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Malignant histiocytosis with marked cellular atypia--an autopsy case with an immunohistochemical study on neoplastic histiocytes.

A 71-year-old male presenting high fever, pancytopenia, liver dysfunction and jaundice died without a confirmed diagnosis. Microscopically, histiocytes with marked atypia and erythrophagocytosis had infiltrated the spleen, enlarged lymph nodes, liver, and bone marrow. From the above features this case was diagnosed as malignant histiocytosis. The infiltrating histiocytes were classified into three categories: 1) phagocytic cells, 2) atypical, mostly non-phagocytic cells, and 3) bizarre cells including multinucleated giant cells. An immunohistochemical study of histiocyte markers demonstrated that lysozyme was positive in the atypical cells and some phagocytic cells, whereas alpha-l-antitrypsin tended to be localized in the phagocytic cells. Bizarre cells were negative for both markers. No S-100 protein was demonstrated in the neoplastic cells. These immunohistochemical features suggested monocyte-phagocytic origin of the tumor in this case.

Aged↗

Growth of malignant histiocytic cells induced by phorbol myristate acetate.

Cells from the spleen of a patient with malignant histiocytosis were cultured in methyl cellulose with and without 100 ng/mL of phorbol myristate acetate (PMA). Colony growth occurred only with PMA; comparing surface marker studies of the cells before and after culture, it was evident that proliferation had occurred among the histiocytic cells as well as the lymphocytes. After exposure to PMA in organ culture for ten days, the histiocytes appeared to be differentiated and showed evidence of continuing phagocytosis by electron microscopy. This suggests that PMA is a mitogen for the histiocytes in this condition and maintains differentiation of the cells.

Adult↗

Histiocytic sarcoma with a granuloma-like component occurring in a large colony of Sprague-Dawley rats.

Tumors from a large colony of over 2000 Sprague-Dawley rats were reviewed by a panel of pathologists under the auspices of Universities Associated for Research and Education in Pathology, In the course of this study, a distinct malignancy in 105 rats was segregated and given the name "histiocytic sarcoma." This report describes the histologic features and anatomic distribution of the tumor, along with its incidence by age and sex of the rat. The neoplasm is characterized by a spectrum of histologic patterns, one extreme resembling a sarcomatous process and the other a granulomatous process. The exact morphologic composition varied from animal to animal, as well as in tumors from the same animal. The sarcomatous pattern is composed of sheets of uniform cells, occasionally exhibiting phagocytosis. The granulomatous pattern contains epithelioid histiocytes, central areas of tumor necrosis surrounded by palisading cells, and multinucleate giant cells. The liver is the organ most commonly containing histiocytic sarcoma, both in animals with multiple tumors and in those with involvement of only one organ. Hepatic invasion is typified by expansion of the portal areas and infiltration of the sinusoids by tumor cells. The lung is the second most common site. The distribution of pulmonary tumors is bronchiolocentric and angiocentric. Other common sites included the lymph node and spleen, along with large soft tissue tumors of the mediastinum and retroperitoneum. Although occasional previous reports apparently have described a similar or identical neoplasm under varying names, no large group of tumors of this unique type in rats has been studied and characterized previously.

Animals↗

[Panniculitis with cellular phagocytosis. Chronic form of histiocytic panniculitis with fever, pancytopenia, polyserositis and lethal hemorrhagic diathesis].

Two cases of what was originally called "Weber-Christian disease" were found to be a chronic, recurrent form of histiocytic panniculitis characterized by histiocytic engulfment of red and white blood cells--"cytophagocytosis." The disease was manifested by recurrent fever, subcutaneous nodules, pancytopenia, and mucosal ulcerations. Hepatosplenomegaly and enlarged lymph nodes were observed. Focal invasion of the reticuloendothelial system by acidophilic or cytophagic histiocytes could be identified. Progressive changes in liver function and hemorrhagic diathesis occurred in both patients.

Adipose Tissue↗

Jacalin, another marker for histiocytes in paraffin-embedded tissues.

Jacalin is a lectin which reacts with D-galactose. We have tested jacalin on 75 samples of different formalin- and alcohol-fixed tissues. A consistent cytoplasmic stain of the histiocytes was observed in paraffin-embedded tissues in all cases studied of reactive sinus histiocytosis, macrophages in clear centres of follicular hyperplasia, in tuberculosis granulomas and in osteoclast-like giant cells in a breast carcinoma. We failed to find any clear binding of jacalin to the cells of eosinophilic granulomas, giant cell tumors of tendon sheath, pleomorphic malignant fibrous histiocytomas, Hodgkin's disease, melanomas, nevi or signet ring cell carcinomas of the breast and stomach. It seems that jacalin is a good marker for free histiocytes/macrophages, not for fixed histiocytes and tumors related to them. This lectin might play a role in differential diagnosis with histiocyte mimicking processes.

