Skull base plasmacytoma in young patients aged below 40 years: Radiological perspectives and clinical outcomes.

BACKGROUND: Plasmacytoma of the skull base is a rare manifestation of plasma cell neoplasm with only a few cases documented in literature involving young adults. Plasmacytoma can be an isolated solitary lesion or a secondary manifestation of multiple myeloma (MM). In this study, we report the clinical and radiological characteristics, management, and outcomes of patients under the age of 40 who presented with skull base plasmacytoma and associated neurological manifestations. Additionally, we share our experience in treating a rare case of skull base plasmacytoma diagnosed during pregnancy, in which the patient exhibited a favorable response to myeloma treatment initiated after delivery. CASE SERIES: Four patients were identified, comprising one pregnant female and three male patients, with a median age of 36 years (range 33-37 years). The main presenting symptoms were headache, dizziness, and cranial nerve palsy. All patients received underwent systemic myeloma therapy and radiotherapy with three patients also underwent autologous stem cell transplantation (ASCT). Notably, all patients achieved complete remission. CONCLUSION: Skull base plasmacytoma represents a rare manifestation of plasma cell neoplasms, underscoring the importance of considering it in the differential diagnosis of skull base lesions to ensure early intervention and avoid potential serious complications. Throughout our series, the cornerstone of therapy involved radiotherapy, systemic myeloma therapy, and ASCT, all of which elicited a favorable response in every case.

Real world evidence of epidemiological trends, clinical presentation, and prognostic outcomes of multiple myeloma (2007-2021).

Background: Multiple myeloma (MM) is one of the most common hematological malignancies globally, and it is projected to increase in the coming years. It occurs more frequently in males and affects older individuals. Presenting symptoms can range from being asymptomatic to severely debilitating. The objective of this study was to determine the epidemiology, clinical features, and prognostic outcomes of patients with MM in the only tertiary cancer hospital in Qatar. Methods: Patients with symptomatic myeloma diagnosed at the National Center for Cancer Care and Research in Qatar between 2007 and 2021 were included. Data on demographics, laboratory work, bone marrow analysis, radiology, and given treatment were collected. Descriptive statistics, survival curves, and multivariable cox regression were used to identify independent mortality risk factors. Results: During the study period of 15 years, a total of 192 patients were diagnosed with MM. The incident rate of myeloma cases in 2021 was 8 patients per million. The median age of patients was 57 years [range 22-88], with 68% being above the age of 50 years at diagnosis. The majority of patients were male (71%) and (85%) were expats. At the time of diagnosis, most patients [n = 169 (88%)] had bone lesions, and 27% had extramedullary plasmacytoma. Anemia, hypercalcemia, and spinal cord compression were reported in 53%, 28%, and 7% of patients, respectively, at presentation. The monoclonal immunoglobulin subtypes were IgG, IgA, and free light chain in 52%, 16%, and 26% of patients, respectively. The overall median survival was 103 months (95% CI 71-135 months). In a multivariate cox-regression analysis for risk factors, only high serum calcium (≥ 2.7 mmol/L) was associated with increased mortality (HR: 2.54, 95% C.I.: 1.40-4.63, p = 0.002). Patients who received an autologous stem cell transplant (ASCT) had significantly better overall survival. Conclusion: In this comprehensive study of patients with MM treated in a country with a small and young general population, centralized hematology care, and free cancer care, we found a low but increasing incidence of MM and a good overall survival. Hypercalcemia was confirmed as a negative risk factor. ASCT had a significant positive impact on survival and should be provided to all patients eligible for this treatment, even in the era of novel agents.

Delayed Diagnosis of Indolent Systemic Mastocytosis as the Cause of Unexplained Skin Rash: A Case Report.

