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Atypical inflammatory histiocytic tumor of the cerebellum. A histological, immunohistochemical, and ultrastructural study.

We report a primary histiocytic tumor involving the cerebellum. Microscopically, the tumor was composed of nests of pleomorphic cells surrounded by thin vascular septa invaded by lymphocytes. Immunocytochemistry and electron microscopy confirmed the histiocytic origin of the tumor. Although we considered several diagnoses, we ultimately concluded that "atypical inflammatory histiocytic tumor of the cerebellum" best characterized the lesion. This case represents another example of the diversity of histiocytic tumors and shows that they can occur in the central nervous system.

Adult↗

Malignant histiocytic neoplasms of the small intestine.

Immunologic studies have demonstrated that the vast majority of hematolymphoid neoplasms previously designated as "histiocytic" are lymphoid in origin. Consequently, malignancies of macrophage lineage are considered rare by most authors; indeed, their existence is doubted by some. Herein we report two cases of malignant histiocytic neoplasms (malignancies of macrophage lineage) of the small intestine. Both patients presented in the 7th decade with symptoms related to an abdominal mass. The polypoid tumors protruded into the intestinal lumen, extended through the entire thickness of the bowel wall, and involved regional lymph nodes. Microscopically, sheets of large pleomorphic histiocytic cells infiltrated around crypts and were associated with an admixture of bizarre giant cells and inflammatory cells. Mitotic figures were easily found. Ultrastructurally, the cells lacked desmosomes and had indented or kidney-shaped nuclei and cytoplasm containing mostly lysosomes and dense lipid droplets. In both cases, paraffin section immunohistochemistry revealed reactivity of tumor cells for CD45RB (LCA), CD45RO (A6), CD68 (KP1), CD15 (LeuM1), and lysozyme. Frozen section immunohistochemistry performed in one case further supported the macrophage phenotype. Southern blot studies of this case did not reveal immunoglobulin or T-cell receptor beta chain gene rearrangements. One patient initially treated by surgery only died of disease 3 years after diagnosis. The second patient is alive and disease-free 2 years following postoperative combination chemotherapy. The diagnosis of malignant histiocytic neoplasms requires the use of a panel of immunohistochemical markers and may be supported by electron-microscopic studies.

Antigens, CD↗

Primary histiocytic lymphoma of the central nervous system: a neoplasm frequently overshadowed by a prominent inflammatory component.

True histiocytic lymphoma, as defined by strict criteria, is a very rare neoplasm. We describe three cases occurring as primary tumors in the central nervous system. The patients, two females and one male, ranged in age from 11 to 69 years. The tumors involved the brain in two cases and spinal cord in one, with a size ranging from 7 to 17 mm. Two patients died at 4 months and 8 months, respectively, and one was alive with disease at 5 months. Pathologically, the tumors comprised groups and sheets of noncohesive large cells with pleomorphic vesicular nuclei, distinct nucleoli, and abundant eosinophilic cytoplasm. A dense inflammatory infiltrate consisting of neutrophils, lymphocytes, plasma cells, and histiocytes was present, with multiple foci of necrosis and abscess formation. All three cases demonstrated an identical immunophenotype: positive for CD68 and lysozyme; focally positive for S-100 protein, CD45RB, and CD4; and negative for CD3, CD20, CD21/CD35, CD1a, CD30, ALK1, myeloperoxidase, glial fibrillary acidic protein, and cytokeratin. The proliferative index ranged from 20% to 35%. Ultrastructural examination further confirmed the histiocytic nature of the tumor cells, characterized by irregularly folded or multisegmented nuclei and abundant cytoplasm containing lysosomes; Birbeck granules, interdigitating cell processes, and cell junctions were not found. Although the presence of abundant inflammatory cells could obscure the neoplastic histiocytes, making the distinction from inflammatory conditions difficult, awareness of this unusual histologic feature and the invariable finding of pleomorphic cells in some areas of the lesion permit the correct diagnosis to be made.

Adult↗

Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy.

