisserenc H, Mourah S, Ingen-Housz-Oro S, Le Corre Y, Bagot M, de Masson A. Cutaneous Gamma Delta T-Cell Lymphoma with indolent evolution: A series of five cases. J Eur Acad Dermatol Venereol 2022; 36:e715-e717. [PMID: 35535450 DOI: 10.1111/jdv.18204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 05/03/2022] [Indexed: 12/01/2022]
Affiliation(s)
- A Galadari
- Department of Dermatology, Saint-Louis Hospital, APHP, Paris, France
| | - C Ram-Wolff
- Department of Dermatology, Saint-Louis Hospital, APHP, Paris, France.,French Cutaneous Lymphomas Study Group, Paris, France
| | - J Al Hage
- Department of Dermatology, Saint-Louis Hospital, APHP, Paris, France
| | - M Battistella
- INSERM U976, Institut de Recherche Saint-Louis, Paris, France.,Université de Paris, Paris, France.,Department of Pathology, Saint-Louis Hospital, APHP, Paris, France.,French Cutaneous Lymphomas Study Group, Paris, France
| | - M D Vignon-Pennamen
- Department of Pathology, Saint-Louis Hospital, APHP, Paris, France.,French Cutaneous Lymphomas Study Group, Paris, France
| | - J Rivet
- Department of Pathology, Saint-Louis Hospital, APHP, Paris, France.,French Cutaneous Lymphomas Study Group, Paris, France
| | - J M Cayuela
- Université de Paris, Paris, France.,Laboratory of Hematology and EA3518, Saint-Louis Hospital, APHP, Paris, France
| | - G Gabison
- Department of Dermatology, Saint-Louis Hospital, APHP, Paris, France
| | - H Moins-Teisserenc
- Université de Paris, Paris, France.,Laboratory of Hematology and INSERM U1160, Saint-Louis Hospital, APHP, Paris, France
| | - S Mourah
- INSERM U976, Institut de Recherche Saint-Louis, Paris, France.,Université de Paris, Paris, France.,Department of Pharmacology and Tumor Genomics, Saint-Louis Hospital, Paris, France
| | - S Ingen-Housz-Oro
- Department of Dermatology, Henri Mondor Hospital, APHP, Créteil, France.,Univ Paris Est Créteil Epiderme, Créteil, France.,French Cutaneous Lymphomas Study Group, Paris, France
| | - Y Le Corre
- Department of Dermatology, Centre University Hospital of Angers, Angers, France.,French Cutaneous Lymphomas Study Group, Paris, France
| | - M Bagot
- Department of Dermatology, Saint-Louis Hospital, APHP, Paris, France.,INSERM U976, Institut de Recherche Saint-Louis, Paris, France.,Université de Paris, Paris, France.,French Cutaneous Lymphomas Study Group, Paris, France
| | - A de Masson
- Department of Dermatology, Saint-Louis Hospital, APHP, Paris, France.,INSERM U976, Institut de Recherche Saint-Louis, Paris, France.,Université de Paris, Paris, France.,French Cutaneous Lymphomas Study Group, Paris, France
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27
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Primary cutaneous lymphoma: the 2018 update of the WHO-EORTC classification. Presse Med 2022; 51:104126. [DOI: 10.1016/j.lpm.2022.104126] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 05/02/2022] [Indexed: 11/22/2022] Open
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28
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Guitart J, Chung C, Torres-Cabala CA. The dilemma of Primary γδ Epidermotropic T-cell lymphoma: Distinction from Mycosis Fungoides, Signs of Cytotoxicity, and Need for More Detailed Analysis. J Cutan Pathol 2022; 49:419-420. [PMID: 35080039 DOI: 10.1111/cup.14204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/19/2022] [Accepted: 01/21/2022] [Indexed: 11/29/2022]
Affiliation(s)
- Joan Guitart
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Christopher Chung
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL
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29
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Primary Cutaneous Gamma-Delta T-Cell Lymphoma Mimicking anaplastic lymphoma kinase-1-Negative Anaplastic Large Cell Lymphoma: A Case Report. Am J Dermatopathol 2022; 44:62-65. [PMID: 34889814 DOI: 10.1097/dad.0000000000002014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
ABSTRACT Primary cutaneous gamma-delta T-cell lymphoma is a rare and aggressive neoplasm, representing less than 1% of all cutaneous T-cell lymphomas. In this article, we report the case of a 49-year-old woman who presented with a history of generalized skin rash and a recent mass on the left upper extremity, as well as right inguinal soft tissue swelling and splenomegaly. Histologic examination of the mass revealed a diffuse subcutaneous infiltrate of large anaplastic and CD30-positive lymphoid cells with rimming of the adipocytes. This case demonstrates unusual cytologic features in primary cutaneous gamma-delta T-cell lymphoma that mimic the features of anaplastic lymphoma kinase-1-negative anaplastic large-cell lymphoma.
