Complete mimicry: a case of alveolar rhabdomyosarcoma masquerading as acute leukemia

Background

A small number of rhabdomyosarcoma (RMS) cases involve the bone marrow. A leukemic presentation of RMS has been reported in a few case series, although almost all cases of leukemic RMS are not completely mimicking leukemia. We encountered a case with RMS cell infiltration of the bone marrow that resembled floating hematological cells.

Case presentation

We encountered a rare case of a 15-year-old boy with a 2-week history of left femoral pain. Upon admission, he was afebrile with no other symptoms. No apparent cause of femoral pain was detected on an initial examination. Laboratory findings revealed normal white blood cell (WBC) count and hemoglobin concentration, with a platelet count of 10.3 × 10⁴/μL. WBCs included 2.0% metamyelocytes, 4.5% myelocytes, and 0.5% blasts. Lactate dehydrogenase concentration was 1299 U/L, creatine kinase was 437 U/L, and C-reactive protein was 1.25 mg/dL. Bone marrow aspiration demonstrated hypercellular marrow (nucleated cell count 1.84 × 10⁴/μL) and 89.0% of blast-like cells of all nucleated cells. The proliferating cells were negative for myeloperoxidase and esterase, and strongly positive for CD56. Positron emission tomography exhibited extensive accumulation of ¹⁸F–fludeoxyglucose with a SUVmax of 7.09. Magnetic resonance imaging revealed T1-low intensity, gadolinium-enhanced, diffuse, and irregular lesions on his pelvis and bilateral femurs. These laboratory and imaging findings suggested hematological malignancy with diffuse bone involvement, suggestive of acute leukemia. However, the pathological diagnosis of bone marrow and basal penile muscle biopsy was alveolar RMS. Karyotype analysis of bone marrow cells revealed the characteristic translocation of t(2;13)(q35;q14). The final diagnosis was alveolar RMS with massive involvement of the bone marrow and the primary site in the perineal muscles. The tumor cells both of the primary site and bone marrow were positive for myogenin.

Conclusions

A literature review found a misdiagnosed case of completely mimicking leukemic RMS as natural-killer (NK)-cell leukemia. Such a misdiagnosis can have critical consequences. We experienced a rare case of alveolar RMS with symmetrical diffuse bone marrow involvement completely masquerading as acute leukemia. The results of a surface marker study showing that the tumor cells had a near NK-cell phenotype were misleading.

     

Bone marrow analysis of the myelodysplastic syndromes: histological and immunohistochemical features related to the evolution of overt leukemia

Bone marrow trephines from 31 patients with an initial diagnosis of myelodysplastic syndromes (MDS) were examined and analyzed histologically and immunohistochemically. In those cases terminating in overt leukemia (6/31, 19%), the number of bone marrow mast cells was significantly reduced, compared with those which did not evolve to overt leukemia. The bone marrow lymphoid cells that may participate in immunosurveillance against the proliferation of blast cells were also significantly reduced in cases terminating in overt leukemia. However, S-100 protein-positive cells, which include histiocytes and suppressor T-cells, were increased in cases terminating in overt leukemia. The results indicated that examination of the bone marrow to determine the proportions of mast cells and lymphoid cells which may be involved in host defense systems may be useful in predicting the evolution to overt leukemia in MDS. In the present series, patients with a hypocellular marrow (5/31, 16%) did not progress to overt leukemia and had a significantly lower bone marrow reticulin content, a significantly lower megakaryocyte count, a relatively higher mast cell count and a significantly higher lymphoid cell count than those with a normocellular or hypercellular marrow. These findings may reflect the initial features of MDS or, possibly, that hypocellular MDS is an independent entity with a low potential for blastic proliferation.     

Pulmonary embolization of fat and bone marrow in cynomolgus Macaques (Macaca fascicularis)

Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma.     

