Hematolymphoid Malignancies Research Articles

Profile of uncommon primary adult hepatic malignancies at a tertiary care center

Background: Hepatocellular carcinoma has been the most common primary malignancy of the liver in adults, followed by cholangiocarcinoma. The less common malignancies are those arising from the vascular endothelial cells, neuroendocrine cells, hematolymphoid tissues, and mesenchymal tissues. Imaging studies alone may pose a diagnostic challenge, due to the variable appearances. Histological review of the tissue specimen along with immunohistochemical stains are imperative for diagnosis. However, a multidisciplinary approach is necessary to make an accurate diagnosis and help in management.
 Materials and methods: The unusual adult primary hepatic malignancies were studied in 2 years period with clinic-radiological and biochemical correlation and also the age and sex distribution were determined. Ethical approval was obtained. Statistical analysis used: SPSS version 23.0.
 Results: A total of 24 liver malignancies were encountered. Metastatic tumors and tumor-like lesions were excluded. The patient's clinico-radiological findings and laboratory investigations were noted. A total of 6 unusual non-hepatocellular malignancies were seen and identified based on morphology and special stains. Out of 6 non-hepatocellular malignancies, 3 were neuroendocrine carcinomas, 2 were leiomyosarcomas and 1 was a hematolymphoid malignancy. Radiologic impression and biochemical parameters helped arrive at a definitive opinion as the lesions were not typical of this location. A high index of suspicion along with the immunohistochemical profile finally facilitated the diagnosis.
 Conclusions: The cases of primary non-hepatocellular malignancies are unexpected. A multidisciplinary approach is mandatory.

The Citrus Flavanone Hesperetin Induces Apoptosis in CTCL Cells via STAT3/Notch1/NFκB-Mediated Signaling Axis.

Hesperetin is a natural compound known for its cholesterol-lowering effect and a wide range of pharmacological activities. Investigating the potential anticancer activities of Hesperetin in malignant hematolymphoid cell lines HuT78 and MJ, derived from patients with Cutaneous T-Cell Lymphomas (CTCL). The cytotoxic effect of Hesperetin on two different CTCL cell lines, HuT78 and MJ, was assessed by MTS-based colorimetric assay. Apoptosis, cell cycle, ROS (Reactive Oxygen Species) and molecular analysis were performed using flow-cytometry and immunoblotting. Hesperetin-treated CTCL cells were arrested at the sub-G1 phase of cell cycle with the concomitant decrease in the expression of the cell cycle regulator protein cyclin B. In addition, the study found that the cellular treatment with Hesperetin caused an induction of apoptosis, which was independent of ROS generation. Hesperetin caused a significant decrease in the expression level of anti-apoptotic protein Bcl-xL and an increase in cleaved caspase-3 and PARP proteins in CTCL cells. Furthermore, Hesperetin treatment in CTCL cells down-regulated the expression of Notch1 and phosphorylation of STAT3 (Tyr705) and inhibited NFκBp65. This study highlights the anticancer properties of Hesperetin. Which induces apoptosis in CTCL cells via STAT3/Notch1/NFκB mediated signaling pathway, suggesting that further development of this novel class of flavonoid may contribute to new drug discovery for certain hematolymphoid malignancies.

Histopathological Profile of Pediatric Solid Malignant Neoplasm in Tertiary Care Centre

Background: There is rise in incidence of pediatric tumors all over the globe. In developing country like India childhood morbidity & mortality is mainly due to malnutrition & infections but there is significant rise in incidence of pediatric neoplasm which is now becoming a distinct & important entity to be dealt upon. Objectives: To study the incidence of solid pediatric malignant neoplasms, the age and sex distribution in cases of solid pediatric malignant neoplasms and various histopathological appearance and patterns of solid pediatric malignant neoplasms. Methods: An observational study of solid pediatric malignant neoplasms in childhood was done over a period of 2 years, from November 2016 to October 2018 in the age group of 0-14 years. The institutional ethical committee Government Medical College & Hospital, Aurangabad- Maharashtra India has given approval for this study. Result: Total 180 cases of solid pediatric neoplasm were studied. The total sample received during study period was 180 out of which 55 were malignant. Out of 55 malignant tumors 30 were observed among males and 25 were observed among females. Most of the malignant tumors were observed among 11-14 yrs age group, followed by those observed among 0-3 years. Conclusion: It can be concluded from our study that common solid malignancies in pediatric age group excluding hemato-lymphoid malignancies include nephroblastoma, retinoblastoma, neoplasms of gonads & bone tumors. Male predominance is a salient feature of childhood tumors. Most common solid tumors of childhood originate from embryonal tissue and tumors of epithelial origin are rare. A larger pediatric population based study would provide us with greater insight details about solid pediatric neoplasms.

