Saggy skin as a presenting sign of angioimmunoblastic T‐cell lymphoma

Angioimmunoblastic T‐cell lymphoma (AITL) is a rare, aggressive form of peripheral T‐cell lymphoma that has a variety of cutaneous manifestations. To our knowledge, saggy skin has not been documented as one of these manifestations. We report a case of a patient with angioimmunoblastic T‐cell lymphoma presenting initially with pruritus and saggy skin, which later progressed into erythroderma despite chemotherapy; the disease eventually resolved with autologous stem cell transplant. Appreciating the cutaneous manifestations of AITL may allow for earlier diagnosis and treatment.     

Nasal-type T/natural killer cell angiocentric lymphoma, Epstein-Barr virus-associated, and showing clonal T-cell receptor gamma gene rearrangement

Nasal-type T/natural killer (NK) cell lymphoma, which often shows an angiocentric growth pattern, is a distinct clinicopathological entity highly associated with the Epstein-Barr virus (EBV). This tumour has a characteristic immunophenotype, whereas the cytological spectrum is broad. It is known that a clonal T-cell receptor (TCR) gene rearrangement is not found in this tumour. However, it is still unresolved as to whether the finding of a clonal TCR gene rearrangement excludes the diagnosis of nasal-type T/NK cell lymphoma. We describe a case of nasal-type T/NK cell angiocentric lymphoma, EBV-associated, and showing clonal TCR gamma gene rearrangement. The patient died of sepsis 5 months after diagnosis in spite of aggressive chemotherapy.     

Dual genotype in cutaneous T cell lymphoma: immunoglobulin gene rearrangement in clonal T cell malignancy

Genomic DNA digests of peripheral blood lymphocytes from 13 patients with the leukemic phase of the T cell neoplasm cutaneous T cell lymphoma were studied by hydridization using probes for the constant region of the beta chain of the T cell receptor, the joining region of the immunoglobulin heavy chain gene, and the kappa and lambda light chain genes. Lymphocytes from all 13 cutaneous T cell lymphoma patients contained DNA with clonal rearrangements of the beta chain gene of the T cell receptor. In addition, DNA from 4 patients contained an immunoglobulin gene rearrangement. T cell enrichment studies of peripheral blood lymphocytes from 2 patients confirmed that the immunoglobulin gene joining region rearrangement was confined to the T cell population. These results demonstrate that cutaneous T cell lymphoma is a clonal T cell malignancy that frequently expresses a dual genotype. A multiparameter approach, including DNA probes for the beta chain of the T cell receptor, as well as the immunoglobulin genes, immunophenotyping, and cytogenetics, is valuable in the diagnosis of cutaneous T cell lymphoma.     

CD8‐positive pseudolymphoma in lues maligna and human immunodeficiency virus with monoclonal T‐cell receptor‐beta rearrangement

A 42‐year‐old Caucasian man suffered from disseminated plaques and ulcerated nodules for 6 weeks. He had weight loss and generalized lymphadenopathy. Underlying diseases were not known up till then. Based on a skin biopsy, the diagnosis of CD8‐positive cutaneous T‐cell lymphoma, type mycosis fungoides was made in a pathological reference center for lymphoma. A reproducible T‐cell receptor (TCR)‐beta rearrangement was detectable. Before starting therapy, a new biopsy was taken and the previous diagnosis was re‐evaluated taking clinical images and symptoms into account. Based on both, the diagnosis of a CD8+ pseudolymphoma in lues maligna and human immunodeficiency virus was made. We highlight histopathologic clues for the correct diagnosis, and we emphasize the indispensability of clinical‐pathological correlation. Furthermore, we discuss the differential diagnosis of CD8+ lymphoproliferative disorders.     

Primary cutaneous T‐cell lymphoma presenting as mycosis fungoides with a T‐/null‐cell phenotype: report of two cases

Variations in the clinical and histological presentation of cutaneous T‐cell lymphoma (CTCL) can hamper diagnosis. We report two cases of a novel presentation of CTCL characterized by an aberrant immunophenotype with complete loss of pan T‐cell antigens including T‐cell receptor β chain and showing the clinical and histopathological appearance of erythrodermic and plaque‐stage mycosis fungoides.     

