Normal Peripheral Smear Research Articles

Clinician-Ordered Peripheral Smear Review by a Pathologist Has Low Clinical Utility-A Reference Laboratory Perspective.

Clinician-ordered peripheral smear review by pathologist (CPSR) is commonly ordered and has been recommended for decades. However, the clinical utility of this labor-intensive test in the reference laboratory has not been examined. The objective of this study is to assess hematologic abnormalities identified in CPSR orders and to correlate them with complete blood count (CBC) and laboratory-derived smear review (LDSR) in the reference laboratory. Two hundred consecutive CPSRs with corresponding CBCs from April 2023 were run by Sysmex® XN-11 analyzers, and their peripheral smears were examined by a board-certified hematopathologist. Hematologic abnormalities of CPSRs were assessed, and the correlation between CPSR and CBC/LDSR was reviewed. Nearly one-third of CPSRs (29%) had normal peripheral smears and CBCs. The majority of CPSRs showed nonspecific quantitative abnormalities. When compared against CPSR results, LDSR criteria identified 100% of hematologic abnormalities appropriately. Samples that were not flagged for review by LDSR rules were also reviewed (n = 174) to rule out clinically meaningful false negatives. One minor discrepancy (0.6% of cases) of small platelet aggregates was observed in a patient with a reported platelet count of 139 K/uL that was missed by the LDSR process. In the reference laboratory setting, our findings demonstrate that LDSR adequately detects significant hematologic abnormalities and, therefore, CPSR should be discontinued.

Acute Liver Failure as a Presenting Feature in an Adolescent with Acute Lymphoblastic Leukemia

Background: Acute lymphoblastic leukemia (ALL) is a common pediatric malignancy, typically manifesting with symptoms of bone marrow and hematolymphoid organ infiltration. Although hepatic involvement in the form of hepatosplenomegaly is seen in nearly two-thirds of the patients, primary presentation as acute liver failure is rare. Clinical Description: A 12-year-old boy presented with complaints of abdominal distention with jaundice for the past 15–20 days, associated with transient fever of 6 days. Examination revealed pallor, icterus, and hepatosplenomegaly. A possibility of acute infectious or autoimmune hepatitis or hemolytic anemia was considered. Management: Liver function tests were deranged with hyperbilirubinemia with modest increase in transaminases and serum alkaline phosphatase along with deranged prothrombin time. The complete blood count showed pancytopenia with normal peripheral smear. Investigations for common infectious causes were noncontributory, as also those for autoimmune hepatitis. The direct Coombs test was also negative. In view of persistent pancytopenia with hyperbilirubinemia and hepatosplenomegaly, a bone marrow evaluation was done, which revealed B-cell ALL (B-ALL). Thus, the child was diagnosed with a case of ALL presenting with acute liver failure. The child was initially managed as a case of acute liver failure and on diagnostic confirmation, he was started on the B-ALL chemotherapy protocol as per his risk stratification with hepatic dose modification of chemotherapy. The child showed complete normalization of the liver functions by about 4 weeks of induction chemotherapy and achieved remission. Conclusions: A child presenting with acute liver failure may be having an underlying undiagnosed, clinically silent ALL. After ruling out common causes of acute liver failure, one must not forget the possibility of leukemic blast infiltration of the liver as a cause of liver failure. With early initiation of advanced chemotherapeutic induction regimens, there can be dramatic resolution of liver injury and remission of ALL.

To Evaluate the Clinical and Laboratory Profiles of Patients with Abdominal Tuberculosis in Western Odisha