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30
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Schönefeldt S, Wais T, Herling M, Mustjoki S, Bekiaris V, Moriggl R, Neubauer HA. The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma. Cancers (Basel) 2021; 13:6212. [PMID: 34944832 PMCID: PMC8699114 DOI: 10.3390/cancers13246212] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 12/02/2021] [Accepted: 12/03/2021] [Indexed: 12/13/2022] Open
Abstract
γδ T cells are unique players in shaping immune responses, lying at the intersection between innate and adaptive immunity. Unlike conventional αβ T cells, γδ T cells largely populate non-lymphoid peripheral tissues, demonstrating tissue specificity, and they respond to ligands in an MHC-independent manner. γδ T cells display rapid activation and effector functions, with a capacity for cytotoxic anti-tumour responses and production of inflammatory cytokines such as IFN-γ or IL-17. Their rapid cytotoxic nature makes them attractive cells for use in anti-cancer immunotherapies. However, upon transformation, γδ T cells can give rise to highly aggressive lymphomas. These rare malignancies often display poor patient survival, and no curative therapies exist. In this review, we discuss the diverse roles of γδ T cells in immune surveillance and response, with a particular focus on cancer immunity. We summarise the intriguing dichotomy between pro- and anti-tumour functions of γδ T cells in solid and haematological cancers, highlighting the key subsets involved. Finally, we discuss potential drivers of γδ T-cell transformation, summarising the main γδ T-cell lymphoma/leukaemia entities, their clinical features, recent advances in mapping their molecular and genomic landscapes, current treatment strategies and potential future targeting options.
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Affiliation(s)
- Susann Schönefeldt
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria; (S.S.); (T.W.); (R.M.)
| | - Tamara Wais
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria; (S.S.); (T.W.); (R.M.)
| | - Marco Herling
- Department of Hematology, Cellular Therapy and Hemostaseology, University of Leipzig, 04103 Leipzig, Germany;
| | - Satu Mustjoki
- Hematology Research Unit Helsinki, Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland;
- iCAN Digital Precision Cancer Medicine Flagship, 00014 Helsinki, Finland
- Translational Immunology Research Program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland
| | - Vasileios Bekiaris
- Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark;
| | - Richard Moriggl
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria; (S.S.); (T.W.); (R.M.)
| | - Heidi A. Neubauer
- Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, 1210 Vienna, Austria; (S.S.); (T.W.); (R.M.)
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Gamma-Delta and CD20 Mycosis Fungoides: Two Cases Uncovered by Broad-Spectrum Immunostaining. Am J Dermatopathol 2021; 43:950-954. [PMID: 34797791 DOI: 10.1097/dad.0000000000002056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
ABSTRACT Mycosis fungoides (MF) expresses T-cell markers and the alpha-beta T-cell receptor (TCR) complex. Here, we describe a case of MF with dual expression of TCR delta and TCR beta and a case of MF expressing the B-cell marker CD20. Both anomalies were detected after we instituted a broad-spectrum immunostaining panel for cutaneous T-cell lymphomas. These findings suggest anomalous immunophenotypes may be more common in MF than previously appreciated. Histopathologists should be aware of unexpected malleability in the immunophenotype of MF to avoid confusion with other subtypes of cutaneous lymphoma. Further research into the prevalence and significance of CD20 and TCR-delta expression in MF is encouraged.
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Chen BJ, Wang RC, Jhuang JY, Chen SW, Su YZ, Tseng CE, Chiang CT, Wu YT, Chuang SS. Primary cutaneous gamma/delta T-cell lymphoma in Taiwan: A series of six cases with frequent solitary presentation and relatively indolent behavior. J Cutan Pathol 2021; 49:350-357. [PMID: 34778979 DOI: 10.1111/cup.14169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 10/22/2021] [Accepted: 11/06/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND Primary cutaneous gamma/delta T-cell lymphoma (PCDG-TCL) is aggressive, frequently presenting as multiple plaques, tumors, and/or subcutaneous nodules. METHODS In this study, we conducted a retrospective study in a tertiary center in Taiwan to characterize this rare tumor. RESULTS We identified six patients. Five presented with a solitary lesion, including two with clinical impression of epidermal inclusion cyst or lipoma. Two of four evaluable cases exhibited epidermotropism, with one mimicking Pautrier microabscess. The neoplastic cells were pleomorphic and mostly medium- to large-sized. In all cases, the neoplastic cells expressed T-cell receptor (TCR)-γ and/or TCR-δ, with four co-expressing βF1. Two of these βF1+ cases co-expressed TCR-γ but not TCR-δ (two different clones). All were negative for Epstein-Barr virus (EBV), low stage, and treated with radiotherapy alone or combined chemotherapy and radiotherapy. In two patients, lymphoma relapsed in 3 and 7 months, respectively, and one patient died of the disease in 7 months. Four other patients were free of disease for 6 to 126 months. CONCLUSION PCGD-TCL cases in Taiwan are more commonly solitary, frequently with indolent courses. The two currently available TCR-δ clones alone might be insufficient to detect all tumors.
