By Abby Van Voorhees, MD, October 01, 2011
In this month’s Acta Eruditorum column, Physician Editor Abby S. Van Voorhees, MD, talks with Jinah Kim, MD, PhD, about her recent Journal of Cutaneous Pathology article, “The frequency of dual TCR-PCR clonality in granulomatous disorders.”
Dr. Van Voorhees: How often are granulomatous infiltrates seen in the setting of mycosis fungoides? Does it complicate the ability of the pathologist to establish a diagnosis?
Dr. Kim: We rarely encounter granulomatous infiltrates associated with mycosis fungoides. Recently in a study by Scarabello et al., a prominent granulomatous component was documented in less than 2 percent of their cases of either primary or secondary cutaneous lymphoma. In addition, the granulomatous process may occur at any point in the lymphoma disease process, that is, before, after, or concurrent with the diagnosis of mycosis fungoides. The granulomatous infiltrate may also have a range of histopathologic patterns, including sarcoidal, granuloma annulare-like, or tuberculoid.
Dr. Van Voorhees: Does this complicate the ability of the pathologist to establish a diagnosis?
Dr. Kim: Yes, definitely. The granulomatous infiltrate may be so exuberant that the neoplastic lymphocytes may not be easily identified. The infiltrate can really obscure the neoplastic lymphocytes to the point that you may suspect a purely granulomatous dermatitis. I think our study shows the importance of combining the clinical and the histopathologic features in this setting. It also highlights the value of clonality, which can be helpful in differentiating the inflammatory from the neoplastic processes.[pagebreak]
Dr. Van Voorhees: How often are monoclonal T-cell clones found in inflammatory conditions? Are these seen in granulomatous inflammatory infiltrates?
Dr. KIM: Molecular PCR [polymerase chain reaction] testing has led to the common detection of T-cell receptor clonal rearrangements in a variety of benign inflammatory including lichen planus, pityriasis lichenoides, and lichen sclerosis et atrophicus in a number of studies (Sander CA et al, 1998; Holm et al, 2002; Dereure O et al, 2000). In 2007, a study by Thurber et al. from Stanford University that was published in the Journal of the American Academy of Dermatology, demonstrated that two of 18 patients with inflammatory dermatoses were found to have a clone in one biopsy specimen (11 percent) and only one patient had positive clonality at two sites. Based this study of inflammatory infiltrates, we know that the analysis of T-cell receptor clonality at two different sites has a higher specificity and sensitivity for mycosis fungoides.
Dr. Van Voorhees: In prior studies where they’ve looked at lichenoid processes, it’s usually a single clone that’s positive, correct? Are there exceptions?
Dr. Kim: Yes, it’s true that there is a single clone present at one biopsy site. And the exception is that in our study, we identified an inflammatory disorder that demonstrated the identical TCR clone at several sites and over several timepoints.
Dr. Van Voorhees: What was the purpose of your study?
Dr. Kim: The purpose of our study was to evaluate the incidence of TCR clonality in granulomatous disorders. Interestingly, one of the patients in the study had an initial skin biopsy that appeared to be a granulomatous dermatitis; however through TCR-PCR, we detected identical clones in several biopsies at different sites and different timepoints. The clinical presentation of the patient also evolved and he was diagnosed with necrobiotic xanthogranuloma. Therefore, through this study we recognize that clonality in isolation may lead to a significant pitfall in diagnosis.[pagebreak]
Dr. Van Voorhees: What did you find? Were there any surprises? Did all granulomatous inflammatory infiltrates have at least one clone? Did the histological findings correlate with the clinical follow up? Were there exceptions granulomatous infiltrates that had the same clone in more than one site beyond your necrobiotic xanthogranulomatous patient?
Dr. Kim: Our results were very surprising. Our index case was the patient with necrobiotic xanthogranuloma who had multiple biopsies over time with an identical clone present in all samples. Another interesting point was that we found that three of our granuloma annulare patients demonstrated TCR clonality at one site but not at two separate sites. So we now know that granuloma annulare can join the list of inflammatory disorders that can have potentially false clonality and that it’s important to examine multiple sites to assist the distinction from granulomatous mycosis fungoides. Of course, the sensitivity and specificity of these tests can be improved with correlation with clinical findings.
Dr. Van Voorhees: Do your findings suggest a strategy for ensuring the highest degree of accuracy when one is trying to distinguish an inflammatory granulomatous infiltrate from one associated with mycosis fungoides?
Dr. Kim: In our Stanford University Multidisciplinary Cutaneous Oncology Clinic, directed by Dr. Youn Kim, we start with the clinical examination and whether the patient has a strong clinical suspicion of cutaneous T-cell lymphoma. In cases that are not clinically diagnostic, we perform at least two biopsies at separate sites to establish the diagnosis. After histopathologic interpretation, the biopsies may be subjected to further molecular testing as an adjunct to diagnosis.
Dr. Van Voorhees: What take-away have we learned about false positive T-cell clonality in granulomatous reactions?
Dr. Kim: For the granuloma annulare we had three positives out of the entire series, meaning that 10 percent of the cases were positive for a single T-cell receptor clone. However, when they were tested again at a second site or a second time point, they were all negative. I think this really brings home the message that if you’re clinically concerned about a site, multiple biopsies over time or at different sites are most helpful to really exclude the possibility of false positives due to the testing.
Dr. KIM is assistant professor of pathology and dermatology, director of dermatopathology, and director of dermatopathology education at Stanford University. Her article was published in the Journal of Cutaneous Pathology, 38(9), 704-709 (September 2011) after being published online June 7, 2011. doi:10.1111/j.1600-0560.2011.01727.x.