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis) complex bacteria, is one of the oldest diseases known to affect humans and the leading cause of mortality worldwide. Milk contaminated with Mycobacterium bovis (reservoir cattle) can transmit tuberculosis to the gastrointestinal tract. TB can affect any portion of the digestive tract, from the buccal cavity to the anus, pancreato-biliary tree, and peritoneum. The peritoneum and ileocecal regions were most frequently affected. Aim: This study aimed to evaluate the clinical and laboratory profiles of patients with abdominal tuberculosis. Materials & Methods: The current study was conducted at the VSS Institute of Medical Sciences and Research (VIMSAR), Burla, located at 21.5027 o N and 83.8865 o E in western Odisha, India, after receiving approval from the Institutional Ethics Committee. Outdoor (OPD) and indoor (IPD) patients of the Division of General Medicine, VIMSAR, Burla The duration of the research was from November 2019 to October 2021 (24 months). This was a cross-sectional study. All patients were admitted to the Department of General Medicine with suspected abdominal tuberculosis. Results: The distribution of socioeconomic status in the study population according to the modified Kuppuswamy scale was predominated by the upper lower class IV population (60.3%), followed by the lower middle group (26%); only 13.7% belonged to class II of the upper middle group. The residential patterns showed that 74% of the cases belonged to the rural population, whereas only 26% lived in urban areas. Anemia was the major finding in comments on peripheral smear examination in 74.2% of the population and pancytopenia in 10.6% of cases. A minimum number of patients (4.5%) had a normal peripheral smear. Erythrocyte sedimentation rate by the Westergren method was increased in 87.7% of cases, and the rest of the population was within the normal range. Conclusion: This study has once again shown how common tuberculosis is in our country, particularly in underdeveloped Western Odisha, due to lack of hygiene and poverty. Abdominal tuberculosis has undergone modification over time because of the rampant and improper use of antibiotics and other drugs, thus creating a clinical dilemma. The irregularity of daily drug intake is another factor leading to the emergence of drug-resistant organisms.

S3238 A Case of Concurrent Cholecystitis and Stauffer Syndrome

Introduction: Stauffer syndrome (SS) is a paraneoplastic syndrome seen in some malignancies, most commonly 4-15% of primary renal cell carcinomas, resulting in nephrogenic hepatic dysfunction. SS commonly results in elevated alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and prothrombin time (PT) as well as decreased albumin in the absence of liver metastasis. The etiology of SS is unknown, although three have been suggested: elevated interleukin-6, elevated colony stimulating factor or, least likely, autoimmune. We describe a case of a woman presenting with right upper quadrant (RUQ) pain who was found to have indirect predominant hyperbilirubinemia and acute cholecystitis and renal mass on ultrasound. Case Description/Methods: An 81-year-old female presented to an outside hospital for RUQ and epigastric pain that worsened after fatty meals. Imaging showed acute cholecystitis as well as a right renal mass. Physical exam at the time was remarkable only for diffuse tenderness to abdominal palpation, most notably in the RUQ. There was no scleral icterus or costovertebral angle tenderness on exam. Labs on presentation can be seen in Table 1. Given the elevated indirect bilirubin, gastroenterology was consulted and suggested Gilbert syndrome (GS) or SS given their concern for renal cell carcinoma (RCC). The next day the patient underwent a laparoscopic cholecystectomy notable for acute gangrenous cholecystitis with cholelithiasis, and had rapid normalization of bilirubin over 48 hours. The patient followed with outpatient urology for renal biopsy, which was positive for clear cell RCC. Follow up imaging revealed scattered pulmonary nodules up to 1.1cm, with concern for metastasis. Surgery was deemed inappropriate and the patient was conservatively managed, given her wishes to prioritize quality of life and not undergo chemotherapy. (Figure) Discussion: This case illustrates an interesting clinical picture where a patient with confirmed cholecystitis also has a new renal mass, with elevated indirect bilirubin and PT, consistent with SS. The diagnosis of SS is made clinically, with hopeful resolution of abnormal lab values upon RCC resection. In this case, surgery was not indicated, hemolysis was ruled out with stable hemoglobin and normal peripheral smear, and the diagnoses of acute cholecystitis and RCC causing SS was made. In addition to hemolysis, GS, and Criggler-Najjar when working up indirect hyperbilirubinemia, it is imperative to include SS on the differential diagnosis.Figure 1.: CT abdomen with right renal mass. Table 1. - Patient labs on presentation and 2 days post-cholecystectomy Lab Admission Post-Op Day 2 Normal WBC Count (103 cells/uL) 17 14 4.1-9.3 Platelet (103/uL) 246 248 130-350 Hemoglobin (g/dL) 10.6 9.8 11-14.7 Albumin (g/dL) 3.3 2.7 3.5-5.2 Total Bilirubin (mg/dL) 2.8 0.9 0.1-1.2 Indirect Bilirubin (mg/dL) 2.4 0-0.9 Alkaline Phosphatase (IU/L) 96 102 30-115 AST (IU/L) 23 20 5-45 ALT (IU/L) 12 16 5-60 Lipase (U/L) 12 11-82 Prothrombin Time (s) 14.3 9.4-12.9 INR 1.2 0.83-1.14 AST = aspartate transaminase, ALT = alanine transaminase.

