Malignant Histiocytes Research Articles

Axc Rat Lymphoma in Tissue Culture; Electron Microscopic Observations

A previous publication documented a sarcomatous transformation observed in a cell line derived from a rat lymphoma growing in monolayer culture. (9) The morphological and cytogenetic changes found, suggested the presence of virus and the differentiation of the malignant lymphoblasts toward malignant histiocytes in culture. The present paper describes, under the electron microscope the structural features of the original tumor, of the cells growing in culture and of the derived sarcoma. This study will serve to complement the prior observations.

Current perspectives on the role of liver transplantation for Langerhans cell histiocytosis: A narrative review.

Langerhans cell histiocytosis (LCH) is a malignant disease of the histiocytes involving various organ systems. The spectrum of liver involvement in LCH ranges from mild transaminitis to end-stage liver disease. The hallmark of hepatic LCH is secondary sclerosing cholangitis, which manifests due to a progressive destruction of the biliary tree by malignant histiocytes. Chemotherapy remains the mainstay of treatment for active LCH. Early recognition, diagnosis and a systematic approach to the management of LCH can ameliorate the disease process. Nonetheless, the liver involvement in these patients may progress despite the LCH being in remission. Liver transplantation (LT) remains central in the management of such patients. Various facets of the management of LCH, especially those with liver involvement remain unclear. Furthermore, aspects of LT in LCH with regards to the indication, timing and post-LT management, including immunosuppression and adjuvant therapy, remain undefined. This review summarises the current evidence and discusses the practical aspects of the role of LT in the management of LCH.

Rosai–Dorfman disease presenting in a child as mediastinal lymphadenopathy

Rosai- Dorfman disease (RDD) or Sinus Histiocytosis with massive lymphadenopathy (SHML) is a rare benign disease with infiltration of lymph nodes or extranodal sites by non malignant histiocytes. It generally presents with fever, painless cervical lymphadenopathy and eleveated inflammaotory markers. Sometimes, it may be associated with night sweats and weight loss mimicking lymphoma. Forty per cent, present with extra nodal manifestations and 10 % have systemic involvement. Though the disease has a predilection for lymph nodes in head and neck region, it can affect any organ. The common extra nodal sites are skin and soft tissue, central nervous system, upper respiratory tract and gastrointestinal tract. Immune dysfunction and viral infections like HPV 6, EBV, parvo virus B19 are reported to be associated with the disease. RDD typically occurs in childhood and early adulthood. Histologially, characteristic finding of emperipolesis is seen. Diagnois is confirmed by Immunohistochemistry with S100 and CD68 positivity. Most of them do not require treatment as it is usually self-limiting. Steroids, surgery, chemotherapy and radiotherapy are considered in refractory disease with systemic involvement or vital organ involvement. We report a case of 4 year old boy who presented with massive bilateral cervical and mediastinal lymphadenopapthy and had complaints of breathing difficulty while lying down since last 3 months. Biopsy was confirmative of Rosai-Dorfman disease and he had a near complete response after 3 months of steroids and is symptom free for the past 1 year.

Extreme neutrophilic leucocytosis and intrathoracic mass in a Fox Terrier

Absrtact Extract An 8-year-old female Fox Terrier was presented for acute anorexia and depression. A haemogram revealed extreme neutrophilic leucocytosis (136×109/L neutrophils). By Day 4, the neutrophilia was more marked (214×109/L segmented; 23×109/L band). Imaging revealed a cranial mediastinal mass, pleural effusion and small pneumothorax. Needle aspiration of the mass showed cells resembling malignant histiocytes against a background of mature neutrophils. On Day 7, the mass was surgically removed. Histologically, it revealed a malignancy suggestive of histiocytic sarcoma intensely infiltrated with neutrophils. Immunocyto-chemical investigations are pending. Post-operatively, the dog's appetite and demeanour improved but breathing was laboured, and neutrophilia persisted (300×109/L on Day 14). The dog was humanely killed on Day 14; post mortem examination revealed no distant metastases. This dog's illness is strongly reminiscent of a rare human condition, inflammatory malignant fibrous his-tiocytoma with leukaemoid reaction (IMFH-LR). In IMFH-LR, neoplastic cells produce cytokines that attract neutrophils to the tumour. Other cytokines stimulate the bone marrow to produce extreme neutrophilia. Although paraneoplastic neutrophilia has previously been described in dogs, this is an extreme example and the condition has not previously been associated with histiocytic or intrathoracic malignancies.