Hypermétabolismes médullaires en TEP au 18F-FDG chez les patients atteints de cancer : signification et comparaison à l’IRM médullaire

Diffuse bone marrow uptake of ¹⁸F-FDG-PET in cancer patients raises the problem of differential diagnosis between marrow involvement and stimulated marrow. In this study, we prospectively included, during a 1-year period, all cancer patients referred for initial staging showing an unexplained diffuse bone marrow uptake and explored consecutively by MRI. The abnormalities described on PET and the conclusion reached about disease status of bone marrow (“benign” or “malignant”) were compared with corresponding MRI results, as well as clinical and biological findings pertinent when bone marrow activity is studied, marrow status considered by referring clinicians, and follow-up data. During 1 year, 60 patients had diffuse bone marrow uptake on ¹⁸F-FDG-PET, 26 underwent MRI examination and were finally included in the study. Results of PET and MRI were concordant in 24 cases (six “malignant” and 18 “benign”) and two cases were discordant, judged “malignant” by MRI and “benign”by PET. The outcome after confrontation of MRI and PET, was “malignant”for one patient and “benign” for the other one. The final results, was “malignant” for seven patients and “benign” for 19 patients and this final diagnosis was retained by referring clinicians. Among the 19 patients with diffuse bone marrow uptake considered as benign, seven patients had a pejorative evolution and four of them developed osteomedullary metastases. In cancer patients, ¹⁸F-FDG-PET identify bone marrow diffuse uptake which seems to correspond well to abnormalities assessed on MRI studies. Notably, heterogenous 18F-FDG uptake and/or foci of increased uptake seems significative of marrow involvement. The limited population size and discordant published findings about bone marrow evaluation by ¹⁸F-FDG-PET compared with MRI can not permit to ensure that these imaging modalities or one of these are sufficient to assess bone marrow status without performing bone marrow biopsy. Some patients with unexplained diffuse bone marrow uptake develop disease progression, such observations could be interestingly assessed by further studies.     

Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology

U. Handa, S. Chhabra and H. Mohan
Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology Objective: Plasma cell tumours represent autonomous proliferation of plasma cells and can manifest as multiple myeloma, monoclonal gammopathy of undetermined significance, variants of plasma cell myeloma or plasmacytoma. Methods: We report 12 cases of plasma cell tumours, which were initially diagnosed as plasmacytoma on fine needle aspiration cytology (FNAC). The patients were further subjected to bone marrow examination, serum electrophoresis, urine examination for Bence–Jones proteins, and x‐ray examination of the skeleton. Results: The cytological smears from all cases were cellular and showed numerous plasma cells in varying degrees of maturity. Subsequent to investigations, five cases were labelled as multiple myeloma with secondary extramedullary plasmacytoma, three as solitary bone plasmacytoma and two as primary extramedullary plasmacytoma. In the remaining two cases, bone marrow and urine examination findings were not available, so a conclusive diagnosis of multiple myeloma or solitary plasmacytoma could not be made. Conclusion: The study highlights the role of FNAC in the diagnosis of plasma cell tumours. Subsequent work‐up and follow‐up of these patients is important to rule out the presence of multiple myeloma.     

Bone Marrow Biopsies with a Silverman Needle

Advantages and disadvantages of bone marrow biopsies taken from the posterior iliac crest using the Silverman needle were evaluated. Sixty-three biopsies were carried out in patients on whom previous aspirations of the bone marrow space were unsuccessful. Open surgical biopsy was thus avoided in all but one case. Only local anesthesia was required. In 12 cases the first attempt to obtain material with the Silverman needle was unsuccessful.Limitations of the method are largely due to crushing of the specimen so obtained, with polarization of nuclei simulating the appearance of fibroblasts seen in cases of myelosclerosis. At times marrow was completely expressed from the spongy bone, leaving a useless specimen of spicules. The quality of histological material is usually inferior to that yielded by successful aspiration.Despite limitations, the Silverman needle method is considered to be preferable to open biopsy in cases in which attempts at aspiration have failed.     

THE TOXIC EFFECTS OF AMPHOTERICIN B IN MAN

Studies of 47 patients with intravenous amphotericin B revealed some impairment of renal function in all cases. Azotemia developed in 46 cases. Microscopic examination in eight cases showed damage to the distal renal tubule. Profound hypokalemia was recognized in two cases; and symptoms suggesting hypokalemia, which were generally ameliorated by potassium administration, were noted in most cases. It is postulated that the initial potassium loss is due to a “tubular leak” and that subsequent potassium depletion leads to further tubular damage.Mild to severe anemia developed in all cases during therapy. Serial red cell indices, bone marrow examinations and red cell survival studies indicated that hemolysis, rather than bone marrow depression, was responsible.The decision to treat, to modify therapy or to terminate treatment must be made on the basis of severity of disease, probability of progression, and renal status.     