Extranodal NK/T-Cell Lymphomas: The Role of Natural Killer Cells and EBV in Lymphomagenesis.

Natural killer (NK) cells are lymphocytes involved in innate and adaptive immune functions. They are the presumed cell of origin of distinct hematolymphoid malignancies, including aggressive NK-cell leukemia and extranodal NK/T-cell lymphoma (ENKTL). This review focuses on the role of NK cells and Epstein–Barr virus (EBV) in ENKTL pathogenesis.

Gynaecological Manifestations of Systemic Malignancies

Context: Round cell tumours and haematolymphoid malignancies presenting with gynaecological symptoms are not infrequent. Often, those are a component of a symptom complex which has a clue towards the aetiology. Round cell tumours or haematolymphoid malignancies presenting solely as structural lesions of the female genital tract are really uncommon. A series of 10 such cases are depicted here. Aims: 1. To study the epidemiological pattern among these patients 2. To assess the prognosis of such cases. Settings and Design: Single institutional observational study. Method and Material: Cases were selected from the case record files and data collected. CT scan of (Thorax + Abdomen + Pelvis)was done in all cases. The diagnosis was established by histopathology and immunohistochemistry in each case. Statistical Analysis Used: Descriptive statistics used for analysis. Results: Median age of presentation was 25 years. Median duration of symptoms was 3 months, most commonly pain abdomen. Fallopian tubes and ovaries were involved in 90% cases, with pelvic and retroperitoneal lymphadenopathy in 80% cases. Majority of the underlying malignancies were haematolymphoid malignancies. Conclusions: Clue to suspicion of underlying round cell tumours or haematolymphoid malignancies are younger age, mass lesion of uterus and adnexa, regional lymphadenopathy and absence of ascites. Earlydiagnosis is necessary since the above group of diseases represent curable malignancies even at advanced stages so we need to treat before their performance score deteriorates.

Bone Lesions of the Hand and Wrist: Systematic Approach to Imaging Evaluation

Hand and wrist bone lesions comprise a special subset of masses. When evaluating these lesions, relative tumor incidence always should be considered. For bone lesions occurring throughout the body, the incidence of primary bone tumors is much lower than that of nonneoplastic bone diseases, metastatic diseases, and hematolymphoid malignancies.1 In the hand, benign bone lesions greatly outnumber malignant lesions, as highlighted in a published case series on hand and foot bone lesions.1 Of 52 bone lesions of the hands and feet evaluated with histopathology, the relative incidence was pseudotumors (38%), benign primary tumors (38%), inflammatory/postinfectious lesions (17%), and malignant tumors (12%).1 A large percentage of benign bone lesions of the hand and wrist will have characteristic features on imaging and will not require histopathologic assessment. Appropriate management for indeterminate bone lesions of the hand and wrist will include imaging surveillance or biopsy. Comprehending relative incidence, relevant clinical features, and typical imaging characteristics of various bone lesions of the hand and wrist will assist in formulating a short and relevant differential diagnosis to guide management.

Role of ancillary techniques in diagnosis of challenging common hematological malignancies

