Managing locally advanced GIST complicated by perforation: A case report and comprehensive review.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, frequently characterized by mutations in the KIT or PDGFRA genes. This case report details the complex clinical course of a 71-year-old female with a history of HIV and metastatic GIST presenting with acute abdominal symptoms indicative of perforated viscus. Initial imaging revealed a massive pneumoperitoneum and a large abdominal mass, necessitating immediate surgical intervention. The patient underwent multiple surgeries, including bowel resections and colostomy creation, to address the extensive tumor burden and complications. Postoperatively, she required intensive care management, including mechanical ventilation, vasopressor support, and hemodialysis for acute kidney injury. Pathological examination confirmed metastatic GIST with extensive mesenteric and omental involvement. Immunohistochemical staining was positive for CD117 (c-KIT) and DOG-1. Despite aggressive surgical and supportive measures, the patient's condition highlighted the significant challenges in managing advanced GIST with perforation. This case highlights the importance of a multidisciplinary approach, integrating surgical, medical, and intensive care to optimize outcomes. The prognosis of GIST varies widely, with localized tumors having favorable outcomes following resection, while metastatic cases often face a poorer prognosis despite advances in targeted therapies. This case exemplifies the critical need for personalized treatment plans and ongoing research to improve the management and prognosis of GIST patients.

A case report of feline mast cell tumour with intertumoral heterogeneity: Identification of secondary mutations c.998G>C and c.2383G>C in KIT after resistance to toceranib.

A 12-year-old male domestic cat with multiple subcutaneous mast cell tumours (MCTs) presented with a 2-week history of pruritus and raw/bleeding skin from self-trauma at Kagoshima University Veterinary Teaching Hospital. Polymerase chain reaction (PCR) and histopathological analyses revealed intertumoral heterogeneity among tumour locations based on the mutation status of KIT. In addition, the expression pattern of KIT was characterized. After failed treatment with vinblastine (2.0-2.2 mg/m2, intravenous administration, two doses in total) or nimustine (25 mg/m2, intravenous administration, two doses in total), toceranib (2.2-2.6 mg/kg, orally administered, every other day) was administered to treat recurrent MCTs harbouring the KIT exon eight internal tandem duplication mutation, achieving a complete response. However, toceranib resistance developed 2 months after treatment initiation. Subsequent PCR analysis was conducted to identify the mutational status of KIT in each MCT and to detect the presence of secondary mutations associated with the acquisition of toceranib resistance. Secondary KIT mutations (c.998G>C and c.2383G>C), which were not initially detected in tumour cells at diagnosis, were identified after the development of resistance to toceranib. This indicates that the tumour cells in feline MCTs in the same case have diverse characteristics. Our findings encourage further investigation into the development of therapeutic strategies for feline MCTs, particularly focusing on the heterogeneous nature of KIT/KIT and overcoming acquired resistance to toceranib.

Clinicopathological Characteristics and the First Mutational Analysis of Gastrointestinal Stromal Tumors From Mexico: A Single Institution Experience.

Background Gastrointestinal stromal tumors (GISTs) arise from Cajal's interstitial cell precursors and display a variety of genetic mutations, primarily in the KIT and PDGFRA genes. These mutations are linked to tumor location, prognosis, and response to treatment. This study delves into the mutational patterns of GISTs in a Mexican population and their impact on overall survival (OS) and disease-free survival (DFS). Methodology This retrospective study examined 42 GIST cases diagnosed at the Oncology Hospital of the National Medical Center XXI Century between January 2018 and December 2020. Clinical, histological, and immunohistochemical data were gathered, and mutational analysis of KIT and PDGFRA genes was conducted using second-generation sequencing. Results The study group consisted of 52.4% females and 47.6% males, with an average age of 62.6 years. The most common tumor site was the stomach (59.5%), followed by the small intestine (26.2%). KIT mutations were detected in 71.4% of cases, predominantly involving exon 11. PDGFRA mutations were observed in 7.1% of cases. Recurrence was noted in 9.5% of patients, all with high-risk tumors. No significant link was identified between specific mutations and OS or DFS. Conclusions This investigation sheds light on the genetic landscape of GISTs in the Mexican population. While no significant association was established between particular mutations and survival outcomes, the study emphasizes the importance of molecular profiling in treatment decision-making. Further studies with larger sample sizes and longer follow-up periods are necessary to validate these results and explore their clinical relevance.