Mastocytosis is a heterogeneous group of disorders in which mast cells exhibit clonal proliferation that infiltrates one or more organs. In cutaneous mastocytosis, the mast cells infiltrate the skin only, whereas systemic mastocytosis is diagnosed when at least one extra-cutaneous site is involved, with or without the skin being affected. Given the rarity of mastocytosis and the fact that skin rash can be a manifestation of different conditions and many clinicians are not familiar with this disorder, an accurate diagnosis may be delayed. We report a delayed diagnosis of indolent systemic mastocytosis in a 40-year-old gentleman who had been complaining of an unexplained skin rash for 6 years.

Concurrent Presentation of Hairy Cell Leukemia and Mantle Cell Lymphoma (Leukemic Non-Nodal Variant): An Extremely Rare Composite Lymphoma.

Herein, we describe the clinicopathologic and genetic characteristics of the first report of simultaneous bone marrow involvement by classical hairy cell leukemia (HCL) and leukemic non-nodal variant of mantle cell lymphoma (L-NN-MCL) with t(11;14)(q13;q32) with BRAF mutation and deletion of TP53. A 40-year-old asymptomatic man was investigated for incidental neutropenia and thrombocytopenia. Flow cytometry showed two distinct monotypic B-cell populations: one expressed CD19 (bright), CD20 (bright), FMC7, CD103, CD25, CD11c, CD123, and IgD (bright) and showed kappa light chain restriction (bright), consistent with HCL and the other kappa-restricted CD5/CD10-negative B-cell population with distinctive immunophenotypic features. The bone marrow biopsy is infiltrated by an abnormal B-lymphoid infiltrate with different patterns of infiltration in different marrow areas. Fluorescence in situ hybridization (FISH) analysis revealed a CCND1/IGH rearrangement, t(11;14)(q13;q32), and deletion of TP53. The BRAF V600E missense mutation was detected by quantitative real-time polymerase chain reaction (PCR). The diagnosis of a composite B-cell neoplasm was composed of HCL together with a second CD5/CD10-negative monotypic B-cell population, with CCND1/IGH fusion, favoring the 2016 WHO new category of L-NN-MCL (CD5/SOX11-negative). Treatment with cladribine and rituximab normalized the blood counts within 6 weeks without significant side effects. L-NN-MCL is one of the smoldering MCL subtypes, recently listed in WHO 2016 as a separate variant, with a particular set of unique features and a less aggressive clinical course compared to classical MCL. To date, the clinicopathological features (including the bone marrow findings) of L-NN-MCL have not been sufficiently characterized in the literature. We describe the first report of synchronous presentation of HCL and L-NN-MCL. This case represents a real challenge from the biologic, diagnostic and therapeutic point of views, due to extremely rare combination of two distinct uncommon B-cell neoplasms. The study of composite lymphomas offers the opportunity to evaluate the etiology and the clonal interrelationship involved in the pathogenesis/evolution of lymphomas.

Acquired Hemophilia A Developed Post COVID-19 Vaccine: An Extremely Rare Complication.

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by circulating autoantibodies (inhibitor) directed against coagulation factor VIII (FVIII). We report a 39-year-old single female who presented to emergency department with sudden onset gross hematuria 10 days following her first dose of Pfizer-BioNTech severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA (coronavirus disease 2019 (COVID-19)) vaccine. Coagulation profile revealed isolated prolongation of the activated partial thromboplastin time due to FVIII deficiency with normal von Willebrand factor and activity. Mixing study revealed time-dependent inhibitor pattern that was successively identified as directed against FVIII using the Nijmegen-modified Bethesda assay. FVIII inhibitor in a titer of 17.2 Bethesda Units/mL was detected. While thrombosis is a frequent complication of severe COVID-19 infection, on the other hand, bleeding is rare in the setting of COVID-19 infection/vaccination with no anticoagulants. Till date, a couple of cases of acquired hemophilia developed after receiving mRNA derived COVID-19 vaccines (Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and Moderna mRNA vaccines) had been reported. It is important to raise the awareness about this rare side effect that might be directly induced by the mRNA COVID-19 vaccine or that the vaccine could have triggered it in a genetically predisposed individual. We recommend considering screening for an inhibitor (by mixing study) in cases with otherwise unexplained onset hemorrhagic disorder and/or isolated activated partial thromboplastin time prolongation.