Background: Usually, hematolymphoid malignancies present as generalized lymphadenopathy, splenomegaly, and cytopenias. However, sometimes, this may not be the scenario, and that is where the challenge arises. These unusual scenarios are present either in extranodal lymphoma or extramedullary acute leukemia, especially occurring at unusual sites and these often lays down a diagnostic dilemma. Aims: This study aims to evaluate the utility of extensive workup with amalgamation of radiological imaging, immunohistochemical panel, and flow-cytometry to diagnose these unusual hematolymphoid malignancies. Materials and Methods: This is a retrospective observational study of results obtained from a series of nine patients with various unusual manifestations of extranodal lymphoma or acute leukemia at tertiary center of Northern India since the past 18 months. Results: All nine cases which showed variable and unusual clinical presentations were studied involving all available ancillary techniques in the form of immunohistochemistry (IHC), flow cytometry (FCM). These cases because of their unusual presentation in the form of recurrent pericardial/peritoneal effusion, abdominopelvic masses, chronic cervicitis, and subacute intestinal obstruction mimicked various neoplastic and nonneoplastic lesions. IHC and/or FCM evaluating CD34, MPO, CD117 along with Tdt and B/T-cell markers played a vital role for a definitive diagnosis of aleukemic myeloid sarcoma primarily involving intestine, T-cell lymphoblastic lymphoma (LBL) in ovary, diffuse large B-cell lymphoma in ovary, cervix, and intestine with peritoneal carcinomatosis. Two cases of mediastinal masses revealed primary thymic B-cell lymphoma and T-cell LBL, respectively. Conclusion: Cases have highlighted the unusual clinical presentation of hematolymphoid malignancies and elicit the importance of providing a definitive opinion, which is mandatory to give appropriate effective and timely management for the best outcome.

Treating hematolymphoid malignancies during COVID-19 in India: Challenges and potential approaches

The rapidity of both the geographical expansion and the sudden increase in the numbers of COVID-19 cases poses critical challenges to public health and has the potential to severely limit non COVID-19 medical care. With early reports from China & Italy suggesting that patients with hematolymphoid malignancies along with the other cancers are at the highest risk of severe infection compared to the normal population; it is a challenge on how to best manage such patients in India. There is a lack of reliable evidence and it is yet unclear as to what the best practices are with regards to patients with hematolymphoid malignancies in this time of crisis. We present a collection of best practices and guidance from literature search, society resources and communications with experts. Despite the unique and unprecedented nature of this challenge, our approach should reflect the principles of beneficence and non-maleficence as outlined in the Hippocratic oath.

Targeted Gene Silencing in Malignant Hematolymphoid Cells Using GapmeR.

Delivery of conventional antisense oligonucleotides or small interfering RNA (siRNA) molecules into hematolymphoid cells for targeted gene silencing has been proven to be difficult. Here, we describe a simple protocol to knockdown specific gene(s) in malignant hematolymphoid cells using "GapmeR." This protocol could be applicable to a wide range of cell-types and thus solves an important problem for researchers working with cell lines or primary cells derived from patients with hematolymphoid malignancies.

Correlation between multidrug-resistant bacteria colonization and bloodstream infections in children with hematolymphoid malignancies in a tertiary cancer center in India

Correlation between multidrug-resistant bacteria colonization and bloodstream infections in children with hematolymphoid malignancies in a tertiary cancer center in India

Incidence and severity of self-reported chemotherapy side-effects in patients with hematolymphoid malignancies: A cross-sectional study

Background: Chemotherapy is an indispensable part of the treatment regimen for most cancer types. However, it is difficult to predict the chemotherapy-related side effects in patients with cancer. Objectives: In this study, we aimed to assess the incidence and severity of self-reported chemotherapy-related side effects in patients with cancer. Materials and Methods: This cross-sectional study, with a univariate descriptive design was conducted on patients with blood cancers, including leukemia, lymphoma, and myeloma. Patients who were admitted to the hemato-oncology department of our tertiary care center in northern India to receive the second cycle of chemotherapy were interviewed. Patients were interviewed regarding the symptoms they experienced after the first cycle of chemotherapy using the chemotherapy symptom assessment scale. The incidence of the chemotherapy side-effects experienced by the patients after the first cycle of chemotherapy was assessed, and the most severe and common symptoms that led to botheration in the patients receiving chemotherapy were identified. Results: A total of 100 patients were enrolled in the study. Majority of the patients were men and aged between 41 and 50 years, with a diagnosis of lymphoma and an Eastern Cooperative Oncology group performance status of 1. The five most common severe symptoms reported by the patients after receiving the first cycle of chemotherapy were nausea, vomiting, constipation, pain, and shortness of breath. The three symptoms that led to maximum botheration in the patients after the first cycle of chemotherapy were nausea, vomiting, and diarrhea. The five symptoms that caused the least botheration in the patients were constipation, pain, change in temperature, problems with the skin, and problems with the mouth. Conclusion: The most common symptom experienced by the patients is nausea (93%), which is also the most commonly experienced severe symptom (80%). Identifying these symptoms and their severity can help in planning symptom management more comprehensively. Moreover, planned health education for patients with cancer can help us provide better evidence-based quality care to those receiving chemotherapy.

