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True histiocytic neoplasm of Langerhans' cell type.

Malignant histiocytic neoplasms of dendritic cell lineage are rare and most are derived from the dendritic cells of the T-cell and B-cell areas of the lymph node, respectively. Only one case of a malignant histiocytic neoplasm of Langerhans' cells, the dendritic cell of the skin, has been reported. We report the occurrence of a true histiocytic neoplasm of Langerhans' cell type in a 23-year-old female patient. The diagnosis of this highly aggressive neoplasm is supported by histochemical, immunohistochemical, ultrastructural, and genotypic analysis--techniques which allow differentiation from malignant melanoma and large cell anaplastic lymphoma.

Adult↗

Postarthroplasty histiocytic lymphadenopathy in a patient with uterine carcinoma.

INTRODUCTION: Postarthroplasty histiocytic lymphadenopathy is a benign reactive sinus histiocytosis. CASE REPORT: We report on the case of a 68-year-old woman presenting with pelvic postarthroplasty histiocytic lymphadenopathy after hysterectomy because of uterine carcinoma. CONCLUSION: This unusual form of histiocytic lymphadenopathy should be included in the differential diagnosis of gynecologic oncology patients who have had joint replacements to avoid misdiagnosis of a neoplasm.

Aged↗

Langerin (CD207) staining in normal pediatric tissues, reactive lymph nodes, and childhood histiocytic disorders.

Langerin is a recently identified lectin for which antibodies can be used as immunohistochemical markers of Langerhans cells (LCs). We describe the distribution of staining in autopsy pediatric tissues, dermatopathic and other reactive lymph nodes, and childhood histiocytic lesions using the 12D6 antibody (Novocastra). We also correlate CD1a (antibody O1O) staining to these factors. Langerin on epidermal LCs has a coarsely granular cell membrane and a cytoplasmic staining pattern that is always associated with CD1a expression. All 6 skin samples had Langerin(+)/CD1a(+) LCs within the epidermis. Six of 8 thymuses showed single scattered dendritic-shaped cells in the medulla and rare cells within Hassall corpuscles that coexpressed Langerin and CD1a. Cortical thymocytes were CD1a(+)/Langerin(-). Four of 8 livers examined showed a sinusoidal lining pattern of Langerin+/CD1a(-). All 15 autopsy lymph nodes showed a similarly strong Langerin(+)/CD1a(-) sinus pattern of staining on fixed tissue elements, mostly in medullary sinuses. All 12 dermatopathic lymph nodes showed accumulation of Langerin(+)/CD1a(+) cells in the pale paracortical nodules. All 24 instances of LC histiocytosis (LCH) were Langerin(+)/CD1a(+). All 12 non-LCH histiocytic disorders are negative for Langerin in the histiocytes of interest. We conclude that Langerin is coexpressed with CD1a on LCs and LCH. Lymph node sinuses and hepatic sinusoids show Langerin(+)/CD1a(-) cells, indicating that, when used alone to confirm LCH infiltration, the 12D6 antibody should be used with caution. At other sites, its diagnostic accuracy is similar to that of CD1a.

Antigens, CD↗

An immunohistochemical study of spontaneous histiocytic tumours in the rat.

Immunocytochemistry was used to examine 18 cases of rat fibrous histiocytic tumours (11 malignant; seven benign). The diagnosis was made by light microscopic criteria and all cases were categorized as pleomorphic-storiform. A selection of polyclonal antibodies to histiocytic, muscle, neural and mesenchymal antigens was used. Fifteen tumours were positive with alpha 1-antitrypsin, four with alpha 1-chymotrypsin, ten with muramidase, five with desmin, 15 with neuron-specific enolase, 14 with S100, one with glial fibrillary acid protein and 12 with vimentin. Many tumours expressed several antigens, highlighting the confusion which has arisen with regard to the histiogenesis of fibrous histiocytic tumours in man, and supporting the concept of differentiation from a primitive mesenchymal common precursor able to differentiate in several directions.

