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PubMed1975

Malignant soft tissue tumors of probable histiocytic origin (malignant fibrous histiocytomas): general considerations and electron microscopic and tissue culture studies.

Correlated light and electron microscopic study of four fibrous histiocytomas of proven malignancy has confirmed the presence of histiocyte-like and fibroblast-like cells in this tumor. In addition, an undifferentiated cell type, giant cells, xanthomatous cells, and rare cells with morphological characteristics intermediate between those of histiocytes and fibroblasts were seen. "Nuclear body" type inclusions were commonly present in both principal cell types in all four cases, as were the somewhat less common cytoplasmic inclusion bodies. Electron microscopic study of a tissue culture of one of these tumors demonstrated only fibroblast-like, histiocyte-like, and xanthomatous cells. The possibility is suggested that both principal cell types in this tumor may derive from the same undifferentiated stem cell.

Adult↗

PubMed1976

Histiocytic medullary reticulosis with parallel increases in serum acid phosphatase and disease activity.

Two months after presenting with autoimmune hemolytic anemia, a 57-year-old man developed increased serum acid phosphatase activity. Subsequently, abnormal histiocytes were found in the bone marrow and blood, and 8 months after the onset of his illness lymph node biopsy led to the diagnosis of histiocytic medullary reticulosis. At that time the level of serum acid phosphatase activity was more than 60 times the upper limit of normal and then paralleled the activity of his disease during temporary responses to chemotherapy, rising to over 90 times normal at the time of his death 1 year after presentation. No prostatic malignancy was demonstrated by biopsies or at autopsy, and electrophoretic studies of the serum enzyme suggested that it was of extraprostatic origin. It is postulated that the acid phosphate present in the serum at levels heretofore described only in metastatic carcinoma of the prostate may have arisen from the abnormal histiocytes.

Acid Phosphatase↗

PubMed1982

Regressing atypical histiocytosis: a cutaneous proliferation of atypical neoplastic histiocytes with unexpectedly indolent biologic behavior.

Regressing atypical histiocytosis (RAH) of skin is a cutaneous noduloulcerative proliferation of atypical neoplastic histiocytes with concomitant polymorphous inflammation, frequently pronounced epidermal hyperplasia, and an unexpectedly indolent biologic course. Spontaneous regression and recurrence without systemic spread were the course in follow-up periods of over six years. Histopathologically, characteristic-appearing atypical mononuclear and multinucleated "RAH" cells showed erythrophagocytosis as well as ultrastructural, surface marker, and enzyme cytochemical features indicating histiocytic differentiation. Cytogenetic analysis showed aneuploidy and several marker chromosomes including 14q+. Its benign biologic course clearly distinguished this entity from malignant histiocytosis, large cell lymphoma, and Hodgkin's disease. The histiocytic atypical cells further distinguished it from the T-cell lesions of the skin, such as mycosis fungoides and lymphomatoid papulosis. This entity is readily confused with malignant lymphoreticular disease, melanoma, or squamous carcinoma.

Acid Phosphatase↗

PubMed1987

Immunosuppressive acidic protein in true histiocytic lymphoma.

Serum immunosuppressive acidic protein (IAP) was determined in patient with true histiocytic lymphoma. The change of serum level of IAP correlated well with the clinical course, i.e., increased at relapse and decreased during remission. Immunohistochemistry showed IAP was present in the cytoplasms of normal granulocytes and histiocytes but not in neoplastic histiocytes.

Aged↗

PubMed1987

Stromal macrophage-histiocytes in Hodgkin's disease. Their relation to fever.

