Neoadjuvant treatment of a duodenal GIST revealed a new imatinib-sensitive exon 11 c-KIT-mutation

The principal treatment for gastrointestinal stromal tumors (GISTs) is surgical; and complete excision is important, but cannot always be achieved. For such cases, neoadjuvant chemotherapy (NAC) with imatinib mesylate (IM) has been recommended. A case of a GIST of the second portion of the duodenum for which pancreatoduodenectomy was indicated, and for which partial resection was made possible as a result of cytoreduction by IM NAC, is reported. A 64-year-old man with pancytopenia due to hepatic cirrhosis caused by hepatitis C infection received repeated blood transfusions because of anemia of unknown origin starting 2 years earlier. Most recently, the patient had melena with hemoglobin of 5.1 mg/dL. Diagnostic imaging showed a solid tumor, 55 × 48 × 65 mm3, in the second portion of the duodenum showing mainly extramural development. Endoscopic aspiration biopsy showed proliferation of KIT-positive spindle-shaped heterotypic cells. GIST was diagnosed, and an exon 11 KIT mutation was found. Because of the exon 11 mutation, neoadjuvant IM was started at 400 mg/day and then eventually maintained at 300 mg/day for 10 months. Regular CT examinations showed gradual tumor shrinkage. At surgery, a tumor with strong extramural growth was found on the outer side of the duodenum that invaded the retroperitoneum. The tumor was excised as a mass, and the duodenum was resected partially. There has been no recurrence at 9 years postoperatively. Evaluating KIT exon mutations and predicting the effectiveness of NAC appear useful for determining the treatment policy for advanced GISTs.

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Differential response of primary or secondary exon 13/14 and exon 17 c-kit mutant to nilotinib and sunitinib: Findings from a cell-based drug-screening platform

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15636 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15636-e15636

Author(s):

C. Chan ◽

L. Chen ◽

Y. Hsueh ◽

W. Chuang ◽

H. Lee ◽

...

Keyword(s):

Double Mutant ◽

Kinase Inhibitors ◽

Acquired Resistance ◽

Differential Response ◽

Imatinib Treatment ◽

Kit Mutation ◽

Mutant Genotype ◽

Exon 9 ◽

Screening Platform ◽

Exon 11

e15636 Background: Gastrointestinal stromal tumors (GIST) are frequently associated with mutation of c-kit oncogene that is accompanied with constitutional activation of c-kit protein. At present, imatinib is the drug of choice for unresectable or metastatic GIST, however, primary or acquired resistance to imatinib is frequently associated with the presence of an exon 13, 14 or 17 c-kit mutation. The current recommendations for GIST refractory to standard (400 mg/day) imatinib treatment include increasing dose of imatinib to 600–800 mg/day for tumors with primary exon 9 mutation or sunitinib. Several molecular targeted agents are also under investigation. With so many potential agents, personalized therapy based on c-kit mutant genotype for imatinib-resistant GIST deserves to explore. Methods: We prepared a series of c-kit cDNA constructs encoding mutant exon 9 (502AY insertion), 11 (V560D substitution and Δ555–576 deletion), 13 (V654A substitution), 14 (T670I substitution) and 17 (D820G and N822K substitutions) either alone or in combination to simulating the frequently occurred primary ± secondary c-kit mutants in GIST. We expressed these constructs in COS-1 cells to study the efficacy of different tyrosine kinase inhibitors (TKIs) on the autophosphorylation of various single or double mutant c- kit. Results: The efficacy of imatinib on single c-kit mutant was V560D > Δ555–576 > 502AY > D820G or N822K, and ineffective for single and double mutants containing V654A or T670I. Sunitinib is a more potent inhibitor for single 502AY, D820G and N822K mutant than imatinib and nilotinib; while single V654A and T670I c-kit mutant are more sensitive to nilotinib. Interestingly, double exon 11 (V560D or Δ555–576)/V654A or T670I mutant c-kit are more sensitive to sunitinib; while exon 11 (V560D or Δ555–576)/D820G or N822K double mutant c-kit are more sensitive to nilotinib. Conclusions: Our system provides a useful platform to select/screen effective TKIs for GIST with single or double mutant c-kit. The findings of differential response of c-kit mutant to nilotinib and sunitinib may help to select therapy for GIST with primary or secondary exon 13 / 14 and exon 17 mutations. [Table: see text]

