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PubMed1983

Malignant histiocytosis and Letterer-Siwe disease. Neoplasms of T-zone histiocyte with S100 protein.

Eight cases with malignant histiocytosis (MH), two cases with systemic Letterer-Siwe disease, and one case with sarcomatous variant of MH were studied clinicopathologically. Characterization of neoplastic histiocytes was performed by immunohistochemical staining for S100 protein, lysozyme, and nonspecific cross reacting antigen with carcinoembryonic antigen (NCA). The immunohistochemical characteristics of histiocytes were S100+lys-NCA- in eight MH and two Letterer-Siwe disease cases and S100-lys+NCA+ in the sarcomatous variant of MH. MH and Letterer-Siwe disease were considered to have derived from a specific S100+ histiocytic cell lineage (T-zone histiocyte with S100 protein) independent of the monocyte--macrophage system, from which a sarcomatous variant was derived. Leukemic change of MH was discussed with special reference to the maturation and differentiation of T-zone histiocytes.

Adult↗

PubMed1983

Lectin histochemistry of malignant tumors. II. Concanavalin A: a new histochemical marker for macrophage-histiocytes in follicular lymphoma.

Concanavalin agglutinin (Con A) binding sites were studied in paraffin embedded lymph node specimens of reactive follicular hyperplasia (12 cases) and follicular lymphoma (37) using the avidin-biotin-peroxidase complex method, and the results were compared with those of Peanut agglutinin (PNA) and lysozyme stains. Very similar to the PNA stain, two categories of Con A receptor sites were observed: cytoplasmic and cell surface. In the reactive lymph nodes, the cells showing cytoplasmic receptor sites (CR+ cells) corresponded to macrophage-histiocytes and possibly dendritic reticulum cells in the H & E stained sections, while those showing cell surface receptor sites (SR+) corresponded to lymphoid cells. Unlike the PNA binding, however, the staining reaction of SR+ lymphoid cells was weak, and another staining pattern, a dot-like stain, was observed in some lymphocytes, both SR+ and SR-. In follicular lymphomas, CR+ histiocytes were distinctly displayed within the follicular centers in 25 of 37 cases, including 12 cases in which PNA stains on adjacent or nearby sections were negative for intrafollicular macrophage-histiocytes. Similarly, Con A stains were positive for the intrafollicular CR+ cells in four of the five cases in which lysozyme stains were negative. Many of these intrafollicular CR+ cells contained inclusion-like cytoplasmic globules and/or vacuoles, a hallmark of the large CR+ cells of germinal centers. These observations suggest that macrophage-histiocytes of presumably germinal center origin are retained in neoplastic follicular centers in varying degrees, and Con A might be a useful marker for macrophage-histiocytes in paraffin-embedded routine pathological specimens, in addition to the currently accepted markers, PNA and lysozyme.

Cell Membrane↗

PubMed1985

Lectin distinction of benign from malignant histiocytes.

Ricinus communis agglutinin (RCA) staining of malignant histiocytosis (two cases) and tissue infiltrates of monoblastic leukemia revealed two distinct macrophage-histiocyte types: one with cytoplasmic staining (RCA+), the other without (RCA-). RCA+ cells corresponded to benign-appearing histiocytes without nuclear atypia, whereas RCA-cells were cytologically malignant. In one case of malignant histiocytosis, many RCA-tumor cells were surrounded by a thin cytoplasmic extension of RCA+ cells, which suggested an interaction between the tumor cells and stromal macrophage-histiocytes. These observations support the view that most benign-appearing histiocytes in malignant histiocytosis are reactive in nature and suggest that RCA staining can be useful in distinguishing between benign and malignant disorders of macrophage-histiocytes.

Adult↗

PubMed1986

Concanavalin A-binding histiocytes in Hodgkin's disease. A predictor of early relapse.

