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Year : 2017  |  Volume : 6  |  Issue : 3  |  Page : 169-173

Primary intracranial granulocytic sarcoma: A case report and review of literature

1 Department of Medical and Paediatric Oncology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
2 Department of Pathology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India

Date of Web Publication25-Sep-2017

Correspondence Address:
Asha S Anand
Department of Medical and Paediatric Oncology, The Gujarat Cancer and Research Institute (M. P. Shah Cancer Institute), New Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
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Granulocytic sarcoma (GS) is a rare extramedullary proliferation of myeloblasts or immature myeloid cells leading to the disruption of normal architecture of tissue in which it is found. It may precede, be concomitant with or appear after diagnosis of acute/chronic leukemia, in acute or relapse setting. Herein, we report a case of 12-year-old male who presented with left-sided hemiparesis. Neuroimaging revealed a space occupying lesion in basal ganglia and thalamus. Stereotactic biopsy with immunohistochemistry (IHC) studies was suggestive of lymphoid malignancy versus GS. However, immunophenotyping (IPT) done on cerebrospinal fluid leukemic blasts was positive for GS. The patient initially received therapeutic cranial radiotherapy with biweekly triple intrathecal chemotherapy followed systemic high-dose cytarabine chemotherapy. Since bone marrow examination failed to reveal any evidence of hematologic malignancy, a diagnosis of aleukemic, primary, or isolated GS of brain was made. Our case emphasizes the importance of early suspicion, diagnostic dilemma associated with GS, the role of histopathology, IHC, and IPT in diagnosis, and various treatment modalities of aleukemic intracranial GS.

Keywords: Brain, chloroma, extramedullary tumor, immunohistochemistry, leukemia, myeloid sarcoma

How to cite this article:
Mehta DP, Trivedi P, Anand AS, Parikh S, Chirmade P. Primary intracranial granulocytic sarcoma: A case report and review of literature. J NTR Univ Health Sci 2017;6:169-73

How to cite this URL:
Mehta DP, Trivedi P, Anand AS, Parikh S, Chirmade P. Primary intracranial granulocytic sarcoma: A case report and review of literature. J NTR Univ Health Sci [serial online] 2017 [cited 2022 Jan 26];6:169-73. Available from: https://www.jdrntruhs.org/text.asp?2017/6/3/169/215531

  Introduction Top

Granulocytic sarcoma (GS) is a rare but well-known extramedullary manifestation of acute/chronic leukemia or myelodysplastic syndrome (MDS), with estimated incidence of 0.7 in 1 million children and 2 in 1 million adults,[1] can occur at any age and can involve any organ throughout the body, such as soft tissues, skin, bones, lymph nodes, gastrointestinal and genitourinary tracts, heart, orbit, head and neck region, mediastinum and sanctuary sites, testis, and central nervous system (CNS).[2] It was first described by Burns in 1811, named chloroma by King in 1853 due to its green color caused by myeloperoxidase (MPO) and renamed GS by Rappaport in 1966 as approximately 25%–30% of tumors were not green.[3],[4] GS is reported in 2.5%–9.1% of patients with acute myeloid leukemia (AML), 3.9% of patients with chronic myelogenous leukemia (CML), and 4.2% of patients at onset of blast crisis in CML.[3],[5] CNS involvement by GS is present in only 0.4% of patients with AML, while aleukemic involvement of brain parenchyma is rarer, mentioned only in case reports/series.[6] Here, we present a case of isolated GS of basal ganglia-thalamus, treated initially with DeAngelis protocol for primary CNS lymphoma on the basis of histopathology and immunohistochemistry (IHC) and then shifted on radiotherapy (RT) and AML systemic chemotherapy after final immunophenotypic (IPT) diagnosis from cerebrospinal fluid (CSF) leukemic blasts, of myeloid sarcoma. We highlight the diagnostic and therapeutic challenges faced by pathologists and medical oncologists in the management of this rare condition.

