Epidermotropic Infiltrate Research Articles

Clinical spectrum of indolent mycosis fungoides with a gamma‐delta (γδ) phenotype: a single institution review including therapy and outcomes

AbstractBackgroundPrimary cutaneous γδ T‐cell lymphoma (CGD‐CTL) is a rare malignancy that classically exhibits an aggressive clinical phenotype.ObjectivesReview cases of mycosis fungoides with a γδ phenotype that demonstrated an indolent clinical course.MethodsRetrospective review of patients diagnosed with MF with a γδ phenotype and an indolent clinical course between 2018 and 2022 treated at the University of Utah.ResultsFive patients ages 4‐81 years old were identified. All presented with clinically persistent patch or plaque‐stage disease, and histopathology showed primarily epidermotropic infiltrates positive for TCR delta via immunostaining. None of these patients have required aggressive treatment with multiagent chemotherapy.ConclusionsThere exists a subset of indolent CGD‐TCL patients who are clinicopathologically distinct from classic CGD‐CTL and clinically resembling indolent MF. Therefore, we prefer the term “MF with γδ phenotype” for these rare cases.

A-172 Atypical Epidermotropic Infiltrate with NK cell immunophenotype Following Systemic Therapy for Atopic Dermatitis - A Case Report

A-172 Atypical Epidermotropic Infiltrate with NK cell immunophenotype Following Systemic Therapy for Atopic Dermatitis - A Case Report

Primary cutaneous, epidermotropic mycosis fungoides-like presentation: critical appraisal and description of two novel cases, broadening the spectrum of ALK+ T-cell lymphoma.

Leading from a two-case series, including two patients receiving a diagnosis of epidermotropic T-cell lymphoma, featuring a mycosis fungoides (MF)-like clinical pattern and ALK expression and molecular alteration, we performed a critical appraisal of ALK+ primary cutaneous T-cell lymphomas (pcTCL). Considering our patients and the literature, 32 cases were retrieved, 7 of which featured an MF-like clinical picture over a 4-to-20-year period. MF-like cases show distinctive histology, comprising a predominantly epidermotropic infiltration of small-to-large, atypical-to-pleomorphic, with few anaplastic cells, negligible-to-intense CD30-expression, and a CD4+/cytotoxic granule+ phenotype. These features should prompt a search for ALK expression captured by the ALK D5F3 clone. Bona fide ALK+ pcTCL is very rare, and existent data suggest the presence of a broader pattern of disease, including instances mimicking MF and/or primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. The major challenges in dealing with this subset include prodromal phases, misinterpreted as inflammatory dermatosis or parapsoriasis/early phase MF both clinically and histologically, while recognition of its ALK-driven biology is hampered both by the unusual clinic-pathologic pattern of the disease, which stands apart from the classical (i.e., nodal) picture of ALK+ anaplastic large cell lymphoma and by the low sensitivity of ALK1 clone. Data on its optimal management are far from being conclusive: An MF-like approach is currently chosen, but depending on CD30 and, most notably, ALK expression, a targeted therapy could be envisaged in advanced stages, as clinical response to ALK inhibition was documented in one patient.

CD8+ aggressive T-cell lymphoma (T-NHL) involving the liver and skin: a case study