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Whole exome analysis of patients (pts) with metastatic GIST (mGIST) demonstrating exceptional survival with imatinib (IM) therapy compared to those with short term benefit.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.11513 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 11513-11513

Author(s):

Eytan Ben Ami ◽

Sophia C. Kamran ◽

Suzanne George ◽

Jeffrey A. Morgan ◽

Andrew J. Wagner ◽

...

Keyword(s):

Zinc Finger ◽

Kinase Inhibitors ◽

Response Modulation ◽

Short Term ◽

Kit Mutation ◽

Whole Exome ◽

Exon 9 ◽

Exon 11 ◽

Term Benefit

11513 Background: Most patients with mGIST initially benefit from IM therapy with durable disease control (DC), i.e. objective responses and stable disease, with median duration of approximately two years. We reported exceptional long-term benefit (LTB) with DC and overall survival (OS) >14 years in a subset of mGIST pts treated with IM. We aimed to characterize tumor and normal genomes of exceptional LTB pts treated with IM and compare with short-term benefit (STB) pts. Methods: Among 87 mGIST pts enrolled between July 2000 and June 2001 in the B2222 trial of IM and followed prospectively at the Dana Farber Cancer Institute, we identified 10 LTB (>14 years of DC) pts, and 6 STB (<2 years of DC) pts on IM. Targeted genotyping ( KIT/PDGFRA)was performed in all tumors (n=16). Whole exome sequencing (WES) was performed on archival FFPE tumor samples from LTB and STB pts prior to any IM treatment. We compared WES results from LTB with STB pts to identify unique features of long-term DC and OS with IM. Results: KIT mutation in LTB pts were as follows: exon 11(6 pts), exon 9 (3 pts), and SDH-deficient with KIT/PDGFRA wild type (1 pt). In STB pts, mutated KITwas found 4 pts (exon 11) and 2 pts (exon 9). WES was successful in six LTB (five exon 11, one exon 9) and three STB (two exon 11, one exon 9) pts. A total of 1211 somatic mutations were observed (546 missense, 37 nonsense, 256 silent, 285 indels, 36 splice mutations). The mean somatic mutational burden was 3.42 mutations/Mb (range 1.18-4.93) and 3.34 mutations/Mb (range 1.06-6.68) among LTB and STB, respectively. Genes mutated in LTB but not in STB were MUC7 (4 pts), H1F0 (3 pts), ZKSCAN1 (3 pts), SLC24A1 (3 pts) and USP4 (2 pts). Conclusions: KRAB domain containing zinc finger (KRAB-ZNF) gene expression signatures have been associated with prediction of response to IM, and a possible role in response modulation to tyrosine kinase inhibitors in GIST. We found variants in ZKSCAN1, a gene encoding a transcriptional regulator of the KRAB subfamily of zinc finger, to be present in LTB but not in STB. KRAB-ZNF family of genes may be linked to LTB and exceptional survival with IM in mGIST; functional analyses will be important to test such hypotheses.

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Prognostic relevance of genetic aberrations in gastrointestinal stromal tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.49 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 49-49

Author(s):

N. N. Mazurenko ◽

I. S. Beliakov ◽

I. V. Tsyganova ◽

E. M. Bardina ◽

O. A. Anurova ◽

...

