Quantification of marrow hematogones following autologous stem cell transplant in adult patients with plasma cell myeloma or diffuse large B-cell lymphoma and correlation with outcome.

In this retrospective study, we quantified the hematogone (normal B-lineage precursor) population by flow cytometric immunophenotyping in post-transplant bone marrow biopsy specimens from adult patients who received an autologous stem cell transplant for either plasma cell myeloma (n = 57) or diffuse large B-cell lymphoma (n = 73). The majority of patients (80%) had <5% marrow hematogones post-transplant. Extreme (>10%) hematogone percentages were quite rare, seen in only four patients, and were not associated with disease progression. There was a positive association between the post-transplant day and hematogone percentage within the first year after transplant, and a negative association thereafter. Plasma cell myeloma patients with ≥5% hematogones in any post-transplant flow cytometry study had a worse overall survival as did plasma cell myeloma patients with increased hematogones (as defined by percentile) at 100 days post-transplant. These findings require further study, ideally in a prospective study design.

Plasma Cell Myeloma in Children and Young Adults: A Report of 4 Cases From a Single Institution and a Review of the Literature.

Plasma cell myeloma (PCM) is rare in children and young adults and therefore may be difficult to diagnose. Here we report the clinicopathologic findings of 4 patients under the age of 30 diagnosed with PCM at our institution and summarize the literature about 48 other cases of PCM in this age group. The male:female ratio was 1.2:1 and the number of cases increased with age. Children and young adults with PCM often present with a plasmacytoma and are less likely to have asymptomatic PCM than their adult counterparts. From the cases that reported ethnicity, the majority (55%) were non-white suggesting a possible ethnic predisposition to PCM in this age group. PCM should be included in the differential diagnosis of mass lesions, especially a destructive bony lesion, after more common causes have been ruled out in this age group. The optimal treatment for PCM in this patient population is unclear and conclusions into this are hampered by the paucity of cases and the lack of standardized follow-up.

Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.

OBJECTIVES: Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. METHODS: By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. RESULTS: Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. CONCLUSIONS: Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care.

Unusual extramedullary hematopoietic neoplasms in lymph nodes.

Myeloid, plasma cell, and lymphoblastic neoplasms are expected findings in bone marrow but are much less commonly diagnosed as primary processes in lymph nodes. The objective of this review is to aid pathologists in recognizing common hematopoietic neoplasms in the unusual setting of initial presentation in lymph nodes. Review of historical background and evolution of testing strategies is presented to improve understanding of the need for accurate diagnosis and classification using current nomenclature. The review is based on peer-reviewed literature and the personal experience of the authors. The University of Minnesota Medical Center, Fairview provides lymph node diagnostic consultation services for its busy oncology and therapeutic hematopoietic cell transplant divisions serving patients from around the globe. Although readily recognizable when they present in bone marrow, myeloid leukemia in the form of myeloid sarcoma, plasmacytoma, and lymphoblastic lymphoma can create diagnostic and classification challenges when they present as primary lymph node pathologies. Use of all diagnostic tools may be necessary to ensure accurate and reproducible diagnoses.

Patients With a History of Chemotherapy and Isolated del(20q) With Minimal Myelodysplasia Have an Indolent Course.

OBJECTIVES: Isolated deletion (20q) is relatively common in myeloid neoplasms and has been rarely reported in cases of therapy-related myelodysplastic syndrome (MDS). Our aim was to characterize cases of isolated del(20q) in bone marrow biopsy specimens from patients with a history of chemotherapy with morphologic findings insufficient for a diagnosis of MDS. METHODS: In this retrospective study from one institution, we identified 22 patients with isolated del(20q) and no or minimal dysplasia and evaluated clinical and pathologic characteristics. RESULTS: Eleven of the patients had a history of chemotherapy for mostly lymphoproliferative disorders. There were no statistically significant differences in peripheral blood or bone marrow features between patients with a history of chemotherapy and those without. Three patients with a history of chemotherapy had died at last follow-up; cause of death was recurrent nonmyeloid neoplasm. None of the patients with a history of chemotherapy subsequently developed a high-grade myeloid neoplasm, whereas one of the patients who had not received prior chemotherapy developed refractory anemia with excess blasts 2. CONCLUSIONS: The presence of del(20q) as an isolated bone marrow cytogenetic abnormality in the absence of morphologic findings sufficient for a diagnosis of acute myeloid leukemia, myeloproliferative neoplasm, or MDS portends an indolent clinical course, regardless of previous exposure to chemotherapy.

