muramidase and Histiocytic-Sarcoma

Histiocytic sarcoma is a rare, aggressive neoplasm that responds poorly to therapy. Histiocytic sarcoma is thought to arise from macrophage precursor cells via genetic changes that are largely undefined. To improve our understanding of the etiology of histiocytic sarcoma we conducted a forward genetic screen in mice using the Sleeping Beauty transposon as a mutagen to identify genetic drivers of histiocytic sarcoma. Sleeping Beauty mutagenesis was targeted to myeloid lineage cells using the Lysozyme2 promoter. Mice with activated Sleeping Beauty mutagenesis had significantly shortened lifespan and the majority of these mice developed tumors resembling human histiocytic sarcoma. Analysis of transposon insertions identified 27 common insertion sites containing 28 candidate cancer genes. Several of these genes are known drivers of hematological neoplasms, like Raf1, Fli1, and Mitf, while others are well-known cancer genes, including Nf1, Myc, Jak2, and Pten. Importantly, several new potential drivers of histiocytic sarcoma were identified and could serve as targets for therapy for histiocytic sarcoma patients.

Topics: Animals; Cell Lineage; DNA Transposable Elements; Genetic Testing; Histiocytic Sarcoma; Mice; Mice, Inbred C57BL; Muramidase; Mutagenesis, Insertional; Promoter Regions, Genetic

Histiocytic sarcoma (HS) is a very rare neoplasm that often shows an aggressive clinical course and systemic symptoms, such as fever, weight loss, adenopathy, hepatosplenomegaly and pancytopenia. It may present as localized or disseminated disease. We describe here a 63-yr-old male who manifested systemic symptoms, including fever, weight loss and generalized weakness. Abdominal and chest computed tomography failed to show specific findings, but there was suspicion of multiple bony changes at the lumbar spine. Fusion whole body positron emission tomography, bone scan and lumbar spine magnetic resonance imaging showed multiple bone lesions, suggesting a malignancy involving the bone marrow (BM). Several BM and bone biopsies were inconclusive for diagnosis. Necropsy showed replacement of the BM by a diffuse proliferation of neoplastic cells with markedly increased cellularity (95%). The neoplastic cells were positive for lysozyme and CD68, but negative for T- and B-cell lineage markers, and megakaryocytic, epithelial, muscular and melanocytic markers. Morphologic findings also distinguished it from other dendritic cell neoplasms.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Marrow; Bone Marrow Neoplasms; Diagnosis, Differential; Histiocytic Sarcoma; Humans; Magnetic Resonance Imaging; Male; Muramidase; Positron-Emission Tomography; Tomography, X-Ray Computed

Histiocytic sarcoma is a rare malignant neoplasm that originates from a histiocytic hematopoietic lineage characterized by histiocytic differentiation and its corresponding immunophenotypic features. Patients with histiocytic sarcoma usually have a poor prognosis due to its aggressive clinical behavior. Here we report a rare case of extranodal histiocytic sarcoma of the stomach which was confirmed through immunohistochemical staining. A 71-year- old man was presented with epigastric pain. Gastroscopy, abdominal CT, and EUS revealed a mass located on the posterior wall of upper body and fundus of the stomach. Grossly, grayish white solid masses were seen extending down to the submucosal layer. Microscopically, the tumor cells had eosinophilic cytoplasm, abundant vacuole, and mitosis. Immunohistochemical staining revealed that the tumor cells were positive for LCA, CD68, and lysozyme. Early detection and accurate diagnosis of this rare neoplasm is important because it can make a great difference in prognostic outcomes. To make an accurate and definitive diagnosis, immunohistochemical staining is essential in the confirmation of histiocytic origin.