Keyword(s):

Tumor Progression ◽

Point Mutation ◽

Prognostic Significance ◽

Specific Gene ◽

Wild Type ◽

Kit Mutation ◽

Genetic Aberrations ◽

Pdgfra Mutation ◽

Prognostic Relevance ◽

Exon 11

49 Background: Gastrointestinal stromal tumours (GISTs) contain oncogenic KIT or PDGFRA tyrosine kinase (TK) mutations leading to disturbance of downstream signaling pathways that contribute to GIST pathogenesis. Additional genetic aberrations were found in GISTs, demonstrating the involvement of other genes important in tumor progression. The aim of the study was to evaluate the prognostic relevance of different TK mutations in GISTs and to analyze the additional genetic aberrations in GISTs according to mutational status. Methods: 180 GIST patients were examined for KIT (9, 11, 13, 17 exons) and PDGFRA mutations (12, 14, 18 exons) by direct sequencing of DNA obtained from microdissected tumor sections. Tumor tissue DNA from 44 GISTs patients was screened for loss of heterozygosity (LOH) at 11 microsatellite loci on 1p, 9p, 14q, 15q and 22q arms. Results: KIT and PDGFRA mutations were identified in 76.1% and 10% of GISTs, respectively. 13.9% GISTs had no mutations (wild type). Most of KIT mutations were located in exon 11 (65%) and exon 9 (9.4%). Prognostic significance of TK mutations was evaluated. There was a trend of better survival for patients with PDGFRA mutation then with KIT mutation or wild type GISTs. The higher overall survival prior to target therapy was shown for patients with duplication or point mutation in KIT exon 11 in comparison to exon 11 deletion. Analysis of LOH revealed allelic deletions in 85% of GISTs, more frequently at 14q arm. There was a different LOH pattern in subgroups of GISTs. GISTs with PDGFRA mutation and with KIT exon 11 point mutation had LOH at 14q, while GISTs with KIT exon 11 deletions revealed high LOH frequency also on 22q, 15q and 1p arms. LOH in wild type GISTs occurred on all chromosomes with low frequency. LOH on 9p was found exclusively in metastatic and recurrent GISTs. Specific gene loci of frequent LOH were identified on 9p, 15q and 22q that may be contributed to GIST progression. Conclusions: Specific mutations are associated with GISTs prognosis. Tumors with point mutations and duplications in KIT exon 11 are associated with a better survival then GISTs with other KIT mutations. Specific pattern of allelic deletions was identified in subgroups of GISTs according to type of mutation and tumor progression. No significant financial relationships to disclose.

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Immune checkpoint inhibitor responses in KIT-mutated metastatic melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.199 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 199-199

Author(s):

Meredith Ann McKean ◽

Junna Oba ◽

Junsheng Ma ◽

Lauren Elaine Haydu ◽

Roland L. Bassett ◽

...

Keyword(s):

Treatment Initiation ◽

Statistical Significance ◽

Univariate Analysis ◽

Response To Therapy ◽

Unknown Primary ◽

Clinical Response Rate ◽

Exon 2 ◽

Kit Mutation ◽

Exon 11

199 Background: KIT-mutated MM is a rare melanoma entity. Response rates of KIT-mutated MM to anti CTLA-4 and anti PD-1 have not previously been reported. Methods: A single-institution retrospective review identified patients (pts) with KIT-mutated MM treated with at least two doses of anti CTLA-4 or anti PD-1 between 2008-2017 with response determined by immune-related response criteria (irRC). Overall survival (OS) was from ICI start to death or last follow-up date, and progression-free-survival (PFS) was from ICI start to date of progression or death if pts deceased without disease progression. Results: Thirty-five pts treated with ipilimumab were identified. Median follow-up was 63.7 months. Median age at MM diagnosis was 65.4 years (range 26-81) and 54.3% were male. Subtypes were 51.4% mucosal, 22.9% acral-lentiginous, 22.9% cutaneous, and 2.9% unknown primary. KIT mutations were 57.1% exon 11, 25.7% exon 17, 11.4% exon 13, and 5.7% exon 2. Anatomical M stage at treatment initiation was 11.4% M1a, 34.3% M1b, and 54.3% M1c. Median OS was 11.8 months (8.4-35.6) and PFS was 3.0 months (2.8-5.8). Responses to ipilimumab were 8.6% complete response (CR), 11.4% partial response (PR), 28.6% stable disease (SD), and 51.4% progressive disease (PD) for a 48.6% clinical response rate (CRR). Twenty pts treated with anti PD-1 were identified. Median follow-up was 7.9 months. Median age at MM diagnosis was 66.7 years (range 42.6-86.8) and 70% were male. Subtypes were 40% mucosal, 30% cutaneous, 20% acral-lentiginous, and 10% unknown primary. KIT mutations were 45% exon 11, 35% exon 17, 10% exon 2, 5% exon 13 and and 5% exon 10. Anatomical M stage at treatment initiation was 10% M1a, 15% M1b, and 75% M1c. Median OS was 22.5 months (7.4-NA ) and PFS was 3.2 months (2.7-NA). Responses to anti PD-1 were 10.0% CR, 25.0% PR, 20.0% SD, and 45.0% PD for a 55.0% CRR. For both anti CTLA-4 and anti PD-1 treated cohorts, univariate analysis demonstrated no statistical significance between tumor response to ICI and clinical pt characteristics or KIT mutation exon. Conclusions: KIT-mutated MM demonstrated CRR of 48.6-55.0% to ICI. There was no correlation between pt characteristics or KIT exon mutation and response to therapy; however, analysis was limited by sample size.

