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.     

Epstein–Barr virus‐associated T‐cell lymphoproliferative disorder affecting skin and lung in an elderly patient

A 70‐year‐old man presented with papular skin lesions and was diagnosed with Epstein–Barr virus (EBV)‐associated T‐cell lymphoproliferative disorder (T‐LPD). The patient showed infiltration of a large number of EBV‐encoded RNA‐positive T cells in the skin and lung, presence of EBV load in the peripheral blood, and expansion of clonal EBV‐infected γδ T cells and CD8⁺ T cells in the blood and skin, as assessed by EBV‐terminal repeat Southern blot, T‐cell receptor polymerase chain reaction and flow cytometric analyses. In the Japanese or East Asian fatal cases of EBV‐associated T/natural killer (NK)‐LPD, there are two peaks in age at death, approximately 20 years and 60 years. The former age group is associated with chronic active EBV infection (CAEBV), and the latter group typically suffers from extranodal NK/T‐cell lymphoma. Our case is characterized not only by the unique skin and lung manifestations but also the late onset age of the disease, indicating that the skin manifestation of CAEBV can be seen even in elderly patients.     

CD30 expression in a case of intravascular large B‐cell lymphoma,cutaneous variant

Intravascular large B‐cell lymphoma (IVLBCL) is one of the rarest B‐cell non‐Hodgkin lymphomas (NHL), with an aggressive clinical behavior and a poor prognosis; in fact, its treatment is still an unmet clinical need, with a 3‐year overall survival (OS) rate of 60% to 81%, and a central nervous system relapse rate of 25%. It usually presents as a widespread disease at diagnosis, with multi‐organ involvement. Previously considered as a diffuse large B‐cell lymphoma variant, it now represents a different extranodal large B‐cell lymphoma entity in the last WHO Classification of tumors of hematopoietic and lymphoid tissues. We hereby describe the case of an 84‐year‐old Italian woman with an IVLBCL, cutaneous variant, who suffered from early relapse after R‐COMP chemotherapy regimen, and was therefore treated with a palliative metronomic chemotherapy. Interestingly, neoplastic cells showed CD30 expression at relapse. CD30 positivity has never been reported in this disease so far, and its expression is known to be involved in NF‐kB activation. CD30 expression may be further studied as for prognostic and therapeutic significance; in fact, new therapeutic strategies, such as antibody‐drug conjugate targeting CD30, are now available.     

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.     

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.     

Methotrexate‐associated EBV‐positive vasculitis in the skin: a report of two cases simulating rheumatoid vasculitis

Rheumatoid vasculitis (RV) is one of the most serious extra‐articular complications of rheumatoid arthritis (RA), generally treated with a high dose of immunosuppressive drugs. Recently, we encountered two cases of ulcerative vasculitis in methotrexate (MTX)‐prescribed RA patients, which simulated RV; however, Epstein–Barr virus (EBV)‐encoded RNA in situ hybridization on their skin biopsies revealed many EBV‐positive lymphocytes (over 50 cells/high‐power field) within the vessel walls and perivascular stroma, which led us to the diagnosis of EBV‐related vasculitis instead of RV. Subsequently, both ulcers regressed after the discontinuation of MTX and no recurrence was noted during the follow‐up period. To prevent unnecessary treatment, EBV‐positive vasculitis should be added in the differential diagnosis of lymphocytic vasculitis observed in MTX‐administered RA patients.     

Acneiform primary cutaneous CD4‐positive small/medium pleomorphic T‐cell lymphoma with prominent necrosis

Primary cutaneous CD4‐positive small/medium pleomorphic T‐cell lymphoma (SMPTCL) is an indolent form of cutaneous lymphoma that usually presents in solitary fashion and is histopathologically characterized by nodular infiltration of small‐ to medium‐sized pleomorphic T‐cells. We report the case of a patient who presented with a 5‐year history of acneiform lesions on his face. Histopathologic examination of two lesions revealed a nodular infiltrate of small to medium‐sized lymphocytes with necrosis in the dermis. The proliferating cells were positive for CD2, CD3 and CD4 and negative for CD8, CD30 and CD56. They were positive for TIA‐1 and negative for perforin and granzyme B. The Ki67 proliferation index was approximately 10%. The neoplastic cells expressed programmed death‐1 and lacked expression of CXCL‐13, bcl‐6 and CD10. In situ hybridization for Epstein–Barr virus‐encoded RNA yielded a negative result. T‐cell receptor gene rearrangement showed identical T‐lymphocyte monoclonality in both lesions. In brief, we report a rare case of acneiform SMPTCL with prominent necrosis.     