Breast Neoplasms↗

Histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi-Fujimoto disease): a report of two cases.

This report describes the clinicopathological features of two Chinese patients with histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi-Fujimoto disease). Both cases presented painless enlarged lymph node in the posterior cervical triangle, neutropenia and lymphocytosis. One patient had detectable serum antinuclear antibody. Microscopically, the lymph node showed distinctive patch fibrinoid necrosis in the paracortical areas. The necrosis was characterized by florid nuclear dusts engulfed by histiocytes or distributed extracellularly and absence of polymorphonuclear leukocytes. Immunohistochemical studies revealed that the cells in necrotic areas were essentially histiocytes or T lymphocytes. This disorder has a good clinical course, and generally heals spontaneously with no treatment. Recognition of this disorder is, otherwise, imperative not only for the frequent concern for malignant lymphoma, but equal for consideration be given to systemic lupus erythematosus.

Adolescent↗

Tumor cell characterization of histiocytic medullary reticulosis.

Tumor cells from a 10-year-old boy was suspected histiocytic medullary reticulosis were examined and were found to have receptor sites for complement, the ability to phagocytize latex beads, and the electron microscopical picture of immature histiocytes. These findings strongly support the diagnosis of histiocytic medullary reticulosis. This disorder and the method of examination of the tumor cells are discussed.

Binding Sites, Antibody↗

Systemic lupus erythematosus with erythema multiforme-like lesions and histiocytic necrotizing lymphadenitis--a case report.

A 9-year-old Chinese girl with systemic lupus erythematosus presented initially with persistent cervical lymphadenopathy without any constitutional symptoms. The histology of the involved lymph node showed histiocytic necrotizing lymphadenitis and the initial clinical diagnosis of Kikuchi-Fujimoto disease was made. The patient subsequently developed fever, oral ulcerations, epistaxis, generalised myalgia and erythema multiforme-like skin lesions over the face and upper arms. Investigations showed anaemia, leucopenia, hypocomplementemia, a positive antinuclear antibody and a positive anti-double-stranded DNA antibody test. The clinical diagnosis was revised to systemic lupus erythematosus. The histological picture of histiocytic necrotizing lymphadenitis can occur in systemic lupus erythematosus and may be indistinguishable from that seen in Kikuchi-Fujimoto disease. The diagnosis of Kikuchi-Fujimoto disease should be confined to a benign clinical subset of histiocytic necrotizing lymphadenitis which resolves spontaneously without treatment. The occurrence of erythema multiforme-like lesions in lupus erythematosus is unusual and together with the characteristic serologic abnormalities, fits Rowell's syndrome.

Child↗

Histiocytic necrotizing lymphadenitis (Kikuchi's disease): in situ end-labeling, immunohistochemical, and serologic evidence supporting cytotoxic lymphocyte-mediated apoptotic cell death.

Histiocytic necrotizing lymphadenitis (Kikuchi's disease) is a benign, self-limited disorder that is sometimes confused with malignant lymphoma. Kikuchi's disease is characterized by collections of histiocytes and lymphocytes surrounding areas of necrosis containing fragments of karyorrhectic nuclear debris. Polymorphonuclear leukocytes are generally absent. The mechanism of cell death involved has not been extensively studied, and a definitive etiology has not been identified. Recent articles proposed that the mechanism of cell death is more characteristic of coagulative necrosis than apoptosis, but, to our knowledge, this has not been studied with the use of currently available assays of apoptosis. To study the mechanism of cell death in Kikuchi's disease, we employed an in situ end-labeling technique on formalin-fixed, paraffin-embedded sections of lymph nodes with Kikuchi's disease. These studies demonstrated that the lymphocytes and histiocytes within and surrounding the areas of necrosis showed nuclear DNA fragmentation, a feature characteristic of early apoptosis. Immunohistochemical studies revealed an increase in CD8(+)-T lymphocytes and lymphocytes containing TIA-1, a cytotoxic granule-associated protein, within foci of cellular debris, with a relative paucity of CD56+ cells. Moreover, TIA-1-positive granules were present within the cytoplasm of many apoptotic bodies. In one of the patients for whom acute phase serum was available, evaluation by enzyme-linked immunosorbent assay demonstrated that the serum concentrations of the T-cell activating cytokines interleukin-2 and interleukin-6 were increased; no such increase was noted in eight patients with other lymphoproliferative disorders. In contrast, the serum concentrations of the immunosuppressive molecules interleukin-10, soluble interleukin-2 receptor, and soluble tumor necrosis factor receptor were expressed at normal levels in the patient with Kikuchi's disease. These findings suggested that the predominate mechanism of cellular destruction in Kikuchi's disease was apoptosis mediated by cytolytic lymphocytes. These data supported the prevailing hypothesis of a viral or autoimmune pathogenesis in Kikuchi's disease.