Staining with Concanavalin agglutinin (Con A) reveals a far greater number of macrophage-histiocytes (M-H) in paraffin sections than any other staining method. With Con A staining, the shapes of stromal M-H are clearly visualized, thus enabling a study of their morphologic variations. Con A staining patterns were also unchanged in specimens left at room temperature for 24 to 28 hours before fixation. The appearance of Con A-binding histiocytes was studied in tumors, recurrent as well as original, of 18 patients with biopsy-proven early relapse (within 26 months of diagnosis), and compared with those of 26 patients who were in complete remission (lasting 48 months at the minimum). The early-relapse patients were diagnosed from 1977 through 1984, and all received intensive combination chemotherapy. The relapse-free patients were treated in various manners, and included six patients diagnosed in the 1960s who were treated with radiation alone. Three forms of Con A-binding histiocytes were easily recognized: medium-sized cells similar to those seen in reactive follicles, characterized by uniform nuclei and distinct, abundant cytoplasm (Type A); cells of varying size and shape with altered cytoplasm, rarefied and ragged with indistinct cell borders, or globular (Type B); and large cells, stellate or spindling (Type C). Large numbers of Type A cells were present in all tumors of the relapse-free patients but were virtually absent in the original and recurrent tumors of the early-relapse group. Conversely, Type B cells were rare in the relapse-free group, but were the most common type in the patients with early relapse. Type C cells were not seen in the former group, but were present in the latter. These observations suggest that the morphologic variations of Con A-binding histiocytes in Hodgkin's disease are associated with tumor behavior. Con A staining, which can best depict stromal histiocytes in paraffin sections, may be used to identify patients at a high risk of early relapse.

Adult↗

PubMed1986

Differences in marker expression among branched histiocytic cells in T-cell areas of the lymphoreticular system and among their epidermis- and mucosa-associated equivalents.

Branched histiocytic cells of the epidermis, the oral and anal mucosa, the tonsillar crypt epithelium, the thymus and of the T-cell-dependent areas of lymph node, spleen, and tonsil were examined with immunohistochemical single- and double-staining techniques. The markers used were a monoclonal anti-T6-antibody, a monoclonal anti-HLA-DR-antibody, heteroantiserum to S-100 protein and peanut agglutinin. Anti-HLA-DR and peanut agglutinin reacted with a considerable number of branched histiocytic cells, whereas anti-T6 and anti-S-100 protein only stained relatively small subpopulations. Concerning the population of branched histiocytic cells, double-staining revealed that the tissue distributions of all the markers used overlapped each other to various degrees; this was demonstrated by the different numbers of double-stained cells obtained in the experiments using all six possible combinations of primary reagents. The number of branched histiocytic cells co-expressing the markers varied depending upon marker combinations, types of tissue and microenvironment. We suggest that much of the immunologic phenotype of branched histiocytic cells is dynamic rather than static.

Anal Canal↗

PubMed1982

Histiocytic necrotizing lymphadenitis without granulocytic infiltration.

Twenty-seven cases of an unusual necrotizing lymphadenitis previously described only in Japan are reported as occurring in West Germany (23 cases), Iran (1 case), Italy (1 case), Korea (1 case) and Spain (1 case). The lesion frequently develops in the cervical lymph nodes of young women. It is characterized by infiltration of the cortex and/or paracortex by large collections of proliferating histiocytes and is devoid of granulocytes. Complete or, more often, incomplete necrosis of lymphoid tissue is seen in all cases. In cases with incomplete necrosis, the histiocytes are interspersed with pyknotic cells and nuclear debris. Based on the histological findings, the term "histiocytic necrotizing lymphadenitis without granulocytic infiltration" is proposed. Lesions to be considered in a differential diagnosis are malignant histiocytic neoplasms and necrotizing lymphadenitis with granulocytic infiltration, which is seen in lupus erythematosus and bacterial infections. The aetiology of histiocytic necrotizing lymphadenitis without granulocytic infiltration is still unclear. Some clinical and histological features indicate the possibility of an underlying viral infection.

Adult↗

PubMed2003

A case of non-selective phagocytosis of hemosiderin and melanin of dermal histiocytes in stasis dermatitis.

A case study was undertaken to determine whether or not the same dermal histiocytes could phagocytose both melanin and hemosiderin simultaneously. A biopsy specimen was taken from a pigmented lesion of the lower leg of a 57-year-old woman with stasis dermatitis. The specimen was processed for histology, conventional transmission electron microscopy and electron-probe X-ray microanalysis. Histologically, numerous histiocytes with their cytoplasm packed with either Prussian blue-positive granules or Fontana-Masson-positive granules were distributed almost equally in the dermis. Electron microscopically, the dermis had many histiocytes with their cytoplasm containing solitary or compound electron-dense substances. The electron-dense substances were classified into three types according to their degree of electron density. By electron-probe X-ray microanalysis, these electron-dense substances were classified into iron-containing and non-iron-containing substances. Both substances were seen in the cytoplasm of the same histiocytes and even in the same compound electron-dense substance. The former were siderosomes and the latter were probably melanosomes. These results show that the same dermal histiocytes probably phagocytose non-selectively both hemosiderin and melanin granules.

