BackgroundMultiple myeloma (MM) is the second most common malignancy in the United States and has a higher incidence in the black and Afro-Caribbean population. There remain limited data on disease presentation and clinical characteristics in this patient group in the United States. The clinical profile of MM in this underrepresented patient group is described here.MethodsThis retrospective study was conducted at Kings County Hospital, an urban New York City hospital in a majority Afro-Caribbean neighborhood. Data from patients diagnosed with MM from 2000 through 2013 were collected from the institution’s tumor registry. Clinical and demographic characteristics of these patients were then analyzed.ResultsPatients with a diagnosis of MM were identified (N = 287). Data were available for 231 patients and of these, 97% self-identified as black. 55% were female, and there was a male-to-female ratio of 1:1.2. The mean age of female patients was 64 years; that of male patients was 63 years. Of the 231 patients, 81% had anemia, 68% had bone lesions, 47% had renal impairment, and 29% had hypercalcemia. Low levels of monoclonal protein were present in 27% of patients and 57% had disease of International Staging System stages I and II. Women had higher BMI than men.ConclusionThe mean age of presentation of MM in Afro-Caribbean patients is similar to that in the standard population; however, unlike the general US population, there was a higher incidence in women; mean BMI of women also was higher than that of male patients. A sizeable percentage of Afro-Caribbean patients with MM presented with low levels of monoclonal protein in the presence of multiorgan involvement and damage, suggesting the need for early and aggressive diagnostic testing.

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Background: RBC size variation and microcytes in B12D are often ascribed, but rarely shown, to be due to co-existing Fe deficiency. Schistocytes (aka poikilocytes) were included in early descriptions of pernicious anemia (PA). As it also causes thrombocytopenia, B12D may be confused with thrombotic thrombocytopenic purpura (TTP). Because of the urgency of PP for TTP, it has sometimes been initial therapy for B12D with schistocytes. Purpose: Here we describe 3 PA patients, and review reports of 15 other severely anemic B12D cases, with schistocytes. As they are smaller than mature RBC, they may normalize the MCV, while raising the RDW. We wished to determine whether primary lab studies help to distinguish B12D from TTP. Case Reports: These patients presented with symptoms of severe anemia: Ferritins were normal or high, haptoglobins <30, anti-intrinsic factor and parietal cell antibodies present, and complete response to B12 therapy occurred. Significant numbers of schistocytes were present in all, as was a distinctive population of minute, hypochromic schistocytes (MHS). Review: We found 15 reports of individual B12D patients with schistocytes, published between 2003 and 2015. All but 2 vegans had PA, 6 being anti-IF Ab+. Median & median ages were 52 & 53, [Hb]'s 5.9 & 6.0, MCV's 120 & 117 (3 normal), platelets 97 & 85, WBC 3200 & 3120, LDH's 4050 & 5860; reticulocyte levels were all low for severe anemia. Iron deficiency anemia was not found; ferritin and/or Fe/TIBC were reported normal in 4. Six legible blood smear microphotographs were included, confirming schistocytosis. Five patients had one or more PP before B12 deficiency was discovered. All 15 responded completely to B12. MHS were also observed on 4 of the 6 legible microphotographs, and noted by authors. For comparison, our survey of 36 reported TTP legible blood smears failed to detect MHC. Conclusions: Schistocytes are observed in some severely anemic B12D, may account for as much as 6.7% of RBC, and alter their indices. Schistocytosis and thrombocytopenia suggest TTP, and may lead to unnecessary PP. But such patients' low reticulocyte counts and very high LDH levels are not typical of TTP. Table Table. