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PubMed2002

The histiocytic marker PG-M1 is helpful in differentiating histiocytes and histiocytic tumors from melanomas.

Previous studies have shown that immunohistochemical stains for histiocytes are immunoreactive for melanomas. Accordingly, their value in differentiating histiocytes and histiocytic lesions from melanomas was questioned. PG-M1, the most specific histiocytic marker, was not evaluated in these studies. Our aims were to assess the reactivity of PG-M1 with a series of primary cutaneous and metastatic melanomas and to establish the potential usefulness of this antibody in the differentiation between histiocytes and histiocytic tumors and melanomas. PG-M1 staining was performed in 50 primary cutaneous and metastatic melanomas. For comparison, additional sections were stained with KP-1 and lysozyme (commonly used as histiocytic markers) and with S-100 and HMB-45 (commonly used as melanoma markers). The intensity (1+, 2+) and extent (1+ to 4+) were recorded semiquantitatively. PG-M1 stained weakly (1+) and focally (2+) only four cases of melanoma (8%). In contrast, histiocytes were strongly reactive for PG-M1 in all cases, being readily differentiated from melanoma cells including the positive cases. KP-1 stained melanoma cells in 44 cases (88%), lysozyme in 11 cases (22%), S-100 in 50 cases (100%), and HMB-45 in 48 cases (96%). No changes were found after restaining of selected KP-1 and lysozyme positive melanomas using an endogenous avidin/biotin blocking kit. PG-M1 is helpful in discriminating histiocytes and histiocytic lesions from melanoma cells. We recommend its inclusion in any antibody panel put together to distinguish between them.

Antigens, CD↗

PubMed1991

Lymphomas of true histiocytic origin. Expression of different phenotypes in so-called true histiocytic lymphoma and malignant histiocytosis.

The authors determined the phenotypes of neoplastic cells in true histiocytic lymphoma and malignant histiocytosis by using a large panel of monoclonal antibodies and enzyme histochemistry procedures. Although the phenotypes overlapped slightly, the authors noted a distinct pattern in these tumors. The tumor cells of malignant histiocytosis generally expressed the monocyte markers CD11b, CD11c, CD14, and CD45, especially after induction with phorbol ester. In contrast, the tumor cells of true histiocytic lymphoma exhibited a marker expression very similar to that of Reed-Sternberg cells in Hodgkin's disease. These cells expressed markers CD30, 2H9, and 1A2, but rarely expressed CD11b, CD11c, CD14, or CD45. Regardless of their cytologic features, the tumor cells from both types of histiocytic lymphoma exhibited diffuse nonspecific esterase and acid phosphatase activities, and they expressed histiocyte markers CD15, CD68, LN5, 1E9, and M387 to varying degrees. The tumor cells from both lymphomas did not exhibit T- or B-cell markers, T-cell receptor or immunoglobulin gene rearrangements, or gene translation products, even when they were induced with phorbol ester. The phenotypic expression in these two histiocytic malignancies suggests that they are derived from different types of histiocytes, or from histiocytes in different stages of maturation or differentiation, or from histiocytes that have distinct mechanisms of tumorigenic transformation. The expression of circulating monocyte markers in malignant histiocytosis suggests that this tumor originates in monocytes or free histiocytes, whereas the phenotype of true histiocytic lymphoma is compatible with an origin in fixed histiocytes, which generally are devoid of the monocyte markers CD11b and CD14.

Adolescent↗

PubMed1993

Cutaneous histiocytic malignancy. Immunohistochemical re-examination of cases previously diagnosed as cutaneous "histiocytic lymphoma" and "malignant histiocytosis".

