Proliferative Disorders Research Articles

Reference gene selection for clinical chimeric antigen receptor T-cell product vector copy number assays

Background aimsReference genes are an essential part of clinical assays such as droplet digital polymerase chain reaction (ddPCR), which measure the number of copies of vector integrated into genetically engineered cells and the loss of plasmids in reprogrammed cells used in clinical cell therapies. Care should be taken to select reference genes, because it has been discovered that there may be thousands of variations in copy number from genomic segments among different individuals. In addition, within the same person in the context of cancer and other proliferative disorders, substantial parts of the genome also can differ in copy number between cells from diseased and healthy people. The purpose of this study was to identify reference genes that could be used for copy number variation analysis of transduced chimeric antigen receptor T cells and for plasmid loss analysis in induced pluripotent stem cells using ddPCR. MethodsWe used The Cancer Genome Atlas (TCGA) to evaluate candidate reference genes. If TCGA found a candidate gene to have low copy number variance in cancer, ddPCR was used to measure the copy numbers of the potential reference gene in cells from healthy subjects, cancer cell lines and patients with acute lymphocytic leukemia, lymphoma, multiple myeloma and human papillomavirus–associated cancers. ResultsIn addition to the rPP30 gene, which we have has been using in our copy number assays, three other candidate reference genes were evaluated using TCGA, and this analysis found that none of the four gene regions (AGO1, AP3B1, MKL2 and rPP30) were amplified or deleted in all of the cancer cell types that are currently being treated with cellular therapies by our facility. The number of copies of the genes AP3B1, AGO1, rPP30 and MKL2 measured by ddPCR was similar among cells from healthy subjects. We found that AGO1 had copy number alteration in some of the clinical samples, and the number of copies of the genes AP3B1, MKL2 and rPP30 measured by ddPCR was similar among cells from patients with the cancer cell types that are currently being treated with genetically engineered T-cell therapies by our facility. ConclusionsBased on our current results, the three genes, AP3B1, MKL2 and rPP30, are suitable for use as reference genes for assays measuring vector copy number in chimeric antigen receptor T cells produced from patients with acute leukemia, lymphoma, multiple myeloma and human papillomavirus–associated cancers. We will continue to evaluate AGO1 on our future samples.

A CLINICO-EPIDEMIOLOGICAL STUDY OF PSORIASIS IN TERTIARY CARE CENTRE: A RETROSPECTIVE ANALYSIS

Background: Psoriasis is an immune-mediated chronic proliferative skin disorder, predominantly involves skin, nails, and joints This research was conducted to study the clinical presentation, and management of psoriasis among patients in tertiary care hospital in South India The medical records of 257 psoriasis pati Methods: ents over the past one year (from January 2022 till December 2022) were examined by the investigators. Data were collected using a semi-structured form. Total 257 patients were Results: included in this study. Majority of patients were belonging to 50 and above age group. Male predominance (63%). Most common clinical variant was chronic plaque psoriasis (65.7%) followed by palmoplantar psoriasis (15.9%). Relapse of psoriasis was seen more among patients with a history of disease exacerbation in winter and in rainy season. Co-morbidities like diabetes mellitus and complications like PsA were associated with greater disease durations among the patients. In the current study, the proporti Conclusion: on of patients with chronic plaque psoriasis was high, most likely due to delayed diagnosis, followed by palmoplantar psoriasis and scalp psoriasis. Topical steroids for psoriasis in limited areas, oral methotrexate, and phototherapy for extensive psoriasis.

Massive synovial chondromatosis at the sinus tarsi

Synovial chondromatosis (SC) is a rare, locally aggressive proliferative disorder affecting the synovial membrane of joints, tendon sheaths and bursae. There is a high incidence of local recurrence but malignant transformation is rare. Manifestations at the foot and ankle are very rare with only a few reported cases so far carrying the risk of delayed diagnosis or misdiagnosis. Here, we report a case of massive SC appearing as an increasingly painful mass over the sinus tarsi in a 52-year old female. Symptoms resolved completely after complete tumor resection. The diagnosis was confirmed by histopathology. A review of the literature is provided.

