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Diagnostics (Basel, Switzerland) Jan 2024Mastocytosis is characterized by an accumulation of clonal mast cells (MCs) in tissues such as the skin. Skin lesions in mastocytosis may be clinically subtle or... (Review)
Review
BACKGROUND
Mastocytosis is characterized by an accumulation of clonal mast cells (MCs) in tissues such as the skin. Skin lesions in mastocytosis may be clinically subtle or heterogeneous, and giving the correct diagnosis can be difficult.
METHODS
This study compiles personal experiences together with relevant literature, discussing possible obstacles encountered in diagnosing skin involvement in mastocytosis and cutaneous mastocytosis (CM).
RESULTS
The nomenclature of the term "CM" is ambiguous. The WHO classification defines CM as mastocytosis solely present in the skin. However, the term is also used as a morphological description, e.g., in maculopapular cutaneous mastocytosis (MPCM). This is often seen in systemic, as well as cutaneous, mastocytosis. Typical CM manifestations (MPCM), including mastocytoma or diffuse cutaneous mastocytosis (DCM), all share a positive Darier's sign, and can thus be clinically recognized. Nevertheless, distinguishing monomorphic versus polymorphic MPCM may be challenging, even for experienced dermatologists. Less typical clinical presentations, such as MPCM with telangiectatic erythemas (formerly called telangiectasia macularis eruptiva perstans), confluent, nodular or xanthelasmoid variants may require a skin biopsy for histopathological confirmation. Because MC numbers in CM have a large overlap to those in healthy and inflamed skin, detailed histopathological criteria to diagnose mastocytosis in MPCM are needed and have been proposed. D816V mutational analysis in tissue is helpful for confirming the diagnosis. Biomarkers allow the prediction of the course of CM into regression or evolution of the disease. Further diagnostic measures should screen for concomitant diseases, such as malignant melanoma, and for systemic involvement.
CONCLUSIONS
Whereas in typical cases the diagnosis of CM may be uncomplicated, less typical manifestations may require specific investigations for making the diagnosis and predicting its course.
PubMed: 38248039
DOI: 10.3390/diagnostics14020161 -
Diagnostics (Basel, Switzerland) Dec 2023Pediatric mastocytosis is mostly a cutaneous disease classified as cutaneous mastocytosis (CM), which is characterized by mast cell (MCs) accumulation in the skin and... (Review)
Review
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.
PubMed: 38066824
DOI: 10.3390/diagnostics13233583 -
Journal For Immunotherapy of Cancer Sep 2021We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund's adjuvant (CFA)) in three preclinical species and in human cancer...
BACKGROUND
We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund's adjuvant (CFA)) in three preclinical species and in human cancer patients.
METHODS
Efficacy and safety were tested in mammary tumors in mice, in mastocytomas in mice and dogs, and in equine melanomas. In mice, survival, tumor growth, and tumor infiltration by six immune cell subsets (by flow cytometry) were investigated and analyzed using Cox proportional hazards, a random slopes model, and a full factorial model, respectively. Tumor growth and histology were investigated in dogs and horses, as well as survival and tumor immunohistochemistry in dogs. Tumor biopsies were taken from human cancer patients on day 5 (all patients) and day 28 (some patients) of treatment and analyzed by histology. CT scans are provided from one patient.
RESULTS
Significantly extended survival was observed in mouse P815 and 4T1 tumor models. Complete tumor regressions were observed in all three non-human species (6/186 (3%) of mouse mastocytomas; 3/14 (21%) of canine mastocytomas and 2/11 (18%) of equine melanomas). Evidence of systemic immune responses (regression of non-injected metastases) was also observed. Analysis of immune cells infiltrating mastocytoma tumors in mice showed that early neutrophil infiltration was predictive of treatment benefit. Analysis of the site of mastocytoma regression in dogs weeks or months after treatment demonstrated increased B and T cell infiltrates. Thus, activation of the innate immune system alone may be sufficient for regression of some injected tumors, followed by activation of the acquired immune system which can mediate regression of non-injected metastases. Finally, we report on the use of CFA in 12 human cancer patients. Treatment was well tolerated. CT scans showing tumor regression in a patient with late-stage renal cancer are provided.
CONCLUSION
Our data demonstrate that intratumoral injection of CFA has major antitumor effects in a proportion of treated animals and is safe for use in human cancer patients. Further trials in human cancer patients are therefore warranted. Our novel treatment provides a simple and inexpensive cancer immunotherapy, immediately applicable to a wide range of solid tumors, and is suitable to patients in developing countries and advanced care settings.
Topics: Animals; Cell Line, Tumor; Dogs; Female; Horses; Humans; Immunotherapy; Male; Mice; Neoplasms
PubMed: 34531247
DOI: 10.1136/jitc-2021-002688 -
International Journal of Molecular... Mar 2021Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to... (Review)
Review
Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier's sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.
