Identification of CD5/SOX11 double-negative pleomorphic mantle cell lymphoma.

Cyclin D1 protein-positive diffuse large B cell lymphoma (DLBCL) has an immunophenotype of CD5(-) cyclin D1(+) SOX11(-), and most cases lack a CCND1 rearrangement and have a gene expression profile of DLBCL. Rarely, cyclin D1 protein-positive DLBCL harbors a CCND1 rearrangement, and some genetic copy number features typical of mantle cell lymphoma (MCL) have been detected. Since gene expression studies have not been performed, whether such CCND1-rearranged cases represent cyclin D1 protein-positive DLBCL or CD5/SOX11 double-negative pleomorphic MCL remains unclear. To date, no cases of CD5/SOX11 double-negative MCL have been reported. In this study, we collected eight cases initially diagnosed as cyclin D1 protein-positive DLBCL, including four with a CCND1 rearrangement and four without. Immunohistochemically, all four CCND1-rearranged cases had >50% of tumor cells positive for cyclin D1 protein, whereas only one (25%) non-rearranged case had >50% positive tumor cells. Analysis of genome-wide copy number, mutational, and gene expression profiles revealed that CCND1-rearranged cases were similar to MCL, whereas CCND1-non-rearranged cases resembled DLBCL. Despite the SOX11 negativity by immunohistochemistry, CCND1-rearranged cases had a notable trend (P = 0.064) of higher SOX11 mRNA levels compared to non-rearranged cases. Here, we show for the first time that CCND1 rearrangement could be useful for identifying CD5/SOX11 double-negative pleomorphic MCL in cases diagnosed as cyclin D1 protein-positive DLBCL. Cases with >50% cyclin D1 protein-positive tumor cells immunohistochemically and higher SOX11 mRNA levels are more likely to have a CCND1 rearrangement, and fluorescence in situ hybridization can be used to detect the rearrangement.

A case report of secondary synchronous diagnosis of multiple myeloma and systemic lupus erythematosus after breast cancer treatment: A CARE-compliant article.

INTRODUCTION: Breast cancer (BC) is the most diagnosed cancer worldwide. Multiple myeloma (MM) is a hematologic malignancy characterized by the overproduction of monoclonal antibodies in the bone marrow. Systemic lupus erythematosus (SLE) is distinguished by the aberrant activity of the immune system with heterogeneous clinical manifestations. The coexistence of more than one major illness in a patient can present a diagnostic challenge for clinical physicians, especially when the comorbid diseases share a similar clinical presentation. Herein, we report an unusual case of secondary synchronous diagnosis of MM and SLE after BC treatment. PATIENT CONCERNS: A 69-year-old female patient with breast cancer experienced severe skin itching and rashes on the face, anterior chest wall, back, and trunk for two days before admission. She had high levels of immunoglobulin and anti-nuclear antibodies; low levels of complements 3 and 4; positive anti-cardiolipin-IgM, anti-beta 2 glycoprotein-1 (anti-ß2GP1) antibodies, and lupus anticoagulant results at serological testing. DIAGNOSIS: The postoperative pathology report showed ductal carcinoma in situ in the right breast. SLE was confirmed based on the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria. IgG-κ type multiple myeloma was confirmed by bone marrow biopsy, and the patient was synchronously diagnosed with SLE and MM after BC treatment. INTERVENTIONS: Glucocorticoids and immunosuppressive agents, including intravenous hydrocortisone (5 g every 8 hours) and oral hydroxychloroquine (Plaquenil) (200 mg twice daily) were administered to treat SLE. One capsule of thalidomide 50 mg was administered orally every night at bedtime for MM. OUTCOMES: The patient died two days later, shortly after the administration of drugs, due to multiple organ failures secondary to pneumonia and respiratory failure. CONCLUSION: This is a case of MM and SLE after BC treatment. The present challenge was the early detection and accurate diagnosis of the secondary major illnesses, as the clinical manifestations were similar and non-specific between these two diseases. Awareness and prompt recognition of the common clinical symptoms of SLE and MM should be considered by clinical physicians to avoid delayed diagnoses and facilitate early treatment for a better prognosis.

The effect of different harvest strategies on the nucleated cell yields of bone marrow collection.

To improve bone marrow (BM) harvest of the volunteer donors in our institute, we changed from the single-hole needle to the multi-side-hole needle after March 2002, and examined the midway total nucleated cell (TNC) counts during collection after September 2004. The aims of this retrospective study were to evaluate BM harvest yields obtained through different strategies and to examine the correlation between final and midway BM harvests. The distribution of BM harvesting by different strategies was 235 donors with single-hole needles (group A), 389 donors with 5-side-hole needles (group B), and 365 donors with 5-side-hole needles and midway TNC counts (group C). The nucleated cell density of the collected BM was significantly improved by modifying the harvest strategy (0.202 × 10(8)/mL in group A, 0.219 × 10(8)/mL in group B, and 0.250 × 10(8)/mL in group C; P < .001). The percentage of unacceptable TNC dose (<2 × 10(8)/kg) was also decreased in all 3 groups (to 5.9%, 3.6%, and 0%, respectively; P < .001). Multiple regression analysis revealed that donor weight, white blood cell count, and harvest strategy were positively correlated with BM TNC density (P < .001), whereas harvested BM volume was negatively correlated with TNC density (P < .001). On linear regression analysis, highly significant correlations were noted between midway and final TNC densities (r = 0.8774; P < .001) as well as between harvested BM volume and TNC count (r = 0.7937; P < .001). Changing the harvesting needle and checking the midway TNC count improved the harvest outcome.

Correlation between characteristics of unrelated bone marrow donor and cell density of total nucleated cell in bone marrow harvest.

The relationship between the features of bone marrow donor and the quality of marrow harvest has been unclear because most of bone marrow registries have multiple collection centers with somewhat different harvest procedures. We are able to address this issue for Tzu Chi General Hospital is the only collection center affiliated with Tzu Chi Taiwan Bone Marrow Registry. Between November 1997 and March 2002, data of 286 healthy unrelated donors was analyzed to correlate with the cell density of total nucleated cell in bone marrow harvests. The harvest procedure was standardized by single-hole harvest needle under general anesthesia. The operation staffs were restricted within the members of Oncology-Hematology division. The results showed that the cell density of bone marrow harvest was positively correlated with donor body weight and peripheral white blood cell count P = 0.0475, P < 0.0001, but negatively correlated with the total volume of bone marrow harvest P < 0.0001. We recommend that if multiple human leukocyte antigen-matched donors are available, donor with higher body weight and/or higher white blood cell count be selected for allogeneic bone marrow transplantation.

Evolutional change of karyotype with t(8;9)(p22;p24) and HLA-DR immunophenotype in relapsed acute myeloid leukemia.

The rare recurrent translocation of (8;9)(p22;p24) with PCM1-JAK2 fusion was recently characterized in diverse hematological malignancies. Most of them are atypical chronic myeloid leukemia (CML) or other myeloproliferative disorders (MPD), and are predominantly in the male. We report a female patient with acute myeloid leukemia (AML) initially presenting with normal karyotype and negative HLA-DR expression who achieved complete remission after standard chemotherapy. The disease relapsed 7 months later with cytogenetic change of t(8;9)(p22;p24). Flow cytometry analysis showed evolutional change of immunophenotype from negative to positive HLA-DR expression and fluorescence in situ hybridization (FISH) analysis demonstrated a PCM1-JAK2 fusion gene. We speculate that the cytogenetic change of t(8;9)(p22;p24) may induce HLA-DR immunophenotypic switch and a coordination of the two evolutional changes may play a role in leukemic cell progression.