Diffuse Infiltrative Pattern Research Articles

Multiple Myeloma: Clinico-hematological profile in a tertiary care hospital: a three years study

Background: To analyze the clinical findings and haematological profile of multiple myeloma patients. Material and methods: All newly diagnosed patients of multiple myeloma between January’ 2013 to December’ 2015 in the department of pathology, Indira Gandhi Medical College, Shimla were the study subjects. The history and clinical findings were recorded. All relevant blood, radiological investigations including peripheral smears, bone marrow aspiration and biopsy were done. Results: Fifty one patients were diagnosed with multiple myeloma and they comprised 19% of all haematological malignancies. Out of these, 30 were males and 21 females with a mean age of presentation 58.38 years. The commonest presenting complaint was bone pain followed by fever, CKD and bleeding disorder. Common clinical findings were anemia, osteolytic lesions and renal insufficiency. M band was seen in 83% of patients on serum protein electrophoresis. On bone marrow examination, majority (53%) of patients had plasmablastic morphology while, 47% had plasmacytic features. Diffuse pattern of infiltration on bone marrow biopsy was observed most commonly in 68.3%patients. Conclusion: The present study concluded that multiple myeloma is a disease of middle age and elderly with male preponderance. The clinical presentation varies with bone pain being the most common presenting complaint. Morphologically,plasmablastic morphology predominated on bone marrow aspiration while diffuse pattern of infiltration was observed on bone marrow biopsy . DOI: 10.21276/APALM.1245

949P - Tumor microenvironment in high serous ovary cancer: Characterization of the infiltration pattern and analysis of its prognostic value

Background: Lymphocytic infiltration areas (immunoreactive) are frequently found in ovarian cancer, which is associated with a better prognosis and increased survival. Therefore, the study of different patterns and degree of infiltration would help us to better understand the relationship between immune and tumor cells and its prognostic implications. Methods: This retrospective study includes samples from 57 patients with high grade serous ovarian cancer (HGSOC) who underwent cytoreductive surgery. The pattern of infiltration, localization and degree of lymphocyte infiltration in the tumor was evaluated. A set of clinical variables such as smoking, age, type of surgery, intention of treatment, type of response, as well as lymphocytic infiltration were evaluated to assess prognosis. Results: In our cohort, the median age was 61.5 years, there were 60% of smokers, and most of the cases were FIGO stages III and IV (15.3%, stage I, 8.5% stage II, 54.3% stage III and 22% stage IV). As expected, patients over 65 years, as well as the group of more advanced stages (III and IV) showed a shorter overall survival (OS, 30.17 vs 99.90 months, p = 0.009; 38.73 months vs NR, p = 0.005, respectively). Smoking status was also analyzed but no significant effect on survival was found (OS, p = 0.935). Interestingly, patients with an intratumoral lymphocyte infiltrate had better prognosis compared to the group that had only a peritumoral pattern (OS, 44.57 months vs NR, p = 0.041). In addition, those with a diffuse infiltration pattern presented a better prognosis compared to those with a focal pattern (OS, 20.20 months vs NR p = 0.003). Finally, a tendency for a better OS was seen for those patients with a strong degree of infiltration in the tumor. Conclusions: HGSOC represents a group of highly immunoreactive tumors. Those with the best prognosis are represented by an intratumoral, diffuse pattern with a strong degree of infiltration, these findings could open a new window for therapeutic approaches in HGSOC. Legal entity responsible for the study: Fundación de Investigación Hospital General de Valenecia Funding: None Disclosure: All authors have declared no conflicts of interest.

EBV driven natural killer cell disease of the central nervous system presenting as subacute cognitive decline

