An Elderly Patient with Myelodysplastic Syndrome and Multiple Cutaneous Infiltrative Nodules - A Rare Case of Granulocytic Sarcoma

BULLETIN FOR MEDICAL PRACTITIONERS

Dr Cheah Kee Leong, Registrar, Singapore General Hospita
Dr Lim Lay Cheng, Consultant, Singapore General Hospital
Dr Chua Sze Hon, Consultant, National Skin Centre

Introduction

Granulocytic sarcoma (GS) is a localized extramedullary neoplastic tumor consisting of immature granulocytic cells and can occur at various sites of the body. It has been reported mainly in association with hematological malignancies. We report a rare case of granulocytic sarcoma in an elderly Chinese lady with myelodysplastic syndrome (MDS) presenting with multiple
infiltrative skin nodules.

Case Report

The patient, a 73-year-old Chinese female, presented to the hospital with symptoms of significant weight loss over the preceding 6 weeks and multiple painless rapidly enlarging skin nodules. The skin nodules measured 15-20 mm in diameter and were distributed randomly over the left anterior chest, right groin and lower back. The lesions were erythematous, firm in consistency and were adherent to the overlying skin (Fig.1). There was no associated epidermal change, necrosis, ulceration or hemorrhage. Other significant physical signs present were hepatosplenomegaly without any lymphadenopathy.

Initial screening blood counts showed a Tw of 14.1X 10 /L, with 4% blasts, 23% myelocytes and 5% metamyelocytes, Hb of 7.4g/dL, and a Plt count of 685 X 10 /L. The bone marrow examination subsequently carried out revealed fibrosis with a few blasts and the cytogenetic study showed clonal aberrations consistent with MDS. An excision skin biopsy of the cutaneous nodule on the lower back was performed. The histology showed a dense infiltrate in the dermis, more cellular in the deeper part, consisting of a monomorphous population of primitive cells as cords and sheets separating collagen bundles and
around nerves and skin appendages. The tumour cells had round vesicular nuclei with prominent nucleoli, and cytoplasm was abundant with a granular or foamy appearance (Fig. 2). Immunohistochemistry with myeloperoxidase shows positive reactivity within the tumor cells. The above features were consistent with granulocytic sarcoma.

2 months after initial presentation, the patient developed increasing drowsiness, progressive hemiparesis and debility. Magnetic resonance imaging scan of her brain showed a small enhancing hypercellular intraventricular lesion at the right foramen of Monro causing an obstructive hydrocephalus. The intracranial lesion was most likely that of a granulocytic sarcoma given her background medical history. A ventriculo-peritoneal shunt was inserted with some reduction in size of the hydrocephalus. Her mental status improved slightly though the weakness remained Cerebrospinal fluid analysis showed the presence of a few abnormal cells. More cutaneous infiltrative nodules were now present and involved the scalp and eyelids as well.

While in hospital, she had an accidental fall and sustained a bilateral acute subdural haematoma which was subsequently drained via a burr hole. Intrathecal chemotherapy was considered, however, due to the persisting subdural haematoma with mass effect, it was withheld. Computer tomographic scan of the chest also revealed nodular infiltrates in the right lung and mediastinal lymphadenopathy. She later received radiotherapy to the mediastinum and cranium as well as to the larger skin nodules. Subsequently, however, she declined further treatment opting for traditional herbal therapy instead. She died soon after from progressive disease and complicating septicemia.

Discussion

Granulocytic sarcoma (GS) was first described by Burns in 1811(1). It was initially coined ‘chloroma’ by King in 1853 because of its characteristic green hue due to the presence of granulocyte myeloperoxidase(2). However, it often has no distinct colour and other colours have also been described(4). Thus, it was given its preferred term ‘granulocytic sarcoma’ by Rappaport in 1966(3). Other less described terms include myeloblastoma, myelocytoma, granulocytic leukosarcoma and chloromyeloma. Recently in 1988, Davey has proposed the encompassing term ‘extra-medullary myeloid tumor’ which includes nonmedullary extra-meningeal leukemic infiltrates(8).

Though GS is a well-established entity, its true incidence is unknown. It is generally considered to be rare and is often found only at autopsy(4,6). It occurs more commonly in children and young adults with hematological malignancies and has a slight male preponderance(4,6. In the case of its association with MDS, patients are generally older as in our case. GS is most commonly associated and usually presents concurrently with acute myeloid leukemia (AML), though it can be a sign of impending or relapsing AML or can develop after the onset of AML(6). With associated myeloproliferative disease or
myelodysplastic syndrome (MDS), it can be a sign of blast transformation(4,6,7). Rarely, GS presents in isolation without a haematological disorder(6).