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Affiliation(s)
- Bo-Jung Chen
- Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.,Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ren Ching Wang
- Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.,Department of Nursing, College of Nursing, HungKuang University, Taichung, Taiwan
| | - Jie-Yang Jhuang
- Department of Pathology, Mackay Memorial Hospital, Taipei, Taiwan
| | - Shang-Wen Chen
- Division of Hemato-Oncology, Department of Internal Medicine, Lioying Chi-Mei Hospital, Tainan, Taiwan
| | - Ying-Zhen Su
- Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan
| | - Chih-En Tseng
- Department of Anatomic Pathology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.,School of Medicine, Tzu Chi University, Hualian, Taiwan
| | - Chien-Ta Chiang
- Department of Anatomic Pathology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - You-Ting Wu
- Department of Pathology, Chia-Yi Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chia-Yi, Taiwan
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33
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Peddi K, Wiggins B, Choudhury O, Ortolani M. Gamma Delta T-Cell Receptor Lymphoma Causing Bilateral Pulmonary Embolism. Cureus 2021; 13:e18072. [PMID: 34692293 PMCID: PMC8523364 DOI: 10.7759/cureus.18072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/18/2021] [Indexed: 11/16/2022] Open
Abstract
Pulmonary embolism is a previously uncharacterized complication of primary cutaneous gamma delta T-cell lymphoma (PCGDTL), a type of cutaneous T-cell receptor lymphoma that accounts for less than 1% of non-Hodgkin’s lymphomas. We report the first documented case of bilateral pulmonary embolism in the setting of PCGDTL in a 30-year-old woman who presented with acute dyspnea.
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Affiliation(s)
- Kanksha Peddi
- Internal Medicine, Ascension Genesys Hospital, Grand Blanc, USA
| | - Brandon Wiggins
- Internal Medicine, Ascension Genesys Hospital, Grand Blanc, USA
| | | | - Mark Ortolani
- Emergency Medicine, Ascension Genesys Hospital, Grand Blanc, USA
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34
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Miyagaki T. Diagnosis and prognostic stratification of cutaneous lymphoma. J Dermatol 2021; 49:210-222. [PMID: 34346516 DOI: 10.1111/1346-8138.16099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Revised: 07/06/2021] [Accepted: 07/16/2021] [Indexed: 11/27/2022]
Abstract
Primary cutaneous lymphomas are a heterogenous group of non-Hodgkin's lymphoma of both T/natural killer-cell and B-cell origin and defined to primarily present in the skin without extracutaneous involvement at diagnosis. In contrast to nodal non-Hodgkin's lymphoma, cutaneous T-cell lymphomas (CTCL) are more generally seen than cutaneous B-cell lymphomas (CBCL). CTCL and CBCL have various subtypes and each subtype has specifically characteristic clinical, pathological, and prognostic features. The diagnostic methods and staging evaluation of cutaneous lymphomas is mostly common in various guidelines created by professional societies. The diagnosis is made comprehensively based on clinical, pathological, laboratory, radiological, and genetic findings. On the other hand, definite prognostic stratification has not been completely established yet in most cutaneous lymphomas. This article focuses on the general and novel diagnostic methods and the current findings about prognostic factors and stratification in cutaneous lymphomas.
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Affiliation(s)
- Tomomitsu Miyagaki
- Department of Dermatology, St Marianna University School of Medicine, Kawasaki, Japan
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Abstract
The cutaneous lymphomas are malignancies of T-cell and B-cell lymphocytes in which the skin is the primary organ of involvement. The cutaneous T-cell lymphomas include variants that can mimic the presentation of common skin diseases or arthropod bites. Mycosis fungoides, the most common cutaneous T-cell lymphoma, usually presents as fixed asymptomatic patches or plaques in sun-protected areas. The cutaneous B-cell lymphomas have fewer variants that often present as papules or nodules that can mimic nonmelanoma skin cancers. Some therapies for cutaneous lymphoma have unique side effects such as central hypothyroidism, hyperlipidemia, and peripheral neuropathy.
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MESH Headings
- Aged
- Aged, 80 and over
- Animals
- Antineoplastic Agents/adverse effects
- Antineoplastic Agents, Immunological/adverse effects
- Arthropods
- Bexarotene/adverse effects
- Bites and Stings/diagnosis
- Brentuximab Vedotin/adverse effects
- Diagnosis, Differential
- Humans
- Hyperlipidemias/chemically induced
- Hypothyroidism/chemically induced
- Lymphoma, Primary Cutaneous Anaplastic Large Cell/diagnosis
- Lymphoma, T-Cell, Cutaneous/classification
- Lymphoma, T-Cell, Cutaneous/diagnosis
- Lymphoma, T-Cell, Cutaneous/therapy
- Lymphomatoid Papulosis/diagnosis
- Mycosis Fungoides/diagnosis
- Peripheral Nervous System Diseases/chemically induced
- Prognosis
- Sezary Syndrome/diagnosis
- Skin Diseases/diagnosis
- Skin Diseases/pathology
- Skin Neoplasms/pathology
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Affiliation(s)
- John A Zic
- Department of Dermatology, VU Cutaneous Lymphoma Clinic, Vanderbilt University Medical Center, Vanderbilt Dermatology, One Hundred Oaks, 719 Thompson Lane, Suite 26300, Nashville, TN 37204-3609, USA.
