Blastic OKT6-positive proliferation preceding malignant histiocytosis

A 45-year old male presented latero-cervical lymphoadenopathy. Biopsy revealed a malignant proliferation of immature "lymphoid" cells bearing T6 antigen and HLA-DR but negative for other lymphoid markers, suggesting a phenotype similar to Langerhans cells. The patient did not receive any therapy and six months later developed a histologically typical malignant histiocytosis, involving spleen and liver. Other reported cases of lymphoid malignancies (two bearing the T6 antigen on blast cells) preceding malignant histiocytosis were found and compared with ours. Most of these cases were characterized by the pediatric age of the patients and were presented as acute leukemias exhibiting, in at least some of them, reliable T-cell markers. Our case appears to represent, on the other hand, a blastic proliferation of precursors of both histiocytes and Langerhans dendritic cells which eventually progressed to malignant histiocytosis. The relevance of this observation in the debate on the origin of Langerhans cells and the relationships existing between macrophages and dendritic cells is discussed.     

Fine needle aspiration cytology of epithelioid angiosarcoma: a case report

BACKGROUND: Malignant vascular tumors are rare. Few studies have described cytomorphologic features of hemangioendothelioma and angiosarcoma on fine needle aspiration cytology (FNAC). Malignant vascular tumor with epithelioid morphology can create diagnostic difficulty, as the cytology may simulate that in other nonvascular malignant tumors. We describe epithelioid angiosarcoma, diagnosed on FNAC, in which a differential diagnosis of histiocytosis and inflammatory granulation tissue was considered. CASE: A 20-year-old man presented with forehead and scalp swellings. The forehead lesion was radiologiocally associated with a lytic lesion in the bone. FNA resulted in high cellular yield, and smears revealed prominent vascular pattern with endothelial cell atypia and histiocytoid/epithelioid neoplastic cells, occasional mitotic figures and a few cells displaying nuclear grooving. Smear background showed a significant number of neutrophils. Epithelioid hemangioendothelioma/angiosarcoma, histiocytosis and inflammatory granulation tissue were considered. A cytologic diagnosis of epithelioid angiosarcoma/epithelioid hemangioendothelioma was suggested and confirmed on histopathologic and immunohistochemical examination. CONCLUSION: Cellular aspirates from malignant epithelioid endothelial tumors involving bone may be cytologically mistaken for histiocytosis and, rarely, inflammatory granulation tissue. However, prominent vascular pattern with striking endothelial cell atypia, presence of mitotic figures and careful search for presence of endothelial differentiation are helpful in accurate cytologic diagnosis.     

Hemophagocytic histiocytosis diagnosed by fine needle aspiration cytology of the spleen. A case report

BACKGROUND: Hemophagocytic histiocytosis (HPS) is an idiopathic, familial or secondary syndrome characterized by mature histiocytes causing intensive erythrophagocytosis. CASE: A 2-month-old male suffering from autoimmune hemolytic anemia, fever, jaundice and hepatosplenomegalia underwent fine needle aspiration cytology of the spleen. Aspiration was performed using a 23-gauge, short needle with a subcostal approach. The smear showed a monomorphous cell population of mature histiocytes with marginal nuclei and wide, well-defined cytoplasm. The cytoplasm was microvaculated and often contained > or = 1 erythrocytes and occasional lymphocytes. Immunostaining performed on cytospin samples showed diffuse positivity for alpha-1-antichymotrypsin and S-100. Differential diagnosis with malignant histiocytosis, Langerhans histiocytosis and sinus histiocytosis with massive lymphadenopathy was established. HPS was diagnosed because of the cytologic and immunocytochemical features and clinical data. CONCLUSION: HPS may be diagnosed using fine needle aspiration of the spleen when other biopsy samples have been unsuccessful. Cytologic, diagnosis of HPS should always be considered in a specific clinical setting, because early treatment can often save the patient's life.     

Langerhans cell histiocytosis in lymph nodes. Cytomorphologic diagnosis and pitfalls

OBJECTIVE: To delineate the cytomorphology of Langerhans cell histiocytosis (LCH) in lymph nodes. STUDY DESIGN: Nine histologically documented LCH cases with a prior lymph node aspirate and five more cases in which a cytologic diagnosis of LCH was rendered in a background of corroborative clinical and radiologic findings were included in a retrospective study over a 12-year period (January 1988-January 2000). Papanicolaou- and May-Grünwald-Geimsa-stained smears were reviewed by two independent observers. Staining for S-100 protein was available in four cases. RESULTS: Nine cases had multisystem involvement, while in five cases only lymph nodes were involved. The ages ranged from 5 months to 27 years, with 11 males and 3 females. An initial cytologic diagnosis of LCH had been rendered in six, suspected in four and missed in four. On review, all were reclassified as LCH except two cases, which were still thought to be reactive and necrotizing lymphadenitis. The pathognomic feature of LCH, the "LCH cell," was identified in 12 of 14 cases along with varying numbers of eosinophils, polymorphs and lymphocytes. Giant cells were seen in six cases, and plasma cells were rarely seen. CONCLUSION: Lymph node involvement by LCH can be identified by fine needle aspiration in 85% of cases. The presence of the LCH cell is a must. The differentials to be considered are dermatopathic lymphadenitis, sinus histiocytosis with massive lymph-adenopathy, Hodgkin's lymphoma and malignant histiocytosis.     