The frequency of dual TCR-PCR clonality in granulomatous disorders

Background: A granulomatous infiltrate in association with cutaneous T‐cell lymphoma is uncommon. The diagnosis of mycosis fungoides can be difficult in the setting of an exuberant granulomatous infiltrate that obscures the neoplastic lymphoid infiltrate, thereby mimicking a granulomatous dermatitis. Therefore, the clinical context and supplemental molecular analysis, such as the demonstration of a monoclonal T‐cell population, may assist in diagnosis. Monoclonal T‐cell populations have been reported in association with inflammatory conditions and serve as a diagnostic pitfall. The frequency of T‐cell clonality in association with granulomatous dermatitides has not yet been established. Methods: We identified 29 patients with granulomatous dermatitis who had biopsies at two distinct body sites. Results were correlated with clinical follow up and with clonal T‐cell receptor‐gamma chain rearrangement as detected by polymerase chain reaction‐based analysis (dual TCR‐PCR). Results: Clinical follow up was obtained in 17 of 29 cases (58.6%). Twenty‐five of 29 cases of granulomatous dermatitis lacked T‐cell monoclonality. Three cases of granuloma annulare contained a T‐cell clone in one of the two biopsies. One case of necrobiotic xanthogranuloma showed an identical T‐cell clone in multiple biopsies. Conclusions: The use of dual TCR‐PCR analysis, that is, T‐cell clonality analysis in biopsy specimens from two different sites, serves as an adjunct to assist in distinguishing granulomatous inflammatory reactions from granulomatous T‐cell lymphoma, including granulomatous mycosis fungoides. The occasional finding of a T‐cell clone in a granulomatous dermatitis underscores the importance of clinicopathological correlation in daily diagnosis. Dabiri S, Morales A, Ma L, Sundram U, Kim YH, Arber DA, Kim J. The frequency of dual TCR‐PCR clonality in granulomatous disorders.     

Pseudocarcinomatous hyperplasia mimicking squamous cell carcinoma in a case of CD56‐positive cytotoxic T‐cell lymphoma

We present the case of an 84‐year‐old patient with a cutaneous CD56 positive cytotoxic T‐cell lymphoma associated with substantial pseudocarcinomatous hyperplasia mimicking squamous cell carcinoma (SCC). The patient presented with a 7‐month history of several progressive, ulcerated plaques on his right forearm. An initial biopsy showed changes consistent with a diagnosis of SCC for which the patient underwent surgical treatment. Several months later, the patient developed recurrent ulcerated plaques on the right forearm of which several biopsies were performed. The biopsies repeatedly showed marked pseudocarcinomatous hyperplasia resembling SCC. Deeper punch biopsies, however, showed a dense superficial and deep infiltrate of markedly atypical lymphocytes. Immunohistochemical analysis revealed strong positive staining for CD3, CD8, CD56 with negative stains for CD30 and Epstein‐Barr virus‐encoded small non‐polyadenylated RNAs (EBER). Staining for beta F1 and gamma‐delta T‐cell receptor (γδ TCR) were both negative. This constellation was most consistent with a diagnosis of cutaneous peripheral T‐cell lymphoma, unspecified in association with marked pseudocarcinomatous hyperplasia. Our case adds cutaneous peripheral T‐cell lymphoma, unspecified to the list of conditions associated with pseudocarcinomatous hyperplasia (PCH) and illustrates once again the potential pitfalls of distinguishing marked pseudocarcinomatous hyperplasia from SCC.     

Cutaneous EBV‐positive γδ T‐cell lymphoma vs. extranodal NK/T‐cell lymphoma: a case report and literature review