Orthopedic manifestation as the presenting symptom of acute lymphoblastic leukemia

IntroductionThe diagnosis of Acute lymphoblastic leukemia (ALL) is delayed due to vague presentation and normal hematological investigations. ObjectiveThe objectives were to identify the frequency of ALL cases presented to the orthopedic department and with normal hematological investigations. Material and methods250 consecutive ALL cases were retrospectively evaluated to identify cases with musculoskeletal manifestations, and laboratory investigations. ResultsTwenty-two patients (4- vertebral compression fractures, 12- joint pain, 6- bone pain), presented primarily to the orthopedic department. Six patients had a normal peripheral smear. ConclusionThe primary physician should maintain a high index of suspicion despite a normal peripheral smear.

PB1961 THREE CHRONIC MYELOID LEUKEMIA CASES THAT PRESENTED LIKE ESSENTIAL THROMBOCYTHEMIA

Background:2016 WHO classification divides myeloprolipherative neoplasms into bcr‐abl positive and bcr‐abl negative neoplasms, not only because of treatment difference also because of the heterogeneity of clinical presentations in Chronic Myeloid Leukemia (CML) patients. Classical CML patients present very high leukocyte count with or without thrombocytosis and splenomegaly. In literature there are few CML cases that have first presentations as Essential Thrombocythemia (ET) with not remarkable leukocytosis.Aims:We report three CML cases presented as classical ET.Methods:54 years old female patient referred to our hematology clinic because of very high platelet count. Platelet count was 2,578,000/mm3 and WBC count was 15,800/mm3. She had no clinical history of thrombosis and no splenomegaly. After bone marrow biopsy we started hydroxyurea 2000 mg/day. After 20 days platelet count was still higher than 2,000,000/mm3. PCR results of JAK‐2 was negative but bcr‐abl IS‐PCR was positive so we started imatinib 400 mg/day. After 10 days of imatinib, platelet count decreased to 1.400,000/mm3 and after one month of the imatinib treatment platelet count decreased to normal levels. The patient had no thrombosis during this period. After three months her PCR‐IS level decreased to 0,16%.Second case is 25 years old female patient that is referred from internal medicine because of high platelet count (678,000/mm3). Her WBC count was normal and JAK‐2 mutation test was negative, so we searched for CALR and MPL mutations for Essential Thrombocytosis and results were negative. Proceeding from the experience of former patient, although there was no leukocytosis, we tested bcr‐abl with PCR‐IS and result was positive. After bone marrow biopsy we started imatinib 400 mg per day. In cytogenetic analysis Philadelphia chromosome was positive. One month later platelet count decreased to normal level. Minimal leukopenia observed. After three months PCR‐IS value decreased to 0.45%.Third patient is 40‐year‐old female patient that is referred our clinic with high platelet count (747,000/mm3) WBC count was 8,800/mm3 and JAK‐2 mutation was negative. Although her WBC count was normal we tested bcr‐abl with IS‐PCR and result was 12% positive. After bone marrow biopsy we started imatinib 400 mg/day. After 20 days her platelet count decreased to normal level. After three months IS‐PCR result was 0.14%.Results:Here we discussed three CML patients with marked thrombocytosis without remarkable leukocytosis. All three female patients had similar clinical findings. All patients had no splenomegaly, had no thrombosis event. They all had minimal basophilia at presentation (1600/mm3, 600/mm3, 600/mm3) that was underestimated because in peripheral smears findings were normal. They all had very good response to imatinib treatment.Summary/Conclusion:CML patients that presents as ET are supposed to be rare but all three patients came to our center at dates between June and August 2018. Two of them had diagnosis of CML because of the experience from first patient. WHO classifications need bcr‐abl negativity for diagnosis of ET. With experience of these three patients we suggest to test all ET patients about bcr‐abl. Even tough normal WBC count and normal peripheral smear findings, absolute basophile count must be reconsidered.