Animals↗

Leucocyte and endothelial cell adhesion molecule expression in porcine histiocytic leiomyofibrosarcoma.

A histiocytic sarcoma was present at birth in a pig. On the basis of ultra-structure and structural-protein composition (presence of alpha-smooth-muscle actin but not keratin), the sarcoma component was identified as a leiomyofibrosarcoma. Lipid-laden macrophages (histiocytes), which permeated the tumour in an apparently random fashion, were somewhat atypical in that they were negative for some macrophage markers; they gave a reaction, however, for CDw14. Despite its aggressive metastatic capacity, this tumour occurred almost exclusively in the subcutis, dermis and skeletal muscle. The tumour was extensively vascularized with many small capillaries which did not express E-selectin (CD69E), MHC class II or the L-selectin (CD69L) ligand, markers characteristic of inflamed (activated) endothelial cells in pig skin. Significant numbers of the histiocytes were positive for the integrins CD18 and VLA-4 (CD49d), indicating involvement of integrin pathways in the spread or growth, or both, of the leiomyofibrosarcoma. Most of the fibrous sarcoma cells also had extensive reactivity with an antibody to the standard variant form of CD44 (CD44s).

Animals↗

EBV-associated Kikuchi's histiocytic necrotizing lymphadenitis with cutaneous manifestations.

The clinical and pathologic findings of Kikuchi's histiocytic necrotizing lymphadenitis may mimic those of malignant lymphoma. We describe a 6-year-old boy with generalized lymphadenopathy, spiking fever, chills, myalgias, malaise, and erythematous, crusted papules. Although cutaneous manifestations have been noted in 16% to 40% of patients with histiocytic necrotizing lymphadenitis, only three publications described skin lesions. The skin lesions and affected lymph nodes revealed histiocytic aggregates, atypical lymphoid cells, karyorrhectic debris, and patchy necrosis. Spontaneous resolution occurred in 2 months. Results of serologic studies, Epstein-Barr virus (EBV) latent membrane protein immunoperoxidase staining, EBER-1 RNA in-situ hybridization, and EBV EBNA-1 DNA polymerase chain reaction implicate EBV as the causative agent.

Biopsy↗

Heterogeneity of systemic extra-nodal Epstein-Barr virus-associated lympho-histiocytic tumor--ten autopsy cases of human immunodeficiency virus-negative Japanese.

Epstein-Barr virus associated T-Cell lymphoma mimicking malignant histiocytosis (MH) has been previously reported. We selected 10 autopsy cases of extranodal lymphoma or histiocytic tumor, which showed an EBV presence in the tumor cells as well as a fulminant clinical course. The detailed clinicopathologic features were thus clarified. A retrospective study was performed on ten adult patients, eight males and two females, and almost all cases presented with a fulminant clinical course, revealing pancytopenia, liver dysfunction and disseminated intravascular coagulopathy. Immunophenotypic and genotypic studies along with in situ hybridization (ISH) were performed. The autopsy findings mainly showed extra nodal involvement in the liver (10 patients), spleen (9 patients), intestinal tract (5 patients), bone marrow (5 patients), nasal cavity, lungs, adrenal glands, kidneys (2 patients) and brain. Histologically atypical pleomorphic lymphoid cells were observed to infiltrate with reactive histiocytes, some of which showed hemophagocytosis. Based on the histological and clinical findings, diagnosis of malignant histiocytosis was made. ISH showed an EBV-presence in almost all the tumor cells. The immunophenotype and/or genotype studies demonstrated T-cell lymphoma (2 patients), Histiocytic tumors (2 patients), B-cell lymphoma (1 patients), natural killer (NK) cell lymphoma (3 patients), and T/NK lymphoma (2 patients), in which T or NK could not be confirmed, due to a lack of fresh materials. Based on the above findings, the histological appearance of EBV-associated MH previously defined was shown to be common to extra-nodal malignant lymphomas having origin in various organs, although the cytological and genetic features were heterogenous.

