Fine-needle aspiration cytology of granulocytic sarcoma and myeloid metaplasia

The fine-needle aspiration (FNA) cytology of two cases of granulocytic sarcoma involving the breast is reported along with the FNA cytology of one case of myeloid metaplasia (extramedullary hematopoiesis) involving an axillary lymph node. Two patients had known myeloproliferative disorders, while granulocytic sarcoma of the breast was the initial presentation of an unsuspected acute granulocytic leukemia in the other patient. Diff-Quik-stained preparations aided in the diagnosis of all three cases. Immunoperoxidase stains for factor VIII-related antigen helped confirm the megakaryocytic differentiation of the cells in the FNA cytology of myeloid metaplasia. Electron microscopic (EM) examination performed on the aspirated material also showed megakaryocytic differentiation of the bizarre cells. FNA cytology can make a specific diagnosis of granulocytic sarcoma and myeloid metaplasia. The workup of these unusual extramedullary myeloproliferative masses was aided when immunocytochemistry and EM were performed on the aspirated material.     

Sclerosing extramedullary hematopoietic tumor: emphasis on diagnosis by renal biopsy

Sclerosing extramedullary hematopoietic tumor (SEMHT) is a rare lesion that typically arises in patients with chronic myeloproliferative disorders. Morphologically, it exhibits atypical megakaryocytes, granulocytic precursors, and erythroid precursors set in a background of dense collagen sclerosis. Sclerosing extramedullary hematopoietic tumor may be easily mistaken for other neoplasms, such as sarcoma, carcinoma, or Hodgkin lymphoma, particularly if pertinent clinical history is not provided. Misdiagnosis may occur because of the difficulty in recognizing the megakaryocytic lineage of the atypical cells and because of the paucity of other hematopoietic elements. We report a case of a 72-year-old man with proteinuria and renal insufficiency who underwent renal biopsy to determine the etiology of the proteinuria. The kidney biopsy demonstrated an unusual tumor in which the initial morphological impression that of sclerosing liposarcoma. However, upon learning of the patient's previous history of chronic idiopathic myelofibrosis and with the aid of immunohistochemistry, the correct diagnosis of sclerosing extramedullary hematopoietic tumor was made. Sclerosing extramedullary hematopoietic tumor should be considered in the differential diagnosis when percutaneous renal biopsy or other intra-abdominal biopsy reveals a sclerotic lesion with interspersed large atypical cells, especially in a patient with a history of chronic myeloproliferative disorder.     

Extramedullary hematopoietic proliferations, extraosseous plasmacytomas, and ectopic splenic implants (splenosis)

Hematopoietic proliferations are well known to present ectopically outside the bone marrow, either in benign or malignant form. As such, they present a distinct problem with respect to morphologic interpretation because of their uncommonality in extramedullary sites and their capacity to simulate other lesions histologically. This review considers extramedullary myeloid tumors ("granulocytic sarcoma," "erythroblastic sarcoma," "megakaryocytic sarcoma"), tumefactive extramedullary hematopoiesis, and the peculiar condition known as "splenosis," with consideration of their clinical, microscopic, and cytohistochemical chararacteristics.     

Fine-needle aspiration of granulocytic sarcomas: a morphologic and immunophenotypic study of seven cases

Granulocytic sarcoma is an uncommon extramedullary, solid tumor of myeloid cells. Only rarely has this entity been diagnosed by fine-needle aspiration (FNA) cytology. This report encompasses the cytologic findings of FNAs from seven patients with granulocytic sarcomas, including four male and three female patients with a mean age of 52 years (range, 12 to 77 years). The aspirates were obtained from skin or subcutaneous tissue (four cases), testis (one case), posterior ileum (one case), lymph node (one case), and abdominal washing (one case). Morphology of the aspirates varied from well-differentiated to poorly differentiated cells showing little or no evidence of myeloid differentiation. Thorough search for evidence of myeloid differentiation and a high index of suspicion of granulocytic sarcoma are of paramount importance. In three cases, flow cytometric and immunocytochemical studies were applied to the FNA materials to confirm the myeloid lineage of the cells and the diagnosis. In the other four cases more than one site was involved by the tumor; once the diagnosis of granulocytic sarcoma was established with a biopsy, the FNA sufficed to confirm the diagnosis at another location. This study demonstrates that FNA cytology in conjunction with appropriate immunophenotyping can provide an accurate diagnosis of granulocytic sarcoma. Fine-needle aspiration can reduce the need for surgical intervention when combined with immunophenotypic studies and when additional anatomic sites are involved.     