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36
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A Previously Unrecognized Granulomatous Variant of Gamma-Delta T-Cell Lymphoma. Dermatopathology (Basel) 2021; 8:221-228. [PMID: 34204191 PMCID: PMC8293259 DOI: 10.3390/dermatopathology8020027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 11/17/2022] Open
Abstract
Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is an extremely rare and aggressive T-cell neoplasm with complex heterogeneity. We present a series of two patients who presented with firm, subcutaneous nodules and were diagnosed with PCGD-TCL. In both cases, biopsies demonstrated a both superficial and deep adnexotropic infiltrate comprised of angiocentric, medium- to large-sized atypical lymphocytes. The infiltrate extended into the panniculus. Immuno–histochemical stains highlighted atypical lymphocytes that expressed CD3, CD8 and CD56 but were negative for EBV ISH. A brisk histiocytic response with focal aggregation into granulomas was highlighted with a PG-M1 stain. The atypical lymphocytes were positive for gene rearrangements on a TCR delta stain and negative for βF-1. CT and PET scan in one of the two patients demonstrated diffuse, subcutaneous, ground-glass foci; hypermetabolic soft tissue nodules; and lymphadenopathy in the lungs, as well as splenomegaly. A diagnosis of histiocyte-rich PCGD-TCL was rendered. A histiocyte-rich, granulomatous variant of γδ T-cell lymphoma is extremely rare. Its potentially misleading resemblance to inflammatory granulomatous conditions could pose a diagnostic pitfall in this already challenging condition. This variant may resemble granulomatous mycosis fungoides and granulomatous slack skin syndrome, but it has a distinct, aggressive clinical outcome.
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37
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Tomasini D, Croci GA, Hotz A, Cione S, Cecchetti C, Ciambelli F, Crivelli F. Gamma/delta T-cell lymphoma with mycosis fungoides-like clinical course transforming to "T-cell-receptor-silent" aggressive lymphoma: Description of one case. J Cutan Pathol 2021; 48:1197-1203. [PMID: 34002416 DOI: 10.1111/cup.14063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 04/28/2021] [Accepted: 05/12/2021] [Indexed: 11/29/2022]
Abstract
Primary cutaneous γδ T-cell lymphomas (PCGDTLs) are a heterogeneous group of lymphomas representing about 1% of primary cutaneous T-cell lymphomas (CTCLs) and mostly regarded as clinically aggressive. Current WHO-EORTC classification recognizes different clinic-pathologic subsets of PCGDTL, but it suggests that cases showing a mycosis fungoides (MF)-like clinical presentation and histopathology should be classified as MF irrespective of phenotype for their indolent course. Herein, we describe a case of γδ-MF, featuring at onset a granulomatous pattern, with subsequent clinical worsening signaled by the development of an ulcero-necrotic lesion and systemic dissemination, leading to death in 5 months. Clinical progression was sustained by a shift to mature T-cell lymphoma composed of medium to large-sized blastoid T-cells featuring a T-cell receptor (TCR) silent immunophenotype.
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Affiliation(s)
- Dario Tomasini
- Medical Department, Division of Dermatology, ASST Valle Olona, Hospital of Busto Arsizio, Busto Arsizio (Va), Italy
| | - Giorgio Alberto Croci
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.,Division of Pathology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Annamaria Hotz
- Department of Diagnostic Services, Division of Pathology, ASST Valle Olona, Hospital of Busto Arsizio, Busto Arsizio (Va), Italy
| | - Stefania Cione
- Department of Diagnostic Services, Laboratory Analysis, ASST Valle Olona, Hospital of Busto Arsizio, Busto Arsizio (Va), Italy
| | - Caterina Cecchetti
- Oncologic Department, Division of Hematology, ASST Valle Olona, Hospital of Busto Arsizio, Busto Arsizio (Va), Italy
| | - Fabrizio Ciambelli
- Oncologic Department, Division of Hematology, ASST Valle Olona, Hospital of Busto Arsizio, Busto Arsizio (Va), Italy
| | - Filippo Crivelli
- Department of Diagnostic Services, Division of Pathology, ASST Valle Olona, Hospital of Busto Arsizio, Busto Arsizio (Va), Italy
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38
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Torres-Cabala CA, Huen A, Iyer SP, Miranda RN. Gamma/Delta Phenotype in Primary Cutaneous T-cell Lymphomas and Lymphoid Proliferations: Challenges for Diagnosis and Classification. Surg Pathol Clin 2021; 14:177-194. [PMID: 34023099 DOI: 10.1016/j.path.2021.03.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Primary cutaneous T-cell lymphomas pose a diagnostic challenge for dermatopathologists, hematopathologists, and general surgical pathologists. Recognition of gamma/delta phenotype in cutaneous T proliferations has been enhanced by the availability of antibodies against TCRgamma and delta for immunohistochemistry. Thus, reporting gamma/delta phenotype in a cutaneous T-cell lymphoid proliferation may indicate a significant change in therapy and a challenge for dermatologists and oncologists who treat these patients. Herein, we discuss primary cutaneous gamma/delta T-cell lymphoma, its differential diagnosis, and other skin lymphoid proliferations that may show gamma/delta phenotype. Awareness of the occurrence of gamma/delta phenotype in both T-cell lymphomas and benign lymphoid proliferations involving skin is crucial for a better interpretation of histopathologic findings. Integration of clinical presentation, morphology, immunoprofile, and molecular findings is key for a correct diagnosis and appropriate therapy of lesions displaying gamma/delta T-cell phenotype.
