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Competing Interests: Conflicts of interest The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Competing Interests: Conflicts of interest None declared.

Competing Interests: Conflicts of interest Dr Mangold reports personal fees from Kirin and grants from Elorac, MiRagen, Solagenix, DUSA/Sun Pharma, and Acetilion, outside the submitted work. Drs Costello, DiCaudo, Comfere, Sluzevich, Rule, Craig, Rosenthal, and Pittelkow and authors Besch-Stokes, Severson, Bhullar, Montoya, and Butterfield have no conflicts of interest to declare.

Primary cutaneous T-cell lymphomas (CTCLs) are defined as lymphomas with a T-cell phenotype that present in the skin without evidence of systemic or extracutaneous disease at initial presentation. CTCLs other than mycosis fungoides and Sézary syndrome (SS) account for approximately one third of CTCLs and encompass a heterogenous group of non-Hodgkin lymphomas, ranging from indolent lymphoproliferative disorders to aggressive malignancies with a poor prognosis. The spectrum of CTCLs continues to broaden as new provisional entities are classified. Given the morphologic and histologic overlap among CTCLs and other diagnoses, a thorough clinical history, physical evaluation, and clinicopathologic correlation are essential in the work up and diagnosis of these rare entities. This article will summarize the epidemiologic, clinical, pathologic, and diagnostic features of CTCLs other than mycosis fungoides and SS., Competing Interests: Conflicts of interest Dr Noor is on the Advisory Board for Kyowa Kirin. Dr Horowitz is a consultant for Janssen, Kura Oncology, Myeloid Therapeutics, Vividion Therapeutics, and C4 Therapeutics; a Principal Investigator for Daiichi Sankyo, Portola Pharmaceuticals, Forty Seven Inc, Trillium Therapeutics, and Aileron; and a Principal Investigator and consultant for Kyowa Kirin, Celgene, Seattle Genetics, Verastem, Takeda, and ADC Therapeutics. Dr Moskowitz is a consultant for Imbrium Therapeutics LP; a Principal Investigator for Miragen, Incyte, Bristol-Myers Squibb; and a Principal Investigator and consultant for Merck and Seattle Genetics. Authors Stoll and Oh and Drs Pulitzer, Willner, and Myskowski have no conflicts of interests to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Cutaneous lymphoma diagnosed after anti-tumor necrosis factor-α therapy (anti-TNF-α) has been reported in the literature, yet a clear link between both events remains elusive., Objective: To review our experience with cutaneous lymphoma diagnosed during or after the use of anti-TNF-α therapies., Methods: This is a multicenter retrospective study and a literature review., Results: A total of 22 cases, including 20 cutaneous T-cell lymphomas (CTCLs) and 2 cutaneous B-cell lymphomas, were identified. In the CTCL group, 75% of the patients received an anti-TNF-α agent for a presumed inflammatory skin condition. Mycosis fungoides and Sézary syndrome were the most common subtypes of CTCL diagnosed. Advanced disease (stage IIB to IVA) was commonly seen at time of diagnosis and required aggressive therapy, including stem cell transplant in 3 patients; 2 patients in whom cutaneous B-cell lymphomas was diagnosed had an indolent course. A total of 31 cases were gathered from a literature search., Limitations: This is a retrospective study., Conclusions: Our findings suggest that the disease of most of the identified patients was misdiagnosed as psoriasis or eczema; therefore, a comprehensive morphologic and molecular review of skin biopsy specimens and peripheral blood samples should be considered before initiation of anti-TNF-α therapy in patients with poorly defined dermatitis or atypical presentations of psoriasis., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Leonine facies (LF) is defined as displaying facial features similar to that of a lion with prominent convexities and furrowed creases. LF develops in a very small population of patients with cutaneous T-cell lymphoma., Objective: We aimed to study the clinicopathologic features and overall prognosis associated with LF in patients with mycosis fungoides and Sézary syndrome., Methods: We conducted a single-center retrospective study, reviewing 1338 patients with mycosis fungoides seen from 1987 to 2015 at a tertiary referral center for cutaneous T-cell lymphoma, and a systematic review of 14 patients in the literature., Results: We identified 10 patients with mycosis fungoides who developed LF. Folliculotropism was seen in all patients with LF who had facial biopsy specimens. Radiation was a beneficial therapy. Complete remission was achieved in 1 patient and overall 5-year survival was 26%. Systematic review of 10 additional patients showed that all patients with LF, including ours, had stage-IV disease and some degree of blood involvement, but not all met criteria for Sézary syndrome., Limitations: This was a retrospective study with a small sample size., Conclusion: LF is associated with stage-IV cutaneous T-cell lymphoma, is often accompanied by folliculotropism and blood involvement, and can be treated with local electron beam therapy., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: There is controversy regarding a potential increased risk of lymphoma in patients with atopic dermatitis (AD)., Objective: To assess the risk of lymphoma and the role of topical treatments in patients with AD., Methods: A systematic literature search and a separate meta-analysis were performed on case control and cohort studies., Results: Of the 3979 articles retrieved, 24 references met the inclusion criteria. In cohort studies, the risk of lymphoma was slightly increased, with a relative risk (RR) of 1.43 (95% confidence interval [CI], 1.12-1.81). In case control studies, no significant increased risk of lymphoma was found, with an odds ratio (OR) of 1.18 (95% CI, 0.94-1.47). Severity of AD was a significant risk factor. Highly potent topical steroids were associated with an increased risk of lymphoma. For topical calcineurin inhibitors (TCIs), a significant