Morphologic variations of Concanavalin A-binding histiocytes were studied in biopsy specimens of 140 untreated patients with Hodgkin's disease (72 asymptomatic, and 68 with constitutional symptoms). Fever was the most common symptom, present in 57 of the 68 patients. Three morphologic types of stromal histiocytes were recognized: medium-sized cells similar to those seen in reactive follicles, characterized by distinct cytoplasm and cell borders, and uniform nuclei (Type A); damaged-appearing Type A cells marked by rarefied or ragged cytoplasm, disrupted or indistinct cell borders, and varying sized nuclei (Type B); and large spindling or stellate cells (Type C). Type A cells were predominant in 52 patients; Type B cells in 51; Type C cells in seven; and Type A cells were mixed with Type B in 30. Fever was present in one of 52 patients (1.9%) with Type A predominance; 43 of 51 (84.3%) with Type B cell predominance; none of seven (0%) with Type C predominance; and 13 of 30 (43.3%) with mixed Type A and B cells. Logistic regression analysis of the data showed that the association of fever with Type B cell predominance was highly significant, and was not attributable to the known association of fever with other variables. Morphologic evidence suggests that fever in Hodgkin's disease may be a clinical manifestation of damaged macrophage-histiocytes rather than an acute-phase response of inflammatory or immune reaction.

Adolescent↗

PubMed1990

Histopathologic, immunophenotypic, and genotypic analysis of Ki-1 anaplastic large cell lymphomas that express histiocyte-associated antigens.

CD30/Ki-1 antigen expression in 243 cases of malignant lymphomas was examined using Ber-H2 monoclonal antibody. Among them 20 cases were categorized as Ki-1 anaplastic large cell lymphoma. In two of these cases histiocyte-associated markers were also expressed. In these cases histopathologic and extensive in situ immunophenotypic analyses were used with genotypic studies in the determination of cell lineage. A sinusoid histologic pattern of involvement with partial lymph node infiltration by pleomorphic neoplastic cells was noticed in the nodes from both patients. Solid areas of node replacement resembling metastatic carcinoma were seen in Patient 1. Immunohistologically, tumor cells of both cases were positive for CD30, CD25, CD71, LN3 (HLA-DR), EMA, CD45, CD74, vimentin, alpha-1-antichymotrypsin, and CD68. Patient 1 was also CD45RO+, CD43+, whereas Patient 2 was positive for alpha-1-antitrypsin and CD4 tumor cells. Genotypic studies revealed that TCR beta and TCR gamma chain genes were clonally rearranged in Patient 1, whereas no rearrangements were detected in Patient 2. This study supports the view that some Ki-1 anaplastic large cell lymphomas may express multiple histiocyte-associated antigens and confirms that this group of neoplasms have immunophenotypic heterogeneity. The results of genotypic analyses used with immunophenotyping does not exclude that the tumor cells in these cases may be of true histiocytic origin despite the Ki-1-positive phenotype.

Adolescent↗

PubMed2003

Fine-needle aspiration cytology: true histiocytic lymphoma/histiocytic sarcoma.

True histiocytic lymphoma/histiocytic sarcoma is an extremely rare, malignant histiocytic tumor. This report is of such a case in a 52-yr-old woman. Fine-needle aspiration (FNA) smears showed large pleomorphic nuclei, prominent nucleoli, moderately dense abundant cytoplasm, and scattered cells with cytoplasmic vacuoles and some with reniform nuclei. Small numbers of background lymphocytes and benign histiocytes were present as well as many multinucleated tumor cells. The immunophenotype was CD45, Lysozyme, CD68 (PGMI), CD43, and S-100 positive. Genotypic analysis revealed a germline configuration. This type of tumor has a large cytological differential diagnosis and immunophenotyping is essential for diagnosis.

Antineoplastic Agents↗

PubMed2004

Histiocytes containing immunoglobulin crystals in the urine of a patient with IgA kappa plasmacytoma of the bladder.

