ALK-positive histiocytosis associated with chronic lymphocytic leukaemia/small lymphocytic lymphoma: a multitarget response under ibrutinib.

ALK-positive histiocytosis is a recently described entity with few reported cases in literature. Herein, we report an unusual case of ALK-positive histiocytosis showing an Erdheim-Chester disease (ECD)-like presentation, occurring in a 37-year-old woman with a 2-year history of chronic lymphocytic leukaemia (CLL). Our CLL patient relapsed 6 months after the end of fludarabine, cyclophosphamide and rituximab frontline therapy and complained of lower limb pains. A bone marrow biopsy was performed and showed concomitant CLL/small lymphocytic lymphoma and ALK-positive histiocytosis with an identical immunoglobulin heavy-chain gene rearrangement in both neoplasms, suggesting clonal relationship. After 4 years under ibrutinib therapy, our patient remains free of both diseases. This report extends the spectrum of composite hematolymphoid neoplasms and shows that ALK rearrangement should be considered in all histiocytosis subtypes. Moreover, both tumours eradication under ibrutinib suggests that BTK inhibitors may also be effective in histiocytic neoplasms.

A colonic mass revealing a disseminated crystal storing histiocytosis secondary to indolent multiple myeloma: a case report with literature review.

BACKGROUND: Crystal storing histiocytosis is a rare disorder associated with monoclonal gammopathy. In this disease, monoclonal heavy and light chains accumulate in the lysosome of macrophages, leading to histiocytic reaction in different organs. It is secondary to the presence of a small B-cell clone, responsible for monoclonal immunoglobulin production. Histological diagnosis is a challenge and differential diagnoses include fibroblastic and histiocytic neoplasm. Clinical manifestations depend on the involved organs, rarely including peritoneum or digestive tract. CASE PRESENTATION: We present a case of a 75-year-old with a medical history of colonic carcinoma. She presented with abdominal pain and inflammatory syndrome revealing a colonic mass. Hemicolectomy was performed. Initial diagnosis was fibroblastic tumour. The patient worsened, and diagnosis of a diffuse crystal storing histiocytosis was finally done. Haematological exploration found an indolent IgG-kappa multiple myeloma. The initial treatment with conventional chemotherapy did not permit an improvement of the patient condition. Immunotherapy with anti-CD38 monoclonal antibody (daratumumab) was proposed with a clinical and biological response. CONCLUSION: This case report emphasizes the histopathological challenge of histiocytic tumours which may involve digestive track. It focuses on the concept of monoclonal gammopathy of clinical significance, which can have a large spectrum of manifestations.

Intravascular histiocytosis: case report of a rare disease probably associated with silicone breast implant

Abstract Intravascular histiocytosis is a rare condition characterized by the aggregate of histiocytes within dilated dermal vessels. The diagnosis is mainly histophatological and immunohistochemical. We describe a case of a 55 year-old female patient presenting erythematous/purple patches on the breasts, back and limbs. She previously presented ductal carcinoma in the right breast in 2006 which was treated with mastectomy and proceeded to silicone breast implant in 2009. Clinical hypothesis was telangiectatic metastatic carcinoma. Histopathology showed vascular ectasia, thrombosis and recanalization of upper dermis small vessels. On immunohistochemistry, intravascular cells were CD 68+ and negative for estrogen and progesterone receptors, CK7, EMA and AE1/AE3 and endothelial cells were CD64+, leading to the diagnosis of intravascular histiocytosis.

Intravascular histiocytosis: case report of a rare disease probably associated with silicone breast implant.