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Molecular Characterization of Relapsed Core-Binding Factor (CBF) Acute Myeloid Leukemia (AML)

Blood ◽

10.1182/blood.v126.23.2586.2586 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2586-2586 ◽

Cited By ~ 1

Author(s):

Mridul Agrawal ◽

Andrea Corbacioglu ◽

Nikolaus Jahn ◽

Lars Bullinger ◽

Maria-Veronica Teleanu ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Genetic Alterations ◽

Molecular Heterogeneity ◽

Nras Mutation ◽

Advisory Committees ◽

Kit Mutation ◽

Mutation Pattern ◽

Exon 11 ◽

The Stability

Abstract Background: CBF-AML is defined by recurrent genetic abnormalities which encompass t(8;21)(q22;q22), inv(16)(p13.1q22) or less frequently t(16;16)(p13.1;q22). Most frequent secondary chromosome aberrations in t(8;21) AML are del(9q) or loss of a sex chromosome, and in inv(16)/t(16;16) AML trisomy 22 or trisomy 8. At the molecular level mutations involving KIT, FLT3, or NRAS were identified as recurrent lesions in CBF-AML. However, the underlying genetic alterations which might trigger relapse in CBF-AML are not well delineated. Thus, the aim of our study was to characterize the clonal architecture of relapsed CBF-AML. Methods: We performed mutational profiling (KIT, FLT3-ITD, FLT3-TKD, NRAS, ASXL1) in paired samples obtained at diagnosis and at relapse from 66 adults with CBF-AML [inv(16), n=43; t(8;21), n=23] who all were treated within the AMLSG studies. Results: In inv(16) AML, the following mutation pattern was identified at diagnosis: KIT 13/40 (33%; exon 8, n=6; exon 17, n=5; exon 8+17, n=1; exon 11, n=1; missing data, n=3), NRAS 18/43 (42%), FLT3-TKD 4/43 (9%); none of the pts harboured FLT3-ITD or ASXL1 mutations. At the time of relapse, there was a shift in the mutation pattern in 26 pts (60%): KIT mutations (exon 8, n=5; exon 17, n=2; exon 8+17, n=1) were lost in 8 pts and 1 pt acquired an exon 17 KIT mutation; similarly, 15 pts lost and 1 pt gained NRAS mutation, respectively. Of note, all FLT3-TKD mutations were lost at the time of relapse, and only one pt gained a FLT3-ITD mutation. Based on these findings we calculated the stability in inv(16) AML for KIT, NRAS and FLT3-TKD mutations as 38%, 17%, and 0%, respectively. AML with t(8;21) presented a different diagnostic mutation profile: KIT 9/23 (39%; exon 17, n=8; exon 11, n=1), FLT3 -ITD 3/23 (13%), NRAS 2/23 (9%), and ASXL1 1/23 (4%); there were no FLT3-TKD mutations. At the time of relapse, the mutation pattern changed in 9 pts (39%); KIT mutations were lost in 4 pts (exon 17, n=3; exon 11, n=1), but acquired in 2 pts with both of them located in exon 17; only 1 pt lost the NRAS mutation. FLT3-ITD was lost in 2 and gained in 3 pts. There was no change in the ASXL1 mutation status. Thus, the stability for KIT, NRAS, FLT3-ITD and ASXL1 mutations in t(8;21) AML was calculated as 56%, 50%, 33% and 100%, respectively. Of note, mutations affecting the KIT and NRAS gene were almost mutually exclusive; there were only 3 pts with concurrent KIT and NRAS mutations at diagnosis [inv(16), n=2; t(8;21), n=1]. Conclusion: CBF-AML cases display a high degree of molecular heterogeneity with shift of the mutation pattern at relapse in both CBF-AML subtypes. The frequent loss of KIT and NRAS mutations at relapse suggests that there might be other important secondary lesions driving relapse. Ongoing high-resolution genome-wide profiling will further unravel the clonal hierarchy and genomic landscape in CBF-AML. Disclosures Götze: Novartis: Honoraria; Celgene Corp.: Honoraria. Greil:Celgene: Consultancy; Ratiopharm: Research Funding; Sanofi Aventis: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; GSK: Research Funding; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; AOP Orphan: Research Funding; Roche, Celgene: Honoraria, Research Funding. Schlenk:Boehringer-Ingelheim: Honoraria; Teva: Honoraria, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Research Funding; Arog: Honoraria, Research Funding.

