Malignant lymphoma of true histiocytic origin: Histiocytic Sarcoma

Summary 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 Fe receptor, strong acid phosphatase and alpha-naphtyl 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 resistent 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 alpha₁-antitrypsin, alpha₁-antichymotrypsin and 5 Nucleotidase activity and the number of lysosomes in the cytoplasm were found. The findings are suggestive of a spectrum of cytological changes 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 alpha₁-antitrypsin and a high number of lysosomes is discussed.     

Malignant histiocytosis (true histiocytic lymphoma) clinicopathological study of 25 cases

Twenty-five cases originally diagnosed as malignant histiocytosis/true histiocytic lymphoma were reviewed according to both pathological and clinical criteria. Microscopically, they were characterized by large, pleomorphic tumour cells showing variable degrees of atypia and phagocytic activity. The growth more often appeared as diffuse, being limited to the sinuses in only two cases. Cytochemistry on touch imprints showed tumour cells strongly positive for acid phosphatase and alpha-naphthyl-acetate esterase in all the samples tested. Immunohistochemistry on paraffin embedded sections using specific antisera showed tumour cell positivity for lysozyme in 12 of 25 cases, for alpha 1-antitrypsin in 24 of 25 cases and for alpha 1-antichymotrypsin in all 25 cases. Immunophenotyping on frozen-sections in three cases displayed a clear-cut reactivity of the neoplastic cells with the monoclonal antibody OKM1. Clinically, the disease more often presented with B-symptoms, lymphadenopathy and mediastinal involvement. In the majority of the patients (18/25) it had a fatal and rapid course, despite therapy (median survival: 9 months; mean survival: 12 months). The presence of B-symptoms and bulky disease appeared as the only factors influencing the prognosis, both suggesting a more aggressive course of the tumour.     

Alpha-1-antitrypsin phenotypes in malignant lymphoma.

The alpha-1-antitrypsin (alpha 1 AT) Pi phenotypes have been determined by isoelectric focusing in a series of 228 patients having a histologically diagnosed malignant lymphoma and in 250 healthy controls. The Pi MZ phenotype occurred in 13 patients with lymphoma (5 . 8%) and in five of 250 healthy individuals (2%). Furthermore, one patient with a Pi SS and three patients with an abnormal unknown phenotype, migrating slower than Z, were found in the lymphoma group. No prevalence for a special lymphoma type was observed among the abnormal Pi phenotype patients. The increased incidence of abnormal Pi phenotypes in malignant lymphoma's support the hypothesis of the possible role of alpha 1 AT in development of immunopathological disorders.     

Concurrent T-cell lymphocytic lymphoma and malignant histiocytosis

A case in which both malignant histiocytosis and T-cell lymphocytic lymphoma occurred together is presented. Examples of malignant histiocytosis-like syndromes associated with lymphoreticular malignancies have been previously reported. Many of these represent reactive haemophagocytic syndromes, probably virally induced. The considerable degree of cytological atypia and frequent mitotic figures seen in the histiocytes in this case were indicative of a true malignant histiocytosis.     

Analysis of the Epstein-Barr viral genome in so-called malignant histiocytosis syndrome

Malignant histiocytosis has been described as a proliferation of morphologically atypical hlstiocytes, but It Is difficult to determine whether or not malignant proliferation is present based on morphology alone. Recently the disorder has been thought to be heterogeneous, and therefore a true histtocytlc origin is considered to be rare. The Epstein-Barr virus (EBV) is thought to have the ability to transform human cells. Therefore, eight cases of malignant MsHocytic (MH) syndrome and five cases of virus-associated hemophagocytic syndrome (VAHS) were analyzed using a polymerase chain reaction (PCR) and the In situ hybridization (ISH) method in order to determine their relationship to EBV Infection. At the same time, the cellular origin of these syndromes was also studied. The results indicated that three of the MH cases were derived from T cells while four the MH cases were from hlstiocytes. The amplification of the EBV-LYDMA region, which was used to determine the monoclonallty, was detected in two MH cases and one VAHS case, and all these cases showed only one band. An ISH study also demonstrated the presence of an EBV in these three cases. One of the EBV-positive cases revealed an amplification of the EBV-LYDMA region by the PCR method before showing any sign of MH clinically. In the VAHS cases, the EBV genome was detected In hemophagocytic cells. The EBV-poslttve cases all demonstrated a rapid clinical course. Based on these results it is possible that EBV infection causes similar rapid clinical features in some cases of both MH and VAHS by the same mechanism.     

Expression of interleukin-1 in Reed-Sternberg cells and neoplastic cells from true histiocytic malignancies.

