Systemic mastocytosis (SM) is characterized by the accumulation of neoplastic mast cells in bone marrow and other organs. Gastrointestinal (GI) symptoms are common in both SM and cutaneous ...mastocytosis urticaria pigmentosa (UP), and are usually caused by the release of histamine and other inflammatory mediators. Occasionally, neoplastic mast cells may also directly infiltrate the GI tract. Previous studies have suggested that enumeration of the mast cells in GI biopsies may help establish the diagnosis of SM. However, mast cells have been reported to be increased in various inflammatory diseases, and mast cell density has not been systematically evaluated in other GI disorders. Recently, expression of CD25 by mast cells in bone marrow has been shown to be specific for SM. The purpose of this study was (1) to quantitate and compare mast cells in mucosal biopsies from patients with SM involving the GI tract, UP with GI symptoms, and a control group of diverse inflammatory disorders, and (2) to determine whether immunostaining for CD25 can be used to distinguish neoplastic from reactive mast cells in GI biopsies. Seventeen GI biopsies from 6 patients with SM; 17 GI biopsies from 5 patients with UP; and 157 control cases including 10 each normal stomach, duodenum, terminal ileum, and colon, Helicobacter pylori gastritis, bile reflux gastropathy, peptic duodenitis, celiac disease, Crohn disease, ulcerative colitis, lymphocytic colitis, and collagenous colitis, 20 biopsies from 16 patients with irritable bowel syndrome, 8 biopsies from 5 patients with parasitic infections, and 9 biopsies from 7 patients with eosinophilic gastroenteritis were immunostained for mast cell tryptase, c-kit (CD117), and CD25. Mucosal mast cells were quantitated, and the presence or absence of CD25 expression on mast cells was determined. In SM patients, mast cells in the small intestine and colon numbered >100/high-power field (HPF) in nearly all cases (mean 196/HPF; range 74 to 339). This was significantly higher than in GI biopsies from UP patients (mean 17/HPF; range 8 to 32, P<0.0001) and all inflammatory diseases (P<0.01). Mast cell density in other disorders ranged from a mean of 12/HPF in H. pylori gastritis to 47/HPF in parasitic infections. Interestingly, all SM biopsies (and none of the other cases) contained aggregates or confluent sheets of mast cells. In addition, mast cells in all SM cases were positive for CD25, whereas GI mucosal mast cells in UP and all other control cases were negative. In conclusion, quantitation of mast cells can be helpful to diagnose SM in GI mucosal biopsies, although mast cells are also markedly increased in parasitic infections. Aggregates or sheets of mast cells are only seen in SM. Immunoreactivity for CD25 in GI mucosal mast cells is specific for SM and can be used to confirm the diagnosis.
Cutaneous mastocytosis (CM) is a rare condition in young dogs characterized by multicentric cutaneous proliferation of neoplastic mast cells. Clinical data from 8 dogs that met inclusion criteria ...(age of onset less than 1.5 years, greater than 3 lesions) were obtained via a standardized survey. Biopsy samples were classified by the Kiupel/Patnaik grading systems and analyzed for c-KIT mutations. The median age of onset was 6 months (range: 2–17 months). Dogs had 5 to more than 50 lesions characterized as nodules, plaques, and papules. Seven dogs were pruritic. Clinical staging in 2 dogs did not reveal visceral involvement. No dogs had systemic illnesses at diagnosis. Histologically, CM was similar to cutaneous mast cell tumor (cMCT). Two dogs had neoplasms classified as high-grade/grade II while 6 dogs had low-grade/grade II neoplasms. No dogs had mutations in c-KIT exons 8 and 11. Treatment included antihistamines (8/8), corticosteroids (7/8), lokivetmab (3/8), and toceranib (1/8). Six dogs were alive with lesions at the end of the study with a median follow-up time of 898 days, while 2 dogs were euthanized. In dogs with high-grade/grade II neoplasms, one continued to develop lesions at 1922 days post-diagnosis, while the other dog was euthanized at 56 days post-diagnosis. One dog was euthanized 621 days post-diagnosis due to rupture of a neoplasm. CM occurs in young dogs and is histologically indistinguishable from cMCT. Current histologic grading systems did not apply uniformly to the dogs of the study and further studies are needed.
Urticaria pigmentosa is a rare dermatologic syndrome in humans, cats, and dogs. This report documents a case of canine urticaria pigmentosa-like disease with unusual features and no C-kit mutation.