Abstract Introduction/Objective Aggressive T-NHL involving cutaneous and visceral organs is rare. We report a case with a complex presentation that was found to have hepatic and skin lesions simultaneously. We emphasize the importance of the clinicopathological correlation and diagnostic work-up for such a rare case Methods/Case Report A 60-year-old male with alcoholic cirrhosis presented with abdominal pain, fever, and night sweats for over two weeks. Detailed physical evaluation revealed a tender, indurated, erythematous papule on the left upper back. Lab results showed leukopenia, anemia, and increased LDH. PET-CT showed multiple hypermetabolic lesions in the liver, skin, and deep soft tissue above and below the diaphragm. A liver biopsy revealed a diffuse sheath of large atypical lymphoid cells with small lymphocytes in the background. Atypical lymphoid cells stained positive for CD45, CD2, CD3, CD8, TIA-1, CD5 (partial), granzyme B (partial), βF1 (partial); and negative for ALK, BCL-2, CD4, CD7, CD10, CD30, CD56, and TCRδ. Ki-67 was 70%. The skin punch biopsy revealed epidermotropic infiltration of lymphocytes with a similar immunophenotype as the liver lesion. Bone marrow biopsy showed no involvement. The differential diagnosis includes primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-NHL with visceral dissemination, peripheral CD8+ T-NHL, lymphomatoid papulosis, CD8-positive mycosis fungoides, and hepatosplenic T-NHL. The visceral involvement excludes lymphomatoid papulosis and CD8-positive mycosis fungoides. The absence of bone marrow involvement excludes hepatosplenic T-NHL. The prominent liver involvement favors the diagnosis of peripheral CD8+ T-NHL. However CD8+ aggressive epidermotropic cytotoxic T-NHL still cannot be entirely excluded due to the epidermotropic CD8 positive T-cell infiltration of the dermis and subcutaneous adipose tissue. Further evaluation for JAK2 mutation and TBX21 amplification can help distinguish it from Peripheral CD8- positive T-NHL. Results (if a Case Study enter NA) NA Conclusion The subclassification of CD8+ T-NHL into distinct entities with overlapping clinical and histological characteristics is challenging without molecular tests. However, clinicopathological correlation with appropriate work-up can help narrow the differential diagnoses.

Widespread and eruptive comedonal lesions with alopecia

A 68-year-old White man presented with a 2-year history of asymptomatic, widespread comedones associated with patchy alopecia of the scalp and eyebrows and total alopecia of axillary and pubic hairs (Fig 1, A to C). Histopathology of a comedonal area demonstrated a dilated, follicular infundibulum with keratotic plugging and a perifollicular band-like CD4-predominant atypical T-lymphocytic infiltrate leading to the detachment and infiltration of the follicles (Fig 1, D and E). Subsequently, erythematous, erosive plaques started to develop on the trunk and limbs of the patient (Fig 1, F), the histopathology of which showed a more extensive, diffused, epidermotropic infiltrate containing CD4-predominant T lymphocytes with sparse medium- to large-sized lymphocytes (Fig 1, G).

Evaluation of Melanocyte Loss in Mycosis Fungoides Using SOX10 Immunohistochemistry.

Mycosis fungoides (MF) is a subtype of primary cutaneous T-cell lymphoma (CTCL) with an indolent course that rarely progresses. Histologically, the lesions display a superficial lymphocytic infiltrate with epidermotropism of neoplastic T-cells. Hypopigmented MF is a rare variant that presents with hypopigmented lesions and is more likely to affect young patients. The etiology of the hypopigmentation is unclear. The aim of this study was to assess melanocyte loss in MF through immunohistochemistry (IHC) with SOX10. Twenty cases were evaluated, including seven of the hypopigmented subtype. The neoplastic epidermotropic infiltrate consisted predominantly of CD4+ T-cells in 65% of cases; CD8+ T-cells were present in moderate to abundant numbers in most cases. SOX10 IHC showed a decrease or focal complete loss of melanocytes in 50% of the cases. The predominant neoplastic cell type (CD4+/CD8+), age, race, gender, histologic features, and reported clinical pigmentation of the lesions were not predictive of melanocyte loss. A significant loss of melanocytes was observed in 43% of hypopigmented cases and 54% of conventional cases. Additional studies will increase our understanding of the relationship between observed pigmentation and the loss of melanocytes in MF.

