Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature

BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.

Utility of Flow Cytometry to Classify Abnormal Plasma Cell Populations in Marrow Samples Collected from Patients with Putative Plasma Cell Neoplasms

Plasma cell neoplasms comprise a spectrum of diseases that include monoclonal gammopathy of undetermined signi-ficance (MGUS) and multiple myeloma (MM). Flow cytometric immunophenotyping has become an invaluable tool as an ancillary and diagnostic test for hematologic malignancies and is being used with increasing frequency in the diag-nosis and monitoring of plasma cell neoplasms. As multiparameter flow cytometry has evolved, faster fluidics and detection systems facilitate the screening of a large number of events and the detection of multiple antigens simultaneously. This review addresses the approaches used to evaluate clonal plasma cell neoplasms and describes different surface and cytoplasmic markers and techniques that are important for the study of these diseases.

Pleural effusion,ascites,colon ulcers and hematochezia:What we can learn from the diagnostic process of a patient with plasma cell myeloma:A case report

BACKGROUND Plasma cell myeloma(PCM)is characterized by hypercalcemia,renal impairment,anemia,and bone destruction.While pleural effusion,ascites,abdominal pain,and bloody stool are common manifestations of lung disease or gastrointestinal disorders,they are rarely observed in patients with PCM.CASE SUMMARY A 66-year-old woman presented with complaints of recurrent chest tightness,wheezing,and abdominal bloating accompanied by bloody stools.Computed tomography revealed pleural effusion and ascites.Pleural effusion tests showed inflammation,but the T-cell spot test and carcinoembryonic antigen were negative.Endoscopy showed colonic mucosal edema with ulcer formation and local intestinal lumen stenosis.Echocardiography revealed enlarged atria and reduced left ventricular systolic function.The diagnosis remained unclear.Further testing revealed elevated blood light chain lambda and urine immunoglobulin levels.Blood immunofixation electrophoresis was positive for immunoglobulin G lambda type.Smear cytology of the bone marrow showed a high proportion of plasma cells,accounting for about 4.5%.Histopathological examination of the bone marrow suggested PCM.Flow cytometry showed abnormal plasma cells with strong expression of CD38,CD138,cLambda,CD28,CD200,and CD117.Fluorescence in situ hybridization gene testing of the bone marrow suggested 1q21 gene amplification,but cytogenetic testing showed no clonal abnormalities.Colonic mucosa and bone marrow biopsy tissues were negative for Highman Congo red staining.The patient was finally diagnosed with PCM.CONCLUSION A diagnosis of PCM should be considered in older patients with pleural effusion,ascites,and multi-organ injury.

Plasma Cell Neoplasms, Clinicopathological Characteristics and Immunophenotype of 21 Patients

Introduction: Plasma cell neoplasms are monoclonal proliferations characterized by the secretion of an immunoglobulin product known as component "M" or monoclonal. The World Health Organization (WHO 2008) defines as plasma cell neoplasms the following: plasma cell myeloma, plasmacytoma and those syndromes defined by immunoglobulin deposits and primary amyloidosis, The objective of the present work was to correlate their clinical, morphological and phenotype characteristics in 21 patients. Material and Methods: A 2-year retrospective review was performed of the files of the surgical pathology laboratory and of the hematology service of the General Hospital of Mexico, searching for patients with a diagnosis of plasma cell neoplasm. We analyzed the following variables: age, gender, clinical symptoms, evolution, localization, laboratory tests, morphology, and expression of immunohistochemical markers. Of the 21 patients, 12 (57.1%) corresponded to plasma cell myelomas and 9 (42.8%) were plasmacytomas (seven extraosseous and two solitary bone plasmacytoma);women predominated with 61.4% and age ranged between 22 and 84 years. Mass and epistaxis were observed in the patients with plasmacytomas, and symptoms of medullary compression and anemia were observed in those patients with plasma cell myeloma. The time of symptomatology varied from 3 to 12 months. Laboratory tests revealed that lactate dehydrogenase (LDH), beta 2 microglobulin, C-reactive protein were altered and that hypercalcemia and anemia were present more in the systemic form of the disease. Treatment depended on the clinical staging and laboratory data. Mature forms predominated morphologically. Immunohistochemical stain revealed a constant expression for CD 138, six patients expressed CD 56, and expression of the Kappa and Lambda light chains was while.

