Imran Mirza

Malignant Eccrine Spiradenoma

Malignant transformation of eccrine spiradenoma is extremely rare. We describe the case of a 70-year-old man with malignant eccrine spiradenoma of the forearm and metastases to the axillary lymph nodes. Surgical excision with adequate margins and lymph node dissection was performed. Tamoxifen therapy was instituted after obtaining positive immunostaining results for estrogen receptor. After 41 months of follow-up, there has been no recurrence or distant metastases. Wide local excision and close follow-up are crucial in the management of malignant eccrine spiradenoma. The role of other therapeutic modalities, including hormonal therapy, remains to be determined.

Reactive hemophagocytic syndrome associated with disseminated histoplasmosis in a heart transplant recipient

We describe a patient who developed multi-organ failure with reactive hemophagocytic syndrome secondary to disseminated histoplasmosis 8 months after orthotopic heart transplantation. The patient responded fully to a prolonged course of therapy with amphotericin B and remains free of recurrence. Disseminated histoplasmosis and reactive hemophagocytic syndrome have rarely been described in the setting of cardiac transplantation and never before in combination.

Transformation of polycythemia vera to chronic myelogenous leukemia.

Transformation of polycythemia vera to chronic myelogenous leukemia is a rare event. We report 2 women with long-standing polycythemia vera who developed chronic myelogenous leukemia. Both patients had no BCR/ABL1 fusion at the time of polycythemia vera diagnosis but were positive for the fusion at chronic myelogenous leukemia onset. Most patients with polycythemia vera have JAK2(V617F) mutation. Analysis of an archival bone marrow aspirate sample from 1 patient showed a heterozygous mutation status. The blood and bone marrow samples from the other patient showed the presence of homozygous JAK2(V617F) mutation and BCR/ABL1 fusion. The possible pathogenesis of such an event is discussed in the light of current literature.

Waterhouse-Friderichsen Syndrome Secondary to Capnocytophaga canimorsus Septicemia and Demonstration of Bacteremia by Peripheral Blood Smear A Case Report and Review of the Literature

Waterhouse-Friderichsen syndrome caused by Capnocytophaga canimorsus septicemia was fatal in a previously healthy 47-year-old woman. The patient died suddenly in less than 12 hours after presentation, in spite of supportive measures, including ventilation, antibiotic coverage, pressor therapy, and multiple transfusions of blood products. The diagnosis of infection due to an unusual organism was suspected earlier in the course of management after review of the peripheral blood smear. The importance of the findings in the blood smear and their correlation with infection due to this organism are discussed.

An Unusual Presentation of Calciphylaxis Due to Primary Hyperparathyroidism

We present the case of a 69-year-old woman with calciphylaxis due to primary hyperparathyroidism. A 0.5-g parathyroid adenoma was surgically removed, which resulted in complete recovery of the patient. Review of the literature revealed 7 other cases of calciphylaxis due to primary hyperparathyroidism and showed that prompt surgical removal of the autonomous parathyroid gland lesion results in clinical recovery of calciphylactic skin lesions.

Immunoglobulin VH somatic hypermutation in mantle cell lymphoma: mutated genotype correlates with better clinical outcome

Mantle cell lymphoma is an aggressive B-cell lymphoma for which the biology is incompletely understood. Previous studies have reported that somatic hypermutation of the variable region of the immunoglobulin heavy chain gene (VH), as commonly defined as <98% homology, can be detected in approximately one-third of mantle cell lymphoma, although the VH mutation status has not been found to significantly correlate with patient survival. In this study, we assessed VH mutation in 55 mantle cell lymphomas using a method slightly different from those used in the previous studies, and we came to different conclusions. Using DNA extracted from formalin-fixed/paraffin-embedded tumors in all cases, we identified monoclonal IGH bands in 54 of 55 cases with the FR1c/JH primer; a monoclonal IGH band was amplified using another IGH primer set, FR256/JH, in the remaining case. Cloning was performed in all cases, and an average of six clones were sequenced and analyzed for each case. Intraclonal heterogeneity was detected in 45 (82%) cases. Further analysis was performed in 53 cases, in which a predominant IGH species was identified. Most (32 of 53 cases, 60%) cases were ‘mutated’, with <98% homology. VH1-69, VH4-59 and VH3-74 were utilized in 29 (55%) cases. Intraclonal evolution and non-productive VH rearrangements were more frequent in the mutated group. Patients with the ‘mutated’ genotype had longer overall survival (P=0.017, Log rank) that is independent of the international prognostic index. To conclude, our data suggest that the VH mutation frequency in mantle cell lymphoma may be higher than previously believed. Importantly, using our methodology, we found that the VH mutation status may be a useful prognostic marker for these patients.