Adult↗

T cell rich and histiocyte rich B cell lymphoma--a case report.

We report one case of Non Hodgkin's Lymphoma which was classified as Histiocyte Rich B cell lymphoma on immunocytochemistry. The diagnosis was difficult on fine needle aspiration cytology and routine histopathological examination as the infiltrate was composed of reactive lymphocytes and numerous histiocytes obscuring the lymphoma cell population. The neoplastic cells were positive for CD20(L26-A Pan B marker) and negative for CD15(Leu M1), CD3(Ber H2) and pan T cell markers. The histiocytes were positive for CD3(UCHL-1). The patient had a rapid downhill course and died. The autopsy showed infiltration in the axillary, cervical, mesenteric, para aortic, peri pancreatic and hilar lymph nodes. The liver, spleen, bone marrow and kidney also showed lymphomatous infiltration.

Adult↗

Osteopontin is strongly expressed by histiocytes in granulomas of diverse etiology.

Granulomatous inflammation is associated with a variety of important pathologic conditions. Osteopontin (OPN), a ligand for the alpha v beta 3 integrin, is a secreted glycoprotein with a glycine-arginine-glycine-aspartate-serine cell-binding domain. In this study, we examined expression of OPN in 22 cases of granulomatous inflammation including cases of sarcoidosis, granulomatous temporal arteritis, histoplasmosis, rheumatoid nodule, granuloma annulare, erythema nodosum, granulomatous gastritis, foreign body giant-cell granulomatous reactions, and lipogranulomas. Strong expression of OPN mRNA and protein was seen in the epithelioid histiocytes and multinucleate histiocytic giant cells in granulomas by in situ hybridization and immunostaining. OPN may play an important role in granulomatous inflammation through the regulation of processes such as histiocyte migration, cell adhesion, and cellular functions including phagocytosis.

Animals↗

Purification, characterization and anti-tumor activity of a new cytokine, histiocyte-secreted-factor (HSF).

Purification of cytokines was carried out while monitoring their in vivo anti-tumor activity and in vitro cytotoxic activities. As a result, purified new cytokines were obtained from culture supernatant of a histiocytic cell line from rabbit serum. Briefly, a new cytokine (HSF, histiocyte-secreted-factor) was purified from the culture of supernatant of the histiocytic cell line (TYH) which we established from the peripheral blood of a malignant-lymphoma patient. The purified samples exhibited suppressive effects on tumor growth but no necrotizing activity towards transplanted murine tumors. The substance displayed no cytotoxic activity against L cells (mouse fibroblast cells). The molecular weight of human HSF was about 42 kDa as estimated by SDS-PAGE. Amino-acid sequencing of the purified HSFD from the culture supernatant was performed, but the N-terminal was blocked. Next, a new cytokine was purified from rabbit serum stimulated with Propionibacterium acnes and elicited with lipopolysaccharide. The rabbit HSF was isolated by the same procedures as those used for the human HSF purification steps. Amino-acid sequencing was carried out after enzyme digestion. Three parts of the amino-acid sequence of the rabbit HSF were determined as LPPGLLAPMRQLRS-, NLEXFTNGMEQHYAQL-, NPAENQAHELPNQLN-. A computer-based homology search demonstrated that these sequences were novel. The molecular weight of HSF as determined using anti-peptide antibodies revealed the following values: human HSF, 41 and 46 kDa; rabbit HSF, 35, 42 and 55 kDa.

Amino Acid Sequence↗

Long-term remission in diffuse histiocytic lymphoma treated with combination sequential chemotherapy.

Seventeen patients with Stage III or IV reticulum cell sarcoma were treated with three cycles of a 5-drug regimen between February, 1969 and December, 1970. Of the 17 patients, 9 attained a complete remission and 6 had a parital remission; 2 were considered unevaluable. Recently, the original biopsies from these patients were reclassified according to the criteria of rappaport et al. The results were: diffuse histiocytic--8; nodular histiocytic--2; diffuse mixed--2; nodular mixed--3; diffuse lymphocytic poorly differentiated--1; nodular lymphocytic poorly differentiated--1. Of the 8 patients with diffuse histiocytic lymphoma 6 attained complete remission, 1 had a partial remission, and 1 was unevaluable. One of the 6 with complete remission relapsed at 7 months and died 2 months later. However, the other 5 are alive and in continued unmaintained remission for 55 to 65 months.

Adolescent↗

Nodular lymphocytic lymphoma eventuating into diffuse histiocytic lymphoma: immunoperoxidase demonstration of monoclonality.