Maturation of Howell-Jolly bodies observed in a case of malignant histiocytosis

The maturation of Howell-Jolly bodies was microscopically observed on the May-Grünwald-Giemsa-stained film of bone marrow obtained from a patient with malignant histiocytosis. The bodies separated from the nucleus at the polychromatophilic normoblast stage and condensed faster than the main nucleus before denucleation in the normoblast stage.     

A case of erythrophagocytic T4 lymphoma. Immunological and morphological peculiarities.

One case of T-cell lymphoma with atypical malignant cells is reported. Some of the clinical features, morphological characteristics and functional activity (erythrophagocytosis) of malignant cells suggested malignant histiocytosis. The malignant disease started with splenomegaly and developed with hepatomegaly, bone marrow infiltration, discrete lymphadenopathy and leukaemic picture. Proliferated cells were characterized by ambiguity. In addition to phagocytic capability, presence of complement receptors and ultrastructural features proper to the macrophagic lineage, the cells expressed T-cell determinants (E receptors, T3, T4 and T11 antigens) and were peroxidase and esterase-negative. Erythrocytes were partially or completely dehaemoglobinized and presented the phenomenon of autolysis in different stages of development. Because this lymphoma is difficult to diagnose and apparently resistant to therapy, its recognition and further study are warranted.     

The malignant histiocytosis sarcoma virus, a recombinant of Harvey murine sarcoma virus and Friend mink cell focus-forming virus, has acquired myeloid transformation specificity by alterations in the long terminal repeat.

The malignant histiocytosis sarcoma virus (MHSV), in contrast to other viruses with the ras oncogene, induces acute histiocytosis in newborn and adult mice. Molecular structure and function studies were initiated to determine the basis of its unique macrophage-transforming potential. Characterization of the genomic structure showed that the virus evolved by recombination of the Harvey murine sarcoma virus (Ha-MuSV) and a virus of the Friend-mink cell focus-forming virus family. Structural analysis of MHSV showed two regions of the genome that are basically different from the Ha-MuSV: (i) the ras gene, which is altered by a point mutation in codon 181 leading to a Cys----Ser substitution of the p21 protein, and (ii) the U3 region of the long terminal repeat, which is largely derived from F-MCFV and contains a deletion of one direct repeat as well as a duplication of an altered enhancer-like region. Biological studies of Ha-MuSV, MHSV, and recombinants between the two viruses show that the U3 region of the MHSV long terminal repeat is essential for the malignancy and specificity of the disease. A contributing role of the ras point mutation in determining macrophage specificity, however, cannot be excluded.     

Thyromegaly secondary to simultaneous papillary carcinoma and histiocytosis X. Report of a case and review of the literature

The cytologic and histologic findings are reported in a case of papillary carcinoma arising within a thyroid gland pathologically enlarged by histiocytosis X. Fine needle aspiration (FNA) biopsies of a thyroid nodule in a patient with longstanding histiocytosis X produced a scanty amount of colloid, a moderately dense mixed inflammatory infiltrate and numerous small papillary fragments lined by cuboidal-to-columnar cells. Both the inflammatory cells and the epithelial cells showed nuclear grooves; the two populations of neoplastic cells were distinguished, and the correct diagnosis of the nodule was made, by recognizing the greater amount of granular cytoplasm of the mononucleated Langerhans' cells. The rare involve-of the thyroid by histiocytosis X is reviewed; this case, which appears to be the first reported instance of the co-occurrence of histiocytosis X and papillary carcinoma of the thyroid, indicates that patients with histiocytosis X should be observed for the development of thyroid carcinoma and that FNA biopsy can make the distinction between the two conditions.     