Topics: Adenocarcinoma; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Diagnosis, Differential; Gastroscopy; Histiocytic Sarcoma; Humans; Leukocyte Common Antigens; Male; Muramidase; Stomach Neoplasms; Tomography, X-Ray Computed; Ultrasonography

To study the morphologic features, immunophenotypes, differential diagnoses and prognosis of histiocytic sarcoma (HS).. The clinical and pathologic findings of 6 cases of HS were reviewed. Immunohistochemical assay (Elivision staining) was also performed. Follow-up information was available in 4 patients.. There were altogether 3 males and 3 females. The age of patients ranged from 12 to 81 years old (median = 54.6 years). The sites of involvement included lymph node (number = 2 cases) and skin or soft tissue (number = 4 cases). The tumor was composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin and large nucleoli. Binucleated form was not uncommon. Two of the cases showed increased pleomorphism with multinucleated tumor giant cell formation. Focal cytoplasmic with foamy appearance was identified in 3 cases. One case demonstrated foci of spindly sarcomatoid appearance. Hemophagocytosis was identified in 2 cases. Mitotic figures were readily identified. The tumor cells were often accompanied by various numbers of inflammatory cells. Immunohistochemical study showed that all cases were diffusely positive for leukocyte common antigen, CD4, CD68 and CD163. Four of the 5 cases studied also expressed lysozyme. Amongst the 4 patients with follow-up information available, 3 died of the disease at 6 to 11 months interval after diagnosis. One patient, whose lesion was localized at the skin and soft tissue, survived for 3 years, with no evidence of tumor recurrence.. Accurate diagnosis of the HS is based on the combination of morphologic examination and immunohistochemical assay. HS often presents with clinically advanced disease and pursues an aggressive clinical course, with a poor response to therapy. However, a subset of cases presenting with clinically localized lesion may carry a relatively favorable long-term outcome.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Renal Cell; Child; Diagnosis, Differential; Female; Follow-Up Studies; Histiocytic Sarcoma; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Male; Melanoma; Muramidase; Prognosis; Receptors, Cell Surface; Skin Neoplasms; Soft Tissue Neoplasms; Young Adult

Histiocytic sarcoma (HS) and histiocyte-associated lymphoma (HAL) of mice are difficult to distinguish histologically. Studies of multiple cases initially diagnosed as HS or HAL allowed us to define HS as round, fusiform, or mixed cell types that were F4/80+, Mac-2+, and PAX5-; that lacked markers for other sarcomas; and that had immune receptor genes in germline configuration. Two other subsets had clonal populations of lymphocytes. The first, HAL, featured malignant lymphocytes admixed with large populations of normal-appearing histiocytes. The second appeared to be composites of lymphoma and HS. Several cases suggestive of B myeloid-lineage plasticity were also observed.

Topics: Animals; Antigens, Differentiation; Biomarkers, Tumor; Female; Galectin 3; Histiocytic Sarcoma; Lymphoma; Male; Mice; Muramidase; PAX5 Transcription Factor; Rodent Diseases

This report is a case of histiocytic sarcoma (HS), in which tumor cells consist of two immunohistopathologically distinct populations (A) oval CD68+lysozyme+CD163- cells and (B) abundant cytoplasm or spindle-shaped CD68+lysozyme-CD163+ cells. Cervical lymph node was infiltrated mainly by population (A), where chemotherapy was quite effective. On the other hand, vast majority of infiltrated tumor cells in the hilar lymph node belonged to population (B), in which the cells were resistant to chemo-radiotherapy. Considering the poor prognosis of HS, the expression of CD163 could be a marker for resistance to chemo-radiotherapy. It is also notable that CD163-negative stage of HS may exist and still be reactive for the treatment.

Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cell Shape; Fatal Outcome; Histiocytic Sarcoma; Humans; Lymph Nodes; Male; Muramidase; Receptors, Cell Surface

Histiocytic sarcoma is a malignant proliferation of cells showing morphologic and immunophenotypic features similar to those of mature tissue histiocytes and is known for its rapid progression and poor prognosis. We describe a case of histiocytic sarcoma diagnosed by bone marrow biopsy. A 64-yr-old male was admitted for fever and weight loss that persisted for 8 months. The patient died undiagnosed on the 7th hospitalization day. A bone marrow biopsy performed just before the patient's death revealed diffuse proliferation of large pleomorphic neoplastic cells with large, round to oval nuclei, vesicular chromatin, and abundant foamy cytoplasm. These cells were positive for histiocytic markers, CD68, lysozyme, CD21, and S-100 protein, but negative for B-cell, T/NK-cell, and epithelial cell markers, thus confirming the presence of histiocytic sarcoma.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Marrow; Fever; Histiocytic Sarcoma; Humans; Male; Middle Aged; Muramidase; Platelet Endothelial Cell Adhesion Molecule-1; S100 Proteins; Tomography, X-Ray Computed