EBV-positive mucocutaneous ulcer in organ transplant recipients: a localized indolent posttransplant lymphoproliferative disorder.

Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBV MCU) is a B-cell lymphoproliferative disorder occurring in elderly or iatrogenic immunocompromised patients. It has not been reported in solid organ transplant recipients. We observed 7 patients with EBV MCU in a cohort of 70 transplant recipients with EBV posttransplant lymphoproliferative disorder (PTLD). Transplants included: 5 renal, 1 heart, and 1 lung. Median patient age was 61; 5 were male. EBV MCU was observed in oral mucosa in 4 and gastrointestinal tract in 3. Duration of immunosuppressive therapy before EBV MCU was 0.6 to 13 years. Ulcers were undermined by inflammatory cells and polymorphic or monomorphic large cell lymphoproliferation. Reed-Sternberg-like cells were present in 5/7. Large B cells were CD20, CD30, and EBV-encoded RNA positive in all cases. Diagnosis in 3 recent patients was EBV MCU; 4 patients diagnosed before familiarity with EBV MCU were classified as monomorphic large cell (n=3) and polymorphic (n=1) PTLD. None of the patients had EBV DNA in their blood (<1000 copies/mL) at diagnosis or follow-up versus 35/44 transplant patients with systemic PTLD (P<0.001). All lesions resolved with reduced immunosuppression (7/7), change in immunosuppression (2/7), and rituximab (3/7). Five patients are living: 4 healthy, 1 awaiting second renal transplant. Two patients died 3 and 5 years after resolution of EBV MCU. No patient recurred with EBV MCU or other PTLDs. EBV MCU mimics more aggressive categories of PTLD but lacks EBV DNA in blood, which may be a useful distinguishing feature. Lesions are likely to resolve with conservative management. Awareness of EBV MCU in the posttransplant setting is necessary for appropriate diagnosis and treatment.

Early diagnosis of intravascular large B-cell lymphoma: clues from routine blood smear morphologic findings.

Intravascular large B-cell lymphoma (IVLBCL) is a mature B-cell neoplasm characterized by malignant lymphoid cells within the lumina of blood vessels and capillaries. Given its varied and nonspecific clinical manifestation, this aggressive disease is often not diagnosed until an advanced clinical stage or even at autopsy. This case highlights a patient presenting with autoimmune hemolytic anemia (AIHA) and fevers. Atypical circulating cells on a screening peripheral smear lead to flow cytometric studies highlighting an increase in large, light chain restricted CD20 positive cells. A diagnostic bone marrow biopsy was performed and trephine cores demonstrated predominantly intrasinusoidal lymphoma cells. In conjunction with additional immunophenotypic data, these studies strongly supported a diagnosis of IVLBCL. Judicious use of flow cytometry and morphology resulted in an early-stage diagnosis and likely contributed to the patient's current complete remission status following anti-CD20 therapy. Differential diagnoses for this presentation are discussed in light of serologic, immunophenotypic, histologic, and cytogenetic findings.

Langerhans cell histiocytosis in acute leukemias of ambiguous or myeloid lineage in adult patients: support for a possible clonal relationship.