  Case Report Top

A 12-year-old male with no previous comorbidities presented with complaints of deviation of angle of mouth to the right side and weakness of the left half of the body for 2 days. He had no complaints of headache, seizures, vomiting, blurring of vision, syncopal episodes, or bleeding from any site of the body. He was first evaluated by a local physician who did magnetic resonance imaging (MRI) of brain [Figure 1]a. MRI showed 65 mm × 43 mm × 49 mm heterogeneously hyperintense lesion with heterogeneous enhancement involving right thalamo-internal capsular region, right cerebral peduncle, right side of midbrain, and pons invading adjacent hypothalamus with midline shift of 6 mm to the left side. The lesion was hypointense on T1w and hyperintense on T2w MRI. A radiological diagnosis of glioma was made. He was referred to neurosurgical department of our institute by a local physician who first evaluated him for further management of primary brain tumor. He was treated with decompressive medications and dexamethasone for 15 days (but no response). The neurosurgeon did stereotactic biopsy of the lesion which revealed normal brain tissue with perivascular collection of small- to medium-sized round cells along with abundant eosinophils [Figure 2]a,[Figure 2]b,[Figure 2]c. Possible morphological diagnosis of histiocytosis or lymphoid malignancy was made. The patient was referred to our department for further management. On examination, he was oriented to time, place, and person. His vitals were within normal range. No lymph nodes were palpable. On neurological examination, pupils were equally reacting to light. Fundus examination was normal with no evidence of papilledema. He had left-sided supranuclear facial palsy with power of 3/5 in muscles of the left half of body. Babinski's sign was present on the left side. There was no neck stiffness or nystagmus. The sensory examination was normal. There was no evidence of spinal tenderness or cord compression. Rest of the systemic examination was normal. The complete blood count (CBC) revealed the following: hemoglobin of 12.5 g/dl, total leukocyte counts of 13,200/mm3, and platelet counts of 36,700/mm3. There were no evidence of blasts on peripheral smear (P/S). Rest of serum biochemistries, including liver and renal function tests, were within normal range. IHC from biopsy sample was positive for vimentin, leukocyte common antigen, cluster of differentiation (CD43), CD117, S-100 and negative for CD3, CD1a, CD20, and CD79a with possible diagnosis of GS versus lymphoid malignancy [Figure 3]. MPO was not done due to nonavailability of the stain at the time. Bone marrow aspiration and trephine biopsy revealed normocellular marrow with no evidence of any malignancy. CSF for routine, microscopy, and cytology was performed as part of workup. CSF was clear and colorless with glucose concentration of 64.42 mg/dl, protein content of 25 mg/dl, chloride concentration of 122.1 mmol/L, and leukocyte count of 40 cell/mm3. CSF cytology examination was positive for malignant cells [Figure 2]d. As there was diagnostic confusion on IHC, CSF was sent for IPT for confirmation of diagnosis. However, in view of deteriorating neurological status, a provisional diagnosis of primary CNS lymphoma was made, and DeAngelis protocol (high-dose methotrexate based) was initiated while waiting for CSF-IPT report. The patient was administered week 1 chemotherapy. CSF-IPT was done with six color flow cytometer (fluorescence – activated cell sorting Canto II) on 26% of blasts gated which was positive for CD13, CD33, MPO, CD117, CD34, and human leukocyte antigen - antigen D related and negative for CD3, CD5, CD7, CD2, CD4, CD8, CD1b, CD19, CD10, CD20, and TdT. A final diagnosis of aleukemic GS was made. In view of patient's increasing left-sided neurological deficits and new symptom of headache with MRI suggestive of midline shift, the patient was started on whole brain RT of 24 Gy in 12 fractions with boost of 10 Gy in 5 fractions to thalamus with biweekly triple intrathecal (IT) chemotherapy (methotrexate 12 mg, cytarabine 30 mg, and prednisolone 10 mg). Triple IT was continued till three CSF cytospin preparations were negative for malignant cells. Follow-up MRI showed significant regression in size of lesion [Figure 1]b. He has now been planned for 3 cycles of high-dose cytarabine (HiDAC) (2 g/m2 3 h infusion, 12 hourly for 6 days). He has successfully completed 2 cycles with complete recovery of neurological functions. Serial CBC and P/S still do not show evidence of leukemia as of today.
Figure 1: (a) Pretreatment magnetic resonance imaging showed 65 mm × 43 mm × 49 mm heterogeneously hyperintense lesion with heterogeneous enhancement involving right thalamo-internal capsular region, right cerebral peduncle, right side of midbrain, and pons invading adjacent hypothalamus with midline shift of 6 mm to the left side. (b) Postwhole brain radiotherapy and triple intrathecal, magnetic resonance imaging show significant regression in size of the lesion

