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Year : 2012  |  Volume : 55  |  Issue : 1  |  Page : 115-116
Masquerade in rosettes


Deparment of Pathology, Regional Cancer Centre, Trivandrum, Kerala, India

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Date of Web Publication11-Apr-2012
 

How to cite this article:
Jacob PM, Nair RA, Nayak N, Nair SP. Masquerade in rosettes. Indian J Pathol Microbiol 2012;55:115-6

How to cite this URL:
Jacob PM, Nair RA, Nayak N, Nair SP. Masquerade in rosettes. Indian J Pathol Microbiol [serial online] 2012 [cited 2014 Oct 25];55:115-6. Available from: http://www.ijpmonline.org/text.asp?2012/55/1/115/94880


The hazards of differentiating neuroblastoma from acute leukemia have been commented upon frequently in literature. Acute leukemia in its presentation as bone pain may be a differential diagnosis for neuroblastoma in the absence of primary localization of the tumor.

An 8-year-old boy, son of a coolie worker, presented with paraperesis and intermittent fever of four months duration. Physical examination revealed grade 1 PEM (protein energy malnutrition), pallor and grade 3 power in both lower limbs. His blood picture was as follows: hemoglobin = 11.3 gm%, total leukocyte count = 4600 cells/mm 3 , and platelet count=496x10 9 /L. To rule out spinal metastasis possibly from neuroblastoma, CT (computerized tomography) scan of thorax, abdomen, as well as MRI (magnetic resonance imaging) study of spine was done, both of which were within normal limits. His peripheral blood and bone marrow aspirate smears were stained with Giemsa and Myeloperoxidase stain for morphological evaluation. His peripheral smear was within normal limits. His bone marrow aspirate revealed atypical cells in rosettes with central eosinophilic fibrillary material, resembling metastases from a neuroblastoma. However, the nuclear features were unusual with immature chromatin, some showing nucleoli, favoring acute leukemia [Figure 1], [Figure 2] and [Figure 3].
Figure 1: Atypical cells scattered singly and forming rosettes with central eosinophilic fibrillary material (GIEMSA, x200)

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Figure 2: Rosettes with atypical cells showing moulding (MPO, x1000)

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Figure 3: Atypical cells are myeloperoxidase negative, nuclei have immature chromatin, some showing nucleoli (MPO, x1000)

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With two possibilities in mind (acute leukemia and metastasis from an occult neuroblastoma), flow cytometric immunophenotyping (FCI) was done by leukocyte common antigen (LCA) gating 74% of cells on the bone marrow aspirate. For FCI, the cells were stained within 24 hours of collection using a whole blood lyse-wash technique. Panel of directly conjugated monoclonal antibodies comprised of CD13 (PE- L138), CD33 (FITC-P67.6), CD117 (APC- 104D2), MPO (FITC- 5B8), CD10 (FITC- HI10a), CD2 (PE- S5.2), CD3(APC-SK7), CD5 (PE- L17F12), CD7 (FITC- 4H9), CD20 (APC-L27), CD34 (PE- 8G12), CD64 (F-10.1), CD19(APC-SJ25C1), CD45 (PERCP- 2D1), and HLA DR (APC- L243) were used.

Six parameter, four color immunophenotyping was performed using a FACS Caliber (Becton Dickinson, San Jose, CA). Minimum 10,000 events were acquired using LCA gating. Data was analyzed with CellQuestpro software (Becton Dickinson). Other clinical, hematological, and biochemical parameters were correlated. The tumor cells were LCA negative, CD19 positive, CD10 positive, CD34 positive, and HLA DRpositive [Figure 4].
Figure 4: Immunophenotype of blasts as revealed by flow cytometry

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Based on the FCI, we concluded the diagnosis of B Lymphoblastic Leukemia (CALLA positive). The patient was started on induction chemotherapy including Vincristine, L'asparaginase, and Prednisolone. The patient tolerated the chemotherapy well. His bone marrow is now in morphological remission. In both the lower limbs, power is improving, and he is now walking with support.