Acquired immune haemolysis by anti A 1 antibody following bone marrow transplantation

In ABO mismatched organ or bone marrow transplants recently some cases of acquired immune hemolysis have been reported. It was felt that these life threatening complications were due to immunosuppressive treatment with cyclosporin-A. A case of severe hemolysis following mismatched BMT is reported. Here no cyclosporin-A treatment was given since the bone marrow was T-cell deprived by an E-rosetting technique. Apparently T-cell purging can under these conditions become dangerous.     

Role of Immunohistochemistry in Staging Diffuse Large B-cell Lymphoma (DLBCL)

The use of immunohistochemistry (IHC) in staging bone marrow in non-Hodgkin''s lymphoma (NHL) is largely limited to ambiguous cases, particularly those with lymphoid aggregates. Its role in routine clinical practice remains unestablished. This study aimed to determine whether the routine use of IHC in diffuse large B-cell lymphoma (DLBCL) would improve the detection of lymphomatous involvement in the bone marrow. It also sought to determine the impact of IHC on predicting survival compared with routine histological diagnosis using hematoxylin and eosin (H&E), Giemsa, and reticulin staining. The bone marrow trephines of 156 histologically proven DLBCL cases were assessed on routine histology, and IHC using two T-cell markers (CD45RO and CD3), two B-cell markers (CD20 and CD79a), and κ and λ light chains. IHC detected lymphomatous involvement on an additional 11% cases compared with histology alone. Although both routine histology and IHC were good predictors of survival, IHC was better at predicting survival on stepwise multivariate Cox regression analysis. IHC performed routinely on bone marrow trephines has the ability to improve detection of occult lymphoma in experienced hands. Furthermore, it is a better predictor of survival compared with routine histological examination alone. (J Histochem Cytochem 56:893–900, 2008)     

Cytologic diagnosis of peripheral T-cell lymphoma manifesting as ascites. A case report

BACKGROUND: Patients with malignant lymphoma seldom present with effusions without a known history of malignancy. Because of this, initial diagnosis of malignant lymphoma by effusion cytology is uncommon, with few reported cases. CASE: A 75-year-old male presented with fatigue, decreased appetite and progressively increasing abdominal girth over five weeks. Cytologic examination of ascitic fluid obtained by paracentesis revealed non-Hodgkin's lymphoma with a T-cell phenotype, confirmed by immunophenotypic and molecular studies. Approximately one week later, histologic examination of liver and bone marrow revealed involvement by lymphoma, demonstrating immunophenotypic and molecular profiles identical to those obtained from neoplastic lymphocytes recovered from the ascites fluid. CONCLUSION: This case demonstrates a rare presentation of peripheral T-cell lymphoma, clinically manifesting as ascites. In cases such as ours, where the effusion consists predominantly of small to intermediate-sized lymphocytes, distinguishing lymphoma from reactive lymphocytosis may be difficult. This case not only demonstrates the value of effusion cytology for lymphoma diagnosis but also illustrates how the use of various immunophenotypic and molecular techniques may assist the pathologist in properly diagnosing these difficult cases.     

Disseminated histoplasmosis with hemophagocytic syndrome in a patient with AIDS: description of one case and review of the Spanish literature

We report a case of disseminated histoplasmosis in a 33-year old Ecuadorian patient with AIDS and a CD4 lymphocyte count of 39 cells/microl. He presented with prolonged fever and cough, was diagnosed with hemophagocytic syndrome and multiple organ failure and died 18 days after admission. Histoplasma capsulatum was isolated post-mortem from bone marrow biopsy and blood culture. In a literature review we found 22 published cases of disseminated histoplasmosis in patients with AIDS in Spain since 1988. All but two were men under 50 years old. Nineteen had been born or had lived in endemic areas. The diagnosis of histoplasmosis was established by culture of bone marrow biopsy in 10 cases. Itraconazole was introduced as a second drug after amphotericin B in ten of the thirteen patients who survived.     

Cytology of the cerebrospinal fluid in primary malignant lymphomas of the central nervous system

Two cases of primary malignant lymphoma of the central nervous system are reported. Clinical and pathologic findings did not indicate systemic lymphomatous involvement of lymph nodes and bone marrow. The patients presented with different neurologic deficits. Cytologic examination of the cerebrospinal fluid was the first and most useful technique for establishing the diagnosis.     