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Complete response in a melanoma patient treated with imatinib

The Journal of Laryngology & Otology ◽

10.1017/s0022215112000527 ◽

2012 ◽

Vol 126 (6) ◽

pp. 638-640 ◽

Cited By ~ 5

Author(s):

M C Brown ◽

R J Casasola

Keyword(s):

Melanoma Patient ◽

Primary Melanoma ◽

Complete Response ◽

Imatinib Therapy ◽

Gastrointestinal Stromal Tumours ◽

Kit Mutation ◽

Kit Gene ◽

Exon 11 ◽

One Year

AbstractBackground:Imatinib therapy has been successful in gastrointestinal stromal tumours containing mutation of the KIT gene. However, there are few reported cases of successful imatinib therapy in patients with melanoma containing KIT gene mutation or c-kit protein expression.Methods and results:A 52-year-old man developed metastatic melanoma from a primary melanoma in the left side of the nasopharynx. The tumour was positive for c-kit protein, and there was a KIT mutation in exon 11. He was treated with imatinib. A follow-up scan one year later showed a complete response. Treatment targeting the biological characteristics of melanoma proved successful in this patient.

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Cytogenetically Normal Acute Myeloid Leukemia with a Novel KIT Mutation in Exon 11 G565V Developing a Sole Trisomy 13 at Relapse: A Clinical Dilemma

Acta Haematologica ◽

10.1159/000360389 ◽

2014 ◽

Vol 133 (1) ◽

pp. 1-5

Author(s):

Maria Jacqueline Nieto ◽

Angela Scalise ◽

Vesna Najfeld

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Donor Cell ◽

Trisomy 13 ◽

High Dose ◽

Unrelated Donor ◽

Kit Mutation ◽

Exon 11 ◽

Acute Myeloid

We describe a patient with acute myeloid leukemia (AML) who had a normal karyotype at diagnosis and was negative for NPM1 and FLT3 mutations, but had a KIT G565V mutation in exon 11. This has not been described previously in AML. The patient received induction and consolidation chemotherapy and was in hematologic remission for 351 days when deletion 7q was cytogenetically detected in 8% of the bone marrow cells. After an initial treatment of azacitidine followed by decitabine, an unrelated trisomy 13 clone was identified, followed by subclonal rearrangement of ETV6. The patient underwent reinduction with high-dose cytarabine and mitoxantrone followed by voluntary-unrelated-donor allogeneic stem cell transplantation with a reduced-intensity conditioning. As of writing, the patient is in complete hematologic and cytogenetic remission with 100% donor cell engraftment.