PET/TC con FDG y nuevos radiofármacos en pacientes con mieloma múltiple

Multiple myeloma is a monoclonal gammopathy, a clonal proliferative disorder of plasma cells that produces a protein called M or myeloma protein in the bone marrow, usually IgG or IgA. It accounts for 1% in the general cancer statistics and represents 10% of all hematologic tumours, with a cumulative incidence in Spain of about 5/100,000/year. The incidence increases with age, so that 50% of cases are diagnosed in patients over 75years of age, being infrequent in the population under 40years of age. This publication details the indications of FDG PET/CT for the staging and response assessment in patients with MM, accepted by the international working group on myeloma, as well as new molecular imaging radiopharmaceuticals with potential value for personalised medicine.

Study of Association of Tear Film Abnormalities in All Grades of Primary Pterygium Cases using Schirmer’s Test 1 & 2

Background: One of the frequent ocular disorders affecting people in their middle and advanced years of age is pterygium. It is a benign, proliferative disorder of the conjunctiva and subconjunctival tissue that has the potential to impair vision. Clinical examination can quickly diagnose and stage it. Sunlight exposure is believed to be the most significant element in the development of pterygium. Dry eyes, smoking, prolonged outdoor activity, low socioeconomic position, and high altitudes are additional risk factors. If it grows onto the cornea's centre, a major problem is the obliteration of the visual axis. Another reason for impaired vision is the development of irregular astigmatism brought on by flattening of the cornea in the horizontal meridian. Aim: The aim of the study was to determine the association of Tear film abnormalities with all grades of pterygium Materials and Methods: The current study was a single-center observational study that was conducted out from December 2020 to July 2022 in the ophthalmology division of Sri Siddhartha Medical College hospital and Research Centre, Tumkur, on patients who attended the OPD with primary pterygium, regardless of treatment. According to the study's inclusion criteria, a total of 91 participants who were diagnosed with pterygium were enrolled. Results: The majority of participants (34.07%) were between the ages of 61 and 70. Pterygium prevalence was higher in females (65.93%) than in males (34.07%) with a 1.96:1 ratio. The majority of the participants (69.23%) had progressive pterygium, followed by regressive pterygium (15.38%) & atrophic pterygium (15.38%). The mean scores of the schirmers tests 1 and 2 in both eyes differed significantly statistically depending on the degree of pterygium (p=0.03). Conclusions: Pterygium is one of the most common ocular conditions in our nation, primarily affecting people from lower socioeconomic backgrounds. Pterygium has been linked to tear film abnormalities. Keywords: Dry eyes, Pterygium, Tear Film.

Langerhans cell histiocytosis as a clonal disease of mononuclear phagocyte system

Langerhans cell histiocytosis (LCH) belongs to histiocytic proliferative diseases, which are rare in clinical practice; however they pose significant challenges both for their diagnosis and choice of therapeutic strategies. Histiocytic proliferative diseases are the scope of oncology; nevertheless, at the diagnostic stage the patients are referred to pediatricians or dermatologists. That is why the interdisciplinary interaction of various specialties and common approaches to their classification, diagnosis and treatment are important for the management of patients with histiocytic proliferative disorders.
 Accumulation of the studies on the LCH pathophysiology has promoted the development of new diagnostic algorithms and treatment methods. After the fact of MAPK signal pathway activation had been established, the potential target for therapy was identified. Neoplastic nature of LCH has been hypothesized. If confirmed, we can expect actual diagnostic algorithms being elaborated, in particular, the potential to predict the disease depending on the tumor clone mutation type. The unique characteristics of LCH including proliferate clonality (presumable of neoplastic nature), the disease course with spontaneous regression and frequent relapses and tropism to certain tissues (target organs) make up the grounds for further in-depth studies of the disease.

