An Atypical Myelomonocytic Cell Infiltrate: Use of Next-Generation Sequencing to Diagnose Indeterminate Cell Histiocytosis

Belina, Morgan E.; Kwock, J.; Al‐Rohil, Rami N.; Fresco, Amber

doi:10.1097/dad.0000000000002167

Cited by 5 publications

(4 citation statements)

References 7 publications

(8 reference statements)

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“…We then selected and included in the study 78 papers, describing 108 patients (Figure 1). 5,8,9,12,32–106 From two case series, we included only some of the described patients, as indicated in Table 1 12,48 …”

Section: Resultsmentioning

confidence: 99%

“…Molecular analyses were conducted in 27/108 cases (24%). Five out of seven tested cases displayed an ETV3::NCOA2 rearrangement, 68,81,105 while pERK pathway genes mutation was detected in 5/19 tested cases and included two patients bearing KRAS mutation, 79,103 and one case each with an NRAS, 60 MAP2K1, 99 and BRAF V600E point mutation. 75 Two cases bore TET2 mutations.…”

Section: Histopathology and Molecular Biologymentioning

confidence: 99%

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Indeterminate cell histiocytosis: A systematic review of the literature with a comprehensive revision of clinical, histopathological, and molecular features

Zanella

Berti

Bonometti

2023

Acad Dermatol Venereol

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Indeterminate cell histiocytosis (ICH) is a very rare histiocytic disorder, primarily involving the skin. It affects more frequently adults, often presenting with a generalized papular eruption, and needs to be differentiated from other neoplastic, paraneoplastic, and infectious diseases through clinical and histological examination. The knowledge on ICH is limited to case reports and small series. Thus, the lack of larger multicentric studies has prevented recognizing and addressing the specific clinical need of the entity. In this systematic review, we comprehensively analysed the medical literature describing histologically‐confirmed cases of ICH and divided the patients into epidemiologically and clinically different groups. We demonstrate that ICH in adulthood is strongly associated with the development of haematological (and especially myeloid) neoplasms. In this subset of patients, we identify blastic morphology of neoplastic cells as a novel independent prognostic factor and an early histopathological predictor of an associated myeloid neoplasm. Moreover, we highlight that even though ICH may also present in childhood, these patients often show indolent behaviour. Genetically, ICH emerges as a heterogeneous condition. While patients with associated myeloid neoplasms are enriched in pERK pathway gene mutations, in others a specific ETV3::NCOA2 rearrangement is described. We finally reviewe the nosology of ICH since its first description, its possible cell of origin, and summarize the therapeutic options reported for each different clinical subgroup. With this work, we hope to foster studies on rare cutaneous histiocytosis and their comprehensive multidisciplinary characterization.

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Section: Resultsmentioning

confidence: 99%

Section: Histopathology and Molecular Biologymentioning

confidence: 99%

Indeterminate cell histiocytosis: A systematic review of the literature with a comprehensive revision of clinical, histopathological, and molecular features

Zanella

Berti

Bonometti

2023

Acad Dermatol Venereol

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“…Recently, amplification of ETV3 has been reported in breast cancer, supporting copy number gain as potent activating mechanism of this oncogene [ 39 ]. Detection of fusion gene ETV3::NCOA2 in independent cell histiocytosis (ICH) underlines a general oncogenic role for ETV3 in hematopoietic malignancies [ 40 , 41 ]. In the myeloid compartment, physiologically expressed ETV3 regulates macrophage differentiation [ 42 , 43 ], highlighting its functional role in developmental processes of myelopoiesis which may be aberrantly reactivated in HL subsets.…”

Section: Discussionmentioning

confidence: 99%

Establishment of the lymphoid ETS-code reveals deregulated ETS genes in Hodgkin lymphoma

2023

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The human family of ETS transcription factors numbers 28 genes which control multiple aspects of development, notably the differentiation of blood and immune cells. Otherwise, aberrant expression of ETS genes is reportedly involved in forming leukemia and lymphoma. Here, we comprehensively mapped ETS gene activities in early hematopoiesis, lymphopoiesis and all mature types of lymphocytes using public datasets. We have termed the generated gene expression pattern lymphoid ETS-code. This code enabled identification of deregulated ETS genes in patients with lymphoid malignancies, revealing 12 aberrantly expressed members in Hodgkin lymphoma (HL). For one of these, ETS gene ETV3, expression in stem and progenitor cells in addition to that in developing and mature T-cells was mapped together with downregulation in B-cell differentiation. In contrast, subsets of HL patients aberrantly overexpressed ETV3, indicating oncogenic activity in this B-cell malignancy. Analysis of ETV3-overexpressing HL cell line SUP-HD1 demonstrated genomic duplication of the ETV3 locus at 1q23, GATA3 as mutual activator, and suppressed BMP-signalling as mutual downstream effect. Additional examination of the neighboring ETS genes ETS1 and FLI1 revealed physiological activities in B-cell development and aberrant downregulation in HL patient subsets. SUP-HD1 showed genomic loss on chromosome 11, del(11)(q22q25), targeting both ETS1 and FLI1, underlying their downregulation. Furthermore, in the same cell line we identified PBX1-mediated overexpression of RIOK2 which inhibited ETS1 and activated JAK2 expression. Collectively, we codified normal ETS gene activities in lymphopoiesis and identified oncogenic ETS members in HL.

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“…We reviewed the current examples of IDCT with cutaneous symptoms treated with chemotherapy medications to assess the efficacy and safety of chemotherapy drugs 1,5,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] (Table 1). We found that remission and relapse occurred in 8 out of 26 chemotherapy-treated patients reported to date.…”

Section: Treatmentmentioning

confidence: 99%

Recurrent Chemotherapy Treated Indeterminate Dendritic Cell Tumor: Case Report and Literature Review

Li,

Zhang,

Xiong

2023

CCID

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Indeterminate dendritic cell tumor (IDCT) is an extremely uncommon histiocytic and dendritic neoplasms subtype that presents as single or multiple papules. There is currently no standard method for diagnosis and treatment, and the selection of therapeutic approaches is mainly based on successful examples of folk medicine. We describe a case of a pathology diagnosed indeterminate dendritic cell tumor, which shows the presence of CD1a, S100, and CD68, but lack langerin. She was treated with multi-chemotherapy regimens used to treat lymphoma and gained good results short term but was easy to recur. In addition, we reviewed the literature on the effectiveness and safety of chemotherapy in IDCT patients.

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An Atypical Myelomonocytic Cell Infiltrate: Use of Next-Generation Sequencing to Diagnose Indeterminate Cell Histiocytosis

Cited by 5 publications

References 7 publications

Indeterminate cell histiocytosis: A systematic review of the literature with a comprehensive revision of clinical, histopathological, and molecular features

Indeterminate cell histiocytosis: A systematic review of the literature with a comprehensive revision of clinical, histopathological, and molecular features

Establishment of the lymphoid ETS-code reveals deregulated ETS genes in Hodgkin lymphoma

Recurrent Chemotherapy Treated Indeterminate Dendritic Cell Tumor: Case Report and Literature Review

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