Histiocytic sarcoma is a rare malignant neoplasm that occurs in lymph nodes, skin, and the gastrointestinal tract. Many previously published cases were likely misdiagnosed examples of non-Hodgkin lymphoma. Only small numbers of bona fide examples exist in the world literature; cases arising primarily at extranodal sites are not well described and often seem to go unrecognized. To characterize these tumors further, 14 extranodal histiocytic sarcomas were analyzed. Hematoxylin and eosin sections were reexamined, immunohistochemistry was performed, and clinical details were obtained from referring hospitals. Eight patients were female and 6 male (median age, 55 years; range, 15-89 years). All patients presented with a solitary mass, ranging in size from 1.8 to 12 cm (median 6.8 cm). Seven tumors arose in soft tissue (6 lower limb; 1 upper limb), 5 in the gastrointestinal tract (1 involving both stomach and colon, 1 ileum, 2 rectum, 1 anus), 1 in the nasal cavity, and 1 in the lung. Three gastrointestinal tract tumors also involved regional lymph nodes, and 1 involved the liver. Most cases had infiltrative margins. The tumors were generally composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin, and large nucleoli. Binucleated cells were common, and 6 cases contained tumor giant cells. Mitoses ranged from 1 to 64 per 10 HPF (median 11 per 10 HPF). Necrosis was present in 8 cases. Nearly all tumors showed a striking inflammatory infiltrate, most often of neutrophils or lymphocytes. All cases were reactive for LCA, CD45RO, and CD68 (KP1 and PG-M1); 13 of 14 (93%) expressed CD4, 12 of 14 (86%) lysozyme, 8 of 10 (80%) CD31, 7 of 14 (50%) S-100 protein, and 5 of 14 (36%) focal CD1a. Two tumors showed weak, focal cytoplasmic positivity for CD30, and 1 for epithelial membrane antigen. The tumors were negative for ALK-1, CD21, CD35, CD3, CD20, CD34, myeloperoxidase, HMB-45, and keratins. Gastrointestinal tract cases were negative for c-kit and desmin. Six patients were treated with postoperative radiation and 7 with chemotherapy (CHOP or ProMACE-MOPP). Follow-up was available for 10 patients (median, 24 months; range, 4 months to 11 years). Two tumors recurred locally, and 5 patients developed distant spread: 3 to lymph nodes, 1 to lung, and 1 to bone. At the last follow-up, 2 patients have died of disseminated disease, 4 and 5 months following initial diagnosis. The patients who died thus far had the largest primary tumors. Histiocytic sarcoma may arise primarily in soft tissue and shows reproducible histologic features, including abundant eosinophilic cytoplasm and a prominent inflammatory infiltrate. Metastatic carcinoma, metastatic melanoma, and large cell non-Hodgkin lymphomas should be excluded by immunohistochemistry. Histiocytic sarcoma has the potential for an aggressive clinical course, most often with lymph node involvement. However, a subset of cases presenting with clinically localized disease have a favorable long-term outcome. Tumor size may be a prognostic factor.

Adolescent↗

True histiocytic lymphoma: histopathologic, immunophenotypic and genotypic analysis.

Five cases of true histiocytic lymphoma (THL) were analysed by immunophenotyping and immunoglobulin/T-cell receptor genotyping. These cases showed striking morphologic diversity but a strong degree of immunophenotypic homogeneity. The malignant cells reacted with multiple histiocytic markers including CD11c (Ki-M1, LeuM5), CD14, CD68 (Ki-M6) and Ki-M8; anti-HLA-DR and non-specific esterase staining was also found in all cases. The malignant cells did not express monoclonal immunoglobulin and did not react with the B- or T-cell monoclonal antibodies used except for those known to be cytoplasmically expressed in monocytes/histiocytes, such as CD4 and CD19; B- and T-cell staining was otherwise limited to background small lymphocytes. By genotypic analysis, three cases showed rearrangements: one with T beta, one with T beta and immunoglobulin heavy chain (JH) and one with both JH and light chain; the remaining two cases retained their immunoglobulin and T-cell receptor genes in germline configuration. The results not only suggest that certain subsets of the histiocyte/reticulum cell system may be capable of rearranging immunoglobulin or T beta genes while simultaneously expressing multiple histiocytic surface antigens but also demonstrate the necessity of using multiple histiocytic-specific monoclonal antibodies and cytochemical staining in diagnosing THL. Gene rearrangement studies must be interpreted in conjunction with immunophenotyping and morphology in the determination of cell lineage.