association between tacrolimus and mostly skin lymphoma was found in 1 study., Limitations: Confusion between severe AD and cutaneous T-cell lymphoma may account for part of the increased risk of lymphoma in patients with AD., Conclusion: This systematic literature review shows a slightly increased risk of lymphoma in patients with AD. Severity of AD appears to be a significant risk factor. The role of topical steroids and TCIs is unlikely to be significant., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Primary cutaneous diffuse large B-cell lymphoma, leg type (cDLBCL-LT) is a well-defined entity of cutaneous B-cell lymphoma affecting predominantly elderly patients, mostly women. The typical clinical presentation is characterized by solitary or multiple, rapidly growing plaques or tumors on 1 leg (rarely both legs)., Objective: We sought to describe a new clinical variant of cDLBCL-LT that deviates from the conventional one., Methods: Clinical, histopathologic, phenotypical, and molecular features of 3 cases of cDLBCL-LT presenting with patches or thin plaques were reviewed (all were women, aged 60, 62, and 87 years; lesions were located on the leg in all patients)., Results: These patients presented with patches or thin plaques that represented the first manifestation of cDLBCL-LT. All 3 patients reported a history of long-standing lesions (present for 6, 9, and 18 months, respectively). Histology revealed moderately dense, perivascular infiltrates of small lymphocytes admixed with variable numbers of large cells that were CD20(+), Bcl-2(+), and MUM-1(+)., Limitations: There were only a small number of cases., Conclusions: We reported an unusual clinical presentation of cDLBCL-LT that deviates from the conventional one and that represents a formidable diagnostic challenge. Biopsy specimens of unusual patches/thin plaques or annular lesions should be obtained from the legs of adult patients if the lesions do not respond to conventional treatment., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: With the exception of erythema migrans, Borrelia infection of the skin manifests much more commonly with B cell-rich infiltrates. T cell-rich lesions have rarely been described., Objective: We report a series of 6 patients with cutaneous borreliosis presenting with T cell-predominant skin infiltrates., Methods: We studied the clinicopathologic and molecular features of 6 patients with T cell-rich skin infiltrates., Results: Half of the patients had erythematous patchy, partly annular lesions, and the other patients had features of acrodermatitis chronica atrophicans. Histopathology revealed a dense, band-like or diffuse dermal infiltrate. Apart from small, well differentiated lymphocytes, there were medium-sized lymphocytes with slight nuclear atypia and focal epidermotropism. An interstitial histiocytic component was found in 4 cases, including histiocytic pseudorosettes. Fibrosis was present in all cases but varied in severity and distribution. In 5 patients, borrelia DNA was detected in lesional tissue using polymerase chain reaction studies. No monoclonal rearrangement of T-cell receptor gamma genes was found., Limitations: This retrospective study was limited by the small number of patients., Conclusion: In addition to unusual clinical presentation, cutaneous borreliosis can histopathologically manifest with a T cell-rich infiltrate mimicking cutaneous T-cell lymphoma. Awareness of this clinicopathologic constellation is important to prevent underrecognition of this rare and unusual presentation representing a Borrelia-associated T-cell pseudolymphoma., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Mycosis fungoides (MF) is a neoplasm of skin-homing CD4(+) helper T (TH) lymphocytes with dysregulation of TH1 and TH2 immunity. Diagnosis of MF is challenging, as there is significant morphologic overlap with other dermatologic entities., Objective: We investigated diagnostic utility of TH1- and TH2-specific markers, T-bet, and GATA-3, respectively, in MF and its reactive and neoplastic mimics., Methods: Immunohistochemical staining for CD3/T-bet and CD3/GATA-3 was performed on inflammatory dermatoses (n = 56), MF (n = 37), Sezary syndrome (SS; n = 8), and cutaneous anaplastic large cell lymphoma (C-ALCL; n = 14)., Results: Inflammatory dermatoses showed epidermal T cells predominantly expressing GATA-3, except psoriasis, which exhibited a mixed GATA-3/T-bet staining. In contrast, neoplastic T cells in patch stage MF showed markedly increased T-bet positivity with minimal GATA-3 expression. Plaque stage MF had a mixed T-bet/GATA-3 phenotype, whereas tumor stage MF and SS exhibited diffuse GATA-3 expression. C-ALCL lacked significant staining for both markers., Limitations: Sample size was relatively small., Conclusions: A predominance of T-bet(+) T cells in the epidermis support patch stage MF over dermatitis. A predominance of GATA-3(+) T cells in the dermis support CD30(+) MF with large cell transformation over C-ALCL. These stains do not allow distinction between dermatitis and cutaneous infiltrates of SS., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The literature on mycosis fungoides (MF) in children/adolescents is sparse., Objective: We sought to evaluate the characteristics of juvenile MF in a large cohort., Methods: Data were collected on all patients with MF, aged 18 years or younger at the time of clinicopathologic diagnosis, who attended the Rabin Medical Center Dermatology Department, Petach Tikva, Israel, between 1994 and 2012 and were followed up prospectively., Results: There were 50 patients (30 male; mean age 11.4 years at diagnosis); 18 (36%) had Fitzpatrick skin type IV or higher. All were given a diagnosis of early-stage disease (IA-IIA) except 1 (tumor stage, IIB). Eight had classic MF lesions only and 42 had other variants, alone or in combination; these were mainly hypopigmented MF (n = 29) and cases with subtle but clear clinicopathologic features of folliculotropic MF (FMF) (n = 18). Among the various skin-targeted therapies, psoralen plus ultraviolet