Topics: Administration, Topical; Adult; Anaphylaxis; Child; Humans; Insect Bites and Stings; Mast Cells; Mastocytosis; Mastocytosis, Systemic; Risk Factors; Skin; Tryptases
PubMed: 33799959
DOI: 10.3390/ijms22052684 -
The Veterinary Record Jul 2023Canine subcutaneous mast cell tumours (ScMCTs) reportedly have a good prognosis. However, biomarkers that can be used to predict outcome are currently limited.
BACKGROUND
Canine subcutaneous mast cell tumours (ScMCTs) reportedly have a good prognosis. However, biomarkers that can be used to predict outcome are currently limited.
METHODS
A multicentre prospective study was conducted to identify new prognostic markers. Dogs with a first occurrence of ScMCT were enrolled upon primary tumour removal and regional lymphadenectomy. In the absence of metastasis, dogs were monitored, while dogs with overtly metastatic lymph nodes (histological node 3, HN3) received adjuvant vinblastine.
RESULTS
Forty-three dogs were enrolled: 15 (34.9%) had at least one HN3 lymph node and received vinblastine, and 28 (65.1%) were monitored. Three tumours harboured exon 8 and 9 c-kit mutations. Eight (18.6%) dogs experienced tumour progression, and five (11.6%) died of MCT-related causes. The 1- and 2-year survival rates were 90% and 77%, respectively. Variables significantly associated with an increased risk of progression included high cytograde, a mitotic count (MC) greater than 4/10 high-power fields (hpf) and Ki67-index greater than 23. An MC greater than 4/10 hpf was also associated with an increased risk of tumour-related death.
LIMITATIONS
Regional rather than sentinel lymphadenectomy was performed in these dogs. Dogs were enrolled in oncology referral centres, constituting a different population compared to previous studies.
CONCLUSIONS
ScMCTs have a good prognosis. However, the metastatic rate at admission was higher in this study than previously reported, and a subset of tumours were associated with a fatal outcome despite multimodal treatment. Proliferative activity and cytograding may predict more aggressive behaviour in ScMCTs.
Topics: Dogs; Animals; Prognosis; Prospective Studies; Mast Cells; Vinblastine; Lymph Nodes; Dog Diseases
PubMed: 37224084
DOI: 10.1002/vetr.2991 -
Journal of Drugs in Dermatology : JDD Mar 2024Mastocytosis is a group of disorders characterized by the pathologic accumulation of mast cells in various tissues. One example of mastocytosis is urticaria pigmentosa,...
Mastocytosis is a group of disorders characterized by the pathologic accumulation of mast cells in various tissues. One example of mastocytosis is urticaria pigmentosa, which presents with mastocytomas that can cause hives and, when irritated, pruritus. To our knowledge, we are describing the first case of urticaria pigmentosa without pruritus. The patient had a positive Darier's sign, stated that they never felt itchy, and denied ever using a topical steroid or antihistamine. Although our patient declined additional testing, patients like this may benefit from a detailed evaluation of their sensory system through both quantitative sensory testing and genetic analysis. J Drugs Dermatol. 2024;23(3): doi:10.36849/JDD.7558e.
Topics: Humans; Urticaria Pigmentosa; Pruritus; Urticaria; Mast Cells; Emotions
PubMed: 38443117
DOI: 10.36849/jdd.7558 -
International Journal of Dermatology May 2023Mastocytosis is a heterogeneous group of rare disorders characterized by the accumulation of clonal mast cells in organs such as the skin and bone marrow. The diagnosis...
BACKGROUND
Mastocytosis is a heterogeneous group of rare disorders characterized by the accumulation of clonal mast cells in organs such as the skin and bone marrow. The diagnosis of cutaneous mastocytosis (CM) is based on clinical findings, positive Darier's sign, and histopathology, if necessary.
METHODS
Medical records of 86 children with CM diagnosed during a 35-year long period were reviewed. Most patients (93%) developed CM during the first year of life (median age 3 months). Clinical features at presentation and during the follow-up period were analyzed. Baseline serum tryptase level was measured in 28 patients.
RESULTS
A total of 85% of patients had maculopapular cutaneous mastocytosis/urticaria pigmentosa (MPCM/UP), 9% had mastocytoma, and 6% had diffuse cutaneous mastocytosis (DCM). Boy to girl ratio was 1.1:1. Fifty-four of 86 patients (63%) were followed from 2 to 37 years (median 13 years). Complete resolution was registered in 14% of mastocytoma cases, 14% of MCPM/UP, and in 25% of DCM patients. After the age of 18, skin lesion persisted in 14% mastocytoma, 7% MCPM/UP, and 25% children with DCM. Atopic dermatitis was diagnosed in 9.6% of patients with MPCM/UP. Three of 28 patients had elevated serum tryptase. Prognosis in all patients was good, and there were no signs of progression to systemic mastocytosis (SM).