Adolescent↗

Histiocytic non-Hodgkin's lymphoma of Waldeyer's ring.

The most common extranodal site for non-Hodgkin's lymphoma in the head and neck is the lymphoid tissue of Waldeyer's ring. Diffuse histiocytic non-Hodgkin's lymphoma is the most frequent type occurring at all head and neck extranodal sites. The rarity of histiocytic lymphoma in the areas comprising Waldeyer's ring tends to make assembly of a large series of patients for retrospective study quite difficult. Of the 804 patients treated for malignancies in Waldeyer's ring during the years 1948 to 1985 at the Charity Hospital of Louisiana, 26 had lesions classified as histiocytic non-Hodgkin's lymphoma. We present, to our knowledge, the largest series of diffuse histiocytic lymphomas involving Waldeyer's ring.

Adolescent↗

Histiocytic medullary reticulosis with involvement of the nose.

A case of histiocytic medullary reticulosis in which nasal involvement was predominant is reported. The patient was a 33-year-old woman with a 14-month history of unilateral nasal stuffiness. The diagnosis was established by antemortem examination of films of bone marrow aspirates and by clinical features including fever, wasting, hepatosplenomegaly, anemia, and leukopenia. The histologic examination of autopsy specimens disclosed proliferation of histiocytes, which ingested nuclear debris and closed proliferation of histiocytes, which ingested nuclear debris and erythrocytes, in the necrotic lesion of the nose, sternal bone marrow, liver, spleen, thymus, uterus, ovali, and ileum. On reviewing literature on this subject, such a case of histiocytic medullary reticulosis which predominantly involves the nose is very rare.

Adult↗

Head and neck manifestations of histiocytic medullary reticulosis.

Histiocytic medullary reticulosis represents a proliferation of malignant histiocytes which produce pancytopenia through marrow involvement and the phagocytosis of granulocytes, leukocytes and platelets. The disease is typically characterized by a fulminant febrile course which results in death from a variety of complications due to pancytopenia or intercurrent infections. Its diagnosis is based on bone marrow aspiration or tissue section in which large histiocytes can be demonstrated phagocytizing red or white blood cells and platelets. Therapy has included irradiation, steroids, antibiotics, antimetabolites, and the like, but with poor results. Two patients with head and neck manifestations of histiocytic medullary reticulosis are described in detail. It is felt that refinements in diagnosis must still be made,, since any patient survival may well be predicated by the early initiation of aggressive cytotoxic therapy.

Adult↗

Radiation sensitivity of human histiocytic lymphomas in vitro.

The radiation sensitivity of five human lymphoma cell lines has been investigated. All cell lines were originated from tumours clinically classified as histiocytic lymphomas. Using biochemical and immunologic techniques it was found that only one of them was a true histiocytic lymphoma. This cell line had an appreciable shoulder on the survival curve and capacity to repair sublethal damage. The survival curves of the other cell lines had no shoulders and the cells had nearly no capacity to repair sublethal damage. Taken together with previously published experimental and clinical observations the results indicate that tumours which by conventional diagnostic techniques are classified as histiocytic lymphomas are very heterogeneous in radiation sensitivity. It is possible that tumours of true histiocytic origin are more resistant to radiation than tumours of lymphocytic origin.

Cell Count↗

Histiocytic sarcoma of the spleen associated with hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia as a possibly unique clinical entity--report of three cases.