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Affiliation(s)
- Carlos A Torres-Cabala
- Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 85, Houston, TX 77030, USA; Department of Dermatology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1452, Houston, TX 77030, USA.
| | - Auris Huen
- Department of Dermatology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1452, Houston, TX 77030, USA
| | - Swaminathan P Iyer
- Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 429, Houston, TX 77030, USA
| | - Roberto N Miranda
- Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 72, Houston, TX 77030, USA
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39
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Successful salvage therapy for refractory primary cutaneous gamma-delta T-cell lymphoma with a combination of brentuximab vedotin and gemcitabine. Exp Hematol Oncol 2021; 10:32. [PMID: 33985594 PMCID: PMC8117509 DOI: 10.1186/s40164-021-00225-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 05/03/2021] [Indexed: 11/10/2022] Open
Abstract
Primary cutaneous gamma-delta T-cell lymphoma (PCGD-TCL) is a very rare lymphoma with an aggressive clinical course and a dismal outcome. The prognosis is linked to a pronounced resistance to chemotherapy and radiotherapy. No standard treatment approach is defined due to the low frequency of the disease and lack of prospective studies. CD30 is expressed in almost half of the cases of PCGD-TCL, which offers a potential therapeutic option. We report the successful treatment of a 68-year-old man who suffered PCGD-TCL with a combination of Brentuximab Vedotin and Gemcitabine after the failure of two lines of previous chemotherapy. CD30 expression was only partial. The treatment was very well tolerated and allowed the patient to benefit from allogeneic hematopoietic stem cell transplantation.
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40
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Turcotte ME, Kelkar AH, Chaffin J, Dang NH. Secondary Gamma-Delta T-Cell Lymphoma Not Otherwise Specified (NOS) From Chronic Immunosuppression. Cureus 2021; 13:e14808. [PMID: 34094764 PMCID: PMC8169379 DOI: 10.7759/cureus.14808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Herein, we present the case of a 63-year-old female with a history of Behçet’s disease managed with long-term prednisone and azathioprine who initially presented for symptomatic anemia, which progressed to pancytopenia with neutropenic fever. Initial workup ruled out infectious etiologies but was indeterminate for immune-mediated or neoplastic causes. Bone marrow biopsy demonstrated a CD8+ gamma-delta T-cell neoplasm; however, imaging and skin biopsy pathology did not support hepatosplenic or cutaneous lymphoma involvement. By the 2017 World Health Organization (WHO) classifications, these findings were defined as gamma-delta peripheral T-cell lymphoma, not otherwise specified (NOS). This is suspected to be secondary to chronic immunosuppression from long-term steroid and azathioprine use. The patient was treated with one cycle of the EPOCH chemotherapy regimen ((etoposide, vincristine, cyclophosphamide, doxorubicin, and prednisone), but the treatment course was complicated by an angioinvasive fungal infection and the patient subsequently transitioned to symptom-focused therapy in a hospice facility.
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Affiliation(s)
- Madeleine E Turcotte
- Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, USA
| | - Amar H Kelkar
- Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, USA
| | - Joanna Chaffin
- Department of Pathology, University of Florida College of Medicine, Gainesville, USA
| | - Nam H Dang
- Division of Hematology and Oncology, University of Florida, Gainesville, USA
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41
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Stoll JR, Willner J, Oh Y, Pulitzer M, Moskowitz A, Horwitz S, Myskowski P, Noor SJ. Primary cutaneous T-cell lymphomas other than Mycosis Fungoides and Sezary Syndrome - Part I: Clinical and histologic features and diagnosis. J Am Acad Dermatol 2021; 85:1073-1090. [PMID: 33940098 DOI: 10.1016/j.jaad.2021.04.080] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/12/2021] [Accepted: 04/26/2021] [Indexed: 11/11/2022]
Abstract
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 (MF) 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 workup and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than MF and SS.
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Affiliation(s)
| | | | - Yuna Oh
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | | | - Sarah J Noor
- Memorial Sloan Kettering Cancer Center, New York, NY.