Relapse of acute myelogenous leukemia as a cerebellar myeloblastoma showing megakaryoblastic differentiation.

Myeloblastomas (granulocytic sarcomas) occurring within the central nervous system (CNS) are extremely rare lesions that may develop in patients with acute or chronic myeloproliferative disorders. The majority of such lesions involve brain or spinal cord by contiguous spread from meningeal or bony sites, rather than originating within the CNS parenchyma. We describe a patient with acute myelogenous leukemia in remission, who developed a purely intraparenchymal cerebellar myeloblastoma with megakaryocytic differentiation. The neoplastic cells expressed the megakaryocytic markers factor VIII-related antigen and platelet glycoprotein-IIIa (CD61), and showed ultrastructural features that were indicative of megakaryocytic differentiation. Clinically, myeloblastomas of the CNS invoke a broad differential diagnosis that includes abscess, hemorrhage, and metastatic neoplasms because of their intraparenchymal location and radiologic features. Although they are rare, myeloblastomas should be included in the histopathologic differential diagnosis of a poorly differentiated neoplasm occurring within the CNS, particularly in a patient with a history of myeloproliferative or myelodysplastic disease.     

Fine-needle aspiration of histiocytic necrotizing lymphadenitis (Kikuchi's disease)

Fine-needle aspiration (FNA) of the lymph node was done in five patients with histiocytic necrotizing lymphadenitis (Kikuchi's disease). In four patients, the aspirates were found to have many small and large atypical lymphocytes, some reactive, phagocytic histiocytes, and intense extracellular debris. Neutrophils, plasma cells, or multinucleated giant cells were not seen. These cytologic findings were considered diagnostic for Kikuchi's disease. In one patient, the aspirate did not show significant histiocytosis or tissue necrosis and was considered nondiagnostic. In patients with both typical clinical features and characteristic cytologic findings in the lymph node aspirates, FNA of the lymph node alone will suffice for diagnosis. In those patients with typical clinical features but nondiagnostic findings in the FNA aspirates, the diagnosis of Kikuchi's disease may have to be established either on repeated nodal FNA or on lymph node biopsy.     

Nonlymphoid hematopoietic malignant disease of the lymph nodes

The extension of myeloproliferative malignant tumors to lymph nodes was studied in seven excision biopsies and 27 autopsies in which lymph nodes were obtained from all nodal regions. We observed the proliferation of poorly, partially, and well differentiated neoplastic cells with a predominance of immature cells of the granulocytic series and fewer cells of the erythroid and megakaryocytic cells lines. Disturbances of the lymph node architecture consisted of invasion by abnormal cells of the trabecular stroma, disrupting the reticulin mesh and extending toward the pericapsular area. In the lymph node a loose network of thin and thick fibers replaced the original framework. Generalized lymph node involvement at autopsy showed preservation of the architecture, both in cases with total replacement of the lymphoid population by abnormal cells and in cases with involvement by single cells or small groups of cells. Partial involvement occurred chiefly in the medullary zone, probably the result of hematogenous dissemination from the vascular plexus in medullary cords. Further abnormal cell development was linked to trabecular infiltration. The extensive involvement seen at autopsy took place by lymphatic dissemination. In lymph nodes studied at autopsy an abnormal immunoblastic reaction was observed. At first these abnormal cells were suspected of representing the myeloproliferative malignant disease, but the application of special staining techniques revealed their polyclonal cytoplasmic immunoglobulins. The chloroacetate esterase stain and the immunohistochemical stains for muramidase and hemoglobulin were especially useful in demonstrating that myeloproliferative diseases develop in the environment found in lymph nodes.     

Fine-needle aspiration of extranodal and extramedullary hematopoietic malignancies