We report three patients with histiocytic sarcoma of the spleen associated with severe hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia. After the clinical diagnosis of splenic tumor of unknown origin was made, all three patients underwent splenectomy. The histiocytic origin of the tumor was confirmed histopathologically and immunohistochemically using a panel of antibodies. In contrast to malignant histiocytosis (MH), which typically reveals severe generalized clinical manifestations and a rapidly fatal course caused by the disseminated proliferation of neoplastic histiocytes, these patients were asymptomatic or showed only mild clinical symptoms for a long period of time until the recurrence was detected by which time the tumor cells had already spread to other organs. All three cases were characteristically associated with hypoalbuminemia, hypo gamma-globulinemia and thrombocytopenia, which returned to normal after splenectomy. Splenic histiocytic sarcoma with the features described here may represent a unique clinical entity, distinct from MH.

Adult↗

In vitro granulocyte production in patients with Hodgkin's disease and lymphocytic, histiocytic, and mixed lymphomas.

The in vitro granulocyte colony formation (CFU-C) was examined in 19 untreated patients with advanced Hodgkin's disease and in 25 untreated patients with histiocytic, lymphocytic, and mixed lymphomas. The patients with Hodgkin's disease and diffuse histiocytic, lymphocytic, and mixed lymphomas produced decreased numbers of granulocyte colinies, whereas patients with nodular histiocytic, lymphocytic, and mixed histiocytic-lymphocytic lymphomas showed normal granulycote colony growth. The acute response of CFU-C to combination chemotherapy (MOPP) is described in two patients followed with sequential marrow cultures through their indiction chemotherapy. The long-term effect of MOPP chemotherapy was examined in five patients who had completed chemotherapy 1.5-6 yr priot to in vitro examination.

Adult↗

[Watershed-based segmentation of histiocytic images].

The task of segmenting histiocyte is a crucial step in the analysis of histiocytic images which is an important application of computer vision to histopathology. The algorithm presented in this article was composed of two steps: (1) the morph-based preprocessing; (2) the ameliorated watershed method. In the first step, the difference between histiocytes was magnified in order to increase the visibility from the view of the computer vision, and then the ameliorated terrace-flooding-simulated watershed method was used to achieve the segmentation of histiocytic images in the second step. To test the performance of the algorithm, different samples of visual quality were tested and the result figures proved successful.

Algorithms↗

[Morphology and immunohistochemistry of true histiocytic lymphoma--report of 4 cases].

True histiocytic lymphoma (THL) is a rare malignancy of histiocyte. It is difficult to diagnose by light microscopy alone. In this paper, 4 cases of THL were reported basing on light and electron microscopic examination, and immunohistochemical study. Histiocytic lymphoma was of Langerhans cell origin in one case and of interdigitating reticulum cell origin in the other. The other 2 patients probably belonged to neoplasm of macrophage or dendritic reticulum cell origin. The differential diagnosis between the true histiocytic lymphoma and other tumors or diseases was briefly discussed.

Diagnosis, Differential↗

[Anti-macrophage monoclonal antibody D-11 in the diagnosis of histiocytic tumors].

Anti-macrophage monoclonal antibody (Mab) D-11 was tested in surgical material and biopsies of non-epithelial tumors and tumor-like lesions from 181 patients in order to assess possibility of using this Mab for diagnosis of histiocytic tumors, malignant fibrous histiocytoma in particular. The study was performed in parallel on cryostat sections and smears by immuno-peroxidase method. It is established that D-11 reacts positively with both histiocytic tumors and tumors of other genesis this being a limiting factor in differential diagnosis of histiocytic tumors. However, taking into consideration 100% of positive results with histiocytic tumors only, this antibody can be used for exclusion of tumors studied from the group of histiocytomas in cases of negative reaction.

Antibodies, Monoclonal↗

Frequent expression of the NPM-ALK chimeric fusion protein in anaplastic large-cell lymphoma, lympho-histiocytic type.

