A correction and update:
Her mutations in our 33 gene myeloid NGS panel were the classic SF3B1 mutation (and not SETBP1 as I originally wrote - SIC!) and an additional BCOR exon 7 mutation of unknown significance.
We have not received her karyotype yet.
A first case/test case to discuss here in this forum or at the HS meeting.
Last week I had this patient referred from our surgeons.
75 year-old Caucasian woman, previously healthy apart from a slowly progressive form of optic nerve atrophy starting around 20 years ago which has rendered her blind. The background for this condition remains unresolved (genetest for Lebers´ / LHON negative). Moreover she have had cardiac ablations due to arrythmias. In 2018 she debuted with an asymptomatic palpable tumor on the underextremity. This was surgically removed by a practicing surgeon. The biopsies revealed inflammation, fibroblast proliferation and plasma cell infiltration (25% IgG4+ cells). The pathologists suggested IgG4-related disease as a possible diagnosis. A PETCT scan was normal and the patient went untreated. Aug 2019 the tumor reforms, size 40*40 mm. The tumor is removed surgically. Due to her eye symptoms, the pathological findings and Slightly increased IgG4 levels she was started on MMF and prednisolone while new pathology is awaited.
The histopathology revealed that she had a histiocytic sarcoma (CD4+, CD14+, CD 163++, CD68 (+), lysozyme (in some cells) and CD31+. The tumor did not stain for S-100, CD1a or langerin (not LDH), no dendritic cell markers (CD21, CD23, CD123). Also negative for cytokeratine, SOX10, desmin, actin, CD34, ERG, EMA, CD15, CD30, ALK, CD 138, CD38, CD3, PAX5 CD20.). The tumor is BRAF negative.
MMF and prednisolone was stopped.
Her tumor has been removed in toto.
She is feeling well without any systemic symptoms. Her hemoglobin is around LLN, her LDH, uric acid level, crp, ferritin, sIL2r and sCD163 levels are normal.
A PET-CT is normal apart from uptake in the colon (colonoscopy planned).
Surprisingly – in spite of the normal biochemistry – her Bone marrow examination was suggestive of myelodysplasia with 15% ringsideroblasts. Initial evaluations of our 33 gene Oncomime myeloid NGS panel reveals that she does infact have “the RARS mutation” SETBP1 (30%). The marrow was not suggestive of a histiocytic disorder. …
How to proceed?:
Given the local relapse of the tumor I assume local RT is recommendable.
Jacobsen E, Updtodate updated sept 19 https://www.uptodate.com/contents/histiocytic-sarcoma?search=histiocytic%20sarcoma&source=search_result&selectedTitle=1~12&usage_type=default&display_rank=1recommends involved fieldRT of 45-50 Gy?
We do not know whether her MDS is clonally related to the HS. If the patient did not have her HS I would not treat her MDS.
A: I do not think that I will change my strategy based upon the MDS – agree?
B: If her changes in the colon are due to her histiocytosis I find that she will need mild systemic treatment. Suggestions?
1.Glucocorticoids?, 2. She does not seem inflamed so I would favor thalidomide (1,2) if tolerated to Etoposide? 3. If lymphoma-like treatment is needed I would go for bendamustine in favor of CHOP or CVP due to toxicity concerns?. 4. Experimental treatment (JAKinhibition?)
C: I will ask the patient if she will participate in the IRHDR registry.
This case will be presented at a poster where I look at the differential diagnoses between IgG4RD and the histiocytosis. The index case for this presentation was a patient suspected for a histiocytosis that had IgG4RD as her primary disease.
D: Would any of you be interested in coauthoring a review for the rheumatological community with a focus on our important diff diagnoses in patients suspected for - or diagnosed with IgG4RD?
I am currently discussing a review of their cases of IgG4RD with the two major rheum departments in my country.
1. Gergis U, Dax H, Ritchie E, et al. Autologous hematopoietic stem-cell transplantation in combination with thalidomide as treatment for histiocytic sarcoma: a case report and review of the literature. J Clin Oncol 2011; 29:e251.
2. Abidi MH, Tove I, Ibrahim RB, et al. Thalidomide for the treatment of histiocytic sarcoma after hematopoietic stem cell transplant. Am J Hematol 2007; 82:932.
Thank you for your time
Daniel El Fassi, Dept of Hematology, Herlev, DK
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