Ishmael Jaiyesimi

Langerhans/dendritic cell sarcoma arising from hairy cell leukemia: a rare phenomenon.

Dear Editor, A 66-year-old female was diagnosed in 2000 with hairy cell leukemia (HCL). Flow cytometry from her bone marrow biopsy (BMB) demonstrated a monotypic B cell population expressing CD11c, CD22, CD25, and CD103. She was successfully treated with cladribine [1]; however, in 2003, she relapsed, and BMB showed a monotypic B cell population. Cytogenetic analysis revealed an abnormal hyperdiploid karyotype in 2 of 20 metaphase cells: 48,XX,+4,del(6)(q23), del(8)(p21)x2,+12,del(14)(q24), add(17)(p13) (Fig. 1). She was again treated with cladribine and rituximab [2]. In 2008, imaging revealed splenomegaly. Splenectomywas performed, and pathology showed HCL. BMB revealed extensive involvement by a monotypic B cell population negative for CD5, CD10, CD103, and CD25. This phenotype was the same as reported on previous BMB, but differed in that it was CD25 and CD103 negative. Five months later, the patient presented with a left pyriform sinus mass (SUV of 32.8 on PET scan) which was biopsied (Fig. 2). BMB revealed involvement by the previously diagnosed HCL with a monoclonal B cell population demonstrating a phenotype similar to that observed in previous studies. Based on histologic and immunophenotypic findings, this tumor was classified as Langerhans/dendritic cell sarcoma (L/DCS) (expression S100, CD1a; negative for B and T cell markers and CD30). Cytogenetic evaluation identified the hyperdiploid complex karyotype: 47,XX,+4,del(6)(q23),del(8)(p21)x2,+12, -13,del(14)(q24),add(17)(p13). This karyotype and the one obtained in 2003 BMB positive for HCL were essentially identical, although L/DCS presented with monosomy 13. In addition, clonal immunoglobulin gene rearrangements identified by polymerase chain reaction from both specimens were also identical. Combined, cytogenetic, and immunoglobulin gene rearrangement studies suggest that both the HCL and L/DCS developed from the same precursor cells. The patient was treated with three cycles of gemcitabine and docetaxel [3]. However, due to significant progression, the patient opted for hospice. Clinical data have shown that two hematopoietic populations in the same patient may share identical genetic changes or abnormalities, raising the possibility that tumors expressing the phenotype of one hematopoietic lineage might “transdifferentiate” into a genetically similar but phenotypically distinct tumor of a different lineage [4]. Histiocytic/dendritic cell sarcomas (H/DCS) arising from follicular lymphoma (FL) have been reported earlier (eight patients) [5]. In six of these patients, both lesions possessed the same genetic aberration, namely the FL-associated IGH/BCL2 gene rearrangement associated with the t(14;18)(q32;q21). The remaining two demonstrated identical BCL2/JH or clonal IGH gene rearrangements or both. Based on these observations, the authors suggested a clonal relationship between FL and H/DCS. Feldman et al. also demonstrated a common clonal origin in a patient with acute lymphoblastic leukemia and subsequent histiocytic sarcoma, based on identical IGH and TCRγ gene rearrangements in both lesions [6]. Zhang et al. described a Electronic supplementary material The online version of this article (doi:10.1007/s00277-011-1399-5) contains supplementary material, which is available to authorized users. A. Muslimani :M. M. Chisti (*) : I. Boxwala : I. Jaiyesimi Department of Hematology and Oncology, Oakland University William Beaumont School of Medicine, William Beaumont Hospital, 3577 W 13 Mile Rd, Suite 202, Royal Oak, MI 48073, USA e-mail: mohsinchisti@yahoo.com

Differences in disease presentation, treatment outcomes, and toxicities in African American patients treated with radiation therapy for prostate cancer.

