Granulomatous slack skin T-cell lymphoma: an important differential diagnosis with giant cell tumor of soft tissue

Granulomatous slack skin is an indolent T-cell lymphoma, considered to be a variant of mycosis fungoides. Clinically it is characterized by areas of redundant skin, wrinkled, inelastic, with variable erythema and infiltration besides a poikilodermic surface. A differential diagnosis unknown to most dermatologists is the giant cell tumor of soft tissue, which is an extremely rare low-grade sarcoma. The authors report a patient who had undergone extensive surgery because of a primary diagnosis of giant cell tumor of soft tissue, but which proved to be granulomatous slack skin after a second interventional procedure with confirmatory histopathology.     

A drug safety evaluation of mogamulizumab for the treatment of cutaneous T-Cell lymphoma

Introduction: Cutaneous T-cell lymphomas (CTCL) are rare non-Hodgkin lymphomas of skin-homing T-cells that initially or mainly manifest cutaneously. Treatment of CTCL is challenging given the disease states’ varying presentation and prognosis. Systemic treatment options often lack comparative evidence and have relatively low response rates and short duration of response. The recent Food and Drug Administration (FDA) approval of mogamulizumab in adult patients with relapsed or refractory (R/R) CTCL after at least one prior line of therapy provided a new treatment option to patients with advanced disease.

Areas covered: The authors discuss basic information about CTCL and mogamulizumab’s mechanism of action. Then, the authors discuss the agent’s efficacy. Finally, the authors evaluate the safety of mogamulizumab in comparison to other agents available in CTCL.

Expert opinion: Mogamulizumab has been shown to be an effective and well tolerated therapy for patients with relapsed and refractory MF/SS with excellent activity in the circulating component of the disease.     

Adolescence Mycosis Fungoides: An Unusual Presentation with Hypopigmentation

Mycosis fungoides (M.F.) is a rare cutaneous malignancy of childhood and adolescence. The disease commonly presents with the classic sequence of erythematous patches and plaques. Hypopigmentation as the presenting symptom is distinctly rare. This is the 9th case report of M.F. presenting with hypopigmentation in a patient under 20 years of age. The disease was only partially controlled with PUVA therapy, necessitating nitrogen mustard treatment.     

Reduction of systemic fungal infections in patients with hematological malignancies,neutropenia, and prolonged fever by early amphotericin B therapy

Summary A rate on autopsy of up to 30% systemic fungal infections and difficulties in diagnosing systemic mycosis antemortem have led to the empiric use of amphotericin B in patients with hematological malignancies, prolonged fever, and neutropenia. Routine empiric antifungal treatment was initiated in our institution in 1982. Amphotericin B was given to granulocytopenic patients with hematological malignancies with (a) unremitting fever after 48–72 h of antibiotic treatment, (b) recurrent fever during antibiotic treatment, or (c) with newly detected pulmonary infiltrates, sinusitis, skin and retinal lesions suggestive of a fungal infection. With this approach the rate of systemic fungal infections decreased significantly from 10% (27 of 270 patients; 1973–1981) to 4% (6 of 153 patients; 1982–1986,P<0.02). The reduction of systemic fungal infections was most prominent in patients with acute myelogenous leukemia, where its proportion decreased from 16% (16 of 98 patients; 1973–1981) to 4% (2 of 50 patients; 1982–1986,P<0.023). Our data support the hypothesis that the incidence of systemic fungal infections in patients with hematological malignancies and especially in acute myelogenous leukemia can be reduced significantly by empirical treatment with amphotericin B.     

Cell-bound IgE and increased expression of Fc epsilon-receptors on dendritic cells in cutaneous infiltrates of mycosis fungoides.