Histiocytic sarcoma is the most frequent hematopoietic tumor in rats. We report here a histiocytic sarcoma infiltrating the liver, the spleen and the pancreas from a Wistar rat. In the liver, the tumor was associated with oval cell and bile duct hyperplasia. The cells looked like neoplastic histocytic cells described in this species but with some particularities (e.g. lack of multinucleated giant cells). At immunohistochemistry, neoplastic cells in the liver were vimentine positive but lysozyme and CD68 negative. In the kidney, lysozyme-positive cytoplasmic droplets were observed. We describe here an atypical case of histiocytic sarcoma in the rat and we compare the nature of these neoplastic cells to other species.

Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Histiocytic Sarcoma; Immunohistochemistry; Kidney; Liver Neoplasms; Male; Muramidase; Pancreatic Neoplasms; Rats; Rats, Wistar; Splenic Neoplasms; Vimentin

A 24-year-old Japanese man was admitted due to bloody phlegm in May 2002. A diagnosis of mediastinal germ cell tumor, mixed type involving seminoma, immature teratoma and embryonal carcinoma, was made by transthoracic needle biopsy. Three months later, his complete blood counts revealed pancytopenia with high fever. Examination of bone marrow revealed increased atypical large histiocytes (5.6%) with hemophagocytosis, and thus, hemophagocytic syndrome related to germ cell tumor was diagnosed. In addition, chromosomal analysis of the bone marrow cells revealed a 47, XY, +9 genotype. Chemotherapies for germ cell tumor and hemophagocytic syndrome were performed without any improvement, and he died of diffuse alveolar damage. Autopsy revealed diffuse infiltration of immature histiocytes with hemophagocytosis in the liver, spleen and bone marrow. The atypical histiocytes were positive for CD68 and lysozyme and negative for lymphoid markers, and the diagnosis of true malignant histiocytosis associated with mediastinal germ cell tumor was made. The rare chromosomal abnormality of trisomy 9, a marker for benzene-related leukemia, was seen in the present case without apparent benzene exposure.

Topics: Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biopsy, Needle; Bone Marrow; Chromosomes, Human, Pair 9; Histiocytes; Histiocytic Sarcoma; Humans; Japan; Liver; Lymphohistiocytosis, Hemophagocytic; Male; Mediastinal Neoplasms; Muramidase; Neoplasms, Germ Cell and Embryonal; Neoplasms, Second Primary; Pulmonary Alveoli; Time Factors; Treatment Failure; Trisomy

A Bernese mountain dog was evaluated because of a gingival mass, multiple abdominal masses, and a pulmonary mass. Malignant histiocytosis was diagnosed based on cytological examination of splenic and bone marrow aspirates and histological examination of a bone marrow biopsy and the gingival mass. The case demonstrates that malignant histiocytosis is difficult to diagnose due to the variety of histiocytic disorders.

Topics: alpha 1-Antitrypsin; Animals; Bone Marrow; Diagnosis, Differential; Dog Diseases; Dogs; Gingiva; Histiocytic Sarcoma; Male; Mandibular Neoplasms; Muramidase; Spleen

