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Presentation with SIRS: An Uncommon Cause
Natural killer (NK) cell malignancies are rare lethal tumors. Their rarity and myriad presentation often leads to a delayed diagnosis.
A 25 year old previously healthy Hispanic male presented with a two-month history of fever, night sweats and weight loss. Physical examination was significant for tachycardia, hypotension, and massive hepatosplenomegaly. He met the criteria for SIRS (systemic inflammatory response syndrome) and was admitted to the unit Admitting laboratory studies revealed pancytopenia, ( WBC 1600/uL, HgB 8.9 g/dl and Platelets 52 k/ul) elevated fibrin split products, ferritin (3817 ng/ml), LDH (1448 U/L ) and liver enzymes. The differential diagnoses included viral infections including HIV, hemophagocytic syndrome , infiltrative diseases and hematologic malignancies . Hemoglobin 8.9 g /dl White Blood Cell count 1600 / uL Platelets 52k /uL Ferritin 3817ng/ml LDH 1448 U/L Fibrin Split Products D-Dimer Fibrinogen Triglycerides
Latinos and Asians. Hepatitis A. splenomegaly (20cm) and bilateral inguinal nodes. influenza. DISCUSSION NK cell lymphomas represent less than 6 % of all lymphomas and are more common in Native Americans. non-nasal type (NNT) and aggressive (NKcLL). methotrexate.B and C. These cells were CD2. Chromosome Analysis on the bone marrow demonstrated deletions of chromosome 6 and isochromosome 17. β . Blood and CSF cultures for bacteria and fungi were negative as were Quantiferon and RPR. L. The bone marrow biopsy and aspirate was hypercellular (95-100%) with rare atypical lymphocytes identified in the aspirate smear( see figure). pancytopenia and DIC. cytoplasmic CD3epsilon positive and CD25. NKcLL has equal sex incidence . etoposide).The liver biopsy contained an infiltrate of identical cells Flow cytometry on the bone marrow demonstrated 11% NK cells(see figure). CT nasal cavities and sinuses was negative.cell receptor (α .CT abdomen-pelvis showed hepatomegaly (22cm). CD30. The patient was started on SMILE regimen of chemotherapy ( steroids. ifosfamide. Occasional hemophagocytic histiocytes were noted An inguinal node demonstrated effacement by a medium-sized monotonous infiltrate of malignant lymphocytes. They are classified as nasal type (NT). . Addition of high dose steroids to empiric antibiotics and hydration produced dramatic clinical improvement Hematology was consulted with bone marrow. cytomegalovirus. CD3 surface and T. Flow cytometry on the inguinal node showed similar findings. Serology for HIV. parainfluenza and adenovirus were negative. lymph node and liver biopsies performed. This pattern determined that this was an aggressive NK cell lymphoma/leukemia (NKcLL). hepatosplenomegaly. peaks in the third decade and presents with symptoms including fevers. Epstein-Barr virus was positive by polymerase chain reaction.asparaginase. CD56. γ and δ ) negative.
Fungal: histoplasmosis. paracoccidioidomycosis d. allopurinol. gold.with many patients dying within days to weeks of diagnosis. primary and secondary syphilis. Malignant diseases a. Primary biliary cirrhosis k. chancroid. hepatosplenomegaly and pancytopenia is extensive. i. epidemic keratoconjunctivitis. leprosy c. atypical mycobacterial infection. Autoimmune lymphoproliferative syndrome 3. carbamazepine. diphtheria. glanders. tuberculosis. primidone. Infectious diseases a. Conventional chemotherapy rarely results in remission . Silicone-associated m. Sjogren's syndrome g.Usually there is minimal involvement of the bone marrow and peripheral blood with extensive organ infiltration. Mixed connective tissue disease d. Viral : infectious mononucleosis syndromes (EBV. Parasitic: toxoplasmosis. tularemia. adenovirus. cat-scratch disease. coccidioidomycosis. Rickettsial: scrub typhus. Drug hypersensitivity: diphenylhydantoin. melioidosis. malignant histiocytosis. Bacterial: streptococci. plague. rubella. Graft-vs. CMV). Q fever 2. Dermatomyositis f. Experimental therapy with stem cell transplants have produced mixed results. filariasis f. hydralazine. herpes simplex. trypanosomiasis. Angioimmunoblastic lymphadenopathy j. varicella-zoster virus. Chlamydial: lymphogranuloma venereum. Systemic lupus erythematosus e. Serum sickness h. rickettsialpox. Rheumatoid arthritis b. hairy cell leukemia. brucellosis. amyloidosis b. leishmaniasis. herpesvirus-6. Immunologic diseases a. HIV. The Differential diagnosis for patients with a triad of fever. measles. DISEASES ASSOCIATED WITH LYMPHADENOPATHY 1. non-Hodgkin's lymphomas. etc. infectious hepatitis.-host disease l. trachoma e. vaccinia. herpesvirus-8 b. Juvenile rheumatoid arthritis c. Metastatic: from numerous primary sites . acute or chronic lymphocytic leukemia. Hematologic: Hodgkin's disease. staphylococci.