Primary cutaneous γδ T‐cell lymphoma and extranodal natural killer (NK)/T‐cell lymphoma (ENKTL), nasal type are two distinct lymphoma entities in the World Health Organization (WHO) classification. We report the case of an aggressive cutaneous lymphoma of γδ T‐cell origin showing overlapping features of both lymphomas. A 78‐year‐old female presented with confluent erythematous plaques with ulcerations over her right thigh. Microscopically, section of the skin showed a diffuse dermal and subcutaneous lymphocytic infiltration with tumor necrosis and angioinvasion. The medium‐ to large‐sized tumor cells expressed CD3, CD8, cytotoxic molecules and T‐cell receptor (TCR)‐γ but not CD4, CD20, CD30, CD56 or βF1. In situ hybridization for Epstein‐Barr virus‐encoded mRNA (EBER) was diffusely positive. Polymerase chain reaction‐based clonality assay showed a clonal TCR‐γ chain gene rearrangement. The features compatible with γδ T‐cell lymphoma include dermal and subcutaneous involvements, cytotoxic phenotype, expression of TCR‐γ, as well as an aggressive course. On the other hand, the diffuse EBER positivity, angioinvasion, tumor necrosis and cytotoxic phenotype may also fit in the diagnosis of an ENKTL of T‐cell lineage. We review the literature on EBER‐positive γδ T‐cell lymphoma and discuss the diagnostic dilemma using the current WHO classification system.     

Primary cutaneous follicular helper T‐cell lymphoma

Follicular helper T‐cells (TFH) represent a specific subset of CD4‐positive helper T‐cells that help B‐cells to differentiate into long‐lived antibody‐secreting plasma cells or memory B‐cells. The expression of TFH markers in neoplastic T‐cells, traditionally related to the angioimmunoblastic (AITL) subgroup of peripheral T‐cell lymphomas, is nowadays well‐known to be more widespread than previously thought. We report hereby a case of cutaneous T‐cell lymphoma in a 75‐year‐old woman, whose morphological and immunophenotypical features raises the differential diagnosis between cutaneous involvement by AITL and the recently described primary cutaneous T‐cell lymphoma with follicular helper‐phenotype.     

CD20 Positive T Cell Lymphoma Involvement of Skin

CD20 positive T cell lymphoma is a rare condition that is associated with the coexpressions of CD20 and T cell markers, such as, CD3, CD5, or UCHL-1. Positivity for CD20 in this tumor represents an aberrant immunophenotype, but the presence of monoclonal T cell receptor (TCR) gene rearrangements and negativity for immunoglobulin heavy chain gene rearrangement indicate that this tumor is a T cell lymphoma. The majority of cases of CD20 positive T cell lymphoma have been reported as immature peripheral T cell lymphoma not otherwise specified. However, we believe that this disease is likely to be re-listed as a new disease entity after its pathogenesis has been elucidated and more cases have been evaluated. Here, we present a case of peripheral T cell lymphoma coexpressing CD20 and T cell markers with a demonstrable TCR gene rearrangement, in a patient who had been misdiagnosed as having B cell type lymphoma 4 years previously. We hypothesize that in this case initially circulating normal CD20+ T cell subsets underwent neoplastic transformation and CD20 positive T cell lymphoma subsequently developed in the lymph node, and then recurred in the skin due to systemic disease or metastasized from the nodal disease.     

Cutaneous gamma‐delta T‐cell lymphoma with central nervous system involvement: report of a rarity with review of literature

Primary cutaneous gamma‐delta (γδ) T‐cell lymphoma is an extremely rare and aggressive variant of cutaneous lymphoma. Central nervous system (CNS) involvement, a rare finding, and hemophagocytic syndrome are two complications that are commonly fatal. We describe a 58‐year‐old patient presenting with skin plaque who subsequently developed subcutaneous nodules diagnosed as cutaneous T‐cell lymphoma (CTCL), clinically resembling ‘mycosis fungoides’. The patient was treated with repeat topical radiation therapies but had frequent relapsed disease. Approximately 4.5 years after, the patient presented with third and sixth cranial nerve palsies and was found to have CNS involvement by lymphoma per positron emission tomography—computed tomography (PET/CT) and a biopsy of foramen magnum. Phenotypically, the tumor cells were CD3(+)/CD4(?)/CD8(?)/CD7(+)/CD5(?)/CD30(?)/TCRαβ(?)/TCRγδ(+). Despite aggressive strategies taken, the patient expired 3 months after the diagnosis of the CNS lesion. A retrospective investigation proved the original CTCL to be γδ T‐cell in origin, confirming an indolent cutaneous γδ T‐cell lymphoma with eventual CNS manifestation. We present this case to draw attention to the entity, which can occasionally present with misleading histopathologic and clinical features. In addition, we provide a review of the literature to summarize clinical and pathologic features of the reported similar cases.     