Mycosis Fungoides and Sézary Syndrome

Mycosis fungoides (MF) and Sézary syndrome (SS) are two subgroups of cutaneous T-cell lymphomas (CTCL), which belong to the extranodal non-Hodgkin lymphomas. These are rare diseases whose etiology is still not fully understood. Regarding pathogenesis, mycosis fungoides and Sézary syndrome derive from different T-helper cell types and are therefore considered two separate entities according to the current concept. Mycosis fungoides is clinically characterized by patch, plaque and tumor stages, although the disease can also manifest as erythroderma. Sézary syndrome is characterized by the presence of erythroderma, defined as redness of the skin covering >80% of the total body surface area. In the blood count of patients with mycosis fungoides, a T-lymphocytosis, especially with CD4-positive cells, can only be observed in advanced stage IV. One of the typical histological findings is an epidermotropic infiltrate of atypical, CD4-positive T-cells. Characteristic features of Sézary syndrome include atypical T lymphocytes (Sézary cells) in the blood and skin infiltrate. The diagnosis of both mycosis fungoides and Sézary syndrome is based on clinical, histological and hematological examinations as well as imaging techniques. Staging is based on the tumor-node-metastasis-blood (TNMB) classification and is a crucial factor in determining the prognosis. The treatment of mycosis fungoides and Sézary syndrome is carried out according to the stage, whereby local therapies such as UVB phototherapy are used as well as systemic forms of treatment, and in addition, in recent years, targeted therapies have increasingly become part of everyday clinical practice.

Mycosis fungoides-clinical and histopathologic features, differential diagnosis, and treatment.

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma. The term MF should be used only for the classical presentation of the disease characterized by the evolution of patches, plaques, and tumors or for variants showing a similar clinical course. MF is divided into 3 clinical phases: patch, plaque, and tumor stage, and the clinical course is usually protracted over years or decades. Histopathologically, MF is characterized by an epidermotropic infiltrate of T lymphocytes that displays in most cases a helper phenotype. Cytotoxic variants are well described and do not have specific clinical, histopathological, or prognostic features. MF should be differentiated from other cutaneous epidermotropic lymphomas and from many inflammatory dermatoses with some similar clinicopathological features. The therapy of MF is planned mainly according to the stage and extent of the disease. In early phases, nonaggressive options represent the first-line strategy (eg, local corticosteroids, psoralen, and ultraviolet A [UV-A] irradiation, etc.). In patients with advanced disease, good results with potential for cure have been obtained with allogeneic stem cell transplantation, but toxicity is a serious limiting factor for this treatment. Conventional systemic chemotherapy and single-agent chemotherapy (eg, gemcitabine) give usually good results in advanced MF, but recurrences are the rule. Monoclonal antibodies directed against cluster of differentiation (CD)52 (alemtuzumab), CD30 (brentuximab vedotin), and chemokine receptor 4 (CCR4; mogamulizumab), as well as several other experimental therapies, have shown promising results and represent a valid alternative.

B-cell lymphofollicular infiltrates in mycosis fungoides.

The histopathological picture of mycosis fungoides can be characterized by heavy reactive infiltrates. These are rarely composed of B lymphocytes with formation of reactive follicles. We collected three cases of mycosis fungoides with a reactive B-cell lymphofollicular reaction at the bottom of the epidermotropic infiltrate. Case 1 showed flat lesions (patches) with a CD4+ neoplastic phenotype; case 2 presented infiltrated lesions (plaques) with a CD8+ immonophenotype; case 3 was characterized by nodular lesions (tumors) with a CD4+ neoplastic component. In all three cases, no clonal gene rearrangement was found with the polymerase chain reaction technique. Among the protean clinicopathological features which mycosis fungoides can show, we underline that a B-cell lymphofollicular component can be encountered at the base of the epidermotropic infiltrate even in clinically flat ("patchy") lesions.

Folliculotropic mycosis fungoides: A case after one-year follow-up

Abstract Mycosis fungoides is the most common form of cutaneous T-cell lymphoma (CTCL); it rarely exhibits a predilection for hair follicle infiltration. We describe a patient with preferential localization of skin lesions in the head and neck region with eyelid involvement, grouped follicular papules and acneiform lesions, severe pruritus and secondary bacterial infections. The histological presentation showed folliculotropic neoplastic lymphoid cells instead of epidermotropic infiltrates. The final diagnosis was folliculotropic mycosis fungoides (FMF), a rare, more aggressive variant of CTCL. Clinical manifestations of FMF may be challenging; thus, multiple, deep biopsy containing adnexal structures, are required to make this crucial diagnosis.