Interleukin-1, a peptide produced by monocytes, histiocytes, and interdigitating reticulum cells, plays an important role in the regulation of immune function. In this styde, we examined the production of interleukin-1 in 115 patients with a variety of human lymphomas by using a rabbit anti-interleukin-1 antibody and the immunoperoxidase technique. Interleukin-1 was detected in Reed-Sternberg cells from 20 patients with Hodgkin's disease as well as in neoplastic cells from 9 patients with true histiocytic lymphoma or malignant histiocytosis. In the other 86 cases, which included T- and B-cell lymphomas, no interleukin-1 could be detected. This result indicates a close relationship between Hodgkin's disease and true histiocytic malignancies and provides additional evidence to support our hypothesis that Reed-Sternberg cells are related to interdigitating reticulum cells.     

Malignant lymphomas of true histiocytic origin. A clinical, histological, immunophenotypic and genotypic study

The clinical, histological, immunophenotypic and genotypic properties of four cases of lymphoma of true histiocytic origin are described. The cases were identified by typing 925 non-Hodgkin's lymphomas by immunophenotypic and/or genotypic techniques, and they all presented with skin lesions. The histological and immunophenotypic examination showed dense, diffuse infiltrates of markedly pleomorphic mononuclear cells that were positive for macrophage-associated markers, and negative for B-cell, T-cell and myeloid cell-associated antigens. Staining for Ki-1 and epithelial membrane antigen was also negative. Gene rearrangements studies were performed in three cases, and all of these showed germline configuration of both T-cell receptor and immunoglobulin genes. In all cases, the clinical course was aggressive with rapid and widespread dissemination to internal organs, poor response to conventional chemotherapy, and short survival times (0.5 to 14 months). This suggests that although true histiocytic tumours are very rare, their recognition may be important for clinical and/or prognostic reasons.     

A comparative marker study of large cell lymphoma, Hodgkin's disease, and true histiocytic lymphoma in paraffin-embedded tissue

A comparative study of large cell lymphoma (LCL) (ten B and ten T), Hodgkin's disease (15 cases), and true histiocytic lymphoma (two cases) was undertaken, using formalin-fixed paraffin-embedded tissue sections, a panel of eight antibodies, and one lectin to determine if any particular antibody or immunologic profile could reliably distinguish between these entities. The antibodies used were against Leu-M1, alpha-1-anti-chymotrypsin (alpha-ACT), alpha-anti-trypsin (alpha-AT), lysozyme, kappa, lambda, leukocyte common antigen (LCA), and S-100 protein. The lectin used was peanut agglutinin (PNA). Although Leu-M1 staining was positive in 11 of 15 cases (73%) of Hodgkin's disease, it was also positive in 4 of 10 cases (40%) of T-cell lymphoma, 2 of 10 cases (20%) of B-cell lymphoma, and 1 of 2 cases (50%) of true histiocytic lymphoma. Peanut-agglutinin staining results were similar to Leu-M1. The only staining profile that emerged was the presence of Leu-M1, PNA-, alpha-ACT, and alpha-AT staining in Reed-Sternberg (RS) cells in 11 of 15 cases of Hodgkin's disease. Leu-M1 and its staining pattern is characteristic, but not entirely specific for RS cells, and it was not positive in at least 25% of the cases of Hodgkin's disease in formalin-fixed, paraffin-embedded tissues. The limitations of this antibody and others should be recognized.     

Co-existence of cutaneous true histiocytic lymphoma with refractory anaemia: report of a case

The case of a 70-year-old man with refractory anaemia who developed cutaneous true histiocytic lymphoma two years after diagnosis, is described. Whether this association is a simple coincidence or indicates some etiopathogenetic relationship between these two unrelated disorders is unknown and needs the analysis of more cases.     

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.     

Langerin在Langerhans细胞组织细胞增生症和非Langerhans细胞组织细胞性疾病中的表达

Langerhans细胞代表着树突抗原提呈细胞的一种亚型，主要位于各种器官的表皮和黏膜。该细胞因特征性表达CDIa抗原和胞质内Birbeck颗粒的存在而不同于其他亚型的树突状细胞。Birbeck颗粒的形成被认为是通过一种名为Langerin的凝聚素家族的新的Ⅱ型跨膜糖蛋白介导的。Langerin是Langerhans细胞和Langerhans细胞组织细胞增生症中病变细胞的一种高度选择性标记物，但对Langerhans细胞组织细胞增生症的特异性还没有明确。     

Ultrastructure of the spleen in malignant histiocytosis.

