Crystalline inclusions in granulocytic sarcoma: report of 2 cases and ultrastructural studies.
The cells of acute granulocytic leukemia have been reported to contain a variety of inclusions, including Auer rods, "hexagonal" or "light green" crystals, pseudo-Chediak-Higashi granules, Charcot-Leyden crystals, and other unclassified inclusions. (1-6) These inclusions have not, to our knowledge, been reported as a histologic feature of granulocytic sarcoma (GS). In this article, we report 2 cases of GS with numerous crystalline inclusions. These cases demonstrated the ultrastructural features of Charcot-Leyden crystals. (7) Recognition of these crystals is important to avoid diagnostic confusion with plasma cell myeloma plasma cell myeloma
A malignant plasmacytoma of bone. or lymphoplasmacytic lymphoma, which may contain morphologically similar immunoglobulin inclusions. (8)
REPORT OF CASES
A 58-year-old woman presented to the oral surgery service with a lytic lytic /lyt·ic/ (lit´ik)
1. pertaining to lysis or to a lysin.
2. producing lysis.
1. Of, relating to, or causing lysis.
2. lesion of the mandible. An incisional biopsy performed at another hospital had been diagnosed as malignant lymphoma. Complete blood count on admission and staging bone marrow biopsy Bone marrow biopsy
A procedure in which cellular material is removed from the pelvis or breastbone and examined under a microscope to look for the presence of abnormal blood cells characteristic of specific forms of leukemia and lymphoma. were within normal limits. Chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine vincristine /vin·cris·tine/ (vin-kris´ten) an antineoplastic vinca alkaloid; used as the sulfate salt in the treatment of various neoplasms, including Hodgkin's disease, acute lymphocytic leukemia, non-Hodgkin's lymphoma, Kaposi's , prednisone) was begun; after 2 cycles of chemotherapy, a rising white blood cell count white blood cell count,
n a diagnostic clinical laboratory test to determine the number and types of leukocytes present in a measured sample of blood. Overall the normal number of leukocytes ranges from 5000 to 10,000/mm3. and circulating blast levels up to 0.60 were noted. Immunophenotypic studies by flow cytometry demonstrated a myeloid phenotype (CD[13.sup.+], CD[33.sup.+]), and a diagnosis of acute granulocytic leukemia was established (French-American-British, M1; World Health Organization, acute myeloid leukemia, not otherwise categorized, without maturation). Crystalline inclusions were not identified in peripheral blood or bone marrow smears. The patient died soon thereafter; autopsy was not obtained. Review of the incisional biopsy was consistent with GS.
A 50-year-old woman presented to the orthopedic service with a lytic lesion of the left os pubis pubis /pu·bis/ (pu´bis) [L.] pubic bone.
n. pl. pu·bes
1. See pubic bone.
2. The hair of the pubic region just above the external genitals. . Complete blood count on admission revealed the following values: hemoglobin, 97 g/L; hematocrit, 0.294; platelets, 646 x [10.sup.9]/L; and white blood cells White blood cells
A group of several cell types that occur in the bloodstream and are essential for a properly functioning immune system.
Mentioned in: Abscess Incision & Drainage, Bone Marrow Transplantation, Complement Deficiencies , 10.6 x [10.sup.9]/L with a normal differential. A core needle biopsy was performed and interpreted as round cell tumor suspicious for lymphoma. Immunohistochemical and ultrastructural studies established a diagnosis of GS, and the patient was referred for radiation and chemotherapy elsewhere.
MATERIALS AND METHODS
Tissue for histology was fixed in 10% neutral buffered formalin and processed for paraffin embedding. Immunohistochemistry was performed on deparaffinized sections by standard techniques. Tissue for ultrastructural-studies was fixed in 3% glutaraldehyde glutaraldehyde /glu·ta·ral·de·hyde/ (gloo?tah-ral´de-hid) a disinfectant used in aqueous solution for sterilization of non-heat–resistant equipment; also used as a tissue fixative for light and electron microscopy. , postfixed in osmium osmium (ŏz`mēəm), metallic chemical element; symbol Os; at. no. 76; at. wt. 190.2; m.p. 3,045±30°C;; b.p. 5,027±100°C;; sp. gr. 22.57 at 20°C;; valence usually +0 to +8. , and stained with uranyl acetate and lead citrate.
Pathology and Immunohistochemistry
Case 1.--The specimen consisted of bone and overlying overlying
suffocation of piglets by the sow. The piglets may be weak from illness or malnutrition, the sow may be clumsy or ill, the pen may be inadequate in size or poorly designed so that piglets cannot escape. mucosa infiltrated by a monotonous population of medium-sized blasts with round to ovoid nuclei and moderately abundant amphophilic cytoplasm. Scattered macrophages were present, containing abundant intracytoplasmic intracytoplasmic /in·tra·cy·to·plas·mic/ (-si?to-plaz´mik) within the cytoplasm of a cell. , eosinophilic eosinophilic /eo·sin·o·phil·ic/ (-fil´ik)
1. readily stainable with eosin.