Cutaneous involvement of pre‐existing Rosai–Dorfman disease via post‐herpetic isotopic response

We report the case of a patient with a long‐standing history of extranodal, sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) and no evidence of original cutaneous involvement as well as a history of herpes zoster of the left flank with post‐herpetic neuralgia who went on to develop multiple, round‐to‐oval, red‐brown, atrophic macules and thin papules at the sites of herpes zoster scars on the left flank. Histopathology showed a dense nodular infiltrate of lymphocytes with some plasma cells and numerous large pale‐staining histiocytes (S100+/CD68+), consistent with Rosai–Dorfman disease. This case showed exclusively cutaneous involvement, as demonstrated by otherwise normal physical examination, laboratory evaluation and imaging. This is the second reported case of Rosai–Dorfman disease occurring at the site of zoster scars, and to our knowledge this represents the first case report of cutaneous involvement of pre‐existing Rosai–Dorfman disease via post‐herpetic isotopic response (Wolf's isotopic response).     

Epstein–Barr virus involvement in the pathogenesis of hydroa vacciniforme: an assessment of seven adult patients with long‐term follow‐up

Background Hydroa vacciniforme (HV) is a chronic papulovesicular photodermatosis of childhood, with some cases persisting through adulthood. In children, the Epstein–Barr virus (EBV) has been detected in typical HV and in HV evolving into natural killer/T‐cell lymphoma. No exploration of EBV infection has been performed in adult patients with HV with long‐term follow‐up. Objectives To assess EBV infection systematically in blood and in experimentally photoinduced lesions in adult patients with HV. Methods Repeated tests for EBV DNA blood load using real‐time polymerase chain reaction (PCR) and serological EBV tests were performed in seven adult patients with long‐term follow‐up. Skin samples from phototest‐induced lesions and surrounding normal skin were studied using PCR, in situ hybridization and electron microscopy. ZEBRA protein was detected using immunostaining. Thirty‐five patients with other photosensitive disorders were included as controls. Results The EBV DNA blood load was strongly positive in the seven patients with HV and negative in 34 of 35 of the patients with other photosensitive disorders (P < 0·001). The levels were higher in photosensitive patients with HV than in patients with HV in clinical remission. Ultrastructurally, viral particles were detected in lymphocytes and also in keratinocytes in three experimentally phototest‐induced lesions; they were not found in the surrounding normal skin. ZEBRA protein was also detected in phototest‐induced lesions, but not in the surrounding normal skin. Conclusion EBV is involved in HV pathogenesis and persists in adult patients with HV. A positive EBV DNA load, specific to HV in the spectrum of photosensitive disorders, might be a useful biomarker in HV.     

CD20‐Positive nodal natural killer/T‐cell lymphoma with cutaneous involvement

CD20‐positive natural killer (NK)/T‐cell lymphoma is extremely rare. We describe a case of a CD20‐positive nodal NK/T‐cell lymphoma with cutaneous involvement in a 32‐year‐old man. The patient presented with fever, night sweats, right inguinal lymphadenopathy and multiple violaceous to erythematous nodules and plaques on the back and bilateral legs. Immunohistochemical analysis showed diffusely and strongly positive staining for CD3, CD3 epsilon, CD43, CD56, TIA‐1 and CD20 but negative staining for other B‐cell markers, including CD79a and PAX‐5 and T‐cell markers CD5 and CD7. The tumor cell nuclei were diffusely positive for Epstein–Barr virus‐encoded RNA in situ hybridization. A partial clinical response was observed after chemotherapy, indicated by the decreased size of the lymph nodes and skin lesions. It is a diagnostic challenge to deal with lymphoma cells that present with the surface proteins of both T‐ and B‐cells.     

Signet‐ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next‐generation sequencing

Signet‐ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85‐year‐old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet‐ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E‐cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next‐generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.     

