ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition.

ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.

Clonal reticulohistiocytosis of the skin and bone marrow associated with systemic mastocytosis and acute myeloid leukaemia.

AIMS: The aims of this study were to define whether diffuse cutaneous reticulohistiocytosis could be underpinned by somatic genetic alterations and represent a precursor of more aggressive forms of disease. METHODS AND RESULTS: A 59-year-old man with diffuse cutaneous reticulohistiocytosis experienced bone marrow localization of the disease, with associated systemic mastocytosis and acute myeloid leukaemia. Cytogenetic analyses of the bone marrow aspirate revealed the presence of a derivative chromosome giving rise to a partial trisomy of chromosome 1q and a partial monosomy of chromosome 9q. Therefore, we characterized the cutaneous lesions before and after chemotherapy by using an integrative approach combining histopathology, electron microscopy, and fluorescence in-situ hybridization. Histologically, the skin lesions belonged to the spectrum of diffuse cutaneous reticulohistiocytoses, as confirmed by immunohistochemistry and ultrastructural analyses. Fluorescence in-situ hybridization in the skin nodules confirmed the presence of the genetic alterations previously detected in the bone marrow. CONCLUSIONS: Here, we provide circumstantial evidence to suggest that at least a subset of cutaneous reticulohistiocytoses harbour clonal molecular alterations. Furthermore, we confirm that these lesions have the potential to arise in the setting of concurrent haematological disorders. In this hypothesis-generating study, two possible tumorigenesis models are proposed.

Spontaneous regression of infantile dural-based non-Langerhans cell histiocytosis after surgery: case report.

The authors report the case of a large left occipital mass lesion in an 8-month-old boy who presented with seizure. Neuroimaging demonstrated an approximately 5-cm extraaxial tumor, and the patient underwent partial resection. The tumor was strongly attached to the tentorium and falx. In the postoperative course the residual lesion regressed spontaneously, and after 5 years only a slight residual tumor remained along the tentorium. Histopathological examination of the tumor revealed non-Langerhans cell histiocytosis (non-LCH). However, the tumor was not diagnosed as juvenile xanthogranuloma (JXG) because it lacked Touton giant cells. Hence, the authors described this lesion as a fibroxanthogranuloma. Most intracraniospinal non-LCHs have been reported as JXG; however, several cases of xanthomatous tumors with histopathological features resembling those of JXG have been described as fibrous xanthoma, xanthoma, fibroxanthoma, and xanthogranuloma. Among JXG and the xanthomatous tumors, a review of the literature revealed several cases of dural-based tumors; these dural-based tumors have had favorable courses, including the case described in this report. In addition, the patient in the present case experienced spontaneous regression of the residual tumor. The authors report this unique case and review the literature on isolated intracraniospinal non-LCHs, especially in cases of dural-based lesion.

[Hemosiderotic fibrohistiocytic lipomatous lesion: a new entity you must remind]. / Tumeurs fibrolipomateuses hémosidérotiques: une nouvelle entité à ne pas méconnaître.

Fatty tissues lesions are the most frequent of both benign (lipoma) and malignant tumor (liposarcoma) of soft tissues in the adult. We here describe the case of female patient having a fatty tissue mass of the ankle corresponding to an hemosiderotic fibrohistiocytic lipomatous lesion (HFHLL). This very rare tumour of recent description is specific of the ankle/foot area of the middle age women. These lesions are always benign and frequently recur following incomplete resection. This tumor may have invasive local growth and metastases have not been described so far. We describe the anatomopathologist's key points of their diagnostic. We discuss the main differentials diagnosis and treatment.

[Polyradicular neural syndrome in a patient with leukemic variant of malignant histiocytosis]. / Zespól wielokorzeniowonerwowy u chorego z bialaczkowa postacia zlosliwej histiocytozy.

Malignant histiocytosis is rapidly progressive, fatal disorder characterised by systemic proliferation of abnormal histiocytic cells. We report a case of a 23-year old patient with leukaemia variant of malignant histiocytosis and nervous system involvement as polyradiculoneural syndrome. The leukaemia variant as well as nervous system involvement are extremely rare in malignant histiocytosis.

[Neoplastic diseases of the hematopoietic system and ischemia of the lower limbs]. / Choroby nowotworowe ukladu krwiotwórczego a miazdzycowe niedokrwienie konczyn dolnych.

The possible interaction between hematopoietic neoplasms and ischemia of the lower limbs in patients with both pathologies was subjected to analysis. Anaemia, polycythemia, thrombocythemia, increased leucocytosis in the peripheral blood, and hyperuricemia exerted unfavourable effect on the blood flow through the arteries of the lower limbs. In some cases effective cytostatic treatment diminished the ischemia of the lower limbs. Interactions between various drugs used in the chronic treatment of both pathologies in the same patient was also examined.

[The initial experience of using isolated ultrafiltration of the blood for the correction of severe respiratory failure in hemoblastosis patients]. / Pervyi opyt primeneniia izolirovannoi ul'trafil'tratsii krovi dlia korrektsii tiazheloi dykhatel'noi nedostatochnosti u bol'nykh gemoblastozami.

To correct acute respiratory failure in patients with hemoblastoses and taking into consideration the low efficacy of standard techniques, 8 operations of isolated ultrafiltration combined with low-flow extracorporeal oxygenation in 6 patients were performed. The first results have been analyzed. To attain the maximum positive result, it is recommended that the method may be included earlier in a complex of intensive therapy measures.