Brain biopsy in patients presenting with subacute encephalopathy is never straightforward, and only undertaken when a ‘treatable condition’ is a realistic possibility.This 63year old right handed, immunocompetent Caucasian woman presented with an 8month history of rapidly progressive right-sided hearing impairment, a 4month history of intermittent headaches, tinnitus, ‘dizziness’, dysphagia, nausea and vomiting, with the subsequent evolution of progressive gait ataxia and a subacute global encephalopathy. The possibility of CJD was raised. Brain biopsy was carried out. Western blot for prion protein was negative. She died 9days later and autopsy brain examination confirmed widespread subacute infarction due to an EBV positive atypical NK/T-cell infiltrate with positivity for CD3, CD56, granzyme B, perforin and EBER with absence of CD4, CD5 and CD8 expression. Molecular studies for T-cell clonality were attempted but failed due to insufficient DNA quality. Serology was consistent with past EBV infection (EBV VCA and EBNA IgG Positive). There was no evidence of disease outside the CNS. Primary central nervous system NK/T-cell lymphoma is extremely rare. The rare reported cases all present with a discrete intracranial mass, unlike the diffuse infiltrative pattern in this case. Whilst the diffuse interstitial pattern is reminiscent of chronic active EBV infection (CAEBV) seen in other organ systems such as the liver and bone marrow, the clinical presentation and epidemiologic profile are not typical for CAEBV.

Interstitielle Prozesse der Lunge im Kindesalter

Interstitial processes in the lungs of children can be due to several underlying diseases. Knowledge of the child's age is important as genetic aberrations play amajor role in diseases in the first 2 years, whereas immunological diseases are more common starting in kindergarden age. In general lung diseases are rare in children, which makes the diagnostics difficult and results in a delayed diagnosis. In addition, pediatric pulmonologists are often very reluctant to perform lung biopsies due to a lack of a specialized pathologist. In order to make a contribution to the diagnostics of pediatric pulmonary diseases, pathologists should be specialized in pulmonary pathology, have agood knowledge of genetic methods and fetal lung development, which includes the genetic factors involved in lung growth and differentiation. Aclose cooperation with the pediatric pulmonologist is necessary and each patient should be discussed jointly on an interstitial lung disease board to promote the quality of diagnostics. The pathologist should be aware that the developing lungs of children are not just asmaller form of adult lungs and often react very differently. In this article, we mainly focus on diffuse infiltration patterns, such as ground glass and reticulonodular infiltrations as described in high-resolution computed tomography (HRCT). Localized interstitial processes, which can sometimes be tumor-like and malformations are not dealt with; however, vascular malformations are included as these often manifest as diffuse interstitial infiltrations and must therefore be taken into consideration for the differential diagnostics.

Pulmonary surfactant protein adenosine triphosphate-binding-cassette-A3 gene composite mutations in infant congenital interstitial lung disease: report of a case and review of literature

6 cases died, and 6 cases survived, including 4 cases with pulmonary function disturbance to different degrees; 12 cases had ABCA3 gene mutations, 9 cases had composite ABCA3 gene mutations, in 11 cases the mutation occured in the exon of coding region, in 1 case in the intron, 9 cases had heterozygous mutations, 3 cases had homozygous mutations. Conclusion: The main phenotypes of ABCA3 mutation associated with ILD were full term neonatal respiratory distress syndrome or progressive tachypnea or dyspnea unexplained in infants. The chest HRCT showed two diffuse pulmonary interstitial changes. ABCA3 mutation mainly was multi-site composite mutations and heterozygous mutations in the exon of coding region.

Clinical Vignettes/Case Reports - Small Intestine/Unclassified.

Peripheral T-Cell Lymphoproliferative Disorder (PTCL) is a rare group of neoplasms and represents less than 5% of all Non-Hodgkin Lymphomas. They occur more commonly in adults with a median age of 60 years but rarely reported in the oldest old (more than 85 years). Usually it's described as diffuse pattern of infiltration by polymorphic atypical neoplastic T-cells. This entity has vague clinical presentation including fever, night sweats and weight loss, frequently difficult to diagnose. This is a functionally independent 86 year old Jamaican Female with history of esophageal reflux known patient of our Gastroenterology service, who came for evaluation of early morning satiety, nausea and significant progressive weight loss in a period of 6 months. Her physical examination was significant only for mild epigastric discomfort. Family and Social history, surgical procedures, laboratory findings, chest radiography and abdominal ultrasound were unremarkable. In the previous year, CT-Scans and MRI of the abdomen because of reflux symptoms were normal. The current imaging found a soft tissue mass 3.9x7 cm in the mid abdomen rising from the small bowel, abnormal loops with thickened wall, indistinct margins and extensive mesenteric and retroperitoneal adenopathy (Figure I). She underwent push enteroscopy exposing a partially circumferential frond-like/villous jejunal friable mass with no bleeding at 50cm beyond the ligament of Treitz, extending 5 cm with non-obstructing characteristics (Figure II). The histology revealed villous blunting, ulceration and mixed inflammatory erosion in the lamina propia and a heavy atypical lymphoid infiltration deeper in the submucosa. The immunohistochemical analysis confirmed positive CD-3 with CD5 & CD4: T-Cell phenotype with negative CD30 and ALK-1. In accordance with the Ann Arbor system, this is considered stage IIE lymphoproliferative disorder. Further evaluation to obtain a final diagnosis was attempted but declined by the patient and the inability to undergo surgical resection considering her very poor pulmonary status. On follow up, no new symptoms were reported. Peripheral T-Cell Lymphoproliferative disorder presenting in the G.I. system is rare and has not been reported in the oldest old (more than 85 years old). Its differential diagnosis includes HTLV-1 or Enteropathy Associated T Cell Lymphoma. The value of this case is its unusual presentation in such uncommon pathology for the geriatric population.Figure 1Figure 2

