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Clinical Updates

Amit G. Pandya, MD

Diagnosing Early Mycosis Fungoides

Amit G. Pandya, MD

Thursday, February 11, 2010

"Doctor, why did it take so long to diagnose my cancer?". The frustration of spending years with itchy patches and plaques of an unknown cause until a diagnosis is finally rendered is one of the most common complaints arising from patients who have mycosis fungoides (MF). Once diagnosed, the frustration is magnified as patients wonder, "why was a disease as serious as cancer so elusive to physicians, both primary care practitioners and dermatologists alike?" Surprisingly for patients who search for an answer to their disease, a diagnosis can take more than 6 years after numerous visits to dermatologists.1 What can be done to improve this scenario?

Unlike most skin diseases, MF has a slow onset and clinical presentation, which includes protein skin manifestations, variable symptoms, multiple distributions and variation in scale, pigmentation and follicular involvement. Of note, these clinical presentations overlap in patients who have benign dermatoses. Histologic findings in early disease are also frequently non-specific and might not correlate with clinical appearance. However, knowledge of common presenting features can be helpful in making the correct diagnosis.

Correct Diagnosis of MF

A first step in the correct diagnosis of MF is conducting a careful history. Patients usually have a history of slow-growing, persistent lesions that do not spontaneously resolve. Unlike drug eruptions, urticaria or other dermatoses, which come and go, MF tends to 'come and stay'. A lack of complete response to topical corticosteroids is a common feature that can be used to help make a diagnosis. Pruritus is variable, and can be severe, but usually not as severe as those patients with contact dermatitis or urticaria.

Most often, MF appears in sun-protected parts of the body. As phototherapy is a common treatment for MF, it is not surprising that the sun actually benefits patients who have MF. It causes the disease to present in the classic 'bathing trunk' or 'boxer short' distribution on the skin. Sunbathing can also be useful for patients who have patch or thin plaque disease and who do not have access to other treatments. After a course of phototherapy, patients will often have residual disease in 'sanctuary sites', such as the gluteal cleft, inferior buttock creases, inguinal regions, inframammary folds and axillae and this emphasizes the sun-protected distribution of MF. Certain variants of MF, for instance, follicular mucinosis, do not show this distribution, but it is common enough to make this a good diagnostic tool.

Presentation of MF 

Patches and plaques of MF are usually large, with most lesions more than 5 cm in diameter. The individual lesions are not uniform in size and shape and this helps it to distinguish from drug eruptions, pityriasis rosea, lichen planus and secondary syphilis, to name a few. Small plaque parapsoriasis is an entity that is usually benign and presents with small patches and plaques on the trunk (Figures 1 and 2) that are 2 to 6 cm in diameter but might also have 'digitate' lesions that resembles the shape of a finger. It can be difficult to distinguish these lesions from MF, even histologically, while some physicians have considered small plaque parapsoriasis an early form of MF.2 The changes in clinical and histologic criteria over the past 20 years have led many dermatologists and dermatopathologists to make a diagnosis of MF in what was previously thought to be a benign disease. This might partially explain the increased incidence of MF.3 

 

Figure 1.  Plaques of mycosis fungoides on anterior trunk

 

Figure 2. Extensive plaque-stage mycosis fungoides on the back

The effect of MF on the papillary dermis causes a unique 'cigarette-paper wrinkling' of lesions, in particular those that are long-standing. Careful examination of lesions from different angles can also help to detect this change. The lesions are usually well circumscribed, unlike atopic dermatitis and other eczemas. Older lesions might also have poikiloderma that correlates with the distribution of the previously active lesions that can be described as mottled hyper and hypo-pigmentation, telangiectasia and epidermal atrophy. Unlike the poikiloderma of MF, dermatomyositis-related poikiloderma leaves poorly circumscribed plaques in its wake. Poikiloderma vasculare atrophicans is a term used to describe the slightly atrophic, wrinkled, well-demarcated older lesions of MF.

