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Bone marrow involvement in cutaneous T-cell lymphoma.

To the Editor:—We read with considerable interest the article by Dr. Salhany and colleagues, which reported a systematic clinicopathologic and immunologic study on a large series of patients with cutaneous T-cell lymphomas (CTCL) aimed at evaluating the rate of bone marrow infiltration and its prognostic significance. The authors conclude that about 20% of their 60 patients displayed bone marrow involvement by morphologically abnormal and immunologically defined (CD45RO+) cutaneous T-cells (CTCs). Bone marrow involvement was often found during the diagnostic staging and correlated with a widespread disease (i.e., extended also to peripheral blood, lymph nodes, and visceral organs) and a shortened survival. In addition, the authors identified patients with marrow involvement limited to abnormal lymphoid nodules and others with a clear infiltrative pattern. The former group interestingly displayed a median survival intermediate between patients with a negative marrow and those with lymphoid infiltrates, raising the question of the clinicobiologic meaning of these abnormal marrow lymphoid nodules in CTCL. In a previously reported series of 23 CTCL patients, we found bone marrow involvement (biopsy and aspirate) in 25% of cases. All patients with a positive marrow displayed also peripheral blood and lymph node disease. Moreover, during a follow-up re-evaluation of those cases, we detected marrow involvement (abnormal lymphoid nodules) in two patients with disease apparently under control and limited to residual skin lesions. Therefore, the clinicopathologic meaning of abnormal lymphoid nodules in the marrow of CTCL patients, as pointed out by Dr. Salhany and colleagues, remains a controversial issue in particular as to their prognostic significance (early marrow involvement by neoplastic T-cells or reactive Tand/or B-lymphocyte proliferation?). Immunophenotyping and gene rearrangement studies might help to clarify this point owing to a rather distinctive phenotypic profile of circulating CTCs, generally CD3+, CD2+, CD4+, CD7, CD8—, and to the presence of clonally rearranged T-cell receptor genes in neoplastic T-cell proliferations such as CTCLs. One of the patients included in our previous reports and referred to us with a diagnosis of stage IV CTCL displayed at presentation bone marrow and peripheral blood involvement by morphologically and immunologically defined CTCslike cells, cutaneous lesions pathologically consistent with CTCL, and a lymph nodal histology compatible with dermatopathic lymphadenopathy. During a later multiparametric re-evaluation of this case, a routine immunophenotypic profile of marrow and peripheral blood lymphocytes evidenced in both specimens the coexistence of a T-cell population (about 50% of lymphocytes) immunologically consistent with CTCs (CD2+, CD3+, CD5+, CD4+, CD8, CD7-) along with a definite clonal excess of K-positive monoclonal B-cells. Immunopathologic analysis of newly excised specimens of skin and lymph nodes revealed a monoclonal (K-positive) B-cell population with an intermediate/mature phenotype along with a population of CD3+, CD4+, CD8, C D 7 T-cells. Lymph node examination disclosed a selective and complete replacement of the B-areas by K chain-restricted B-cells, with disappearance of follicles and widening of the medullary cords (B: zone pattern)? an expanded T-zone showing features consistent with dermatopathic lymphadenitis and well-preserved sinuses. Since atypical lymphocytes, detected in peripheral blood and bone marrow, although morphologically compatible with CTCs consisted actually of a double population of monoclonal B-cells and CD3+, CD4+, CD8, CD7— T-cells, a suggestion was made of a possible coexistence of a B-cell lymphoma along with a CTCL in this patient. DNA rearrangement studies of lymph node tissues and of peripheral blood and marrow lymphocytes revealed in all samples clonally rearranged heavy and light (K) immunoglobulin genes and germline T-cell receptor genes (TCR/3 and TCR7). In addition, a weak smear due to multiple rearrangements of polyclonal T-cells was present, being particularly evident in bone marrow and peripheral blood samples. The complete clinical data and immunopathologic findings in this patient have been reported. During the follow-up (9 years) abnormal lymphoid nodules were always detected in repeated bone marrow biopsies of this patient affected by a "CTCL-mimicking B-cell lymphoma" (low grade) with an associated dermatopathic lymphadenitis probably responsible in turn for the CD4+ T-cell polyclonal expansion. Therefore, in pathological specimens from this patient the histologic picture of the underlying B-cell lymphoma with a B-zone pattern, that of dermatopathic lymphadenitis associated with skin lesions, the polyclonal reactive expansion of CD3+, CD4+, CD8, C D 7 T-lymphocytes and the presence of abnormal lymphoid nodules in bone marrow biopsies led to the erroneous initial diagnosis of CTCL. The presenting clinicopathologic features of this case were even more misleading because the immunologic phenotype of reactive T-cells, probably related to the dermatopathic lymphadenitis, closely resembled that of neoplastic cells in CTCL (CD4+, CD7-) . ' The recognition of such "CTCL-mimicking B-cell lymphoma" deserves great attention because of its practical implication in the differential diagnosis and prognostic evaluation of CTCL patients with bone marrow and peripheral blood involvement. A light chain clonal excess flow cytometric testing in the diagnostic workup of patients with a tentative diagnosis of CTCL, especially in those with nodular bone marrow involvement and a suspect peripheral blood picture, could be of help in this regard. We are actually evaluating a second similar lymphoma case, also histologically displaying a lymph node B-zone pattern (B: zone lymphoma), and feel that this clinicopathologic entity will be increasingly recognized after its initial identification. ANTONIO PINTO, M.D. VlTTORINA ZAGONEL, M.D. ANTONINO CARBONE, M.D. Divisions of Experimental Oncology 2 Medical Oncology and Pathology Leukemia Unit Centro di Riferimento Oncologico Aviano, Italy