Adolescent↗

True histiocytic lymphoma as a second neoplasm in a follicular centroblastic-centrocytic lymphoma.

We report on a patient who developed a true histiocytic lymphoma, 16 years after initial diagnosis of a follicular low grade centroblastic-centrocytic lymphoma with several recurrences. We consider, out of gene rearrangement and immunohistochemical studies, that in this case, true histiocytic lymphoma is a second neoplasm in the evolutive course of the low grade lymphoma. The natural history of a low grade malignant lymphoma is to develop into a high grade large cell lymphoma and, if a second neoplasm appears, it is usually an epithelial tumor. This fact makes our report unique, as it would be, to our knowledge, the first case of true histiocytic lymphoma as the second neoplasm of another lymphoma.

Antigens, CD↗

True histiocytic lymphoma: is it an entity?

Monocytes and macrophages are closely related in origin, structure and function. True histiocytic lymphoma is a neoplasm of phagocytic histiocytes and is treated as non-Hodgkin's lymphoma. Tissue involvement with myeloid leukemia, including monocytic leukemia, is called extramedullary myeloid cell tumor or granulocytic sarcoma and treated with antileukemic chemotherapy. Differentiating true histiocytic lymphoma from tissue involvement with monocytic leukemia is a rather impossible task using available morphologic, cytochemical, immunocytochemical and molecular methods. The two entities need to be unified probably more appropriately as extramedullary myeloid cell tumor of monocytic origin, and should therefore be treated as such.

Antineoplastic Combined Chemotherapy Protocols↗

Effects of lipopolysaccharide on a macrophage-like cell line (HS-P) from a rat histiocytic sarcoma.

Lipopolysaccharide (LPS) is a major modulator of macrophage functions. To characterize a newly established rat histiocytic sarcoma-derived cell line (HS-P), immunophenotypic changes and cellular growth responses of HS-P cells exposed to LPS were investigated and compared with those of MT-9 cells isolated from a rat malignant fibrous histiocytoma. MT-9 cells have somewhat histiocytic features, because occasional cells react to rat macrophage-specific antibodies. Addition of LPS to cultured HS-P cells increased the numbers of cells immunopositive to ED1 (rat macrophage-specific antibody) and ED2 (rat histiocyte-specific antibody) and stimulated the phagocytosis of latex beads, whereas LPS-treated MT-9 cells did not show such immunophenotypic changes. LPS-treated HS-P cells showed enhanced immunolabelling of alpha-smooth muscle actin, suggesting a possible modulation of macrophages towards myofibroblastic cells. To evaluate cellular growth after the addition of LPS or fetal bovine serum, DNA synthesis was examined by measuring tritiated thymidine incorporation, and the mRNA expression of c- jun and c- myc (immediate early genes in the cell cycle) was examined by Northern blot analysis. In HS-P cells, the addition of serum greatly increased DNA synthesis and induced high expression of c- jun and c- myc; in contrast, LPS markedly depressed DNA synthesis and reduced the expression of c- jun and c- myc. HS-P cells were more sensitive than MT-9 cells to the growth-promoting effect of serum and the growth-inhibiting effect of LPS. The study demonstrated that HS-P cells are highly LPS-responsive, indicating that they would be useful for studies of macrophage functions.

Animals↗

Interstitial granulomatous dermatitis with histiocytic pseudorosettes: a new histopathologic pattern in cutaneous borreliosis. Detection of Borrelia burgdorferi DNA sequences by a highly sensitive PCR-ELISA.