High levels of periostin correlate with increased fracture rate, diffuse MRI pattern, abnormal bone remodeling and advanced disease stage in patients with newly diagnosed symptomatic multiple myeloma.

Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls. We found high levels of periostin in the supernatants of myeloma cell lines compared with ovarian cancer cell lines that were not influenced by the incubation with the stromal cell line HS5. In NDMM patients the bone marrow plasma periostin was almost fourfold higher compared with the serum levels of periostin and correlated with the presence of fractures and of diffuse magnetic resonance imaging pattern of marrow infiltration. Serum periostin was elevated in NDMM patients compared with healthy controls, MGUS and SMM patients and correlated with advanced disease stage, high lactate dehydrogenase, increased activin-A, increased bone resorption and reduced bone formation. Patients at first relapse had also elevated periostin compared with healthy controls, MGUS and SMM patients, while even patients at the plateau phase had elevated serum periostin compared with healthy controls. These results support an important role of periostin in the biology of myeloma and reveal periostin as a possible target for the development of antimyeloma drugs.

The Role of Magnetic Resonance Imaging in the Investigation and Management of Invasive Lobular Carcinoma-A 3-Year Retrospective Study in Two District General Hospitals.

Invasive lobular carcinoma (ILC) accounts for 5-15% of breast cancers. In comparison to other types of breast cancer, ILC is more likely to be associated with multifocal and contralateral breast involvement as well as a tendency to a diffuse infiltrative growth pattern which can represent a diagnostic challenge. The National Institute of Clinical Excellence guidelines in 2009 recommended the use of magnetic resonance imaging (MRI) in the preoperative assessment of ILC. This study aims to assess compliance with the guidelines in two District General Hospitals and the utility of MRI in the investigation of ILC. All cases of ILC between 2011 and 2013 were retrospectively identified from the pathology database and their breast imaging findings, pathology report, and operative intervention were reviewed. A total of 126 patients were identified with ILC, of these 46 had MRI preoperatively (36.5%). MRI upgraded mammography/ultrasound diagnoses in 10 patients (21.7%). MRI showed multicentric unilateral disease in 17 patients (37.0%) occult on ultrasound/mammogram, with these patients undergoing mastectomy and 16/17 (94.1%) confirmed multifocality on pathology. MRI showed a contralateral lesion in 9 patients (19.6%), four (8.7%) of which were malignant and had bilateral surgery, and five (10.9%) were benign on further imaging/biopsy. MRI also downgraded three patients (6.5%) to unifocal disease with reported multifocal appearances on mammography/ultrasound, and these patients underwent breast-conserving surgery. MRI adds significant additional information to mammograms/ultrasound in ILC and should be undertaken in all such cases preoperatively assuming no contraindication.