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42
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Walker CJ, Martinez-Escala ME, Tan TL, Espinosa ML, Guitart J. High incidence of adnexotropism in cytotoxic cutaneous lymphomas. J Cutan Pathol 2021; 48:1231-1238. [PMID: 33759218 DOI: 10.1111/cup.14017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Revised: 02/28/2021] [Accepted: 03/15/2021] [Indexed: 12/01/2022]
Abstract
BACKGROUND Primary cutaneous gamma-delta T-cell lymphoma (PCγδTCL) and primary cutaneous aggressive epidermotropic T-cell lymphomas (PCAETCL) are rare aggressive cytotoxic cutaneous lymphomas (CyCL) often difficult to diagnose. Histopathologically, PCAETCL and PCγδTCL may resemble mycosis fungoides (MF) and the presence of adnexotropism in CyCL (CyCL) contributes to this diagnostic challenge, especially in the setting of atypical and double-negative phenotypes. METHODS In this retrospective study clinical data and histopathological section of 91 patients were analyzed for signs of clinical and histopathological signs adnexotropism. RESULTS Adnexotropism was identified in 48.4% (44/91) of cases, including PCAETCL (40.9%, 18/44), PCγδTCL and cytotoxic cutaneous lymphomas, not otherwise specified (CyCTCL, NOS) (43.2%, 19/44 and 15.9%, 7/44). Comparison between disease-related mortality with Kaplan-Meier survival analysis of non-adnexotropic vs adnexotropic CyCL did not show any significant difference between the two groups (P = 0.8). Clinically they present with patches, plaques, and tumors and commonly with ulceration, but follicular prominence or alopecia are rare. Clinical signs of adnexotropism such as alopecia and hypo- or anhidrosis were rarely seen. CONCLUSION Adnexotropism is a common finding in CyCL, especially in PCAETCL. Adnexotropic CyCL may be histopathologically difficult to distinguish from folliculotropic mycosis fungoides. A comprehensive IHC panel should be routinely performed in such cases.
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Affiliation(s)
- Christina J Walker
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | | | - Timothy L Tan
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Maria L Espinosa
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Joan Guitart
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
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43
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Hrin M, Newsom M, Ghamrawi R, Niehaus A, Feldman S, Sigmon J, Strowd L. Primary cutaneous gamma-delta T-cell lymphoma: Two cases and a review of the literature. JOURNAL OF DERMATOLOGY & DERMATOLOGIC SURGERY 2021. [DOI: 10.4103/jdds.jdds_54_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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44
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Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma With Secondary Cutaneous Involvement: A Diagnostic Challenge. Am J Dermatopathol 2020; 43:300-304. [PMID: 33264131 DOI: 10.1097/dad.0000000000001855] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
ABSTRACT A 45-year-old woman presented with a solitary breast nodule that histologically corresponded to a dense dermal/subcutaneous infiltration of atypical cytotoxic T-lymphocytes (CD3+, CD8+, CD56+, TIA-1+, CD5-, CD4-, CD30-, EBV-), resembling subcutaneous panniculitic T-cell lymphoma. The presence of TCRδ gene rearrangement and the absence of βF1 expression let to suspect the diagnosis of primary cutaneous γδT-cell lymphoma. As a consequence of jejunum perforation following chemotherapy treatment, a mucosal atypical lymphoid infiltration with marked epitheliotropism was observed in the resected intestinal sample, and the diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) was finally established. Disease progression appeared with multiple erythematous plaques showing a dense lichenoid atypical cytotoxic T-cell infiltrate with intense epidermotropism, mimicking primary cutaneous epidermotropic aggressive CD8+ T-cell lymphoma. MEITL is an uncommon and aggressive peripheral T-cell lymphoma that often presents in adults with gastrointestinal symptoms. Secondary cutaneous involvement is a rare phenomenon that may show clinicopathologic and immunohistochemical features that overlap with different subtypes of primary cutaneous cytotoxic T-cell lymphomas. In the absence of gastrointestinal symptoms, the diagnosis may be challenging, and only the evidence of underlying MEITL may allow to establish the definite diagnosis.