Ki-1 positive large cell lymphoma of the orbit

Anaplastic large cell lymphoma (ALCL) positive for the cell marker Ki-1/CD30 is a recently recognized high grade lymphoma. The authors present a case of a three-year-old female child with a rapidly growing sino-orbital lesion with central nervous system extension, suggestive of rhabdomyosarcoma. The child presented a clinical challenge for prompt diagnosis and treatment.Histologically, the unusual tumor showed a mixture of large malignant lymphocytes and histiocytes. Immunohistochemically, the malignant lymphocytes showed positive reactivity to LCA, Ki-1, CD3, UCHL-1. The histiocytes were positive for KP-1 and lysozyme.There was complete resolution of the lymphoma. To the authors' knowledge, this is the first case of Ki-1+ ALCL lymphoma involving the orbit of a child.

Malignant histiocytosis: A study on clinicopathological features and cell origin

Thirty-one autopsy cases previously diagnosed as malignant histiocytosis (MH) were studied by means of immunohistochemical staining. Antibodies detecting the formalin resistant epitopes on T-cells, B-cells and those of histiocyte/monocyte origin were used. It was shown that the malignant histiocytes reacted only to the cell markers derived from histiocyte/monocyte, and only a part of lymphocytes showed positive reaction to the T and B cell markers. It is suggested that the histiocyte/monocyte lineage is the possible origin of the malignant proliferating cells in MH. The clinicopathological features and the differentiation of MH from familial erythrophagocytic lymphohistiocytosis, virus-associated hemophagocytic syndrome and malignant lymphoma are described. The pathogenesis, the causes of death and the points for attention in the treatment of MH are also discussed.

Cutaneous Histopathologic, Immunohistochemical, and Clinical Manifestations in Patients With Hemophagocytic Syndrome

• Background and Design.— The hemophagocytic syndrome (HPS) is characterized by fever, wasting, generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia, often with associated coagulopathy. The most common cutaneous manifestations are panniculitis and purpura. Cytophagic histiocytic panniculitis fits within the spectrum of HPS, and the most consistent histopathologic feature in HPS is a proliferation of mature histiocytes that exhibit prominent erythrophagocytosis and cytophagocytosis. The clinical spectrum, the underlying causes, and the histopathologic features found in HPS are broad. The characteristic phagocytic histiocytes seen in HPS have been confused with malignant histiocytes in the past, but are now known to be reactive. The clinical findings, histologic, and immunohistochemical features of 10 cases of HPS with cutaneous lesions were reviewed. Immunohistochemical markers included KP-1, βF-1, UCHL-1, L-26, MAC-387, factor XIIIa, and S100 protein. Results.— The HPS was associated with T-cell lymphoma and/or viral infection. Most biopsy specimens showed edema and hemorrhage with a lymphohistiocytic infiltrate and prominent histiocytic cells showing erythrophagocytosis and, in some cases, cytophagocytosis. The histiocytic cells showed positive reactions for KP-1 and negative reactions for the lymphoid markers. In all cases the lymphoid cells showed a mixed pattern with most cells positive for βF-1 and UCHL-1, and a small percentage positive for L-26. Conclusion.— In HPS, the prominent phagocytic histiocytes are reactive and are stimulated by T-cell lymphocytes, either neoplastic or in response to viral infection. Many of the findings in the HPS may also be due directly or indirectly to cytokines produced by proliferating T-cell lymphocytes and/or reactive phagocytic histiocytes. ( Arch Dermatol. 1992;128:193-200)

Cutaneous histopathologic, immunohistochemical, and clinical manifestations in patients with hemophagocytic syndrome. Military Medical Consortium for Applied Retroviral Research (MMCARR)