Cytology of primary cutaneous Langerhans cell histiocytosis with a malignant phenotype. A case report

BACKGROUND: Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells, but the nature of LCH, whether reactive, benign, or malignant and neoplastic, is controversial. We encountered a case of LCH showing a malignant phenotype initially localized in the skin of an elderly woman. Since there is no other report on the cytologic appearance of primary cutaneous LCH or on LCH with a malignant phenotype, we compared the cytologic features of this case with those of benign cases at other sites reported in the literature. CASE: A 74-year-old woman presented with a gradually enlarging and partially ulcerated skin lesion expanding both sides of her right hand. On histologic and ultrastructural analyses of surgically resected tissue, we diagnosed the lesion as Langerhans cell histiocytosis originating in the skin. Although the patient had no recurrence or metastases for six months after surgical resection of the primary skin lesion and radiation therapy, the tumor extended multisystemically, and the patient died of multiple organ failure 14 months after the initial diagnosis. CONCLUSION: Imprint and scrape cytology of multiple skin lesions six months after surgery was useful in immediately diagnosing the recurrent LCH. The tumor cells had indented, twisted or grooved nuclei, and some had intranuclear inclusions. Immunocytochemically the cells were positive for CD1a and S-100 protein. Numerous eosinophils were seen in the background.     

Status of allogeneic bone marrow transplantation in childhood in the GDR

Of 25 HLA-identical, MLC negative transplants 10 patients had acute lymphoblastic leukaemia (ALL), 8 acute nonlymphoblastic leukaemia (ANLL), 3 severe aplastic anaemia, 2 malignant histiocytosis, 1 patients neuroblastoma and 1 Fanconi anaemia. 3 HLA nonidentical, MLC positive transplants were performed, two children had malignant infantile osteopetrosis and 1 child had a severe combined immunodeficiency disease. Patients with ALL and ANLL received cyclophosphamide and single dose total body irradiation. 3 patients received fractionated TBI. The results for the allogeneic group overall indicate that the actuarial disease free survival rate is 0.62. 16 of 25 patients are in continuous complete remission (CCR) periods of 3-78 months posttransplant. All three transplanted children with severe aplastic anaemia alive disease-free for periods of 21-81 months. 10 patients with ALL were transplanted (2 in first remission for high risk ALL, 8 in second remission). 7 of 10 patients are alive and disease-free (CCR rate 0.67). 8 patients underwent BMT for ANNL while in first remission in 7 patients and in third partial remission in 1 patient. 4 of 8 patients are alive and disease-free for periods of 25-56 months (CCR rate 0.50). 1 patient with neuroblastoma stage IV survives 24 months, 1 child with Fanconi anemia died on day +25 of GVHD and septicaemia. 1 of the 2 patients transplanted for malignant histiocytosis relapsed 3 months posttransplant, 1 patient is alive and disease-free 5 months posttransplant. In none of the HLA-nonidentical and MLC positive transplantations T-cell depleted marrow engrafted.     

Chronic monocytic leukemia terminating in blastic transformation

Chronic monocytic leukemia (CMoL) is a rare disorder, closely related to malignant histiocytosis, but a separate entity. The clinical course of the patient described in this case report was characterized by persistent monocytosis without response to cytotoxic therapy, and a large number of infections. On two occasions a clone of cells containing an extra chromosome 20 was observed. The disease terminated in a phase with rapidly increasing numbers of immature monocytoid cells, corresponding to blastic transformation.     

Microvascular closure in malignant histiocytosis.

Two patients with malignant histiocytosis were found to have capillary occlusion by aggregates of neoplastic histiocytes, in skeletal muscle in one, and in renal glomeruli in the other. One patient had clinical evidence of similar occlusions in the arterioles and capillaries of the ocular fundi. Occlusion of small vessels by tumour cells may explain the confusion of both patients.     

Autozygosity mapping,to chromosome 11q25, of a rare autosomal recessive syndrome causing histiocytosis,joint contractures,and sensorineural deafness.

We describe a highly consanguineous family, originating from Pakistan, displaying histiocytosis, joint contractures, and sensorineural deafness. The form of histiocytosis exhibited by this family does not fit readily into any of the recognized classes of this disease. It appears to represent a novel form of familial histiocytosis demonstrating autosomal recessive inheritance. Using autozygosity mapping, we have identified a homozygous region of approximately 1 cM at chromosome 11q25, in affected individuals. A maximum two-point LOD score of 3.42 (recombination fraction straight theta = .00) was obtained with marker D11S968. This is the first genetic locus to be described that is involved in the molecular pathogenesis of histiocytosis.     

The Cytology of Langerhans Cell Histiocytosis (Histiocytosis X)

The cytomorphology of 13 cases of Langerhans cell histiocytosis is described. The most striking features were the presence of intranuclear clefts, pale nuclei and inconspicuous nucleoli, together with ample pale cytoplasm, only slight cellular pleomorphism, and an admixture of varying numbers of eosinophils, macrophages and degenerated cells. In 13 of 16 cases investigated ultrastructurally, characteristic Birbeck granules were detected. Out of six cases tested, four exhibited positivity for S-100, and of three cases tested, all were positive for CD1a (leu 6) and HLA-DR. In one case malignant transformation occurred, terminating in monocytic leukaemia.     