FDG-PET/CT and new radiopharmaceuticals in patients with multiple myeloma

Multiple myeloma is a monoclonal gammopathy, a clonal proliferative disorder of plasma cells that produces a protein called M or myeloma protein in the bone marrow, usually IgG or IgA. It accounts for 1% in the general cancer statistics and represents 10% of all hematologic tumours, with a cumulative incidence in Spain of about 5/100,000/year. The incidence increases with age, so that 50% of cases are diagnosed in patients over 75 years of age, being infrequent in the population under 40 years of age. This publication details the indications of FDG PET/CT for the staging and response assessment in patients with MM, accepted by the international working group on myeloma, as well as new molecular imaging radiopharmaceuticals with potential value for personalised medicine.

Comparative Expression Analysis of Breakpoint Cluster Region-Abelson Oncogene in Leukemia Patients.

Leukemia is a proliferative disorder of myeloid and lymphoid cells that may lead to death. Different types of leukemia have been reported, and several genetic and environmental factors are involved in their development. The Philadelphia chromosome causes the most common mutation known as breakpoint cluster region-Abelson oncogene (BCR-ABL1), which shows abnormal protein tyrosine kinase (PTK) activity. Basically, this activity is accountable for activating multiple pathways, including the inhibition of cell differentiation, controlled proliferation, and cell death. As a result of the absence of kinase activity, this mutation leads to the uncontrolled proliferation of leukocytes, causing chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and chronic lymphocytic leukemia (CLL). This study aimed to evaluate the level of BCR-ABL1 expression in patients with these types of leukemias through qPCR. In brief, PBMCs were isolated from blood samples of patients, RNA was extracted from PBMCs, cDNA was synthesized, and the transcript levels of BCR-ABL1 in patients with each type of leukemia were determined by qPCR. The clinical, demographical, and experimental data were analyzed among CML, AML, and ALL patients. Results: The BCR-ABL1 expression levels are variable in all studied groups and are 90, 30-35, and 1-2.5% in CML, ALL, and AML, respectively. Demographic characteristics such as gender, BMI, age, family history, and clinical parameters along with CBC are also associated with the prevalence and diagnosis of leukemia. In a comparative expression analysis, the expression of BCR-ABL1 is onefold high in AML, but four- and sevenfold high in ALL and CML, respectively, as compared with normal levels. Conclusions: In this study, a significant difference was observed in the expression levels of BCR-ABL1 between CML (p = 0.0043) and ALL (p = 0.0006) and between CML and AML groups, and a high expression of BCR-ABL1 was noted in CML as compared with ALL and AML.

Control of Mitochondrial Activity by the Ubiquitin Code in Health and Cancer.

Cellular homeostasis is tightly connected to the broad variety of mitochondrial functions. To stay healthy, cells need a constant supply of nutrients, energy production and antioxidants defenses, undergoing programmed death when a serious, irreversible damage occurs. The key element of a functional integration of all these processes is the correct crosstalk between cell signaling and mitochondrial activities. Once this crosstalk is interrupted, the cell is not able to communicate its needs to mitochondria, resulting in oxidative stress and development of pathological conditions. Conversely, dysfunctional mitochondria may affect cell viability, even in the presence of nutrients supply and energy production, indicating the existence of feed-back control mechanisms between mitochondria and other cellular compartments. The ubiquitin proteasome system (UPS) is a multi-step biochemical pathway that, through the conjugation of ubiquitin moieties to specific protein substrates, controls cellular proteostasis and signaling, removing damaged or aged proteins that might otherwise accumulate and affect cell viability. In response to specific needs or changed extracellular microenvironment, the UPS modulates the turnover of mitochondrial proteins, thus influencing the organelle shape, dynamics and function. Alterations of the dynamic and reciprocal regulation between mitochondria and UPS underpin genetic and proliferative disorders. This review focuses on the mitochondrial metabolism and activities supervised by UPS and examines how deregulation of this control mechanism results in proliferative disorders and cancer.