Techniques to Help Diagnosis

As histopathologic features of early MF can be very difficult to distinguish from benign dermatoses, it is important to take biopsies from multiple sites and, if unclear the first time, sequential biopsies over time. Physicians should also advise patients to stop the use of topical corticosteroids for several weeks prior to biopsy so that histopathologic changes are fully manifested at the time of biopsy. Atypical lymphocytes in the epidermis without spongiosis, clusters of atypical epidermal lymphocytes forming 'Pautrier's microabscesses', lining up of lymphocytes along the epidermal-dermal junction, a superficial lichenoid infiltrate and papillary dermal fibrosis are all histologic hallmarks of MF (Figure 3). Unfortunately, previous studies showed a high-degree of interobserver variability when dermatopathologists were asked to make a diagnosis of MF based on histologic criteria alone.4

More recent techniques, such as detection of T-cell clonality using PCR assays, can be helpful in making the diagnosis, but given that many benign dermatoses, such as contact dermatitis, can also demonstrate clonality, this test is not sufficient in and of itself to make the diagnosis. Similarly, patterns of staining for T-cell markers, might suggest a diagnosis of MF. For example, diminished expression of CD 5 and CD 7 could be seen in MF, particularly discordance between expression of these markers in the epidermis compared with the dermis.

Many pieces of the puzzle must fit together to make a diagnosis of MF. An experienced physician, using key components from the history, physical and biopsy results, can combine these various pieces of information to make a clinical judgment regarding the presence or absence of MF. The International Society for Cutaneous Lymphomas has created a diagnostic algorithm that uses clinical, histologic, molecular and T-cell marker studies to make a diagnosis of early MF. According to this system, a total of four points confirms a diagnosis of MF. This is a good first step in overcoming the difficulty of diagnosing early MF, however, this system has yet to be validated. Future studies testing the reliability and validity of this diagnostic algorithm should be performed in order to determine its applicability. While it might not apply to less common forms of MF, such as follicular or palmoplantar MF, this could be a future solution to the problem of early diagnosis of MF. Perhaps in the future, patients will have less uncertainty regarding their diagnosis as a result of such efforts, which can help in the prevention of unnecessary treatment in patients with benign disease and earlier treatment in those with true lymphoma.

Figure 3. Tumor-stage cutaneous T-cell lymphoma on cheek

Conclusion

In summary, the diagnosis of early MF is facilitated by the use of an experienced dermatologist and dermatopathologist; clinicopathologic correlation; multiple exams and biopsies over time; specialized studies of biopsy materials, including T-cell markers and gene rearrangement studies; occasional use of ancillary studies, such as flow cytometry of peripheral blood and X-ray studies and a high index of suspicion in the right clinical setting.

References

  1. Hymes KB. Cutaneous T-cell lymphoma: Mycosis fungoides and S├ęzary syndrome. In: Cancer of the Skin, Rigel DS, Friedman RJ, Dzubow LM, Reintgen DS, Bystryn J-C, Marks R Eds. Philadelphia: Elsevier Saunders; 2005.
  2. Ackerman AB. If small plaque (digitate) parapsoriasis is a cutaneous T-cell lymphoma, even an 'abortive one', it must be mycosis fungoides! Arch Dermatol. 1996;132:562-566.
  3. Weinstock MA, Gardstein B. Twenty-year trends in the reported incidence of mycosis fungoides and associated mortality. Am J Public Health. 1999;89:1240-1244.
  4. Olerud JE, Kulin PA, Chew DE, et al. Cutaneous T-cell lymphoma. Evaluation of pretreatment skin biopsy specimens by a panel of pathologists. Arch Dermatol. 1992;128:501-507.
  5. Pimpinelli N, Olsen EA, Santucci M, et al. Defining early mycosis fungoides. J Am Acad Dermatol. 2005;53:1053-1063.
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