Pediatric CD8+CD56+ Non-poikilodermatous Mycosis Fungoides

Mycosis fungoides (MF) displays a broad spectrum of clinical, histological, and phenotypic variants with different prognostic impact. CD8⁺CD56⁺MF is very rare. So far, only 5 patients with CD8⁺CD56⁺ MF were reported to date. All of the previously described patients with this phenotypic variant were adults at the time of diagnosis and often manifested with widespread poikilodermatous skin lesions. Here we describe the clinicopathological features of a juvenile form of CD8⁺CD56⁺ non-poikilodermatous MF in a 10-year-old girl. In our patient, the disease displayed an indolent course and excellent prognosis with complete remission after treatment with UV light, topical steroids, and methotrexate. The differential diagnosis of CD8⁺ epidermotropic lymphocytic infiltrates in children is discussed, and the cases of CD8⁺CD56⁺ MF reported in the literature are reviewed.

Two Cases of Primary Cutaneous Lymphoma With a γ/δ+ Phenotype and an Indolent Course

Cutaneous γ/δ+ T-cell lymphoma (CGD-TCL) is a rare but aggressive lymphoma associated with a poor prognosis in most patients. The clinicopathological spectrum is variable including predominantly epidermotropic infiltrates manifesting with patches and plaques or tumors with dermal and/or subcutaneous infiltrates. The diagnosis of CGD-TCL requires the demonstration of a γ/δ+ phenotype by immunohistochemistry. We report 2 patients with epidermotropic cutaneous T-cell lymphomas displaying a γ/δ+ phenotype, but exhibiting an indolent course. In one patient, the clinical presentation was similar to mycosis fungoides in patch and plaque stage, but recurrent blister formation within the lesions was observed accompanied by fever and arthralgias, whereas the second patient presented with 2 localized erosive plaques on the left temple and dense epidermotropic and dermal diffuse and folliculotropic infiltrates of atypical small-to-medium-sized lymphocytes. These cases corroborate the view that expression of a γ/δ+ phenotype in cutaneous T-cell lymphomas per se does not portend a worse prognosis and that CGD-TCL may represent a clinically and prognostically heterogeneous group.

CD8-positive mycosis fungoides bullosa

ejd.2012.1763 Auteur(s) : Kazuha Kasugai1, Takeshi Yanagishita1 takeshit@aichi-med-u.ac.jp, Tomohiro Takeo1, Emiko Takahashi2, Yasuhiko Tamada1, Yoshinari Matsumoto1, Daisuke Watanabe1 1 Department of Dermatology, 2 Divison of Pathology, Aichi Medical University school of Medicine, Nagakute, Aichi, 480-1195, Japan Mycosis fungoides (MF), the most common type of cutaneous T cell lymphoma (CTCL), is characterized by an epidermotropic skin infiltrate of atypical T-helper phenotype lymphocytes. However, fewer [...]

FOXP3 in Sequential Biopsies of Progressive Mycosis Fungoides

A recent report has suggested that the numbers of regulatory T cells correlate with stage of disease and prognosis in mycosis fungoides (MF). To evaluate the role of FOXP3+ Tregs in different stages of MF, we investigated sequential biopsies in 14 patients with patch/plaque and subsequent tumor stage using FOXP3 antibody. Our data neither show a significant difference in the percentage of FOXP3+ cells between patch/plaque and tumor stage biopsies of MF nor demonstrate a predictable shift of Tregs in the course of disease progression. Additionally, we could observe FOXP3-expressing neoplastic cells in 4 patch/plaque stage biopsies, where they represented almost 100% of the epidermotropic infiltrate. Only in one of these patients, FOXP3+ cells could also be detected in the tumor stage biopsy, indicating that FOXP3 expression can be acquired or lost during the course of the disease, comparable to other phenotypic markers.

