Sep2008: Cytodiagnosis of Granulocytic Sarcoma ...

Case Reports

Cytodiagnosis of Granulocytic Sarcoma of Liver Arising in a Milieu of Myeloid Metaplasia A Case Report Nitin Gangane, M.D., D.N.B., Hemlata Kamra, M.D., Anshu, M.D., D.N.B., Deepti Joshi, M.D., and Anupama Gupta, M.D.

Background Granulocytic sarcoma is an extramedullary tumor that is composed of granulocytic precursor cells. We report an unusual case of granulocytic sarcoma of the liver that arose in the background of myeloid metaplasia. Fine needle aspiration cytology (FNAC) was instrumental in making the diagnosis in absence of previously known hematologic abnormality. Case

kept. Cells of all 3 lineages may not be always seen in myeloid metaplasia, and 1 cell line may predominate, causing a diagnostic dilemma.(Acta Cytol 2008;52:619–622) Keywords: aspiration cytology, fine-needle; liver; liver, myeloid metaplasia; sarcoma, granulocytic; tumor, extramedullary myeloid.

Granulocytic sarcoma is a great mimic and can be easily missed if a high index of suspicion is not maintained.

A 65-year-old woman presented with multiple nodules in the liver. USG-guided FNAC was performed on them. The aspirates showed many myeloid blasts, myelocytes, metamyelocytes, erythroid precursors and lymphoglandular bodies. We considered a differential diagnosis of granulocytic sarcoma and myeloid metaplasia. The presence of erythroid precursors prompted us to consider myeloid metaplasia as a differential diagnosis of granulocytic sarcoma. Peripheral smear showed a leukoerythroblastic reaction. The patient died, and necropsy from the liver revealed extensive infiltration by undifferentiated blast cells with areas of myeloid metaplasia showing maturing erythroid, myeloid and megakaryocytic elements. Conclusion

When a dual population of predominant myeloid blasts and normoblasts is encountered, a suspicion of granulocytic sarcoma arising in a background of myeloid metaplasia must be

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ranulocytic sarcoma is an uncommon extramedullary tumor composed of immature cells of the granulocytic series.1 Granulocytic sarcoma can occur in any anatomic site and is known to involve the lymph nodes, bone, soft tissue, skin and breast.2-4 It usually presents along with acute myelogenous leukemia, chronic myelogenous leukemia or other myeloproliferative disorders.2-5 The morphologic recognition of this condition is challenging because of its diverse clinical presentations. Myeloid metaplasia or extramedullary hematopoiesis refers to the production of hematopoietic cells outside the bone marrow. It occurs at the extremes of ages. In the elderly, myeloid metaplasia occurs when the marrow elements are dysfunctional or replaced as in myeloproliferative disease. In fine needle aspirates, granulocytic sarcoma and myeloid metaplasia are considered as differential diag-

From the Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Wardha, Maharashtra, India. Dr. Gangane is Professor and Head. Drs. Kamra and Joshi are Lecturers. Address correspondence to: Nitin Gangane, M.D., D.N.B., Department of Pathology, Mahatma Gandhi Institute of Medical Sciences, Sevagram 442102, Wardha, Maharashtra, India ([email protected]). Financial Disclosure: The authors have no connection to any companies or products mentioned in this article. Received for publication September 15, 2006. Accepted for publication November 20, 2006.

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Drs. Anshu and Gupta are Readers.

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noses for each other, because myeloid metaplasia can resemble the blastic, immature and differentiated forms of granulocytic sarcoma. We report an unusual case of granulocytic sarcoma of the liver arising in a background of myeloid metaplasia in which fine needle aspiration cytology

Lymphoglandular bodies, so often quoted as a hallmark of lymphoid neoplasms, can also be seen in myeloid lesions.

Case Report A 65-year-old woman presented to the medicine outpatient department with complaints with fever, breathlessness, vomiting and abdominal pain of 5 days duration. On examination, she was icteric and had pedal edema. She had moderate hepatomegaly. Ultrasonographic examination of the abdomen showed multiple liver nodules varying from 1.5 to 3 cm. The radiologic impression was secondaries in the liver. Ultrasonography also revealed peripancreatic and periaortic lymphadenopathy. FNA was performed on the liver nodules under ultrasonographic guidance using a 23-gauge spinal nee-

Figure 1 Smear showing benign hepatocytes, myelocytes and mature myeloid cells (Giemsa stain, × 400).