Exfoliative cytology specimens from patients with plasma cell dyscrasias are rarely diagnostic, though there are reports of neoplastic plasma cells observed in pleural fluid and urine. Immunoglobulin concretions or crystals associated with neoplastic plasma cell populations have been well described. These crystals may be found within plasma cell nuclei or cytoplasm, extracellularly, or within cells of histiocytic lineage where they are presumably derived by phagocytosis. To the best of our knowledge, this is the first report of immunoglobulin crystals within histiocytes in the urine of a patient with plasmacytoma. A 61-year-old male underwent routine cystoscopy and urine collection to evaluate hematuria. The bladder biopsy demonstrated IgA kappa-producing plasmacytoma. Urine cytopsin preparations did not contain plasma cells, but there were histiocytic cells with degenerative nuclei and eccentrically located cytoplasmic spherical refractile hyaline crystals thought to be immunoglobulin crystals. This was supported by immunocytochemical staining.

Crystallization↗

PubMed1986

Identification of histiocytic reticulum cells by the immunohistochemical demonstration of factor XIII (F-XIIIa) in human lymph nodes.

Morphologically and enzyme histochemically distinguishable tissue macrophages and stromal cells of human reactive lymph nodes were characterized by the cytoplasmic presence of the subunit A of factor XIII and by the expression of surface antigenic determinants reacting with monoclonal antibodies directed against monocyte/macrophage populations (Mo 1, Leu M3) and HLA-DR antigens. The distribution of F-XIIIa positive cells was studied on formaldehyde-fixed paraffin-embedded sections with immunoperoxidase techniques. established on cryostat section with double immunofluorescence. Alpha-Naphthyl acetate esterase (ANAE) reaction was The immunophenotype was established on cryostat sections with double immunofluorescence. Alpha-Naphthyl acetate esterase (ANAE) reaction was carried out on these cryostat sections to identify tissue macrophages. The antibody against F-XIIIa detected histiocytes in both intra- and extra-sinusoidal locations which were ANAE+, Mo 1+, Leu M3+ and HLA-DR-. F-XIIIa was also present in fibroblast-like mesenchymal cells with the following phenotypic characteristics: ANAE-, Mo 1+, Leu M3+ and HLA-DR+. The anti F-XIIIa antibody did not stain lymphoid cells, granulocytes, epithelial cells, endothelial cells and mast cells. The immunohistochemical detection of F-XIIIa works on formaldehyde-fixed paraffin-embedded sections. The most promising application seems to be the identification of histiocytes in lymphoid and histiocytic proliferations.

Antigens, Surface↗

PubMed1975

Certain notable clinical attributes of the histiocytic sarcomas of the central nervous system.

By the term reticulum cell sarcoma we denote any tumor composed predominantly of undifferentiated cells, some of which have the qualities of histiocytes. The origin of such CNS tumors may be traced to circulating monocytes, perithelial ro meningeal histiocytes or microgliocytes. The ubiquity of cells of the monocyte-histiocyte series allows six possibilities of CNS involvement: a) primary in the brain: b) secondarily involve the brain or spinal cord by extending from a cranial bone or vertebra to the epidural space c) rarely to involve intraneuronal tissues (lymph nodes, bone, viscera) and then later to localize to the brain substance d) to spread from brain outside the nervous system e) to evoke any one or several of the paraneoplastic diseases (polymyositis, polyneuritis, cerebellar degeneration, f) to permit widespread infections of the nervous system such as multifocal leucoencephalitis. Clinical attributes to be emphasized are the relative rarity of hematogenous metastases (2 of 121 cases), the relatively high incidence of such tumors in immunologically suppressed individuals (12 of 5000 cases), the frequency of primary tumors of CNS (23 of 144 cases), the high incidence of epidural and dural involvement from osseous lesions (13 of 121 cases); the rapid evolution of clinical phenomena; the rarity of paraneoplastic syndromes; the occasional spontaneous and frequent therapeutic regression upon x-radiation. The common invasion of pia and ependyma by the tumor cells and their natural tendency to phagocytosis opens unrealized possibilities of clinical diagnosis by cytological examination and culture of CSF. Early diagnosis by these methods permits avoidance of surgery and the use of radiation and possibly chemotherapy, which may be rewarded by symptomatic regression and potential cure.