Disseminated Juvenile Xanthogranuloma with a Novel MYH9-FLT3 Fusion Presenting as a Blueberry Muffin Rash in a Neonate

Juvenile xanthogranuloma (JXG) is a benign proliferative histiocytic disorder of the dendritic cell phenotype. It mostly presents in the pediatric age group as a solitary skin lesion. We describe a rare case of an infant born with disseminated JXG who presented with a blueberry muffin rash at birth. A term infant was noted to have multiple petechiae, purple nodules, and macules (1 mm-2 cm in diameter) and hepatosplenomegaly, at the time of birth. Further investigations revealed thrombocytopenia and direct hyperbilirubinemia and a magnetic resonance imaging showed scattered tiny foci of restricted diffusion in multiple areas of the brain. Patient received multiple platelet transfusions in the first few weeks with gradual improvement in thrombocytopenia. Ultimately, a biopsy of one of the lesions revealed the diagnosis of disseminated JXG with notable atypical features. Somatic mutation analysis showed a novel MYH9-FLT3 fusion, but a bone marrow biopsy was negative. The lesions faded over time, relative to patient's growth and normal neurodevelopment was noted at 18 months of age. JXG should be considered in the differentials of blueberry muffin rash in an infant. Although, JXG is mostly a self-limited condition, congenital disseminated JXG may be associated with significant morbidity and mortality.

Extranodal Rosai-Dorfman Disease of the Nasal Septum: A Case Report

Rosai-Dorfman Disease (RDD) is a rare, benign histiocytic proliferative disorder mostly involving the lymph nodes. Extranodal disease can occur in the skin and soft tissue including the mucosal surface, central nervous system, gastrointestinal tract, and breast. Here, a case of a 17-year-old Indo-asian girl is presented, who came to the Ear Nose Throat (ENT) Outpatient Department (OPD) with a mass in her left nostril for the past two years. A sessile globular mass from the left nasal septum was seen during diagnostic visual endoscopy. A Computerised Tomography (CT) scan of the paranasal sinus revealed a rather large right maxillary sinus with a soft tissue density lesion filling it and obliterating the osteomeatal complex, while blood tests revealed an increased eosinophilic count. The nasal tumour was removed, and its histological analysis revealed characteristics of RDD. This is typically sporadic histiocytosis with emperipolesis in the cells. Clinically, the condition is benign, and all that is required is conservative therapy and periodic monitoring of its progression. Surgical excision is rarely advised until the disease has grown to an unmanageable size and is causing respiratory impairment or a cosmetic deformity. Currently, therapy revolves around surgical and immunosuppressive treatments, but the optimal diagnostic and therapeutic management of RDD remains to be defined.

Disparity in the detection of chromosome 15 centromere in patients of African ancestry with a plasma cell neoplasm

PurposeFluorescence in situ hybridization (FISH) is the current gold standard assay that provides information related to risk stratification and therapeutic selection for individuals with plasma cell neoplasms. The differential hybridization of FISH probe sets in association with individuals’ genetic ancestry has not been previously reported. MethodsThis retrospective study included 1224 bone marrow samples from individuals who had an abnormal plasma cell proliferative disorder FISH result and a concurrent conventional G-banded chromosome study. DNA from bone marrow samples obtained from the G-banded chromosome study was genotyped, and a biogeographical ancestry prediction was carried out. ResultsUsing a cohort of individuals with a plasma cell neoplasm, we identified reduced hybridization of a chromosome 15 centromere FISH probe (D15Z4). Metaphase FISH studies of cells with 2 copies of chromosome 15 demonstrated a failure of the D15Z4 FISH probe to hybridize to one chromosome 15 centromere, revealing a false-positive monosomy 15 FISH result in some individuals. Surprisingly, individuals with a monosomy 15 FISH result had a median African ancestry of 77.2% (95% CI 74.1%-80.3%), compared with a median African ancestry of 2.2% (95% CI 2.0%-2.5%) in the non–monosomy 15 cohort (P value = 9.4 × 10−10). Thus, individuals with African ancestry had an 8.02-fold (95% CI 3.73-17.25) increased probability of having a false-positive monosomy 15 result (P value = 9.92 × 10−8). ConclusionThis study emphasizes a concern regarding the reliability of diagnostic genomic tools and their application in interpreting genetic testing results in diverse patient populations. We discuss alternative methodologies to better represent different ancestry groups in clinical diagnostic testing.

