Comparison between the histopathological and immunophenotypical features of hypopigmented and nonhypopigmented mycosis fungoides: A retrospective study.

BACKGROUND: Mycosis fungoides (MF), the commonest primary cutaneous T-cell lymphoma, has classic and variant types which include hypopigmented MF (HMF). Previous studies have identified distinct clinicopathological profiles in HMF. This study aims to objectively compare the clinicopathological features of HMF with non-HMF lesions in order to characterize salient features of HMF. METHODS: This cross-sectional, retrospective study analyzed biopsy specimens of 87 patients with MF. HMF and non-HMF groups were compared using clinical data, immunophenotypic features and scores given for six histopathological features: dermal infiltrate, basilar and superficially extending epidermotropism, Pautrier microabscesses and dermal and epidermotropic lymphocytic atypia. RESULTS: Seventy-six patients had HMF. Presentation in females (59.21%; p = .04) and patch stage (88.16%; p = .01) in HMF were significant, and HMF presented at a younger mean age when compared to non-HMF. Both groups had equal intensity of epidermotropism, with HMF showing milder dermal infiltrates and significantly less dermal atypia. Pautrier microabscesses were significantly commoner in non-HMF (LR 10.76; p < .01). 94.74% of HMF were CD4-/CD8+. CONCLUSION: HMF presents at a lower age and earlier stage with female predominance compared to non-HMF. Because of milder dermal infiltrates, less dermal atypia, and Pautrier microabscesses, the diagnosis of HMF requires correlation with clinical features and careful assessment of epidermotropic cells.

Impact of clinical photographs on the accuracy and confidence in the histopathological diagnosis of mycosis fungoides.

BACKGROUND: The histopathological diagnosis of MF is challenging, and there is significant overlap with benign inflammatory processes. Clinical features may be relevant in the assessment of skin biopsies. METHODS: We provided photomicrographs to board-certified dermatopathologists and one hematopathologist with and without accompanying clinical photographs and assessed accuracy and confidence in diagnosing MF. RESULTS: We found that access to clinical photographs improved diagnostic accuracy in both MF and non-MF (distractors); the degree of improvement was significantly higher in the non-MF/distractor category. Across all categories, diagnostic confidence level was higher when clinical images were available. CONCLUSION: These findings suggest that clinical images are useful in making an accurate diagnosis of MF, and may be particularly helpful in ruling it out when an inflammatory disorder is clinically suspected.

Aproximación al diagnóstico dermatopatológico de las lesiones figuradas / Approaches to the Dermatopathologic Diagnosis of Figurate Lesions

Las lesiones cutáneas figuradas son muy frecuentes en la práctica diaria, y en la mayoría de las ocasiones requieren una adecuada correlación clínico-patológica para llegar a un diagnóstico correcto. En algunos casos la biopsia mostrará hallazgos específicos que permitirán hacer el diagnóstico, pero en la mayor parte de ellos los datos serán inespecíficos. En un intento de aproximarnos al diagnóstico de estas dermatosis hemos clasificado las lesiones anulares según el tipo de infiltrado inflamatorio: linfocitario, neutrofílico-eosinofílico, granulomatoso y con células plasmáticas; y hemos incluido un último apartado para las lesiones anulares neoplásicas. Entre las primeras destacamos el eritema anular centrífugo (superficial y profundo) y su amplio diagnóstico diferencial. Con infiltrado neutrofílico-esinofílico incluimos: psoriasis anular, vasculitis, dermatitis IgA lineal, dermatitis eosinofílica, eritema marginado reumático y eritemas anulares de la infancia. La sarcoidosis y el granuloma anular son los prototipos de lesiones anulares con granulomas, y la sífilis secundaria con células plasmáticas. La micosis fungoide es la principal neoplasia cutánea que puede iniciarse con lesiones anulares (AU)