A (systemic/bath) proved beneficial for FMF. During a follow-up period of 0.25 to 15 years (mean 4.5), 2 patients progressed from stage IA to IB or IIA., Limitations: Relatively short follow-up is a limitation., Conclusions: This case series shows that FMF is not uncommon in children and adolescents. It is characterized by more superficial clinical features and less heavy perifollicular lymphocytic infiltrates than adult FMF, and responds well to psoralen plus ultraviolet A. The prognosis of childhood FMF remains unclear., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Mycosis fungoides is the prototype of primary cutaneous T-cell lymphoma and is more common in the West than in the East, whereas nonmycotic primary cutaneous T-cell lymphoma is more frequent than mycosis fungoides among Asians. Nonmycotic primary cutaneous T-cell lymphomas comprise several categories of neoplasms and might pose diagnostic challenges because of the rarity of these lesions and overlapping features among certain entities. The authors recommend diagnostic approaches including histopathological evaluation, immunohistochemical markers, and ancillary studies. Diagnostic dilemma in certain entities and cases with atypical clinicopathological features are discussed., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Mycosis fungoides (MF) and Sézary syndrome (SS) comprise approximately 53% of cutaneous lymphomas. Both MF and SS may clinically and histologically mimic benign skin conditions, posing a diagnostic challenge to the dermatologist. Precise clinicopathologic correlation is necessary to support a diagnosis, especially in the early stages of disease. In addition to the identification of histopathologic criteria, ancillary studies, including the identification of CD4(+) T cells with aberrant immunophenotypes and T-cell receptor gene rearrangements within skin lesions and peripheral blood are used to support the diagnosis. Recent studies evaluating the pathogenesis of MF have found that the skin microenvironment, including immune cells, such as dendritic cells and reactive cytotoxic and regulatory T cells, plays a crucial supporting role in MF. The skin-homing ability of malignant T cells is the result of chemokines, cytokines, adhesion molecules, and defective apoptosis, and is believed to play a role in disease pathogenesis and progression. In addition, recent studies have also suggested that MF and SS arise from distinct memory T cell subsets and advanced/erythrodermic MF and SS may be distinguished by identification of certain molecules, including Programmed-Death-1., (Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Primary cutaneous aggressive epidermotropic CD8(+) T-cell lymphoma is a rare cytotoxic lymphoma characterized clinically by aggressive behavior and histologically by prominent epidermotropism of atypical CD8(+) lymphocytes. Despite the continuous addition of new case reports, no definite diagnostic criteria have been established, and an optimum treatment is still awaiting. Herein, we study and analyze the different clinical, histopathological, and immunohistochemical features described in the reported cases. Different therapeutic modalities and their impact on the prognosis of the tumor are also evaluated and presented. We propose two sets of diagnostic criteria. The first comprises constant clinical, histopathological, and immunohistochemical features that are always present in every case, and the combination of which is necessary for the diagnosis. The second set helps to avoid missing cases and includes variable features that may be present in some cases, and to which any emerging finding could be added. Although different therapeutic options have been used, either as single agents or in combinations, there is no standard therapy for primary cutaneous aggressive epidermotropic CD8(+) T-cell lymphoma and the tumor still represents a therapeutic challenge with very poor prognosis., (Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Angioimmunoblastic T-cell lymphoma (AITL) accounts for 18% of peripheral T-cell lymphomas worldwide. Skin involvement occurs in up to 50% of patients but poses a diagnostic dilemma because of the limited number of reported cases and subsequent lack of established diagnostic criteria., Objective: The purpose of this review is to examine common clinical, histologic, and molecular findings in cases of AITL with the hope of improving the diagnostic accuracy of this challenging condition., Methods: We present a case of AITL and conducted a review of the literature., Results: The common clinical and histologic features in cases of AITL are nonspecific. However, newer immunohistochemical stains and gene rearrangement studies appear very promising at improving diagnostic capabilities., Limitations: There was a paucity of reported cases of AITL in the literature, and this review is retrospective., Conclusion: AITL presents with nonspecific clinical and histologic findings, but immunohistochemical stains and gene rearrangements can help establish the diagnosis., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Lymphoma-associated hemophagocytic syndrome (LAHS) is a rare clinicopathological entity. It has been described with primary cutaneous lymphomas, mostly of the subcutaneous panniculitis-like T-cell type, and only once with cutaneous T-cell lymphoma (CTCL)., Methods: We report the cases of 5 patients with epidermotropic CTCL who developed LAHS and died shortly thereafter. Unlike LAHS associated with systemic lymphomas, these CTCL-associated LAHS were late events, occurring several years after the initial lymphoma diagnosis., Limitations: The small number of patients reported renders definite conclusions difficult. Further reports would be needed to confirm our statements., Conclusion: LAHS is probably underdiagnosed in CTCL patients with acute inflammatory symptoms suggestive of infections but should be considered, especially when cytopenia and elevated triglyceride and ferritin levels are present., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