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Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience

South Asian Journal of Cancer ◽

10.4103/sajc.sajc_275_16 ◽

2017 ◽

Vol 06 (03) ◽

pp. 113-117 ◽

Cited By ~ 2

Author(s):

Trupti Pai ◽

Munita Bal ◽

Omshree Shetty ◽

Mamta Gurav ◽

Vikas Ostwal ◽

...

Keyword(s):

Gastrointestinal Stromal Tumors ◽

Complete Analysis ◽

Cancer Center ◽

Kit Mutation ◽

Stromal Tumors ◽

Molecular Alterations ◽

Kit Gene ◽

Exon 9 ◽

Substitution Mutations ◽

Exon 11

Abstract Background: Primary mutations in the KIT gene are the driving force for gastrointestinal stromal tumors (GIST) tumorigenesis. Predictive role of KIT mutation status aids oncologists in patient management. There is a paucity of comprehensive data on the frequency of mutations in the KIT gene in GIST affecting Indian patients. The aims of this study were to determine the frequency and spectrum of molecular alterations affecting the KIT gene and assess their association with clinicopathologic features in a cohort of patients of GIST. Materials and Methods: Morphological and immunohistochemically confirmed GIST cases (n = 114) accessioned from August 2014-June 2015 were analyzed for mutations in KIT exons 9, 11, 13, and 17 and subjected to Sanger sequencing onto the ABI 3500 Genetic Analyzer. The sequences were analyzed using sequence analysis software: SeqScape® and Chromas Lite. Results: KIT mutations were seen in 70% of cases and the majority of KIT mutations involved exon 11 (57%), followed by exon 9 (10%), exon 13 (3%), and exon 17 (1%). Most common exon 11 mutations were in-frame deletions (61.4%) followed by substitution mutations (19.3%). Exon 9 mutations showed identical duplication of Ala-Tyr at codons 502–503. Simultaneous mutations affecting exon 11 and 13 were discovered. Novel variations, namely, p.Q556E (c.1666C>G), p.Q556dup (c.1666_1668dupCAG), p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT), p.Y503_F504insTY (c.1509_1510insACCTAT), and p.K642R (c.1925A>G) involving exons 11, 9, and 13, respectively, were observed. Interpretation and Conclusions: First study with complete analysis of all 4 exons of KIT (exons 9, 11, 13, and 17) in Indian GIST patients. Along with well-described KIT mutations, several rare double mutations as well as novel alterations were reported in this series.

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Rare and unknown canine systemic mastocytosis: clinical and laboratory features of an aberrant c-Kit mutation neoplasia

Brazilian Journal of Veterinary Research and Animal Science ◽

10.11606/issn.1678-4456.bjvras.2021.175896 ◽

2021 ◽

Vol 58 ◽

pp. e175896

Author(s):

Carla Sofia Soares ◽

Leonor Delgado ◽

Sónia Morgado ◽

Pedro Pires Carvalho ◽

Luís Carlos Barros

Keyword(s):

Systemic Mastocytosis ◽

Myeloproliferative Neoplasms ◽

World Health ◽

Base Pairs ◽

Kit Mutation ◽

Laboratory Features ◽

Exon 11 ◽

Serra Da Estrela ◽

Health Organization ◽

Reported Data

Systemic mastocytosis (SM) pathology is extremely rare in canine practice, with insufficient reported data. The knowledge of the clinical behavior of this pathology is scarce. In human medicine, SM has been widely investigated, being defined as a rare hematopoietic disorder by the World Health Organization (2016), within the type of myeloproliferative neoplasms. Herein, we describe a systemic mastocytosis case in a Portuguese Serra-da-Estrela dog, where a cutaneous grade III/high-grade MCT was also diagnosed. The clinical decline of the animal and owner’s insistence throughout anamnesis that the dog was markedly different after the cytologic exam performed in another clinic, along with both severe eosinophilia and hepatomegaly, led to the clinical suspicion of SM. The animal passed away 7 days later. Post-mortem investigation confirmed SM pathology, and a deletion of 15 base pairs change on c-Kit gene exon 11 was identified. Contemplating the low number of cases described in the literature, this publication aims to disclose clinical and laboratory features of rare and poorly described canine SM, taking into consideration human outcomes described in the literature.

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