Nasir Bakshi

The Current Lymphoma Classification: New Concepts and Practical Applications—Triumphs and Woes

The World Health Organization (WHO) classification of lymphomas updated in 2008 represents an international consensus for diagnosis of lymphoid neoplasms based on the recognition of distinct disease entities by applying a constellation of clinical and laboratory features. The 2008 classification has refined and clarified the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. Rather than being a theoretical scheme this classification has used data from published literature. Recent knowledge of molecular pathways has led to identification and development of new diagnostic tools, like gene expression profiling, which could complement existing technologies. However, some questions remain unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors. In general, practical considerations and economics preclude a heavily molecular and genetic approach. The significance of early or precursor lesions and the identification of certain lymphoid neoplasms is less clear at present, but understanding is evolving. The borderline categories having overlapping features with large B-cell lymphomas, as well as some of the provisional entities, are subject to debate and lack consensus in management. Lastly, the sheer number of entities may be overwhelming, especially, for the diagnosing pathologist, who do not see enough of these on a regular basis.

Cancer Vaccines: Past, Present, and Future.

Cancer is a common and potentially deadly disease. Some of the cancers may be difficult to treat by conventional means such as surgery, radiation, and chemotherapy, but may be controlled by the stimulation of the immune response of the body with the help of cancer vaccines. The use of vaccines for preventing infections by oncogenic viruses such as hepatitis B virus and human papilloma virus has been extremely successful in reducing the incidence of cancers resulting from these infections. The use of vaccines for treating cancers that are not due to viral infections and that are already established is currently the object of numerous clinical trials. Several types of cancer vaccines are being tried. These include antigen vaccines, tumor cell vaccines, dendritic vaccines, deoxyribonucleic acid vaccines, and viral vector vaccines. The development of these therapeutic vaccines is proving difficult with only 1 recent success. However, there is significant enthusiasm and optimism regarding the development of effective therapeutic vaccines stemming from the fact that our understanding regarding the cancer immunology is considerably enhanced in recent years. This expanded knowledge regarding the mechanisms that cancers use to escape the immune system is likely to open new avenues in modulating the immune response to cancer, thus enhancing the effectiveness of therapeutic cancer vaccines.

Successful treatment of steroid-refractory autoimmune thrombocytopenia associated with Castleman disease with anti-CD-20 antibody (rituximab)

Multicentric Castleman disease (MCD) is a lymphoproliferative disorder of incompletely understood etiology and with various clinical presentations. The best therapeutic option for this disease is not well established. MCD is known to be associated with autoimmune phenomena. A 70-year-old female patient of MCD with progressive nodal disease associated with autoimmune thrombocytopenia failed steroid treatment and showed a transient response to intravenous immunoglobulin. The patient achieved complete recovery of her platelet count and a very good response in nodal disease after 3 weekly doses of anti-CD-20 antibody (rituximab). Anti-CD20 antibody treatment could be a good therapeutic option for MCD, mainly when associated with immune-related disorders.

Donor-derived extramedullary acute promyelocytic leukemia post kidney transplant.

Dear Editor, Here, we describe what to our knowledge is the only case in the literature of donor kidney-derived extramedullary acute promyelocytic (EM-APL). A 54-year-old physician with diabetes mellitus, hypertension, and ischemic heart disease, who had received a renal transplant of indeterminate origin for end stage kidney disease in China 2 years before presentation, was referred to our hospital with gross hematuria, deteriorating renal function, jaundice, and multiple subcutaneous nodules. PET CT scan of the body revealed multiple FDG avid masses as shown in Fig. 1a. Biopsy of the transplanted kidney and subcutaneous nodule (FNA) was consistent with granulocytic sarcoma based on flow performed on the submitted specimen (axillary mass) showing a population of cells in the blast gate that co-express MPO, CD11b, CD13, CD33, CD34, CD38, and CD117 and HLA-DR (dim). Bone marrow was uninvolved and a FISH panel including t(15;17) was negative. Attempted cytogenetic analysis from FNA of the nodules failed. A resection of the kidney was offered but the patient declined, and immunosuppression was continued with lowdose FK506 and prednisone; MMF was stopped. The final diagnosis at that stage was granulocytic sarcoma. Given the comorbidities, he was given upfront idarubicin and cytarabine “2+5” with a suboptimal response based on PET scan; then, he received salvage fludarabine/Ara-c (FA) protocol resulted in complete metabolic response. As per standard operating procedure at our hospital, PML-RARa is not sent from a diagnostic tissue sample other than bone marrow. In order to characterize the disease further, a FISH panel on the axillary biopsy was done and revealed positivity for t(15;17). The patient was then given ATRA/idarubicin (AIDA) induction followed by 25 doses of arsenic trioxide (ATO) consolidation and then maintenance ATRA; mercaptopurine and methotrexate were not given due to cytopenias. As the initial lesion seemed to be in the transplanted kidney, we sought to determine whether the leukemia may have been of donor origin. In order to address this hypothesis, DNA was extracted from the previously excised axillary block. This was compared with DNA from the patient’s blood. To our surprise, DNA by short tandem repeat analysis revealed that axillary mass was not of recipient origin as shown (Fig. 1b). Eighteen months on since first presentation, he has no demonstrable disease based on PET scan with good quality of life and stable renal function. A case reported in Blood by Girsberger et al. described a case of donor kidney derived AML [1]. Kidney transplant recipients are at increased risk for development of malignancy compared with the general population [2]. There are case reports of AML post solid organ transplantation [3, 4]. Donor-derived APL has been reported [5]; however, the aleukemic extramedullary presentation in our case is unique. Treatment of acute leukemia in solid organ transplant remains one of the main challenges facing the hematologist with sparse literature focusing on this issue. A. Alhuraiji (*) :W. Chebbo :G. El-Gohary :N. Chaudhri : F. Almohareb :K. Ibrahim : S. A. Osman Hematology Section, Oncology Centre, KFSHRC, Riyadh 11211, Saudi Arabia e-mail: aalhuraiji@gmail.com

