[Show abstract][Hide abstract] ABSTRACT: A case of acute promyelocytic leukemia (APL) with
insertion to 7q is described and compared to reported cases of APL with negative retinoic acid receptor alpha (
) abnormality. In this report, we describe the case of a 2-year-old boy who presented with bone pain and was found to have pancytopenia. Bone marrow examination showed morphologic and immunophenotypic findings typical of APL, but conventional cytogenetics, fluorescence in situ hybridization (FISH), and real-time polymerase chain reaction (RT-PCR) showed no evidence of
rearrangements. The only cytogenetic abnormality found was a small insertion in 7q, and three copies of
. Gene sequencing results became available after initiating therapy but were not informative. We describe the rarity of such cases and discuss how the typical morphologic and immunophenotypic findings of APL, coupled with the definite absence of
rearrangement (by FISH and RT-PCR), present a diagnostic and classification dilemma, raising the possibility of an unknown alternative mechanism for the leukemogenesis and maturation arrest seen in other APL variants. The diagnostic challenges and urgent management issues this unusual case raises may justify including it, along with similar cases, in a separate subtype of acute myeloid leukemia (AML) in future classifications.
[Show abstract][Hide abstract] ABSTRACT: Abstract Whole Slide Imaging (WSI) is rapidly transforming educational and diagnostic pathology services. Recently, the College of American Pathologists Pathology and Laboratory Quality Center (CAP-PLQC) published recommended guidelines for validating diagnostic WSI. We prospectively evaluated the guidelines to determine their utility in validating pediatric surgical pathology and cytopathology specimens. Our validation encompassed varied pediatric specimen types, including complex or less common diagnoses in a manner according to the guidelines. We completed WSI review of 60 surgical pathology cases and attempted WSI review of 21 cytopathology cases. For surgical pathology cases, WSI diagnoses were highly concordant with glass slide diagnoses; a discordant diagnosis was observed in 1 of 60 cases (98.3% concordance). We found that nucleated red blood cells and eosinophilic granular bodies represented specific challenges to WSI review of pediatric specimens. Cytology specimens were more frequently discordant or failed for technical reasons, with overall 66.7% concordance. Review of pediatric cytopathology specimens will likely require image capture in multiple focal planes. This study is the first to specifically evaluate WSI review for pediatric specimens, and demonstrates that specimens representing the spectrum of pediatric surgical pathology practice can be reviewed using WSI. Our application of the proposed CAP-PLQC guidelines to pediatric surgical pathology specimens is to our knowledge the first to report prospective implementation of the CAP-PLQC guidelines.
[Show abstract][Hide abstract] ABSTRACT: Myeloproliferative neoplasms (MPNs) are a group of clonal disorders characterized by hyperproliferation of hematologic cell lines and have been associated with tyrosine kinase JAK2-V617F mutations. Secondary acute myeloid leukemia (sAML) is a known complication of JAK2-V617F+ MPNs and bears a poor prognosis. Although the evolution of a JAK2-V617F+ MPN to a mixed-lineage leukemia has been reported in the pediatric population, no evolutions into sAML have been described. We present a case of a one-year-old girl diagnosed with JAK2-V617F+ MPN with evolution into sAML. Despite initial morphologic remission, she eventually relapsed and succumbed to her disease.
Case Reports in Medicine 03/2014; 2014:473297. DOI:10.1155/2014/473297
[Show abstract][Hide abstract] ABSTRACT: Bone marrow macrophages containing other cells, or large pieces of other cells, represent a distinctive feature of diseases such as Hemophagocytic Lymphohistiocytosis (HLH) and Rosai-Dorfman disease. We describe a distinct variation of phagocytic histiocyte morphology, featuring histiocytes containing predominantly fragments of neutrophil nuclei. We retrospectively reviewed initial bone marrow samples for Hodgkin lymphoma, Burkitt lymphoma, Ewing sarcoma, or evaluation for nonneoplastic conditions, scoring the presence or absence of the above-described histiocytes. We find that these histiocytes, which we term "fragmentophages," are associated with staging marrow sampling for malignancy, especially Hodgkin lymphoma (Hodgkin lymphoma: 28/34 or 82.4%, Ewing sarcoma: 11/26 or 42.3%, Burkitt lymphoma: 4/13 or 30.8%). These cells are significantly less common in marrow samples for nonneoplastic conditions (4/21 or 19.0%). Fragmentophages are significantly associated with malignancy, especially Hodgkin lymphoma, and their recognition has the potential to provide a clue to an underlying malignancy.