Sarcomatoid malignant mesothelioma: A clinicopathologic and immunohistochemical analysis of 22 cases

To elaborate on the clinical and pathologic features of sarcomatoid malignant mesothelioma (SMM), its diagnostic criteria and differential diagnoses. Twenty-two cases of SMM retrieved from in-house and consultation files (between January 2009 to September 2013) were reviewed with emphasis on the clinicopathologic characteristics, immunophenotypes and the prognostic impact. The mean age of the patients was 54 years (ranged from 24-73 years). There was no sexual predilection and the majority of the patients did not have history of asbestos exposure. Overall, 14 tumors developed in the pleura and 8 cases arose from the peritoneal cavity. Clinically, patients presented signs and symptoms in accord with the location of the tumors, notably coughing, shortness of breath, and chest pain for patients with pleural origin, and nausea, abdominal distention and abdominal pain for those with peritoneal primary. In most cases, CT and MRI scan demonstrated lobulated masses (8/11). However, diffuse infiltrative growth patterns were observed exclusively in a minority of pleural cases (3/11). No visceral lesion was observed in any case. Histologically, 19 cases had either fibrosarcomatous or undifferentiated pleomorphic sarcoma-like appearance. Two cases were consistent with desmoplastic mesothelioma. One case contained osteosarcomatous element. All cases expressed pan-cytokeratin (AE1/AE3), and most cases were also positive for D2-40 (15/20). The staining of calretinin (9/21) and WT1 (10/14) was generally weak and focal. They were all negative for TTF-1, napsin A, SP-A, p63 and CD34. Follow-up information (range from 1 to 36 months) was available in 11 cases, 6 of which were alive with unresectable tumor, 1 patient with recurrent disease and 4 patients succumbed to disease. The overall survival was 5 months (mean 8 months). The diagnosis of SMM is achieved by comprehensive evaluation of medical history, imageological and pathological findings. Since calretinin immunoreactivity is infrequently observed in SMM, application of pan-cytokeratin and D2-40 immunostains offers a reasonable alternative for diagnosis. Diagnosis of SMM can be made by excluding a variety of spindle cell neoplasms with overlapping features, such as sarcomatoid carcinoma, synovial sarcoma, solitary fibrous tumor and fibrous pleuritis.

Bone marrow uptake of indolent non-Hodgkin lymphoma on PET/CT with histopathological correlation.

To evaluate the diagnostic accuracy of PET/computed tomography (CT) in detecting marrow infiltration in indolent non-Hodgkin lymphoma (NHL) with histopathological correlation. All treatment-naive newly diagnosed indolent NHL with staging PET/CT were retrospectively evaluated for marrow infiltration and categorized on the basis of the PET/CT uptake pattern: normal (PET/CT negative), focal/diffuse (PET/CT positive). Bone marrow biopsy (BMB) was considered the standard, except in focal PET/CT uptake, which was confirmed to be positive or negative by serial PET/CT. The BMB pattern was assessed as diffuse and nondiffuse and the degree of lymphoid infiltration was documented. Forty-six patients (mean age 59 ± 15 years) were evaluated. In the PET/CT-positive group of 22 cases (diffuse = 15, focal = 7), BMB was positive in 21 cases. In 80% of diffuse PET/CT uptake cases, a diffuse BMB infiltrative pattern was observed. However, in cases with focal PET/CT uptake, no predominant histological pattern was observed. No correlation was found between semiquantitative uptake and degree of lymphoid infiltration on BMB (r = 0.2, P = 0.434). In the PET/CT-negative group of 24 cases, 20 cases were BMB negative and four cases were positive. The overall diagnostic accuracy of PET/CT in determining marrow infiltration was 89% (sensitivity 84%, specificity 95%, positive predictive value 95% and negative predictive value 83%). PET/CT showed high specificity and positive predictive value with moderate accuracy in detecting marrow disease in indolent NHL. The metabolic uptake lacked a significant correlation with the degree of lymphoid infiltration, but a potential relationship may exist between the pattern of metabolic uptake and the BMB infiltrative pattern.

Miositis proliferativa con metaplasia ósea. Reporte de un caso

Proliferative myositis is a rare, benign lesion and the presence of osseous metaplasia is even more infrequent. Its rapid growth and diffuse infiltration pattern may cause it to be confused with a malignant tumour. We present a case of proliferative myositis in a 68 year old male with a history of low grade fibromyxiod sarcoma who presented with swelling in the anterior left shoulder.An ill-defined, 2×1cm whitish lesion was found in the deltoid muscle. A proliferation of spindle cells, pseudoganglion cells and calcified osteoid was observed. Immunohistochemistry showed positivity for vimentin, β-catenin (cytoplasmic), Ki 67 (6%) and focal positivity for actin and myosin smooth muscle in spindle cells, negativity for MYO-D1, myogenin, CD34, desmin, caldesmon. A diagnosis of proliferative myositis with foci of osseous metaplasia was made.