A Study of Rapid Leishman Stain on Peripheral Blood Smear

Background: Romanowsky stains are universally used for routine staining of peripheral blood smears. Among these Leishman stain is most commonly used in hematology laboratories worldwide. This study was done to stain peripheral blood smears with modified Leishman stain (MLS) on Day 1, Day 5, Day 10 of preparation of the stain and to assess the quality of staining by scoring the stained smears by calculating the Quality Index (QI) and comparing the scores with normal peripheral smear. Methods: Study was done in the hematology section of our institute from December 2016 to February 2017 on a sample size of hundred and one. (MLS) was prepared by adding phenol to the Leishman stain. All cases were stained with modified Leishman stain on day 1, 5 and 10 after preparing the stain. All the smears were scored based on overall staining, cytoplasmic staining, nuclear morphology, red cell staining and platelet staining. Quality index was calculated by dividing the score obtained by maximum score possible. Result: Overall staining, cytoplasmic staining, nuclear morphology, red cell staining and platelet staining were better on day 10 after preparation of MLS when compared to day 1 and day 5. The Quality Index of stained smears normal leishman stained smear was 0.95, score on day 1 of preparing stain was 0.71, score on day 5 was 0.73 and day 10 of preparing stain was 0.89. Conclusion: MLS can be used for staining of thin peripheral blood smears in 4 minutes, unlike the conventional Leishman stain method which takes about 10-15 minutes.

Cytomegalovirus Primary Infection in an Immunocompetent Female with Mononucleosis Features: A Review of Mononucleosis-Like Syndromes

Background
 The clinical triad of fever, pharyngitis, and lymphadenopathy was first described in 1889 as “glandular fever” and later defined as infectious mononucleosis. We present a case report and review of mononucleosis-like syndromes in an immunocompetent patient. The review of common etiologies includes Epstein-Barr virus (EBV), acute human immunodeficiency virus (HIV), human herpesvirus 6 (HHV-6), cytomegalovirus (CMV), and Toxoplasmosis gondii.
 Case Vignette
 A 37-year- old, immunocompetent female presented with a three-week history of fever, pharyngitis, fatigue, night sweats, and abdominal pain. Physical examination revealed hepatosplenomegaly, but no lymphadenopathy, rashes, or tender joints. Investigations showed lymphocytosis and a normal peripheral smear. A Hematology consultation excluded hematologic malignancy. Her CD4/CD8 ratio was 0.2 in keeping with a viral infection, but EBV monospot test was negative. Serology for hepatitis B and C were negative. Human immunodeficiency virus (HIV) testing was not done in the absence of risk factors. Quantitative PCR for CMV was positive with a value of 965.25 units/mL. The patient was diagnosed with CMV viremia and treated with a two-week course of valganciclovir with resolution of symptoms. A two-month follow-up revealed a normal complete blood count and resolving hepatosplenomegaly.
 Conclusions
 In immunocompetent patients presenting with symptoms of mononucleosis, the differential diagnosis should include EBV, CMV, HHV-6, acute HIV and Toxoplasmosis gondii. CMV commonly affects young patients and is less associated with tonsillitis, pharyngitis, and lymphadenopathy. HHV-6 can present with headaches, encephalitis, and abdominal pain. Consideration of acute HIV mononucleosis should prompt early serologic testing. Toxoplasmosis is often associated with undercooked food or cat excrement, requiring anti-IgM antibody testing to distinguish from EBV. Although EBV infectious mononucleosis may be suspected, the general practitioner should consider a complete review of other infectious etiologies.

