Volume 2, Issue 2, September 2017

Case Report

A Novel RPL35A Mutation Associated with Diamond-Blackfan Anemia: Report of a Case and Review of the Literature Page 69-74
Guang Yang, Jun Wang, Brissa Martin, Edward Rowsell, and Ross Fisher

Diamond Blackfan anemia (DBA) is a genetically and clinically heterogeneous disorder characterized by pure red blood cell aplasia, variable congenital anomalies, and a predisposition to cancer. The genes implicated in DBA all encode ribosomal proteins associated with either the small or large ribosome subunits. We report a novel variant of unknown significance in the RPL35Agene (p.R76P) in an Asian male presenting with macrocytic anemia, neutropenia, genitourinary malformations, and growth retardation without significant erythroid hypoplasia in bone marrow. We postulate that this variant is likely pathogenic and contributing to this patient’s DBA phenotype; the variant has never been reported in the general population, it changes a highly conserved amino acid, and is predicted to be deleterious by in silico models, while clinically this patient responded well to steroid treatment.


Pathology in the Molecular Era: Challenges and Opportunities Page 75-83
X. Frank Zhao

Pathology as a discipline can be traced to the 17th Century, B.C. Over the past 4,000 years, pathology has experienced four eras: the morphological, immunological, genetic, and molecular eras. Molecular pathology emerged in 1970s when Southern blot was employed to detect gene rearrangements in cancer cells. DNA sequencing and polymerase chain reaction (PCR) further revolutionized the diagnosis of human diseases. Gene profiling array and next generation sequencing are being applied in clinical diagnostics. While marveling at the advancement of new technologies, pathologists should be aware of the many challenges over the horizon. These include: 1) atypical morphology and aberrant gene expression make it more and more difficult to classify cancers; 2) genetic studies that play more and more important roles in diagnosing diseases; 3) precision medicine which renders morphology-based diagnosis less and less meaningful; 4) the reality of robust and affordable global sequencing of tumors. With development of various omics, traditionally morphology-based pathology will face even more challenges. However, these challenges can also be opportunities for pathologists, such as diagnosing diseases based on biology; classifying diseases based on therapeutic targets; getting more involved in clinical decision making; and discovering new biomarkers and therapeutic targets. Seizing these opportunities will be essential for pathology to play a central role in the 21st Century medicine.


Chimerism Assessment is not a Reliable Surrogate for Disease Monitoring after Stem Cell Transplantation Page 84-95
M. Gabriela Kuba, Jonathan J. Douds, Delecia LaFrance, Adam C. Seegmiller, Claudio A. Mosse, Cindy L. Vnencak-Jones, and Annette S. Kim

Aims: There is a paucity of evidence-based guidelines supporting test selection after allogeneic stem cell transplantation for the assessment of residual disease and bone marrow chimerism, although common clinical practice typically includes some measures of both. This study aims to evaluate the accuracy of chimerism studies to predict residual disease and clinical outcome.
Methods: We retrospectively reviewed both chimerism and residual disease studies associated with 334 bone marrow samples from 143 patients with a range of hematologic malignancies, with a mean of over 2 years of additional follow-up to assess relapse rate.
Results: Of 334 cases, 266 showed no histologic evidence of disease. Ancillary tests for residual disease were available in 260/266 cases, with negative results in 87% (227/260) of cases. Mixed chimerism (MC) was found in 48% (108/227) of these cases. In addition, 30.3% of cases with residual disease by ancillary testing demonstrated complete engraftment (CE). No significant difference in relapse rates between MC (19.5%) and CE (16.3%) patients was found in patients who received reduced intensity chemotherapy conditioning regimens (RIC) (p=0.69). Similarly, relapse rates of MC and CE in patients who received myeloablative conditioning (MAC) were 11.1% and 17.5%, respectively (p=0.47).
Conclusions: Bone marrow engraftment analysis did not reliably correlate with residual disease status as measured by a number of different methods in the setting of typical preparative regimens (classified as either RIC or MAC). In addition, we found no uniform association between chimerism status and relapse. This study raises concerns about the value of chimerism studies to predict clinical outcomes related to disease status.


De Novo Splenic Myeloid Sarcoma Masquerading as Mesenteric Artery Occlusion Associated Acute Abdomen Page 96-102
Jonathon H. Gralewski, George D. Smith, Yogesh Jethava, Muthu K. Veeraputhiran, and Daisy Alapat

We present a case of a 41-year-old male who was admitted to an outside hospital for abdominal
pain with increasing severity and reported past medical history of seizures and pancreatitis. Abdominal CT imaging revealed acute mesenteric ischemia and a splenic infarction. Concurrently, the patient’s white blood cell count showed minimal leukocytosis with relative monocytosis. Patient underwent a laparotomy that resulted in a mesenteric embolectomy and splenectomy. Reviewing the histological sections of the spleen, accessory spleen and mesenteric emboli clot sections along with additional studies performed at our institution confirmed the diagnosis of an isolated de-novo myeloid sarcoma with monocytic differentiation. Staging of the disease included trephine bone marrow biopsy and ancillary testing on the bone marrow aspirate (i.e. cytogenetics and FISH studies). These studies were negative for bone marrow involvement by acute myeloid leukemia. Follow up positron emission tomography/computed tomography highlighted no new sites of involvement. To the best of our knowledge, this is the second reported case in the literature of an isolated splenic myeloid sarcoma without bone marrow involvement and no history of receiving any treatment. This is the first reported case in the medical literature of this disease entity clinically presenting as mesenteric artery occlusion.