The hemophagocytic syndrome (HPS) is characterized by fever, wasting, generalized lymphadenopathy, hepatosplenomegaly, and pancytopenia, often with associated coagulopathy. The most common cutaneous manifestations are panniculitis and purpura. Cytophagic histiocytic panniculitis fits within the spectrum of HPS, and the most consistent histopathologic feature in HPS is a proliferation of mature histiocytes that exhibit prominent erythrophagocytosis and cytophagocytosis. The clinical spectrum, the underlying causes, and the histopathologic features found in HPS are broad. The characteristic phagocytic histiocytes seen in HPS have been confused with malignant histiocytes in the past, but are now known to be reactive. The clinical findings, histologic, and immunohistochemical features of 10 cases of HPS with cutaneous lesions were reviewed. Immunohistochemical markers included KP-1, beta F-1, UCHL-1, L-26, MAC-387, factor XIIIa, and S100 protein. The HPS was associated with T-cell lymphoma and/or viral infection. Most biopsy specimens showed edema and hemorrhage with a lymphohistiocytic infiltrate and prominent histiocytic cells showing erythrophagocytosis and, in some cases, cytophagocytosis. The histiocytic cells showed positive reactions for KP-1 and negative reactions for the lymphoid markers. In all cases the lymphoid cells showed a mixed pattern with most cells positive for beta F-1 and UCHL-1, and a small percentage positive for L-26. In HPS, the prominent phagocytic histiocytes are reactive and are stimulated by T-cell lymphocytes, either neoplastic or in response to viral infection. Many of the findings in the HPS may also be due directly or indirectly to cytokines produced by proliferating T-cell lymphocytes and/or reactive phagocytic histiocytes.

Unusual clinical presentation of malignant histiocytosis in a 70-year-old woman

A 70-year-old woman was admitted for evaluation of hepatosplenomegaly, fever and elevated serum LDH levels. A biopsy specimen of the liver revealed histiocytic proliferation at the portal triad, and a mild degree of hepatitis. A bone marrow biopsy specimen showed proliferation of histiocytes with minimal immaturity and atypism, and haemophagocytosis by the proliferated histiocytes. Fever, hepatosplenomegaly and elevation of LDH levels all disappeared spontaneously, and presumptive diagnosis of benign reticulosis with haemophagocytosis was made. One year later, fever, hepatosplenomegaly and elevation of LDH levels redeveloped, and the liver and bone marrow biopsy specimen showed proliferation of unequivocally malignant histiocytes. The patient died as a result of disseminated intravascular coagulation with shock 20 d later. We concluded that, in this case, malignant histiocytosis first presented as benign haemophagocytic reticulosis and, 1 year later, there was a typical malignant presentation.

Hematophagic Histiocytosis

The clinical and laboratory features of 23 new patients as well as 50 previously reported patients with the syndrome of hematophagic histiocytosis are reviewed. The syndrome occurs more often in men than women but has no age predilection. Common presenting features include fever, hepatic and splenic enlargement, lymphadenopathy, and profound depression of blood counts. The clinical course is generally fulminant and may be complicated by coagulation abnormalities, hepatic dysfunction and renal failure. In the majority of patients, however, the syndrome is self-limited with resolution of the clinical and laboratory abnormalities within several weeks. Hematophagic histiocytosis generally occurs in patients who develop infections in the setting of preexisting immunologic abnormalities or neoplasms. Viral infections are most commonly involved, but virtually any other infectious agent can precipitate this syndrome. The characteristic morphologic feature of the hematophagic histiocytosis is the proliferation of mature histiocytes actively ingesting other blood cells. These hematophagic histiocytes most commonly involve the bone marrow but may also be present in the lymph nodes, spleen and liver. Other bone marrow abnormalities include hypocellularity with preservation of megakaryocytes, and myelofibrosis. The principal features of this syndrome that distinguish it from malignant histiocytosis are the cytologic maturity and degree of hematophagic activity of the histiocytes as well as its more favorable prognosis. In some patients, however, a clear distinction of malignant from reactive histiocytosis will not be possible until a clonal marker for malignant histiocytes is identified. Based in our experience, the syndrome of hematophagic histiocytosis appears to be more common than malignant histiocytosis.