Pediatric cancers in Bihar: A retrospective tertiary cancer center study.

Background:There is lack of information regarding pattern of distribution of pediatric cancers in Bihar. Aim: The aim of this study is to identify the pattern of distribution of pediatric cancers.Objectives:To analyze demographic data, type, and pattern of pediatric cancers in Bihar by retrospective clinical audit.Materials and Methods:All individual consecutive patients between ages 0 and 18 years registered in the Department of Medical and Pediatric Oncology from January 1, 2018 till December 31, 2018, were enrolled in this study. Data pertaining to age, sex, and type of cancer were retrieved from clinical database by retrospective audit and stratified into hematolymphoid and solid pediatric cancer cohorts. Frequency distribution and descriptive statistics were used to analyze the data using SPSS version 17.0.Results:A total of 247 pediatric cancers were registered, of which 142/247 (57%) and 15/247 (43%) were pediatric hematolymphoid and solid cancers, respectively. The median age was 9 years, while male-to-female ratio was 2.26. Acute lymphoblastic leukemia (ALL), 76/247 (31%) was the most common pediatric cancer overall. Hodgkin's lymphoma, 27/142 (19%) was the second most common hematolymphoid malignancy, after ALL was 76/142 (54%). Among solid tumors, Wilms’ tumor was the most common, 28/105 (27%) followed by Ewing's sarcoma, 16/105 (15%), and germ cell tumor, 15/105 (14%). Central nervous system malignancies were among the least common solid tumor cancers, 3/105 (3%).Conclusion:ALL and Hodgkin's lymphoma are the most common pediatric cancers. Among solid malignancies, Wilms tumor, Ewing's sarcoma, and Germ cell tumor are predominant.

Prevalence of Vitamin D deficiency in treatment-naive individual consecutive cancer patients

Background: There is a lack of information regarding Vitamin D deficiency in treatment-naive cancer patients.Aim: The aim of this was to study the prevalence of Vitamin D deficiency in cancer patients.Objectives: The objective was to measure the extent of Vitamin D insufficiency and deficiency in treatment-naive consecutive individual cancer patients from Eastern India.Materials and Methods: All consecutive new patients seen between April 2019 and September 2019 were offered a baseline test to measure serum 25-hydroxy Vitamin D [25 (OH) D] levels along with routine investigations. Vitamin D insufficiency was diagnosed when serum 25 (OH) D level was between 20 and 30 ng/mL, whereas patients with a level <20 ng/mL were designated as Vitamin D deficient. Patients with a Vitamin D level <10 ng/mL were termed as having severe Vitamin D deficiency. Descriptive statistics and frequency distribution were used in SPSS software, and Pearson's Chi-squared test was used to compare between the categorical variables.Results: Of 252 patients, 140 (56%) were female; median age was 51 years (range, 19–84 years) and 204 (81%) were diagnosed with solid organ malignancies. Mean (±standard deviation) Vitamin D level was 18.94 (±10.4). 169/252 (67%) had Vitamin D deficiency, whereas another 52/252 (21%) had Vitamin D insufficiency. Among these, 44/169 (26%) had severe Vitamin D deficiency. Females were more deficient compared to males, 76% versus 55% (P = 0.002). Vitamin D deficiency in younger (<50 years) and older (>50 years) population was 73% and 61% (P = 0.144); while that in solid versus hematolymphoid malignancies was 69% versus 58% (P = 0.173). In the three most common tumors, namely breast (21%), colorectal (8%), and ovary (8%), Vitamin D deficiency was noted in 75% of patients in each group. Vitamin D deficiency was the highest (84%) in esophageal and stomach cancer patients.Conclusion: More than two-thirds of Indian cancer patients are Vitamin D deficient. Patients with upper gastrointestinal, breast, colorectal, and ovarian cancers and female patients are the most vulnerable groups.