We report on a patient with malignant histiocytosis (MH) presenting as multiple erythematous plaques and cutaneous depigmentation on her neck and chest. In a biopsy of an erythematous plaque, atypical large, foamy histiocytes infiltrated the dermis and positively stained with antibodies to lysozyme, leukocyte common antigen, and KP-1 (CD68). A few similar atypical cells were present in the superficial dermis focally in the depigmented areas. With use of immunohistochemical studies, most cases previously diagnosed as MH have been reclassified as T-cell lymphoma, B-cell lymphoma, or Ki-1-positive anaplastic large cell lymphoma. However, a few cases of "true" MH characterized by authentic histiocytes have been reported, presenting usually as red nodules. To our knowledge, our patient is the first with MH to present with erythematous plaques and vitiligo-like depigmentation.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Diagnosis, Differential; Erythema; Female; Histiocytic Sarcoma; Humans; Hypopigmentation; Leukocyte Common Antigens; Middle Aged; Muramidase; Skin Diseases; Skin Neoplasms

Involvement of the thyroid gland by Langerhans' cell histiocytosis is quite rare. We describe the case of a 58-year-old man referred for treatment of a progressively enlarging goitre. The trachea was severely stenotic and adjacent structures such as the left carotid vein and the thyroid cartilage were also involved. Central diabetes insipidus and severe combined immunodeficiency were associated. Although fine needle aspiration biopsy of the thyroid was initially interpreted as papillary carcinoma, anaplastic thyroid cancer was suspected. Treatment with prednisolone, doxorubicin and irradiation controlled the tracheal compression. A diagnosis of thyroid Langerhans' cell histiocytosis was finally made on the basis of the presence of Birbeck granules and CD1a and CD4 antigen in the thyroid tumour cells. Furthermore, positive staining for CD68 and lysozyme suggested that the tumour cells may have had the character of phagocytic cells in addition to their dendritic cell nature. This is the first case of thyroid involvement by malignant histiocytosis of Langerhans' cell type with unusual phagocytic markers.

Topics: Antigens, CD; Antigens, CD1; Antigens, Differentiation, Myelomonocytic; Biomarkers; Biopsy, Needle; CD4 Antigens; Diagnosis, Differential; Histiocytic Sarcoma; Histiocytosis, Langerhans-Cell; Humans; Male; Microscopy, Electron; Middle Aged; Muramidase; S100 Proteins; Thyroid Gland; Tomography, X-Ray Computed

Topics: Adolescent; Adult; Antigen-Antibody Complex; Biopsy; Diagnosis, Differential; Ferritins; Fever of Unknown Origin; Histiocytic Sarcoma; Histiocytosis, Langerhans-Cell; Humans; Interferons; Iron; Leukocytes, Mononuclear; Liver; Middle Aged; Muramidase; Phagocytes

Three cases of malignant histiocytosis were immunohistochemically studied. The cases included the following three patients: a 38-year-old man, a 44-year-old man, and a girl aged 5 years 9 months. All three patients died within 3 months of hospitalization. They had a high fever (temperature over 38.5 degrees C), lymph node swelling, hepatosplenomegaly, and pancytopenia. Blastoid and hemophagocytic cells proliferated in the bone marrow and lymph nodes, especially in the sinuses of the latter. We diagnosed malignant histiocytosis in the three cases based on clinical features, extremely poor prognoses, and the morphologic features and growth pattern of blastoid and hemophagocytic cells. Blastoid and hemophagocytic cells expressed phenotype Mac-387+/KP1+/lysozyme+/polyclonal CD3+. The Mac-387 and KP1 antigens and lysozyme are markers for monocytes/macrophages, and polyclonal CD3 is a marker for T lymphocytes. Therefore, we suggest that a certain number of cases of malignant histiocytosis have a biphenotypic nature, namely, the T cell and macrophage, although many cases of malignant histiocytosis have been reported as expressing only T-lymphocyte antigens.