True histiocytic lymphoma (THL) and malignant histiocytosis (MH) have been defined by clinical and histologic findings and enzyme histochemistry. We reviewed cases previously diagnosed as cutaneous histiocytic lymphoma (HL) and MH with cutaneous lesions. These cases had been classified as "histiocytic" on the basis of previous enzyme histochemistry profiles of frozen tissue. Cutaneous tumor cells were reevaluated using a panel of immunohistochemical stains in formalin-fixed, paraffin-embedded tissue in correlation with histopathologic examination. The antibodies used in this study were directed against CD45 (leukocyte common antigen [LCA]), CD20 (L26) for B cells, CD3 and CD45RO (UCHL-1) for T cells, CD68 (KP-1) and lysozyme for histiocytes, as well as CD30 (BerH2) for Ki-1 positive cells. On re-evaluation, the seven cases originally classified as HL were reclassified as one case of THL with neoplastic cells positive for CD68 (KP-1) and lysozyme, two cases with immunohistochemical features of Ki-l lymphoma (including one of T-cell lineage), three cases of T-cell lymphoma, and one case of B-cell lymphoma, all associated with variable degrees of reactive histiocytosis. The four cases originally classified as MH were reclassified as two cases of MH and two cases of uncertain lineage. Although rare, histiocytic malignancies do exist. However, the diagnosis of histiocytic malignancy should be made only after careful correlation of atypical tumor cells in histopathologic sections and sections stained immunohistochemically. Erroneous classification of reactive histiocytes as neoplastic histiocytes using only enzyme histochemistry in frozen sections is a pitfall to be avoided.

Adult↗

PubMed2005

Histiocytic sarcoma: a study of five cases including the histiocyte marker CD163.

Histiocytic sarcoma (HS) is a rare but controversial hematopoietic neoplasm. In the past, malignancies have been misclassified as histiocytic tumors due to overlapping histologic features and inadequate phenotypic data. CD163, a recently characterized hemoglobin scavenger receptor, appears to be a 'specific' marker of histiocytic lineage and a promising diagnostic tool for evaluating histiocytic neoplasms. Five cases of HS were studied to further elucidate the clinicopathologic features of these rare tumors and to demonstrate the diagnostic utility of CD163. Criteria for diagnosis included histologic and immunohistochemical evidence of histiocytic differentiation, CD45 positivity, and exclusion of lymphoid, epithelial, melanocytic and dendritic cell phenotype. Sites of disease included the colon (two cases), palate, inguinal lymph node, and testis. The clinical course was aggressive in 4/5 patients (survival=2-15 months). One patient with localized disease of the palate, survived 17 years after diagnosis. All patients with poor survival had tumors > or =3.5 cm. Histologically, all cases showed diffuse architecture with large, discohesive polygonal cells. Spindling of cells was focally noted. Hemophagocytosis was identified in 3/5 cases. A prominent inflammatory background was present in 4/5 tumors. All cases were immunoreactive for CD45, CD163, CD68, and lysozyme. S-100 was focally positive in 4/5 cases. Antibodies for melanocytic, epithelial, lymphoid, and dendritic cell markers were negative. Molecular studies showed monoclonal IgH gene rearrangements in three cases. Our findings suggest that HS is an uncommon neoplasm frequently extranodal in presentation and aggressive in behavior, with rare exceptions. Stage of disease and possibly tumor size are significant prognostic indicators. Molecular studies remain controversial in the diagnosis. The morphologic and phenotypic features are relatively uniform; however, the diagnosis requires exclusion of more common neoplasms by extensive immunophenotypic studies. CD163 appears to be a specific histiocytic marker and is important in establishing the diagnosis of HS.

Adult↗

PubMed1988

Diagnostic significance of histiocyte-related markers in malignant histiocytosis and true histiocytic lymphoma.