Gleason grading of prostate cancer in needle core biopsies: a comparison of general and urologic pathologists.

BACKGROUND AND OBJECTIVES The Gleason grading of prostate carcinoma (PCa) in needle core biopsies is a major determinant used in management planning. The objective of this study was to evaluate the concordance between general pathologists Gleason grading and that of a urologic pathologist in our community. DESIGN AND SETTING Retrospective review conducted at three tertiary care hospitals in Jeddah and Riyadh for all prostatic biopsies with carcinoma from January 2002 to January 2011. METHODS Gleason scores assigned by the original pathologist were compared with that of the reviewing urologic pathologists. Biopsies were originally obtained and diagnosed at different referring hospitals and independent laboratories. The kappa test was used to evaluate agreement between the original and review scores. RESULTS For 212 biopsies the exact concordance of the Gleason score assigned by the original pathologist and the reviewer was 38.7% (82/212). However, when grouped into the main four-score categories of 2–4, 5–6, 7, and 8 or greater, disagreement was noted in 88 (41.5%) biopsies; 87 were upgraded and 1 was downgraded on review. When grouped into two-score categories of low grade (≤6) and high grade (≥7), disagreement was noted in 32 (15%) of the biopsies. CONCLUSION Gleason grade score shows that there was only slight to fair agreement between outside and review scoring (kappa=0.43). When using only low versus high grade categorization, there was good agreement (kappa=0.69). Almost all of the cases with score disagreement were upgraded on review.

Spectrum of bone marrow pathology and hematological abnormalities in methylmalonic acidemia

Patients with isolated methylmalonic acidemia (MMA) may present with a wide range of hematological complications including anemia, leukopenia, thrombocytopenia, and pancytopenia. However, there are very limited data on the development of hemophagocytosis or myelodysplasia in these patients. We report three patients with isolated MUT related MMA who presented with severe refractory pancytopenia during acute illness. Their bone marrow examination revealed a wide spectrum of pathology varying from bone marrow hypoplasia, hemophagocytosis to myelodysplasia with ring sideroblasts. We discuss their management and outcome. This report emphasizes the need for bone marrow examination in these patients with refractory or unexplained severe cytopenia, to confirm bone marrow pathology, and to rule out other diseases with similar clinical presentation for a better clinical outcome.

Prevalence and relative proportions of CLL and non-CLL monoclonal B-cell lymphocytosis phenotypes in the Middle Eastern population

http://dx.doi.org/10.1016/j.hemonc.2016.09.003 1658-3876/ 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). * Corresponding author at: Oncology Center, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia. E-mail address: maljurf@kfshrc.edu.sa (M. Aljurf).

Local recurrence of primary central nervous system lymphoma due to tumor seeding.

Ann Saudi Med 2013 May-June www.annsaudimed.net 310 A 48-year old male, initially presented to the local hospital with generalized tonic-clonic seizure episodes for almost eight months. He had no previous head trauma, family history or chronic illness. There was no focal neurological deficit. Computed tomography scan of brain revealed small left parietal lobe lesions. Repeated brain imaging after two months showed progressive brain lesions. He had brain MRI which showed 3.1×4.3 soft tissue mass Local recurrence of primary central nervous system lymphoma due to tumor seeding