Histiocytic sarcoma: secondary neoplasm or “transdifferentiation” in the setting of B-acute lymphoblastic leukemia

Thakral, Beenu; Khoury, Joseph D.

doi:10.1182/blood-2016-08-735795

Cited by 11 publications

(8 citation statements)

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“…To our knowledge, this is the first reported case of PCM transformation to a secondary tumor with monocyte-macrophage lineage. As in other reports, the response to chemotherapy and prognosis is poor with patients dying from progressive disease [ 18 , 19 , 23 , 25 , 26 ]. This study highlights the importance of molecular analysis to establish a clonal relationship in metachronous or synchronous tumors, as addressed by other reports [ 47 , 48 ].…”

Section: Discussionsupporting

confidence: 53%

Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequencing

Gralewski¹,

Post²,

Rhee³

et al. 2018

Diagn Pathol

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Background: Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes with molecular heterogeneity. Although therapy-related myeloid neoplasms are common in plasma cell myeloma patients after chemotherapy, transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been reported in literature. Here we report a very rare case of myeloid neoplasm transformed from plasma cell myeloma. Case presentation: A 60-year-old man with a history of plasma cell myeloma with IGH-MAF gene rearrangement and RAS/RAF mutations developed multiple soft tissue lesions one year following melphalan-based chemotherapy and autologous stem cell transplant. Morphological and immunohistochemical characterization of the extramedullary disease demonstrated that the tumor cells were derived from the monocyte-macrophage lineage. Next generation sequencing (NGS) studies detected similar clonal aberrations in the diagnostic plasma cell population and post-therapy neoplastic cells, including IGH-MAF rearrangement, multiple genetic mutations in RAS signaling pathway proteins, and loss of tumor suppressor genes. Molecular genetic analysis also revealed unique genomic alterations in the transformed tumor cells, including gain of NF1 and loss of TRAF3. Conclusion: To our knowledge, this is the first case of myeloid sarcoma transdifferentiated from plasma cell neoplasm. Our findings in this unique case suggest clonal evolution of plasma cell myeloma to myeloma neoplasm and the potential roles of abnormal RAS/RAF signaling pathway in lineage switch or transdifferentiation.

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Section: Discussionsupporting

confidence: 53%

Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequencing

Gralewski¹,

Post²,

Rhee³

et al. 2018

Diagn Pathol

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“…However, it is not unreasonable to infer that some of the same pathways that drive LCH could also drive LCS. Interestingly, a recent report of histiocytic sarcoma transdifferentiation from B-lymphoblastic leukemia demonstrated NRAS p.G12D mutation, further suggesting RAS pathway alterations may be important in the transdifferentiation process [ 46 ]. It is also possible that other genetic or epigenetic changes which are as yet uncharacterized may contribute to lineage conversion and phenotypic switch seen during transdifferentiation.…”

Section: Discussionmentioning

confidence: 99%

KRAS mutation in secondary malignant histiocytosis arising from low grade follicular lymphoma

et al. 2018

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BackgroundTransformation of follicular lymphoma most typically occurs as diffuse large B-cell lymphoma, however other forms of transformation such as classic Hodgkin lymphoma and lymphoblastic transformation can occur. Secondary malignant histiocytosis also represents a rare form of transformation, which is thought to occur due to a process of transdifferentiation whereby the lymphoma cells exhibit lineage plasticity and lose all evidence of B-cell phenotype and instead acquire the phenotype of a histiocytic neoplasm. Little is known about the underlying genetic alterations that occur during this unusual process. Comparative genetic analysis of pre- and post-transformation/transdifferentiation would be one tool by which we could better understand how this phenomenon occurs.Case presentationHere we report the clinical, immunophenotypic and genetic features of a rare case of secondary malignant histiocytosis, Langerhans cell-type (Langerhans cell sarcoma) arising from a previous low grade follicular lymphoma. FISH analysis confirmed the presence of IgH/BCL2 rearrangement in both the low grade follicular lymphoma (FL) and transformed Langerhans cells sarcoma (LCS) samples, demonstrating a clonal relationship. Comparative whole exome sequencing was then performed, which identified a KRAS p.G13D mutation in the LCS that was not present in the FL.ConclusionsThis report highlights genetic alterations, in particular an acquired somatic KRAS mutation, that may occur during transdifferentiation, with additional significance of KRAS mutation as a possible therapeutic target in cases which otherwise would have limited treatment options.Electronic supplementary materialThe online version of this article (10.1186/s13000-018-0758-0) contains supplementary material, which is available to authorized users.

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“…They reported that bone sarcoma, thyroid cancers, melanoma, and CNS malignancies were the most frequent SMNs [32]. Other reports also suggest sarcomas as common SMNs in childhood cancer survivors [33][34][35][36][37]. These studies show the global trend of sarcoma as common SMNs in childhood survivors.…”

Section: Literature Reviewmentioning

confidence: 81%

Sarcoma as Second Cancer in a Childhood Cancer Survivor: Case Report, Large Population Analysis and Literature Review

et al. 2020

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The majority of pediatric patients are cured of their primary cancer with current advanced developments in pediatric cancer therapy. However, survivors often experience long-term complications from therapies for primary cancer. The delayed mortality rate has been decreasing with the effort to reduce the therapeutic exposure of patients with pediatric cancers. Our study investigates the incidence of sarcoma as second cancer in pediatric cancer survivors. We present a 9-year-old male who survived embryonal hepatoblastoma diagnosed at 22 months of age. At 4.5 years of age, he presented with a non-metastatic primitive neuroectodermal tumor (PNET) of the left submandibular area. He has no evidence of recurrence of either cancer for 51 months after finishing all chemotherapy and radiotherapy. We used the Surveillance, Epidemiology, and End Results (SEER) database to identify the current rate of second sarcomas in pediatric cancer survivors. Our literature review and large population analysis emphasize the impact of sarcoma as a second malignancy and provide help to physicians caring for pediatric cancer survivors.

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Histiocytic sarcoma: secondary neoplasm or “transdifferentiation” in the setting of B-acute lymphoblastic leukemia

Cited by 11 publications

References 0 publications

Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequencing

Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequencing

KRAS mutation in secondary malignant histiocytosis arising from low grade follicular lymphoma

Sarcoma as Second Cancer in a Childhood Cancer Survivor: Case Report, Large Population Analysis and Literature Review

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