Incidental findings involving the temporomandibular joint on computed tomography and magnetic resonance imaging.

The temporomandibular joint (TMJ) is frequently imaged in head and neck computed tomography (CT) and magnetic resonance imaging (MRI) studies. Depending on the indication for the study, an abnormality of the TMJ may be an incidental finding. These findings encompass both intra- and extra-articular disorders. They may also be related to local, regional or systemic conditions. Familiarity with these findings along with pertinent clinical information helps narrow the list of differential diagnoses. While definitive diagnosis may not be immediately apparent, a systematic approach contributes to improved discussions between clinicians and radiologists and better patient management.

Arf1 facilitates mast cell proliferation via the mTORC1 pathway

Mast cells are one of major players in allergic responses. Mast cell activation via the high affinity IgE receptor (FcεRI) causes degranulation and release of de novo synthesized proinflammatory cytokines in a process that involves vesicle trafficking. Considering that the GTPase ADP-ribosylation factor 1 (Arf1) orchestrates and maintains membrane traffic and organelle structure, it seems likely that Arf1 contributes to mast cell activation. Actually, it has been reported that pharmaceutical blockade of the Arf1 pathway suppresses cytokine secretion and mast cell degranulation. However, physiological roles of Arf1 in mast cells remain elusive. Here, by using a genetic approach, we demonstrate that Arf1 is required for optimal mTORC1 activation upon IL-3 and facilitates mast cell proliferation. On the other hand, contrary to our expectation, Arf1-deficiency had little impact on FcεRI-induced degranulation nor cytokine secretion. Our findings reveal an unexpected role of Arf1 in mast cell expansion and its potential as a therapeutic target in the mast cell proliferative disorders.

Arginase-1+ bone marrow myeloid cells are reduced in myeloproliferative neoplasms and correlate with clinical phenotype, fibrosis, and molecular driver.

Philadelphia-negative myeloproliferative neoplasms (MPN) are clonal myeloid proliferative disorders characterized by sustained systemic inflammation. Despite its renowned importance, the knowledge concerning the inflammatory pathophysiology of these conditions is currently limited to studies on serum cytokines, while cellular immunity has rarely been investigated. In the present study, we targeted Arginase-1 immunosuppressive myeloid cells in the bone marrow of MPN patients and healthy controls and investigated their clinical and prognostic significance. We demonstrated that MPN are characterized by a significant reduction of bone marrow immunosuppressive cells and that the number of these cells significantly correlates with several clinical and histopathological features of diagnostic and prognostic importance. Moreover, we identified an unreported correlation between a reduction of Arginase-1+ bone marrow cells and the presence of CALR mutations, linking tumor-promoting immunity and molecular drivers. Finally, we postulate that the reduction of bone marrow Arginase-1+ immunosuppressive cells may be due to the migration of these cells to the spleen, where they may exert systemic immunomodulatory function. Altogether, this study preliminary investigated the contribution of cellular immunity in the pathogenesis of myeloproliferative neoplasms and identified a possible interesting therapeutic target as well as a set of new links that may contribute to unraveling the biological mechanisms behind these interesting hematological neoplasms.

Eliminating Senescent Cells Can Promote Pulmonary Hypertension Development and Progression.