Topics: Adult; Antigens, CD; Antigens, Neoplasm; Bone Marrow; CD3 Complex; Child, Preschool; Female; Histiocytic Sarcoma; Humans; Immunophenotyping; Ki-1 Antigen; Lymph Nodes; Male; Muramidase; Prognosis

The relatively frequent association of hematologic neoplasia and primary mediastinal germ cell tumors has been reported. Of these hematologic malignancies, nine were classified as malignant histiocytosis or acute monoblastic leukemia, and all occurred in males. We now report on a patient who was phenotypically female, with 46XY gonadal dysgenesis, and who developed a true histiocytic malignancy that presented as a large hepatic tumor and also involved the spleen, right kidney, and lymph nodes. Twenty-six months before the development of the histiocytic malignancy, an ovarian malignant teratoma with yolk sac elements was removed; the patient subsequently received chemotherapy. The neoplasm was composed of large pleomorphic cells and the histiocytic nature was established by cytologic, cytochemical, immunologic, and ultrastructural studies. In the course of her illness, the patient developed classic acute monoblastic leukemia 8 months after the diagnosis of histiocytic malignancy. Karyotypic analysis of the hepatic tumor, bone marrow, and blood showed 46XY gonadal dysgenesis. We believe that this is the first reported case of a phenotypically female patient who developed these two rare malignancies. It suggests that the association between germ cell tumors and histiocytic malignancy in genotypically male individuals may not be coincidental or secondary to therapy, but may be a phenomenon related to dysgenetic gonads in the presence of a Y chromosome.

Topics: Adolescent; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; CD11 Antigens; DNA, Neoplasm; Female; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Gonadal Dysgenesis, 46,XY; Histiocytic Sarcoma; Humans; Immunohistochemistry; Karyotyping; Liver; Lymphocytes; Muramidase; Ovarian Neoplasms; Phenotype; S100 Proteins; Teratoma

Tumor tissues from 36 autopsy cases of malignant histiocytosis were collected for studying the distribution of lysozyme (LyS), alpha 1-antichymotrypsin (ACT) and alpha 1-antitrypsin (AT) by double peroxidase anti-peroxidase staining. The positive rates of LyS, ACT and AT were 97.14%, 91.67% and 77.78% respectively. LyS was seen mainly in the well-differentiated histiocytes. No phagocytosis was found in these cells. ACT existed in some well-differentiated histiocytes in which phagocytosis was often seen. A few atypical histiocytes also showed positive reaction to ACT. AT-positive cells were mainly atypical histiocytes and atypical multinuclear-giant-histiocytes. This study not only confirms that the tumor cels of malignant histiocytosis originate from histiocytes, but also indicates that staining of LyS, ACT and AT is useful for classification and differential diagnosis of tumor cells in malignant histiocytosis.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Histiocytic Sarcoma; Humans; Immunohistochemistry; Muramidase

Immunohistochemically, the presence of lysozyme (LZ) has been detected by the antibody against human LZ in cytoplasm of cells from granulomatous and histiocyte-proliferative skin diseases. To detect LZ in these cells morphologically, I have done electron microscopic observations of the following skin diseases; sarcoidosis, lupus vulgaris, lupus miliaris disseminatus faciei (LMDF), tattoo granuloma, lichen nitidus, foreign body granuloma, granuloma annulare, xanthelasma, xanthoma tuberosum, xanthoma planum, juvenile xanthogranuloma, giant cell tumor of tendon sheath, dermatofibroma, malignant fibrous histiocytoma, dermatofibrosarcoma protuberans, granulation tissue of burn, hypertrophic scar, and histiocytosis X. From both the immunohistochemical and the electron microscopic features it was concluded that a) immunohistochemically LZ-positive cells from lesions of sarcoidosis, lupus vulgaris, LMDF and tattoo granuloma had a number of electron-lucent bodies (ELB) or microvesicles in their cytoplasm, b) lichen nitidus and xanthoma tuberosum had few LZ-positive cells and the ELB were not observed, and c) the other diseases were LZ-negative, and the ELB were also absent. It is suggested that LZ is present in the ELB which are observed electron microscopically.