Both clinical and pathologic findings must be considered when diagnosing figurate skin lesions, which are often seen in routine practice. Although a skin biopsy may sometimes be diagnostic, more often the information provided is nonspecific. In an attempt to offer an approach to diagnosing these dermatoses, we have classified annular lesions according to the presence of lymphocytic, neutrophilic-eosinophilic, or granulomatous infiltrates, and infiltrates containing plasma cells. Neoplastic annular lesions are included in a separate group. Lesions containing lymphocytic infiltrates include superficial and deep erythema annulare centrifugum and the differential diagnosis includes a large number of conditions. In the neutrophilic-eosinophilic class, we include annular psoriasis, vasculitis, linear immunoglobulin A dermatosis, eosinophilic dermatitis, erythema marginatum rheumatica, and annular erythema of infancy. Sarcoidosis and granuloma annulare are the prototypical annular lesions containing granulomas. Secondary syphilis is typical of lesions containing plasma cells. Mycosis fungoides is the principal skin tumor that may initially manifest with annular lesions (AU)

Diagnostic value of combining immunostaining for CD3 and nuclear morphometry in mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common skin lymphoid neoplasm. In initial stages, differential diagnosis of MF from other benign dermal lymphoid infiltrates (BDLI) may be impossible on morphological basis alone. In previous studies, only deletion of CD7 in MF proved to be of diagnostic help, but not the ratio between immunoexpression of CD4 and CD8. METHODS: 30 cases of MF and 11 cases of BDLI were analysed, in order to compare morphometric parameters, which could be of diagnostic aid. As CD7 is frequently deleted in MF, immunohistochemical detection of T-cells was made using an antibody to CD3. Images of 100 CD3-positive cells per case in both groups were captured and analysed using a simple computer program for nuclear perimeter, area, diameter and nuclear contour index. RESULTS: All parameters showed statistically significant higher values for MF. Area was the variable with the strongest discriminating power between the two groups of patients. Thus even if morphological evaluation is not accurate to distinguish benign versus malignant dermal lymphoid infiltrates, due to the variability of size and shape of these cells, a more sensitive method promptly shows this difference. CONCLUSION: Results suggest that morphometry of CD3-positive lymphoid cells may add valuable information in the differential diagnosis of MF and benign dermatoses.

Immunogold detection of CD3 and CD4 antigens in patients with Mycosis fungoides.

In this study, we analyzed the distribution of CD3 and CD4 antigens at the ultrastructural level in tissue samples from mycosis fungoides patients using double-immunogold labeling. We observed clusters composed of CD3 and CD4 antigens on the plasma membrane and intracellular. There were also clusters only of one type of the antigen and we could observe more often CD4 than CD3. Labeling of CD3 and CD4 was not found in control cells incubated with non-immune serum. In conclusion, our ultrastructural studies not only visualized pattern distribution and relationship between CD3 and CD4 antigens but might also suggest that the type and form of distribution provides new clues to their possible translocation in mycosis fungoides cells.

Carbamazepine-induced pseudo mycosis fungoides.

OBJECTIVE: To report a case of pseudo mycosis fungoides due to carbamazepine. CASE SUMMARY: A 54-year-old man experienced a skin lesion resembling mycosis fungoides without any systemic symptoms or signs 2 months after he had begun carbamazepine treatment for his seizures. Skin-punch biopsy specimens revealed mycosis fungoides-like histopathologic appearance. After drug discontinuation, the patient experienced complete remission of the clinical and pathologic findings. This suggests a diagnosis of pseudo mycosis fungoides due to carbamazepine. DISCUSSION: Mycosis fungoides is the cutaneous T-cell lymphoma of the skin that needs aggressive chemotherapy and radiation treatment. Pseudo mycosis fungoides is a condition caused by certain drugs that has a similar clinical and histopathologic appearance to mycosis fungoides. When the causative drug is discontinued, the lesions resolve completely. CONCLUSIONS: An objective causality assessment revealed that carbamazepine was highly probable as the cause of the adverse reaction. Patients who are diagnosed with mycosis fungoides should be asked about any drug use, and clinicians should recognize signs of pseudo mycosis fungoides.

[The ultrastructural characteristics of the early diagnosis of mycosis fungoides]. / Ul'trastrukturni osoblyvosti rann'oï diahnostyky hrybovydnoho mikozu.