[Show abstract][Hide abstract] ABSTRACT: Xanthogranulomatous inflammation is a well-described inflammatory process, which may involve any organ but is most frequently encountered in the gall bladder and the kidney. There are rare reports of xanthogranulomatous appendicitis (XA) in the adult population, but only one brief mention of such a diagnosis in a child. In this report, we describe the case of an 11-year-old boy who presented with clinical signs and symptoms of acute appendicitis necessitating appendectomy. Upon microscopic examination, the appendix showed the typical features of XA. To the best of our knowledge, this is the first well-described case XA in a noninterval appendix in a child. We also reviewed the limited medical literature on the subject.
Case Reports in Medicine 09/2013; 2013:498191. DOI:10.1155/2013/498191
[Show abstract][Hide abstract] ABSTRACT: Platelet hyperreactivity is an important but under-recognized cause of idiopathic arterial thrombosis. We describe a case of arterial thrombosis in a previously healthy 12-year-old girl after minor trauma to the knee, resulting in lower extremity amputation. Family history was positive for arterial and venous thrombosis, but an extensive work-up for the usual inherited thrombophilia risk factors was negative. The patient was eventually diagnosed with platelet hyperreactivity and remains on life-long antiplatelet therapy.Consideration of platelet hyperreactivity in the evaluation of unusual arterial thrombotic events allows for targeted therapy, potential avoidance of future events, and timely screening of family members.
Laboratory hematology: official publication of the International Society for Laboratory Hematology 12/2012; 18(4):22-6. DOI:10.1532/LH96.12006
[Show abstract][Hide abstract] ABSTRACT: Burkitt's leukemia (BL) constitutes a small but important fraction of acute leukemias in children. It is an aggressive type of leukemia that is responsive to high-intensity, short-duration chemotherapy with complete remission possible in 75% to 90% of cases. The recognition and proper designation of BL is important because treatment differs from that of precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Burkitt's leukemia is separated by its typical morphologic features (blasts with typical French-American-British [FAB] L-3 morphology compared to FAB L-1/L-2 morphology in pre-B ALL) and a classic immunophenotype (blast positivity for CD45 [bright], CD20 [bright], CD10, CD19, surface immunoglobulin [SIg], Ig light chain restriction, and negative terminal deoxynucleotidyl transferase [TdT]) compared to pre-B ALL blasts (which are positive for CD45 [dim], CD10, CD19, and TdT and negative for CD20 and SIg). The diagnosis of Burkitt's leukemia is confirmed by the characteristic cytogenetic findings.The combination of Burkitt's morphology with precursor B-cell immunophenotype may present a diagnostic pitfall, resulting in delay of proper management.We describe such an atypical case in a 12-year-old girl and emphasize that correct classification and treatment starts with proper morphologic/immunophenotypic correlation, and the awareness of the overlapping features in some cases.
Laboratory hematology: official publication of the International Society for Laboratory Hematology 12/2011; 17(4):27-31. DOI:10.1532/LH96.11004
[Show abstract][Hide abstract] ABSTRACT: A 10-year-old female with Williams Syndrome (WS) presented with a two-month history of fatigue, weight loss, and bilateral ovarian masses. Histologic, immunophenotypic, and cytogenetic studies confirmed the diagnosis of Burkitt lymphoma (BL). While there is no established association between the two disorders, this is the third case in the literature of Burkitt lymphoma in a patient with Williams Syndrome.