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Introduction Monoclonal gammopathy of undetermined significance (MGUS) is defined as the presence of monoclonal immunoglobulin (Ig), without the diagnosis of multiple myeloma (MM), while the diagnosis of MM requires the presence of a monoclonal immunoglobulin (Ig) ≥ 3g/dl or Bence-Jones protein (BJP) ≥ 500mg/24h, with bone marrow involvement of greater than 10% clonal plasma cells. Kings County Hospital (KCH) is an institution that serves a large population of Afro-Caribbean population. In our institution, an increased number of patients were observed to present with MM with monoclonal Ig <3g/dl but yet have end organ damage. The clinical characteristics of Afro-Caribbean population have not been well studied and further characterization may have diagnostic implications. Methods This is a retrospective study conducted at KCH. Data regarding the clinical profile of patients diagnosed with MM from 2000- 2013 was collected from the institution's tumor registry. Patients with monoclonal Ig < 3g/dl and BJP <500mg/24h were analyzed and compared to standard MM patients with monoclonal Ig ≥ 3g/dl or BJP ≥ 500mg/24h. Data was collected for lab parameters which included quantity and type of monoclonal Ig, serum free light chains and ratio, monoclonal plasma cell percentage in the bone marrow, International staging system (ISS) stage, cytogenetics, presence of anemia, hypercalcemia, renal failure and lytic lesions. Epidemiologic parameters age and gender were also collected. Results were analyzed by a Chi-square test to calculate a mid-P exact. Results A total of 287 patients with MM were screened, of which 56 patients with incomplete electronic records were excluded. Of the remaining 231 patients, 63 (27%) had monoclonal Ig <3 g/dl without the presence of BJP ≥ 500mg/24h. These patients were labeled hyposecretory MM. 168 (73%) patients had standard MM, with monoclonal Ig ≥ 3g/dl or BJP ≥ 500mg/24h. In the hyposecretory MM group, 35% of patients presented with International staging system (ISS) stage I vs. 13% in the standard MM group (P= 0.0001). IgG monoclonal Ig was present in 75% of patients with hyposecretory MM compared to 62% in the standard MM group (P=0.04). Mean plasma cell percentage in the bone marrow was similar in both groups, 40% in the hyposecretory MM group compared to 51% in standard MM. Average age of presentation was 64 yrs in the hyposecretory MM group as compared to 63 yrs in the standard MM group. There were more females than males in both groups, 61% females in hyposecretory MM and 53% in standard MM group. The most common presenting symptom was anemia in both groups and there were no statistically significant differences noted in gender, presence of hypercalcemia, presence of bone lesions, and renal dysfunction. Cytogenetic data was insufficient. Conclusion In our study, a substantial number of Afro-Caribbean patients with low levels of serum monoclonal Ig without the presence of Bence-Jones protein were diagnosed with active multiple myeloma. The results of our study underline the importance of an aggressive diagnostic approach with a bone marrow biopsy at initial presentation with MGUS in Afro-Caribbean population. This may prevent disease progression and end organ damage. Unlike the general population with MM, there were more females. Disclosures No relevant conflicts of interest to declare.

BackgroundThe diagnosis of giant cell arteritis (GCA) is confirmed by temporal artery (TA) biopsy findings of internal elastic lamina disruption, activated macrophages and T-lymphocytes infiltrating the arterial layers. The immune microenvironment in GCA becomes T helper-1 polarized after steroid therapy and consists of potential anti-tumor cytokines including interferon-gamma (IFG) and interleukin-12 (IL-12) which can be protective against the development of cancer. We have previously identified folate receptor beta positive macrophages in GCA, which can serve as a target for hacking this immune microenvironment.ObjectivesTo compare the tumor outcomes in our cohort of GCA vs controls who had TA biopsies.To select a line-up of CD3, IFG, IL12 and FRB as potential anti-tumor proteins and compare their expression in GCA+ TA tissue that did not develop tumors versus GCA -negative tissues that developed tumors.To assess the persistence of this line-up over time.MethodsWe performed a retrospective chart review of GCA subjects and controls to assess development of tumors over long-term follow up.Formalin-fixed paraffin embedded tissue sections were obtained from both groups and immunohistochemical