2026-06-29 | Hidden in Plain Sight: Systemic Mastocytosis Manifesting as Isolated Hepatosplenomegaly in the Absence of Cutaneous and Classical Manifestations-A Case Report and Literature Review.

Systemic mastocytosis (SM) is a rare clonal myeloproliferative neoplasm typically characterized by cutaneous lesions and mediator-release symptoms. Presentations dominated by visceral organ involvement without skin findings are uncommon and pose a significant diagnostic challenge, often mimicking hematologic malignancies. We report a 50-year-old male presenting with generalized weakness, fatigue, and progressive abdominal distension. Examination revealed significant hepatosplenomegaly with no cutaneous manifestations. Investigations demonstrated severe leukocytosis (peak WBC 112.8 × 103/μL) with a leucoerythroblastic picture, persistently elevated alkaline phosphatase, and anemia. Initial bone marrow morphology suggested chronic myeloid leukemia (CML), showing marked hypercellularity (95-100%) and granulocytic hyperplasia (M:E ratio 32:1). Cytogenetics revealed a normal male karyotype (46, XY), and BCR-ABL1 testing was negative, excluding CML. Comprehensive molecular profiling identified a pathogenic KIT p.D816V mutation, confirming systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). The patient was treated with cladribine (40 mg over five days) followed by maintenance hydroxyurea (300 mg twice daily), with significant clinical improvement at eight-week follow-up. This case underscores that SM-AHN can present with isolated hepatosplenomegaly and profound leukocytosis without cutaneous signs, and highlights the critical role of integrated molecular profiling, including KIT mutation analysis, in the diagnostic workup of atypical hematologic presentations.

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2026-06-26 | Unmasking Indolent Systemic Mastocytosis in Patients with Unexplained or Treatment-Refractory Osteoporosis: A Case Series with Diagnostic and Therapeutic Implications.

Indolent systemic mastocytosis (ISM) is an under-recognised cause of secondary osteoporosis, and skeletal fragility may be the only presenting feature, delaying diagnosis. We describe four adults referred to a tertiary endocrinology service for unexplained osteoporosis or low-trauma fractures, in whom systemic mastocytosis (SM) was identified during work-up. All had elevated basal serum tryptase (41.4-87.0 µg/L), bone-marrow biopsy showing atypical mast cells and the KIT D816V variant; cutaneous lesions were absent in every case. Three patients fulfilled WHO 2022 criteria for ISM. The fourth had coexistent JAK2 V617F-positive post-essential-thrombocythaemia myelofibrosis and was classified as SM with associated haematological neoplasm (SM-AHN); his mast cell clone (tryptase 43.7 µg/L; KIT D816V VAF 0.391%) behaved indolently and contributed clinically through osteoporosis alone, illustrating that an indolent mast cell component can be overlooked when a chronic myeloid neoplasm dominates the picture. Presentations ranged from an isolated low-energy L5 fracture in a 55-year-old man, to multiple vertebral compression fractures despite denosumab in a 71-year-old woman with primary hyperparathyroidism, to severe wasp-sting anaphylaxis in a 43-year-old man. After multidisciplinary review, all received intravenous zoledronic acid with vitamin D repletion; KIT-targeted therapy is under consideration in selected patients. Although causal inferences cannot be drawn from four retrospectively identified cases, the series illustrates how ISM may be missed in unexplained or treatment-refractory osteoporosis-particularly in younger men, those with prior severe anaphylaxis, and those fracturing on antiresorptive therapy-and supports combining basal serum tryptase with high-sensitivity peripheral-blood KIT D816V testing, in line with the WHO/ICC/AIM-ECNM 2022-2024 criteria. Prospective studies are needed.

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