We describe a patient who presented with Epstein-Barr virus-positive tumor-stage primary cutaneous lymphoma. Our patient had previously been treated with oral methotrexate for long-standing rheumatoid arthritis. Tissue analysis revealed large tumor cells that were surface CD2- and CD3-positive; T-cell-restricted intracellular antigen-positive; CD56-, CD20-, and CD30-negative; and stained positively for Epstein-Barr virus. Our case is noteworthy for several reasons. Although the presence of rheumatoid arthritis and therapy with methotrexate are putative risk factors for the development of immune suppression-related and Epstein-Barr virus-related lymphomas, the vast majority of lymphomas in this setting are of B-cell origin, and rarely are these primary cutaneous in nature. In addition, our patient's tumor displayed an unusual phenotype, with immunophenotypic features suggestive of an atypical natural killer-/T-cell lymphoma. Methotrexate was withdrawn, and our patient was successfully treated with local radiotherapy. She has remained in complete remission 28 months since diagnosis.

The definitive diagnosis of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL) is difficult because a cumulative set of information is typically required: clinical features, histopathology, and special diagnostic tests (typically immunophenotyping and T-cell receptor gamma [TCRgamma] gene rearrangement). Fresh tissue is not always available for the special tests. We report a simple and readily available procedure evaluating the staining pattern on formalin-fixed, paraffin-embedded skin that can help with the diagnosis of patch/plaque stage MF. We reviewed 92 cases of MF or probable MF that had clinical information, immunophenotyping and TCRgamma gene rearrangement studies and that had been evaluated in our multidisciplinary lymphoma conference. We used antibodies to the isoforms of CD45, CD45RO for mature T cells and CD45RB for subsets of T cells. When atypical CD45RB-positive/CD45RO-negative cells were seen in nonspongiotic epidermis, the individuals had a high cumulative clinical and histologic score for MF. In contrast, 15 cases of known contact dermatitis showed a reactive pattern of both CD45RB- and CD45RO-positive cells in spongiotic epidermis. We compared the epidermal CD45RB-positive/CD45RO-negative staining pattern with CD7 deficiency by immunophenotyping and TCRgamma gene rearrangement, two commonly used methods in the diagnosis of MF. The epidermal CD45RB-positive/CD45RO-negative staining pattern is comparable and may be better in equivocal cases of possible MF. Therefore immunostaining for CD45RB and CD45RO on paraffin sections is a simple, reliable, and convenient modality in the diagnosis of MF.