stains were performed using CD3, IFG, IL12 and FRB antibodies.Results40 GCA and 40 controls demonstrated similar follow-up durations (76.9 vs 70.1 years; NS), time-to-incident cancer (21 vs 62 mos; NS) and deaths from cancer (5% vs 17.5%;NS). GCA subjects were older than controls (77.2 vs 69.7 years; p= 0.004). Cancer incidence is lower in GCA than controls (25% vs.47.5%; p=0.036). The incident cancers in GCA include 8 basal or squamous cell skin cancer(BCC/SCC) and 1 each of chronic lymphocytic leukemia, thyroid, esophageal and angiosarcoma. The controls had 6 BCC/SCC, 2 each of breast, skin melanoma and lymphoma, and 1 each of tonsil, parotid, colon, lung, renal, prostate, myelodysplastic syndrome and metastatic disease of unknown primary.Histopathology/IHC Findings: FRB was selectively expressed in macrophages and correlated with IFG, IL12 and CD3 expression. FRB, IFG, IL12 and CD3 expression were higher in GCA without incident cancer compared to controls with cancer: FRB (14 vs 2.3;p=0.006), IFG (3 vs 1;p=0.005), IL12 (1.5 vs 0;p=0.003), CD3 (79 vs 0;p=0.004). This multi- protein expression persisted for years in 3 repeat biopsies.ConclusionGCA has a lower risk of cancer which was associated with a chronic FRB+-macrophage and Th1-polarized anti-tumor autoimmunity.References[1]Deng J, Younge BR, Olshen RA, et al. Th17 and Th1 T-cell responses in giant cell arteritis.Circulation. 2010;121:906-915.[2]Bruni D, Angell HK, Galon J. et al. The immune contexture and immunoscore in cancer prognosis and therapeutic efficacy.Nat Rev Cancer2020;20:662-680.[3]Fridman WH, Pagès F, Sautès-Fridman C, et al. The immune contexture in human tumours: impact on clinical outcome.Nat Rev Cancer. 2012;12:298-306.[4]Smyth MJ, Taniguchi M, Street SE The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent.J Immunol2000;165:2665-70.[5]Albano-Aluquin S, Malysz J, Aluquin VR, et al. An immunohistochemical analysis of folate receptor beta expression and distribution in giant cell arteritis: a pilot study.Am J Clin Exp Immunol. 2017;6:107-114.[6]Xia W, Hilgenbrink W, Matteson L, et al. A functional folate receptor is induced during macrophage activation can be used to target drugs to activated macrophages.Blood2009;113:438-446Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Purpose of StudyTo demonstrate the presence and attributes of microcytes in Pernicious Anemia (PA) patients with high Red blood cell (RBC) distribution widths (RDW), but without iron deficiency or thalassemia trait. Marked macrocytosis is typical of PA, but their RDW are usually elevated (>21%).Methods Used Cases and MethodsWe report two patients with severe anemia, B12 deficiency, and elevated RDW's.Patient 1: 55 y/o African–American man, with dyspnea, finger paresthesias without gait disturbance. WBC 2.4 K/uL, Hb 4.8 g/dL, MCV 84.8 fL, RDW 30%, reticulocyte count 15 K/uL, iron 234 µg/dL, ferritin 880 ng/dL, platelets 70 K/uL, LDH 5980 U/L, B12 <30 pg/mL.Patient 2: 37 y/o African-American woman with long hx of anemia, recent weakness, and gait disturbance. WBC 3.5, Hb 6.3, MCV 114, RDW 29.5%, reticulocyte count 27, iron 108, TIBC 304 mg/dL, ferritin 50, platelets 45, LDH 2484, B12 60.Both patients' hematologic parameters normalized within 1–7 months after B12 treatment.Summary of ResultsMicrocytes constituted 32.8% of 1000 RBC in patient 1, whose MCV was normal, and 19.3% in patient 2. They were minute, irregular or twisted cells, often with two very unequal dimensions. They were often normochromic, or even hypochromic. Twenty of the small cells were measured, and their smallest dimension ranged from 2–4 microns, with an average of 3.0 microns. The larger dimension averaged 1.5–2.0 times greater than the smaller. The larger cells were circular or elliptical, with equal dimensions ranging from 6.2 to 13 microns.ConclusionsAlthough the coexistence of macrocytic and normocytic RBC may help to explain PA patients' high RDW, a significant percentage of their RBC may be microcytic. These microcytes are smaller than those in iron deficiency or thalassemia, have very irregular shapes (micro-poikilocytes), and resemble neither other types of microcytes nor schistocytes. The microcytes in one patient reduced his MCV to a normal level. These microcytes may be the result of megaloblastic dyserythropoiesis.