Interrelationships of immunologic and enzymatic markers of histiocytes have been studied in malignant neoplasms of histiocytic/monocytic origin and in differential diagnostically relevant, large cell non-Hodgkin's lymphomas. Cryostat sections required for demonstrating cell surface antigens by monoclonal antibodies are inadequate for studying cellular detail, enzymatic maturation by alpha-naphthyl acetate esterase (ANAE), and demonstrating the classical cytoplasmic markers of histiocytes like lysozyme, alpha-1-antitrypsin (AT), and alpha-1-antichymotrypsin (ACT). These markers have been compared in gently fixed and vacuum paraffin-embedded material. The reactivity for monoclonal anti-human monocyte 1 (Mo 1) has also been preserved by this method. Malignant histiocytosis (MH) is characterized by a heterogeneous cell population. The mature, ANAE-positive cells with macrophage morphology usually show a diffuse cytoplasmic positivity for AT and ACT. Lysozyme is moderately positive to negative in these cells, but it is more efficient than these markers in revealing smaller cells resembling monocytes by focal positivity in the cytoplasm. The expression of Factor XIIIa (F-XIIIa) is connected with the phagocytic activation of histiocytic cells. F-XIIIa positive cells usually form a minority of the neoplastic population in MH, but the large cytophagocytic marcophages are invariably positive. Reactive macrophages in large cell non-Hodgkin's lymphomas are characterized by a coexpression of ANAE, AT, ACT, lysozyme, F-XIIIa and Mo 1. Typical cases of true histiocytic lymphoma (THL) are made up of a homogeneous population showing the above mature, phagocytizing phenotype. In MH, Mo 1 and ANAE recognize different subpopulations. The reciprocal relation of these markers is an abnormal phenotypic feature. The results presented in this article prove the diagnostic value of ANAE and lysozyme in confirming the histiocytic differentiation of malignant cells. Monoclonal anti-human monocyte 1 is useful for identifying the immature component in MH. Factor XIIIa can be considered a functional marker of mature phagocytic histiocytes and an aid in the diagnosis of THL.

Antigens, Differentiation, Myelomonocytic↗

PubMed1984

True histiocytic lymphoma of the thymus. Report of a case and a study of the distribution of histiocytic cells in the fetal and adult thymus.

The thymus was the site of a true histiocytic lymphoma. Immunohistochemical demonstration of lysozyme and alpha-1-antitrypsin in the tumor cells indicated the histiocytic nature of the tumor. Five fetal and five adult thymus glands were studied for the presence and distribution of true histiocytic cells. Histiocytes were demonstrated predominantly in the connective tissue septa and constituted approximately 2% of cells in these thymuses. Histiocytes are therefore a normal constituent of the thymus, which may become the primary site of true histiocytic lymphoma.

Adult↗

PubMed1986

Utilization of cytoplasmic lysozyme immunoreactivity as a histiocytic marker in canine histiocytic disorders.

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.

Animals↗

PubMed1977

Two distinctive types of lipid histiocytes appearing in the spleen of idiopathic thrombocytopenic purpura. Sea-blue histiocyte and foam cell.

In 11 of 18 spleens surgically removed from patients with idiopathic thrombocytopenic purpura (ITP), the occurrence of sea-blue histiocytes or foam cells were observed. In a few cases, sea-blue histiocytes were found in the lymph nodes or bone marrow. Histochemically the sea-blue histiocytes were proved to contain ceroid or ceroid-like pigments in their cytoplasm. Ultrastructurally numerous intracytoplasmic membrane-bound inclusions, mostly containing tightly laminated materials and intermingling electron-dense amorphous materials or osmiophilic lipid droplets, were present in these cells. In the foam cells, accumulation of excess amounts of phospholipids was histochemically demonstrated in frozen sections, often accompanied by deposition of cholesterol, particularly in advanced cases. Electron microscopically, vacuolar membrane-bound inclusions were found to predominate in their cytoplasm, most of which contained irregularly or loosely laminated materials. Transitional cells between both types of cells were also found light or electron microscopically and ultrastructural transition of sea-blue histiocytes to foam cells was traced. Enhanced phagocytosis of blood cells, including platelets, by sea-blue histiocytes, and gradual transition of the ingested blood cells to the inclusions were confirmed.

Adolescent↗

PubMed1984

Histiocytic sarcoma (true histiocytic lymphoma): a clinicopathological study of 20 cases.

Large-cell non-Hodgkin's lymphomas (T- and B-immunoblastic, centroblastic and true histiocytic lymphomas) have a heterogeneous clinical course. In the present study the clinical and morphological data of 20 cases of histiocytic sarcoma (true histiocytic lymphoma) are presented. Diagnosis was supported by immunohistochemistry, cytochemistry, rosette assays and/or electron microscopy. Although the follow-up was relatively short (up to 144 months, mean 26 months), the clinical data differed clearly from the series of large-cell non-Hodgkin lymphomas, recorded in the literature. Differences were found in age distribution with a peak in the third decade, in organ involvement showing a preference for skin, gastrointestinal tract and bone, and in response to therapy. In general, histiocytic sarcoma appears to have a more favourable response to therapy and clinical course than the other large-cell lymphomas (T- and B-immunoblastic and centroblastic lymphomas). Moreover, preliminary observations in the group of histiocytic sarcomas suggested that the presence of lysozyme and/or 5-nucleotidase and the absence of alpha 1-antitrypsin in the cytoplasm is associated with a better response to therapy and favourable clinical course.