Coexistence of Prefibrotic Myelofibrosis with Monoclonal Gammopathy of Undetermined Significance: A Case Report.

The coexistence of dual hematological neoplasms is an unusual and challenging presentation due to the different combination of etiopathology. The presentation of synchronous dual hematological malignancies can be one of the 3 types: myeloid + lymphoid or dual lymphoid or dual myeloid. Here, we are reporting a case of a 53-year-old male with simultaneous presence of JAK2 V617F-positive myeloproliferative neoplasm with features favoring prefibrotic phase of primary myelofibrosis (pre-PMF) in combination with monoclonal gammopathy of undetermined significance (MGUS). In such cases of simultaneous existence of dual hematological neoplasm management, it is recommended to treat the more aggressive one. Currently, our management plan is focusing on treating the pre-PMF and observation of MGUS with regular monitoring for transformation to MM.

Cardiac Amyloidosis Presenting with Pre-Excitation Syndrome, Heart Failure, and Severe Factor X Deficiency as Part of Systemic Amyloid Light-Chain (AL) Amyloidosis - A Fatal Combination.

BACKGROUND Amyloid light-chain (AL) amyloidosis is a disease that results in systemic amyloid deposition, which may present with multi-organ dysfunction. It carries a poor prognosis at the time of diagnosis. CASE REPORT A 37-year-old patient with a history of Wolff-Parkinson-White syndrome and thyroiditis presented with syncope and hypovolemia. ECG showed non-specific T wave inversions in the lateral leads with no signs of ischemia. Laboratory investigations revealed deranged coagulation parameters with prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) and follow-up factor assays revealed severe factor X deficiency. A transthoracic echocardiogram and subsequent cardiac MRI showed signs of cardiac amyloidosis. Bone marrow biopsy was consistent with AL amyloidosis, demonstrating period acid-Schiff (PAS)-positive adipose deposits and interstitial infiltration by clusters of lambda restricted plasma cells with aberrant expression of CD 56 and CD 117.The patient was treated with bortezomib, cyclophosphamide, and dexamethasone, but died early during his treatment due to cardiac arrest, suspected to be secondary to conduction abnormalities caused by cardiac infiltration. CONCLUSIONS This case represents a novel pattern of disease in AL amyloidosis with cardiac, thyroid, and hematological involvement as a result of systemic amyloid deposition.Our report highlights the need for physicians to be aware of cardiac amyloidosis-related complications and the morbidity and mortality associated with concurrent hematological involvement in these cases.

P190 BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature.

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 BCR-ABL1) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

Aberrant Acquisition of T-cell Associated Markers in Plasma Cell Neoplasms: An Aggressive Disease with Extramedullary Involvement and Very Short Survival.

BACKGROUND: Plasma cell neoplasms can show aberrant expression of different lineage-related antigens; however, co-expression of T-cell-associated markers on malignant plasma cells is extremely rare. MATERIAL AND METHODS: This report describes clinicopathologic characteristics of three myeloma patients with emergent plasmablastic morphology and aberrant acquisition of T-cell-associated markers diagnosed in our center. An extensive literature search for similar cases was conducted, and the relevant pathologic, clinical, and prognostic characteristics were summarized. RESULTS: A total of 22 cases of plasma cell neoplasm (including the three cases reported here) showed aberrant co-expression of T-cell markers. We found an evident association between aberrant expression of T-cell markers on malignant plasma cells and extramedullary involvement, aggressive morphologic features, high proliferative index ki67 >90%, aggressive clinical course, an adverse outcome, and short survival. DISCUSSION & CONCLUSION: Due to the rarity of this aberrant phenotype and scarcity of the published data, the precise causative mechanism and its clinical implications have not yet been elucidated.