Bortezomib-Induced Bilateral Eye Swelling and Cutaneous Adverse Reaction in a Patient with Plasma Cell Leukemia—A Case Report

Bortezomib, a proteasome inhibitor, is an established therapy against plasma cell leukemia—a variant of plasma cell dyscrasias. Its most frequent side effects have been listed as peripheral neuropathy, neuropathic pain, thrombocytopenia, and gastrointestinal problems. Allergic skin reaction is a rarely documented side effect in patients receiving bortezomib-based chemotherapy. A combination therapy consisting of intravenous bortezomib, oral Revlimid tablets, and oral dexamethasone tablets has been prescribed for the patient after his recent diagnosis of plasma cell leukemia. While receiving his third treatment cycle, he developed an allergic reaction (skin rash) involving the neck, and wrists, and mild bilateral eye swelling. The infusion was stopped immediately and then ciprofloxacin ophthalmic solution and oral diphenhydramine 25 mg were prescribed to the patient with significant improvement in his clinical condition. He was temporarily taken off bortezomib. At a follow-up visit a week later, a significant improvement was noticed in his condition. Rash had reduced on neck and wrists, and eye swelling had reduced as well. As of the time of writing this case report, he has been temporarily taken off bortezomib, but other medications in the treatment regimen were continued as prescribed.

From Myeloma to Plasma Cell Leukemia, Persistent Inequalities

Multiple myeloma (MM) is both a complex and heterogeneous disease. Cytogenetic and molecular abnormalities lead to resistance to treatment and transformation to plasma cell leukemia, which is defined by the presence in circulating blood of plasma cells over 2 G/L, or more than 20% of leukocytes. It is an uncommon hematological malignancy with a poor prognosis. Against this backdrop, we report an observation of multiple myeloma transformed into plasma cell leukemia diagnosed at the Hôpital Principal de Dakar (HPD) that occurred on a 64-year-old man with a history of thyroidectomy followed for multiple myeloma presenting with Salmon et Durie stage IIIA and ISS stage I. Despite a marked improvement in management strategy, myeloma remains an almost invariably incurable disease. However, the development of genetic and molecular biomarkers is necessary to improve its prognosis.

Multiple Myeloma: Modification and Adaptation of Plasma Cell Morphology Algorithm for the Prognosis of Congolese Patient

Objectives: To determine the multiple myeloma (MM) prognostic formulas applicable in Congolese with many aberrant and/or immature plasma cells according to GOASGUEN’s plasma cell morphology algorithm (PMA). Methods: The prospective, observational and descriptive study was carried out at the Ngaliema Clinic in Kinshasa from July 2016 to December 2019. The variables studied were the plasma cell types and the prognosis groups according to GOASGUEN and ZANDECKI. The nucleolus, the chromatin and the N/C ratio of 2 for each plasma cell encountered in multiple myeloma are examined in order by asking three successive questions as follows: 1) Is the nucleolus present? If yes, we denote 1;if not, note 0;2) Is the chromatin thin? If yes, we score 1;if not we score 0;3) The N/C ratio is greater than 6, if so, 1 is noted;if not, we note 0. We obtain a number with 3 successive digits preceded by the letter P for each plasma cell. Results: The overall rate of immature plasma cells and aberrant plasma cells in MM among Congolese was high at 26.6%. Their integration in the prognostic formulas showed for group A" = 22 patients, group B" = 5 patients and group C" = 32 patients. Examination of plasma cell types in the deceased showed that 14/17 had a P001 plasma cell count ≥ 15%. Conclusion: The high rate of aberrant and/or immature plasma cells, the P001 plasma cell type at a rate ≥ 15%, found mostly in group C" with poor prognosis, are responsible for the aggressive nature of MM in Congolese Blacks.

Endoscopic submucosal tunnel dissection for largesuperficial esophageal squamous cell neoplasms

Endoscopic submucosal dissection(ESD)is a wellestablished treatment for superficial esophageal squamous cell neoplasms(SESCNs)with no risk of lymphatic metastasis.However,for large SESCNs,especially when exceeding two-thirds of the esophageal circumference,conventional ESD is time-consuming and has an increased risk of adverse events.Based on the submucosal tunnel conception,endoscopic submucosal tunnel dissection(ESTD)was first introduced by us to remove large SESCNs,with excellent results.Studies from different centers also reported favorable results.Compared with conventional ESD,ESTD has a more rapid dissection speed and R0 resection rate.Currently in China,ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique,as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria.However,not all patients with SESCNs are candidates for ESTD,and postoperative esophageal strictures should also be taken into consideration,especially for lesions with a circumference greater than three-quarters.In this article,we describe our experience,review the literature of ESTD,and provide detailed information on indications,standard procedures,outcomes,and complications of ESTD.

