Comment
Clinical Presentation of MF
Mycosis fungoides, a non-Hodgkin lymphoma of T-cell origin, is the most commonly diagnosed cutaneous lymphoma worldwide.1 It has an annual incidence of approximately 0.36 per 100,000 persons, and this number continues to rise.2,3 The median age of diagnosis is 55 to 60 years, and MF occurs twice as often in men versus women.4
The clinical presentation of MF varies and is classified by stages including patches, plaques, tumors, and erythroderma.5 Classically, MF is slowly progressive and begins as pruritic erythematous patches that have a predilection for non–sun-exposed areas of the skin. Over time, these patches may evolve into plaques and tumors. Early or patch-stage MF often presents as well-demarcated lesions of various sizes and shapes that tend to enlarge.6 These lesions may resemble eczema or psoriasis if there is scaling, such as in our patient. At the tumor stage, flat or dome-shaped nodules that may vary in color and are deeper than plaques begin to appear. Ulcerations, which were absent in our case, may often be seen.
Because of the diverse clinical manifestations of MF, which can mimic other common dermatoses, diagnosis often is challenging for clinicians. Furthermore, histology can yield nonspecific diagnostic results and may even resemble chronic inflammatory dermatoses.7 As a result, patients frequently are subjected to multiple skin biopsies to establish the diagnosis,8 and diagnosis may be delayed, with the median time from onset of skin symptoms to diagnosis being approximately 6 years.9
Reflectance Confocal Microscopy
In vivo RCM is a noninvasive technique that allows visualization of the skin at a cellular level and recently has been evaluated as a diagnostic tool for many skin conditions.10,11 Reflectance confocal microscopy findings have been well established for many cutaneous malignancies as well as inflammatory conditions such as psoriasis and atopic dermatitis.12,13 Specifically, 2 preliminary descriptive studies utilized RCM to visualize the characteristic features of MF in vivo.14,15 These studies reported the histopathologic correlation of RCM findings in biopsy-proven MF lesions. Consistent in all stages of MF is the presence of small, weakly refractile, round to oval cells within the spinous layer that correlate with atypical lymphocytes, in addition to hyporefractile basal cells surrounding the dermal papillae. Patch-stage MF lesions have more subtle epidermal findings compared to plaque-stage lesions, which tend to have more prominent vesiclelike dark spaces filled with collections of monomorphous, weakly refractile, round to oval cells corresponding with Pautrier microabscesses and evidence of spongiosis.14,15 The first descriptive study of RCM in the diagnosis of MF failed to identify features of tumor-stage MF that would distinguish it from patch- or plaque-stage disease. The investigators also stated that deep nodular collections of atypical lymphocytes seen on histopathology in tumor-stage MF were missed on RCM evaluation.14 Furthermore, the second descriptive study of RCM and MF, which included 2 patients with tumor-stage disease, also failed to differentiate tumor-stage MF from the patch or plaque stages.15
Because of these 2 descriptive studies, a pilot study was conducted to determine the applicability and reproducibility of RCM findings for MF diagnosis.16 Two blinded confocalists were asked to diagnose RCM images as MF when compared to either normal skin or a variety of lymphoproliferative disorders. Of 15 patients, the confocalists correctly diagnosed MF in 84% and 90% of cases, respectively. Additionally, they reported the specificity and sensitivity of the following RCM features in the diagnosis of MF: spongiosis, 88.9% and 94.7%; loss of demarcation, 88.9% and 94.7%; disarray of the epidermis, 77.8% and 89.5%; hyporefractile rings, 88.9% and 78.9%; junctional atypical lymphocytes, 100% and 73.7%; and vesiclelike structures (Pautrier microabscesses), 100% and 73.7%. Importantly, this study did not evaluate the specificity and sensitivity of MF diagnosis compared to other eczematous or inflammatory conditions that may share similar RCM findings; therefore, these results are not generalizable, and many of the RCM findings characteristically seen in MF are not specific to its diagnosis.16
One study assessed the diagnostic accuracy of RCM in evaluating erythematosquamous diseases including MF, psoriasis, contact dermatitis, discoid lupus, and subacute cutaneous lupus.17 In this study, 3 blinded confocalists achieved a 95.41% and 92.89% specificity and 89.13% and 63.33% sensitivity for psoriasis and MF, respectively. Typical features of psoriasis on RCM included parakeratosis, reduction or absence of the granular layer, papillomatosis, acanthosis with normal honeycomb pattern of the epidermis, and dilated vessels in the upper dermis. Features that were more specific to MF included epidermotropic atypical lymphocytes, interface dermatitis, pleomorphic tumor cells, and dendritic cells.17 However, atypical lymphocytes and interface dermatitis also may be seen in cutaneous lupus; therefore, additional studies are still needed to validate RCM’s utility in differentiating between erythematosquamous skin diseases, including psoriasis, cutaneous lupus, and MF. Currently, RCM findings must be interpreted in conjunction with the clinical and histologic picture.
Importantly, RCM also is limited when evaluating MF due to its limited depth of visualization, as it allows imaging only to the superficial papillary dermis. Furthermore, any infiltrative process such as epidermal hyperplasia, spongiosis, or scaling, which can be seen in MF, may further impair the imaging quality of the deeper dermis.
Conclusion
Despite its limitations, RCM has the potential to be advantageous in evaluating skin lesions suspicious for MF in real time and is a promising technology for a quick noninvasive bedside adjunct tool. Its utility in selecting the optimal site for biopsy for better yield of histopathologic results in suspected MF cases has been demonstrated.16 However, large-scale studies still are needed to evaluate RCM in the diagnosis of the wide diversity of MF lesions as well as its efficacy in selecting optimal biopsy sites.