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Significance The United States is in an acceleration phase of the COVID-19 pandemic. Currently there is no known effective therapy or vaccine for treatment of SARS-CoV-2, highlighting urgency around identifying effective therapies. Objective The purpose of this study was to evaluate the role of hydroxychloroquine therapy alone and in combination with azithromycin in hospitalized patients positive for COVID-19. Design Multi-center retrospective observational study. Setting The Henry Ford Health System (HFHS) in Southeast Michigan: large six hospital integrated health system; the largest of hospitals is an 802-bed quaternary academic teaching hospital in urban Detroit, Michigan. Participants Consecutive patients hospitalized with a COVID-related admission in the health system from March 10, 2020 to May 2, 2020 were included. Only the first admission was included for patients with multiple admissions. All patients evaluated were 18 years of age and older and were treated as inpatients for at least 48 h unless expired within 24 h. Exposure Receipt of hydroxychloroquine alone, hydroxychloroquine in combination with azithromycin, azithromycin alone, or neither. Main outcome The primary outcome was in-hospital mortality. Results Of 2,541 patients, with a median total hospitalization time of 6 days (IQR: 4–10 days), median age was 64 years (IQR:53–76 years), 51% male, 56% African American, with median time to follow-up of 28.5 days (IQR:3–53). Overall in-hospital mortality was 18.1% (95% CI:16.6%–19.7%); by treatment: hydroxychloroquine + azithromycin, 157/783 (20.1% [95% CI: 17.3%–23.0%]), hydroxychloroquine alone, 162/1202 (13.5% [95% CI: 11.6%–15.5%]), azithromycin alone, 33/147 (22.4% [95% CI: 16.0%–30.1%]), and neither drug, 108/409 (26.4% [95% CI: 22.2%–31.0%]). Primary cause of mortality was respiratory failure (88%); no patient had documented torsades de pointes. From Cox regression modeling, predictors of mortality were age > 65 years (HR:2.6 [95% CI:1.9–3.3]), white race (HR:1.7 [95% CI:1.4–2.1]), CKD (HR:1.7 [95%CI:1.4–2.1]), reduced O2 saturation level on admission (HR:1.5 [95%CI:1.1–2.1]), and ventilator use during admission (HR: 2.2 [95%CI:1.4–3.3]). Hydroxychloroquine provided a 66% hazard ratio reduction, and hydroxychloroquine + azithromycin 71% compared to neither treatment (p Conclusions and relevance In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact.

We describe a 40-year-old woman with severe, persistent macroglossia following prone positioning as part of treatment for COVID-19. We used the treatment method of lingual compression with satisfactory results.

B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as “double-hit” lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathological features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathological spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we performed case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32-91). Six patients had a history of grade 1-2 follicular lymphoma (FL); review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 months) was inferior to both BL (p=0.002) and IPI-matched DLBCL (p=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (p

Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population.

Multiple malignancies may occur in the same patient, and a few reports describe cases with multiple hematologic and non-hematologic neoplasms. We report the case of a patient who showed the sequential occurrence of four different lymphoid neoplasms together with a squamous cell carcinoma of the lung. A 62-year-old man with adenopathy was admitted to the hospital, and lymph node biopsy was positive for low-grade follicular lymphoma. He achieved a partial remission with chemotherapy. Two years later, a PET-CT scan showed a left hilar mass in the lung; biopsy showed a squamous cell carcinoma. Simultaneously, he was diagnosed with diffuse large B cell lymphoma in a neck lymph node; after chemo- and radiotherapy, he achieved a complete response. A restaging PET-CT scan 2 years later revealed a retroperitoneal nodule, and biopsy again showed a low-grade follicular lymphoma, while a biopsy of a cutaneous scalp lesion showed a CD30-positive peripheral T cell lymphoma. After some months, a liver biopsy and a right cervical lymph node biopsy showed a CD30-positive peripheral T cell lymphoma consistent with anaplastic lymphoma kinase-negative anaplastic large cell lymphoma. Flow cytometry and cytogenetic and molecular genetic analysis performed at diagnosis and during the patient’s follow-up confirmed the presence of two clonally distinct B cell lymphomas, while the two T cell neoplasms were confirmed to be clonally related. We discuss the relationship between multiple neoplasms occurring in the same patient and the various possible risk factors involved in their development.