As a result of studies made (biopsy specimens of damaged skin from seven patients presenting with the erythrodermic stage of mycosis fungoides) a conclusion was reached that at the given stage the following two processes take place: (1) a rise in the proliferative activity of keratinocytes and (2) disturbances their differentiation. These ultrastructural manifestations can serve as criteria for a well-timed diagnosis of mycosis fungoides to be made.

The small-cell variant of mycosis fungoides. A clinicopathological and quantitative electron microscopic study on 14 patients.

Small-cell variants of Sézary syndrome and mycosis fungoides (MF) have been described. However, in these studies the nuclear area of the small-cell variant of MF (SC-MF) as compared to histological classical MF (CL-MF) was not characterized objectively by quantitative electron microscopy. In a 14-year follow-up period, of a total of 76 patch/plaque stage MF patients seen in the Department of Dermatology of the University Hospital Utrecht, 14 (18%) had an infiltrate composed of atypical lymphocytes characterized by a distinctly smaller cell diameter and smaller, hyperchromatic, deeply indented nuclei as compared to the usual cell type of MF. The aim of the investigation was to confirm this observation objectively using quantitative electron microscopy (morphometry) and to define SC-MF as compared to CL-MF. The study was performed on the 14 patients with SC-MF, and 10 patients with clinical and histological CL-MF and 4 patients with chronic eczema. Electron micrographs of sections obtained from each biopsy were analysed by computer to produce the following data: a nuclear contour index (NCI), the mean nuclear area (MNA), the mean nuclear area of the cells above the 75th percentile (P75NA) and the percentage of cells larger than 30 microm2. The values of MNA differed significantly between patients with SC-MF and those with CL-MF (17.6 vs 23.2 microm2; P = 0.02), as did the values of P75NA (20.7 vs 27.9 microm2; P = 0.01). The NCI of the SC-MF and CL-MF patients were similar. These results are consistent with our observations that SC-MF does indeed exist.

Estimates of nuclear volume in plaque and tumor-stage mycosis fungoides. A new prognostic indicator.

It is well documented that mycosis fungoides (MF), a cutaneous T-cell lymphoma, has a variable clinical course. Unbiased stereological estimates of three-dimensional volume-weighted mean nuclear size (nucl vV) of mycosis cells were obtained in a retrospective study of 18 patients with a total of 34 biopsies of cutaneous plaque and tumor-stage MF. The value of nucl vV in the first sampled biopsy, as well as the average and highest values, were determined in biopsies from each patient. The patients were divided into two groups, either above or below the group median. There was a strong positive correlation between shorter survival and an average value of nucl vV > 104 microns 3 or a highest value of nucl vV > 126 microns 3 (2p = 0.002 and 0.003, respectively). A nucl vV > 91.6 microns 3 in the first biopsy was also suggestive of a shorter survival (2p = 0.07). There was no clear pattern of nucl vV evolution in the patients with multiple biopsies, but the impact of various therapeutic regimens cannot be assessed. Certain estimates of nucl vV appear to be good prognostic indicators in plaque and tumor-stage MF, but further study of a larger series of patients is needed to corroborate these results and assess the impact of differing therapeutic regimes.

Pitiríase versicolor: atualizaçäo bibliográfica / Tinea versicolor: bibliographic review

Com base em importantes trabalhos da literatura internacional realizados na última década sobre Pitiríase versicolor, os autores fazem uma extensa revisäo bibliográfica do tema, abordando especialmente aspectos históricos, etiológicos, etiopatogênicos, epidemiológicos, histopatológicos, clínicos, diagnósticos e terapêuticos

[A comparative study of the quantitative distribution and ultrastructure of Langerhans cells in the epidermis of patients with chronic benign dermatoses and mycosis fungoides]. / Sravnitel'naia otsenka kolichestvennogo raspredeleniia i ul'trastruktury kletok Langergansa v épidermise bol'nykh khronicheskimi dobrokachestvennymi dermatozami i gribovidnym mikozom.