Bone Neoplasms↗

PubMed1986

Immunohistological study of histiocytic necrotizing lymphadenitis.

Immunohistological study of 18 cases of histiocytic necrotizing lymphadenitis (HNL) demonstrated numerous helper/inducer cells (OKT-4) and suppressor/cytotoxic cells (OKT-8) with activation (Tac) and proliferation (OKT-9) markers, and histiocytes (lysozyme, alpha-1 anti-chymotrypsin, OK-M1) in the affected areas. However, B cells (B-1), NK cells (Leu-7 and Leu-11), complement proteins and receptor (C4 and C3d receptor), and neutrophils (chloroacetate esterase) were scanty or absent in these foci. Activity of NK cells was also decreased in the peripheral blood of 2 cases examined. The results suggest that HNL might be induced by the abnormal T cell-histiocyte response against some causative agents which induce a similar reaction of delayed hypersensitivity type.

Adolescent↗

PubMed2003

Atypical histiocytic infiltration simulating diffuse-type carcinoma in a gastric ulcer due to non-steroidal anti-inflammatory drugs.

A 83-year old man treated with naproxen during two years was admitted because of hypovolemia and peritoneal irritation. A panendoscopic study was performed and an ulcer localized at the large curvature of the stomach was disclosed. In the gastrectomy specimen the ulcer showed necrosis, edema, fibrosis, chronic inflammatory infiltrate with lymphocytes and plasma cells. Additionally, atypical cells with irregular and hyperchromatic nuclei or vacuolated cytoplasm were seen in the lamina propia and infiltrating the muscular layers; isolated signet-ring-like cells were also seen. Histochemical study with periodic acid-Schiff, mucicarmin, and colloidal stains revealed mucosubstances in these cells. A poorly differentiated carcinoma was initially diagnosed. However, the immunohistochemical study were positive for histiocytic markers (CD-68, S-100 protein) and negative for epithelial markers (cytokeratin; and epithelial membrane antigen). The positivity of mucus stains in the histiocytes could be explained in this case by phagocytosis of mucous substances released from broken hyperplastic glands in the vicinity of the ulcer. To our knowledge, atypical histiocytic infiltration in gastric ulcers has not been previously described; thus, it should be included in the group of gastric carcinoma mimicks.

Aged↗

PubMed1977

Adult Niemann-Pick disease: its relationship to the syndrome of the sea-blue histiocyte.

Three unrelated female patients with adult Niemann-Pick disease are described. All the patients had reduced coagulation factors and involvement of the marrow, liver, spleen and lungs. Two patients were shown to have abnormal platelet function; two patients also had pingueculas and a late onset of a menarche. Foam cells and sea-blue histiocytes were seen in the marrow and livers in all three patients, in the spleen in two patients in the lymph nodes in one patient. The clinical presentation, the histologic appearance, the histochemical staining reactions, the lipid analysis and the ultrastructure were all consistent with a diagnosis of adult Niemann-Pick disease. On the basis of these observations, it is clear that adult Niemann-Pick disease is a cause of the syndrome of the sea-blue histiocyte. The existence of the syndrome of the sea-blue histiocyte as a separate entity is also questioned.

Adolescent↗

PubMed1986

Sinus histiocytes in axillary lymph nodes from patients with breast cancer: macrophage characteristics and activation level.

Cell suspensions from 16 tumour-free axillary lymph nodes from breast cancer patients were prepared, using collagenase digestion to free the sinus histiocytes from the fibrous stroma of the nodes. The histiocytic cells so obtained were then characterized using four surface markers: Fc(IgG) receptors, C3 receptors, DR antigen and a macrophage-associated antigen (defined by the monoclonal antibody VEP-7). In addition phagocytosis was assessed using IgG-coated red cells, and both lysozyme and alpha-1-antitrypsin were localized by means of immunoperoxidase staining. The results demonstrated that the majority of sinus histiocytes carried surface macrophage markers, but that a minority displayed phagocytosis and the presence of lysozyme or alpha-1-antitrypsin.