CONCLUSION
To the best of our knowledge, our results represent the longest single-center follow-up study of childhood-onset CM. We found no complications of massive mast cell degranulation or progression to SM.
Topics: Male; Female; Humans; Child; Infant; Follow-Up Studies; Tryptases; Mastocytosis; Urticaria Pigmentosa; Mastocytosis, Cutaneous; Mast Cells; Mastocytosis, Systemic; Mastocytoma
PubMed: 36807903
DOI: 10.1111/ijd.16612 -
Arerugi = [Allergy] 2022Cutaneous mastocytosis (CM) usually appears in childhood and improves substantially before adolescence. The c-KIT mutation of D816V is present in 36% and 20% of patients... (Review)
Review
Cutaneous mastocytosis (CM) usually appears in childhood and improves substantially before adolescence. The c-KIT mutation of D816V is present in 36% and 20% of patients with childhood-onset CM and diffuse cutaneous mastocytosis (DCM), respectively. In some cases of childhood-onset DCM, the disease can progress to systemic mastocytosis; in others, it resolves spontaneously. Thus, assessing the prognosis is difficult. Herein, we described a case of DCM in an 11-month-old, male patient without a c-KIT mutation. The patient presented with dark brown macules and sporadic erythema topped by bullous lesions. A skin biopsy of the macule on the abdomen revealed accumulation of mast cells which were round to oval-shaped with amphophilic cytoplasm within the upper dermis. The patient had received H1 inhibitor until age 3 years and continued to experience blisters on the trunk. However, no severe symptoms, such as anaphylaxis, occurred. Included in this manuscript is a review of previous reports of childhood-onset DCM in Japan and cases specifically seen at our dermatology clinic.
Topics: Adolescent; Child, Preschool; Humans; Infant; Male; Mast Cells; Mastocytosis, Cutaneous; Prognosis; Proto-Oncogene Proteins c-kit; Skin
PubMed: 35831165
DOI: 10.15036/arerugi.71.397 -
Medical Engineering & Physics Dec 2021Electrochemotherapy (ECT) requires covering the entire tumor and safe margins with a suitable pulsed electric field (PEF). The PEF distribution depends on the biological...
Electrochemotherapy (ECT) requires covering the entire tumor and safe margins with a suitable pulsed electric field (PEF). The PEF distribution depends on the biological and electrical parameters. The biological tissue may have diffractive geometry with non-linear conductivity behavior due to electroporation. That characteristic may provoke ECT-insufficient electric field regions, also known as blind spots. The conductive gels can fill holes and bumps, being a tool to homogenize the electric field. We executed an in vitro vegetal tissue experiment to validate a numerical model under different gels conditions. We used a study case in silico experiment to investigate gel influence on PEF distribution and electrical current. We propose a case-oriented methodology to optimize the gel during the ECT pre-treatment. Results show that the optimized gel completely treats a region of interest while avoiding unnecessary current increase and damage to healthy tissue by over treatment. The optimized gel conductivity may be lower than the previously reported (0.5 to 1 S/m) and may be in the range of the commercially available gels. For a veterinary mastocytoma exophytic nodule ECT case study, using needles electrode, the 0.2 S/m gel is the optimum gel.
Topics: Computer Simulation; Computers; Electric Conductivity; Electrochemotherapy; Electroporation; Gels
PubMed: 34848032
DOI: 10.1016/j.medengphy.2021.10.011 -
Clinics in Dermatology 2019Cutaneous disease can present with lesions of all colors of the visible spectrum. Lesions of the skin, nail, and mucous membranes with an orange color can be due to a... (Review)
Review
Cutaneous disease can present with lesions of all colors of the visible spectrum. Lesions of the skin, nail, and mucous membranes with an orange color can be due to a variety of etiologies. The conditions may appear as purely orange, yellow-orange, red-orange, tan, or brown with an orange hue. The orange color may also present as a transient phase of a disease process. As with all dermatologic pathology, a key way to distinguish orange-colored lesions is by distribution and morphology. The sclera, palate, lips, gingiva, and nails may also be involved. A literature review using PubMed with keywords, including orange, skin, mucosa, cutaneous, xanthoderma, and granuloma, was conducted to gather all dermatologic conditions that can present with an orange color. The relevant diseases were categorized by etiology and include inflammatory, infectious, neoplastic, and exogenous causes.
Topics: Color; Histiocytosis, Non-Langerhans-Cell; Humans; Leishmaniasis, Cutaneous; Lupus Vulgaris; Mastocytoma; Mastocytoma, Skin; Mouth Mucosa; Pigmentation Disorders; Pityriasis Rubra Pilaris; Sarcoidosis; Sebaceous Gland Neoplasms
PubMed: 31896407
DOI: 10.1016/j.clindermatol.2019.07.014