Pediatric acute myeloid leukemia with t(8;21) and KIT mutation treatment with avapritinib post-stem cell transplantation: a report of four cases.

Acute myeloid leukemia (AML) with t(8;21) (q22;q22), which forms RUNX1::RUNX1T1 fusion gene, is classified as a favorable-risk group. However, the presence of mutations in KIT exon 17 results in an adverse prognosis in this group. Avapritinib, a novel tyrosine kinase inhibitor, was designed to target KIT mutation. We report a retrospective study of four pediatric patients with AML with t(8:21) and KIT exon 17 mutation who were treated with avapritinib, three of them failed to demethylate drugs and donor lymphocyte infusion targeting RUNX1::RUNX1T1-positivity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). So far, all patients with RUNX1::RUNX1T1 positivity had turned negative after 1, 9, 7, 2 months of avapritinib treatment. The common adverse effect of avapritinib is neutropenia, which is well-tolerated. This case series indicates that avapritinib may be effective and safe for preemptive treatment of children with AML with t(8;21) and KIT mutation after allo-HSCT, providing a treatment option for preventing relapse after allo-HSCT.

Multicolor flow cytometric immunophenotyping is highly sensitive and specific in identifying aberrant mast cells in the diagnostic workup of systemic mastocytosis.

OBJECTIVES: Flow cytometric immunophenotyping (FCI) is a fast and sensitive method for characterizing hematolymphoid neoplasms. It is not widely used in the workup of systemic mastocytosis (SM), in part because of the technical challenges and in part because the utility of FCI in assessing mast cells is not well understood. The objectives of this study were to assess the diagnostic utility of FCI in establishing a diagnosis of SM and distinguishing SM from nonneoplastic mast cells and to examine the immunophenotypic findings among SM subtypes. METHODS: We performed FCI on bone marrow samples suspicious for SM using a panel consisting of CD2, CD25, CD30, CD45, CD117, and HLA-DR. RESULTS: The cohort included 88 SM cases: 67 without an associated hematologic neoplasm (AHN) (PureSM) and 21 with an AHN (SM-AHN). We also assessed 40 normal/reactive controls. Overall, FCI was adequate for interpretation in 87 of 88 (99%) cases and detected at least 1 immunophenotypic aberrancy in 100% of SM cases. CD2, CD25, and CD30 were positive in 78%, 98%, and 90% of SM cases vs 0%, 13%, and 13% of cases with normal/reactive mast cells (P < .0001 for all). Two or 3 abnormalities were observed in 92% of SM cases but not in normal/reactive mast cells. Among SM cases, SM-AHN showed statistically significant less CD2 (38% vs 91%, P < .0001) and less co-expression of all 3 aberrant markers (CD2, CD25, and CD30 positive in 38% vs 86% of cases; P < .0001) than PureSM. Immunohistochemical analysis showed consistently weaker or focal expression of CD2, CD25, and CD30 than FCI, with CD2 and CD30 being falsely negative in 40% and 50% cases, respectively. A KIT D816V mutation was detected in 67% of PureSM cases and 76% of SM-AHN cases. CONCLUSIONS: Flow cytometric immunophenotyping is a quick, sensitive, high-yield tool for evaluating the immunophenotype of mast cells. An abnormal FCI finding should prompt careful histologic evaluation and sensitive KIT D816V mutation testing to address the possibility of SM. CD2, CD25, and CD30 are important markers for the detection of immunophenotypic aberrancy of mast cells, and their frequencies of aberrancy differ across SM subtypes.

Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial.

Mucosal (MM) and acral melanomas (AM) are rare melanoma subtypes of unmet clinical need; 15%-20% harbor KIT mutations potentially targeted by small-molecule inhibitors, but none yet approved in melanoma. This multicenter, single-arm Phase II trial (NICAM) investigates nilotinib safety and activity in KIT mutated metastatic MM and AM. KIT mutations are identified in 39/219 screened patients (18%); of 29/39 treated, 26 are evaluable for primary analysis. Six patients were alive and progression free at 6 months (local radiology review, 25%); 5/26 (19%) had objective response at 12 weeks; median OS was 7.7 months; ddPCR assay correctly identifies KIT alterations in circulating tumor DNA (ctDNA) in 16/17 patients. Nilotinib is active in KIT-mutant AM and MM, comparable to other KIT inhibitors, with demonstrable activity in nonhotspot KIT mutations, supporting broadening of KIT evaluation in AM and MM. Our results endorse further investigations of nilotinib for the treatment of KIT-mutated melanoma. This clinical trial was registered with ISRCTN (ISRCTN39058880) and EudraCT (2009-012945-49).

Poor Applicability of Currently Available Prognostic Scoring Systems for Prediction of Outcome in KIT D816V-Negative Advanced Systemic Mastocytosis.

Within our nationwide registry, we identified a KIT D816V mutation (KIT D816Vpos.) in 280/299 (94%) patients with advanced systemic mastocytosis (AdvSM). Age, cytopenias and the presence of additional somatic mutations confer inferior overall survival (OS). However, little is known about the characteristics of KIT D816V-negative (D816Vneg.) AdvSM. In 19 D816Vneg. patients, a combination of clinical, morphological and genetic features revealed three subgroups: (a) KIT D816H- or Y-positive SM (KIT D816H/Ypos., n = 7), predominantly presenting as mast cell leukemia (MCL; 6/7 patients), (b) MCL with negative KIT sequencing (KITneg. MCL, n = 7) and (c) KITneg. SM with associated hematologic neoplasm (KITneg. SM-AHN, n = 5). Although >70% of patients in the two MCL cohorts (KIT D816H/Ypos. and KITneg.) were classified as low/intermediate risk according to prognostic scoring systems (PSS), treatment response was poor and median OS was shorter than in a KIT D816Vpos. MCL control cohort (n = 29; 1.7 vs. 0.9 vs. 2.6 years; p < 0.04). The KITneg. SM-AHN phenotype was dominated by the heterogeneous AHN (low mast cell burden, presence of additional mutations) with a better median OS of 4.5 years. We conclude that (i) in MCL, negativity for D816V is a relevant prognostic factor and (ii) PSS fail to correctly classify D816Vneg. patients.

KIT/PDGFRA Variant Allele Frequency as Prognostic Factor in Gastrointestinal Stromal Tumors (GISTs): Results From a Multi-Institutional Cohort Study.

BACKGROUND: The patient selection for optimal adjuvant therapy in gastrointestinal stromal tumors (GISTs) is provided by nomogram based on tumor size, mitotic index, tumor location, and tumor rupture. Although mutational status is not currently used to risk assessment, tumor genotype showed a prognostic influence on natural history and tumor relapse. Innovative measures, such as KIT/PDGFRA-mutant-specific variant allele frequency (VAF) levels detection from next-generation sequencing (NGS), may act as a surrogate of tumor burden and correlate with prognosis and overall survival of patients with GIST, helping the choice for adjuvant treatment. PATIENTS AND METHODS: This was a multicenter, hospital-based, retrospective/prospective cohort study to investigate the prognostic role of KIT or PDGFRA-VAF of GIST in patients with radically resected localized disease. In the current manuscript, we present the results from the retrospective phase of the study. RESULTS: Two-hundred (200) patients with GIST between 2015 and 2022 afferent to 6 Italian Oncologic Centers in the EURACAN Network were included in the study. The receiver operating characteristic (ROC) curves analysis was used to classify "low" vs. "high" VAF values, further normalized on neoplastic cellularity (nVAF). When RFS between the low and high nVAF groups were compared, patients with GIST with KIT/PDGFRA nVAF > 50% showed less favorable RFS than patients in the group of nVAF ≤ 50% (2-year RFS, 72.6% vs. 93%, respectively; P = .003). The multivariable Cox regression model confirmed these results. In the homogeneous sub-population of intermediate-risk, patients with KIT-mutated GIST, the presence of nVAF >50% was statistically associated with higher disease recurrence. CONCLUSION: In our study, we demonstrated that higher nVAF levels were independent predictors of GIST prognosis and survival in localized GIST patients with tumors harboring KIT or PDGFRA mutations. In the cohort of intermediate-risk patients, nVAF could be helpful to improve prognostication and the use of adjuvant imatinib.