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Figure 2 Smear shows normoblasts and undifferentiated blast cells (Papanicolaou stain, × 400).

dle and 10-mL syringe. Both air-dried and ethanolfixed smears were prepared. The air-dried smears were stained with Giemsa stain, and the ethanol-fixed smears were stained with Papanicolaou stain. Cytologic Findings Aspirates from the liver showed normal and reactive hepatocytes singly placed or arranged in small sheets. In the background, a large number of mature and immature granulocytic precursors were observed (Figure 1). These granulocytic precursors were difficult to recognize on the Papanicolaou-stained smears, where they had eosinophilic gray cytoplasm with an eccentrically located nucleus (Figure 2). However, the Giemsa-stained smears clearly showed the presence of a large number of myeloid blasts, myelocytes and metamyelocytes. The blasts were 2.5–4 times the size of a small lymphocyte, with a moderate amount of pale blue to bluegray cytoplasm, round to oval nuclei, finely dispersed chromatin and prominent nucleoli. Immature myeloid precursor cells with eccentrically placed nuclei and moderate amounts of cytoplasm containing azurophilic cytoplasmic granules were identified in the Giemsa smears. Although eosinophilic myelocytes could be discerned, we did not see any cells with Auer rods. A significant number of normoblasts were also seen with the granulocytic precursors. The smears also showed lymphoglandular bodies, which were best observed in Giemsa-stained smears. We initially considered a differential diagnosis of granulocytic sarcoma and myeloid metaplasia. The absence of megakaryocytes, which would have otherwise made the diagnosis of myeloid metaplasia

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(FNAC) was instrumental in making the diagnosis in absence of any previously known hematologic abnormality. The diagnosis of granulocytic sarcoma was confounded by the presence of a large number of erythroid precursors in the background, which represented myeloid metaplasia.

Figure 3 Predominant blastic elements in focus with normal and reactive hepatocytes (hematoxylin-eosin, × 400).

evident, was cause for diagnostic dilemma. No megakaryocytes could be seen in any of the smears despite diligent search. Nevertheless, we were unable to explain the presence of myeloid blasts and erythroid precursors together in any other manner. A diagnosis of granulocytic sarcoma arising in the backdrop of myeloid metaplasia was offered. Peripheral smear examination showed a leukoerythroblastic reaction. The total nucleated cell count was 15 × 109 cells/L. Of these, almost 50% were normoblasts. The corrected total leukocyte count was 7.5× 109 cells/L. The differential count was myeloblasts 12%, promyelocytes 6%, myelocytes and metamyelocytes 36% and band forms and neutrophils 56%. Platelets were reduced on the peripheral smear. The patient died on the day after admission. Trephine biopsy showed only cortical bone with no hematopoietic elements. Necropsy material from the liver revealed extensive replacement of the hepatic parenchyma by blast cells and other precursors of the granulocytic series (Figure 3). There was also evidence of myeloid metaplasia in other foci of the hepatic parenchyma. Discussion Granulocytic sarcoma is a rare tumor of the extramedullary sites that is composed of granulocytic precursors and, occasionally, a significant number of cells with a relatively high degree of granulocytic differentiation. Granulocytic sarcoma has been reported in a large number of sites, including lymph nodes, bone, soft tissue and skin.2-4 Granulocytic sarcoma involving the liver has also been reported by a few authors.4,6,7 Granulocytic sarcoma is a lesion that is usually missed at initial diagnosis because of its diverse clini-