Prevalence and clinical significance of antiphospholipid antibodies in patients with coronavirus disease 2019 admitted to intensive care units: a prospective observational study.

Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19-induced coagulopathy, its clinical significance remains uncertain. Therefore, this study aimed to evaluate the prevalence and clinical significance of aPLs among critically ill patients with COVID-19. This prospective observational study included 60 patients with COVID-19 admitted to intensive care units (ICU). The study outcomes included prevalence of aPLs, and a primary composite outcome of all-cause mortality and arterial or venous thrombosis between antiphospholipid-positive and antiphospholipid-negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. A total of 60 critically ill patients were enrolled. Among them, 57 (95%) were men, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found be antiphospholipid-positive; 21 of them were positive for lupus anticoagulant, whereas one patient was positive for anti-ß2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during their ICU stay did not differ between antiphospholipid-positive and antiphospholipid-negative patients (4 [18%] vs. 6 [16%], adjusted odds ratio 0.98, 95% confidence interval 0.1-6.7; p value = 0.986). The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

High-Grade Epstein-Barr Virus-Negative Biphenotypic Lymphoma with Expression of B- and T-Cell Markers and Leukemia Presentation: Case Report and Literature Review.

Lymphomas are presently categorized according to their origin from B or T lymphocytes. The co-expression of CD3 in B-cell lymphomas or CD20 in T-cell lymphomas has been rarely reported. Immature and less often mature lymphomas may incorporate the rearrangements of both B- and T-cell antigen receptor genes (dual genotype or bigenotype). Lymphoma cells with a sole genotype hardly concurrently express both B- and T-cell markers (biphenotypic lymphomas). We describe a 63-year-old female who was presented with obstructive jaundice and epigastric pain of 10 days. Initial CBC revealed 43×103/µL white blood cells, 11.2 g/dL hemoglobin, and 88x103/µL platelets. CT abdomen revealed hepatomegaly and suspected pancreatic mass with large retroperitoneal lymph nodal mass. Peripheral smear showed 56% lymphoid cells with blast morphology. The bone marrow (BM) aspirate smear was infiltrated by 83% immature-looking cells. BM biopsy showed interstitial to diffuse extensive infiltration by primitive-looking cells, positive for pan-B-cell antigens CD20, CD79, and PAX5 as well as the T-cell antigen CD4, CD5, CD3, while negative for all immaturity markers (CD34, TdT, and CD1a). In situ hybridization for Epstein-Barr virus (EBV)-encoded small RNA (EBER) was negative. Flow cytometry on BM aspirate showed an abnormal population (50%) expressing the B-cell antigens (CD19, CD20, CD79, CD22) and CD10, and showed lambda light chain restriction as well as the T-cell antigens cCD3 and CD4 with partial CD5. The analysis showed, also, another abnormal population of lambda restricted monotypic B cells (8%) with dimmer CD45 (blast gate) and showed the same immunophenotype (expressing the B-cell antigens), but negative for CD10, cCD3, CD5, and CD4. Conventional cytogenetic revealed complex karyotype. Molecular studies revealed rearrangements of the immunoglobulin heavy chain region consistent with a clonal B-cell population. TCR gene rearrangement analysis was equivocal concerning clonality but was not conclusive for clonal T-cell disease. Our final diagnosis was peripheral blood and BM involvement by EBV-negative high-grade lymphoid neoplasm (in leukemic phase with blast morphology) and an ambiguous immunophenotype with a differential diagnosis that may include the rare entity of bigenotypic lymphoma or an unusual case of high-grade B-cell lymphoma with aberrant expression of T-cell markers (biphenotypic lymphomas).

Transient Pleural Fluid Infiltration by Clonal Plasma Cells Associated with Pulmonary Tuberculosis.