Traumatic Ulcerative Granuloma with Stromal Eosinophilia: CD30 analysis and clonality for T cell receptor gene re-arrangement

IntroductionTraumatic Ulcerative Granuloma with Stromal Eosinophilia (TUGSE) is a rare oral ulcerated lesion of uncertain etiology, showing eosinophil-rich granulation tissue, with occasional large atypical CD30 positive mononuclear cells. It had been suggested that it may represent an oral counterpart of cutaneous lymphomatoid papulosis, with a potential to evolve into CD30 + T cell lymphoma ObjectivesTo compare TUGSE and non-specific oral ulcers (NSU) clinically, histopathologically and by clonality analysis for T-cell receptor re-arrangement, aiming to determine whether TGUSE with atypical cells is a lymphomatous premalignant condition, and whether therapeutic approach should be radical or conservative. Materials and methodsRetrospective archival analysis included 17 TUGSE and 8 NSU cases. Histopathological parameters included mean eosinophil number per high power field (HPF), presence of infiltration of deep soft tissues and presence of atypical cells. Immuno-morphometry comprised of the mean number of CD30+ atypical cells per HPF. T-cell receptor (TCR) gene rearrangement by polymerase chain reaction (PCR) was performed in all cases showing atypical cells. Clinical and follow up data were retrieved from files. ResultsTUGSE showed a significantly higher mean eosinophil number/HPF in comparison to NSU (7.0 + 4.2 cells and 2.3 + 1.72, respectively; p < 0.001). Atypical cells were found in 9 (53%) cases of TUGSE and in only 1 (11%) case of NSU. CD30+ atypical cells were found in 7 (41%) cases of TUGSE and only in 1 (11%) case of NSU. Mean number of CD30+ cells/HPF was 0.23 + 0.19 (range 0 – 0.54 cells/HPF) for TUGSE. In the only NSU case with CD30+ cells, their density was 0.52/HPF. All lesions with atypical cells were polyclonal for TCR. All cases were self-limiting, with no recurrences, after 3–9 years (mean 4.6 years) follow up. ConclusionsAnalysis found no support to the suggestion that TUGSE with atypical cells represents the oral counterpart of lymphomatoid papulosis or predisposes the lesions for a hematolymphoid malignancy. Suggestions for radical therapeutic approach and long-term follow-up are probably unjustified, with no recurrences or malignancy recorded following conservative treatment alone for a period of up to 9 years of follow-up. Staining for CD30 and PCR for TCR gene rearrangement should be reserved only for rare cases with abundant large atypical cells and/or unusual clinical behavior.

1266. Cancer among HIV-Positive Patients in Cali, Colombia: A Retrospective Hospital-Based Study

BackgroundCancer has been a significant feature of the HIV epidemic from the beginning, being the most frequent Kaposi sarcoma (KS) and hematolymphoid malignancies. However, the behavior of these two diseases is limited in our context. The study aimed to determine the trends of cancer among HIV/AIDS patients between 2011 and 2016.MethodsA retrospective hospital-based study was conducted at Fundación Valle del Lili, Cali, Colombia. The study included HIV-positive patients diagnosed with cancer after infection. HIV registry was cross-linked with a population-based cancer registry to obtain IARC/WHO ICD-O-3 classification and follow-up information on all patients. A descriptive analysis of the variables was performed. Survival analysis was carried out using the Kaplan–Meier method. Differences between cancer survival were assessed through the log-rank test.ResultsFrom 2,051 HIV-positive patient’s records between 2011 and 2016, 95 patients were diagnosed with cancer after HIV infection. The median age was 43 years (IQR=33–57), and 88% were male. Types of cancer were: Kaposi’s sarcoma 17%, hematolymphoid malignancies 21% and other cancer 62%. The probability of cancer diagnosis after HIV diagnosis was 36.26% (CI 95% [26.53–46.05]) at one-year follow-up for all malignancies. Overall survival of the patients was 77.41% (CI 95% [64.76–86]) at 5 years follow-up, since HIV diagnostic. Hematolymphoid malignancies and KS survival were 50% (CI 95% [20.85–73.61]) and 65.63% (CI 95% [35.80–84.14]) at 5 years follow-up, respectively. There was a statistically significant difference between KS, hematolymphoid and other cancer cases survival (P = 0.0178).ConclusionThis study showed the role of HIV in cancer survival for KS and hematolymphoid malignancies mainly, in a developing country. It is necessary to join efforts in our context to reduce HIV cases and associated malignancies.Disclosures All authors: No reported disclosures.