A magnetic resonance imaging-based prognostic scoring system to predict outcome in transplant-eligible patients with multiple myeloma.

Diffuse and focal bone marrow infiltration patterns detected by magnetic resonance imaging have been shown to be of prognostic significance in all stages of monoclonal plasma cell disorders and have, therefore, been incorporated into the definition of the disease. The aim of this retrospective analysis was to develop a rapidly evaluable prognostic scoring system, incorporating the most significant information acquired from magnetic resonance imaging. Therefore, the impact of bone marrow infiltration patterns on progression-free and overall survival in 161 transplant-eligible myeloma patients was evaluated. Compared to salt and pepper/minimal diffuse infiltration, moderate/severe diffuse infiltration had a negative prognostic impact on both progression-free survival (P<0.001) and overall survival (P=0.003). More than 25 focal lesions on whole-body magnetic resonance imaging or more than seven on axial magnetic resonance imaging were associated with an adverse prognosis (progression-free survival: P=0.001/0.003 and overall survival: P=0.04/0.02). A magnetic resonance imaging-based prognostic scoring system, combining grouped diffuse and focal infiltration patterns, was formulated and is applicable to whole-body as well as axial magnetic resonance imaging. The score identified high-risk patients with median progression-free and overall survival of 23.4 and 55.9 months, respectively (whole-body-based). Multivariate analyses demonstrated that the magnetic resonance imaging-based prognostic score stage III (high-risk) and adverse cytogenetics are independent prognostic factors for both progression-free and overall survival (whole-body-based, progression-free survival: hazard ratio=3.65, P<0.001; overall survival: hazard ratio=5.19, P=0.005). In conclusion, we suggest a magnetic resonance imaging-based prognostic scoring system which is a robust, easy to assess and interpret parameter summarizing significant magnetic resonance imaging findings in transplant-eligible patients with multiple myeloma.

Primary cutaneous diffuse large B-cell lymphoma, leg type: a study of clinicopathology, immunophenotype and gene rearrangement

To study the clinicopathologic features, immunophenotype and gene rearrangement of primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL). Seven cases of PCLBCL were enrolled into the study. Clinicopathologic analysis, immunohistochemical staining and gene rearrangement for IgH and Igκ were undertaken in the study. All the seven cases were male, and the median age was 72 years. Patients usually presented with multiple purple tumors, nodules, papules and infiltrative plaques. Two patients had a history of leg injury before onset, and one had mosquito bites. Histologically, the tumor involved the dermis and subcutis with dense and diffuse infiltrative pattern composing of centroblasts and/or immunoblasts. Immunohistochemical staining showed that seven cases (7/7) expressed CD20, six (6/6) expressed bcl-2, four (4/4) expressed MUM-1, four (4/5) expressed CD79a, four (4/5) expressed PAX-5 and four (4/6) expressed bcl-6, respectively. All cases did not express CD3ε, CD45RO, CD10 and CD30. IgH gene rearranged bands were detected in three (3/6) cases and Igκ was detected in one (1/5) case. Six of the seven cases died and the remaining patient, who was 44-year-old, was alive after 22 months of follow-up. PCLBCL is rare, predominantly affects elderly male patients. PCLBCL has poor prognosis and high mortality, but younger patients seem to have better prognosis. Some cases had a history of trauma or mosquito bites. The relationship between the history and the onset of PCLBCL needs further evaluation.