Skin biopsies of 31 non-atopic patients, 20 with mycosis fungoides, six with psoriasis and five with contact dermatitis, and of five non-atopic healthy controls were compared for the presence of cell-bound IgE and vacant IgE binding sites. IgE+ cells were demonstrated in the cutaneous infiltrate of nine (45%) patients with mycosis fungoides, two (33%) with psoriasis and one (20%) with contact dermatitis. Following pre-incubation of skin sections with IgE myeloma protein to saturate vacant IgE-binding sites, 14 out of 16 patients (88%) with stage I mycosis fungoides, five (83%) patients with psoriasis and one (20%) with contact dermatitis showed an increase in the number of IgE+ cells. While cell-bound IgE was positively related to serum IgE levels the expression of IgE-binding sites was not. All IgE+ cells were HLA-DR+ dendritic cells identified as either macrophages (CD68+, CD14+) or Langerhans cells (CD1+). Skin biopsies of non-atopic healthy controls or clinically uninvolved skin in mycosis fungoides had neither any IgE+ cells nor any vacant binding sites. Inhibition studies with IgG1, IgG4 and IgE myeloma proteins as well as with several enzymatic fragments of IgE demonstrated that IgE interacted with Fc epsilon-receptors through isotype-specific structures on the Fc epsilon-fragment. Four anti-CD23 monoclonal antibodies, however, were unable to stain vacant Fc epsilon-receptors nor could they block IgE-binding. We hypothesize that locally-secreted lymphokines, like IL-4 or interferon-gamma, induce Fc epsilon-receptors on dendritic cells in the cutaneous infiltrate and that these receptors become occupied in parallel with elevated serum IgE levels.     

Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

Summary To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of ³H-thymidine-labeled infiltrating cells (³H-index).A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the ³H-index is moderately elevated in stage I and high in stage III.The ³H-index is within normal range in dermal infiltrate of Sézary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis.In parapsoriasis en plaques two groups can be distinguished: in the smallplaque variant (chronic superficial dermatitis) the ³H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity.Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.Zusammenfassung Um die Bedeutung der lokalen Zellproliferation im dermalen Infiltrat bei cutanen malignen Lymphomen zu untersuchen, bestimmten wir den Prozentsatz der ³H-Thymidin-markierten Infiltratzellen (³H-Index.Zwischen dem klinischen Stadium der Mycosis fungoides und der Proliferationsaktivität des dermalen Infiltrats besteht eine lineare Beziehung; im Stadium I ist die Proliferation niedrig, im Stadium III sehr hoch.Nicht erhöht ist der ³H-Index im dermalen Infiltrat beim Sézary-Syndrom, diffusen lymphocytischen Lymphom sowie bei Lymphocytoma benigna cutis.Bei der Parapsoriasis en plaques müssen zwei Formen unterschieden werden: bei der kleinfleckigen Form (chronic superficial dermatitis) ist der ³H-Index niedrig, während die großfleckige Form (Präretikulotisches Poikiloderm) eine starke Proliferationsaktivität aufweist.Die Untersuchung des Proliferationsverhaltens gibt neue Einblicke in die Pathogenese des dermalen Infiltrats cutaner Lymphome.     

A new molecular paradigm in mycosis fungoides and Sézary syndrome

Mycosis Fungoides (MF) and Sézary Syndrome (SS) are clonal proliferations of mature T-cells manifesting as lymphoproliferative disorders in which the neoplastic cells show a strong propensity for skin-homing. While the predominant site of presentation in MF is the skin, the peripheral blood carries a significant tumor burden in Sézary Syndrome such that it resembles a “leukemic” disease. While the genetic basis of these diseases has been studied using different approaches in the previous years, recent genome-wide studies employing massively parallel sequencing techniques now offer new insights into the molecular pathogenesis of these diseases. In this chapter, we discuss the recent findings elucidating the genomic landscape of MF and SS. The pathways targeted by mutational alterations are discussed and a model for understanding the pathogenesis of these diseases is proposed. It is anticipated that prognostic stratification and therapeutic targeting based on mutational signatures will be achieved in the near future based on the improved understanding of the molecular pathogenesis of these diseases.