Case Reports in Medicine 05/2011; 2011(12):327263. DOI:10.1155/2011/327263
[Show abstract][Hide abstract] ABSTRACT: Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) 677C>T mutation (MTHFR TT) has been linked to an increased risk for stroke, coronary artery disease, and migraine headaches. The authors analyzed the potential link between MTHFR 677C>T homozygosity and childhood stroke. A true association might facilitate screening, recurrence risk stratification, and treatment in patients with cerebrovascular disease. They performed a retrospective chart review of children tested for the MTHFR 677C>/T mutation; 533 patients underwent MTHFR testing, and 8% were homozygous for the MTHFR 677C>T mutation. There was no difference in the cohort compared with the prevalence in the general population. This suggests that the MTHFR 677 C>T polymorphism played a minimal role or no role in stroke risk. However, the data suggest that the MTHFR TT genotype may influence migraine susceptibility in children because there was a higher proportion of migraine patients (28.6%) with the MTHFR TT homozygous genotype.
[Show abstract][Hide abstract] ABSTRACT: Rosai–Dorfman disease (RDD) otherwise known as sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disease of unknown etiology that commonly involves cervical lymph nodes. Tonsillar involvement is extremely rare. We present a case of tonsillar involvement in a 4-year-old boy who presented with a 4-month history of cervical lymphadenopathy and enlarged tonsils causing hoarseness of voice. We also review the literature and discuss the pathologic and clinical characteristics of this disease.
International Journal of Pediatric Otorhinolaryngology Extra 01/2011; 6(1):17-19. DOI:10.1016/j.pedex.2009.12.003
[Show abstract][Hide abstract] ABSTRACT: Despite the impressive advances in pathology and microbiology of recent years, the morphologic recognition of an organism remains a major component in rendering a specific diagnosis of an infectious process, or at minimum, a trigger in the process of identifying an infectious agent. Artifacts and mimickers may pose difficulty to the unwary, and may cause a potential "wild goose chase" that can result in wasted valuable time and resources. Fibrin, collagen exogenous fibers, and bacteria may mimic fungal hyphae. Morphologically altered or treated bacteria and Russel bodies may be mistaken for fungal yeasts, etc. Examples of artifacts and mimickers that may simulate infectious organisms are presented in this article. In addition, a review of literature on the subject, demonstrating a surprising dearth of published articles, despite the frequent encounters of this issue in the daily practice.
[Show abstract][Hide abstract] ABSTRACT: The presentation of Hodgkin Lymphoma in a thymic cyst is rare. We describe a case in a 9 year-old boy, with a long follow-up course, complicated by two secondary neoplasms and a post bone marrow transplant lymphoproliferative disorder. We also review the literature on such presentations and second malignant neoplasms in childhood.
Case Reports in Medicine 06/2010; 2010:795037. DOI:10.1155/2010/795037
[Show abstract][Hide abstract] ABSTRACT: Congenital peribronchial myofibroblastic tumor (CPMT) is a solid pulmonary tumor found in fetuses and neonates with pathology characterized by a proliferation of bland spindled cells with or without irregular cartilaginous islands. It has previously been reported in the literature as a fibrosarcoma, leiomyosarcoma, and hamartoma, among other names. Although complications such as fetal hydrops can occur, the prognosis is generally good if the infant can survive long enough for mass resection. We present a case of a CPMT resected by antenatal fetal surgery at 23 weeks in gestation, with additional tumor resected following birth when the infant was 6 weeks of age. The pathology of this lesion showed a marked increase in the cartilaginous component after birth as well as a decrease in cellularity and mitotic activity. This case presents a unique opportunity to examine the progression of a congenital tumor excised by prenatal and postnatal resections.
[Show abstract][Hide abstract] ABSTRACT: Eosinophilic esophagitis is increasingly recognized as a cause of dysphagia or food impaction in pediatric patients. It has a high male predominance and is often associated with a history of allergy or asthma.
To correlate fluoroscopic findings in eosinophilic esophagitis with the endoscopic and histologic findings.
We retrospectively reviewed the upper gastrointestinal (UGI) findings of eosinophilic esophagitis and correlated them with the clinical, endoscopic and histologic findings in a series of 17 children (12 boys, 5 girls).
UGI findings were normal in 12 children, including 4 who had a normal UGI exam after endoscopic disimpaction for an obstructing food bolus. Five children had strictures identified on UGI: one was demonstrated with endoscopy. This suggests that the impactions and strictures were due to an esophageal dysmotility rather than a fixed anatomic abnormality.
