Adnexotropism as a Histopathological Clue for the Diagnosis of Primary Cutaneous CD4+ Small/Medium-Sized T-Cell Lymphoproliferative Disorder.

Abstract

To the Editor: Primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder (PCSM-TCLPD) is considered as a World Health Organization provisional entity, histopathologically characterized by diffuse or nodular infiltrates of small- to medium-sized pleomorphic T lymphocytes with CD3+/CD4+/CD8−/CD30− phenotype, sometimes admixed with less than a 30% of large pleomorphic cells. Recognition of this disorder requires differential with other neoplastic and inflammatory disorders in the skin, including primary cutaneous marginal zone B-cell lymphoma, insect bite inflammatory reaction, mycosis fungoides, and T cell helper follicular primary cutaneous T-cell lymphoma, a neoplastic condition that may present similarities but portends a worse prognosis We have recently reviewed all the biopsies of lymphomas in our hospital from January 2010 to January 2018 to select 33 cases with clinical or histopathological diagnosis of PCSM-TCLPD diagnosed in our department. We applied the diagnostic criteria described within the last updated World Health Organization classification of hematological malignancies.1,2 Our patients clinically correspond to 16 women and 10 men with a mean age of 55.1 years (range 29–86) and with no other epidemiological features showing differences with the previously described.FIGURE 1.: A, Panoramic view of a PCSM-TCLPD with nodular infiltrates showing a rounded interface with the subcutaneous fat, (B) atypical lymphocytes surrounding and partially destructing the hair follicle, (C) infiltration by the tumoral cells in the eccrine ducts, and (D) infiltration of the piloerector muscle by the same medium-sized atypical lymphocytes.FIGURE 2.: A, Eccrine ducts that show areas with partial destruction and (B–D) different fields showing the eccrine ducts infiltration by the tumoral cells. Double immunohistochemistry LEF1 (peroxidase)/E-cadherin (alkaline phosphatase).The more striking histopathological feature, to our eyes, was a distribution showing nodules mostly located in the dermis, which tends to embrace the adnexal structures and presenting in the deeper areas a rounded pushing interface (Fig. 1A). Moreover in a lymphoma where finding epidermotropism is an exclusion criterion, was striking to find infiltration by the tumoral cells in the eccrine ducts as well as in the hair follicle in all the cases (Figs. 1B–D). This finding, adnexotropism, was first described by Beltraminelly and cols,3 and it is also observed in the larger series, although these articles have not highlighted this finding enough.3,4 In our experience, this adnexotropism is very characteristic, and the finding of an atypical lymphocytic infiltrate with these features and with scarce or lacking epidermotropism should raise the suspicion of PCSM-TCLPD. It was also striking to find infiltration by the tumoral cells in the epithelium of the eccrine ducts involving both the superficial epithelium and the basal layer that also are hyperplastic. The gland presented a multilobulated contour due to the hyperplasia of both components. In all the cases, the affected eccrine ducts showed areas with partial destruction. It was also quite characteristic to find an infiltration of the piloerector muscle by the same atypical cells.5 In these lesions is also quite frequent to find scarce nonclustered CD30-positive cells, in less than 10% of the tumoral lymphocytes and some B-cell lymphocytes. PD1 staining showed clusters of cells in all the studied cases as previously described (Fig. 2). Is important to how that syringotropism does not equal malignancy, it may be observed in several different dermatoses.6 In conclusion, precise diagnosis of PCSM-TCLPD is still a challenge, but a multilobulated nodular infiltrate of slightly atypical lymphoid cells infiltrating hyperplastic eccrine ducts that is presence of siringotropism is a useful marker that, in the appropriate context, may facilitate its recognition of PCSM-TCLPD. In this context, an immunohistochemical panel including T-cell markers, PD1, and CD30 will confirm the correct diagnosis.