Disease Characteristics and Prognosis of Myelodysplastic Syndrome Presenting with Isolated Thrombocytopenia

▪BackgroundMyelodysplastic syndrome (MDS) presenting with isolated thrombocytopenia (TCP) represents a rare subset of this heterogenous malignancy. Prior small studies have suggested an indolent course. However, because this presentation is uncommon, there are clinical challenges in diagnosis and management. The aim of this study is to better define the morphologic, cytogenetic, and prognostic features of MDS presenting with isolated TCP.MethodsUsing the Northwestern University Electronic Data Warehouse, MDS patients were selected between 2004 and 2014 using ICD-9 codes and billing data. The diagnosis of MDS was determined by a practicing hematologist/oncologist according to World Health Organization criteria and confirmed with bone marrow biopsy results. Inclusion criteria were patients with isolated thrombocytopenia as defined by (PLT) <100×109/L, absolute neutrophil count (ANC) > 1.5×109/L and hemoglobin (Hgb) > 10 g/dl. Those with rapidly progressive TCP, confounding bone marrow disorders or those with suspected secondary causes of cytopenia were excluded. Data obtained from patient charts included demographics, peripheral blood counts, bone marrow biopsy results, bleeding complications, treatment history, and disease progression. IPSS-R scores were calculated on all patients. Overall survival rate and acute myeloid leukemia (AML) free event rates were determined via the Kaplan Meier method and compared between risk groups using the log-rank test. A P-value < 0.05 was considered statistically significant.ResultsBaseline characteristics:Of 404 MDS patients, 50 (12%) presented with isolated TCP. Among these 50, the median age was 72 and 34 were men (68%). Fourteen patients had TCP for greater than 2 years before diagnosis. Idiopathic thrombocytopenic purpura (ITP) was the presumed diagnosis in 17 patients. Median cell counts at the time of diagnosis were hemoglobin 12.0 g/dl, WBC 4.4 x 109/L and PLT 64 x 109/L. The most common cytogenetic profile was normal (n=28), and del 20q was the most common mutation seen in isolation (n=4) or in combination (n=3). Seven patients had complex cytogenetic profiles. Twenty-four patients fell into IPSS-R low or very low risk categories, 18 patients were IPSS-R intermediate (Int) risk and 7 patients were IPSS-R high or very high risk.Treatment + outcomes:Ten patients developed AML, 3 with low risk disease, 4 with Int-risk disease, 4 with high or very high-risk disease and 1 with an unknown IPSS-R score. Twenty-three patients were treated with hypomethylating agents including 5-Azacitidine or Decitabine. Three patients received thrombopoietin (TPO) receptor agonists. It is unclear by retrospective chart analysis if treatment resulted in improved outcomes. Fourteen of the 50 MDS patients presenting with isolated TCP died. Causes of death included AML (n=6), sepsis (n=4), intracranial bleeding (n=1), and unknown (n=1). Nine of the 14 patients who died were treated with hypomethylating agents, TPO agonists or both. There were 2 cases of major bleeding events, each intracranial and each in patients with PLT counts over 50.DiscussionIn our tertiary care center, the prevalence of isolated TCP in MDS was 12%. Patients with isolated TCP and MDS had similar demographics compared to patients with MDS at large. There were 17 patients (34%) that were first diagnosed with ITP. Need for bone marrow biopsy in asymptomatic patients with isolated TCP and normal peripheral smears is not clearly defined, however may be indicated in patients with demographics more typical of MDS (older male). The patients in this study distributed across all IPSS-R categories and many had an aggressive course. This is in contrary to previous studies that have suggested that MDS with isolated TCP has a relatively favorable prognosis. Next generation sequencing may uncover additional mutations in these patients that would help with risk stratification and development of targeted therapies. For example RUNX1 mutation carriers have been shown to present with thrombocytopenia and an increased risk of MDS/AML, and GATA2 mutants present with rapid onset MDS and often have a poor prognosis. Despite varying degrees of thrombocytopenia, incidence of major bleeding events was low. Treatment remains uncertain in this unique MDS subgroup. More studies are needed to address treatment options, including safety and efficacy of TPO agonists for this patient population. DisclosuresStein:Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Re-evaluation of Need for Bone Marrow Examination in Patients with Isolated Thrombocytopenia Contributors.