Clinical and Prognostic Significance of Bone Marrow Imaging of Appendicular Skeletons By Low-Dose Multi-Detector Computed Tomography in Patients with Aplastic Anemia and Myelodysplastic Syndorme

▪Background: Myelodysplastic syndrome (MDS) and aplastic anemia (AA) comprise a heterogeneous group of bone marrow failure disorders. As both show profound hypocellular marrow with minimal morphological atypia, differentiation of MDS and AA is often difficult by bone marrow and laboratory examination alone. Red to yellow marrow conversion occurs with age in the appendicular skeleton (AS), where red marrow is converted to yellow marrow until the early 20s. Although an abnormal distribution of red marrow in AS has previously been reported in small numbers of patients with MDS, along with leukemia and lymphoma by MRI, there have been no further reports to date. Here, we examined the distribution of red marrow in AS by low-dose multi-detector CT (MDCT) in AA and MDS. We analyzed the relationships between the abnormal medullary pattern in AS and laboratory variables, subsequent development of leukemic transformation, and survival in MDS patients.Patients: We performed low-dose MDCT of the humerus and femur in 103 untreated adult patients with AA (n = 32) and MDS (n = 71). We retrospectively reviewed the medical records of patients with AA and MDS diagnosed in the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa, Japan, from July 2008 to June 2014. A retrospective review of clinical and laboratory features, including complete blood count, % bone marrow blasts, chromosomal analysis, and International Prognostic Scoring System (IPSS), was performed. WHO classification of MDS patients was as follows: RA (n = 22), RARS (n = 2), RCMD (n = 17), RAEB 1 (n = 18), RAEB 2 (n = 11), and MDS unclassified (n = 1). Overall survival (OS) and leukemia-free survival (LFS) were analyzed in 71 MDS patients by the Kaplan–Meier method and differences between curves were calculated by two-sided log-rank test.CT image acquisition and image analysis: Non-enhanced CT examinations were performed from the base of the skull down to the knee joint with an MS-CT scanner (AQUILION 64; Toshiba, Tokyo, Japan). The bony canals of the humeral and femoral bones were visualized by coronal and sagittal axis image reconstruction. The effective radiation dose associated with whole-body MD-CT was 10.1 mSv (ICRP 26). The dose was comparable to whole-body CT (2.4 mSv). Medullary CT density of the humerus and femur were measured and the results are expressed in Hounsfield units (HU). As the normal adult bone marrow was composed of rich adipocytes and called yellow marrow, it is represented by a low-density CT value between –30 and –100 HU. A value above –30 HU observed in long bony canals was considered to indicate a high-density lesion. The medullary pattern of the appendicular skeleton was categorized as follows: (1) fatty, showing a low signal density marrow; (2) focal, showing abnormally focal high-density lesions; (3) diffuse, showing uniformly high-density marrow.Results: All 15 patients with AA showed a fatty (n = 12, 37.5%) or focal (n = 20, 62.5%) pattern in medullary AS on MDCT, and none showed a diffuse pattern. Among the 71 patients with MDS, 22 (30.9%) had a fatty pattern, 32 (45.1%) had a focal pattern, and 17 (23.9%) had a diffuse pattern. Seventeen patients with diffuse infiltration pattern on MDCT had significantly shorter LFS (P < 0.01, P = 0.02) compared to 23 patients with fatty pattern and 32 patients with focal medullary pattern (median LFS: 18 months vs. not reached vs. not reached, respectively). Seventeen patients with a diffuse infiltration pattern on MDCT had significantly shorter OS (P = 0.04) compared to 23 patients with a fatty pattern, but the difference was no significant compared to 32 with a focal medullary pattern (P = 0.15) (median OS: 22 months vs. not reached vs. not reached, respectively). The characteristics of the patients with diffuse pattern did not differ significantly in terms of sex, age, WBC count, platelet count, karyotype, WT1, or IPSS classification from those of patients with a fatty or focal pattern, but patients with a diffuse infiltration pattern on MDCT had a significantly low hemoglobin concentration compared to those with a fatty or focal medullary pattern (P = 0.03).Conclusions: This study showed that MDCT imaging of the appendicular skeleton provided important information for the diagnosis and prognosis of patients with MDS and AA. In patients with MDS, a diffuse pattern on MDCT emerged as an independent negative prognostic indicator on LFS and OS. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Characterization of multiple myeloma osseous lesions and diffuse infiltration pattern by 18F-FDG-PET/CT, static MRI and diffusion-weighted MR Imaging (DWI-MRI): a comparative multimodality imaging study