In the newly revised World Health Organization (WHO)-European Organization for Research and Treatment of Cancer (EORTC) consensus classification for cutaneous lymphomas, cutaneous gamma/delta T-cell lymphoma (CGD-TCL) has been included as a provisional entity. This type of lymphomas, when involving the subcutaneous fat, can mimic both clinically and histologically other more indolent conditions, such as subcutaneous panniculitic T-cell lymphomas (SPTCL) and lupus erythematosus profundus (LEP), and multiple biopsies may be needed to obtain a correct diagnosis. A good correlation of the clinical data with the histopathology and immunohistochemistry are required for diagnosis. Herein, we describe a patient whose initial histopathologic findings ressembled LEP but presented an aggressive clinical course. A new biopsy was performed during the follow-up, and a final diagnosis of CGD-TCL was made.

Background: Mycosis fungoides (MF) is an epidermotropic cutaneous T-cell lymphoma in which the tumor cells express a mature T-helper memory phenotype, ie, CD3(+), CD4(+), CD8(-), CD45RO(+), with a T-cell receptor (TCR) of the alpha/beta heterodimer. A minority of patients have an unusual immunohistochemical profile consisting of a CD4(-), CD8(+) mature T-cell phenotype. An aberrant CD4/CD8 double-negative (DN) immunophenotype in patients with early MF has rarely been reported., Objectives: We sought to evaluate the frequency of CD4/CD8 DN immunophenotype in patients with early MF, and to study their clinical, histopathologic, and immunohistochemical features, and the course of their disease., Methods: Our departmental archives were searched for patients with early-stage MF and CD4/CD8 DN immunophenotpye., Results: Of the 140 patients with early MF immunophenotyped in our laboratory, 18 (12%) showed CD4 and CD8 expression in less than 10% of their intraepidermal T cells on fresh-frozen and paraffin-embedded samples. The group included 13 male and 5 female patients; 14 adults and 4 children; and 15 Jews and 3 Arabs. In all, 8 had classic MF and 10 had unusual clinical variants (5 hypopigmented, 3 localized, 1 ichthyosiform, 1 purpuric). All received skin-targeted therapies and all had an indolent course (mean follow-up 3.5 years). Histopathology revealed early MF. Results of immunohistochemical analysis of the intraepidermal lymphocytes were as follows: CD3(+), CD4(-), CD8(-) in all patients; CD7(-) in all of 17; CD45RO(+) in 15 of 16; T-cell-restricted intracellular antigen-1(+) in 11 of 15; CD30(+) in 2 of 16; and CD56(+) in 2 of 16. A betaF1(+)/delta(-) phenotype, indicating a TCR of the alpha/beta heterodimer, was found in 8 of 16; betaF1(-)/delta(+) phenotype, indicating a TCR of the gamma/delta heterodimer, in 1 of 16; betaF1(-)/ delta(-) in 5 of 16; and no determinable phenotype in 2 of 16. The TCR gamma gene was clonally rearranged in 10 of 16 patients., Limitation: This was a single-center case series., Conclusions: There is a subgroup of patients with early MF that exhibit a CD4/CD8 DN immunophenotype. In our region, this aberrant immunophenotype is not as rare as reflected in the literature, is overrepresented in the unusual clinical variants of MF, and does not seem to have prognostic significance. Like CD4(+) MF, the tumor cells represent memory T cells and in many cases express alpha/beta TCR, but unlike CD4(+) MF, they have a mostly cytotoxic phenotype. We suggest that CD4/CD8 DN MF should be recognized as another immunohistochemical variant of this lymphoma.