Four patients presented with acute leukemia of ambiguous or myeloid lineage in association with Langerhans cell histiocytosis and provide evidence suggesting a common origin of the two neoplasms. One patient had a non-constitutional trisomy 21 in both the leukemic blasts and the Langerhans cells indicative of a clonal relationship. A second case expressed CD2, CD13, and CD117 on both the Langerhans cells and the blasts suggesting a possible clonal relationship. All four cases exhibited geographic intermingling of the Langerhans cell histiocytosis and acute leukemia and shared unique features including extramedullary leukemia involving lymph nodes in all cases with Langerhans cell histiocytosis only present in sites involved by acute leukemia. T-cell antigen expression was present in all cases with one meeting criteria for mixed phenotype acute leukemia, T/myeloid, not otherwise specified. These findings support the concept that coexistent Langerhans cell histiocytosis and acute leukemia is clonally related in some cases. Furthermore, these cases of acute myeloid or acute leukemia of ambiguous lineage with Langerhans cell histiocytosis share some unique features suggesting a common underlying neoplastic hematopoietic stem cell.

Video-assisted thoracic surgery versus open lobectomy for lung cancer: a secondary analysis of data from the American College of Surgeons Oncology Group Z0030 randomized clinical trial.

OBJECTIVE: Video-assisted thoracoscopic lobectomy remains controversial. We compared outcomes from participants in a randomized study comparing lymph node sampling versus dissection for early-stage lung cancer who underwent either video-assisted thoracoscopic or open lobectomy. METHODS: Data from 964 participants in the American College of Surgeons Oncology Group Z0030 trial were used to construct propensity scores for video-assisted thoracoscopic versus open lobectomy (based on age, gender, histology, performance status, tumor location, and T1 vs T2). Propensity scores were used to estimate the adjusted risks of short-term outcomes of surgery. Patients were classified into 5 equal-sized groups and compared using conditional logistic regression or repeated measures analysis of variance. RESULTS: A total of 752 patients (66 video-assisted and 686 open procedures) were analyzed on the basis of propensity score stratification. Median operative time was shorter for video-assisted thoracoscopic lobectomy (video-assisted thoracoscopy 117.5 minutes vs open 171.5 minutes; P < .001). Median total number of lymph nodes retrieved (dissection group only) was similar (video-assisted thoracoscopy 15 nodes vs open 19 nodes; P = .147), as were instances of R1/R2 resection (video-assisted thoracoscopy 0% vs open 2.3%; P = .368). Patients undergoing video-assisted thoracoscopic lobectomy had less atelectasis requiring bronchoscopy (0% vs 6.3%, P = .035), fewer chest tubes draining greater than 7 days (1.5% vs 10.8%; P = .029), and shorter median length of stay (5 days vs 7 days; P < .001). Operative mortality was similar (video-assisted thoracoscopy 0% vs open 1.6%, P = 1.0). CONCLUSION: Patients undergoing video-assisted lobectomy had fewer respiratory complications and shorter length of stay. These data suggest video-assisted thoracoscopic lobectomy is safe in patients with resectable lung cancer. Longer follow-up is needed to determine the oncologic equivalency of video-assisted versus open lobectomy.

Characterization of immunophenotypic aberrancies in 200 cases of B acute lymphoblastic leukemia.

Morphologic distinction of leukemic lymphoblasts in B acute lymphoblastic leukemia (B-ALL) from their nonneoplastic counterparts in bone marrow (hematogones) can be difficult. Thus, the presence of aberrant antigen expression detectable by flow cytometry may be critical for diagnosis of B-ALL and detection of minimal residual disease. The current study examined the immunophenotype of B-lineage leukemic lymphoblasts in 200 consecutive, unique, pretreatment patient specimens. We found that all cases of B-ALL exhibited multiple immunophenotypic aberrancies by which they can be distinguished from hematogones. The most frequent aberrancies were uniform or a spectrum of expression of terminal deoxynucleotidyl transferase and CD34, underexpression of CD45, overexpression of CD10, underexpression of CD38, and underexpression of CD20. Asynchronous coexpression of CD34 and CD20 was also frequently observed. Of the 200 cases, 86.5% expressed myeloid-associated antigens, and 19.0% expressed 3 or more. Of 200 cases, 9.0% aberrantly expressed T cell-associated antigens. There were significant differences in antigen-expression patterns between adult and pediatric B-ALL. Specific aberrancies correlate with recurrent cytogenetic abnormalities in B-ALL.