Diagnosis of immune thrombocytopenia (ITP) is based on clinical suspicion and normal peripheral smear except for thrombocytopenia. Bone marrow examination is carried out to rule out leukemia, myelodysplastic syndrome or aplastic anemia. However, in most cases, clinical diagnosis is not altered after the bone marrow reports. Hence, this present study was carried out to evaluate the justification for bone marrow examination in the setting of isolated thrombocytopenia. All patients presenting to the hematology OPD with isolated thrombocytopenia and suspected diagnosis of ITP, between October 2011 and April 2013, were included in the study. Data was collected from bone marrow reports and outpatient records. A total of 353 cases were found. 319 cases had features of typical ITP and the rest had some form of organomegaly and/or lymphadenopathy. Bone marrow examination in all cases revealed normal hematopoietic elements and prominence of megakaryocytes including juvenile forms with no novel diagnosis in any patient. Routine use of bone marrow examination in the diagnostic workup of isolated thrombocytopenia is not required in our center even if steroids are planned as a first line therapy. However, a detailed history, thorough examination with complete hemogram and peripheral smear examination are essential.

258 The Optic Nerve Sheath Diameter in Cerebral Infections

258 The Optic Nerve Sheath Diameter in Cerebral Infections

Index of Suspicion

Index of Suspicion

Index of Suspicion * Case 1: Lymphadenopathy, Prolonged Hematuria, Proteinuria, and Weight Loss in a Teenage Boy * Case 2: Red, Swollen, Painful Eye in a 12-year-old Boy With Methylmalonic Acidemia * Case 3: Ptosis and Diplopia After a Respiratory Infection in a 7-year-old Girl

* Abbreviations: ACE: : angiotensin converting enzyme CNIII: : cranial nerve III CNS: : central nervous system CSF: : cerebrospinal fluid CT: : computed tomography ESR: : erythrocyte sedimentation rate Ig: : immunoglobulin LN: : lupus nephritis RBC: : red blood cell SLE: : systemic lupus erythematosus TB: : tuberculosis WBC: : white blood cell A 14-year-old African American boy presents with fever, right-sided neck swelling, and weight loss of 20 lb over 2-month period. He denies night sweats, illness contacts, or recent travel. He was seen 1 month ago for fatigue, body aches, decreased appetite, and 10 lb weight loss over the previous month. Due to a family history of diabetes, urinalysis was performed, which revealed moderate hemoglobin, protein of 200 mg/dL, white blood cell (WBC) count of 13/high power field, and red blood cell (RBC) count of 5/high power field. He was scheduled to be re-evaluated in 1 week but has been lost to follow-up. The boy appears tired. His weight is 54.2 kg (>50th percentile), height is 165 cm (75th percentile), temperature is 38.9°C, heart rate is 106 beats/minute, respiratory rate is 20 breaths/minute, and blood pressure is 113/64 mm Hg. Physical examination reveals a 3 × 4 cm, tender, nonerythematous, nonfluctuant, slightly mobile right cervical mass located behind the sternocleidomastoid muscle. Findings on the rest of the examination are normal. Complete blood count reveals a WBC count of 5.5 × 103/μL, with 65% granulocytes, 30% lymphocytes, and 5% monocytes, platelet count of 267 × 103/μL, hemoglobin level 9.5 g/dL, hematocrit 29%, mean corpuscular volume 71 fL, RBC distribution width 15.2%, and normal peripheral smear. His erythrocyte sedimentation rate (ESR) is 65 mm/h, and C-reactive protein (CRP) level is 1.081 mg/dL. Metabolic panel reveals a sodium concentration of 141 mEq/L, potassium 4.5 mEq/L, chloride 111 mEq/L, bicarbonate 24 mEq/L, serum urea nitrogen 33 mg/dL, creatinine 1.7 mg/dL, total protein 6 g/dL, and albumin 1.9 g/dL. Urinalysis reveals a protein of 200 mg/dL and rare granular casts. Chest radiograph is normal. Blood and urine cultures are obtained, and a tuberculin test is performed on admission. Additional evaluation reveals the …