Lymphoma occurring after organ transplantation has been well described. The majority of cases are B-cell lymphomas and are usually associated with Epstein-Barr virus. Only a minority of posttransplant lymphomas are of T-cell origin, and primary cutaneous T-cell lymphoma (CTCL) is extremely rare. In this article, we report a case of cutaneous peripheral T-cell lymphoma, pleomorphic CD30+ large-cell type, and review the literature relating to posttransplant primary CTCL. Of the 23 cases of posttransplant primary CTCL, 5 patients had erythrodermic disease, and 8 had primary cutaneous anaplastic large cell lymphoma. In addition, there are two cases of mycosis fungoides, one case of subcutaneous panniculitis-like T-cell lymphoma, one case of CD30+ lymphomatoid papulosis, and 6 cases of peripheral T-cell lymphoma, of which 3 were CD30+ large cell lymphomas. Seventeen cases had renal transplants and the majority received both cyclosporine and azathioprine. No consistent viral association was noted among these cases. The sex ratio was 18:5 (male/female), and the mean age at diagnosis was 53 years. Mean time from transplantation to diagnosis is 6.4 years and mean survival time from diagnosis is 14.5 months. The prognoses normally associated with particular subsets of CTCL do not apply in the posttransplant setting.

We describe 2 adolescent boys with facial swelling and/or subcutaneous nodules and fever. Extensive evaluation, including several biopsy specimens, led to a diagnosis of subcutaneous panniculitic T-cell lymphoma, an entity rarely seen in children. Both patients were treated with oral cyclosporine in an effort to suppress the cytokine release from T-cells that has been thought to induce the hemophagocytic syndrome. The patients responded dramatically to cyclosporine treatment with defervescence of the fever and reduction in number and size of the subcutaneous nodules. Subsequent therapy with multidrug chemotherapy achieved complete remission in the first patient. This report suggests the value of cyclosporine as a first-line agent coupled with chemotherapy in the treatment of patients with subcutaneous panniculitic T-cell lymphoma. A clinicopathologic review of 8 described pediatric cases of subcutaneous panniculitic T-cell lymphoma is also presented.

Secondary syphilis most commonly presents with a papulosquamous eruption that involves the palms, soles, and mucous membranes. The papulonodular variant has only been described 11 times in the literature. We describe a case of papulonodular secondary syphilis presenting as an atypical lymphoid hyperplasia suggestive of cutaneous lymphoma.

Small to medium-sized pleomorphic cutaneous T-cell lymphomas represent a provisional entity in the new European Organization for Research and Treatment of Cancer classification. We describe 3 patients with a localized and outstanding stable variant of this tumor. A median follow-up period of 50 months did not reveal any spread into regional lymph nodes or to distant sites in any patient.

Unlabelled: Accurate evaluation of patients with suspected or known cutaneous lymphoma requires the integration of many sources and types of information, including clinical evaluation, microscopic analysis of tissue, immunophenotyping, gene rearrangement studies, clinical staging, and longitudinal observation. Diagnoses should be based on knowledge of specific lymphoma types as described in modern classification systems. Management of patients with cutaneous lymphoma requires collaboration among dermatologists, dermatopathologists, hematopathologists, and medical, surgical and radiation oncologists. (J Am Acad Dermatol 2002;46:325-57.), Learning Objective: At the conclusion of this learning activity, participants should better understand how to evaluate and manage patients for suspected or established lymphoma of the skin. Components include the clinical history and physical examination, optimal biopsy and tissue handling, interpretation of pathology and adjunctive test results, clinicopathologic correlation, and therapy. Participants should also understand the basis for establishing a specific diagnosis of cutaneous lymphoma based on current classification and staging.

We report 6 cases of pseudoepitheliomatous hyperplasia (PEH) mimicking squamous cell carcinoma in association with an atypical CD30+ dermal infiltrate. Three patients had lymphomatoid papulosis type A, and 3 patients had cutaneous CD30+ lymphoma. All 6 cases showed histologic evidence of PEH with keratinocyte atypia. In 4 cases there was significant atypia to prompt a diagnosis of squamous cell carcinoma. Three of these received treatment with wide local excision and 2 had been engrafted. Immunohistochemical staining for epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) showed similar expression in lesional and perilesional skin. Epidermal growth factor receptor (EGFR) expression by the proliferating epithelium was similar to that of the suprabasal adjacent normal epidermis. There was no aberrant expression of EGF, TGF-alpha, and EGFR by atypical lymphocytes. These cases demonstrate that PEH associated with CD30+ lymphoproliferative disease may closely resemble squamous cell carcinoma, thereby leading to inappropriate diagnosis and treatment.