5'-Nucleotidase↗

PubMed1997

Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society.

Pathologists and pediatric hematologist/ oncologists of the World Health Organization's Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell-related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage-related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided.

Cell Lineage↗

PubMed1981

Malignant lymphoma of true histiocytic origin: histiocytic sarcoma. A morphological, ultrastructural, immunological, cytochemical and clinical study of 10 cases.

Ten tumors of true histiocytic origin (Histiocytic Sarcoma) are presented. The tumor cells were identified as histiocytes by immunological, cytochemical and ultrastructural criteria (cytoplasmic lysozyme activity, presence of C3 and Fc gamma receptor, strong acid phosphatase and alpha-naphthyl acetate esterase activity, presence of lysosomes, absence of cell junctions and evidence of phagocytosis). The tumors identified in this way showed the following histological characteristics: diffuse proliferation of large tumor cells with ample cytoplasm, containing granular or occasionally diffuse diastase resistant PAS positive material, erythrophagocytosis, and haemosiderin pigment. The large or enormous nuclei were irregular, with occasional deep indentations, sharply defined nuclear membrane, coarse chromatin and conspicuous nucleoli. Despite the uniformity of these criteria differences in presence of alpha 1-antitrypsin, alpha 1-antichymotrypsin and 5 Nucleotidase activity and the number of lysosomes in the cytoplasm were found. The findings are suggestive of a spectrum of cytological in these Histiocytic Sarcomas. The clinical picture ranged from monolocalization in a lymphoid organ to that of a diffuse Malignant Histiocytosis. The relationship between good response to therapy and complete remission and the absence of alpha 1-antitrypsin and a high number of lysosomes is discussed.

Adult↗

PubMedDate not supplied

[Histiocytic sarcoma from phagocyting histiocytes].

Histiocytic sarcoma consisting of phagocyting histiocytes is a rare variant of histiocytic sarcoma. It is hard to detect because of its similarity with large cell lymphomas, in particular with anaplastic large cell lymphoma. Histological and immunohistochemical findings are presented. Differential diagnosis with tumours of hematopoietic and non-hematopoietic nature is described.

Brain Neoplasms↗

PubMed1995

Leukemia after true histiocytic lymphoma: another type of acute monocytic leukemia with histiocytic differentiation (AML-M5c)?

The case of a 44-year-old man diagnosed of a true histiocytic lymphoma who, after autologous bone marrow transplantation, developed leukemia with histiocytic cells is reported. Morphologic, cytochemical, immunophenotypic and genotypic characteristics of malignant cells are described, and the literature about this and related entities is reviewed. In addition, comparison with a recent report of malignant histiocytosis with leukemic involvement is established and its inclusion in the recently proposed subtype of monocytic leukemia with histiocytic differentiation (M5c), suggested.

Adult↗

PubMed1980

T-cell lymphomas of large cell type. A variety of malignant lymphomas: "histiocytic" and mixed lymphocytic-"histiocytic".

Clinical and morphologic features of seven T-cell lymphomas of the large cell type are described. The tumors were grouped into those with irregular (3 cases) and those with round and regular nuclei (4 cases). In both groups, variation in cell size, numerous histiocytes and vessels, and many mitoses were distinguishing features. In only 1 case in the round and regular nucleus group was there relatively little variation in cell size and a paucity of histiocytes. Abundant polyribosomes, long strands of rough endoplasmic reticulum, and lysosomal granules were prominent electron microscopic features in both groups of tumors. The clinical presentations and courses varied considerably, especially in patients with tumors of the round nucleus type. One patient presented initially with chronic lymphocytic leukemia, 1 with Lennert's lymphoma, another with bone marrow infiltration, and a fourth with subcutaneous tumors. Two patients with the round nucleus type are still alive one and a half and two years after the original diagnosis. Two patients died two years after the onset of symptoms. Each of the 3 patients with tumors of the irregular nucleus type had a rapid clinical course and died within ten months.

