Cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (CSTCL) is a cutaneous T-cell lymphoma defined by a predominance of small-to-medium-sized CD4 pleomorphic T cells, with a favorable clinical course. Cases are also characterized by the presence of a rich infiltrate of reactive B cells. Recently, it has been reported that follicular helper T cells (TFH cells) display a distinct gene expression profile, positive for PD-1, CXCL13, and BCL-6. We report for the first time the expression of PD-1 and other TFH cell markers in CSTCLs and discuss its biologic significance. Sixteen CSTCLs were included in this study, and also 20 reactive inflammatory conditions, 10 primary cutaneous marginal zone, 10 follicular center lymphomas, and 5 primary CD30 cutaneous lymphomas. They were immunohistochemically analyzed for a large panel of markers. Double immunoperoxidase labeling of paraffin sections was performed for PD-1, OCT-2, and BCL-6. Clonal Ig and T-cell receptor rearrangements and Epstein-Barr virus-encoded RNA expression were also evaluated. Morphologic and clinical data were reviewed. Histologic examination showed a dense polymorphic lymphoid infiltrate throughout the dermis. Atypical large CD4 cells were positive for PD-1, CXCL13, and BCL-6 in all cases, and were attached in small clusters, or formed rosettes around CD30/OCT-2+ B blast cells. Epstein-Barr virus was not apparent in any of the cases. A dominant T-cell clone was identified in 14 cases, whereas polymerase chain reaction IgH gene rearrangement studies showed that all cases were polyclonal. None of the patients had lymphadenopathy or showed any evidence of systemic disease, nor did they have any previous history of mycosis fungoides or drug reactions. FTH cell markers are not exclusive to angioimmunoblastic lymphadenopathy but may also be seen in neoplastic cells of CSTCLs. Moreover, these findings suggest that B-cell stimulation by FTH could also take place in some cutaneous T-cell lymphomas.
Eight of 18 patients (44%) were morbidly obese, of whom 6 had undergone weight loss surgery (all by Roux-en-Y gastric bypass). Additional frequent comorbidities were alcoholism (8 [44%]), hepatic cirrhosis (8 [44%]), hepatitis C virus infection (5 [28%]), or a large, chronic, nonhealing postsurgical wound or ulcer (4 [22%]).Results of skin biopsies demonstrated the classic epidermal pallor in 7 of 18 patients (39%), whereas the remaining 11 lacked this finding, demonstrating a predominantly spongiotic, psoriasiform, or atrophic epidermal pattern with overlying confluent parakeratosis and intracorneal splitting. Coincidence of zinc, albumin, and/or niacin deficiency and hepatitis C virus infection was common, with 13 patients (72%) harboring at least 2 abnormalities and 5 (28%) with at least 3. Combined deficiency in zinc and protein was most common (11 of 18 [61%]). Three patients (17%) were found to have concomitant thiamine deficiency. Follow-up data were available on all patients with mean (SD) follow-up of 16.8 (21.5) months and median of 7 months (range, 1-71 months). All-cause mortality was 72% (13 patients), with an estimated survival time of 1 to 54 months (mean, 14 months; median, 5 months; 95% CI, 4.7-23.8 months). Detailed review of the final clinical course preceding 7 of 13 deaths unveiled a common picture characterized by an irreversible, nonseptic, distributive, cardiovascular shock with anasarca and multiple-organ failure. Comparative Kaplan-Meier survival analysis using the log-rank test revealed that hypoalbuminemia of less than 3.4 g/dL (to convert to grams per liter, multiply by 10) was associated with a median survival time of 4.0 months (compared with 54.5 months for albumin level of ≥3.4 g/dL [P = .03]). Being 50 years or younger at time of dermatologic diagnosis was also associated with lower median survival of 2 months (compared with 34 months for those aged >50 years [P = .03]) (Figure).
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