Methods 55 Patients diagnosed according to the International Myeloma Working Group criteria (2003) were referred to consecutive imaging diagnostics including 18F-FDG PET/CT, T1-weighted and short-tau inversion recovery (STIR) whole-body MRI (WB-MRI) as well as diffusion weighted MRI (DWI). Images were reviewed and matched on a lesion-by-lesion basis for the location and number of focal osseous MM lesions by two radiologists and one nuclear medicine physician, grading the conspicuity of each lesion in CT, T1w, T2 STIR, DWI and ADC-Map separately. PET/CT data were compared based on qualitative and semi-quantitative (SUV) evaluation. A scoring system was used, with a certainty score as the reference for each lesion resulting from an evaluation considering all imaging modalities simultaneously. The analysis was carried out without knowledge of the previous treatment or the stage of disease. Results In static MRI and DWI different infiltration patterns were observed and PET/CT revealed comparable patterns of tracer uptake: negative, focal, diffuse and mixed. MRI including DWI demonstrates both active as well as inactive MM lesions and displays numerous additional PET-negative lesions.

Immunohistochemical study of bone marrow angiogenesis in multiple myeloma and its correlation with clinicopathological factors

Background: In recent years, bone marrow angiogenesis was reported to be involved in the pathogenesis and progression of certain hematological malignancies like multiple myeloma, leukemias, and lymphomas. Recent studies have suggested that bone marrow angiogenesis plays an important role in the pathogenesis and prognosis of multiple myeloma.Objectives: at the present study, bone marrow angiogenesis in multiple myeloma was examined using immunohistochemical staining for CD34, and correlated with various pathological and clinical parameters.Patients and methods: This is a retrospective study; where by archival paraffin-embedded tissue blocks along with the clinical and hematological records of fifty-two patients with multiple myeloma and twenty controls were obtained from the Department of Hematology of the Medical City Teaching Laboratories in the period from January 2010 to January 2013. Bone marrow angiogenesis was studied by immunohistochemical staining for CD34 to identify microvessels.Results: There was a significant association between higher angiogenesis grades and advanced clinical stage of the disease (p = 0.002), and higher plasma cell percent in the bone marrow (p = 0.03), and increasing immaturity of the plasma cell (p = 0.001), and diffuse pattern of bone marrow infiltration by plasma cells (p = 0.007).Conclusions: Patients with increased plasma cell burden, immature plasma cell morphology, and diffuse pattern of infiltration had a higher microvessel density.

English

BACKGROUND: Plasma cell myeloma comprises about 1% of malignant tumors, 10-15% of hematopoietic neoplasms and causes 20% of deaths from hematologic malignancies. Several clinical, laboratory and histological/cytological variables help us in determining the prognosis of the disease. There have been very few studies from India evaluating bone marrow histology of plasma cells in myeloma. The present study is aimed at analyzing and studying the various clinical presentations, biochemical, hematologic and histological parameters determining immediate prognosis (mortality) in myeloma. MATERIAL AND METHODS: Prospective study was conducted from April 1 st 2008 to March 2010. 48 patients were diagnosed with multiple myeloma during study period; 41 were available for follow-up.ie for a minimum 6 months from the time of diagnosis. Among these seven cases expired i.e. in the period of 6 months from the respective time of diagnosis. Biochemical and hematological variables of those expired (seven) and those alive available for follow- up (thirty-Four) were compared. Results of biochemical investigations were collected from the case sheet. Peripheral smear, Bone marrow aspiration and biopsy were done for all cases. STATISTICAL ANALYSIS USED: student's t test and chi square test. RESULTS: Among the variables considered mean hemoglobin level in expired vs. alive was 4.2 vs. 7.5 g/dl. Mean ESR was 133 vs. 102 mm/hr. Mean blood urea was 97.3 vs. 38.5 mg/dl. A/G reversal was present in 85.7% of expired and in 50% of alive patients. Average plasma cell percentage in the bone marrow aspirate in expired vs. alive was 74.7% and 43.1%.Plasmablastic variety was present in 71.4% expired and 17.6% of alive patients. Diffuse pattern of infiltration was present in 85.7% of expired and 44.1% of alive patients. Grade III fibrosis was present in 85.7% of expired and 20.6% of alive patients. All variables except A/G reversal had p <.005. CONCLUSION: Immediate Prognostication of Multiple myeloma requires both hematological and laboratory data. Low hemoglobin, raised blood urea, and elevated ESR, plasma cell percentage, plasmablastic variety, diffuse pattern of infiltration and grade III fibrosis were proved to have a direct link to immediate mortality.