Comparison of antimicrobial activity between ceftolozane–tazobactam and ceftazidime–avibactam against multidrug-resistant isolates of Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa

OBJECTIVE This study compared the activity of ceftolozane-tazobactam and ceftazidime-avibactam against 120 bacterial strains, including extended-spectrum beta-lactamase (ESBL) producers, carbapenem-resistant Enterobacteriaceae (CRE), and Pseudomonas aeruginosa, isolated from patients admitted to Cleveland Clinic Abu Dhabi, United Arab Emirates. METHODS In vitro susceptibility was tested using the Etest strip minimum inhibitory concentration (MIC) method, and PCR was used to characterize the carbapenemase enzymes produced by CRE strains. RESULTS All 29 ESBL isolates were susceptible to ceftazidime-avibactam (MIC50 0.125μg/ml), whereas all but one were susceptible to ceftolozane-tazobactam (MIC50 0.38μg/ml). Twenty-seven (45%) CRE isolates were susceptible to ceftazidime-avibactam (MIC50 ≥256μg/ml), whereas only six (10%) isolates were susceptible to ceftolozane-tazobactam (MIC50 ≥256μg/ml). Very few NDM-1 isolates were susceptible to ceftazidime-avibactam, whereas the majority of OXA-48 isolates were susceptible. Twenty-nine (94%) P. aeruginosa isolates were susceptible to ceftazidime-avibactam (MIC50 1.5μg/ml), whereas 30 (97%) isolates were susceptible to ceftolozane-tazobactam (MIC50 0.75μg/ml). CONCLUSIONS Ceftolozane-tazobactam and ceftazidime-avibactam showed comparable activity against ESBL and P. aeruginosa, with ceftazidime-avibactam having lower MICs against ESBL isolates and ceftolozane-tazobactam having lower MICs against P. aeruginosa. Ceftazidime-avibactam showed better activity against all CRE isolates except for those carrying the NDM-1 enzyme.

Competency-Based Education for the Molecular Genetic Pathology Fellow: A Report of the Association for Molecular Pathology Training and Education Committee

The following report represents guidelines for competency-based fellowship training in Molecular Genetic Pathology (MGP) developed by the Association for Molecular Pathology Training and Education Committee and Directors of MGP Programs in the United States. The goals of the effort were to describe each of the Accreditation Council for Graduate Medical Education competencies as they apply to MGP fellowship training, provide a summary of goals and objectives, and recommend assessment tools. These guidelines are particularly pertinent to MGP training, which is a relatively new specialty that operates within a rapidly changing scientific and technological arena. It is hoped that this document will provide additional material for directors of existing MGP programs to consider for improvement of program objectives and enhancement of evaluation tools already in place. In addition, the guidelines should provide a valuable framework for the development of new MGP programs.

Cytogenetic profile of a thymoma. A case report and review of the literature.

Cytogenetic analysis of mixed lymphocyte and epithelial thymoma in a nonmyasthenic female patient revealed deletion of part of the short arm of chromosome 6. To our knowledge, this cytogenetic abnormality in a benign thymoma has not been previously described in the literature, which is reviewed.

Testing for JAK2V617F mutation across specimen types yields concordant results

Chronic myeloproliferative neoplasms (CMPN) are a group of hematopoietic stem cell disorders associated with abnormal blood cell production and bone marrow (BM) morphology. Myeloid cells from the majority of polycythemia vera (PV) patients and approximately half of essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients carry the JAK2 V617F mutation.1-3 Recent proposed revisions to the World Health Organization (WHO) diagnostic criteria for these disorders include the presence of JAK2V617F mutation as a major criterion for diagnosis.4 Although various studies have shown that JAK2 mutation testing can be successfully performed on peripheral blood (PB),1-3 bone marrow aspirate (BMA),5 or BM biopsy,6, 7 comparison of results across different sample types has not been performed.