Skin involvement as the first symptom of rapidly progressive ALK‐positive systemic anaplastic large cell lymphoma

Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T‐cell non‐Hodgkin lymphomas that are characterized by CD30 expression. Anaplastic lymphoma kinase (ALK)‐positive ALCL is a type of sALCL that commonly involves lymph nodes and extranodal sites. Skin involvement usually presents as tumours, nodules and ulcers. We describe an unusual case of ALK‐positive ALCL in an 11‐year‐old Chinese boy, who initially presented with skin eruption with rapid progression and poor prognosis. This case emphasizes the value of clinical factors to predict the prognosis of ALK‐positive sALCL, and we recommend close collaboration between dermatologists, pathologists and haematologists/oncologists to assure the correct diagnosis and treatment.     

Characteristics of primary cutaneous lymphoma according to WHO‐EORTC classification in Korea

Background.  Primary cutaneous lymphoma (PCL) is an extranodal non‐Hodgkin lymphoma with primary involvement of the skin. Epidemiological data on PCLs according to the World Health Organization/European Organization for Research and Treatment of Cancer classification (WHO‐EORTC) has not been investigated in Korea to date. Aim.  To evaluate the demographic characteristics, clinical and histological features, and survival data of patients with PCL according to the WHO‐EORTC classification. Methods.  In total, 93 patients with PCL were retrospectively identified from an extensive review of medical records over a 16‐year period. Results. The tumours found included primary cutaneous CD30+ lymphoproliferative disorders, extranodal natural killer/T‐cell lymphoma and primary cutaneous diffuse large B‐cell lymphoma. We found that 81.6% of the patients had primary cutaneous T‐cell and natural killer‐cell lymphoma, and 16.2% had primary cutaneous B‐cell lymphoma, with 2.2% having precursor haematological neoplasms. The median age was 52 years (range 3–95) and the male : female ratio was 1 : 1.16. The 5‐year survival rate was 92.5%. Conclusions.  The incidence rates of many PCL subtypes in Koreans differ from those of other countries.     

Dermal infiltrates of cutaneous T‐cell lymphomas with epidermotropism but not other cutaneous lymphomas are abundant with langerin+ dendritic cells

Background The Langerhans cell (LC) hypothesis suggests that cutaneous T‐cell lymphomas (CTCL) are diseases of chronic T‐cell stimulation by LC‐mediated antigen presentation. Objective To investigate a broad panel of CTCL and cutaneous B‐cell lymphomas (CBCL) for the spatial association of langerin⁺ dendritic cells (DC) with T and B cells in the skin, respectively. Methods Fifty‐five specimens of CTCL and 10 of CBCL were double‐stained with monoclonal antibodies against langerin and CD3 or CD20, respectively, and evaluated by confocal laser scan microscopy. Results Dermal infiltrates in mycosis fungoides (n = 38), primary cutaneous CD4+ small/medium‐sized pleomorphic T‐cell lymphoma (n = 3) and primary cutaneous peripheral T‐cell lymphoma, unspecified (n = 3) were characterized by a high frequency of dermal langerin⁺ DCs. These cells were exclusively present in the malignant infiltrates. No direct co‐localization of CD3 and langerin could be resolved. Dermal langerin⁺ cells were detected only in one of six primary cutaneous anaplastic large cell lymphomas (C‐ALCL), characterized by epidermotropism. In other C‐ALCL cases (five of six), in lymphomatoid papulosis (n = 3), subcutaneous panniculitis‐like T‐cell lymphoma (n = 2), and all variants of CBCL no dermal langerin⁺ DCs could be found. Conclusions Langerin⁺ DCs are abundant in the dermal infiltrates of T‐cell lymphomas with specific involvement of the epidermis. This might indicate that immature LC and neoplastic T cells interact and gives rise to further studies to characterize the phenotype of the langerin⁺ cell population described here and its role in the pathology of CTCL.     

Cutaneous peripheral T-cell lymphoma of cytotoxic phenotype mimicking extranodal NK/T-cell lymphoma