No indication of aberrant neutrophil extracellular trap release in indolent or advanced systemic mastocytosis.

In disease states with chronic inflammation, there is a crosstalk between mast cells and neutrophil granulocytes in the inflamed microenvironment, which may be potentiated by tryptase. In systemic mastocytosis (SM), mast cells are constitutively active and tryptase is elevated in blood. Mast cell activation in SM leads to symptoms from various organs depending on where the active mast cells reside, for example, palpitations, flush, allergic symptoms including anaphylactic reactions, and osteoporosis. Whether neutrophil function is altered in SM is not well understood. In the current study, we assessed nucleosomal citrullinated histone H3 (H3Cit-DNA) as a proxy for neutrophil extracellular trap release in plasma from 55 patients with indolent and advanced SM. We observed a strong trend towards a correlation between leukocyte count, eosinophil count and neutrophil count and H3Cit-DNA levels in patients with advanced SM but not in indolent SM; however, no differences in H3Cit-DNA levels in SM patients compared with healthy controls. H3Cit-DNA levels did not correlate with SM disease burden, tryptase levels, history of anaphylaxis or presence of cutaneous mastocytosis; thus, there is no evidence of a general neutrophil extracellular trap release in SM. Interestingly, H3Cit-DNA levels and leukocyte counts were elevated in a subgroup of SM patients with aberrant mast cell CD2 expression, which warrants further investigation. In conclusion, we found no evidence of global increase in neutrophil extracellular trap release in SM.

Current Challenges in the Diagnosis of Pediatric Cutaneous Mastocytosis.

Pediatric mastocytosis is mostly a cutaneous disease classified as cutaneous mastocytosis (CM), which is characterized by mast cell (MCs) accumulation in the skin and the absence of extracutaneous involvement. Based on the morphology of skin lesions, CM can be divided into three major forms: maculopapular CM (MPCM), diffuse CM (DCM) and mastocytoma of the skin. A positive Darier's sign is pathognomonic for all forms of CM. MPCM is the most common form, presenting with red-brown macules or slightly raised papules. Mastocytoma is characterized by solitary or a maximum of three nodular or plaque lesions. DCM is a rare, severe form which presents as erythroderma, pachydermia and blistering in the infantile period of the disease. CM is associated with MC mediator-related symptoms, most commonly including pruritus, flushing, blistering, diarrhea and cramping. Anaphylactic shock occurs rarely, mainly in patients with extensive skin lesions and a significantly elevated serum tryptase level. Childhood-onset MPCM and mastocytoma are usually benign diseases, associated with a tendency for spontaneous regression, while DCM is associated with severe mediator-related symptoms, an increased risk of anaphylaxis and, in some cases, underlying systemic mastocytosis (SM). In contrast to adults, SM is a rare finding in children, most commonly presenting as indolent SM. However, advanced SM sporadically occurs.

A phase II study on the efficacy of regorafenib in treating patients with c-KIT-mutated metastatic malignant melanoma that progressed after previous treatment (KCSG-UN-14-13).

