Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder: Diagnosis and management

To the Editor: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCS-TCLPD) is a rare, indolent, and poorly understood disease.1Willemze R. Cerroni L. Kempf W. et al.The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas.Blood. 2019; 133: 1703-1714Google Scholar, 2Bradford P.T. Devesa S.S. Anderson W.F. et al.Cutaneous lymphoma incidence patterns in the United States: a population-based study of 3884 cases.Blood. 2009; 113: 5064-5073Google Scholar, 3Beltraminelli H. Leinweber B. Kerl H. et al.Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma: a cutaneous nodular proliferation of pleomorphic T lymphocytes of undetermined significance? A study of 136 cases.Am J Dermatopathol. 2009; 31: 317-322Google Scholar, 4Grogg K.L. Jung S. Erickson L.A. et al.Primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma: a clonal T-cell lymphoproliferative disorder with indolent behavior.Mod Pathol. 2008; 21: 708-715Google Scholar, 5von den Driesch P. Coors E.A. Localized cutaneous small to medium-sized pleomorphic T-cell lymphoma: a report of 3 cases stable for years.J Am Acad Dermatol. 2002; 46: 531-535Google Scholar There are no clear diagnostic or treatment guidelines. Herein, we report PCS-TCLPD and cases with PCS-TCLPD identified using a histopathologic differential diagnosis during long-term follow up. The clinical features, comorbidities, treatment, and outcomes were analyzed for patients with suspected and definite PCS-TCLPD. A retrospective study of PCS-TCLPD was performed across the Mayo Clinic enterprise. Pathology reports from 61 patients with PCS-TCLPD were identified using the histopathologic differential diagnosis between the years 1999 and 2019. A chart review was performed to ensure that the cases fit the definition of PCS-TCLPD. All the cases lacked a preceding history of mycosis fungoides or clinical or radiologic features concerning PTCL-NOS, displayed a CD3+/CD4+/CD8−/CD30− phenotype, when tested, had a T-follicular immunophenotype (most often with diffuse programmed cell death protein 1 positivity), and lacked epidermotropism. Most (74.4%) cases were clonal and/or displayed pleomorphism. A total of 51 patients were found to meet the final diagnostic criteria for PCS-TCLPD. Forty-five patients had clinical follow-up information and were included in the treatment outcome analysis. All the reviewed treatment data were tabulated, and basic statistics were analyzed for PCS-TCLPD. The demographics and clinical features are listed in Table I. There were no associated lymphomas. The workup included positron emission tomography/computerized tomography scans, which were completed in 45.1% of the patients, with 30.4% of the scans revealing an abnormal finding. The most reported abnormal finding on positron emission tomography was low-level or nonspecific fluorodeoxyglucose uptake. None of these abnormal findings were found to be clinically significant or affecting patient management. Bone marrow evaluation was performed on 17.6% of the patients, and all the patients tested negative for disease.Table IDemographic and clinical dataPatient demographicsValueClinical informationValueAdditional studiesValueAge at the time of diagnosis (years)Associated autoimmune conditionPET/CT Mean (SD)53.9 (14.5) None41 (80.4%) No28 (54.9%) Median54.0 Crohn disease1 (2.0%) Yes23 (45.1%) Range(30.0-88.0) Grave disease1 (2.0%)Abnormal PETVital status Hashimoto thyroiditis1 (2.0%) No15 (65.2%) Alive49 (96.1%) Sarcoidosis1 (2.0%) Yes7 (30.4%) Deceased2 (3.9%) Unknown6 (11.8%) Unknown1 (4.3%)RaceLocation of biopsyBone marrow biopsy Other1 (2.6%) Abdominal and genital4 (7.8%) No42 (82.4%) White37 (97.4%) Chest10 (19.6%) Yes9 (17.6%) Unknown13 Head and neck31 (60.8%)Abnormal bone marrowEthnicity Left side of the upper portion of the leg1 (2.0%) No9 (100%) Hispanic or Latino3 (5.9%) Lower portion of the back and buttock1 (2.0%) Not Hispanic or Latino39 (76.5%) Right side of the upper portion of the arm1 (2.0%) Unknown9 (17.6%) Upper portion of the back3 (5.9%)SexTumor size, greatest dimension (cm) F24 (47.1%) Mean (SD)1.7 (0.9) M27 (52.9%) Median1.7 Range(0.5-4.0) Unknown23TNM classification T1aN0M025 (92.6%) T2aN0M01 (3.7%) T3aN0M01 (3.7%) Unknown24CT, Computerized tomography; F, female, M, male; PET, positron emission tomography; SD, stable disease; TNM, tumor, nodes, metastasis."Unknown" indicates insufficient records. Open table in a new tab CT, Computerized tomography; F, female, M, male; PET, positron emission tomography; SD, stable disease; TNM, tumor, nodes, metastasis. "Unknown" indicates insufficient records. Clinical management varied between the patients (Table II). The overall response rate was 100% for patients who received treatment (87.9% complete response [CR], 12.1% partial response). One case had recurrent disease at a new site. Of 9 patients who were observed, 8 had a CR after initial biopsy, with 1 lacking clinical follow-up information. Thirteen cases were treated with excision, without recurrence. Eleven cases were treated with topical steroids: CR (3/9; 33.3%), partial response (3/9; 33.3%), and stable disease (3/9; 33.3%). Two cases lacked follow-up information. Of the 3 cases with stable disease, 2 subsequently responded to excision, and 1 responded to pulsed dye laser. All the 4 cases were treated with radiation therapy and had a CR, with a new disease developing at a previously untreated site in 1 case. All cases of intralesional steroids had a partial response. One case treated with phototherapy and the 1 case treated with pulsed dye laser had a CR. There were no disease-specific deaths.Table IITreatment and treatment outcomesTreatmentOutcomesExcision n = 19CR = 19 (100.0%)Topical steroids n = 11CR = 3 (33.3%)PR = 3 (33.3%)SD = 3 (33.3%)Unknown = 2Observation n = 9CR = 8 (100.0%)Unknown = 1Radiation therapy n = 4CR = 4 (100.0%)Injected steroids n = 2PR = 2 (100.0%)Light therapy n = 1CR = 1 (100.0%)Pulsed dye laser n = 1CR = 1 (100.0%)Any treatment n = 42CR = 29 (87.8%)PR = 4 (12.1%)Unknown = 9CR, Complete response; PR, partial response; SD, stable disease."Unknown" indicates insufficient records. Open table in a new tab CR, Complete response; PR, partial response; SD, stable disease. "Unknown" indicates insufficient records. PCS-TCLPD is an indolent disease with no long-term risk of secondary lymphomas. Imaging modalities and bone marrow evaluations are of a relatively low diagnostic value and may not be necessary for all patients with PCS-TCLPD. Clinical observation can be considered as an initial management strategy, given the lack of clinically significant sequelae. Conservative, local treatment modalities can be used with a high degree of success and should be considered before invasive or systemic treatments. Dr Mangold reports personal fees from Kirin and grants from Elorac, MiRagen, Solagenix, DUSA/Sun Pharma, and Acetilion, outside the submitted work. Drs Costello, DiCaudo, Comfere, Sluzevich, Rule, Craig, Rosenthal, and Pittelkow and authors Besch-Stokes, Severson, Bhullar, Montoya, and Butterfield have no conflicts of interest to declare.