Intravascular histiocytosis is a rare condition characterized by the aggregate of histiocytes within dilated dermal vessels. The diagnosis is mainly histophatological and immunohistochemical. We describe a case of a 55 year-old female patient presenting erythematous/purple patches on the breasts, back and limbs. She previously presented ductal carcinoma in the right breast in 2006 which was treated with mastectomy and proceeded to silicone breast implant in 2009. Clinical hypothesis was telangiectatic metastatic carcinoma. Histopathology showed vascular ectasia, thrombosis and recanalization of upper dermis small vessels. On immunohistochemistry, intravascular cells were CD 68+ and negative for estrogen and progesterone receptors, CK7, EMA and AE1/AE3 and endothelial cells were CD64+, leading to the diagnosis of intravascular histiocytosis.

Intrahepatocellular crystal storing mimicking a clinical liver disease during monoclonal gammopathy: report of a case and review of the literature.

We present an unusual case of liver involvement in monoclonal gammopathy with generalized crystal-storing histiocytosis (G-CSH).A bone marrow storage disease was diagnosed in a 79-year-old man with monoclonal gammopathy of uncertain significance (MGUS). The patient presented with pleural effusion, an osteolytic lesion of the humerus, and an increase of aspartate transaminase and cholestatic markers that raised the clinical suspect of liver disease. A second bone marrow biopsy confirmed the diagnosis of MGUS with a histiocytic component suggestive for G-CSH.Liver biopsy showed an unremarkable histology, no significant inflammatory infiltrates, and intrasinusoidal foamy histiocytes. PAS and Masson's trichrome stains, showed, in the cytoplasm of both histiocytes and hepatocytes, rod-shaped eosinophilic crystals, which were immunoreactive for kappa light chains. Transmission electron microscopy performed on reprocessed histological sections confirmed the presence of crystals in the hepatocyte cytoplasms. Immunogold labeling intensely stained crystals for kappa light chains.To the best of our knowledge, this is the second case in which an intrahepatocellular crystal storage is described during liver involvement in G-CSH. The present case also suggests that an increase in liver serum enzymes may support the clinical diagnosis of liver CSH in a patient with MGUS.

Crystal-Storing Histiocytosis in Bone Marrow: A Clinicopathologic Study of Eight Cases and Review of the Literature.

OBJECTIVES: We report the clinicopathologic characteristics of eight cases of crystal-storing histiocytosis (CSH) with bone marrow (BM) involvement (BM-CSH) and review CSH cases published in the English literature. METHODS: We queried our pathology database for BM cases with CSH mentioned in the final diagnosis/comments from June 2011 to August 2016. RESULTS: Eight cases of BM-CSH were identified. The underlying diagnoses consisted predominantly of plasma cell disorders (88%) associated with monotypic κ light chain. In BM aspirates, crystals within histiocytes exhibited a morphologic spectrum including brightly eosinophilic, needle-like, or globule-like. In BM core biopsies, the histiocytes were often in aggregates with intracellular needle-like and/or globular, refractile inclusions. CONCLUSIONS: BM-CSH is a rare phenomenon and exhibits a heterogeneous crystalline and histiocytic appearance warranting accurate recognition to avoid misinterpretation of a granulomatous condition or storage disorder. In addition, prompt assessment for an underlying B-cell lymphoma or clonal plasmacytic neoplasm is indicated.

Intralymphatic Histiocytosis: A Report of 2 Cases. / Histiocitosis intralinfática, a propósito de 2 casos.

Intralymphatic histiocytosis is a benign condition characterized by poorly defined erythematous plaques (sometimes forming a reticular pattern) as well as the presence of nodules and vesicles. Its etiology and pathogenesis appear to be related to chronic inflammation in the affected area, prior surgery, or systemic disease, particularly rheumatoid arthritis. We report on 2 new cases, both associated with joint surgery in the affected area and osteoarticular disease (primary synovial osteochondromatosis and rheumatoid arthritis). This is a chronic disease and there is no specific treatment. Different treatment options were chosen in the 2 cases described. A spectacular response to treatment with oral pentoxifylline and topical tacrolimus was observed in 1 of the patients.

Tick bite mimicking indeterminate cell histiocytosis.