We report 3 patients with granulomatous cutaneous T-cell lymphoma (CTCL) who showed necrobiosis histologically with palisading granulomas. Although granulomatous change may be present in up to 4% of cases of CTCL, necrobiosis is rare. Misdiagnosis may occur if epidermotropism is minimal or if atypical cells are masked by the granulomatous infiltrate. T-cell receptor gene analysis confirmed the presence of clonal T-cell populations in lesional skin from all 3 cases.

Syringolymphoid hyperplasia with alopecia is an uncommon chronic dermatosis of which 9 cases have been reported, with or without follicular mucinosis or cutaneous T-cell lymphoma. We report a patient with cutaneous T-cell lymphoma and syringolymphoid hyperplasia and follicular mucinosis and review the previously reported cases. All reported cases with syringolymphoid hyperplasia were men (10 of 10), with the clinical findings of alopecia (9 of 10) and anhidrosis (3 of 10). Only 3 of 10 cases had associated follicular mucinosis. Of the 7 cases investigated, 6 were found to hve cutaneous T-cell lymphoma. Three patients were not investigated for cutaneous T-cell lymphoma. Although syringolymphoid hyperplasia can be idiopathic, it can also reflect a syringotropic cutaneous T-cell lymphoma. Careful follow-up with a biopsy of persistent lesions is recommended to evaluate for the presence of lymphoma.

Background: We attempted to determine the frequency and clinical relevance of antinuclear antibody (ANA) testing and positive ANA test results in patients with cutaneous T-cell lymphoma (CTCL)., Methods: A retrospective chart and computer record review was conducted to determine the frequency of ANA testing in CTCL patients and the rate of seropositivity. Patients with a positive ANA were further examined to define possible explanations of the positive test., Results: Of 381 patients with CTCL, 66 (17%) had ANA tests; 8 of these (12.1%) were found to have an ANA titer greater than or equal to 1:40. Of patients with a positive ANA test, one was found to have chronic cutaneous lupus erythematosus histologically and clinically mimicking CTCL. Others were found to have a comorbid connective tissue disorder, some had apparent drug-induced antinuclear antibodies, and some had no identifiable reason for a positive ANA test., Conclusion: ANA seropositivity does not appear to be increased in CTCL patients, and the ANA test remains a useful screening tool for differentiating between CTCL and connective tissue disorders.

Two patients with nasal lymphoma were seen with cutaneous lesions. Multiple biopsy specimens, immunohistochemical techniques, and gene rearrangement studies were required to establish the diagnosis.

Background: The serum concentration of soluble alpha chain of the interleukin-2 receptor (sIL-2R) correlates with tumor burden in cutaneous T-cell lymphoma (CTCL). Therefore the sIL-2R level may be useful to monitor the condition of patients treated with extracorporeal photopheresis or other treatments., Objective: Our goal was to determine the utility of serum sIL-2R as a test in monitoring of patients with advanced CTCL., Methods: Serum sIL-2R was measured serially in 36 patients with advanced CTCL treated with extracorporeal photopheresis and other modalities (interferon alfa, methotrexate, topical nitrogen mustard, electron beam)., Results: Serum concentrations of sIL-2R as well as lactate dehydrogenase (LDH) correlated strongly with lymph node size, but only sIL-2R correlated significantly with the severity of skin manifestations in erythrodermic patients. In addition, serum sIL-2R, but not LDH, was significantly higher in patients with nodal involvement. The level of sIL-2R also was significantly higher in patients with large-cell transformation in the skin or lymph nodes compared with patients without transformed disease. During treatment, serum concentrations of both serum sIL-2R and LDH correlated with changes in clinical status, but only sIL-2R showed statistically significant differences in mean levels for different relative global response scores. Pretreatment levels of both sIL-2R and LDH correlated significantly with survival, but only sIL-2R retained significance when both were entered into the Cox proportionate hazards model., Conclusion: The concentration of serum sIL-2R correlates well with disease status and is more useful than LDH or Sézary cell counts to monitor clinical change in patients with advanced CTCL. Moreover, our data suggest that sIL-2R is produced at a relatively low rate by tissue-based lymphoma cells, and that large-cell transformation in CTCL results in marked increase in sIL-2R production in some patients.