Aged↗

PubMed2004

Cutaneous true histiocytic malignancy: true histiocytic lymphoma.

True histiocytic malignancies (THM) are controversial disorders that are being re-evaluated with modern cellular and molecular biology techniques. True histiocytic lymphoma (THL) is a low-incidence, poor-prognosis THM. It mainly affects the skin, gastrointestinal tract, and bone tissues. Occasionally, skin lesions are the presenting clinical features. A patient with initially cutaneous THL is described. This and other reported cases confirm that THM are a nosologic entity by themselves.

Aged↗

PubMed1975

Immunologic and cytochemical properties of histiocytic and mixed histiocytic-lymphocytic lymphomas.

Lymph nodes were biopsied from seven patients with the presumptive clinical diagnosis of lymphoma and studied for their ability to form spontaneous rosettes with sheep erythrocytes (T cell marker), for surface immunoglobulins (B cell marker), for cytochemical reactivity with peroxidase, alpha-naphthyl acetate and butyrate esterases, naphthol ASD chloroacetate esterase, acid phosphatase, periodic acid-Schiff, Sudan black B, and Wright-Giemsa on touch preparations, as well as in hematoxylin and eosin-stained sections. Lymph nodes from patients without hematologic malignancy served as control. Diagnoses of diffuse histiocytic lymphoma were made in five cases and diffuse mixed histiocytic-lymphocytic lymphoma in 2 cases. The cytochemical staining of the lymphoma cells were typical of lymphoid cells rather than macrophages. In five cases neoplastic cells contained surface immunoglobulins, suggesting a B cell origin, and in one case a paucity of cell surface markers was found. Cells from uninvolved nodes of lymphoma patients could not be differentiated from those of the control group.

Animals↗

PubMed1985

Macrophage-histiocytes in Hodgkin's disease. The relation of peanut-agglutinin-binding macrophage-histiocytes to clinicopathologic presentation and course of disease.

The authors studied the occurrence of peanut agglutinin (PNA)-binding cells in paraffin-embedded specimens of 145 patients with Hodgkin's disease (HD). The staining reaction of lymphocytes was consistently negative. A positive staining reaction was observed in two types of cells: macrophage-histiocytes (M-H), and Reed-Sternberg (R-S) cells and their variants. Diffuse or globular cytoplasmic staining was found in M-H, which was easily distinguished from a unique "cell surface and cytoplasmic" staining pattern of R-S and related cells. Thus defined, M-H were numerous in lymphocyte depletion and mixed cellularity, less common in lymphocyte predominance, and least frequent in the nodular sclerosis type. Numerous M-H correlated with B-symptoms and a poor response to therapy. Among the asymptomatic patients with localized disease at presentation, the presence of large numbers of M-H was associated with a high incidence of relapse within 2 years of therapy. These findings suggest that the number of non-neoplastic M-H in HD may be an important determinant in the clinical presentation and course of disease. Peanut agglutinin staining may be useful for the detection of M-H in routine diagnosis and classification of HD, which has not been feasible by conventional methods.

Adolescent↗

PubMed1983

Morphologic studies on a murine reticulum cell sarcoma (histiocytic sarcoma) of histiocytic origin and its metastases.

The M5076 tumor, a reticulum cell sarcoma of histiocytic origin that arose spontaneously in the ovary of a C57BL/6 mouse, is highly invasive and metastatic. Regardless of the site of the primary tumor, this neoplasm rapidly and preferentially metastasizes to the liver and spleen, killing the host. Numerous other organs also are involved, including the lungs and bone marrow. This tendency to metastasize to osseous tissues appears to be a characteristic of the M5076 tumor that rarely is found with other rodent neoplasms. However, these extrahepatic foci are evident only microscopically and are seen relatively late in the progression of tumor growth. We describe the sequential gross and microscopic lesions that develop in syngeneic mice during the metastatic spread of the M5076 tumor. Since viable tumor cells form small tumor colonies in most organs, we suggest that the gross pattern of metastasis, with the apparent predilection for hepatic tissue, is caused by variations in tumor cell proliferation rather than by distinctive patterns of neoplastic cell spread and entrapment.

Animals↗