Pleural effusion is a rare presentation of plasma cell myeloma, occurring in around 6% of patients during the course of their disease, most commonly as a consequence of a concurrent disease process like heart failure secondary to amyloid deposition. Direct infiltration of the pleural fluid by malignant cells leading to myelomatous pleural effusion is a rare mechanism occurring in less than 1% of patients with plasma cell myeloma, and it is associated with a worse prognosis. There are few case reports of myelomatous pleural effusion as an initial presentation of multiple myeloma. Pleural fluid infiltration by monoclonal plasma cells in the absence of an underlying plasma cell myeloma was not reported before in the literature. Tuberculosis is a known cause of polyclonal gammaglobulinemia, however few case reports described the coexistence of monoclonal gammopathy of undetermined significance and tuberculosis. Here we present an interesting case of pleural fluid infiltration by an abnormal looking clonal plasma cells associated with active pulmonary tuberculosis and parapneumonic effusion in a patient with a background of acute myeloid leukemia. Interestingly, the clonal plasma cell proliferation was confined to the pleural fluid without any evidence of an underlying plasma cell neoplasms (including monoclonal gammopathy of undetermined significance and plasmacytomas). Since our patient had an underlying meyloid neoplasm, we though about the possibility of secondary malignancy. However, in almost all patients with coexisting myeloid and plasma cell neoplasms, myeloid neoplasms developed following chemotherapeutic treatment of plasma cell neoplasms not the other way around. Given that, one must conclude localized extramedullary (pleural) plasma cell proliferation probably represents a transient reactive process to pulmonary tuberculosis which is an extremely rare phenomenon and not described before.

T-Cell Large Granular Lymphocytic Leukemia with Extremely Rare Immunophenotype (CD4/CD8 Double-Positive) Followed by Multiple Myeloma Diagnosis.

T-cell large granular lymphocytic leukemia is characterized by clonal expansion of a CD3+/CD57+ subpopulation, which are typically CD8+ positive cytotoxic T- cells, and can only be diagnosed if there is a persistent, greater than 6 months, elevation of LGL in the blood (usually 2-20 × 109/L), in the absence of an identifiable cause. T-LGLL has been associated with reactive conditions such as autoimmune diseases and viral infections and has also been reported in association with hematologic and non-hematologic malignancies. We report a case of asymptomatic CD4/CD8 double-positive T-LGLL. Flow cytometry on peripheral blood revealed a subpopulation of CD4/CD8 double-positive T cells expressing CD57 and cTIA. Clonality was established by flow cytometric analysis of T-cell receptor V(â) region repertoire which showed that >70% of the cells failed to express any of the tested V(â) regions. Clonality was further confirmed by PCR with the detection of clonal TCR beta and TCR gamma gene rearrangements. Six months later, she presented with persistent lower back pain and diagnosed with IgG kappa multiple myeloma. CD4/CD8 double-positive T-large granular leukemia is the first case reported in the literature. This rare phenotype is either underreported or a truly rare clinical entity. More studies are warranted to characterize the pathogenesis and clinical characteristics of this group of patients and to further assess the relationship between multiple myeloma and T-LGLL as a cause-and-effect relationship or simply related to the time at which diagnosis has been made.

A Rare Case of Systemic Mastocytosis with Associated Hematologic Neoplasm (SM-AHN) Involving Chronic Myeloid Leukemia: A Case Report and Literature Review.