Fine needle capillary sampling of eyelid masses. A study of 70 cases

OBJECTIVE: To study the cytomorphology of eyelid tumors, correlate it with histopathology and determine the diagnostic accuracy of fine needle capillary (FNC) sampling (nonaspiration) in the evaluation of lid tumors. STUDY DESIGN: A prospective study of 70 cases of eyelid masses carried out using FNC, with confirmation by histology in 66 cases and peripheral blood smear and bone marrow examination in 3. Histology was not done in 1 case, and 11 cases were inadequate on cytology. The diagnostic accuracy of cytology was 94.73%, and false negativity was 5.17%. RESULTS: The ages of the patients ranged from 3 to 75 years, with a mean of 40.4. The male/female ratio was nearly equal (37:33). The upper eyelid was affected in 45 cases and lower lid in 25 cases. The right eye was affected in 35 cases, left eye in 34 cases and both eyes in 1 case. Fifteen benign, 35 malignant and 9 infectious/inflammatory lesions were encountered, with 11 inadequate smears. CONCLUSION: FNC sampling is an effective method of sampling eyelid tumors because it causes little discomfort to the patient and allows the operator to maintain better control over the procedure. A distinction between inflammatory, benign and malignant lesions and between the types of malignant tumors can be made.     

Acute Brucellosis Treated with Trimethoprim and Sulphamethoxazole

Four patients with acute brucellosis are described, none of whom had any connexion with farming or milk industry, the source of infection being different in each case. The diagnosis was made by serological tests, and in three of the four cases was confirmed by positive cultures from bone marrow (one case) and liver biopsy (two cases). Treatment with the combination of trimethoprim/sulphamethoxazole was successful in three out of four cases, and in the fourth case failure may have been due to the development of trimethoprim resistance.     

Disseminated Fusariosis Secondary to Neuroblastoma with Fatal Outcome

Disseminated fusariosis is an uncommon clinical condition in immunocompromised patients. We report a fatal case of disseminated fusariosis secondary to neuroblastoma in a male patient, 15 years old, who underwent a bone marrow transplant. The patient was admitted to the pediatric intensive care unit (PICU) of a public hospital in Recife-PE, Brazil, presenting bone marrow aplasia, severe leukopenia, and thrombocytopenia. After 15 days, the patient developed right knee effusion. Synovial fluid and blood samples were analyzed at the Medical Mycology Laboratory of the Federal University of Pernambuco. Mycological diagnosis was based on the presence of hyaline septate hyphae on direct examination and the isolation of Fusarium oxysporum in culture, confirming the case of disseminated fusariosis. In vitro, the isolate showed fluconazole resistance and sensitivity to amphotericin B, anidulafungin, and voriconazole. Therapy with voriconazole in combination with liposomal amphotericin B led to an improved clinical response; however, due to underlying disease complications, the patient progressed to death.     

Megakaryocytes emperipolesis in bone marrow of the patients with non-Hodgkin's lymphoma

Emperipolesis of hematopoietic cells within the cytoplasm of the megakaryocytes was most often described in association with various pathologic conditions. The aim of the research was estimation of the incidence of emperipolesis in the bone marrow of the patients with non-Hodgkin's lymphoma (NHL). 30 patients with different histological types of NHL (chronic lymphocytic leukaemia--CLL, hairy cell leukaemia--HCL, multiple myeloma--MM) in compliance with clinical stage of the disease, patient's age and sex were analyzed. Trephine biopsies of the bone marrow were carried out in fixative solution and paraffin embedding. Hematoxylin and eosin and monoclonal antibody CD 61 were applied on thin sections. Phenomenon of megakaryocytic emperipolesis in human bone marrow was found in 6 cases: in 5 cases in CLL and in 1 case in HCL. In most of them emperipolesis was related to single megakaryocytes. We observed in the cytoplasm of the megakaryocytes single hematopietic cells-most often lymphocytes, rarely eosinophilic granulocytes. We found no correlations between histological types of NHL, clinical stage of the disease, patients' age, sex and the incidence of megakaryocytic emperipolesis.     

Posttransplantation lymphoproliferative disorder mimicking a nonspecific lymphocytic pleural effusion in a bone marrow transplant recipient. A case report

BACKGROUND: Serous effusions are rare complications of bone marrow transplantation (BMT) and result mainly from infections or tumor relapse. CASE: We report a case of posttransplantation lympho-proliferative disorder (PTLD) revealed by cytodiagnostic examination of serous effusions in a BMT recipient. The effusion was initially considered reactive, but morphologic, immunocytologic and molecular studies subsequently revealed PTLD. CONCLUSION: This case demonstrates the importance of cytologic examination of effusions in BMT or organ recipients. Since most PTLDs are Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders and T cells predominate in reactive effusions, appropriate initial immunostaining, including CD3, CD79a and EBV latent membrane protein, should aid in their early detection.     

