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Abstract Mycosis fungoides is the most common type of primary CTCLs. It is characterized by malignant proliferation of CD4+ T cells with epidermotropism in the skin and generally has a prolonged clinical course. In early stages, it typically presents in the form of erythematous patches and/or plaques that may progress to tumors and erythrodermic stages. The diagnosis of MF requires the integration of clinical and histopathologic data which depends on identification of epidermotropism and/or a dermal infiltrate of atypical T-cells. Recently, YKL-40 has been described as a new diagnostic marker for CTCL. YKL-40 has a role in cancer cell proliferation, survival, and invasiveness, in the inflammatory process around the tumor, angiogenesis, and remodeling of the extracellular matrix. and its aberrant expression is associated with the pathogenesis of inflammatory diseases and cancers, such as glioblastoma, adenocarcinoma, squamous cell carcinoma and melanoma. The aim of this work was to study the immunohistochemical expression of YKL-40 in MF patients in comparison to healthy control to find out if YKL-40 is playing a possible role in the etiopathogenesis of MF. Patients and Methods: This study included 25 patients with different clinical types and stages of MF, and 10 normal skin specimens from matched healthy individuals served as control. All participants were subjected to: I. Clinical evaluation: • Complete careful history taking. • Thorough general and dermatological examinations. • Clinical assessment of MF stage according to TNMB classification system recognized by ISCL/EORTC staging. II. Laboratory evaluation: • Routine laboratory investigations • After taking written informed consent, 4 mm punch skin biopsy specimens were taken under local anesthesia and complete aseptic technique. Specimens were fixed in neutral formalin 10% and processed for paraffin blocks. • Four sections were cut from each block and were subjected to: a) Hematoxylin & Eosin (H&E) staining. b) CD4, CD8 and YKL-40 immunohistochemical staining. The results of this study revealed the followings: I. Clinical Results • The male to female ratio in MF patients’ group was1.7:1, and in the control group, it was 1.5:1. • The age of MF patients ranged from 24 to 70 years with a mean of. 38.92 ± 12.27. While the age of control subjects ranged from 24 to 69 years with a mean of 38.30 ± 13.79. • The duration of the disease in the studied MF patients ranged from 1 – 15 years with a mean of 4.76 ± 3.60 and median 4.0. • The clinical types of MF were as follows: 16 classic MF (64%), 5 hypopigmented MF (20%), one hyperpigmented MF (4%), one poikilodermatous MF (4%), one folliculotropic MF (4%) and one eryhtrodermic MF (4%). • The clinical presentation of the 16 classic MF patients were as follows; 7 patients with patch stage (43.8%), 5 patients with plaque stage (100%), and 4 patients with tumor stage (100%). While the remaining 9 MF patients were all presenting with patch stage. • TNMB Staging of the studied MF patients were as follows: 9 patients at stage IA (36%), 10 patients at stage IB (40%), 5 patients at stage IIB (20%) and one patient at stage IIIA (4%). II. Histopathological Results: A. Hematoxylin and Eosin staining: • Patch stage MF, showed upper dermal lymphocytic infiltrate encroaching on the edges of the basal cell layer with epidermotropism of atypical mononuclear cells. • Plaque stage MF, showed psoriasiform hyperplasia, epidermotropism with Pautrier’s microabscess. The upper dermis showed a dense band-like lymphocytic infiltrate with atypical nuclei as well as lymphocytic alignment along the basal cell layer. • Tumor stage MF, showed diffuse and dense dermal infiltrate of medium-sized and large atypical lymphocytes with minimal epidermotropism. B. Immunohistochemical Results: • CD4 immunostaining was positive in 24 MF specimens (96%) and only one MF specimen was negative. • CD8 immunostaining was negative in 19 MF specimens (76%) and 6 MF specimens (24%) were positive. • Intensity of YKL-40 immuonostaining showed statistically significant increase of YKL-40 immunohistochemical expression in both the epidermis and dermis of MF specimens in comparison to normal skin of control specimens with P. value <0.001*. Relation between the intensity of YKL-40 expression in mycosis fungoides specimens and the studied clinical parameters: • There was no statistically significant relation between the intensity of YKL-40 expression and the clinical type of MF. • There was statistically significant increase in the expression of YKL-40 in both the epidermis and dermis of MF specimens with the progression of the skin lesions from patches to plaques, tumors and eventually erythroderma, with P.value <0.001*. • There was statistically significant increase in the expression of YKL-40 in both the epidermis and dermis of MF specimens with the increase in the TNMB staging of MF with P.value =0.018*, 0.002* respectively. Correlations between intensity of YKL-40 expression and the studied clinical parameters of mycosis fungoides patients • There was statistically significant positive correlation between intensity of YKL-40 immunohistochemical expression in both the epidermis and dermis of MF specimens with the age of MF patients with rs=0.498, P.value =0.011* and rs= 0.618, P.value= 0.001*respectively. • There was statistically significant positive correlation between intensity of YKL-40 immunohistochemical expression in both the epidermis and dermis of MF specimens with the duration of MF lesions with rs= 0.557, P.value =0.004* and rs= 0.425 and P.value =0.034* respectively. • There was statistically significant positive correlation between YKL-40 expression in both the epidermis and dermis of MF specimens and the clinical presentation of the disease with rs=0.789, rs=0.834 respectively, and P.value <0.001*. • There was statistically significant positive correlation between YKL-40 expression in both the epidermis and dermis of MF specimens and TNMB staging of the disease with rs=0.470, P.value =0.018*and rs=0.557 and P.value =0.004* respectively. |