The clinical and histopathologic features of specific skin infiltrates in patients with B-cell chronic lymphocytic leukemia (B-CLL) have rarely been reported in detail. In this study we analyzed the clinical, histopathologic, immunophenotypic, and molecular features of 84 skin lesions from 42 patients (M:F = 1.3:1; mean age, 66.0 years; range, 42-83 years) with specific cutaneous manifestations of B-CLL. The duration of B-CLL before skin manifestations varied from 0 to 142 months (mean, 39 months). In seven patients (16.7%), skin lesions represented the first sign of disease. Clinical presentations included localized or generalized erythematous papules, plaques, nodules, and large tumors. Ulceration was uncommon. In six patients lesions were confined at the sites of scars from previous herpes zoster (four patients) or herpes simplex (two patients) eruptions. Histologically, three main patterns were recognized: (a) patchy perivascular and periadnexal, (b) nodular-diffuse, and (c) band-like. Cytomorphologically, small monomorphous lymphocytes predominated. Proliferation centers were observed in only four specimens. In two patients presenting with tumors, a high content of large cells with feature of centroblasts and immunoblasts was found (Richter's syndrome). Immunohistologic analyses were performed on paraffin-embedded specimens in 40 biopsies from 20 patients and on cryostat sections in 17 biopsies from 11 patients. Neoplastic B lymphocytes in all cases showed an aberrant phenotype (paraffin sections: CD20+/CD5+/CD43+; cryostat sections: CD19+/CD5+; immunoglobulin light-chain restriction). Proliferation markers (Ki67, PCNA, MIB1) stained 5 to 80% of cells (mean, 25%; median, 20%). Polymerase chain reaction performed in nine cases on paraffin-embedded tissues using consensus primers for immunoglobulin heavy-chain genes showed a monoclonal population of B lymphocytes in all cases. Several discrete bands in addition to the prominent ones were noted in five cases, indicating the additional presence of B lymphocytes whose immunoglobulin genes were not monoclonally but oligoclonally rearranged. Follow-up data could be obtained from 31 patients. The two patients with Richter's syndrome died after 5 and 8 months, respectively. The 5-year survival of patients with small-cell cutaneous B-CLL was 66.6%. Our study indicates that cutaneous specific manifestations of B-CLL present with characteristic histologic, immunophenotypic, and molecular patterns. Prognosis in these patients is probably not affected by skin involvement.
With the increasing number of available predictive biomarkers, clinical management of cancer is becoming increasingly reliant on the accurate serial monitoring of tumor genotypes. We tested whether tumor-specific copy number changes can be inferred from the peripheral blood of patients with cancer. To this end, we determined the plasma DNA size distribution and the fraction of mutated plasma DNA fragments with deep sequencing and an ultrasensitive mutation-detection method, i.e., the Beads, Emulsion, Amplification, and Magnetics (BEAMing) assay. When analyzing the plasma DNA of 32 patients with Stage IV colorectal carcinoma, we found that a subset of the patients (34.4%) had a biphasic size distribution of plasma DNA fragments that was associated with increased circulating tumor cell numbers and elevated concentration of mutated plasma DNA fragments. In these cases, we were able to establish genome-wide tumor-specific copy number alterations directly from plasma DNA. Thus, we could analyze the current copy number status of the tumor genome, which was in some cases many years after diagnosis of the primary tumor. An unexpected finding was that not all patients with progressive metastatic disease appear to release tumor DNA into the circulation in measurable quantities. When we analyzed plasma DNA from 35 patients with metastatic breast cancer, we made similar observations suggesting that our approach may be applicable to a variety of tumor entities. This is the first description of such a biphasic distribution in a surprisingly high proportion of cancer patients which may have important implications for tumor diagnosis and monitoring.
<p>PDF file - 1362K, Evaluation of available material from patient #38. (a-b) Array CGH profiles of the primary tumor (a) and liver metastasis (b).</p>
Diagnosis of acquired AATP which finally progressed to SAA was established in an eight-yr-old boy. PBSCT from an HLA-identical unrelated donor using high numbers of CD34+ selected stem cells was performed and resulted in complete remission for almost two yr. However, SAA reoccurred with 100% donor hematopoiesis and was reversed by a second CD 34+ selected PBSCT from the same donor. Declining blood cell counts after an interval of two yr indicated second relapse. Chimerism analysis in PB and BM aspirates revealed a small autologous cell population of 4-12% and 2-11%, respectively. Finally, a third transplantation with unmanipulated BM from the same donor resulted in sustained remission with 100% donor hematopoiesis. The patient is in complete remission for more than five yr following the third SCT. Late graft failure or late graft rejection known to occur after transplantation of highly purified CD34+ cells, or even graft exhaustion caused by stromal dysfunction due to the underlying disease necessitated a third transplantation. Regardless of the cause of relapse, transplantation of unmanipulated BM instead of highly purified PBSCTs led to a permanent and stable engraftment in a third attempt after two previous PBSCTs.