Because the UGI findings are frequently normal in eosinophilic esophagitis, radiologists need to have a high index of suspicion for this disease. In children with a strong clinical history, especially impaction in the absence of an esophageal stricture, endoscopy and biopsy are indicated for further evaluation.
[Show abstract][Hide abstract] ABSTRACT: The diagnosis and management of alpha-thalassemia may be complicated by the variability of the phenotype, which is due to the interaction of coinherited alpha-thalassemia and the variable severity of beta-thalassemia mutations. A well-documented case of complex beta- and alpha-thalassemia coinheritance is described. Laboratory and clinical data for the patient and her family are reviewed. The patient is an asymptomatic girl, one of identical twins. She presented at 1 month of age for follow-up of an abnormal newborn-screening result (hemoglobin F only), which initially suggested homozygosity for beta-thalassemia. Extensive studies on the patient and family revealed that she had coinherited alpha-thalassemia traits and homozygous beta-thalassemia. This case demonstrates the interaction of coinherited alpha- and beta-thalassemia with the resultant amelioration of the clinical phenotype. It also highlights the importance of family studies and close follow-up in diagnosing complex hemoglobinopathies.
Laboratory hematology: official publication of the International Society for Laboratory Hematology 09/2009; 15(3):30-3. DOI:10.1532/LH96.09002
[Show abstract][Hide abstract] ABSTRACT: Juvenile myelomonocytic leukemia (JMML) is a rare, aggressive, clonal hematopoietic disorder of childhood with features of both myelodysplasia (thrombocytopenia, anemia) and myeloproliferation (leukocytosis, monocytosis). In most cases there is marrow hypercellularity, splenomegaly, and extramedullary involvement. In 1997 an international consensus on terminology was reached and guidelines/criteria for diagnosis were proposed. A recent World Health Organization classification described the current diagnostic criteria of JMML. Although the diagnosis of JMML has been facilitated, it can be challenging, especially in the early stages or when it 1st presents as an extramedullary tumor. We report a series of 7 cases diagnosed over a period of 10 years (from January 1, 1996, to December 31, 2005). Two cases had interesting associated findings that would potentially lead to delay in diagnosis or misdiagnosis. Two other cases had extramedullary involvement with symptoms referable to the organs of involvement at presentation. Clinical and pathologic findings are summarized with a review of relevant literature.
[Show abstract][Hide abstract] ABSTRACT: We report the case of a rare hemoglobin variant, "Hemoglobin J", discovered while performing hemoglobin electrophoresis following exchange transfusion of a sickle cell disease patient. It is usual practice in our institution to confirm the hemoglobin S level in sickle cell disease patients after red cell exchange. The patient had received 5 red cell units and the source of this variant was traced back to two of those units. Due to the uncertain clinical impact of this variant, and the lack of specific guidelines, the two donors were deferred from future donations to our institution.
[Show abstract][Hide abstract] ABSTRACT: Leukemias are neoplasms that arise from the hematopoetic cells of bone marrow and usually spread first to peripheral blood. Involvement of extramedullary tissue during the course of a leukemia is common and usually does not represent a major diagnostic challenge when the history is available and specimen triage is optimal. In the context of a myeloid origin, extramedullary leukemias are referred to as granulocytic sarcomas, extramedullary myeloid tumors, extramedullary leukemias, or myeloid sarcomas. In the lymphoid category, leukemia involvement of tissue is conventionally distinguished from lymphoma by establishing the presence of 20% or more blasts in the bone marrow. A leukemia with an initial presentation outside the bone marrow mimicking a solid tumor is a rare but well-documented clinical encounter. Diagnostic difficulties may arise, especially when a specimen is not triaged properly due to the clinical presumption of a nonhematopoietic tumor. Systematic handling and proper triaging of biopsies are the keys to reducing diagnostic error and facilitating a timely diagnosis in this category. We report 4 case examples in the pediatric population, presenting in different anatomic sites. The value of fresh specimens and performing touch imprints is discussed and emphasized.