The revised European-American lymphoma classification recognizes a subtype of anaplastic large-cell lymphoma (ALCL), termed lympho-histiocytic because of its peculiar cytological composition. As in the case of classical ALCL, this tumor usually occurs in young patients and shows an excellent response to chemotherapy, but some authors have suggested that in reality this is a nonanaplastic T-cell lymphoma rich in histiocytes. In this paper, we show that three of five cases of lympho-histiocytic ALCL stain with anti-ALK antibodies and can therefore be presumed to express the chimeric NPM/ALK protein secondary to (2;5) translocation. These findings further support the inclusion of this as a type of ALCL and not among the nonanaplastic peripheral T-cell lymphomas. Furthermore, they indicate that staining for ALK proteins is a powerful tool for the diagnosis of lympho-histiocytic ALCL, the recognition of which may be difficult on morphological grounds.

Adolescent↗

Myeloperoxidase expression by histiocytes in Kikuchi's and Kikuchi-like lymphadenopathy.

Forty-five examples of Kikuchi's lymphadenitis (KL), 5 Kikuchi-like lupus erythematosus lymphadenopathies, 25 nonnecrotizing lymphadenitidies (5 toxoplasmic, 5 sarcoid-like, 6 dermatopathic, 4 suppurative, 3 tubercular, 2 with sinus histiocytosis), 4 examples of hyaline-vascular Castleman disease (CD), 2 plasmacytoid monocyte tumors (PM-Ts), and 61 accessory cell neoplasms were studied by a panel of antibodies, including the PG-M1 (against a macrophage-restricted CD68 epitope) and a polyclonal anti-myeloperoxidase (MPO). In KL and Kikuchi-like lupus erythematosus lymphadenopathies, 25 to 75% of CD68(+) histiocytes co-expressed MPO. This did not occur in nonnecrotizing lymphadenitidies and accessory cell neoplasms. MPO(+)/CD68(+) elements corresponded to nonphagocytosing mononuclear cells and some crescentic macrophages and phagocytosing histiocytes. Typical PMs were MPO(-)/CD68(+) in all cases, including CD and PM-T. Our observations suggest that in KL and KL-like lymphadenopathies: 1) MPO(+)/CD68(+) blood monocytes might be attracted into tissues because of the lack or paucity of granulocytes and the need of MPO for oxidative processes; 2) PMs are more likely to be involved in the cytotoxic immune reaction than in phagocytic phenomena; 3) the peculiar phenotype of the histiocytic component can be usefully used for the differentiation from malignant lymphoma and PM-T.

Adolescent↗

Primary malignant histiocytosis of the brain: a clinical, radiological and morphological study with cytological and immunohistochemical demonstration of atypical histiocytes.

Clinical, radiological and morphological findings in the case of a 79-year-old patient with a primary malignant histiocytosis of the brain are reported. The tumor was exclusively situated in the brain as proven by autopsy and was spreading on the inside of the lateral ventricles. The demonstration of atypical histiocytic cells in the CSF and the immunohistochemical demonstration of lysozyme, alpha 1-antitrypsin and alpha 1-antichymotrypsin which are typical for histiocytes, underline the histiocytic origin of the tumor.

Aged↗

Cutaneous histiocytic proliferations.

The classification of histiocytic proliferations in the skin is confusing, largely due to faulty use of terms such as reticulum-cell sarcoma and reticulosis. Immunohistochemical staining procedures and ultrastructural studies have made it possible to differentiate the different cells of the mononuclear phagocyte system. The proliferations discussed here were those of the mononuclear phagocyte system that are associated with characteristic skin manifestations. They include proliferations of monocytes (acute monocytic leukemia), proliferations of tissue macrophages or histiocytes (histiocytic sarcoma and its disseminated form, malignant histiocytosis; familial histiocytoses; and multicentric reticulohistiocytosis), proliferations of Langerhans' cells (histiocytosis X), and proliferations of as yet undefined cells of the mononuclear phagocyte system (sinus histiocytosis with massive lymphadenopathy). Clinical features were presented, and special emphasis was placed on incidence, form, localization, histopathology, and marker profile of the proliferating cells in the skin lesions. The close relationship of the different entities was discussed, as was the importance of immune dysfunction.

Cell Division↗