Author disclosures Alejandro Ariel Gru is a paid consultant for Seattle Genetics and has an ongoing relationship with Innate Pharma. John Zic is a site principal investigator for clinical trials for products from Elora and Galderma. The other authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the US Government, or any of its agencies. The manufacturers did not provide equipment or other forms of material support.
The diagnosis of MF relies on a combination of clinical, pathologic, and immunophenotypic findings where it is desired or preferred that at least 2 biopsies are done from different sides of the body. In addition to having a good clinical history that supports the diagnosis, a history of patches, plaques, and sometimes tumors in advanced stages in particular locations that are covered from the light (eg, trunk, buttocks, upper thighs, etc) combined with specific histopathologic criteria are capital to establish an accurate diagnosis.
In the biopsies, we look particularly for a lymphoid infiltrate that shows extension to the epidermis. We use the term epidermotropism to imply that these abnormal or neoplastic lymphocytes extend into the epidermis. They are also cytologically atypical. We see variations in the nucleus. In the size, we see a different character of the chromatin where they can be hyperchromatic. We also look for immunophenotypic aberrations, and particularly we analyze for patterns of expression of T-cell markers. Most cases of MF belong to a subset of T cells that are called CD4-positive or T-helper cells. We look for a patterned ratio of the CD4 and CD8 between the epidermis and an aberrant loss of the CD7 T-cell marker. Once we establish that we can see significant loss of these markers, we can tell where there is something wrong with that T-cell population, and likely belong to a neoplastic category.
In addition, we also rely on the molecular evaluation and search of a clonal population of T cells, by means of a T-cell receptor gene rearrangement study. Ideally, we like to see the establishment of a single clone of T cells that is matched in different biopsy sites. Proving that the same clone is present in 2 separate biopsies in 2 separate sites is the gold standard for diagnosis.6
John Zic. To recap, a biopsy is indicated for patients who have patches or plaques (that are slightly raised above the skin) in sun-protected areas that are fixed; rather than completely go away in the summer and come back in the winter, they are fixed if they have been present > 6 to 12 months. Many of these patients are diagnosed with eczema, psoriasis, allergic contact dermatitis, and other skin diseases before the clinician starts to think about other diagnoses, such as CTCL.
I agree that I would not rule out the diagnosis with 1 biopsy that does not show classic histologic changes. Also, I think that it’s important to alert the pathologist that you’re considering a diagnosis of T-cell lymphoma, either MF or some of the other subtypes, because that will certainly alert them to look a little closer at the infiltrating cells and perhaps do some of the other testing that was mentioned. Once we establish the MF diagnosis, staging studies may be indicated.
Lauren Pinter-Brown. Early stage would be patients with patches or plaques. Stage IA would be < 10% body surface area, and stage IB would be > 10%. I don’t perform scans for early-stage patients, but I do a very thorough physical and perform blood tests. For patients that have more advanced disease, such as tumors, erythroderma, or Sézary syndrome, I would conduct the same thorough examination and blood tests and scan the patient either with a computed tomography (CT) or a positron emission tomography (PET)/CT to detect adenopathy. We have to recognize that most of the adenopathy that is detected in these patients is peripheral, and we can feel it on physical examination.