ObjectivesWe analyzed differences in disease presentation, outcomes, and toxicities between African American (AA) and White (W) men treated with definitive radiation therapy for their prostate cancer. MethodsThree thousand one hundred eighty cases of prostate cancer treated with various radiation modalities at a single institution were reviewed. The cohort consisted of 92% W patients and 8% AA patients. Clinical and pathologic characteristics at presentation, treatment outcomes, and related toxicities were analyzed between the 2 groups. The median follow-up was 6.6 years (0.6 to 22.4 y). ResultsAt presentation, AA men were younger (P<0.001) and more likely to have a Gleason score of ≥7 (47.9% vs. 39.2%, P=0.006). No difference in the 5 or 10-year rates of biochemical failure, disease-free survival, or distant metastases were noted. Although there was a trend for improved 10-year overall survival for AA men (65.3% vs. 57.4%, P=0.06), cause-specific survival was significantly improved at 10 years (98.6% vs. 90.6%, P=0.002). Similar findings were seen when controlling for radiation therapy dose, the use of hormonal therapy, and modality of radiation therapy used. Overall, genitourinary/gastrointestinal toxicities were similar regardless of the modality used. ConclusionsDespite differences in presenting characteristics, AA men did not have inferior clinical outcomes but rather improved cause-specific survival when treated with standard of care radiation therapy. Regardless of the treatment modality used, toxicities between AA and W men were comparable.

BCR-ABL Testing by Polymerase Chain Reaction in Patients With Neutrophilia: The William Beaumont Hospital Experience and the Case for Rational Laboratory Test Requests

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from the fusion of the BCR-ABL genes, forming the Philadelphia chromosome. The diagnosis is often suspected when there is leukocytosis with left shift and basophilia. Confirmation of the diagnosis requires a demonstration of BCR-ABL by polymerase chain reaction. Using data from the William Beaumont laboratory data registry, we conducted a retrospective review of all the orders for BCR-ABL tests sent to the clinical pathology laboratory between March 11, 2014 and September 12, 2014. We concluded that the presence of concurrent neutrophilia and basophilia has a sensitivity of 100% (95% CI, 69.15% to 100%) and specificity of 100% (95% CI, 93.15% to 100%) in the initial diagnosis of CML. Our results suggest that the presence of both neutrophilia and basophilia should be used as a threshold for the placement of orders for BCR-ABL in the initial diagnosis of CML in patients with leukocytosis with left shift and provide a basis for a reduction in health care spending. Restricting BCR-ABL tests to this population would save approximately

Ibrutinib as a Bruton Kinase Inhibitor in the Management of Chronic Lymphocytic Leukemia: A New Agent With Great Promise

198 million annually in national health care spending.

Evaluation of a Case of Inflammatory Breast Cancer with 18F-FDG PET/CT

The recent discovery of the role of the B-cell antigen receptor (BCR) signaling pathway in the propagation and maintenance of both normal B-cell function and in B-cell malignancies has highlighted the importance of many protein kinases involved in BCR signal propagation. Considerable research attention has focused on the Bruton tyrosine kinase (BTK) as a potential therapeutic target in B-cell malignancies. Treatment paradigms including ibrutinib, a potent inhibitor of the BTK recently approved by the US Food and Drug Administration, have significantly improved disease outcome among high-risk and relapsed/refractory cases of chronic lymphocytic leukemia. This has provided additional treatment options, especially among the elderly, where improved disease response has been accompanied by more manageable treatment-associated toxicity than commonly found with chemoimmunotherapy. In this review, we provide a synopsis of the current data on the efficacy and clinical utilization of ibrutinib and management of its resistance in the treatment of chronic lymphocytic leukemia.

Predictive and Prognostic Markers in Adults with Acute Myeloid Leukemia; a Single Institution Experience

Inflammatory breast cancer is a rare and aggressive form of cancer characterized by dermal lymphatic invasion and tumor embolization resulting in erythema and edema. In many cases, by the time of diagnosis there is already distant metastasis. Mammography, sonography, CT, and MRI are usually performed for initial staging; however, PET/CT can also be used for initial staging as it offers additional diagnostic information.

Effective Immunotherapy in Bone Marrow Metastatic Melanoma Presenting with Disseminated Intravascular Coagulopathy

