Variant nature of CTCL dianostic challenge

"CTCL can go misdiagnosed for months to years before the primary practitioner refers a patient to a dermatologist, or, at times, even until a dermatologist recognizes the condition," says Dr. Michael Girardi, M.D., associate professor at the Yale University School of Medicine in New Haven, Conn.

He adds, "This is not necessarily the practitioner's fault. He or she may be actively pursuing the possibility of CTCL, but the disease has not clearly defined itself in its evolution."

Dr. Girardi notes that in general, CTCL can look like atypical eczema or atypical psoriasis, and it can be treated as such long before it is accurately identified.

CTCL severity is measured by tumor involvement of the skin, nodal involvement, and metastatic involvement, the factors commonly called TMN. Dr. Girardi notes that "at the very early T1 stages, which involve less than 10 percent of the body surface area with patches or plaques, CTCL is more easily treated and potential mortality is less of a concern." However, the condition can progress to T2, where more surface area is involved; T3, where it can manifest as tumors in the skin; and T4, which is characterized by erythroderma.

Variants differ in morphology

Clinical variants of CTCL can be characterized according to morphology or distribution.

CTCL most commonly manifests as a patch/plaque variant known as mycosis fungoides. These lesions can vary in thickness and may appear as patches that are annular, oval or atypical in shape. They can also form plaques that can coalesce to form larger plaques. Lesions can be scaly or not scaly, and can vary in color from hyperpigmented to pink, red or purple.

Furthermore, some forms only show themselves as hyperpigmentation of the skin with no evidence of plaques. These variants can be confused with vitiligo or post-inflammatory pigmentation. More rare forms can cause a loosening of the skin, or granulomatous-like skin.

Distribution, character of lesions

Dr. Girardi explains that although lesions can occur anywhere on the skin, certain CTCL lesions can have an affinity for certain parts of the skin.

"A very commonly misdiagnosed form is the pigmented purpuric form, which manifests as petechiae or purpura in skin folds. These areas can look like atypical eczema or psoriasis."

Some variants have affinities for hair follicles, and others, for sweat glands. Disease progression may be accompanied by development of more poorly defined areas of erythema that may appear to develop spontaneously.

When more than 80 percent of the body surface is covered by the erythema, as is the case of erythrodermic mycosis fungoides, the patient is more likely to have leukemic involvement. This clinical variant is known as "Sezary syndrome," a general term used to describe patients with mycosis fungoides with erythroderma and morphologically abnormal circulating cells.

While recognizing this condition is key, further analysis of the molecular and histological characteristics of the condition will provide more detailed diagnostic information. In these more advanced forms of CTCL, monitoring of peripheral blood involvement is crucial because patients can become leukemic. Molecular analysis by PCR and cellular analysis by flow cytometry can be used to identify certain T-cell receptor clones, changes in CD4:CD8 ratio or expression of T-cell surface markers.

Dr. Girardi emphasizes that continual diagnostic efforts are important when CTCL is suspected.

"In cases where we are aware of the possibility of CTCL, we perform multiple biopsies at different times. We do analyses not just on a simple histologic evaluation but also on immunohistochemistry and molecular studies of T-cell clonality using PCR," he says.

An incorporation of the clinical, histologic and molecular characteristics of the condition can help clinicians reach a proper diagnosis of CTCL.

Disclosure: Dr. Girardi reports no conflicts of interest relevant to this article.