Electron Probe Microanalysis↗

PubMed1988

High frequency of spontaneous histiocytic sarcomas in BDII/Han rats.

Histopathological findings and anatomical distribution of histiocytic sarcomas found in an uncommonly high frequency (50 of 399 rats) in the BD II/Han inbred strain are reported. The incidence of the tumours in male rats was significantly higher than in females. This was in part attributed to a shorter life expectancy of female rats. Tumours identified were composed of histiocytic cells. Other histological features included Langhans-type giant cells, palisading of histiocytes around necrosis and granuloma-like arrangements of cells. The highest incidence of histiocytic sarcomas was found in the subcutis. Other organs frequently involved were lungs and liver. The histopathological findings in BD II/Han rats are compared with previously reported histiocytic sarcomas in other strains of rat.

Animals↗

PubMed1997

Histiocyte-rich B-cell lymphoma.

This is the second report of histiocyte-rich B-cell lymphoma and the first case analyzed by flow cytometry and cytogenetic study. The immunophenotype determined by flow cytometry was that of a B-cell antigen-positive, surface immunoglobulin-negative B-cell lymphoma with 79% CD11c positive histiocytes. The lymphoid cells were composed of 76% neoplastic B-cells and 24% reactive T-cells. Immunohistochemical staining showed large numbers of histiocytes positive for CD68 and lysozyme in the lymph node and the bone marrow. Neoplastic lymphoid cells were positive for CD20, CD45, CD74 and CDw75. The monoclonality of the tumor cells was established by the evidence of rearrangements of the heavy chain and kappa light chain genes and a complex clonal cytogenetic abnormalities including t(8;14)(q11;q32). The tumor cells were large, pleomorphic lymphoid cells and showed no features resembling those of the L/H cells of Hodgkin's disease as previously reported. The rapidly progressive clinical course in the present case is consistent with the clinical features shown in the original study. The histiocytic component in this tumor is presumably recruited by a lymphokine with the nature of a growth factor from the tumor cells that may also be responsible for the rapid proliferation of the tumor cells and the aggressive clinical course. This entity merits special recognition because it leads to a predictable poor prognosis and because of its potential of being misdiagnosed as true histiocytic lymphoma.

Aged↗

PubMedDate not supplied

[Type B Niemann-Pick disease and sea-blue histiocytes syndrome].

We report two new cases, in the same family, of type B Niemann-Pick disease associated with sea-blue histiocytes syndrome. In one patient the disease was revealed by spontaneous rupture of the spleen. The sea-blue histiocytes syndrome is due to the histiocytes being overloaded by ceroids, and it usually occurs in a context of blood disease or thesaurismosis. Twenty-five cases of sea-blue histiocytes syndrome associated with type B Niemann-Pick disease have been reported, with rupture of the spleen in two of them. The link between the two conditions is the transformation into ceroids of the sphyngomyelin accumulated in histiocytes.

Ceroid↗

PubMed1999

Origin of histiocyte-like cells and multinucleated giant cells in malignant fibrous histiocytoma: neoplastic or reactive?

The origin of histiocyte-like cells in malignant fibrous histiocytoma (MFH) remains controversial. To determine whether histiocyte-like cells and multinucleated giant cells show reactive or neoplastic proliferation, we transplanted human storiform-pleomorphic MFH to nude mice and investigated the origin of histiocyte-like cells using the DNA in situ hybridization (ISH) system. In addition, we analyzed the mRNA expression of mouse c-fms and human colony stimulating factor-1 (CSF-1); immunohistochemical expression of markers detectable in cells of monocyte/macrophage lineage. The DNA ISH revealed neoplastic proliferation of fibroblastic cells and bizarre multinucleated giant cells of human origin. Monocyte/macrophage lineage cells were seen in parental tumors, whereas they did not participate in neoplastic proliferation in transplanted tumors. The parental tumors expressed human CSF-1 mRNA and the histiocyte-like cells in transplanted tumors expressed 'mouse' c-fms mRNA. These results suggest that MFH induce infiltration of monocyte/macrophage and CSF-1 is one of the mediators involved in this phenomenon, because the human CSF-1 can act as a ligand to the mouse c-fms. Histiocyte-like cells in MFH should be considered as a reactive monocyte/macrophage lineage rather than as an element of neoplasm.