Ticks are a well-known vector for viral, bacterial, and rickettsial infections, many of which are accompanied by cutaneous eruptions, but the bite itself can induce a spectrum of inflammatory reactions, including foreign body granuloma, tick bite alopecia, and cutaneous lymphoid hyperplasia. We describe the development of an indeterminate cell histiocytic infiltrate at the site of a tick bite. Although the etiology of intermediate cell histiocytosis is not well understood, this case raises the possibility that such infiltrates may represent an inflammatory reaction in some patients.

Cutaneous Indeterminate Cell Histiocytosis of Donor Origin After Allogeneic Hematopoietic Stem-Cell Transplantation.

Allogeneic hematopoietic stem-cell transplantation and solid-organ transplantation are associated with an increased risk of secondary neoplasms. Indeterminate cell histiocytosis (ICH) is a rare disease composed of so-called indeterminate cells, an alleged cutaneous dendritic cell subset displaying histological and some ultrastructural and immunophenotypic features of Langerhans cells but lacking Birbeck granules. We report a case of cutaneous ICH occurring after allogeneic hematopoietic stem-cell transplantation for a myelodysplastic syndrome in a 56-year-old man. Microsatellite analysis demonstrated that the neoplastic cells were derived from the donor's hematopoietic system. This case broadens the spectrum of complications after stem-cell transplantation and demonstrates that cutaneous ICH in the setting of myelodysplastic syndromes may have a nonrelated origin to dysplastic myeloid cells.

Multicentric Reticulohistiocytosis: an Unknown Source of Embolic Stroke.

Multicentric reticulohistiocytosis (MRH) is a rare inflammatory disorder that presents with diverse systemic infiltrative manifestations. We report the first case of biopsy-proven MRH that presented with acute ischemic stroke in an embolic pattern. We discuss the clinical presentation, imaging findings, and diagnostic approach in our case. We also discuss the plausible etiology and mechanism of stroke associated with this rare disorder. MRH with its systemic involvement could present with neurological manifestations including ischemic infarcts.

Solitary pulmonary MALT lymphoma presenting crystal-storing histiocytosis.

Crystal-storing histiocytosis (CSH) is characterized by the accumulation of large histiocytes with intracytoplasmic crystallized immunoglobulin and is typically associated with hematological malignancies. A 69-year-old man, who had a history of left nephrectomy and chemotherapy for renal pelvic cancer six years earlier, had received a CT scan every year thereafter and a small nodule was found in the left lower lobe of his lungs two years prior to the current presentation. Because of progression of this pulmonary nodule, he underwent pulmonary lobectomy on suspicion of lung cancer. He was ultimately diagnosed as having CSH accompanied by mucosa-associated lymphoid tissue lymphoma stage IAE. In the absence of further treatment, he has been well with no recurrence of the disease for 10 months postoperatively. Because CSH could reportedly be an initial presentation of hematological malignancies, careful observation and evaluation for the presence of these blood disorders is essential.

Tumor necrosis factor antagonists in the treatment of multicentric reticulohistiocytosis: Current clinical evidence.

Multicentric reticulohistiocytosis (MRH) is a rare and debilitating systemic disorder characterized by cutaneous nodules and destructive polyarthritis. Due to its unknown etiology, the treatment of MRH varies with different rates of success, which causes treatment options to be rather independent and empirical. In the present study, a case of a 48­year­old woman with a 12­month history of polyarthralgia and skin nodules was reported. Biopsy samples, which were obtained from her skin eruption exhibited dermal infiltration with histiocytes and multinucleated giant cells. Immunohistochemical staining indicated positivity for CD68. The patient was diagnosed with MRH and treated with a combination therapy of infliximab, prednisolone and methotrexate. Her symptoms improved markedly within 2 weeks. Following the results of this case study, a systematic review of 17 cases of MRH treated with tumor necrosis factor (TNF) antagonists was performed, and the efficacy of anti­TNF treatment in MRH was analyzed.