The CD4+ small/medium-sized pleomorphic T-cell lymphoma (SMPTCL) is a type of primary cutaneous lymphoma included as a provisional entity in the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas.1 This lymphoma is characterized by a predominance of CD4+ small/medium-sized pleomorphic T cells and presents a favorable clinical course.

A 62-year-old man with no past medical history of interest presented an asymptomatic tumor that had appeared on his right cheek a month earlier and had shown rapid growth. Physical examination revealed a well-defined erythematous nodule measuring 2×1.5cm. The nodule had a rubbery consistency and presented a central erosion (Fig. 1A).

Figure 1.

A, Well-defined erythematous nodular lesion on the right cheek, with an erosion affecting part of the surface. B, Complete resolution of the lesion after 4 weeks, with a scar corresponding to the site of biopsy.

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The lesion was biopsied. On histology, a diffuse, dense infiltrate was seen to occupy the full thickness of the dermis, with extension into the subcutaneous cellular tissue; there was no evidence of epidermotropism (Fig. 2). This was a polymorphous infiltrate formed mainly of lymphocytes, histiocytes, and plasma cells. The predominant cells in the neoplastic infiltrate were small- and medium-sized lymphocytes with marked pleomorphism. Immunohistochemistry (Fig. 3) was intensely positive for CD3, CD4, and CD5, and was negative for CD8 and CD30. Poorly defined infiltrates rich in CD20+ cells without light chain restriction were also evident. The sample was also positive for PD1 and Bcl-6. Molecular biology study revealed a monoclonal rearrangement of the T-cell receptor (TCR) beta gene. The Ki67 cell proliferation index was below 20%. Epstein-Barr virus expression was negative. Further tests included an analysis of lymphocyte populations and immunoglobulin levels, computed tomography of the neck, chest, abdomen, and pelvis, and a bone-marrow biopsy. All the results were normal or negative.

Figure 2.

A, The low-power image shows a dense dermal infiltrate that extends into the subcutaneous cellular tissue but shows no epidermotropism. Hematoxylin and eosin, original magnification ×4. B, The infiltrate is formed mainly of small- and medium-sized pleomorphic lymphocytes. Hematoxylin and eosin, original magnification ×40.

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Figure 3.

A and B, Immunohistochemistry stains show the cells to be strongly positive for CD4 and very weakly positive for CD8. CD4 and CD8 stains, original magnification ×4.C, Poorly defined infiltrates rich in CD20+ cells. CD20 stain, original magnification ×4. D and E, Cell expression of Bcl-6 and PD1. Bcl-6 and PD1 stains, original magnification ×40.

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After 4 weeks of follow-up, the tumor lesion underwent spontaneous regression until its complete disappearance, leaving only a scar at the site of biopsy (Fig. 1B). No changes were observed in pigmentation, and the area was not infiltrated or indurated to palpation. After a year of follow-up, the patient remained asymptomatic, with no evidence of tumor recurrence.

Since the description of SMPTCL as a provisional entity in 2005, the disease has been reported in adults and children,2 but it accounts for only 2% of all primary cutaneous lymphomas.1 Clinical presentation is usually as a solitary, fast-growing plaque or tumor, typically on the face, neck, or upper part of the trunk.3

Histologically there is a dense, nodular, or diffuse dermal infiltrate that extends into the subcutaneous cellular tissue. There is a predominance of small/medium-sized pleomorphic CD4+ T cells, although up to 30% of the population can be large pleomorphic cells.4 A mixed inflammatory infiltrate of lymphocytes, plasma cells, eosinophils, and histiocytes can be observed in some cases.3,5,6 By definition, these lymphomas have a CD3+, CD4+, CD8−, CD30− immunophenotype, sometimes with a loss of T-cell markers. A monoclonal rearrangement of the TCR gene is detected in the majority of cases.

Various studies have evaluated the expression of follicular helper T cells (TFH) markers in this type of primary cutaneous lymphoma.4,5 The TFH cell is a specific subtype of CD4+ TH cell, usually found in the germinal center of lymphoid follicles.7 The function of these particular lymphocytes is to regulate the immune response of B cells, favoring their differentiation into immunoglobulin-secreting plasma cells or memory B cells. A number of criteria exist to differentiate TFH lymphocytes from other TH cell subtypes, including the expression of a series of markers such as CXCL13, CD10, Bcl-6, ICOS, and PD1. None of these markers is wholly specific to TFH cells, as some of them have occasionally been detected in cases of mycosis fungoides and Sezary syndrome, as well as in adult T-cell lymphomas and leukemias.8 However, the combined expression of various of these markers in a lymphoproliferative disease is highly specific to an origin in neoplastic TFH lymphocytes.8 In our case, the cells were positive for the markers Bcl-6 and PD-1. This expression of TFH-cell markers in the neoplastic lymphocytes may explain the foci of CD20+ B-cell infiltrates typically found in SMPTCL,3,5 as occurred in our case.

The prognosis of these lymphomas is excellent, particularly in cases with isolated lesions.1,6 In localized lesions, surgical excision or local radiotherapy are the preferred alternatives.1 Only 2 cases of spontaneous regression of untreated SMPTCL have been reported.9,10 The heterogeneous nature of this entity has led some authors to propose the term cutaneous proliferation of pleomorphic T lymphocytes of undetermined significance to refer to cases in which it is impossible determine the benign or malignant nature of the disease, and thus avoid forcing a diagnosis to be made.3,9

Although it is sometimes difficult to distinguish this type of cutaneous T-cell lymphoma from reactive lymphoproliferative disorders, SMPTCL is a recognizable disease with characteristic expression of TFH-cell markers. In conclusion, we have presented an atypical case of SMPTCL with rapid, spontaneous resolution, and with expression of the markers Bcl-6 and PD1, which suggests a TFH cell origin of the neoplastic disease.