36例皮肤天然杀伤细胞/T细胞淋巴瘤临床病理学研究

目的 探讨皮肤天然杀伤细胞(NK)/T细胞淋巴瘤临床病理学特点、与EB病毒的关系及预后。方法 收集2000—2010年北京大学医学部病理学系确诊为皮肤NK/T细胞淋巴瘤36例,分为原发与继发两组,分别观察临床病理学特点及与EB病毒的关系,并进行随访。结果 36例皮肤NK/T细胞淋巴瘤中,原发13例,继发20例,未能明确原发或继发3例。原发性与继发性皮肤NK/T细胞淋巴瘤均以男性好发,但两组男女性别比差异无统计学意义(P＞0.05)。与原发者相比,继发者发病年龄早(中位年龄,43.5比54岁,P＜ 0.05)、且临床上出现B症状(包括发热、盗汗或体质量下降)及多发皮损改变的频率较高(P值分别为＜0.05和＜0.01)。EB病毒在原发和继发病例中的检出率类似,分别为92.3％和85％。36例皮肤NK/T细胞淋巴瘤中位生存期为8个月,其中继发性皮肤NK/T细胞淋巴瘤中位生存期为6个月,明显短于原发者(18个月,x2= 6.074,P＜0.05)。结论 皮肤NK/T细胞淋巴瘤是一组与EB病毒密切相关、临床侵袭性强的肿瘤。但原发者较继发者发病年龄晚、预后较好。     

Cutaneous localization of plasmablastic multiple myeloma with heterotopic expression of CD3 and CD4: Skin involvement revealing systemic disease

Plasmablastic multiple myeloma is an uncommon morphological variant of multiple myeloma with aggressive clinical course and poor outcome. Its differential diagnosis includes plasmablastic lymphoma, a variant of diffuse large B‐cell lymphoma with frequent extranodal presentation, which usually affects immunosuppressed patients and is virtually indistinguishable from plasmablastic multiple myeloma on the basis of histology solely. Differential diagnosis relies on close clinical‐pathological correlation. Herein, the authors report a case of aggressive multiple myeloma occurring in a 48‐year‐old patient with pure plasmablastic morphology, expression of T‐cell markers CD3 and CD4, and cutaneous involvement as first presenting sign. Heterotopic expression of T‐cell markers has been described in literature for both plasmablastic multiple myeloma and plasmablastic lymphoma. The causative mechanisms underlying this aberrant phenotype have not yet been elucidated; nevertheless the possibility of this rare finding should be considered to avoid misinterpretations. Remarkably, despite occurring rarely, cutaneous involvement could be observed at an early stage or even be the first manifestation of disease in particularly aggressive forms of myeloma. As a consequence, the presence of cutaneous lesions should not favor a straightforward diagnosis of plasmablastic lymphoma. The importance of a correct differential diagnosis lies in its therapeutical implications.     

Subcutaneous Panniculitis‐Like T‐Cell Lymphoma with Hemophagocytic Syndrome in a Child

Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) characterized by subcutaneous infiltration of pleomorphic T‐cells of the α/β phenotype rarely affects children. Development of hemophagocytic syndrome (HPS) leads to a poor prognosis with this otherwise indolent lymphoma. We report a case of SPTCL in a 5‐year‐old child complicated by HPS treated successfully with combination chemotherapy. We discuss the potential pitfalls in reaching an early diagnosis and challenges in its management. Previously reported cases of SPTCL with HPS in children are briefly reviewed.     

Peripheral T cell lymphoma presenting as dermatomyositis-like eruption

Background: There are several conditions reported to mimic the cutaneous manifestations of dermatomyositis, including lymphoproliferative disorders. Objective: This case report presents an unusual case of peripheral T cell lymphoma mimicking dermatomyositis and discusses the clinical and pathologic features that distinguish it from dermatomyositis. Methods and Results: A 62-year-old woman presented with a two-month history of a progressive painful cutaneous eruption and interstitial infiltrates on chest x-ray. Skin biopsy revealed peripheral T cell lymphoma. The diagnosis was confirmed by lung biopsy. Conclusions: Although rare, a lymphoproliferative disorder must be included in the differential diagnosis of a cutaneous dermatomyositis-like eruption.     