We examined the ultrastructure of the spleen surgically removed from a patient with the in vivo diagnosis of malignant histiocytosis. The findings showed sinuses greatly dilated and lined by large atypical histiocytic cells. Erythrophagocytosis was prominent. These findings, as well as the histologic features of the bone marrow and later autopsy specimens, confirmed the diagnosis of malignant histiocytosis. The somewhat unusual confinement of histiocytes to sinusoids raised the possibility that this may represent a rare subvariant, histiocytic sinus reticulosis, first described by Robb-Smith in his original paper.     

Congenital histiocytosis. A heterogeneous group of diseases, one presenting as so-called congenital self-healing histiocytosis

Three cases of congenital histiocytic disorders--generalized Langerhans cell histiocytosis, generalized juvenile xanthogranuloma and so-called congenital self-healing histiocytosis are compared using histiochemical, immunohistochemical and ultrastructural methods. The results showed a typical morphological pattern of Langerhans cell histiocytosis (S 100+, CD 1+, alpha-mannosidase +) with an unusual self-healing cutaneous phenomenon. The congenital self-healing histiocytosis showed a non-Langerhans cell immunophenotype (CD 14+, CD 1-, S 100-) and morphological appearance resembling the evolutive "early" stage of juvenile xanthogranuloma. A diffuse cellular positivity of alpha-mannosidase in juvenile xanthogranuloma and congenital self-healing histiocytosis differed from a typical perinuclear globular positivity of this enzyme in Langerhans cell histiocytosis. It is concluded that congenital self-healing histiocytosis may in some cases be of non-Langerhans cell type and under this term a clinically characteristic syndrome of histiocytic proliferation of Langerhans cells or tissue histiocytes may be included.     

Fatal hematophagic histiocytosis after granulocyte-macrophage colony-stimulating factor and chemotherapy for high-grade malignant lymphoma

Fatal hematophagic histiocytosis occurred in two patients after they had received granulocyte-macrophage colony-stimulating factor (GM-CSF) in addition to chemotherapy for malignant non-Hodgkin's lymphoma. In one patient GM-CSF promoted the activity of subclinical hematophagic histiocytosis, resulting in severe pancytopenia and multiorgan failure. In the other patient the syndrome that caused persistent bone marrow failure began after the institution of GM-CSF therapy. Exogenous GM-CSF appears to upregulate preexisting hematophagic histiocytosis and may even contribute to its de novo initiation. It is therefore conceivable that endogenous GM-CSF also plays an essential role in the pathogenesis of this syndrome.Abbreviations CMV cytomegalovirus - G-CSF granulocyte colony-stimulating factor - GM-CSF granulocyte-macrophage colony-stimulating factor Correspondence to: A. Schaffner     

EBM/11 reactivity in malignant histiocytosis.

A patient presented initially with a testicular mass, which on biopsy had morphological features consistent with malignant histiocytosis. The tumour cells labelled strongly with EBM/11, a murine monoclonal antibody with high specificity for cells of the human mononuclear phagocyte system. Subsequent clinical and laboratory studies confirmed the diagnosis. As poorly differentiated tumour cells reacted with EBM/11, this antibody may be useful in positively identifying malignant tumours with histiocytic differentiation from malignancies of other types where morphological detail alone is inconclusive in tumour classification.     

反义端粒酶基因表达抑制人癌细胞恶性表型

目的 观察端粒酶基因ｈＴＲＴ,ｈＴＲ反义表达对癌细胞生物学行为的影响,探讨改变端粒酶基因表达在肿瘤治疗中的作用。方法 通过反义ｈＴＲＴ基因转染人ＨｅＬａ细胞系,反义ｈＴＲ寡核苷酸处理人肺巨细胞癌系ＰＧ,观察其对肿瘤细胞生长及恶性表型的影响。     

Malignant histiocytosis (histiocytic medullary reticulosis) with spindle cell differentiation and tumour formation.

Malignant histiocytosis (histiocytic medullary reticulosis) in a 45-year-old white man is described. Unusual features were presentation as a surgical emergency with signs of obstruction and peritonitis due to an ileal tumour and extensive spindle cell differentiation. Problems in the differential diagnosis of malignant histiocytosis are briefly discussed.     

The histiocytic origin of the multinucleated giant cells in myeloma kidney.

A recent case of myeloma kidney disease was studied to determine the cellular origin of the syncytial multinucleated giant cell. Light, immunofluorescence, and electron microscopy of the giant cells revealed features characteristic of histiocytes. This finding contradicts the generally accepted conclusion that the giant cell represents a syncytial mass of degenerating or reactive tubular epithelial cells. We conclude that the giant cells arise in the interstitial tissues, migrate through breaks in the tubular basement membrane, and engulf and surround intratubular protein casts.