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Figure 2: Granulocytic sarcoma of brain: (a) brain tissue shows monotonous round cell infiltration (H and E, ×4). (b and c) Large monotonous cells showing eosinophilic cytoplasm with irregular hyperchromatic nucleus with scattered eosinophils (H and E, ×40). (d) Cerebrospinal fluid cytology shows malignant cells

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Figure 3: Immunohistochemistry: (a) CD43 positive (×10), (b) CD79a negative (×10), (c) c-kit positive (×40), and (d) leukocyte common antigen positive (×10)

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  Discussion Top

GS has been classified into four groups depending on the clinical situation as (1) primary GS in 0.6% of cases, (2) GS during active phase of AML, (3) GS as isolated recurrence of AML (new isolated focus of GS that occurs during bone marrow remission and not followed by medullary relapse in <30 days), and (4) GS with concurrent bone marrow relapse with GS developing after allogeneic hematopoietic stem cell transplantation (HSCT) in 0.2%–1.3% of patients.[1] Certain sites such as CNS and reproductive organs are commonly involved by GS during relapse due to their being sanctuary sites for leukemic cells, which survive treatment with chemoradiotherapy due to inherent barriers.[7],[8] The pathogenesis of intracranial GS involves infiltration of leukemic cells into superficial arachnoid veins with local proliferation leading to the formation of solid mass. This expanding leukemic mass infiltrates the underlying brain parenchyma through pial-glial membrane or through Virchow–Robin space leading to interference with local perfusion.[4]

The common sites of intracranial GS in decreasing order of frequency are temporal lobe, frontal lobe, cerebellum, parietal lobe, occipital lobe, cerebellopontine angle cistern, corpus callosum, basal ganglia, and subdural space.[6] Our patient had GS involving thalamo-internal capsular region invading adjacent structures such as cerebral peduncle, midbrain, pons, and hypothalamus. Radiologically intracranial GS is mostly extra-axial masses and is typically isodense to hyperdense on computed tomography, hypointense or isointense on T1w MRI, and heterogeneously isointense to hyperintense on T2w MRI,[1] as was in our case. GS is subclassified depending on degree of maturation into three variants: (1) blastic with predominance of myeloblasts, (2) immature with mix of myeloblasts and promyelocytes, and (3) differentiated with promyelocytes, mature granulocytes, and abundant eosinophils.[8] GS is commonly misdiagnosed typically as non-Hodgkin lymphoma (NHL) in approximately 46% of patients.[7] Other differentials include other forms of NHL, Ewing's sarcoma, undifferentiated carcinoma or melanoma, extramedullary hematopoiesis, malignant histiocytosis, and malignant mastocytosis with atypical mast cells. The definitive diagnosis of GS is usually based on IHC and/or IPT. The markers expressed in decreasing order of frequency are: CD 68/KP-1, MPO, CD43, lysozyme, CD117, CD45, CD99, CD68/PG-M1, CD34, TdT, CD56, CD61, CD30, glycophorin, CD4, CD79a, CD20, CD3, and CD10. CD13, CD33, CD117, and MPO are most common markers in flow cytometric analysis of GS with myeloid differentiation and CD14, CD163, and CD11c in GS with monoblastic differentiation.[8] In our case, IPT on CSF was sent for diagnostic confirmation as IHC was inconclusive.