Autoimmune pancreatitis with IgG4-positive plasma cell infiltration in salivary glands and biliary tract

A 62-year-old male was referred to our hospital because of liver dysfunction, diffuse pancreatic swelling, and trachelophyma. At admission, the patient was free of pain. Physical examination showed enlarged and palpable bilateral submandibular masses, but no palpable mass or organomegaly in the abdomen. Laboratory findings were as follows： total protein 90 g/L with γ-globulin of 37.3% （33 g/L）, total bilirubin 4 mg/L, aspartate aminotransferase 39 IU/L, alanine aminotransferase 67 IU/L,γ-glutamyl transpeptidase 1 647 IU/L, and amylase 135 IU/L. Autoantibodies were negative, and tumor markers were within the normal range. Serum IgG4 level was markedly elevated （18 900 rag/L）. Computed tomography （CT） showed diffuse swelling of the pancreas and dilatation of both common and intra-hepatic bile ducts. Endoscopic retrograde pancreatography （ERP） revealed diffuse irregular and narrow main pancreatic duct and stenosis of the lower common bile duct. Biopsy specimens from the pancreas, salivary gland and liver showed marked periductal IgG4-positive plasma cell infiltration with fibrosis. We considered this patient to be autoimmune pancreatitis （AIP） with fibrosclerosis of the salivary gland and biliary tract, prescribed prednisolone at an initial dose of 40 mg/d. Three months later, the laboratory data improved almost to normal. Abdominal CT reflected prominent improvement in the pancreatic lesion. Swelling of the salivary gland also improved. At present, the patient is on 10 mg/d of prednisolone without recurrence of the pancreatitis. We present here a case of AIP with fibrosclerosis of salivary gland and biliary tract.

Venetoclax in combination with chidamide and dexamethasone in relapsed/refractory primary plasma cell leukemia without t(11;14):A case report

BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma(RRMM)with t(11;14).There are very few studies published on the use of venetoclax in pPCL without t(11;14).Similarly,histone deacetylase inhibitors are considered effective for the treatment of RRMM,but there are no reports on their use in pPCL.CASE SUMMARY A 57-year-old woman with severe anemia,thrombocytopenia,multiple bone destruction,impaired renal function,and 42.7%of peripheral plasma cells is reported.After multiple chemotherapy regimens and chimeric antigen receptor Tcell treatment,the disease progressed again.The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.

Haploidentical stem cell transplantation used in treating primary plasma cell leukemia: a case report

Here we report a successful protocol in treatment of a patient with primary plasma cell leukemia (PPCL) using haploidentical stem cell transplantation (hi-HSCT). During first complete remission after routine chemotherapy, the patient received autologous blood stem cell transplantation, but he had relapse later. He gained a second CR after chemotherapy and underwent hi-HSCT from his daughter, who had HLA mismatched at three loci. Recovery of hemopoiesis was found at day 14 and complete donor chimerism was confirmed by PCR-STR on day 34, 95 and 238. The patients have survived disease-free for 56 months since hi-HSCT, without serious graft-versus-host-disease.

PRIMARY PLASMA CELL LEUKEMIA(A COMPREHENSIVE ANALYSIS OF 44 CASES)

Four cases of primary plasma cell leukemia (PPCL) admitted to Zhongshan Hospital from 1959 to 1987 are reported with a review on additional 40 cases reported in China. Comparing with the 57 cases of multiple myeloma (MM) treated in our hospital, the following features were observed in PPCL: (1) The age was younger, with a mean of 45.2 years, 34.1% of the patients were under 40 years. (2) Onset was abrupt. Duration from onset to diagnosis was 2 months or less in 77% patients but never beyond 6 months. (3) 81.8% patients had liver enlargement, 59.1% splenomegaly and 61.4% sternum tenderness. (4) All patients showed marked anemia with an average hemoglobin of 65 g/L. BPC count was less than 100 × 109/L in 76% patients and WBC was more than 10×109/L in 77%. (5) Plasma cell number in the marrow was markedly increased with an average of 69%, of which the blast cells and immature forms were predominant. (6) No destruction of bones was shown on X-ray film in 68.3% patients. (7) The response to chemotherapy was poor with a total response rate of 18% and a mean survival of 2 months. All the above-mentioned clinical features were significantly different from those of MM. In addition, these two diseases were also different in cytology, cytogenetics and ultrastructure. Therefore, PPCL should be considered as a special type of acute leukemia distinct from MM. High dose of alkylating agents in combination with autologous bone marrow transplantation might improve the prognoses.