Aged↗

PubMed2003

Phagocytosis of terminally differentiated acute promyelocytic leukemia cells by marrow histiocytes during treatment with all-trans retinoic acid.

It has been established that acute promyelocytic leukemia (APL) cells are induced to terminally differentiate by all-trans retinoic acid (ATRA), however, the clearance of differentiated APL cells in vivo has not been well understood. Here, we documented the elimination of terminally differentiated APL cells by histiocytes in bone marrow during differentiation induction therapy. In two ATRA-treated APL patients, bone marrow showed the striking phagocytosis of differentiated APL cells by histiocytes just before the achievement of complete remission. Histiocytes phagocytosed APL cells at the terminal stage of differentiation prior to the late apoptotic event of cell lysis. Engulfed APL cells then undergo morphological features of late apoptosis and finally fragmentation in the cytoplasm of histiocytes. This swift and efficient elimination of APL cells undergoing apoptosis by the histiocytes in bone marrow may be possible pathway, at least partially, for the clearance of differentiated APL cells.

Aged↗

PubMed1988

Immunologic marker analysis of normal and malignant histiocytes. A comparative study of monoclonal antibodies for diagnostic purposes.

The authors investigated the phenotype of "monocyte-derived histiocytes/macrophages" on frozen sections of various human tissues, in 12 histiocytic tumors, and in 15 large cell non-Hodgkin's lymphomas. The monoclonal antibodies (MAbs) considered specifically directed against antigens associated with monocytes/histiocytes included the following: Leu-M1, Leu-M3, Leu-M5, My4, My7, My8, My9, anti-Monocyte 1, anti-Monocyte 2, RFD-7, RFD-9, OKM1, and FMC17. The histiocytes in normal tissues and the tumor cells of the histiocytic malignancies expressed these antigens in various degrees. They were not reactive with MAbs specific for lymphocytes, myeloid cells, or Reed-Sternberg cells (Ki-1 antigen). Out of these 13 MAbs, only the labeling by MAb Leu-M3, Leu-M5, anti-Monocyte 1, and RFD-7 was restricted to normal and malignant monocytes/histiocytes. In combination with their broad labeling of different types of monocytes/macrophages, these MAbs are of value in differential diagnostic purposes to distinguish histiocytic malignancies from large cell lymphomas. However, none of the 13 MAbs can be considered as pan-histiocytic reagents because they did not recognize all cell types belonging to the mononuclear/phagocytic system.

Adolescent↗

PubMed1988

Familial hypercholesterolemia with unusual foamy histiocytes. Report of a case with myelophthisic anemia and xanthoma of the maxillary sinus.

Accumulation of phagocytic histiocytes with a foam cell morphology has been described in a number of diseases. Familial hypercholesterolemia, one such disease, is characterized by foamy histiocytic accumulation in cutaneous or tendinous xanthomas and within atheromatous lesions. This report describes a patient with familial hypercholesterolemia who had two unusual manifestations of foamy histiocytic accumulation: a maxillary sinus xanthoma, which presented as an expansile mass, and diffuse bone marrow replacement with foamy histiocytes, which was associated with myelophthisic anemia. The accumulation of foamy cells in both locations resembled that seen in many of the storage diseases. The possibility of foamy histiocytic accumulation should be considered in the differential diagnosis of patients with these disease entities who present with space-occupying lesions.

Adult↗

PubMed1992

True histiocytic malignancy associated with a malignant teratoma in a patient with 46XY gonadal dysgenesis.

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.

Adolescent↗

PubMed1994

Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic proliferation induced by cobalt-chromium and titanium.

Six men who had undergone hip replacements for degenerative joint disease or trauma subsequently had radical prostatectomies or cystoprostatectomies with bilateral pelvic lymph node dissections for adenocarcinoma of the prostate or transitional cell carcinoma of the urinary bladder. The hip prostheses implanted in three patients were known to contain cobalt-chromium alloy and titanium. The pelvic lymph nodes ipsilateral to the hip prosthesis in five patients and the bilateral pelvic nodes in the only patient with bilateral hip prosthesis had dark brown or black cut surfaces. These lymph nodes did not contain carcinoma but showed florid sinus histiocytosis characterized by large polygonal histiocytes filling and expanding sinuses and interfollicular regions. The foamy histiocytes contained cobalt-chromium and titanium microparticles by light microscopy, ultrastructure, and energy-dispersive x-ray microanalysis. The lymph nodes uninvolved by the histiocytic reaction lacked the heavy metal microparticles. Four cases were found to have a small number of polyethylene particles, which might have contributed to the histiocytic response. By immunohistochemistry, the foamy cells displayed immunoreactivity for lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and cathepsin D, providing additional support for their histiocytic derivation. To our knowledge, this is the first time that microparticles of cobalt-chromium and titanium that migrate from hip prostheses to pelvic lymph nodes have been shown to elicit a distinctive type of florid sinus histiocytosis. Pathologists should be aware of this characteristic foreign-body tissue response to avoid confusion with other types of sinus histiocytosis or with metastatic carcinoma.