BACKGROUND: The cutaneous manifestations of Borrelia burgdorferi infection include an early phase of erythema chronicum migrans and a late stage of acrodermatitis chronica atrophicans lesions. OBJECTIVE: We describe 11 patients with peculiar cutaneous manifestations and distinctive histopathologic findings as the result of B burgdorferi infection. METHODS: Eleven patients with B burgdorferi detected by polymerase chain reaction or polymerase chain reaction enzyme-linked immunosorbent assay in their cutaneous lesions were included in this study. We analyzed clinical data and histopathologic findings in all patients. The inflammatory infiltrate was also immunohistochemically investigated. RESULTS: Most patients showed a peculiar clinical setting of morphea, and a few cases presented the characteristic appearance of erythema chronicum migrans instead of acrodermatitis chronica atrophicans, as would be expected in a late phase of B burgdorferi infection. The histopathologic findings were similar in all cases and consisted of an interstitial inflammatory infiltrate mostly composed of histiocytes dispersed among the collagen bundles of the dermis and focal areas of small pseudorosette formation, characterized by small histiocytes radially disposed around thick collagen bundles. In some cases there were also a few plasma cells intermingled with the histiocytes. CONCLUSION: Cutaneous lesions with clinical appearance similar to that of morphea and histopathologic features closely resembling those of the interstitial type of granuloma annular may be seen in intermediate-stage cutaneous lesions of B burgdorferi infection. These clinical and histopathologic findings represent a constellation of findings that have not been previously characterized as a cutaneous manifestation of B burgdorferi infection.

Adult↗

Unusual histiocytic reaction to Monsel's solution.

Monsel's solution for hemostasis was applied to a wound produced at the site of a punch excision biopsy from the wrist of a 51-year-old white man. The biopsy specimen showed an incompletely excised basal cell carcinoma. Thirty days later, the residual carcinoma was excised. Adjacent to a basal cell carcinoma in the second biopsy specimen was an intradermal nodule composed of large polygonal cells and multinucleated histiocytic giant cells containing granules and clumps of dark brown and black pigment. This pigment was strongly positive for iron when stained by Perl's method. This unusual histiocytic reaction to topically applied ferric subsulfate must be differentiated from malignant melanomas and from histiocytic neoplasms with siderosis.

Biopsy↗

Dermatofibrosarcoma protuberans metastatic to lymph nodes and showing a dominant histiocytic component.

Dermatofibrosarcoma protuberans is a neoplasm composed of cells that have morphologic characteristics of fibroblasts and histiocytes. We report the eighth documented case of dermatofibroma protuberans metastatic to regional lymph nodes. The metastases consisted predominantly of cells that appeared to be atypical histiocytes. This case is considered to be an example of dermatofibroma protuberans in which primitive histiocytic cells have not acquired secondarily acquired fibroblastic characteristics.

Adult↗

An immunohistochemical study of dermatofibrosarcoma protuberans supports its fibroblastic character and contradicts neuroectodermal or histiocytic components.

Paraffin-embedded material from 26 cases of dermatofibrosarcoma protuberans (DFSP) was investigated by the peroxidase-antiperoxidase technique. Antibodies to S-100 protein, Leu-7 antigen, and neuron-specific enolase (neural markers); to lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin (histiocytic markers); and to cytokeratin, desmin, vimentin, and factor VIII were used. The tumor cells reacted only for vimentin. In addition, 12 cases showed positive reactions with histiocytic markers (1-3% of the cells; in two cases, up to 10%). These results support a fibroblastic and contradict a neural or histiocytic histogenesis of DFSP.

Fibroblasts↗

True histiocytic lymphoma (monocytic sarcoma)

The clinical, histological, immunophenotypic, and genotypic characteristics of two cases of cutaneous genuine histiocytic lymphoma are described. Both cases presented as cutaneous lesions. Both patients remain alive and free of disease at 26 and 10 months after the diagnosis and after having been treated with polychemotherapy. Neither peripheral blood nor bone marrow infiltration was detected in either case. Histological and immunophenotypic examination showed dense, diffuse dermic infiltrates of mononuclear cells with positive macrophage-associated markers (CD11c, CD68), and negative T- or B-cell-associated antigens. A germline configuration of both T-cell receptor and immunoglobulin genes was observed in gene rearrangement studies. Although most of the cases that have been diagnosed as histiocytic lymphoma or malignant histiocytosis in the past turned out to be B- or T-large-cell lymphomas, a small number of cases (two in our consecutive series of 350 cases) show characteristics of monocyte-macrophage tumors. We stress the importance of the CD68 marker in the diagnosis of true histiocytic lymphoma, suggest a therapeutic approach based on similarities with monocytic leukemia, and propose the use of the term monocytic sarcoma for this clinicopathological presentation.