Vascular endothelial growth factor (VEGF) expression in induction phase chemotherapy of acute lymphoblastic leukemia

Background Leukemia is a hematolymphoid malignancy originating from bone marrow. The progression of hematolymphoid malignancies depends on new formation of vasculature, called angiogenesis. Angiogenesis is regulated by vascular endothelial growth factor (VEGF), which is secreted by paracrine and autocrine signaling mechanisms.&#x0D; Objective To evaluate VEGF expression in induction phase chemotherapy of acute lymphoblastic leukemia (ALL) patients. &#x0D; Methods This prospective, cohort study was conducted in ALL patients admitted to Dr. Wahidin Sudirohusodo Hospital, Makassar, South Sulawesi, from October 2016 to October 2017. Subjects’ VEGF levels were measured at diagnosis and at the end of induction chemotherapy.&#x0D; Results VEGF levels were analyzed in 59 patients, 29 of whom were diagnosed with standard risk ALL and 30 patients with high risk ALL. VEGF levels were significantly decreased after induction phase chemotherapy in standard risk ALL and in high risk ALL subjects. There was no significant difference in VEGF levels before induction phase chemotherapy between the standard and high risk groups (P=0.405). There was also no significant difference in VEGF levels after induction phase chemotherapy between the two risk groups (P=0.094).&#x0D; Conclusion The VEGF level is significantly lower after ALL induction phase chemotherapy in both the standard risk and high risk ALL groups. However, there are no significant differences in VEGF levels between the standard and high risk groups before as well as after induction phase chemotherapy.

RETROSPECTIVE ANALYSIS OF MULTIPLE MYELOMA PATIENTS IN A TERTIARY CARE CENTRE OF UTTARAKHAND

Introduction: Multiple myeloma (MM) is a hemato-lymphoid malignancy of B-cell type. It occurs due to the accumulation of malignant monoclonal plasma cells. The exact incidence of MM in India is not well-known. The current study presented the clinical characteristics, radiological findings and laboratory findings of MM patients who were initially treated at the tertiary care centre, Dehradun, Uttarakhand (India).&#x0D; Material and methods: Retrospective analysis of the medical records of 123 consecutive patients with MM who were initially presented to Hemato-Oncology department during the period from January 2014 to December 2018. Peripheral blood finding, bone marrow diagnosis, flow-cytometry analysis, serum protein and immunofixation electrophoresis finding, biochemical parameter, histo-pathological and cytological diagnosis, if any, urine examination finding and radiological examination of cases shall be compiled and tabulated. Diagnosis of symptomatic multiple myeloma was done based on The International Myeloma Working Group criteria for the diagnosis of MM.&#x0D; Result: The study included 123 cases of multiple myeloma with male: female ratio of 2:1, mean age of 59.88 ±11.08 years and range of 32-87 years. The back pain (n=106, 86.2%) was the common presenting complaint followed by inability to walk (n=90,73.2%). CT scan and/or MRI scan finding of MM patients, the lytic lesion was found in 107 patients (87%) and was found significant with its correlation with ISS/DS plus staging system (pvalue 0.013). The most location was dorso-lumbar spine (n=72, 67.28%) followed by skull (n=37, 34.58%) and ribs (n=19, 17.75%). Hemoglobin (Hb) analysis showed 92.7 % (n=114) cases were anemic with mostly had normocytic (n=95,77.2%). 62.6%(n=77) of cases showed rouleaux formation while 23.57% (n=29) cases were circulating plasmacytoid lymphocytes or plasma cells. The raised ESR values was found in 89.33% (n=67) of cases. Diagnosis of cases shows 99.2% (n=122) of cases diagnosed as secretory MM while 1 (0.8%) case diagnosed as non-secretory MM.&#x0D; Conclusion: MM is a disease with a inconsistent clinical presentation with multiple system involvement. Younger age of disease onset is some noteworthy features of myeloma in Uttarakhand state of India. Bony pain associated with generalized weakness is the commonest presentation, normocytic normochromic anemia with rouleaux formation, raised ESR, raised total protein with hypoalbuminemia, hypercalcemia, presence of M band and presence of &gt;10% plasma cell in bone marrow is clue to diagnosis in MM cases .&#x0D; Keywords: Multiple Myeloma, Uttrakhand, Hemato-lymphoid malignancy