Short term results of endoscopic submucosal dissection in superficial esophageal squamous cell neoplasms

AIM: To evaluate the efficacy of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. METHODS: Between July 2007 and March 2009, 27 consecutive superficial esophageal squamous cell neoplasms in 25 enrolled patients were treated by endoscopic submucosal dissection. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The mean size of the lesions was 21 ± 13 mm (range 2-55 mm); the mean size of the resection specimens was 32 ± 12 mm (range 10-70 mm). The enblock resection rate was 100% (27/27), and en block resection with tumor-free lateral/basal margins was 88.9% (24/27). Perforation occurred in 1 patient who was managed by conservative medical treatments. None of the patients developed local recurrence or distant metastasis in the follow-up period. CONCLUSION: Endoscopic submucosal dissection is applicable to superficial esophageal squamous cell neoplasms with promising results.

Refractory gastric ulcer with abundant IgG4-positive plasma cell infiltration: A case report

We describe a 77-year-old man with refractory gastric ulcer that worsened after Helicobacter pylori eradication therapy.Pathology showed marked infiltration of IgG4-positive plasma cells in the gastric lesions,which led us to suspect IgG4-related sclerosing disease.To the best of our knowledge,this is the first report of IgG4-related gastric ulcer without the main manifestation of autoimmune pancreatitis.

Recurrent hepatitis C virus after transplant and the importance of plasma cells on biopsy

Hepatitis C virus(HCV) is the leading indication for liver transplantation in the United States.It recurs universally after transplant but the rate of fibrosis and the development of graft failure is variable.Different donor and recipient features have been demonstrated to impact fibrosis.Plasma cell hepatitis,a histologic finding,is one feature associated with poor graft and patient outcomes.The pathogenic mechanism resulting in plasma cell hepatitis is poorly understood,with evidence suggesting a role for both the HCV and the immune system.A recent publication described plasma cell hepatitis in a larger context of immune medicated graft dysfunction in transplant recipients receiving interferon based therapy.This manuscript will highlight the topic of plasma cell hepatitis and provide commentary on the lack of recognition,the data regarding pathophysiologic mechanisms and the potential management options.

Cronkhite-Canada syndrome polyps infiltrated with IgG4-positive plasma cells

Cronkhite-Canada syndrome(CCS) is a rare but serious protein-losing enteropathy, but little is known about the mechanism. Further more, misdiagnosis is common due to non-familiarity of its clinical manifestation. A 40-year-old male patient was admitted to our hospital because of diarrhea and hypogeusia associated with weight loss for 4 mo. On physical examination, skin pigmentation, dystrophic nail changes and alopecia were noted. He had no alike family history. Laboratory results revealed low levels of serum albumin(30.1 g/L, range: 35.0-55.0 g/L), serum potassium(2.61 mmol/L, range: 3.5-5.5 mmol/L) and blood glucose(2.6 mmol/L, range: 3.9-6.1 mmol/L). The erythrocyte sedimentation rate was elevated to 17 mm/h(range: 0-15 mm/h). X-ray of chest and mandible was normal. The endoscopic examination showed multiple sessile polyps in the stomach, small bowel and colorectum. Histopathologic examination of biopsies obtained from those polyps showed hyperplastic change, cystic dilatation and distortion of glands with inflammatory infiltration, eosinophilic predominance and stromal edema. Immune staining for IgG 4 plasma cells was positive in polyps of stomach and colon. The patient was diagnosed of CCS and treated with steroid, he had a good response to steroid. Both histologic findings and treatment response to steroid suggested an autoimmune mechanism underling CCS.

The new proof of neuro-endocrine-immune network-expression of islet amyloid polypeptide in plasma cells in gastric mucosa of peptic ulcer patients

INTRODUCTION Peptic ulcer,as a common disease,seriouslyaffected people’s,work and life.Its occurrence,development and change have close relationshipwith the change of people’s moods.Animalexperiment proved that significant changes occurredin the endocrine system of the gastric ulcer rats.

