Prognostic factors for histiocytic and dendritic cell neoplasms

Shimono, Joji; Miyoshi, Hiroaki; Sato, Kensaku; Furuta, Takeshi; Muto, Reiji; Yanagida, Eriko; Sasaki, Yuya; Kurita, Daisuke; Kawamoto, Keisuke; Nagafuji, Koji; Ohshima, Koichi

doi:10.18632/oncotarget.21920

Cited by 20 publications

(26 citation statements)

References 34 publications

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“…Histiocytic and dendritic cell neoplasms encompass a group of proliferative entities with variable clinical behaviors and prognosis in humans (1). Among them, histiocytic sarcoma (HS) is by far the most aggressive disorder with the worst prognosis (2). It is a rare hematologic malignancy (<1% of all hematopoietic neoplasms) (3,4) that affects all ages, but mostly adults, with a male predominance (5).…”

Section: Introductionmentioning

confidence: 99%

“…It is a rare hematologic malignancy (<1% of all hematopoietic neoplasms) (3,4) that affects all ages, but mostly adults, with a male predominance (5). Existing data show that HS develops within lymph nodes and at extranodal sites including the gastrointestinal tract, spleen, lungs, and head and neck (2,5,6). Given the limited occurrence, there is no consensus on standard-of-care treatment for HS in human patients.…”

Section: Introductionmentioning

confidence: 99%

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Targeting MEK in a Translational Model of Histiocytic Sarcoma

Takada

Hix

Corner

et al. 2018

Molecular Cancer Therapeutics

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Histiocytic sarcoma in humans is an aggressive orphan disease with a poor prognosis as treatment options are limited. Dogs are the only species that spontaneously develops histiocytic sarcoma with an appreciable frequency, and may have value as a translational model system. In the current study, high-throughput drug screening utilizing histiocytic sarcoma cells isolated from canine neoplasms identified these cells as particularly sensitive to a MEK inhibitor, trametinib. One of the canine cell lines carries a mutation in PTPN11 (E76K), and another one in KRAS (Q61H), which are associated with the activation of oncogenic MAPK signaling. Both mutations were previously reported in human histiocytic sarcoma. Trametinib inhibited sensitive cell lines by promoting cell apoptosis, indicated by a significant increase in caspase 3/7. Furthermore, findings were successfully recapitulated in an intrasplenic orthotopic xenograft mouse model, which represents a disseminated aggressive form of histiocytic sarcoma. Mice with histiocytic sarcoma xenograft neoplasms that were treated with trametinib had significantly longer survival times. Target engagement was validated as activity of ERK, downstream of MEK, was significantly downregulated in neoplasms of treated mice. Additionally, trametinib was found in plasma and neoplastic tissues within projected therapeutic levels. These findings demonstrate that in dogs, histiocytic sarcoma may be associated with a dysfunctional MAPK pathway, at least in some cases, and may be effectively targeted through MEK inhibition. Clinical trials to test safety and efficacy of trametinib in dogs with histiocytic sarcoma are warranted, and may provide valuable translational information to similar diseases in humans..

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting MEK in a Translational Model of Histiocytic Sarcoma

Takada

Hix

Corner

et al. 2018

Molecular Cancer Therapeutics

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“…He was lost to follow-up and he died a year later, and further details from his medical history were unavailable. There is no standardized treatment for ICH (Table 1) (14)(15)(16)(17). As ICH has a benign clinical course, conservative management is the best approach.…”

Section: Discussionmentioning

confidence: 99%

Indeterminate Cell Histiocytosis – Case Report and Review of Literature

Vojvodić

Mijušković

Sekulović

2018

Serbian Journal of Dermatology and Venereology

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Introduction. Indeterminate cell histiocytosis is a rare proliferative disorder of indeterminate dendritic cells, reported in only 50 case reports so far. It is clinically presented as yellow, red or brown papules and nodules that appear in otherwise healthy adult individuals. Indeterminate cells are distinct dendritic cells of the skin that have ultrastructural similarities to the epidermal Langerhans cells but do not contain the characteristic Birbeck’s granules and they are also langerin-negative, unlike LCH. Indeterminate cell histiocytosis is an exceptional entity with variable clinical, histopathologic or immunohistochemical findings, sharing morphologic and immunophenotypic features with both Langerhans- and non-Langerhans cell histiocytoses. Case Report. We present a case of indeterminate histiocytosis in a 77-year-old man with 3-year history of asymptomatic, multiple reddish and brown papules and nodules over the entire body, including the oral mucosa. Skin biopsy was done, and histopathological analysis with immunohistochemistry was performed. The positive ICH staining of cells for CD68, CD1a, and S-100 enabled us to diagnose ICH in our patient. Also, BRAF V600E mutation was detected in tumor tissue. The treatment was started with methotrexate that was effective for 6 months, but due to the disease recurrence, further therapy with thalidomide was advised, without effect. Conclusion. Indeterminate histiocytosis is a rare disease, therefore no standardized treatment has been established and the treatment options are limited.

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“…Langerhans cell sarcoma (LCS) is a very rare histiocytic and dendritic cell neoplasm originating from Langerhans cells . In contrast to Langerhans cell histiocytosis (LCH), LCS is often observed in adults, and in general has a poor prognosis . The 5‐year disease specific survival is reported to be 28% .…”

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confidence: 99%

“…1 In contrast to Langerhans cell histiocytosis (LCH), LCS is often observed in adults, and in general has a poor prognosis. 1,2 The 5-year disease specific survival is reported to be 28%. 3 Although there have been reports on the effect of multimodality therapy that combines chemotherapy and radiation therapy, there is currently no specific chemotherapy regimen recommended.…”

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confidence: 99%

Synchronous case of follicular lymphoma and Langerhans cell sarcoma in the same lymph node

Shimono

Miyoshi

Abe

et al. 2018

Pathology International

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Langerhans cell sarcoma (LCS) is a very rare histiocytic and dendritic cell neoplasm originating from Langerhans cells. There are case reports of histiocytic and dendritic cell neoplasms synchronously or sequentially observed in patients with malignant lymphoma. We present a case in which LCS and follicular lymphoma (FL) grade 3a were observed within the same lymph node. A 66‐year‐old male visited our hospital with a general malaise. Pleural effusion and systemic lymph adenopathy were detected. Biopsy of an inguinal lymph node was performed. The lymph node had regions with follicular structure and regions with acidophilic cytoplasm and large proliferating atypical cells. The tumor cells in the regions with follicular structure showed positivity for CD20 and BCL2 consistent with an FL grade 3a diagnosis. The tumor cells in the regions without follicular structure showed positivity for CD1a and S‐100 and were consistent with an LCS diagnosis. Both tumor cells showed the positivity of BCL6 split by FISH. PCR detected IgH clonality in DNA collected from each region, and direct sequence analysis of cells from both tumors detected almost identical amino acid sequences. This finding is important for future research on the development of very rare histiocytic and dendritic cell neoplasms.

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Prognostic factors for histiocytic and dendritic cell neoplasms

Cited by 20 publications

References 34 publications

Targeting MEK in a Translational Model of Histiocytic Sarcoma

Targeting MEK in a Translational Model of Histiocytic Sarcoma

Indeterminate Cell Histiocytosis – Case Report and Review of Literature

Synchronous case of follicular lymphoma and Langerhans cell sarcoma in the same lymph node

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