BACKGROUND Single or multiple cell line dysplasia is a characteristic feature of myelodysplastic syndrome. However, significant dysgranulopoiesis is not a feature of chronic myeloid leukemia (CML). Systemic mastocytosis (SM) with an associated hematologic neoplasm (SM-AHN) comprises 5% to 40% of cases of SM. All types of hematologic neoplasms have been previously reported, although CML has been rarely encountered. CASE REPORT A 28-year-old male presented with a 3-month-history of weight loss and massive splenomegaly. Peripheral blood revealed marked leukocytosis, shift to left with 13% blasts. There was evident dysgranulopoiesis that raised a provisional diagnosis of myelodysplastic/myeloproliferative neoplasm. Bone marrow (BM) examination revealed granulocytic hyperplasia with 10% blasts and significant dysgranulopoiesis. Unexpectedly, cytogenetic analysis revealed t(9;22) with BCR/ABL1 rearrangement, diagnostic of chronic myeloid leukemia in an accelerated phase. The patient was started on dasatinib 100 mg upfront, however, he failed to respond, with increasing leukocytosis. Repeat BM examination showed persistence of the findings with 8% blasts. At this time, aggregates of mast cells with aberrant expression of CD25 were elicited, thus concluding the diagnosis of SM-AHN. The patient failed multiple lines of treatment (dasatinib, nilotinib, hydroxyurea, cytarabine subcutaneous, 6-mercaptopurine and interferon) and progressed to the blast phase a few months later. CONCLUSIONS We report an unusual case of CML, presented with significant dysgranulopoiesis with an aggressive clinical course including SM uncovered during the disease course with subsequent transformation to the blast phase. The different biological behavior of this case underscores the need for studies on a larger number of cases to explore the significance of the aforementioned coexistent features.

Plasma Cell Myeloma with an Aggressive Clinical Course and Anaplastic Morphology in a 22-Year-Old Patient: A Case Report and Review of Literature.

BACKGROUND Plasma cell myeloma is a neoplastic plasma cell disorder that usually presents after the fifth decade of life; it is rarely described in younger population especially under 30 years of age. However, there are conflicting reports in the literature about the clinical behavior and overall survival in younger age groups. In approximately 2% of plasma cell myeloma, the morphology of the neoplastic cells is highly pleomorphic, quite anaplastic, and may resemble metastatic tumor cells. While this poses a challenge for morphological interpretation during diagnosis, it has been demonstrated that bone marrow morphologic features (including diffuse sheet growth pattern, immature cell morphology and high mitotic index) significantly correlates with high risk disease. Moreover, there is limited description available about the morphology of the neoplastic cells when correlating the age at presentation with the clinical outcome/biological behavior; hence, the need to report and collect such cases. CASE REPORT We report a case of plasma cell myeloma in a 22-year-old male who presented with non-specific clinical features and posed a diagnostic challenge during clinical, radiological, and laboratory examination. The pathology specimens showed anaplastic morphology. Unfortunately, after diagnosis, despite treatment with brotezomib, his disease had an aggressive clinical course and he passed away 4 months after diagnosis. CONCLUSIONS Although plasma cell myeloma is rare in patients younger than 30 years, it must be considered in the differential diagnosis and investigated properly especially in patients with clinical suspicion of a metastatic non-hematological tumor. The anaplastic variant in a young patient is a diagnostic challenge and is associated with bizarre morphology, aggressive presentation, adverse cytogenetics, resistance to chemotherapy, and poor, short-term, survival.

Composite Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Mantle Cell Lymphoma; Small Cell Variant: A Real Diagnostic Challenge. Case Presentation and Review of Literature.

BACKGROUND Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL) both have a common origin arising from mature CD5+ B-lymphocytes. Their distinction is crucial since MCL is a considerably more aggressive disease. Composite lymphoma consisting of CLL/SLL and MCL has been rarely reported. This type of composite lymphoma may be under-diagnosed as the 2 neoplasms have many features in common, both morphologically and immunophenotypically. CASE REPORT We report the case of a 57-year-old male patient who presented with a 4-month history of recurrent abdominal pain and distention with hepatosplenomegaly. Peripheral blood showed a high leukocytes count (46.7×10³/uL) with marked lymphocytosis of 35.0×10³/uL, mostly small mature-looking, with some showing nuclear irregularities, with approximately 3% prolymphocytes. Immunophenotyping by flow cytometry and immunohistochemistry revealed 2 immunophenotypically distinct abnormal CD5+monotypic B-cell populations. Fluorescence in situ hybridization (FISH) on peripheral blood demonstrated IGH/CCND1 rearrangement consistent with t(11;14) in 65% of cells analyzed. Accordingly, based on compilation of findings from morphology, flow cytometry, immunohistochemistry, and FISH, A diagnosis of composite lymphoma consisting of MCL; small cell variant and CLL/SLL was concluded. CONCLUSIONS We describe a case of composite lymphoma of MCL (small cell variant) and CLL/SLL that emphasizes the crucial role of the multiparametric approach, including vigilant cyto-histopathologic examination, immunophenotyping by flow cytometry and immunohistochemistry, as well as genetic testing, to achieve the correct diagnosis.

