Pitfalls in Assessing Measurable Residual Disease in Plasma Cell Myeloma: a Comparison between Common Laboratory Tests.

BACKGROUND: Measurable residual disease (MRD) in plasma cell myeloma is one of the most important determinants for patients' outcome. Several laboratory tests exist to assess for the presence of MRD with variable accuracy. The aim of this study is to examine the sensitivity of immunofixation electrophoresis (IFE), serum free light chain (FLC), bone marrow immunohistochemistry (IHC), and multicolor flow cytometry (FC) and to address potential caveats of each test. METHODS: Forty patients of plasma cell myeloma who were diagnosed with a positive MRD were retrospectively included in this study. The results of IFE and serum FLC at the time of bone marrow biopsy were collected. RESULTS: In all cases, malignant plasma cells constituted less than 5% of bone marrow cells. MRD was detected by FC in 38 cases (95%) and by IHC in 28 cases (70%). In 2 cases, residual malignant plasma cells appeared in the subcortical area which is difficult to aspirate, and thus they were detected by IHC but not by FC. Among the entire cohort, 38 patients (95%) had positive IFE at the time of bone marrow biopsy, while serum FLC abnormality was detected in 19 patients (48%) only. CONCLUSIONS: Both FC and IFE exhibited high sensitivity in detecting MRD in plasma cell myeloma with comparable results. IFE remains less invasive and less expensive than FC. Despite the lower sensitivity of bone marrow IHC staining, its diagnostic role is essential and can be superior to FC in a subset of cases, for which its routine examination is recommended. Serum FLC test provided the least sensitivity among all tests.

Clinical and technical determinants of positive temporal artery biopsy: a retrospective cohort study.

Temporal artery biopsy (TAB) is one of the diagnostic tools to confirm the diagnosis of giant cell arteritis (GCA). We aim to evaluate the clinical and technical determinants of a positive biopsy. Demographics, clinical, technical, and laboratory data of all TAB's performed between 2007 and 2019 at a single academic medical center. 107 biopsies performed for 103 patients were included; 72.9% were female, and 27.1% were male. The mean age at the time of biopsy was 67.1 ± 9.3 years. One biopsy was excluded for lack of arterial tissue content. Of the remaining 106, 19.6% were positive. The length of the biopsy and the number of arterial cross-sections were not significantly associated with its result. A positive biopsy was seen more in patients with low albumin (p = 0.010) and hypothyroidism (p = 0.017) but less in those with prior glucocorticoids treatment (p = 0.028). Predictors of a positive biopsy included male gender [OR 4.029, 95% CI (1.330-12.209), p = 0.014]; elevated ESR [OR 3.998, 95% CI (1.908-6.787), p = 0.023]; polymyalgia rheumatica (PMR) symptoms [OR 5.121, 95% CI (2.094-9.872), p = 0.001]; and advancing in age (6.5% per every additional year), [OR 1.065, 95% CI (1.005-1.130), p = 0.033]. 53.7% of the patients were eventually diagnosed with GCA; 39.2% of them were based on positive biopsy. In conclusion, old age, male gender, elevated ESR, and PMR symptoms increase the odds of positive TAB. Technical factors, such as biopsy length and the number of cross-sections, did not influence eventual biopsy results, highlighting the pivotal role of the clinical presentation of the patients in selecting patients for TAB.

Combined utility of CD177, P53, CD105 and c-kit immunohistochemical stains improves the detection of myelodysplastic syndrome.

The diagnosis of myelodysplastic syndrome (MDS) relies primarily on identifying peripheral blood cytopenia and morphologic dysplasia as well as detecting cytogenetic aberrations in a subset of patients. Accumulating data points to the importance of examining certain immunophenotypic changes characteristic of MDS, most of which are tested by flow cytometry. The role of immunohistochemistry in the diagnostic workup of MDS is less known. In this study, we used immunohistochemistry to survey the expression patterns of CD177, P53, CD105 and c- kit in a cohort of MDS bone marrow specimens (n = 57) and compared the results with a control group of patients who had cytopenia for other benign conditions (n = 49). MDS cases showed significant higher rates of: CD177-loss (13/57, 23% vs 1/49, 2%; P = .0016), P53 overexpression (8/57, 14% vs none; P = .005) and the presence of clusters of CD105-positive cells (6/57, 11% vs none; P = .021). Increased c-kit-positive cells was more common in MDS patients, but not statistically significant (17/57, 30% vs 8/49, 16%; P = .102). On multivariate analysis, only loss of CD177 expression was significantly higher in MDS group (P = .014). These findings suggest that a panel of immunohistochemical stains could serve as an adjunct tool in investigating unexplained cytopenias and warrant further comparative studies with flow cytometry.

The epidemiology of lymphoma in Jordan: A nationwide population study of 4189 cases according to World Health Organization classification system.

