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Mycosis fungoides: criteria for histopathologic diagnosis Flavia Flavia CB CB Lisboa, Lisboa, Sueli Sueli Carneiro, Carneiro, Juan Juan Piñeiro-Maceira Piñeiro-Maceira Sector of Dermatology and Department of Pathology-HUCFF/U FRJ and Post-Graduation Course, School of Medicine, Universidade Federal do Rio de Janeiro, Brazil INTRODUCTION Mycosis fungoides (MF) is a T cell cutaneous lymphoma (CTCL) characterized by patch, plaque and tumor stages, and erythroderma during its evolution. The diagnosis of the patch stage is often difficult, clinically and histopathologically, because patients with patch stage mycosis fungoides present erythematous patches or plaques minimally infiltrated resembling inflammatory lesions, that may persist for a long time. The histologic findings of such stage are subtle. The same difficulty is seen in patients with erythroderma.1,2 Figure 1: Photomicrography of initial lesion (patch stage). Epidermotropism of lymphocytes and discrete mononuclear infiltrate in the dermis (HE, 100X) Frequently many biopsies taken over a long period of time are necessary before a definitive diagnosis can be reached.3 On the other hand, established plaque-stage MF rarely causes difficulties in its clinical or 4 histopathological diagnosis. OBJECTIVE To identify the most relevant criteria for the histopathologic diagnosis of mycosis fungoides, specially in the patch stage and in the erythrodermic form, through the observation of the histopathologic features present in patients with a clinical evolution characteristic of the disease. Figure 2: Photomicrography of initial lesion (patch stage). Irregular acantosis and dense mononuclear infiltrate occupying the dermis (HE, 100X) MATERIAL AND METHODS Sixty-five patients with the histologic diagnosis of mycosis fungoides were recovered from the files of the Department of Pathology of HUCFF/UFRJ in the period of 1978-1998. After reviewing their records, 27 patients were included in the study. All of them had the diagnosis of MF confirmed by clinical evolution. Major characteristic aspects of the patients and material and summarized in tables 1, 2, 3 and 4. Forty two hematoxilin-eosin-stained skin sections were evaluated for the presence of parakeratosis, acanthosis, epidermal atrophy, dyskeratosis, spongiosis, exocytosis, disproportionate epidermotropism, Pautrier's microabscess, basal layer damage, papillary fibrosis, papillary edema, telangiectasia, perieccrine lymphocytes, follicular epidermotropism, epithelioid granulomas and eosinophils, haloed lymphocytes, single basal lymphocytes and dermal and epidermal lymphocytes with hyperconvoluted nuclei. Figure 5: Photomicrography of erythrodermic form. Hyperconvoluted nuclei lymphocyte in the epidermis (HE, 1000X) Figure 4: Photomicrography of erythrodermic form. Irregular acantosis and discrete mononuclear infiltrate in the dermis (HE, 100X) Figure 6: Photomicrography of erythrodermic form. Hyperconvoluted nuclei lymphocytes in the dermis (HE, 1000X) RESULTS Figure 3: Photomicrography of erythrodermic form. Parakeratosis, irregular acantosis, disproportionate epidermotropism of lymphocytes and mononuclear infiltrate occupying the dermis (HE, 100X) Figure 7: Photomicrography of eryhtrodermic form. Halloed lymphocytes with hyperconvoluted nuclei aligned in the basal layer (HE, 1000X) Table 1: Relation between number of patients and skin samples available for the study according to clinical diagnosis Hyperconvoluted nuclei lymphocytes within the epidermis (81,25%) and haloed lymphocytes (75,0%) were the most frequent findings in the patch stage. In the erythrodermic form, disproportionate epidermotropism was seen in 92,3% of the cases. Hyperconvoluted nuclei lymphocytes within the epidermis and dermis appeared in equal proportions (88,46%), while the haloed lymphocytes were seen in 84,61%. Pautrier microabscesses were seen only in about one fourth of the cases Initial phase Erythrodermic form Total Patients Skin samples 9 16 18 26 27 42 Figure 8: Photomicrography of initial lesion. Pautrier's microabscess (HE, 400X) Table 2: Number of patients according to inclusion criteria Disease form Evolution to tumoral lesions or spread of the disease Initial Erythrodermic Total 3 12 15 Follow up for at least 5 years, with typical evolution, although without disease progression 6 6 12 Total 9 18 27 The prevalence of each criteria is represented in Graphic 1, for both initial and erythrodermic forms. Granulomas Table 3: Clinical and epidemiological aspects of initial phase patients Dermal edema Erytrodermic form Telangiectasia Age of N Sex disease onset Initial phase Eosinophils Exocytosis 1 F 61 Spongiosis 2 F 40 Dyskeratosis Epidermal atrophy 3 M 49 8 M 62 13 M 60 15 M 71 18 F 60 20 F 61 Parakeratosis Graphic 1: Prevalence of histopathological criteria in both forms of MF studied. Acantosis Perieccrine lymphs Papillary fibrosis Pautrier's microabscess Single basal lymphs 21 Haloed lymphs Convoluted dermal lymphs M 27 Age at the Follow