The Role of Integrated Positron Emission Tomography/Computed Tomography (PET/CT) and Bone Marrow Examination in Staging Large B-Cell Lymphoma.

INTRODUCTION: In the era of routine use of positron emission tomography/computed tomography (PET/CT) for staging, it is not yet clear whether PET/CT can replace bone marrow biopsy for the assessment of bone marrow involvement in large B-cell lymphoma. OBJECTIVES: To compare the clinical utility of bone marrow biopsy and PET/CT scanning in the staging of large B-cell lymphoma. METHODS: This was a retrospective analysis of all patients who presented to single center over a 4-year period with large B-cell lymphoma who had concurrent PET/CT and bone marrow biopsy performed in the assessment and staging of the lymphoma. RESULTS: Out of 89 patients, 24 had bone marrow involvement either by PET/CT, by bone marrow biopsy, or by both. Bone marrow biopsy identified 12 patients (sensitivity 50%, specificity 100%, negative predictive value 84%), whereas PET/CT identified 23 patients (sensitivity 96%, specificity 100%, negative predictive value 98%). No patients were upstaged by the bone marrow biopsy result, and no patients had their treatment plan changed based on the bone marrow biopsy result. CONCLUSION: The results show that PET-CT is more sensitive and has better negative predictive value than bone marrow biopsy. This suggests that PET-CT could replace bone marrow biopsy in detecting bone marrow involvement for staging of large B-cell lymphoma.

A Rare Case of Hairy Cell Leukemia with Unusual Loss of CD123 Associated with COVID-19 at the Time of Presentation.

Coronavirus disease 2019 (COVID-19) pandemic has been a serious threat and has been reported with different presentations and complications. Older age, along with comorbidities such as diabetes, hypertension, or cardiac disease, increases the risk factors for COVID-19 severity and death [N Engl J Med. 2020;382(18):1708-20 and Lancet Respir Med. 2020 05;8(5):475-81]. It is proposed that cancer patients have a significantly higher incidence of severe incidents including admission to the intensive care unit, the necessity for assisted ventilation, and even death after catching the virus compared with non-cancer patients [Lancet Oncol. 2020;21(3):335-7]. It is also described that cancer patients appear to be twice as likely to contract infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) [JAMA Oncol. 2020;6(7):1108-10]. Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder, with patients typically presenting with cytopenias, marked splenomegaly in 80-90% of patients, circulating leukemia cells, bone marrow infiltration and the presence of BRAF V600E somatic mutation [Indian J Hematol Blood Transfus. 2014;30(Suppl 1):413-7]. Leukemic cells classically have central nuclei and abundant cytoplasm with hairy-like projections and express CD11c, CD25, CD103, and CD123 [Indian J Hematol Blood Transfus. 2014;30(Suppl 1):413-7]. Loss of CD123 in HCL has been rarely reported in the literature [Am J Hematol. 2019;94(12):1413-22]. We describe a unique case of a COVID-19-positive male who presented with severe respiratory symptoms, deteriorated quickly, and was intubated. Workup of severe progressive pancytopenia and bone marrow examination revealed HCL without splenomegaly and with atypical unusual loss of CD123. To our knowledge, this is the first case of CD123-negative HCL without splenomegaly associated with COVID-19 infection as the initial presentation.