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cal and morphologic presentations. It usually presents in concert with a hematologic malignancy such as acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) or other myeloproliferative disorders.2-5 It rarely precedes the onset of leukemia.1,8 In this case, no hematologic abnormality was suspected until the aspirates showed a large number of immature granulocytic precursors. No overt malignancy was detected on the peripheral smear, and only a leuko-erythroblastic picture was seen. Krause8 reported 6 cases of granulocytic sarcoma that preceded peripheral smear or bone marrow manifestations of AML. The significance of granulocytic sarcoma in patients without evidence of acute leukemia is difficult to assess at the time of initial presentation because it may not develop in every patient with granulocytic sarcoma. Myeloid metaplasia or extramedullary hematopoiesis must be considered in the differential diagnosis of granulocytic sarcoma.4 The differential diagnosis varies depending on the predominating cell line or the level of cellular maturity. Myeloid metaplasia is usually associated with myeloproliferative disorders and myelophthisic anemia in the elderly. Myeloid metaplasia can be associated with granulocytic sarcoma.3,9 Unlike granulocytic sarcoma, myeloid metaplasia demonstrates hematopoietic cells of all 3 lineages— erythroid, myeloid and megakaryocytic, although any single lineage can predominate.10,11 Granulocytic sarcoma lacks megakaryocytic and erythroid cell lines.11 We did not see megakaryocytes in the aspirates. However, the large number of normoblasts still favored a diagnosis of myeloid metaplasia. A large number of lymphoglandular bodies were seen in the aspirates. Raab et al11 noted that lymphoglandular bodies are seen in lymphoid lesions and are absent in extramedullary hematopoiesis. The liver necropsy specimen confirmed the simultaneous presence of granulocytic sarcoma and myeloid metaplasia. The areas of granulocytic sarcoma showed mostly myeloid blasts, with few mature myeloid cells, whereas the areas of myeloid metaplasia showed maturing myeloid and erythroid cells. There was no myeloid blast predominance in the areas showing myeloid metaplasia. Granulocytic sarcoma is a great mimic and can be easily missed if a high index of suspicion is not maintained. It must be suspected even in patients who do not have a previous history of hematolymphoid neoplasm, as our case demonstrates. It is essential to remember that it can arise in a background of myeloid metaplasia. A diagnosis of myeloid metaplasia must be considered even if cells of all 3 lineages are not present, because any single lineage may predominate. It is also important to note that lymphoglandular bodies, so often quoted as a hallmark of lymphoid neoplasms,

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can also be seen in myeloid lesions.

Sales Maicas MA, Ferrandez Izquierdo A, Roman Sanchez P: Hepatic granulocytic sarcoma: An unusual presentation. Ann Med Intern (Paris) 2003;20:141–144

1. Muss HB, Moloney WC: Chloroma and other myeloid tumors. Blood 1973;42:721–728 2. Sisack MJ, Dunsmore K, Sidhu-Malik N: Granulocytic sarcoma in absence of myeloid leukemia. J Am Acad Dermatol 1997; 37:308–311 3. 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. Best-Aguilera CR, Vazquez-Del Mercado M, Munoz-Valle JF, Herrera-Zarate L, Navarro-Hernandez RE, Martin-Marquez BT, Oregon-Romero E, Ruiz-Quezada S, Bonilla GM, Lomeli-Guerrero A: Massive myeloid sarcoma affecting central nervous system, mediastinum, retroperitoneum, liver and rectum associated with acute myeloblastic leukemia: A case report. J Clin Pathol 2005;58:325–327 8. Krause JR: Granulocytic sarcoma preceding acute leukemia: A report of 6 cases. Cancer 1979;44:1017–1021

4. Suh YK, Shin HJC: Fine needle aspiration biopsy of granulocytic sarcoma: A clinicopathologic study of 27 cases. Cancer (Cancer Cytopathol) 2000;90:364–372

9. Roy EP 3rd, Rogers JS 2nd, Riggs JE: Intracranial granulocytic sarcoma in postpolycythemia myeloid metaplasia. South Med J 1989;82:1564–1567

5. Inverardi D, Lazzarino M, Morra E, Bernasconi P, Merante S, Canevari A, Pagnucco G, Bernasconi C: Extramedullary disease in Ph1-positive chronic myelogenous leukemia: Frequency, clinical features and prognostic significance. Hematologica 1990;75:146–148

10. Silverman JF, Geisinger KR, Park HK, Strausbauch PR, Frable WJ: Fine needle aspiration cytology of granulocytic sarcoma and myeloid metaplasia. Diagn Cytopathol 1990;6:106–111

6. Alama Zaragoza MA, Robles Iniesta A, Roca Adelanatado I,

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11. Raab SS, Silverman JF, McLeod DL, Geisinger KR: Fineneedle aspiration cytology of extramedullary hematopoiesis (myeloid metaplasia). Diagn Cytopathol 1993;9:522–526



References