Immune recovery after allogeneic stem cell transplantation: study of 19 patients

The aim of this study was to access average delays for novogeneration of myeloid and lymphoid cells after allogeneic bone marrow transplantation (BMT) outcome and factors affecting this organization. A prospective analysis over 2 years (01/01/07 to 31/12/08) enrolling 19 children treated with allogeneic intrafamilial bone marrow transplantation. Indications for bone marrow transplantation were: aplastic anemia (3 cases), bemoglobinopathies (9 cases), myelodysplastic syndrome (1 case) and primary immunodeficiency (6 cases). Different conditioning regiments were used according to the indication. The study of immune reconstitution was based on the quantitative determination of immunoglobulin and lymphocyte subpopulation. These tests were routinely requested to 1 month, 2 months, 3 months, 6 months, 9 months and 12 months. The average time of engraftment was 18 days (12-24). A rate of CD4+T lymphocytes>200/mm3 was provided within an average of 2,5 months (1-7). The average time to obtain CD8+T lymphocytes>200/mm3 was 2 months (1-5). The humoral immune reconstitution was made within an average of 2 months (1-4). A report of CD4+/CD8+T lymphocytes>I was obtained within 10 months and a half (1-24). Univaried analysis showed a correlation between the bone marrow sex matched and the faster reorganization of CD8+T cells (p=0.042). A quantity of CD34+>6 10(6)/kg was significantly associated with the recapture of a formula lymphocyte CD4+/CD8+T>1 (p=0.03) Immune recovery post bone marrow transplantation in children begins with myeloid lineage then lymphoid B then lymphoid T The inversion of the report CD4+/CD8+T lymphocytes, seems to be influenced by the high contain of CD34+cells in the graft as well as the type of conditioning.     

Pediatric visceral leishmaniasis diagnosis in Tunisia: comparative study between optimised PCR assays and parasitological methods

There has been a steady increase of visceral leishmaniasis during the past 20 years in Tunisia. In this study, we assess the value of two optimised PCR versus those of classical methods for the diagnosis of human visceral leishmaniasis. 106 samples were collected from 53 cases of pediatric visceral leishmaniasis. Peripheral blood and bone marrow samples were analysed both by parasitological methods (direct examination, leukocytoconcentration (LCC) and culture) and by PCR methods with two primer pair (R221/R332 and Lei 70L/Lei 70R). We diagnosed visceral leishmaniasis in all patients: 44 cases were diagnosed by culture (83%), 42 by direct examination of bone marrow (79%), 17 by LCC (32%), and 53 positive cases with both PCR assays (R221/R332 and/or Lei 70L/Lei 70R) (100 %). Regarding each PCR assay, for blood samples, the difference between the sensitivities of PCR Lei 70L/Lei 70R (86,8%) and PCR R221/R332 (17 %) is statistically significant with p-value 0.025. For bone marrow, the sensitivities of the two PCR methods were respectively 96,2% (Lei 70L/Lei 70R) and 75,5% (R221/R332). On the whole, PCR Lei 70L/Lei 70R was more effective than PCR R221/R332 and conventional methods for the two biological samples. Moreover, the requirement of less invasive sample using blood has the advantage of being repeatable for screening and for post therapeutic monitoring.     

Haematologic changes in gastritic cancer

Haematologic disturbances in 13 cases of gastric cancer are described. All the patients had anemia of different origin. Increased leukocytosis was observed in half of the cases, leukaemia reaction in one third. Haemolysis was present in 50% of cases. Thrombocytopenia coexisted most frequently with disseminated intravascular coagulation in 4 patients. Bone metastases were visualised as osteolytic foci with radiological methods or increased capture of isotopic marker in the bones under scintigraphic examination. Under the microscope neoplastic metastases were found in bone marrow smears of 5 patients. All patients displayed symptoms of gastric ulcer disease acute or chronic phase. In some cases only repeated gastroscopic examination and mucosa biopsy was the only way to confirm cancer. In other cases the diagnosis was made after the histopathologic examination of the resected stomach, in still others by a section.