Using histoenzymatic assay for ATPase activity and electron microscopy, Langerhans' cells (LC) in biopsy specimens taken from skin lesions of 20 patients with chronic benign dermatoses (CBD) and of 28 patients suffering from mycosis fungoides (MF) were identified. In the early lesions of MF the reduction of the number of cell dendrites, disappearance of normal arrangement and the reduced absolute quantity of LC were observed on comparison with patients with CBD. Ultrastructurally, the destroyed forms of LC were predominantly observed in MF lesions, while in cases of CBD most of the LC were functionally active. The authors suggest that the examination of functional activity, quantitative distribution and ultrastructural features of LC should be used as an early morphologic test for differential diagnosis of early signs of MF and CBD this being of vital importance for an adequate and due treatment.

[The isolation and characteristics of long-term continuous lymphoid cell lines (IK-10 and IK-12) from patients with mycosis fungoides]. / Poluchenie i kharakteristika dlitel'no perevivaemykh limfoidnykh kletochnykh linii (IK-10 i IK-12) ot bol'nykh gribovidnym mikozom.

Examinations of 26 cell cultures have detected in two cases continuous IK-10 and IK-12 cell lines from patients with mycosis fungoides. Studies of these cell ultrastructure, carried out by transmission electron microscopy, have shown organoids of all types, that are characteristic of both minor and medium lymphocytes and of lymphoblasts. Markers of T-, B-cells and mononuclears are also detectable in these cell lines. The cells express surface immunoglobulins and interleukin-2 receptors. Noteworthy that association of these cells in a population may be in vitro cultivated for more than 2 years.

Differentiation of interdigitating reticulum cells and Langerhans cells in the human skin with T-lymphoid infiltrate. An immunocytochemical and ultrastructural study.

The differentiation of two types of T-lymphocyte accessory cells, i.e., interdigitating reticulum cells and Langerhans cells, was studied immunocytochemically and ultrastructurally on cutaneous lesions from patients with mycosis fungoides, a neoplasm of mature T-lymphocytes. In such a condition the lymphoid infiltrate creates, adjacent to the epidermis, a microenvironment in the dermis similar to that of T-cell areas of lymphoid organs. Immunocytochemistry revealed that CD11c+ CD1a- putative monocytic cells co-exist with CD11c+ CD1a+ putative mature accessory cells. By electron microscopy, large numbers of interdigitating reticulum cells in the dermal infiltrate and Langerhans cells in the epidermis were found. Furthermore, monocytes were frequently observed, at times with cells showing intermediate features between monocytes and interdigitating reticulum cells on the one hand and Langerhans cells on the other. In the absence of proliferative phenomena of the above cells, it is conceivable that both interdigitating reticulum cells and Langerhans cells originate from locally migrated monocytes. A possible role of the local tissue micro-environment--namely the T-lymphoid microenvironment for interdigitating reticulum cells and the epidermal microenvironment for Langerhans cells--in inducing the differentiation of monocytes into the two kinds of accessory cells is proposed.

Morphometrical analysis of mycosis fungoides on paraffin-embedded sections.

Morphometry was carried out on H&E stained paraffin sections of 29 cases of contact dermatitis (CD) and 35 cases of mycosis fungoides (MF) (patch stage 12; plaque stage 11; tumor stage 12); 9 nuclear parameters, mean thickness of the infiltrate and 5 stereological parameters were assessed for each slide. Application of a non-parametric discriminant analysis (k-nearest neighbour method) which is based on median of nuclear areas, mean maximal nuclear diameter, volume density and numerical density of nuclei provided discrimination between CD and patch stage MF at an efficiency of 82.9% (specifity 86.7%, sensitivity 61.5%). Efficiency of discrimination between CD and plaque stage was 92.5% (specifity 89.7%, sensitivity 91.7%) and between CD and tumor stage 100% when discriminant analysis was based on the mean thickness of the infiltrate. Although unequivocal discrimination between CD and MF cannot be achieved in each individual case, morphometry on routine paraffin material obviously provides additional objective criteria for the diagnosis of early MF.

Unilesional mycosis fungoides: a distinct entity.

