SYSTEMIC MASTOCYTOSIS: RADIOLOGICAL POINT OF VIEW

Radiological diagnosis of systemic mastocytosis (SM) can be hard to establish. This is mainly due to the variable radiological features involving many organ systems (e.g., respiratory, cardiovascular, lympho-reticular, digestive systems, and most commonly skin), and the broad spectrum of skeletal findings, in particular. Skeletal involvement is the most common and prominent imaging feature in patients with SM and represents a prognostic factor as it may entail an aggressive course of the disease. Diagnosis, which is largely established by histological evaluation of a bone marrow trephine biopsy specimen supplemented by imaging modalities such as radiography, CT, and magnetic resonance imaging, requires a team approach between the hematologist, radiologist, and pathologist. The general radiologist needs to be familiar with the imaging findings because they may be the first to suggest the correct diagnosis. The primary purposes of this article were to equip clinicians with pertinent radiological semiotics and present relevant radiological features that assist early diagnosis and selection of an effective treatment.

Structure and signifi cance of cytogenetic abnormalities in patients with multiple myeloma

Introduction. Cytogenetic and genomic traits of tumour cells are considered the key mediating factors in multiple myeloma (MM). Selected chromosomal abnormalities are prognostic of therapeutic response and patient survival in MM.Aim — to assess of the diversity and rate of chromosomal abnormalities in MM patients and their association with the disease course.Materials and methods. The study enrolled 134 MM patients with pre-treatment bone marrow FISH assay screening for chromosomal abnormalities: t(11;14), t(4;14), t(14;16), t(14;20), t(6;14), hyperdiploidy, del13q14/-13, del17p13/TP53, amp1q21, t(8q24)/cMYC. The studied criteria at the MM onset were: hemogram, lactate dehydrogenase (LDH) activity, calcium, β2-microglobulin and creatinine concentrations, punctate cytology, bone marrow trephine biopsy and/or soft tissue biopsy histology, bone X-ray, immunochemical variant of MM, disease staging. A median follow-up was 20 months (3.2–77.4).Results. The primary chromosomal abnormality rate was 82.9 %, among them t(14q32)/IGH — 29.1 %, multiple trisomies — 46.3 % and their combination — 7.5 %. The rates of particular t(14q32)/IGH): t(11;14) — 16.4 %, t(4;14) — 12.7 %, t(14;16) and t(14;20) — 3.7 and 2.2 %, respectively. The secondary chromosomal abnormality rate was 69.4 %, among them del13q14/-13 — 40.3 %, amp1q21 — 39.6 %, t(8q24)/cMYC — 17.2 %, del17p13/TP53 — 12.7 %, del1p32 — 2.2 %. Analyses of the primary–secondary abnormality combinations showed that del13q14/-13 is more frequently combined with t(4;14) and less frequently with trisomies (p < 0.05). Amp1q21 occurs more frequently with t(4;14) and less — with t(11;14) (p<0.05). Patients with t(4;14) more frequently (p < 0.05) had anemia at a hemoglobin level<100 g/L, and the presence of amp1q21 and del17p13/TP53-enhanced serum LDH activity (p < 0.05). Abnormality t(8q24)/cMYC more often co-occurred with higher serum β2-microglobulin concentrations (p < 0.05). A three-year overall survival (OS) in del17p13/TP53-positive patients was 35.5 vs. 71.3 % in the negative (p = 0.002) and 50.8 vs. 67 % — in t(8q24)/cMYC-positive and negative patients, respectively (p = 0.001). Patients without amp1q21, with one, with two or more additional 1q21 copies had a five-year OS 79.4, 67.3 and 20.9 %, respectively (p = 0.0016), and a two-year progression-free survival (PFS) 83, 50 and 0 %, respectively (p = 0.005).Conclusion. We establish a negative impact of del17p13/TP53 and t(8q24)/cMYC on patients’ OS in MM, as well as unfavourable effect of amp1q21 on OS and PFS in the presence of two or more additional copies of 1q21 loci.

Myelodysplastic syndrome: Discordant involvement of the marrow as observed in the bone marrow biopsy sections

Myelodysplastic syndromes (MDS) are a diverse group of hematological disorders that affect the blood and bone marrow. Laboratory diagnosis of MDS is almost exclusively based on the morphology of hematopoietic cells observed in smears of peripheral blood and bone marrow and this depends solely on the presence of dysplastic changes observed in the granuloid, erythroid, and megakaryocytic cells [1,2]. Up until now evaluation of sections of bone marrow trephine biopsy specimen did not play a significant role in its diagnosis.