There is relatively little information concerning the use of fine-needle aspiration (FNA) to diagnose extranodal and extramedullary hematopoietic malignancies. Seventy-one such cases diagnosed by FNA form the basis of this study. Seventy-one cases of FNAs performed between 1988 and 1998 on extranodal and extramedullary hematopoietic malignancies were reviewed in order to evaluate the usefulness of this technique in diagnosing these entities as well as to assess patterns of relapse. There were 45 male and 26 female patients ranging in age from 29-86 years (mean, 68 years). Sixty-six patients had a previous history of a hematopoietic malignancy. Aspirates from 65 of these patients were consistent with the patient's known primary. One aspirate of a paravertebral mass from a multiple myeloma patient showed extramedullary hematopoiesis. The remaining five aspirates were cases of multiple myeloma that first presented as soft tissue masses. The most common malignancies were lymphoma: 52 cases (73%), 48 large cell lymphomas, four mixed small and large cell lymphoma; followed by multiple myeloma: 12 cases (17%); leukemia: four cases (5.4%); Hodgkin disease: two cases (2.8%); and one case of extramedullary hematopoiesis. The aspirate sites were soft tissue: 23 cases (32%); bone: 17 cases (24%); kidney: 14 cases (20%); liver: 11 cases (15%); lung: three cases (4%); adrenal: two cases (3%); and eye: one case. The interval between primary diagnosis and FNA was 1-36 months (mean, 13 months). In conclusion, 98% of the aspirates were neoplastic in patients with a known history of hematopoietic malignancies. The most common site of involvement was soft tissue in 23 (32%) cases. In five patients with multiple myeloma, the FNA diagnosis prompted a work-up to find the primary site of involvement. FNA is a useful technique in assessing extranodal and extramedullary hematopoietic malignancies.     

Mediastinal mature teratoma with coexistence of angiosarcoma, granulocytic sarcoma and a hematopoietic region in the tumor: A rare case of association between hematological malignancy and mediastinal germ cell tumor

An association between mediastinal germ cell tumors (MGCT) and hematological malignancies (e.g. acute leukemia, malignant histlocytosis) has been recognized since 1984. A rare case of mediastinal mature teratoma with angiosarcoma, a hematopoietic region and granulocytic sarcoma is reported in a 29-year-old male. The resected tumor was 9.0 × 6.5 cm, weighed 65 g and showed extensive necrosis, forming a cyst. The hlstological features of the tumor showed a mature teratoma, which contained a large gland lined by ciliated epithelium, hyalinous cartilage, a paraganglion-like structure, well-diierentiated angiosarcoma with atypical hematopoiesis composed of CD34-positive cells, and mallgnant round cells. The malignant round cells did not stain for CD34 but were positive for leukocyte common antigen (LCA) and c-kit product. From these findings, the round cells were dlagnosed as granulocytic sarcoma. The patient died of metastasis of the granulocytic sarcoma in the tonsils and cervical lymph nodes 8 months after surgery. A leukemic condition was not present throughout the clinical course. The association between MGCT and hematological malignancy is a distinctive syndrome. However, its pathogenesis is still obscure and the origin of the hematopoietic malignancy has not been fully elucidated. In this particular case, it Is suggested that the granulocytic sarcoma might have arisen from the abnormal hematopoietlc area in the mediastlnal teratoma.     

EXTRAMEDULLARY HEMATOPOIESIS PRESENTING AS MEDIASTINAL TUMOR

An autopsy revealed extramedullary hematopoietic foci scattered along the thoracic vertebrae and between the ribs in a patient who died of lung cancer. One of them formed a tumor-like mass adhering to the 10th vertebra, and measured 8 × 6 × 2 cm. The cellular components included erythrocytic, granulocytic and megakaryocytic series at various stages of maturation as well as abundant iron-pigmented histiocytes. The patient also suffered from chronic hemolytic anemia and secondary hemochromatosis. The intimate relationship of the intrathoracic tumor-like masses of extramedullary hematopoietic tissue with chronic hemolytic anemia is briefly reviewed.     

Immunocytochemical analysis of lymph node aspirates in patients with human immunodeficiency virus infection.

Thirty four patients positive for human immunodeficiency virus (HIV) who had lymphadenopathy were investigated using fine needle aspiration. Cytological analysis included immunocytochemical investigation with the alkaline phosphatase-antialkaline phosphatase (APAAP) method. All patients had confirmation of cytological diagnosis by lymph node biopsy. Fifteen aspirates with follicular hyperplasia were evaluated. Eleven patients showed B cell predominance. The B cell population did not show light chain restriction. Ten patients with B cell non-Hodgkin's lymphoma (five with Burkitt's lymphoma and five with B cell immunoblastic lymphoma) were investigated. Nine out of 10 cases were monoclonal with respect to their light chain determinants; only one case with Burkitt's lymphoma with partial lymph node metastasis did not show light chain restriction. The cytological diagnosis included two mycobacterial infections and four cystic lesions. Histological investigation was necessary to diagnose the extent of lymph node disease caused by Kaposi's sarcoma. These findings indicate that the immunocytological investigation of lymph node aspirates is useful for evaluating lymphadenopathy in HIV positive patients.     

Extramedullary haemopoietic tumours complicating polycythaemia vera.