Senescent cells (SCs) are involved in proliferative disorders, but their role in pulmonary hypertension remains undefined. We investigated SCs in patients with pulmonary arterial hypertension and the role of SCs in animal pulmonary hypertension models. We investigated senescence (p16, p21) and DNA damage (γ-H2AX, 53BP1) markers in patients with pulmonary arterial hypertension and murine models. We monitored p16 activation by luminescence imaging in p16-luciferase (p16LUC/+) knock-in mice. SC clearance was obtained by a suicide gene (p16 promoter-driven killer gene construct in p16-ATTAC mice), senolytic drugs (ABT263 and cell-permeable FOXO4-p53 interfering peptide [FOXO4-DRI]), and p16 inactivation in p16LUC/LUC mice. We investigated pulmonary hypertension in mice exposed to normoxia, chronic hypoxia, or hypoxia+Sugen, mice overexpressing the serotonin transporter (SM22-5-HTT+), and rats given monocrotaline. Patients with pulmonary arterial hypertension compared with controls exhibited high lung p16, p21, and γ-H2AX protein levels, with abundant vascular cells costained for p16, γ-H2AX, and 53BP1. Hypoxia increased thoracic bioluminescence in p16LUC/+ mice. In wild-type mice, hypoxia increased lung levels of senescence and DNA-damage markers, senescence-associated secretory phenotype components, and p16 staining of pulmonary endothelial cells (P-ECs, 30% of lung SCs in normoxia), and pulmonary artery smooth muscle cells. SC elimination by suicide gene or ABT263 increased the right ventricular systolic pressure and hypertrophy index, increased vessel remodeling (higher dividing proliferating cell nuclear antigen-stained vascular cell counts during both normoxia and hypoxia), and markedly decreased lung P-ECs. Pulmonary hemodynamic alterations and lung P-EC loss occurred in older p16LUC/LUC mice, wild-type mice exposed to Sugen or hypoxia+Sugen, and SM22-5-HTT+ mice given either ABT263 or FOXO4-DRI, compared with relevant controls. The severity of monocrotaline-induced pulmonary hypertension in rats was decreased slightly by ABT263 for 1 week but was aggravated at 3 weeks, with loss of P-ECs. Elimination of senescent P-ECs by senolytic interventions may worsen pulmonary hemodynamics. These results invite consideration of the potential impact on pulmonary vessels of strategies aimed at controlling cell senescence in various contexts.

Selective inhibition of integrin αvβ6 leads to rapid induction of urinary bladder tumors in cynomolgus macaques.

Administration of a novel and selective small molecule integrin αvβ6 inhibitor, MORF-627, to young cynomolgus monkeys for 28 days resulted in the rapid induction of epithelial proliferative changes in the urinary bladder of 2 animals, in the absence of test agent genotoxicity. Microscopic findings included suburothelial infiltration by irregular nests and/or trabeculae of epithelial cells, variable cytologic atypia, and high mitotic rate, without invasion into the tunica muscularis. Morphologic features and patterns of tumor growth were consistent with a diagnosis of early-stage invasive urothelial carcinoma. Ki67 immunohistochemistry demonstrated diffusely increased epithelial proliferation in the urinary bladder of several monkeys, including those with tumors, and αvβ6 was expressed in some epithelial tissues, including urinary bladder, in monkeys and humans. Spontaneous urothelial carcinomas are extremely unusual in young healthy monkeys, suggesting a direct link of the finding to the test agent. Inhibition of integrin αvβ6 is intended to locally and selectively block transforming growth factor beta (TGF-β) signaling, which is implicated in epithelial proliferative disorders. Subsequent in vitro studies using a panel of integrin αvβ6 inhibitors in human bladder epithelial cells replicated the increased urothelial proliferation observed in monkeys and was reversed through exogenous application of TGF-β. Moreover, analysis of in vivo models of liver and lung fibrosis revealed evidence of epithelial hyperplasia and cell cycle dysregulation in mice treated with integrin αvβ6 or TGF-β receptor I inhibitors. The cumulative evidence suggests a direct link between integrin αvβ6 inhibition and decreased TGF-β signaling in the local bladder environment, with implications for epithelial proliferation and carcinogenesis.

Long-term Outcomes of Diffuse or Recurrent Tenosynovial Giant Cell Tumor Treated with Postoperative External Beam Radiation Therapy