2. pertaining to eosinophils.
3. pertaining to or characterized by eosinophilia. , needlelike crystals (Figure 1). Immunohistochemical studies showed the blasts were positive for CD43 and myeloperoxidase, and negative for CD20 and CD79a. The intracytoplasmic crystals were negative for myeloperoxidase.
[FIGURE 1 OMITTED]
Case 2.--The specimen consisted of a core biopsy infiltrated by a monotonous population of medium-sized blasts with round to ovoid nuclei and moderately abundant amphophilic cytoplasm. Scattered clusters of extracellular, eosinophilic, needlelike crystals were present, particularly in areas of necrosis (Figure 2). Immunohistochemical studies showed the blasts were positive for myeloperoxidase and leukocyte common antigen, and negative for CD20, CD79a, and terminal deoxynucleotidyl transferase. Cytochemical staining (Leder stain) showed the blasts were positive for chloroacetate esterase esterase /es·ter·ase/ (es´ter-as) any enzyme which catalyzes the hydrolysis of an ester into its alcohol and acid.
Any of various enzymes that catalyze the hydrolysis of an ester. , whereas the crystals were negative for myeloperoxidase and chloroacetate esterase.
[FIGURE 2 OMITTED]
Electron microscopy was performed on tissue from case 2. Semithin sections were examined to select areas containing crystals. Electron microscopy demonstrated characteristic electron-dense, bipyramidal structures (Figure 3).
[FIGURE 3 OMITTED]
Acute granulocytic leukemia may contain a variety of intracellular inclusions, including Auer rods, hexagonal or light green crystals, pseudo--Chediak-Higashi granules, Charcot-Leyden crystals, and other unclassified inclusions. (1-6) These inclusions have not, to our knowledge, been reported as a histologic feature of GS. In the present study, we describe 2 cases of GS with numerous needlelike crystals, which had the ultrastructural features of Charcot-Leyden crystals. (7) These crystals were present as intracytoplasmic inclusions in macrophages (crystal-storing histiocytes) in case 1 and as clusters associated with foci of necrosis in case 2. Eosinophils Eosinophils
A leukocyte with coarse, round granules present.
Mentioned in: Histiocytosis X
eosinophils were not a prominent feature in either case.
Charcot-Leyden crystals are bipyramidal needlelike crystals that are usually found in association with eosinophils, most characteristically in the sputum of patients with allergic asthma, but also in tissue in other allergic and hematologic disorders. (6) Charcot-Leyden crystals are composed of the enzyme lysophospholipase (also referred to as Charcot-Leyden crystal protein), which is present in the granules of eosinophils and basophils. (9) Charcot-Leyden crystals have been reported rarely in cases of acute granulocytic leukemia, (6) but have not, to our knowledge, been previously reported as a histologic feature of GS. The presence of Charcot-Leyden crystals in these cases may reflect the potential of the leukemic blasts to differentiate into eosinophils and basophils; Charcot-Leyden crystal protein is inducible in the human acute promyelocytic leukemia acute pro·my·e·lo·cyt·ic leukemia
A severe bleeding disorder that is a form of leukemia and is characterized by low concentrations of plasma fibrigen, defective coagulation, and infiltration of the bone marrow with abnormal promyelocytes and cell line, HL-60. (10)
The presence of Charcot-Leyden crystals in GS is a potential cause of diagnostic confusion, since morphologically similar crystalline inclusions may be found in cases of myeloma and lymphoplasmacytic lymphoma. (8) The latter are typically positive for periodic acid--Schiff reaction and contain immunoglobulin. The presence of crystals contributed to the misdiagnosis mis·di·ag·no·sis
n. pl. mis·di·ag·no·ses
An incorrect diagnosis.
mis·diag·nose of malignant lymphoma in case 1, because the crystal-containing macrophages mimicked the findings in crystal-storing histiocytosis histiocytosis /his·tio·cy·to·sis/ (-si-to´sis) a condition marked by an abnormal appearance of histiocytes in the blood.
acute disseminated Langerhans cell histiocytosis Letterer-Siwe disease. associated with lymphoplasmacytic lymphoma. (8) The correct diagnosis was only established retrospectively, when the patient developed overt acute granulocytic leukemia, prompting review of the previous biopsy.
In summary, pathologists should be aware of the possible presence of Charcot-Leyden--like crystals in cases of GS; these structures should be distinguished from morphologically similar crystals in plasma cell myeloma and lymphoplasmacytic lymphoma.
Accepted for publication June 8, 2001.
From the Department of Pathology, Mount Sinai School of Medicine
Mount Sinai School of Medicine is a medical school found in the borough of Manhattan in New York City. , New York, NY.
Reprints: James A. Strauchen, MD, Department of Pathology, Mount Sinai School of Medicine, One Gustave Levy PI, New York, NY 10029 (e-mail: firstname.lastname@example.org).
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