OBJECTIVE/BACKGROUND: Lymphoma is a common human cancer that shows a variable geographic incidence worldwide. It is the fourth most common cancer in Jordan. Systemic reports of descriptive epidemiology on lymphoma from the Middle East are limited. METHODS: A nationwide multi-institutional retrospective study was conducted covering all major hospitals and laboratories that provide diagnostic services. We collected data on all cases diagnosed with lymphoma between 2014 and 2019. The included variables were patients' age, gender, anatomic site, and the histologic type according to the World Health Organization classification system. RESULTS: A total of 4189 cases were diagnosed with lymphoma. There was a statistically significant gender difference (p < .05), as 57.5% of patients were males. The peak incidence occurred at age 25-55 years. There were 1,652 (39%) cases of Hodgkin lymphoma (HL) and 2,537 (61%) of non-Hodgkin lymphoma (NHL), where nodular sclerosis (67%) and diffuse large B-cell lymphoma (53%) were the most common subtypes, respectively. The average age-adjusted incidence rates per 100,000 population were 8.01 for all lymphomas, 4.33 for NHL, and 3.16 for HL and all remained stable over the 6 years. CONCLUSION: HL is the most common lymphoma in Jordan, with a percentage higher than most of reported studies in Asian and Western countries. It also shows a unimodal distribution of age-specific incidence rates, with a single peak in young adults. The incidence rate of HL is higher than Eastern countries but comparable to the West. In contrast, NHL demonstrates a lower incidence rate than Western countries but a similar distribution of subtypes, as mature T/natural killer-cell lymphomas were rare.

Pregabalin inhibits in vivo and in vitro cytokine secretion and attenuates spleen inflammation in Lipopolysaccharide/Concanavalin A -induced murine models of inflammation.

Immune system alteration has been implicated in the pathogenesis of chronic pain conditions, epilepsy and generalized anxiety disorder. Targeting cytokines has recently been proposed for the management of such conditions. Pregabalin (PGB) is an antiepileptic agent used for the management of these conditions. However, little is known about its immunomodulatory effects on cytokine secretion in vivo and in vitro. Hence, a mitogen (Lipopolysaccharide [LPS] or Concanavalin A [ConA])-induced murine model of inflammation was used to investigate the effect of PGB on in vivo and in vitro IL-1ß, IL-6, TNF-α and IL-2 cytokine secretion using ELISA. In addition, PGB effect on spleen histology, as a lymphoid organ, was examined. Our results revealed that PGB significantly inhibited the secretion of ConA-induced IL-6 secretion, basal and ConA-induced TNF-α and IL-2 secretion in splenocytes in vitro. In vivo, PGB inhibited basal and LPS/ConA-induced IL-6 and TNF-α secretion in addition to LPS-induced IL-1ß and ConA-induced IL-2 secretion. Moreover, PGB attenuated mitogen-induced inflammatory changes in the spleen. These findings provide an evidence of the anti-inflammatory properties of PGB on cytokine secretion and lymphoid organ inflammation. This might give insights into the role of PGB in the management of the inflammatory state in PGB-indicated conditions.

Pseudomyogenic Hemangioendothelioma.

First described in 2003 as epithelioid-sarcoma-like hemangioendothelioma and later in 2011 as pseudomyogenic hemangioendothelioma, this rare vascular tumor is of intermediate malignant potential. It was officially included for the first time in the most recent World Health Organization's Classification of Tumours of Soft Tissue and Bone. It typically affects young adults with a predilection for the distal lower extremity. This tumor lacks morphologic features of vascular differentiation but shows unequivocal evidence of such differentiation with the use of relevant immunohistochemical stains such as FLI1, ERG, and CD31. Pseudomyogenic hemangioendothelioma can be diagnostically challenging and might be confused with other tumors, such as epithelioid sarcoma. In this review we discuss the clinical, morphologic, and immunohistochemical features of this tumor with particular emphasis on the differential diagnosis. Salient molecular and prognostic features are also reviewed.

Concomitant lymphoplasmacytic lymphoma and plasma cell myeloma, a diagnostic challenge.

BACKGROUND: Lymphoplasmacytic lymphoma and plasma cell myeloma are two B cell lymphoproliferative neoplasms derived from mature B-lymphocytes in different differentiation stages. The coexistence of these two tumors in the same patient is exceedingly rare and can be difficult to diagnose. CASE PRESENTATION: A 76-year-old male presented with a pathologic fracture after a fall. Radiography showed a lytic lesion in the pelvis. Serum immunofixation showed distinct IgM kappa and IgA kappa monoclonal protein bands. Bone marrow examination revealed aggregates of small, mature lymphoid cells with admixed plasma cells. Immunohistochemical studies and flow cytometric analysis showed the lymphoid cells were CD10-/CD5- kappa restricted monoclonal B cells. The plasma cells were monoclonal with kappa light chain restriction. The majority of plasma cells were positive for IgA and cyclin D1 with a few plasma cells positive for IgM. Additional studies showed the presence of both a positive MYD88 L265P mutation and a CCND1/IGH fusion. A diagnosis of concomitant lymphoplasmacytic lymphoma and plasma cell myeloma was rendered. CONCLUSION: Concomitant lymphoplasmacytic lymphoma and plasma cell myeloma can be rarely encountered and is diagnostic challenging. It is commonly associated with biclonal monoclonal proteins. This case demonstrates the importance of a comprehensive work-up in the diagnosis of this disease combination and highlights the diagnostic role of MYD88 mutation study.