Tenosynovial giant cell tumor (TGCT) is a rare proliferative disorder of synovial membrane that previously was known as pigmented villonodular synovitis. Primary treatment involves surgical resection; however, complete removal of all disease involvement is difficult to achieve. Radiation may be useful to reduce the risk of recurrence. We report and update our institutional experience treating diffuse and recurrent TGCT with postsurgical external beam radiation therapy. We performed a retrospective chart review of 30 patients with TGCT from 2003 to 2019 treated with radiation therapy. Each patient was evaluated for demographics, radiation treatment parameters, surgical management, complications, and outcome. With mean follow-up of 82 months (range, 3-211), 24 patients (80%) who underwent surgery followed by radiation therapy did not experience any further relapse, and all 30 patients achieved local control (100%) with additional salvage therapy after radiation therapy. The most common site of disease was the knee (n=22, 73%), followed by the ankle (n=5, 16%) and the hand (n=3, 10%). Seven patients (24%) presented at time of initial diagnosis and 23 (76%) presented with recurrent disease after surgical resection, with an average of 2.6 surgical procedures before radiation therapy. After resection, 18 of 30 patients (67%) demonstrated residual TGCT by imaging. The median radiation therapy dose delivered was 36 Gy (range, 34-36 Gy) in 1.8 to 2.5 Gy/fractions for 4 weeks. In the assessment of posttreatment joint function, 26 sites (86%) exhibited excellent or good function, 2 (7%) fair, and 2 poor (7%) as determined by our scoring system. There were no cases of radiation-associated malignancy. Among patients with diffuse or recurrent TGCT, postsurgical external beam radiation therapy provided excellent local control and good functional status, with minimal treatment-related complications. Postsurgical radiation therapy is a well-tolerated noninvasive treatment that should be considered after maximal cytoreductive resection to prevent disease progression and recurrence.

Plasma cell mucositis masquerading as squamous cell carcinoma- a surgical dilemma: a rare case report and review of literature

<p>Plasma cell mucositis is a rare, idiopathic, multifocal, benign proliferative disorder affecting upper aerodigestive tract. It is a very rare condition and less than 50 cases reported in literature. A 62 years old female patient reported with complaints of oral discomfort, superficial erosive ulceration on the tongue, and burning sensation on eating food for last 2 years. Initially, Incisional biopsy of the involved mucosal area confirmed the diagnosis of well differentiated squamous cell carcinoma for which hemi-glossectomy was done. However histopathological examination submitted revealed a hyperplastic epithelium with a dense infiltrate of mature polyclonal plasma cells in the superficial layer of lamina propria, for which plasma cell mucositis was made a diagnosis. Plasma cell mucositis is a diagnosis of exclusion, to be differentiated from other infective, reactive, autoimmune, allergic and neoplastic disorders with plasma cell infiltrates. Management includes topical, intralesional, systemic corticosteroids and debulking procedures. Regular follow-up is essential due to the possibility of its clinical persistence and chances of malignant transformation.</p>

Family History of Hematologic Malignancies and Risk of Multiple Myeloma in Black Americans

Introduction: Multiple Myeloma (MM) is the most common hematologic malignancy in Black Americans. Standardized incidence rates are increasing, consistent with an aging population, and are 2- to 3- fold higher among Black Americans compared to White Americans for reasons that remain unclear. Methods: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE) study of myeloma (955 MM cases; 1,316 sex-, race-, age-, geography- matched controls), we investigated the risk of MM associated with family history of cancer and differences by race. We estimated risk using odds ratios and corresponding 95% confidence intervals adjusted for confounders calculated from logistic regression. Results: Overall, MM risk in cases with a first degree relative affected with any hematologic malignancy was significantly elevated compared to controls (OR=1.36, 95% CI 1.02-1.82; P=0.038). Myeloma risk associated with a family history of MM was higher than the risk associated with any hematologic malignancy (OR=2.13, 95% CI 1.20-3.79; P=0.001), and the magnitude of this effect was greater for Black Americans (OR=4.88, 95% CI 1.90-12.51; P=0.001) than White Americans (OR=1.03, 95% CI 0.45-2.32; P=0.951) with similar relationships observed among first degree relatives with any plasma cell proliferative disorder (ORBlack=5.34, 95% CI 2.11-13.54; P=0.0004 and ORWhite=1.18, 95% CI 0.59-2.37;P=0.642) and with increasing numbers of affected relatives (P-trend=0.001). Conclusions: Findings confirm our previous report that the excess risk of MM observed in Black Americans may be attributed to shared germline and environmental susceptibility. Studies, which include family history of plasma cell proliferative disorders, to determine screening effectiveness in high-risk populations are warranted.