Case of the Month

50 year old woman presets with “white spots all over my body.” They started and developed gradually over the past 12 months. She is taking medicines for high blood pressure and high cholesterol. She reports no flu-like symptoms, fevers or night sweats. She says the lesions may a bite scaly on top, but it is difficult to determine because her skin is usually dry.

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Diagnosis: Cutaneous T Cell Lymphoma (a.k.a. Mycosis Fungoides)

Discussion

DEFINITION

A systemic lymphoma of T lymphocytes that manifests itself first in the skin as macules and then patches that often are scaly. Most people with the disease have only scaly macules and patches for a lifetime, but some patients may develop papules, plaques, nodules, tumors, and ulcerated tumors. As a rule, only those with extensive nodular and tumorous lesions die of the systemic effects of the disease.

If particular importance to note that in skin of color, mycosis fungoides can often present as white macules and patches. In fact, in skin of color, with a rapid onset of white round-to-oval patches, mycosis fungoides should be near the top of the differential diagnosis, if not at the top of the list.

ADJUNCTIVE DIAGNOSTIC TESTS

Assessment of peripheral blood and examination for staging may be undertaken in order to determine the extent of systemic disease.

COURSE

Most patients with mycosis fungoides have only patches of the disease for a lifetime. Some patients, however, have subtle plaques in addition to patches. Only uncommonly do nodules and tumors develop in patients with mycosis fungoides. Once a patch of mycosis fungoides develops, it tends to persist; rarely does a lesion of mycosis fungoides of any kind disappear in the absence of therapy. Patients who have nodules and tumors usually have patches and plaques as well. Once thick lesions of mycosis fungoides have come into being, whether they be thick plaques, nodules, or tumors, the prognosis changes from good or excellent to poor. Patients with mycosis fungoides who have very thick lesions usually die of systemic lymphoma.

PATHOLOGY

INTEGRATION: UNIFYING CONCEPT

Mycosis fungoides is a systemic lymphoma that usually manifests itself first in the skin as macules and then patches. The macules and ellipsoid patches take the form of what is known usually as “digitate dermatosis,” and the larger patches of what is called "parapsoriasis en plaques. When patches have a yellowish hue, they are designated “xanthoerythroderma perstans,” and when they have a reticulated pattern they are referred to as "parakeratosis variegate." When, in time, patches become atrophic, they are termed "poikiloderma vasculare atrophicans.” Digitate dermatosis also is referred to as "small-plaque parapsoriasis, and all the other expressions of mycosis fungoides just alluded to are known as "large-plaque parapsoriasis."

All of this terminology is confusing to students of the subject, because all of the lesions, clinically and histopathologically, are really those of mycosis fungoides and should be identified straightforwardly as mycosis fungoides. That diagnosis in itself does not denote a fatal end, any more than does a diagnosis of lupus erythematosus or melanoma. The fact is that the overwhelming majority of patients with mycosis fungoides (and with lupus erythematosus or melanoma) do not die of that malignant neoplastic process.

All of the lesions called small-plaque and large-plaque parapsoriasis have in common superficial perivascular infiltrates of lymphocytes and lymphocytes aligned as solitary units in the basal layer of the epidermis, in the spinous zone in conjunction with scant spongiosis, and sometimes in the upper reaches of die epidermis, such as the granular zone. That constellation of findings is diagnostic of mycosis fungoides. Sometimes lymphocytes within the epidermis are larger than those within the dermis. Wiry bundles of collagen in a haphazard array are often present in the upper part of the dermis in association with patchy lichenoid infiltrates of lymphocytes. In short, there is no need to invoke terms like small- and large-plaque parapsoriasis, digitate dermatosis, parapsoriasis en plaques, xanthoerythroderma perstans, parakeratosis variegata, and poikiloderma vasculare atrophicans; the diagnosis is mycosis fungoides.

Other distinctive clinical expressions of mycosis fungoides include plaques of pagetoid reticulosis near an ankle, pendulous lesions of granulomatous slack skin near axillary and inguinal regions, and the erythroderma of Sézary syndrome.

There is no need for any of those terms, except as descriptive modifiers of the diagnosis of mycosis fungoides, just as is the case for nodules and tumors of mycosis fungoides that are referred to universally as simply those of mycosis fungoides. In short, what has just been described represents the spectrum of morphologic findings of the systemic lymphoma called mycosis fungoides.

The original concept of mycosis fungoides, as it was set forth by Alibert in 1806 was limited and incorrect. Alibert conceived of mycosis fungoides as a disease that consisted of papules, nodules, and tumors, but not of macules, patches and plaques, and as a condition that, in his view, led inevitably to death. For almost two centuries, Alibert's was the accepted concept of mycosis fungoides among dermatologists, general pathologists, and dermatopathologists. Furthermore, it was asserted repeatedly that mycosis fungoides could not be diagnosed, clinically or histopathologically, when lesions were flat. Small- and large-plaque expressions were said to be "pre-mycosis fungoides" that in a small percentage of patients "converted" or "transformed" into authentic mycosis fungoides. In actuality, mycosis fungoides is mycosis fungoides from the very outset. Not only can mycosis fungoides be diagnosed with specificity when lesions are flat, but most patients with mycosis fungoides have only flat lesions for a lifetime. Practically never do those patients die of mycosis fungoides.

In conclusion, mycosis fungoides should not be thought of as an invariably fatal disease, but as that kind of systemic lymphoma that manifests itself first in the skin as flat lesions which usually remain flat for a patient's lifetime.

Dermatopathology

Histologic sections demonstrate a punch biopsy or Skin involved by an atypical epidermotropic lymphocytic inflammatory infiltrate. It is characterized by lymphocytes along the dermal/epidermal junction and exhibiting minimal pagetoid spread. Cytologically, these lymphocytes are small to medium in size with irregular hyperchromatic nuclei. The lymphocytes have clear cytoplasm. Within the superficial dermis is a mild perivascular chronic inflammatory infiltrate containing similar-appearing lymphocytes as well as small, round, mature-forms. Immunostains show the atypical lymphocytes to be CD-3, CD-8 - positive T-cells. A minority of background CD-4 - positive T-lymphocytes are seen predominately and dermis.

The clinical, histologic, immunophenotypic findings are of a mycosis fungoides (WHO/URTC) classification

FINAL DIAGNOSIS:

MYCOSIS FUNGOIDES
Andrew Larson, D.O. (Dermatopathologist)
Erick Jacobson. M.D. (Dermatopathologist)

THERAPY

Topical and oral retinoids, phototherapy including UVB, narrowband UVB, and UVA-1, or topical corticosteroids, photopheresis, or chemotherapy(alone or in combination) are all reported to be beneficial. A dermatologist specializing in the treatment of CTCL and/or an oncologist can help design the best therapeutic strategy for each specific case.

Reference:

A CLINICAL ATLAS OF 101 COMMON SKIN DISEASES
With Histopathologic Correlation br>A. BERNARD ACKERMAN, HELMET KERL, JORGE SANCHEZ, YING GUO, ANGELIKA HOFER, PAUL KELLY, TETSU KIMURA, GIOVANNI BORRONI, CHARLES CRUTCHFIELD, VOLKER STEINKRAUS, WOLFGANG WEYERS

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