BACKGROUND: c-KIT mutations are found in approximately 15% of patients with malignant melanoma in the Asian population. Regorafenib, an oral multikinase inhibitor, acts against both wild-type and mutant KIT. OBJECTIVE: This multi-institutional, phase II, single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harbouring c-KIT mutations. METHODS: Patients with metastatic melanoma positive for c-KIT mutations, upon progression after at least one line of systemic treatment, were enroled. Patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was disease control rate (DCR), and secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 23 patients were enrolled. c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving complete response, 5 (21.7%) achieving partial response, and 10 (43.5%) showing stable disease. ORR was 30.4% (7/23). The median follow-up period was 15.7 months (95% confidence interval [CI], 9.6-21.3), and median OS and PFS were 21.5 months (95% CI, 15.1-27.9) and 7.1 months (95% CI, 5.0-9.2), respectively. Circulating tumour DNA analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumour mutational profiles. The most common adverse events (AEs) were skin reactions, including palmar-plantar erythrodysesthesia (52.2%), and grade 3 AEs were reported in 39.1% (9/23) of the patients. CONCLUSION: Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harbouring c-KIT mutations.

From KIT-mutated into wild-type: dedifferentiation of gastrointestinal stromal tumor in adolescent patient-a case report.

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract, usually found in elderly adults. It is infrequent among pediatric patients and usually differs from adult-type disease in terms of histopathology and molecular features. Case Description: We describe the management of the disease in a 10-year-old female patient diagnosed with a GIST of the stomach. In total, she has undergone successively total tumor resection, unsuccessful imatinib treatment and subtotal gastric resection at relapse. The first genetic test from primary tumor confirmed KIT mutations in exons 13 and 17, while the repeated genetic screening using tumor sample from subtotal gastric resection revealed no KIT or platelet-derived growth factor receptor α (PDGFRA) genes mutations. Such dedifferentiation from adult type (thus KIT-mutated) into wild-type (without KIT or PDGFRA mutation) has not been reported so far to the best of our knowledge. Currently, the patient is observed, and no further pharmacological nor surgical treatment has been administered. Conclusions: The case underlines the importance of genetic profiling combined with non-standard diagnostics (both histopathological and radiological) due to the treatment efficacy prediction. We moreover emphasize the necessity to create worldwide standards on the diagnostics and treatment of GIST in pediatric patients that would include options of targeted therapies.

Increased TIM-3 and galectin-9 serum levels in patients with advanced systemic mastocytosis.

BACKGROUND: Systemic mastocytosis is characterized by expansion of clonal mast cells in various tissues. Several biomarkers with diagnostic and therapeutic potential have recently been characterized in mastocytosis, such as the serum marker tryptase and the immune checkpoint molecule PD-L1. OBJECTIVE: We aimed to investigate whether serum levels of other checkpoint molecules are altered in systemic mastocytosis and whether these proteins are expressed in mastocytosis infiltrates in the bone marrow. METHODS: Levels of different checkpoint molecules were analyzed in serum of patients with different categories of systemic mastocytosis and healthy controls and correlated to disease severity. Bone marrow biopsies from patients with systemic mastocytosis were stained to confirm expression. RESULTS: Serum levels of TIM-3 and galectin-9 were increased in systemic mastocytosis, particularly in advanced subtypes, compared with healthy controls. TIM-3 and galectin-9 levels were also found to correlate with other biomarkers of systemic mastocytosis, such as serum tryptase and KIT D816V variant allele frequency in the peripheral blood. Moreover, we observed expression of TIM-3 and galectin-9 in mastocytosis infiltrates in bone marrow. CONCLUSIONS: Together, our results demonstrate for the first time that serum levels of TIM-3 and galectin-9 are increased in advanced systemic mastocytosis. Moreover, TIM-3 and galectin-9 are expressed in bone marrow infiltrates in mastocytosis. These findings provide a rationale for exploring TIM-3 and galectin-9 as diagnostic markers and eventually therapeutic targets in systemic mastocytosis, particularly in advanced forms.