Four cases of solitary lesions showing the histologic features of mycosis fungoides are described. Three patients had an erythematous scaling plaque, whereas the fourth had a solitary nodule. The lesion was located on the arm in two patients, on the foot in one patient, and on the back in one patient. No preceding factors were noted, and no lymphadenopathy or other significant illness was found on examination. Histologic examination demonstrated features of a cutaneous T cell lymphoma with epidermotropism. Monoclonal markers on frozen and paraffin sections revealed a predominant T cell infiltrate. Three patients were treated with local excision. The remaining patient was treated with radiotherapy. The lesions have not recurred, and no new lesions have developed after individual follow-up of 7 months, 7 1/2 months, 13 years, and 18 years. These cases appear to be unique reports of solitary mycosis fungoides behaving in a biologically benign manner. The relationship to Woringer-Kolopp disease and lymphomatoid papulosis is discussed.

Angiocentric T-cell lymphoma of the skin. An aggressive lymphoma distinct from mycosis fungoides.

Among 37 consecutive cases of malignant lymphoma in which the skin was either the only site of disease or one of the prominent sites of initial involvement, 19 cases had a distinctive histological appearance. These cases corresponded to what has been termed "angiocentric lymphoma," and all were found to exhibit a T-cell phenotype either by frozen-section immunohistochemistry or by using monoclonal antibodies reactive in paraffin sections. There were nine men and 10 women; the mean age was 48.2 years. The lesions were nodular and were either ulcerated or had intact skin. One case presented with involvement of one anatomical region of skin, five had involvement of multiple regions of skin, and 13 had concurrent extracutaneous disease. The disease pursued an aggressive course and was not uncommonly resistant to treatment. Histologically, the lymphomatous infiltrate occurred predominantly in the mid to deep dermis with involvement of the subcutaneous layer. The pattern was mainly perivascular and peri-adnexal with or without confluence; the overlying epidermis and papillary dermis were often spared. A prominent feature was invasion of small or large blood vessels by lymphoma cells. Eight cases showed extensive coagulative necrosis of the neoplastic and normal tissues, and 12 cases showed intraneural invasion. The neoplastic lymphoid cells consisted of either a monomorphous population or a variable mixture of small, medium-sized, and large cells with stippled chromatin and distinct nucleoli. Although the nuclei were often irregularly folded, few exhibited a cerebriform configuration. The cytoplasm was pale to clear. These cases exhibit a remarkable histological similarity to the T-cell lymphomas of the nasal/nasopharyngeal region; in addition, there are features that overlap with so-called lymphomatoid granulomatosis of the skin.

Interdigitating reticulum cells in the dermal infiltrate of mycosis fungoides. An ultrastructural and immunohistochemical study.

In order to provide insight into the role of accessory cells in lymphoproliferative neoplasms, 7 cases of mycosis fungoides at various clinical stages--patches, plaques and nodules--were studied ultrastructurally and immunohistochemically. The aim was to establish whether interdigitating reticulum cells are a constant finding in the dermal infiltrate. Their possible relationships with mycosic cells were also investigated. This study revealed that interdigitating reticulum cells were present in all the skin lesions examined, were present in considerable number in the patches and plaques and became sparse in the nodules. Furthermore, in the lesions at various clinical stages these cells showed varying ultrastructural features, probably related to different developmental stages. The close contacts between interdigitating reticulum cells and mycosic cells, the expression of antigenic markers of activation by mycosic cells and the morphological and immunohistochemical signs of progressive de-differentiation of mycosic cells in the more advanced stages suggest that interdigitating reticulum cells are involved in stimulating proliferation and--possibly--neoplastic progression of mycosic cells. A role for the T-cell microenvironment created in the dermis by lymphoid infiltrate in inducing the differentiation of interdigitating reticulum cells from their precursors is proposed.

Ultrastructural characteristics of the interdigitating dendritic cell in dermatopathic lymphadenopathy of mycosis fungoides patients.

The ultrastructure of interdigitating dendritic cells in dermatopathic lymphadenopathy from patients with mycosis fungoides was investigated. The most remarkable findings were: a marked hypertrophy of the smooth endoplasmic reticulum with a peculiar concentric arrangements of the cisternae around lipid droplets, an abundance of cytoplasmic lipid droplets and the presence of paranuclear chromatoid-like bodies. It is suggested that these ultrastructural features may correspond to some unknown functional capability of the interdigitating dendritic cell.