GS can be found in any part of the body, the most common sites being bone, soft tissue, skin, CNS and lymph
nodes(4,6,12). The mode of presentation is usually due to tumor growth, adjacent tissue destruction or compressive
effects(4,6). Our patient had initial skin lesions only at presentation but subsequently developed tumor involvement of the brain and mediastinum.

On the skin, GS usually appears as rapidly growing firm papulonodular lesions. It can be solitary, multiple or
disseminated(10). It is most commonly found on the scalp, trunk and face(6). It has been postulated that trauma leads
to extravasation of myelodysplastic cells which replicate in the skin(5). The skin is the most common site of
involvement in cases of GS occurring in association with MDS(11) . Our patient had skin masses which were nodular
and multiple, mostly on the trunk but she later developed lesions on her scalp and eyelids as well.

GS often presents as an initial diagnostic dilemma. Histologically, it is characterized by the presence of eosinophilic myelocytes in the well-differentiated stage. However, in most cases, it occurs at various stages of differentiation. When it is poorly differentiated, it is not easily recognised and frequently misinterpreted as lymphoma(6,7,9). The use of a broad panel of tests involving immunohistochemical (e.g. stain for myeloperoxidase, lysozyme, CD43) and cytochemical studies (e.g. Leder stain for naphthol-ASD-chloro-acetateesterase) which aid in the diagnosis GS are recommended(8,14).

The therapeutic options for GS include chemotherapy, radiation and surgery. Chemotherapy has been found to prolong life and may prevent the development or relapse of leukemia in cases of isolated GS and GS associated with leukemia(12,13). The treatment of GS in other settings is less clear. Generally, isolated GS, GS preceding AML, and GS in the presence of myeloproliferative disorders and MDS have a poor prognosis(6,11).

References

1. Burns A. Observations on the Surgical Anatomy of the Head and Neck. Edinburgh: Thomas Bryce and Co, 1811:364-366
2. King A. A case of chloroma. Monthly J Med 1853; 17:97.
3. Rappaport H. Tumors of the hematopoietic system. Atlas of tumor pathology. Washington, DC Armed Forces Institute of Pathology, 1966:241-243.
4. Liu PI, Ishimaru T, McGregor DH, Okada H, Steer A. Autopsy study of granulocytic sarcoma (chloroma) in patients with myelogenous leukemia, Hiroshima-Nagasaki 1949-1969. Cancer 1973; 31:948-955.
5. Barton JC, Conrad ME, Poon M. Pseudochloroma:extramedullary hematopoetic nodules in chronic myelogenous leukemia. Ann Intern Med 1979; 91:735-738.
6. Neiman RS, Barcos M, Berard C, Bonner H, Mann R, Rydell RE, Bennett JM. Granulocytic sarcoma: A clinicopathologic study of 61 biopsied cases. Cancer 1981; 48:1426-1437.
7. Meis JM, Butler JJ, Osborne BM, Manning JT. Granulocytic sarcoma in non-leukemic patients. Cancer 1986; 58:2697-2709.
8. Davey FR, Olson S, Kurec AS, Eastman-Abaya R, Gottlieb AJ, Mason DY. The immunophenotyping of extramedullary myeloid cell tumors in paraffin-embedded tissue sections. Am T Surg Pathol 1988; 12:699-707.
9. Fellbaum C, Hansmann ML. Immunohistochemical differential diagnosis of granulocytic sarcomas and malignant lymphomas on formalin-fixed material. Virchows Arch 1990; 416:351-355.
10. Lin CK, Liang R, Ma L, et al. Myelodysplastic syndrome presenting with generalized cutaneous granulocytic sarcomas. Acta Haematology 1990; 83:89-93
11. List AF, Ganzalez-Osete G, Kummet T, Doll DC. Granulocytic sarcoma in myelodysplastic syndromes: clinical marker of disease acceleration. Am J Med 1991; 90(2):274-276
12. Byrd JC, Edenfield WJ, Shields DJ, Dawson NA. Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: A clinical review. J Clin Oncol 1995; 13:1800-1816.
13. Byrd JC, Edenfield WJ, Dow NS, Aylesworth C, Dawson N. Extramedullary myeloid cell tumors in myelodysplastic syndromes: Not a true indication of impending acute myeloid leukemia. Leukemia Lymphoma 1996; 21:153-159.
14. Menasce LP, Banerjee SS, Beckett E, Harris M: Extramedullary myeloid tumour (granulocytic sarcoma) is often misdiagnosed: A study of 26 cases. Histopathology 1999;34:391-398.
     

DEDICATED TO EXCELLENCE IN DERMATOLOGY
By National Skin Centre (Singapore)
Copyright (C) 1995 - National Skin Centre (Singapore)

 

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