A 52 year old man with newly diagnosed polycythaemia vera in proliferative phase developed widespread extramedullary haemopoiesis (EMH), and died as a result of cervical cord compression. At necropsy, microscopic areas of primitive cells characteristic of granulocytic sarcoma were found within a large tumour of EMH in the right retroperitoneal region. Ultrastructural analysis showed unusual hexagonal inclusions within the cytoplasm of these primitive cells. Clinicians should be aware of the possibility of discrete haemopoietic tumours, whether EMH or granulocytic sarcoma, in patients with polycythaemia vera as well as in other myeloproliferative disorders.     

Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis

Extramedullary hematopoiesis occurs in patients with a variety of hematologic diseases, and the spleen is a common site. Extramedullary hematopoiesis is very common in chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The pathogenesis of extramedullary hematopoiesis is unknown. Using JAK2 V617F mutation as a molecular marker, we assessed paired spleen and bone marrow samples of 15 patients with various types of chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The diagnosis was chronic idiopathic myelofibrosis (n=8), polycythemia vera (n=3), and chronic myelomonocytic leukemia (n=4). DNA was extracted from fixed, paraffin-embedded tissue and assessed for JAK2 V617F by real-time polymerase chain reaction assay followed by melting curve analysis. Concordant JAK2 mutation was detected in the paired samples in 7 patients. A discordant result with JAK2 V617F found in the spleen but not bone marrow was noted in 1 patient. These results indicate that extramedullary hematopoiesis in patients with chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases is a clonal process and lend support to the theory that the cells of extramedullary hematopoiesis are carried from the bone marrow.     

Granulocytic sarcoma in the absence of acute myeloid leukemia: a case report

Granulocytic sarcoma is an extramedullary tumor composed of immature granulocytic precursor cells. The most common sites of presentation are bone, periosteum, soft tissue, lymph node, skin, and infrequently small intestine. The tumor may develop during the course of acute myeloid leukemia, chronic myeloid leukemia or other myelodysplastic disorders. It can occur without blood or bone marrow manifestations of leukemia and in this case, the diagnosis is difficult. Our patient was initially diagnosed as a case of T-cell non Hodgkin's lymphoma and received one cycle of CHOP with only transient improvement in his symptoms. Subsequently, his biopsy slides were reviewed at our centre and were reported as granulocytic sarcoma.     

Morphologic and immunohistochemical evaluation of splenic hematopoietic proliferations in neoplastic and benign disorders.

Spleen is a common site of extramedullary hematopoiesis. Extramedullary hematopoiesis seen in non-neoplastic conditions can occasionally be extensive and raise concerns for a myeloid neoplasm. We compared the morphologic and immunohistochemical features of splenic hematopoietic proliferations seen in neoplastic myeloid disorders (eg chronic myeloproliferative disorders, myelodysplastic/myeloproliferative disorders and acute myeloid leukemias) to extramedullary hematopoiesis seen in a variety of reactive conditions. In all, 80 spleen specimens were reviewed. The presence of each marrow-derived lineage, dysplasia and immunohistochemical results were evaluated (CD34, CD117, myeloperoxidase, CD68, p53, TdT, CD42b and hemoglobin). Neoplastic hematopoietic proliferations in chronic myeloproliferative disorders are characterized by trilineage hematopoiesis with significant dysplasia in all cell lineages. Acute myeloid leukemia showed an increase in immature forms, which were highlighted by immunohistochemistry. Reactive extramedullary hematopoiesis showed variability in histologic features. Post-bone marrow transplant and thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome spleens showed extramedullary hematopoiesis with some morphologic features of immaturity, which could simulate chronic myeloproliferative disorder. However, they lacked characteristic immunohistochemical features of neoplastic myeloid disorders such as positivity for CD34 or CD117.     

Complex pathological diagnosis of granulocytic sarcoma: apropos of a case

The diagnosis of granulocytic sarcoma can be very difficult when there is no demonstrable abnormality in the peripheral blood or bone marrow. We present the diagnostic algorithm of granulocytic sarcoma by reporting on a case mimicking large cell lymphoma without previous manifestation of acute myeloid leukemia or a myeloproliferative disorder. After standard histoprocessing, we used immunohistochemical and molecular biological methods to analyze our case. The lymph node showed diffuse infiltration of immature blast cells resembling large cell lymphoma. However, immunohistochemistry did not support this diagnosis. The tumor cells showed LCA, bcl-2, CD43, CD34 and myeloperoxidase positivity. We also detected bcl-2 gene rearrangement. In case of a lack of a specific histological picture, particularly in poorly differentiated tumors, only some minor histological signs in combination with immunohistochemistry and molecular diagnostic methods can help to render the correct diagnosis.     