Background: Acute myeloid leukemia (AML) is a heterogeneous malignancy with diverse genetic abnormalities, clinical presentations, and outcomes. Known predictive and prognostic factors in AML include age, performance status, comorbidities, cytogenetics, and molecular mutations. Identifying prognostic and predictive factors can inform the choice of induction therapy and outcomes prediction. Patients and Methods: A retrospective review was performed of 137 adult AML patients from 2010 to 2015. Predictors of complete remission (CR) and overall survival (OS) were determined for patients treated with 3+7 (3 days of anthracycline and 7 days of cytarabine) or hypomethylating agent. Variables associated with CR or OS were assessed using univariate Cox regression and a multivariate Cox model. Results: The average age was 65 years and 91 patients (66%), sample size is 137 patients had primary AML. Patients in the 3+7 induction group were younger, had a higher bone marrow blast percentage, and more de novo AML compared with those in the hypomethylating agent group (P < .001, P < .001, P = .005, respectively). Univariate logistic regression for CR showed a significant association between age (P < .001), choice of induction (P < .001), and monosomy (P = .015), although only induction with 3+7 (P < .001) and absence of monosomy (P = .042) remained significant in multivariate analysis. Univariate Cox regression indicated that age (P = .003), AML status (de novo or secondary; P = .0277), choice of induction (P = .030), and monosomy (P = .010) had a significant association with OS. Only younger age (P = .018) and absence of monosomy (P = .022) were predictive of OS in multivariate Cox analysis. Conclusion: Positive predictors of CR in adult AML include absence of monosomy and induction treatment with 3+7; whereas positive predictors of OS are younger age and absence of monosomy. Micro‐Abstract Outcomes in acute myeloid leukemia (AML) have been correlated with predictive and prognostic factors including age, performance status, comorbidities, cytogenetics, and molecular mutations. Retrospective review of 137 adult AML patients identified 3+7 (3 days of anthracycline and 7 days of cytarabine) induction and absence of monosomal karyotype to positively predict complete remission whereas positive predictors of overall survival were younger age and the absence of monosomal karyotype.

Apixaban for treatment of confirmed heparin-induced thrombocytopenia: a case report and review of literature

Malignant melanoma is responsible for the majority of skin cancer deaths and is increasing in prevalence. Bone marrow (BM) involvement by melanoma is rare in the absence of widespread visceral disease. Here, we report the case of a 30-year-old female who presented to the hospital with back pain, low-grade fever, and easy bruising. She was found to be bicytopenic and in disseminated intravascular coagulopathy (DIC). Surprisingly, BM biopsy showed extensive involvement by metastatic malignant melanoma in the absence of visceral or brain metastasis. The unique presentation of this case and the challenge of management of a potentially treatable cancer in a critically ill patient are discussed, alongside a review of published cases of metastatic melanoma in the BM and an exploration of currently available treatment options. The excellent response of our patient to combined immune checkpoint inhibitors has yet to be paralleled in the available literature.

Programmed cell death-1/Programmed cell death ligand-1(PD-1/PD-L1) inhibitors, heralding a new era of immunotherapy in the management of advanced Non-Small Cell Lung Cancer (NSCLC)

BackgroundHeparin-induced thrombocytopenia (HIT) is a life and limb-threatening condition caused by the binding of platelet-activating antibodies (IgG) to multimolecular platelet factor 4 (PF4)/heparin complexes because of heparin exposure. The by-product of this interaction is thrombin formation which substantially increases the risk of venous and/or arterial thromboembolism. Currently, only one anticoagulant, argatroban, is United States Food and Drug Administration-approved for management of HIT; however, this agent is expensive and can only be given by intravenous infusion. Recently, several retrospective case-series, case reports, and one prospective study suggest that direct oral anticoagulants (DOACs) are also efficacious for treating HIT. We further review the literature regarding current diagnosis and clinical management of HIT.Case presentationA 66-year-old male patient developed HIT beginning on day 5 post-cardiovascular surgery; the platelet count nadir on day 10 measured 16xa0×xa0109/L. Both the PF4-dependent ELISA and Serotonin-release assay were strongly positive. Despite initial anticoagulation with argatroban (day 6), the patient developed symptomatic Doppler ultrasound-documented bilateral lower extremity deep vein thrombosis on day 14 post-surgery. The patient was transitioned to the DOAC, apixaban, while still thrombocytopenic (platelet count 108) and discharged to home, with platelet count recovery and no further thrombosis at 3-month follow-up.ConclusionsWe report a patient with serologically confirmed HIT who developed symptomatic bilateral lower limb deep vein thrombosis despite anticoagulation with argatroban. The patient was switched to oral apixaban and made a complete recovery. Our patient case adds to the emerging literature suggesting that DOAC therapy is safe and efficacious for management of proven HIT.