Cutaneous peripheral T-cell lymphoma unspecified is a rare neoplasm that is infrequently associated with Epstein-Barr virus (EBV) infection. In contrast, extranodal natural killer (NK)/T-cell lymphoma, although also rare, is known to be strongly associated with EBV and occurs most commonly in the nasal region. We report the case of a 55-year-old male who presented with fever and an indurated cutaneous plaque with ulceration. This cutaneous neoplasm showed diffuse dermal lymphomatous infiltration and tumor necrosis, with neoplastic cells expressing CD2, cytoplasmic CD3 (CD3ε), CD8, CD16, CD30, T-cell intracellular antigen-1, and granzyme B but not CD56, BF1, or T-cell receptor (TCR) δ1. Furthermore, the tumor cells were noted to be diffusely positive for EBV by in situ hybridization. A monoclonal TCR gene rearrangement was demonstrated. The disease showed an aggressive clinical course, and the patient died within 3 weeks of diagnosis without complete staging or chemotherapy. According to the 2005 World Health Organization/European Organization for Research and Treatment of Cancer scheme for cutaneous lymphoma and the 2008 WHO classification for lymphoid neoplasms, our case would have been classified as a nasal type extranodal NK/T-cell lymphoma with T-cell lineage. However, the expressions of CD8 and CD16, in addition to a monoclonal TCR gene rearrangement, are unusual findings in NK/T-cell lymphoma, and we believe such a phenotype/genotype should be more appropriately classified as an EBV-positive peripheral T-cell lymphoma, unspecified with a cytotoxic phenotype. Detailed clinicopathologic and molecular studies of similar cases may shed light on the prognostic impact of NK vs. T-cell lineage on extranodal NK/T-cell lymphomas.     

Primary cutaneous B‐cell lymphoma is associated with somatically hypermutated immunoglobulin variable genes and frequent use of VH1‐69 and VH4‐59 segments

Background Accurate assessment of the somatic mutational status of clonal immunoglobulin variable region (IgV) genes is relevant in elucidating tumour cell origin in B‐cell lymphoma; virgin B cells bear unmutated IgV genes, while germinal centre and postfollicular B cells carry mutated IgV genes. Furthermore, biases in the IgV repertoire and distribution pattern of somatic mutations indicate a possible antigen role in the pathogenesis of B‐cell malignancies. Objectives This work investigates the cellular origin and antigenic selection in primary cutaneous B‐cell lymphoma (PCBCL). Methods We analysed the nucleotide sequence of clonal IgV heavy‐chain gene (IgVH) rearrangements in 51 cases of PCBCL (25 follicle centre, 19 marginal zone and seven diffuse large B‐cell lymphoma, leg‐type) and compared IgVH sequences with their closest germline segment in the GenBank database. Molecular data were then correlated with histopathological features. Results We showed that all but one of the 51 IgVH sequences analysed exhibited extensive somatic hypermutations. The detected mutation rate ranged from 1·6% to 21%, with a median rate of 9·8% and was independent of PCBCL histotype. Calculation of antigen‐selection pressure showed that 39% of the mutated IgVH genes displayed a number of replacement mutations and silent mutations in a pattern consistent with antigenic selection. Furthermore, two segments, VH1‐69 (12%) and VH4‐59 (14%), were preferentially used in our case series. Conclusions Data indicate that neoplastic B cells of PBCBL have experienced germinal centre reaction and also suggest that the involvement of IgVH genes is not entirely random in PCBCL and that common antigen epitopes could be pathologically relevant in cutaneous lymphomagenesis.     

Cutaneous manifestations of peripheral T‐cell lymphoma,not otherwise specified: A case series highlighting the diagnostic challenges for this heterogeneous group

Peripheral T‐cell lymphoma, not otherwise specified (PTCL, NOS) is a rare, heterogeneous group of nodal and extranodal mature T‐cell lymphomas that do not correspond to any of the defined T‐cell entities, according to the World Health Organization classification. Most cases present with late stage nodal disease; however extranodal involvement is common. Skin and subcutaneous involvement is reported in approximately 20% of cases. Little attention has been given to the highly variable skin manifestations in the literature. It is our experience that lesions can present in ways other than previously described nodular or tumourous lesions that often ulcerate. We present a case series from a large tertiary institution of seven cases of PTCL, NOS with skin involvement, highlighting the variable presentations and diagnostic challenges for this heterogeneous group.     

Subcutaneous panniculitis-like T-cell lymphoma: a clinicopathological,immunophenotypic and molecular analysis of six patients