Unusual presentation of granulocytic sarcoma in the breast: a case report and review of the literature

This is a case of granulocytic sarcoma presenting as bilateral breast masses in a 40-yr-old woman with concurrent unsuspected chronic myeloid leukemia diagnosed by fine-needle aspiration. The granulocytic differentiation was recognized on Diff-Quik-stained cytology smears and confirmed rapidly on flow cytometry on the same day. The breast has been reported to be an uncommon site for granulocytic sarcoma. We found that 38.8% of granulocytic sarcomas diagnosed by fine-needle aspiration in the English-language literature occurred in the breast. In the absence of clinical history or hematological abnormality, granulocytic sarcoma may be misdiagnosed, depending on the degree of myeloid differentiation present within the tumor. The differential diagnosis includes large-cell non-Hodgkin's lymphoma, lobular carcinoma of the breast, undifferentiated carcinoma, malignant melanoma, extramedullary hemopoiesis and inflammation. The key morphological features and useful ancillary tests are discussed.     

Splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms: heterogeneous morphology and cytological composition

We studied 24 spleens with extramedullary hematopoietic proliferation (EMHP), a key feature of advanced-stage Philadelphia chromosome-negative myeloproliferative neoplasms, obtained from 24 patients (14 primary myelofibrosis, 7 polycythemia vera and 3 unclassifiable). Hematoxylin and eosin, reticulin and trichrome stains, and immunohistochemical stains for myeloperoxidase, glycophorin-C, CD42b, CD34, CD117, CD8, nerve growth factor receptor and smooth muscle actin were evaluated. Clinical information was correlated with the morphological findings. Three distinct histological patterns of EMHP were recognized: diffuse (12), nodular (5), and mixed-nodular and diffuse (7). The preponderant lineage was granulocytic in diffuse, trilineage in nodular and erythroid in mixed EMHP. Erythropoiesis was largely intravascular, granulopoiesis was within the splenic cords and megakaryopoiesis was observed in both locations. The stromal changes paralleled the histological pattern with preservation of the splenic stromal and vascular architecture in the diffuse areas as opposed to areas of nodular EMHP. The morphological features of the splenic EMHP did not correlate with specific subtypes of myeloproliferative neoplasms. The mean duration of follow-up from initial diagnosis was 80 months. A total of 15 of the 24 patients died of disease: 8 of 12 (67%) with diffuse, 2 of 5 (40%) with nodular and 5 of 7 (71%) with mixed growth patterns. The mean duration from diagnosis to splenectomy was shorter in patients with diffuse (83 months) as compared with those with nodular EMHP (127 months). Our study demonstrates that splenic extramedullary hematopoietic proliferation in Philadelphia chromosome-negative myeloproliferative neoplasms shows distinct histological patterns that do not correlate with disease subtypes, but appear to suggest a trend between the histological patterns and clinical behavior. These results suggest a different biology of the disease in the nodular and diffuse extramedullary hematopoietic proliferation groups.     

Lobular carcinoma with cytoplasmic granules

We report on a case of invasive lobular carcinoma of the breast with a previously undescribed cytologic feature. Diff-Quik-stained cytologic preparations showed uniform single cells with prominent coarse cytoplasmic granules. Ultrastructurally, the granules showed features suggestive of autophagosomes and/or degenerative mitochondria. The cytologic differential diagnosis included granulocytic sarcoma, metastatic melanoma, extramedullary hematopoiesis, large granulocytic leukemia/lymphoma, and mast-cell tumor. Adjunctive studies were helpful in the diagnosis of carcinoma. Histologic study of the mastectomy specimen showed classic type of invasive lobular carcinoma.     

Granulocytic sarcoma of the rectum: a rare complication of myelodysplasia

A 67 year old man with myelodysplasia was admitted as an emergency with a six week history of rectal bleeding and diarrhoea. Barium enema showed an irregular polypoid filling defect in the lateral wall of the proximal rectum near the rectosigmoid junction. Histology showed this to be a granulocytic sarcoma (extramedullary granulocytic leukaemia; chloroma) infiltrating the bowel. A low index of suspicion of this lesion results in an incorrect diagnosis in many such cases. A chloroacetate esterase immunoperoxidase stain will confirm the granulocytic nature of the tumour cells.