Index of Suspicion in the Nursery

A pair of twin sisters in the nursery remain persistently jaundiced at 1 month of age. The dichorionic diamniotic twins were born at 32 weeks’ gestation to a 29-year-old Asian woman. This was her third pregnancy, and she has a 1½-year-old daughter at home. The pregnancy and delivery were uncomplicated, with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively, for the twins. Twin A weighed 1,333 g and twin B weighed 1,469 g. The initial course for these appropriately grown twins was unremarkable, except for some respiratory distress requiring nasal cannula supplemental oxygen, thermoregulation in an isolette, gavage feedings with human milk, and apnea and bradycardia treated successfully with caffeine. They now are in cribs, receiving human milk exclusively, and otherwise well.The mother's blood type is O Rh-positive and the babies’ blood type is B Rh-positive. Results of a direct Coombs test are negative. Serum bilirubin profile, hemoglobin, and phototherapy treatment for one of the twins are outlined in Table 1; the profile is similar for both twins. Physical examination yields unremarkable findings except for jaundice. Both infants are growing along the 25th to 50th percentile for weight and occipitofrontal circumference. No hepatosplenomegaly or pallor is noted. An additional piece of history guides the diagnosis and prevents expensive evaluation.A history of prolonged jaundice in the older sibling while breastfeeding strengthened the suspicions of human milk jaundice. She had remained jaundiced for 3 months and is developmentally normal.Jaundice (serum bilirubin >10 mg%) beyond 2 weeks in a term or a preterm neonate is defined as prolonged jaundice and demands evaluation. The causes and evaluation are different for indirect and direct hyperbilirubinemia.Parenteral nutrition; sepsis, including urosepsis; and anatomic abnormalities of the intra- and extrahepatic biliary tract (biliary atresia) cause direct bilirubinemia. Jaundice caused by parenteral nutrition is diagnosed by history. Urosepsis causing jaundice is diagnosed by blood and urine culture. Abdominal ultrasonography, radioisotope scanning, and liver biopsy are used for diagnosing anatomic abnormalities. Congenital intrauterine infection is suspected in small-for-gestational age babies who have hepatosplenomegaly, microcephaly, chorioretinitis, and intracerebral calcifications in varying combinations.Indirect hyperbilirubinemia can be due to hemolytic and nonhemolytic disorders. Blood group incompatibility, structural abnormalities of the red cell membrane, red cell enzymatic defects, and disorders of hemoglobin synthesis are causes of hemolytic anemia and hemolytic jaundice.Congenital hypothyroidism, galactosemia, bowel obstruction, constipation, and human milk jaundice are examples of nonhemolytic causes of indirect hyperbilirubinemia. Crigler Najjar syndrome is a rare variety of nonhemolytic unconjugated hyperbilirubinemia.The twins in this case had indirect hyperbilirubinemia. Stable hemoglobin values, absence of hepatosplenomegaly, and appropriate reticulocytosis (6% at 1 month of age) made hemolytic anemia and hemolytic jaundice unlikely. A normal peripheral smear, obtained as part of a routine complete blood count, did not reveal abnormal red cell morphology. The state screen results were normal, ruling out galactosemia and hypothyroidism. The family history of human milk jaundice and absence of hemolytic disorders in the family (especially due to their Asian descent) pointed to the diagnosis of human milk jaundice. No confirmatory test can prove the diagnosis, but a trial off human milk on day 32 provided typical results (Table 2).Human milk jaundice, initially described by Arias and associates in 1963, is a poorly understood condition. Postulated mechanisms include: None of the mechanisms has been demonstrated consistently, and conflicting findings between in vivo observations and in vitro experiments have prevented clarification of the pathogenesis.Cessation of breastfeeding resulting in a decline in the serum bilirubin values, with rebound after reintroduction of human milk, was demonstrated in 1963 by Newman and Gross. The rebound generally does not lead to bilirubin concentrations noted before cessation of human milk feeding. No long-term neurodevelopmental effects result from human milk jaundice.Human milk jaundice differs from jaundice associated with breastfeeding or early breastfeeding jaundice. During the period that first-time breastfeeding mothers establish their milk supply, intake in their exclusively breastfed infants may be insufficient. The infants become dehydrated, lose weight, are constipated, develop jaundice, and may develop hypernatremia. Encouraging breastfeeding while supplementing with formula for a limited time resolves the jaundice. Phototherapy and intravenous fluids may be needed, depending on the serum bilirubin value and severity of dehydration. American Academy of Pediatrics guidelines for phototherapy should be reviewed to decide on the indication for phototherapy. Follow-up evaluation of breastfed babies after discharge by their primary pediatricians is recommended to recognize and institute appropriate management of this complication of breastfeeding.Human milk jaundice is a diagnosis of exclusion, but a history of a similar affliction in siblings and lack of hemolytic disorders in the family can be reasonable indicators of the diagnosis and help avoid expensive evaluation.