Comparison of peanut agglutinin and S100 stains in the paraffin tissue diagnosis of Langerhans cell histiocytosis

We compared peanut agglutinin and S100 stains on paraffin embedded material from a variety of sites involved in Langerhans cell histiocytosis (LCH). The two techniques were comparable in terms of ease of performance, time taken and cost. Peanut agglutinin produced dense cell surface and paranuclear staining of the characteristic LCH cells seen in lesions, which was easier to distinguish than the more diffuse cytoplasmic staining produced by the S100 technique. This characteristic staining pattern is more specific than that for the S100 protein which is present in a variety of different cells, including some malignant histiocytes. We recommend that peanut agglutinin be used as a routine diagnostic test for all samples suspected of being LCH.

Malignant histiocytosis in childhood: clinical, cytochemical, and immunohistochemical studies of seven cases.

Tissue specimens obtained at autopsy from seven childhood cases of malignant histiocytosis were studied by immunohistochemistry. Clinically, the majority of the cases showed sustained fever, hepatosplenomegaly, pancytopenia, and DIC. The pretreatment diagnosis was based on their typical clinical manifestations and bone marrow smear findings. Although three patients temporarily responded to exchange transfusion and chemotherapy, all seven patients eventually died of active disease. Postmortem examination revealed the proliferation of atypical histiocytes appearing in variable degrees of maturation in the lymph nodes, liver, spleen, bone marrow, lungs, and central nervous system. Immunohistochemical staining for lysozyme, nonspecific cross-reacting antigen (NCA), alpha 1-antitrypsin (alpha 1 AT), alpha and beta subunits of S100 protein (S100 alpha, beta), and concanavalin A receptors (ConAR) in cytoplasm demonstrated the presence of two subtypes of malignant histiocytes, ie, S100 beta+/NCA-/ConAR+ (4 cases) and S100 beta-/NCA+/ConA R+ (three cases). The results of lysozyme, alpha 1 AT, and S100 alpha staining were inconsistent. A survey of the literature disclosed that the incidence of S100 protein-positive cases in children was higher than in adults (12/21 v 5/19; chi 2, P less than .05). Further large scale investigation is necessary to confirm the independence and significance of these two subtypes of histiocytes in malignant histiocytosis.

Malignant histiocytosis

Malignant histiocytosis, also known as histiocytic medullary reticulosis, is a rare neoplasm of malignant histiocytes. Clinical findings include fever, weight loss, hepatosplenomegaly, lymphadenopathy, anemia, thrombocytopenia, and a rapidly worsening course. Approximately 7 percent of patients have skin manifestations early in the course of their disease. In these patients, diagnosis based on examination of a skin biopsy specimen may be crucial. A case of malignant histiocytosis is presented in which the diagnosis was first suggested by findings on the skin biopsy specimen.

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.

Comparative immunohistochemical investigation of markers for malignant histiocytes

The presence of lysozyme, alpha 1-antitrypsin (AT), alpha 1-antichymotrypsin (ACT), and cytoplasmic receptors for peanut and soy bean agglutinin and for concanavalin A (PNA, SBA, and ConA, respectively) was investigated in formalin-fixed, paraffin-embedded material from 16 cases of malignant histiocytosis. The tumors in these cases did not show phenotypic characteristics of T or B cells. Lysozyme and AT especially were found less frequently in tumor cells from malignant histiocytosis than in normal histiocytes, whereas ACT and binding sites for the lectins were maintained during malignancy. Specimens from 44 per cent of the cases were positive for lysozyme, 56 per cent for AT, 82 per cent for ACT, 88 per cent for PNA receptors, 94 per cent for SBA receptors, and 100 per cent for ConA receptors. Tumor cells from B- and T-cell lymphomas were negative for these markers. Plasma cells, granulocytes, and fibroblasts sometimes bound ConA, but not PNA or SBA. The cases of malignant histiocytosis were subdivided into three groups on the basis of grade of differentiation. The tumor cells from the cases in group 1 showed the highest degree of differentiation, those from group 2 an intermediate degree, and those from group 3 the lowest degree. Mitotic activity was present mainly in groups 1 and 2. Lysozyme was present most frequently in groups 1 and 3 and in cases with the least mitotic activity. Expression of AT was decreased in groups 2 and 3. The presence of phagocytosis, which is not obligatory for the diagnosis, was always correlated with ACT staining. The presence of binding sites for these lectins can be considered a useful marker for malignant histiocytes.