Intérêt de la scintigraphie osseuse dans l’histiocytose langerhansienne: À propos d’un cas

We present one case of bone-Langerhans’ cell histiocytosis in a three-year-old male child presenting osseous lesions in the skull and the femur, which are very frequent localisations in histiocytosis. Bone scintigraphy is useful for both initial staging and follow-up associated with other imaging modalities.     

Transformation of single myeloid precursor cells by the malignant histiocytosis sarcoma virus (MHSV): generation of growth-factor-independent myeloid colonies and permanent cell lines

Direct single-cell assays for oncogenic transformation are available for fibroblasts but not for other cell types. Using malignant histiocytosis sarcoma virus (MHSV), a member of the ras family of retroviruses, in vivo-infected granulocyte/macrophage and macrophage precursor cells lost the requirement for externally added hematopoietic growth factors. Factor-independent growth was demonstrated by colony-transfer experiments. More than 25% of the independent colonies were established as permanent macrophage cell lines following a phase of adaptation to tissue culture conditions. Factor-independent colony growth was also obtained by in vitro infection of single cells. As many as 50% of all myeloid precursor cells were target cells for MHSV as measured by this assay. About 2 x 10(-3) of these colony-forming cells acquired growth factor independence and immortality after in vitro infection. Cell lines derived from these colonies did not require adaptation to tissue culture conditions.     

朗格罕细胞组织细胞增生症颅内垂体影像表现及相关临床表现

目的:探讨朗格罕细胞组织细胞增生症累及垂体的MR表现及相关临床表现。方法:搜集了6例确诊为朗格罕细胞组织细胞增生症并垂体表现异常的患儿,男5例,女1例,年龄2～11岁,平均(6±3)岁,对其影像及临床表现进行回顾性分析。结果:临床患儿主要以头面部包块,多饮、多尿等就诊。头颅MR平扫(T1WI)表现6例患儿神经垂体高信号全部消失,垂体柄增粗5例,垂体柄著征1例,垂体饱满1例,其中3例治疗后复查垂体及垂体柄均有变化。结论:神经垂体高信号消失,垂体柄增粗或著征为朗格罕细胞组织细胞增生症累及垂体的头颅MR表现。累及垂体者临床几乎都有多饮、多尿表现。目前,MRI是诊断朗格罕细胞组织细胞增生症累及垂体的唯一可靠的影像学检查方法,并对治疗后病情随访有重要作用。     

Langerhans cell histiocytosis: report of a single organ involvement in a child

Langerhans cell histiocytosis is a rare disorder characterized by abnormal proliferation of Langerhans cells that can affect various organ systems. The disease usually presents as a unifocal lytic bone lesion and can affect any age group. Less frequently it presents as a disseminated disease with multisystem involvement. Hepatic manifestation in Langerhans cell histiocytosis is relatively rare and usually presents as a part of a disseminated process. We report a case of Langerhans cell histiocytosis involving only the liver in a 9-years-old child.     

Analysis of Trace Elements in Bronchoalveolar Lavage of Patients with Diffuse Lung Diseases

Airborne trace elements are implicated in the etio-pathogenesis of a large number of pulmonary diseases. The aim of this study was to evaluate the reliability and effectiveness of direct determination of Cd, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn concentrations in bronchoalveolar lavage (BAL) samples from patients with sarcoidosis, idiopathic pulmonary fibrosis, and Langerhans cell histiocytosis and healthy (smoking and non-smoking) controls. A total of 44 individuals were recruited among sarcoidosis, idiopathic pulmonary fibrosis, and Langerhans cell histiocytosis patients and healthy (smoking and non-smoking) controls. Average Mn concentrations in BAL from patients were 45% lower than in controls (p < 0.01) and remarkable decreases in average concentrations of Cr, Ni and Zn were also found in BAL from patients with idiopathic pulmonary fibrosis and Langerhans cell histiocytosis. As these diseases are characterized by the enhanced activation of certain immunomodulatory cells and by generation of free radicals, the depressed Mn, Zn, Cr and Ni concentrations in BAL from patients may be due to oxidative stress. These preliminary results indicate that assessment of the elemental composition of BAL is a promising approach to study the pathogenesis of diffuse lung diseases and Langerhans cell histiocytosis.     

Monoclonal antibody against histiocytosis X cells.

Monoclonal antibody against histiocytosis X cells (HXCs) was established. The antigen was the cell membrane of HXCs from the submandibular lesion of a 63-year-old man who had been diagnosed as an adult type of histiocytosis X (HX) and whose HXCs had numerous Birbeck granules (BGs). The obtained monoclonal antibody, named MI1, reacted with the antigenic cell membrane of HXC. Immunoblotting showed that MI1 bound to the cell membrane of 28500 mw. MI1 also reacted with interdigitating reticulum cells (IDCs) in the tonsil and Langerhans cells (LCs) in the epidermis. MI1 reacted with the BGs which connected to the cell membrane, but not with those located near the nucleus.