Agressive Lymphoma without Lymphadenopathy

Hepatosplenic T cell lymphomas are among a rare breed of aggressive non Hodgkin tumors that usually comprise of immature cytotoxic T cells. They most commonly involve young adults who generally present with constitutional symptoms of fever, weight loss and night sweats. Diagnosis can be challenging in the absence of lymphadenopathy and paucity of bone marrow findings. The discovery of neoplastic cells in peripheral blood is often a finding late in the clinical course. Demonstation of sinusoidal infiltration of T cells on either liver or splenic biopsy is ususally diagnostic. These cells are positive for clonal rearrangement of the γ gene of the T cell receptor which is a hallmark of this disease. Prognosis remains poor and most patients die within two years of diagnosis. We report a case of a patient who presented with unexplained fever and hepatosplenomegaly and after extensive workup was diagnosed with hepatosplenic T cell lymphoma.A 42 year old male with no significant past medical history presented with complains of abdominal pain, fever, malaise and 30lb weight loss over a period of six weeks. Pain was described as intermittent episodes of bilateral flank fullness associated with nausea and vomiting. He had traveled to Mexico 8 weeks earlier and according to him his symptoms began soon after his trip. He denied any headaches, cough, shortness of breath,. No dysuria, and no diarrhea. No smoking alcoholism or illicit drug use was reported. No sick or new sexual contacts. Family history was noncontributory. Vital signs were significant for temperature of 101 F. Physical examination revealed presence of marked hepatosplenomegaly. There was no lympadenopathy as well as no murmurs or rubs. Labs showed pancytopenia with blood counts of 2.7, 9.8 and 101 for WBC, Hb and platelets respectively. Additionally, alkaline phosphatase was elevated while rest of the liver functions was normal. Preliminary diagnosis of infectious versus malignant etiology was made. Peripheral smear did not show any malignant cells. Infectious workup returned negative for HIV, hepatitis, histoplasma, brucella, leptospira, coccidioidomycosis, syphilis, leishmaniasis as well as malaria and dengue fever. A bone marrow biopsy was performed for further evaluation and showed moderately hypercellular bone marrow with erythroid and megakaryocytic hyperplasia but no evidence of malignancy or granulomatous process. Meanwhile patient remained persistently febrile without any growth on blood cultues. An echo was normal with no evidence of endocarditis. Tuberculin test was non reactive. Given the results of the bone marrow biopsy and hepatosplenomegaly without any lymphadenopathy it was thought that a localized infiltrative process of he liver or spleen was likely. Patient thus underwent a liver biopsy disclosing intra sinusoidal collections of atypical CD3, CD7, TIA-1 and CD56 positive lymphocytes also bearing T cell receptor clonal rearrangement consistent with a diagnosis of hepatosplenic T-cell lymphoma which was further classified as gammadelta type.. He was subsequently started on ECHOP regimen and is currently in remission on a three month followup Hepatosplenic lymphoma, though is a rare tumor, should be considered in patients with unexplained hepatosplenomegaly without lymphadenopathy and normal peripheral smear. Liver biopsy is diagnostic most of the time.

Acute Myelogenous Leukemia with Splenic Infarcts Presenting as Fulminant Multi-organ Failure

A 60-year-old male was admitted with leukopenia, thrombocytopenia, splenic infarcts and a normal peripheral smear. Within few hours he rapidly deteriorated with fatal multi-organ failure. Autopsy revealed massive infiltration of leukemic cells in several organs. Acute myelogenous leukemia should be considered in a patient presenting with unexplained multiorgan failure.

Aleukemic leukemia cutis: Juvenile chronic granulocytic leukemia presenting with figurate cutaneous lesions

We report a 3 1/2-year-old girl who developed a figurate cutaneous eruption. Distinctive findings in her skin biopsies, as well as unusual red cell characteristics, in the presence of a normal peripheral smear and bone marrow biopsy, led us to suspect the diagnosis of preleukemic juvenile type chronic granulocytic leukemia. This is the first case we know of in which this diagnosis was suspected prior to abnormal findings in the peripheral smear or bone marrow.