Antigens, Surface↗

PubMed2006

The PTEN and INK4A/ARF tumor suppressors maintain myelolymphoid homeostasis and cooperate to constrain histiocytic sarcoma development in humans.

Histiocytic sarcoma (HS) is a rare malignant proliferation of histiocytes of uncertain molecular pathogenesis. Here, genetic analysis of coincident loss of Pten and Ink4a/Arf tumor suppressors in the mouse revealed a neoplastic phenotype dominated by a premalignant expansion of biphenotypic myelolymphoid cells followed by the development of HS. Pten protein loss occurred only in the histiocytic portion of tumors, suggesting a stepwise genetic inactivation in the generation of HS. Similarly, human HS showed genetic or epigenetic inactivation of PTEN, p16(INK4A), and p14(ARF), supporting the relevance of this genetically engineered mouse model of HS. These genetic and translational observations establish a cooperative role of Pten and Ink4a/Arf in the development of HS and provide mechanistic insights into the pathogenesis of human HS.

Animals↗

PubMed1981

Cytophagic histiocytic panniculitis with fever, cytopenia, liver failure, and terminal hemorrhagic diathesis.

We have seen five adult patients with a clinical picture of recurrent histiocytic, cytophagic panniculitis, cytopenia, abnormal liver function tests, and a terminal, febrile bleeding diathesis. Originally thought to have Weber-Christian disease, these patients, we believe, represent a unique syndrome: lobular, histiocytic, cytophagic panniculitis. Erythrophagocytosis and cytophagocytosis are readily observed, but the cells do not show malignant features. Histiocytosis can be found at times in the bone marrow, lymph nodes, liver, spleen, and serosal tissues, as well as in the skin and subcutaneous tissues. The terminal hemorrhage in these patients is characterized by features of pancytopenia, liver failure, and intravascular coagulation. This disease may be separated from malignant histiocytosis by the chronic course, the primary involvement of the adipose tissue, and the benign histiocytes in the infiltrate. It has some similarities to other regional histiocytoses such as sinus histiocytosis, intestinal histiocytosis, and splenic histiocytosis.

Adult↗

PubMed2003

Histiocytic lesions involving the bone marrow.

Histiocytic lesions involving the bone marrow include a number of reactive and neoplastic disorders. This article discusses the morphologic, immunophenotypic, and genotypic features of a variety of diseases associated with histiocytes and/or monocytes. Lysosomal storage disorders and hemophagocytic syndromes are often first diagnosed by bone marrow examination. Granulomas involving the bone marrow may also be the first indication of a systemic disorder. Apart from acute and chronic monocytic leukemias, the bone marrow is rarely involved by malignant histiocytic disorders, of which Langerhans cell histiocytosis is the most common.

Bone Marrow↗

PubMed1996

Sea-blue histiocyte syndrome in bone marrow secondary to total parenteral nutrition including fat-emulsion sources: a clinicopathologic study of seven cases.

Bone marrow examination revealed a lipid-laden histiocytosis in seven patients undergoing long-term total parenteral nutrition necessitated by extensive short-bowel surgical resection. Clinical abnormalities occurred during this treatment which required bone marrow examination. These included hepatosplenomegaly and peripheral blood cytopenia; the median time to the detection of these abnormalities was 64 months. The most striking change within the bone marrow was the presence of many pigment-laden histiocytes which had the typical morphology of sea-blue histiocytes seen in the so-called idiopathic sea-blue histiocyte syndrome. The occurrence of sea-blue histiocytosis in the bone marrow in association with long-term parenteral nutrition for short-bowel syndrome has not, to our knowledge, been reported previously and should now be considered in the differential diagnosis of bone marrow sea-blue histiocytosis.

Adult↗