BACKGROUND: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma of the skin. In the World Health Organization classification of T-cell and natural killer cell lymphoma it is listed as an example of extranodal lymphoma. In practice, however, it is most likely to present to a dermatologist. OBJECTIVES: To describe the clinicopathological, immunophenotypic and molecular features of six U.K. patients with SPTCL. METHODS: The clinical, histological and immunophenotypic features were reviewed. T-cell receptor (TCR) gene analysis was performed on blood and tissue samples using polymerase chain reaction/single-strand conformational polymorphism analysis of the TCR-gamma gene using consensus primers. In situ hybridization was performed on lesional skin to detect mRNA for Epstein-Barr virus (EBV). RESULTS: All patients presented with subcutaneous nodules, plaques or ulceration, and three had systemic symptoms. All biopsies exhibited an infiltrate of medium to large pleomorphic cells involving the subcutis with characteristic rimming of fat spaces. Five showed areas of necrosis, but only one showed marked cytophagia. In three cases the neoplastic cells did not express TCR-beta. One was strongly p53 positive, and the other two were CD56 positive. Both these patients showed epidermal involvement with lichenoid changes histologically, and both developed the haemophagocytic syndrome. The other three cases were TCR-beta positive, CD8 positive and CD56 negative. All cases were positive with pan T-cell markers and also for the cytotoxic granule protein T-cell intracellular antigen-1 and granzyme B. All cases were EBV negative both by immunostaining (latent membrane protein-1) and by in situ hybridization (EBV-encoded mRNA). TCR gene analysis revealed a T-cell clone in four of five cases; two of these patients had an identical T-cell clone in the peripheral blood. The median survival was 16 months. However, two of the three TCR-beta-negative patients have died, whereas none of the TCR-beta-positive patients has died. CONCLUSIONS: This is the first series of SPTCL patients to be reported in the U.K. and the data support the view that there are two subsets of SPTCL: those derived from gammadelta T cells which carry a poor prognosis, and are usually CD56 positive, and a more indolent group derived from alphabeta T cells.     

ALK‐negative systemic intravascular anaplastic large cell lymphoma presenting in the skin

Systemic cases of the CD30‐positive T‐cell neoplasm, anaplastic large cell lymphoma (ALCL), are typically anaplastic lymphoma kinase (ALK)‐positive. The failure to express ALK protein has been shown to portend a worse prognosis. We describe a case of ALK‐negative systemic ALCL that presented as a violaceous plaque on the scalp of a 79‐year‐old man. Interestingly, the neoplastic cells were confined largely within vascular spaces, a configuration that is exceedingly rare in the skin and is more typically seen with intravascular large B‐cell lymphoma. In addition, bcl‐2 immunohistochemical staining was strongly positive in this case, which may portend a more aggressive clinical course. To our knowledge, this report represents the first case of an ALK‐negative ALCL to present intravascularly in the skin. Therefore, the recognition of systemic anaplastic T‐cell lymphoma present within the intravascular spaces is important to avoid misdiagnosis. Rieger K, Polidore T, Warnke R, Kim J. ALK‐negative systemic intravascular anaplastic large cell lymphoma presenting in the skin.     

Paucity of intraepidermal FoxP3‐positive T cells in cutaneous T‐cell lymphoma in contrast with spongiotic and lichenoid dermatitis

Background: FoxP3 is the most specific available marker for regulatory T cells (Tregs). Tumor‐associated FoxP3‐positive Tregs have been identified in various neoplasms, including cutaneous T‐cell lymphoma (CTCL). FoxP3 expression in CTCL varies across groups; few studies have compared CTCL with inflammatory conditions. Methods: Lesional skin biopsies from 20 patients with CTCL [13 mycosis fungoides (MF); 7 Sézary syndrome (SS)] and 22 with inflammatory dermatoses (11 spongiotic; 11 lichenoid or interface) were examined for FoxP3 expression by immunohistochemistry. Epidermal FoxP3‐positive lymphocytes were counted as a percentage of the total epidermal CD3‐positive T‐cell population. Results: FoxP3‐positive T cells composed the minority of infiltrate in all major categories. Lower numbers of epidermal FoxP3‐positive T cells were observed in CTCL, particularly MF, than in inflammatory dermatoses (P < .001). CTCL neoplastic T cells did not express FoxP3. Conclusion: FoxP3‐positive T cells are less frequently encountered in MF than in inflammatory dermatoses. FoxP3‐positive T cells occur in higher proportions in the dermis than in the epidermis and probably correlate with coexisting inflammatory components. CTCL neoplastic cells do not typically express a Treg phenotype and are associated with low numbers of FoxP3‐positive Tregs in the infiltrate. FoxP3 expression by immunohistochemistry may aid histologic evaluation of these conditions. Wada DA, Wilcox RA, Weenig RH, Gibson LE. Paucity of intraepidermal FoxP3‐positive T cells in cutaneous T‐cell lymphoma in contrast with spongiotic and lichenoid dermatitis.