Summary
Mastocytosis is a heterogeneous group of diseases characterized by abnormal proliferation of mast cells. Systemic mastocytosis (SM), in which abnormal mast cells are present in tissues beyond ...the skin, is divided into seven subcategories with varying degrees of severity and prognosis. Very little is known about the epidemiology of SM and its subcategories. This retrospective cohort study of 548 adults with SM diagnosed 1997–2010 was constructed using linked Danish national health registries. The most common subtype of mastocytosis was indolent SM (including urticaria pigmentosa) (n = 450; 82%), followed by SM with subtype unknown (n = 61; 11%), SM with associated clonal haematological non‐mast cell lineage disease (n = 24; 4%), aggressive SM (n = 8; 2%), and mast cell leukaemia (n = 5; 1%). The incidence rate for SM (all subtypes including urticaria pigmentosa) was 0·89 per 100 000 per year. Cumulative incidence was 12·46 per 100 000, and the 14‐year limited‐duration prevalence as of 1 January, 2011 was 9·59 per 100 000. This nationwide cohort from Denmark is the first population‐based epidemiological study of mastocytosis. In this cohort of patients aged 15 years and older, SM was found to be overall relatively rare with notable variation by subtype for patient characteristics, survival and epidemiological measures.
Summary
Paediatric mastocytosis was previously considered to be a benign and spontaneously regressing disease. However, this evolution is impossible to predict. To clarify the characteristics and ...course of paediatric mastocytosis, we performed a literature review of 1747 cases published between 1950 and April 2014. Lesions occurred before the age of 2 years in 90% of cases, and presented as urticaria pigmentosa (75% of cases), mastocytoma (20%) or diffuse cutaneous mastocytosis (5%). The male‐to‐female ratio was 1·4. KIT D816V mutation was detected in 34% of 215 tested patients. Clinical regression (complete or partial) occurred in 67% of cases and stabilization in 27%. However, the outcome was fatal in 2·9% of patients.
What's already known about this topic?
The clinical and genetic features and outcomes of mastocytosis differ for the adult and paediatric forms.
Since paediatric mastocytosis was linked to mutations in c‐Kit in 2010, it has been considered a clonal disease.
In 1963, Caplan reported that spontaneous regression occurs in the majority of cases of paediatric mastocytosis, and no predictive factors have been identified.
What does this study add?
This extensive review points out that the outcome in some paediatric cases is fatal, that KIT mutations are rarely studied and that predictive factors are still unknown.
We suggest that long‐term follow‐up of children is necessary and that prospective studies are warranted to evaluate the prognostic value of sequencing KIT.
Mastocytosis is an accumulation of clonal mast cells within tissues and it is most commonly caused by an activating mutation in the KIT gene. In this study, we report a neonatal case who presented ...with diffuse cutaneous mastocytosis (CM) at birth. In China, nine other cases of neonatal-onset CM have been reported in the literature since 2006. In those cases, diffuse CM and urticaria pigmentosa were the main symptoms, and mutations in exon 17 at codon 816 in KIT were identified.
The association between Hymenoptera venom‐triggered anaphylaxis (HVA) and clonal mast cell‐related disorders (cMCD) has been known for decades. However, recent breakthroughs in peripheral blood ...screening for KIT p.D816V missense variant have revealed the true extent of this clinical association whilst adding to our understanding of the underlying aetiology. Thus, recent large studies highlighted the presence of KIT p.D816V among 18.2% and 23% of patients with severe Hymenoptera venom‐triggered anaphylaxis. A significant proportion of those patients have normal serum basal tryptase (BST) levels, with no cutaneous findings such as urticaria pigmentosa or other systemic findings such as organomegaly that would have suggested the presence of cMCD. These findings of an increased prevalence suggest that the impact of cMCD on anaphylaxis could be clinically underestimated and that the leading question for clinicians could be changed from ‘how many patients with cMCD have anaphylaxis?’ to ‘how many patients with anaphylaxis have cMCD?’. The discovery of hereditary α‐tryptasemia (HαT)—a genetic trait caused by an increased copy number of the Tryptase Alpha/Beta 1 (TPSAB1) gene‐, first described in 2016, is now known to underlie the majority of cases of elevated BST outside of cMCD and chronic kidney disease. HαT is the first common heritable genetic modifier of anaphylaxis described, and it is associated with increased risk for severe HVA (relative risk = 2.0), idiopathic anaphylaxis, and an increased prevalence of anaphylaxis in patients with cMCD, possibly due to the unique activity profile of α/β ‐tryptase heterotetramers that may potentiate immediate hypersensitivity reaction severity. Our narrative review aims to highlight recent research to have increased our understanding of cMCD and HαT, through recent lessons learned from studying their association with HVA. Additionally, we examined the studies of mast cell‐related disorders in food and drug allergy in an effort to determine whether one should also consider cMCD and/or HαT in cases of severe anaphylaxis triggered by food or drugs.
Non‐clonal mast cell disease, hereditary alpha‐tryptasemia, and anaphylaxis. Hereditary alpha‐tryptasemia (HαT) is strongly associated with clonal mast cell disease (cMCD). Either of those conditions alone is a predisposing factor for severe IgE‐dependent and IgE‐independent anaphylaxis however, the presence of HαT in patients with cMCD serves to further increase the severity of anaphylactic reactions.
PDF