   Discussion Top


A review of literature revealed few studies which say that neuroblastoma can express B cell markers like CD19, CD20, and CD10 (CALLA). [1],[2] To confound things further, we also came across studies which state that neuroblastoma cells can express the hematopoietic progenitor cell antigen CD34 as detected at surface protein and mRNA level. [3] There are a few studies which advocate a specific panel for detecting neuroblastoma cells. Certain studies advocate a panel for detecting neuroblastoma in bone marrow. It is known that NB cells express CD45(-)/CD44(+)/CD56(+)/CD81(+)/CD9(+) antigens. It is an effective method to rapidly detect NB cells in bone marrow. [4] There are plenty of case reports of neuroblastoma mimicking acute leukemia. [5] However, we did not come across any case reports of B Lymphoblastic Leukemia presenting with rosettes on bone marrow aspirate.

Features that could have lead to a mistaken diagnosis of neuroblastoma infiltrating bone marrow in our case were the following:

  1. Tumor cells were LCA negative (rarely lymphoblastic lymphomas are LCA negative)
  2. Absence of aberrant phenotype. There was no coexpression of myeloid associated antigens as is commonly seen
  3. Rosettes are characteristic of neuroblastoma, Which are very rarely described in acute leukemias
  4. Neuroblastoma can rarely express B cell markers and CD34. [1],[2],[3]


In our case, as the FCI showed a classical B-lymphoblastic leukemia profile and as radiologically and biochemically, there was no evidence of primary neuroblastoma we came to a diagnosis of a B Lymphoblastic Leukemia.

This case illustrates the fact that acute leukemia can rarely present as rosettes and closely mimic a neuroblastoma infiltrating bone marrow. The immunophenotype of these 2 entities may also prove to be a close mimicker, if the leukemia in question is a CALLA positive B- Lymphoblastic Leukemia. Hence, the immunophenotype coupled with the cytomorphological characteristics and the complete clinical picture should help one avoid a misdiagnosis of these two close mimickers. In centers where immunophenotypic panel is usually decided on the basis of morphology with limited antibodies, this may result in an erroneous typing of such an unusual morphological picture. Hence, it is important to be aware of the fact that acute leukemia can present as rosettes on the bone marrow aspirate and it is important to confirm the diagnosis of acute leukemia by using a comprehensive panel of antibodies for immunophenotypic analysis.

 
   References Top

1.Mandel M, Rechavi G, Neumann Y, Biniaminov M, Brok-Simoni F, Bojanover Y, et al. Bone marrow cell populations mimicking common acute lymphoblastic leukemia in infants with stage IV-S neuroblastoma. Acta Haematol 1991;86:86-9.  Back to cited text no. 1
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2.Mandel M, Rechavi G, Neumann Y, Biniaminov M, Rosenthal E, Toren A, et al. CD10+ cell population in the bone marrow of patients with advanced neuroblastoma. Med Pediatr Oncol 1994;22:115-8.  Back to cited text no. 2
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3.Voigt A, Häfer R, Gruhn B, Zintl F. Expression of CD34 and other haematopoietic antigens on neuroblastoma cells: Consequences for autologous bone marrow and peripheral blood stem cell transplantation . J Neuroimmunol 1997;78:117-26.  Back to cited text no. 3
    
4.Koksal Y, Reisli I, Dogu F, Ucar C, Acar H, Çalifan U. Can Flow cytometry be used at diagnosis and follow up in neuroblastoma with bone marrow involvement? Turk J Cancer 2006;36:27-30.  Back to cited text no. 4
    
5.Panovska-Stavridis I, Ivanovski M, Hadzi-Pecova L, Ljatifi A, Trajkov D, Spiroski M, et al. A case report of aggressive adult neuroblastoma mimicking acute leukemia with fulminant course and fatal outcome. Prilozi 2010;31:349-59.  Back to cited text no. 5
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Correspondence Address:
Rekha A Nair
Department of Pathology, Regional Cancer Centre, Trivandrum - 695 011, Kerala
India
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DOI: 10.4103/0377-4929.94880

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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