A study of clinicopathologic profile of 15 cases of hypopigmented mycosis fungoides

Mycosis fungoides (MF) is cutaneous lymphoma of the T-cell lineage. Hypopigmented MF is a clinical variant of MF, described mainly in Asians. This is a retrospective clinicopathologic analysis of hypopigmented MF at a tertiary care center. To describe the clinicopathologic profile of hypopigmented MF. Records of clinicopathologic notes over a 5-year period ranging from January 2005 up to December 2009 were reviewed over a period of 3 months, of which 15 cases were diagnosed with hypopigmented MF based on clinicopathologic correlation. Hypopigmented MF was found to be more common in males, and between second and fourth decades of life. The latent period between onset and diagnosis was around 3.83 years. Most of the patients were asymptomatic 80% (12/15), with skin changes of subtle atrophy in 46.66% (7/15), scaling in 20% (3/15) and focal changes of poikiloderma in 26.66% (4/15) patients. Most common sites of distribution of the lesions were the trunk and extremities. Many of the cases had been clinically mistaken for Hansen's disease prior to correct diagnosis. Marked epidermotropism and tagging of epidermis by large lymphocytes characterizes the condition histopathologically. Of the 15 cases, immunohistochemistry was possible in 10 cases, of which 8 showed predominant CD8 positive epidermotropic infiltrates and two cases showed absence of CD8 positive and CD4 positive lymphocytic infiltrate in the epidermis. Hypopigmented MF presents as hypopigmented asymptomatic patches without any erythema or infiltration in its early stage and mimics Hansen's disease. Skin biopsy clinches the diagnosis.

B-cell Lymphofollicular Infiltrates in Mycosis Fungoides

The histopathological picture of mycosis fungoides can be characterized by heavy reactive infiltrates. These are rarely composed of B lymphocytes with formation of reactive follicles. We collected three cases of mycosis fungoides with a reactive B-cell lymphofollicular reaction at the bottom of the epidermotropic infiltrate. Case 1 showed flat lesions (patches) with a CD4+ neoplastic phenotype; case 2 presented infiltrated lesions (plaques) with a CD8+ immonophenotype; case 3 was characterized by nodular lesions (tumors) with a CD4+ neoplastic component. In all three cases, no clonal gene rearrangement was found with the polymerase chain reaction technique. Among the protean clinicopathological features which mycosis fungoides can show, we underline that a B-cell lymphofollicular component can be encountered at the base of the epidermotropic infiltrate even in clinically flat ("patchy") lesions.

Pagetoid Reticulosis After Radiotherapy of Primary Cutaneous Anaplastic Large-Cell Lymphoma

We describe a 60-year-old man with a history of primary cutaneous anaplastic large cell lymphoma on the chest, who presented with a new scaly red plaque on the same site 11 years after radiation therapy. Histological examination revealed a dense epidermotropic infiltrate of atypical mononuclear cells consistent with pagetoid reticulosis. Immunohistochemistry revealed the infiltrate to be CD4, CD8, and CD30. Remarkably, all the atypical cells were strongly CD30, and furthermore, the CD30 cells were found exclusively in the epidermis. In the initial cutaneous anaplastic large cell lymphoma lesion, the CD4, CD8, and focally CD30 atypical cells were well confined within the dermis with no epidermal component. To our knowledge, the present case seems to be the first description of pagetoid reticulosis presenting at the site of a previously treated dermal anaplastic large cell lymphoma. This case also represents an extreme presentation of epidermotropism and CD30 expression in pagetoid reticulosis.