Introduction: Epidemiologic research in hematologic malignancies has been dependent on three sources of data; SEER data, patients accrued to large clinical trials, and databases generated by individual providers or departments. Each of these sets of data have major limitations. In theory the adoption of computerized databases by pathology departments and the adoption of electronic medical records should have greatly expanded the ability to identify patients with particular types of malignancies. In practice the need to manually classify tens of thousands of free text pathology reports has made this resource unavailable. We have developed a computer program to extract and codify the final diagnoses described in free text pathology reports according to the World Health Organization (WHO) classification of hematologic malignancies. This enables us to identify sets of cases of desired pathologies for further study. Methods: A medical records review protocol was approved by the Dana Farber Harvard Cancer Center Institutional Review Board. Using our clinical lymphoma database we collected records of patients at Massachusetts General Hospital (MGH) Cancer Center who carried a diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).The program is modified from one developed to extract diagnoses from discharge summaries in a different context [Long, AMIA 2007]. The approach is to use punctuation and a few words (conjunctions and some common verbs) to divide the text into phrases and then use a search procedure to find the most specific matching concepts in the UMLS (Unified Medical Language System). The search uses all of the alternate phrases for each concept as included in the UMLS normalized string table, matched against normalized subphrases from the text. We mapped UMLS concepts to the desired WHO concepts. To ensure a complete list of UMLS concepts we used the hierarchical relations in the UMLS and examined both more specific and more general concepts for possible inclusion in the search. Since not all diseases in a report are part of the diagnosis, we developed pattern matching procedures to identify the parts of the pathology report containing the final diagnosis (as opposed to “note” or “clinical data” that might have patient specific clinical information that are not diagnosed in the current pathology report). The program also uses a strategy for identifying modifiers that change the sense of the diagnosis (“suggestive of”, “rule out”, “no”, etc.) to exclude diseases that are absent or only possible. Results: We used the system to identify cases of FL and DLBCL and compared the results to lists of cases generated manually. The current program was 90% accurate in automatically classifying pathology reports as describing follicular lymphoma. Of 150 cases of FL, the program found 133 (eg, MALIGNANT LYMPHOMA, FOLLICLE CENTER) and 3 were in reports not available to the program (133/147 90%). Of 100 DLBCL cases, 76 were available and 63 were found (83%) (eg, HISTIOCYTE-RICH LARGE B-CELL LYMPHOMA). There were several reasons for the missed cases. Most commonly (13) the diagnosis was not in the identified diagnosis section, either because the section was divided by a note or the diagnosis was in an addendum. Only 3 cases had phrases not found in the UMLS. For 2 others, the program missed because the phrase was not contiguous (eg, B-CELL LYMPHOMA, CONSISTENT WITH FOLLICLE CENTER CELL TYPE). In 5 of the DLBCL cases the stated final diagnosis was more general than the desired diagnoses and 2 of the FL cases were listed as “strongly suggestive” which the program concluded was not a definite diagnosis. Discussion: This program is useful for identifying desired cohorts of cases and can be improved with better identification of the sections containing the diagnosis, the addition of a few missing phrases as they are discovered, and the addition of techniques for handling common discontinuities in disease descriptions (eg, allowing “consistent with” in the phrase). We have shown that very simple natural language techniques are sufficient to extract most of the desired disease descriptions from free text reports, enabling automatic selection of cases and greatly enhancing the usefulness of large repositories of pathology reports.

Abstract 1806 Poster Board I-832 Plasmacytomas are rare clonal proliferations of plasma cells that though cytologically identical to plasma cell myeloma, present with osseous or extraosseous growth pattern. Understanding their molecular characteristics can provide crucial insights into their pathogenesis and risk of progression to multiple myeloma (MM). To investigate the differences between extramedullary (EMP) and medullary plasmacytomas (MP) and MM without plasmacytomas, we sought to molecularly profile these tumors by tissue microarrays, gene expression, microRNA, and FISH. We identified 85 patients from our data base with a pathological diagnosis of plasmacytoma. Of the 85 patients, 13 patients presented with EMP, and 72 had MP. Among the patients with EMP (n=13), 2 patients presented with multiple lesions. Three of 13 (23%) patients progressed to develop MM at a median of 12 months. 72 patients presented with MP, of which 21 had solitary lesions and 27 (37%) progressed to MM at a median of 20.5months. There was a male preponderance (67% vs 33%) and the median age at diagnosis was 60.5 years (range 27.7-87.6). The mean overall survival for patients with EMP was 121 months (95% confidence interval[CI] 97-144 months) and for patients with MP was 102 months (95% CI 93-128 months) { p=0.025} MicroRNA (miRNAs) profiling was performed on MP (n=19) and MM samples (n=66). Data was normalized using U6 endogenous control. Three hundred and one miRNAs out of a total 665 were significantly differentially expressed between MP vs MM samples. Gene expression profiling performed on MP will be correlated with the miRNA data to identify genes and transcripts of interest which will be functionally validated. Tissue microarrays were performed on 52 patients (8: EMP, 44: MP,) in whom paraffin-embedded tissue was available. Of samples analyzed, CD56 positivity was observed in 55% MP and 71% EMP samples (p=0.67). Additional staining for cyclin D1, Bcl 2 and FISH analysis will be reported. Differential expression patterns of factors involved in proliferation, survival, adhesion, and stroma-tumor cell interactions may help explain plasmacytoma biology and identify factors responsible for progression to MM. These insights may help identify new therapeutic approaches and targets in the treatment of these plasma cell disorders. Disclosures Hochberg: Enzon: Consultancy, Speakers Bureau; Biogen-Idec: Speakers Bureau; Genentech: Speakers Bureau; Amgen: Speakers Bureau. Anderson:Millennium: Research Funding. Raje:Celgene, Norvartis, Astrazeneca: Research Funding.