We describe a patient with severe fatal histiocytic phagocytic panniculitis caused by a pleomorphic T-cell lymphoma. Analysis by polymerase chain reaction revealed clonality for both the T-cell receptor gamma-chain gene and the immunoglobulin heavy-chain gene. We also review 44 reported cases of primary or secondary lymphoma affecting the subcutaneous fat.

The first reported case of phenytoin-induced generalized nodular cutaneous pseudolymphoma without symptoms of the phenytoin hypersensitivity syndrome is presented. Despite the malignant histologic appearance of the dermal infiltrate, T-cell receptor gene rearrangement studies did not demonstrate monoclonality. The cutaneous nodules resolved within 2 weeks after discontinuation of phenytoin therapy. The literature is reviewed with regard to the spectrum of cutaneous reactions to phenytoin and particularly with regard to the occurrence of lymphoma, pseudolymphoma, and phenytoin hypersensitivity syndrome. We suggest the use of T-cell receptor gene rearrangement studies in similar situations of phenytoin hypersensitivity syndrome and lymphadenopathy. A brief period of discontinuation of the drug will demonstrate the regression associated with benign lymphoproliferation and will forestall needless treatment.

Cutaneous T-cell lymphoma is a malignancy of T cells that express a clone-specific heterodimer T-cell receptor for antigen. The second recognized case of an epidermotropic malignancy of T-cells expressing gamma/delta T-cell receptor-expressing cells is reported. The immunophenotype of the malignant T-cells was CD3+, CD2+, CD7+, gamma/delta T-cell receptor+, CD4-, CD8-, and alpha/beta T-cell receptor-. The clinical features were remarkable for extreme epidermotropism with a scant dermal lymphomatous infiltrate. Profound keratinocyte necrosis occurred in areas of malignant skin infiltrates. Despite cutaneous lesions covering more than 50% of the skin surface of the patient, no adenopathy or splenomegaly was detected. The intense epidermotropism of this patient's gamma/delta T-cell receptor-expressing cells and the putative cytolytic properties of CD4- CD8- gamma/delta contributed to the destruction of epidermis. Remission was induced with a combination of electron beam and extracorporeal photochemotherapy.

Background: The clonotypic 90 kd Ti heterodimer of the human T-cell antigen receptor is composed of two distinct chains (alpha beta or rarely tau delta) that result from the recombination of variable (V), constant, joining, and, in the case of beta chains, additional diversity regions., Objective: The variable region expression of human cutaneous T-cell lymphoma (CTCL) was studied., Methods: Biopsy specimens from 13 patients with CTCL (7 plaque, 3 tumor stage, 3 Sézary syndrome) were examined immunohistochemically by a panel of seven commercially available monoclonal V-region antibodies., Results: Two patients had significant anti-V-region staining. One patient with Sézary syndrome had two lesions, subjected to biopsy 4 months apart, that reacted with beta V5(a), a specificity previously documented by flow cytometry of leukemic cells. A patient with plaque-stage CTCL, negative for T-cell gene rearrangement by Southern blot, demonstrated reactivity with beta V5(c) largely limited to epidermotropic lymphocytes., Conclusion: Panels of V-region antibodies should be useful reagents for diagnosis and follow-up of CTCL.

Central nervous system disease in cutaneous T cell lymphoma is uncommon and is usually not considered in standard therapeutic regimens. We report three patients who had cutaneous T cell lymphoma with involvement of the central nervous system and review the cases of 28 such patients reported in the literature. Potential risk factors, the reliability of various diagnostic tests, and potential therapeutic modalities are discussed.

Between 1970 and 1984 in Rochester, Minnesota, rare skin cancers developed in 15 local residents: cutaneous T cell lymphoma (six subjects), dermatofibrosarcoma protuberans (four), adenocarcinoma of sweat glands (two), Merkel cell carcinoma (one), liposarcoma (one), and extramammary Paget's disease (one). These cases were identified through a unique computerized retrieval system that is maintained at the Mayo Clinic for the population of Rochester, Minnesota. The annual incidences of these cancers in the Rochester population were 0.9, 0.5, 0.3, 0.2, 0.2, and 0.2 per 100,000 residents, respectively (standardized to 1980 U.S. population). To our knowledge, this is the first report of the incidences of these rare skin cancers in a well-defined population.