The recent guidelines from Bakst et al. recommend the use of AML-like induction therapy for isolated GS, followed by consolidation with RT. RT is considered in patients of isolated GS, poor response to chemotherapy, recurrence after HSCT, and for rapid symptom relief of vital structure compression (as was in our case). RT dose of 24 Gy in 12 fractions is usually recommended,[7] but a higher RT dose is needed when tumor is large (more than 6 cm or 30 cm2),[2] as was in our case. Since our patient had positive CSF cytospin preparation, we administered him with triple IT chemotherapy. The proof that GS is extremely radiosensitive tumor was provided by repeat MRI post-RT which showed marked reduction in the size of lesion with symptom relief. However, RT alone may prolong failure-free survival but not overall survival (OS) in patients of isolated GS. It has been established that OS is longer in patients who are given AML-based induction regimens.[8] We preferred to give HiDAC to our patient post-RT to avoid radiation recall associated with anthracyclines and to achieve higher therapeutic concentrations in brain tissue and perivascular space. Isolated GS may be associated with superior event-free survival and OS as compared to AML when patients are treated with AML-based regimens; however, median survival is <24 months.[9] It has been reported that 87% of patients who were diagnosed as aleukemic GS but did not receive chemotherapy developed acute leukemia at mean of 10.5 months after diagnosis of GS. However, 25% of patients who did receive chemotherapy did not develop leukemia during follow-up period of 3.5–16 years after diagnosis of GS.[6] Patients of GS accompanying AML have better outcomes than GS with CML or MDS.[8] Allo-HSCT can be potentially efficient treatment modality in patients of isolated GS with 5-year OS, leukemia-free survival, and nonrelapse mortality rate of 48%, 36%, and 17%, respectively.[9] Hence, allo-HSCT should be considered as first-line therapy even in patients of isolated GS who achieve complete remission following AML type therapy.

  Conclusion Top

Isolated primary intracranial GS is extremely rare, but relevant clinical information, including symptomatology, past or present history of any hematologic malignancy, proper neuroimaging, prompt pathological evaluation with use of IHC and IPT (from CSF when feasible) studies, and early start of systemic AML-like chemotherapy with cranial RT and HSCT, would promise a longer survival to these patients who are mostly young. Our case emphasizes the importance of the above and also highlights the diagnostic dilemmas associated with GS. Furthermore, continuous monitoring of such patients is needed for early detection of systemic leukemia.

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There are no conflicts of interest.

  References Top

Samanta DR, Mohanty KR, Roopesh K, Senapati SN. Primary granulocytic sarcoma of meninges and mediastinum as diagnostic dilemma. Indian J Hematol Blood Transfus 2013;29:102-5.  Back to cited text no. 1
Song JH, Son SH, Lee JH, Chung SM, Jang HS, Choi BO, et al. Defining the optimal dose of radiation in leukemic patients with extramedullary lesions. BMC Cancer 2011;11:428.  Back to cited text no. 2
Kulkarni RS, Anand AS, Patel AA, Shah SA, Panchal HP, Parikh SK, et al. Aleukemic granulocyticsarcoma and leukemia cutis: A report of two rare cases and review of literature. J Appl Hematol 2016;7:70-5.  Back to cited text no. 3
  [Full text]  
Huanyu W, Hong W, Quanfeng M, Yiyang C. Intracranial granulocytic sarcoma: Two cases and literature review. Int J Clin Exp Med 2015;8:19586-90.  Back to cited text no. 4
Koudstaal MJ, Van der Wal KGH, Lam KH, Meeuwis CA, Speleman L, Levin MD. Granulocytic sarcoma (chloroma) of oral cavity: Report of a case and literature review. Oral Oncol Extr 2006;42:70-7.  Back to cited text no. 5
Cervantes GM, Cayci Z. Intracranial CNS manifestations of myeloid sarcoma in patients with acute myeloid leukemia: Review of the literature and three case reports from the author's institution. J Clin Med 2015;4:1102-12.  Back to cited text no. 6
Bakst RL, Tallman MS, Douer D, Yahalom J. How I treat extramedullary acute myeloid leukemia. Blood 2011;118:3785-93.  Back to cited text no. 7
Avni B, Koren-Michowitz M. Myeloid sarcoma: Current approach and therapeutic options. Ther Adv Hematol 2011;2:309-16.  Back to cited text no. 8
Chevallier P, Labopin M, Cornelissen J, Socié G, Rocha V, Mohty M, et al. Allogeneic hematopoietic stem cell transplantation for isolated and leukemic myeloid sarcoma in adults: A report from the acute leukemia working party of the European group for blood and marrow transplantation. Haematologica 2011;96:1391-4.  Back to cited text no. 9


  [Figure 1], [Figure 2], [Figure 3]

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