Localized pagetoid reticulosis (Woringer-Kolopp disease) in early childhood

Localized pagetoid reticulosis, also known as Woringer-Kolopp disease, is an uncommon cutaneous lymphoproliferative disorder classified as a solitary variant of mycosis fungoides. We describe a case of localized pagetoid reticulosis that occurred in early childhood. A 6-year-old boy presented with an erythematous plaque on the left thigh. His parents had first noted brownish erythema of his thigh a few months after birth. The size and elevation of the plaque gradually increased. Physical examination showed well-demarcated reddish plaque, 6.2 x 2.3 cm, with central erosion. Histopathological examination showed an epidermotropic infiltrate of medium atypical lymphocytes with hyperchromatic and pleomorphic nuclei. The atypical cells infiltrated as individual cells or clusters in the epidermis. Immunohistologically, the phenotype of the atypical cells was CD3(+), CD4(-), CD8(+), CD45RO(+), CD20(-), CD30(-), and CD79a(-). We discuss the characteristics of this rare disease, including the differential diagnoses.

Ichthyosiform eruptions in association with primary cutaneous T-cell lymphomas

Malignant lymphoma is occasionally complicated by ichthyosiform eruptions. To analyse histopathologically the ichthyosiform eruptions associated with cutaneous lymphomas. We reviewed the files of patients with malignant lymphoma seen in our dermatology department between January 2001 and May 2006 to search for patients with ichthyosiform eruptions. In our series, nine of 106 patients with malignant lymphomas had ichthyosiform eruptions during their clinical courses, including three (30%) of 10 patients with anaplastic large cell lymphoma (ALCL) and six (14%) of 44 patients with mycosis fungoides (MF). None of the 18 patients with cutaneous B-cell lymphoma had ichthyosiform eruptions. The three patients with ALCL had ichthyosiform eruptions histopathologically consistent with acquired ichthyosis (AI) in which packed horny layers and thin granular layers were present without lymphocytic infiltration. In contrast, four of the six patients with MF (stages Ib and IIb) had ichthyosiform eruptions with epidermotropic infiltration of atypical lymphocytes, as observed in ichthyosiform MF (IMF). Of the remaining two patients, one showed histopathological features overlapping AI and IMF, and the other had AI alone. These two patients (stages IVa and IIb) had tumours composed of CD30+ cells. Filaggrin expression was markedly diminished in both AI and IMF-like eruptions, similar to that of inherited ichthyosis vulgaris. Ichthyosiform eruptions are often associated with ALCL and MF and can be classified into three groups: AI associated with ALCL and MF expressing CD30, IMF, and their overlap.

Papulonecrotic tuberculid‐like eruptions after Bacille Calmette‐Guerin vaccination

One of the specific skin lesions occurring after Bacille Calmette-Guerin (BCG) vaccination is generalized tuberculid-like eruptions, which occur rarely, but have a tendency to heal spontaneously. Their pathogenesis and relationship to "true" tuberculids are poorly understood. This report presents a case of a 6-month-old girl who developed generalized papulonecrotic tuberculid-like eruptions after BCG vaccination. The skin lesions healed spontaneously in 3 months. Culture of blood, gastric juice and reverse transcription polymerase chain reaction (RT-PCR) of papulonecrotic skin biopsies were all negative for Mycobacterium tuberculosis. Histopathology of papulonecrotic eruptions revealed marked epidermal necrosis, perivascular lymphocytic infiltrates and epidermotropic infiltration of lymphocytes showing markers of CD3(+) lymphocytes (90-95% of all infiltrating cells), CD4(+) (40-50%), CD8(+) (40-50%), and CD45RO(+) (70%). In contrast, the BCG vaccination site revealed intradermal granuloma with epithelioid cells, occasional giant cells and infiltration of lymphocytes consisting of CD3(+) (60-70%), CD4(+) (40-50%), CD8(+) (30-40%), CD45RO(+) (40%), CD79a(+) (30-40%), and CD20(+) (20-30%). Our patient did not reveal any signs indicative of tuberculosis. Papulonecrotic lesions were therefore called papulonecrotic tuberculid-like eruptions, rather than tuberculids, that occurred after BCG vaccination and appeared to derive from a hypersensitive reaction mediated by immune lymphocytic infiltration.