Topics: Granuloma; Histiocytes; Histiocytic Sarcoma; Histiocytoma, Benign Fibrous; Histiocytosis, Langerhans-Cell; Humans; Immunohistochemistry; Microscopy, Electron; Muramidase; Skin Diseases; Skin Neoplasms

The distribution of ferritin in 36 autopsy cases of malignant histiocytosis was investigated by immunocytochemical staining, together with the detection of alpha 1-antichymotrypsin, alpha 1-antitrypsin, lysozyme, S-100 protein, and ricinus communis agglutinin in the consecutive sections. The results showed that ferritin-positive tumor cells were present in every case. The quantity of cellular ferritin in well-differentiated histiocytes was higher than that in atypical histiocytes. Double labeling showed that ferritin and alpha 1-antichymotrypsin might be located either in one tumor cell or in separate cells. Our data suggest that ferritin may be a tumor associated antigen in malignant histiocytosis, playing a regulatory role for tumor cell differentiation.

Topics: Adult; Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Biomarkers, Tumor; Female; Ferritins; Histiocytic Sarcoma; Humans; Immunoenzyme Techniques; Male; Mitosis; Muramidase; Phagocytosis; S100 Proteins

Topics: Animals; Cat Diseases; Cats; Female; Histiocytic Sarcoma; Immunoenzyme Techniques; Muramidase

Tissue specimens obtained at autopsy from seven childhood cases of malignant histiocytosis were studied by immunohistochemistry. Clinically, the majority of the cases showed sustained fever, hepatosplenomegaly, pancytopenia, and DIC. The pretreatment diagnosis was based on their typical clinical manifestations and bone marrow smear findings. Although three patients temporarily responded to exchange transfusion and chemotherapy, all seven patients eventually died of active disease. Postmortem examination revealed the proliferation of atypical histiocytes appearing in variable degrees of maturation in the lymph nodes, liver, spleen, bone marrow, lungs, and central nervous system. Immunohistochemical staining for lysozyme, nonspecific cross-reacting antigen (NCA), alpha 1-antitrypsin (alpha 1 AT), alpha and beta subunits of S100 protein (S100 alpha, beta), and concanavalin A receptors (ConAR) in cytoplasm demonstrated the presence of two subtypes of malignant histiocytes, ie, S100 beta+/NCA-/ConAR+ (4 cases) and S100 beta-/NCA+/ConA R+ (three cases). The results of lysozyme, alpha 1 AT, and S100 alpha staining were inconsistent. A survey of the literature disclosed that the incidence of S100 protein-positive cases in children was higher than in adults (12/21 v 5/19; chi 2, P less than .05). Further large scale investigation is necessary to confirm the independence and significance of these two subtypes of histiocytes in malignant histiocytosis.

Topics: Acid Phosphatase; Adolescent; Antigens, Neoplasm; Cell Adhesion Molecules; Child, Preschool; Female; Glycoproteins; Histiocytes; Histiocytic Sarcoma; Humans; Infant; Liver; Lymph Nodes; Male; Muramidase; Naphthol AS D Esterase; Periodic Acid-Schiff Reaction; Receptors, Concanavalin A; S100 Proteins; Spleen

Immunoreactive lysozyme was readily detectable in canine histiocytic disorders including systemic histiocytosis, malignant histiocytosis and granulomatous panniculitis. Lysozyme was less reliable as a histiocytic marker in cutaneous histiocytoma; forty percent of these tumors were negative for lysozyme expression. The marked heterogeneity in lysozyme expression in cutaneous histiocytoma may indicate that a proportion of these tumors show relatively primitive histiocytic differentiation and do not express lysozyme. Alternatively, this same proportion may exhibit a phenotype akin to cutaneous Langerhans cells which do not contain lysozyme. Lysozyme was not detectable in the tumor cells in lymphomatoid granulomatosis, atypical cutaneous histiocytoma, and histiocytic lymphosarcoma. Other evidence that these three disorders do not represent true histiocytic proliferative disorders is discussed.

Topics: Animals; Cytoplasm; Dog Diseases; Dogs; Histiocytes; Histiocytic Sarcoma; Histiocytoma, Benign Fibrous; Lymphoma, Large B-Cell, Diffuse; Lymphomatoid Granulomatosis; Lymphoproliferative Disorders; Muramidase

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Antigens, Surface; Child, Preschool; Female; Histiocytic Sarcoma; Humans; Male; Middle Aged; Muramidase; S100 Proteins