A Rare Case of a Rectal Gastrointestinal Stromal Tumor (GIST) Discovered During a Routine Colonoscopy.

A gastrointestinal stromal tumor (GIST) is a rare malignancy, accounting for only 0.1% to 3% of all gastrointestinal (GI) malignancies. Although GISTs are the most common mesenchymal tumor of the GI tract, they are primarily found within the stomach, with rectal GISTs rarely reported. They may present with rectal bleeding, constipation, pain, or a palpable mass while some are found incidentally. The incidence of GISTs has been on the rise, possibly due to advancements in diagnostic technology. In this case report, we present a 50-year-old female who presented with intermittent constipation and rectal pain and was found to have a submucosal rectal mass during a routine diagnostic colonoscopy. Further evaluation confirmed the presence of a spindle-cell neoplasm, which was mildly cellular and showed positive expression of CD34 and CD117 on immunohistochemistry, consistent with the diagnosis of GIST of the rectum. This case report emphasizes the importance of routine colonoscopies in the early detection of neoplastic lesions of the colon and highlights the rare incidence of GISTs, their risk factors, pathogenesis, and common sites of occurrence.

Predictive Value of a Radiomics Nomogram Model Based on Contrast-Enhanced Computed Tomography for KIT Exon 9 Gene Mutation in Gastrointestinal Stromal Tumors.

OBJECTIVES: To establish and validate a radiomics nomogram model for preoperative prediction of KIT exon 9 mutation status in patients with gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: Eighty-seven patients with pathologically confirmed GISTs were retrospectively enrolled in this study. Imaging and clinicopathological data were collected and randomly assigned to the training set (n = 60) and test set (n = 27) at a ratio of 7:3. Based on contrast-enhanced CT (CE-CT) arterial and venous phase images, the region of interest (ROI) of the tumors were manually drawn layer by layer, and the radiomics features were extracted. The intra-class correlation coefficient (ICC) was used to test the consistency between observers. Least absolute shrinkage and selection operator regression (LASSO) were used to further screen the features. The nomogram of integrated radiomics score (Rad-Score) and clinical risk factors (extra-gastric location and distant metastasis) was drawn on the basis of multivariate logistic regression. The area under the receiver operating characteristic (AUC) curve and decision curve analysis were used to evaluate the predictive efficiency of the nomogram, and the clinical benefits that the decision curve evaluation model may bring to patients. RESULTS: The selected radiomics features (arterial phase and venous phase features) were significantly correlated with the KIT exon 9 mutation status of GISTs. The AUC, sensitivity, specificity, and accuracy in the radiomics model were 0.863, 85.7%, 80.4%, and 85.0% for the training group (95% confidence interval [CI]: 0.750-0.938), and 0.883, 88.9%, 83.3%, and 81.5% for the test group (95% CI: 0.701-0.974), respectively. The AUC, sensitivity, specificity, and accuracy in the nomogram model were 0.902 (95% confidence interval [CI]: 0.798-0.964), 85.7%, 86.9%, and 91.7% for the training group, and 0.907 (95% CI: 0.732-0.984), 77.8%, 94.4%, and 88.9% for the test group, respectively. The decision curve showed the clinical application value of the radiomic nomogram. CONCLUSION: The radiomics nomogram model based on CE-CT can effectively predict the KIT exon 9 mutation status of GISTs and may be used for selective gene analysis in the future, which is of great significance for the accurate treatment of GISTs.

[Mastocytosis in children]. / Mastozytose bei Kindern.