Construction of Larger Area Density-Uniform Plasma with Collisional Inductively Coupled Plasma Cells

The plasma density and electron temperature of a multi-source plasma system composed of several collisional inductively coupled plasma （ICP） cells were measured by a doubleprobe. The discharges of the ICP cells were shown to be independent of each other. Furthermore, the total plasma density at simultaneous multi-cell discharge was observed to be approximately equal to the summation of the plasma density when the cells discharge separately. Based on the linear summation phenomenon, it was shown that a larger area plasma with a uniform density and temperature profile could be constructed with multi-collisional ICP cells.

Development of plasma cell dyscrasias in a patient with chronic myeloid leukemia:A case report

BACKGROUND Chronic myeloid leukemia(CML)is a clonal hematopoietic stem cell disorder.Plasma cell dyscrasias are a rare heterogeneous group of hematological disorders.The co-occurrence of CML and plasma cell dyscrasias in the same patient is an extremely rare incident and has been reported in several cases in the literature.CASE SUMMARY In the present report,we described a rare case of the co-occurrence of CML and plasma cell dyscrasias in a 48-year-old man,and we discussed the reason why monoclonal gammopathy of undetermined significance progressed to smoldering multiple myeloma and eventually to multiple myeloma while being treated with dasatinib for CML.The tyrosine kinase inhibitor treatment and cytogenetic change may contribute to this phenomenon,and clonal hematopoiesis of indeterminate potential may lead to both CML and multiple myeloma cells in a patient.Future studies are warranted to further explain the hidden reasons.CONCLUSION This case highlights that gene translocation may contribute to initiation and sustainability of clonal proliferation.Moreover,the treatment with tyrosine kinase inhibitor and cytogenetic change may contribute to progression from monoclonal gammopathy of undetermined significance to smoldering multiple myeloma and eventually to multiple myeloma.

Three Cases of Plasma Cell Leukemia

Introduction: Plasma cell leukemia (PL) is a rare lymphoproliferative disorder characterized by the monoclonal proliferation of plasma cells in the marrow and blood peripheral. It is defined by a blood plasmacytosis greater than 2 G/l or a plasma cell level greater than 20% of leukocytes. It can be primitive or secondary to multiple myeloma (MM). We reported 3 cases of PL. Observations: Case 1: A 59 years old woman with fever, anemia with 7 g/dl, hyperleukocytosis 9200/mm3, thrombopenia 86 G/l inflammatory biological syndrome with CRP at 129 mg/l, hypercalcemia at 120 mg/l, renal failure with serum creatinine at 35 mg/l, urea at 0.85 g/l and 24-hour proteinuria at 0.98 g/24h. Β2 microglobulin at 10.34 mg/l. The blood smear shows dysmorphic plasma cells at 68% and the bone marrow at 79% of dysmorphic plasma cells. The immunophenotyping of blood cells, the electrophoretic serum protein, shows PL CD38+, secondary of a MM LAMBDA. Case 2: A 65-year-old man with type 2 diabetes presented, right femoral neck, anemia, hyperleukocytosis at 22 G/l, and thrombocytopenia at 99 G/l. There was no hypercalcemia, or kidney failure. The blood smear showed 28% of plasma cells and 9% of blasts. On the myelogram, the marrow was normal richness with significant medullary plasmacytosis (31%) made up of dysmorphic plasma cells. The CT scan showed a settling of the body of D5 with heterogeneous osteocondensation. The patient was transferred to hematology where she was treated with polychemotherapy. The evolution was unfavorable following a death due to malignant hypercalcemia. Case 3: A 62-year-old woman who had a 5-year follow-up of Ig G kappa multiple myeloma was treated with Melphalan, Prednisone, and thalidomide with a therapeutic break for 2 months. She came back to the Internal Medicine department with: severe global dehydration, anemia with externalized bleeding gingivorrhagia, pain in mechanical bones of the ribs, lower limbs, and pelvis, bilateral pneumonia. The biology found hyperleukocytosis at 99 G/l, anemia at 4.7 g/dl, thrombocytopenia at 31 g/l, hypercalcemia at 190 mg/l, renal failure with creatinine at 34 mg/L, and urea at 1.08 g/l, a biological inflammatory syndrome with CRP 294 mg/l. The smeared blood had shown 93% blood plasma cells and immunophenotyping showed CD38+. The patient died before specific treatment for the disease. Conclusion: Plasma cell leukemia is a rare atypical variant, complicating essentially multiple light chain myeloma. She must be suspected especially when there are cytological abnormalities such as major leukocytosis or thrombocytopenia, which are unusual in classical myeloma. Evolution is usually a very bad prognosis, with a median survival of 12 to 14 months for the form primary and 2 to 3 months for the secondary form.