parasitic) Infectious mononucleosis AIDS Viral hepatitis Cytomegalovirus Subacute bacterial endocarditis Bacterial septicemia . Tangier 5. Mucocutaneous lymph node syndrome (Kawasaki's disease) h. Lymphomatoid granulomatosis e. Lipid storage diseases: Gaucher's. Congestive heart failure DISEASES ASSOCIATED WITH SPLENOMEGALY Enlargement Due to Increased Demand for Splenic Function Reticuloendothelial system hyperplasia (for removal of defective erythrocytes) Spherocytosis Early sickle cell anemia Ovalocytosis Thalassemia major Hemoglobinopathies Paroxysmal nocturnal hemoglobinuria Pernicious anemia Immune hyperplasia Response to infection (viral. bacterial. fungal. Castleman's disease (giant lymph node hyperplasia) b. Sarcoidosis c. Inflammatory pseudotumor of lymph node m. Other disorders a.4. Vascular transformation of sinuses l. Dermatopathic lymphadenitis d. Histiocytic necrotizing lymphadenitis (Kikuchi's disease) f. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) g. Fabry. Histiocytosis X i. Niemann-Pick. Familial mediterranean fever j. Severe hypertriglyceridemia k. Endocrine diseases: hyperthyroidism 6.
intrahepatic or extrahepatic Cavernous transformation of the portal vein Splenic vein obstruction Splenic artery aneurysm Hepatic schistosomiasis Congestive heart failure Hepatic echinococcosis Portal hypertension (any cause including the above): "Banti's disease" Infiltration of the Spleen Intracellular or extracellular depositions Amyloidosis Gaucher's disease . radiation. leukemias. strontium Marrow infiltration by tumors. Gaucher's disease Enlargement Due to Abnormal Splenic or Portal Blood Flow Cirrhosis Hepatic vein obstruction Portal vein obstruction.Congenital syphilis Splenic abscess Tuberculosis Histoplasmosis Malaria Leishmaniasis Trypanosomiasis Ehrlichiosis Disordered immunoregulation Rheumatoid arthritis (Felty's syndrome) Systemic lupus erythematosus Collagen vascular diseases Serum sickness Immune hemolytic anemias Immune thrombocytopenias Immune neutropenias Drug reactions Angioimmunoblastic lymphadenopathy Sarcoidosis Thyrotoxicosis (benign lymphoid hypertrophy) Interleukin 2 therapy Extramedullary hematopoiesis Myelofibrosis Marrow damage by toxins.
. lymphoid. lymphangiomas Splenic cysts Unknown Etiology Idiopathic splenomegaly Berylliosis Iron-deficiency anemia SPLENOMEGALY WITH APPROPRIATE HYPERSPLENISM Hereditary hemolytic anemias Hereditary spherocytosis Hereditary elliptocytosis Thalassemia Sickle cell anemia (infants) Autoimmune cytopenias Idiopathic thrombocytopenia Essential neutropenia Acquired hemolytic anemia Infections and inflammations Infectious mononucleosis Subacute bacterial endocarditis Miliary tuberculosis Rheumatoid arthritis (Felty SPLENOMEGALY WITH INAPPROPRIATE HYPERSPLENISM Congestion (Banti syndrome) Cirrhosis of the liver Portal vein thrombosis Splenic vein obstruction Budd-Chiari syndrome Congestive heart failure Infiltrative disease Leukemias. chronic and acute Lymphomas Polycythemia vera Agnogenic myeloid metaplasia Gaucher disease Niemann-Pick disease Glycogen storage disease . essential thrombocytosis) Angiosarcomas Metastatic tumors (melanoma is most common) Eosinophilic granuloma Histiocytosis X Hamartomas Hemangiomas.g.Niemann-Pick disease Tangier disease Hurler's syndrome and other mucopoly-saccharidoses Hyperlipidemias Benign and malignant cellular infiltrations Leukemias (acute. chronic. myeloid. monocytic) Lymphomas Hodgkin's disease Myeloproliferative syndromes (e. polycythemia vera. fibromas.