Erythema multiforme‐like cutaneous lesions in monomorphic epitheliotropic intestinal T‐cell lymphoma: a rare case report

Monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL), also known as Type II enteropathy‐associated T‐cell lymphoma (EATL), is an aggressive peripheral T‐cell lymphoma. EATL generally presents in adults with gastrointestinal symptoms. Skin involvement is very rare, found only in approximately five percent of patients. The authors report a 67‐year‐old Asian male who presented with chronic diarrhea and developed erythema multiforme‐like cutaneous lesions. A skin biopsy revealed extensive pagetoid spread of atypical lymphocytes in the epidermis. The results of an immunohistochemistry test led to a diagnosis of MEITL. This report points to the need for dermatologists and dermatopathologists to consider a possible diagnosis of MEITL when encountering similar cases.     

Functional characterization of neurotensin receptors in human cutaneous T cell lymphoma malignant lymphocytes

Cutaneous T cell lymphomas are a clonal proliferation of CD4+ T lymphocytes primarily involving the skin. Mycosis fungoides is an epidermotropic CD4+ cutaneous T cell lymphoma, and a more aggressive form, Sezary syndrome, occurs when the malignant cells become nonepidermotropic. The role of neuropeptides in the growth and chemotaxis capacity of cutaneous T cell lymphoma cells remains unknown. In this report, we found that cutaneous T cell lymphoma cells, similarly to normal resting or activated peripheral lymphocytes, were able to bind neurotensin. We used an interleukin-2-dependent cutaneous T cell lymphoma malignant T cell line derived from cutaneous T cell lymphoma lesions in order to study the role of neurotensin in the proliferation and migration of these malignant cells. First, we determined that the malignant cells expressed neurotensin receptors on their cell membrane. Functional results indicated that neurotensin did not stimulate the growth of the cell line. In contrast, this neuropeptide inhibited the proliferation of the tumor cells in response to exogenous interleukin-2. Furthermore, we found that neurotensin enhanced both spontaneous and chemoattractant-induced migration of the malignant cells. This suggests that neurotensin in skin can play a role in the disease by locally limiting the growth of the cutaneous T cell lymphoma tumor cells in response to cytokines and by enhancing their chemotaxis capacity.     

Concurrent mycosis fungoides and precursor B cell lymphoblastic lymphoma in a 6-year-old child

We report a 6-year-old boy with mycosis fungoides on the dorsal surface of his left hand, a diagnosis supported by positive T cell receptor gamma gene rearrangement findings. Precursor B cell lymphoblastic lymphoma of the left orbit developed subsequently. He was treated with chemotherapy and remained under control.     

Nasal‐type extranodal natural killer/T‐cell lymphoma presenting with extensive leg ulcers

Primary cutaneous T‐cell lymphomas are rare and can be difficult to classify precisely. We present a case of extranodal natural killer (NK)/T‐cell lymphoma in a previously healthy, immunocompetent man who presented with extensive necrotic leg ulcers and disseminated skin nodules. Immunohistochemical studies revealed that the tumour cells were positive for CD3, CD30, granzyme B and T‐cell intracellular antigen‐1, and negative for CD5 and CD56, with positive staining for Epstein–Barr virus (EBV) RNA on in situ hybridization. A diagnosis of extranodal NK/T‐cell lymphoma was made, based on the presence of cytotoxic granules and positive EBV RNA staining. The patient was treated with a regimen of chemotherapy comprising corticosteroids, intravenous methotrexate, ifosphamide, L‐asparginase and etoposide with initial response.     

Nasal NK/T cell lymphoma presenting as a lethal midline granuloma

Nasal NK/T cell lymphomas are aggressive, locally destructive, midfacial, necrotizing lesions. The nonspecific clinical symptoms constitute a major stumbling block in the early diagnosis and management of these lymphomas. We report here a case of probable nasal NK/T cell lymphoma in an apparently healthy male that progressed rapidly in a short span of time and was managed subsequently with chemotherapy and external beam irradiation with which the lesion regressed.