Mastocytosis in children is a rare disease characterized by an abnormal accumulation of tissue mast cells. Mastocytosis in children presents with typical skin alterations that are classified as maculopapular cutaneous mastocytosis, diffuse cutaneous mastocytosis, or mastocytoma. Some patients also develop mast cell mediator symptoms, such as pruritus, flush, and anaphylaxis. In many children, the disease is characterized by a benign and usually self-limiting course; systemic mastocytosis with extracutaneous involvement and a chronic or progressive course is found only rarely. Therapeutically, H1 antihistamines are primarily used on an as-needed basis or as continuous treatment, depending on the severity. Children, parents and caregivers should be thoroughly educated about the clinical picture and possible trigger factors of mast cell mediator release. For children with extensive skin alterations and severe symptoms, the prescription of an epinephrine auto-injector is recommended for emergency treatment.

KIT Gene Mutation Causing Piebaldism Associated with Multiple Café Au-Lait Like Macules and Freckling: Delineating a Cause of this Coexistence.

Piebaldism is a rare genetic disorder of congenital leukoderma caused by mutation in KIT proto-oncogene receptor tyrosine kinase. We present a 10-year-old boy with congenital depigmented macules suggestive of piebaldism associated with café au lait macules and skin fold freckling complicating the diagnosis. A diagnosis of piebaldism was made via exome sequencing that showed a pathogenic variant of KIT gene with no pathogenic variants of NF1 or SPRED1 gene. Our current understanding of the KIT tyrosine kinase function may provide a better explanation into this phenotypic coexistence and does not necessarily represent an overlap with Neurofibromatosis type 1.

Mast Cell Leukemia: An Update with a Practical Review.

Mast cell leukemia (MCL) is the leukemic form of SM with at least 20% mostly immature mast cells on bone marrow aspirate. MCL may develop de novo, in the absence of a prior SM, or it may represent a progression from a previous SM. MCL may be sub-divided into the more frequent, aggressive acute form with signs of organ damage (C-findings) and the chronic form lacking C-findings and presenting a more stable course, although over time, progression to acute MCL is common. The 2022 WHO subtype of MCL with an associated hematological neoplasm was renamed MCL with an associated myeloid neoplasm in the 2022 International Consensus Classification (ICC). The relevance of the distinction between the leukemic and aleukemic forms based on the percentage of circulating mast cells is a matter of debate. The current knowledge on MCL is restricted mainly to single reports or case series with a limited number of larger studies. Our aim is to provide a comprehensive overview of this rare disease in terms of clinical manifestations, morphology, phenotype, molecular characteristics, differential diagnosis, outcome and treatment. A general overview on mastocytosis is also included.

Benefit of Continuation of Low-Dose Imatinib for Gastrointestinal Stromal Tumors despite Adverse Events with Regular-Dose Imatinib.

Tyrosine kinase inhibitors (TKIs) such as imatinib improve the prognosis of patients with gastrointestinal stromal tumors (GISTs). However, treatment options for GISTs are still limited, and the continuation of TKIs is difficult due to adverse events in some cases. The effectiveness of low-dose imatinib is unclear. We report 2 cases to show effectiveness of low-dose imatinib in patients with adverse events. The first case is a male in his early 60s with a history of intestinal GIST resection who was diagnosed with recurrent GIST with peritoneal dissemination. He was started on low-dose imatinib (300 mg) because of a history of subconjunctival hemorrhage after receiving postoperative imatinib. Follow-up contrast-enhanced ultrasonography revealed that the tumors had shrunk in size and number after 2 months of treatment with 300-mg imatinib. He continued this treatment and showed partial response for 8 months. The second case is a female in her late 70s with rectal GIST who was treated with imatinib 400 mg. Due to a severe skin lesion, she changed her treatment to sunitinib 2 months after initiation. However, new metastasis in the liver was confirmed after 4 months of administration of sunitinib. She underwent surgical esection of the rectal tumor to reduce the volume. After the surgery, low-dose imatinib (300 mg) with oral steroids was adopted. Follow-up confirmed the absence of recurrence at the rectum and no increase in hepatic tumor size for 18 months. Aggressive treatment with low-dose imatinib instead of discontinuation or alteration of treatment may benefit patients with unresectable and postoperative GISTs with sensible mutation to imatinib.