DISEASES ASSOCIATED WITH MASSIVE SPLENOMEGALYa Chronic myelogenous Gaucher's disease leukemia Lymphomas Chronic lymphocytic leukemia Hairy cell leukemia Sarcoidosis Myelofibrosis with myeloid Autoimmune hemolytic anemia metaplasia Polycythemia vera Diffuse splenic hemangiomatosis a The spleen extends greater than 8 cm below left costal margin and/or weighs more than 1000 g. DISORDERS ASSOCIATED WITH HEPATOMEGALY Inflammation Viral hepatitis Idiopathic neonatal hepatitis Bile acid enzyme defects Canalicular bile acid transport defects Hepatic abscess Toxin and drug reaction Cholangitis Kupffer cell hyperplasia Sepsis . DISEASES ASSOCIATED WITH MASSIVE SPLENOMEGALYa Chronic myelogenous leukemia Gaucher's disease Lymphomas Chronic lymphocytic leukemia Hairy cell leukemia Sarcoidosis Myelofibrosis with myeloid Autoimmune hemolytic anemia metaplasia Polycythemia vera Diffuse splenic hemangiomatosis a The spleen extends greater than 8 cm below left costal margin and/or weighs more than 1000 g.syndrome) Lupus erythematosus Sarcoidosis Brucellosis Leishmaniasis Schistosomiasis Malaria Amyloidosis TABLE 60-3. TABLE 60-3.
Granulomatous hepatitis Vitamin A toxicity Congestion Congestive heart failure Pericardial tamponade Budd-Chiari syndrome Infiltration Erythroblastosis fetalis Metastatic tumor Langerhans cell histiocytosis Leukemia Lymphoma Storage Glycogen storage diseases Mucopolysaccharidoses Gaucher disease Niemann-Pick disease a1-Antitrypsin deficiency Amyloidosis Hepatic porphyria Steatosis (fatty liver) Malnutrition (kwashiorkor) Hyperalimentation Cystic fibrosis Fatty acid oxidation defects Diabetes mellitus Galactosemia Wolman disease Reye syndrome Steatohepatitis Mitochondrial enzyme defects Tumors Congenital hepatic fibrosis/polycystic liver disease Hereditary hemorrhagic telangiectasia Hepatoblastoma Hepatocellular carcinoma CAUSES OF MASSIVE SPLENOMEGALY Chronic myeloid leukemia Gaucher disease Hairy cell leukemia Idiopathic and secondary myelofibrosis .
Early biopsies of affected organs must be obtained and appropriate ancillary studies must be performed prior to initiating definitive therapy. Leukemia 2005 .Leishmaniasis (kala azar) Lymphoma Malaria Thalassemia major When a diagnosis is elusive and the response to empiric treatment is poor. REFERENCES 1 Kwong YL. L-asparaginase and etoposide (SMILE) chemotherapy for advanced–stage. Lancet Oncology 2009. ifosfamide. Suzuki R. methotrexate. 10: 1093-1101 3 Yamaguchi M. 19: 2186-94 2 Kwong YL. Diagnosing rare conditions such as NKcLL lymphoma requires a high index of suspicion. Cancer Science 2008. Natural killer – cell malignancies: diagnosis and treatment. Phase I study of dexamethasone. relapsed or refractory extranodal natural killer (NK/T-cell lymphoma and leukemia. then “thinking out of the box” is warranted. 99: 1010-20 . Kwong YL et al. Management of T cell and natural – killer cell neoplasms in Asia: consensus statement from the Asian Oncology Summit 2009. Anderson BO. Advani R et al.
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