Appearance of monoclonal plasma cell diseases in whole‐body magnetic resonance imaging and correlation with parameters of disease activity

The aim of our study was to assess in which way different infiltration patterns of monoclonal plasma cell diseases in whole-body (wb) magnetic resonance imaging (MRI) are associated with clinical stages, plasma cell content in bone marrow samples and established serum markers of disease activity. Institutional review board approval was obtained. We performed wb-MRI in 547 consecutive, unselected and untreated patients with monoclonal gammopathy of undetermined significance (MGUS, n=138), smoldering myeloma (SMM, n=157) and multiple myeloma (MM, n=252) on two 1.5 T MRI-scanners with body array coils. The studies were evaluated in consensus by two experienced radiologists blinded to the diagnosis. We observed focal lesions in 23.9% (MGUS), 34.4% (SMM) and 81.3% (MM), respectively. A diffuse infiltration pattern was detected in 38.4%, 45.9% and 71%, respectively. The differences between all infiltration patterns were significant (p<0.0001). The presence of focal lesions and the presence of a diffuse bone marrow infiltration was associated with an increased plasma cell percentage in bone marrow samples (median 22% vs. 14%, 26% vs. 10%, both p<0.0001) and monoclonal protein concentration (median 18 g/dl vs. 13 g/dl, p=0.003, 20 g/dl vs. 11 g/dl, p<0.0001). Further categorization of the diffuse infiltration patterns in wb-MRI into "salt-and-pepper," moderate and severe identified significant associations with M-protein (median g/dl for S+P/moderate/severe 23/18/25, p=0.04), plasma cell percentage in the bone marrow (median 25%/24%/40%, p=0.02), and age (median years 67/60/57, p<0.0001). Bone marrow infiltration in wb-MRI is significantly different between the various stages of plasma cell disease and correlates well with established markers of disease activity.

Infiltration patterns in monoclonal plasma cell disorders: correlation of magnetic resonance imaging with matched bone marrow histology

ObjectivesTo investigate how plasma cell infiltration patterns detected by MRI match the plasma cell distribution in bone marrow biopsy. MethodsWe assessed 50 patients with monoclonal plasma cell disorders of all clinical stages. MRI infiltration pattern was compared with matched BM histology from the same anatomic region. ResultsMRI revealed a minimal (n=11, 22%), focal (n=5, 10%), diffuse (n=14, 28%) and mixed (n=20, 40%) infiltration pattern. Diffuse MRI pattern was predominant in smoldering myeloma patients whereas the MRI patterns with “focal component” (i.e. focal and mixed) were most common in symptomatic myeloma (p<0.01). In histology an interstitial (n=13, 26%), nodular (n=23, 46%) and packed marrow (n=14, 28%) was found respectively. All three histological types of infiltration were observed in patients with diffuse and mixed MRI patterns. Minimal MRI pattern was found in all MGUS patients and was associated with an interstitial BM infiltration. In two patients with minimal MRI pattern an extensive micro-nodular BM infiltration was found in histology. ConclusionsInfiltration patterns in MRI represent different histological growth patterns of plasma cells, but the MRI resolution is not sufficient to visualize micro-nodular aggregates of plasma cells.

Leukemia and the Peripheral Nervous System: A review

The fate of patients with leukemia has greatly improved in the past decades. Survival has been increased and the once stereotypic pattern of Cerebrospinal fluid (CSF) infiltration and diffuse infiltration of nerves and muscles has entirely changed. Peripheral nervous structures as cranial nerves, nerve roots, plexus and peripheral nerves can be affected in different types of leukemia, by different mechanisms and at different time points. Treatment side effects become more apparent, as the number of long term survivors increases. In some cases also isolated relapses of leukemia in the nervous system occurs and effects of stem cell transplantation on the nervous system became apparent. Diagnostically the cranial nerves, nerve roots, cauda equina, nerve plexus and the peripheral nerves have become more accessible to investigation due to improved imaging methods as ultrasound and MRI, thus facilitating the earlier diagnosis and treatment of nerve involvement.