Female↗

Immunohistochemical distinction of epithelioid histiocytic proliferations from epithelioid melanocytic nevi.

Histiocytic tumors can be confused with melanocytic nevi and malignant melanoma and vice versa. To explore the use of immunohistochemistry for this diagnostic problem, we examined the expression of S-100 protein, gp100 (the antigen recognized by HMB-45), tyrosinase (T311), Melan-A (A103), Factor XIIIa (FXIIIa), and CD68 in 10 juvenile xanthogranulomas (JXGs), five epithelioid histiocytomas (EHs), and 15 melanocytic nevi composed of large epithelioid cells. All epithelioid melanocytic nevi were immunoreactive for Melan-A, tyrosinase, and S-100 protein in most melanocytes. Four nevi were completely negative with HMB-45. Nine nevi had only a minor HMB-45-positive component in the superficial dermis. Two nevi were diffusely HMB-45-positive. Melanocytes in all nevi were completely negative for FXIIIa. Thirteen nevi were completely negative for CD68. Two nevi contained rare cells with weak staining for CD68. All 15 histiocytic proliferations were completely negative for Melan-A, tyrosinase, and gp100. They lacked expression of S-100 protein or had at most 10% immunopositive cells. In JXGs, most cells were strongly reactive for CD68, although only a few were positive for FXIIIa. In EHs, 40% to 60% of cells were immunoreactive for FXIIIa, and only 20% to 30% were positive for CD68. Our results demonstrate that Melan-A and tyrosinase are sensitive and specific markers to distinguish epithelioid melanocytic nevi from epithelioid histiocytic tumors.

Antigens, CD↗

Successful treatment of cytophagic histiocytic panniculitis with modified CHOP-E. Cyclophosphamide, adriamycin, vincristine, predonisone, and etoposide.

A 27-year-old woman developed generalized subcutaneous painful nodules, fever, abnormal liver function, a bleeding tendency, and pancytopenia. Skin biopsies revealed the lobular panniculitis with a morphologically benign histiocytic infiltration with prominent phagocytosis. Leukophagocytosis and erythrophagocytosis were also present in the bone marrow. The diagnosis of cytophagic histiocytic panniculitis was made. The patient received polychemotherapy with cyclophosphamide, Adriamycin, and vincristine on day 1, prednisone on day 1-5 (modified CHOP), with the addition of etoposide (E). This regimen was repeated 8 times every 3 weeks. The patient obtained a complete clinical remission that has lasted almost 2 years after the completion of chemotherapy. Thus we suggest modified CHOP-E chemotherapy for an effective treatment for the aggressive form of cytophagic histiocytic panniculitis.

Adult↗

A histiocytic medullary reticulosis-like syndrome as the terminal event in lymphocytic lymphoma.

Histiocytic medullary reticulosis is a rare disease of the reticuloendothelial system. The diagnosis of this disorder has generally been established by postmortem examination following a rapidly fatal clinical course characterized by fever and pancytopenia. Originally described as a de novo disease of unknown etiology, a histiocytic medullary reticulosis-like syndrome has been more recently found in association with a number of other disorders, the majority being lymphoreticular neoplasms. This report describes a patient with a 9-year history of lymphocytic lymphoma which terminated in a rapidly fatal disease which, clinically and pathologically, was consistent with a diagnosis of histiocytic medullary reticulosis.

Bone Marrow↗