Role of Bone Marrow Trephine Biopsies in the Diagnosis of Hematological and Non-Hematological Disorders

Introduction: Bone marrow examination has become increasingly important for the diagnosis and treatment of hematologic and other illnesses. Bone marrow aspirates along with their peripheral smears and bone marrow trephine biopsies are considered to be complementary.Materials and Methods: This hospital-based, cross-sectional study was carried out in the Department of Pathology for one year (March 2011 to March 2012) at BPKIHS, Dharan. Fortyeight adequate bone marrow aspirates along with peripheral blood smears and trephine biopsies were selected and examined. Bone marrow trephine biopsies performed simultaneously with aspirate were correlated with the other two fi ndings to arrive at a conclusive diagnosis.Results: Bone marrow aspiration and trephine biopsy were found as complementary tests in 51.8% of cases. Bone marrow trephine biopsy provided a conclusive diagnosis in 25.9% of cases where bone marrow aspiration was inconclusive. Bone marrow aspiration alone was diagnostic in 22.2% of cases. In 43.7% of cases both aspiration and trephine biopsy were unable to provide a specificdiagnosis. Bone marrow biopsy was the diagnostic investigation in cases like aplastic anemia, myelofi brosis, and hypoplastic marrow.Conclusions: This study concludes that bone marrow aspiration smear along with peripheral smear findings and marrow trephine biopsy is required to arrive at a conclusive result.

Automated digital enumeration of plasma cells in bone marrow trephine biopsies of multiple myeloma

AimsDetermination of the number of plasma cells in bone marrow biopsies is required for the diagnosis and ongoing evaluation of plasma cell neoplasms. We developed an automated digital enumeration platform to assess plasma cells identified by antigen expression in whole bone marrow sections in multiple myeloma, and compared it with manual assessments.MethodsBone marrow trephine biopsy specimens from 91 patients with multiple myeloma at diagnosis, remission and relapse were stained for CD138 and multiple myeloma oncogene 1 (MUM1). Manual assessment and digital quantification were performed for plasma cells in the entire trephine section. Concordance rates between manual and digital methods were evaluated for each antigen by intraclass correlation analyses (ICC) with associated Spearman’s correlations.ResultsThe digital platform counted 16 484–1 118 868 cells and the per cent CD138 and MUM1-positive plasma cells ranged from 0.05% to 93.5%. Overall concordance between digital and manual methods was 0.63 for CD138 and 0.89 for MUM1. Concordance was highest with diffuse plasma cell infiltrates (MUM1: ICC=0.90) and lowest when in microaggregates (CD138: ICC=0.13). Manual counts exceeded digital quantifications for both antigens (CD138: mean=26.4%; MUM1: mean=9.7%). Diagnostic or relapse threshold counts, as determined by CD138 manual assessments, were not reached with digital counting for 16 cases (18%).ConclusionsAutomated digital enumeration of the entire, immunohistochemically stained bone marrow biopsy section can accurately determine plasma cell burden, irrespective of pattern and extent of disease (as low as 0.05%). This increases precision over manual visual assessments which tend to overestimate plasma burden, especially for CD138, and when plasma cells are in clusters.

An Unusual Cause of Cranial Dural Thickening

We describe an unusual cause of cranial dural thickening in an elderly female with a chronic meningeal inflammatory process. A 70-year-old ethnically Chinese, Singaporean female presented with a history of chronic daily headache with no other meningeal signs. Serial MRI brains showed progressive pachymeningeal and leptomeningeal enhancement in the left frontal region with underlying vasogenic oedema, similar appearances in the right frontal region to a lesser extent, and persistent inflammatory changes in her bilateral paranasal sinuses. Investigative work-up showed a chronically raised ESR with a normal CRP, negative ANCA, and a chronically raised serum IgA kappa paraprotein. Bone marrow trephine biopsy was suggestive of a low level plasma cell disorder. Olfactory cleft biopsy showed no evidence of IgG4-related disease or vasculitis and no significant plasma cell infiltrate. Histopathological examination from a meningeal biopsy revealed a diagnosis of an en-plaque meningioma (the WHO, 2016; Grade I) causing an unusual granulomatous reaction. We discuss the radiological and histological relations of this rare form of meningioma. Clinicians can consider en-plaque meningioma in the differential diagnosis of linear dural thickening and enhancement.