Malignant Histiocytosis Resistant to Anthracycline

A 36-year-old woman, presenting with fever, pancytopenia, hepatosplenomegaly, and striking effacement of the bone marrow by true malignant histiocytes, was found to have no benefit from the systemic administration of cyclophosphamide, vincristine sulfate, doxorubicin, prednisone, and high-dose methotrexate with calcium leucovorin rescue. Striking histologic and clinical improvement was noted after the administration of two cycles of etoposide and amsacrine, each cycle consisting of 100 mg/sq m/day of each agent for five days. We believe that this therapy should be considered for future patients demonstrating aggressive presentations of malignant histiocytosis.

Malignant histiocytosis in childhood: Morphologic Considerations

Eight cases diagnosed over a ten-year period as malignant histiocytosis (MH; histiocytic medullary reticulosis) were reviewed to clarify diagnostic criteria for the childhood disease and to identify sources of diagnostic confusion. Five of the eight cases met the authors' criteria for diagnosis; i.e., they were characterized by loose mixed infiltrates composed of three cell types--well-differentiated histiocytes, prohistiocytes, and malignant histiocytes--and they had no leukemic phase. Three cases did not share these features and were reclassified. The liver was found to be the organ most useful in premortem diagnosis, and immunoperoxidase staining for immunoglobulins and lysozyme was also helpful. The clinical and morphologic features of the five cases confirm the authors' view that diagnoses of MH should be limited to cases in which there is a loose pleomorphic population of all three types of histiocytes and that cases with monomorphous populations of aggregated malignant cells should be classified as lymphomas.

Immunohistochemical differentiation between histiocytic and lymphoid neoplasms

Lysozyme has, until recently, been accepted as the only reliable immunohistochemical marker of benign and malignant histiocytes. Using this marker, very few lymphoreticular neoplasms of histiocytic origin are recognized and more recently alpha-1-anti-trypsin has been shown to be a better marker of malignant histiocytes. By immunizing rabbits with highly purified human blood monocytes we have obtained an antiserum (S22) which stains histiocytes and neutrophils in paraffin sections with a high degree of specificity. Using this antiserum and antisera to lysozyme and alpha-1-anti-trypsin we have stained paraffin sections of tissues containing reactive histiocytes, histiocytic proliferations, leukaemic infiltrates and lymphoreticular tumours of histiocytic and T-cell origin. Our results show that alpha-1-anti-trypsin is the most reliable marker of malignant histiocytes but that the as yet uncharacterized antigen defined by S22 may offer a promising alternative.

Histiocytosis-X

Pathologic interpretation of an osteolytic lesion from the skull of a 13-month-old boy was amplified by histocytochemistry of cells grown in a methylcellulose clonal culture system. Electron microscopy demonstrated the presence of X granules in the cytoplasm of malignant histiocytes, confirming a diagnosis of histiocytosis-X. Freshly fixed tissue containing histiocytosis-X cells and granulocytes showed histiocytosis-X cells that were positive for alpha-naphthyl acetate esterase (non-specific esterase) and negative with naphthol AS-D chloracetate as the esterase substrate (specific esterase). Clonal cell aggregates, harvested after 6 days' growth in culture, showed histiocytosis-X cells that were positive for both the nonspecific and specific esterases. Differences in staining reactions for the histiocytosis-X cells may be explained on the basis of immaturity of the histiocytosis-X cells growing in culture. This interpretation would support their origin from monocytes, monocytic precursors, or a still less differentiated myelomonocytic precursor cell. Furthermore, gel systems of clonally cultured cells appear to provide a useful tool for the growth and analysis of histiocytosis-X cells.

Renal Involvement in Malignant Histiocytosis. An Immunoperoxidase Marker Study

In two patients who had malignant histiocytosis, renal involvement was present at an early stage of their diseases and consisted clinically of proteinuria and renal failure. The associated renal lesion was characterized by a diffuse and global endocapillary hypercellularity of the glomeruli imputable to atypical cells occluding the capillary loops. Immunoglobulins were absent from this lesion. The atypical cells were positively identified by lysozyme immunoperoxidase study as malignant histiocytes. It is suggested that renal biopsy complemented by marker study could play a role in the diagnosis of malignant histiocytosis.