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45
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Yasuda MR, Roller LA, Fagenholz PJ, Hoang MP. Case 33-2020: A 55-Year-Old Man with Abdominal Pain, Joint Swelling, and Skin Lesions. N Engl J Med 2020; 383:1664-1671. [PMID: 33085865 DOI: 10.1056/nejmcpc1916257] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Mariko R Yasuda
- From the Departments of Dermatology (M.R.Y.), Radiology (L.A.R.), Surgery (P.J.F.), and Pathology (M.P.H.), Massachusetts General Hospital, and the Departments of Dermatology (M.R.Y.), Radiology (L.A.R.), Surgery (P.J.F.), and Pathology (M.P.H.), Harvard Medical School - both in Boston
| | - Lauren A Roller
- From the Departments of Dermatology (M.R.Y.), Radiology (L.A.R.), Surgery (P.J.F.), and Pathology (M.P.H.), Massachusetts General Hospital, and the Departments of Dermatology (M.R.Y.), Radiology (L.A.R.), Surgery (P.J.F.), and Pathology (M.P.H.), Harvard Medical School - both in Boston
| | - Peter J Fagenholz
- From the Departments of Dermatology (M.R.Y.), Radiology (L.A.R.), Surgery (P.J.F.), and Pathology (M.P.H.), Massachusetts General Hospital, and the Departments of Dermatology (M.R.Y.), Radiology (L.A.R.), Surgery (P.J.F.), and Pathology (M.P.H.), Harvard Medical School - both in Boston
| | - Mai P Hoang
- From the Departments of Dermatology (M.R.Y.), Radiology (L.A.R.), Surgery (P.J.F.), and Pathology (M.P.H.), Massachusetts General Hospital, and the Departments of Dermatology (M.R.Y.), Radiology (L.A.R.), Surgery (P.J.F.), and Pathology (M.P.H.), Harvard Medical School - both in Boston
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46
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Diagnosis of gamma/delta mycosis fungoides requires longitudinal clinical observation. J Am Acad Dermatol 2020; 85:1352-1353. [PMID: 33065170 DOI: 10.1016/j.jaad.2020.10.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 08/21/2020] [Accepted: 10/06/2020] [Indexed: 11/24/2022]
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47
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An Enteropathy-like Indolent NK-Cell Proliferation Presenting in the Female Genital Tract. Am J Surg Pathol 2020; 44:561-565. [PMID: 31609783 DOI: 10.1097/pas.0000000000001387] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Natural killer (NK) cell enteropathy is a lymphoproliferative disorder, initially described by Mansoor and colleagues, that presents in the gastrointestinal tract, and is often mistaken for extranodal NK/T-cell lymphoma on first assessment. This population of cells in this process have an NK-cell phenotype (CD3, CD56, CD2, CD7), lacks evidence of Epstein-Barr virus infection, has germline rearrangement of the T-cell receptor, and a very indolent clinical course. Indeed, many of such patients had been originally diagnosed as having an NK/T-cell lymphoma, and subsequently received chemotherapy. We report a unique case where an indolent lymphoproliferative disorder with features that resemble NK-cell enteropathy is encountered for the first time outside the gastrointestinal tract, specifically in the female genitourinary tract. We provide morphologic, immunophenotypic, and molecular documentation of such, in association with a completely indolent clinical behavior of this type of process.
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Isufi I, Seropian S, Gowda L, Wilson LD, Roberts K, Girardi M, Perreault S, Foss F. Outcomes for allogeneic stem cell transplantation in refractory mycosis fungoides and primary cutaneous gamma Delta T cell lymphomas. Leuk Lymphoma 2020; 61:2955-2961. [DOI: 10.1080/10428194.2020.1790555] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Iris Isufi
- Hematology and Bone Marrow Transplantation, Yale University School of Medicine, New Haven, CT, USA
| | - Stuart Seropian
- Hematology and Bone Marrow Transplantation, Yale University School of Medicine, New Haven, CT, USA
| | - Lohith Gowda
- Hematology and Bone Marrow Transplantation, Yale University School of Medicine, New Haven, CT, USA
| | - Lynn D. Wilson
- Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA
| | - Kenneth Roberts
- Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA
| | - Michael Girardi
- Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA
| | - Sarah Perreault
- Department of Pharmacy, Yale New Haven Hospital, New Haven, CT, USA
| | - Francine Foss
- Hematology and Bone Marrow Transplantation, Yale University School of Medicine, New Haven, CT, USA
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Daniels J, Doukas PG, Escala MEM, Ringbloom KG, Shih DJH, Yang J, Tegtmeyer K, Park J, Thomas JJ, Selli ME, Altunbulakli C, Gowthaman R, Mo SH, Jothishankar B, Pease DR, Pro B, Abdulla FR, Shea C, Sahni N, Gru AA, Pierce BG, Louissaint A, Guitart J, Choi J. Cellular origins and genetic landscape of cutaneous gamma delta T cell lymphomas. Nat Commun 2020; 11:1806. [PMID: 32286303 PMCID: PMC7156460 DOI: 10.1038/s41467-020-15572-7] [Citation(s) in RCA: 70] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 03/10/2020] [Indexed: 12/14/2022] Open
Abstract
Primary cutaneous γδ T cell lymphomas (PCGDTLs) represent a heterogeneous group of uncommon but aggressive cancers. Herein, we perform genome-wide DNA, RNA, and T cell receptor (TCR) sequencing on 29 cutaneous γδ lymphomas. We find that PCGDTLs are not uniformly derived from Vδ2 cells. Instead, the cell-of-origin depends on the tissue compartment from which the lymphomas are derived. Lymphomas arising from the outer layer of skin are derived from Vδ1 cells, the predominant γδ cell in the epidermis and dermis. In contrast, panniculitic lymphomas arise from Vδ2 cells, the predominant γδ T cell in the fat. We also show that TCR chain usage is non-random, suggesting common antigens for Vδ1 and Vδ2 lymphomas respectively. In addition, Vδ1 and Vδ2 PCGDTLs harbor similar genomic landscapes with potentially targetable oncogenic mutations in the JAK/STAT, MAPK, MYC, and chromatin modification pathways. Collectively, these findings suggest a paradigm for classifying, staging, and treating these diseases.