The patient described here had a nodular, poorly differentiated lymphocytic lymphoma associated with a serum monoclonal protein, IgG lambda. Following a three year period of radiation-induced clinical remission she developed generalized diffuse histiocytic lymphoma. Direct immunoperoxidase staining of the tissue sections demonstrated that the neoplastic cells of each biopsy only contained IgG lambda immunoglobulin, identical to the serum monoclonal protein. This is presumptive evidence that these two histopathologically distinctive malignant lymphomas, occurring consecutively in the same patient, were responsible for the synthesis and secretion of the same serum M component. This strongly suggests that both lymphoid neoplasms arose from the same malignant clone. The results 1) confirm the light microscopic observation that nodular lymphocytic lymphoma may progress to diffuse histiocytic lymphoma and 2) offer further evidence that histiocytic lymphomas arising in patients with previous B cell malignancies are most probably related to the original B cell proliferation and do not represent the emergence of a second, separate malignant clone.

Female↗

Coexistence of leukemic reticuloendotheliosis and histiocytic lymphoma: a case report.

A 65-year-old woman had pancytopenia, splenomegaly, and an inaspirable bone marrow. Diagnostic evaluation demonstrated that she had both leukemic reticuloendotheliosis (LRE), or hairy cell leukemia, and an additional lympho-reticular neoplasm, most likely a "histiocytic" lymphoma. The diagnosis of LRE was based on the histopathology of spleen tissue and of a bone marrow biopsy specimen. The diagnosis of diffuse "histiocytic" lymphoma was based on the histopathology of a splenic hilar and a mesenteric lymph node, tumor nodules in the kidney and spleen, and tissue from a mass obstructing a ureter. This is the first well-documented association of a second lympho-reticular neoplasm with LRE. Even relatively gently treatment of the "histiocytic" lymphoma resulted in fatal pancytopenia, illustrating the restricitons on therapy imposed by the marrow impairment due to the LRE.

Aged↗

Virus-associated hemophagocytic syndrome: a benign histiocytic proliferation distinct from malignant histiocytosis.

Nineteen patients whose bone marrow smears showed histiocytic hyperplasia with prominent hemophagocytosis were found to have a clinicopathologic syndrome associated with active viral infection. High fever, constitutional symptoms, liver function, and coagulation abnormalities and peripheral blood cytopenias were characteristic findings. Hepatosplenomegaly, lymphadenopathy, bilateral pulmonary infiltrates, and skin rash were often present. Fourteen of the patients were immunosuppressed. Active infection by herpes group viruses was documented in 14 patients and by adenovirus in 1. The bone marrow of most patients also showed decreased granulopoiesis and erythropoiesis with normal to increased numbers of megakaryocytes. Treatment generally consisted of supportive therapy and withdrawal of immunosuppressive drugs. Thirteen patients recovered. Lymph node biopsy and autopsy material showed generalized histiocytic hyperplasia with hemophagocytosis. The relationship of this disorder to familial hemophagocytic reticulosis, familial erythrophagocytic lymphohistiocytosis, histiocytic medullary reticulosis, and malignant histiocytosis is discussed. Immunosuppressive and cytotoxic therapy may be contraindicated in the treatment of this virus-associated syndrome.

Adolescent↗

Lactic acidosis and diffuse histiocytic lymphoma (DHL).

Four patients with advanced diffuse histiocytic lymphoma who developed lactic acidosis are described. All four patients demonstrated disturbed liver function tests. In two of the patients, the lactic acidosis was unresponsive to treatment. The third patient responded successfully to the early initiation of combination chemotherapy with achievement of a clinical remission and correction of the lactic acidosis. The fourth patient responded to the initiation of chemotherapy with abatement of his lactic acidosis, but expired probably as the result of a pulmonary embolus. It seems likely that extensive hepatic infiltration may be one of the factors contributing to lactic acidosis in patients with diffuse histiocytic lymphoma. The early initiation of antineoplastic therapy may be important in the management of patients with histiocytic lymphoma and lactic acidosis.

Acidosis↗

Establishment and characterization of a human histiocytic lymphoma cell line (U-937).

A human hematopoietic cell line (U-937) with exceptional characteristics was derived from a patient with generalized histiocytic lymphoma. The morphology of the cell line was identical to that of the tumor cells in the pleural effusion from which the line was derived. Since Epstein-Barr virus (EBV) carrying diploid lymphoblastoid cell lines unrelated to the tumor population often become established in vitro from non-Burkitt lymphoma explants, several parameters were studied to discriminate the U-937 from such lines: morphology in vitro, growth characteristics, cytochemistry, surface receptor pattern, Ig production, lysozyme production, beta2-microglobulin production, presence of EBV genome and karyotype. In all these respects U-937 differed from prototype lymphoblastoid cell lines. The histiocytic origin of the cell line was shown by its capacity for lysozyme production and the strong esterase activity (naphtol AS-D acetate esterase inhibited by NaF) of the cells. It is therefore concluded that the U-937 is a neoplastic, histiocytic cell line.

Adult↗