up time of duration Evolution Death diagnosis (years) Improved with 63 5 N topical treatment Worsened with 44 4 N tumoral lesions Improved with 55 5 N topical treatment Worsened with 63 2 N tumoral lesions Worsened with 62 2 N tumoral lesions Improved with 71 7 N topical treatment Improved with 65 10 N topical and systemic treatment Improved with 63 5 N topical treatment Improved with 34 7 topical and systemic N treatment M: male; F: female; N: no; Y:yes Convoluted epidermal lymphs Table 4: Clinical and epidemiological aspects of erythrodermic patients Age of Age at the Follow up N Sex disease time of duration Evolution onset diagnosis (years) Improved with topical and systemic 4 M 47 47 5 treatment 5 M 38 39 1/dez Spread of the disease 6 M 82 82 2 S zary cells on peripheral blood Improved with topical and systemic 7 F 29 62 13 treatment 9 M 45 51 8 Improved with systemic treatment 10 M 56 76 1/dez Spread of the disease 11 M 63 63 11 Improved with systemic treatment 12 M 74 79 5 Worsened with tumoral lesions 23 F 50 67 1/dez S zary cells on peripheral blood 25 M 59 63 5 S zary cells on peripheral blood 26 M 66 72 1 Worsened with tumoral lesions 28 M 53 54 1/dez S zary cells on peripheral blood Improved with topical and systemic 29 M 61 62 7 treatment 31 F 65 66 2 Worsened with tumoral lesions Bone marrow infiltration by 32 M 65 70 6 hiperconvoluted lymphocytes 33 M 53 53 3 CNS infiltration 36 M 82 83 4 S zary cells on peripheral blood Improved with topical and systemic 37 F 68 71 5 treatment Death N Y N N N Y N Y* N N Y Y N N N Y Y N M: male; F: female; N: no; Y: yes; *non-MF related death Disproporcionate exocytosis 10 20 30 40 50 60 70 80 90 100 DISCUSSION Cutaneous T cell lymphomas, especially mycosis fungoides, are subject of update discussion, mostly about their pathogeny, classification and diagnostic criteria. The recent proposed classifications5,6 and the debates about the applicability and the reproducibility of criteria suggested by them7,8 prove such affirmative. We performed a systematic study in which we could confirm the sensibility of important histological criteria, as referred in the 3,4,9,10,11 literature. Specially in erythrodermic forms, hyperconvoluted dermal lymphocytes and disproportionate epidermotropism 11 may be considered of great importance, as described earlier. Despite these results, the absence of these criteria in a small part of the skin samples show that sometimes even the most prevalent criteria will not be seen in initial and erythrodermic forms of MF. Pautrier's microabscesses were considered specific findings by Smoller et al,3 since they are present almost exclusively in cases of 11,12 MF, although, these abnormal lymphocyte collections within the epidermis are present in the minority of cases of MF. They were seen only in about 25% of our cases. It seems that they are a specific finding, but not a sensible one, and thus are not necessary for the diagnosis of MF. We believe that in any patient with a clinical picture suggestive of mycosis fungoides, the presence of such prevalent histologic findings, can make the diagnosis possible, even in initial and erythrodermic forms. On the other hand, the absence of the histological findings can not exclude the diagnosis in a clinical suggestive setting. REFERENCES CONCLUSIONS Disproportionate epidermotropism, hyperconvoluted nuclei lymphocytes (within the epidermis and dermis), halloed lymphocytes and a dermal infiltrate with eosinophils are the most relevant histopathologic findings in patch stage and erythrodermic mycosis fungoides. E-mail: [email protected] 1. Shapiro PE, Pinto FJ. The histological spectrum of mycosis fungoides/Sézary syndrome (cutaneous T-cell lymphoma): a review of 222 biopsies including newly described patterns and the earliest pathological changes. Am J Surg Pathol 1994;18(7):645-67. 2. LeBoit PE, McCalmont TH. Cutaneous lymphomas and leukemias. In: Elder D, Elenitsas R, Jaworsky C, Johnson B, eds. Histopathology of the skin. 8th ed. Philadelphia: Lippincott-Raven; 1997. p 805-46. 3. Smoller BR, Bishop K, Glusac E, Kim YH, Hendrickson M. Reassessment of histologic parameters in the diagnosis of mycosis fungoides. Am J Surg Pathol 1995;19:1423-30. 4. Smith NP. Histologic criteria for early diagnosis of cutaneous T-cell lymphoma. Dermatol Clin 1994;12:315-22. 5. Harris NL, Jaffe ES, Stein H et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994;84:361-92. 6. Willemze R, Kerl H, Sterry W, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the cutaneous lymphoma study group of the European organization for research and treatment of cancer. Blood 1997;90:354-71. 7. Santucci M, Biggeri A, Feller AC et al. 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Histologic criteria for the diagnosis of erythrodermic mycosis fungoides and Sézary syndrome: a critical reappraisal. J Cutan Pathol 1997;24:292-7. 18. Sanchez JL, Ackerman AB. The patch stage of mycosis fungoides. criteria for histologic diagnosis. Am J Dermatopathol 1979;1:5-26. HUCFF-UFRJ TECNOARTE (21) 2286-7657 0