Germline Predisposition to Hematolymphoid Neoplasia.

The 2017 Workshop of the Society for Hematopathology/European Association for Haematopathology aimed to review clinical cases with germline predisposition to hematolymphoid neoplasms. The Workshop Panel reviewed 51 cases with germline mutations and rendered consensus diagnoses. Of these, six cases were presented at the meeting by the submitting pathologists. The cases submitted to the session covering germline predisposition included 16 cases with germline GATA2 mutations, 10 cases with germline RUNX1 mutations, two cases with germline CEBPA mutations, two germline TP53 mutations, and one case of germline DDX41 mutation. The most common diagnoses were acute myeloid leukemia (15 cases) and myelodysplastic syndrome (MDS, 14 cases). The majority of the submitted neoplasms occurring in patients with germline predisposition were myeloid neoplasms with germline mutations in GATA2 and RUNX1. The presence of a germline predisposition mutation is not sufficient for a diagnosis of a neoplasm until the appearance of standard diagnostic features of a hematolymphoid malignancy manifest: in general, the diagnostic criteria for neoplasms associated with germline predisposition disorders are the same as those for sporadic cases.

A Survey of Somatic Mutations in 41 Genes in a Cohort of T-Cell Lymphomas Identifies Frequent Mutations in Genes Involved in Epigenetic Modification.

Here, we utilize a high throughput sequencing panel that covers several genes known to be recurrently mutated in certain T-cell lymphoma subtypes as well as genes frequently mutated in other hematolymphoid malignancies, including myeloid neoplasms. This panel was applied to formalin-fixed, paraffin-embedded tissue from 84 biopsies from 78 patients selected for this study. The biopsies included ones a with a diagnosis of T-cell lymphoma (n=79), including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS; n=26) and angioimmunoblastic T-cell lymphoma (AITL; n=13), as well as 5 cases of atypical T-cell proliferations. KMT2C and KMT2D, which code for proteins involved in histone modifications, were the 2 most frequently mutated genes in our cohort and were altered across a range T-cell lymphomas. Mutations in TET2 and DNMT3A, which are involved in regulating DNA methylation, were also found in a variety of T-cell lymphoma categories. The RHOA G17V mutation that is frequently found in AITL was identified 5 of 13 (40%) cases of AITL and in 3 of 26 (12%) cases of PTCL-NOS, but not in biopsies involved by other T-cell proliferations. Our study adds to the already significant evidence from other investigators that, among T-cell lymphomas, the RHOA G17V variant is specific for AITL and PTCL-NOS. In contrast, variants in epigenetic modifier genes do not appear to be particularly specific for T-cell lymphoma subcategories evaluated in our study.

UNUSUAL PRESENTATION OF HAIRY CELL LEUKEMIA: A CASE REPORT

Hairy cell leukemia is a chronic B cell lymphoproliferative disorder,which is uncommon and constitutes around two percent of hematolymphoid malignancies. HCL commonly involves bone marrow and spleen and rarely peripheral blood . Splenomegaly is a prominent feature and is seen in around 70 to 100% of HCL cases as reported in various case reports. Sometimes the absence of splenomegaly rules out the diagnosis of HCL and is misdiagnosed as aplastic anemia. Thus the aim of our study is to understand the importance and keep a high level of suspicion in such cases. As in present case there was no evidence of splenomegaly clinically or radiology, but the morphologic features on biopsy had suggested HCL which was further confirmed on immunophenotyping. The purpose of this case report is to highlight the importance of the fact that HCL can present even without splenomegaly.&#x0D; Keywords: Hairy cell leukemia, Splenomegaly, Immunohistochemistry