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MESH Headings
- Amino Acid Sequence
- Antigens, CD1d/metabolism
- Chromatin Assembly and Disassembly
- Epitopes/immunology
- Genome, Human
- HEK293 Cells
- Humans
- Lymph Nodes/pathology
- Lymphoma, T-Cell, Cutaneous/genetics
- Lymphoma, T-Cell, Cutaneous/pathology
- Models, Biological
- Mutation/genetics
- Phenotype
- Principal Component Analysis
- Receptors, Antigen, T-Cell, gamma-delta/metabolism
- Signal Transduction
- Skin/pathology
- Skin Neoplasms/genetics
- Skin Neoplasms/pathology
- Transcription, Genetic
- Transcriptome/genetics
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Affiliation(s)
- Jay Daniels
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Peter G Doukas
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Maria E Martinez Escala
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Kimberly G Ringbloom
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - David J H Shih
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jingyi Yang
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Kyle Tegtmeyer
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Joonhee Park
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jane J Thomas
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Mehmet E Selli
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Can Altunbulakli
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Ragul Gowthaman
- University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, USA
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA
| | - Samuel H Mo
- University of Illinois College of Medicine, Chicago, IL, USA
| | - Balaji Jothishankar
- Department of Medicine, Section of Dermatology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA
| | - David R Pease
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Barbara Pro
- Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Farah R Abdulla
- Division of Dermatology, City of Hope Comprehensive Cancer Center, Duarte, CA, USA
| | - Christopher Shea
- Department of Medicine, Section of Dermatology, University of Chicago Pritzker School of Medicine, Chicago, IL, USA
| | - Nidhi Sahni
- Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX, USA
- Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, TX, USA
| | - Alejandro A Gru
- Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA
- Department of Dermatology, University of Virginia Health System, Charlottesville, VA, USA
| | - Brian G Pierce
- University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, USA
- Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA
| | - Abner Louissaint
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
| | - Joan Guitart
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
| | - Jaehyuk Choi
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
- Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
- Center for Genetic Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
- Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
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50
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Gru AA, McHargue C, Salavaggione AL. A Systematic Approach to the Cutaneous Lymphoid Infiltrates: A Clinical, Morphologic, and Immunophenotypic Evaluation. Arch Pathol Lab Med 2020; 143:958-979. [PMID: 31339758 DOI: 10.5858/arpa.2018-0294-ra] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT.— The evaluation of cutaneous lymphoid infiltrates, both neoplastic and inflammatory, occurs very frequently in routine dermatopathologic examination and consultation practices. The "tough" cutaneous lymphoid infiltrate is feared by many pathologists; skin biopsies are relatively small, whereas diagnostic possibilities are relatively broad. It is true that cutaneous lymphomas can be difficult to diagnose and that in many circumstances multiple biopsies are required to establish a correct diagnostic interpretation. As a reminder, one should understand that low-grade cutaneous lymphomas are indolent disorders that usually linger for decades and that therapy does not result in disease cure. It is also important to remember that in most circumstances, those patients will die from another process that is completely unrelated to a diagnosis of skin lymphoma (even in the absence of specific therapy). OBJECTIVE.— To use a clinicopathologic, immunophenotypic, and molecular approach in the evaluation of common lymphocytic infiltrates. DATA SOURCES.— An in-depth analysis of updated literature in the field of cutaneous lymphomas was done, with particular emphasis on updated terminology from the most recent World Health Organization classification of skin and hematologic tumors. CONCLUSIONS.— A diagnosis of cutaneous lymphoid infiltrates can be adequately approached using a systematic scheme following the proposed ABCDE system. Overall, cutaneous T- and B-cell lymphomas are rare and "reactive" infiltrates are more common. Evaluation of lymphoid proliferations should start with a good sense of knowledge of the clinical presentation of the lesions, the clinical differential considerations, and a conscientious and appropriate use of immunohistochemistry and molecular tools.
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Affiliation(s)
- Alejandro A Gru
- From the Departments of Pathology (Drs Gru and Salavaggione) and Dermatology (Dr Gru), University of Virginia, Charlottesville; and the Department of Dermatology (Dr McHargue), Henry Ford Health System, Detroit, Michigan
| | - Chauncey McHargue
- From the Departments of Pathology (Drs Gru and Salavaggione) and Dermatology (Dr Gru), University of Virginia, Charlottesville; and the Department of Dermatology (Dr McHargue), Henry Ford Health System, Detroit, Michigan
| | - Andrea L Salavaggione
- From the Departments of Pathology (Drs Gru and Salavaggione) and Dermatology (Dr Gru), University of Virginia, Charlottesville; and the Department of Dermatology (Dr McHargue), Henry Ford Health System, Detroit, Michigan
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