Aged↗

PubMed1998

Lesions described as nodular mesothelial hyperplasia are primarily composed of histiocytes.

It is known that, on occasion, histiocytic proliferations can be confused with reactive mesothelial cell hyperplasia or with a malignant process. We report four cases of histiocytic proliferation, two occurring in the pleura in a 23-year-old woman and a 78-year-old woman, respectively, one in a hernial sac of a 2-year-old boy, and one in the lamina propria of the bladder of a 74-year-old man with a noninvasive papillary transitional cell carcinoma. The morphologic features of the pleural lesion of the 23-year-old woman and of the hernial sac lesion of the 2-year-old boy, as well as the bladder lesion, were similar to those reported in cases of the so-called nodular mesothelial hyperplasia. The pleural lesion in the 78-year-old woman consisted of a proliferation of cells with a signet ring-like morphology that was originally interpreted as either an unusual form of mesothelial hyperplasia or a metastatic signet ring cell adenocarcinoma. Because of mitotic activity and some cellular atypia in the bladder lesion, the possibility of invasive transitional cell carcinoma into the lamina propria was considered before immunohistochemical studies were performed. Staining for keratin showed only a few positive cells in the hernial sac and pleural lesions, whereas most cells reacted for the histiocytic marker CD68. Immunohistochemical studies on the bladder lesion also demonstrated strong staining for CD68, but no reactivity for keratin was observed. Based on these results, it is concluded that all of the lesions are primarily reactive histiocytic proliferations and because they may occur in other locations aside from the serosal membranes, the designation "nodular histiocytic hyperplasia" appears to be more appropriate than that of nodular mesothelial hyperplasia. It is important that the reactive nature of these lesions be recognized because on occasion they may present high mitotic activity or may show signet ring-like morphology and thus they can be confused with a malignancy.

Adult↗

PubMed2000

Histochemical and immunohistochemical characterization of foamy histiocytes (muciphages and xanthelasma) of the rectum.

Despite being relatively common in the rectum, foamy histiocytes have received scant attention as to the antecedent lesion that causes them to form or their histologic characterization on the types of muco-substances they accumulate. One-hundred consecutive tissue sections of the rectum from an equal number of patients were reviewed for the presence of foamy histiocytes, evaluated for their associated histologic features, and examined histochemically for five types of mucin. Immunohistochemical and electron microscopic studies were performed. Forty (40%) of the rectal biopsy tissues contained foamy histiocytes. Patients presented with diarrhea, hematochezia, intestinal habit change, constipation, hemorrhoids, and abdominal pain. Endoscopically, 19 patients were thought to have rectal nodules or polyps. Histologically, 25 of the patients had regenerative changes in the adjacent mucosa and 14 had hyperplastic changes. In 36 patients (90%), the foamy histiocytes were located superficially in the lamina propria. Associated changes indicated that they are found in areas that are subject to an injury that is in a healing phase. These changes included mild fibrosis and chronic inflammation of lamina propria with mild architectural distortion. Thirty-five (88%) cases showed staining for D-PAS, Alcian blue stain pH 2.5, and the cocktail Alcian blue stain/PAS. Mucicarmine was positive in 25 (63%) cases. The Alcian blue stain pH 1.0 was positive in 19 (59%) of 32 cases. Ultrastructural studies showed electron-dense globules. Two cases were histologically identical to the other 38 but they did not stain for any mucin. Ultrastructural features disclosed clear vacuoles and thus represent a xanthelasma of the rectum. The foamy cells in all cases were confirmed to be histiocytes by immunohistochemistry and electron microscopy. Although muciphages and xanthelasma of the rectum may mimic polyps endoscopically, they are not related to any specific symptom or clinical finding, despite the fact that they probably represent remnants of a previous injury. Muciphages contain neutral, weakly acidic or strongly acidic mucin. The main type of acidic mucin is sialomucin with a smaller component of sulfated mucin.

Adult↗